Chronic Constrictive Pericarditis: Pending Issues

Indian Heart J 2003; 55: 305–309 Kothari et al. Chronic Constrictive Pericarditis 305

Chronic Constrictive Pericarditis: Pending Issues

SS Kothari, Ambuj Roy, VK BahlDepartment of Cardiology, All India Institute of Medical Sciences, New Delhi

Chronic constrictive pericarditis (CCP) is a wellcharacterized clinical entity.1–3 With advances in the

understanding of hemodynamics, Doppler echocardio-graphy, and cardiac cross-sectional imaging, the diagnosisof CCP has been straightforward. However, it oftenmasquerades as chronic liver disease, cardiomyopathy,unexplained heart failure, etc. Furthermore, there is aremarkable paucity of information regarding thepathogenesis, and the optimal management of patientswith CCP. In this article, we provide a brief perspective onthe recent advances in CCP, and highlight the need for moreevidence-based data regarding a disease that is still commonin India.

Etiology

Identifying the etiology of CCP has been notoriouslydifficult. The vast majority of patients with idiopathic CCPare suspected to have had tuberculosis in the past. Whileproven tubercular pericarditis may present with densefibrosis without any direct evidence of tuberculosis, suchfibrosis may follow other etiologies of CCP as well. Thereported prevalence of idiopathic CCP has varied from 24%to 61% in Indian studies,4–6 depending on the criteria usedto diagnose tubercular CCP. Tuberculosis remains acommon cause of CCP in developing countries, with areported incidence of 38%–83%.4,7–9 The etiology of CCPin the western world has now undergone a significantchange, with tuberculosis reported in only 0%–1% of casesin some recent series.10,11 The leading identifiable causes ofCCP are following cardiac surgery and radiation therapy,besides viral pericarditis.10–12 The incidence of CCPcomplicating cardiac surgery is between 0.025% and0.15% of patients undergoing open heart surgery.13

However, the lack of reports of post-surgical and post-radiation CCP from India is remarkable. An informalinquiry in the five major Indian medical college hospitalsdid not yield cases of CCP following cardiac surgery. Possiblysuch cases are being missed.

Pathogenesis

The precise pathogenesis of CCP remains unknown, and isscantily investigated. CCP may result from the progressionof an acute pericarditis from a dry stage through an effusive,absorptive, and constrictive phase sequentially; or it mayresult from a smouldering fibrosis with no previous historyof an acute pericarditis (as occurs in the majority ofpatients). The factors responsible for the resolution ofinflammation or its progression to severe fibrosis remainunknown. For example, in nearly half the patients withtubercular pericardial effusion resolution occurs withoutconstriction, while the rest develop CCP despite adequateand similar antitubercular therapy.14 The virtual absenceof CCP following rheumatic fever,15 and its low incidencein tubercular pericarditis in HIV-positive patients arenoteworthy.16 Little research has been done to unravel theinflammatory repertoire of the pericardial tissue.17 The roleof cytokines in tubercular pericardial effusion has beeninvestigated recently. It appears that tubercular pericarditisis a hypersensitivity reaction to antigens such astuberculoproteins. The increased production of interferon-gamma, tumor necrosis factor-alpha, and interleukin-1 andinterleukin-2 in tubercular pericardial effusion suggest thatthe inflammation is orchestrated by T-helper-1lymphocytes.18 T-lymphocytes and activated macrophagesseem to play an important role in granuloma formationand fibrosis.19 However, the exact mechanism has not beenelucidated. Similarly, the mechanisms of constriction inpostoperative patients, in patients with collagen vasculardisease, or those with the rare but interesting hereditarydisease mulibreynanism remain unexplored andunexplained.

Mechanism of Fluid Retention

In general, patients with CCP retain more water andsodium than patients with myocardial disease. The ascitesin CCP is out of proportion to edema, and also occursearlier than peripheral edema, a sequence opposite to thatseen with other causes of congestive heart failure (CHF).The cause of this “ascites precox” has never beensatisfactorily explained. It could simply be a reflection ofvery high right atrial pressures compared to other causes

Editorial

Correspondence: Professor VK Bahl, Department of Cardiology,All India Institute of Medical Sciences, New Delhi 110029e-mail: [email protected]

EDITORIAl-New.p65 11/19/2003, 11:23 PM305

306 Kothari et al. Chronic Constrictive Pericarditis Indian Heart J 2003; 55: 305–309

of CHF. Increased venous pressures, hypoalbuminemiaresulting from protein-losing enteropathy, cardiaccirrhosis, increased capillary permeability, and impedanceto lymph flow have been suggested but appear to beinadequate explanations.

The mechanisms of fluid retention in CCP have beenexplored in a systematic fashion in only one study.20 In 16patients with untreated CCP, it was found that themagnitude and mechanisms of sodium and water retentiondiffered somewhat from a similar congestion resulting fromdecreased cardiac output due to myocardial failure. For acomparable reduction in cardiac output, volume retentionwas higher and vascular resistance was lower in patientswith CCP compared to those with myocardial disease.20 Theactivation of the renin–angiotensin–aldosterone andsympathetic systems were found to be similar in CCP andother causes of CHF.20 The atrial natriuretic peptide (ANP)levels in patients with CCP were five times higher than thosein normal controls, but were only one-third of those seenin myocardial disease.20,21 The ANP levels in CCP are lessthan what might be expected on the basis of right atrialpressures alone. This may be primarily due to less distensibleatria caused by the constrictive process in CCP, as ANPrelease is mediated by atrial stretch. The greater salt andwater retention in CCP could be due to smaller increase inANP levels. The ANP hypothesis has been suggested toexplain the lack of pulmonary edema in CCP andtamponade despite very high central pressures.22 ANP isshown to increase capillary hydraulic conductivity, andenhance transcapillary fluid movement.22 To the best of ourknowledge, ANP in restricted cardiomyopathy (RCM) hasnot been studied systematically.

Interestingly, other neurohumoral or autonomic effectsmay also be important. In CCP, severe autonomicdysfunction was reported in all segments of the autonomicnervous system.23 In contrast, autonomic dysfunction wasmuch less in patients with RCM, and involved theparasympathetic efferent pathway.24 Thus, mechanismsother than ANP may also be operative.

Prevention of Constrictive Pericarditis

Nonsteroidal anti-inflammatory drugs, colchicines, andsteroids may reduce the chances of CCP by preventingrecurrence of pericarditis. However, the data on this aspectare scanty and inconclusive. Limited information isavailable regarding even the commonly occurringtubercular pericarditis. The oft-quoted South African trial25

in 240 patients of tubercular pericarditis reported asignificant reduction in the need for repeat pericardio-centesis in patients randomized to receive steroids for 11

weeks. But steroids did not reduce the need forpericardiectomy at 24 months.25 The study has beencriticized as it did not include all-cause mortality, did notanalyze data on the basis of intention-to-treat, and excludedpatients not adhering to the protocol. A re-analysis of thistrial by Ntsekhe et al.26 also did not give definite answers.In the other trial of steroids in patients with establishedCCP, 2 of the 53 patients (4%) treated with prednisoloneand 7 of the 61 patients treated with a placebo (11%) diedfrom pericarditis, and 11 (21%) and 18 (30%), respectively,required pericardiectomy. However, these differences werenot statistically significant.27

Corticosteroids could have an adverse impact on thealready compromised immune status of patients with HIVand tubercular pericarditis. However, in a recent trial of58 patients, steroids led to a significant reduction in all-cause mortality in HIV-positive patients with tubercularpericarditis on 18-month follow-up.16 Interestingly, a re-analysis of the trial data failed to show the benefit ofsteroids.26 Thus, there is still a need for large, multicentric,prospective controlled trials to accurately assess the benefitof adjuvant steroids in tubercular pericarditis.

Role of pericardial drainage: Usually, large effusionsthat are unresponsive to treatment, unexplained effusionsor effusions that last for longer than 3 months warrantpericardiocentesis. Such pericardiocentesis is curative inhalf the cases.1 Whether routine drainage of pericardialeffusion is helpful in preventing the occurrence of CCP hasrarely been investigated.25,28 Strang et al.25 randomizedpatients with tubercular pericarditis to open drainage, orno drainage, and followed them up for up to 24 months toassess their outcome. Open pericardial drainage did notdecrease mortality or improve clinical outcome at follow-up. The routine drainage of pericardial fluid in tubercularpericarditis does not seem to be useful, especially in areaswith a high prevalence. It may be useful in areas wheretuberculosis is an uncommon cause of pericarditis as it mayhelp to obtain pericardial fluid for examination. In a studyof 71 patients with large pericardial effusion (>2 cm onechocardiography) of different etiologies, routine drainagedid not yield significant diagnostic information, and wasnot useful in preventing the occurrence of cardiactamponade or CCP.28

The efficacy of pericardiocentesis in preventing CCP inhemorrhagic effusion has not been tested specifically. Inpurulent pericarditis, adequate drainage and fibrinolyticagents seem to reduce the occurrence of CCP, but againthe data are limited.29 In one study of 6 children withpyopericardium, instillation of intrapericardialstreptokinase at a dose of 10 000 to 15 000 U/kg twice



daily for a mean of 6 days led to the resolution ofpericarditis, and freedom from CCP on follow-up.29

Diagnosis of CCP

Hemodynamics: The hemodynamic criteria to diagnoseCCP, viz. elevated diastolic pressures, typical pressurewaveforms, and equilibration of pressure of all fourchambers in diastole, have been discussed widely, yet thesemay not be diagnostic in individual cases. In one study, one-fourth of the patients could not be identified by these criteriaof equalization of the right and left ventricular diastolicpressures within 5 mmHg, pulmonary artery systolicpressure less than 50 mmHg, and right ventricular end-diastolic pressure more than one-third of the rightventricular systolic pressure.30 Evidence of dissociation ofintracardiac and intrathoracic pressures, and the presenceof ventricular interdependence (i.e. reciprocal respiratoryvariation in right ventricular/left ventricular pressures)have improved the accuracy. Ventricular interdependencehad 100% sensitivity and 95% specificity for distinguishingCCP from RCM.31 However, in real-world situations severalpatient-related or other factors complicate theinterpretation of laboratory data. The presence of localizedconstriction, associated myocardial dysfunction, othervalve disease, obesity, obstructive airway disease, previousinfarction, and other co-morbidities may influence theirmeasurement. For example, a disproportionately elevatedpulmonary artery wedge pressure was seen in patients withmitral valve disease,32 and even evidence of ventricularinterdependece was reportedly lacking in a patient with alocalized constriction.33

Doppler echocardiography: Doppler echocardiographicparameters have been a very valuable addition to thediagnosis of CCP, and in its differentiation from RCM. Theinitial study that suggested a cut-off of 25% respiratoryvariation in mitral valve inflow velocities was based on thedata from only 7 patients with CCP.34 Subsequently, a largerstudy found that 12% of patients did not show diagnosticchanges in these echocardiographic parameters.35 Severalcaveats need to be considered in individual cases. Forexample, a very high preload may be one reason for theabsence of respiratory variation,36 and a reduction inpreload may be required to bring out the typical pattern,or fluid challenge may be required to diagnose patients withoccult CCP.37 In addition, irregular breathing, irregularheart rate, and short diastolic periods resulting fromtachycardia may cause difficulty in the interpretation ofrespiratory variation of Doppler velocities. The additionaluse of tissue Doppler imaging (TDI) may further enhance

the diagnostic utility of echocardiography. Reduced mitralannular velocity on TDI was reported in RCM, whereasthese parameters were normal in patients with CCP in theinitial reports.38,39

Cross-sectional imaging: The other commonly usedinvestigation for the diagnosis of CCP is cross-sectionalimaging with computerized tomography (CT) and magneticresonance imaging (MRI). The diagnostic hallmark of thesetests is the presence of pericardial thickening with orwithout calcification. While a minimal amount ofpericardial calcification is better detected by CT scan, MRIprovides better soft tissue characterization.40 Pericardialthickening of more than 3 mm is usually taken asabnormal; the usual thickening of the pericardium being1–2 mm. The actual thickness of the pericardium is 0.4–1mm, and this discrepancy between MRI and pathologicalmeasurement is most likely due to a combination of volumeaveraging, chemical shift artifact, motion artifact, and theinclusion of a small amount of pericardial fluid in MRImeasurements.40 Though commonly used, the data on thediagnostic utility of CT/MRI in CCP are not robust. In onesmall study of 29 patients, pericardial thickening on MRIwas found to be 88% sensitive and 100% specific fordetecting CCP.41

It is important to look for additional findings suggestiveof CCP, such as dilated inferior vena cava (IVC), enlargedatria, tubular-shaped ventricles, ascites and pleural effusionon CT/MRI images. Myocardial tagging has also beensuggested as a new method of mitral/tricuspid annularmovement. As normal ventricles contract, there is aslippage between the myocardium and pericardium;however, once pericardial adhesions develop, this slippageis absent and the tag lines passing through the myocardiumand pericardium are not deformed during the cardiaccycle.42 The presence of abnormal diastolic motion of theseptum on cine MRI may also be a useful finding to diagnoseCCP, and to distinguish it from RCM.43

Thus, no single test in isolation should be considereddiagnostic of CCP.

CCP with Normal Pericardial Thickness

It is well known that pericardial thickening may be presentwithout CCP; however, it is not as well recognized that CCPmay occur with normal thickness of the pericardium,which was reported in 18% of 143 patients in a recentlypublished series from the Mayo Clinic. These patients mostcommonly had post-surgical and post-radiation CCP.12

Their clinical characteristics were similar to patients withCCP with a thickened pericardium, and pericardiectomy


308 Kothari et al. Chronic Constrictive Pericarditis Indian Heart J 2003; 55: 305–309

was very effective in relieving the symptoms. Microscopyof the excised pericardium was abnormal in all the patients,and included the presence of focal fibrosis, focal calcificationor inflammation. Thus, pericardiectomy should not bedenied to patients with typical clinical and hemodynamicfeatures of CCP but with a normal pericardial thickness onimaging.

Transient CCP

It is conceivable that occasionally, the inflammatoryexudates causing clinical CCP may resolve with no featuresof constriction on follow-up.44,45 Such an event occurredin 15% of patients with tubercular pericarditis in one reportfrom South Korea.46 The resolution occurred within 2months in the majority of patients. Perhaps transient CCPcould occur even more often with purulent pericarditis.However, decisions regarding the management of thesepatients should be based on the overall clinical profile.

Surgical Aspects

Pericardiectomy is the definitive treatment for CCP but itstiming, surgical approach, and preoperative stabilizationneed careful consideration. Various approaches topericardiectomy, i.e. median sternotomy, lateralthoracotomy and bilateral thoracotomy with or withoutthe use of cardiopulmonary bypass, and anterior or totalremoval of the pericardium have been described dependingon patient population or personal preferences. The surgicalmortality of pericardiectomy continues to be high, and hasbeen generally reported to be 6%–12%4,10,47.A subgroup ofpatients with calcific CCP had a mortality of 19% in a recentseries.48 The negative predictors of survival afterpericardiectomy include NYHA class IV, low-voltage ECGcomplex, markedly increased atrial pressure, associatedorgan failure, and post-radiation CCP.10,46,47,49

The optimal timing of pericardiectomy is important.Pericardiectomy is unwarranted too early or too late in thecourse of the disease.1 Long-standing CCP may lead tomyocardial atrophy. Medical therapy may be better in somepatients with CCP having adverse risk factors in whom thesurgical mortality approaches 30%–40%.1 In purulentpericarditis, it is important not to intervene in the subacutestage when a plane of cleavage has not developed clearly.50

The occurrence of low cardiac output following CCP is oftena reflection of the chronicity of CCP and associatedmyocardial atrophy. Acute cardiac dilatation and failurefollowing pericardiectomy may occur unpredictably,51 andis not well characterized. Preoperative inotropes for 48

hours,47 and preoperative digitalization are often used toreduce the chances of postoperative heart failure but theireffectiveness is not clear. The improvement followingpericardiectomy may be rapid but, at times, occurs over afew weeks.1 However, residual CCP or recurrence of CCPdue to epicardial constriction remains a persistent problem.Multiple incisions into the fibrous epicardium whileprotecting the myocardium and coronary arteries are usefulin relieving the constriction (waffle procedure).52 In patientswith extensive calcific plaques, where large plaques do notpermit the development of cleavage planes, wedge incisionsthat reach up to the epicardium help release constriction.47

More recently, ultrasonic decalcification has been used intough calcific lesions.48

Conclusion

CCP continues to intrigue and engage clinicians despiteadvances in knowledge about the disease. No single test ordiagnostic finding should be considered pathognomic ofCCP. A combination of clinical and investigative resultsshould be thoughtfully analyzed to prevent misdiagnosis.Further research is required to understand thepathogenesis, prevention, and optimal treatment of CCP.

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22. Spodick D. Low atrial natriuretic factor levels and absent pulmonaryedema in pericardial compression of the heart. Am J Cardiol 1989;63: 1271–1272

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26. Ntsekhe M, Wiysonge C, Volmink JA, Commerford PJ, Mayosi BM.Adjuvant corticosteroids for tuberculous pericarditis: promising, butnot proven. QJM 2003; 96: 593–599

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310 Enas et al. Prudent Diet and Preventive Nutrition Indian Heart J 2003; 55: 310–338

Prudent Diet and Preventive Nutrition From Pediatricsto Geriatrics: Current Knowledge and Practical

Recommendations

Enas A Enas, A Senthilkumar, Hancy Chennikkara, Marc A BjurlinCoronary Artery Disease in Asian Indians (CADI) Research Foundation, and University of Illinois, Chicago, USA

man is what he eats” (German proverb). Foodprovides not only the essential nutrients for life but

also other bioactive compounds for the promotion of healthand the prevention of disease.1–3 The results of 50 years ofintensive worldwide research support the conclusion thatdiet is the major environmental cause of atherosclerosisand cardiovascular diseases (CVD), especially in geneticallysusceptible individuals.4 A high-caloric diet, combined withlimited physical activity, contributes to dyslipidemia, insulinresistance, diabetes, and obesity. All these abnormalitiesincrease the risk of CVD. Over the past few decades, theprevalence of obesity has doubled in adults, and quadrupledin teenagers in the USA. A similar pattern is emerging inIndia, where an epidemic of coronary artery disease (CAD)and diabetes is under way, with no signs of a downturn.Whereas the rates of CAD have declined by 60% in the US,the rates have increased by 300% in India over the past 30years.5 The public and physicians are constantly bombardedwith confusing and conflicting dietary advice. This reviewanalyzes the important recent developments in the fieldsof diet and nutrition for the prevention and treatment ofCVD and diabetes, with particular attention to AsianIndians.

Facts and Myths about Cholesterol, Fats, and Meats

The modern understanding of the role of nutrition in heartdisease began in 1903 when Anitschkow and Chalatowfound that a diet of meat, milk, and egg producedatherosclerosis in rabbits. A decade later, serum totalcholesterol (TC) level was found to be the agent responsible.Contrary to common belief, the contribution of dietarycholesterol to serum TC is small (<10 mg/dl). The averageadult on a western diet consumes about 300 mg ofcholesterol daily, which is about the size of 3 toothpicks,and hardly 3 cal. Nonetheless, high intakes of dietarycholesterol increase the number of circulating low-density

lipoprotein (LDL) particles.6 Dietary cholesterol is foundonly in the animal kingdom; 3 oz of beef, lamb, or porkcontains 75 mg of cholesterol. Most of the cholesterol inpoultry is in the skin, and some in dark meat. One cup ofmilk has 33 mg, 2 egg yolks have 560 mg, and 100 g ofbrain has 2000 mg of cholesterol. One hundred grams ofshrimp contain about 150 mg of cholesterol but <1 g ofsaturated fat. The recommended dietary intake ofcholesterol and various types of fat is given in Table 1.1,6–12

The contribution of dietary saturated fat to serum TC isvery large—10 times greater than that of dietarycholesterol. Fats are substances consisting of a combinationof fatty acids, which are classified as saturated (SAFA),monounsaturated (MUFA), polyunsaturated (PUFA), andtransunsaturated (TRAFA), depending on the location andnumber of double bonds.13 It is not often appreciated thatthe quality of the fat is more important than the quantityof fat consumed. The National Cholesterol EducationProgram (NCEP) recommends an intake of total fat of 25%–35%, MUFA up to 20%, PUFA up to 10%, and SAFA <7%of the total energy14 (Table 1). Although many affluentAsian Indians consume 50% of energy from fat, the averageconsumption is about half this amount (20%–25% of theenergy). Increasing the MUFA intake to 20%, and total fatintake to 35% of the energy appears to be appropriate forAsian Indians because of the beneficial effects on high-density lipoprotein (HDL) and triglycerides (TG) . The NCEPdietary guidelines for PUFA and SAFA seem appropriate forAsian Indians without any modification.

Saturated fatty acids, the arch villain ofatherosclerosis: Excessive consumption of SAFA is theprincipal dietary culprit contributing to elevated serumTC level, which is the primary determinant ofatherosclerosis.15,16 Differences in CAD mortality worldwideare explained by differences in SAFA intake and theresulting serum TC levels in 40 countries, except for France,Finland, and India.16–18 Intake of SAFA suppresses the LDL-receptor activity and decreases the clearance of LDL fromthe circulation, resulting in a marked elevation of its level.19

Review Article

Correspondence: Dr Enas A Enas, CADI Research Foundation, 1935, GreenTrails, Lisle IL, 60523 USA. e-mail: [email protected]

“A

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Indian Heart J 2003; 55: 310–338 Enas et al. Prudent Diet and Preventive Nutrition 311

SAFA raises the serum TC level thrice as much as PUFA,and MUFA lowers it. For example, substitution of 20% ofthe daily energy intake of carbohydrate by SAFA increasesthe TC level by 30 mg/dl, whereas PUFA and MUFA lower itby 10 mg/dl.13 Most of this increase is due to an increase inLDL. Although some increase in HDL also occurs, it is notsufficient to offset the atherogenicity and thrombogenicityresulting from marked elevation of LDL.6,20

Our diet contains SAFA of different chain lengths withvarying atherogenic properties. According to their chainlengths, SAFA can be classified as short chain (4:0–6:0),medium chain (8:0–10:0), long chain (12:0–18:0), andvery long chain (20:0–24:0) fatty acids. Stearic acid(C18:0) is desaturated to oleic acid soon after its absorption,and hence does not raise the TC level.21,22 Therefore, its useneed not be restricted and, in fact, it can be recommended.23

SAFA with chain lengths of 12–16 have the mostcholesterol-raising properties.24 These are lauric acid(C12:0), myristic acid (C14:0), and palmitic acid (C16:0).These 3 fatty acids account for only 25%–30% of the totaldietary fat but 60%–70% of SAFAs in western diets.24

Palmitic acid is the most common fatty acid in the humandiet, and the principal SAFA in both animal fats and palmoil. In a study conducted in a metabolic ward, 40% ofenergy as palmitic acid raised the TC by 25 mg/dl v. 15 mg/dl with lauric acid.21 Myristic acid is the most powerfulcholesterol-raising SAFA, and increases the TC level 50%more than palmitic acid. Replacement of 20% of energyfrom carbohydrate with myristic acid raises the blood TClevel by 46 mg/dl, compared to 30 mg/dl with palmitic acid,and 20 mg/dl with lauric acid.25 Most of the rise in the TClevel is due to an increase in LDL, the respective contributionfrom HDL being 16 mg/dl, 8 mg/d and 12 mg/dl.25 Themajor sources of myristic acid are butter and tropical oils(Table 2).6,20–25 The TC-raising potential of lauric acid is 33%less than that of palmitic acid, and it is the principal SAFAin coconut and palm kernel oils, both containing 48%.23–25

Coconut and palm oils are also high in myristic acid (18%),and this explains why the consumption of these oils raisesthe LDL level in a fashion similar to that of butter(Fig. 1).25,26 Studies in laboratory animals indicate thatcoconut oil increases both TG and LDL levels;6,27,28 the claim

Table 1. Recommended daily energy intake and major sources of dietary fats1,6–12

Recommended Current Major sourcesintake intake

(USA)

Total fat 30%–35% 34% Dairy products and animal flesh are the major sources of dietary fat; the(40–75 g) former contribute more than the latter.

Cholesterol <200 mg 270 mg Egg yolk, brain, organ meat, beef, lamb, pork, poultry (thigh and skin), shellfish, shrimp, prawn, full-fat milk (especially buffalo milk), high-fat dairyproducts (cream, ice cream, milk shake, cheese, curd)

SAFA <7% 12% Beef, lamb, pork, bacon, sausage, ribs, poultry with skin, butter, ghee,(10–15 g) vanaspathi (vegetable ghee), desserts, bakery products (cakes, biscuits,

cookies, donut), cheese, ice cream, full-fat milk, tropical oils (coconut, palmkernel, and palm oils)

TRAFA Avoid <2% Hard margarine, vegetable shortening, frying fats (especially those usedrepeatedly), bakery products (cakes, Danish pastry, donuts, crackers, rusk,biscuits, cookies, white bread), French fries, fried chicken, peanut butter,nondairy creamer, tortillas, pizza, and virtually all “crispy and crunchyfoods”

MUFA Up to 20% 14% Olive oil, canola oil, mustard oil, peanut oil, macadamia nuts, hazelnuts,pecans, peanuts, almonds, cashew nuts, pistachio nuts, avocado, dairyproducts, beef, lamb, mutton, poultry

n-6 PUFA 7%–8 % 6%–8% Vegetable oils (soybean, corn, safflower, sunflower, and cottonseed)

n-3 PUFA 2%–3% <1% Fatty fish (mackerel, halibut, lake trout, herring, sardines, albacore tuna,salmon), meat, poultry, vegetables (tofu, soybeans, pinto beans, flax seeds),vegetable oils (soybean, canola), salad dressing, whole grains, and DHA-enriched egg, nuts (walnuts, butternut, flax seeds, pecans)

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that lauric acid does not raise TC is not supported by scientificdata.21,23 Recent studies have shown that caprylic acid (C:8)and capric acid (C:10) raise the LDL level to about 50% thatof palmitic acid, and raise the TG level.6,23–25 Coconut oilcontains 14% of these two cholesterol-raising SAFA.

Replacing 5% of the daily energy intake of SAFA withMUFA and PUFA could reduce the risk of CAD by 42%.29

Therefore, substituting MUFA and PUFA for SAFA andTRAFA is more effective in lowering the risk of CAD than

simply reducing the total amount of fat.30 Since 1970, thetotal fat intake decreased from 42% to 34%, and SAFA from18% to 12% in the USA, as a result of nationwide changesin dietary habits.2,31 This change in dietary fat intake isprimarily responsible for the decrease in serum TC level from220 to 200 mg/dl in the US population. This decrease inTC level is principally responsible for the dramatic reductionin CAD, during a period when the rates of obesity anddiabetes doubled in Americans.32

Table 2. Chemical characteristics and atherogenicity of major fatty acids6, 20–25

Fatty acids Chemical Atherogenicity Commentsstructure

SAFA Highly atherogenic and thrombogenic. Markedly increases LDL level.Slightly increases HDL level.

Lauric acid C12:0 ⇑ Coconut oil 48%, palm oil 48%, and butter fat 3%.

Myristic acid C14:0 ⇑⇑⇑ Most potent cholesterol-raising SAFA. Coconut 18%, palm kernel oil18%, butter fat 18%, animal fats 1%–5%

Palmitic acid C16:0 ⇑⇑ Most common and reference standard of SAFA. Palm oil 45%,butter fat 26%, beef fat 26%, mutton fat 24%, chicken fat 23%,pork fat 25%, cocoa butter 26%, coconut oil 9%, and palm kerneloil 8%.

Stearic acid C18:0 ⇔ Raises HDL level without raising LDL level. Butter fat 13%, beef fat22%, mutton fat 25%, chicken fat 6%, pork fat 12%, cocoa butter35%, coconut oil 3%, and palm oil 4%.

TRAFA Increases Lp(a), TG, small, dense LDL levels. Decreases HDL level; 3-fold increase in cardiac arrest.

Elaidic acid C18:1 n-9 trans ⇑⇑⇑ Fried food, crispy food, cakes, biscuits, donuts, pizza, reused fryingoils.

MUFA Significantly lowers LDL level.Raises HDL level.Lowers insulin resistance.Antiatherogenic and antithrombogenic.

Oleic acid C18:1 n-9 ⇓⇓ Butter fat 28%, beef fat 39%, mutton fat 33%, chicken fat 42%,pork fat 45%, cocoa butter 35%, coconut oil 7%, palm kernel oil14%, and palm oil 39%.

n-6 PUFA Lowers LDL levels.Lowers HDL level to a small extentAntiatherogenic.

Linoleic acid C18:2 n-6 ⇓⇓ Predominant PUFA in western diets.

n-3 PUFA Decreases LDL, and TG levels, blood pressure, and risk of suddendeath.Increase HDL level, heart rate variability.Antiarrhythmic and antithrombogenic effects

Alpha-linolenic acid C18:3 n-3 ⇔ Precursor to EPA and DHA.(ALNA) Flaxseed oil 50%, canola oil 10%, mustard oil 10%

Eicosapentaenoic acid C20:5 n-3 ⇔ Fatty fish (sardines, mackerel, salmon)(EPA)

Docosahexaenoic acid C22:6 n-3 ⇔ Fatty fish (sardines, mackerel, salmon)(DHA)

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Transfatty acids (TRAFA)—the hardened fat thathardens arteries fast: TRAFA is formed during the partialhydrogenation of vegetable oils, a process that converts oilsinto solid or semisolid fats for subsequent use in foodproducts. This process not only improves the texture andfirmness but also markedly increases the shelf-life of foodby minimizing oxidative spoilage.33 Elaidic acid (n-9 trans18:1) is the principal TRAFA, although several other transisomers are also formed.23 Such oils are used in commercialbaked goods, and for cooking in most fast-food chains inwestern countries.34 Perhaps an equally important andoften neglected cause of TRAFA formation is thespontaneous hydrogenation of vegetable oils during deep-frying.35 Very small amounts of TRAFA are also found inbeef and dairy products (Table 1).

Consumption of TRAFA has a greater adverse effect onlipoproteins than that of SAFA.36 Whereas both SAFA andTRAFA increase LDL levels considerably, TRAFA alsodecreases HDL levels, thereby increasing the TC/HDL ratio,the single best lipid-related risk factor for CAD.37 Replacing9% of calories from SAFA with TRAFA results in a 20%decrease in HDL level.38 Other important adverse effects ofTRAFA consumption include increases in lipoprotein(a)(Lp[a]), TG, and small, dense LDL levels,34,38–44 as well asincreased platelet aggregation, endothelial dysfunction,and sudden death.34 TRAFA are stronger predictors of CADand diabetes than SAFA and carbohydrates.1,45–47 In theNurses’ Health Study, women in the highest versus thelowest quartile of TRAFA consumption had a 50% higherrisk of CAD.48 It is estimated that a substitution of 2% ofcalories from TRAFA with MUFA and PUFA results in a 53%reduction in CAD risk—a risk double that of substitutionof calories from SAFA.29 TRAFA consumption also markedlyincreases the postprandial insulin response in diabeticpatients.49 Replacing 2% of energy from TRAFA with PUFA

would lead to a 40% reduction in diabetes.45 SAFA caloriesshould not be replaced by TRAFA calories; doing so is likejumping from the frying pan to the deep-fat fryer.50

The average consumption of TRAFA in the USA andEurope is low (<2% of energy or 11–27 g/day).51,52

However, TRAFA accounts for about 5% of fat in Americandiets, and 5% of fat stored in adipose tissue.33,50,53 Buttercontains 60% SAFA, whereas stick margarine contains16% TRAFA. The tub or soft margarine contains only 2 gof TRAFA per 15 ml. Therefore, the fat-spread of choiceremains soft margarine;54 olive oil may be an even bettersubstitute. Although many margarines and shorteningspreviously contained up to 50% of TRAFA, in most westerncountries, these products currently have a low TRAFAcontent due to recent manufacturing changes.47 However,frying fats used in fast-food outlets still contain over 30%of TRAFA. French fries sold in these outlets provide 7–8 gof TRAFA per portion. About one-third of TRAFA in thewestern diet comes from French fries, fried chicken, pizza,and cookies.

The TRAFA consumption is likely to be high in AsianIndians because deep-frying is a favorite mode of cookingat home as well as in restaurants. Deep-frying is associatedwith spontaneous hydrogenation and TRAFA formation,and repeated re-use of oils previously used for deep-fryingmay further increase the TRAFA content. These practicesappear to be the norm rather than the exception, and maybe of enormous public health importance, especially withregard to elevated Lp(a) levels, and high rates of CAD inthis population. There is an urgent need to ascertain anddisseminate the TRAFA content of vanaspathi (vegetableghee) and frying oils used in India. As of today, we are notaware of any industrial manufacturing changes aimed atlowering the TRAFA content of Indian foods, as has beendone in western countries.

MUFA, the good fat that raises the good cholesterol:Diets high in MUFA (oleic acid C18:1) make LDL resistantto oxidation, restore LDL-receptor activity, and markedlylower LDL levels. Substitution of 20% of energy fromcarbohydrates with MUFA decreases TC by 10 mg/dl. Thereduction in TC is 3-fold higher when MUFA replaces SAFA.For example, TC decreases by 40 mg/dl when 20% of energyfrom SAFA is replaced with MUFA.13, 25 The effect on small,dense LDL is even greater. Other beneficial effects of MUFAinclude the favorable influence on blood pressure,endothelial activation, inflammation, and thrombogenesis.

A higher intake of MUFA lowers insulin resistanceand diabetes, unlike SAFA and TRAFA, which increaseit.45,49,55–60 Consumption of MUFA offers the unique

Fig. 1. Predicted change in HDL and LDL when all fat in Dutch diet is replacedby a particular oil.

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advantage of effectively lowering LDL levels withoutlowering HDL or raising TG levels. Individuals with low HDLlevels have a high risk of CAD.61,62 Subjects with high TG,especially those with the metabolic syndrome and diabetes,are highly sensitive to the TG-raising effects of a highcarbohydrate load. A high carbohydrate diet is associatedwith highly atherogenic, small, dense LDL particles, whilehigh-fat diets are associated with less atherogenic, buoyantLDL particles. Thus, replacing SAFA with MUFA is moreeffective in preventing CAD than reducing the total fatintake, especially in Asian Indians, a population with highrates of prevalence of the metabolic syndrome and diabetes.The NCEP III has recommended up to 20% of total caloriesfrom MUFA (Table 1). This recommendation seemsparticularly appropriate for Asian Indians.32

In Mediterranean countries, the high intake of MUFAin the form of olive oil is inversely related to CAD.15 TheNurses’ Health Study and other studies of almost 300 000Americans showed that a diet rich in MUFA in the form ofcanola oil also reduces the risk of CAD.29,63,64 Contrary tocommon belief, energy-controlled, high-MUFA diets do notpromote weight gain, and are more acceptable than low-fat diets for weight loss in obese subjects. The addition ofMUFA should be at the expense of SAFA and carbohydrates.Since all fats are high in calories (9 cal/g), failure to decreasethe energy from carbohydrates and SAFA would invariablyresult in weight gain, and mitigate most of the beneficialeffects of MUFA.

