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Cardiology TODAY

VOLUME XXI No. 5SEPTEMBER-OCTOBER 2017

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EDITORIAL

Generic Medicines – A Cause for Concern ? 172OP YADAVA

REVIEW ARTICLEEndothelial Cell Dysfunction (ECD) Modulation by Diet, Exercise and Drugs 174GS SAINANI, RAJESH SAINANI

REVIEW ARTICLEFrom Irregular Pulse to Slurring of the Speech: Echocardiographic AF Evaluation: Relevant at all Stages 180SHRADDHA RANJAN, MANISH BANSAL, RAVI R KASLIWAL, H K CHOPRA

REVIEW ARTICLEArrhythmias in Acute Coronary Syndrome: Etiopathogenesis and Management 189CHANDRA BHAN MEENA, DAULAT SINGH MEENA

Cardiology Today VOL.XXI NO. 5 SEPTEMBER-OCTOBER 2017 169

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IMAGEEchocardiography of Hypertrophic Cardiomyopathy 197SR MITTAL

ECG OF THE MONTHST Segment Elevation 203SR MITTAL

PICTORIAL CMEDouble Orifice Mitral Valve 211MONIKA MAHESHWARI

170 Cardiology Today VOL. XXI NO. 5 SEPTEMBER-OCTOBER 2017


Generic Medicines – A Cause for Concern ?

EDITORIAL

DR. OP YADAVACEO and Chief Cardiac Surgeon

National Heart Institute,New Delhi


REFERENCE1. Leclerc J, Blais C, Rochette L, Hamel D, Guenette L, Poirier P. Impact of the commercialization of three generic Angiotensin

II Receptor Blockers on adverse events in Quebec, Canada: A population based time series analysis. Circ Cardiovasc Qual Outcomes 2017. October 01;10(10) e003891.


Endothelial Cell Dysfunction (ECD) Modulation by Diet, Exercise and Drugs

REVIEW ARTICLE

GS SAINANI, RAJESH SAINANIKeywordsendotheliumantioxidant vitaminshyperhomocysteinemiamediterranean dietnebivolol

Dr. GS Sainani is Emeritus Director, Dept of General Medicine Dr. Rajesh Sainani is Consultant Gastroenterologist, Jaslok Hospital & Research Centre, Mumbai, Maharashtra

Abstract

through continuous modulation of vascular tone. This is primarily accomplished by balanced release of endothelial relaxing and contractile factors. The healthy endothelial cells are essential for maintenance of vascular homeostasis involving antioxidant, anti-

effects. Oppositely, endothelial dysfunction is primarily characterized by impaired regulation of vascular tone as a result of reduced endothelial nitric oxide (NO) synthase activity, lack of cofactors for NO synthesis, attenuated NO release, or increased NO degradation.

approaches in improving/reversal of endothelial dysfunction for improving endothelial dysfunction in different pathological conditions.

INTRODUCTIONOver last some decades, endothelium has assumed a vital role. Earlier endothelium was considered to be a smooth, intact non-thrombogenic lining of the arterial walls. But now it is clear that endothelium produces several vasoactive substances which regulate vascular tone and structure. The endothelium is now considered as the largest endocrine organ. The endothelial factors that help to regulate vasomotion are divided into two groups–endothelial derived relaxing

factors (EDRF) and endothelial derived constricting factors (EDCF). Endothelial derived relaxing factors include nitric oxide (NO) and prostacyclin (PG2) and endothelial derived constricting factors include endothelin 1 (ET1) and thromboxane A2 (TxA2). These factors

vascular structure as shown in Figure 1.

Our aim should be to maintain smooth endothelial lining (Figure 2) by proper diet, exercise and healthy lifestyle.


Nitric oxide (NO) has been the most important molecule which is the key vasodilator and endothelin (ET-1) is the key vaso constrictor.

Endothelial cells regulate the homeostasis of the arterial wall. Healthy endothelium is not leaky, not sticky and is able to relax. Risk factors such as hypertension, diabetes mellitus dyslipidemia, smoking causes endothelial cell dysfunction. Damaged endothelium is leaky, sticky and unable to relax.

DIETARY FACTORS WHICH MODULATE ECD:(1) Long-chain n-3 fatty acids. (Omega-3 fatty acids) (2) Fatty acids (3) Anti-oxidant vitamins (4) Folic acid and vitamin B12 (5) L-arginine (6) Soya proteins (7) Mediterranean diet.

1) Intake of n-3 fatty acids and risk of CV disease Cardiovascular disease (CVD) is uncommon in populations with a very

Native Americans,1 Greenland Eskimos23 which

atherosclerosis.

Prospective cohort studies assessed the

populations concluded that consumption

disease (CHD).4

Effects of n-3 fatty acids on endothelial functionThere is growing evidence regarding the

5

Overall experimental studies showed that n-fatty acids particularly DHA, decrease expression of VCAM-1 on the vascular endothelium and decrease leukocyte rolling and adhesion to the endothelium. In an interesting ex-vivo study,6 hypercholesterolemic patients and control subjects received either

3 months. Before and after 3 months of supplementation, a sample of skin and gluteal fat was biopsied, small

arterial segments were removed and vasodilation was assessed in response to acetylcholine (endothelium dependent) and nitroprusside (endothelium independent). Peripheral small arteries of the hypercholesterolemic patients

endothelium dependent relaxation after

those from the control subjects.

fatty acid supplementation on endothelium dependent vasomotor function. In one study, Fleischhauer et al.,7 assessed the

EPA plus DHA on endothelium dependent vasodilator responses of coronary arteries to intracoronary acetylcholine infusion in heart transplant recipients.7 After 3 weeks of treatment, patients treated

response to normal levels, whereas control patients showed vasoconstrictor response. In another study, Goodfellow et al.,8 randomly assigned 30 hypercholesterolemic subjects to a treatment group with n-3 fatty acids at a dosage of 4g/dL or to a placebo group.8 At baseline hypercholesterolemic patients showed impaired endothelium-dependent vasodilation compared with healthy subjects. After 4 months of treatment, the patients supplemented with n-3 fatty acids

dependent vasodilation compared with control subjects.

2) Fatty acidsVogel et al.,9 showed that high fat meal containing predominantly saturated and trans fatty acids induced acute decrease

correlated with the postprandial elevation of triglyceride rich lipoproteins in the plasma.9 The chronic consumption of low fat diets and mediterranean-style diets improve endothelial function compared to a high fat western type diet.10

In conclusion, with the exception of n-3 fatty acids, acute or chronic high-fat meals

function. This function is improved by the simultaneous administration of

Figure 1. Factors produced by the endothelium balancing in healthy person

Figure 2. Normal vascular endothelium with smooth non thrombotic luminal surface


natural antioxidants such as red wine,

these fatty acids in endothelial function and cardiovascular disease prevention.

3) Antioxidant vitaminsThere is enough epidemiologic evidence linking intake of antioxidant vitamins particularly vitamin E, vitamin C with reduced risk of coronary artery disease. The Nurses Health Study11 and the Professionals Follow up Study12showed that vitamin E consumption caused reduction in risk of CHD. Kenkt et al13 reported an inverse association between dietary vitamin E intake and coronary mortality in healthy persons. The Iowa women’s study showed that dietary vitamin E intake as opposed to supplemental vitamin was inversely associated with risk of death from CHD.14 Losonczy et al15 found a reduced risk of all-cause mortality and coronary artery disease mortality with increased vitamin E intake (including dietary and supplements). They also found that supplementation with both vitamin E and C further reduced the risk suggesting a

Experimental studies have shown that anti-oxidants improve endothelium dependent vasodilation16 after incubation with antioxidants. In addition to invitro evidence, there is enough clinical

anti-oxidants on endothelial function.

Apart from vitamin E, vitamin C

polyphenols containing foods such as red wine, tea, onions, garlic, apple and other fruits also have anti-oxidant properties as their intake is associated with reduced CV risk. Short and long-term black/green tea consumption reverses endothelial dysfunction in CAD patients.

4) Folic acid and vitamin B12Several epidemiologic studies examined the association between folate intake and CVD. The Nurse’s Health Study17which included 80082 women who were followed up for 14 years, folate intake

Chee and Stamler18inverse association between folate intake and mortality from all causes and CVD in 6426 men from the Multiple Risk Factor Intervention Trial (MRFIT) usual care group. The primary mechanism for

plasma homocysteine which causes endothelial cell dysfunction.19 Woo et al20 showed that 10 mgm folic acid

vasodilation in 17 healthy persons with relative hyperhomocysteinemia. The

mediated vasodilation in healthy persons or patients with hyperhomocystinemia.

of folic acid and by other mechanisms such as anti-oxidant properties and direct NO production.21 Folate and vitamin B12 improved insulin resistance and ECD along with lowering of homocysteine.

5) L-arginine There are several reports of L-arginine

function. Taken together, the results of

of L-arginine on endothelial function in patients with hypercholesterolemia or existing coronary artery disease. In several large epidemiologic studies, a high consumption of nuts (high arginine content) was associated with

22 In patients with CAD, most studies have shown that L-arginine improves both endothelium dependent vasodilation and abnormal interactions of vascular cells, platelets and monocytes.23 L-arginine

dyslipidemia or cigarette smoking.

6) Soya ProteinDietary soya protein has several

reduction of cholesterol and triglycerides concentrations.24 In addition soy protein has anti-oxidant properties.24 These

genistein. In vitro studies showed that genistein relaxes rat arteries by a NO-dependent mechanism, thus suggesting

7) Mediterranean diet, life style factors, and 10 year mortality in elderly European men and women. The HALE PROJECT25Mediterranean diet, moderate alcohol consumption, moderate to high physical activity levels, non-smoking were associated with lower mortality rates from all causes, CHD, CVD, cancer and other causes during the 10 year follow up.

