1CT Jan-Feb 2019 Content - CIMS · 2020-04-15 · Cardiology TODAY VOLUME XXIII No. 1...

Cardiology TODAY

VOLUME XXIII No. 1JANUARY-FEBRUARY 2019

PAGES 1-40

Rs. 1700/- ISSN 0971-9172 RNI No. 66903/97

www.cimsasia .com

MANAGING DIRECTOR & PUBLISHERDr. Monica Bhatia

EDITOR IN CHIEFOP Yadava

SECTION EDITORSSR Mittal (ECG, CPC), David Colquhou n (Reader’s Choice)

NATIONAL EDITORIAL ADVISORY BOARDArun K Purohit, Arun Malhotra, Ashok Seth, Ashwin B Mehta, CN Manjunath, DS Gambhir, GS Sainani, Harshad R Gandhi, I Sathyamurthy, Jagdish Hiremath, JPS Sawhney, KK Talwar, K Srinath Reddy, KP Misra, ML Bhatia, Mohan Bhargava, MR Girinath, Mukul Misra, Nakul Sinha, PC Manoria, Peeyush Jain, Praveen Jain, Ramesh Arora, Ravi R Kasliwal, S Jalal, S Padmavati, Satyavan Sharma, SS Ramesh, Sunil Kumar Modi, Yatin Mehta, Yogesh Varma, R Aggarwala.

INTERNATIONAL EDITORIAL ADVISORY BOARDAndrew M Tonkin, Bhagwan Koirala, Carlos A Mestres, Chuen N Lee, David M Colquhoun, Davendra Mehta, Enas A Enas, Gerald M Pohost, Glen Van Arsdell, Indranill Basu Ray, James B Peter, James F Benenati, Kanu Chatterjee, Noe A Babilonia, Pascal R Vouhe,Paul A Levine, Paul Simon, P K Shah, Prakash Deedwania, Salim Yusuf, Samin K Sharma, Sanjeev Saxena, Sanjiv Kaul, Yutaka Imoto.

DESK EDITORGandhali

DESIGNER A run Kharkwal

OFFICES CIMS Medica India Pvt Ltd(Previously known as UBM Medica India Pvt Ltd.)Registered OfficeMargosa Building, No. 2, 3rd Floor, 13th Cross, Margosa Road, Malleshwaram, Bengaluru -560 003 Karnataka, IndiaTel: +91-80-4346 4500Fax: +91-80-4346 4530

Corporate OfficeBoomerang (Kanakia Spaces), Wing-B1, 403,4th Floor, Chandiwali Farm Road, ChadiwaliPowai, Mumbai - 400 072Tel.: +91-22-6612 2600 Fax : +91-22-6612 2626

Regional Off ice709, 7th Floor, Devika Tower, Nehru Place, New Delhi-110 019, India. Tel: +91-11-4285 4300Fax: +91-11-4285 4310

EDITORIALCircadian Rhythm of the Body - Is it the Holy Grail ? 3OP YADAVA

REVIEW ARTICLEContrast Induced Nephropathy: How to Predict and Prevent? 5RAGHAV BANSAL, VIVEKA KUMAR

REVIEW ARTICLEHow do I Manage My Patients with Heart Failure with Preserved Ejection Fraction? 10MOHAMMED SADIQ AZAM, DAYASAGAR RAO V

REVIEW ARTICLEPractical Approach to Constrictive Pericarditis 15MONIK MEHTA

Cardiology Today VOL.XXIII NO. 1 JANUARY-FEBRUARY 2019 1

FOR MARKETING QUERIESAparna Mayekar: +91-9930937020+91-22-6612 [email protected]

FOR EDITORIAL QUERIESDr Gandhali : +91-22-6612 [email protected]

©2019 CIMS Medica India Pvt Ltd (Previously known as UBM Medica India Pvt Ltd) Copyright in the material contained in this journal (save for advtg. and save as otherwise indicated) is held by CIMS Medica India Pvt Ltd Margosa Building, No. 2, 3rd Floor, 13th Cross, Margosa Road, Malleshwaram, Bengal uru-560 003, Karnataka, India. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, photocopying or otherwise, without prior permission of the publisher and copyright owner.

The products and services advertised are those of individual advertisers and are not necessarilty endorsed by or connected with the publisher or with Cardiology Today or CIMS Medica India Pvt Ltd. Cardiology Today does not guarantee, directly or indirectly, the quality or efficacy of any product or services described in the advertisements in this issue, which are purely commercial in nature.

The editorial opinions expressed in this publication are those of individual authors and not necessarily those of the publisher. Whilst every effort has been made to ensure the accuracy of the information in this publication, the publisher accepts no responsibility for errors or omissions.

For reprints (minimum order: 500) contact the production Department. Further copies of Cardiology Today are available from CIMS Medica India Pvt Ltd, 709, Devika Tower, Nehru Place, New Delhi-110 019, India.

Cardiology Today is Published and Printed by CIMS Medica India Pvt Ltd, Margosa Building, No. 2, 3rd Floor, 13th Cross, Margosa Road, Malleshwaram, Bengaluru - 560 003, IndiaTel: +91-80-4346 4500 (Board); Fax: +91-80-4346 4530

Printed at Modest Print Pack (P) Ltd., C-52, DDA Sheds Okhla Industrial Area, Phase-I, New Delhi-110 020.

REVIEW ARTICLETransesophageal Echocardiography in Children with Congenital Heart Defects 18SNEHAL KULKARNI

REVIEW ARTICLEWhen to Refer for CABG in Today’s Era of Affordable Stents and PTCA and Wide Application of Technologies 24C N MANJUNATH, PRABHAVATHI, C RAGHAVENDRA

ECG OF THE MONTHCause of Increase in P Wave Amplitude During Exercise Induced Tachycardia 30

SR MITTAL

PICTORIAL CMEIsolated Tricuspid Valve Prolapse 31SR MITTAL

Congenital Fused Cervical Vertebrae 38MONIKA MAHESHWAR

2 Cardiology Today VOL.XXIII NO. 1 JANUARY-FEBRUARY 2019

Cardiology Today VOL.XXIII NO. 1 JANUARY-FEBRUARY 2019 3

Circadian Rhythm of the Body - Is it the Holy Grail ?

EDITORIAL

Existence of a circadian rhythm for the activities of the brain is a given and a common knowledge, but that there is a similar peripheral clock in gastro-intestinal tract and other organs and tissues is not that well appreciated. It is intuitive that when one defi es nature, some penalties would have to be paid, but it is only now that scientifi c sanctity has been accorded to this rather obvious fact of life. Long duration manipulation and disruption of the circadian rhythm has been associated with metabolic disorders like obesity, diabetes, hypertension etc. But it is not clear, whether this is modulated through the central pacemaker in the brain, or to certain products of metabolism, which too have a circadian rhythm.

In a recent study conducted at the Washington State University, two groups - one having a night-shift sleep routine and the other a day-shift pattern were studied1. Melatonin and Cortisol were used as markers of the brain master clock and another 132 metabolites were used to study the peripheral clock of other organs and tissues. It was found that both Melatonin and Cortisol showed only negligible diff erences between the day and night shift patterns, suggesting that the master clock of the brain is resistant to the shift patterns. However, of the 132 other metabolites, nearly half (65) had a signifi cant daily rhythm and only 3 metabolites (Taurine, Serotonin and Sarcosine) mirrored Melatonin and Cortisol, the markers of the brain's master clock. Metabolites that were aff ected by the night-shift sleep pattern were found to be related to the liver, pancreas and the gastrointestinal tract, prompting Van Dongen, the lead author, to comment, 'no one knew that the biological clocks in people's digestive organs are so profoundly and quickly changed by shift-work schedules, even though the brain's master clock barely adapts to such schedules. As a result, some biological signals in shift workers' bodies are saying its day, while other signals are saying its night, which causes disruption of metabolism.'1

These fi ndings assume special importance for countries in Asia, especially India, which have become back offi ce data analysis and storage repositories for North America. As such, we have genetic predisposition for metabolic syndrome, and if to this 'nature', we add another confounder in terms of the 'nurture', and that too in a young work force, then it is going to have disastrous consequences for the country, besides the individuals and their families. Lack of exercise and frequent unhealthy snacking, that is attendant to the night shift workers' profi le, complemented by the unhealthy genes, make matters worse.

DR. OP YADAVACEO and Chief Cardiac Surgeon

National Heart Institute,New Delhi

4 Cardiology Today VOL.XXIII NO. 1 JANUARY-FEBRUARY 2019

The Business Process Outsourcing (BPO) model therefore needs to be regulated and norms drawn to protect the health of individuals involved, as they may not be aware of the occult health issues attendant to night shifts. They should be suitably counselled and informed and healthy behaviours inculcated by cajoling and regulations, besides voluntary self discipline in culinary matters.

Could this circadian rhythm be applicable to the gut microbiome too? This is indeed another interesting thought and worthy of scientifi c pursuance, as it has not been evaluated till date. In these two facets - the circadian rhythm of the human body and the gut microbiota, and their interaction, may lie the answers to a lot of imponderables on causation of disease.

REFERENCE1. Skene DJ, Skornyakov E, Chowdhury NR, Gajula RP, Middleton B, Satterfield BC, Porter KI, Van Dongen HPA, Gaddameedhi,

S. Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism. S. Proc Natl Acad Sci U S A. 2018 Jul 10. Epub ahead of print. PMID: 29991600.

Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019 5

Contrast Induced Nephropathy: How to Predict and Prevent?

REVIEW ARTICLE

RAGHAV BANSAL, VIVEKA KUMARKeywords contrast media acute kidney injury renal replacement therapy european society of cardiology rec-

ommendation

Dr. Raghav Bansal is Associate Consultant, Cardiology, Max Super Speciality Hospital, Saket, New Delhi & Dr. Viveka Kumar is Senior Director, Cath Lab, Max Heart and Vascular Institute, Saket, New Delhi

AbstractContrast-induced nephropathy (CIN) is a serious complication of angiographic procedures resulting from the administration of contrast media (CM). CIN is usually transient, with serum creatinine levels peaking at 2–3 days after administration of contrast medium and returning to baseline within 7–10 days after administration. Multiple studies have been conducted using a variety of therapeutic interventions in an attempt to prevent CIN. Of these, careful selection of patients, using newer radiocontrast agents, maintenance of hydration status, and avoiding nephrotoxic agents pre- and post-procedure are the most effective interventions to protect against CIN. This review focuses on the basic concepts of CIN and summarizes our recent understanding of its pathophysiology. In addition, this article provides practical recommendations with respect to CIN prevention and management.

INTRODUCTIONContrast-induced nephropathy (CIN) represents the iatrogenic renal injury secondary to exposure to iodinated contrast media used during interventional cardiology procedures and contrast enhanced computed tomography scans. CIN remains a feared complication after a percutaneous coronary intervention (PCI) as it is associated with poor cardiovascular outcomes even after achieving a good procedural success. CIN was fi rst described in the 1950s as fatal renal toxicity after contrast

exposure for intravenous pyelography in multiple myeloma patients with already compromised kidneys.1 With the ever-expanding number of diagnostic and interventional procedures involving contrast media, the risk of CIN continues to haunt every interventional cardiologist and radiologist. Even after signifi cant advances of our understanding, CIN remains common, being the cause of hospital acquired acute kidney injury (AKI) in one third of all the cases.2 Although it aff ects only 1 to 2% of the general patient population, it affl icts

6 Cardiology Today VOL. XXIII NO. 1 JANUARY-FEBRUARY 2019

up to 50% of patients in high risk groups.3 Considering the adverse events and increased healthcare costs which CIN portends, the importance of risk prediction followed by prevention of CIN cannot be overemphasized.

DEFINITION AND PATHOPHYSIOLOGICAL CONSIDERATIONSThe generally accepted defi nition of CIN has threefold considerations (Figure 1). There is an AKI component which is defi ned as 0.5 mg/dL or >25% increase in serum creatinine values from the baseline value. The AKI should occur within 72 hours of contrast exposure. And lastly, to label as CIN there should not be any apparent alternative explanation for the AKI.3 Thus, there is a defi nite time course of CIN. It begins within 24 to 48 hours of contrast exposure and usually peaks at 3-4 days. There is an array of proposed novel biomarkers including Cystatin C, Urinary Kim-1, Interleukin 18 and NGAL that may be helpful for earlier identifi cation of CIN. Unfortunately, to date, these biomarkers have yet to progress beyond the realms of clinical research. CIN may be oliguric or non-oliguric. Non-oliguric CIN resolves in most of the patients within a time period of 7 days. In contrast, the oliguric CIN is more ominous with the greater requirement of renal replacement therapy and often taking a longer time (typically 1 to 3 weeks) to recover. Risk of progression of underlying chronic kidney disease (CKD) and acute injury becoming a chronic problem with partial recovery is present in each case, even when the renal dysfunction is mild and transient in most of the cases.

Pathophysiology of CIN is related to medullary ischaemia and direct toxicity after contrast exposure.4 All iodinated contrast media contain concentrated iodinated benzene compounds which are cytotoxic to a variable extent depending upon the ionic strength, viscosity and osmolality.5 The initially used high osmolar contrast media were highly nephrotoxic and had been subsequently phased out. Though the low osmolar or the latest generation iso-osmolar contrast media are less nephrotoxic, they entail a greater risk of ischaemia to the renal medulla. Viscosity is inversely proportional to osmolality. Thus the newer generation compounds are more viscous and interfere with normal renal blood fl ow. In addition, the contrast media is vasoactive. Within minutes of contrast exposure a state of prolonged vasoconstriction sets in with imbalance of many vascular mediator compounds including nitrous oxide, adenosine, endothelin, prostaglandin and reactive oxygen species.6 The outer medullary portion of the kidneys is the most ischaemia sensitive and generally the worst hit area.7 In cases of pre-existing CKD, the oxygen requirement of the overburdened nephrons is higher than normal and thus suff er a greater ischaemic injury.8

WHY CIN IS IMPORTANT: CORRELATION WITH ADVERSE EVENTSCIN is mostly transient with more than 80% of the cases resolving within 3 weeks.9 In view of a number of short term and long term adverse events in a small proportion but a signifi cant

number of cases CIN is still considered ominous. Observational studies have demonstrated a fi ve-fold increase in in-hospital mortality in patients who develop CIN as compared to those who do not.10 In a sample size of 1826 patients, McCullough et al demonstrated an in-hospital mortality rate of 7.1% in patients developing CIN as compared to patients who do not.10 The 1-year mortality rate was also signifi cantly higher in a study by Gruberg et al.11 Thus, long term mortality rates on 1 year and 5 years follow-up may also be up to four-fold higher in patients who develop CIN.11 The risk of persistent renal dysfunction is also signifi cant with almost one-fi fth of patients having persistent dysfunction after CIN in an observational study by Maioloi et al.12 Renal replacement therapy may be required in a number of cases ranging from 0.7 to 7%.13-14 The healthcare costs thus incurred are signifi cant.15

However, a direct causal association of CIN with mortality is diffi cult to prove as there are many confounders. CIN more commonly develops in patients with high risk features such as diabetes, pre-existing CKD, left ventricular dysfunction and severe cardiac disease. Thus, CIN may be a marker of severe disease leading to increased cardiovascular mortality. In a recent meta-analysis by James et al, development of CIN was associated with an increased mortality.16 But when the baseline risk factors were compared, the group developing CIN was already at a higher risk of mortality due to strong risk factors. Although adjustment is done in most of the studies, interpreting causality from observational data may be fl awed in present of confounders. There remains

REVIEW ARTICLE

Figure 1. The three important considerations of definition of CIN.

>0.5 mg/dL absolute or 25% as compared

to baseline creatinine value

48-72 hours after contrast exposure, peaks at 3-5 days

Absence of alternate causes

of AKI

Co

ntr

ast

med

ia

Figure 2. Pathogenesis of CIN.

Direct ToxicityDirect cytotoxicity of iodine compounds

Ischaemic injury

Reactive oxygen species, Decreased anti-oxidant enzyme activity

Imbalance of vasoactive mediators (Nitric oxide, prostaglandin, adenosine and endothelin)

Increased viscosity leading to impaired blood flow in microvessels

Increased oxygen consumption


medications is also considered as a risk marker. These commonly include metformin, NSAIDs and nephrotoxic antibiotics. However, the risk with ACE inhibitors and angiotensin receptor blockers (ARBs) is less well defi ned and it is considered safe to continue these medications if already a part of standard therapy received by the patient.18

Procedural factors for contrast media volume used and history of previous contrast media exposure within 72 hours are also considered as important risk factors.22 Total contrast volume of > 350 ml or > 4 ml/kg is considered a risk factor for CIN.20 Laskey et al demonstrated that a volume of contrast to eGFR (estimated Glomerular Filtration Rate) greater than 3.7:1 is strongly correlated with risk of CIN.23 The presence of hemodynamic instability in the peri-procedural period also plays a signifi cant role. Thus in a PCI done on inotropic or balloon support, one should be wary of development of CIN and should try to limit the volume of contrast media as far as possible.

A number of scoring systems are available for the prediction of development of CIN. The most commonly employed is the one proposed by Mehran et al (Table 2).20 But the major drawback of this system is that it gives risk prediction only after the procedure is over as it also involve procedural factors. It is often desirable for risk prediction to be accurate before the procedure. For this purpose, another scoring system by Miaoli et al has often been employed.22

a void of large randomized controlled trials regarding this to prove causality, which remain almost impossible with ethical and cost considerations involved. It can be said that prognosis of patients developing is signifi cantly worse as compared to patients who do not.

PREDICTION OF CINRisk assessment remains an important tool in clinical medicine to improve the yield of interventions. Same holds true for the case of CIN. If it can be identifi ed that which patient is going to develop CIN then special precautions in these cases may be warranted to improve outcomes. Employing preventive interventions universally, may not be cost eff ective and may complicate things unnecessarily as most of the patients undergoing contrast exposure are not going to develop CIN. There are many risk factors which have an implication for the development of CIN (Table 1). Most of these risk factors can be assessed with history, examination and routine biochemical investigations. The most important of the risk factors is the pre-existing CKD. In 1999, the risk of signifi cant CIN was defi ned by a creatinine level above 1.3 mg/d in males and 1.0 in females by the European society of urogenital radiology consensus working panel.17 These fi gures were found to correlate with a eGFR level of 60 ml/min/1.73 m.2 CKD stage 3-5 corresponding with an eGFR level of 60 ml/min/1.73 m2 or below is now generally recognized as the CIN risk threshold.18 Thus, serum creatinine remains the most eff ective and a simple tool to screen for risk of CIN. The creatinine value is an insensitive marker of renal dysfunction, however, and thus fails to predict many cases of CIN.