Meat and dairy products, which are also rich in SAFA,provide most of the MUFA in western diets. Olive oil andcanola oil are good sources of MUFA (Table 3),65 canola oilappears to be even better as it contains less SAFA and morePUFA, especially alpha-linolenic acid (ALNA). Mustard oilis high in MUFA but also high in erucic acid, which is knownto have toxic effects on the heart. Canola oil is geneticallyengineered mustard oil without erucic acid. Nuts andavocado are excellent sources of MUFA and arerecommended, provided the quantity is no more than 50–100 g/day.66 Groundnut (peanut) products are a rich sourceof MUFA; they are inexpensive and widely available inIndia.67

PUFA, another healthy substitute for SAFA: There are2 series of PUFA that are deemed essential. Linoleic acid(C18:2 n-6) is the predominant omega-6 or n-6 PUFA. Thepredominant (parent) omega-3 or n-3 PUFA is linolenic acid(18:3 n-3).23 Linoleic acid increases the fecal excretion ofsteroids, and inhibits the hepatic synthesis of apo B-containing lipoproteins. Replacing SAFA with PUFAreverses the suppression of LDL-receptor activity bycholesterol-raising SAFA (similar to that of MUFA).6,68

Substituting 20% of energy from SAFA with PUFAdecreases the TC level by 40 mg/dl. Most of the reductionis in LDL, and the number of apo B particles.23,25 PUFA doesnot raise the TG level, and sometimes lowers it.69 The twoundesirable effects of PUFA are increased susceptibility forperoxidation, and lowering of the HDL level.10,70–72 HDLlevels are reduced by about 1% for every 2% of MUFA orSAFA energy substituted with PUFA.6,70–72

The substitution of PUFA for SAFA calories has played amajor role in reducing TC levels and CAD in the USA. TheCAD mortality rate declined by 60% in the past 3 decadesin the USA.73 About a third of the decline in CAD rates isattributed to a 6%–8% decrease in the serum TC level inthe population; this, in turn, was due to an increase in theconsumption of PUFA from 3% to 6%, and a decrease inSAFA consumption from 16% to 12% of the energy. Theimportance of PUFA is further underscored by the markeddifferences in PUFA consumption, which parallel the 4-folddifference in CAD rates between France and Finland.16

Vegetable oils, such as soybean, corn, safflower, sunflower,and cottonseed, are the primary sources of n-6 PUFA(Table 1). Their average consumption in the western diet is6%–8% of energy, (17 g/day for men, and 12 g/day forwomen).74

Contrary to previous fears, n-6 PUFA do not antagonizethe anti-inflammatory effects of n-3 PUFA nor do they raisethe risks of breast, colorectal, or prostate cancer in

Table 3. MUFA, PUFA, and SAFA content (%) in 100 g ofvarious cooking oils65

MUFA PUFA SAFA

Sunflower oil, high oleic (>70%) 84 4 10Safflower oil, high oleic (>70%) 75 14 6Olive oil 74 8 14Almond oil 70 17 8Mustard oil 59 21 12Canola oil 59 30 7Cod liver oil 47 23 23Peanut oil 46 32 17Sunflower oil, linoleic (<60%) 45 40 10Sesame oil 40 42 14Rice bran oil 39 35 20Palm oil 37 9 49Cocoa butter 33 3 60Corn oil 24 59 13Soybean oil 23 58 14Walnut oil 23 63 9Sunflower oil, linoleic (>60%) 20 66 10Cottonseed oil 18 52 26Safflower oil, linoleic (>70%) 14 75 6Palm kernel oil 11 2 82Coconut oil 6 2 92

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humans.75,76 However, a very high n-6 PUFA to n-3 PUFAratio may increase the thrombogenicity through increasedproduction of arachidonic acid and thromboxane A

2. This

is because linoleic and linolenic acids use the same set ofenzymes for desaturation and chain elongation.77 An n-6PUFA to n-3 PUFA ratio of 3:1 appears to be optimum.78–80

Japan, which has one of the highest rates of fishconsumption, has recently changed the recommendationof this ratio from 4:1 to 2:1;81 this ratio may be advisablefor vegetarians).9

Fish, a tasty way to prevent sudden death: Fish do notdie from myocardial infarction (MI), and populations thatconsume large amounts of marine foods have a lowprevalence of CVD death.82–99 Replacing high-fat meat withfish is also associated with a decreased risk of CAD. Theresults of several large studies show that one or two fishmeals per week are associated with a 30%–50% reductionin sudden death.84,95,98 In a meta-analysis of 11 prospectivestudies involving 116 764 individuals, fish consumptionwas inversely related to CAD death. This report suggeststhat 40–60 g/day of fish consumption is optimal, andresults in a 40%–60% risk reduction.100 Greater intake hasno additional benefits, and suggests a threshold effect.101,102

However, a recent large study of 5103 women with diabetesshowed a dose–response relationship. Consumption of fish1–3 times per month was associated with a 40% riskreduction, and a 64% risk reduction was seen among thosewho consumed fish >5 times per week.102,103 The benefit isseen in people with and without prior heart disease.104

These benefits persist as long as the fish consumption iscontinued.

Fish is a tasty food that contains many essentialnutrients, such as selenium, iodine, vitamin D, and n-3PUFA.97,105 The beneficial effects of fish are largely mediatedthrough n-3 PUFA, which displace arachidonic acid fromplatelet phospholipid stores, thereby reducing the availablesubstrate for thromboxane A

2 synthesis.106,107 The principal

ef fects of n-3 PUFA are antithrombogenic andantiarrhythmic, whereas that of n-6 PUFA isantiatherogenic.108–117 The serum levels of n-3 PUFA areinversely related to sudden death.66,82,89,93,95,118–121 Theconsumption of n-3 PUFA decreases blood pressure, andhomocysteine level, increases HDL level, and improveshemostatic factors (Table 4).10,75,122–132 A 30%–50%reduction in TG can be achieved by taking 3–5 g/day of n-3 PUFA.130

The major n-3 PUFA in fish oils are eicosapentaenoicacid (EPA) (20:5 n-3) and docosahexaenoic acid (DHA)(22:6 n-3); together they constitute 26% of fish oil fattyacids.23 The benefits from n-3 PUFA are greater with DHA

and EPA found in fatty fish, shellfish, and marine mammalsthan with ALNA found in canola oil, soybean oil, andwalnut.108 It is important to distinguish between lean andfatty fish for cardioprotection, because the content of n-3PUFA is highest in fatty fish.119 Fatty fish, such as mackerel,sardine, and salmon, are widely available and inexpensive.Heating is associated with significant loss of n-3 PUFA.9

Frying fish is associated with an even greater loss of EPAand DHA, and may be particularly harmful if fried inSAFA.133 The current intake of DHA and EPA is only 200mg/day, and needs to be increased 5-fold to meet the dietarygoals.11

Both plant-based (ALNA), and fish-based (EPA and DHA)supplements have shown benefits in secondaryprevention.89,90,134,135 In one such trial of 605 French menrecovering from an MI, there was a 70% reduction in totaland cardiac death during a follow-up of 27 months in thosewho received an experimental “Mediterranean diet” usingcanola oil-based margarine, enriched with n-3 PUFA.136 Inanother large randomized study of 11 324 survivors of arecent MI, there was a 20% reduction in total deaths, 30%reduction in CVD deaths, and 45% reduction in suddendeaths among those who received n-3 PUFA 1g/day.90 Thetotality of the data suggest that n-3 PUFA can be consideredas the best antiarrhythmic agent and antifibrillatorytreatment.106,117,133,135 Cardiologists and their patientsshould pay serious attention to this new paradigm in thediet–heart hypothesis, and increase the intake of fish andfish oil.133,137

The amount of n-3 PUFA necessary for cardioprotectionis surprisingly low. The current recommendation is to take2–3 fish meals per week (200–300 g/week of fish). A less

Table 4. Omega-3 fatty acids and CVD10,75,122–132

• Decrease the risk of ventricular fibrillation and sudden deathIncrease cell membrane PUFAFavorably alter cardiac ion channel function and actionpotentialDecrease the ventricular fibrillation thresholdIncrease heart rate variability

• Decrease the risk of stroke and MI• Decrease platelet reactivity, aggregability, and the risk of

thrombosis• Reduce monocyte reactivity• Reduce inflammatory cytokines and response• Improve endothelial function• Reduce the expression of vascular adhesion molecules• Markedly lower the TG and remnant lipoprotein levels• Decrease the growth of atherosclerotic plaques• Decrease homocysteine levels• Improve insulin sensitivity and reduce the risk of diabetes• Slightly lower blood pressure

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attractive alternative is to consume 1000 mg/day of n-3PUFA (contained in 3000 mg of fish oil capsules).10,11,74,96,133

The current intake of n-3 PUFA in the US is 1600 mg/dayor 0.7% of the calories, which is about half therecommendation.11 Fish is more beneficial than fish oil, butthe latter may be required in most patients with CAD toobtain the required amount of n-3 PUFA.90 Patients withCAD should consume about 1800 mg/day of n-3 PUFA(DHA and EPA) as the best insurance against sudden death.

Alpha-Linoleic acid (ALNA)—the n-3 PUFA of theplant kingdom: There is no DHA and EHA in a vegetariandiet. Vegetarians derive their n-3 PUFA almost exclusivelyfrom ALNA, which is also the major type of n-3 PUFA inomnivores.138 There is increasing evidence for thecardioprotective effects of ALNA, albeit less than EPA andDHA.139 In a large study involving 43 700 men, increasedintake of ALNA reduced the risk of MI by 60%.64 A similarrisk reduction was also observed in the Nurses’ HealthStudy and Multiple Risk Factor Intervention Trial(MRFIT).93,140 Some vegetable oils are high in ALNA(flaxseed oil 50%, canola oil 10%, mustard oil 10%, soybeanoil 7%) while others are low (groundnut oil <0.5%).141

Walnuts are a rich source of ALNA; small concentrationsare found in green leafy vegetables, corn oil, almonds,hazelnuts, cereals, pulses, millets, and spices.78,142 Walnutsand canola oil account for most of the ALNA in the westerndiets.78,101 The recommended intake of ALNA is 2% ofenergy but the current intake in the USA is 0.6% ofenergy.11,74

ALNA is readily converted to EPA, and more slowly toDHA; the latter being the major component of phospholipidmembranes of the brain and retina.78 The beneficial effectsof ALNA are less than half that of DHA and EPA, becausethe conversion of ALNA to the more active longer-chainmetabolites is inefficient: <5%–10% for EPA, and 2%–5%for DHA.80,141,143 This explains why vegetarians have lowerlevels of n-3 PUFA than omnivores, and also higher plateletaggregability.77 Since the biological effects of plant n-3PUFA are significantly lower than marine n-3 PUFA, therequirements may be higher (3% of energy) for vegetariansthan for nonvegetarians.9,74,77

Protein: Americans eat 80–90 g/day of protein, which istwice the daily requirement, and most of this comes frommeat, which is also high in SAFA. Up to 25% of daily energyfrom protein (but not more than 100 g/day) is permissibleif the major source of protein is plant-based. Nuts areimportant sources of plant protein along with soy, bran,beans, and legumes. Substituting protein for carbohydratesincreases HDL and lowers TG levels.144,145 In a meta-analysis

of 38 controlled human clinical trials, consumption of soyprotein (47 g/day) was associated with a significant 13%decrease in LDL, 10% decrease in TG, and a 2% increase inHDL levels.146 This led to FDA approval for the use of foodlabels for the health claim that soy protein can reduce therisk of heart disease.

Meat: Although meat contains a significant amount ofSAFA, almost half the SAFA is stearic acid, which does notraise TC levels. In addition, meat contains up to 45% ofcholesterol-lowering MUFA. Furthermore, lean meat hasmuch less SAFA than fatty cuts of meat (Table 5).6,147 Leanbeef is an excellent source of protein and MUFA, and hasless SAFA than chicken (dark meat); 6 oz of lean beefcontains 3.0 g of SAFA v. a chicken thigh which contains5.2 g of SAFA (the term loin or round signifies lean meatwhereas prime or rib signifies fat cuts with very high SAFAin the USA). Chicken and lean beef (not fatty meat) havesimilar ef fects on plasma lipoproteins, and areinterchangeable in a healthy diet.30,148,149

Glycemic Load: A Potent Predictor of theMetabolic Syndrome and Diabetes

The source, nature, and amount of carbohydrates have aprofound influence on postprandial glycemia, which in turnis directly associated with the risk of CAD in patients withdiabetes.6,150,151 Foods containing the same amount ofcarbohydrate (carbohydrate exchange) may have up to a5-fold difference in glycemic impact, depending on thedifferences in the digestion and absorption.152,153 Theglycemic index is an extension of the fiber hypothesis, andwas proposed in 1981 as a physiological system for theclassification of carbohydrate-containing foods.154,155

Table 5. Atherogenic, antiatherogenic, and neutral fattyacids in selected meats and cooking oils6,147

Fat Total Cholesterol- Stearic Oleic acid:SAFA raising acid: cholesterol-

(%) SAFA cholesterol lowering (%) neutral MUFA (%)

SAFA (%)

Beef fat 51 29 22 39Mutton fat 54 29 25 33Chicken fat 30 24 6 42Pork fat 39 27 12 45Butter fat 66 53 13 28Cocoa butter 61 26 35 35Coconut oil 92 89 3 7Palm kernel oil 74 71 3 14Palm oil 50 46 4 39

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Carbohydrate classified by glycemic index, in contrast to itstraditional classification as either simple or complex, is abetter predictor of CAD in epidemiological studies.156 Theglycemic index is a scientific measure of the glycemicresponse to various foods, and is obtained from publishedfood tables. The hierarchy of the glycemic index begins withbeans, lentils, rice, spaghetti, potatoes, white bread (withrefined flour), and refined grain cereals.150 A high glycemicindex indicates a lower quality of carbohydrate associatedwith low HDL levels, and low rates of satiety. 157,158 Fruits,nonstarchy vegetables, parboiled rice, and legumes have alow glycemic index.159 The glycemic index of potato is102%, white bread 100%, whereas that of apple is 55%,and broccoli 13%. Glycemia observed after consuming driedpeas is only one-third that of an equivalent amount ofpotatoes. Since peas are also high in fiber, theirconsumption needs to be encouraged, especially in patientswith diabetes.153,160

Glycemic load is the product of the glycemic value ofthe food and its carbohydrate content (per serving) dividedby 100. For example, carrot has a high glycemic index buta low glycemic load (Table 6).152,161 The overall daily dietaryglycemic load is calculated by adding the glycemic loads ofall the different foods consumed in a given day. Accordingly,the glycemic load can be decreased by reducing the amountof carbohydrate intake and/or by consuming foods with alow glycemic index.162 In addition to the quality andquantity of carbohydrates consumed, the glycemic load alsorepresents diet-induced insulin demand.163,164 PAI-1 levelsare significantly increased with high glycemic load, anddecreased with low glycemic load.165

Dietary carbohydrates drive TG much more than dietaryfat.6 A high glycemic load produces only mild incrementsin TG levels in individuals with normal TG levels butmarked elevation in those with fasting lipemia and/orobesity.6,166–168 A low HDL level is a strong risk factor forCAD, even when the TC level is not elevated.169,170 A highglycemic load produces a low HDL, particularly whensubstituted for MUFA or PUFA.23,157,166,171–179 In a prospectivestudy of 75 521 women followed up for 10 years, those inthe highest quintile of glycemic load had double the risk ofCAD after adjustment for age, smoking status, total energyintake, and other risk factors (p<0.0001).156

More importantly, a glycemic load promotes diabetes,especially in those with insulin resistance.156,161,180–183

(Fig. 2)183 This is particularly true for refined carbohydrates,sweets, white bread, and potatoes.45,156,183,184 Thus, a highglycemic load may be considered a risk factor of equalimportance as high SAFA diet in precipitating diabetes. Alow glycemic load can reduce insulin secretion in patients

Table 6. Glycemic index of common foods152,161

Glycemic Serving Carbohydrate Glycemicindex size per serving load

Basmati rice 58 150 g 38 22Brown rice (South India) 50 150 g 33 16Parboiled rice (Canada) 48 150 g 36 26White rice (Uncle Ben’s) 45 150 g 36 16Curry rice (Japan) 67 150 g 61 41Jasmine rice 109 150 g 42 46White bread 70 2 slices 30 21Uppuma 18 150 g 33 6Upittu 68 150 g 42 28Chapati 76 60 g 30 23Dosai 77 150 g 39 30Idli 77 250 g 52 40Poori 70 150 g 41 28Pongal 68 250 g 52 35Millet/ragi 104 70 g 50 52Barley 43 150 g 37 16Tapioca 70 250 g 18 12Kellogg’s cornflakes 81 30 g 26 24Milk, full-fat 27 250 g 12 3Yogurt 36 200 g 9 3Orange juice(reconstituted USA) 57 250 ml 26 15Pineapple 59 120 g 13 7Plums 39 120 g 12 5Prunes 29 60 g 33 10Raisins 64 60 g 44 28Cantaloupe 65 120 g 6 4Plantain, green 38 120 g 21 8Banana, unripe 70 120 g 45 31Banana 53 170 g 25 13Strawberry jam 51 30 g 20 10Laddu 27 50 g 31 8Black-eyed beans 42 150 g 30 13Chickpeas 10 150 g 30 3Kidney beans (rajmah) 13 150 g 25 3Lentils 30 150 g 17 5Lima beans 32 150 g 30 10Pinto beans 39 150 g 26 10Soy beans 15 150 g 6 1Sweet corn 59 80 g 18 11Green peas 39 80 g 7 3Carrot 47 80 g 6 3Beet root 64 80 g 7 5Potato 85 150 g 30 26Split peas 32 150 g 19 6Snicker bar 55 60 g 35 19Pizza Hut supreme

pan pizza 36 100 g 24 9Coca Cola 58 250 g 26 14Instant noodles 47 180 g 40 19Macaroni 45 180 g 49 22Spaghetti 68 220 g 27 19

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with type 2 diabetes, decrease insulin requirements in type1 diabetes, and improve glycemic control in both types ofdiabetes. The incremental benefit from low glycemic loadis similar to that offered by pharmacological agents thatalso target postprandial hyperglycemia, such as alpha-glycosidase inhibitors.185,186 The benefit of low glycemic loadon the development of diabetes is similar to MUFA, PUFA,whole grains, fiber, fruits, and vegetables.

Whole Grains: The Foundation of Healthy Food

Whole grains have been the staple food worldwide forcenturies, especially among vegetarians.187,188 Whole grainand legume consumption not only decreases blood sugarand insulin resistance but also prevents the developmentof diabetes, particularly in people with the metabolicsyndrome.185,186 Whole-grain products are a good sourceof fiber, minerals, as well as several vitamins, includingvitamins B and E. In a 12-year follow-up of 42 898 men,the risk of developing diabetes was 42% lower in those withthe highest intake of whole grains. The risk was reducedby 52% in those who also engaged in physical activity, and87% in those who also had a low BMI.189 The risk reductionwas attributed to higher intakes of cereal fiber andmagnesium. Intake of whole-grain cereal is inverselyassociated with hypertension, CAD, stroke, and CVDmortality190,191 (Table 7).192–206 In another study, 25% –30%reduction in stroke was observed with the intakeof whole grains—similar in magnitude to that ofstatins.206–208 In sharp contrast, intake of refined grainsincreases the risk of diabetes, stroke and CVD.191,205–212

These prospective data highlight the importanceof distinguishing whole-grain from refined-graincereals in the prevention of CVD and diabetes.209 Efforts

Fig. 2. Risk of diabetes in 65 173 US women during 6 years of follow-up:influence of glycemic load and fiber

Table 7. CVD risk reduction demonstrated with selectedfood groups192–206

Author CVD risk reduction (%)

Fruits and vegetables (15%–48%)Bazzano et al.192 25Liu et al.193 15Joshipura et al.194 30Joshipura et al.195 20Gaziano et al.196 48Knekt et al.197 35

Nuts (19%–48%)Albert et al.198 48Ellsworth et al.199 19Hu et al.200 35Fraser et al.201 38Fraser et al.202 40Jiang et al.203 21 (diabetes)

Whole grains (32%–44%)Jacobs et al.204 33Fraser et al.201 44Liu et al.205 32Liu et al.206 32 (stroke)

should be made to replace refined-grain with whole-grainfoods.189

A whole-grain food includes all the edible parts of thegrain: the bran, the germ, and the endosperm.213 Grindingor milling, using modern technology, leads to the loss ofmany beneficial micronutrients, antioxidants, minerals,phytochemicals, fiber, and much of the germ.214 As a result,refined grain products are devoid of most vitamins andessential fatty acids, and contain more starch.215 Becauseof the loss of bran and pulverization of the endosperm,refined grains are digested and absorbed rapidly, resultingin a large increase in the levels of blood sugar and insulin.215

The common grains consumed in the West include wheat,oats, rye, rice, barley, and corn.213 In the USA, rye bread isan important source of whole grain consumption, andresults in a lower glucose response than white bread.152,212

Whole-grain, ready-to-eat cereal contains >25% wholegrain content by weight.189 The recommended intake is atleast 6 servings of grain (but not more than 11) with atleast 3 being whole grains. The current intake of wholegrains is less than half a serving/day or 15% of the grainintake. Only 2% of the 150 lb of wheat flour consumed percapita in the USA is whole-grain flour.216 Commonlyconsumed refined grain foods include white rice (idli, dosa),refined wheat and flour (white bread), pancakes, cakes,sweet rolls, English muffins, muffins, waffles, rolls, biscuits,pizza, and refined-grain ready-to-eat breakfast cereal, andtheir use should be minimized.

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Nuts: A Wholesome Food and Powerhouse ofHealthy Fats and Nutrients

Extensive studies during the past decade have transformedthe image of nuts from fattening snacks to a wholesomeand heart-healthy food to be consumed daily.198–202,215 Nutsare rich sources of protein, antioxidants, fiber, vitamins andminerals (especially potassium and magnesium). Nuts yield5%–10% fiber, and 12%–25% protein. The consumptionof nuts is also associated with a reduced risk of CAD inseveral studies.198–202,217,218 Yet, nuts are not generallyrecommended as snacks because of their high fat content.Although nuts contain 45%–80% fat, most of the fats arethe highly beneficial MUFA and PUFA (Table 8).65

Nuts, particularly almonds, significantly improve lipidprofiles because of the high fiber and MUFA component.The dose–response effects of almonds were compared withlow-SAFA (<5% energy), whole-wheat muffins used as thecontrol diet in a randomized crossover study involving 27dyslipidemic men and women. Three isoenergeticsupplements each (mean 423 kcal/day; 22% of energy)were consumed for 1 month. The supplement consisted offull-dose almonds (73 g/day), half-dose almonds plus half-dose muffins, and full-dose muffins. Full-dose almondsproduced a highly significant decrease in the Lp(a) level(8%), LDL:HDL ratio (8%), and oxidized LDL (14%)compared to the control diet.219 A 9% decrease in the LDLlevel occurred with 73 g/day of almonds, and 4% decreasewith 37 g/day (handful) of almonds. This result translatesto a 1% reduction in LDL for every 7 g/day of almonds, andis consistent with other studies.220,221 More importantly,there was no difference in body weight between the almondand muffin diet.222 Nuts are energy-dense, and contain

160–200 cal/oz. It cannot be overemphasized that energyfrom nuts should replace the unhealthy calories from SAFAand refined grains to prevent weight gain.

Consumption of other nuts (except coconuts) is equallybeneficial. For example, a 10% reduction in the LDL levelcan be achieved by the daily consumption of 40 g ofwalnuts, peanuts or pistachios, 70 g almonds, 100 gmacadamia nuts, and 110 g of pecans.223–230 Nuts are aseffective as increasing physical activity and trimmingcalories to increase HDL levels. Adding 2 oz or 60 g of nutsto a diet is a delicious way to decrease the TC/HDL ratioand CAD risk.8,14,23,231,232 Nuts also improve insulinsensitivity and prevent diabetes.233 In a prospective studyof 83 818 women, 3206 new cases of type 2 diabetes wereobserved during a follow-up of 16 years.203 Consumptionof nuts was inversely associated with the risk of type 2diabetes after adjustment for age, body mass index (BMI),physical activity, smoking, alcohol use, and dietary factors(total calories, fat calories, and fiber). The risk of diabeteswas reduced by 27% in those who consumed >5 oz/weekof nuts or peanut butter compared to those who almostnever ate these products.203 The proscription of nuts canno longer be justified. In fact, regular nut consumption asreplacement for refined grains and high-fat meats isstrongly recommended.161,234

Fruits and Vegetables, the Natural Way to ConsumeAntioxidants and Flavonoids

Fruits and vegetables are rich in a myriad of nutrients andphytochemicals, including fiber, vitamins B and C,antioxidants, potassium, and flavonoids.190,215

Phytochemicals are bioactive nonnutrient plant

Table 8. MUFA, PUFA, and SAFA content (in g) in tree nuts and fruit (all nuts are dry roasted without salt except coconut)65

Calories per 100 g Fat content per 100 g MUFA PUFA SAFA

NutsMacadamia nuts 718 76 59 1 12Hazelnuts 646 62 47 8 5Pecans 710 74 44 21 6Almonds 597 53 34 13 4Cashew nuts 574 46 27 8 9Pistachio nuts 570 46 24 14 6Walnuts 607 57 13 37 4Flax seed 492 34 7 22 3Coconut meat, creamed 684 69 3 1 61Coconut meat, sweetened, shredded 501 35 2 0 31

FruitsAvocados, California 177 17 11 2 3Olives 115 11 8 1 1Avocados, Florida 112 9 5 1 2

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compounds linked to a reduced risk of chronic diseases.Fruits and vegetables decrease blood pressure,homocysteine, and cancer, especially that of the GItract.211,235,236 Since fruits and vegetables are rich inpotassium, their liberal intake is recommended for theprevention and treatment of hypertension.237 Good sourcesof potassium include bananas, oranges, beans, fish, anddairy products. While you can get an overdose of potassiumfrom pills, you cannot get an overdose of potassium fromfood. Moreover, dietary supplements do not have the healthbenefits associated with a diet rich in fruits and vegetables.For example, the antioxidant value of 100 g of apple isequivalent to 1500 mg of vitamin C.3

Several large studies, including one comprising 84 000women and 42 000 men, have shown a significant inverseassociation between the consumption of fruits andvegetables and CVD mortality190,194,195 (Table 8). Therelationship is particularly strong with vitamin C-richfruits, green leafy vegetables, and carotenoid vegetables(carrots, broccoli, spinach, lettuce, tomatoes, and yellowsquash).192–196,238,239 Consuming fruits and vegetables (3times/day compared with <1 time/day was associated witha 27% lower incidence of stroke, a 42% lower strokemortality, a 24% lower CAD mortality, a 27% lower CVDmortality, and a 15% lower all-cause mortality afteradjustment for standard CVD risk factors.192 In sharpcontrast, consumption of potatoes and French fries increasethe risk of CAD and stroke.152,215

The landmark study of the Dietary Approaches to StopHypertension (DASH)240 has yielded tremendous insightsinto the benefits of increased intakes of various types offruits and vegetables. The DASH diet is rich in vegetables,fruits, and low-fat dairy products (9 servings of fruits andvegetable combined per day).240 As compared with thecontrol diet with a high sodium, the DASH diet with a lowsodium intake led to a decrease in systolic blood pressureof 7 mmHg in normotensive individuals, and 11.5 mmHgin hypertensive individuals. The benefits of the DASH dieton lipoprotein levels were equally spectacular, with an 11mg/dl decrease in LDL and a 4 mg/dl increase in HDL levelswithout significant effects on TG levels. Men had a greaterreduction in LDL level than women, with no differencebetween Whites and Blacks. These results suggest that theDASH diet is likely to reduce the risk of CAD and can berecommended as an overall eating plan.241 The currentintake of fruits and vegetables is 3 servings/day each in theUSA; only 23% consume the recommended 5 servings/dayeach.242 The DASH diet is feasible in the real world, unlikethe array of drastic diets which are impossible to continuefor more than a few months.240

Flavonoids: Flavonoids are secondary metabolites thatplants use to attract pollinators, repel predators, and tocolor flowers, leaves, and fruits.243 Important biologicaleffects of flavonoids include the scavenging of oxygen-derived free radicals, inhibition of LDL oxidation, increasein HDL levels, and protection against CVD and severalchronic diseases.244–248 The beneficial effects of thesenatural products on health were known long before thediscovery of flavonoids. The major sources of flavonoids arevegetables (onions, kale, broccoli), fruits (apples, grapes,berries), olive oil, and beverages such as tea andwine.244,248,249 Other sources include grains, bark, roots,stems, and flowers. Flavonoids present in red wine couldbe partly responsible for the low CAD mortality seen in redwine drinkers (“French Paradox”). Red wine is the majorsource of flavonoid in France and Italy (40%), onions andapples in Finland, and olive oil in Greece.250 The strong tasteof extra-virgin olive oil is partly caused by the abundanceof flavonoids.

Antioxidants: Oxidative modification of LDL acceleratesatherosclerosis whereas dietary antioxidants prevent LDLoxidation. These antioxidants include vitamin C, vitaminE, beta-carotene, selenium, flavonoids, magnesium, andMUFA.251 It is worth emphasizing that vitamin pills are nosubstitute for a healthy diet. Although an earlier studysuggested some benefits from antioxidant vitaminsupplementation, several subsequent studies involvingmore than 100 000 patients have consistently failed todemonstrate any benefit. More recent studies suggest thatpossible harm may outweigh the benefit of thesevitamins.252–254 In a recent study, the use of vitamins E andC reduced the lipid-lowering efficacy of statins and niacinby 50%. More importantly, the clinical event reduction waslowered from 90% to 60%.255 The current scientificevidence does not support any protective role of vitaminsE, C, and beta-carotene supplements; their use only createsa diversion away from proven therapies.256 The USPreventive Service Task Force (USPSTF) recommendsagainst the use of beta-carotene supplements.257 It is worthnoting that the oxidative modification of LDL continues tobe relevant, and people should obtain their antioxidantvitamins from food sources. (However, folic acid fortificationis recommended in women who are pregnant or mightbecome pregnant.)

Non-nutritive Food Adjuncts

Fiber: The term dietary fiber was coined to describe theplant cell wall removed during the refining process.258

Dietary fiber improves coagulation, fibrinolysis, insulin

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sensitivity, LDL, and blood pressure levels.259–265 Fiber isparticularly concentrated in bran. Insoluble fiber shortensthe intestinal transit, resulting in less time for carbohydrateabsorption.266 Soluble (viscous) fiber, such as beta-glucan,which is found in oat bran, delays gastric emptying, andslows the absorption and digestion of carbohydrates. Theseprocesses lead to a slower release of glucose into thecirculation, resulting in a reduced demand forinsulin.187,189,267 An intake of 16 g of total fiber is associatedwith a 12% decrease in CAD risk.268 FDA has permittedcardiovascular health claims to be made by the industryfor 2 viscous fibers, beta-glucan and psyllium.269 Psylliumsupplementation significantly lowers TC and LDL levels; itis safe and well tolerated.270

The benefit of whole grains appears to be mediatedprimarily through the greater intake of fiber, and is greaterwith cereal fiber than vegetable or fruit fiber.212,263,264,271,272

Approximately one-fourth of the fiber provided by cerealsources is water soluble.268 Cereal fiber consumption isassociated with a 21% lower risk of incident CVD, and 30%lower risk of diabetes.164,188,259,273 (Fig. 2). Cereal fiberconsumption may reduce the risk of CVD via thesubstitution effect, replacing the intake of other foodshaving potentially detrimental effects. In addition to cerealgrains, legumes are also excellent sources of water-solubledietary fiber. Half a cup of cooked beans contains, on anaverage, 6 g of total fiber and 2 g of soluble fiber.274

The current ADA recommendation for a healthy diet isto consume 25 g/day of fiber with about one-third fromsoluble fiber. In one study, type 2 diabetics consuming 50g/day of fiber (25 g soluble, 25 g insoluble) lowered theblood sugar by 13 mg/dl, plasma TC by 7%, and TG levelsby 10%.275 Thus, a high intake of dietary fiber, above thelevel recommended by the ADA, particularly of the solubletype, improves glycemic control, insulin levels, and plasmalipid concentrations in patients with type 2 diabetes.275

Plant sterols and stanols: Plant sterols and stanols arestructural analogues of cholesterol. Low-fat plant stanol-containing margarines lower plasma LDL levels (by as muchas 12%) in those with hypercholesterolemia by suppressingcholesterol absorption.276–279 In one randomized controlledstudy, the reduction in LDL with such supplements wassimilar to 20 mg of lovastatin (30% with statin v. 28.6%with diet).280 Various plant supplements have been shownto reduce LDL by 40% (Table 9).146,219,265,280–283

Spices: Plants have the capacity to synthesize a diversearray of chemicals. Spices are aromatic vegetablesubstances, the significant function of which is foodseasoning rather than nutrition. Typically, spices are the

Table 9. A portfolio of dietary factors useful for LDLreduction146,219,265,280–283

Decrease in LDL(%)

SAFA intake <7% 10Dietary cholesterol intake <200 mg 5Body weight 5 kg 5Plant sterols/stanols 1–3 g/day 5Soy protein 25 g/day 5Nuts (almonds) 50 g/day 5Viscous fiber intake 5–10 g/day 5Total LDL reduction Full portfolio 40

dried aromatic parts of plants, generally the seeds, berries,roots, pods, and sometimes leaves, that mainly grow intropical countries. Common spices include turmeric,paprika, saffron, cinnamon, nutmeg, red and black pepper.In contrast, herbs used in cooking are typically composedof leaves and stems.284

Caffeine: Caffeine is found in coffee, tea, soft drinks,chocolate, and some nuts. Finland has one of the highestrates of per capita coffee drinking (13 kg/year).285 In aprospective study of 20 179 Finnish adults, coffee drinkingwas not associated with an increased risk of MI. However,consumption of large quantities of boiled unfiltered coffeeraises cholesterol and homocysteine levels.285–287 In anexperiment involving 10 volunteers, who consumed theequivalent lipid content of 6–7 cups of boiled unfilteredcoffee daily for 6 weeks, the LDL levels increased by 33 mg/dl.288–290 These data suggest that daily consumption of 1–2cups of coffee is safe with no particular health benefits orrisks.

Tea: Tea, the most widely consumed beverage in the worldother than water, has been associated with lowercardiovascular risk.291–295 Unlike coffee, tea consumption isassociated with a substantial reduction in LDL levels. Tea isrich in flavonoids. Green tea contains catechins, whereasblack tea, formed from the polymerization of catechins,contains theaflavins.291 In one recent study, theaflavin-enriched green tea extract reduced the LDL level by 16%.296

Tea is the major source of flavonoid intake in Japan (>80%);the Japanese consume an estimated 7 cups/day of teacompared to half a cup/day in the USA. Adding milk totea, as is common in the UK and India, abolishes thebeneficial effect of tea.297

Alcohol: Moderate intake of alcohol (one drink a day forwomen and 2 drinks a day for men) may decrease the riskof CAD.298 Recently, it has been shown that only one drinkper week is enough to provide cardiac protection (45 ml ofspirits or 350 ml of beer or 120 ml of wine); the

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cardioprotection is similar for beer, wine, whiskey, brandy,vodka, rum, and drinks in equivalent amounts.299,300 Morethan 2 drinks per day does not provide any additionalprotection and, in fact, the net effect may be harmful untilthe age of 45 years in men and 55 years in women.301 Likecarbohydrates, consumption of large quantities of alcoholraises TG levels.6,302 Other dangers of excessive alcoholconsumption includes alcohol dependence, liver disease,high blood pressure, obesity, stroke, traffic accidents,spousal abuse, suicide, and breast and other cancers. Giventhese risks, the American Heart Association cautionspeople against increasing their alcohol intake or startingto drink if they do not already do so.

Weight Gain and Weight Loss Diets

Excess calories and obesity: Diets of any type containingmore energy than needed or expended will lead to obesityand dyslipidemia.303 A calorie is a calorie whether it comesfrom carbohydrates, fat, or protein. Excess calories of anykind will eventually be converted by insulin to body fat.304

A common misconception is that dietary fat of any kind isfattening, while low-fat and high-protein diets haveslimming properties. It is absolutely vital that bothphysicians and the public understand that it is the excesscalories and not diet composition that causes weightgain.304–309 There is no evidence of weight gain with a highMUFA diet, compared with a high carbohydrate diet, underisoenergetic conditions.310,311

Obesity is not only a reflection of overnutrition but alsoan important contributor to the mass dyslipidemia seen inIndia and western countries.6 Obesity in general isaccompanied by the increased production of apo B and adecrease in the HDL levels.6,312 Humans have a limitedcapacity to store energy as carbohydrates. Whencarbohydrate intake exceeds storage and oxidationcapacities, the excess is converted to fat by de novolipogenesis that leads to high TG levels.313 This process isincreased several-fold in people with the metabolicsyndrome which, if left untreated, leads to overt diabetes(25-fold risk).312 Body fatness and not lean body mass isthe principal determinant of diabetes and prediabetes.314

At a given BMI, Asian Indians have 7%–10% higher bodyfat; accordingly, BMI <23 is termed optimum; BMI 23–25overweight, and >25 obese in Asian Indians. Likewise, theoptimum waist circumference is lower in Asian Indiansthan Whites with a cut-off <90 cm in men and <80 cm inwomen.315 Although obesity and dyslipidemia areuncommon in less affluent societies, some individuals maybe excessively sensitive to caloric excess.6

Fast foods rapidly produce plaques. The averageAmerican gained 9 lb in the past decade. A third ofvegetable taken in the USA are either French fries or potatochips.305 In one study, overweight subjects who consumedfairly large amounts of sucrose (28% of energy), mostly asbeverages, had increased energy intake, body weight, fatmass, and blood pressure after 10 weeks. These effects werenot observed in a similar group of subjects who consumedartificial sweeteners.316 Restricting the dietary cholesterolcan achieve a 3% reduction in TC level, whereas losingweight from trimming extra calories can reduce LDL by 5%to 20%.8

Weight loss: The recipe for effective weight loss is acombination of motivation, physical activity and caloricrestriction; maintenance of weight loss is a balance betweencaloric intake, and physical activity, with life-longadherence. Each pound of body fat contains 3500 cal.Therefore, a person who consumes 500 cal less than hespends each day can lose 1 lb of fat a week. Any higherweight loss is due to a more severe caloric restriction orwater loss rather than fat loss. The minimum caloric intakein a medically unsupervised weight loss diet is 1500 cal/day for men, and 1200 cal/day for women. Superior long-term participation and adherence is observed in a high-fatdiet rather than a low-fat diet (35% v. 20%), especially inwestern cultures.309 The greater success rate is due to higherpalatability of the high-fat diet provided by mixed nuts andlean meat.309 Furthermore, the long-term outcome of areduced-fat diet consumed ad libitum for weight control isdismal. In one study, compared with the control group,weight decreased in the reduced-fat diet group significantlyby 3 kg in 1 year but diminished to an insignificant 1 kg by5 years.317 Until more information becomes available, “theprudent diet,” which is a balanced diet, is the one to followfor young and old alike.318

Very low fat diet: Some experts have argued for a verylow-fat diet (<10%).319 Since these diets are not high-protein diets (like the Atkins diet), they are in reality veryhigh in carbohydrate. High-carbohydrate diets (theMacrobiotic diet) increase insulin resistance and induce themetabolic syndrome. In controlled trials, low-fat, high-carbohydrate diets decreased HDL levels. Replacing 10%of energy from SAFA with carbohydrate lowers the HDLlevels by 5 mg/dl, even when the carbohydrate consumedis complex.62,173,320,321 There is also a marked increase in TGlevel, which makes LDL small, dense, and moredangerous.173,320–322 The ef fect is strongest whencarbohydrates replace SAFA but is also seen whencarbohydrates replace MUFA and PUFA. The effect is seen

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in both short- and long-term trials, and is therefore not atransient phenomenon. Therefore, replacement of SAFAmust be achieved through increasing MUFA and not bycarbohydrates. The adverse effects of high-carbohydratediets (high glycemic load) in the metabolic syndrome anddiabetes have not received due attention, especially in theIndian literature. The recommended carbohydrate intakeis <50% of calories in people with the metabolic syndromeor diabetes (NCEP).

