Roopali Khanna

Association of 25 bp Deletion in MYBPC3 Gene with Left Ventricle Dysfunction in Coronary Artery Disease Patients

Rationale Mutations in MYBPC3 encoding cardiac myosin binding protein C are common genetic cause of hereditary cardiac myopathies. An intronic 25-bp deletion in MYBPC3 at 3′ region is associated with dilated (DCM) and hypertrophic (HCM) cardiomyopathies in Southeast Asia. However, the frequency of MYBPC3 25 bp deletion and associated clinical presentation has not been established in an unrelated cohort of left ventricular dysfunction (LVD) secondary to coronary artery disease (CAD) patients. Objective We sought to determine the role of MYBPC3 25 bp polymorphism on LVD in two cohorts of CAD patients. Methods and Results The study included 265 consecutive patients with angiographically confirmed CAD and 220 controls. MYBPC3 25 bp polymorphism was determined by polymerase chain reaction. Our results showed that carrier status of MYBPC3 25 bp deletion was associated with significant compromised left ventricle ejection fraction (LVEF ≤45) in CAD patients (p value  =  <0.001; OR = 4.49). To validate our results, we performed a replication study in additional 140 cases with similar clinical characteristics and results again confirmed consistent findings (p = 0.029; OR = 3.3). Also, presence of the gene deletion did not have significant association in CAD patients with preserved ejection fraction (LVEF>45) (p value  = 0.1; OR  = 2.3). Conclusion The frequency of MYBPC3 DW genotype and D allele was associated with compromised LVEF implying that genetic variants of MYBPC3 encoding mutant structural sarcomere protein could increase susceptibility to left ventricular dysfunction. Therefore, 25 bp deletion in MYBPC3 may represent a genetic marker for cardiac failure in CAD patients from Southeast Asia.

Cardiac abnormalities in HIV-positive patients: results from an observational study in India.

Background: The clinical presentation of cardiac abnormalities in HIV-infected patients may be atypical or masked by concurrent illnesses that lead to misdiagnosis or they remain undiagnosed; therefore, this study was aimed to determine the frequency of cardiac abnormalities in HIV-infected patients. Material and Methods: Consecutive HIV-infected patients of age >13 years were studied for 3 months, after obtaining their consent. After clinical assessment, chest x-ray, electrocardiogram, 2-dimensional echocardiography and serum Troponin T levels were done. Results: A total of 100 patients were studied, cardiomegaly was observed in the x-ray of 15% of them, abnormal electrocardiogram was seen in 18%, 2-dimensional echocardiography was abnormal in 67%; and diastolic dysfunction (42.8%) was the commonest abnormality followed by dilated cardiomyopathy (17.6%). Serum troponin T was elevated in 8%. The variables, opportunistic infections (OIs), antiretroviral therapy (ART), stage of HIV disease, and CD4 counts, did not affect the frequency of diastolic dysfunction. Conclusion: The diastolic dysfunction is the most common cardiac abnormality observed in HIV-infected patients.

Intermediate outcomes of rheumatic mitral stenosis post-balloon mitral valvotomy.

Background Balloon mitral valvotomy is a standard therapeutic modality for managing rheumatic mitral stenosis. Data on intermediate outcomes of this procedure are limited. Thus we investigated the intermediate outcome after balloon mitral valvotomy performed at a large tertiary center in India. Methods Case records and follow-up data of 2330 patients who underwent valvotomy from June 1999 to December 2005 were retrieved from the hospital information system and analyzed. Results The median age of the patients was 32 ± 11 years, 1363 were female including 36 who were pregnant, and 379 were in atrial fibrillation. Follow-up ranged from 1 to 14 years (mean 4.5 years, median 4.0 years). The procedural success rate was 93%. Atrial fibrillation, higher functional class, and worse valve morphology were independent predictors of a poor procedural outcome. Patients with sinus rhythm had better event-free survival (10.43 years, 95% confidence interval: 10.1–10.7) compared to those with atrial fibrillation (8.17 years, 95% confidence interval: 7.5–8.8). Patients who achieved a valve area >1.75 cm2 had a better event-free survival (11.7 years, 95% confidence interval: 11.4–12.0) than those with a valve area of 1.5–1.74 cm2 (9.3 years, 95% confidence interval: 9.0–9.7). On multivariate analysis, higher functional class, worse valve morphology, and new significant mitral regurgitation were predictors of a poor outcome. Achieved mitral valve area >1.75 cm2 was an independent predictor of a good outcome. Conclusion Patients with sinus rhythm, less gross valve deformity, and a post-balloon mitral valvotomy area >1.75 cm2 had better intermediate outcomes.