The next major risk factor for CIN is dehydration. Being primarily a clinical diagnosis it has been impossible to quantitate and directly study its eff ects. But a surrogate in the form of hypotension, defi ned by systolic pressure of less than 80 mmHg for more than 60 minutes, is a recognized risk marker for CIN. Hypotension, secondary to cardiogenic shock and even excessive vasodilation (as seen in septic shock and anaphylaxis), is also a signifi cant risk marker for CIN. Hypotension adversely aff ects renal perfusion and predisposes to greater renal injury with contrast media. Congestive heart failure, acute myocardial infarction and left ventricular dysfunction with ejection fraction less than 45% are also associated with renal hypo-perfusion, and thus increased risk of CIN.19 There is ample of data now available which suggest diabetes as a major risk factor for CIN, especially when associated with CKD.19 Other common risk factors include elderly age group (>75 years of age)20 and anemia (haematocrit of <0.39 in males and <0.36 in females).21 Co-administration of other nephrotoxic

Table 1. Risk Factors for CINNon ModifiableNon Modifiable ModifiableModifiable

1. Elderly1. Elderly

2. Diabetic Nephropathy2. Diabetic Nephropathy

3. CKD with eGFR <60 ml/min/1.73m3. CKD with eGFR <60 ml/min/1.73m22

4. Proteinuria4. Proteinuria

5. CHF/Cardiogenic shock5. CHF/Cardiogenic shock

6. Acute Myocardial infarction6. Acute Myocardial infarction

7. Intra-aortic balloon pump7. Intra-aortic balloon pump

1. Volume depletion1. Volume depletion

2. Hypotension2. Hypotension

3. Volume and type of contrast3. Volume and type of contrast

4. Anaemia/ blood loss4. Anaemia/ blood loss

5. Diuretics5. Diuretics

6. NSAIDs6. NSAIDs

7. Other nephrotoxins7. Other nephrotoxins

Table 2. Mehran risk score for the prediction of CIN.20

Risk Factors ScoreRisk Factors Score

Hypotension (SBP <80 mm Hg or >1 h of inotropic support) 5Hypotension (SBP <80 mm Hg or >1 h of inotropic support) 5

Intra-arterial balloon pump therapy 5Intra-arterial balloon pump therapy 5

Chronic heart failure, (NYHA III/IV or recent pulmonary oedema) 5Chronic heart failure, (NYHA III/IV or recent pulmonary oedema) 5

Age >75 years 4Age >75 years 4

Diabetes mellitus 3Diabetes mellitus 3

Anaemia (male: HCT<0.39, female: HCT<0.36) 3Anaemia (male: HCT<0.39, female: HCT<0.36) 3

Estimated glomerular filtration rate <20 mL/min 6Estimated glomerular filtration rate <20 mL/min 6

Estimated glomerular filtration rate 20–40 mL/min 4Estimated glomerular filtration rate 20–40 mL/min 4

Estimated glomerular filtration rate 40–60 mL/min 2Estimated glomerular filtration rate 40–60 mL/min 2

Contrast media volume 1 per ccContrast media volume 1 per cc

Score <5 6-10 11-16 >16Score <5 6-10 11-16 >16

CIN risk Low 7.5% Moderate 14% High 26.1% Very High 57.3%CIN risk Low 7.5% Moderate 14% High 26.1% Very High 57.3%

Dialysis risk 0.04% 0.12% 1.09% 12.6%Dialysis risk 0.04% 0.12% 1.09% 12.6%


24 hours before the procedure and for 48 hours following the contrast media exposure (Table 3). Metformin should also be discontinued for the fear of lactic acidosis and not for nephrotoxicity per se. Limiting the contrast exposure to as low as reasonably possible forms an important principle for the prevention of CIN. Using biplane catheterization laboratories for patients at high-risk may be preferred to limit contrast exposure. The current guidelines recommend the use of iso-osmolar or low osmolar contrast media over high osmolar ones. The comparison

Newer risk markers are continuously being evaluated for even more accurate prediction of CIN. However, none of these have percolated down into the clinical practice yet.

PREVENTION OF CINIn all the patients who are referred for contrast media based procedures, it is essential to perform a comprehensive review of indication and to evaluate whether the procedure can be avoided in view of alternate options. Every patient should undergo an assessment for the risk of development of CIN, especially if the eGFR is <60 ml/min. If two procedures involving are to be done, they should be spaced out by at least 72 hours. The second procedure should be further delayed up to the complete resolution of nephropathy if there is development of CIN after the fi rst procedure. All said, it is also important to remember that the patients who are at high risk of CIN are also at higher risk of cardiovascular complications and poor outcomes, and thus an indicated procedure should not be unnecessarily delayed.

All the patients should be advised to stop all nephrotoxic medications at least

of various contrast media is given in Table 4.

Till date, adequate hydration remains the most important prophylactic measure for prevention of CIN. Suffi cient intravascular volume ensures adequate dilution of contrast media along with generous blood fl ow to the kidneys. In patients who are at low risk, even oral hydration may suffi ce. However, intravenous hydration with crystalloids is preferred in patients who are at higher risk of development of CIN. The nature of crystalloid to be preferred still remains a matter of debate. The general fl uid of choice remains isotonic saline (0.9% NaCl solution), with soda-bicarbonate being still used at many centres. The initial trials had shown some benefi t with the use of bicarbonates over saline, however, a contemporary randomized controlled trial (PRESERVE trial) failed to show superiority of bicarbonate solution over normal saline.24 The current guidelines recommend hydration with normal saline at the rate of 1 to 1.5 ml/kg/hour for 12 hours pre-procedure and 24 hours post procedure.27 Small trials have suggested benefi t of left ventricular end diastolic pressure guided intravenous hydration and also hydration with intravenous furosemide to maintain good urine output.25-26 These methods may help in the prevention of CIN at the same time precipitating less heart failure events. All patients who are at risk should be assessed at 48-72 hours after the procedure to screen for the development of CIN. It is essential to rule out athero-embolic

REVIEW ARTICLE

Table 3. Nephrotoxic medications requiring withdrawal 24 hours before contrast media exposure.Drug Class ExamplesDrug Class Examples

NSAIDs Naproxen, Ibuprofen, Diclofenac, CelecoxibNSAIDs Naproxen, Ibuprofen, Diclofenac, Celecoxib

Antibiotics Aminoglycosides (Amikacin, Gentamicin, Tobramycin)Antibiotics Aminoglycosides (Amikacin, Gentamicin, Tobramycin)

Antifungals Amphoterecin BAntifungals Amphoterecin B

Antivirals Acyclovir, Tenfovir, FoscarnetAntivirals Acyclovir, Tenfovir, Foscarnet

Immunomodulatory Cyclosporin AImmunomodulatory Cyclosporin A

Antineoplastic Cisplatin, Ifosfamide, MitomycinAntineoplastic Cisplatin, Ifosfamide, Mitomycin

Table 4. Classification of contrast dyes.High Osmolar Contrast Medium Osmolality ~ 1500 mOsmHigh Osmolar Contrast Medium Osmolality ~ 1500 mOsm

Diatrizoate (Gastrograffin, Hypaque)Diatrizoate (Gastrograffin, Hypaque)

Iothalamate (Conray) Iothalamate (Conray)

Low Osmolar Contrast Medium Osmolality ~ 320-800 mOsmLow Osmolar Contrast Medium Osmolality ~ 320-800 mOsm

Iohexol (Omnipaque)Iohexol (Omnipaque)

Ioxaglate (Hexabrix)Ioxaglate (Hexabrix)

Ioversol (Optiray)Ioversol (Optiray)Iomeprol (Imeron)

Iopromide (Ultravist)

Iopamidol (Isovue, Iopamiro, Niopam) Higher rate of AKI

Lower rate of AKI

Iso-Osmolar Contrast Medium Osmolality ~ 290 mOsm

Iodixanol (Visipaque) Iodixanol (Visipaque)

Recommendation Class GradeRecommendation Class Grade

Risk assessment for CI-AKI before CAG IIa CRisk assessment for CI-AKI before CAG IIa C

Hydration with isotonic saline I AHydration with isotonic saline I A

Low or Iso-osmolar contrast media (Contrast volume/GFR <3.4) I ALow or Iso-osmolar contrast media (Contrast volume/GFR <3.4) I A

Short term high dose statin IIa AShort term high dose statin IIa A

Iso-osmolar preferred over Low-osmolar contrast media IIa AIso-osmolar preferred over Low-osmolar contrast media IIa A

Volume of contrast should be minimized IIa BVolume of contrast should be minimized IIa B

Furosemide with matched hydration in patients at high-risk IIb AFurosemide with matched hydration in patients at high-risk IIb A

N-Acetylcysteine III AN-Acetylcysteine III A

Sodium Bicarbonate 0.84$ infusion III ASodium Bicarbonate 0.84$ infusion III A

Prophylactic hemodiafiltration 6 hrs before complex PCI in CKD patients IIb BProphylactic hemodiafiltration 6 hrs before complex PCI in CKD patients IIb B

Prophylactic renal replacement therapy in CKD III BProphylactic renal replacement therapy in CKD III B

Figure 3. European Society of Cardiology CIN prevention guidelines, 2014.27


renal insult before making a diagnosis of CIN. In athero-embolic renal disease, the rise in serum creatinine occurs a later (typically 1 to 3 weeks), and does not resolve as commonly as in CIN. Other peripheral signs of athero-embolism, peripheral eosinophilia, low complement levels, and proteinuria with WBCs on urinalysis help in clinching the diagnosis of athero-embolic renal involvement.

Many pharmacological interventions have been tried for the prevention of CIN, but none has proved to be eff ective in the long run. The most commonly used of these agents is N-Acetyl Cysteine (NAC). However, it has gone out of favour after it failed to show benefi t in the randomized controlled PRESERVE trial.25 Other agents that have been considered as preventive in this regard include adenosine receptor antagonists, ascorbic acid, atrial natriuretic peptides, diuretics, dopamine and prostaglandins. But none of them have proved to be an eff ective and thus their use is not recommended. There is some data that suggest statins may be helpful for prevention of CIN, but still, they need to be tested in larger trials before being universally recommended. Lastly, it remains important to remember that there is no role of prophylactic renal replacement therapy for the prevention of CIN. And renal replacement therapy should be considered only for standard indication after the development of CIN. The European society of cardiology recommendation for the prevention of CIN has been presented in Figure 3. SUMMARYCIN remains fairly common and has increasing prevalence with increasing numbers and complexity of contrast media based procedures. Although resolving spontaneously in 80% of the cases, it remains an important cause of signifi cant morbidity leading to increased health care costs. Association of CIN with adverse cardiovascular outcomes is defi nite, thus making CIN ominous. Assessment

of risk by careful evaluation to employ targeted intervention in those who are at high-risk. Pre-existing CKD, diabetes, left ventricular dysfunction, hypotension, elderly age group, anaemia and use of other nephrotoxic drugs are the most important risk markers. The importance of avoiding interventions, that are not essential, cannot be over-emphasized. Till date, intravenous hydration with normal saline, avoiding nephrotoxic drugs and limiting contrast media exposure to as minimum as possible remains the most eff ective preventive measures for CIN. Pharmacological interventions are not recommended at present for the prevention of CIN.

REFERENCES1. Bartels ED, Brun GC, Gammeltoft A, et al. Acute anuria

following intravenous pyelography in a patient with myelomatosis. Acta Med Scand 1954;150:297–302.

2. Hou SH, Bushinsky DA, Wish JB, et al. Hospital-acquired renal insufficiency: a prospective study. Am J Med 1983; 74:243–8.

3. Mehran R, Nikolsky E. Contrast-induced nephropathy: definition, epidemiology, and patients at risk. Kidney Int Suppl 2006:S11–15.

4. Sendeski MM. Pathophysiology of renal tissue damage by iodinated contrast media. Clin Exp Pharmacol Physiol 2011;38:292–9.

5. Heinrich MC, Kuhlmann MK, Grgic A, et al. Cytotoxic effects of ionic high-osmolar, nonionic monomeric, and non-ionic iso-osmolar dimeric iodinated contrast media on renal tubular cells in vitro. Radiology 2005;235:843–9.

6. Tumlin J, Stacul F, Adam A, et al., Panel CINCW. Pathophysiology of contrast-induced nephropathy. Am J Cardiol 2006;98:14K–20K.

7. Brezis M, Rosen S. Hypoxia of the renal medulla—its implications for disease. N Engl J Med 1995;332:647–55.

8. Pruijm M, Hofmann L, Vogt B, et al. Renal tissue oxygenation in essential hypertension and chronic kidney disease. Int J Hypertens 2013;2013:696598.

9. McCullough PA, Sandberg KR. Epidemiology of contrast-induced nephropathy. Rev Cardiovasc Med 2003;4(Suppl 5):S3–9.

10. Finn WF. The clinical and renal consequences of contrast-induced nephropathy. Nephrol Dial Transplant 2006;21:i2–10.

11. Levy EM, Viscoli CM, Horwitz RI. The effect of acute renal failure on mortality. A cohort analysis. JAMA 1996;275:1489–94.

12. Maioli M, Toso A, Leoncini M, et al. Persistent renal damage after contrast-induced acute kidney injury: Incidence, evolution, risk factors, and prognosis. Circulation 2012; 125: 3099–107.

13. McCullough PA, Wolyn R, Rocher LL, et al. Acute renal failure after coronary intervention: incidence, risk factors, & relationship to mortality. Am J Med 1997;103:368–75.

14. Gruberg L, Mintz GS, Mehran R, et al. The prognostic implications of further renal function deterioration within 48 h of interventional coronary procedures in patients with pre-existent chronic renal insufficiency. J Am Coll Cardiol 2000; 36:1542–8.

15. Weisbord SD, Chen H, Stone RA, et al. Associations of increases in serum creatinine with mortality and length of hospital stay after coronary angiography. J Am Soc Nephrol 2006;17:2871–7.

16. James MT, Samuel SM, Manning MA, et al. Contrast-induced acute kidney injury and risk of adverse clinical outcomes after coronary angiography: a systematic review and meta-analysis. Circ Cardiovasc Interv 2013;6:37–43.

17. Lameire N, Adam A, Becker CR, et al., Panel CINCW. Baseline renal function screening. Am J Cardiol 2006; 98: 21K–6K.

18. Stacul F, van der Molen AJ, Reimer P, et al., Contrast Media Safety Committee of European Society of Urogenital R. Contrast induced nephropathy: updated ESUR contrast media safety committee guidelines. Eur Radiol 2011;21: 2527–41.

19. Rihal CS, Textor SC, Grill DE, et al. Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention. Circulation 2002; 105: 2259–64.

20. Mehran R, Aymong ED, Nikolsky E, et al. A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation. J Am Coll Cardiol 2004;44:1393–9.

21. Nikolsky E, Mehran R, Lasic Z, et al. Low hematocrit predicts contrast-induced nephropathy after percutaneous coronary interventions. Kidney Int 2005;67:706–13.

22. Maioli M, Toso A, Gallopin M, et al. Preprocedural score for risk of contrast-induced nephropathy in elective coronary angiography and intervention. J Cardiovasc Med (Hagerstown) 2010;11:444–9.

23. Laskey WK, Jenkins C, Selzer F, et al. Volume-to-creatinine clearance ratio: a pharmacokinetically based risk factor for prediction of early creatinine increase after percutaneous coronary intervention. J Am Coll Cardiol 2007;50:584–90.

24. Weisbord SD, Gallagher M, Jneid H, et al. Outcomes after angiography with sodium bicarbonate and acetylcysteine. N Engl J Med 2018;378:603-14.

25. Brar SS, Aharonian V, Mansukhani P, et al. Haemodynamic guided fluid administration for the prevention of contrast-induced acute kidney injury: The PSOEIDON randomised controlled trial. Lancet 2014;383:1814–23.

26. Briguori C, Visconti G, Focaccio A, et al. Renal insufficiency after contrast media administration trial ii (REMEDIAL ii): RenalGuard system in high-risk patients for contrast-induced acute kidney injury. Circulation 2011;124:1260–9.

27. Windecker S, Kolh P, Alfonso F, et al., Authors/Task Force members. 2014 ESC/EACTS guidelines on myocardial revascularization: the task force on myocardial revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS) developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Eur Heart J 2014;35:2541–619.


How do I Manage My Patients with Heart Failure with Preserved Ejection Fraction?

REVIEW ARTICLE

MOHAMMED SADIQ AZAM, DAYASAGAR RAO VKeywords preserved ejection fraction natriuretic peptide pharmacologic therapy nonpharmacologic therapy hypertension tailored management approach systolic heart failure

Dr. Mohammed Sadiq Azam, Dr. Dayasagar Rao V, Department of Cardiology, Krishna Institute of Medical Sciences, Secunderabad

AbstractHeart failure with preserved ejection fraction (HF-PEF) is the clinical syndrome of heart failure associated with normal or near-normal systolic function. Because inhibition of the adrenergic and renin-angiotensin-aldosterone systems has been so effective in the treatment of systolic heart failure, these therapies have been the subject of recent clinical trials of HF-PEF. In this review, we examine the current evidence about treatment of HF-PEF, with particular emphasis on reviewing the literature for large-scale randomized clinical studies. The lack of signifi cant benefi t with neurohormonal antagonism in HF-PEF suggests that this condition might not involve neurohormonal activation as a critical pathophysiologic mechanism. Perhaps heart failure, as we traditionally think of it, is the wrong paradigm to pursue as we try to understand this condition of volume overload known as HF-PEF.

INTRODUCTION“Medicine is a science of uncertainty

and an art of probability”- Sir William Osler

Patients with heart failure can be broadly classifi ed as those with heart failure with reduced (≤50%) ejection fraction (HFrEF) and heart failure with preserved (>50%) ejection fraction (HFpEF). Irrespective of the ejection fraction (EF) all these patients have the clinical syndrome of heart failure (HF).

They share many features including abnormal left ventricular (LV) fi lling dynamics, elevated LV diastolic pressure, LV systolic and diastolic dysfunction, neurohormonal activation, impaired exercise tolerance, frequent hospitalization, and reduced survival.1-4

When compared to patients with HFrEF, those with HFpEF tend to be older and mostly females with atleast 85% of them having associated systemic hypertension.5 Despite having a preserved EF, patients with HFpEF have a mortality


rate that approaches 60% and a 6 month hospitalization rate of around 50% and debilitating symptoms.6 Hence, early recognition and appropriate management are essential to reduce the mortality and morbidity associated with HFpEF.