The allure and dangers of very low-carbohydrate,high-protein diets: High-protein diets that are extremelylow in carbohydrates are touted as a new strategy forsuccessful weight loss by many.323 Most such diets contain<10% carbohydrates, 25%–35% protein, and 55%–65%fat. Because the protein is provided mainly by animalsources, these diets are high in SAFA and cholesterol. Thus,these diets are truly high-fat diets masquerading as high-protein diets. Advocates of this diet often promote seriousmisconceptions about carbohydrates, insulin resistance,ketosis, and fat burning as the mechanisms of action forweight loss. To avoid excess load on the kidneys, the totalprotein intake should not exceed 100 g/day.324 Moreimportantly, the body has an obligatory requirement forglucose of about 100 g/day, largely determined by themetabolic demands of the brain.324,325

In randomized studies, the extent of weight loss wassmall (4 kg), and adherence to the diet was low.326,327 Inone study, although a low-carbohydrate diet produced a 4%greater weight loss at 6 months than did the conventionaldiet, the differences did not persist at 1 year. Furthermore,adherence was poor, and attrition was high in both thehigh- and low-carbohydrate groups. Longer and largerstudies are required to determine the long-term safety andefficacy of low-carbohydrate, high-protein, high-fat diets.326

Two recent studies have provided insight into high-proteindiets; the initial weight loss is due to fluid loss and ketosis-induced appetite suppression. The monotony of this dietalso results in involuntary caloric restriction.326,327

The beneficial ef fects on blood lipids and insulinresistance are due to the weight loss, and not the change incaloric composition. Such diets increase LDL but decreaseTG levels, in sharp contrast to high-carbohydrate diets,which increase TG, and decrease HDL levels. Althoughthese diets may not be harmful for most healthy people overa short period of time, there are no long-term scientificstudies to support their overall efficacy and safety. Markedlyatherogenic profiles have also been reported in childrenwith ketogenic diets. At 6 months, the high-fat ketogenicdiet significantly increased plasma LDL levels by 50 mg/dl,

triglycerides 58 mg/dl, apo B 49 mg/dl, and non-HDLcholesterol 63 mg/dl. The mean HDL-cholesterol levelsdecreased significantly.328 These lipid abnormalities inchildren are more than likely to translate into a high riskof heart disease as young adults.

High-protein diets also do not provide the variety of foodsneeded to continue the diet on a long-term basis. High-protein diets are not recommended, and are perhapsdangerous because they restrict most healthful foods thatprovide essential nutrients, especially fruits and vegetables.Individuals who follow these diets are therefore at risk forcompromised vitamin and mineral intake, as well aspotential cardiac, renal, bone, and liver abnormalitiesoverall.324 The consumption of a very low-carbohydrate dietfor 6 weeks delivers a high acid load to the kidney, increasesthe risk of stone formation, decreases body calcium, andmay increase the risk of bone loss and fractures.329 A high-protein diet is the ultimate antithesis of the prudent diet. Itis important to realize that diets are not for 6 weeks, 6months or 6 years, but for a lifetime. Although most quick-fix diets have a short-term success rate >90%, the long-term failure rate is 100%.

Healthy and Contaminated Vegetarian Diets

Omnivores or nonvegetarians outnumber vegetarians 10to 1 in western cultures. Vegetarians include vegans whodo not consume any animal products, ovo-vegetarians whoconsume egg, lacto-vegetarians who consume milk, ovo-lacto-vegetarians who consume egg and milk, and semi-lacto-vegetarians who eat small amounts of meat (<1 time/week). Ironically, most self-defined vegetarians in westerncountries consume red meat and poultry, albeitinfrequently, and in very small quantities. In a recentsurvey, only 1% of self-reported vegetarians did not eat meatin the USA, whereas about 6% of Americans who do notconsume any meat did not identify themselves asvegetarians.330–332

Western vegetarians generally consume a healthier dietthan omnivores; healthy foods such as soy, nuts, legumesand vegetables replace meat.333 They generally have twicethe fish consumption of nonvegetarians.330 This is not thecase with Indian vegetarians who shun fish. US vegetarianseat more whole-grain products, dark green and deep yellowvegetables, whole-wheat bread, brown rice, soy milk, tofu,meat substitutes, legumes, lentils, garbanzos, walnuts, andpecans.330 However, they eat the same amount of food asomnivores (1000 kg/year) but are usually thinner.334 Ahealthy vegetarian diet is characterized by more frequent

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consumption of fruits and vegetables, whole grains,legumes and nuts, resulting in higher intakes of dietaryfiber, antioxidants and phytochemicals.335 Thus avegetarian diet contains a portfolio of natural products thatcan improve both the carbohydrate and lipid abnormalitiesin diabetes.187

Vegetarians eat about two-thirds of SAFA, and one-halfof cholesterol as omnivores; vegans consume one-half ofSAFA and no cholesterol.9,336 Cholesterol levels amongwestern vegetarians are 15–25 mg/dl lower thanomnivores.337–340 Vegans have very low levels of LDL.341,342

Nuts, viscous fibers (from oats and barley), soy proteins,and plant sterols in vegetarian diets improve serum lipidlevels.337 Furthermore, substituting soy or other vegetableproteins for animal proteins reduces the risk of developingnephropathy in type 2 diabetes.

With the exception of tropical oils, calories from plantsources are negatively correlated with CAD mortality,whereas calories from animal sources are positivelycorrelated.16 Olive oil, fresh fruits, and vegetables areprotective against heart disease, and seem to play a greaterrole in the French paradox than wine.16 Greaterconsumption of whole milk and other animal productswere important contributors to Finland having the highestrates of CAD.16 In a prospective study of 4671 vegetariansand 6225 nonvegetarians, followed up for 10–12 years,BMI, TC, and CAD mortality was substantially lower amongvegetarians than in the nonvegetarians. Other studies alsosuggest a protective effect of vegetarianism against manydiseases. Vegetarians in western countries, but not in India,enjoy remarkably good health, exemplified by low rates ofobesity,334,343 diabetes,344 CAD345–347 and cancer,337 and a 3–6 year increase in life expectancy.333,348 It is not clearwhether this is due to abstinence from meat or to a greaterconsumption of heart-healthy food.349

Indian vegetarianism, a form of “contaminatedvegetarianism”: Most Asian Indians are lacto-ovo-vegetarians, unlike western vegetarians. About 50% ofAsian Indians are vegetarians, but their lipoprotein levels,and rates of diabetes and CAD are no different from thoseof nonvegetarians.350,351 This phenomenon is due tocontaminated vegetarianism, wherein vegetarians manageto consume excessive amounts of SAFA and TRAFA. In theCADI study, Asian Indian physicians in the USA followed aheart-healthy diet, with 32% energy from total fat, and 8%from SAFA, which is the recommendation by the NCEP.350

This appears to be an exception rather than the rule. In aCanadian study, Asian Indians consumed more fried foodsand high-fat dairy products, such as full-fat milk than White

Canadians.352 Although the intake of fat is 20%–25%energy in most Asian countries, many affluent AsianIndians consume >50% of their calories from fat.

Indian vegetarians consume liberal amounts of bakeryproducts, butter, ghee, cheese, ice cream, curd, and otherdairy products to overcompensate for not using meat.Contrary to popular belief, dairy products are the majorsource of SAFA, even in the western diet. It is worthhighlighting that SAFA intake from high-fat dairy productsincreases LDL levels 3 times as much as it raises the HDLlevel.353 Meat is expensive, and consumed in very smallquantities by Indian omnivores because of cultural andfinancial reasons. This is in sharp contrast to an annualper capita consumption of 124 kg meat and 23 kg fish byAmericans.354 Prolonged cooking of vegetables, as ispractised in India, virtually destroys every nutrient beforeit is consumed. A major problem overlooked in the Indiandiet is the high glycemic load, resulting in high TG and lowHDL levels.355 There appears to be a threshold forcarbohydrate consumption with an intake >280 g/dayoften resulting in atherogenic dyslipidemia.350

Deep-frying and reuse of frying oil: Deep-frying, acommon form of cooking among Asian Indians, isassociated with spontaneous hydrogenation, and theformation of TRAFA. Reuse of oil used for deep-frying hasbeen shown to produce endothelial dysfunction.356

Repeated reuse of such oil is exceedingly common amongAsian Indians.357 HDL inhibits LDL oxidation primarilythrough its paraxonase activity; reuse of frying oil reducesparaxonase activity, and thus reduces the ability of HDL toprevent LDL oxidation.356–360 Fats that have been heated forprolonged periods in air contain many dangerous productsfrom oxidation and breakdown of lipids. These compoundsinclude hydroxy peroxides, aldehydes, polymers, hydroxyfatty acids, hydroperoxy epoxides, and hydroperoxyalkenals.361 In one study, fast-food restaurant cooking oil,just before the weekly change, was compared to unused oil.The repeatedly used oil had 4 times higher peroxide levels,7 times higher carbonyl levels, and 17 times higher levelsof acids.357

Ghee: Ghee is one of the most important sources of dietaryfat and a common cooking medium.362,363 Use of ghee fordeep-frying is considered gourmet among Asian Indians.Ghee or clarified butter is anhydrous milk fat, and is rich inMUFA (32%) and SAFA (62%), most of which arecholesterol-raising (myristic acid 17%, palmitic acid 26%).It is perhaps more harmful than butter due to the addedpresence of cholesterol oxides, which are generated during

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its preparation by prolonged heating of butter.362–364 Liberaldietary exposure to cholesterol oxides from ghee is a likelycontributor to the high frequency of CAD among AsianIndians.364 There are conflicting data on the risk of heartdisease with ghee.365,366 We are unaware of any biologicalexplanation as to why Asian Indians can be immune to theunfavorable effects of butter and/or ghee. In addition to milkghee, vegetable ghee (vanaspathi) is also immensely popularin Indian cooking, which exerts similar adverse effectsthrough its high TRAFA content.

Tropical oils: The term tropical oils refers to coconut, palmkernel, and palm oils. These oils contain a very highpercentage of SAFA, unlike other vegetable oils such asrapeseed oil (mustard oil), sesame oil, and rice bran oil,which are low in SAFA and high in MUFA (Table 3). Tropicaloils are more atherogenic and thrombogenic than muttonand beef fat; the latter contains <5% myristic acidcompared to 18% in coconut and palm kernel oils.104 Infact, these oils contain more TC-raising SAFA than animalfats—coconut oil 89%, palm kernel oil 71%, and palmoil 46% compared to <30% for butter fat, beef fat, porkfat, and chicken fat (Table 5).6,147 Tropical oils accountfor <2% of energy (<4 g/day) in the USA. but 25%or more in many other countries.147,367 Tropical oils arealso found in commercially baked cakes, biscuits, cookies,and “snack foods”. In Mauritius, a regulated change in theSAFA content by substituting soybean oil for palm oilresulted in a dramatic 32 mg/dl fall in TC level, andunderscores the crucial role of cooking oils in populationlevels of TC.368

Coconut oil: Coconut oil contains mostly cholesterol-raising SAFA (8% caprylic, 6% capric, 45% lauric, 17%myristic, and 8% palmitic acid).369 Rabbits fed a commercialchow diet containing 0.5% cholesterol and 14% coconutoil developed more severe dyslipidemia and atherosclerosisthan rabbits fed the same diet containing olive oil insteadof coconut oil. The average plasma TC level was 2-fold, andTG level 20-fold higher in the coconut oil-fed rabbits thanin the olive oil-fed rabbits.28 Cox et al.369,370 have reportedthe cholesterol-raising effects of coconut oil to be similarto that of butter. In a comparative study of diets rich inbeef fat versus coconut oil, the plasma TC, LDL, and HDLresponses were lower with beef fat than coconut oil,commensurate with the lower proportion of cholesterol-raising SAFA in beef (29%) than coconut oil (89%)371 (Table5). A Malaysian study in which 22% of the energy intakewas substituted with coconut oil found an increase of 40mg/dl in TC, 29 mg/dl in LDL, 36 mg/dl in TG, and 4 mg/dlin HDL levels.372 The impact on LDL and HDL by using

various fats as the sole source of fat in a Dutch populationis shown in Fig. 1. Note the marked increase in LDL incontrast to HDL with the use of coconut oil.

Kerala, renowned for the universal and liberal consump-tion of coconut milk and oil, not only has the highest levelof TC in India, but also the highest rate of CAD.373 Theproportion of subjects with high TC (>239 mg/dl) in Keralais almost double that of the USA. (32% v. 18%).374 This isin sharp contrast to the Japanese among whom only 6%have high TC.375 In Sri Lanka, which also has a very highrate of CAD, about 80% of the fat in the habitual diet comesfrom coconut.134,374,376

Consumers need to be educated about the atherogenicand antiatherogenic effects of various cooking oils, as wellas animal and vegetable ghee. There is little awareness, andeven controversy, about the atherogenic effects of certainfoods and oils, especially in regions where the production,sale, and consumption of such oils have a profound impacton the regional economy.

Prudent Diet for All Ages and the EntirePopulation

The traditional Mediterranean diet is characterized byabundant plant foods (vegetables, breads, pastas, beans,nuts, and seeds). Fresh fruit is the typical daily dessert, andolive oil is used as the principal source of fat. Dairy products(principally cheese and yogurt), fish, and poultry areconsumed in low-to-moderate amounts. Red meat and eggare consumed in low amounts (0–4 eggs weekly). Wine isconsumed in low-to-moderate amounts, normally withmeals. This diet is typically high in total fat (35%–45%) butlow in SAFA (7%–8% of energy). Greater adherence to thetraditional Mediterranean diet is associated with asignificant reduction in total mortality.377 The 6 beneficialcomponents of this diet have recently been elucidated. Theyare vegetables, legumes, whole-grain cereal, fish, fruit, andnuts, which form the basis for the “prudent diet”377

(Table 10).199–203,225–227,231–236

According to the new paradigm, dietary pattern ratherthan individual nutrients appears to be more important.Recent research suggests the existence of a food synergy inwhich the beneficial effects of healthy foods are magnifiedwhen several different types of foods are consumed.213 Huet al. have developed the concept of “prudent diet” (modifiedfrom the Mediterranean diet).30,378–380 The “prudent diet”has a higher intake of vegetables, fruits, legumes, wholegrains, fish, and poultry, whereas the “western diet” ischaracterized by a higher intake of red meat, processedmeat, refined grains, sweets, desserts, French fries, and

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high-fat dairy products.378,380 The “prudent diet” isassociated with a 24% decreased risk of CVD compared toa 46% increased risk with the western diet.215,380

Consumers are bombarded on a daily basis with theBabel of nutritional breakthroughs.381 Food companiesadvertize their products, nutrition researchers publicizetheir latest results, and the media are more interestedin a controversial story than in scientific facts.30 Trivialreports are often publicized as major breakthroughs bythe media, and cause confusion among consumers. It isdifficult for most journalists and consumers to tell thedifference between a major research finding and a trivialreport.381

The dangers of the current western diet and thecontaminated vegetarian diet, and the remarkable benefitsof the prudent diet need to be disseminated amongcardiologists, physicians, and the public. This diet can besustained lifelong but needs to be adapted to Indianingredients and cooking methods. Several countries havedeveloped dietary guidelines to reduce nutritionalinformation anarchy. The Indian consensus on the prudentdiet should incorporate scientific facts, and the culturalpreferences appropriate for different parts of India. Such

information needs to be adopted by the scientificcommunity, and adapted by the food industry.

Current Knowledge on Preventive andTherapeutic Nutrition

Randomized, controlled clinical trials, meta-analysis, andsystematic reviews are considered the ultimate tests of thebenefits of therapeutic interventions. Such reviews haveshown a 24% reduction in major coronary events in dietarytrials lasting >2 years.382 The TC/HDL ratio is the single bestlipid predictor of CVD. This ratio is determined by 3 partlyopposing dietary factors—the proportion of energy fromSAFA, which raises TC; the proportion of energy from totalfat, which raises HDL; and the excess in total energy intake,which produces obesity and secondarily lowers HDL.20 Thegreatest reduction in CVD risk is achieved by LDL-loweringby reducing SAFA intake. Decreasing SAFA intake is bestaccomplished by reducing the intake of high-fat dairyproducts, and increasing fiber-rich foods. A dietincorporating lean beef, skinless chicken, and fatty fish hasbeen shown to improve the lipid profile by 5%–10%.383

The preferred replacement for SAFA is MUFA or PUFA

Table 10. The benefits and sources of selected heart-healthy foods199–203, 225–227, 231–236

Category Benefits Sources/preferred foods

Whole grains Good source of fiber, minerals, and Whole wheat, oats, rye, barley, corn, brown ricevitamins E and B and wild rice

Delay gastric emptying and blunts postprandial Whole-grain oatmeal, whole-grain, insulin response pumpernickel, rye or dark bread

Improve insulin sensitivity Whole-grain, ready-to-eat cereal⇓ Insulin secretion Cooked cereal⇓ Insulin resistance, and diabetes PastaImprove lipids (⇑ HDL) Popcorn⇓ Hypertension Bran⇓ CVD incidence and CVD mortality Buckwheat, cracked wheat, wheat germ

Fruits and vegetables Rich in fiber, flavonoids, and antioxidants Green leafy vegetables⇓ Blood pressure Carotenoid vegetables (carrots, broccoli, spinach,⇓ LDL lettuce, tomato, and yellow squash)⇑ HDL⇓ Homocysteine Citrus (vitamin C-rich) fruits⇓ CVD and mortality Temperate fruits (cantaloupe, apple, pear)⇓ Cancer, especially GI tract Tropical fruits (mango, papaya, pineapple,⇓ All-cause mortality jackfruit, guava, banana)

Viscous fiber ⇓ LDL Cereal grains (oats—beta glucan)⇓ Postprandial glycemia Legumes, Psyllium (Metamucil)

Soy protein ⇓ LDL Soy bean

Plant sterols and stanols ⇓ LDL Low-fat plant stanols containing margarines

Nuts ⇓ LDL See Table 6⇑ HDL

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and not carbohydrates (Table 11). Replacing SAFA withcarbohydrates decreases the LDL levels but makes LDLsmall, dense, and more dangerous by increasing the TGlevels.30 Substituting carbohydrates with MUFA decreasesthe LDL level, and increases the HDL level. PUFA and MUFAincrease insulin sensitivity, and decrease the risk of type 2diabetes.45,384–386 Substantial evidence indicates that dietsusing MUFA and PUFA as the predominant form of dietaryfat, an abundance of fruits and vegetables, and adequaten-3 fatty acids can offer significant protection against CAD,stroke and diabetes (Table 8). Adequate consumption offruits and vegetables provides most of the necessaryantioxidants, and are preferable to dietary supplements inthe form of pills. Replacing a high glycemic with a lowglycemic index, and reducing the glycemic load can reducethe risk of diabetes161 (Table 6).

Nuts, once deemed unhealthy because of their high fatcontent, have become an important part of diets designedto control weight, lower blood pressure and cholesterol, andachieve secondary prevention of CAD, besides addingvariety, texture and flavor to dishes.145,211,215,387 Unless abeneficial effect is clearly demonstrated by well-designedscientific studies, the liberal use of butter, ghee, palm oil,

and coconut (oil and milk) should be discouraged. However,in diets with a negligible intake of fish, meat, milk, and dairyfat, the modest use (<7% of energy) of such oils may bepreferable to no fat at all.

Practical Recommendations

Better food habits can help reduce the risk of diabetes, MI,stroke, and death. A healthy eating plan means choosingthe right foods to eat, and preparing them in a healthy way.A healthy diet involves a decrease in the use of refinedgrains, tropical oils, egg yolks, animal, dairy, andhydrogenated fats, and an increase in the consumption ofwhole grains, vegetables, nuts, legumes, and fruits.7

Increasing the MUFA intake up to 20% of energy, as areplacement for SAFA and carbohydrates, may help preventand treat the metabolic syndrome, diabetes, and CVD. Sucha strategy can also significantly reduce the need for lipid-optimizing drugs. Since meat contains one-third MUFA andone-third cholesterol–neutral stearic acid, its consumptioncan also be incorporated into a healthy diet, provided leancuts are used, and the quantity limited to 150 g/day.6

Practical recommendations on diet are given in Table 12.

Table 11. Summary of current knowledge on diet

• Quality of fat is more important than the quantity of fat consumed.• SAFA is the principal determinant of elevated LDL levels. Reduction in energy intake from SAFA is the cornerstone of dietary

modification. Dairy products provide more SAFA than meat, even in western diets.• Contrary to common belief, MUFA and PUFA can significantly lower LDL levels. Replacement of 20% of energy from SAFA with

MUFA or PUFA decreases TC level by 40 mg/dl.• The atherogenicity and thrombogenicity of tropical oils are several times higher than meat.• Increase in LDL level from lean meat is no higher than chicken, and need not be eliminated from a healthy diet.• n-3 PUFA found in fatty fish is antithrombotic, antiarrhythmic, and prevents sudden death.• The adverse effects from TRAFA consumption are greater than those from SAFA, because of increase in LDL and Lp(a) levels, and

decrease in HDL level.• Both quality (glycemic index) and quantity (glycemic load) of carbohydrates are important determinants of insulin resistance and

the metabolic syndrome. A high glycemic index or load portends an inferior quality of carbohydrates.• Although carbohydrates do not raise LDL levels, a high glycemic load is the major determinant of postprandial lipemia.• Vegetarian diet is unhealthy if it contains large amounts of SAFA and TRAFA.• Nuts, fruits, vegetables and whole grains can each reduce the risk of CVD by 15%–45%.• Nuts are wholesome and nutritious food.• The risk from alcohol outweighs the benefit in men <45 years and women <55 years of age.• Drinking coffee does not increase the risk of heart disease but consumption of large amounts of unfiltered coffee can increase TC

levels.• Tea is rich in antioxidants and flavonoids, and is associated with a reduced risk of CAD; however, most of the beneficial effects are

neutralized with the addition of milk.• A calorie is a calorie, whether derived from carbohydrates, protein or fat.• Obesity is a reflection of overnutrition (caloric excess), and a major cause of dyslipidemia.• Caloric excess, irrespective of the composition of food, can raise LDL and lower HDL levels as a secondary effect of obesity.• Weight reduction seen in high protein diets is due to the involuntary caloric restriction from the monotony of the diet rather than

the diet composition.

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Conclusions

People eat specific foods because of their taste, easyavailability and affordability, but are often unaware of thehealth benefits and risks. Dietary modifications remain thecornerstone of both the treatment and prevention ofdiabetes and CVD, the twin epidemics of the twenty-firstcentury.234,388–391 A prudent diet together with regularphysical activity, avoidance of smoking, and maintenanceof a healthy body weight may prevent the majority ofdiabetes and CVD in the Indian population.30 Aggressivedietary interventions may reduce CVD events to a similarmagnitude as that achieved with statins. Compared withmedical or surgical interventions, nutritional interventionis low-risk, low-cost, and readily available.259 A variety ofwhole grains, not refined grains, as well as various types offruits and vegetables should be the main form ofcarbohydrates.242 Prolonged cooking of vegetables shouldbe avoided. It is important to realize that the vegetarian dietis healthy only when it is low in SAFA, and the predominantenergy is from foods with a low glycemic index.215 The bestway to counter the perils of contaminated vegetarianismis by substituting full-fat dairy products with low-fat dairyproducts. Cooking oils containing high SAFA should bereplaced with those containing high MUFA. Deep-frying,especially with previously used oils, should be discouraged.Nuts are healthy, wholesome foods, and their use shouldbe encouraged as a replacement for unhealthy calories.

A diet rich in fish has multiple benefits, including raisingHDL, and lowering TG levels, and preventing suddendeath.383 Consumption of fish is preferable to taking a largenumber of fish oil capsules. There is increasing evidencethat dietary and lifestyle modifications begun in childhoodare likely to have benefits later in life.392 Therefore, thesedietary guidelines are applicable to all Asian Indians >2years of age, and not just those with diabetes or heartdisease.

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352. Enas EA, Yusuf S. Third meeting of the International WorkingGroup on Coronary Artery Disease in South Asians. 29 March1998, Atlanta, USA. Indian Heart J 1999; 51: 99–103

353. Sacks FM, Ornish D, Rosner B, McLanahan S, Castelli WP, KassEH. Plasma lipoprotein levels in vegetarians. The effect of ingestionof fats from dairy products. JAMA 1985; 254: 1337–41

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355. Abbasi F, McLaughlin T, Lamendola C, Kim HS, Tanaka A, Wang T,et al. High carbohydrate diets, triglyceride-rich lipoproteins, andcoronary heart disease risk. Am J Cardiol 2000; 85: 45–48

356. Williams MJ, Sutherland WH, McCormick MP, de Jong SA, WalkerRJ, Wilkins GT. Impaired endothelial function following a meal richin used cooking fat. J Am Coll Cardiol 1999; 33: 1050–1055

357. Sutherland WH, Walker RJ, de Jong SA, van Rij AM, Phillips V,Walker HL. Reduced postprandial serum paraoxonase activity aftera meal rich in used cooking fat. Arterioscler Thromb Vasc Biol 1999;19: 1340–1347

358. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, FogelmanAM, et al. Protective effect of high density lipoprotein associatedparaoxonase. Inhibition of the biological activity of minimallyoxidized low density lipoprotein. J Clin Invest 1995; 96: 2882–2891

359. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet1994; 344: 793–795

360. Steinberg D. Lewis A. Conner Memorial Lecture. Oxidativemodification of LDL and atherogenesis. Circulation 1997; 95:1062–1071

361. Thompson JA, May WA, Paulose MM, Peterson RJ, Chang SSChemical reactions involved in the deep-fat frying of foods. VII.

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362. Vijaya Kumar M, Sambaiah K, Lokesh BR. The anhydrous milk fat,ghee, lowers serum prostaglandins and secretion of leukotrienesby rat peritoneal macrophages. Prostaglandins Leukot Essent FattyAcids 1999; 61: 249–254

363. Simmons D, Williams R. Dietary practices among Europeans anddifferent South Asian groups in Coventry. Br J Nutr 1997; 78:5–14

364. Jacobson MS. Cholesterol oxides in Indian ghee: possible cause ofunexplained high risk of atherosclerosis in Indian immigrantpopulations. Lancet 1987; 2: 656–658

365. Gupta R, Prakash H. Association of dietary ghee intake withcoronary heart disease and risk factor prevalence in rural males. JIndian Med Assoc 1997; 95: 67–9, 83

366. Lip GY, Malik I, Luscombe C, McCarry M, Beevers G. Dietary fatpurchasing habits in whites, blacks and Asian peoples in England–implications for heart disease prevention. Int J Cardiol 1995; 48:287–293

367. Mendis S, Samarajeewa U, Thattil RO. Coconut fat and serumlipoproteins: effects of partial replacement with unsaturated fats.Br J Nutr 2001; 85: 583–589

368. Dowse GK, Gareeboo H, Alberti KG, Zimmet P, Tuomilehto J, PurranA, et al. Changes in population cholesterol doncentrations andother cardiovascular risk factor levels after five years of the non-communicable disease intervention programme in Mauritius.Mauritius Non-communicable Disease Study Group. BMJ 1995;311: 1255–1259

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370. Cox C, Sutherland W, Mann J, de Jong S, Chisholm A, Skeaff M.Effects of dietary coconut oil, butter and safflower oil on plasmalipids, lipoproteins and lathosterol levels. Eur J Clin Nutr 1998; 52:650–654

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373. Kutty VR, Balakrishnan KG, Jayasree AK, Thomas J. Prevalence ofcoronary heart disease in the rural population ofThiruvananthapuram district, Kerala, India. Int J Cardiol 1993;39: 59–70

374. Joseph A, Kutty VR, Soman CR. High risk for coronary heart diseasein Thiruvananthapuram city: a study of serum lipids and otherrisk factors. Indian Heart J 2000; 52: 29–35

375. Burchfiel CM, Abbott R, Curb S, Rodriguez B, Yano K. Distributionand correlates of lipids and lipoproteins in elderly Japanese-American men: the Honolulu Heart Program. Artherioscler ThrombVasc Biol 1996; 16: 1356–1364

376. Mendis S. Cardiovascular disease in Sri Lanka: Sri Lanka: Ministry ofHealth, 1998

377. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherenceto a Mediterranean diet and survival in a Greek population. N EnglJ Med 2003; 348: 2599–2608

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381. Truswell S. Practical and realistic approaches to healthier dietmodifications. Am J Clin Nutr 1998; 67(Suppl): 583S–590S

382. Hooper L, Summerbell CD, Higgins JP, Thompson RL, Capps NE,Smith GD, et al. Dietary fat intake and prevention of cardiovasculardisease: systematic review. BMJ 2001; 322: 757–763

383. Beauchesne-Rondeau E, Gascon A, Bergeron J, Jacques H. Plasmalipids and lipoproteins in hypercholesterolemic men fed a lipid-lowering diet containing lean beef, lean fish, or poultry. Am J ClinNutr 2003; 77: 587–593

384. Meyer KA, Kushi LH, Jacobs DR Jr, Folsom AR. Dietary fat andincidence of type 2 diabetes in older Iowa women. Diabetes Care2001; 24: 1528–1535

385. Hu FB, van Dam RM, Liu S. Diet and risk of type II diabetes: therole of types of fat and carbohydrate. Diabetologia 2001; 44:805–817

386. Summers LK, Fielding BA, Bradshaw HA, Ilic V, Beysen C, ClarkML, et al. Substituting dietary saturated fat with polyunsaturatedfat changes abdominal fat distribution and improves insulinsensitivity. Diabetologia 2002; 45: 369–377

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388. Ros E. Dietary cis-monounsaturated fatty acids and metaboliccontrol in type 2 diabetes. Am J Clin Nutr 2003; 78 (Suppl):617S–625S

389. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H,Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus bychanges in lifestyle among subjects with impaired glucosetolerance. N Engl J Med 2001; 344: 1343–1350

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Indian Heart J 2003; 55: 339–343 Lateef et al. Displacement of the Precordial Leads and ECG 339

Vertical Displacement of the Precordial Leads AltersElectrocardiographic Morphology

Fatimah Lateef, Narayan Nimbkar, Zhuang Kun Da, Foo Rui MinDepartment of Emergency Medicine, Singapore General Hospital, Singapore,

Uniformed Services University of Health Sciences Bethesda, Maryland, USA; National University of Singapore

Electrocardiography (ECG), introduced by Einthoven in1902, is the graphical display of electrical potential

differences of an electric field originating in the heart andrecorded on the body surface. It represents a uniquetechnology that is safe, simple, and reproducible.1 AccurateECG interpretation assumes that technical standards areadhered to during the acquisition and recording of tracings.A number of technical factors may alter the quality ofrecorded ECG. Some of these are patient-related, some areoperator dependent, and others relate to the equipmentutilized for recording.2

The exact placement of electrodes for ECG depends onthe interpretation and skill of the person performing it (e.g.nurses, technicians, medical students). Placement ofprecordial electrodes for the recording of a 12-lead ECG issubject to variation. Technical variability represents thelargest source of error for variations in the amplitude and

waveform of the chest lead ECG. Precordial leads arecommonly placed either too high, too low or horizontallydisplaced from their anatomically defined sites. Personsrecording ECGs should ensure that the chest leads areplaced in the proper positions, and electrodes have good skincontact to minimize artefacts. Incorrect placement maylead to false diagnosis of infarction or cause alterations inthe ECG interpretation.3,4 In practice, the effect of thedisplacement on individual ECGs is unknown.

The present study was done to assess if verticaldisplacement of electrodes af fects the waveform ofprecordial leads of the ECG in healthy adult volunteers.

Methods

This was a clinical experimental investigation. FollowingECGs in supine position were performed in healthy, adultvolunteers, with no history of ischemic heart disease (IHD).

(i) a standard 12-lead ECG with the usual accepted,surface precordial lead placement;

Original Article

Correspondence: Fatimah Lateef, Department of Emergency Medicine,Singapore General Hospital, Outram Road, Singapore 169608.e-mail: [email protected]

Background: The present study was undertaken to assess whether the vertical displacement of electrodesaffects the waveforms of precordial leads.Methods and Results: Two hundred forty healthy, adult volunteers had a standard 12-lead electrocardiogram,a 12-lead electrocardiogram with the precordial leads displaced 2 cm cranially, and another with the precordialleads displaced 2 cm caudally from the standard positions. All the three sets of electrocardiograms were visuallycompared, and changes noted. One hundred twenty male and 120 female volunteers, 20–68 years of age, wereanalyzed. Fifty-four males (45.0%) and 2 females (1.7%) showed no difference between the 3 sets ofelectrocardiograms, while 66 males (55.0%) and 118 females (98.3%) had some changes. R wave amplitudechanges were noted in 63 male (52.5%) and 111 female (92.5%) volunteers; S wave amplitude changes wereseen in 59 males (49.2%) and 99 females (82.5%); T wave changes in 5 males (4.2%) and 3 females (2.5%); STsegment changes in 1 male (0.8%) and none of the females; and QRS morphologic changes in 1 male (0.8%)and 12 females (10.0%).Conclusions: Precordial electrocardiographic waveform changes were seen with the vertical displacement ofthe precordial leads. This will have implications on the interpretation of serial electrocardiograms. Healthcareproviders should take into consideration this deviation when interpreting serial ECGs. (Indian Heart J 2003;55: 339–343)

Key Words: Electrocardiography, Precordial leads, Lead placement

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340 Lateef et al. Displacement of the Precordial Leads and ECG Indian Heart J 2003; 55: 339–343

(ii) a 12-lead ECG, as in (i), but with all the precordial leads(i.e. V

1 to V

6) shifted 2.0 cm cranially; and

(iii) a 12-lead ECG as in (i), but with all the precordial leadsshifted 2.0 cm caudally.

Measurements were done with a standard ruler. All thethree ECGs for each volunteer were visually compared, andthe differences documented (e.g. R and S wave amplitudechanges, changes in the QRS morphology, ST segmentchanges, T wave morphology and appearance/disappearance of Q waves). T wave changes refer to eitheran upright, inverted or flattened T wave. ST segmentchanges may represent an isoelectric ST segment, or STelevation, or depression. The morphological changes wouldrefer to changes such as the appearance of a bundle branchblock pattern.

The standard 12-lead ECG for each person was used asthe control against which the other two ECGs, which haddeliberate alterations in the positions of the precordial leads,were compared. When the tracings with the displacedelectrodes did not resemble the standard ECG tracings, thevariations were confirmed by repeating the tracings.

The study was approved by the hospital ethicscommittee.

Results

There were a total of 240 volunteers, 20–68 years of age.One hundred and twenty were males and 120 females.Fifty-four males (45.0%) and 2 females (1.7%) showed nodifferences when their three sets of ECGs were compared,while 66 males (55.0%) and 118 females (98.3%) had somechanges noted. R wave amplitude changes were noted in63 male (52.5%) and 111 female (92.5%) volunteers; Swave changes in 59 males (49.2%) and 99 females (82.5%)(Figs 1a–c); T wave changes in 5 males (4.2%) and 3 females(2.5%) (Fig. 2a–c); ST segment changes in 1 male (0.8%)and none of the females; and QRS morphological changesin 1 male (0.8%) and 12 females (10.0%) (Figs 2a–e)(Table 1). There was no Q wave appearance ordisappearance noted in the group studied. Table 1demonstrates the confidence intervals at p=0.01.

R and S wave changes were mainly amplitude changes(i.e. the height of the R wave and depth of the S wave). Therange of R wave amplitude change was from +3 mm to+15 mm (positive indicates above the isoelectric baseline),while that for S was –2 mm to –15 mm (negative indicatesbelow the isoelectric baseline) (Figs 1a–c). All the volunteerswho had S wave changes also had R wave changes.

Analysis of the changes showed that these werecommonest in leads V

1, V

2, and V

3, irrespective of whether

the displacement was cranial or caudal (Tables 2 and 3).

Fig. 1a. Normal position: amplitude of the R wave in V3 (+27 mm).

Fig. 1b. 2 cm cranial: amplitude of the R wave in V3 (+9 mm).