One may conclude that diet rich in fats, red and processed meats, sweets, desserts,

endothelial cell dysfunction. Whereas diet rich in fruits, vegetables, legumes,

folic acid, soya protein and anti-oxidants (vitamins C, E, Beta carotene, leutin,

green tea, almonds, walnuts improve endothelial cell function.

EXERCISE AND ENDOTHELIAL FUNCTIONAerobic exercise, one of life style

morbidity and mortality. Exercise training improves endothelial function in animal models of hypertension and in patients with essential hypertension.

dysfunction in hypertension is reversible. Exercise increases NO production and decrease NO inactivation, leading to an increase in NO bioavailability.26

Regular physical exercise which is known to promote a favourable cardiovascular state, improves endothelial function via several mechanisms. It augments blood

with increased nitric oxide production

function can be mediated in a number of ways, including synthesis of molecular

REVIEW ARTICLE


mediators, changes in neurohormonal release and oxidant/antioxidant balance. In addition exercise can also elicit systemic molecular pathways connected with angiogenesis and chronic anti-

type and intensity of exercise. While strenuous exercise increases oxidative metabolism and produces a pro-oxidant environment whereas regular moderate exercise promotes an antioxidant state and preserves endothelial function. Thus

on the development of cardiovascular disease through preserving endothelial function.26

Although the mechanism of improvement in endothelial function during exercise

that regular aerobic exercise increases nitric oxide (NO) production with up regulation of endothelial NO synthase (eNOS), gene expression and vascular endothelial growth factor (VEGF) induced angiogenesis. It also decreases NO inactivation with augmented antioxidant system, such as superoxide dismutase (SOD) and glutathione peroxidase (GPs) and attenuation of nicotinamide adenine dinucleotide phosphate (NADH/NADPH) oxidase activity, leading to an increase in NO bioavailability.

EPIDEMIOLOGIC STUDIES ON EXERCISEEpidemiologic studies have shown that daily exercise such as walking, jogging, cycling or swimming lowers blood pressure. It is clinically important to select the appropriate intensity, duration,

intense exercise can be hazardous to human vessels. (Abraham et al., 1997,27Bergholm et al, 1999).28 The moderate

exercise training that is recommended from the preventive general viewpoint of cardiovascular diseases.

EXERCISE AND ENDOTHELIAL FUNCTIONPhysical exercise enhanced endothelium

dependent vaso dilatation in forearm circulation in hypertensive patients (Higashi et al,29 Goto et al30). The authors have reported that long term moderate intensity exercise but not mild or high intensity exercise augmented endothelium dependent vasodilation in healthy subjects (Goto et al, 2003).30 A large number of studies have shown that even in normal control animals (Wang et al,31 Sessa et al32 and Bernstem et al33) and healthy subjects (Green et al,34 Kingwell et al35) exercise augments endothelial function.

INCREASE IN NITRIC OXIDE PRODUCTIONThere is an increase in NO bioavailability (increase in NO production and/or decrease in NO inactivation). Exercise training, probably by an increase in

on endothelial function by activation of several signal transduction pathways (Traub & Berk).36 Heat shock proteins (HSP) are present in mast cells, including endothelial cells and play an important role in cellular homeostasis and cell protection from damage in response to stress stimuli (Garcia-Cardina et al).37Exercise is a physiological stimulus factor of HSP. Several investigators have focused on the interaction of eNOS with HSP90 (Gracia Cardena et al,37 Fleming & Busse,38 Russell et al39).

VASCULAR ENDOTHELIAL GROWTH FACTOR : ANGIOGENESISExercise training increases capillary

skeletal muscles in humans (Hudicka et al40). Various angiogenetic factors, such as

play an important role in angiogenesis in animals as well as in humans (Lee and Feldman).41

DECREASE IN NITRIC OXIDE INACTIVATION (OXIDATIVE STRESS)It has been shown in animals and humans that endothelial dysfunction is associated with an increase in reactive oxygen species (ROS) (Dijhorst-Oei et al,42 43). Several

interaction contributes to improvement in endothelial function. The action of increased ROS that inactivates No was removed by increased NO production. Moderate intensity exercise predominantly increases NO production compared with ROS production, leading to augmentation of endothelial function in healthy subjects.

Nicotinamide adenine dinucleatide (NADH), nicotinamide dinucleotide phosphate oxidase (NADPH)NADH/NADPH oxidase is the most important source of superoxide in the vasculature (Cai & Harrison44, Sowers45).It is thought that inactivation of NADH/NADPH oxidase may contribute to the improvement in endothelial cell function

suggest that aerobic exercise may improve ECF through decrease in ROS production with inactivation of NADH/NADPH oxidase.

PROSTAGLANDINS AND ENDOTHELIUM DERIVED HYPERPOLARIZING FACTOROther endothelium dependent vasodilators, such as prostaglandins and endothelium-derived hyperpolarizing factor (EDHF) may also contribute to

et al46 showed that exercise improves endothelium-dependent vasodilation in the coronary artery of the swine after chronic coronary occlusion through an increase in production of NO and EDHF.

of exercise, such as lowered lipoprotein level, increased shear stress, reduced vasoconstrictors and lowered blood pressure, may independently contribute to improvement in endothelial function through increase in NO release and/or inhibition of NO degradation. In healthy persons, shear stress induced increase in eNOS activity predominantly contributes to the augmentation of endothelial function during exercise.

DRUGS AND ENDOTHELIAL FUNCTIONShindle et al., have discussed the drugs


to improve endothelial function.47Most important molecule NO is potent vasodilator, it also inhibits platelet aggregation, vascular smooth muscle proliferation, leukocyte adherence and LDL exudation all of which are atherogenic.48 Endothelial nitric oxide synthese (eNOS) is responsible for majority of endothelium derived production of NO from the substrate L-arginine and the cofactor NADPH and tetrahydrobio-pterin.49 It is well known that conditions which contribute to CVD such as DM, HTN and dyslipidemia work in large part by disruption of endothelial function and increased production of reactive oxygen species (ROS) in endothelial cells. A variety of drugs eg ACE inhibitors (ACE1), angiotension receptor blockers (ARB), statins, insulin sensitizing agents, beta-blockers, calcium channel blockers, endothelin receptor antagonists, L-arginine and various antioxidants improve endothelial cell function.

ACE-INHIBITORS AND ANGIOTENSIN RECEPTOR BLOCKERSBoth ACE1 and ARBs have been found

endothelial function independent of their 50 ARBs protect

endothelium by reduction of the activity of the NO antagonist endothelin-1.51

LIPID LOWERING AGENTSSeveral large scale studies have shown that statin therapy may improve prognosis in patients at risk for CVD.52 Statins upregulate by activation of eNOS and thus improve endothelial cell function. Statins also inhibit several cholesterol intermediaries which enhance oxidative stress and vascular smooth muscle sensitivity to calcium. Statins increase

protein levels and improve FMD.

INSULIN SENSITIZING AGENTS (PIOGLITAZONE)Thiazolidinediones decrease lipid peroxidation, inhibit NADPH oxidase activity, decrease plasma levels of NOS

inhibitor asymmetric dimethy L-arginine and reduce C reactive protein (CRP) levels and Inter Cellular Adhesion Molecule 1 (ICAM1) expression.53

Biguanides (Metformin)Metformin activates adenosine monophosphate activated protein kinase (AMPK)54 which increases the expression of both eNOS and neuronal No synthase (nNOS).55,56

In human studies, metformin has been shown to enhance brachial artery endothelial function in NIDDM.57

Beta BlockersOnly nebivolol enhances arterial blood

suggesting that this particular betablocker

function58. It relaxes smooth muscle by L-arginine – NO and cyclic GMP pathway.

CALCIUM CHANNEL BLOCKERSAmongst calcium channel blockers, Nifedipine improves endothelial dependent vasodilatation in patients with

not observed with amlodipine.59 Long acting nifedipine reverses ECD and causes vasculoprotection by mechanisms independent of Ca channels as endothelial cell membranes do not have Ca channels.

and reduces LDL-C deposition in sub-endothelial layer.

L-ARGININEL-arginine is the substrate from which eNOS produces NO. Supplementation of L-arginine boosts NO production. L-arginine improves coronary and peripheral vascodilation in hypercholesterolemic patients via endothelium dependent mechanisms.60

Probucol – It improves brachial artery

L-carnitine

with CVD, exerting improvement in endothelial function manifested by

61

One may conclude that potential for endothelial active drugs to modulate endothelial dysfunction is important. ACEI and ARB appear to hold great promise in this regard. Whereas statins and insulin sensitizers may play a potentially useful role. In addition

as nebivolol may be a useful alternatives

REFERENCES1. Newman WP, Propst MT, Middaugh JP, Rogers DR.

Atherosclerosis in Alaska natives and non-natives. Lancet 1993;341:1056-7.

2. Kromann N, Green A. Epidemiological studies in Upernavik District, Greeland. Acta Med Scand 1980;208:401-6.

3. Hirai A, Hamazaki T, Terano T, et al. Eicosapentaenoic acid and platelet function in Japanese. Lancet 1980;2:1132-3

4. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet 1989;2:757-61.

5. De Caterina R, Liao JK, Libby P. Fatty acid modulation of endothelial activation. Am J Clin Nutr 2000;71 (suppl):213S-23S.

6. Gojode GK, Garcia S, Heagerty AM. Dietary supplementation with marine fish oil improves in vitro small artery endothelial function in hypercholesterolemic patients. Circulation 1997;96:2802-7.

7. Fleischhauer FJ, Yan WD, Fischell TA. Fish oil improves endothelium-dependent coronary vasodilation in heart transplant recipients. J Am Coll Cardiol 1993;21:982-9.