DIAGNOSISDiagnosis of HFpEF as with any case of heart failure is primarily based on clinical signs and symptoms which should be present in association with an EF greater than 50% with a normal LV end-diastolic volume along with a presence of expected antecedent or comorbid conditions and an exclusion of all non-cardiac causes of the signs and symptoms. The presence of these fi ndings is suffi cient to make the diagnosis of HFpEF as per major society guidelines of the AHA, ACC, HFSA and ESC. If these criteria are insuffi cient or lead to an ambiguous diagnosis a fourth set of data using noninvasive and invasive methods to gather evidence of cardiac dysfunction should be used to arrive at the diagnosis of HFpEF.7

ROLE OF BIOMARKERS IN THE DIAGNOSIS OF HFPEFThe most useful and best-characterized biomarkers in patients with HFpEF are the natriuretic peptides - BNP and N-terminal (NT)-proBNP. Circulating levels of these are elevated in patients with HFpEF when compared to persons without HF but are lower than in patients with HFrEF. The increase in BNP is directly related to LV diastolic fi lling pressure and end-diastolic wall stress. For any given LV diastolic fi lling pressure in patients with HFpEF, BNP levels are lower in obese patients (for every 1 kg/m2 increase in BMI above 25, natriuretic peptide levels fall by 4%)8 and higher in women, elderly, in those with associated COPD, pulmonary hypertension and pulmonary embolism and in patients with renal dysfunction. An elevated BNP also has a prognostic value as it predicts the risk of future events, even in asymptomatic persons. Soluble ST2 and Galectin 3 have been approved by USFDA and TIMP-1 is under development as a biomarker to aid in diagnosis, prognosis and management of HFpEF.9

THERAPYMany therapies have been proposed for the management of this unique subset of patients, but sadly, there is a huge lacuna in evidence based therapies, that have shown to reduce mortality and morbidity in patients with HFpEF.

The practical management of patients with HFpEF has three main components. The fi rst is reduction and prevention of pulmonary and peripheral venous congestion, which can be achieved using a combination of fl uid and salt restriction, diuretics, nitrates, and, prudent use of neurohormonal modulation therapies. The second component is an aggressive

treatment of comorbid diseases, of which the most important is hypertension. Control of blood pressure at rest as well as modifying the blood pressure response to exercise, controlling blood sugar, treatment of ischemia, maintaining renal function and maintaining a healthy body weight form the crux of this component. The third component is optimisation of cardiac functional status-avoiding a demand-supply mismatch, preventing inappropriate heart rate response to exercise as well as metabolic stress, maintenance or restoration of sinus rhythm and control of ventricular rate during episodes of atrial arrhythmias.

Table 1: Summary of major clinical trials of drugs for HFpEF10

Trial Drug Salient featuresTrial Drug Salient features

DIG Trial Digoxin In the HFpEF group (EF >45%) in sinus rhythm, digoxin DIG Trial Digoxin In the HFpEF group (EF >45%) in sinus rhythm, digoxin

did not alter the primary endpoint of HF-related did not alter the primary endpoint of HF-related

hospitalization or CV mortality but did reduce the hospitalization or CV mortality but did reduce the

number of such hospitalizations. number of such hospitalizations.

CHARM Candesartan Fewer patients in the candesartan group than in the CHARM Candesartan Fewer patients in the candesartan group than in the

placebo group reached the primary endpoint of CV placebo group reached the primary endpoint of CV

death or HF-related hospitalization. No impact on death or HF-related hospitalization. No impact on

mortality.mortality.

PEP-CHF Perindopril Enrollment and event rates were lower than expected.PEP-CHF Perindopril Enrollment and event rates were lower than expected.

Study did not show significant reduction in primary Study did not show significant reduction in primary

endpoint. Some trend towards benefit was seen in endpoint. Some trend towards benefit was seen in

a post-hoc analysis at 1 year driven by a decrease in a post-hoc analysis at 1 year driven by a decrease in

hospitalizations for HF.hospitalizations for HF.

I-PRESERVE Irbesartan Irbesartan did not effect any of the prespecified I-PRESERVE Irbesartan Irbesartan did not effect any of the prespecified

outcomes.outcomes.

SENIORS Nebivolol Included elderly patients without an EF requirement.SENIORS Nebivolol Included elderly patients without an EF requirement.

A modest but significant reduction in primary endpoint A modest but significant reduction in primary endpoint

of all cause mortality or CV hospitalizations was observed of all cause mortality or CV hospitalizations was observed

in the nebivolol arm driven primarily by the effect on in the nebivolol arm driven primarily by the effect on

hospitalizations.hospitalizations.

Included very few patients with EF >50%. Included very few patients with EF >50%.

TOPCAT Spironolactone Hospitalization for HF was significantly lower in the TOPCAT Spironolactone Hospitalization for HF was significantly lower in the

spironolactone group than the placebo group.spironolactone group than the placebo group.

RELAX Sildenafil Sildenafil did not improve exercise capacity or clinical RELAX Sildenafil Sildenafil did not improve exercise capacity or clinical

status.status.

NEAT-HFpEF Isosorbide Patients who received isosorbide mononitrate were lessNEAT-HFpEF Isosorbide Patients who received isosorbide mononitrate were less

mononitrate active and did not have better quality of life or mononitrate active and did not have better quality of life or

submaximal exercise capacity than patients who received submaximal exercise capacity than patients who received

placebo.placebo.

PARAMOUNT-HF ARNI Phase II trial.PARAMOUNT-HF ARNI Phase II trial.

At 36 weeks, sacubitril/valsartan (ARNI) significantly At 36 weeks, sacubitril/valsartan (ARNI) significantly

reduced LA volume by approximately 5% and also reduced LA volume by approximately 5% and also

improved NYHA functional class compared with improved NYHA functional class compared with

valsartan (ARB).valsartan (ARB).

PARAGON-HF ARNI Trial underway to test if the findings of PARAMOUNT HF PARAGON-HF ARNI Trial underway to test if the findings of PARAMOUNT HF

will translate into improved clinical outcomes.will translate into improved clinical outcomes.


PHARMACOLOGICAL THERAPYPharmacological therapies like ACE inhibitors, ARBs, beta blockers, mineralocorticoid antagonists, nitrates/hydralazine, that have an indisputable benefi t in HFrEF have failed to show a clear benefi t in patients with HFpEF. Eight large RCTs have enrolled patients with HFpEF of which six had HF hospitalisation or CV death as the primary endpoint, two had exercise or activity level endpoints. Six of these RCTs had a neutral outcome, and one study in a post-hoc analysis demonstrated a reduction in HF hospitalization or CV death in patients with HFpEF and were treated with spironolactone, and one demonstrated that therapy could be facilitated using an implantable hemodynamic sensor. The salient features of the RCTs are summarized in Table 1.

NONPHARMACOLOGIC THERAPYAttention to well-being and overall health of an individual is of paramount importance in the management of patients with HFpEF which includes an attention to diet and a healthy lifestyle, regular physical activity, weight monitoring, patient education and close medical follow-up taking the advantage of home monitoring systems. Sodium restriction to <2g/day and maintaining a fl uid intake, balanced to renal function, is important.

TREATMENT OF COMORBIDITIESApproximately >85% of the patients with HFpEF have associated systemic hypertension (either current or previous).Untreated hypertension is a strong risk factor for the development of HF. Treatment of systolic hypertension in the elderly is associated with a >50% reduction in HF frequency. Recent studies (SPRINT, HOPE 3) have demonstrated the benefi t of an aggressive BP targets (systolic BP <120) even in the elderly population.11,12 However, it has to be kept in mind that due to the arterial stiff ening that develops with age, achieving the targets may not always be easy. Another signifi cant cause of falls and frequent morbidity in the elderly population is the development of orthostatic hypotension. Some authors have hence advised the

measurement of standing blood pressure to adjust antihypertensive drug therapy in the elderly population. Adequate treatment of hypertension not only includes control of the blood pressure but also prevention of LV hypertrophy or measures to induce regression of the hypertrophy which will lead to reduced mortality and morbidity, improved exercise tolerance and diastolic function.13

Diabetes and obstructive sleep apnea are often commonly associated with HFpEF and their treatment has demonstrated an improvement in diastolic function and benefi t in clinical status and better outcomes compared to untreated cases.

Many patients with HFpEF are found to have associated obesity. In the ADHERE registry, for example, >25% of patients weighed >200 pounds.14 Obesity leads to impaired exercise tolerance and also contributes to the development of diabetes, hypertension and obstructive sleep apnea. BMI is an important predictor of outcomes in patients with HFpEF. Hence, weight loss through pharmacological and nonpharmacological therapies such as diet and bariatric surgery may form important interventional strategies for patients with HFpEF.

The eff ect of obesity on natriuretic peptide levels as mentioned above has to be kept in mind since a high BMI may lead to a falsely low level of BNP despite the patient having HF. Ergo, over-reliance on BNP alone in such cases might lead to an underdiagnosis of HF.

Chronic kidney disease is frequently associated with HFpEF and a decline in GFR generally signals a drop in the prognosis for the patient. Anemia in patients with HFpEF is generally multifactorial with causes ranging from associated CKD to iron defi ciency. Anaemia, irrespective of its etiology, is generally associated with a worse prognosis in patients with HFpEF and hence forms an important therapeutic target in these patients.

SENSOR-BASED STRATEGIESThese are novel therapies that provide facilitated management of HFpEF using

remote monitoring-based tailored therapy. These include implantable hemodynamic monitors (IHMs), subcutaneous and cutaneous sensors, noninvasive monitors (assess volume status, heart rate, rhythm, sympathetic tone and activity), and serum/plasma-measured biomarkers.

REMOTE MONITORING SYSTEMS - TAILORED MANAGEMENT APPROACHThe COMPASS-HF (Chronicle Off ers Management to Patients with Advanced Signs and Symptoms of Heart Failure) trial studied patients in whom an IHM was implanted that measured an estimated pulmonary artery diastolic pressure (which in the absence of pulmonary vascular disease equals to PCWP). This study demonstrated that many patients who were considered clinically to be well-compensated by their physicians demonstrated measures of elevated fi lling pressures which rose on decompensation and that these changes in fi lling pressures predicted outcomes - including rates of HF hospitalization and CV mortality.15-18 The investigators hypothesized that off ering a tailored treatment that was modifi ed on the basis of data obtained from an IHM device would decrease baseline pressure, prevent an increase in pressure, and lower HF events in HFpEF.

This hypothesis was tested in the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA class III Heart Failure Patients (CHAMPION) trial. Those patients in the active treatment arm demonstrated a 152% decrease in pulmonary artery diastolic and systolic pressures and a 52% decrease in HF-related events and a decrease in CV mortality rate. In addition to implantable devices, noninvasive systems measuring indices of impedance and heart rate variability, rhythm, and activity are under development.19-22

DEVICE THERAPY FOR HEART FAILUREAn elevated left atrium (LA) pressure is central to the pathogenesis of HFpEF. Hence there has been a lot of research into methods to reduce LA pressure and

REVIEW ARTICLE


an important technological update in this area is the development and testing of devices that reduce the LA pressure and improve the diastolic function. Devices aim to mediate a selective reduction of the LA pressure, such that there is a symptomatic improvement, without the complications of pharmacological therapy such as diuresis and hypotension.

THE RATIONALE OF INTERATRIAL SEPTOSTOMYLA is an elastic chamber receiving blood from pulmonary vein passively which modulates LV fi lling by acting as an active booster during atrial systole. The LA buff ers pressure and fl ow coupling between the LV and the pulmonary circulation due to the cyclic nature of cardiac hemodynamics.23 At identical mean LA pressure in patients with heart failure, HFrEF patients had larger LA volumes while HFpEF patients had higher LA peak pressures and higher LA stiff ness. LA function has been related to mortality in HFpEF patients but not in HFrEF patients.24

There are multiple established techniques for creating large interatrial communication like percutaneous perforation, balloon dilation, and stent implantation. However, complications of these procedures include excessive desaturation, spontaneous fenestration closure, stent occlusion or migration, diffi culties in adjusting shunt size to achieve the desired hemodynamic eff ect, and the inability to remove or close the shunt.25 Now, there are three percutaneously deployed innovative devices which avoid these complications and are currently undergoing clinical trials.

INTER ATRIAL SHUNT DEVICES The Inter Atrial Shunt Device (Corvia Medical Inc., Tewksbury, MA, USA) (Figure 1a) is a nitinol device percutaneously inserted in the interatrial septum to produce a permanent 8-mm atrial septal communication. The device is deployed after trans-septal puncture of the mid-fossa ovalis. The device achieves bidirectional fl ow with a Qp:Qs ratio of 1.3:1. Antiplatelets are recommended for

1 year after device placement and aspirin indefi nitely. The REDUCE LAP-HF study showed that 52% of patients had a reduction in PCWP at rest and 58% of had a lower PCWP during exertion with 39% fulfi lling both these criteria. Mean exercise PCWP was lower at 6 months than at baseline, both at 20-W workload and at peak exercise. Sustained device patency at 6 months was confi rmed with shunt ratio of 1.3:1. Using this data IASD received CE mark approval in May 2016.26

The V wave device (V-Wave Ltd., Or Akiva, Israel) (Figure 1b), in the fi rst generation, consisted of an hourglass shaped, self-expanding nitinol frame that contains a tri-leafl et porcine pericardium tissue valve sutured inside, which allowed unidirectional fl ow from the LA to the RA, if the pressure gradient exceeded 2 mmHg achieving a Qp:Qs of 1.1-2.1. The valve prevents reverse shunting of blood and prevents paradoxical embolism. The V wave device (Figure 1b) was evaluated in 10 HFrEF patients in a single center in Canada using the special access process to prove the concept. The patients were evaluated at 3 months after the index procedure and in this small population, there was a reduction in NYHA class, improved their 6-min walk distance, and reported improved quality of life (QoL) and physical function. At 1-year follow-up, resting shunt fraction had declined from a mean of 1.2:1 to 1.1:1, with 14% of patients having no interatrial fl ow. This occurred in conjunction with pannus thickening of the bioprosthetic leafl ets and lumen loss, which prompted the creation of a second-generation device, with an expanded ePTFE coating and without a unidirectional valve, including a hood to prevent potential thromboemboli

from opposing the right atrial side of the implant.27

ATRIAL FLOW REGULATORThe atrial fl ow regulator (AFR) (Occlutech, Istanbul, Turkey) (Figure 1c) is a self-expandable double-disc wire mesh device constructed from 0.004–0.0075-in. nitinol braided into two fl at discs connected by a waist of 1–2 mm and central fenestration, which enables bidirectional fl ow. The fi rst clinical utilization of the device followed a compassionate use approval from the US Food and Drug Administration. The patient was a 54-year-old woman with severe and irreversible pulmonary artery hypertension. Implantation was associated with immediate right-to-left shunting and a corresponding decrease in arterial saturation (from 95 to 89%). She reported functional improvement at 6 weeks.28 This experience was later extended to 12 patients (mean age 28.3 ± 8.5 years) with severe irreversible pulmonary arterial hypertension [U29]. All the patients were receiving optimal doses of two oral pulmonary vasodilators of which one belonged to endothelin receptor antagonists and the other belonged to phosphodiesterase-5 inhibitors. All procedures were successful without any major complications and antiplatelets were given to maintain patency of the device. All patients had relief of syncope and 6-min walk distance improved signifi cantly. The cardiac index and systemic oxygen transport also showed a signifi cant improvement.29 Complete endothelialization of nitinol atrial septal occluders was demonstrated within a few months after implantation, permitting withdrawal of antiplatelets after 6–12 months.

Figure 1: Devices being studied for HFpEF: a) Corvia Inter Atrial Shunt Device, b) V wave, c) Atrial flow regulator


CoROLLACoRolla (CorAssist Inc., Haifa, Israel) is an intraventricular device invented by Dr. Yair Field which is designed to be implanted by minimally invasive, transapical approach, off the pump. It is an elastic self-expanding internal spring like device which is based on mechanical principles of energy transfer from systole to diastole. The device applies direct internal expansion forces distributed on the left ventricle wall and septum to directly improve diastolic function. The device improves fi lling performance and diastolic dynamics without needing an external power source. Preclinical studies have shown safety over the 24-month duration and fi rst in human implantation was carried out in RAMBAM medical center, Haifa, Israel, in July 2017.30

CONCLUSIONHeart failure with preserved ejection fraction is currently one of the greatest enigmas facing cardiologists all over the globe. It is in this regard that the quote by Sir William Osler, with which we began this article, is so apt because never before has the treatment of a disease in cardiology been so full of uncertainties but still so full of possibilities. While many drug therapies have been tried, not a great many of them have shown any benefi t. In those that have shown a benefi t, the benefi t is limited to a reduction in hospitalization with a drug yet to demonstrate a mortality benefi t. Aldactone in the TOPCAT trial has shown a defi nite reduction in hospitalization for HF in patients with HFpEF, while digoxin and candesartan have also demonstrated a similar benefi t to a lesser extent in their respective trials. While ARNI has shown benefi t in PARAMOUNT-HF with respect to improvement in LA volume and NYHA functional class, the ongoing PARAGON-HF trial will answer the important question of whether this will translate into an improvement in clinical outcomes or not. Many novel device therapies have been tried and initial trials

have given promising results which has lead to regulatory approval. The atrial fl ow regulator is notable amongst these to have received USFDA approval for clinical use. However, costs and availability around to globe continue to be limiting factors and also long term data with these devices is lacking. To sum it up we are standing at an exciting frontier in the management of HFpEF and the results of ongoing trials as well as long term data with the use of devices for HFpEF might set the stage for a defi nitive therapy soon.

REFERENCES1. Little WC, Zile MR. HFpEF. Cardiovascular abnormalities

not just co-morbidities. Circ Heart Fail. 2012;5:669.2. Lam CSP, Roger VL, Rodeheffer RJ, et al. Cardiac structure

and ventricular-vascular function in persons with heart failure and preserved ejection fraction: from Olmstead County, Minnesota. Circulation. 2007;115:1982.

3. Kitzman DW, Little WC. Left ventricle diastolic dysfunction and prognosis. Circulation. 2012;125:743.

4. Iwano H, Little WC. Heart failure: What does ejection fraction have to do with it? J Cardiol. 2013;62:1.

5. McMurray JJ, Carson PE, Komajda M, et al. Heart failure with preserved ejection fraction:clinical characteristics of 4,133 patients enrolled in the I-Preserve trial. Eur J Heart Fail. 2008;10:149.

6. Little WC, Zile MR, Klein A, et al. Effect of losartan and hydrochlorothiazide on exercise tolerance in exertional hypertension and left ventricular diastolic dysfunction. Am J Cardiol. 2006;98:383.

7. Ponikowski P, Voors AA, Anker SD, and Authors/Task Force Members. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2016;37(27):2129–2200.

8. Frankenstein L, Remppis A, Nelles M, et al. Relation of N-terminal pro-brain natriuretic peptide levels and their prognostic power in chronic stable heart failure to obesity status. Eur Heart J. 2008;29:2634–2640.

9. Chow SL, Maisel AS, Anand I, et al. the role of biomarkers for the prevention, assessment, and management of heart failure. a consensus statement for healthcare professions from the American Heart Association. Circulation. 2017;135:e1054–e1091.

10. Zile MR, Litwin SE. Heart Failure with a Preserved Ejection Fraction. In: Zipes, Libby, Bonow, Mann Tomaselli (Eds.). Braunwald’s Heart Disease - A Textbook of Cardiovascular Medicine. 11th edition. Elsevier. 2018:523-542.

11. Wright JT Jr, Williamson JD, Whelton PK, et al. SPRINT Research Group. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103– 2116.

