Neeraj Parakh

Golden jubilee of hypertrophic cardiomyopathy: is alcohol septal ablation the gold standard?

In the golden jubilee year of the first recognition of hypertrophic obstructive cardiomyopathy, we are discussing the intricacies and impact of alcohol septal ablation (ASA) in the treatment of this clinical entity. Since its first revelation 14 years ago, ASA has become a well-established treatment modality for symptomatic hypertrophic obstructive cardiomyopathy patients. With better recognition of the implication of first septal branch and right dose of alcohol to be used for ablation, the incidence of complications like complete heart block are coming down along with better procedural success rates. In appropriately selected patients and in expert hands ASA has produced excellent results. Surgical myectomy, even though it has produced excellent results, is available only at a few centers and patient preference is tilted more for a less invasive procedure like ASA. This has contributed towards far more ASAs being performed worldwide than surgical myectomies. While more than 5000 ASAs have been performed in the last 14 years, the number of patients who have had myectomy remains around 3000-4000. The pendulum of gold standard may have started swinging away from surgical myectomy towards ASA.

Rate Control with Ivabradine

The importance of heart rate in human health and disease has been well known to clinicians for quite some time. Recent epidemiologic studies have further strengthened this concept. Modulation of heart rate by pharmacologic as well as non-pharmacologic means has affected cardiovascular mortality and morbidity in various trials and observational studies. Conventional rate-control agents, such as β-adrenoceptor antagonists (β-blockers), calcium channel blockers, and digoxin, have contributed greatly to the management of various diseases where heart-rate reduction is required; however, these agents have effects beyond rate control that may be unacceptable.Ivabradine has recently been recognized as a pure heart-rate-reducing agent and is being extensively studied. It is the latest addition to the class of drugs used to control angina. It is indicated in cases of β-blocker intolerance or when β-blockers fail to achieve a heart rate of <60 beats/min. The pure heart-rate-reducing effect of ivabradine has also been reported in smaller studies and anecdotal case reports. The theoretical possibilities of the utility of ivabradine are many and have opened up a whole new field of research for the future. The BEAUTIFUL trial enrolled approximately 10 000 patients with coronary artery disease (CAD) and left ventricular dysfunction, with the aim of assessing the effect of ivabradine versus atenolol on various cardiovascular outcomes. Although ivabradine failed to achieve favorable results for primary endpoints, it appeared effective in achieving a favorable secondary endpoint in a subgroup of patients who had a heart rate of >70 beats/min. Other large trials are also underway to assess the effects of ivabradine on heart failure, acute coronary syndromes, CAD, and other cardiovascular disorders. In this review, we discuss the pharmacologic basis of the action of ivabradine and its role in angina control, as well as in other conditions being actively studied or in which a role for ivabradine has been hypothesized.

Linkages between oral commensal bacteria and atherosclerotic plaques in coronary artery disease patients

Coronary artery disease is an inflammatory disorder characterized by narrowing of coronary arteries due to atherosclerotic plaque formation. To date, the accumulated epidemiological evidence supports an association between oral bacterial diseases and coronary artery disease, but has failed to prove a causal link between the two. Due to the recent surge in microbial identification and analyses techniques, a number of bacteria have been independently found in atherosclerotic plaque samples from coronary artery disease patients. In this study, we present meta-analysis from published studies that have independently investigated the presence of bacteria within atherosclerotic plaque samples in coronary artery disease patients. Data were collated from 63 studies covering 1791 patients spread over a decade. Our analysis confirms the presence of 23 oral commensal bacteria, either individually or in co-existence, within atherosclerotic plaques in patients undergoing carotid endarterectomy, catheter-based atherectomy, or similar procedures. Of these 23 bacteria, 5 (Campylobacter rectus, Porphyromonas gingivalis, Porphyromonas endodontalis, Prevotella intermedia, Prevotella nigrescens) are unique to coronary plaques, while the other 18 are additionally present in non-cardiac organs, and associate with over 30 non-cardiac disorders. We have cataloged the wide spectrum of proteins secreted by above atherosclerotic plaque-associated bacteria, and discuss their possible roles during microbial migration via the bloodstream. We also highlight the prevalence of specific poly-microbial communities within atherosclerotic plaques. This work provides a resource whose immediate implication is the necessity to systematically catalog landscapes of atherosclerotic plaque-associated oral commensal bacteria in human patient populations.Heart disease: Links to oral bacteriaA review of bacterial populations in the mouth and in diseased arteries will help research into the role of bacteria in heart disease. Amit Sharma and colleagues at the International Centre for Genetic Engineering and Biotechnology, with co-workers at the All India Institute of Medical Sciences, both in New Delhi, India, analyzed 63 studies covering 1791 patients spread over a decade. They summarize evidence of 23 types of oral bacteria that are also found in atherosclerotic plaques in artery walls. The review also cataloged the proteins secreted by the bacteria and discussed possible involvement of these proteins in the migration of bacteria through the bloodstream. Full genetic details are available for 19 of the 23 bacterial species, which should greatly assist further investigations into the significance of bacteria in the onset of heart disease.