8. Goodfellow J. Bellamy MF, Ramsey MW, Jones CJ, Lewis MJ. Dietary supplementation with marine omega-3 fatty acids improve systemic large artery endothelial function in subjects with hypercholesterolemia. J Am Coll Cardiol 2000;35:265-70.

9. Vogel RA, Corretti MC, Plotnick GD. Effect of a single high fat meal on endothelial function in healthy subjects. Am J Cardiol 1997;79:350-354.

10. Fluenties F, Lopez-Miranda J, Sanchez E, Sanchez F, Paez J, Paz-Rojas E, Marin C, Gomez P, Jimenez-Perez J, Ordovas JM, Perez-Jimenez F. Mediterranean and low fat diets improve endothelial function hyerprcholesterolemic men. Ann Intern Med. 2001;134:1115-1119.

11. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B, Willett WC. Vitamin E consumption and the risk of coronary disease in women. N Engl J Med 1993;328:1444-9.

12. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC. Vitamin E consumption and the risk of coronary heart disease in men. N Engl. J Med 1993;328:1450-60.

13. Knekt P, Reunanen A, Jarvinen R, Seppanen R, Heliovaara M, Aromma A. Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol 1994;139:1180-9.

14. Kushi LH, Folsom AR, Prineas RJ, Mink PJ, Wu Y, Bostick RM. Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women, N Engl J Med 1996;334:115-62.

REVIEW ARTICLE


15. Losonczy KG, Harris TB, Havlik RJ. Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons; the Established Populations for Epidemiologic Studies of the Elderly. Am J Clin Nutr 1996;64:190-6.

16. Fontona L, McNeill KL, Rinter JM, Chowienczyk PJ. Effects of vitamin C and of a cell permeable superoxide dismutase mimetic on acute lipoprotein induced endothelial dysfunction in rabbit aortic rings. Br J Pharmacol 1999;120:730-4.

17. Rimm EB, Willett WC, Hu FB, et al. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women. JAMA 1998;279-359-64.

18. Chee D, Stamler J. Dietary folate and risk of cardiovascular mortality: results from the Multiple Risk Factor Intervention Trial (MRFIT). Circulation 1999;100:I-869.

19. Haynes WG. Vascular effects of homocysteine: therapeutic implications. Heart Failure 1999;15:153-63.

20. Woo KS, Chook P. Lolin YL, Sanderson JE, Metreweli C, Celermajer DS. Folic acid improves arterial endothelial function adults with hyeprhomocystinemia. J Am Coll Cardiol 1999;34:2002-6.

21. Doshi SN, McDowell IF, Moat SI, Lang D, Newcombe RG, Kredan MB, Lewis MJ, Goodfellow J. Folate improves endothelial function in coronary artery disease: an effect mediated by reduction of intracellular superoxide? Arterioscler Thromb Vasc Biol. 2001;21(7):1196-1202.

22. Hu FB, Stampfer MJ. Nut consumption and risk of coronary heart disease: a review of epidemiologic evidence. Curr Atherosclerosis Rep 1999;I:204-9.

23. Goumas G, Tenlolouris C, Tousoulis D, Stefanadis C, Toutouzas P. Therapeutic modification of the arginine-eNOS pathway in cardiovascular disease. Atherosclerosis 2001;154:255-267.

24. Lichtenestein AH. Soy protein, isoflavones and cardiovascular disese risk. J Nutr 1998;128:1589-1592.

25. Knoops KTB, Lisette CPGM, de Groot, Daan Krombout, Anne-Elizabeth Perrin, Olga Moreiras-Varela, Alessandro Menotti, Wija A van Staveren. Mediterranean diet, life style factors, and 10 year mortality in elderly European men and women in The Hale Project. Jr. Am. Med Assoc. 2011, 292;1433-1439.

26. Higashi Y, Yoshizumi M. Exercise and endothelial function: Role of endothelium derived nitric oxide and oxidative stress in healthy subjects and hypertensive patients. Pharmacology & Therapeutics 2004;102:87-96.

27. Abraham P, Saumet JL, Chevalier JM. External iliac artery endofibrosis in athletes. Sports Med. 1997;24:221-226.

28. Bergholm R. Makimattila S. Valkomen M, Liu M L. Lahdempera S, Taskinen MR, Sovijarvi A, Malmberg P, Yki-Jarvinen H. Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilation in vivo. Atherosclerosis 1999;145:341-349.

29. Higashi Y, Sasaki S, Ssaki N, Nakagava K, Ueda T, Yoshimizy A, Kuriso S Matsuura H, Kajiyama G, Oshima T. Daily aerobic exercise improves reactive hyperemia in patients with essential hypertension, Hypertension 1999a;33:591-597.

30. Goto C, Higashi Y. Kimun M. Noma K, Hara K, Nakagava K, Kawamura M, Chayana K, Yoshizumi M, Nara I. The

effect of different intensities of exercise on endothelium-dependent vasodilation in humans: role of endothelium-dependent nitric oxide and oxidative stress. Circulation 2003;108:530-535.

31. Wang J, Wolin MS, Hintze TH. Chronic exercise enhances endothelium-mediated dilation of epicardial coronary artery in conscious dogs. Clin Res 1993;73:829-839.

32. Sessa WC, Pritchard K, Seyedi N, Wang J, Hintze T. Chronic exercise in dogs increases coronary vascular nitric oxide production and endothelial cell nitro oxide synthase gene expression. Circ Res. 1994;74:349-353.

33. Bernstem R D, Ochon FY, Xu X, Forfia P, Shen W, Thompson CI, Hintze TH. Function and production of nitric oxide in the coronary circulation of the conscious dog during exercise. Circ Res. 1996;79:840-848.

34. Green D J, Cable T, Fox C, Rankin JM, Taylor RR. Modification of forearm resistance vessels by exercise training in young men. J Appl Physiol 1994;77:1829-1833.

35. Kingwell BA, Sherrard B, Jennings GL, Dart AM. Four weeks of cycle training increases basal production of nitric oxide from the forearm. Am J Physiol 1997;272:H1070-H1077.

36. Traub O, Berk BC. Laminar shear stress: Mechanisms by which endothelial cells transducer an atheroprotective force. Arteroscler Thromb Vasc Biol 1998;18:677-685.

37. Garcia-Cardenia G. Fan R. Shah V, Sorrentino R, cinno G, Papape-triopoulas A, Sessa WC. Dynamic activation of endothelial nitric oxide synthase by Hsp90. Nature 1998;392:821-824.

38. Fleming I, Busse R. Signal transduction of eNOS activation. Cardiovas: Res 1999;43:532-541.

39. Russell KS, Haynes MP, Caulin-Glaser T, Rosneck J, Sessa WC, Bender JR, Estrogen stimulates heat shock protein 90 binding to endothelial nitric oxide synthase in human vascular endothelial cells. Effects on calcium sensitivity and NO release. J Biol Chem 2000;275:5026-5030.

40. Hudicka O, Brown M, Egginton S. Angiogenesis in skeletal and cardiac muscle. Physiol Rev. 1992;72:369-417.

41. Lee JS, Feldman AM. Gene therapy for therapeutic myocardial angiogenesis a promising synthesis of two emerging technologies. Nat Med 1998;4:739-742.

42. Dijhorst-Oci LT, Stores ES, Koomans HA, Rabelink TJ. Acute simultaneous stimulation of nitric oxide and oxygen radicals by angiotensin II in humans in vivo J Cardiovas Pharmacol 1999;33:420-424.

43. Romero JC, Reckelhoff JE. Role of angiotensin and oxidative stress in essential hypertension. Hypertension 1999;34:943-949.

44. Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress. Circ Res 2000; 87:840-844.

45. Sowers JR. Hypertension angiotensin II and oxidative stress. N Engl J Med. 2002;346:1999-2001.

46. Griffin KL, Laughlin MH, Parker JL. Exercise training improves endothelium-mediated vasorelaxation after chronic coronary occlusion. J Appl Physiol 1999;87:1948-1956.

47. Shindel AW, Kishore S, Lue TF. Drugs designed to improve endothelial function. Effects on erectile dysfunction,

Current Pharmaceutical design, 2008;14:3758-3766.48. Davignon J, Ganz P. Role of endothelial dysfunction in

atherosclerosis. Circulation 2004;109:1127-32.49. Fenster BE, Tsao PS, Rockson SG. Endothelial dysfunction:

Clinical strategies for treating oxidant stress Am Heart J 2003;146:218-26.

50. Mancini GB, Henry GC, Macaya C, O’Neil BJ, Pucilo AL, Carere RG. et al. Angiotensin-converting enzyme inhibition with quinapril improves endothelial vasomotor dysfunction in patients with coronary artery disease. The TREND (Trial on Reversing Endothelial Dysfunction) Study Circulation 1996;94:258-65.

51. Ghadoni L, Virdis A, Magagna A, Taddei S, Salvetti A. Effects of the angiotensin II type 1 receptor blocker candesartan on endothelial function in patients with essential hypertension. Hypertension 2000;35:501-6.

52. The long term intervention with Pravastatin in ischaemic Disease (LIPID) Study Group Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of mitral cholesterol levels. New engl K Med 1998;339:1349-57.

53. Fryer LG, Hajduch E, Rencurel F. Salt IS, Hundal HS, Hardie DG, et al. Activation of glucose transport by AMP-activated protein kinase via stimulation of nitric oxide synthase Diabetes 2000;49:1978-85.

54. Garg R, Kumbkami Y. Ajada A, Mohanty P, Ghanim H, Hamouda W. et al. Troglitazone reduces reactive oxygen species generation by leukocytes and lipid peroxidant and improves flow-mediated vasodilatation in obese subjects. Hypertension, 2000;36:430-5.