12. Lonn EM, Bosch J, López-Jaramillo P, et al; HOPE-3 Investigators. Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374: 2009–2020.

13. Solomon SD, Janardhanan R, Verma A, et al. Effect of angiotensin receptor blockade and antihypertensive

drugs on diastolic function in patients with hypertension and diastolic dysfunction: a randomised trial. Lancet. 2007;369:2079.

14. Fonarow GC, Stough WG, Abraham WT, et al. Characteristics, treatments, and outcomes of patients with preserved systolic function hospitalized for heart failure. J Am Coll Cardiol. 2007;50:768.

15. Zile MR, Bennett TD, El Hajj S, et al. Intracardiac pressures measured using an implantable hemodynamic monitor: relationship to mortality in patients with chronic heart failure. Circ Heart Fail. 2017;10(1).

16. Stevenson LW, Zile M, Bennett TD, et al. Chronic ambulatory intracardiac pressures and future heart failure events. Circ Heart Fail. 2010;3:580.

17. Zile MR, Adamson PB, Cho YK, et al. Hemodynamic factors associated with acute decompensated heart failure. Part 1. Insights into pathophysiology. J Card Fail. 2011;17:282.

18. Adamson PB, Zile MR, Cho YK, et al. Hemodynamic factors associated with acute decompensated heart failure. Part 2. Use in automated detection. J Card Fail. 2011;17:366.

19. Zile MR, Sharma V, Johnson JW, et al. Prediction of all-cause mortality based on the direct measurement of intrathoracic impedance. Circ Heart Fail. 2016;9:e002543.

20. Bourge RC, Abraham WT, Adamson PB, et al. Randomized controlled trial of an implantable continuous hemodynamic monitor in patients with advanced heart failure: the COMPASS-HF study. J Am Coll Cardiol. 2008;51:1073.

21. Abraham WT, Adamson PB, Bourge RC, et al. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet. 2011;377:658.

22. Ritzema J, Troughton R, Melton I, et al. Hemodynamically Guided Home Self-Therapy in Severe Heart Failure Patients (HOMEOSTASIS) Study Group. Physician-directed patient self-management of left atrial pressure in advanced chronic heart failure. Circulation. 2010;121:1086

23. Braunwald E, Frahm CJ. Studies on starling’s law of the heart: IV. Observations on the hemodynamic functions of the left atrium in man. Circulation. 1961;24:633–42.

24. Melenovsky V, Hwang SJ, Redfield MM, Zakeri R, Lin G, Borlaug BA. Left atrial remodeling and function in advanced heart failure with preserved or reduced ejection fraction. Circ Heart Fail. 2015;8: 295–303.

25. Sivaprakasam M, Kiesewetter C, Veldtman GR, Salmon AP, Vettukattil J. New technique for fenestration of the interatrial septum. J Interv Cardiol. 2006;19:334–6.

26. Hasenfuss G, Hayward C, Burkhoff D, Silvestry FE, McKenzie S, Gustafsson F, et al. investigators RL-Hs. A transcatheter intracardiac shunt device for heart failure with preserved ejection fraction (REDUCE LAP-HF): a multicentre, open-label, single-arm, phase 1 trial. Lancet. 2016;387:1298–304.

27. Stone GW R-CJ, Amat-Santos IJ, Ben Gal T, et al. Interatrial shunting for heart failure: the V-wave shunt. Presented at transcatheter therapeutics (TCT); October 31. 2017; Denver, Colorado.

28. Patel MB, Samuel BP, Girgis RE, et al. Implantable atrial flow regulator for severe, irreversible pulmonary arterial hypertension. EuroIntervention. 2015;11:706–9

29. Ramasamy R, Pavithran S, Sivakumar K, Vettukattil JJ. Atrial septostomy with a predefined diameter using a novel occlutech atrial flow regulator improves symptoms and cardiac index in patients with severe pulmonary arterial hypertension. Catheter Cardiovasc Interv. 2017;90:1145–53.

30. Gupta A, Bailey SR. Update on Devices for Diastolic Dysfunction: Options for a No Option Condition? Current Cardiology Reports. 2018;20:85.

REVIEW ARTICLE


Practical Approach to Constrictive Pericarditis

REVIEW ARTICLE

MONIK MEHTA

Keywords pericardial sac edema portopulmonary venous pressure pericardiectomy doppler echocardiography

Dr. Monik Mehta is Consultant Cardiologist, Artemis Hospital, Department of Cardiology, Sector 51, Gurgaon, Haryana, India.

AbstractConstrictive pericarditis (CP) represents a form of severe diastolic heart failure (HF), secondary to a noncompliant pericardium. The true prevalence of CP is unknown but it is observed in 0.2-0.4% of patients who have undergone cardiac surgery or have had pericardial trauma or infl ammation due to a variety of etiologies. Despite its poor prognosis if untreated, CP is a potentially curable disease and surgical pericardiectomy can now be performed at low perioperative mortality in tertiary centers with surgical expertise in pericardial diseases. Cardiologists should have a high index of suspicion for CP in patients presenting with predominant right-sided (HF), particularly when a history of cardiac surgery, pericarditis or pericardial effusion is present. Transthoracic two-dimensional and Doppler echocardiography is usually the fi rst diagnostic tool in the evaluation of HF and can reliably identify CP in most patients by characteristic real-time motion of the heart and hemodynamic features. Cardiac catheterization has been the gold-standard for the diagnosis of CP, but may not be necessary if non-invasive test(s) demonstrate diagnostic features of CP; it should then be reserved for selected cases or for assessment of concomitant coronary disease. Although most patients with CP require pericardiectomy, anti-infl ammatory therapy may be curative in patients presenting with subacute symptoms, especially when evidence of marked ongoing infl ammation is seen.

INTRODUCTIONConstrictive pericarditis (CP) is characterized by impaired ventricular fi lling, secondary to a scarred pericardium. The scarred pericardium, involving both parietal and visceral layers may be thickened or calcifi ed, with resultant loss of normal elasticity of the pericardial sac.

The common causes include idiopathic etiology, post cardiac surgery and systemic diseases aff ecting the pericardium such as tuberculosis, collagen vascular diseases, malignancy, renal

diseases or radiation therapy.1,5 The risk of developing constrictive pericarditis is however rare post-acute viral pericarditis, as compared to specifi c aetiologies such as tuberculosis.12

CLINICAL FEATURESAfter a detailed history taking is done patient is clinically evaluated. The predominant symptoms are dyspnea with peripheral oedema and on clinical evaluation, there is evidence of systemic venous congestion with hepatomegaly


and ascites.Clinically the patient will present as

a case of predominant right heart failure2 and CP will be an important diff erential diagnosis in this setting. Other conditions, which will need to be excluded, would be restrictive cardiomyopathy, pathologies causing failure of the right side of heart e.g. tricuspid stenosis, pulmonary stenosis, ebstein's anomaly, cor pulmonale and other diseases such as liver cirrhosis, superior vena cava (SVC) obstruction and portopulmonary stenosis etc.

The clinical fi ndings in vast majority refl ect elevated systemic venous congestion such as increased jugular venous pressure (JVP) and hepatomegaly. Venous pressure often paradoxically increases with inspiration (Kussmaul sign) due to an inability of the right heart to accept increased venous return with inspiration and a prominent y descent (Freidrich sign) may be discernable. With high atrial pressures, the rapid right ventricular fi lling causes the ventricle to “knock” onto the rigid thickened pericardial shell in very early diastole – the “pericardial knock”.

The important bedside clues, which one should remember, are a prominent “y” descent on JVP, a pericardial knock (to be diff erentiated from opening snap which is higher pitched, occurring later in diastole and best heard in expiration), absence of a palpable apex beat and a silent heart with no regurgitant murmurs.

INVESTIGATIONSThe next step should be to confi rm the diagnosis and investigations are accordingly ordered i.e. ECG, Pericardial imaging studies, serum NTpro-BNP, and lastly cardiac cath study.

ECG may show low voltage complexes. Depolarization abnormalities (such as bundle branch block), ventricular hypertrophy, pathologic Q waves, or impaired atrioventricular conduction would, however, favor restrictive cardiomyopathy. Thus there are no characteristic ECG fi ndings in CP.3

Elevation of Serum NT proBNP values would again point against CP. Pericardial imaging may be done by X-ray chest, Echocardiography, CT

scan or MRI. Radiological presence of calcifi cation should be looked for in left lateral projections suggestive of CP. An enlarged cardiac silhouette in X-Ray PA view would be suggestive of pericardial eff usion or eff usive-constrictive pericarditis and the diff erence would become apparent when there would be persistently elevated right atrial pressures post pericardiocentesis in the latter. A pericardial thickness exceeding 4 mm on echocardiography, CT scan or MRI is highly suggestive of CP, with the former being the least sensitive. However, CP can also occur in the setting of a non- thickened pericardium.

Doppler of the hemodynamics is extremely helpful in diagnosing CP in which the pathologically increased pericardial restraint results in an enhanced ventricular interaction or interdependence and prevents transmission of intrathoracic pressures into the cardiac chambers. The respiratory variation in ventricular fi lling velocity in restrictive cardiomyopathy is usually minimal (less than 10 percent), while patients with CP may have respiratory variations as high as 30 to 40 percent in ventricular fi lling velocity (similar to that seen in cardiac tamponade). Similar fi ndings may be present in COPD patients but in them additionally, a marked increase in inspiratory superior vena cava systolic fl ow velocity would also be seen.

Measurement of hepatic venous fl ows is also helpful as a reversal of forward fl ow during expiration is seen in CP, while it happens during inspiration in restrictive cardiomyopathy.

Tissue Doppler imaging records the velocity of the myocardium and has signifi cant diagnostic value. The early diastolic Doppler tissue velocity at the mitral annulus (Ea) is decreased (<8 cm/sec, normally >10cm/sec) in restrictive cardiomyopathy, due to decreased myocardial relaxation in myocardial diseases, but is preserved or even increased in CP. Therefore, if the Ea is more than 8 cm/s in a patient of heart failure one should consider CP. Additionally this preserved, or even accentuated Ea value, gets refl ected in the relationship between Transmitral infl ow

early velocity (E)/ Ea with the LV fi lling pressures which is usually positive and linear in primary myocardial diseases but gets reversed (annulus paradoxus) in CP.7

Cardiac cath study fi ndings demonstrate increase in right atrial pressures, equalization of diastolic fi lling pressures i.e. <5 mm diff erence between mean right atrial (RA) pressure, right ventricular (RV) diastolic pressure, pulmonary- artery (PA) diastolic pressure, and pulmonary capillary wedge pressure (PCWP) and pericardial pressures, dip and plateau confi guration of right and left ventricular diastolic waveforms while the simultaneous LV and RV systolic pressure tracings in CP will show discordant changes with respiration i.e. LV systolic will decrease with inspiration while RV systolic will increase.

To summarize patient will present as a case of right heart failure. History taking should aid in identifying systemic disorders or infections. Clinical evaluation followed by logical usage of various investigative modalities should help in arriving at the diagnosis of constrictive pericarditis. Cardiac cath may not be required in every case, if the other tests produce a decisive conclusion.

MANAGEMENTMedical management has a limited role with diuretics and salt restriction to relieve volume overload, digoxin for atrial fi brillation with fast ventricular rates, anti-infl ammatory agents if there are features of pericardial infl ammation and treatment of specifi c aetiologies e.g. TB. Once the diagnosis of CP is made defi nitive therapy i.e. complete surgical pericardiectomy should be done in addition to management of comorbidities if any.8

Pericardiectomy usually leads to rapid hemodynamic and symptomatic improvement in 80-90% of patients who achieve symptomatic improvement to NYHA Class I or II postoperatively.

The surgical procedure itself can often be a technically complex procedure with high mortality9 requiring extensive surgical experience and aim should be to achieve as extensive pericardial decortication as possible.

REVIEW ARTICLE


If the surgery is performed early in the course of the disease as evidenced by less pericardial calcifi cation and no myocardial dysfunction, then the outcomes are excellent.10-12 In others especially if patients, particularly those with left ventricular systolic dysfunction, advanced New York Heart Association (NYHA) functional class, concomitant myocardial disease and also comorbidities, symptoms may persist after surgery.

Patients with endstage CP manifested by cachexia reduced resting cardiac output, hypoalbuminemia or liver dysfunction form a group with markedly increased operative risk and hence pericardectomy may not be benefi cial in such cases.8

REFERENCES1. Andreu Porta-Sánchez, Jaume Sagristà-Sauleda, Ignacio

Ferreira-González, Asunción Torrents-Fernández, Ivo Roca-Luque, David García-Dorado. Constrictive Pericarditis: Etiologic Spectrum, Patterns of Clinical Presentation, Prognostic Factors, and Long- term Follow-up .Spanish Journal of Cardiology (Revista Española de Cardiología, English Edition).December 1, 2015. Volume 68, Issue 12. Pages 1092-1100.

2. William R. Miranda and Jae K. Oh : Progress in Cardiovascular Diseases,2017-01-01, Volume 59,Issue 4, Pages 369-37

3. Martin M. Lewinter and Massimo Imazio.Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 83, Pericardial Diseases; 1662-1680.

4. Welch TD. Constrictive pericarditis: diagnosis, management and clinical outcomes. Heart 2018; 104:725.

5. Bertog SC, Thambidorai SK, Parakh K, et al: Constrictive pericarditis: etiology and cause-specific survival after pericardiectomy. J Am Coll Cardiol 2004; 43: pp. 1445- 1452.

10. Ariyoshi T, Hashizume K, Taniguchi S, Miura T, Tanigawa K, Matsukuma S, et al. Surgical experience with chronic constrictive pericarditis. Gen Thorac Cardiovasc Surg. 2012;60:796–802.

11. NL Landex, N Ihlemann, PS Olsen, F Gustafsson.

“Constrictive pericarditis in a contemporary Danish cohort: aetiology and outcome”. Scand Cardiovasc J. 2015; 49(2):101–8.

12. Lin Y, Zhou M, Xiao J, Wang B, Wang Z. Treating constrictive pericarditis in a Chinese single-center study: A five-year experience. Ann Thorac Surg. 2012; 94:1235–40.

8. Adler Y, Charron P, Imazio M, et al. 2015 ESC Guidelines for the diagnosis and management of pericardial diseases: The Task Force for the Diagnosis and Management of Pericardial Diseases of the European Society of Cardiology (ESC)Endorsed by: The European Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J 2015; 36:2921.

9. Vistarini N, Chen C, Mazine A, et al. Pericardiectomy for Constrictive Pericarditis: 20 Years of Experience at the Montreal Heart Institute. Ann Thorac Surg 2015; 100:107.

7. Ha JW1, Oh JK, Ling LH, Nishimura RA, Seward JB, Tajik AJ .Transmitral Flow Velocity to Mitral Annular Velocity Ratio Is Inversely Proportional to Pulmonary Capillary Wedge Pressure in Patients With Constrictive Pericarditis. Circulation. 2001;104:976–978.

6. Risk of Constrictive Pericarditis After Acute Pericarditis: Massimo Imazio, Antonio Brucato, Silvia Maestroni, Davide Cumetti, Riccardo Belli, Rita Trinchero, and Yehuda Adler .Circulation. 2011;124:1270–1275.


Transesophageal Echocardiography in Children with Congenital Heart Defects

REVIEW ARTICLE

SNEHAL KULKARNI

Keywords transesophageal echocardiography transcatheter interventions congenital heart defects

Dr Snehal Kulkarni is Chief-Division of Pediatric Cardiology, Kokilaben Ambani Hospital & Research Center, Mumbai

AbstractIntraoperative transesophageal echocardiography (TEE) is a valuable diagnostic and monitoring tool during surgical repair of congenital heart defects (CHD). It also has a vital role in the cardiac catheterization laboratory during transcatheter interventions in children. With the development of miniaturized probes and novel techniques, applications for TEE in children for management of congenital heart defects will continue to expand.

INTRODUCTIONTransesophageal echocardiography (TEE) is regularly used in the adult cardiac population because of its ability to provide important diagnostic information in older patients with congenital and acquired heart diseases in various outpatient, intraoperative, and even intensive care unit settings. Its use in the pediatric population is always limited, because of non-availability of small- sized probes for pediatric population. In addition, with the development of newer higher end echocardiography machines and imaging techniques with excellent echocardiography windows in children, its regular use in outpatient clinics has become signifi cantly less. In addition children need anesthesia during the procedure, so it becomes an invasive procedure in these situations.

At the same time there is always a need for intraoperative monitoring and assessment of residual defects after

repair of complex congenital heart defects. With the availability of smaller sized transesophageal echocardiography probes, the use of this technique is expanding.1,2,3 As the transcatheter interventions are increasing for treatment of complex congenital heart defects, the need for imaging during the procedures also started increasing. In addition the number of adult congenital heart defects with diffi cult transthoracic windows is increasing, where the transesophageal echocardiography is regularly being used.

The fi rst TEE probe for use in children (1989) consisted of a single plane, phased-array, 28-element, 5-MHz unit mounted on an endoscope measuring 6.8 mm in diameter. Then the biplane probe came in use and now the newer TEE probes are multiplane probes. The smaller probes don’t have the facility for 3 dimensional imaging. The adult probes, which can be used in bigger children above 15kg weight, have the facility for


3 D imaging as well. Availability of transesophageal probes

[Figure 1] Micro TEE – 2.75 Kg onwards Pediatric TEE – 3.5 Kg onwards Adult TEE – 2D, 3D – 15 Kg and

above Micro TEE and pediatric TEE probes

don’t have facility for 3 D imaging.

SPECIFIC APPLICATIONS FOR TEE IN CHILDREN Most of the TEE studies in children are performed under general anesthesia with intubation or under heavy sedation. Pediatric TEE probe should be inserted after ensuring empty stomach. A nasogastric tube need to be inserted to aspirate the stomach content prior to inserting the TEE probe.