Comparison of different cardiovascular risk score calculators for cardiovascular risk prediction and guideline recommended statin uses

Objective The accuracy of various 10-year cardiovascular disease (CVD) risk calculators in Indians may not be the same as in other populations. Present study was conducted to compare the various calculators for CVD risk assessment and statin eligibility according to different guidelines. Methods Consecutive 1110 patients who presented after their first myocardial infarction were included. Their CVD risk was calculated using Framingham Risk score- Coronary heart disease (FRS-CHD), Framingham Risk Score- Cardiovascular Disease (FRS-CVD), QRISK2, Joint British Society risk calculator 3 (JBS3), American College of Cardiology/American Heart Association (ACC/AHA), atherosclerotic cardiovascular disease (ASCVD) and WHO risk charts, assuming that they had presented one day before cardiac event for risk assessment. Eligibility for statin uses was also looked into using ACC/AHA, NICE and Canadian guidelines. Results FRS-CVD risk assessment model has performed the best as it could identify the highest number of patients (51.9%) to be at high CVD risk while WHO and ASCVD calculators have performed the worst (only 16.2% and 28.3% patients respectively were stratified into high CVD risk) considering 20% as cut off for high risk definition. QRISK2, JBS3 and FRS-CHD have performed intermediately. Using NICE, ACC/AHA and Canadian guidelines; 76%, 69% and 44.6% patients respectively were found to be eligible for statin use. Conclusion FRS-CVD appears to be the most useful for CVD risk assessment in Indians, but the difference may be because FRS-CVD estimates risk for several additional outcomes as compared with other risk scores. For statin eligibility, however, NICE guideline use is the most appropriate.

Assessment of endothelial dysfunction in Asian Indian patients with chronic kidney disease and changes following renal transplantation

Endothelial dysfunction may explain increased cardiovascular risk in patients with chronic kidney disease (CKD).

Inoue balloon atrial septostomy in severe persistent pulmonary hypertension following surgical ASD closure

Balloon atrial septostomy (BAS), which involves artificially creating a communication across the interatrial septum following trans-septal puncture and repetitive balloon dilatation, is known to be associated with therapeutic benefit in patients with severe pulmonary artery hypertension (PAH). Adult patients with large shunts and consequent severe PAH are not uncommon in the developing world, since they often seek medical attention late in the course of the disease. Often PAH in such cases is reversible with amelioration of symptoms after closure of the defect. We report a case of large atrial septal defect (ASD) with severe PAH who developed gross right heart failure following surgical closure of the ASD. A successful bail out BAS was performed using an Inoue balloon, avoiding the need for a redo surgery. The case highlights for the first time the use of Inoue balloon for performing a successful BAS.

Abdominal angina: an unusual presentation of Takayasu's arteritis.

Takayasu’s arteritis (TA) is an idiopathic large vessel vasculitis of young adults that affects the aorta and its major branches. The authors hereby present a case of TA that presented with abdominal aorta thrombosis. She was put on low-molecular weight heparin, antiplatelets, corticosteroids, cyclophosphamide along with haematinics and was referred to Department of Cardiothoracic and Vascular Surgery for further management.