Fig. 1c. 2 cm caudal: amplitude of the R wave in V3 (+10 mm).

Changes were not observed in the ramaining precordialleads, namely leads V

4, V

5, and V

6.

As the volunteers did not have any history ofcardiovascular problems, none of them presented with anycardiorespiratory symptoms. There was one volunteer whowas detected to have left ventricular hypertrophy on ECG,which was repeated for reconfirmation. She wassubsequently offered assessment by a cardiologist as anoutpatient.

Discussion

There are numerous potential clinical uses of the 12-lead

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Fig. 2c. 2 cm caudal: QRS complex in V1 shows RS pattern with T waveinversion in V3.

Table 1. Changes observed when comparing the 3electrocardiograms

Changes Number of Number ofobserved males (%) females (%)

None 54 (45.0) 2 (1.7)CI: 33.87–56.65 CI: 0.33–8.07

Changes 66 (55.0) 118 (98.3)CI: 43.35–66.13 CI: 91.3–99.67

R wave amplitude 63 (52.5) 111 (92.5)CI: 40.94–63.80 CI: 83.85–96.70

S wave amplitude 59 (49.2) 99 (82.5)CI: 37.77–60.65 CI: 71.93–89.66

T wave 5 (4.2) 3 (2.5)QRS morphological 1 (0.8) 12 (10.0)ST segment 1 (0.8) 0

CI: confidence intervalNote: Some patients had more than one category of change (e.g. patientA had both R wave and S wave amplitude changes), therefore, the totalnumber of changes may be more than the number of volunteers.For male volunteers, T wave, QRS morphology, and ST segment changeswhen taken together, the CI at p=0.01 was 33.87%–56.65%.For female volunteers, the CI at p=0.01 was 6.64%–22.29%.

Table 2. Detailed changes among male volunteers

Changes Leads Cranial Caudaldisplacement displacement

R wave V1

6 9V

229 34

V3

42 38

S wave V1

0 0V

219 22

V3

40 37

T wave V1

0 1V

23 1

V3

3 3

QRS complex V1

1 0

ST segment V1

0 0V

21 0

V3 0 0

Note: Some volunteers showed changes in more than one lead, and alsochanges in either one or both of the cranial and caudal displacement leads.For these reasons, the numbers may not tally, and may be more than thetotal number of male volunteers.

Fig. 2a. Normal position: QRS complex in V1 showing an RS pattern with Twave inversion in V3.

Fig. 2b. 2 cm cranial: QRS complex in V1 showing an RSR' pattern with uprightT wave in V3.

Fig. 2d. Enlargement of Fig. 2a (normal) V1: RS pattern

Fig. 2e. Enlargement of Fig. 2b (2cm cranial) V1: RSR' pattern

ECG. The ECG may reflect changes associated with primaryand secondary myocardial processes, metabolic andelectrolyte abnormalities, as well as toxic or therapeuticeffects of drugs or devices. ECGs are composed of a numberof waveforms, each with its own sensitivity and specificity,

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342 Lateef et al. Displacement of the Precordial Leads and ECG Indian Heart J 2003; 55: 339–343

and each influenced by a variety of pathologic andpathophysiologic factors. For example, although STsegment and T wave changes are the commonest and mostsensitive, these changes are also the least specific.3–5

There is continuing uncertainty about standardizedprocedures for the placement of ECG chest electrodes.Technical variability represents the largest source of errorfor short-term variations in amplitude and waveforms ofthe chest lead ECG. There is uncertainty about locating themid-clavicular line and, thus, the position of V

4,

particularly in obese persons, and females. Appropriateselection of the position for chest leads may help inremoving the inconsistencies in ECG interpretation andselection criteria for therapy, thus improving comparabilityof treatment results.6

Amplitude changes are not uncommon. Previous studieson modified positions of the limb leads have shownconsiderable amplitude and waveform changes in thefrontal plane ECG.7,8

The R wave (QRS complex) reflects the depolarizationphase of the ventricles. It has been shown that in thosewith coronary artery disease/ischemic heart disease, thereis often poor progression of the R wave as one moves acrossthe precordial leads and approaches V

6.9

As for extrasystoles, Michaelides et al.10 in a study usingangiographic confirmation, showed that the R wave of theextrasystoles is positively correlated with the number ofobstructed coronary arteries, Barnhill et al.11 studied R andS waves (terminal portion of the QRS complex) in patients

with myocardial infarction (MI), and concluded that thesewere commonly affected, and very sensitive to changes andvariations.

Feldman et al.,12 in a study that examined R waveamplitude and left ventricle chamber size, concluded thatthere is a direct and dynamic correlation between the twofactors. Chamber size and distance from the left ventricleto leads V

5 and V

6 were major determinants of the R wave

amplitude. R and S wave amplitudes are also important indiagnostic criteria such as left ventricular hypertrophy(LVH).

The morphology of the ECG depicts the resultantelectrical vector in 3 dimensions, with time being the fourthdimension. Hence, it is natural that the morphology of theECG is known to be affected by the position of the heart,position of the unipolar leads in relation to the heart, aswell as the pathway between the heart and unipolarelectrodes. For example, with alteration in position of theprecordial electrodes, the current may have to pass througha different, more circuitous route, if there is nonconductivetissue encountered along the more direct pathway. Otherfactors that have been shown to affect ECG morphologyinclude body position,13 and age.14 There have been somestudies on ethnicity, and its effect on ECGs.15–16 However,most of these studies are small and may be applicable tothe local, ethnic population only.

It has often been thought that with changes in theplacement of leads, there will be ST segment alterationsaffecting our interpretation of MI (i.e. ST segmentelevation), especially when comparing serial ECGs.17 In thisstudy, there was only one male patient (0.8%) in whom STsegment change was noted. This assumption may not beas common as previously thought.

There is intra-individual precordial voltage variation inserial ECGs. It is necessary to improve reproducibility andprecision in the performance of ECGs. There is also a needto emphasize how electrode placement is taught to nurses,as well as their accountability for this duty.18,19

A new device known as the precordial ECG BELT, usinga 6-lead precordial application, has been used in studies tocompare its accuracy with standard precordial leadapplication. Results have indicated disagreement betweenthe two methods.20 The most obvious weakness of the ECGBELT was the inability to obtain a reading with a stablebaseline. The findings suggest that the ECG BELT is notadequate for clinical application in its current form.20

Another alternative may be a device with less surfaceconnections, such as the EASI ECG. This device uses only 5surface connections to derive the 12-lead ECG. Perhaps withless connections, there would be less placement error and

Table 3. Detailed changes among female volunteers

Changes Leads Cranial Caudaldisplacement displacement

R wave V1

4 0V

256 46

V3

71 73

S wave V1

1 3V

227 32

V3

71 64

T wave V1

1 0V

21 2

V3

1 1

QRS complex V1

2 3V

27 4

V3

3 5

Note: Some volunteers showed changes in more than one lead, and alsochanges in either one or both of the cranial and caudal displacement leads.For these reasons, the numbers may not tally, and may be more than thetotal number of female volunteers.

IHJ-455-03.p65 11/19/2003, 11:24 PM342


variations. The EASI system has been favorably comparedwith the standard 12-lead ECG.

Therefore, to reduce inconsistencies, the practice ofmarking precordial lead positions for short-term serial ECGsshould be encouraged. Physicians should also be morecognizant of ECG changes caused by precordial leaddisplacement when comparing serial ECGs.

This study has shown that variations do exist amongnormal individuals. It is the first time this has been provenobjectively on normal individuals. This suggests the needfor standardization, or the use of a device to assist in leadplacement, which can ensure accuracy, reproducibility, andobjectivity.

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5. Kadish AH, Buxton AE, Kennedy HL, Knight BP, Mason JW, SchugerCD, et al. ACC/AHA clinical competence statement on electro-cardiography and ambulatory electrocardiography. A report ofthe ACC/AHA/ACP-ASIM Task Force on Clinical Competence(ACC/AHA Committee to Develop a Clinical Competence Statementon Electrocardiography and Ambulatory Electrocardiography).J Am Coll Cardiol 2001; 38: 2091–2100

6. Rautaharju PM, Park L, Rautaharju FS, Crow R. A standardizedprocedure for locating and documenting ECG chest electrodepositions: consideration of the effect of breast tissue on ECGamplitudes in women. J Electrocardiol 1998; 31: 17–29

7. Rautaharju PM, Prineas RJ, Crow RS, Seale D, Furberg C. The effect

of modified limb electrode positions on electrocardiographic waveamplitudes. J Electrocardiol 1980; 13: 109–113

8. Takuma K, Hori S, Sasaki J, Shinozawa Y, Yoshikawa T, Hand S, et al.An alternative limb lead system for electrocardiographs in emergencypatients. Am J Emerg Med 1995; 13: 514–517

9. Chia BL. Ischaemic heart disease. In: Clinical electrocardiography.3rd ed. World Scientific Publishers. pp. 11-37

10. Michaelides AP, Vyssoulis GP, Paraskevas PG, Skouros CG, TsiamisEG, Toutouzas PK. Significance of R wave changes in exercise-induced supraventricular extrasystoles. Angiographic correlates. JElectrocardiol 1993; 26: 197–206

11. Barnhill JE 3rd, Tendera M, Cade H, Campbell WB, Smith RF.Depolarization changes early in the course of myocardial infarction:significance of changes in the terminal portion of the QRS complex.J Am Coll Cardiol 1989; 14: 143–149

12. Feldman T, Borow RM, Neumann A, Lang RM, Childers RW. Relationof electrocardiographic R-wave amplitude to changes in leftventricular chamber size and position in normal subjects. Am J Cardiol1985; 55: 1168–1174

13. Adams MG, Drew BJ. Body position effects on the ECG: implicationsfor ischemia monitoring. J Electrocardiol 1997; 30: 285–291

14. Bachman S, Sparrow D, Smith LK. Effects of aging on theelectrocardiogram. Am J Cardiol 1981; 48: 513–516

15. Mansi IA, Nash IS. Ethnic differences in the ST segment of theelectrocardiogram: a comparative study among six ethnic groups.Am J Emerg Med 2001; 19: 541–554

16. Chen CY, Chiang BN, Macfarlane PW. Normal limits of theelectrocardiogram in a Chinese population. J Electrocardiol 1989; 22:1–15

17. Herman MV, Ingram DA, Levy JA, Cook JR, Athans RJ. Variability ofelectrocardiographic precordial lead placement: a method to improveaccuracy and reliability. Clin Cardiol 1991; 14: 469–476

18. Bupp JE, Dunger M, Lawrence C, Wingate S. Placement of cardiacelectrodes: written, simulated, and actual accuracy. Am J Crit Care1997; 6: 457–462

19. McConnell EA. Applying cardiac monitor electrodes. Nursing 1998;28: 26

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344 Shrivastava et al. Coronary Calcium and CAD Indian Heart J 2003; 55: 344–348

Coronary Calcium and Coronary Artery Disease:An Indian Perspective

Sameer Shrivastava, Vinayak Agrawal, Ravi R Kasliwal, Dhanraj R Jangid,Ashok Sen, Atul Verma, Naresh Trehan

Departments of Cardiology and Nuclear Medicine, Escorts Heart Institute and Research Centre, New Delhi

Calcification is closely associated with atheromatousplaque, and is a recognized marker for coronary artery

disease.1 Until recently, it was believed that calcium presentin the atheromatous plaques is in the form of calciumphosphate, precipitated in a passive manner. However,recent findings indicate that calcification is an activeprocess and calcium is deposited as hydroxyapatite, similarto that in active bone formation.2 It is known that theamount of calcium in the coronary arteries is better

correlated with the amount of atherosclerosis in differentindividuals and, to a lesser extent, with the segments ofthe coronary tree in the same individual. It is not knownwhether the quantity of calcium tracks the quantity ofatherosclerosis over time in the same individual. There arenumerous articles on the correlation of coronary calciumwith angiographically proven coronary artery disease(CAD); however, there are no such large studies from India.This study was aimed at using helical computedtomography (CT) scan for calculating coronary calciumscores (CCSs) in the Indian population.

Original Article

Background: Coronary artery calcification is a part of the development of atherosclerosis. It occurs exclusivelyin atherosclerotic arteries and can be used as a noninvasive marker of coronary atherosclerosis. As there is nolarge-scale study on coronary calcium score reported in the Indian population till date, this study was undertakenfor calculating the score in Indians at intermediate-to-high risk of coronary artery disease, and to correlate itwith angiographically proven coronary artery disease.Methods and Results: A total of 388 consecutive patients who underwent coronary calcium scoring andcoronary angiography were included in the study. Calcium scoring was performed based on a modification ofthe Agatston Score using a high-speed computed tomography scanner (GE® CT/i scanner). Coronary calciumscores were correlated with the presence or absence of significant coronary artery disease (defined as ≥70%stenosis of at least one major epicardial coronary artery) on angiography. Out of 388 patients who underwentcoronary angiography, 298 were found to have significant coronary artery disease. Mean coronary calciumscore was significantly higher in patients with angiographically proven coronary artery disease (226.7±65.2)as compared to those who had normal angiograms (20.29±56.7; p value<0.0001). All the 72 patients whohad a score >400 had an abnormal angiogram (sensitivity 23.1%, specificity 100%, positive predictive value100%, and negative predictive value 24.1%). On the other hand, among the patients who had a score >0, 298were found to have abnormal angiograms, while 16 had normal angiograms (sensitivity 95.5%, specificity78.9%, positive predictive value 94.9%, and negative predictive value 81.1%).Conclusions: Detection of coronary calcium score by a helical computed tomography scanner is a useful toolfor predicting the presence of significant coronary artery disease in intermediate-to-high risk patients. Anabsolute score of 0 has a high negative predictive value for the presence of coronary artery disease, and mayobviate the need to perform coronary angiogram in intermediate-risk patients. On the other extreme, score>400 is highly predictive of the presence of coronary artery disease, and virtually confirms the presence ofsignificant coronary artery disease in intermediate-to-high risk patients. (Indian Heart J 2003; 55:344–348)

Key Words: Coronary artery disease, Coronary calcium score, Computed tomography

Correspondence: Dr Vinayak Agrawal, 103, Siddhartha Enclave, NewDelhi. e-mail: [email protected]

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Indian Heart J 2003; 55: 344–348 Shrivastava et al. Coronary Calcium and CAD 345

Methods

The study included 388 consecutive patients whounderwent coronary calcium scoring as well as coronaryangiography. These included patients who had presentedwith either typical symptoms suggestive of ischemic heartdisease (with or without a positive stress test), or atypicalsymptoms with a positive stress test for reversiblemyocardial ischemia, putting these patients into a pretestprobability of intermediate-to-high risk category. All thepatients underwent detailed clinical evaluation,biochemical tests, coronary calcium scoring, and coronaryangiography. Biochemical tests included fasting and post-prandial blood sugar, and fasting lipid profile.

Assessement of CCSs was done by using a high-speedCT scanner (GE® CT/i scanner). Scores were computergenerated using an advanced software “smart-scorecalcium” adapting a modification based on Agatston Score.Total CCSs thus obtained were correlated with the presenceor absence of significant CAD. Significant CAD was definedas ≥70% stenosis of at least one of the major epicardialcoronary arteries on coronary angiography. Informedconsent was obtained from the entire patient populationenrolled in the study. The study was approved by thehospital ethics committee.

Statistical analysis : The data obtained were maintainedon a Microsoft excel spreadsheet. The differences in variousparameters between the different groups were assessed byusing Chi-square and t tests, as indicated. Sensitivity,specificity, positive predictive value (PPV), and negativepredictive value (NPV) for dif ferent risk scores werecalculated. A p value <0.05 was considered significant. Allthe statistical analyses were done on SPSS 10.0 forWindows.

Results

A total of 388 consecutive patients underwent coronarycalcium scoring and coronary angiograms to rule outsignificant CAD. Three hundred twenty-five patients(83.8%) were male while 63 (16.2%) were female. Themean age of the patients was 52.3±11.3 years (range 15–78 years). Out of these patients, 76.2% were less than 60years of age, and 23.8% were more than 60 years of age.For the purpose of analysis, patients were divided into fourgroups according to CCS: 0, 1–100, 101–400, and >400.There was no statistically significant difference in theprevalence of various conventional cardiovascular riskfactors in different calcium score groups (Tables 1 and 2).The presence or absence of significant CAD on coronary

angiography in different calcium score groups is presentedin Table 3. Sensitivity, specificity, PPV, and NPV for theprediction of significant CAD were calculated for threedifferent calcium scores, namely >0, >100, and >400(Table 4). All the 72 patients who had CCSs >400 hadabnormal angiograms, yielding a sensitivity of 23.1%,specificity 100%, PPV 100%, and NPV 24.1%. Twohundred thirty-six patients with CCS>100 had abnormalangiograms, with only 4 patients having normalangiogram (sensitivity 75.6%, specificity 94.7%, PPV98.3%, and NPV 51.3%). Out of 314 patients who had

Table 1. Incidence of various risk factors in relation to thecalcium score

Risk factor Calcium score p value

≤100 101–400 >400(n=148) (n=168) (n=72)

Age (years) 47.2±10.7 51.3±10.6 49.2±10.1 nsMale (%) 86.5 80.4 86.1 nsHypertension (%) 12.5 11.1 14.7 nsDiabetes (%) 3.8 5.6 8.8 nsFamily history (%) 11.5 11.1 8.8 nsSmoking (%) 5.4 3.7 2.9 ns

ns: not statistically significant

Table 2. Correlation of calcium score with lipid profile

Lipid profile (mg/dl) Calcium score p value

≤100 101–400 >400(n=148) (n=168) (n=72)

Total cholesterol 204±45 220±57 216±10 nsTriglycerides 220±47 181±41 129±33 nsHigh-density 42±11 44±9 41±13 ns

lipoproteinsLow-density 125±37 142±47 140±18 ns

lipoproteinsVery low-density 40±9 34±8 25±7 ns

lipoprotein

ns: not statistically significant

Table 3. Coronary calcium score correlation with coronaryangiography findings

Calcium scores>400 101–400 1–100 0

(n=72) (n=168) (n=74) (n=74)

Abnormal angiogram 72 164 62 14Normal angiogram 0 4 12 60

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CCSs >0, 298 were found to have abnormal angiogramswhile 16 patients had normal angiograms (sensitivity95.5%, specificity 78.9%, PPV 94.9%, and NPV 81.1%).

Discussion

Quantification of calcium in the coronary arteries has beenshown to reflect the total atherosclerotic plaque burden.3,4

This quantification can be determined in a straightforwardmanner by using advanced high-speed CT scans includinghelical CT scans, multi-slice CT scans, and electron-beamCT (EBCT) scans. In several studies, detection andquantification of coronary artery calcification with EBCTin suspected CAD patients has been compared with widelyavailable conventional helical CT scan. Although imagesof the heart from conventional CT scans may suffer fromcardiac motion artifacts, calcium scoring with spiral ormulti-slice CT scanners has the potential to identify patientswith CAD with an accuracy similar to that of EBCT scan.5–7

Protocols with prospective or retrospective electrocardio-graphy triggering can be used, which appear to yield resultssimilar to Agatston CCS with EBCT scans, despite technicaldifferences.8

Calcification is not found in normal coronary arteries.The atherosclerotic process starts in the second decade oflife, when calcium deposition begins. The calciumdeposition increases with age, and with progression ofatherosclerotic lesions. Coronary artery calcification istemporally related to vascular inflammation and the demiseof lipid-laden macrophages.9,10 The exact mechanism isunclear, and may be due to the deposition of extracellularcalcium from dying cells, or the formation of bone-likestructure by calcifying cells.11,12 Since calcium is depositedonly in the atherosclerotic plaques and not in the normalvessels, and since atherosclerosis is a diffuse process, a highcoronary calcium burden reflects the presence of moreextensive coronary atherosclerosis (Fig. 1). Hence, higherCCSs are associated with the presence of significant CAD

and future risk of adverse coronary events. Moreover,contrary to popular belief, coronary calcium depositionmay represent a type of plaque instability, namely plaquerupture. It was earlier believed that calcified areas areunlikely to be associated with the sites of plaque rupture.13

However, the stiffened calcific area can induce stress at thejunction of the calcified and noncalcified sections, whichis a common site of plaque rupture.14 Burke et al.15 foundthat, contrary to expectations, the degree of calcificationwas greatest for acute and healed plaque ruptures, and leastfor plaque erosion. It has been suggested that the presenceof calcium within a heterogeneous, fat-laden plaquerenders the plaque more susceptible to stress cracking, ascompared to a plaque that contains no calcium.16

However, calcium deposition as detected by coronarycalcium scoring does not correlate with the site and severityof luminal narrowing on coronary angiography. Theobservation that coronary plaque burden is poorlycorrelated with luminal narrowing has been confirmed bystudies using intravascular ultrasound (IVUS), and can beexplained by the process of vascular remodeling.17–19 As theatherosclerotic plaque accumulates in the coronary arterywall, there is an outward remodeling leading to thepreservation of luminal size.20 However, the likelihood ofplaque rupture leading to acute MI is not decreased andmay even be increased. Thus, the apparent lower specificityof CCS for angiographic obstruction in some studies mayin fact be due to the inability of angiography to detectextraluminal plaque.21 However, an increased CCS wouldmean the likelihood of significant CAD elsewhere or atanother site.

Our data also suggest that in symptomatic patients, themere presence of calcium is a very sensitive index for thepresence of significant CAD somewhere in the coronaryarteries. Any CCS >0 has a high sensitivity and reasonablygood specificity, with good PPV to predict the presence ofobstructive CAD. There have been numerous studies that

Table 4. Sensitivity, specificity, positive predictive value,and negative predictive value of different calcium scoresfor predicting the presence or absence of significantcoronary artery disease

Calcium scores

>400 >100 0

Sensitivity 23.1 75.6 95.5Specificity 100 94.7 78.9Positive predictive value 100 98.3 94.9Negative predictive value 24.1 51.3 81.1

Fig. 1. Normal and high calcium score images.

Zero Calcium Socre High Calcium Socre

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Indian Heart J 2003; 55: 344–348 Shrivastava et al. Coronary Calcium and CAD 347

combined to obtain complementary information.35 Anegative (<0) calcification generally excludes obstructiveCAD. Hence, this technique can be used to evaluate patientswith atypical chest pain. If the CCS is zero, the source ofpain is unlikely to be due to CAD. If the CCS is very high(>400), the chances of the presence of obstructive CADare steep.

Since coronary calcium scoring is a screening tool, atechnique that has a very high sensitivity for the predictionof obstructive CAD is desirable. In our study, which involvedintermediate-to-high risk patients, a CCS >0 had a veryhigh sensitivity for obstructive CAD with fairly highspecificity. There was a progressive increase in PPV withincreasing CCS, suggesting that high CCSs are increasinglyassociated with obstructive CAD. Thus, a CCS of zero maybe used to obviate the need for coronary angiography inintermediate-risk patients and in selected high-risk patients,when coronary angiography is not the preferred methoddue to concomitant co-morbid conditions (such as renaldysfunction, terminal illnesses, etc.). In such patients, ahigh CCS, particularly >400, virtually confirms thepresence of significant CAD, and can help in devisingfurther management strategies.

Limitations: Our study suffered from certain limitations.It involved only those individuals who were at intermediate-to-high risk of having significant CAD. Patients at low riskof CAD could not be included because of obvious ethicalreasons. Hence, there was a definite selection bias that couldnot have been avoided.

References

1. Rifkin RD, Parisi AF, Folland E. Coronary calcification in the diagnosisof coronary artery disease. Am J Cardiol 1979; 44: 141–147

2. Doherty TM, Detrano RC. Coronary artery calcification as an activeprocess: a new perspective on an old problem. Calcif Tissue Int 1994;94: 1597–1604

3. Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS.Coronary artery calcium area by electron-beam computedtomography and coronary atherosclerotic plaque area. Ahistopathologic correlative study. Circulation 1995; 92: 2157–2162

4. Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J,Fitzpatrick LA, et al. Arterial calcification and not lumen stenosis ishighly correlated with atherosclerotic plaque burden in humans: ahistologic study of 723 coronary artery segments usingnondecalcifying methodology. J Am Coll Cardiol 1998; 31: 126–133

5. Becker CR, Knez A, Jakobs TF, Aydemir S, Becker A, Schoepf UJ, et al.Detection and quantification of coronary artery calcification withelectron-beam and conventional CT. Eur Radiol 1999; 9: 620–624

6. Carr JJ, Crouse JR 3rd, Goff DC Jr, D’Agostino RB Jr, Peterson NP,Burke GL. Evaluation of subsecond gated helical CT for quantificationof coronary artery calcium and comparison with electron beam CT.AJR Am J Roentgenol 2000; 174: 915–921

7. Knez A, Becker C, Becker A, Leber A, White C, Reiser M, et al.Determination of coronary calcium with multi-slice spiral computed

have proved coronary calcium scoring to be an excellentpredictor of the presence of angiographically provenobstructive CAD, and future risk of adverse cardiovascularevents. In a large study conducted by Budoff et al.22 in 710symptomatic subjects with a mean age of 56 years,comparing EBCT scan with coronary angiography, thesensitivity, specificity, and NPV were 95%, 44%, and 84%,respectively. Breen et al.23 and Kaufmann et al.24

demonstrated the relationship between CCS and coronaryartery lumen obstruction as assessed by coronaryangiography. Kaufmann et al.24 studied 160 symptomaticindividuals 23–59 years of age and compared CCS withcoronary artery stenosis. Sensitivity, specificity, and accuracyranged from 81% to 86%. Several other groups25–30 haveconfirmed the association of increased CCS with increasedpresence and severity of CAD.

He et al.31 studied nearly 400 asymptomatic patientsusing EBCT scan and SPECT, and showed that none of thepatients with a CCS <10 had an abnormal SPECT. Out ofof these, 2.6% of patients with CCS 10–100, 11.3% witha CCS of 101–399, and 46% with CCS>400 had a SPECTshowing ischemia. This high sensitivity and low specificityprobably relates to the fact that only 20% of theatherosclerotic plaque is calcified. However, the absence ofcalcification seems to indicate a lack of significant luminalstenosis.

In the Rotterdam Coronary Calcification Study,32 astrong and graded association was found between coronarycalcification and MI. In a similar study of patients withsuspected CAD, CT scan showed a 65% sensitivity, and 87%specificity for coronary artery calcification.33 According tothe American Heart Association Expert Consensusdocument on the use of EBCT for the diagnosis andprognosis of CAD,34 a meta-analysis of the relationshipbetween CAD and calcium prevalence in patientsundergoing EBCT and cardiac catheterization to determinethe diagnostic accuracy of EBCT in catheterized patientsdemonstrated a high sensitivity of EBCT for CAD, a muchlower specificity and an overall predictive accuracy of 70%in typical CAD patient populations. The test has proven tohave a predictive accuracy approximately equivalent to thealternative methods for diagnosing CAD, but was not foundto be superior to alternative noninvasive tests such as SPECTimaging. A positive calcium score might be valuable indetermining whether a patient who appears to be atintermediate risk of CAD is actually at high risk. Conversely,a low or absent calcium score may also prove useful indetermining a low likelihood of developing CAD. Theabsence of coronary calcification identifies patients withfalse-positive exercise treadmill testing, and the two can be

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tomography: a comparative study with electron-beam CT. Int JCardiovasc Imaging 2002; 18: 295–303

8. Schmermund A, Mohlenkamp S, Erbel R. The latest on the calciumstory. Am J Cardiol 2002; 90: 12L–14L

9. Stary HC. The sequence of cell and matrix changes in atheroscleroticlesions of coronary arteries in the first forty years of life. Eur Heart J1990; 11 (Suppl): 3–19

10. Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull WJr, et al. A definition of advanced types of atherosclerotic lesions anda histological classification of atherosclerosis. A report from theCommittee on Vascular Lesions of the Council on Arteriosclerosis,American Heart Association. Circulation 1995; 92: 1355–1374

11. Parhami F, Bostrom K, Watson K, Demer LL. Role of molecularregulation in vascular calcification. J Atheroscler Thromb 1996; 3:90–94

12. Watson KE, Abrolat ML, Malone LL, Hoeg JM, Doherty T, Detrano R,et al. Active serum vitamin D levels are inversely correlated withcoronary calcification. Circulation 1997; 96: 1755–1760

13. Cheng GC, Loree HM, Kamm RD, Fishbein MC, Lee RT. Distributionof circumferential stress in ruptured and stable atheroscleroticlesions. A structural analysis with histopathological correlation.Circulation 1993; 87: 1179–1187

14. Demer LL, Watson KE, Bostrom K. Mechanism of calcification inatherosclerosis. Trends Cardiovasc Med 1994; 4: 45–49

15. Burke AP, Farb A, Malcom GT, Liang YH, Smialek J, Virmani R.Coronary risk factors and plaque morphology in men with coronarydisease who died suddenly. N Engl J Med 1997; 336: 1276–1282

16. Schwarz U, Buzello M, Ritz E, Stein G, Raabe G, Wiest G, et al.Morphology of coronary atherosclerotic lesions in patients with end-stage renal failure. Nephrol Dial Transplant 2000; 15: 218–223

17. Klingensmith JD, Vince DG, Kuban BD, Shekhar R, Tuzcu EM, NissenSE, et al. Assessment of coronary compensatory enlargement bythree-dimensional intravascular ultrasound. Int J Card Imaging 2000;16: 87–98

18. Nissen SE. Shortcomings of coronary angiography and theirimplications in clinical practice. Cleve Clin J Med 1999; 66: 479–485

19. Nissen SE, Yock P. Intravascular ultrasound: novel pathophysiologicalinsights and current clinical applications. Circulation 2001; 103:604–616

20. Fishbein MC, Siegel RJ. How big are coronary atherosclerotic plaquesthat rupture? Circulation 1996; 94: 2662–2666

21. Baumgart D, Schmermund A, Goerge G, Haude M, Ge J, Adamzik M,et al. Comparison of electron beam computed tomography withintracoronary ultrasound and coronary angiography for detectionof coronary atherosclerosis. J Am Coll Cardiol 1997; 30: 57–64

22. Budoff MJ, Georgiou D, Brody A, Agatston AS, Kennedy J, WolfkielC, et al. Ultrafast computed tomography as a diagnostic modality inthe detection of coronary artery disease: a multicenter study.Circulation 1996; 93: 898–904

23. Breen JF, Sheedy PF 2nd, Schwartz RS, Stanson AW, Kaufmann RB,Moll PP, et al. Coronary artery calcification detected with ultrafast

CT as an indication of coronary artery disease. Radiology 1992; 185:435–439

24. Kaufmann RB, Peyser PA, Sheedy PF, Rumberger JA, Schwartz RS.Quantification of coronary artery calcium by electron beamcomputed tomography for determination of severity of angiographiccoronary artery disease in younger patients. J Am Coll Cardiol 1995;25: 626–632

25. Bielak LF, Kaufmann RB, Moll PP, McCollough CH, Schwartz RS,Sheedy PF 2nd. Small lesions in the heart identified at electron beamCT: calcification or noise? Radiology 1994; 192: 631–636

26. Rumberger JA, Schwartz RS, Simons DB, Sheedy PF 3rd, EdwardsWD, Fitzpatrick LA. Relation of coronary calcium determined byelectron beam computed tomography and lumen narrowingdetermined by autopsy. Am J Cardiol 1994; 73: 1169–1173

27. Agatston AS, Janowitz WR, Kaplan G, Gasso J, Hildner F, ViamonteM Jr. Ultrafast computed tomography-detected coronary calciumreflects the angiographic extent of coronary arterial atherosclerosis.Am J Cardiol 1994; 74: 1272–1274

28. Kajinami K, Seki H, Takekoshi N, Mabuchi H. Noninvasive predictionof coronary atherosclerosis by quantification of coronary arterycalcification using electron beam computed tomography:comparison with electrocardiographic and thallium exercise stresstest results. J Am Coll Cardiol 1995; 26: 1209–1221

29. Stanford W, Travis ME, Thompson BH, Reiners TJ, Hasson RR,Winniford MD. Electron-beam computed tomographic detection ofcoronary calcification in patients undergoing percutaneoustransluminal coronary angioplasty: predictability of restenosis. Apreliminary report. Am J Card Imaging 1995; 9: 257–260

30. Budoff MJ, Georgiou D, Brody A, Agatston AS, Kennedy J, WolfkielC, et al. Ultrafast computed tomography as a diagnostic modality inthe detection of coronary artery disease: a multicenter study.Circulation 1996; 93: 898–904

31. He ZX, Hedrick TD, Pratt CM, Verani MS, Aquino V, Roberts R, et al.Severity of coronary artery calcification by electron beam computedtomography predicts silent myocardial ischemia. Circulation 2000;101: 244–251

32. Vliegenthart R, Oudkerk M, Song B, van der Kuip DA, Hofman A,Witteman JC. Coronary calcification detected by electron-beamcomputed tomography and myocardial infarction. The RotterdamCoronary Calcification Study. Eur Heart J 2002; 23: 1596–1603

33. Masuda Y, Naito S, Aoyagi Y, Yamada Z, Uda T, Morooka N, et al.Coronary artery calcification detected by CT: clinical significance andangiographic correlates. Angiology 1990; 41: 1037–1047

34. O’Rourke RA, Brundage BH, Froelicher VF, Greenland P, Grundy SM,Hachamovitch R, et al. American College of Cardiology/AmericanHeart Association Expert Consensus Document on electron-beamcomputed tomography for the diagnosis and prognosis of coronaryartery disease. J Am Coll Cardiol 2000; 36: 326–340

35. Lamont DH, Budoff MJ, Shavelle DM, Shavelle R, Brundage BH, HagarJM. Coronary calcium scanning adds incremental value to patientswith positive stress tests. Am Heart J 2002; 143: 861–867

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Indian Heart J 2003; 55: 349–353 Malhotra et al. Prehospital Delay in Treatment of AMI 349

Prehospital Delay in Patients Hospitalized WithAcute Myocardial Infarction in the Emergency Unit of a

North Indian Tertiary Care Hospital

S Malhotra, M Gupta, KK Chandra, A Grover, P PandhiDepartments of Pharmacology and Cardiology, Post Graduate Institute of Medical Education and Research, Chandigarh

Acute myocardial infarction (AMI) results fromprolonged myocardial ischemia, precipitated in most

cases by an occlusive coronary thrombus at the site of apre-existing atherosclerotic plaque. It is a major cause ofmortality and morbidity in the general population.Currently, the prevalence of coronary artery disease (CAD)in the age group of 40–50 years in urban India is 4-foldhigher than in the United States1 (10% v. 2.5%).

Numerous studies have demonstrated the benefits ofthrombolytic therapy for patients with evolving AMI.2 Thusattention has shifted towards efforts to increase the use ofthis therapy. However, the benefits of thrombolytic therapyare greater in the first few hours after the onset ofsymptoms.3 Hence, patient-associated delay in therecognition of symptoms of heart attack has been identifiedas a major obstacle to the widespread use of thrombolytictherapy.4 The duration of prehospital delay includes the

time required to recognize the symptoms, decision to seekcare, arrange transportation, travel to the hospital, and thetime required for diagnosis.5

A large number of factors have been attributed toprehospital delay; these include sociodemographic,behavioral, clinical, and situational constraints.6 The aimof the present study was to examine the extent of, andfactors associated with, delay in seeking medical care(usually thrombolytic therapy) in patients with AMI.

Methods

The study was conducted in patients presenting with AMIadmitted to the medical emergency or coronary care unitof the Nehru Hospital, Post Graduate Institute of MedicalEducation and Research, Chandigarh from December 2001to June 2002. One hundred four consecutive patients ofMI were interviewed using a pre-designed proforma. Thechief constituents of the questionnaire included thedemographic characteristics of the patient, nature and timeof onset of symptoms, pre-existing illness and treatment

Original Article

Background: Prompt treatment of patients presenting with acute myocardial infarction decreases the incidenceof death from early arrhythmia, and maximizes the potential benefit of thrombolytic therapy. Prehospital delayhas been identified as a major obstacle to the widespread use of thrombolytic therapy. The aim of the presentstudy was to examine the extent of, and factors associated with, delay in seeking medical care (usuallythrombolytic therapy) in patients with acute myocardial infarction.Methods and Results: The study was conducted in patients visiting the medical emergency unit of the NehruHospital, Post Graduate Institute of Medical Education and Research, Chandigarh. A total of 104 patientsdiagnosed with acute myocardial infarction were interviewed using a pre-designed proforma. Pain-to-door, anddoor-to-drug times, were the main outcome measures. The corrected mean (SEM) and median (range) pain-to-door times were 8.5 (0.8) hours and 5.2 (0.5–24) hours, respectively. Out of 104 patients, 38 did not receivethrombolytic therapy. In those who did not receive thrombolytic therapy, prior therapy at local health centers,lack of knowledge of symptoms, and transportation problems were the main reasons for hospital delay. Themean (SEM) and median (range) of door-to-drug times were 1.2 (0.1) hours and 1 (0.2–3.5) hours, respectively.(Indian Heart J 2003; 55: 349–353)

Key Words: Prehospital delay, Thrombolytic therapy, Acute myocardial infarction

Correspondence: Dr (Mrs) P Pandhi, Department of Pharmacology, PostGraduate Institute of Medical Education and Research, Chandigarh 160012.e-mail: [email protected]

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350 Malhotra et al. Prehospital Delay in Treatment of AMI Indian Heart J 2003; 55: 349–353

received, and any previous knowledge about symptoms ofheart attack. The patients were then asked about the timeat which they presented to the emergency unit and receivedmedical care. The main outcome measures included: (i)pain-to-door time (time interval between the onset ofsymptoms suggestive of AMI and arrival in the emergencyunit); and (ii) door-to-drug time (time interval betweenarrival in the emergency unit and administration ofthrombolytic therapy).