Heart failure in India: The INDUS (INDia Ukieri Study) study

Introduction: There are few data on heart failure (HF) burden and none available on the community prevalence of HF in India. We conducted a study aimed at determining the HF prevalence in a rural community as well as tertiary hospital care setting in North India. We also reviewed the existing literature regarding the estimated and projected prevalence of HF in India. Methodology: All adults (>20 years) with chronic breathlessness in six villages under a primary health care center in Northern India were identified and evaluated with standardized questionnaire and physical examination by trained health care workers. HF was diagnosed by standardized criteria and a transthoracic echocardiogram was performed in all subjects. In the hospital study, 500 consecutive patients presenting to our tertiary referral hospital were evaluated for the diagnosis of HF. For the systematic review, all published studies addressing HF or the burden of risk factors in India were identified. Projections for the absolute HF burden were made using local data and global studies of HF incidence, morbidity, and mortality. Results: Among the surveyed rural adult population of 10,163 patients, chronic breathlessness was present in 128 (1.3%). HF was present in 9% (n = 12), of which 67% (n = 8) had preserved left ventricular (LV) systolic function and 33% (n = 4) had LV systolic dysfunction. Therefore, the prevalence of HF in this general community was 1.2/1000. All patients with HF and preserved ejection fraction had poorly controlled hypertension. In the hospital study, of 500 consecutive patients, 20.4% had HF. Rheumatic heart disease (52%) was the most common cause followed by ischemic heart disease (17%). The mean age of presentation was 39 ± 16 years. The prevalence of HF in the outpatient department patients was 22.5% below 30 years and 14.9% above 50 years, reflecting the young population of HF. For the estimates concerning HF burden in India, projections were made using both age-specific extrapolations from developing countries and data regarding development of HF in the presence of risk factors. The estimated prevalence of HF is about 1% of the total population or about 8–10 million individuals. The estimated mortality attributable to HF is about 0.1–0.16 million individuals per year. Conclusions: While our hospital data are consistent with the HF burden and etiology expected in a government tertiary hospital setting, our community-based study is the first of its kind reported from India. The community study demonstrates a surprisingly low prevalence of symptomatic HF in the surveyed villages. This could be partially explained by the rural farming-based community setting but is also likely due to under-reporting of symptoms. Our review of the projected national estimates suggests an alarming burden of HF in India despite a younger population than the developed nations. A significant proportion of this burden may be preventable with better screening and early and adequate treatment of the risk factors.

Effect of Ivabradine vs Atenolol on Heart Rate and Effort Tolerance in Patients With Mild to Moderate Mitral Stenosis and Normal Sinus Rhythm

BACKGROUND Patients with mitral stenosis become symptomatic at a higher heart rate. We studied the comparative efficacy of heart rate control with ivabradine or atenolol and its effect on effort tolerance in patients with mild-moderate mitral stenosis in normal sinus rhythm. METHODS AND RESULTS Fifty patients with mild-moderate mitral stenosis in sinus rhythm were randomized to receive ivabradine or atenolol for 4 weeks each in an open-label, randomized, crossover design trial. A 24-hour Holter and treadmill test was performed at baseline and after each active treatment period. In the first treatment period, 23 patients were allocated to ivabradine (22 analyzed), and 27 were allocated to atenolol (26 analyzed). In the second period, all 48 patients were analyzed. Ivabradine increased the mean total exercise time to 500.7 seconds (SD 99.7) from a baseline of 410.3 seconds (SD 115.4), and atenolol increased it to 463.7 seconds (SD 113.1). The point estimate (absolute difference between ivabradine and atenolol) was 35.27 seconds (95% CI 15.24-55.20; P = .0009). The point estimate for decrease in the maximum exercise heart rate and mean heart rate were 7.64/min (95% CI 0.37-15.9; P = .04) and 5.61/min (95% CI 2.51-8.71; P = .0007), respectively. CONCLUSIONS Ivabradine is more effective than atenolol for effort related symptoms in patients with mild-moderate mitral stenosis and normal sinus rhythm.

