Rishi Sethi

Obstructive Sleep Apnea and Cardiovascular Events After Percutaneous Coronary Intervention

Background— There is a paucity of data from large cohort studies examining the prognostic significance of obstructive sleep apnea (OSA) in patients with coronary artery disease. We hypothesized that OSA predicts subsequent major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing percutaneous coronary intervention. Methods and Results— The Sleep and Stent Study was a prospective, multicenter registry of patients successfully treated with percutaneous coronary intervention in 5 countries. Between December 2011 and April 2014, 1748 eligible patients were prospectively enrolled. The 1311 patients who completed a sleep study within 7 days of percutaneous coronary intervention formed the cohort for this analysis. Drug-eluting stents were used in 80.1% and bioresorbable vascular scaffolds in 6.3% of the patients, and OSA, defined as an apnea-hypopnea index of ≥15 events per hour, was found in 45.3%. MACCEs, a composite of cardiovascular mortality, nonfatal myocardial infarction, nonfatal stroke, and unplanned revascularization, occurred in 141 patients during the median follow-up of 1.9 years (interquartile range, 0.8 years). The crude incidence of an MACCEs was higher in the OSA than the non-OSA group (3-year estimate, 18.9% versus 14.0%; p=0.001). Multivariate Cox regression analysis indicated that OSA was a predictor of MACCEs, with an adjusted hazard ratio of 1.57 (95% confidence interval, 1.10–2.24; P=0.013), independently of age, sex, ethnicity, body mass index, diabetes mellitus, and hypertension. Conclusions— OSA is independently associated with subsequent MACCEs in patients undergoing percutaneous coronary intervention. Evaluation of therapeutic approaches to mitigate OSA-associated risk is warranted. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01306526.

Lipoprotein (a) levels in relation to severity of coronary artery disease in north Indian patients

Background: Lipoprotein (a) [Lp (a)] is an established risk marker of coronary artery disease which is independent from other risk factors. Objective: The aim was to address the association between Lp (a) and CAD risk in North Indians. To evaluate whether high levels of lipoprotein (a) [Lp (a)] is a predictor of risk and is related to the severity of CAD. Materials and Methods: This was a cross-sectional study done on 360 patients presenting with chest pain. Coronary angiography revealed CAD in 270 patients and 90 patients without CAD. Lipoprotein (a) level, lipid profile, fasting blood glucose, anthropometric and clinical parameters were analyzed. Results: Lipoprotein (a) 21.0 mg/dL is associated with the presence of coronary lesions (P = 0.0001). A highly significant difference in Lp (a) levels was observed between normal coronaries vs. single-vessel disease, double-and triple-vessel disease ( P < 0.0001). Body mass index (BMI) was significantly raised in CAD group compared to normal coronary. Conclusion: Multivariate analysis found that Lp (a) was considered an independent predictor for severity of CAD and Lp (a) levels 21.0 mg/dL are associated with severe patterns of coronary atherosclerosis.

Essential hypertension: A filtered serum based metabolomics study

Despite the easy and reliable methods of blood pressure measurement, the screening of essential hypertension (EH) is usually ignored due to delayed onset of symptoms. A probe into the biochemical changes in hypertension would serve as a welcome asset to provide insight into the mechanistic aspects of EH. Filtered serum samples from 64 EH patients and 59 healthy controls (HC) were analysed using 800 MHz nuclear magnetic resonance (NMR) spectroscopy. Application of principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) following receiver operating characteristic (ROC) curve of NMR data reveals significantly perturbed metabolites: alanine, arginine, methionine, pyruvate, adenine, and uracil. This set of metabolites correctly classified 99% of cases from HC and also showed excellent correlation in both isolated elevated diastolic blood pressure (DBP) cases and combined elevated systolic-diastolic blood pressure cases. Proton NMR metabolomics of EH may prove helpful in defining associated biomarkers and serve as an alternate diagnostic tool with judicious clinical assessment.

Surgical treatment for coronary artery aneurysm: a single-centre experience

OBJECTIVES Coronary artery aneurysm is a rare condition with a reported incidence of 0.14-4.9% in patients undergoing coronary angiography and 0.3-5.3% in patients after percutaneous transluminal coronary angioplasty (PTCA). Optimum surgical therapy for this entity is difficult to standardize. We present here a series of 4 cases with the aim of establishing an optimal surgical therapy for this rare entity. METHODS Four cases of coronary artery aneurysm were admitted in the Department of Cardiology and Department of Cardiothoracic and Vascular Surgery, King Georges Medical University, Lucknow, from April 2010 to April 2012. All patients underwent a surgical procedure that involved ligation and plication of the aneurysm with coronary artery bypass grafting. RESULTS Out of the four coronary artery aneurysm patients, 1 was atherosclerotic and the remaining 3 patients developed coronary artery aneurysm after PTCA with a drug eluting stent to the left anterior descending artery. After surgery, all patients recovered uneventfully without any recurrence of symptoms in the follow-up. CONCLUSIONS Coronary artery aneurysm is a rare entity and is being seen more frequently with the increasing use of stents during PTCA. Proximal ligation and plication of the aneurysm with coronary artery bypass grafting in the present series provided good results. With this case series, we seek to establish an optimal surgical therapy for this rare entity.