55. Zhou G, Myers R, Li Y. Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated kinase in mechanism of metformin action. J Clin Invest 2001;108:1167-74.

56. Davis BJ, Xie Z, Viollet B, Zou MH. Activation of the AMP activated kinase by antidiabetes drug metformin stimulates nitric oxide synthase in vivo by promoting the association of heat shock protein 90 and endothelial nitric oxide synthase. Diabetes 2006;55:496-505.

57. Mather KJ, Verma S, Anderson TJ. Improved endothelial function with metformin type 2 diabetes mellitus J A, Coll Cardiol 2001;37:1344-50.

58. Cockgroff JR, Chowenzyj PJ. Brett SE, Chen CP, Dupont AG, Van Nueten L. et al. Nebivolol vasodilates human forearm vasculature: evidence for an L-arginine/NO-dependent mechanism. J Pharmacol Exp Ther 1995;274:1067-71.

59. Verhaar MC, Honing ML, van Dam T, Zwart M, Koomans HA, Kastelein JJ et al. Nifedipine improves endothelial function in hypercholesterolemia, independently of an effect on blood pressure or plasma lipids Cardiovas Res. 1999;42:757-60.

60. Adams MR, McCredie R, Jessup W, Robinson J, Sullivan D, Celermajer DS. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease. Atherosclerosis1997;129:261-9.

61. Morano S. Mandosi E. Fallarina M, Gatti A. Tiberti C. Sensi M, et al Antioxidant treatment associated with sildernafil reduces monocyte activation and markers of endothelial damage in patients with diabetic erectile dysfunction a double-blind, placebo=controlled study Eur Uro 2007, 52:1768-74.


From Irregular Pulse to Slurring of the Speech: Echocardiographic AF Evaluation: Relevant at all Stages

REVIEW ARTICLE

SHRADDHA RANJAN, MANISH BANSAL, RAVI R KASLIWAL, H K CHOPRA

Keywords left atrial appendage transesophageal echocardiographic

Dr. Shraddha Ranjan is Senior Resident Cardiology; Dr. Manish Bansal is Associate Director Cardiology; Dr. Ravi R Kasliwal is Chairman, Clinical and Preventive Cardiology; at Medanta- The Medicity, Gurgaon, Haryana and Dr. H K Chopra is Chief Cardiologist Moolchand Medcity, New Delhi

Abstract

in clinical practice. Recent advances in technology and in the

setting, echocardiography has a unique and important role in the

value, echocardiography has become established in guidelines for

particularly of transoesophageal echocardiography to guide direct current cardioversion or detect cardiac sources of embolism. Even more recently the development of intracardiac echocardiography has led to real-time guidance of percutaneous interventions, including radiofrequency ablation and left atrial appendage closure procedures

INTRODUCTIONThe incidence and prevalence of atrial

The 2010 rates are higher than 1990 rates with estimated numbers of men and women with AF 20.9 million and 12.6 million, thus showing increase in

both prevalence and incidence rates in both sexes. This increase in AF burden increases with age from 2% incidence in population less than 40 years of age to almost 10% in that with more than 80 years.1,2 This potentially could be linked to better detection of silent AF alongside


attention is sought later and records are not meticulously maintained, making it all the more essential for developing echocardiography as a modality which can give us most of the answers with limited resources. In this article, we try to do the same by reviewing the role of echocardiography in the evaluation and management of patients with AF.

ROLE OF ECHOCARDIOGRAPHY IN AF MANAGEMENTLeft atrial/ left atrial appendage clotThe primary indication for performing assessment of the LAA is to rule out the presence of a thrombus. The risk of systemic emboli, probably arising in the LA cavity or LAA as a result of circulatory stasis, is an important consideration in AF. TEE is highly accurate for this purpose with some studies reporting sensitivity

100% and 99% respectively9 (Figures 1, 2, 3). Cardioversion carries an intrinsic risk of stroke in non-anticoagulated patients (up to 7% of patients) which is reduced substantially by the administration of anticoagulation.10,11 Patients who have been in AF for longer than 48 hours should start OAC at least 3 weeks before cardioversion and continue it for at least 4 weeks afterwards.2 However, when acute onset AF is encountered and early cardioversion is desired, TEE can exclude the majority of left atrial thrombi, allowing immediate cardioversion. The advantages of TEE-guided early cardioversion with short-term anticoagula-tion over the conventional strategy include the following: 1) On TEE, if no thrombus is seen the total duration of anticoagulation can be reduced by

increasing longevity and risk factors such as hypertension, obesity and metabolic syndrome etc. The prevalence of AF in our population is not well studied but a study done in the UK found 6292 patients

adjusted prevalence of 0.63% (1.2% white, 0.4% black African/Caribbean and 0.2% South Asian). South Asian patients though had a lower prevalence but were at higher stroke risk than white patients.3It is a well-known fact AF is associated with higher morbidity and mortality, for example data from the Framingham Heart Study suggested that the presence of AF is associated with a near doubling of both overall and cardiovascular mortality

public health policy and healthcare costs.4 The main cause of mortality remains stroke as 50% of patients with AF related stroke die within a year. It becomes imperative now to have a proper understanding of the disease to have a

therapeutic approach. Among the various diagnostic tools, echocardiography has an important role in both the evaluation of cardiac structure and function and risk

and perhaps the most helpful modality for the initial workup of all patients with AF, for assessing left atrium (LA) and left ventricle (LV) size and function along with presence of valvular, myocardial, pericardial and congenital heart disease which may predispose to AF.

Undoubtedly, the most dreaded complication of AF is stroke and various risk factors are associated with the occurrence of stroke in AF patients. To be more presumptive several risk scores have been developed to predict the risk of ischemic stroke and guide the decision to treat them with anticoagulants. The CHADS2 risk score is the simplest score and assigns points to the presence of congestive heart failure, hypertension, age >75, diabetes, and stroke.5 To better identify patients that are truly at low risk, the CHA2DS2-VASc risk score was developed that also included vascular disease, age between 65 and 74 years, and sex.6 The European Society of Cardiology (ESC) and National Institute

for Health and Care Excellence (NICE) guidelines recommend that if the patient has a CHA2DS2-VASc score of 2 and above, oral anticoagulation therapy (OAC) is recommended.2 Recently a new clinically based risk score, the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) study risk score, was developed and validated which uses factors incorporated in the CHADS2 risk score, along with renal dysfunction.7

Role of transesophageal echo-cardiographic (TEE) evaluation in ruling out left atrial thrombi to allow for early cardioversion with new-onset AF is undebatable and has become a dictum in everyday cardiology practice. But apart from that, it is discouraging to see that in all these risk scores there has been no consideration of echocardiographic parameters which can be of immense value in management of AF patients. The study Stroke Prevention in Atrial Fibrillation

TEE for predicting thromboembolism. It showed that the rate of stroke was increased over threefold when TEE evidence of dense spontaneous echo contrast (SEC) was present, increased by threefold for reduced (


weeks, potentially reducing the risk of bleeding. 2) Early cardioversion with a TEE-guided approach might prevent the atrial remodelling due to AF and enable higher rates of sinus conversion and maintenance. So, the assessment of LA and LAA anatomy, function and presence or absence of clot carries immense

further sections of the article.

Left atrial sizeLA is directly exposed to the hemodynamic agitations taking place within the LV during diastole as it is in direct communication with the LV. As a result, with development of left ventricular diastolic dysfunction, or a mitral valve pathology there is progressive increase in mean LA pressure. The increase in mean LA pressure eventually leads to an increase in the LA size.12,13evidence to suggest that the left atrial size is an independent predictor of recurrence

failure related hospitalization and risk of overall mortality.14-26

LA size can be assessed by measuring

it’s antero-posterior diameter, area or volume at the end of the ventricular systole when the chamber size is at its maximum. LA diameter and area are

of LA size. However, they may not be true representative of the size in disease states as the LA often enlarges non-uniformly.27,28 Therefore, measurement of volume is considered to be the most accurate method for estimation of left atrial size and is recommended by the American Society of Echocardiography (ASE).29

LA volume can be calculated either by the biplane area-length method based on ellipsoid model or by the Simpson’s method. In past, the biplane area-length method has been the preferred method (Figure 4) as most of the existing data is derived using this method only. However, the more recent guidelines have recommended the biplane Simpson’s method for estimation of LA volume (Figure 5).29

Using the biplane area-length method, LA volume can be calculated as-

Left atrial volume= 8/3 (A1 X A2 /L) A1 is the planimetric LA area in the four-chamber viewA2 is the planimetric LA area in the two-chamber viewL is the length of the LA, measured as the perpendicular distance from the mid-point of mitral annular plane to the superior aspect of the left atrium (Figure 4).

The length is measured in both the four-chamber and the two-chamber views and the shorter of the two is used

foreshortening is avoided and pulmonary veins and the LAA are not included in the measurement. Irrespective of the method, the estimated LA volume should always be indexed to the body-surface area. The normal value of indexed LA volume is

2.The estimation of LA volume by the

Simpson’s method (Figure 5) is based on the same principles as for left ventricular volume estimation. LA endocardial border is trace in both the apical four-chamber and the two-chamber views and the software inbuilt in the echocardiography machine automatically calculates the LA volume. While tracing the endocardial border, same precautions need to be exercised as described above for the area-length method.

Left atrial function assessmentLA function, in addition to LA size, is also an important determinant of adverse outcomes in various diseases

the left atrium. Furthermore, in some situations, LA function may even have

Figure 2. Small clot in one of the lobes of the left atrial appendage. The clot is visualized only in one plane (A) but not in the orthogonal plane (B).

Figure 3. Large layered thrombus in the left atrium (arrow). Spontaneous echo contrast is also seen filling the whole of the left atrium.