Unruptured sinus of Valsalva aneurysm mimicking as right atrial tumor

Sinus of Valsalva aneurysm is a rare congenital cardiac abnormality and is usually diagnosed when it ruptures. An asymptomatic 55‐year‐old male of unruptured sinus of Valsalva aneurysm of noncoronary cusp was on medical follow‐up. At 2‐year follow‐up, there was thrombus formation in the aneurysm, mimicking right atrium tumor on 2D transthoracic echocardiography. Cardiac computed tomography showed filling defect in the aneurysm suggestive of thrombus. Considering the high risk of systemic emboli surgery was performed, and aneurysm was repaired with Dacron patch.

Left main PCI: An observational analysis from large single-centre experience.

Background Although trials have shown efficacy of unprotected left main percutaneous coronary intervention (uLMPCI), data from Indian subcontinent are lacking. Hence, we planned this observational analysis of single-center uLMPCI data. Objectives To study long-term outcome after uLMPCI and identify predictors of adverse outcome. Methods Case details of 62 consecutive patients of uLMPCI between 2006 and 2013 were retrieved from a computerized database wherein detailed records were maintained. Results Mean follow-up duration was 669.8 ± 404.2 days. Procedural success rate was 98.4%. Primary endpoint was composite of major adverse cardiovascular and cerebrovascular events (MACCE), which included cardiac death (CD), cerebrovascular accident (CVA), myocardial infarction (MI), and need for repeat intervention (RI) at three years. MACCE occurred in 13 (20.9%) patients. Cardiac death (CD), (including possible stent thrombosis), RI, and CVA occurred in 6 (9.7%), 5 (8%), and 2 (3.2%) patients, respectively. Overall three-year MACCE-free survival rate was 76.7%. Event-free survival rate was similar among patients who underwent uLMPCI alone and patients who underwent uLMPCI along with additional one-vessel PCI [(88.9% vs 81.8%), p = 0.492], while survival rate was lower in patients who underwent uLMPCI along with PCI of additional two or more vessels (40%, p = 0.036). Patients with syntax score ≤32 had higher event-free survival rate than those with syntax score >32 [(87.1% vs 33.3%), p = 0.001]. Syntax score >32 was the only independent predictor of adverse outcome. Conclusion uLMPCI is safe and effective alternative to CABG for LM alone and LM plus single-vessel disease with syntax score ≤32.

Heart rate manipulation in dilated cardiomyopathy: Assessing the role of ivabradine

Background Heart rate (HR) reduction is of benefit in chronic heart failure (HF). The effect of heart rate reduction using Ivabradine on various echocardiographic parameters in dilated cardiomyopathy has been less investigated. Methods Of 187 patients with HF (DCM, NYHA II–IV, baseline HR > 70/min), 125 patients were randomized to standard therapy (beta blockers, ACEI, diuretics, n = 62) or add-on Ivabradine (titrated to maximum 7.5 mg BD, n = 63). Beta-blockers were titrated in both the groups. Results At 3 months both groups had improvement in NYHA class, 6 min walk test, Minnesota Living With Heart Failure (MLWHF) scores and fall in BNP, however the magnitude of change was greater in Ivabradine group. Those on Ivabradine also had lower LV volumes, higher LVEF (28.8 ± 3.6 vs 27.2 ± 0.5, p = 0.01) and more favorable LV global strain (11 ± 1.7vs 12.2 ± 1.1, p = <0.001), MPI (0.72 ± 0.1 vs 0.6 ± 0.1, p = <0.001), LV mass (115.2 ± 30 vs 131.4 ± 35, p = 0.007), LV wall stress (219.8 ± 46 vs 238 ± 54) and calculated LV work (366 ± 101 vs 401 ± 102, p = 0.05). The benefit of Ivabradine was sustained at 6 months follow up. The % change in HR was significantly higher in Ivabradine group (−32.2% vs −19.3%, p = 0.001) with no difference in blood pressure. Resting HR < 70/min was achieved in 96.8% vs 27.9%, respectively in the two groups. Conclusion Addition of Ivabradine to standard therapy in patients with DCM and symptomatic HF and targeting a heart rate < 70/min improves symptoms, quality of life and various echocardiographic parameters.