CONTRAINDICATIONS FOR TRANSESOPHAGEAL ECHOCARDIOGRAPHY IN CHILDREN Absolute contraindications

Esophageal obstruction or stricture Unrepaired tracheoesophageal fi stula Severe respiratory decompensation Inadequate airway control Perforated hollow viscus

Relative Contraindications Esophageal varices or diverticulum Gastric or esophageal bleeding Severe coagulopathy Vascular ring/arch anomaly C-spine injury or deformity Oropharyngeal injury or deformity History of esophageal surgery

INTRAOPERATIVE TRANSESOPHAGEAL ECHOCARDIOGRAPHYThough there are specifi c recom-mendations for use of transesophageal echocardiography in all children undergoing open heart surgeries for repair of congenital heart defects, there are institutional protocols for its regular use in operating rooms. It depends upon the availability of specifi c machines with small TEE probes and the expertise for doing the examination. Intraoperative TEE should not stand alone as the sole diagnostic study, since there are inherent limitations in imaging certain important structures by TTE (i.e, transverse aortic arch, aortic isthmus, distal left pulmonary artery, and collateral pulmonary vessels). The detailed diagnosis should always be made prior to taking the patient for

surgery. In addition, there is always limited time to perform complete study, Doppler alignment with TEE may not be optimal. It usually confi rms the preoperative fi ndings and assesses the immediate preoperative hemodynamics and ventricular function. The same information can be communicated to the surgical team just prior to the operation. Preoperative TEE may also facilitate the placement of central venous catheters, selection of anesthetic agents, and use of preoperative inotropic support by demonstrating ventricular systolic function and size. Multiple studies have defi ned the need for going on bypass immediately after the recognition of residual defects.4,5 It has major impact on morbidity, mortality after surgical repair of the defects. It also reduces the postoperative stay in the intensive care units, reducing the cost for the procedures as well. TEE can assess heart function after cardiac surgery very well and helps in adjusting inotropes in the intensive care units. Performance of TEE in the patient with CHD immediately after surgery, but before chest closure, has been a contributor to the overall excellence in the outcomes of congenital heart surgery. Based upon the TEE and clinical fi ndings, the surgeon, in conjunction with the TEE echocardiographer and anesthesiologist, determines whether the surgical repair is acceptable. TEE provides the opportunity to detect signifi cant and potentially treatable disease before disconnection of bypass cannula, sternal closure, and return to the intensive care unit.6 In addition, it assesses cardiac function, presence of intracardiac air, and may aid in the diagnosis of cardiac rhythm abnormalities.

TEE IN SPECIFIC CONGENITAL LESIONS IN OPERATING ROOMAtrial Septal defects (ASD)Though its use in regular surgical closures is not warranted, it has specifi c role in patients with sinus venosus defects especially when the echocardiography windows are suboptimal in adult patients. It confi rms the presence of the defect and its size. After surgical repair, it assesses complete closure and smooth fl ows from

Figure 1. Description of micro TEE probe


superior vena cava to right atrium and right upper pulmonary vein to left atrium. Ventricular septal defectsIts mandatory to have TEE prior to surgeries for multiple VSDs. The number, location of the defects can be demonstrated very well. In addition prolapse of aortic valve with degree of aortic regurgitation and need for aortic valve repair can be assessed well (Figure 2). As the incidence of residual ventricular defects can be high, its very important to image the ventricular septum

after the surgery.

Atrioventricular septal defectThis defect can be seen very well on TEE. Though the transthoracic echocardiography windows are excellent in this group, it may be important to revise these details prior to surgery. All these patients defi nitely need postoperative assessment on the table. Residual VSD, degree of atrioventricular valve (AV valves) regurgitation, pulmonary hypertension and ventricular function should be assessed in all the patients before shifting the patient out of operating room. There is a high chance for reoperation if there are residual signifi cant defects (Figure 3).

Surgery for AV valves Intraoperative TEE plays a very important role in surgical repair of AV valves. Repair of Ebstein’s anomaly will defi nitely need postoperative assessment for revision / replacement of tricuspid valve (Figure 4). Surgery for congenital abnormalities of left sided AV valves is always a challenge in pediatric practice. Preoperative TEE helps in proper assessment of AV valve, especially for demonstration of supramitral membrane, subvalvar assessment. Postoperative TEE will help in assessment of residual lesion which have major impact on postoperative recovery.

Intracardiac repair for Tetralogy of Fallot ( TOF), Double outlet right ventricle (DORV)With advanced imaging techniques, preoperative assessment for these lesions is usually complete by transthoracic echocardiography, computed tomography or angiography if required. TEE plays a major role in postoperative assessment as residual lesions are common which have major impact on immediate postoperative recovery as well as long term outcomes. TEE should evaluate residual VSDs, outfl ow tracts, residual obstruction, pulmonary regurgitation and ventricular function. Though the distal branch pulmonary arteries are diffi cult to defi ne, the proximal right ventricular outfl ow tract can be seen well (Figure 5).

Surgery for outfl ow tractsUsually preoperative assessment is performed prior to surgery. TEE just prior to surgery will help the surgical team to freshen up their assessment especially in complex surgical procedures like ROSS operations. Postoperative TEE helps in assessment of right ventricular outfl ow tract and degree of pulmonary regurgitation. It has a major role in assessment of left ventricular outfl ow tract and degree of aortic regurgitation and need for replacement of valves. (Figure 6).

Figure 2. Preoperative TEE showing large subaortic VSD with prolapse of right coronary cusp

Figure 3. Postoperative TEE after repair of atrioventricular septal defect showing moderate left AV valve regurgitation

Figure 4. Postoperative TEE after repair of Ebstein’s anomaly of tricuspid valve

Figure 5. Postoperative TEE after repair of Tetralogy of Fallot showing wide open right ventricular outflow tract with no evidence of pulmonary regurgitation

REVIEW ARTICLE


Atrial switch operationsWith the practice of early diagnosis of transposition of great vessels in neonatal life, atrial switch operations are performed less frequently. During the preoperative assessment. It is important to assess the size of left ventricle and AV valve regurgitation, if any. Postoperative TEE has an important role in assessment of systemic and pulmonary venous baffl es, baffl e obstruction or leak.

TEE IN THE CARDIAC CATHETERIZATION LABORATORY With the advent of newer complex

procedures in catheterization laboratory, TEE is a very important tool during the procedure. Regular procedures like closure of atrial septal defects, ventricular septal defects are performed under the guidance of transesophageal echocardiography.7,8 Three dimensional TEE probes are available. These probes can be used safely in bigger children during the procedures, where the structures can be shown in 3 dimensions and the structures like ASDs, VSDs and paravalvar leaks can be closed with proper assessment.

Figure 6. Postoperative TEE after surgical closure of perimembranous VSD showing mild aortic regurgitation

Figure 7. Preprocedural TEE prior to transcatheter closure of atrial septal defect showing deficient retroaortic rim

Closure of intracardiac defects in the cardiac catheterization laboratoryTranscatheter closure of atrial septal defects is solely performed under the guidance of transesophageal echocardiography. It gives very important information to the operator, like size of the defects, number of defects, size of the surrounding rims, quality of the rims and its proximity to the AV valves (Figure 7,8). Proper sized device can be chosen, just on the assessment of preprocedural TEE. Placement of the device is done only under the guidance of TEE. After the deployment, the defect and the device are completely assessed (Figure 9). TEE gives important information regarding proper placement of device, residual shunt, impingement of the device on the AV valves causing AV valve regurgitation. Transesophageal echocardiography has become integral part of the procedure for transcatheter closure of ASD.9

Certain perimembranous and muscular VSDs can be closed successfully in the cardiac catheterization laboratory. TEE

Figure 8. Preprocedural TEE prior to transcatheter closure of ASD – Bicaval view showing adequate SVC and IVC rims

Figure 9. Postprocedural TEE showing ASD closure-device in position


Figure 10. TEE in a patient with peri-membranous VSD prior to transcatheter closure

Figure 11. The same VSD is shown in colours

plays an important role in the assessment of size, number of defects, the margins surrounding VSD for suitability (Figure 10,11). After deployment of device, it is very important to see the proper placement of device , assessment of aortic and tricuspid valve regurgitation if any. As more and more complex procedures are being performed in the catheterization laboratory, TEE plays an important role during the procedures like trans-septal puncture in children, closure of paravalvar leaks and placement of stents across right ventricular outfl ow tracts.

USE OF TEE IN THE OUTPATIENT CLINICS As the echocardiographic windows are excellent in children, there is no need for regular use of TEE in children. In addition as there is a need for anesthesia during the procedure in children, it

becomes an invasive procedure in them. At the same time there is a growing population of adult congenital heart defects. The echocardiographic windows are suboptimal in patients because of prior multiple surgeries. TEE has bigger potential for its use in adult patients with repaired or palliated congenital heart defects.10

Like in adult population, TEE is sometimes performed in children for assessment of patent foramen ovale or presence of thrombus in children with stroke. It is also used in children with prolonged fever of unknown origin to see for vegetations.

SIDE EFFECTS AND COMPLICATIONS Overall incidence of complications reported in many series is 1-3%.11 It most likely occurs in the smaller patients

Most frequent are oropharyngeal or esophageal trauma

Hoarseness Dysphagia Laceration or perforation of the

oropharynx, esophagus or stomach Ventilatory Compromise

Airway Obstruction Bronchospasm, Laryngospasm Position the probe in hypopharynx

when there is no active imaging to reduce the airway related problems

Thermal pressure trauma Arrhythmias Compression of other adjacent

structures like atria, descending aorta causing hypotension.

KNOWLEDGE, SKILLS AND TRAINING REQUIRED FOR PERFORMING TEE IN CHILDRENThe physician performing TEE in pediatric patients requires training, skill and complete knowledge of congenital heart defects. As every patient has a diff erent spectrum of the disease, the physician need to know complete anatomical details of the cardiac defect and how to assess the surgical results after the procedure. They needs to give clear and complete information to the

surgical team and the interventional cardiologist during the procedure for need of reintervention or change of plan. The experience can be obtained only by performing many procedures with diff erent anatomical spectrum.

IMPACT OF TRANSESOPHAGEAL ECHOCARDIOGRAPHY ON OUTCOMES Preoperative information changes the surgical plan in approximately 2% of patients. It is usually in complex surgical procedures like routability of VSDs in patients with double outlet right ventricle or need for repair of AV valves. In 3-5% of patients, postoperative fi ndings prompt for immediate revision. These are mainly for residual outfl ow obstructions, residual ventricular septal defects which need closure or repair of AV valves after surgical repairs of AV septal defects . In addition there are minor postoperative fi ndings on TEE, which may not need immediate revision, but may need close follow-up on long term.

RECOMMENDATIONS FOR INFECTIVE ENDOCARDITIS PROPHYLAXIS Though transient bacteremia may occur after the endoscopies, infective endocarditis attributable to endoscopy is very rarely reported. Endocarditis antibiotic prophylaxis is not recommended for TEE procedures.

SUMMARY TEE in pediatric patient requires special skills and complete knowledge of congenital heart defects. It has substantial positive impact on management of children with congenital heart defects. There is growing need for advanced imaging in assessment of complex heart defects. In this situation the scope of TEE is going to expand in future.

REFERENCES1. Stümper OF, Elzenga NJ, Hess J, Sutherland GR.

Transesophageal echocardiography in children with congenital heart disease: An initial experience. J Am Coll Cardiol 1990;16:433-41.

REVIEW ARTICLE


2. Weintraub R, Shiota T, Elkadi T, Golebiovski P, Zhang J, Rothman A, et al. Transesophageal echocardiography in infants and children with congenital heart disease. Circulation 1992;86:711-22.

3. Ritter SB. Transesophageal real-time echocardiography in infants and children with congenital heart disease. J Am Coll Cardiol 1991;18:569-80.

4. Stevenson JG, Sorensen GK, Gartman DM, Hall DG, Rittenhouse EA. Transesophageal echocardiography during repair of congenital cardiac defects: Identification or residual problems necessitating reoperation. J Am Soc Echocardiogr 1993;6:356-65

5. Ungerleider RM, Kisslo JA, Greeley WJ, Li JS, Kanter RJ, Kern FH, et al. Intraoperative echocardiography during congenital heart operations: Experience from 1000 cases. Ann Thorac Surg 1995;60:S539-42.

6. Rosenfeld HM, Gentles TL, Wernovsky G, et al. Utility of transesophageal echocardiography in the assessment of residual cardiac defects. Pediatr Cardiol 1998;19:346-51.

7. Tumbarello R, Sanna A, Cardu G, Bande A, Napoleone A, Bini Rm. Usefulness of transesophageal echocardiography in the pediatric catheterization laboratory. Am J Cardiol 1993;71:1321-5.

8. Rigby ML. Transesophageal echocardiography during interventional cardiac catheterization in congenital heart disease. Heart 2001;86:1123-9.

9. Elzenga NJ. The role of echocardiography in transcatheter closure of atrial septal defects. Cardiol Young 2000;10:474-83.

10. Masani ND. Transesophageal echocardiography in adult con-genital heart disease. Heart 2001;86:1130-40.

11. Stevenson JG. Incidence of complications in pediatric transesophageal echocardiography: experience in 1650 cases. J Am Soc Echocardiogr 1999;12:527-32.


When to Refer for CABG in Today’s Era of Affordable Stents and PTCA and Wide Application of Technologies

REVIEW ARTICLE

C N MANJUNATH, PRABHAVATHI, C RAGHAVENDRAKeywords

percutaneous transluminal coronary angioplasty (PTCA)

drug-eluting stents percutaneous coronary interventions left main coronary artery disease stable ischemic heart disease

Dr C N Manjunath is Professor of Cardiology, Director, Sri Jayadeva Institute of Cardiovascular Sciences & Research, Bannerghatta Road, 9th Block Jayanagar, Bangalore

AbstractPercutaneous transluminal coronary angioplasty (PTCA) reduces symptoms of angina, but its application has been limited in patients with multivessel coronary artery disease (CAD) because of signifi cant risk of periprocedural ischemic complications and moderate long-term effi cacy. In contemporary clinical practice, coronary artery bypass grafting (CABG) is recommended for treatment of complex patients, including those with multivessel coronary artery disease (MVCAD), while percutaneous coronary intervention (PCI) is preferred in patients with single-vessel disease or acute myocardial infarction (MI). Technological advancement in PCI, such as the introduction drug-eluting stents (DES) in the past decade, however, revived the debate of whether PCI is appropriate for patients with complex multivessel disease, leading to several randomized clinical trials (RCTs) investigating the clinical and cost-effectiveness of CABG compared with PCI with DES. Recent trials also showed that compared with bare-metal stents (BMS), DES were associated with signifi cantly lower restenosis rates, higher initial procedural costs, small but signifi cant risk of very late stent thrombosis, and similar mortality rates.

BACKGROUNDSince its introduction in the 1960s, coronary artery bypass grafting (CABG) has become the standard-of-care for patients with multivessel coronary artery disease.1–5 However, due to the rapid evolvement of percutaneous coronary interventions (PCI), the number of CABGs performed has continuously decreased over the past two decades,6,7 even though several multicentre trials

demonstrate a signifi cant survival benefi t when compared with PCI in certain subset of patients.8–11 The introduction of drug-eluting stents (DESs) into interventional cardiology has further catalyzed the trend to perform coronary revascularization more frequently by a percutaneous approach and less frequently by surgery. Currently, 70% to 75% of all coronary revascularization is performed by a percutaneous approach.12


An ideal revascularization modality cannot be generalized to all patient groups. The decision to choose PCI as a revascularization strategy should be based not only on whether it can be done safely and successfully, based on the coronary anatomy, but it should be done based on evidence and favorable immediate and long-term outcomes when compared to the alternative medical or surgical treatment.

Indications for CABG in current era in diff erent subsets of patients are dealt separately.

STABLE ISCHEMIC HEART DISEASE (SIHD)The indications for revascularization in patients with SIHD who receive guideline-recommended medical treatment are persistence of symptoms despite medical treatment and/or for improvement of prognosis.13

WHY IS CABG BETTER THAN PCI?PCI treats an isolated lesion in the proximal vessel. CABG bypasses the proximal 2/3rd of the vessel, where the current lesion and future threatening lesions occur. This advantage of CABG will persist, even if stent restenosis is zero.

PCI VS CABGPredicted surgical mortality, the anatomical complexity of CAD, and the anticipated completeness of revascularization are important criteria for decision making with respect to the type of revascularization (PCI or CABG).

COMPARISON OF CABG AND PCIFollowing is a table comparing

advantages and disadvantages of PCI vs CABG (Table 1).

ISOLATED PROXIMAL LEFT ANTERIOR DESCENDING (LAD) CADComparing CABG and PCI among patients with isolated proximal LAD disease, the available evidence suggests similar outcomes in terms of death, Myocardial infarction (MI), and stroke, but a higher risk of repeat revascularization with PCI.13a,13b,13c

LEFT MAIN (LM) CORONARY ARTERY DISEASEAvailable evidence from Randomized control trials (RCTs) and meta-analyses comparing CABG with PCI using DES among patients with LM disease suggests equivalent results for the safety composite of death, MI, and stroke up to 5 years of follow-up.17 A signifi cant interaction with time is notable, providing early benefi t for PCI in terms of MI and peri interventional stroke, which is subsequently off set by a higher risk of spontaneous MI during long-term follow-up. The need for repeat revascularization is higher with PCI than with CABG.

The EXCEL trial compared CABG with PCI using new-generation DES [everolimus eluting stent (EES)] among 1905 patients with signifi cant LM disease.18 At 3 years of follow-up, the primary endpoint of death, stroke, or MI occurred with similar frequency in the CABG and PCI group (14.7 vs 15.4%; HR 1.00, 95% CI 0.79–1.26, P = 0.98).

The pre-planned land mark analysis from 30 days to 3 years showed a signifi cant diff erence for the primary endpoint in favour of CABG (7.9 vs. 11.5%, P = 0.02).

The NOBLE (Nordic-Baltic-British Left Main Revascularization Study) trial compared CABG with PCI using new-generation DES [biolimus-eluting stents (BES)] among 1201 patients with signifi cant LM disease (mean SYNTAX score of 23).19 At a median follow-up of 3.1 years, the primary endpoint of death, non-procedural MI, stroke, and repeat revascularization occurred more frequently in the PCI than the CABG group (29 vs. 19%; HR 1.48, 95% CI 1.11–1.96,P = 0.007).

Current evidence indicates that PCI is an appropriate alternative to CABG in LM disease and low-to-intermediate anatomical complexity.21 Among patients with LM disease and low anatomical complexity, there is evidence that the outcomes with respect to major clinical endpoints are similar for PCI and CABG, resulting in class I recommendation in ESC guidelines for revascularization (ESC-2018).1

Among patients with LM disease and high anatomical complexity, the number of patients studied in RCTs is low due to exclusion criteria. The risk estimates and contraindications are imprecise, but suggest a trend towards better survival with CABG.

MULTIVESSEL CADThe observation of survival advantage of CABG over PCI has been consistent among patients with severe three-vessel CAD (intermediate to high SYNTAX score), and has been attributed at least in part to the placement of bypass grafts to the mid coronary vessels providing prophylaxis against the development of new proximal disease.

CABG is preferred revascularization modality over PCI especially in patients with Multivessel CAD with diabetes or patients with left ventricular ejection fraction (LVEF) <35% as shown in trials.26 Even with newer generation stents like EES, trials like BEST showed benefi t of CABG in reducing primary endpoint

Table 1.Advantages of CABG Advantages of PCIAdvantages of CABG Advantages of PCI

Angina relief Initially cost effective Angina relief Initially cost effective

Complete revascularization Fast recovery / Angina reliefComplete revascularization Fast recovery / Angina relief

Mortality benefit in selected patient groups Reduced acute complicationsMortality benefit in selected patient groups Reduced acute complications

(eg: stroke) (eg: stroke)

Reduced reintervention Non surgical Reduced reintervention Non surgical

Complex anatomy Complex anatomy

DisadvantagesDisadvantages Disadvantages Disadvantages

Potential high costs, morbidity Potential high costs, morbidity

InvasiveInvasive

Higher rate of strokeHigher rate of stroke

Results are not uniform across countries Repeat revascularizationResults are not uniform across countries Repeat revascularization


[death, target vessel revascularization (TVR), MI].