Figure 4. Measurement of left atrial volume by the biplane area-length method. Left atrial

area and length are measured in both the apical four and two-chamber views and used in

the equation (please see text for the details).

REVIEW ARTICLE


superior prognostic value than LA size alone.30 The recent advent of speckle tracking echocardiography (STE) with its application for LA strain measurement has rendered assessment of LA function much easier, providing a renewed impetus to evaluating its role in clinical practice.

Strain is basically a measure of

as the percent change in the length of a myocardial segment during a given phase of cardiac cycle. When the myocardial segment undergoes shortening, strain assumes a negative value whereas lengthening would result in positive strain.

Unlike LV where myocardial deformation is multidirectional and strain is described along three principle directions- longitudinal, radial and circumferential, in case of LA most of the shortening and lengthening occurs in longitudinal directional only and therefore only longitudinal strain is measured for all practical purposes.

There are primarily two methods for measurement of myocardial strain- Doppler-based and the gray-scale based or STE-based.31 Doppler-based strain is technically more time consuming and less accurate. In comparison, STE is simpler to use and, because of its relative angle independence, can be used to strain measurement in any cardiac chamber and in any direction hence currently the preferred modality for measurement of LA strain.

For LA strain measurement, gray-

apical 4-chamber and 2-chamber views along its maximal dimensions, during breath-hold with a stable ECG recording. These images are analyzed using the same registered speckle-tracking software

which are used for LV strain analysis. The LA endocardial border is manually traced in the end-systolic (ventricular systole) frame, excluding pulmonary vein ostia and LA appendage. The software then automatically generates epicardial border tracing and creates a region of interest which can be manually adjusted to conform to the contour of the LA wall. The software then divides LA

circumference in to 6 segments and tracks myocardial motion for each segment frame-by-frame and generates strain curves for each myocardial segment (Figure 6). This process is repeated for both the 4-chamber and the 2-chamber views, yielding 12 (6 for each view) segmental strain curves.

The shape of the LA strain curve varies depending on whether QRS onset or beginning of the P-wave is used as the reference point.31,32 QRS onset is used more often and hence only this method will be discussed here (Figure 6). QRS onset marks the beginning of ventricular systole and the time when the left atrium is smallest in size. During progression of ventricular systole, the left atrium increases in size resulting in positive strain that reaches its peak just before the mitral valve opening. Once

Figure 5. Measurement of left atrial volume by the biplane Simpson’s method

Figure 6. Measurement of left atrial strain by speckle tracking echocardiography. A. The colored curves depict segmental strain whereas the white dotted curve depicts the average of all the segments. B. Left atrial strain waveform using QRS as the reference point. There is an initial positive wave during ventricular systole which is followed by reduction in strain during early rapid filling phase and subsequently during active atrial contraction. PACS- peak atrial contraction strain; PALS- peak atrial longitudinal strain


mitral valve opens, the left atrium rapidly decreases in size resulting in reduction in strain. This early rapid emptying phase is followed by a phase of diastasis in which the strain curve plateaus. With the onset of atrial contraction, marked by P-wave on the ECG, the left atrium shortens again, resulting in second phase of strain reduction. The strain curve eventually reaches the baseline by the onset of QRS. Since QRS is used as the reference point, most of the nomenclature for LA strain is based on this method only.32 The peak atrial longitudinal strain (PALS), measured at the end of the ventricular systole represents the reservoir function of the LA; the reduction in strain from this peak to the plateau phase indicates

phase of LA strain reduction during atrial contraction (termed peak atrial contraction strain or PACS) represents the booster function. PALS averaged for all 12 segments (or all analyzed segments) is used as global LA strain. Global PACS can also be calculated. In addition, LA contraction strain index can also be calculated as global PACS X 100/global PALS and represents the contribution to the LA active contraction to the total LV

with short-duration AF but gradually recovers with time,33,34 unless there have been chronic structural changes in LA myocardium. If AF persists, there is structural and functional remodelling of left atrium characterized by increased

patients, LA strain is persistently reduced and is a determinant of adverse clinical outcomes. Several studies have demonstrated close correlation between

35 In a study patients with persistent AF were found to

with paroxysmal AF36 Apart from AF, LA remodelling also occurs whenever the left atrium is chronically exposed to elevated

been shown to be impaired, before other echocardiographic manifestations of LA structural remodelling appear in patients with hypertension, diabetes and heart failure with preserved LV ejection fraction.37

Role of LA function assessment in clinical decision making Abnormalities of LA strain have several important clinical implications in patients with or, at risk of developing AF. It’s role in clinical decision making is discussed below-

LA strain if reduced predicts occurrence of AF in numerous clinical settings. Few studies which were done on patients undergoing coronary artery bypass surgery or valve surgery showed that LA

impaired in patients who developed post-operative AF and were independent predictors of the development of AF in the overall cohort.38-40 LA strain can be helpful in predicting the risk of AF in non-surgical patients also specially in rheumatic mitral stenosis.41,42

Prediction of stroke riskStroke is the most feared but possibly preventable complication of AF. LA strain can also be a useful parameter along with the validated risk scores when prevention of stroke is the matter on hand. Hsu et al followed up 190 patients with persistent AF and found that baseline LA strain was found to be a predictor of stroke event in these patients and had incremental value over CHA2DS2-VASc score.43In another study with 286 consecutive patients of paroxysmal or persistent AF with or without acute embolism global LA strain was found to be lower not only in patients with acute embolism, it had an incremental value over the CHA2DS2-VASc score.44 Several other studies have demonstrated association between LA strain and the CHA2DS2-VASc score,45,46previous history of stroke47 and the future occurrence of stroke.48 Moreover, impairment of LA strain has also been demonstrated in patients with stroke of undetermined etiology where it may indicate the possibility of undiagnosed paroxysmal AF.49

Outcomes after cardioversionIn patients undergoing electrical cardioversion for AF, reduced LA strain before the cardioversion or a dampened increase in LA strain immediately after

cardioversion has been shown to predict failure of conversion and associated with lower probability of maintenance of sinus rhythm respectively.50

Catheter ablation of AF is an invasive procedure which is associated with some risk of peri-procedural complications and roughly 30-40% risk of AF recurrence during follow-up.30,52 So, accurate selection of patients is crucial to optimize long-term clinical outcomes of this procedure. Several studies have shown that LA strain can be a useful predictor of the recurrence of AF after catheter ablation.30,52-54 Recently, a meta-analysis of 8 studies was performed evaluating role of LA strain for prediction of AF recurrence after catheter ablation.55 A total of 686 patients were included in this analysis. LA strain was strongly associated with the recurrence of AF with

interval 18.8-30%) yielding a sensitivity

have also been shown to predict reverse LA remodelling after catheter ablation for AF.56

Left atrial appendage structure and functionIn conventional teaching LAA was believed to be a vestigial structure with no active role and hence was not studied. However, with the advancements of

become apparent that the LAA is an actively contracting structure which plays an important role in cardiac hemodynamics. More than that, dysfunction of LAA is the substrate for thrombus formation which can lead to potentially devastating embolic complications.57-61 Therefore, a comprehensive assessment of LAA structure and function should be done to guide therapeutic decision-making in a number of cardiac illnesses. Echocardiography, particularly TEE, is currently the modality of choice for evaluation of the LAA. It allows complete

REVIEW ARTICLE


with detailed assessment of its function in most of the patients.

Echocardiographic assessment of LAA structureThe LAA is a small, pyramidal usually a multi-lobed structure situated on the lateral aspect of the LA, extending between the pulmonary artery above and the LV. Internally LAA is trabeculated with the trabeculations, known as pectinate muscles which run parallel to each other, giving it a comb-like structure. In an autopsy study of 500 normal human hearts, the LAA was bilobed in 54% and multilobed (>2 lobes) in 80% of hearts.62Although the LAA can be visualized on TTE also, in most patients a detailed assessment is not possible due to the posterior location of the LAA. Whereas, TEE, with the close proximity of the transducer to the LAA, allows excellent imaging of the LAA and is therefore compulsory for LAA assessment. On TEE, the LAA is best visualized in the mid-esophageal two-chamber view (80-100°) and the mid-esophageal aortic valve short-axis view (30-60°) and are therefore the recommended views for this purpose.63 However, to exclude thrombus, it is essential to image the LAA from multiple imaging planes. This can be easily accomplished by

aortic valve short-axis view (30-60°)

rotating the multiplane angle from 0° to 180°. This approach allows complete assessment of LAA anatomy, its

(Figure 7). Sometimes it may be almost

from the pectinate muscles or artefacts. The administration of ultrasound contrast can be of great help in such situations.64-66The recent availability of live-three dimensional TEE should render imaging of the complex LAA anatomy much easier now.67

In addition to delineation of thrombus, TEE is also helpful in detection of LAA SEC. SEC is a smoke-like swirling pattern seen in two-dimensional imaging and

resulting from stasis of the blood. SEC has been shown to be the harbinger of thrombus formation and therefore, a predictor of thromboembolic risk in many studies.68-70

Echocardiographic assessment of LAA functionIt has become obvious that an estimate of LAA function can provide incremental information about the risk of clot formation, embolic events, success of cardioversion etc. Therefore, evaluation of the LAA function by doppler

is currently the preferred method of assessment of LAA function.71 It is now often undertaken as part of the standard echocardiographic examination of the

pulsed-wave Doppler can be obtained from any of the standard imaging planes on TEE by keeping the pulsed-wave sample-volume in the proximal one-third segment (towards LA) of the LAA.71,72In patients with sinus rhythm, a typical

can be seen consisting of early diastolic emptying velocity followed by the most important phase of late diastolic emptying

results from active LAA contraction and is thus a marker of LAA contractile function. It correlates with LAA ejection fraction, LA size and pressure and is a

risk.73 This is followed by a negative

which is an indirect measure of LAA function, measurement of tissue velocity provides direct estimate of the LAA contractility. On tissue velocity imaging, a similar wave pattern is seen as in the

Figure 7: Multilobed anatomy of the left atrial appendage. A- Only one lobe (arrow) is visualized in this plane; B- The complete extent of the left atrial appendage is visualized in an orthogonal plane (open arrows mark the boundary of the appendage). Pectinate muscles are also clearly visualized (arrow).