Ruptured Anterior Mitral Leaflet Aneurysm in Aortic Valve Infective Endocarditis—Evaluation by Three‐Dimensional Echocardiography

Ruptured aneurysm of the anterior mitral leaflet is a rare but a devastating complication secondary to aortic valve infective endocarditis. We report a case of 30‐year‐old male with native aortic valve endocarditis who was referred to us for evaluation of worsening of heart failure after an initial period of responsiveness to antibiotics. Detailed evaluation with two‐dimensional and three‐dimensional transthoracic echocardiography revealed ruptured anterior mitral leaflet aneurysm with severe eccentric mitral regurgitation along with a large vegetation on the aortic valve. The patient underwent successful surgical closure of the defect along with aortic valve replacement.

Cardiological Society of India: Position statement for the management of ST elevation myocardial infarction in India

Santanu Guha*, Rishi Sethi, Saumitra Ray, Vinay K. Bahl, S. Shanmugasundaram, Prafula Kerkar, Sivasubramanian Ramakrishnan, Rakesh Yadav, Gaurav Chaudhary, Aditya Kapoor, Ajay Mahajan, Ajay Kumar Sinha, Ajit Mullasari, Akshyaya Pradhan, Amal Kumar Banerjee, B.P. Singh, J. Balachander, Brian Pinto, C.N. Manjunath, Chandrashekhar Makhale, Debabrata Roy, Dhiman Kahali, Geevar Zachariah, G.S. Wander, H.C. Kalita, H.K. Chopra, A. Jabir, JagMohan Tharakan, Justin Paul, K. Venogopal, K.B. Baksi, Kajal Ganguly, Kewal C. Goswami, M. Somasundaram, M.K. Chhetri, M.S. Hiremath, M.S. Ravi, Mrinal Kanti Das, N.N. Khanna, P.B. Jayagopal, P.K. Asokan, P.K. Deb, P.P. Mohanan, Praveen Chandra, (Col.) R. Girish, O. Rabindra Nath, Rakesh Gupta, C. Raghu, Sameer Dani, Sandeep Bansal, Sanjay Tyagi, Satyanarayan Routray, Satyendra Tewari, Sarat Chandra, Shishu Shankar Mishra, Sibananda Datta, S.S. Chaterjee, Soumitra Kumar, Soura Mookerjee, Suma M. Victor, Sundeep Mishra, Thomas Alexander, Umesh Chandra Samal, Vijay Trehan

Effects of Ethnicity on the Prevalence of Obstructive Sleep Apnoea in Patients with Acute Coronary Syndrome: A Pooled Analysis of the ISAACC Trial and Sleep and Stent Study

BACKGROUND Obstructive sleep apnoea (OSA) is an emerging risk factor for acute coronary syndrome (ACS). We sought to determine the effects of ethnicity on the prevalence of OSA in patients presenting with ACS who participated in an overnight sleep study. METHODS A pooled analysis using patient-level data from the ISAACC Trial and Sleep and Stent Study was performed. Using the same portable diagnostic device, OSA was defined as an apnoea-hypopnoea index of ≥15 events per hour. RESULTS A total of 1961 patients were analysed, including Spanish (53.6%, n=1050), Chinese (25.5%, n=500), Indian (12.0%, n=235), Malay (6.1%, n=119), Brazilian (1.7%, n=34) and Burmese (1.2%, n=23) populations. Significant differences in body mass index (BMI) were found among the various ethnic groups, averaging from 25.3kg/m2 for Indians and 25.4kg/m2 for Chinese to 28.6kg/m2 for Spaniards. The prevalence of OSA was highest in the Spanish (63.1%), followed by the Chinese (50.2%), Malay (47.9%), Burmese (43.5%), Brazilian (41.2%), and Indian (36.1%) patients. The estimated odds ratio of BMI on OSA was highest in the Chinese population (1.17; 95% confidence interval: 1.10-1.24), but was not significant in the Spanish, Burmese or Brazilian populations. The area under the curve (AUC) for the Asian patients (ranging from 0.6365 to 0.6692) was higher than that for the Spanish patients (0.5161). CONCLUSION There was significant ethnic variation in the prevalence of OSA in patients with ACS. The magnitude of the effect of BMI on OSA was greater in the Chinese population than in the Spanish patients.