Statistical analysis: The data were expressed as mean(±SEM) and median. To examine the differences betweendifferent delay groups for continuous variables, t tests andanalysis of variance (ANOVA) were used. A value of p<0.05was considered statistically significant.

Results

Of the 104 consecutive MI patients studied, 66 receivedthrombolytic therapy. We initially examined the associationbetween demographic and clinical factors, and durationof prehospital delay (Table 1). The average and mediandelay times increased with advancing age. Men did notexperience significant delay as compared to women. Also,delay was not significant in patients with respect to thelocation and type of MI. Patients with a history of anginaexhibited prolonged delay compared with patients withoutangina (13.4 v. 3.2 hours). However, patients with ahistory of diabetes and hypertension did not experiencesignificant delays as compared with patients without theseconditions. Patients seeking treatment from localphysicians delayed longer than those who camestraightaway to the emergency unit (16.1 v. 6 hours) (Fig.1). We also found that patients who did not know thesymptoms of heart attack delayed longer than those whohad a good knowledge (Fig. 1).

Pain–door–drug times: The mean (SEM) and median(range) pain-to-door times were 13 (2.1) hours and 5.2(0.5–12) hours, respectively. The corrected (delay equals24 hours for those delaying 24 hours or more) mean (SEM),and median (range) pain-to-door times were 8.5 (0.8) hoursand 5.2 (0.5–24) hours, respectively (Fig. 2).

Fig. 1. Effect of treatment order and patients’ knowledge of disease symptomson prehospital delay.

Fig. 2. Prevalence of prehospital delay (pain-to-door time in patients with acutemyocardial infarction).

The mean (SEM) and median (range) of door-to-drugtimes were 1.2 (0.1) hours and 1 (0.2–3.5) hours,respectively (Table 2).

Prehospital delay was the cause for 30 of the 38 patients(79%) not receiving any thrombolytic therapy. In theremaining 8 patients, the causes for not receivingthrombolysis were: unaffordability of urokinase (3),unaffordability of streptokinase (1), associatedcontraindications for thrombolysis (2), and already receivedthrombolysis (2) (Fig. 3). Prior therapy at local healthcareservices, lack of knowledge of symptoms, andtransportation problems were the main reasons forprehospital delay in nonthrombolyzed patients.

Fig. 3. Reasons for not receiving thrombolytic therapy.

Prior local treatment None No Yes

Treatment color Knowledge of disease symptoms

Preh

ospi

tal d

elay

[cor

rect

ed m

ean

(SEM

) hou

rs]

Prehospital delay

Unaffordability of urokinase

Unaffordability of streptokinase

Associated contraindications forthrombolysis

Already thrombolized

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Discussion

This study describes prehospital delay times for the sampleof patients admitted to the emergency unit of our institutefor the evaluation of suspected AMI from December 2001to June 2002. In this study population, the overall mediandelay time was 5.2 hours, and door-to-drug time was 1hour. A review of the data from studies published between

1969 and 1987 shows that the median prehospital delayfor patients with AMI ranged from 2.5 to 7 hours.7 Thesediffering delay times are likely attributable to varyingdemographic and clinical characteristics of the samplesunder study, definitions of symptom onset time used, andperiod during which the study was conducted. In our study,delays were not significant with respect to age and sex. In

Table 1. Demographic and clinical characteristics associated with prehospital delay

Delay time (hours)

Factor n Median Mean p value Corrected mean p value(SEM) (SEM) (hours)

Age (years)<35 4 3.5 10 (7.4) 0.130 8 (5.4) 0.03335–44 11 3 9 (6.3) 4.7 (2)45–54 28 6.8 8.8 (1.4) 8.6 (1.3)55–64 32 9.5 22.1 (5.3) 12 (1.6)65–74 23 3 9.9 (4.4) 6.1 (1.5)>75 6 0.8 4.6 (3.9) 4.6 (3.9)

SexMale 85 5 12.7 (2.3) 0.830 8.3 (0.9) 0.771Female 19 5.3 14 (5.3) 9 (2)

AMI orderInitial 93 5.5 13.6 (2.3) 0.235 8.7 (0.8) 0.25Prior 11 3.5 8 (3.9) 6 (2.1)

AMI locationAnterior and /or 72 5.2 9.7 (1.9) 0.082 7.7 (0.9) 0.281

lateralInferior or 29 4.5 20.6 (5.7) 9.9 (1.8)

posteriorDay of the week

Weekend 32 5.4 6.9 (1.2) 0.013 6.7 (1.1) 0.137Weekday 72 4.5 14.7 (2.9) 8.9 (1)

Time of the day6:00–11:59 am 34 4 12.6 (4.5) 0.719 7.1 (1.2) 0.257Noon–5:59 pm 22 4.25 15.6 (4.9) 10.4 (2.1)6:00–11:59 pm 26 3.8 8.8 (2.9) 6.7 (1.5)Midnight 22 7.75 14 (4) 9.7 (1.5)

PainPresent 102 5.2 13.1 (2.2) 0.334 8.5 (0.8) 0.778Absent 02 7 7 (4) 7 (4)

DyspneaPresent 30 4.8 16.7 (5.3) 0.369 8.9 (1.6) 0.623Absent 74 4.9 11.5 (2.1) 8 (0.9)

SweatingPresent 44 4 15.6 (4.3) 0.340 8.3 (1.3) 0.787Absent 60 6.3 11.1 (1.9) 8.8 (1.9)

NauseaPresent 15 2 6.4 (3.2) 0.061 4.8 (1.9) 0.054Absent 89 6 14.1 (2.4) 9 (0.9)

Transport facilitiesAmbulance 27 6.5 6.9 (1.2) 0.015 6.9 (1.2) 0.246Others 77 4.5 14.4 (2.8) 8.7 (1)

AMI: acute myocardial infarction

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352 Malhotra et al. Prehospital Delay in Treatment of AMI Indian Heart J 2003; 55: 349–353

Table 2. Duration of prehospital delay and timing ofadministration of thrombolytic therapy in patients withacute myocardial infarction

Pain-to-door Door-to-drug times (hours)time. Duration n Median Mean (SEM) p value*of prehospitaldelay (hours)

<1 6 0.8 1.0 (0.3) 0.6271–1.9 16 0.8 0.1 (0.1)2–3.9 16 0.7 1.2 (0.2)4–5.9 10 1.4 1.4 (0.2)6–11.9 16 1 1.4 (0.3)>12 2 1.5 1.5 (0.5)Total 66 1 1.2 (0.1)

*p value denotes the comparison of mean door-to-drug times in the variousgroups of patients with different durations of prehospital delay.

an ambulance can quickly transport patients directly to thetertiary-care center if necessary. Secondly, generalpractitioners can be formally trained to administerstreptokinase themselves, and deal with the complicationsarising from streptokinase therapy.

In the present study, out of 104 patients, 66 werethrombolyzed. Also, prehospital delay was significantlylonger in the nonthrombolysed patients (corrected mean15 hours v. 4.6 hours). There is overwhelming evidence ofthe beneficial effects provided by reperfusion strategies inpatients with AMI.10 Although various contraindicationsto the administration of thrombolytic therapy presentlyexist, including prolonged prehospital delay, thrombolytictherapy is underutilized in the management of AMI.Findings from the Worcester Heart Attack Study show thatpatients who delayed for more than 6 hours were 6.5 timesless likely to receive thrombolytic agents compared topatients who arrived within 1 hour of the onset of AMI.8

In the present study, out of 38 nonthrombolysed patients,30 presented to the hospital after 6 hours; the remainingeither could not afford thrombolytic therapy or werealready thrombolysed. Another aspect of prehospital delayhighlighted by our study is knowledge regarding heartattack symptoms. Patients who knew about the symptomsof heart attack delayed less than those who were ignorant(2.9 v. 11.9 hours). Thus, educational approaches areessential to reduce the extent of patient delay, and toenhance widespread use of time-dependent managementstrategies in patients hospitalized with AMI.

Hospital-associated delays in administeringthrombolytic therapy: In our study, mean and mediandoor-to-drug times in thrombolysed patients were 1.2 (0.1)hours and 1 (0.2–3.5) hours, respectively. However, aprevious study suggests an association of increasing delaysin thrombolytic therapy with increasing duration of pre-hospital delay. The National Heart Attack Alert Programhas appropriately called attention to reduction of door-to-drug times. However, a few studies have examined therelationship between the extent of prehospital and hospitaldelay with thrombolytic therapy.

Limitations of the study: There are several limitationsof the present study. The effect of prehospital delay ondisease outcomes was not studied. Patients who died of AMIoutside the hospital and those with silent MI were notstudied. Appropriate caveats need to be planned for theinterpretation of study findings, since different delaypatterns may have existed in patients with poorly definedtime of onset of symptoms. The number of patientsincluded in the study was also small. However, our data

contrast, earlier studies suggested that older individualstook longer to access medical care than youngerindividuals.8 This might be due to the still prevalent jointfamily norms in Indian society. The median delay in patientswith a past medical history of ischemic heart disease wasnot significantly different from that in patients without sucha history. Thus, the patient’s behavior was not modified bythe past experience of an acute attack. It is also interestingto note that the majority of patients studied had no historyof angina (100 v. 4), diabetes (93 v. 11), or hypertension(87 v. 17). It could be speculated that patients with theabove diseases were more health conscious, and tookmedicines regularly. Also, prehospital delay was notdifferent in patients with or without the above diseases. Ourresults are contradictory to those of previous studies wherepatients with a history of MI and diabetes delayed longerthan those without the disease.7

Pain was the most common presenting symptom in ourstudy (102 v. 2). However, it was found that presentingsymptoms such as pain, dyspnea, sweating, and nausea arenot related to pain-to-door time. It has been seen that thebehavior of patients with collapse, pain or pathologicalbreathlessness after MI is at an instinctive level, though tosome extent, it may be culturally related.9

In contrast to previous studies, the day of the week andtime of presentation did not affect the prehospital time.Prehospital delay was significantly higher in patients (9.9v. 5.2 hours, p=0.002) who had visited a local practitionerthan those who came straightaway to the emergency unitof the hospital. While the reasons for such a practice maybe speculative, we suggest that this delay in time can bereduced if there is a 24-hour ambulance service with ahotline and facilities for fascimile transmission of ECG. Such

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are representative of a typical tertiary care hospital and,therefore, such data can be generalized to other hospitalsas well.

In conclusion, prehospital delay is the main reason fornot receiving thrombolytic therapy. The main factorscontributing to prehospital delay are: poor knowledge ofsymptoms, prior treatment from local practitioners, andunavailability of rapid transport facilities. Targeteducational efforts, and provision of rapid transportationfacilities can help reduce the excessive case fatality ratesattributed to prehospital delay.

References

1. Enas EA, Garg A, Davidson MA, Nair VM, Huet BA, Yusuf S. Coronaryheart disease and its risk factors in first-generation immigrant AsianIndians to the United States of America. Indian Heart J 1996; 48:343–353

2. Effectiveness of intravenous thrombolytic treatment in acutemyocardial infarction. Gruppo Italiano per lo Studio dellaStreptochinasi nell’ Infarto Miocardico (GISSI). Lancet 1986; 1:397–402

3. Second International Study of Infarct Survival (ISIS-2) SteeringCommittee. Intravenous streptokinase given within 0–4 hours of

onset of myocardial infarction reduced mortality in ISIS-2. Lancet1987; 1: 502–508

4. Goldberg RJ, McGovern PG, Guggina T, Savageau J, Rosamond WD,Luepker RV. Prehospital delay in patients with acute coronary heartdisease: concordance between patient interviews and medicalrecords. Am Heart J 1998; 135: 93–99

5. Goff DC Jr, Feldman HA, McGovern PG, Goldberg RJ, Simons- MortonDG, Cornell CE, et al. Prehospital delay in patients hospitalized withheart attack symptoms in the United States: the REACT trial. RapidEarly Action for Coronary Treatment (REACT) Study Group. AmHeart J 1999; 138: 1046–1057

6. Hackett TP, Cassem NH. Factors contributing to delay in respondingto the signs and symptoms of acute myocardial infarction. Am JCardiol 1969; 24: 651–658

7. Yarzebski J, Goldberg RJ, Gore JM, Alpert JS. Temporal trends andfactors associated with extent of delay to hospital arrival in patientswith acute myocardial infarction: the Worcester Heart Attack Study.Am Heart J 1994; 128: 255–263

8. Goldberg RJ, Yarzebski J, Lessard D, Gore JM. Decade-long trends andfactors associated with time to hospital presentation in patients withacute myocardial infarction: the Worcester Heart Attack Study. ArchIntern Med 2000; 160: 3217–3223

9. Rawles JM, Haites NE. Patient and general practitioner delays in acutemyocardial infarction. Br Med J 1988; 196: 882–884

10. Goff DC, Nichoman NZ, Ramsay DJ, et al. A population basedassessment of the use and effectiveness of thrombolytic therapy: theCorpus Christi Heart Project. Ann Epidemiol 1995; 5: 171–178

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354 Roy et al. Mitral Valve Repair for Nonrheumatic Mitral Regurgitation Indian Heart J 2003; 55: 354–357

Mitral Valve Repair for NonrheumaticMitral Regurgitation

Swapnadeep Roy, Shiv Kumar Choudhary, Arkalgud Sampath KumarDepartment of Cardiothoracic and Vascular Surgery, All India Institute of Medical Sciences, New Delhi

Surgical treatment of severe mitral regurgitation (MR)currently involves either mitral valve (MV) repair or

replacement (mechanical prosthesis/bioprosthesis).Although valve replacement has been the widely acceptedmodality, there are numerous complications associatedwith this procedure such as thrombosis, thromboembolism,anticoagulant-related hemorrhage, and bioprostheticdegeneration over a period of 7–15 years, necessitating asecond surgical procedure. Therefore, repair as thepreferred option, whenever possible, is gaining popularityamong cardiac surgeons.

The etiology of the MR may be rheumatic ornonrheumatic. In the latter category, there are numerouscauses such as congenital (often associated with atrialseptal defect), myxomatous degeneration, ischemic, andinfective. While the results of repair for rheumatic valvedisease often have a late phase of deterioration due to

progression of the rheumatic valvulitis, the reported resultsof repair in nonrheumatic cases have generally been moresatisfactory. We report our experience with repair in thissubset of patients.

Methods

From January 1988 to April 2002, 116 patients with severeMR of nonrheumatic etiology underwent MV repair. Theage range of the patients was 2–67 years (mean age 26.4years). Of these patients, 59 were males (50.8%), and 57females (49.2%). The causes of nonrheumatic MR werecongenital in 56 patients (47.4%), myxomatousdegeneration with cusp prolapse in 44 (37.9%), infectiveendocarditis in 7 (6%), and ischemic in 9 (7.7%). Six of thepatients had a primum ASD (partial atrioventricular septaldefect), and 46 had a secundum ASD. An isolated cleft MVwas responsible for the MR in 4 patients.1 In patients withmyxomatous degeneration, there was cusp prolapse withchordal elongation/rupture, predominantly in the posterior

Original Article

Background: We studied the results of mitral valve repair in patients with severe mitral regurgitation ofnonrheumatic etiology.Methods and Results: Between January 1988 and April 2002, 116 patients, of which 59 were male and 57female, with severe mitral regurgitation of nonrheumatic etiology, underwent mitral valve repair using a varietyof techniques. Their mean age was 26.4 years (range 2–67 years). The cause of mitral regurgitation wascongenital in 56 patients, myxomatous in 44, infective endocarditis in 7, and ischemic in 9. Ninety patientswere in preoperative New York Heart Association class III, and 26 in class IV. Reparative procedures includedposterior teflon felt collar annuloplasty (modified Cooley’s) in 80 patients, chordal shortening in 37, cusp excisionin 34, cleft closure in 8, chordal transfer in 6, and neochordae in 3. The early mortality was 3.4% (4 patients).Follow-up ranged from 1 to167 months (mean 47 months), and was 95% complete. There were 2 late deaths(1.7%). Six patients (5.2%) underwent reoperation for severe mitral regurgitation post-repair. Of the remaining104 patients, 90 (86.5%) had no or trivial mitral regurgitation at the last follow-up. Actuarial, reoperation-free, and event-free survival at 130 months was 93%±3.6%, 89.9%±6%, and 69.7%±13.7%, respectively.Ninety-two patients (88.5%) were in New York Heart Association class I at the last follow-up.Conclusions: Mitral valve repair in nonrheumatic mitral regurgitation patients provides satisfactory resultswith current surgical techniques, and is the preferred option in this subset of patients. (Indian Heart J 2003;55: 354–357)

Key Words : Mitral regurgitation, Mitral valve repair, Valvular heart disease

Correspondence: Professor A Sampath Kumar, Department ofCardiothoracic and Vascular Surgery, Cardiothoracic Centre, AIIMS,New Delhi 110029. e-mail: [email protected]

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Indian Heart J 2003; 55: 354–357 Roy et al. Mitral Valve Repair for Nonrheumatic Mitral Regurgitation 355

mitral leaflet. In the ischemic category, we included patientswith chronic ischemia only, in whom the MR was due topapillary muscle dysfunction or chordal elongation/rupture. Associated annular dilatation was present in allthese patients due to left ventricular dilatation. In patientswith infective endocarditis, there were primarily localizedareas of leaflet destruction, and repair was undertaken onlyafter an adequate course of antibiotics (at least 2 weeks).

Seventy-four patients (63.8%) were in sinus rhythmpreoperatively, and 42 in atrial fibrillation (36.2%). Thepredominant presenting symptom was dyspnea onexertion. Ninety patients were in New York HeartAssociation (NYHA) class III, and 26 were in class IV.

Preoperative transthoracic echocardiography wasperformed in all the patients. Cardiac catheterization andcoronary arteriography were performed in patients above40 years of age, or if there was a suspicion of associatedaortic valve disease, or coronary artery disease. The severityof MR was assessed by echocardiography and/orangiography.

Surgical technique: After induction of generalanesthesia, transesophageal echocardiography (TEE) wasperformed in all the patients after 1994. Intraoperatively,the surgical approach was either a mid-sternotomy(n=100) or a right anterolateral thoracotomy (n=16). Thelatter approach was primarily used for cosmetic reasons inyoung females. Before 1996, moderately hypothermic(32 oC) cardiopulmonary bypass (CPB), and since 1996,normothermic perfusion was used in all the patients. Cold-blood cardioplegia and topical ice-slush was used for theprotection of the myocardium. Bicaval cannulation wasused in all the patients. The MV was exposed through astandard incision in the left atrial wall behind the interatrialgroove. In patients with an ASD, the approach was throughthe right atrium. After assessing the morphology, a varietyof reparative techniques were utilized, as described earlier.2–5

The adequacy of repair was confirmed by injecting salineinto the left ventricular cavity and observing the coaptationof the leaflets. At the end of the procedure afterdiscontinuing CPB, TEE was performed in all the patientstreated after 1994 to confirm the adequacy of repair.

The various procedures utilized for the MV repair are asfollows: (i) posterior teflon felt collar annuloplasty (modifiedCooley’s)2 in 80 patients (68.9%); (ii) chordal shortening3

in 37 (31.9%); (iii) cusp excision (quadrangular resectionof posterior mitral leaflet) in 34 (29.3%); (iv) cleft closurein 8 (6.9%); (v) chordal transfer in 6 (5.2%); and (vi)neochordae in 3 (2.6%).

Associated procedures performed in these patients

included the following: (i) aortic valve replacement(prosthetic) in 8 (primarily for aortic regurgitation);(ii) aortic valvuloplasty in 15; (iii) closure of atrial septaldefect in 52; (iv) coronary artery bypass grafting in 5 (3 ofthe other 4 patients with ischemic MR had prior successfulangioplasty of the diseased target vessels; the remainingpatient had scarred myocardium with no reuptake onthallium scan).

Follow-up ranged from 1 to 168 months (mean 47months). The follow-up was 95% complete. At each follow-up visit, a transthoracic echocardiogram (TTE) wasperformed in all these patients to assess the status of theMV repair, besides looking for any associated lesions.Statistical analysis was performed using SPSS software ona Windows operating system. Kaplan–Meier survivalestimates were derived for this group of patients.

Results

All the patients survived the operation. The mean bypasstime was 51 min (range 28–70 min), and the mean aorticcross-clamp time was 37 min (range 21–58 min). Themean intensive care unit stay was 2 days (range 1–6 days),and the mean postoperative ventilation was for a period of8 hours (range 6–72 hours). The mean postoperative staywas 5 days (range 4–9 days).

Early mortality (30-day) was seen in 4 patients (3.4%).In 1 patient, the cause of death was persistent low outputfollowing the repair (preoperatively the patient was incongestive heart failure unresponsive to medicalmanagement). The second patient developed acute renalfailure in the immediate postoperative period andsuccumbed. Two other patients died of persistentintractable ventricular arrhythmias.

In the surviving patients, a pre-discharge TTE wasperformed to evaluate the status of the MV repair. In allthe 112 patients, there was no or mild MR that correlatedwell with the TEE, performed at the end of operation in theoperating room.

There were 2 late deaths (1.7%). Both patients haddeveloped severe left ventricular dysfunction secondary tosevere MR and succumbed before reoperation. Six patients(5.2%) underwent reoperation for severe MR. Of thesepatients, 5 had congestive heart failure, and the sixthpatient was in NYHA class III prior to reoperation. In 5 ofthe 6 patients, the cause of failure of the original repairwas due to suture dehiscence of the annuloplasty, or thoseused for chordal shortening. In one of them, there wasprogression of the original myxomatous degeneration withchordal rupture of originally uninvolved chordae. All the

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356 Roy et al. Mitral Valve Repair for Nonrheumatic Mitral Regurgitation Indian Heart J 2003; 55: 354–357

6 patients had a prosthetic MV replacement, and survived.Of the 104 late survivors, 92 (86.5%) are in NYHA class

I, and 12 in NYHA class II at the last follow-up. Eightypatients (76.9%) are in sinus rhythm, while the rest are inchronic atrial fibrillation (AF) (all of them were also in AFpreoperatively). One of the 104 late survivors (0.9%) hada thromboembolic complication (the patient was in AFpostoperatively). There were no other complications. Ofthose who were reoperated, all have improved to NYHAclass II status.

At the last follow-up, 90 of the 104 surviving patientshave no or trivial MR on echocardiography, 6 have mildMR, and 8 have moderate-to-severe MR.

The actuarial, reoperation-free, and event-free survivalin the group of operative survivors at 130 months was93%±3.6%, 89.9%±6%, and 69.7%±13.6%, respectively(Kaplan–Meir estimates). Freedom from thromboembolicevents at 108 months was 98.6% (Figs 1–3).

Discussion

In India, rheumatic heart disease remains the predominantcause of MR. However, MR due to nonrheumatic causes isnot uncommon.

Repair of the MV has gradually become widely accepted,ever since it was popularized by Carpentier.7 For non-rheumatic severe MR, repair of the MV has shown excellentlong-term durability. The Carpentier group6–8 has reporteda 15-year actuarial survival of 72.4%, with freedom fromreoperation at 15 years being 92.7%. This grouppredominantly used a prosthetic ring in most of theirannuloplasty procedures. Galloway et al.9 reported on theirresults with Carpentier-type MV reconstructions with anoperative mortality of 5%, and a 5-year freedom fromreoperation rate of 94.4%. Actuarial freedom fromthromboembolic complications was 93.9% at 15 years, and96.5% were free from anticoagulant-related hemorrhage.Similar results have been reported by other groups also.Overall, the results are better than those reported withprosthetic MV replacement.10

Our results compare favorably with other reports in theliterature. Our 10-year survival of about 93% with areoperation-free rate of 89% is comparable to most reportedseries. Functional rehabilitation and the absence ofmedication are marked advantages. Preservation of leftventricular function is another advantage.

Conclusion: Repair of the MV rather than its replacementshould be the procedure of choice in patients with non-rheumatic MR.

Probability 100 100 99 99 99 99 97.3 95.3 92.9 92.9at risk 111 103 86 74 69 60 52 41 17 6

Fig. 1. Probability of actuarial survival in patients of mitral valve repair fornonrheumatic mitral regurgitation (Kaplan–Meier estimates).

Probability 100 99 99 97.8 97.8 97.8 97.8 95.6 95.6 89.9at risk 111 103 86 76 70 64 53 42 18 4

Fig. 2. Probability of reoperation-free survival in patients after mitral valverepair for nonrheumatic mitral regurgitation (Kaplan–Meier estimates).

Probability 100 99 98 96.8 96.8 96.8 96.8 90.5 83.7 83.7at risk 111 103 86 77 74 63 52 41 19 6

Fig. 3. Probability of event-free survival in patients after mitral valve repair fornonrheumatic mitral regurgitation (Kaplan–Meier estimates).

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Indian Heart J 2003; 55: 354–357 Roy et al. Mitral Valve Repair for Nonrheumatic Mitral Regurgitation 357

Acknowledgments

The authors acknowledge the help provided by the residentsof the department for the excellent record-keeping thatgreatly facilitated the analysis of results. We would also liketo thank Mr Rajbir of the Department of Biostatistics, forthe statistical analysis.

References

1. Mohanty SR, Choudhary SK, Ramamurthy S, Kumar AS. Isolatedcongenital anterior mitral leaflet cleft: a rare cause of mitralinsufficiency. J Heart Valve Dis 1999; 8: 67–70

2. Kumar AS, Kumar RV, Shrivastava S, Venugopal P, Sood AK, GopinathN. Mitral valve reconstruction. Early results of a modified Cooleytechnique. Tex Heart Inst J 1992; 19: 107–111

3. Kumar AS, Bhan A, Kumar RV, Shrivastava S, Sood AK, Gopinath N.Cusp-level chordal shortening for rheumatic mitral regurgitation.Early results. Tex Heart Inst J 1992; 19: 47–50

4. Kumar AS, Rao PN. Restoration of pliability to the mitral leafletsduring reconstruction. J Heart Valve Dis 1995; 4: 251–253

5. Choudhary SK, Talwar S, Dubey B, Chopra A, Saxena A, Kumar AS.Mitral valve repair in a predominantly rheumatic population. Long-term results. Tex Heart Inst J 2001; 28: 8–15

6. Deloche A, Jebara AV, Relland JY, Chauvaud S, Fabiani JN, Perier P,et al. Valve repair with Carpentier techniques. The second decade. JThorac Cardiovasc Surg 1990; 99: 990–1001

7. Carpentier A. Cardiac valve surgery—the “French correction”. JThorac Cardiovasc Surg 1983; 86: 323–337

8. Carpentier A, Chauvaud S, Fabiani JN, Deloche A, Relland J, LessanaA, et al. Reconstructive surgery of mitral valve incompetence: ten-year appraisal. J Thorac Cardiovasc Surg 1980; 79: 338–348

9. Galloway AC, Colvin SB, Baumann FG, Grossi EA, Ribakove GH,Harty S, et al. A comparison of mitral valve reconstruction withmitral valve replacement: intermediate-term results. Ann Thorac Surg1989; 47: 655–662

10. Sand ME, Naftel DC, Blackstone EH, Kirklin JW, Karp RB. Acomparison of repair and replacement for mitral valve incompetence.J Thorac Cardiovasc Surg 1987; 94: 208–219

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358 Srimannarayana et al. Left Atrial Thrombus in Mitral Stenosis Indian Heart J 2003; 55: 358–361

Prevalence of Left Atrial Thrombus in Rheumatic MitralStenosis With Atrial Fibrillation and its Response to

Anticoagulation: A TransesophagealEchocardiographic Study

J Srimannarayana, RS Varma, S Satheesh, R Anilkumar, J BalachanderDepartment of Cardiology, Jawaharlal Institute of Postgraduate Medical Education and Research, Pondicherry

Rheumatic mitral stenosis with atrial fibrillation (AF) isa common clinical problem in India. It is associated

with a very high risk of embolic cerebrovascular accidents,which is reported to be as much as seventeen times greaterthan in unaffected controls.1

Transesophageal echocardiography (TEE) is wellestablished as the gold standard for detecting thrombi inthe left atrium (LA) and the LA appendage. The sensitivityand specificity of TEE are reported to be 100% and 99%,respectively.2 The semi-invasive nature and safety of the testmake it ideal for serial follow-up of thrombi in the LA bodyand appendage. Though it is known that thrombi arecommon in patients with mitral stenosis and AF, only smallstudies have documented the exact frequency of occurrence

of these thrombi, and their fate on optimal oralanticoagulation.

The objectives of this study were to document thefrequency of occurrence of LA body and appendage clotsin patients with severe mitral stenosis and AF, and to studythe effect of oral anticoagulation on clot dissolution.

Methods

Consecutive patients with severe mitral stenosis and AF,who were being evaluated for percutaneous transvenousmitral commissurotomy (PTMC), underwent TEEevaluation. Patients were excluded from the study if therewas considerable mitral regurgitation or aortic valve disease.A total of 490 patients (343 females [70%], and 147 males[30%]) were included in the study. The mean age of thesepatients was 27.4±8.41 years (range 21–65 years).

Original Article

Correspondence: Professor R Anilkumar, Department of Cardiology,JIPMER, Pondicherry 605006. e-mail: [email protected]

Background: The frequency of occurrence of left atrial thrombi, and the effect of anticoagulation in patientswith rheumatic mitral stenosis and atrial fibrillation is not well established. This study was conducted to evaluatethe occurrence of left atrial body and left atrial appendage clots in patients with rheumatic mitral stenosis andatrial fibrillation, and to document the effect of long-term anticoagulation on clot dissolution.Methods and Results: Consecutive patients with severe rheumatic mitral stenosis and atrial fibrillation wereassessed by transesophageal echocardiography. Those with left atrial body or left atrial appendage clots wereanticoagulated with oral nicoumalone. Transesophageal echocardiography was then repeated in patients onanticoagulation who were on regular follow-up, and in whom percutaneous transvenous mitral commissurotomycould be considered. Of the 490 patients studied, 163 had left atrial body or left atrial appendage clots. A repeattransesophageal echocardiographic examination was done in 50 patients who had optimal anticoagulation fora period of 6 months. Only 2 of the 17 patients who had left atrial body clots had successful clot dissolution afterlong-term anticoagulation, while the left atrial appendage clots disappeared in 31 of 33 patients (p<0.001).Conclusions: Left atrial clots are present in a third of patients with severe rheumatic mitral stenosis and atrialfibrillation. Isolated left atrial appendage clots in patients with rheumatic mitral stenosis and atrial fibrillationcan disappear with long-term anticoagulation, while thrombi that extend into the left atrial body may persistdespite optimal anticoagulation. (Indian Heart J 2003; 55: 358–361)

Key Words: Rheumatic mitral stenosis, Left atrial thrombi, Echocardiography

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Indian Heart J 2003; 55: 358–361 Srimannarayana et al. Left Atrial Thrombus in Mitral Stenosis 359

No clots were detected on repeat TEE in 31 out of 33patients (93.9%) with isolated LA appendage clots (Figs 1and 2). These 31 patients underwent PTMC successfully.Only 2 out of 17 patients (11.8%) with a previous LA bodyclot had no detectable clots. Patients with persistent LA clotswere referred for an open mitral valvotomy andthrombectomy. A comparison between those in whom theclot disappeared, and those in whom the clot persistedrevealed that the location of the LA clot (isolated LAappendage v. LA body) alone was a significant predictor ofthrombus dissolution. There were no statistically significantdifferences in other parameters, such as valve orifice, LAsize, mitral regurgitation, age, gender, and INR valuesbetween these groups.

An ACUSON 128-XP echocardiographic systemequipped with omniplane and biplane transesophagealprobes was used for this study. TEE was performed accordingto the standard procedure after obtaining informed consent.All the patients were put on oral anticoagulation withnicoumalone. The international normalized ratio (INR) wasmaintained between 2.5 and 3.5. Repeat TEE wasperformed after 6 months in patients (i) with LA body orLA appendage clots; (ii) on regular anticoagulation, andfollow-up with INR; and (iii) with valve morphologysuitable for PTMC.

Patients who were very sick (in NYHA class IV), andthose whose valve morphology precluded PTMC wereimmediately referred for appropriate surgery.

Of the patients undergoing repeat TEE, patients with anisolated LA appendage clot (group A) were compared withpatients in whom the thrombus extended into the LA bodyor who had isolated LA body clots (group B). The groupwith successful clot dissolution, and the group withpersistence of the thrombus were also compared.

Continuous variables were expressed as mean valueswith standard deviation, while proportions were presentedas numbers and percentages of the total. The significanceof differences between means was tested by the Student’st test, while that between proportions was tested with theChi-square test. A p value <0.05 was considered significant.

Results

Incidence and location of thrombi: Of the 490 patientswho underwent TEE, LA clots were present in 163 (33.2%).Isolated LA appendage clots were found in 88 patients(18%). Isolated LA body clots or LA appendage clotsextending into the LA body were found in 75 patients(15.3%). LA spontaneous echocardiographic contrast(LASEC) was present in 365 patients (74.5%). None of thepatients had right atrial thrombi.

Resolution of thrombi: TEE was repeated after 6 monthsof optimal oral anticoagulation in 50 out of 163 patients.These patients had maintained their INR in the range of2.5–3.5, and were on regular follow-up. Nearly half thepatients (48%) were above the age of 35 years (range 21–55 years). None of these patients had any other risk factors,such as diabetes mellitus, hypertension or smoking. Acomparison of the baseline characteristics, echocardio-graphic parameters, and mean INR between the group ofpatients with isolated LA appendage clots (n=33) and thegroup with clots extending to the LA body (n=17) is givenin Table 1. There were no statistically significant differencesamong these parameters between the two groups.

Table 1. Comparison of patients who underwent repeatTEE with isolated LA appendage clot versus those withclots extending to the LA cavity

Characteristic Group A Group B p value(n=33) (n=17)

Mean age (years) 33.91±7.82 33.8±9.01 nsMales 10 (30.3%) 9 (52.9%) nsFemales 23 (69.7%) 8 (47.1%)Mean MVO (cm2) 0.9±0.15 0.96±0.14 nsMean MPG (mmHg) 20.15±4.7 22.06±4.51 nsMean LA size (AP diameter, cm) 3.73±0.6 3.71±0.5 nsMitral regurgitation (grade 1/4) 7 (21.2%) 4 (23.5%) nsMean INR 2.87±0.3 2.89±0.23 ns

Group A: patients with isolated LA appendage clot; Group B: patients with clotsextending to the body of the LA or isolated LA body clots; MVO: mitral valve orifice;MPG: mean pressure gradient; AP: anteroposterior; INR: international normalizedratio; ns: not significant; LA: left atrial; TEE: transesophageal echocardiography

Discussion

Conventional transthoracic echocardiography (TTE) has apoor yield in the detection of LA appendage thrombi.3 Theposterior location of the LA in the chest as well as the poor

Fig. 1. Isolated left atrial appendage clot before anticoagulation.

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visualization of the LA appendage contribute to the lack ofaccuracy of TTE. On the other hand, TEE is an excellentmethod for detecting atrial thrombi, especially those locatedin the LA appendage.

There are few reports on the prevalence of LA body andLA appendage clots in patients with severe mitral stenosisand AF. In a small group of 50 patients with mitral stenosisand AF, Hwang et al.4 observed an LA thrombus in 28patients (56%) by TEE. In another small study of 22 patientswith mitral stenosis and AF, Karatasakis et al.5 observedan LA thrombus in 12 patients (54%). In our study of 490patients, the prevalence was 33.5%. Considering the sizeof the study group, this can be considered a representativefigure for the prevalence of LA thrombi in patients withsevere mitral stenosis and AF. Thus, it can be stated that 1out of every 3 patients with severe mitral stenosis and AFwill have an LA thrombus.

Anticoagulation is conventionally used to reduce the riskof the thromboembolic events associated with AF. Oralanticoagulants act by inhibiting the synthesis of vitaminK-dependent coagulation factors. This prevents newthrombus formation, and promotes adherence andorganization of old thrombi to the surroundingendocardium.6–8 However, recent studies have supportedan alternative hypothesis of benefit that includes not onlythe prevention of new thrombus formation but also theresolution of existing thrombi.9

In situations in which a thrombus is already present,anticoagulation prevents further thrombus extension,thereby facilitating the action of endogenous fibrinolysis.A study conducted by Kandpal et al.10 showed that 41.7%of isolated LA appendage clots resolved in contrast to 12.5%of LA body clots in patients with mitral stenosis after 6months of oral anticoagulation. Resolution of atrial

thrombi after oral anticoagulation in patients withnonvalvar AF has also been examined in several studies.11,12

In the present study, it was seen that thrombi in the LAappendage disappeared on anticoagulation, whereasthrombi in the LA body did not. Success in resolving LAappendage thrombi vis-à-vis LA body thrombi is crucial,given that most clinically encountered thrombi are locatedin the LA appendage. This difference is possibly explainedby the fact that patients with an LA body clot have a higherclot burden, which does not permit dissolution withendogenous fibrinolysis despite optimal anticoagulation. Itis probable that clots localized to the LA appendage, with amuch smaller clot burden, are dissolved by endogenousfibrinolysis, while effective oral anticoagulation preventsfresh thrombus formation.