Figure 8. Left atrial appendage (LAA) flow pattern. A. Schematic diagram showing different flow waves during sinus rhythm. B. Pulsed-wave Doppler tracing of LAA flow in sinus rhythm. C. Pulsed-wave doppler tracing of LAA flow in atrial fibrillation. Modified from- Bansal M, Kasliwal RR. Echocardiography for left atrial appendage structure and function. Indian Heart J. 2012;64:469-75


to have good feasibility and correlated with the presence of LAA SEC or thrombus, history of thromboembolic

contractile dysfunction in mitral stenosis, hypertension or HCM even in absence of AF.61,74-78

Role of assessment of LAA structure and function in clinical practiceAssessment of LAA anatomy and function plays an important role in the diagnostic work-up and management of many clinical conditions. It may be a mandatory investigation prior to performance of intervention procedures such as BMV, or can be routinely sought when the cause of ischemic stroke is not apparent and a cardiac source needs to be ruled out. In addition to these well-known indications research has revealed newer indications for which LAA function assessment may be warranted. The most practical indications are discussed here-

Cardioembolic strokes account for > 15% of all ischemic strokes79 among which LAA is the source of embolus in majority of the cases. Approximately, 90% of intracardiac thrombi in non-rheumatic AF and 60% of patients with rheumatic mitral valve disease form within the LAA.80 In patients with recent embolic event and AF, LAA thrombus is found in roughly 14% patients with short duration AF (started 48 hours

duration in patients who have not been on te anticoagulation.

LAA dysfunction has been shown to be a strong predictor of thrombus formation and the risk of embolic events, even if no clot is found at the time of initial examination.57-59,81 In the SPAF III (Stroke Prevention in Atrial Fibrillation III) TEE substudy that included patients with AF, 17% patients with LAA contraction velocities


8. Zabalgoitia M, Halperin JL, Pearce LA, Blackshear JL, Asinger RW, Hart RG. Transesophageal echocardiographic correlates of clinical risk of thromboembolism in nonvalvular atrial fibrillation. Stroke Prevention in Atrial Fibrillation III Investigators. Journal of the American College of Cardiology 1998;31:1622-6.

9. Manning WJ, Silverman DI, Gordon SP, Krumholz HM, Douglas PS. Cardioversion from atrial fibrillation without prolonged anticoagulation with use of transesophageal echocardiography to exclude the presence of atrial thrombi. N Engl J Med 1993;328:750-5.

10. Airaksinen KE, Gronberg T, Nuotio I et al. Thromboembolic complications after cardioversion of acute atrial fibrillation: the FinCV (Finnish CardioVersion) study. Journal of the American College of Cardiology 2013;62:1187-92.

11. Hansen ML, Jepsen RM, Olesen JB et al. Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy. Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology 2015;17:18-23.

12. Tsang TS, Barnes ME, Gersh BJ, Bailey KR, Seward JB. Left atrial volume as a morphophysiologic expression of left ventricular diastolic dysfunction and relation to cardiovascular risk burden. The American journal of cardiology 2002;90:1284-9.

13. Simek CL, Feldman MD, Haber HL, Wu CC, Jayaweera AR, Kaul S. Relationship between left ventricular wall thickness and left atrial size: comparison with other measures of diastolic function. J Am Soc Echocardiogr 1995;8:37-47.

14. Abhayaratna WP, Seward JB, Appleton CP et al. Left atrial size: physiologic determinants and clinical applications. J Am Coll Cardiol 2006;47:2357-63.

15. Benjamin EJ, D'Agostino RB, Belanger AJ, Wolf PA, Levy D. Left atrial size and the risk of stroke and death. The Framingham Heart Study. Circulation 1995;92:835-41.

16. Bouzas-Mosquera A, Broullon FJ, Alvarez-Garcia N et al. Left atrial size and risk for all-cause mortality and ischemic stroke. Cmaj 2011;183:E657-64.

17. Di Tullio MR, Sacco RL, Sciacca RR, Homma S. Left atrial size and the risk of ischemic stroke in an ethnically mixed population. Stroke 1999;30:2019-24.

18. Dini FL, Cortigiani L, Baldini U et al. Prognostic value of left atrial enlargement in patients with idiopathic dilated cardiomyopathy and ischemic cardiomyopathy. Am J Cardiol 2002;89:518-23.

19. Modena MG, Muia N, Sgura FA, Molinari R, Castella A, Rossi R. Left atrial size is the major predictor of cardiac death and overall clinical outcome in patients with dilated cardiomyopathy: a long-term follow-up study. Clin Cardiol 1997;20:553-60.

20. Moller JE, Hillis GS, Oh JK et al. Left atrial volume: a powerful predictor of survival after acute myocardial infarction. Circulation 2003;107:2207-12.

21. Nagarajarao HS, Penman AD, Taylor HA et al. The predictive value of left atrial size for incident ischemic stroke and all-cause mortality in African Americans: the Atherosclerosis Risk in Communities (ARIC) Study. Stroke 2008;39:2701-6.

22. Ristow B, Ali S, Whooley MA, Schiller NB. Usefulness of left atrial volume index to predict heart failure hospitalization and mortality in ambulatory patients with coronary heart disease and comparison to left ventricular ejection fraction (from the Heart and Soul Study). Am J Cardiol 2008;102:70-6.

23. Sabharwal N, Cemin R, Rajan K, Hickman M, Lahiri A, Senior R. Usefulness of left atrial volume as a predictor of mortality in patients with ischemic cardiomyopathy. Am J Cardiol 2004;94:760-3.

24. Takemoto Y, Barnes ME, Seward JB et al. Usefulness of left atrial volume in predicting first congestive heart failure in patients > or = 65 years of age with well-preserved left ventricular systolic function. Am J Cardiol 2005;96:832-6.

25. Tsang TS, Barnes ME, Bailey KR et al. Left atrial volume: important risk marker of incident atrial fibrillation in 1655 older men and women. Mayo Clin Proc 2001;76:467-75.

26. Tsang TS, Barnes ME, Gersh BJ, Bailey KR, Seward JB. Risks for atrial fibrillation and congestive heart failure in patients >/=65 years of age with abnormal left ventricular diastolic relaxation. Am J Cardiol 2004;93:54-8.

27. Lester SJ, Ryan EW, Schiller NB, Foster E. Best method in clinical practice and in research studies to determine left atrial size. Am J Cardiol 1999;84:829-32.

28. Loperfido F, Pennestri F, Digaetano A et al. Assessment of left atrial dimensions by cross sectional echocardiography in patients with mitral valve disease. Br Heart J 1983;50:570-8.

29. Lang RM, Bierig M, Devereux RB et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440-63.

30. Yasuda R, Murata M, Roberts R et al. Left atrial strain is a powerful predictor of atrial fibrillation recurrence after catheter ablation: study of a heterogeneous population with sinus rhythm or atrial fibrillation. Eur Heart J Cardiovasc Imaging 2015;16:1008-14.

31. Mor-Avi V, Lang RM, Badano LP et al. Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr 2011;24:277-313.

32. Cameli M, Lisi M, Righini FM, Mondillo S. Novel echocardiographic techniques to assess left atrial size, anatomy and function. Cardiovasc Ultrasound 2012;10:4.

33. Donal E, Ollivier R, Veillard D et al. Left atrial function assessed by trans-thoracic echocardiography in patients treated by ablation for a lone paroxysmal atrial fibrillation. Eur J Echocardiogr 2010;11:845-52.

34. Kaya EB, Tokgozoglu L, Aytemir K et al. Atrial myocardial deformation properties are temporarily reduced after cardioversion for atrial fibrillation and correlate well with left atrial appendage function. Eur J Echocardiogr 2008;9:472-7.

35. Her AY, Choi EY, Shim CY et al. Prediction of left atrial fibrosis with speckle tracking echocardiography in mitral valve disease: a comparative study with histopathology. Korean Circulation Journal 2012;42:311-8.

36. Kuppahally SS, Akoum N, Burgon NS et al. Left atrial strain and strain rate in patients with paroxysmal and persistent atrial fibrillation: relationship to left atrial structural remodeling detected by delayed-enhancement MRI. Circ Cardiovasc Imaging 2010;3:231-9.

37. Mondillo S, Cameli M, Caputo ML et al. Early detection of left atrial strain abnormalities by speckle-tracking in hypertensive and diabetic patients with normal left atrial size. J Am Soc Echocardiogr 2011;24:898-908.

38. Gabrielli L, Corbalan R, Cordova S et al. Left atrial dysfunction is a predictor of postcoronary artery bypass atrial fibrillation: association of left atrial strain and strain rate assessed by speckle tracking. Echocardiography 2011;28:1104-8.

39. Her AY, Kim JY, Kim YH et al. Left atrial strain assessed by speckle tracking imaging is related to new-onset atrial fibrillation after coronary artery bypass grafting. Can J Cardiol 2013;29:377-83.

40. Cameli M, Lisi M, Reccia R et al. Pre-operative left atrial strain predicts post-operative atrial fibrillation in patients undergoing aortic valve replacement for aortic stenosis. Int J Cardiovasc Imaging 2014;30:279-86.