Obstructive Sleep Apnea and Diabetes Independently Add to Cardiovascular Risk After Coronary Revascularization

Obstructive sleep apnea (OSA) has been shown to be associated with accelerated coronary atherosclerosis (1–3). In the multicenter Sleep and Stent Study, we found that OSA was an independent predictor of major adverse cardiac and cerebrovascular events (MACCE) and cardiovascular mortality after percutaneous coronary intervention (PCI), with adjusted hazard ratios (HR) of 1.57 (95% CI 1.10–2.24) and 2.11 (95% CI 0.91–4.91), respectively (4). Diabetes mellitus (DM) is an established risk factor of MACCE after PCI and was present in 42% of the patients in the Sleep and Stent Study (4). In this post hoc analysis, we hypothesized that patients with combined OSA and DM were at a particularly high risk of developing MACCE after PCI. The Sleep and Stent Study was an observational study evaluating the effects of OSA on cardiovascular outcomes in patients undergoing PCI. The detailed methodology and inclusion and exclusion criteria have been published previously (5). After an overnight sleep study, the recruited patients were classified as OSA(+) (apnea-hypopnea index ≥15 events per hour) or OSA(−) (<15 events per hour). Studies have suggested the possible interaction between DM and OSA in glycemic control and the progression of chronic diabetic complications (6–8). As such, the primary aim of this post hoc analysis was to determine whether the effects of OSA in the occurrence of cardiovascular outcomes, defined as MACCE composed of cardiovascular mortality, nonfatal myocardial infarction, or nonfatal stroke, may be modified …

1H NMR-derived metabolomics of filtered serum of myocardial ischemia in unstable angina patients

BACKGROUND Despite continuing research for development of accurate biomarkers of myocardial ischemia in unstable angina, lack of biochemical biomarkers is alarming. We sought to develop accurate biomarkers using high throughput proton nuclear magnetic resonance ((1)H NMR) spectroscopy and filtered serum (lacking proteins and lipoproteins) based metabolomics for detecting myocardial ischemia in unstable angina patients with utmost precision. METHODS Study includes 127 filtered serum samples from myocardial ischemia in unstable angina patients (UA; n=65) and healthy controls (HC; n=62). High resolution NMR spectra were obtained to highlight metabolic perturbations of small metabolites. A supervised orthogonal partial least square discriminant analysis was applied to generate a prediction model. Receiver operating characteristic (ROC) curve analysis was performed to reveal the clinical utility of signature biomarkers. RESULTS Five biomarkers--valine, alanine, glutamine, inosine and adenine--could differentiate 95% of UA from HC with 96% sensitivity and 95% specificity. CONCLUSIONS (1)H NMR-based filtered serum metabolic profiling appears to be an assuring, least invasive and faster way to screen and identify myocardial ischemia in unstable angina patients.

Effect of Ivabradine on Heart Rate and Duration of Exercise in Patients With Mild-to-Moderate Mitral Stenosis: A Randomized Comparison With Metoprolol.

Background: Symptoms in mitral stenosis (MS) are heart rate (HR) dependent. Increase in HR reduces diastolic filling period with rise in transmitral gradient. By reducing HR, beta-blockers improve hemodynamics and relieve symptoms, but the use may be limited by side effects. The present randomized crossover study looked at comparative efficacy of ivabradine and metoprolol on symptoms, hemodynamics, and exercise parameters in patients with mild-to-moderate MS (mitral valve area, 1–2 cm2) in normal sinus rhythm. Material and Methods: Baseline clinical assessment, treadmill stress testing, and an echocardiographic Doppler evaluation were performed to determine resting HR, total exercise duration, mean gradient across mitral valve, and mean pulmonary artery systolic pressure (PASP). Patients were then allocated to either metoprolol or ivabradine to maximal tolerated doses over 6 weeks (metoprolol: 100 mg twice a day, ivabradine: 10 mg twice a day). Reevaluation was done at the end of this period, and all drugs stopped for washout over 2 weeks. Thereafter, the 2 groups were crossed over to the other drug that was continued for another 6 weeks. Assessment was again performed at the end of this period. Results: Thirty-three patients of 34 completed the protocol. Fifteen were male, mean age was 28.9 ± 6.6 years, all were in New York Heart Association class 2, and mean resting HR was 103.5 ± 7.2/min. Mean mitral valve area was 1.56 ± 0.16 cm2, mean PASP was 38.1 ± 5.1 mm Hg, and mean gradient across mitral valve was 10.6 ± 1.6 mm Hg. Significant decrease in baseline and peak exercise HR was observed at the end of follow-up with both drugs. Reduction in mitral valve gradient after ivabradine (42%) and metoprolol (37%) and reduction in PASP after both ivabradine (23%) and metoprolol (27%) were to a similar extent. Significant reduction in total exercise duration after both ivabradine and metoprolol therapy was observed. One patient developed blurring of vision with ivabradine therapy but did not require discontinuation of drug. An improvement in dyspnea of one grade was observed in all the patients by treatment with both ivabradine and metoprolol. Conclusions: Both metoprolol and ivabradine reduced symptoms and improved hemodynamics significantly from baseline to a similar extent. Ivabradine thus can be used effectively and safely in patients with MS in normal sinus rhythm who are intolerant or contraindicated for beta-blocker therapy.