A study conducted by Murillo et al.13 showed that PTMCcan be performed in patients with an LA appendage clotwith TEE guidance and fluoroscopic control. However, thiscan be fraught with the risk of embolism. Hence, theinterventional cardiologist will always prefer the LA andLA appendage to be free of clots before embarking onballoon mitral valvotomy. Based on our study, it is possibleto evolve a strategy of treatment in patients with severemitral stenosis, AF, and LA thrombus. Patients with an LAthrombus extending well into the LA body can be directlyreferred for surgery, since they are unlikely candidates forclosed procedures. However, patients with isolated LAappendage clot and mitral stenosis can afford to be onanticoagulation for a period of 6 months, and then undergoa repeat TEE, especially if they can be stabilized to NYHAclass II or less. If the clot resolves, as in a good percentageof our subjects, these patients can undergo PTMC.

Some limitations of our study have to be emphasized. Arepeat TEE was done in only about one-third of the patientswith LA clots. The rest of the patients did not undergo arepeat TEE as part of the study because of one or more ofthe following reasons: valve morphology precluded PTMC,NYHA class III or class IV patients who were judged to needearly surgical treatment, suboptimal anticoagulation, andirregular follow-up. Thus, the results of the study shouldbe interpreted with some caution, and a further, large-scalestudy may be necessary to confirm the findings of our study.The effect of anticoagulation on LASEC was not studiedsince the mere presence of LASEC was not considered to bea contraindication for PTMC. Also, it was not practicallypossible to determine the duration of AF in these patients,and correlate it with clot prevalence and resolution.

Conclusions: One-third of patients with severe mitralstenosis and AF have LA body or LA appendage clots.Isolated LA appendage clots in patients with rheumatic

Fig. 2. The same patient as in Fig. 1, showing no left atrial appendagethrombus after anticoagulation for 6 months.

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Indian Heart J 2003; 55: 358–361 Srimannarayana et al. Left Atrial Thrombus in Mitral Stenosis 361

mitral stenosis and AF can disappear with long-termanticoagulation. Such patients may become favorablecandidates for PTMC. Clot dissolution with oralanticoagulation is unlikely in those with an LA body clot.These patients can be referred early for open mitralvalvotomy and thrombectomy.

References

1. Kannel WB, Abbott RD, Savage DD, McNamara PM. Epidemiologicfeatures of chronic atrial fibrillation: the Framingham study. N EnglJ Med 1982; 306: 1018–1022

2. Manning WJ, Weintraub RM, Waksmonski CA, Haering JM, RooneyPS, Maslow AD, et al. Accuracy of transesophageal echo-cardiography for identifying left atrial thrombi. Ann Intern Med 1995;123: 817–822

3. Aschenberg W, Schluter M, Kremer P, Schroder E, Siglow V, BleifeldW. Transesophageal two-dimensional echocardiography for thedetection of left atrial appendage thrombus. J Am Coll Cardiol 1986;7: 163–166

4. Hwang JJ, Chen JJ, Lin SC, Tseng YZ, Kuan P, Lien WP, et al. Diagnosticaccuracy of transesophageal echocardiography for detecting leftatrial thrombi in patients with rheumatic heart disease havingundergone mitral valve operations. Am J Cardiol 1993; 72: 677–681

5. Karatasakis GT, Gotsis AC, Cokkinos DV. Influence of mitralregurgitation on left atrial thrombus and spontaneous

echocardiographic contrast in patients with rheumatic mitral valvedisease. Am J Cardiol 1995; 76: 279–281

6. Goldman M. The management of chronic atrial fibrillation. ProgCardiovasc Dis 1960; 2: 465–479

7. Mancini GB, Goldberg AL. Cardioversion of atrial fibrillation:consideration of embolization, anticoagulation, prophylacticpacemaker, and long-term success. Am Heart J 1982; 104: 617–621

8. Tsai LM, Hung JS, Chen JH, Lin LJ, Fu M. Resolution of left atrialappendage thrombus in mitral stenosis after warfarin therapy. AmHeart J 1991; 121: 1232–1234

9. Collins LJ, Silverman DI, Douglas PS, Manning WJ. Cardioversion ofnonrheumatic atrial fibrillation. Reduced thromboemboliccomplications with 4 weeks of precardioversion anticoagulation arerelated to atrial thrombus resolution. Circulation 1995; 92: 160–163

10. Kandpal B, Garg N, Anand KV, Kapoor A, Sinha N. Role of oralanticoagulation and inoue balloon mitral valvulotomy in presenceof left atrial thrombus: a prospective serial transesophgealechocardiographic study. J Heart Valve Dis 2002; 11: 594–600

11. Corrado G, Tadeo G, Beretta S, Tagliagambe LM, Manzillo GF, SpataM, et al. Atrial thrombi resolution after prolonged anticoagulationin patients with atrial fibrillation. Chest 1999; 115: 140–143

12. Jaber WA, Prior DL, Thamilarasan M, Grimm RA, Thomas JD, KleinAL, et al. Efficacy of anticoagulation in resolving left atrial and leftatrial appendage thrombi: a transesophgeal echocardiographic study.Am Heart J 2000; 140: 150–156

13. Murillo H, Ayala F, Lepe L, Madrid R, Solorio S, Lara A, et al.[Percutaneous mitral commissurotomy in patients with mitral valvestenosis and thrombosis of the left atrium.] Arch Inst Cardiol Mex1999; 69: 134–138

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362 Mishra et al. Percutaneous Balloon Angioplasty of Membranous Obstruction Indian Heart J 2003; 55: 362–364

Percutaneous Balloon Angioplasty of MembranousObstruction of the Inferior Vena Cava

TK Mishra, SN Routray, M Behera, UK Patnaik, C SatapathyDepartment of Cardiology, SCB Medical College, Cuttack, Orissa

Membranous obstruction of the inferior vena cava(MOVC) is relatively common in Asia and Africa.1

Many cases have been reported from India.2 MOVC is oneof the important causes of Budd–Chiari syndrome.Intervention is often necessary, as medical treatment isineffective. The disease should be managed early, becauselong-standing MOVC can result in hepatocellularcarcinoma.1 Till the introduction of balloon dilatation fortreating MOVC cases, surgery was the only option available.Here, we report our experience with balloon angioplastyfor managing these cases.

Methods

Between January 1999 and January 2002, 19 patients whowere clinically diagnosed to have inferior vena cava (IVC)obstruction were taken up for the study. The disease wassuspected when the patients presented with ankle edema,ascites, and prominent veins over the abdomen and back,with the direction of blood flow from below upwards. Aftertaking a careful history, detailed physical examination was

carried out in all the patients. Hematological tests,coagulation profile, liver function tests, and abdominalultrasound with Doppler study of the IVC was undertaken.

After clinical diagnosis, the patients were taken up forinferior vena cavography, and subsequent angioplasty.Catheterization and angiography of the IVC was donethrough the femoral vein with a pigtail catheter.Simultaneous right atrial catheterization was done throughthe antecubital vein for simultaneous measurement of thepressure gradient between the IVC and right atrium (RA).

If the vena cavography demonstrated a completeobstruction, the IVC was first punctured by the stiff end ofa guidewire inserted through a multipurpose catheter.Predilatation of the lesion was initially done with aperipheral angioplasty balloon (3×20 mm) if the Josephballoon could not be negotiated across the site of the lesion.Angioplasty was attempted with the Joseph balloon, whichis commonly used for balloon mitral valvotomy. The size ofthe balloon used varied from 22 to 24 mm, depending uponthe size of the IVC. After the balloon was placed across thelesion, it was inflated and deflated 2–3 times. Repeatvenography was done to show blood flow towards the RA.The success of the procedure was confirmed bydemonstrating reduction or disappearance of the gradientbetween the IVC and RA.

Original Article

Correspondence: Dr SN Routray, Department of Cardiology, Qr. No. 3R-8,Near Cancer Wing, SCB Medical College, Cuttack 753007.e-mail: [email protected]

Background: Membranous obstruction of the inferior vena cava is common in African and Asian countries.Methods and Results: Between January 1999 and January 2002, 19 patients were prospectively studied. Themean age of the patients was 38±6.9 years. All of them had swelling of the abdomen and ankle edema. Fivepatients (26.3%) had jaundice, 9 (47.3%) had hepatomegaly, and 5 (26.3%) splenomegaly. Ultrasonographycould detect the site of obstruction in 18 patients (94.7%). Vena cavography demonstrated obstruction of theinferior vena cava at the level of the diaphragm, with 2 patients (10.5%) having additional intrahepaticobstruction. The mean pressure gradient was 22±3.5 mmHg. Seventeen patients underwent balloon angioplastyusing a Joseph balloon. The procedure was successful in 15 patients (88.2%). The post-angioplasty mean pressuregradient was 5±1.4 mmHg. On follow-up, 3 patients (20%) developed features of restenosis; out of them, 2underwent successful redilatation.Conclusions: Balloon angioplasty of membranous obstruction of the inferior vena cava is feasible with a highsuccess rate, without any rupture of the inferior vena cava. (Indian Heart J 2003; 55: 362–364)

Key Words: Inferior vena cava obstruction, Balloon angioplasty, Percutaneous intervention

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Results

Nineteen patients were initially diagnosed to have MOVC.The mean age at presentation was 38±6.9 years. The meanduration of illness was 3.5±0.6 years. The male:femaleratio was 16:3. The chief complaints were pain in theabdomen in 15 patients (79%), and anorexia in 18 (94.7%).All the patients complained of swelling of the abdomen andankle edema: 5 (26.3%) had jaundice. In all the patients,the veins of the anterior abdominal wall and back wereprominent, with the direction of blood flow from belowupwards. Nine patients (47.3%) had hepatomegaly, and 5(26.3%) splenomegaly.

The mean hemoglobin concentration was 8±1.3 g/dl.The TLC and platelet count were normal. One patient hada prolonged prothrombin time. Abnormal liver function,as assessed by serum albumin and alanine transferase, waspresent in 5 patients (26.3%).

Ultrasonography and Doppler study of the IVCdemonstrated the site of obstruction in 18 patients (94.7%).Before the ultrasound examination, 5 patients (26.3%)were diagnosed to have cirrhosis of the liver. Inferior venacavography demonstrated the site of obstruction of the IVCat the level of the diaphragm in all the patients. Two patients(10.5%) had an additional obstruction in the hepatic vein;they were referred for surgical intervention. Of theremaining 17 patients selected for angioplasty, 13 (76.4%)had complete obstruction, and 4 (23.6%) had partialobstruction, with a meatus <3 mm. The mean pressuregradient between the IVC and RA was 22±3.5 mmHg.

Fifteen patients (88.2%) underwent successful balloondilatation without any rupture of the IVC. The procedurewas abandoned in 2 patients (11.8%), because of inabilityto cross the lesion. The post-procedure mean gradient insuccessful cases was 5±1.4 mmHg.

All the 15 patients who underwent successful dilatationwere followed up for a mean period of 8 months (range 3–24 months). Three patients (20%) developed recurrenceof symptoms such as ascites. Two of them underwentsuccessful redilatation following the demonstration ofrestenosis in the cavogram. One patient refused a repeatprocedure.

Discussion

Chronic Budd–Chiari syndrome can be due to multiplecauses. The impediment to blood flow can occur anywherefrom the RA to the small radicles of the hepatic vein. MOVCaccounts for 40% cases of Budd–Chiari syndrome inAfrica.3 It is still not known whether the obstructingmembrane is congenital or acquired. Yamamoto et al.4 have

classified MOVC into 3 groups. In group A, there wasincomplete obstruction of the IVC, in group B theobstructing membrane was complete and thin; in group Cthe membrane was complete and thick. Of the 17 patientswho were taken up for angioplasty in our series, themembrane was complete in 13 (76.4%).

The mean age at presentation in our patients was38±6.9 years. The majority of MOVC patients were alsobetween 30–40 years of age in the series reported fromSouth Africa by Simson.1 In our series, jaundice was evidentin 5 cases (26.3%). It was present in 5.8% of patients inthe series reported by Kohli et al.5 The high incidence ofjaundice in our cases was probably due to late presentationof the patients. Ultrasound examination revealed the siteof obstruction in 94.7% of our patients. Kohli et al.5 couldidentify obstruction of the IVC by plain ultrasonography in91% of cases.

In our series, 2 patients (10.5%) had additionalobstruction of the hepatic vein. Combined obstruction hasbeen reported in 7 out of 75 cases studied by Kohli et al.5

Medical treatment is ineffective.6 Previously, surgicaloptions included membranotomy, done by a finger7 or metalbougie,8 or cavoatrial shunts done to bypass theobstruction.

Angioplasty has become the treatment of choice forMOVC. Successful dilatation has been reported in 93.3%–100% of cases from India.5,9 In our series, proceduralsuccess was 88.2%. In all our successful cases, the site ofcomplete obstruction could be punctured by the stiff endof the guidewire. The obstruction can also be pierced byBrockenbrough’s septal puncture needle, which was usedby Kar et al.9 and Patel et al.10 with excellent results.

In earlier studies, either a pulmonary balloon 8 or Inoueballoon11,12 has been used to dilate an obstruction of theIVC. We attempted dilatation using a Joseph balloon withgratifying results. It is safe with a high success rate. Theballoon could be reused several times, which is important,as the majority of our patients are poor.

Restenosis was detected in 20% of our patients duringfollow-up. 14.3% of cases developed restenosis in the seriesby Kohli et al.5 Tyagi et al.,13 however, reported a very highincidence (36.4%) of restenosis.

Conclusions: Membranous obstruction of the IVC can giverise to substantial morbidity because of massive ascites andankle edema. A high index of suspicion is necessary, as thedisease is often confused with cirrhosis of the liver.Ultrasonography with Doppler study of the IVC can bediagnostic, though vena cavography is required forconfirmation. In the majority of patients, obstruction canbe successfully tackled by balloon angioplasty without

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fear of rupture of the IVC. Long-term follow-up of post-angioplasty patients is necessary to further validate thesuccess of the procedure.

References

1. Simson IW. Membranous obstruction of the inferior vena cava andhepatocellular carcinoma in South Africa. Gastroenterology 1982;82: 171–178

2. Victor S, Jayanthi V, Kandaswamy I, Ratnasabapathy A,Madanagopalan N. Retrohepatic cavoatrial bypass for coarctationof inferior vena cava with a polytetrafluoroethylene graft. J ThoracCardiovasc Surg 1986; 91: 99–105

3. Schafer OF, Sorrell MF. Vascular diseases of liver. In: Sleisenger andFordtran’s gastrointestinal and liver diseases. 6th ed. 1998. p. 1189

4. Yamamoto S, Yokoyama Y, Takeshige K, Iwatsuki S. Budd–Chiarisyndrome with obstruction of the inferior vena cava. Gastroenterology1968; 54: 1070–1084

5. Kohli V, Pande GK, Dev V, Reddy KS, Kaul U, Nundy S. Managementof hepatic venous outflow obstruction. Lancet 1993; 342: 718–722

6. Ahn SS, Yellin A, Sheng FC, Colonna JO, Goldstein LI, Busuttil RW.Selective surgical therapy of Budd–Chiari syndrome providessuperior survivor rates than conservative medical management.J Vasc Surg 1987; 5: 28–37

7. Hirooka M, Kimura C. Membranous obstruction of the hepaticportion of the inferior vena cava. Surgical correction and etiologicalstudy. Arch Surg 1970; 100: 656–663

8. Rogers MA, Chesler E, Ou Plesis L, Jeffe N, Jouvert E. Membranousobstruction of the hepatic segment of inferior vena cava. Br J Surg1967; 54: 221–225

9. Kar AK, Mandal M. Percutaneous balloon angioplasty of inferiorvena cava stenosis. Cardiology Today 1999; 5: 221–228

10. Patel T, Shah S, Sanghvi K, Fonseca K. Successful stenting of acomplex inferior vena cava stenosis using a modified sharprecanulization technique. Catheter Cardiovasc Interv 2001; 52:492–495

11. Bahl VK, Bhargava B, Chandra S. Percutaneous balloon dilatationof IVC obstruction using Inoue Catheter. Indian Heart J 1997; 49:427–428

12. Yang XL, Cheng TO, Chen CR. Successful treatment by percutaneousballoon angioplasty of Budd–Chiari syndrome caused bymembranous obstruction of inferior vena cava: 8-year follow-upstudy. J Am Coll Cardiol 1996; 28: 1720–1724

13. Tyagi S, Jain BL, Kumar N, Lahoti D, Arora R. Balloon dilatation ofinferior vena cava stenosis in Budd–Chiari syndrome. J AssocPhysicians India 1996; 44: 378–380

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Indian Heart J 2003; 55: 365–367 Goel et al. Thrombin Injection for Femoral Artery Pseudoaneurysm 365

Sonographically Guided Thrombin Injection for theTreatment of Femoral Artery Pseudoaneurysm

Pravin K Goel, Nitin Modi, Sanjay Saran Baijal, Manoj Kathuria, Surendra K AgrawalDepartments of Cardiology, Radiology, and Cardiovascular and Thoracic Surgery,

Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow

Femoral artery pseudoaneurysm is an uncommon butwell-recognized complication after percutaneous

arterial catheterization. The incidence of pseudoaneurysmformation is reported to be up to 1% after diagnostic studies,and 3.2% after interventional procedures.1,2 Traditionally,these pseudoaneurysms require reparative surgery. In1986, Cope et al. described the technique of percutaneousthrombin injection for small pseudoaneurysm in the iliac,femoral, and popliteal arteries.3 There is, however, limitedexperience with this technique on large aneurysms. Wedescribe a case of a large pseudoaneurysm successfullymanaged with percutaneous intra-aneurysmal injection ofbovine thrombin.

Case Report

A 66-year-old hypertensive, nondiabetic, nonsmoker maleunderwent diagnostic cardiac catheterization through theright femoral artery using 6 F arterial sheath. Five thousandunits of heparin was given during the procedure, and postprocedure, the right lower limb was immobilized for 6hours. After 6 hours, the patient was allowed to carry outhis routine activities and was to be discharged the followingday. However, about 18 hours post procedure, the patientcomplained of severe pain in the right groin with obviousswelling of the thigh. There was no external bleeding fromthe puncture site. Doppler study of the femoral artery

showed a large pseudoaneurysm (10×4×4 cm) with anarrow neck of 0.5 cm. The aneurysm was largely locatedanterior to the femoral artery all along its length, for up toabout 10 cm below the puncture site. Ultrasound-guidedcompression of the neck was tried but was not successful.Considering the large size of the aneurysm,ultrasonographically guided thrombin injection into thepseudoaneurysm was planned.

Technique: After taking informed consent, a completeDoppler assessment of the aneurysm and the patency ofdistal run-off was obtained. The right groin was prepared,draped and an echo-probe placed directly over thepseudoaneurysm. The flow into the aneurysm was assessedby both the color and angio modes on the HP Sonos 5500machine. Obliteration of flow into the aneurysm wasconfirmed by compression of the neck of thepseudoaneurysm with the color mode on. Under localanesthesia, a 22-gauge spinal needle was then passedpercutaneously directly into the pseudoaneurysm cavityunder ultrasonographic guidance. The tip of the needle waspositioned within the center of the cavity, to keep it awayfrom the neck. A small 2 ml syringe containing bovinethrombin (Parke Davis) 1000 U/ml concentration wasattached to the needle and 1 ml injected into the cavity withcontinuing compression of the neck. The echogenicitywithin the aneurysm was seen to increase immediately, buton color Doppler study repeated after 3–4 min, some flowinto the cavity was still seen. Thrombin injection wasrepeated using the same technique and, this time, dense

Brief Report

Correspondence: Dr PK Goel, Department of Cardiology, SGPGIMS, RaeBareli Road, Lucknow 226014. e-mail: [email protected]

The formation of pseudoaneurysm in the femoral artery after cardiac catheterization is a well-recognizedcomplication occurring in 1%–4% of cases. It is traditionally managed surgically and has a high morbidity.Prolonged ultrasound-guided compression of the neck of the pseudoaneurysm, and ultrasound-guided injectionof thrombin into the aneurysm are newer modalities of treatment especially for small aneurysms. We describethe case of a giant pseudoaneurysm of the right femoral artery, post-arteriography, which was successfullymanaged with ultrasonographically guided percutaneous thrombin injection. (Indian Heart J 2003; 55:365–367)

Key Words: Pseudoaneurysm, Femoral artery, Thrombin

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occurs in 1%–3% of cases following percutaneous arterialcatheterization.1,2 The treatment options are surgical repair,covered stents, coil embolization or, ultrasound-guidedcompression and direct percutaneous thrombin injection.Operative repair is usually associated with high morbiditysecondary to delayed ambulation and/or wound infection.Fellmeth4 in 1991 described ultrasound-guidedcompression repair. With this treatment, flow into thepseudoaneurysm is halted by applying pressure with theultrasound probe to the neck of the pseudoaneurysm andmaintaining such pressure until spontaneous thrombosisof the aneurysm cavity occurs. This procedure, however, isoften very painful, and has an overall success rate as low as45% to up to 100%, but a recurrence rate of up to 30%.5–7

The technique of ‘clotting aneurysm’ by direct injectionof diluted thrombin was first described in 1986 by Cope etal.3 For the next decade, however, not much attention wasgiven to this technique, and it is only in the past 1–2 yearsthat there has been a resurgence of interest, with multiplestudies showing success rates of 96%–100% (Table1). Theoverall complication rate of this technique is less than 2%and the most dreaded complication is downstreamembolization.18 Samal et al.10 described the technique ofballoon occlusion of the neck of the aneurysm by using acontralateral approach to prevent spillover of thrombin intothe distal circulation in 4 cases. We in our limited

echogenicity developed within seconds. Repeat study after3–4 min showed no flow into the cavity, without anyarterial compression. Good distal run-off on color Dopplerwas confirmed before the end of the procedure. As aprecautionary measure the patient was kept on bed restwith the right lower limb immobilized for another 6 hoursto ensure clotting of any small nonthrombosed lobulationthat might have been left. Repeat Doppler study done after24 and 48 hours showed total thrombosis within thepseudoaneurysm cavity, which by then had also regressedin size, and there was no flow into the aneurysm cavity.

Discussion

With the increasing number of cardiac catheterizationprocedures being performed, the total number ofcases with complications are bound to increase.Pseudoaneurysm formation of the the femoral artery

Table 1. Results from different studies for ultrasound-guided thrombin injection for the obliteration of femoralartery pseudoaneurysm

Number Success Number ofof cases (%) complications

Friedman et al.8 40 98 2Edgerton et al.9 47 94 1Samal et al.10 4 100 0Sheiman et al.11 (Simple) 45 100 0

(Complex) 9 56 0Paulson et al.12 26 96 0Kang et al.13 74 100 0La Perna et al.14 70 94 0Hughes et al.15 9 100 0Sievert et al.16 29 100 0Morrison et al.17 39 100 0Brophy et al.18 15 100 0Lennox et al.19 30 100 0Pezzullo et al.20 23 96 1Tamim et al.21 10 100 0Vermeulen et al.22 8 100 0Taylor et al.23 29 93 0Wixon et al.24 11 100 0Liau et al.25 5 100 0

Figs. 1–6. Ultrasonographic pictures in angio mode demonstrating thrombininjection into the femoral artery pseudoaneurysm and thrombus formation. (a)Origin of the pseudoaneurysm from the femoral artery with a narrow neck seenin the angio mode. (b) Giant pseudoaneurysm and blood flow into the aneurysmseen in the angio mode, (c) Injection needle positioned into the aneurysm whilemaintaining compression on the neck of pseudoaneurysm. (d) Thrombin beinginjected into the aneurysm while continuing pressure on the aneurysmal neck.The injection stream is highlighted in the angio mode with no other flow intoaneurysm during the injection. (e) Formation of post-injection thrombus, i.e.density of aneurysm changed within 3 min. (f) Compression released and still noflow occurring into the aneurysm with the pseudoaneurysm neck seen as a stump.

a b

c d

e f

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experience, however, found that a transient compressiongiven to the proximal femoral artery during injection ofthrombin, and confirmation of no flow into the aneurysmwith color/angio mode, may be as good a method to avoidspillover, which also avoids the need for further invasivehandling of the already damaged site. We do feel, however,that caution must be exercised with AV fistula andaneurysm involving bifurcation of the femoral artery as insuch cases a spillover could occur using ultrasound-guidedcompression alone. Most failures/recurrences wereobserved in patients with complex aneurysms, i.e.multilobed aneurysms. Other possible complications couldinclude allergy to bovine thrombin and the formation of alocal abscess formation. Reviewing the literature, themaximum volume of aneurysmal sac thrombosed by thistechnique has been 55 cm3. Our case, on the other hand,had a giant pseudoaneurysm with a volume of nearly80 cm3 and was successfully managed using 2000 unitsof thrombin, without any complications.

Among the other nonsurgical approaches, it may beworth mentioning the technique of temporary coilplacement in the pseudoaneurysm sac, described recentlyby Trehan et al.26 This technique, however, is more invasivewith a 5 F sheath being placed directly into the aneurysmsac, and a PDA coil (8 mm) kept in place for over 2 hoursbefore its final removal. Experience with this technique islimited to a small aneurysm only.

We conclude that sonographically guided directthrombin injection into the aneurysmal sac is a safe, quick,and ef fective technique for managing a giantpseudoaneurysm at the the puncture site. It is well toleratedby the patient, with low morbidity, and avoids the need forsurgery, and could thus be considered as a first-line therapyin these patients.

References

1. Zahn R, Thoma S, Fromm E, Lotter R, Zander M, Seidl K, et al.Pseudoaneurysm after cardiac catheterization: therapeuticinterventions and their sequelae: experience in 86 patients. CathetCardiovasc Diagn 1997; 40: 9–15

2. Chatterjee T, Do DD, Kaufmann U, Maier F, Meier B. Ultrasound-guided compression repair for treatment of femoral arterypseudoaneurysm: acute and follow-up results. Cathet Cardiovasc Diagn1996; 38: 335–340

3. Cope C, Zeit R. Coagulation of aneurysm by direct percutaneousthrombin injection. AJR Am J Roentogenol 1986; 147: 383–387

4. Fellmeth BD, Roberts AC, Bookstein JJ. Postangiographic femoralartery injuries: nonsurgical repair with US-guided compression.Radiology 1991; 178: 671–675

5. Agarwal R, Agrawal SK, Roubin GS, Berland L, Cox DA, Iyer SS, etal. Clinically guided closure of femoral arterial pseudoaneurysmscomplicating cardiac catheterization and coronary angioplasty.Cathet Cardiovasc Diagn 1993; 30: 96–100

6. Dean S, Olin ZW, Piedmonte MA. Ultrasound-guided compressionclosure of postcatheterisation pseudoaneurysms during concurrent

anticoagulation. J Vasc Surg 1995; 23: 28–357. Cox GS, Young JR, Gray BR, Grubb MW, Hertzer NR. Ultrasound-

guided compression repair of postcatheterization pseudoaneurysms:results of treatment in one hundred cases. J Vasc Surg 1994; 19: 683–686

8. Friedman SG, Pellerito JS, Scher L, Faust G, Burke B, Safa T.Ultrasound-guided thrombin injection is the treatment of choice forfemoral pseudoaneurysms. Arch Surg 2002; 137: 462–464

9. Edgerton JR, Moore DO, Nichols D, Lane BW, Magee MJ, Dewey TM,et al. Obliteration of femoral artery pseudoaneurysm by thrombininjection. Ann Thorac Surg 2002; 74: S1413–S1415

10. Samal AK, White CJ, Collins TJ, Ramee SR, Jenkins JS. Treatment offemoral artery pseudoaneurysm with percutaneous thrombininjection. Catheter Cardiovasc Interv 2001; 53: 259–263

11. Sheiman RG, Brophy DP. Treatment of iatrogenic femoralpseudoaneurysms with percutaneous thrombin injection: experiencein 54 patients. Radiology 2001; 219: 123–127

12. Paulson EK, Sheafor DH, Kliewer MA, Nelson RC, Eisenberg LB,Sebastian MW, et al. Treatment of iatrogenic femoral arterialpseudoaneurysms: comparison of US-guided thrombin injectionwith compression repair. Radiology 2000; 215: 403–408

13. Kang SS, Labropoulos N, Mansour MA, Michelini M, Filling D, BaublyMP, et al. Expanded indications for ultrasound-guided thrombininjection of pseudoaneurysms. J Vasc Surg 2000; 31: 289–298

14. La Perna L, Olin JW, Goines D, Childs MB, Ouriel K. Ultrasound-guidedthrombin injection for the treatment of postcatheterisationpseudoaneurysms. Circulation. 2000; 102: 2391–2395

15. Hughes MJ, McCall JM, Nott DM, Padley SP. Treatment of iatrogenicfemoral artery pseudoaneurysms using ultrasound-guided injectionof thrombin. Clin Radiol 2000; 55: 749–751

16. Sievert H, Baser A, Pfeil W, Fach A, Scherer D, Spies H, et al. [Thetreatment of iatrogenic spurious aneurysm of the femoral artery bydirect thrombin injection.] Dtsch Med Wochenschr 2000; 125: 822–825

17. Morrison SL, Obrand DA, Steinmetz OK, Montreuil B. Treatment offemoral artery pseudoaneurysms with percutaneous thrombininjection. Ann Vasc Surg 2000; 14: 634–639

18. Brophy DP, Sheiman RG, Amatulle P, Akbari CM. Iatrogenic femoralpseudoaneurysms: thrombin injection after failed US-guidedcompression. Radiology 2000; 214: 278–282

19. Lennox AF, Delis KT, Szendro G, Griffin MB, Nicolaides AN, CheshireNJ. Duplex-guided thrombin injection for iatrogenic femoral arterypseudoaneurysm is effective even in anticoagulated patients. Br JSurg 2000; 87: 796–801

20. Pezzullo JA, Dupuy DE, Cronan JJ. Percutaneous injection ofthrombin for the treatment of pseudoaneurysms aftercatheterization: an alternative to sonographically guidedcompression. AJR Am J Roentgenol 2000; 175: 1035–1040

21. Tamim WZ, Arbid EJ, Andrews LS, Arous EJ. Percutaneous inducedthrombosis of iatrogenic femoral pseudoaneurysms followingcatheterization. Ann Vasc Surg 2000; 14: 254–259

22. Vermeulen EG, Umans U, Rijbroek A, Rauwerda JA. Percutaneousduplex-guided thrombin injection for treatment of iatrogenic femoralartery pseudoaneurysms. Eur J Vasc Endovasc Surg 2000; 20: 302–304

23. Taylor BS, Rhee RY, Muluk S, Trachtenberg J, Walters D, Steed DL, etal. Thrombin injection versus compression of femoral arterypseudoaneurysms. J Vasc Surg 1999; 30: 1052–1059

24. Wixon CL, Philpott JM, Bogey WM Jr, Powell CS. Duplex-directedthrombin injection as a method to treat femoral arterypseudoaneurysms. J Am Coll Surg 1998; 187: 464–466

25. Liau CS, Ho FM, Chen MF, Lee YT. Treatment of iatrogenic femoralartery pseudoaneurysm with percutaneous thrombin injection. JVasc Surg 1997; 26: 18–23

26. Trehan VK, Mukhopadhyay S, UmaMahesh CR, Yusuf J, SuryavanshiS, Aora R. Successful closure of iatrogenic femoral arterypseudoaneurysm: a new minimally invasive technique. Indian HeartJ 2002; 54: 702–704

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368 Trehan et al. Stenting of a Septal Perforator Post-MI Indian Heart J 2003; 55: 368–369

Stenting of a Septal Perforator for Post-MyocardialInfarction Angina

Vijay Trehan, Saibal Mukhopadhyay, Umamahesh C Rangasetty, Jamal Yusuf, Mohit D Gupta, UA KaulDepartment of Cardiology, GB Pant Hospital, New Delhi

Acute myocardial infarction (AMI) is usually caused bythe thrombotic occlusion of a major epicardial vessel.

Branch occlusion alone, causing AMI in the absence ofinvolvement of a major epicardial artery, is unusual. Wereport a case in which a patient with anteroseptalmyocardial infarction (MI) and intractable post-MI anginawas found to have isolated 90% obstruction of the firstseptal perforator artery, which was successfully dilated andstented.

Case Report

A 52-year-old male, a known hypertensive on irregulartreatment, presented to us with refractory post-MI angina.He had had an anteroseptal MI 48 hours earlier for whichhe was thrombolized with streptokinase (1.5 million U over1 hour) within 3 hours of the onset of chest pain. Thepatient was taken up for coronary angiography and possiblerevascularization. Coronary angiogram revealed athrombus-containing 90% discrete stenosis of the firstseptal perforator artery just after its origin (Figs 1a and 1b).The left anterior descending coronary artery (LAD) alongwith the other epicardial vessels were normal. The patientwas taken up for angioplasty. He was given a bolus ofabciximab (0.25 mg/kg body weight) followed by aninfusion of 10 µg/min for 12 hours. The lesion in the septalperforator artery was crossed with a Luge Wire (BostonScientific Scimed, Inc., USA), and serially dilated with a2.5×12 mm and 3×13 mm balloon. Following balloon

dilatation, a check angiogram revealed TIMI 2 flow with50% residual stenosis. A mounted stent of 3×13 mm (BxVelocity, Cordis, USA) was deployed at 14 bars, andpersistent TIMI 3 flow was achieved (Fig. 2). There were nocomplications during or after the procedure. The patientbecame asymptomatic and was discharged after 72 hours.On follow-up of nearly a year, the patient is asymptomatic.

Discussion

The interventricular septum (IVS) forms the vital wall forboth the ventricles, and constitutes about one-third of thetotal left ventricular (LV) mass.1 The septal perforator

Brief Report

Correspondence: Dr Umamahesh C Rangasetty, Department ofCardiology, GB Pant Hospital, New Delhi 110002.e-mail: [email protected]

Occlusion of a septal perforator branch alone, without the involvement of the left anterior descending coronaryartery, leading to acute myocardial infarction is unusual. We report a case in which an isolated severely stenoticthrombus-containing first septal artery causing intractable post-myocardial infarction angina was successfullydilated and stented. (Indian Heart J 2003; 55: 368–369)

Key Words: Septal artery, Stents, Myocardial infarction

Fig. 1a. Anteroposterior cranial view showing significant eccentric stenosis inthe first septal perforator artery just after its origin.

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case reports of isolated septal artery obstruction.3,4 Therehave also been reports of angioplasty of the septalperforators, usually done in patients with critical stenosisor total occlusion of the LAD.5,6 Recently, there have been acouple of reports of stenting of a septal perforator artery.One was in a post-coronary bypass surgery patient withan occluded LAD,7 while the other was in a patient withmultivessel disease.8 However, to the best of our knowledge,there have been no reports of angioplasty or stenting of anisolated culprit septal artery. The first septal perforator,apart from supplying the IVS, also supplies the bundle ofHis, and in 50% hearts, the atrioventricular node.9 Ourpatient, with refractory post-MI angina due to occlusionof the first septal perforator, was at increased risk ofreinfarction that could have disrupted either the conductionsystem or the IVS, causing its rupture. Unlike the epicardialarteries, septal arteries are subjected to a higher extraneouspressure. Although long-term results of angioplasty of theseptal perforator have not shown increased rates ofrestenosis,5 the behavior of stents in response to a highextrinsic pressure needs to be observed. This situation issimilar to the stenting of myocardial bridges.

References

1. Kaul S. The interventricular septum in health and disease. Am HeartJ 1986; 112: 568–581

2. Banka VS, Agarwal JB, Bodenheimer MM, Helfant RH.Interventricular septal motion: biventricular angiographicassessment of its relative contribution to left and right ventricularcontraction. Circulation 1981; 64: 992–996

3. Nishimura RA, Tajik AJ, Seward JB. Distinctive two dimensionalechocardiographic appearance of septal infarct secondary to isolatedocclusion of first septal perforator artery. Rev Cardiovasc Ultrasound1984; 1: 97–101

4. Plokker HM, Ernest SM, Van Tellingen C, Bruschke AV. Isolatedobstruction of large septal perforators. Am J Cardiol 1988; 62: 142–143

5. Vemuri DN, Kochar GS, Maniet AR, Banka VS. Angioplasty of theseptal perforators: acute outcome and long-term clinical efficacy. AmHeart J 1993; 125: 682–686

6. Comazzi JL, Jang GC, Marsa RJ, Willis WH Jr, Anderson DL, WarehamEE. Percutaneous transluminal angioplasty of a large septal artery.Cathet Cardiovasc Diagn 1983; 9: 181–186

7. Ozdemir M, Timurkaynak T, Cemri M, Boyaci B, Yalcin R, Cengel A,et al. Stenting of the septal perforator coronary artery. J InvasiveCardiol 2001; 13: 694–697

8. Regar E, Kozuma K, Ligthart J, et al. Coronary stent implantation inseptal perforator artery. Jpn Circ J 2000; 64: 802–804

9. Pujadas G (ed). Coronary angiography. New York: McGraw-Hill BookCompany, Inc. 1980; p. 72

Fig. 1b. Left anterior oblique cranial view showing the thrombus in the lesion.