41. Cameli M, Lisi M, Righini FM, Focardi M, Alfieri O, Mondillo S. Left atrial speckle tracking analysis in patients with mitral insufficiency and history of paroxysmal atrial fibrillation. Int J Cardiovasc Imaging 2011.

42. Pourafkari L, Ghaffari S, Bancroft GR, Tajlil A, Nader ND. Factors associated with atrial fibrillation in rheumatic mitral stenosis. Asian Cardiovasc Thorac Ann 2015;23:17-23.

43. Hsu PC, Lee WH, Chu CY et al. Prognostic role of left atrial strain and its combination index with transmitral E-wave velocity in patients with atrial fibrillation. Sci Rep 2016;6:17318.

44. Obokata M, Negishi K, Kurosawa K et al. Left atrial strain provides incremental value for embolism risk stratification over CHA(2)DS(2)-VASc score and indicates prognostic impact in patients with atrial fibrillation. J Am Soc Echocardiogr 2014;27:709-716 e4.

45. Shavarov A, Yusupov A, Kiyakbaev G, Moiseev V. 5a.06: Correlation of Thromboembolic Risk with Global Left Atrial Strain in Hypertensive Patients with Atrial Fibrillation. J Hypertens 2015;33 Suppl 1:e65.

46. Saha SK, Anderson PL, Caracciolo G et al. Global left atrial strain correlates with CHADS2 risk score in patients with atrial fibrillation. J Am Soc Echocardiogr 2011;24:506-12.

47. Shih JY, Tsai WC, Huang YY et al. Association of decreased left atrial strain and strain rate with stroke in chronic atrial fibrillation. J Am Soc Echocardiogr 2011;24:513-9.

48. Cameli M, Lisi M, Focardi M et al. Left atrial deformation analysis by speckle tracking echocardiography for prediction of cardiovascular outcomes. Am J Cardiol 2012;110:264-9.

49. Sanchis L, Montserrat S, Obach V et al. Left Atrial Function Is Impaired in Some Patients With Stroke of Undetermined Etiology: Potential Implications for Evaluation and Therapy. Rev Esp Cardiol (Engl Ed) 2016;69:650-6.

50. Costa C, Gonzalez-Alujas T, Valente F et al. Left atrial strain: a new predictor of thrombotic risk and successful electrical cardioversion. Echo Res Pract 2016;3:45-52.

51. Shaikh AY, Maan A, Khan UA et al. Speckle echocardiographic left atrial strain and stiffness index as predictors of maintenance of sinus rhythm after cardioversion for atrial fibrillation: a prospective study. Cardiovasc Ultrasound 2012;10:48.

52. Motoki H, Negishi K, Kusunose K et al. Global left atrial strain in the prediction of sinus rhythm maintenance after catheter ablation for atrial fibrillation. J Am Soc Echocardiogr 2014;27:1184-92.

53. Hwang HJ, Choi EY, Rhee SJ et al. Left atrial strain as predictor of successful outcomes in catheter ablation for atrial fibrillation: a two-dimensional myocardial imaging study. J Interv Card Electrophysiol 2009;26:127-32.

54. Sarvari SI, Haugaa KH, Stokke TM et al. Strain echocardiographic assessment of left atrial function predicts recurrence of atrial fibrillation. Eur Heart J Cardiovasc Imaging 2016;17:660-7.

55. Ma XX, Boldt LH, Zhang YL et al. Clinical Relevance of Left Atrial Strain to Predict Recurrence of Atrial Fibrillation after Catheter Ablation: A Meta-Analysis. Echocardiography 2016;33:724-33.

56. Tops LF, Delgado V, Bertini M et al. Left atrial strain predicts reverse remodeling after catheter ablation for atrial fibrillation. J Am Coll Cardiol 2011;57:324-31.

57. Transesophageal echocardiographic correlates of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators Committee on Echocardiography. Ann Intern Med 1998;128:639-47.


58. Mugge A, Kuhn H, Nikutta P, Grote J, Lopez JA, Daniel WG. Assessment of left atrial appendage function by biplane transesophageal echocardiography in patients with nonrheumatic atrial fibrillation: identification of a subgroup of patients at increased embolic risk. J Am Coll Cardiol 1994;23:599-607.

59. Li YH, Lai LP, Shyu KG, Hwang JJ, Kuan P, Lien WP. Clinical implications of left atrial appendage flow patterns in nonrheumatic atrial fibrillation. Chest 1994;105:748-52.

60. Saygi S, Turk UO, Alioglu E et al. Left atrial appendage function in mitral stenosis: is it determined by cardiac rhythm? J Heart Valve Dis 2011;20:417-24.

61. Tenekecioglu E, Karabulut A, Yilmaz M. Comparison of tissue Doppler dynamics with Doppler flow in evaluating left atrial appendage function by transesophageal echocardiography in prehypertensive and hypertensive patients. Echocardiography 2010;27:677-86.

62. Veinot JP, Harrity PJ, Gentile F et al. Anatomy of the normal left atrial appendage: a quantitative study of age-related changes in 500 autopsy hearts: implications for echocardiographic examination. Circulation 1997;96:3112-5.

63. Shanewise JS, Cheung AT, Aronson S et al. ASE/SCA guidelines for performing a comprehensive intraoperative multiplane transesophageal echocardiography examination: recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography. J Am Soc Echocardiogr 1999;12:884-900.

64. Ruiz-Arango A, Landolfo C. A novel approach to the diagnosis of left atrial appendage thrombus using contrast echocardiography and power Doppler imaging. Eur J Echocardiogr 2008;9:329-33.

65. von der Recke G, Schmidt H, Illien S, Luderitz B, Omran H. Use of transesophageal contrast echocardiography for excluding left atrial appendage thrombi in patients with atrial fibrillation before cardioversion. J Am Soc Echocardiogr 2002;15:1256-61.

66. von der Recke G, Schmidt H, Illien S et al. Transesophageal contrast echocardiography distinguishes a left atrial appendage thrombus from spontaneous echo contrast. Echocardiography 2002;19:343-4.

67. Shah SJ, Bardo DM, Sugeng L et al. Real-time three-dimensional transesophageal echocardiography of the left atrial appendage: initial experience in the clinical setting. J Am Soc Echocardiogr 2008;21:1362-8.

68. Jaber WA, Prior DL, Thamilarasan M et al. Efficacy of anticoagulation in resolving left atrial and left atrial appendage thrombi: A transesophageal echocardiographic study. Am Heart J 2000;140:150-6.

69. Black IW, Hopkins AP, Lee LC, Walsh WF. Left atrial spontaneous echo contrast: a clinical and echocardiographic analysis. J Am Coll Cardiol 1991;18:398-404.

70. Kasliwal RR, Mittal S, Kanojia A et al. A study of spontaneous echo contrast in patients with rheumatic mitral stenosis and normal sinus rhythm: an Indian perspective. Br Heart J 1995;74:296-9.

71. Agmon Y, Khandheria BK, Gentile F, Seward JB. Echocardiographic assessment of the left atrial appendage. J Am Coll Cardiol 1999;34:1867-77.

72. Donal E, Yamada H, Leclercq C, Herpin D. The left atrial appendage, a small, blind-ended structure: a review of its echocardiographic evaluation and its clinical role. Chest 2005;128:1853-62.

73. Agmon Y, Khandheria BK, Meissner I et al. Left atrial appendage flow velocities in subjects with normal left ventricular function. Am J Cardiol 2000;86:769-73.

74. Bauer F, Verdonck A, Schuster I et al. Left atrial appendage function analyzed by tissue Doppler imaging in mitral stenosis: effect of afterload reduction after mitral valve commissurotomy. J Am Soc Echocardiogr 2005;18:934-9.

75. Cayli M, Acarturk E, Demir M, Kanadasi M. Systolic tissue velocity is a useful echocardiographic parameter in assessment of left atrial appendage function in patients with mitral stenosis. Echocardiography 2007;24:816-22.

76. Vijayvergiya R, Sharma R, Shetty R, Subramaniyan A, Karna S, Chongtham D. Effect of percutaneous transvenous mitral commissurotomy on left atrial appendage function: an immediate and 6-month follow-up transesophageal Doppler study. J Am Soc Echocardiogr 2011;24:1260-7.

77. Yakar Tuluce S, Kayikcioglu M, Tuluce K et al. Assessment of left atrial appendage function during sinus rhythm in patients with hypertrophic cardiomyopathy: transesophageal echocardiography and tissue doppler study. J Am Soc Echocardiogr 2010;23:1207-16.

78. Uretsky S, Shah A, Bangalore S et al. Assessment of left atrial appendage function with transthoracic tissue Doppler echocardiography. Eur J Echocardiogr 2009;10:363-71.

79. Cardiogenic brain embolism. Cerebral Embolism Task Force. Arch Neurol 1986;43:71-84.

80. Odell JA, Blackshear JL, Davies E et al. Thoracoscopic obliteration of the left atrial appendage: potential for stroke reduction? Ann Thorac Surg 1996;61:565-9.

81. Li YH, Hwang JJ, Lin JL, Tseng YZ, Lien WP. Importance of left atrial appendage function as a risk factor for systemic thromboembolism in patients with rheumatic mitral valve disease. Am J Cardiol 1996;78:844-7.

82. Santiago D, Warshofsky M, Li Mandri G et al. Left atrial appendage function and thrombus formation in atrial fibrillation-flutter: a transesophageal echocardiographic study. J Am Coll Cardiol 1994;24:159-64.

83. Grimm RA, Stewart WJ, Arheart K, Thomas JD, Klein AL. Left atrial appendage "stunning" after electrical cardioversion of atrial flutter: an attenuated response compared with atrial fibrillation as the mechanism for lower susceptibility to thromboembolic events. J Am Coll Cardiol 1997;29:582-9.