The available evidence suggests that in multivessel CAD without diabetes and low anatomical complexity, PCI and CABG achieve similar long-term outcomes with respect to survival and the composite of death, MI, and stroke, justifying a class I recommendation for PCI (ESC 2018).1

In patients with multivessel CAD and intermediate-to-high anatomical complexity, the two large trials using DES, SYNTAX30 and BEST,31 found a signifi cantly higher mortality and a higher incidence of death, MI, and stroke with PCI even in the absence of diabetes. Consistent results were also obtained for patients with multivessel CAD in the recent individual patient-level meta-analysis.21

A collaborative, individual patient data pooled analysis of 11,518 patients with multivessel or LM disease randomized to

CABG or PCI with stents, all-cause death was signifi cantly diff erent after CABG (9.2%) and PCI (11.2%) (P = 0.0038), which was evident in patients with diabetes (10.7 vs. 15.7%, respectively; P = 0.0001) but not in patients without diabetes (8.4 vs. 8.7%, respectively; P = 0.81) (P interaction= 0.0077).2 Current evidence continues to favour CABG as the revascularization modality of choice in patients with MVD and diabetes.20,21 When patients present with a comorbidity that increases surgical risk, the choice of revascularization method is best decided by multidisciplinary individualized risk assessment (Table 2).

IMPORTANCE OF COMPLETENESS OF REVASCULARIZATIONThe aim of myocardial revascularization is to minimize residual ischaemia. In support of this concept, the nuclear substudy of the COURAGE (Clinical Outcomes Utilizing Revascularization

and Aggressive Drug Evaluation) trial demonstrated an incremental benefi t in reducing the risk of death and MI by reducing residual stress induced ischemia from >10% of the myocardium to <5%.14

In SYNTAX trial, anatomical complete revascularization was defi ned as PCI or bypass of all epicardial vessels with a diameter exceeding >1.5 mm and a luminal reduction of >50% in at least one angiographic view.15 Not all CABG patients undergo complete revascularization as commonly believed. In SYNTAX trial, only 63.2% had complete revascularization (56.7% by PCI). Anatomical incomplete revascularization was associated with inferior long-term outcomes after both CABG and PCI.15 A residual SYNTAX score >8 after PCI was associated with signifi cant increase in the 5-year risk of death and of the composite of death, MI, and stroke. Any residual SYNTAX score >0 was associated with the risk of repeat intervention.16 The benefi t of complete revascularization was independent of the treatment modality.

Off pump procedure may lead to in-complete revascularization which was shown in older trials (ROOBY).28 But newer trials (CORONARY) have shown no signifi cant diff erence between com-pleteness of revascularization between off pump and on pump.29

CHOICE OF REVASCULARIZATIONWhen patient is eligible for both modalities of revascularization, over all decision of PCI vs CABG depends on multiple factors like clinical, anatomical and technical aspects (Table 3).

Summary of recommendations for the type of revascularization (CABG or PCI) in patients with SIHD with suitable coronary anatomy for both procedures and low predicted surgical mortality are summarized in Table 3 ( ESC – 2018).1

NON ST ELEVATION ACUTE CORONARY SYNDROME (NSTE-ACS):Approximately 5–10% of NSTE-ACS patients require CABG,22 and they represent a challenging subgroup given their high-risk characteristics compared with patients undergoing elective

Table 2: Subset of people who benefi t most from CABGPatients with survival benefit after CABG versus PCI Patients with survival benefit after CABG versus PCI

Three-vessel disease with high syntax scoresThree-vessel disease with high syntax scores

Multivessel disease including proximal LADMultivessel disease including proximal LAD

Diabetics and Multi vessel diseaseDiabetics and Multi vessel disease

MVD with decreased ejection fractionMVD with decreased ejection fraction

Table 3: Characteristics of patients which decide PCI vs CABGFAVOURS PCI FAVOURS CABGFAVOURS PCI FAVOURS CABG

Clinical characteristics Clinical characteristicsClinical characteristics Clinical characteristics

Presence of severe co-morbidity DiabetesPresence of severe co-morbidity Diabetes

(not adequately reflected by scores) (not adequately reflected by scores)

Advanced age/frailty/reduced life Reduced LV function (EF<35%)Advanced age/frailty/reduced life Reduced LV function (EF<35%)

expectancyexpectancy

Restricted mobility and conditions that Contraindication to DAPTRestricted mobility and conditions that Contraindication to DAPT

affect the rehabilitation process affect the rehabilitation process

Recurrent diffuse in-stent restenosis Recurrent diffuse in-stent restenosis

Anatomical & technical aspects Anatomical & technical aspectsAnatomical & technical aspects Anatomical & technical aspects

MVD with SYNTAX score 0–22 MVD with SYNTAX score >22MVD with SYNTAX score 0–22 MVD with SYNTAX score >22

Anatomy likely resulting in incomplete Anatomy likely resulting in incompleteAnatomy likely resulting in incomplete Anatomy likely resulting in incomplete

revascularization with CABG due to poor revascularization with PCIrevascularization with CABG due to poor revascularization with PCI

quality or missing conduits CTOquality or missing conduits CTO

Severe chest deformaties or scoliosis Severely calcified coronary artery lesionsSevere chest deformaties or scoliosis Severely calcified coronary artery lesions

limiting lesion expansion limiting lesion expansion

Sequelae of chest radiation Need for concomitant interventionsSequelae of chest radiation Need for concomitant interventions

Porcelain aorta a) Ascending aortic pathology with Porcelain aorta a) Ascending aortic pathology with

indication for surgery indication for surgery

b) Concomitant valve surgery b) Concomitant valve surgery

REVIEW ARTICLE


CABG.23 In the absence of randomized data, optimal timing for non-emergent CABG in NSTE-ACS patients should be determined individually. The risk of ischemic events possibly related to suboptimal antiplatelet therapy while awaiting surgery is <0.1%, while that of perioperative bleeding complications associated with platelet inhibitors is >10%.24 In patients with ongoing ischemia or hemodynamic instability with an indication for CABG, emergency surgery should be performed and not postponed as a consequence of antiplatelet treatment exposure.

PCI VS CABG IN STABILIZED PATIENTS WITH NSTE-ACS:There is no randomized comparison of PCI vs. CABG in the specifi c setting of NSTE-ACS. The currently available evidence indirectly suggests that the criteria applied to patients with SIHD to guide the choice of revascularization modality should be applied to stabilized patients with NSTE-ACS.25 Recent individual-patients data analysis from the BEST, PRECOMBAT, and SYNTAX

studies compared the outcome of CABG with that of PCI in 1246 patients with stabilized NSTE-ACS and multivessel or LM disease.25 The 5-year incidence of the primary outcome (composite of death, MI, or stroke) was signifi cantly lower with CABG than with PCI (13.4 vs.18%, P = 0.036). The fi ndings of this meta-analysis were consistent with the main fi ndings of the studies included, thus supporting the concept that the principles of SIHD should apply to stabilized patients with NSTE-ACS as well.

ST ELEVATION MI (STEMI) PATIENTS:In the setting of STEMI, PCI as primary PCI or as pharmocoinvasive is the preferred reperfusion strategy. CABG should be considered in patients with ongoing ischaemia and large areas of jeopardized myocardium if PCI of the infarct related artery (IRA) cannot be performed (class IIa, ESC 2018).

OTHER SUBSETS OF PATIENTS REFERRED FOR CABG:A. EMERGENCY CABG FOR PCI:Despite the increase in high-risk

patients undergoing PCI, there has been a marked decrease in the incidence of patients requiring emergency CABG. This is because of improvement in PCI techniques and ability to manage complications of PCI. Most common indication being iatrogenic coronary artery dissection not amenable for PCI.

B) REVASCULARIZATION IN-PATIENTS REQUIRING CONCOMITANT VALVE INTERVENTIONSCABG is recommended in patients with a primary indication for aortic/mitral valve surgery and coronary artery diameter stenosis >70%. (class I ESC2018) and 50–70% (class IIa ESC2018).

C) ISCHEMIA POST CABGIn this subset of patients redo CABG has two to four fold increased mortality compared with fi rst-time CABG, and repeat CABG is generally performed infrequently. In view of the higher risk of procedural mortality with redo CABG and the similar long-term outcome, PCI is the preferred revascularization strategy in patients with amenable anatomy.27

NEWER SURGICAL TECHNIQUES:During the last decade, newer

techniques have been introduced for CABG to improve the surgical outcomes.1) Multiple arterial grafts: Various

arterial conduits are being used like bilateral internal mammary artery, gastro epiploic artery, radial artery. But real-world usage of multiple arterial grafts is still less.

2) Minimally invasive direct CABG (MIDCAB)

3) Hybrid MIDCAB approach4) Robotic assisted CABG5) Instrumentation: Introduction of

cardiac stabilization devices for off pump CABG like octopus and star fi sh, Intra operative graft fl ow assessment techniques.

6) Methods to extend saphenous vein graft patency

a) Endoscopic vein harvesting b) Research on SVG External

Stenting:

SYNTAX score calculation information is available at http://www.syntaxscore.comSYNTAX score calculation information is available at http://www.syntaxscore.comCABG = coronary artery bypass grafting, CAD = coronary artery disease; LAD = left anterior descending coronary artery; PCI = percutaneous coronary CABG = coronary artery bypass grafting, CAD = coronary artery disease; LAD = left anterior descending coronary artery; PCI = percutaneous coronary intervention; SYNTAX = Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. intervention; SYNTAX = Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery. aaClass of recommendation. Class of recommendation. bbLevel of evidence. Level of evidence. ccPCI should be considered if the Heart Team is concerned about the surgical risk or if the patient refuses PCI should be considered if the Heart Team is concerned about the surgical risk or if the patient refuses CABG after adequate counselling by the Heart Team.CABG after adequate counselling by the Heart Team.ddFor example, absence of previous cardias surgery, severe morbidities, frailty, or immobility precluding CABDFor example, absence of previous cardias surgery, severe morbidities, frailty, or immobility precluding CABD

Table 4: Recommendation for the tye of revascularization in patients with stable coronary artery disease with suitable coronary anatomy for both procedures and low predicted surgical mortalityd


Low patency rates of saphenous vein grafts remain a major predicament in surgical revascularization. The expandable SVG external support system was found to be effi cacious in reducing SVGs non-uniform dilatation and neointimal formation in an animal model early after CABG. This novel technology may have the potential to improve SVG patency rates after surgical myocardial revascularization.

GAPS IN EVIDENCE IN MODERN ERA1) FFR-guided surgical revasculari-

zation has been associated with improved graft patency, but more studies are needed to investigate whether it improves clinical outcomes.

2) Real world usage of newer surgical techniques is still not widespread.

3) Role of CABG in era of percutaneous valve repair/replacement (TAVR, Mitraclip etc..,). Studies are needed to compare outcomes of CABG + valve repair/replacement vs PCI + concomitant valve procedures.

SUMMARYAlthough the past two decades has seen a diminishing role for CABG in the management of CAD, CABG continues to play an important role in patients with diabetes and multivessel CAD and LM with high syntax scores. Further decrease in morbidity rate associated with CABG and increasing use of arterial grafts can help in increasing graft patency. Final

decision of revascularization modality for patients who are eligible for both CABG and PCI should be individualized, considering associated comorbidities of patient, and should be discussed by Heart team containing Interventional cardiologist, Cardiac surgeon, and Cardiac anesthetist. Patient choice plays an important role in taking fi nal decision.

Improvement in PCI techniques and wide spread use of newer imaging modalities for assisting PCI may improve outcomes of PCI and can further reduce the indications for CABG especially in complex CAD.

REFERENCE1. Franz-Josef Neumann et al., 2018 ESC/EACTS Guidelines

onmyocardialRevascularization. European Heart Journal (2018) 00, 1–96.

1a. Windecker S et al ,2014 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J. 2014;35:2541-619.

2. Fihn SD et al, 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: J Am Coll Cardiol. 2012;60:e44-e164.

3. Fihn SD et al,.2012ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: Circulation. 2012;126:e354-471.

4. Kolh P and Windecker S. ESC/EACTS myocardial revascularization guidelines 2014. Eur Heart J. 2014;35:3235-6.

5. Kolh P et al ,2014 ESC/EACTS Guidelines on myocardial revascularization: Eur J Cardiothorac Surg. 2014;46:517-92.

6. Aldea GS, Bakaeen FG, Pal J, Fremes S, Head SJ, Sabik J, Rosengart T, Kappetein AP, Thourani VH, Firestone S, Mitchell JD and Society of Thoracic S. The Society of Thoracic Surgeons Clinical Practice Guidelines on Arterial Conduits for Coronary Artery Bypass Grafting. Ann Thorac Surg. 2016;101:801-9.

7. Head SJ, Borgermann J, Osnabrugge RL, Kieser TM, Falk V, Taggart DP, Puskas JD, Gummert JF and

Kappetein AP. Coronary artery bypass grafting: Part 2--optimizing outcomes and future prospects. Eur Heart J. 2013;34:2873-86.

8. Farkouh ME,et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367:2375-84.

9. Mohr FW, Morice MC, Kappetein AP, Feldman TE, Stahle E, Colombo A, Mack MJ, Holmes DR, Jr., Morel MA, Van Dyck N, Houle VM, Dawkins KD and Serruys PW. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381:629-38.

10. Velazquez EJ, Lee KL, Jones RH, Al-Khalidi HR, Hill JA, Panza JA, Michler RE, Bonow RO, Doenst T, Petrie MC, Oh JK, She L, Moore VL, Desvigne-Nickens P, Sopko G, Rouleau JL and Investigators S. Coronary-Artery Bypass Surgery in Patients with Ischemic Cardiomyopathy. N Engl J Med. 2016;374:1511-20.

11. Weintraub WS, Grau-Sepulveda MV, Weiss JM, O'Brien SM, Peterson ED, Kolm P, Zhang Z, Klein LW, Shaw RE, McKay C, Ritzenthaler LL, Popma JJ, Messenger JC, Shahian DM, Grover FL, Mayer JE, Shewan CM, Garratt KN, Moussa ID, Dangas GD and Edwards FH. Comparative effectiveness of revascularization strategies. N Engl J Med. 2012;366:1467-76.

12. Mack MJ, Prince SL, Herbert M, et al. Current 18-month clinical outcomes of percutaneouscoronary intervention in coronary artery bypass grafting: the CARE (Coronary ArteryREvascularzation) Study. Ann Thorac Surg. 2008.

13. Montalescot G, Sechtem U, Achenbach S, Andreotti F, Arden C, BudajA,Bugiardini R, Crea F, Cuisset T, Di Mario C, Ferreira JR, Gersh BJ, GittAK,Hulot JS, Marx N, Opie LH, Pfisterer M, Prescott E, RuschitzkaF,SabateM,Senior R, Taggart DP, van der Wall EE, Vrints CJ. 2013 ESC guidelines on themanagement of stable coronary artery. Eur Heart J 2013;34:2949–3003.

13a. Thiele H, Neumann-Schniedewind P, Jacobs S, Boudriot E, Walther T, Mohr FW, Schuler G, Falk V. Randomized comparison of minimally invasive direct coronary artery bypass surgery versus sirolimus-eluting stenting in isolated proximal left anterior descending coronary artery stenosis. J Am CollCardiol 2009;53:2324–2331.

13b. Hannan EL, Zhong Y, Walford G, Holmes DR Jr, Venditti FJ, Berger PB, Jacobs AK, Stamato NJ, Curtis JP, Sharma S, King SB III. Coronary artery bypass graft surgery versus drug-eluting stents for patients with isolated proximal left anterior descending disease. J Am CollCardiol 2014;64:2717–2126.

13c. Blazek S, Rossbach C, Borger MA, Fuernau G, Desch S, Eitel I, Stiermaier T Lurz P, Holzhey D, Schuler G, Mohr FW, Thiele H. Comparison of sirolimuseluting stenting with minimally invasive bypass surgery for stenosis of the left anterior descending coronary artery: 7-year follow-up of a randomized trial.JACCCardiovascInterv 2015;8:30–38.

14. Shaw L J et al, COURAGE Investigators. Optimal medical therapy with or without percutaneous coronary intervention to reduce ischemic burden: Results from the ClinicalOutcomes Utilizing Revascularization and Aggressive Drug Evaluation(COURAGE) trial nuclear substudy. Circulation 2008;117(10):1283–1291

15. Farooq V et al. The negative impact of incomplete angiographicrevascularization on clinical outcomes and its association with totalocclusions: The SYNTAX (Synergy Between Percutaneous CoronaryIntervention with Taxus and Cardiac Surgery) trial. J Am Coll Cardiol2013;61:282–294.

16. Farooq V, Serruys PW, Bourantas CV, Zhang Y, Muramatsu T, Feldman T,Holmes DR, Mack M, Morice MC, Stahle E, Colombo A, de Vries T, Morel MA, Dawkins KD, Kappetein AP, Mohr FW. Quantification of incomplete revascularizationand its association with five-year

REVIEW ARTICLE

Unsupported SVG to OMUnsupported SVG to OM Supported SVG to RCASupported SVG to RCA


mortality in the synergy between percutaneouscoronary intervention with taxus and cardiac surgery (SYNTAX)trial validation of the residual SYNTAX score. Circulation 2013;128:141151.

17. Giacoppo D, Colleran R, Cassese S, Frangieh AH, Wiebe J, Joner M, Schunkert, H, Kastrati A, Byrne RA. Percutaneous coronary intervention vs coronary artery bypass grafting in patients with left main coronary artery stenosis: A systematic review and meta-analysis. JAMA Cardiol 2017;2:1079–1088.

18. Stone GW,et al; EXCEL Trial Investigators. Everolimus-eluting stents or bypass surgery for left main coronary artery disease. N Engl J Med 2016;375:2223–2235.

19. MakikallioT,et al; NOBLE Study Investigators. Percutaneous coronary angioplasty versus coronary artery bypass grafting in treatment of unprotected left main stenosis (NOBLE): a prospective, randomised, open-label, non-inferiority trial. Lancet 2016;388:2743–2752.

20. Ramanathan K, Abel JG, Park JE, Fung A, Mathew V, Taylor CM, Mancini GBJ, Gao M, Ding L, Verma S, Humphries KH, Farkouh ME. Surgical versus percutaneous coronary revascularization in patients with diabetes and acute coronary syndromes. J Am CollCardiol 2017;70:2995–3006.

21. Head SJ, et al.Mortality after coronary artery bypass grafting versus percutaneous coronaryintervention with

stenting for coronary artery disease: A pooled analysis of individualpatient data. Lancet 2018;391:939–948.