Fig. 2. Angiographic result following stenting of the septal artery.

branches of the LAD2 contribute blood supply to theanterior two-thirds of the IVS. Obstruction of the septalperforators in patients with diffuse coronary artery diseaseis common. However, isolated obstruction of a septalperforator artery is very rare. Till date, there have been 2

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370 Bedi et al. MV Replacement on a Beating Heart Indian Heart J 2003; 55: 370–372

Mitral Valve Replacement on a Beating Heart

Harinder S Bedi, Raman P Singh, Vipin Goel, Purshottam LalMetro Heart Institute, Noida

Cardioplegic techniques carry with them the almostobligatory sequel of some degree of reperfusion injury.1

Any technique that avoids the ischemic component ofcardioplegia and an arrested heart by keeping the heartbeating will go a long way in reducing iatrogenic damageto the heart. While the heart–lung machine can be avoidedin most cases of coronary artery bypass grafting (CABG),2

it is still mandatory in open heart valvular surgery. Wepresent a case of a high-risk mitral valve operationperformed on a beating heart.

Case Report

A 15-year-old girl presented with orthopnea and congestiveheart failure. She was a known case of rheumatic heartdisease with severe mitral regurgitation, moderate mitralstenosis, severe pulmonary artery hypertension, and severefunctional tricuspid regurgitation. The diagnosis wasconfirmed by echocardiography. She did not show muchimprovement with aggressive medical therapy, and wastaken up for emergency surgery. Since she would have beenat a high risk of reperfusion injury if standard techniquesof cardioplegic arrest were used, a technique of on-pumpbeating heart surgery was planned.

The operation was performed through a mediansternotomy. After heparinization, total cardiopulmonarybypass (CPB) was established by aortic and bicavalcannulation. The patient was actively warmed to 36.5°C,and pulsatile flow maintained at the highest pressure thatwas safely possible, keeping the mean systemic pressure

above 60 mmHg. The pump flow was kept at 2.5 L/min/m2,and the FiO2 was kept at 100%.

A retrograde self-inflating coronary sinus cannula(Medtronic DLP, Grand Rapids, MI) was inserted by astandard closed technique. The position was confirmed bypalpation, and the balloon positioned as close to thecoronary sinus ostium as possible to avoid right ventricularmalperfusion. The central perfusion port was connected tothe standard cardioplegic line circuit, and oxygenatedunmodified (noncardioplegic) blood primed into thecannula. With an aortic root vent and maximal venousdrainage, retrograde perfusion was started, andsimultaneously the aorta was cross-clamped. Retrogradeperfusion flow was maintained at 250–300 ml/min withconstant monitoring of the intracoronary sinus pressurevia its integral pressure line, keeping a mean coronary sinuspressure of 40 mmHg. A phosphodiesterase inhibitor—milrinone 0.5 µg/kg/min—was infused in the retrogradeline by a syringe pump to increase the retrograde perfusionflow by inducing vasodilatation. Samples of the bloodentering the coronary sinus and of the blood in the aorticroot vent were taken for analysis and calculation of theoxygen extraction ratio across the myocardium.3 The leftatrium was now opened and mitral valve replacement withpreservation of the posterior mitral apparatus carried outon the beating heart (Figs 1 and 2). At the end of theprocedure, the cardiac cavities were filled with blood (byinflating the lungs) and with warm saline, and the leftatrium was closed. The aortic root vent was kept on suction,the aortic cross-clamp released, and the retrograde coronarysinus cannula removed. The right atrium was opened, and astandard repair (DeVega annuloplasty) of the tricuspid valvecarried out.

Brief Report

We report the case of a patient who needed mitral valve replacement but was at a high risk of myocardial injurywith the conventional technique (cardioplegic arrest on cardiopulmonary bypass). Valve replacement was carriedout on a beating heart on cardiopulmonary bypass by perfusing the heart continuously with oxygenatednoncardioplegic normothermic blood via the coronary sinus. (Indian Heart J 2003; 55: 370–372)

Key Words: Mitral valve replacement, Cardiopulmonary bypass, Beating heart

Correspondence: Dr Harinder Singh Bedi, Chief Cardiac Surgeon andChairman, Cardio-Vascular Surgery, Metro Heart Institute, X-1, Sector 12,Noida, NCR, Delhi. e-mail: [email protected]; [email protected]

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Good visualization of the mitral valve apparatus waspossible, and the procedure was completed without anytechnical difficulty. Despite the motion of the heart, the on-pump and totally decompressed state of the heart causedby cardiac venting resulted in a good quality of the visualfield, equaling that of the conventional technique, andtechnical accuracy was not affected.

An oxygen extraction ratio of 52% across the myocar-dium was noted:Oxygen extraction ratio across the myocardium =

O2CS– O2AR_________________ × 100O2A

where, O2CS: arterial O2 content (i.e. going into the coronarysinus);

O2AR: O2 content of blood from the aortic root;O2A: O2 content (arterial).

[O2 content = 1.36 ml O2 /g × Hb × O2 saturation + (0.003 × pO2)]

The high extraction is suggestive of the fact that themyocardium uses up the oxygen being delivered by theretrograde route.

The CPB time was 98 min while the aortic cross-clamptime was 52 min. The heart continued to be in sinus rhythmduring and after the procedure. There was no evidence ofischemia—no ST segment changes and no rhythmdisturbance occurred during the retrograde perfusion. Thepatient was weaned away from CPB without any inotropicsupport, and was extubated within 5 hours of reaching theICU. She made an uneventful recovery, and was dischargedon postoperative day 6.

Discussion

In spite of improvements in myocardial protectiontechniques, some perioperative adverse ef fects ofmyocardial ischemia caused by aortic cross-clamping,cardioplegia, and reperfusion remain. Even withcontinuous warm blood cardioplegia (considered by someas the best form of myocardial protection as it keeps theheart in an aerobic state), some degree of perioperativemyocardial stunning still occurrs.1 Cardiac dysfunctionmay be caused by myocardial edema intrinsic to thediastolic state of the arrested heart,4 and the inevitablereperfusion injury that follows the unclamping of thearrested heart. Ischemia followed by reperfusion isinvariably followed by the generation of oxygen-freeradicals, which produce myocardial injury. To counter this,various scavengers of oxygen-free radicals have been addedto cardioplegic solutions in an attempt to inhibit theinjury.5,6 Keeping the heart beating results in lessmyocardial edema, and better cardiac function.4

Retrograde coronary sinus perfusion as a method ofmyocardial perfusion is not new. In 1956, Lillehei et al.7

reported an aortic valve replacement using coronary sinusperfusion at 125 ml/min. Oxygenated blood is perfusedfrom the coronary sinus and reaches the myocardium viathe coronary venous system and the capillaries, and goesout via the arterial end as in retrograde cardioplegia. Wehave previously used retrograde perfusion on the beatingheart to perform CABG without CPB.2,3 The technique ofbeating heart valve surgery involves the constantretrograde perfusion of pure normothermic oxygenatedblood into the coronary sinus.

Matsumoto et al.8 recently performed a beating heart

Fig. 1. A line diagram showing the operative technique. ACC: aortic cross-clamp;IVC: cannula in the inferior vena cava; MV: prosthetic mitral valve; R: retrogradecoronary sinus cannula; SVC: cannula in the superior vena cava; V: aortic rootvent

Fig. 2. A photograph taken during surgery. ACC: aortic cross-clamp; SVC:cannula in the superior vena cava; MV: prosthetic mitral valve; IVC: cannula inthe inferior vena cava; V: aortic root vent; R: retrograde coronary sinus cannula

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valve procedure on 25 patients with good results. Theyshowed, by intraoperative monitoring, that myocardialtissue oxygen saturation (SO2) levels were maintained atthe preoperative physiologic values throughout theprocedure. A good myocardial oxygen consumption, asnoted by us, indicates that the myocardium is in a state ofaerobic metabolism that is maintained by the retrogradecoronary sinus perfusion.

The advantages of the technique are: a perfused beatingheart that does not have to ‘‘work’’ (pump blood); noreperfusion injury (as there is no ischemia); anuninterrupted performance of the operation; a long periodof continuous oxygenated blood delivery that maintains thebeating of the heart; appropriate pH, effective delivery ofsubstrates, and removal of acid metabolites; more uniformoxygenated blood distribution in the presence of anyassociated coronary artery stenosis; testing of the mitralvalve repair, when performed, can be done under the actualphysiologic conditions of a normal left ventricular tone withpreserved three-dimensional architecture of the beatingheart (with conventional techniques, the mitral valve is ina motionless flaccid state that may not accurately reflectits function in the beating heart); avoidance of injury tothe ostia of the coronary arteries; and the possibility ofperforming ablation for atrial fibrillation on the beatingheart. The normothermic state of the blood ensuresmaximal vasodilatation of the cardiac veins, and steady,uniform flow and distribution. Should the flow beinadequate or if there is malperfusion, it will be reflectedby ECG changes (ST segment changes, bradycardia,arrhythmias, etc.), and the flow can be suitably adjusted.The option of converting to the conventional technique—cardiac arrest with hyperkalemic blood cardioplegia— isalways immediately available, if the surgeon is not satisfied

with the beating heart technique.The beating heart technique is thus a useful addition to

the armamentarium of the cardiac surgeon in dealing withpatients undergoing high-risk valve surgery. A comparisonof this procedure versus the arrested heart technique in alarge group of patients is required to judge the superiorityof the beating heart technique.

References

1. Misare BD, Krukenkamp IB, Lazer ZP, Levitsky S. Recovery ofpostischemic contractile function is depressed by antegrade warmcontinuous blood cardioplegia. J Thorac Cardiovasc Surg 1993; 105:37–44

2. Bedi HS, Suri A, Kalkat MS, Sengar BS, Mahajan V, Chawla R, et al.Global myocardial revascularization without cardiopulmonarybypass using innovative techniques for myocardial stabilization andperfusion. Ann Thorac Surg 2000; 69: 156–164

3. Bedi HS. Selective graft and coronary sinus perfusion in off pumpCABG: is it necessary? [Reply]. Ann Thorac Surg 2001; 71: 1070–1072

4. Mehlhorn U, Allen SJ, Adamus DL, Davis KL, Gogola GR, WartersRD. Cardiac surgical conditions induced by beta blockade: effect onmyocardial fluid balance. Ann Thorac Surg 1996; 62: 143–150

5. Vinten-Johansen J, Ronson RS, Thourani VH, Wechsler AS. Surgicalmyocardial protection. In: Gravlee GP, Davis RF, Kurusz M, Utley JR(eds). Cardiopulmonary bypass—principles and practice. 2nd ed.Phliladelphia: Lippincott Williams and Wilkins; 2000. p. 214

6. Kirklin JW, Barratt-Boyes BG. Myocardial management duringcardiac surgery with cardiopulmonary bypass. In: Kirklin JW,Barratt-Boyes BG (eds). Cardiac surgery. Morphology, diagnostic criteria,natural history, techniques, results and indications. 2nd ed. New York:Churchill Livingstone; 1993. p. 129

7. Lillehei CW, DeWall RA, Gott VL, Varco RL. The direct visioncorrection of calcific aortic stenosis by means of a pump oxygenatorand retrograde coronary sinus perfusion. Dis Chest 1956; 30:123–131

8. Matsumoto Y, Watanabe G, Endo M, Sasaki H, Kasashima F, KosugiI. Efficacy and safety of on-pump beating heart surgery for valvulardisease. Ann Thorac Surg 2002; 74: 678–683

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Transcatheter Closure of Native Pulmonary Artery for theElimination of Accessory Pulmonary Blood Flow After

Bidirectional Glenn Shunt

Anil Sivadasan Radha, Bhava RJ Kannan, Raman Krishna KumarDivision of Pediatric Cardiology, Amrita Institute of Medical Sciences and Research Centre, Kochi

Bidirectional Glenn shunt (BDGS) is frequentlyperformed as part of a multistaged palliation of

congenital heart disease in patients with a single ventriclephysiology to decrease the volume overload in patients whoare candidates for future Fontan type repair.1,2 It is oftenadvocated as an intermediary step for high-risk patients.3

Traditionally, accessory sources of pulmonary blood flow,such as from the native pulmonary valve, are eliminatedto minimize pulmonary artery (PA) pressure aftercavopulmonary anastomosis (Glenn shunt). Recently,however, there is a growing trend towards preservation ofblood flow through the native pulmonary valve to improvesaturation. However, occasionally patients can developheart failure when blood flow through the nativepulmonary valve is excessive. We report a child whopresented with elevated PA pressures due to excessiveantegrade pulmonary blood flow after a Glenn shunt andthe successful interruption of this additional flow using anAmplatzer duct occluder (ADO).

Case Report

The patient was an 11-year-old boy with severe cyanosis(basal saturation of 65%) and marked limitation of physicalactivity. The anatomic diagnosis was situs solitus, D-loop,levocardia, bilateral superior vena cava (SVC), double outletright ventricle, multiple muscular ventricular septal defects

(VSDs), and severe infundibular and valvar pulmonicstenosis. At the age of 3 years, the child underwent atrialseptectomy with Brock procedure (enlargement of rightventricular outflow in relation to the pulmonary valve).Cardiac catheterization at admission showed elevated rightatrial (mean: 18 mmHg) and PA pressures (29/17 mmHg,mean: 23 mmHg) with a pulmonary-to-systemic blood flowratio of 3:1, and the calculated indexed pulmonary vascularresistance was 0.14 Wood units/m2. He underwent right-sided cavopulmonary anastomosis with ligation of the leftSVC and enlargement of the atrial septal defect. Ligationof the PA could not be done as planned due to denseadhesions in the region of the main pulmonary artery(MPA). His immediate postoperative course was uneventful.On postoperative day 11, it was noticed that he hadprominent neck vein pulsations, and prominent chest wallveins, which were seen to drain from above downwards.Besides, he had an overt right heart failure with ascites andhepatomegaly. Echocardiography showed systolicretrograde pulsatile flow in the right SVC due to excessiveantegrade flow from the right ventricle into the PA.

Informed consent was taken and cardiac catheterizationwas performed under conscious sedation. The femoralvessels and the right subclavian vein were cannulatedpercutaneously. The SVC pressure tracing showed abiphasic wave pattern and was markedly elevated (38/18mmHg, mean 26 mmHg). The PA angiogram showednormal branch pulmonary arteries with rapid wash-off ofthe contrast, and the PA annulus measured 12.5 mm. Thepulmonary valve was crossed in a retrograde fashion witha 0.035" exchange length (300 cm) Roadrunner wire

Brief Report

We report a case where excessive accessory pulmonary blood flow via the native pulmonary valve aftercavopulmonary anastomosis resulted in pulmonary hypertension and heart failure. This flow was successfullyeliminated in the cardiac catheterization laboratory using an Amplazter duct occluder that was placed acrossthe native pulmonary valve. (Indian Heart J 2003; 55: 373–375)

Key Words: Catheter intervention, Amplatzer duct occluder, Cavopulmonary shunt

Correspondence: Dr R Krishna Kumar, Division of Pediatric Cardiology,Amrita Institute of Medical Sciences and Research Centre, Elamakkara PO,Kochi 682026. e-mail: [email protected]

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(Cook Inc.) and Judkins Right 4 catheter (Cook Inc.). Thewire was snared with a 10 mm Amplatz gooseneck snare(Microvena Corp., MN, USA), and was brought out of theleft femoral venous sheath to form a veno-venous wire loop.A 7 F Swan–Ganz catheter was passed over the wire fromthe groin and the balloon at the tip of the catheter wasinflated (Fig.1) to occlude the MPA. The PA pressures onballoon occlusion decreased to 25/14 mmHg (mean: 17mmHg) without any fall in aortic saturation. A 9 F longsheath (Cook Inc., Bloomington, IN, USA) was introducedfrom the subclavian vein and across the pulmonary valveinto the right ventricular outflow tract. A 16/14 ADO(AGA Medical, MN, USA) device was advanced through thesheath, and a small part of the retention disc was extrudedfrom the sheath into the ventricle just below the valve andthen pulled against the pulmonary valve. The device wasdeployed such that the waist straddled the pulmonary valve(Fig. 2). Gentle pulling and pushing of the device underechocardiographic and fluoroscopic guidance was done toensure stability of the device. The device was released afterconfirming that the flow across the cavopulmonaryanastomosis was unobstructed. The patient recovereduneventfully. Three months later, he had gained weight(2.5 kg) and restarted attending his school after a gap of 2

years. He had a resting saturation of 88% and wassymptom-free.

Discussion

Cavopulmonary anastomosis is used as an intermediarystage prior to completion of a Fontan type of repair in thosewith a single ventricle physiology.1–3 It is controversialwhether an additional source of systemic-to-pulmonaryartery flow is beneficial.3–5 In some instances, it is thoughtto improve oxygenation, decrease the incidence ofpulmonary arteriovenous fistula formation, and promotethe growth of the pulmonary arteries.3,4 However, it mayresult in elevation of the SVC pressure, with interferenceof the blood flow to the pulmonary arteries. Additionally,depending on its magnitude, it may add an additionalvolume load on the left ventricle. In our patient, the SVCpressure was markedly elevated. The pressure tracing priorto closure was suggestive of pulsatile flows. Temporaryballoon occlusion of the MPA resulted in a substantialdecrease in the SVC pressures and eliminated venouspulsatility. This conclusively showed that excessivepulmonary blood flow through the native pulmonary valvewas responsible for the adverse hemodynamics.

Even though the ADO is conventionally used for closureof a patent ductus arteriosus, it was well suited for thispurpose, as its flat retention disc allows positioning of thedevice without interfering with the flow through the Glennanastomosis.6,7 It allows easy testing of the stability of the

Fig. 1. Temporary balloon occlusion: a veno-venous loop has been formed fromthe right superior vena cava to the femoral vein. A 7F Swan–Ganz catheter hasbeen passed from the femoral vein, and the balloon of this catheter has beeninflated in the main pulmonary artery to temporarily occlude antegrade flows.A hand injection has been made through the sheath passed via the right subclavianvein. RPA: right pulmonary artery; LPA: left pulmonary artery.

Fig. 2. A hand injection via the side arm of the sheath, just prior to the releaseof the device, shows the position of the device (Amplatzer duct occluder [ADO]).

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device before release. We chose an oversized duct occluderinstead of a muscular VSD occluder because it is lessexpensive. The precise positioning of the device such thatit straddles the pulmonary valve is critical. If the device istoo far into the ventricle, it could slip down and getembolized through the systemic circuit. If the device isplaced entirely distal to the pulmonary valve, it can migratedistally and can occlude the branch pulmonary arteries.Because of the absence of a retention disc on the pulmonaryarterial aspect, we chose to oversize the device substantially.

Conclusions: This report demonstrates theunconventional use of an ADO for occlusion of the nativepulmonary valve. This offers an easy and nonsurgicalsolution in this subset of patients who would otherwiseneed repeat surgical procedures. Temporary balloonocclusion is a useful maneuver to ascertain the contributionof accessory pulmonary blood flow so that the benefits ofeliminating this flow can be predicted.

References

1. Mazzera E, Corno A, Picardo S, Di Donato R, Marino B, Costa D, et al.Bidirectional cavopulmonary shunts: clinical applications as stagedor definitive palliation. Ann Thorac Surg 1989; 47: 415–420

2. Allgood NL, Alejos J, Drinkwater DC, Laks H, Williams RG.Effectiveness of the bidirectional Glenn shunt procedure for volumeunloading in the single ventricle patient. Am J Cardiol 1994; 74:834–836

3. Masuda M, Kado H, Shiokawa Y, Fukae K, Suzuki M, Murakami E, etal. Clinical results of the staged Fontan procedure in high-riskpatients. Ann Thorac Surg 1998; 65: 1721–1725

4. Mainwaring RD, Lamberti JJ, Uzark K, Spicer RL. Bidirectional Glenn.Is accessory pulmonary blood flow good or bad? Circulation 1995;92 (Suppl 9): II294–II297

5. Migliavacca F, de Leval MR, Dubini G, Pietrabissa R. A computationalpulsatile model of the bi-directional cavopulmonary anastomosis:the influence of pulmonary forward flow. J Biomech Engineer 1996;11: 520–528

6. Masura J, Walsh KP, Thanopoulous B, Chan C, Bass J, Goussous Y, etal. Catheter closure of moderate- to large-sized patent ductusarteriosus using the new Amplatzer duct occluder: immediate andshort-term results. J Am Coll Cardiol 1998; 31: 878–882

7. Ebeid MR, Masura J, Hijazi ZM. Early experience with the Amplatzerductal occluder for closure of the persistently patent ductusarteriosus. J Interv Cardiol 2001; 14: 33–36

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376 Singh et al. LA–CS Dissociation After RFA for AP Indian Heart J 2003; 55: 376–378

Left Atrial–Coronary Sinus Dissociation Following anAttempt at Radiofrequency Ablation for a Left Lateral

Accessory Pathway

Balbir Singh, Rakesh Sapra, Ripen K Gupta, Tapan Ghose, Rahul Trehan, Upendra KaulDepartment of Cardiology, Batra Hospital and Medical Research Centre, New Delhi

Radiofrequency (RF) ablation for accessory pathways(APs) is safe and effective.1,2 The mapping of APs

involves the use of multipolar electrodes placed at differentsites. Coronary sinus (CS) electrograms assume animportant role (particularly for left-sided pathways), andgenerally represent the sequence of left atrial (LA)activation.3 We report a case of an orthodromic tachycardiausing a concealed left lateral AP in which the activationsequence in CS electrograms reversed following an attemptat RF ablation without altering the AP conduction.

Case Report

A 23-year-old man was referred to our institute forrecurrent episodes of supraventricular tachycardia (SVT)lasting for several hours. He was taken up for anelectrophysiologic study and possible ablation. The AHinterval was 110 ms while the HV interval was 45 ms.Retrograde conduction on ventricular pacing was eccentric,with earliest activation at the distal CS (Fig. 1a). An SVTwith a cycle length (CL) of 330 ms could easily be induced

with a single atrial extrastimulus, with a retrograde atrialactivation sequence similar to that during ventricularpacing (Fig. 1b).

After a trans-septal puncture, a 7 F ablation catheter(Cordis Webster) was introduced to map the left free wallAP along the lateral mitral annulus. During ventricularpacing, a site with the shortest VA interval preceding allother atrial activations was chosen for the application ofRF energy (Fig. 2). During the RF application, it was realizedthat the retrograde activation sequence had changed to oneresembling concentric activation (Fig. 3a).

The RF lesion was completed after 60 s, and thestimulation protocols repeated. An SVT could be inducedagain but with a different activation sequence (proximal tothe distal CS sequence, and earliest activation at the Hisbundle site) (Fig. 3b). On observing this change in the atrialactivation sequence, this tachycardia was thought to beeither an atypical atrioventricular nodal re-entranttachycardia or a slow conducting anteroseptal AP. Adiagnosis of ectopic atrial tachycardia was excluded byoverdrive pacing from the right ventricle. This resulted inentrainment of the tachycardia with the same atrialsequence and, on abrupt termination of pacing, the returnsequence was an A–V electrogram favoring re-entry ratherthan atrial tachycardia.4 However, on mapping with theablation catheter around the mitral annulus, it was soon

Brief Report

Coronary sinus electrograms generally represent the sequence of left atrial activation, and are very helpful inlocalizing and differentiating left lateral accessory pathway-mediated tachycardia from other supraventriculartachycardias. The activation of the coronary sinus from the left atrium occurs through muscle bridges, whichmay be discrete or form an intermingled continuum. These muscle bridges, if disconnected, may dissociate thecoronary sinus from the left atrium, in which case the coronary sinus electrograms do not represent left atrialactivation, and do not help to understand, or may cause misinterpretation of, the mechanism of supraventriculartachycardia. We report one such case of orthodromic supraventricular tachycardia mediated through the leftlateral accessory pathway in which the coronary sinus got dissociated from the left atrium during radiofrequencyablation. (Indian Heart J 2003; 55: 376–378)

Key Words: Left lateral accessory pathway, Coronary sinus, Radiofrequency ablation

Correspondence: Dr Balbir Singh, Senior Consultant, InterventionalCardiology and Cardiac Electrophysiology, Batra Hospital and Medical ResearchCentre, 1, Tughlakabad Institutional Area, Mehrauli Badarpur Road, New Delhi110062.

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Indian Heart J 2003; 55: 376–378 Singh et al. LA–CS Dissociation After RFA for AP 377

Fig. 1. Intracardiac recording during ventricular pacing (a) and following theinduction of supraventricular tachycardia (b). The earliest retrograde atrialactivation is in the distal coronary sinus recordings. HRA: high right atrium;HBp: His bundle-proximal; HBd: His bundle-distal; PCS: proximal coronarysinus; MCS: mid-coronary sinus; DCS: distal coronary sinus

Fig. 2. Intracardiac recordings obtained from a 7 F ablation catheter placed atthe lateral mitral annulus (MAP) following trans-septal puncture. The VAinterval here is the shortest compared to all the other recordings. HRA: highright atrium; HBp: His bundle-proximal; HBd: His bundle-distal; PCS: proximalcoronary sinus; MCS: mid-coronary sinus; DCS: distal coronary sinus

a ba b

Fig. 3. Intracardiac recording showing that the retrograde activation sequenceduring ventricular pacing (a) and supraventricular tachycardia (b) followingthe RF lesion has changed to a concentric activation sequence with earliestactivation at the site of the bundle of His followed by PCS, MCS, and DCS. PCS:proximal coronary sinus; MCS: mid-coronary sinus; DCS: distal coronary sinus;HRA: high right atrium; HBp: His bundle-proximal; HBd: His bundle-distal;RVA: right ventricular apex

Fig. 4. Intracardiac recording showing the shortest VA interval in the mappingcatheter at the lateral mitral annulus. HBp: His bundle-proximal; PCS: proximalcoronary sinus; MCS: mid-coronary sinus; DCS: distal coronary sinus; HRA:high right atrium; MAP: lateral mitral annulusrealized that the shortest VA interval was still around the

lateral mitral annulus with the CS electrograms not trulyreflecting the activation sequence in the LA (Fig. 4).Delivering another RF pulse at this site, which was slightlymore anterior to the previous site, resulted in terminationof the tachycardia with a retrograde conduction block.Subsequent ventricular pacing demonstrated a compete VAblock (Fig. 5), and no tachycardia could be induced despiteisoprenaline infusion, and multiple atrial and ventricularextrastimuli.

Discussion

The diagnosis of an orthodromic tachycardia using a lateralconcealed AP was confirmed by the earliest retrogradeactivation sequence recorded at the distal CS during thetachycardia. This was similar to the atrial activation patternduring ventricular pacing. During the RF pulse, the changein the atrial activation sequence from an eccentric to a

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concentric sequence during ventricular pacing made usbelieve that the AP had been eliminated. However, whenSVT could easily be induced thereafter, careful mapping wasperformed to understand the mechanism of this “new”tachycardia. The mapping at the lateral mitral annulusclearly demonstrated that this was the same orthodromictachycardia but with an altered sequence of activation inthe CS electrograms. The atrial signal on the ablationcatheter preceded the atrial recording on the His bundleand proximal CS recordings (Fig. 4). Therefore, atrialactivation was not concentric (as suggested by CS and Hisbundle recordings). This was confirmed by the fact that anRF pulse at this site resulted in the termination of SVT witha retrograde block, after which a VA block wasdemonstrated, and the SVT could not be reinitiated. Thischange in epicardial (CS) sequence without a change inendocardial activation probably resulted from the initial RFpulse, which could have caused a dissociation between theLA and CS. Recent histologic studies have demonstratedthat the lumen of the CS contains myocardium that iscontinuous with CS ostial–right atrial myocardium.5,6 Theproximal CS is separated from the LA by adipose tissue,while the rest of the CS has discrete muscle bridgesconnecting these two structures. Considerable variations

are known, ranging from 1 to 2 fascicles to intermingledcontinuum.4 It is possible that there was a discrete bridgeconnecting the LA to the distal CS in this patient, whichgot disconnected following the initial RF pulse, and resultedin a change of sequence without a change in themechanism of the tachycardia.

CS recordings generally represent LA activation. It is,however, important to understand the complex histologyand interconnections between the LA and CS. The examplein this report represents the disconnection between the LAand CS following the initial RF pulse. Chauvin et al.6

recently demonstrated an electrical dissociation betweenthe CS and LA in a group of patients with atrial flutter andatrial fibrillation. In a series of 159 patients, Luria et al.7

discussed an intra-atrial conduction block along the mitralannulus during AP ablation. Alberte et al.8 andVasconcecos et al.9 have described a case each in whichdissociation quite similar to the present report occurredfollowing an attempt at ablation of the lateral AP. It isimportant to understand these mechanisms since aninability to recognize the dissociation could have resultedin the erroneous diagnosis of a second tachycardia leadingto inappropriate treatment.

References

1. Jackman WM, Wang XZ, Friday KJ, Roman CA, Moulton KP,Beckman KJ, et al. Catheter ablation of accessory atrioventricularpathways (Wolff–Parkinson–White syndrome) by radiofrequencycurrent. N Engl J Med 1991; 324: 1605–1611

2. Calkins H, Langberg J, Sousa J, el-Atassi R, Leon A, Kou W, et al.Radiofrequency catheter ablation of accessory atrioventricularconnections in 250 patients. Abbreviated therapeutic approach toWolff–Parkinson–White syndrome. Circulation 1992; 85: 1337–1346

3. Kuck KH, Schluter M, Geiger M, Siebels J, Duckeck W. Radiofrequencycurrent catheter ablation of accessory atrioventricular pathways.Lancet 1991; 337: 1557–1561

4. Knight BP, Zivin A, Souza J, Flemming M, Pelosi F, Goyal R, et al. Atechnique for the rapid diagnosis of atrial tachycardia in theelectrophysiology laboratory. J Am Coll Cardiol 1999; 33: 775–781

5. Antz M, Otomo K, Arruda M, Scherlag BJ, Pitha J, Tondo C, et al.Electrical conduction between the right atrium and the left atriumvia the musculature of the coronary sinus. Circulation 1998; 98:1790–1795

6. Chauvin M, Shah DC, Haíssaguerre M. The anatomic basis ofconnections between the coronary sinus musculature and the leftatrium in humans. Circulation 2000; 101: 647–652

7. Luria DM, Nemec J, Etheridge SP, Compton SJ, Klein RC, Chugh SS,et al. Intra-atrial conduction block along the mitral valve annulusduring accessory pathway ablation: evidence for a left atrial“isthmus”. J Cardiovasc Electrophysiol 2001; 12: 744–749

8. Alberte C, Hadian D, Miller JM, Olgin JE. A changing tachycardiathat did not change. J Cardiovasc Electrophysiol 2002; 13: 727–729

9. Vasconcecos JTM, Costa ERB, Galvaofilho SDS. Block of the mitral–pulmonary isthmus during ablation of a single left-sided accessorypathway causing different patterns of retrograde atrial activation.Arq Bras Cardiol 2002; 78: 504–509

Fig. 5. Ventricular pacing following the ablation (at the site on the lateral mitralannulus as shown in Fig. 4) shows complete VA dissociation. HBp: His bundle-proximal; PCS: proximal coronary sinus; MCS: mid-coronary sinus; DCS: distalcoronary sinus; MAPp: lateral mitral annulus-proximal; MAPd: lateral mitralannulus-distal

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Indian Heart J 2003; 55: 379–381 Chockalingam et al. Left Atrial Appendage Aneurysm 379

Left atrial appendage (LAA) aneurysm is a rarelyencountered congenital defect. Most LAA aneurysms

are diagnosed incidentally. They can result in arrhythmiasor systemic embolization.1 We report a child with massiveLAA aneurysm who presented with effort intolerance andarrhythmias.

Case Report

A previously healthy 12-year-old boy presented with a6-month history of effort intolerance, retrosternal prickingtype of chest discomfort, and palpitations. His NYHAfunctional status had progressed to class III. The pulse,blood pressure, and jugular venous pressure were normal.His cardiac examination revealed normal apical impulsein the left 5th intercostal space. Heart sounds were normalwithout murmurs or gallops. The initial electrocardiogram(ECG) was normal, and when repeated during palpitations,showed narrow QRS nodal re-entrant tachycardia at a rateof 235/min.

Chest X-ray PA view showed cardiomegaly with a CTratio of 64% with straightening of the left heart border. Itshowed filling out of the cardiac bay (Fig. 1). The lateralview X-ray confirmed that the enlarged chamber was theleft atrium (LA). Lung markings were unremarkable.

Transthoracic echocardiography revealed a very large(15×10 cm) echo-free space compressing the left ventricle

(Figs 2, 3). The chamber connected to the LA in the regionof the LAA. Autocontrast was present within the LAAaneurysm due to sluggish flow (Fig. 2). To-and-fro bloodflow was demonstrated using Doppler echo (Fig. 3). Therelative size and location of the aneurysm was delineatedby magnetic resonance imaging (MRI) (Fig. 4). Cardiaccatheterization confirmed normal chamber pressures andsaturations. The LA injection by trans-septal punctureopacified a large chamber adjacent to the left heart (Fig. 5).

The patient was operated on cardiopulmonary bypass.The aneurysm was resected and the histopathology reportconfirmed benign cardiac and fibrous tissue. His symptomsimproved rapidly and he is now doing well 10 months afterthe resection without recurrence of palpitation.

Brief Report

Correspondence: Dr Anand Chockalingam, Madras Medical College andResearch Institute, 9 A Taylors Road, Kilpauk, Chennai 600010.e-mail: [email protected]

Left atrial appendage aneurysm is a rarely reported condition. Symptoms are absent in childhood and diagnosisis usually incidental. Systemic embolization or arrhythmia can bring these cases to medical attention. We reportthe case of a 12-year-old male with massive left atrial appendage aneurysm who presented with effort intoleranceand supraventricular arrhythmia. The diagnosis was made by transthoracic echocardiography. Magneticresonance imaging and left atriogram were also done before surgical resection. (Indian Heart J 2003; 55:379–381)

Key Words: Left atrial appendage, Supraventricular tachycardia, Echocardiography

Massive Left Atrial Appendage Aneurysm Presenting asSupraventricular Tachycardia

Anand Chockalingam, R Alagesan, M Nandakumar, G GnanaveluDepartment of Cardiology, Madras Medical College and Research Institute, Chennai

Fig. 1. Chest X-ray in posteroanterior view showing filling out of the cardiacbay, altering the left cardiac border.

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life on routine chest X-ray. It is likely that an aneurysm ofthe LAA is initially small and asymptomatic, and becomesobvious only after years of enlargement. Stasis in theaneurysmal cavity accounts for thrombosis and systemicembolization.1

LAA aneurysms can present with chest pain,palpitations or systemic embolization. Nevertheless, mostcases are asymptomatic. Although our case had a massiveLAA aneurysm and autocontrast, he did not have anyembolic episodes.

Fig. 2. Transthoracic echocardiogram in apical 4-chamber view showing themassive left atrial appendage (LAA) aneurysm from the left atrium (LA).Autocontrast is seen within the LAA aneurysm. The left ventricle (LV) iscompressed by the LAA aneurysm, while the right atrium (RA) and rightventricle (RV) are normal.

Fig. 3. Transthoracic echocardiogram in modified parasternal short-axis viewshowing massive left atrial appendage (LAA) aneurysm arising from the leftatrium (LA) in the region of LAA. The aortic (AO) valve is seen in cross-section.

Discussion

Aneurysm of the LAA can be secondary to left ventriculardysfunction, mitral valve pathology, or herniation of theLAA through a pericardial defect.1,2 Primary congenitalaneurysm of the LAA with an intact pericardium is a rareanomaly.1–3 Intrapericardial LAA aneurysm is due tocongenital weakness involving the LAA or LA free wall.4

Aneurysm may mimic a mediastinal or cardiac tumor.Although congenital in origin, most cases are

asymptomatic in childhood.5 In most of the patients, thecondition is diagnosed in the second to fourth decades of

Fig. 4. MRI in sagittal section clearly defining the extent and relations of theleft atrial appendage (LAA) aneurysm.

Fig. 5. Left atrial angiogram by trans-septal puncture opacifying the left atrialappendage (LAA) aneurysm. The delayed clearance and swirling motion ofcontrast differentiate the LAA aneurysm from the cardiac chambers.

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Indian Heart J 2003; 55: 379–381 Chockalingam et al. Left Atrial Appendage Aneurysm 381

Physical examination is often unrevealing.6 ECG mayreveal tachyarrhythmia, as in our case. A radiographicdifferential for filling out of the cardiac bay region (Fig. 1)includes partial absence of the pericardium along withatrial herniation through the defect, paracardiac tumorsor cysts, enlarged coronary sinus, aneurysmal dilatationof the LA due to mitral valvular disease, and pulmonaryartery aneurysm.