84. Hwang JJ, Li YH, Lin JM et al. Left atrial appendage function determined by transesophageal echocardiography in patients with rheumatic mitral valve disease. Cardiology 1994;85:121-8.

85. Reddy VG, Rajasekhar D, Vanajakshamma V. Effect of percutaneous mitral balloon valvuloplasty on left atrial

appendage function: transesophageal echo study. Indian Heart J 2012;64.

86. Mitusch R, Garbe M, Schmucker G, Schwabe K, Stierle U, Sheikhzadeh A. Relation of left atrial appendage function to the duration and reversibility of nonvalvular atrial fibrillation. Am J Cardiol 1995;75:944-7.

87. Tanabe K, Yoshitomi H, Asanuma T, Okada S, Shimada T, Morioka S. Prediction of outcome of electrical cardioversion by left atrial appendage flow velocities in atrial fibrillation. Jpn Circ J 1997;61:19-24.

88. Manabe K, Oki T, Tabata T et al. Transesophageal echocardiographic prediction of initially successful electrical cardioversion of isolated atrial fibrillation. Effects of left atrial appendage function. Jpn Heart J 1997;38:487-95.

89. Perez Y, Duval AM, Carville C et al. Is left atrial appendage flow a predictor for outcome of cardioversion of nonvalvular atrial fibrillation? A transthroacic and transesophageal echocardiographic study. Am Heart J 1997;134:745-51.

90. Verhorst PM, Kamp O, Welling RC, Van Eenige MJ, Visser CA. Transesophageal echocardiographic predictors for maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation. Am J Cardiol 1997;79:1355-9.

91. Palinkas A, Antonielli E, Picano E et al. Clinical value of left atrial appendage flow velocity for predicting of cardioversion success in patients with non-valvular atrial fibrillation. Eur Heart J 2001;22:2201-8.

92. Tabata T, Oki T, Iuchi A et al. Evaluation of left atrial appendage function by measurement of changes in flow velocity patterns after electrical cardioversion in patients with isolated atrial fibrillation. Am J Cardiol 1997;79:615-20.

93. Grimm RA, Leung DY, Black IW, Stewart WJ, Thomas JD, Klein AL. Left atrial appendage "stunning" after spontaneous conversion of atrial fibrillation demonstrated by transesophageal Doppler echocardiography. Am Heart J 1995;130:174-6.

94. Falcone RA, Morady F, Armstrong WF. Transesophageal echocardiographic evaluation of left atrial appendage function and spontaneous contrast formation after chemical or electrical cardioversion of atrial fibrillation. Am J Cardiol 1996;78:435-9.

95. Omran H, Jung W, Rabahieh R et al. Left atrial chamber and appendage function after internal atrial defibrillation: a prospective and serial transesophageal echocardiographic study. J Am Coll Cardiol 1997;29:131-8.

96. Sparks PB, Jayaprakash S, Vohra JK et al. Left atrial "stunning" following radiofrequency catheter ablation of chronic atrial flutter. J Am Coll Cardiol 1998;32:468-75.

97. Grimm RA, Stewart WJ, Maloney JD et al. Impact of electrical cardioversion for atrial fibrillation on left atrial appendage function and spontaneous echo contrast: characterization by simultaneous transesophageal echocardiography. J Am Coll Cardiol 1993;22:1359-66.

REVIEW ARTICLE


Arrhythmias in Acute Coronary Syndrome: Etiopathogenesis and Management

REVIEW ARTICLE

CHANDRA BHAN MEENA, DAULAT SINGH MEENAKeywords ST- elevation myocardial infarction Ventricular arrhythmias AV block

Dr Chandra Bhan Meena is Senior Professor Cardiology and Dr Daulat Singh Meena is Senior Resident. Department of Cardiology at SMS Medical College, Jaipur

AbstractAcute myocardial infarction can be complicated by both atrial and ventricular arrhythmias, that carry important prognostic implications. The pathogenic mechanisms of arrhythmias in AMI are varied and

therapeutic options for arrhythmias in acute coronary syndrome

modulation.

INTRODUCTION Coronary heart disease (CHD) is one of the leading cause of death and as per World Health Organization (WHO) report; cardiovascular disease (CVD) cause 30% death that occurred worldwide.1The ST- elevation myocardial infarction (STEMI) have a 4-fold higher risk for ventricular arrhythmias in comparison to non-ST-elevation myocardial infarction (NST-ACS) and majority (90%) of arrhythmias in STEMI patients occur

prophylactic antiarrhythmic strategies is controversial and management of the arrhythmias is mostly driven by hemodynamic and symptomatic

status of patient. The increased uses of primary PCI, beta-blocker, and AICD all

of arrhythmias after acute myocardial infarction.

MECHANISMS OF ARRHYTHMIAS IN ACS

atrial arrhythmia in ACS with the reported incidence varying from 4.4 to 21.9%.2-13

is cause by regional heterogeneity in local conduction, increase in action potential duration, heterogeneous cytokine


increase in atrial wall stress due to pressure or volume overload. All contribute to generate heterogeneous electrical and structural milieu that contributes to the onset of focal discharges and providing a substrate for re-entry at the border zones, and lead to initiation and maintenance of

14-17

Sustained ventricular arrhythmias complicate up to 20% of acute myocardial infarction (MI) presentations and are associated with a poor prognosis. The ischemia leads to (a) increase in resting membrane potential from -80 mV to -60 mV, due to intracellular accumulation of Ca2+ and inhibition of the inward rectifying potassium current (Ik1), (b) a decrease in action potential amplitude, upstroke velocity and duration of ischemia related activation of the substrate related potassium current (IKAPT), and (c) non- uniform anisotropy and cellular uncoupling due to of loss of functional gap junctions.18 These ischemia induce abnormality to lead alterations in conduction, refractoriness, and automaticity, which in-turn provides the substrate for reentry. The centre for a reentrant circuit is formed by an area of functional conduction block.19 However,

and may recover causing constantly changing re-entrant circuits leading to polymorphic or often irregular ventricular arrhythmias.

These reentries are initiated by premature depolarization arising from

in reperfusion after prolonged periods of ischemia. The premature depolarization occur due to impaired Na+/ Ca2+ exchange pump opening, activation of delayed

of sarcoplasmic reticulum,20 all these result in the intracellular Ca2+ overload and will result in spontaneous Ca2+oscillations that trigger early and delayed after depolarizations and induce ectopic beats.21 Thus reentries as the dominant mechanism for arrhythmias occur early after ischemia, whereas triggered activity appears to be the dominant mechanism of arrhythmias occuring after reperfusion.22

High-grade AV block and asystole develop in about 23-35% of acute

MI patients with cardiogenic shock, especially in inferior infarctions with proximal right coronary artery (RCA) occlusion. Bradyarrhythmias are induced by either autonomic imbalance or ischaemia and necrosis of the conduction system.23-24 The AV node and His bundle are supplied by the AV nodal artery that takes origin from the RCA in 90% of the

in 10% of the patients. The right bundle branch and the anterior fascicle of the left bundle branch are supplied by septal perforators in 90% of cases arising from the proximal left anterior descending coronary artery, whereas the posterior fascicle of the left bundle branch (BB) is supplied by the conus branch of the RCA.25 Therefore the LAD occlusion will induce a right bundle branch block (RBBB) or an anterior left fascicular block. The occlusion of both proximal LAD and RCA lead to development of a new onset LBBB.

SUPRAVENTRICULAR TACHYARRHYTHMIAS IN ACSThe physiological over activity of the sympathetic system, atrial

stretch, ischemia or infarction, all can contribute for development of AF,

tachyarrhythmias26-27 and their incidence is further increased in presence of heart failure, cardiogenic shock and advanced age.28-29 AF can cause hemodynamic worsening due to decrease in the left

30

AF increases risk of short and long-term (>1 year) mortality up to 40 % in patients with AMI.31

The management of AF in the setting of acute MI should be individualized taking consideration of rhythm or rate control and the use of anticoagulation. In patients with AF with fast ventricular rate,

dihydropyridine calcium antagonists (Table-1). The use of beta-blockers or calcium antagonist should be avoided in presence of severe LV dysfunction, heart failure and hypotension, in these patients rate control should be achieved by using intravenous amiodarone and/or digitalis.32

In presence of severe hemodynamic instability or intractable ischemia, or

Table 1: ESC guideline32 for management of atrial fibrillation in the acute phase Recommendations

Rhythm control should be considered in patients with atrial fibrillation

secondary to a trigger or substrate that has been corrected (e.g.

ischaemia).

Acute rate control of atrial fibrillation

Intravenous beta-blockers or non-dihydropyridine CCB (e.g. diltiazem,

verapamil) are indicated if there are no clinical signs of acute heart

failure.

Amiodarone or i.v. digitalis is indicated in case of rapid ventricular

response in the presence of concomitant acute heart failure or

hypotension.

Cardioversion

Immediate electrical cardioversion is indicated when adequate rate

control cannot be achieved promptly with pharmacological agents

in patients with atrial fibrillation and on-going ischaemia, severe

hemodynamic compromise or heart failure.

Intravenous amiodarone is indicated for conversion to sinus rhythm in

stable patients with recent onset atrial fibrillation and structural heart

disease.

Digoxin (LoE A), verapamil, sotalol, metoprolol (LoE B) and other beta-

blocking agents (LoE C) are ineffective in converting recent onset

Cardiology TodayCover Sep-Oct 2017 - CIMS...Cardiology TODAY VOLUME XXI No. 5 SEPTEMBER-OCTOBER 2017...

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Transcript of Cardiology TodayCover Sep-Oct 2017 - CIMS...Cardiology TODAY VOLUME XXI No. 5 SEPTEMBER-OCTOBER 2017...