22. Ranasinghe I, Alprandi-Costa B, Chow V, Elliott JM, Waites J, CounsellJT,Lopez-Sendon J, Avezum A, Goodman SG, Granger CB, Brieger D. Risk stratificationin the setting of non-ST elevation acute coronary syndromes 1999-2007.Am J Cardiol 2011;108:617–624.

23. Fukui T, Tabata M, Morita S, Takanashi S. Early and long-term outcomes of coronaryartery bypass grafting in patients with acute coronary syndrome versusstable angina pectoris. J ThoracCardiovascSurg 2013;145:1577–1583.

24. Malm CJ, Hansson EC, Akesson J, Andersson M, Hesse C, Shams Hakimi C,Jeppsson A. Preoperative platelet function predicts perioperative bleeding complicationsin ticagrelor-treated cardiac surgery patients: A prospective observationalstudy. Br J Anaesth 2016;117:309–315

25. Chang M, Lee CW, Ahn JM, Cavalcante R, Sotomi Y, Onuma Y, Han M, ParkDW, Kang SJ, Lee SW, Kim YH, Park SW, Serruys PW, Park SJ. Comparison ofoutcome of coronary artery bypass grafting versus drug-eluting stent implantationfor non-ST-elevation acute coronary syndrome. Am J Cardiol2017;120:380–386.

26. Bangalore S, Guo Y, Samadashvili Z, Blecker S, Hannan EL. Revascularization inpatients with multivessel coronary artery disease and severe left ventricular

systolicdysfunction: Everolimus-eluting stents versus coronary artery bypass graft surgery. Circulation 2016;133:2132–2140.

27.Brener SJ, Lytle BW, Casserly IP, Ellis SG, Topol EJ, Lauer MS. Predictors ofrevascularization method and long-term outcome of percutaneous coronaryintervention or repeat coronary bypass surgery in patients with multivessel coronarydisease and previous coronary bypass surgery. Eur Heart J2006;27:413–418.

28. A. L. Shroyer, F. L. Grover, B. Hattler et al., “On-pump versusoff-pump coronary-artery bypass surgery,” The New EnglandJournal of Medicine, vol. 361, no. 19, pp. 1827–1837, 2009.

29.Lamy A, et al CORONARYInvestigators. Off-pump or on-pump coronary-artery bypass grafting at 30 days.NEngl J Med 2012;366:1489–1497.

30.Mohr FW, et al, Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet2013;381:629–638.

31.Seung-Jung Park, M.D..et al.,Trial of Everolimus-Eluting Stents or Bypass Surgery for Coronary Disease for the BEST Trial investigators ,N Engl J Med 2015; 372:1204-1212.


Cause of Increase in P Wave Amplitude During Exercise Induced Tachycardia

ECG OF THE MONTH

SR MITTAL

AbstractAmplitude of P wave during exercise induced tachycardia is due to fusion of U and P waves.

Keywords electrocardiography exercise stress testing U wave

It is a common observation that P wave amplitude increases during exercise induced stress testing. Mechanism of this change is not clear. We observed an interesting fi nding during treadmill stress testing.

Treadmill stress test was performed on an asymptomatic middle aged man as a part of routine health check up. He was a non-smoker and had normal

Dr. SR Mittal is Head, Department of Cardiology at Mittal Hospital and Research Centre, Ajmer, Rajasthan

blood sugar and lipid profi le. Th ere was no family history of premature coronary artery disease. He had no symptoms or abnormal clinical fi ndings during exercise and 6 minute recovery. Blood pressure and pulse rate response were normal. Th ere were no ST-T changes during exercise and recovery.

While looking at the electro-cardiographic recordings, we observed that during second minute of recovery, there was sinus arrhythmia. In cycles with short R-R interval, P (marked x) wave started soon aft er T wave. U wave was not visible and P wave had increased amplitude. In the next cycle with relatively longer R-R interval (marked y), T and U waves were separated by a clear U wave and P wave amplitude decreased.

Our observation suggests that during tachycardia, P wave moves towards T wave due to shortening of diastole. P wave encroaches on the U wave. Fusion of U wave and P wave increases amplitude of P wave. At a relatively slower rate, P wave moves away from T wave, U wave separates from P wave and amplitude of P wave decreases. Th ese fi ndings suggest that increase in the amplitude of P wave during exercise induced tachycardia is due to fusion of U and P waves.

Figure 1. Electrocardiographic recording during second minute of recovery following a treadmill stress test. Cycle ‘X’ shows absence of U wave and increased amplitude of P wave (P1) cycle ‘y’ shows clear u wave with decrease in amplitude of following P wave (P2).


Isolated Tricuspid Valve Prolapse

PICTORIAL CME

SR MITTAL

AbstractTricuspid valve prolapse is mostly associated with mitral valve prolapse. Isolated tricuspid valve prolapse is rare with occasional case reports. It occurs mostly due to congenital abnormalities of the tricuspid valve apparatus or myxomatous degeneration. Most of the patients are asymptomatic and are diagnosed during routine echocardiography. There may be no abnormal fi ndings on clinical examination of cardiovascular system. Some patients may have non-ejection click and / or mid to late systolic murmur in the left lower parasternal region. Inspiratory delay in click and / or inspiratory increase in intensity of murmur strongly suggest the diagnosis of tricuspid valve prolapse but are usually not apparent on clinical examination. Electrocardiogram and skiagram of chest do not give any diagnostic information. Echocardiography shows buckling of one or more tricuspid leafl ets into right atrium during systole. Evaluation of posterior leafl et may be diffi cult on 2-dimensional echocardiography. Three-dimensional echocardiography allows simultaneous evaluation of all three leafl ets. Tricuspid regurgitation is usually mild to moderate. Severe tricuspid regurgitation and right ventricular dysfunction are rare. Clinically, it is diffi cult to differentiate the tricuspid valve click from other causes of non-ejection click. Detailed echocardiographic evaluation helps in differentiating various causes of isolated low-pressure tricuspid regurgitation. Patients with isolated tricuspid valve prolapse without severe tricuspid regurgitation have normal life span, except for the risk of infective endocarditis. Patients with severe tricuspid regurgitation should have surgical intervention. Repair of the tricuspid valve is preferred over valve replacement.

Keywords echocardiography non ejection click right ventricle systolic murmur tricuspid valve prolapse tricuspid regurgitation

INTRODUCTIONTricuspid valve prolapse is mostly asso-ciated with mitral valve prolapse, or is a part of polyvalvular prolapse.1,2 Isolated tricuspid valve prolapse is rare.3 Diagno-

Dr. SR Mittal is Head, Department of Cardiology at Mittal Hospital and Research Centre, Ajmer, Rajasthan

sis is usually made during 2-dimensional echocardiography which shows buckling of tricuspid leafl ets into right atrium in systole. We are reporting a case of isolated tricuspid valve prolapse in the setting of


PICTORIAL CME

idiopathic pulmonary artery hyperten-sion. Literature on isolated tricuspid valve prolapse is reviewed.

CASE REPORTA 25 years female presented with palpita-tions and progressively increasing breath-lessness. Pulse was regular at a rate of around 78/minute. Jugular venous pres-sure was normal with prominent ‘a’ wave. Liver was not palpable and there was no dependent oedema. Palpation of precar-dium revealed left parasternal systolic lift . Systolic pulsations and second sound

were palpable in left second intercostal space. A Grade 3/6 mid systolic murmur was audible along left lower sternal bor-der. It showed no signifi cant variation with posture or respiration. Th ere was no click. Examination of other systems was normal.

Electrocardiogram showed mild right axis deviation. Skiagram of chest was unremarkable. Two dimensional echocardiography revealed dilated right atrium and right ventricle with prolapse of tricuspid leafl ets (Figure 1). Th ere was systolic as well as diastolic fl attening of

interventricular septum with D shaped left ventricular cavity (Figure 2) suggestive of signifi cant increase in right ventricular pressure. Left atrium, mitral valve and left ventricle were normal (Figure 1).

Color Doppler evaluation revealed moderate tricuspid regurgitation TR (Figure 3). Doppler evaluation of tricuspid regurgitation fl ow revealed peak gradient of 67mm Hg (Figure 4). Tricuspid forward fl ow revealed impaired relaxation of right ventricle (Figure 5). Mitral valve fl ow was normal (Figure 6). Doppler evaluation of hepatic vein fl ow revealed prominent

Figure 1. Apical four chamber view showing prolapse of tricuspid valve (TVP), dilated right atrium (RA) and right ventricle (RV). Left atrium (LA), mitral valve (MV) and left ventricle (LV) are normal.

Figure 2. Short axis view in end diastole (ED) and end systole (ES) showing flattening of interventricular septum (IVS). RV- right ventri-cle. LV- left ventricle.

Figure 3. Apical four chamber with color Doppler showing moderate tricuspid regurgitation (TR).

Figure 4. Pulsed Doppler evaluation of tricuspid regurgitation jet showing right ventricular systolic pressure of 67.7mm Hg.


atrial reversal wave (Figure 7) suggestive of impaired relaxation of right ventricle.

Findings are suggestive of idiopathic pulmonary artery hypertension with isolated prolapse of tricuspid valve and moderate tricuspid regurgitation.

REVIEW OF LITERATURE ON ISOLATED TRICUSPID VALVE PROLAPSEA. Etiology Isolated tricuspid valve prolapse occurs

mostly due to congenital abnormalities of the tricuspid valve apparatus4,5 or myxo-matous degeneration.6,7 Rarely it may be secondary to infective endocarditis8 or trauma to tricuspid valve.9 In other cases, there may be no apparent cause on clini-cal examination and echocardiography. Cause may be clear only on surgery7 or at autopy.5 Most of the case reports have not mentioned any comorbidity.10-15 Some case reports have mentioned some sys-temic, pulmonary or cardiac diseases in patients with isolated tricuspid valve pro-lapse (Table 1). Th ere is, however, no evi-dence that these conditions have any etio-logical role in the development of isolated tricuspid valve prolapse. We feel that most

of these are coincidental or age related co-morbidities. Pulmonary artery hyperten-sion and / or dilatation of right ventricle can exaggerate tricuspid regurgitation but are unlikely to produce tricuspid valve prolapse of their own. In one case closure of associated atrial septal defect resulted in aggravation of tricuspid valve prolapse and tricuspid regurgitation.16 Reduction in right ventricular dimension following closure of ASD, probably unmasked the actual severity of prolapse.

B. Symptoms Isolated tricuspid valve prolapse per se is asymptomatic10,13,15,17 even when as-sociated with tricuspid regurgitation.18

Figure 7. Pulsed Doppler evaluation of hepatic vein flow showing prominent atrial reversal wave (A). S- systolic wave, D-Diastolic wave.

Figure 5. Pulsed Doppler evaluation of triscuspid flow showing A wave larger than E wave.

Figure 6. Pulsed Doppler evaluation show-ing normal mitral flow.

Table 1: Comorbidities reported in some cases of isolated tricuspid valve prolapse Comorbidity Comorbidity

Systemic disordersSystemic disorders

(a)- Polyarticular arthritis (a)- Polyarticular arthritis

(b)- Rheumatoid arthritis (b)- Rheumatoid arthritis

2. Systemic hypertension 2. Systemic hypertension

- with concentric left ventricular hypertrophy - with concentric left ventricular hypertrophy

- with diabetes mellitus and Ischemic left - with diabetes mellitus and Ischemic left

ventricular systolic dysfunction. ventricular systolic dysfunction.

3. Coronary artery disease.3. Coronary artery disease.

4. Idiopathic hypertrophic subaortic stenosis4. Idiopathic hypertrophic subaortic stenosis

5. Dilated cardiomyopathy5. Dilated cardiomyopathy

6. Mitral stenosis 6. Mitral stenosis

7. Mitral regurgitation secondary to chordal 7. Mitral regurgitation secondary to chordal

rupture rupture

8. Congenital heart disease8. Congenital heart disease

- PFO with atrial septal aneurysm. - PFO with atrial septal aneurysm.

- Atrial septal defect - Atrial septal defect

- Post ASD repair - Post ASD repair

- Ebstein anomaly of Tricuspid valve with - Ebstein anomaly of Tricuspid valve with

ASD.ASD.

- Congenitally bicuspid aortic valve. - Congenitally bicuspid aortic valve.

9. Chronic lung disease9. Chronic lung disease

- Corpulmonale - Corpulmonale

- Progressive respiratory insufficiency - Progressive respiratory insufficiency

- Sarcoidosis and systemic hypertension - Sarcoidosis and systemic hypertension

- Idiopathic pulmonary artery hypertension - Idiopathic pulmonary artery hypertension

- Pulmonary artery hypertension (cause not - Pulmonary artery hypertension (cause not

mentioned. mentioned.

Number of Number of

patientspatients

OneOne

OneOne

OneOne

OneOne

ThreeThree

OneOne

OneOne

OneOne

OneOne

OneOne

OneOne

ThreeThree

OneOne

OneOne

One One

TwoTwo

OneOne

OneOne

One One

One One

ReferenceReference

Liddell NE et al (19)Liddell NE et al (19)

Bettegowda S et al (17)Bettegowda S et al (17)

Weinreich DJ et al (5) Weinreich DJ et al (5)

Weinreich DJ et al (5)Weinreich DJ et al (5)

Chandraratna PAN et al (6)Chandraratna PAN et al (6)


Tei C et al (22)Tei C et al (22)


Werner JA et al (9) Werner JA et al (9)

Kocabay G et al (3)Kocabay G et al (3)

Horgan JH et al (38)Horgan JH et al (38)




Jacques AM et al (7)Jacques AM et al (7)

Shimada E et al (39)Shimada E et al (39)

Werneich et al (5)Werneich et al (5)

Sassel & Froelich CR (24)Sassel & Froelich CR (24)

Karayannis E et al (40)Karayannis E et al (40)

Eren H et al (4)Eren H et al (4)


Symptoms are usually due to associated illness.5 Patients with gross tricuspid re-gurgitation may complain of palpitation.14 Progressive fatigue, dyspnoea on exertion and lower extremity oedema suggest right ventricular failure.19 Orthopnoea and paroxysmal nocturnal dyspnoea should suggest additional pulmonary and/or left ventricular disease. C. Signs Th ere are no diagnostic fi ndings on sys-temic examination. Like mitral valve pro-lapse, some patients may have skeletal abnormalities20 or features of connective tissue disease like Marfan syndrome. Th ese fi ndings have no signifi cance for diagnosis of isolated tricuspid valve pro-lapse.

Pulse is normal. No arrhythmias have been reported even in patients with gross tricuspid regurgitation with enlargement

of right atrium and right ventricle.3,7,19 Jugular venous pressure is normal.18,19 Jugular venous pulse wave form in usually normal18 even in presence of tricuspid incompetence.19 Severe tricuspid incompetence may produce prominent ‘V’ wave with rapid ‘Y’ descent. Liver is non pulsatile except in severe TR. Distension of jugular veins, pulsatile enlargement of liver and dependent oedema suggest right ventricular failure.

Th ere may be no abnormal fi nding on clinical examination of precordium. Usually it is found coincidentally on echocardiography performed for some other indication. Palpation of precordium is normal. Apical impulse is normal. Prominent or displaced apical impulse should suggest additional left ventricular disease. Th ere is no parasternal heave as right ventricular systolic pressure is normal. Presence of a systolic thrill should suggest another etiology. Auscultation may reveal non ejection click and / or mid to late systolic murmur (Figure 8). In some patients a non ejection click may be the only fi nding.10,17 Tricuspid valve prolapse click should be more prominent at lower left sternal border and should move towards second sound during inspiration.5,17,18 Inspiration increases diastolic volume of right ventricle resulting in delayed prolapse of tricuspid valve. Click of mitral valve prolapse occurs earlier or exhibits no changes with inspiration19 (Figure 9). Inspiratory delay in the click may be diffi cult to appreciate clinically. Simultaneous high

speed recording of phonocardiogram and respirometer tracing may be required for diagnosis.18 In absence of such diagnostic fi ndings, it may be diffi cult to diff erentiate a tricuspid valve prolapse click from click of mitral valve prolapse which is relatively more common. Signifi cant tricuspid regurgitation is uncommon.21 Mild regurgitation may be detected only on color Doppler imaging and may not produce an audible murmur.22 A systolic murmur best audible along lower left sternal border suggests tricuspid incompetence. Murmur may not show appreciable variation with respiration or other maneuvers.18 Murmur clearly increasing in intensity on inspiration strongly supports the diagnosis of tricuspid regurgitation.3,7,14,19,23

D. Electrocardiogram Th ere are no diagnostic fi ndings.5,17 Rhythm is sinus. Isolated tricuspid valve prolapse, per se, does not produce any arrhythmia, intraventricular conduction defects or repolarization abnormalities. Any abnormalities are due to associated diseases.

E. Skiagram of chestIt does not give any diagnostic informa-tion.5,17 Abnormalities are due to associ-ated disease.

F. Echocardiography M-mode echocardiography can only detect signifi cant prolapse of anterior tricuspid leafl et.6,9,24 However, prolapse

Figure 9. Diagram showing effect of respiration on click of tricuspid valve prolapse (TVP) and mitral valve prolapse (MVP). S1- First heart sound, C- non ejection click, M-mid to late systolic murmur, A2 aortic component of second heart sound, P2 – pulmonary component of second heart sound.

PICTORIAL CME

Figure 8. Diagram showing auscultatory findings in isolated tricuspid valve prolapse (i) isolated non ejection click (c) (ii) multiple non ejection clicks(c) (iii) Non ejection click (c) and mid to late systolic murmur (m) (iv) isolated mid to late systolic murmur (m). S1- First heart sound, S2- second heart sound.

(i)(i)

(ii)(ii)

(iii)(iii)

(iv)(iv)


can be localized to other leafl ets.15,22 In such situation, diagnosis is likely to be missed with M-mode echocardiography. 2-dimensional echocardiography shows buckling of the leafl ets into right atrium in systole (Figure 10). Th is modality can evaluate all the three leafl ets.5 Right ven-tricular infl ow view shows anterior leafl et

Figure 10. Diagram (A) showing normal closure of tricuspid valve (B) showing systolic buckling of tricuspid leaflets in isolated tricuspid valve prolapse. LA- left atrium, LV- left ventricle,, RA- right atrium, RV- right ventricle, MV- Mitral valve, TV- tricuspid valve, TVP- tricuspid valve prolapse.

attached to the right ventricular free wall and septal leafl et attached to the inter-ventricular septum (Figure 11-a). Poste-rior leafl et is not seen in this view. Apical four chamber view also shows septal and anterior leafl ets (Figure 11-b). Posterior leafl et is again not seen. Long axis plane of the right ventricular infl ow shows an-terior and posterior leafl et5 (Figure 11c). However imaging of this view may be dif-fi cult at times.3 Apical four chamber view with posterior tilt (showing coronary si-nus) shows septal and posterior leafl et25

(Figure 11d). Inspite of using these mul-tiple views, all three leafl ets may be vis-ualized only in 75% patients.26 Besides detection of buckling of the leafl ets, 2-di-mensional echocardiography also allows assessment of other fi ndings e.g. leafl et redundancy, thickening, eccentric coop-tation and annular dilatation.