Echocardiography, radionuclide angiography, CT scan,MRI, and cardiac catheterization have been used toestablish the diagnosis. Angiography requires trans-septalpuncture, and may not detect an LAA aneurysm filled witha thrombus. In our case, the diagnosis was made duringscreening echocardiography. Due to adequatedemonstration of the aneurysm and its origin bytransthoracic windows, transesophageal echocardiography(TEE) was not required.

Foale et al. proposed the following criteria to diagnosecongenital LAA aneurysm:8

(i) origin from an otherwise normal LA; (ii) well-definedcommunication with the LA; (iii) position within thepericardium; and (iv) distortion of the LV free wall by theaneurysm.

Our patient fulfilled all the 4 criteria for the diagnosis of anLAA aneurysm.

Associated anomalies such as atrial septal defect (ASD),persistent left superior vena cava, anomalous pulmonary

venous drainage, and renal artery anomalies have beenreported.9,10 Aneurysmectomy abolishes recurrentarrhythmias and thromboembolism. Thus, surgicalresection, with or without cardiopulmonary bypass, isrecommended even in asymptomatic patients.

References

1. Bramlet DA, Edwards JE. Congenital aneurysm of left atrialappendage. Br Heart J 1981; 45: 97–100

2. Tanabe T, Ishizaka M, Ohta S, Sugie S. Intrapericardial aneurysm ofthe left atrial appendage. Thorax 1980; 35: 151–153

3. Godwin TS, Avager P, Key JA. Intrapericardial aneurysmal dilatationof left atrial appendage. Circulation 1988; 37: 397–400

4. Shaher RM, Alley R, Anis W, Mintzer J. Congenital enlargement ofthe left atrium. J Thorac Cardiovasc Surg 1972; 63: 292–299

5. Behrendt DM, Aberdeen E. Congenital aneurysm of the left atrium.Ann Thorac Surg 1972; 13: 54–59

6. Krueger SK, Ferlic RM, Mooring PK. Left atrial appendage aneurysm:correlation of noninvasive with clinical and surgical findings: reportof a case. Circulation 1975; 52: 732–738

7. Comess KA, Labate DP, Winter JA, Hill AC, Miller DC. Congenital leftatrial appendage aneurysm with intact pericardium: diagnosis bytransesophageal echocardiography. Am Heart J 1990; 120: 992–996

8. Foale RA, Gibson TC, Guyer DE, Gillam L, King MF, Weyman AE.Congenital aneurysms of the left atrium: recognition by cross-sectional echocardiography. Circulation 1982; 66: 1065–1069

9. Parmley LF. Congenital atriomegaly. Circulation 1982; 25: 553–55810. Labarre TR, Stamato NJ, Hwang MH, Jacobs WR, Stephanides L,

Scanlon PJ. Left atrial appendage aneurysm with associatedanomalous pulmonary venous drainage. Am Heart J 1987; 114:1243–1245

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382 Mukhopadhyay et al. Noncompacted LV With Dysplastic Tricuspid Valve Indian Heart J 2003; 55: 382–383

Noncompacted Left Ventricle in Association WithDysplastic Tricuspid Valve

Saibal Mukhopadhyay, Jamal Yusuf, Umamahesh C Rangasetty, Vijay TrehanDepartment of Cardiology, GB Pant Hospital, New Delhi

A 20-year-old normotensive female admitted with right-sided hemiparesis of acute onset due to a cerebral

infarct was referred from the neurology ward forechocardiography to rule out a cardiac source of embolism.Two-dimensional (2-D) echocardiography revealed anormal-shaped, nondilated left ventricle with prominent

Cardiovascular Images

Correspondence: Dr Jamal Yusuf, Department of Cardiology, GB PantHospital, New Delhi 110002

Fig. 1. Transthoracic four-chamber view showing prominent trabeculations withdeep recesses in the lateral wall (↑↑) of the left ventricle. The single arrow (↑)shows the thick, incompletely coapting septal and anterior tricuspid leaflets,and the enlarged right atrium.

Fig. 2. Short-axis view of the left ventricle at papillary muscle level showingthick, spongy endocardium and thin, compact epicardium.

Fig. 3. Color Doppler showing a laminar jet of severe tricuspid regurgitationacross the tricuspid valve.

Fig. 4. Continuous-wave Doppler revealing a peak velocity of the tricuspidregurgitant jet of 1 m/s.

trabeculations and deep intertrabecular recesses (Fig. 1,double arrow). The trabeculations were localizedpredominantly in the mid and apical segments of the leftventricular lateral, anterior and inferior walls. The ratio ofthe noncompacted to the compacted layer measured at end-systole was greater than 2:1 (Fig. 2). The affected segmentsrevealed hypokinesia, and the overall left ventricularejection fraction was 38%. On color Doppler echocardio-graphy, the deep intertrabecular recesses were seen fillingwith blood from the left ventricular cavity during diastole

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Indian Heart J 2003; 55: 382–383 Mukhopadhyay et al. Noncompacted LV With Dysplastic Tricuspid Valve 383

with reversed flow in systole. No thrombus could bedetected in the intertrabecular recesses. The mitral andaortic valves were normal. The right atrium was enlarged(Fig. 1) and the septal and anterior leaflets of the tricuspidvalve appeared thickened with incomplete coaptation insystole (Fig. 1, single arrow). There was no excessive apicaldisplacement of the septal leaflet as seen in Ebstein’sanomaly. Color Doppler echocardiography across thetricuspid valve revealed a laminar jet of severe tricuspidregurgitation (TR) (Fig. 3) with continuous-wave Dopplerrevealing a peak velocity of the regurgitant jet of 1 m/s(Fig. 4). Thus, a diagnosis of dysplastic tricuspid valve wasmade. The right ventricle and pulmonary valve werenormal.

Noncompacted myocardium has been frequentlyreported in patients with congenital left or right ventricularoutflow tract obstruction. In these patients with a “spongymyocardium”, the recesses represent “persisting sinusoids”that fail to regress during ontogenesis due to persistentpressure overload, and communicate with the coronaryarteries.1–3 In contrast, isolated ventricular noncompaction(IVNC) is considered a congenital anomaly due to the arrestof compaction of the loose myocardial meshwork duringfetal ontogenesis,4 when the intertrabecular recessescovered with endothelial cells are filled with blood from theventricular cavity without evidence of communication tothe epicardial coronary artery system.2,5 These recessespredispose to local thrombus formation but are often missedon echocardiography when associated with prominenttrabeculations.6

Noncompacted myocardium and tricuspid valvedysplasia as individual conditions are well described. Ourpatient had all the characteristic echocardiographicfeatures of left ventricular noncompaction as described byJenni et al.4 along with a coexistent congenital anomaly—tricuspid valve dysplasia—a combination not yet reported

in the literature, to the best of our knowledge. Earlydiagnosis of ventricular noncompaction and the correctmanagement of such patients is crucial, as the clinicalmorbidity includes heart failure, caused by progressiveventricular dysfunction, arrhythmias and systemic embolicevents.7

Our patient presented with asymptomatic leftventricular dysfunction detected incidentally onechocardiography, but there was no clinical evidence ofright ventricular systolic dysfunction. The patient was puton medical therapy with a combination of beta-blockersand ACE inhibitors (to arrest negative remodeling and theprogression of heart failure), and oral anticoagulants toprevent the formation of thrombi in the left ventricle.

References

1. Dusek A, Osadal B, Duskova M. Postnatal persistence of spongymyocardium with embryonic blood supply. Arch Pathol 1975; 99:312–317

2. Angelini A, Melacini P, Barbero F. Evolutionary persistence of spongymyocardium in humans [Abstr]. Circulation 1999; 99: 247S

3. Lauer RM, Fink RM, Petry EL, Dunn MI, Deihl AM. Angiographicdemonstration of intramyocardial sinusoids in pulmonary valveatresia with intact ventricular septum and hypoplastic right ventricle.N Engl J Med 1964; 271: 68–72

4. Jenni R, Oechslin E, Schneider J, Jost CA, Kaufmann PA.Echocardiographic and pathoanatomical characteristics of isolatedleft ventricular non-compaction: a step towards classification as adistinct cardiomyopathy. Heart 2001; 86: 666–671

5. Oechslin E, Jost CA, Rojas JR, Kaufmann PA, Jenni R. Long term followup of 34 adults with isolated left ventricular non-compaction: adistinct cardiomyopathy. J Am Coll Cardiol 2000; 36: 493–500

6. Boyd MT, Seward JB, Tajik AJ, Edward WD. Frequency and locationof prominent left ventricular trabeculations at autopsy in 474normal human hearts: implications for evaluation of mural thrombiby two-dimensional echocardiography. J Am Coll Cardiol 1987; 9:323–326

7. Ichida F, Hamamichi Y, Miyawaki T. Clinical features of isolated non-compaction of left ventricle. J Am Coll Cardiol 1999; 34: 233–240

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384 Letters to the Editor Indian Heart J 2003; 55: 384–385

The search for new risk factors that can satisfactorilyexplain the prevalence and severity of coronary heart

disease (CHD) has brought into focus the role of infections,particularly the association of Helicobacter pylori (H. pylori)Chlamydia pneumoniae (C. pneumoniae), and cytomegalo-virus with CHD.1 Although many such studies are availablefrom western countries, studies in the Indian context arelacking. Identification of a causal linkage of any kind ofinfection with CHD can lead to timely intervention withantibiotics, which may decrease the disease burden.

One hundred and seventeen angiographically provenpatients (35–79 years of age) with unstable angina (UA),and 16 patients with chronic stable angina (CSA) werematched with 90 healthy blood donors (20–60 years ofage) free from clinical CHD confirmed by 12-lead restingECG. Fasting serum samples were drawn from these healthycontrols and patients. C. pneumoniae and H. pylori-specificIgG was detected by the ELISA technique.

A total of 59 (58%), 9 (56%), and 48 subjects (53%)were seropositive for H. pylori in the UA, CSA, and controlgroups, respectively. The number of subjects seropositivefor C. pneumoniae in the UA, CSA, and control groups were67 (66%), 15 (94%), and 73(81%), respectively. Nosignificant statistical difference in seropositivity was found

Seropositivity of Chlamydiapneumoniae and Helicobacter pyloriAmong Coronary Heart DiseasePatients and Normal Individuals ina South Indian Population

between the study group and the controls, either for H.pylori or for C. pneumoniae. The prevalence of H. pylorireported in our study is within the range reported in studiesfrom India (40%–74%).2 There has been no report on theseropositivity of C. pneumoniae from India till date. Our studyshowed a high prevalence of C. pneumoniae (70.1% inpatients, and 81% in controls), which is in agreement withthe normal Chinese population (61.5%).3

It has been postulated that in countries with poorsocioeconomic conditions, there may be a link betweenCHD and some undefined environmental exposures,including infections. It is possible that cardiovascular riskincreases with cumulative or earlier exposure to morepathogens or specific potentially atherogenic microbes.4

References

1. Danesh J, Collins R, Peto R. Chronic infections and coronary heartdisease: is there a link? Lancet 1997; 350: 430–436

2. Kate V, Ananthakrishnan N, Ratnakar C, Badrinath S. Anti H. pyloriIgG seroprevalence rates in asymptomatic children and adults fromSouth India. Indian J Med Microbiol 2000; 19: 73–78

3. Ni AP, Lin GY, Yang L, He HY, Huang CW, Liu ZJ, et al. A seroepi-demiologic study of Chlamydia pneumoniae, Chlamydia tranchomatisand Chlamydia psittaci in different populations on the mainland ofChina. Scand J Infect Dis 1996; 28: 553–557

4. Taylor C. Workshop on emerging issues in microbial infections andcardiovascular diseases, October 1998. NIAID Council News 1999;8: 5

Abhijit Chaudhury, D Rajasekhar, SAA Latheef,G Subramanyam

Departments of Microbiology and CardiologySri Venkateswara Institute of Medical Sciences, Tirupati

Letters to the Editor

Letter-to-Editors.p65 11/19/2003, 11:28 PM384

Indian Heart J 2003; 55: 384–385 Letters to the Editor 385

Delayed Tamponade Following theSudden Braking of a SpeedingVehicle

Motor vehicle accidents often cause blunt cardiactrauma with pericardial hemorrhage and rapid

tamponade.1 We describe a patient who presented withbleeding, not to the emergency services, but to thecardiologist.

A 63-year-old hypertensive male on beta-blockerspresented with a 3-day history of dyspnea on exertion andprofound weakness. His symptoms started 1 day after thesudden braking of his car while he was travelling in theback seat without a seat belt. He reported having protectedhimself by holding onto the seat in front of him, and deniedimpact to the chest. He was well for a few hours butdeveloped pain in the back of the neck the same night. Overthe next 3 days, he developed progressive weakness anddyspnea. On examination, his pulse rate was 80 bpm (onatenolol) and the blood pressure 140/90 mmHg with apulsus paradoxus of 10 mmHg. The jugular venouspressure was elevated to 15 mmHg and heart sounds werefaint. The ECG showed a relative decrease in the QRSvoltages compared to the previous recording. A chest X-ray showed an enlarged cardiac silhouette with acardiothoracic ratio of 70%.

The patient's hemoglobin level was 12 g%; it had been14.5 g% during a routine health checkup 3 months earlier.Serum transminases and alkaline phosphatase wereelevated three-fold, as is common in subacute tamponade.

The troponin T concentration was normal (<0.01 ng/ml).Echocardiography revealed a moderate-size pericardialeffusion with collapse of the right atrium, and exaggeratedrespiratory variation in the tricuspid and mitral Dopplerflow velocities. The patient underwent a therapeutictapping of the pericardial fluid. Seven hundred and twentyml of bloody fluid was aspirated via the subxiphoidapproach and a pigtail catheter left inside for 24 hours.There was no recurrence of effusion, and the patient madean uneventful recovery. The fluid had a hemoglobin contentof 10 g%, was sterile on culture and had no malignant cells.The patient was doing well on follow-up at 6 months.

We believe that the bleeding resulted from an injurycaused by the sudden deceleration of the car.2 Subacutetraumatic pericardial bleeds should be managed andfollowed up like other cases of pericardial hemorrhage,including long-term follow-up for the development ofconstrictive pericarditis.2

References

1. Rashid MA, Wikstrom T, Ortenwall P. Cardiac injuries: a ten-yearexperience. Eur J Surg 2000; 166: 18–21

2. Karmy-Jones R, Yen T, Cornejo C. Pericarditis after trauma resultingin delayed cardiac tamponade. Ann Thorac Surg 2000; 74: 239–241

Rajiv Bajaj, Harbans Singh WasirDepartment of Cardiology

Batra HospitalNew Delhi

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386 Selected Summaries Indian Heart J 2003; 55: 386–389Selected Summaries

Comparison of Carvedilol and Metoprolol on Clinical Outcomes inPatients With Heart Failure in the Carvedilol or Metoprolol

European Trial (COMET): Randomized Controlled Trial

PA Poole-Wilson et al. COMET Investigators. Lancet 2003; 362: 7–13

Summary

COMET was a multicenter, randomized, double-blind,parallel-group trial comparing the effects of carvedilol andmetoprolol on the clinical outcome of patients with chronicheart failure (CHF). The study involved 3029 patients from341 centers in 15 European countries. Symptomatic NYHAclasses II–IV (<5% were class IV) CHF patients receivingboth angiotensin-converting enzyme inhibitors (ACE-I) anddiuretics for at least 2 weeks were included in the study. Allof them had left ventricular (LV) systolic dysfunction asevidenced by ejection fraction (EF) <35% or left ventricularend-diastolic dimension (LV-EDD) >6 cm, and fractionalshortening (FS) <20%. Patients with an unstable medicalcondition, uncontrolled hypertension or recent change intreatment were excluded from the study. Carvedilol (1511patients) was started at 3.125 mg twice daily, and doubledevery 2 weeks to achieve a target dose of 25 mg twice daily.Metoprolol was started at 5 mg twice daily, and stepped upto 50 mg twice daily. The patients were followed up for amean duration of 58±6 months. The baselinecharacteristics were similar in both the groups. The meanage was 62±11 years, one-fifth were female, mean durationof CHF was >40 months, and more than 50% had anischemic etiology. The mean EF was 26%±7%. About 60%of patients were receiving digitalis but very few patientswere receiving angiotensin receptor blockers (ARBs). Theprimary end-point of the study was all-cause mortality.Later, a composite end-point of all-cause mortality or all,cause admission was admitted as a second primary end-point in recognition of its importance, after publication ofthe findings of the MERIT-HF study. The all-cause mortalitywas 17% lower with carvedilol (34% v. 40%; 95% Cl: 0.74–0.93, p=0.0017). The survival advantage was apparentwithin 6 months, and was consistent among all thesubgroups. The composite end-point was also 6% lower inthe carvedilol group, though this was statisticallynonsignificant (74% v. 76%; 95% CI: 0.86–1.02, p=0.122).Sudden cardiac death was the most common mode ofdeath, accounting for 43% of deaths in the carvedilol group,and 44% in the metoprolol group. Circulatory heart failurecontributed to one-third of deaths in both the groups.Three-fourth of the patients in the carvedilol arm reachedthe target dose (mean dose 41.8±14.6 mg), whereas 78%achieved the target dose in the metoprolol group (meandose achieved 85±28.9 mg). However, the reduction inheart rate was greater in the carvedilol group (13.3 beats/min v. 11.7 beats/min; 95% CI: 2.7 to –0.6). The incidenceof side-effects and drug withdrawals (32%) were similar inboth the groups. The authors concluded that carvedilolextends a survival advantage vis-a-vis metoprolol inpatients with symptomatic CHF.

Comments

In patients with symptomatic CHF, the aims of treatmentare two-fold. The first and foremost is to relieve symptomsand second, even more important than the first, is toimprove survival. While diuretics and digoxin are wellknown for the symptom relief they provide in CHF, theyconfer very little, if any, survival advantage. In this context,the only drugs that improve survival are ACE-I, beta-blockers, aldosterone antagonists, and ARBs. However, thebenefit achieved by a combination of these renin–angiotensin–aldosterone system (RAAS) modifying drugsis still controversial. For instance, the VAL-HEFT studyshowed that while a combination of ACE-I with ARB, orbeta-blocker (BB) with ARB was beneficial, the combinationof all three agents (ACE-I + BB + ARB) is actuallydetrimental. The second issue has been the actual drugused. Among the beta-blockers, carvedilol (COPERNICUS,CHRISTMAS, CAPRICORN), metoprolol (MDC, MERIT-HF),and bisoprolol (CIBIS I and II) have all been shown to beuseful. However, which of these beta-blockers, if any, ismore beneficial is still uncertain. Theoretically, metoprololand bisoprolol are both β

1- selective, and should therefore

be more effective. Carvedilol is not only β1- and β

2-active,

but also blocks the α1-adrenergic receptors. However,

carvedilol has several other mechanisms by which it canbe useful in patients with CHF. It increases insulinsensitivity, and has potent antioxidant action, therebyimproving endothelial dysfunction and reducing apoptosis.Indeed, a recent meta-analysis has suggested that the useof carvedilol led to a greater improvement in EF (one of theprime mechanisms for improvement of survival) ascompared to metoprolol. The COMET trial is the first largestudy to compare these two drugs head-on. This studysuggests that carvedilol is superior to metoprolol not onlyin reducing the combined rate of mortality and hospitaladmission but, more importantly, in improving survival (asmuch as 17% over a 5-year period). However, this study isnot without limitations. The mean dose of metoprolol, i.e.85 mg, is much lower than that achieved in the MERIT-HFstudy (>162 mg). Secondly, the salt of metoprolol, i.e.metoprolol tartarate, is also different from metoprololsuccinate (metoprolol CR/XL) used in the MERIT-HF study.Some studies have shown that the tartarate salt may haveat least 30%–35% reduced bioavailability as compared tothe succinate salt. Indeed, the reduction in heart rate andblood pressure was higher in the carvedilol arm, perhapsreflecting inadequate dosage in the metoprolol arm.Another important limitation of the study was that follow-up EF values were not obtained.

IHJ-Selected Summary.p65 11/19/2003, 11:27 PM386

Indian Heart J 2003; 55: 386–389 Selected Summaries 387

Summary

EUROPA was a randomized, double-blind, placebo-controlled, largest-ever trial of the angiotensin-convertingenzyme inhibitor (ACE-I) perindopril, evaluating thereduction of cardiac events in low-risk patients with provencoronary artery disease (CAD) but with no evidence of CHF.It enrolled 13 655 patients ≥18 years of age, anddocumented CAD as evidenced by previous MI, coronaryrevascularization, angiographically proven CAD (>70%stenosis) or positive stress test in men. Patients withevidence of CHF, hypotension/uncontrolled hypertensionor due for PCI, recent use of ACE-I or angiotensin receptorblockers (ARBs), renal insufficiency or elevated serumpotassium (>5.5 mmol/L) were excluded from the study.The primary end-point was combined CVS mortality +nonfatal AMI + survival of sudden cardiac death (SCD).Patients initially received 4 mg perindopril for 4 weeks,increased to 8 mg for another 4 weeks. Patients were thenrandomized to receive either 8 mg perindopril or a placebofor at least 3 years, the dose being reduced to 4 mg if it wasnot tolerated. The mean follow-up was 4.2 years. Overall,baseline characteristics were similar in both the groups. Themean age was 60±9 years, and 85% were male. They weregenerally low-risk CAD patients, 92% on platelet inhibitors,62% on beta-blockers, and 48% on statins. Perindoprilsignificantly reduced the combined end-point from 9.9%in the placebo group to 8% (RR 20%, p=0.0003). Thebeneficial effect became apparent at 1 year of treatment,and was seen in all the sub-groups. Perindopril use wasassociated with a reduction in all the secondary end-pointsas well. Total mortality reduced by 11% (ns), MI decreasedby 23.9% (p=0.001), and CHF decreased by 39.2%(p=0.002). About 50 patients needed to be treated withperindopril over 4 years to prevent one major CVS event,and this benefit was over and above the medications alreadybeing used.

Comments

The HOPE study has already established the role of ACE-I,especially ramipril, in patients with high-risk CAD. In theEUROPA study, perindopril was chosen because of itsantiischemic and antiatherogenic effects, its Effects oncardiovascular remodeling, and its blood pressure-loweringeffect. The baseline characteristics of the EUROPA studywere different from those of the HOPE study. In the HOPE

Efficacy of Perindopril in Reduction of Cardiovascular Events Among Patients WithStable Coronary Artery Disease: Randomized, Double-Blind, Placebo-Controlled,

Multicenter Trial (the EUROPA Study)

KM Fox et al. The EUROPA Trial Investigators. Lancet 2003; 362: 782–788

study, all the patients were >55 years, whereas in theEUROPA study, at least one-third of patients were <55years. In addition, more HOPE patients had diabetesmellitus, hypertension, stroke, and obstructive peripheralvascular disease. This difference is well reflected in theplacebo event rates, where the total mortality in the HOPEstudy versus the EUROPA study was 12.2% v. 7.4%; CVSmortality 8.1% v. 4.4%, and Q wave MI 3.2% v. 2.1%. Withthis background, the results of the EUROPA study were evenmore remarkable and, indeed, may appear to extend theindication of ACE-I to even low-risk CAD patients. However,if we look carefully, even the CAD patients enrolled in thetwo studies were different. In the HOPE trial, only aboutone-third of the patients were post-MI, whereas in theEUROPA trial, nearly two-thirds were post-MI. The role ofACE-I in post-MI is already well established. If we considersubgroup analysis, the benefit in the non-MI patients wasnot statistically significant in the EUROPA study. In otherwords, perindopril is effective in only those patients whohave suffered a prior MI. Thus, these results cannot bedirectly extrapolated to the garden variety of CAD patients;rather, they are more applicable to the post-MI population.Furthermore, another important limitation of the EUROPAstudy is that the ejection fraction was not considered. Sincemost patients in the EUROPA study were post-MI, it is likelythat the mean ejection fraction in this study would be low.The role of ACE-I in patients with a low ejection fraction isagain well established. It can be argued that the effect ofperindopril could be due to its antihypertensive effect.However, the BP reduction was small, 5/2 mmHg, whichcould not account for the large reduction in CVS events. Tobetter understand the mechanism of CVS event reduction,5 substudies of EUROPA are under way. The PERTINENTstudy is evaluating the predictive value of several plasmaand serum markers associated with atherosclerosis, and theeffect of perindopril on these levels. The PERFECT studywill measure blood flow in the brachial artery using B-modeimaging. The PERSPECTIVE study aims to investigate theeffects of perindopril on progression and regression indiabetics, and the PERGENE study will geneticallycharacterize the EUROPA population. The results of thesestudies are expected within a year. Another interestingpoint that has emerged from the EUROPA study is thatmortality reduction was superior in the subgroup ofpatients on beta-blockers. The reduction of events inpatients not on beta-blockers was statistically insignificant.Further studies will be required to clarify this concept.


388 Selected Summaries Indian Heart J 2003; 55: 386–389

Beneficial Effect of Immediate Stenting After Thrombolysisin Acute Myocardial Infarction

B Scheller et al. SIAM III study group. J Am Coll Cardiol 2003; 42: 634–641

Summary

The Southwest German Interventional Study in Acute MyocardialInfarction (SIAM III) study is a multicenter, randomized,prospective, controlled trial in which immediate stenting after fullthrombolysis was compared with the conservative approach ofdelayed stenting after 2 weeks in patients presenting with acuteSTEMI. The study included patients presenting within 12 hoursof the onset of symptoms with diagnostic electrocardiograms whohad no contraindication to thrombolysis. Angiographic inclusioncriteria were an infarct-related coronary artery >2.5 mm,diameter stenosis of at least 70% or TIMI flow <grade 3. Patientswere recruited from community hospitals located within 34 kmof an interventional center. Reteplase was administered in 2boluses of 10 IU 30 min apart. Patients also received 250 mgaspirin IV, and a bolus of 5000 IU heparin, followed by an infusionadjusted to maintain an activated partial thromboplastin time of50 to 70 ms. During thrombolysis, the patients were randomizedto either immediate or elective stenting. Patients randomized toimmediate stenting were shifted to interventional centers within6 hours where the infarct-related artery was stented; 2 weeks later,a repeat angiography was performed. The second groupunderwent elective angiography and stenting performed at 2weeks. Patients in both the groups were clinically followed up atregular intervals, and repeat angiography was scheduled at 6months. A total of 163 patients were included in the study. GroupI (immediate stenting group) had a significant reduction in thecombined end-point of ischemic events, death, reinfarction, andtarget lesion revascularization at 6 months (25.6% v. 50.6%,p=0.001). This beneficial effect was largely driven by a reductionin recurrent ischemic events (4.9% v. 28.4%, p=0.01). On anintention-to-treat basis, immediate stenting was also associatedwith a reduction in the 6-month combined end-point of death,reinfarction, and target vessel revascularization (27.7% v. 39.8%,p=0.049). Patients with stenting showed an improvement in LVfunction at 2 weeks with further improvement at 6 months,whereas the delayed stenting group (group II) showed nostatistically significant improvement in LV function. Majorbleeding complications occurred in 9.8% of patients whounderwent immediate stenting versus 7.4% in the delayed stentinggroup (p=0.374). There were 5 deaths in group II within 48 hoursof thrombolysis, whereas all the patients in group I survived theacute phase. Immediate stenting after thrombolysis is significantlymore beneficial compared to delayed stenting.

Comments

Thrombolysis results in TIMI-3 flow in only 60% of patients withacute MI. Moreover, around a third of those thrombolyzed haverecurrent ischemia. Numerous studies have shown that primaryPCI is superior to pharmacologic thrombolysis with higherreperfusion rates, and improved event-free survival. The maindrawback remains the immediate availability of centers with thefacility for PCI. Hence, in a real-world situation, a considerabletime delay is usually encountered in transportation of the patient,and mobilization of appropriate resources. As we are aware, time

is all-important in salvage of the myocardium. The ACC/AHArecommends a door-to-balloon time of 90±30 min, but in a day-to-day situation, this is usually not possible. In the NationalRegistry of Myocardial Infarction (NRMI), there was a mediantreatment time delay of >2 hours in almost 90% of patients. Inthe recently published results of the DANAMI-2 study, there wasa lower composite end-point of death, MI or stroke at 30 days inpatients who were transferred from community hospitals totertiary care centers with intervention facilities, compared withpatients receiving on-site thrombolysis (8.5% v. 14.2%, p=0.002).A similar benefit has been seen in the PRAGUE study, as well asthe AIR-PAMI study. Though these trials have shown that the timedelay in PCI is offset by the superiority of the results of angioplastyover thrombolysis, the door-to-balloon time remains important.In the NRMI registry, a door-to-balloon time >2 hours wasassociated with an increase in mortality. Numerous fibrinolysistrials have shown that the time from the onset of symptoms tovessel recanalization is a predictor of myocardial salvage andsurvival. Given the lack of widespread availability of PCI centers,alternative approaches with a combination of pharmacologic andmechanical revascularization methods are being tried. Therationale behind facilitated PCI was to improve outcomes byattempting to achieve earlier reperfusion while awaiting definitiveintervention at a center with PCI facility. This combinationapproach is an attempt to buy time, and widen the therapeuticwindow for revascularization. Moreover, patients have a betterTIMI flow grade and lesser thrombus burden, thus reducing thechances of microvascular embolization, improving lesion focus,and improving the overall results. However, earlier attempts withthis complementary therapy were not encouraging. Data from theThrombolysis and Angioplasty in Myocardial Infarction (TAMI-1) study, and the European Cooperative study group showed nobenefit in survival or ventricular function, and were in factassociated with a higher complication rate. However, thedevelopment of bolus thrombolytics with enhanced fibrinsensitivity, and excellent safety and efficacy profiles, along withimprovement in PCI hardware, including thrombectomy anddistal protection devices, have led to a resurgence in the use offacilitated PCI.

In this trial, the time to angiography was 6.7 hours, exceedingthe currently recommended time. But the setting was a real-worldsituation that would be commonly encountered in practice. In theSIAM III study, over 60% of patients in the immediate stentinggroup had TIMI-3 flow; this figure increased to 98%. Thistranslated into an improved LV function at 2 weeks and 6 months.Despite the long time taken till intervention, there was a clearbenefit, and no increase in the complication rates. In conclusion,this trial has proved the relative superiority of thrombolysisfollowed by immediate stenting, despite the time involved intransfer to the tertiary care center. The use of Gp IIb/IIIaantagonists would further improve the outcome of immediatestenting. In conclusion, immediate stenting after thrombolysis issafe, and improves event-free survival as well as ventricularfunction compared with elective stenting at 2 weeks following MI.


Indian Heart J 2003; 55: 386–389 Selected Summaries 389

Summary

The SIRIUS investigators conducted a randomized double-blind trial in 1058 patients with a newly diagnosed singlelesion in a native coronary artery, comparing a sirolimus-eluting stent with a standard stent. Although previous trialshave shown a reduction in restenosis rates with sirolimusstents, the patients enrolled were at a lower risk forrestenosis with discrete lesions. This study enrolled patientswith more challenging coronary lesions with the majority(56%) having class B

2 or C lesions (ACC/AHA classi-

fication). The average vessel diameter was 2.8 mm, and themean lesion length was 14.4 mm. There were 533 patientsin the sirolimus stent group, and 525 in the standard stentgroup. The groups were well matched with respect todemographical characteristics, cardiac risk profile,symptomatology, lesion anatomy, and procedural factor.Follow-up angiography (performed in around 85% ofpatients in both groups) showed that the minimal luminaldiameter stenosis, and the late lumen loss in the in-stentzone as well as the in-segment zone were significantly(p=0.001) better in the sirolimus stent group.

There was a higher rate of in-stent restenosis and in-segment stenosis (35.4% and 36.3%, respectively) in thestandard stent group compared with the medicated stentgroup (3.2% and 8.9%, respectively). Intravascularultrasound revealed a reduced neointimal volume in thein-stent zone (4.4 mm3 v. 57.6 mm3, p<0.001). Theprimary end-point of target vessel failure rate (compositeof death from cardiac causes, myocardial infarction, andrepeat revascularization) within 270 days was reduced by58% with sirolimus stents (110 patients v. 56 patients,p<0.001). This reduction was driven largely by a decreasein the frequency of the need for revascularization of thetarget vessel (16.6% v. 4.1%, p<0.001)). Diabetes wassignificantly associated with an increased risk of restenosisalong with reference vessel diameter and lesion length.However, sirolimus stents showed a consistent benefit evenin these high-risk subgroups as compared with standardstents.

Comments

Sirolimus (rapamycin) is a macrolide antifungal withpowerful immunosuppressant properties; it inhibits severalregulators of cell-cycle progression, and the migration ofvascular smooth muscle cells. This unique property led toits use in coronary artery stents to prevent neointimalproliferation. The Randomized Study with the SirolimusEluting Bx Velocity Balloon Expandable Stent (RAVEL)showed a significant reduction in the frequency of in-stentrestenosis (from 26.6% to 0%). The present study enrolledpatients with a higher frequency of cardiac risk factors,such as diabetes and hypercholesterolemia, more complexmorphology, and longer lesions. In the RAVEL study, therewere no type C lesions, and the mean lesion length was9.58±3.25 mm compared with 14.4±5.8 mm in thepresent study. Similarly, only 19% of the patients haddiabetes and 40% dyslipidemia compared with 26% and74% in this study, respectively. Intravascular ultrasoundrevealed a 92% reduction in neointimal volume, a 77%reduction in the rate of target lesion revascularization, andan 85% reduction in the rate of non-QMI. The highfrequency of in-segment restenosis compared to in-stentrestenosis (8.9% v. 3.2%) in the sirolimus stent group wasdue to a higher rate of restenosis at the proximal marginof the stent, and is attributed to balloon injury to the vesselprior to stent deployment. The authors recommend the useof shorter balloons and longer stents that would have noexposed balloon-injured area. The restenotic lesions werefocal compared with diffuse disease with standard stents,and hence more amenable to complex balloon angioplasty.The encouraging results from the trial suggest that specialstents may maintain their superiority over standard stentsin a diverse patient population. As sirolimus-coated stentsmove into general use, and with a longer follow-up, it islikely that the rate of restenosis will be higher. This trialhas shown the beneficial effect of sirolimus-coated stentsin a population at a higher risk, and with more complexdisease than previous studies.

Sirolimus-Eluting Stents Versus Standard Stents in PatientsWith Stenosis in a Native Coronary Artery

Moses et al. SIRIUS Investigators. N Engl J Med 2003; 349: 1315–1323


Calendar of Conferences Indian Heart J 2003; 55: 390

November 14–15, 2003, 4th Annual Conference ofNuclear Cardiological Society of India, Vellore, IndiaContact: Organizing Secretary

Department of Nuclear MedicineChristian Medical CollegeVellore, Tamil Nadu, IndiaFax: 0416 2232103e-mail: [email protected]

December 4–7, 2003, 55th Annual Conference ofCardiological Society of India, Kolkata, IndiaContact: Dr Asok Kumar Kar, Organizing Secretary

Indian Heart HouseP-60, CIT Road, Scheme VIIM,Kankurgachi, Kolkata 700054, IndiaFax: 033 355 6308e-mail: [email protected]

January 9–11, 2004, Joint Meeting of InternationalSociety for Heart Research and InternationalAcademy of Cardiovascular Sciences, Lucknow, IndiaContact: Professor VK Puri, Organizing Secretary

Department of CardiologyCSM Medical UniversityLucknow, IndiaFax: 0522 225 5830e-mail: [email protected]

May 6–9, 2004, 4th Congress of the Asian PacificSociety of Atherosclerosis and Vascular Disease, Bali,IndonesiaContact: Dr Slamet Suyono, MD

Pacto Convex Ltd, Lagoon Tower Level B-1Jagarta Hilton InternationalJI Gatot Subroto, Jakarta 10270, IndonesiaFax: 62 21 5705798e-mail: [email protected]

November 7–10, 2004, 77th Scientific Session,American Heart Association (AHA), New Orleans,Louisiana, USAContact: American Heart Association

7320 Greenville AvenueDallas TX 75231, USATel: 1 214 373 6300Fax: 1 214 373 3406

November 26–28, 2004, 3rd International Congresson Cardiovascular Disease, Taipei, TaiwanContact: Dr CE Chiang

Taiwan Society of Cardiology7F, No. 27, Min-Chuan, West RoadTaipei 104, TaiwanFax: 886 2 25076180e-mail: [email protected]; [email protected]

November 28–30, 2004, 10th World Congress onClinical Nutrition, ThailandContact: Dr Buncha Ooraikul

or Dr Tapan Basu, Department of Food Scienceand Nutrition, University of Alberta, EdmontonCanada T6G 2MFax: 403 4924821e-mail: [email protected]

May 21–25 2005, 4th International Conference onPreventive Cardiology, Foz do Iguassu, BrazilContact: Dr Mario Maranhao, Chairman, Congress

Internationales SA/Lidy Groot Congress EventsP.O. Box 83005 1080, AA AmsterdamThe NetherlandsFax: 3120 6758236e-mail: [email protected]

Cal of Conference.p65 11/19/2003, 11:22 PM390

Chronic Constrictive Pericarditis: Pending Issues

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