Catheter-induced left main coronary artery spasm.

A dramatic illustration of catheter-induced left main coronary artery spasm is described. Timely recognition of spasm and use of intracoronary nitroglycerine confirmed this condition and saved a young woman from an unnecessary coronary artery bypass graft operation.

The metabolite Trimethylamine-N-oxide is an emergent biomarker of human health.

Trimethylamine-N-oxide (TMAO) is a low molecular weight metabolite whose production is dependent on metabolism of its precursors choline, carnitine, creatinine, betaine or lecithin by host gut microbes resulting in the synthesis of trimethylamine (TMA), which is subsequently oxidized to TMAO via hepatic flavin monooxygenase (FMO). TMAO is associated with microbial dysbiosis and is being studied for its linkage with cardiovascular disorders. In addition, dysregulated levels of TMAO have been linked with renal diseases, neurological disorders and cancer. Here we discuss the enzymatic and metabolic landscape that results in TMAO production, and in addition, collate data from numerous clinical studies that have assessed TMAO as a biomarker for various disease conditions. We also summarize the interaction of TMAO with modern and traditional drugs that together affect circulating TMAO levels in the human body.

Development of macaronic Hindi-English ‘Hinglish’ text message content for a coronary heart disease secondary prevention programme

Background Coronary heart disease (CHD) is a leading cause of morbidity and mortality in India. Text message based prevention programs have demonstrated reduction in cardiovascular risk factors among patients with CHD in selected populations. Customisation is important as behaviour change is influenced by culture and linguistic context. Objectives To customise a mobile phone text message program supporting behaviour and treatment adherence in CHD for delivery in North India. Methods We used an iterative process with mixed methods involving three phases: (1) Initial translation, (2) Review and incorporation of feedback including review by cardiologists in India to assess alignment with local guidelines and by consumers on perceived utility and clarity and (3) Pilot testing of message management software. Results Messages were translated in three ways: symmetrical translation, asymmetrical translation and substitution. Feedback from cardiologists and 25 patients was incorporated to develop the final bank. Patients reported Hinglish messages were easy to understand (93%) and useful (78%). The software located in Australia successfully delivered messages to participants based in Delhi-surrounds (India). Conclusions Our process for customisation of a text message program considered cultural, linguistic and the medical context of potential participants. This is important in optimising intervention fidelity across populations enabling examination of the generalisability of text message programs across populations. We also demonstrated the customised program was acceptable to patients in India and that a centralised cross-country delivery model was feasible. This process could be used as a guide for other groups seeking to customise their programs. Trial registration number TEXTMEDS Australia (Parent study)—ACTRN 12613000793718.

NT pro B type natriuretic peptide levels in constrictive pericarditis and restrictive cardiomyopathy.

BACKGROUND The differentiation of constrictive pericarditis (CP) from restrictive cardiomyopathy (RCM) may be clinically difficult and may require multiple investigations. Even though brain natriuretic peptide (BNP) is shown to be higher in patients with RCM as compared to CP, the clinical utility is not fully established especially in Indian patients known to have advanced CP and myocardial involvement. METHODS AND RESULTS We measured NT-pro-BNP levels in 49 patients suspected of having either CP or RCM, diagnosed on the basis of echocardiography, computed tomography, magnetic resonance imaging, endomyocardial biopsy and cardiac catheterization data as needed. Twenty nine patients (Mean age - 26 yrs, 24 males) had CP and 20 patients (Mean age - 39 yrs, 14 males) had RCM. The median plasma NT-pro-BNP levels were significantly higher in RCM as compared to CP [1775 (208-7500) pg/ml vs 124 (68-718) pg/ml, respectively; p = 0.001]. A cut off value of 459 pg/ml had sensitivity, specificity and overall accuracy of 90%, 86% and 88% respectively, for differentiating CP from RCM. CONCLUSIONS The NT-pro-BNP levels are significantly elevated in RCM as compared to CP.

Pseudo-aneurysm of mitral aortic intervalvular fibrosa: Two case reports

The fibrous body between the mitral and aortic valve, known as mitral-aortic intervalvular fibrosa (MAIVF) is prone to infection and injury resulting in pseudo-aneurysm formation. Because of its relative rarity, we are far from making any conclusion regarding the natural history and appropriate therapeutic strategy for this condition. We report two cases of this condition with two different and rare etiologies with strikingly different natural courses, providing insight into the natural course and timing of surgery in this rare entity.