Th ree dimensional echocardiography allows simultaneous assessment of morphology and prolapse of all three

leafl et27 (Figure 12). It also allows correct measurement of entire oval shaped tricuspid annulus, something which is not possible by 2D echocardiography.26 Transesophageal echocardiography has been used for evaluation of isolated tricuspid valve prolapse.3,19 It is useful if thoracic window is not adequate.

Color Doppler evaluation usually shows mild to moderate tricuspid regurgitation. Severe regurgitation is uncommon. Right ventricular functions are mostly normal.

G. AngiographyIt is not required. It does not give any ad-ditional information. Risks of right heart catheterization and the problem of cath-eter induced leafl et distortion and regur-gitation are additional problems.5

H. Diff erential diagnosis Isolated non-ejection clicks

(a) Isolated mitral valve prolapseClicks of mitral valve prolapse are

better audible over cardiac apex but may be widely audible. Mitral valve prolapse clicks occur earlier with inspiration. On the other hand clicks of isolated tricuspid valve prolapse are better audible in left lower parasternal region17 and are delayed during inspiration18 (Figure 9).

(b) Other causes Non ejection click have also been

reported in some other conditions. Such clicks are rare. Clinical diagnosis of etiology is diffi cult. Simultaneous recording of echophonocardiography is needed before a non ejection click can be attributed to these conditions. It is also necessary to exclude any concomitant atriventricular valve prolapse. Exact pathogenesis of such clicks is not clear. (i) Atrial septal aneurysm28 During ventricular systole, left atrial

pressure exceeds right atrial pressure. Sudden movement of atrial septal aneurysm to right (Figure 13) could produce a non ejection click.

(ii) Adhesive pericarditis29

In adhesive pericarditis, there are fi brous adhesions between epicar-dium and visceral pericardium. Dur-ing systole, myocardium contracts and moves away from the thickened

Figure 11. Diagram showing various leaflets of tricuspid valve in different 2-D echocardio-graphic view (a) right ventricular inflow view (b) apical four chamber view (c) long axis view of right ventricular inflow (d) posteriorly tilted apical four chamber view, A- anterior, S- septal, P – posterior, CS- coronary sinus.


pericardium. Th is results in sudden stretching of these fi brous adhesions (Figure 14). Th is can produce a non ejection click.

(iii) Atrial myxoma29

Pedunculated myxoma prolapses across atrioventricular valve during diastole. During ventricular systole it is pushed back into the atrium (Fig-ure 15). Th is sudden movement can

produce a non ejection click. (iv) LV aneurysm29 True left ventricular aneurysm is

thin walled. During systole it bulges out due to increase in intraventricu-lar pressure (Figure 16). Th is sudden outward movement can produce a non ejection click.

(v) Aneurysm of ventricular septum as-sociated with a VSD29

During systole, left ventricular pres-sure rises rapidly above right ventric-ular pressure. Th is suddenly pushes the aneurysm covering the ventricu-lar septal defect towards right ventri-cle (Figure 17) and can produce a non ejection click.

(vi) Left sided pneumothorax29

During systole, heart rotates along its long axis and apex moves anteriorly and touches anterior chest wall. If left pneumothorax is in contact with the apex of heart, during rotation the car-diac apex strikes against the pneumo-thorax (Figure 18) and can produce a non ejection click.

REFERENCES1. Rippe JM. Angoff Y, Stoss LJ, Wynne J, Alpert JS. Multi-

ple floppy valves; an echocardiographic syndrome. Am J Med. 1979;66:817-24.

2. Desai HM, Amonkar GP. Idiopathic mitral valve prolapse with tricuspid, aortic and pulmonary valve involvement: an autopsy case report. Indian J Pathol Microbiol 2015; 58 : 217-9.

3. Kocabay G, Sirma D, Mert, M, Tigen K. Isolated tricuspid valve prolapse: identification using two and three dimen-sional echocardiography and transesophageal echocardi-ography. Cardiovascular Journal of Africa, 2011; 22:272-3.

4. Eren H, Kalcik M, Kahveci G, Ozkan M. Tricuspid valve prolapse secondary to excessive long chordae evaluated by transthoracic echocardiography. Arch Turk Soc Cardiol 2014;42:789.

Figure 12. Diagrammatic representation of position of various tricuspid leaflets on three dimensional echocardiography. A- anterior, S- septal, P- posterior.

Figure 13. Diagram showing sudden movement of atrial septal aneurysm (A) towards right atrium during systole. D- Diastole, S-systole.

Figure 14. Diagram showing sudden tens-ing of adhesion (A) between visceral peri-cardium (P) and epicardium (E) during sys-tole, D- Diastole, S-systole, M- myocardium.

Figure 15. Diagram showing sudden move-ment of atrial myxoma(M) back in atrium during systole (S), D-diastole.

Figure 16. Diagram showing sudden dis-tension of ventricular aneurysm (A) during systole, D- diastole, S- systole.

Figure 17. Diagram showing sudden pushing of aneurysms (A) covering the ventricular septal defect towards right during systole.

Figure 18. Diagram showing cardiac apex striking against left sided pneumothorax (P) during systole, L- left lung, D- Diastole, S-Systole.

PICTORIAL CME


5. Weinreich DJ, Bruke JF, Bharti S, Lev M. Isolated prolapse of the tricuspid valve. J Am Coll Cardiol 1985;6:475-8.

6. Chandraratna PAN, Lopez JM, Fernandez JJ, Cohen LS. Echocardiographic detection of tricuspid valve prolapse. Circulation 1975;51:823-6.

7. Jacques AM van Son, Miles CM, Starr A. Tricuspid valve prolapse associated with myxomatous degeneration. Ann Thorac Surg 1995;15:1237-9.

8. Bashour T, Lindsay J Jr. Mid systolic click originating from tricuspid valve structures : a sequela of heroin induced endocarditis. Chest 1975;67:620-1.

9. Werner JA, Schiller NB, Prasquier R. Occurrence and sig-nificance of echocardiographically demonstrated tricus-pid valve prolapse. Am heart J 1978;96:180-6.

10. Arosio G, Ettori F, Niccoli L. Isolated tricuspid valve pro-lapse and meso-Lelesystolic click, Echocardiographic di-agnosis. G Ital Cardiol 1980;10:915-20.

11. Jackson D, Gibbs HR, Zee- Cheng CS. Isolated tricuspid valve diagnosed by echocardiography. Am J Med 1986; 80 :281-4.

12. Moro E, Nicolosi GL, D’ Angelo G, Zanuttini D. Isolated tricuspid valve prolapse: identification using 2- dimen-sional and Doppler echocardiography. G Ital Cardiol 1987;17:206-10.

13. Kriwisky M, Froom P, Ribak J, Cyjon A, Lewis B, Gross M. Isolated tricuspid valve prolapse. Cardiology 1988;75: 145-8.

14. Mittal SR, Swaroop A, Gokhroo R. Gross tricuspid incom-

petence due to isolated tricuspid valve prolapse. Int J Cardiol 1990;29:85-6

15. Patane S, Marte F, Di Bella G, Di Tommaso E, Pagano GT, Chiribiri A. Isolated tricuspid prolapse in young child. Int J Cardiol 2009; 136:e37-8.

16. Chandraratna PAN, Littman BB, Wilson D. The association between atrial septal defect and prolapse of the tricuspid valve. Chest 178;73:839-42.

17. Bettegowda S, Iyengar VS. Pillappa SK, Koinde P. Isolated tricuspid valve prolapse with rheumatoid arthritis- an unusual association. Asian Pac Health Sci 2014; 1 : 500-1.

18. Farrar MW, Engel PJ, Eppert D, Plummer S. Late systolic click from isolated tricuspid valve prolapse simulating paradoxical splitting of the second heart sound. J Am Coll Cardiol 1985;5:793-6.

19. Liddell NE, Stoddard MF, Talley JD, Guinn VL, Kupersmith J. Transesophageal echocardiographic diagnosis of iso-lated tricuspid valve prolapse with severe tricuspid regur-gitation. Am Heart J 1992;123:230-2.

20. Mardelli TJ, Morganroth J, Chen CC, Naito M, Vergel J. Tricuspid valve prolapse diagnosed by cross sectional echocardiography. Chest 1981;79:201-5.

21. Di Luzio V, Ciampani N, Capestro F, Purcaro A. Tricuspid valve prolapse. Clincial significance and diagnostic prob-lems. G Ital Cardiol 1979;9:374-82.

22. Tei C, Shah PM, Cherian G, Trim PA, Wang M, Ormiston JA. Echocardiographic evaluation of normal and pro-

lapsed tricuspid valve leaflets. Am J Cardiol 1983;52: 796-801.

23. Seder CW, Suri RM, Rehfeldt K, Pislaru S, Burkhart HM. Robot assisted repair of tricuspid leaflet prolapse using standard valvuloplastic techniques. J Heart Valve Dis 2012; 21:749-52.

24. Sasse L, Froelich CR. Echocardiographic tricuspid pro-lapse and non ejection systolic click. Chest 1978;73: 869-70.

25. Bruce CJ, Connolly HM. Right sided valve disease. In Otto CM (ed). The practice of clinical echocardiography. Else-vier, Philadelphia; 2012:646-62.

26. Brown AK, Anderson V. Two dimensional echocardiogra-phy and the tricuspid valve. Leaflet definition and pro-lapse. Br Heart J 1983;49:495-500.

27. Leeson P, Augustine D, Mitchell ARJ, Becher H. Transtho-racic anantoms and pathology: valves. In Leeson P, Au-gustine D, Mitchell ARJ, Becher H ed. Echocardiography. Oxford, United kingdom 2012;105-189.

28. Otto CM, Bonow RO. Valvular heart disease. In Mann DL, Zipes DP, Bonow RO (ed) Braunwald’s Heart Disease. El-sevier, Philadelphia; 2015:1446-1514.

29. Walsh RA, O’ Rourke RA, Shaver JA. The history, physical examination and cardiac suscultation. In Fuster V, Walsh RA, Harrington RA (eds). Hurst’s The Heart. Mac Grow Hill, New York; 2011: 239-306.


PICTORIAL CME

MONIKA MAHESHWARI

Dr. Monika Maheshwari is Professor, Jawahar Lal Nehru Medical College, Ajmer, Rajasthan

Congenital Fused Cervical Vertebrae

Th e anomalies of cervical region like fused cervical vertebrae (FCV) is of interest to anatomists, orthopedists, neurosurgeons, orthodontists and even cardiologist. It’s overall incidence of 0.4 to 0.7% and have clinical and embryological importance. In FCV two vertebrae appear both structurally and functionally as one. Th is fusion may be congenital or acquired. Acquired FCV is generally associated with diseases like tuberculosis, juvenile rheumatoid arthritis and trauma. Congenital fused cervical vertebrae is caused because of the combination of environment and genetic factors which occur during the 3rd week of pregnancy. Clinical symptoms may vary from asymptomatic to limitation of the neck movement, muscular weakness, atrophy and neurological sensory loss or associated with Klippel-Feil syndrome (fusion of at least two vertebrae of the neck, low posterior hairline, a short webbed neck, and limited neck range of motion). Recently, we encountered one such case, which is picturized herein (Figure-1) .

Figure 1: Cervical skiagram (lateral view) showing fused C2 and C3 vertebrae.


MANUSCRIPT Manuscripts must be neatly typed in double space typing throughout on one side of the sheet of good quality bond pa-per of the size 28 x 22cm with 3cm margins on both sides. Words should not be hyphenated at the end of a line.Authors are requested to send the article on e-mail ([email protected]) or CD with one orginal copy of the type script should be submitted alongwith to the Publisher, CIMS Medica India Pvt Ltd, 709, Devika Tower, Nehru Place, New Delhi-1100 19.Material received for publication will be acknowledged and the decision regarding publication will be communicated to the “Author for correspondence”. The manuscript of case reports/studies and original articles should be arranged in the following sequence : Title page, Abstract, Key Words, Introduction, Material and Methods, Results, Discussion, Acknowledgments, References, Tables

Article title: Title should be concise, easier to read and should include all information in the title that will make electronic re-

department(s) and institution(s) to which the work should be attributed.Disclaimers, if any, Source(s) of support in the form of grants,

Interest Contact information for corresponding authors: The name, mailing address, telephone and fax numbers, and e-mail ad-dress of the author responsible for correspondence about the manuscript (“corresponding author-may or may not be the “guarantor” for the integrity of the study). The name and ad-dress of the author to whom requests for reprints should be addressed or a statement that reprints are not available from the authors.Abstract: Structured abstracts are preferred for all original research, systematic reviews articles and case studies. The abstract should provide the background for the study or the article. In case of original research article abstract should

principal conclusions, and funding sources. Introduction: Provide a context or background for the study

often more sharply focused when stated as a question. Both

only directly pertinent references, and do not include data or conclusions from the work being reported.Methods: The Methods section should include only informa-tion that was available at the time the plan or protocol for the study was being written; all information obtained during the study belongs in the Results section.Selection and Description of Participants: Describe your selection of the observational or experimental participants (patients or laboratory animals, including controls) clearly, including eligibility and exclusion criteria and a description of the source population. Because the relevance of such vari-

clear, authors should explain their use when they are included in a study report—for example, authors should explain why only participants of certain ages were included or why women were excluded. The guiding principle should be clarity about how and why a study was done in a particular way. When authors use such variables as race or ethnicity, they should

relevance.Technical Information: Identify the methods, apparatus (give the manufacturer’s name and address in parentheses), and

results. Give references to established methods, including statistical methods (see below); provide references and brief descriptions for methods that have been published but are not

give the reasons for using them, and evaluate their limita-

CARDIOLOGY TODAYINSTRUCTIONS TO AUTHORS

tions. Identify precisely all drugs and chemicals used, includ-ing generic name(s), dose(s), and route(s) of administration.Authors submitting review manuscripts should include a sec-tion describing the methods used for locating, selecting, ex-tracting, and synthesizing data. These methods should also be summarised in the abstract.Statistics: Describe statistical methods with enough detail to enable a knowledgeable reader with access to the original data to verify the reported results. When possible, quan-

intervals). Avoid relying solely on statistical hypothesis test-ing, such as P values, which fail to convey important informa-tion about effect size. References for the design of the study and statistical methods should be to standard works when

-viations, and most symbols. Specify the computer software used.Results: Present your results in logical sequence in the text, tables, and illustrations, giving the main or most important

-lustrations in the text; emphasise or summarise only the most important observations. Extra or supplementary materials and technical detail can be placed in an appendix where they

or they can be published solely in the electronic version of

When data are summarised in the Results section, give nu-meric results not only as derivatives (for example, percent-ages) but also as the absolute numbers from which the de-rivatives were calculated, and specify the statistical methods

needed to explain the argument of the paper and to assess supporting data. Use graphs as an alternative to tables with many entries; do not duplicate data in graphs and tables. Avoid nontechnical uses of technical terms in statistics, such as “random” (which implies a randomising device), “normal,”

variables as age and sex should be included.Discussion: Emphasise the new and important aspects of the study and the conclusions that follow from them in the context of the totality of the best available evidence. Do not repeat in detail data or other information given in the Introduction or the Results section. For experimental studies, it is useful

-ings, then explore possible mechanisms or explanations for

relevant studies, state the limitations of the study, and ex-

for clinical practice.Link the conclusions with the goals of the study but avoid

-ported by the data. In particular, avoid making statements on

the appropriate economic data and analyses. Avoid claiming priority or alluding to work that has not been completed. State new hypotheses when warranted, but label them clearly as such.Examples:1. Malik V, Roy D. Management of locally advanced breast

cancer. Cardiology Today 1997;2(5):45-51.(for Journal)2. Sambasivan M. References to central nervous system in

the ancient texts: In: S. Venkatraman (ed). Progress in Clinical Neurosciences, 11th Ed, Mediworld Publications 1996:116-118. (for Chapter in a Book)

For full details, please refer to International Committee of -

324:424-8. BMJ 1991;302:338-341.Tables: Tables should capture information concisely and dis-

Give each column a short or an abbreviated heading. Authors should place explanatory matter in footnotes, not in the head-ing. Explain all nonstandard abbreviations in footnotes. Iden-

tify statistical measures of variations, such as standard devia-tion and standard error of the mean. Be sure that each table is cited in the text. If you use data from another published or unpublished source, obtain permission and acknowledge that source fully.Illustrations (Figures): Figures should be either professionally drawn and photographed, or submitted as photographic-qual-

-ent throughout, and large enough to remain legible when the

self-explanatory as possible, since many will be used directly in slide presentations. Titles and detailed explanations belong in the legends—not on the illustrations themselves.Photomicrographs should have internal scale markers. Sym-bols, arrows, or letters used in photomicrographs should con-trast with the background.

-companied by written permission to use the photograph.Figures should be numbered consecutively according to the

been published previously, acknowledge the original source and submit written permission from the copyright holder to

authorship or publisher except for documents in the public domain.

-quires color negatives, positive transparencies, or color prints. Accompanying drawings marked to indicate the region

publish illustrations in color only if the author pays the ad-ditional cost.

Legends for Illustrations (Figures): Type or print out legends for illustrations using double spacing, starting on a separate page, with Arabic numerals corresponding to the illustrations. When symbols, arrows, numbers, or letters are used to iden-tify parts of the illustrations, identify and explain each one clearly in the legend. Explain the internal scale and identify the method of staining in photomicrographs.UNITS OF MEASUREMENTMeasurements of length, height, weight, and volume should be reported in metric units (meter, kilogram, or liter) or their decimal multiples.Temperatures should be in degrees Celsius/ Fahrenheit. Blood pressures should be in millimeters of mercury, unless

Journals vary in the units they use for reporting hematologic, clinical chemistry, and other measurements. Authors must

and should report laboratory information in both local and International System of Units (SI). Editors may request that authors add alternative or non-SI units, since SI units are not universally used. Drug concentrations may be reported in ei-ther SI or mass units, but the alternative should be provided in parentheses where appropriate.ABBREVIATIONS AND SYMBOLSUse only standard abbreviations; use of nonstandard ab-breviations can be confusing to readers. Avoid abbreviations in the title of the manuscript. The spelled-out abbreviation followed by the abbreviation in parenthesis should be used

measurement.

Address submissions to:The Publisher

CARDIOLOGY TODAYCIMS Medica India Pvt Ltd,

709, 7th Floor, Devika Tower, Nehru Place, New Delhi-110 019.

Tel: 011-4285 4300, Fax: 011-4285 4310E-mail: [email protected]

1CT Jan-Feb 2019 Content - CIMS · 2020-04-15 · Cardiology TODAY VOLUME XXIII No. 1...

Documents

Transcript of 1CT Jan-Feb 2019 Content - CIMS · 2020-04-15 · Cardiology TODAY VOLUME XXIII No. 1...