Jayaraman Balachander

Association of sympathovagal imbalance with obesity indices, and abnormal metabolic biomarkers and cardiovascular parameters

PROBLEM Pathophysiological mechanisms contributing to abnormal cardiovascular (CV) parameters in obesity have not been fully elucidated. Role of sympathovagal imbalance (SVI) in the prediction of abnormalities in CV functions in obesity has not been studied. METHODS Anthropometric indices, CV parameters, autonomic function tests (AFTs) such as spectral heart rate variability (HRV) analysis, heart rate and blood pressure response to standing, deep breathing, and isometric-handgrip, and biochemical parameters like insulin resistance (HOMA-IR), lipid risk factors and inflammatory marker [high-sensitive C-reactive protein (hsCRP)] were assessed in control group (non-obese, n=43) and obese group (n=45). Association of anthropometric indices and abnormal CV parameters with low-frequency to high-frequency ratio (LF-HF) of HRV was performed by Pearsons correlation. Independent contribution of anthropometric indices and abnormal CV parameters to LF-HF was assessed by using a multiple regression analysis. LF-HF prediction of rate-pressure product (RPP), the indicator of CV dysfunction was assessed by logistic regression. RESULTS LF-HF, the marker of SVI was more in obese group compared to control group. AFTs of sympathetic activity were increased and of parasympathetic activity were reduced in obese group. Anthropometric indices, HOMA-IR, lipid risk factors and hsCRP were correlated with LF-HF. These metabolic biomarkers had independent contribution to SVI. Among, anthropometric indices, waist-to-height ratio (WHtR) had maximum association with LF-HF. LF-HF had significant prediction of RPP in obese group. CONCLUSION SVI in obesity is due to both increased sympathetic and decreased vagal activity. Abnormal CV parameters in obesity are linked to SVI, which is contributed by insulin resistance, dyslipidaemia and low-grade inflammation. LF-HF predicts abnormal CV parameters in obesity.

Candidate Gene Polymorphisms of Renin Angiotensin System and Essential Hypertension in a South Indian Tamilian Population

Abstract Genetic variants of renin angiotensin system (RAS) gene play a significant role in the pathogenesis of essential hypertension and cardiovascular diseases. In the present study, we investigated the association of RAS gene polymorphisms with hypertension by analyzing the polymorphisms ACE ID, AGT T207M, M268T and AGT1R A1166C in 462 hypertensive patients and 444 healthy subjects. Genotyping was determined by allele specific PCR, PCR-RFLP and RT-PCR Taqman assay. The ACE ID heterozygous (OR=1.5: 95% CI: 1.0-2.3, p < 0.05) and ACE DD homozygous genotype (OR=1.7: 95% CI: 1.2-2.8, p<0.01) was found to be significantly associated with hypertension. There was no significant association between AGT T207M, M268T and AGT1R A1166C gene polymorphisms and hypertension. Gender-specific analysis showed ACE ID heterozygous genotypes were positively associated with hypertension among male hypertensives (OR=1.9: 95% CI: 1.1-2.6, p<0.01). Significant gene-gene interaction was observed between ACE ID and AGT M268T polymorphisms (OR=2.0; 95% CI: 1.2-3.5, p<0.01). Our results suggest that ACE ID polymorphism is associated with hypertension. Further, gene-gene interaction between ACE ID and AGT M268T gene polymorphisms further modified the risk of essential hypertension.

Decrease in Left Atrium Volume after Successful Balloon Mitral Valvuloplasty: An Echocardiographic and Hemodynamic Study

Background: Left atrium (LA) remodeling has a crucial adverse impact on outcome and prognosis in mitral stenosis. Few studies have reported the effect of balloon mitral valvuloplasty (BMV) on LA volume. The aim of this study was to assess the evolution of LA volume immediately and 1 month after successful BMV in patients in sinus rhythm. Methods: Thirty‐three consecutive patients (70% women; age 31 ± 8 years; range 19–45) with moderate to severe mitral stenosis (mitral valve area ≤1.5 cm2) who underwent successful BMV were included prospectively. Using two‐dimensional echocardiography, and according to the prolate ellipse method, LA volume and LA volume indexed to body surface area were determined before BMV, and 24 hours and 1 month after BMV. Tricuspid and pulmonary regurgitation jets were recorded systematically using continuous‐wave Doppler. Pulmonary artery–right ventricular (PA–RV) gradients, reflecting pulmonary pressures, and pulmonary vascular resistance were measured. Results: Mitral valve area increased from 0.88 ± 0.16 to 1.55 ± 0.26 cm2 (P < 0.0001). Mean mitral valve gradient (MVG) decreased from 16 ± 6 to 6 ± 2 mmHg (P < 0.0001) immediately after BMV. Indexed LA volume fell from 56 ± 14 to 48 ± 12 mL/m2 (P = 0.0002) immediately after BMV and to 45 ± 13 mL/m2 at 1 month (P < 0.0001). Only patients with a median LA volume ≥55 mL/m2 before BMV had a significant reduction in LA volume (P = 0.0001). Decrease in LA volume was correlated with decreases in PA–RV peak diastolic gradient (r = 0.45, P = 0.008) and MVG (r = 0.35, P = 0.04). Conclusion: In patients with mitral stenosis in sinus rhythm, successful BMV results in an immediate decrease in LA volume. This reduction, maximal immediately after BMV, correlates with decreases in MVG and PA–RV peak diastolic gradient, and is significant only when LA volume before BMV is severely enlarged. (Echocardiography 2011;28:154‐160)

Genetic Polymorphisms of β1 Adrenergic Receptor and Their Influence on the Cardiovascular Responses to Metoprolol in a South Indian Population

Background and Objective: Beta-blockers show interindividual and interethnic variability in their response. Such variability might be due to the polymorphic variations in the β1 adrenergic receptor genes viz, Ser49Gly and Arg389Gly. The study evaluated the influence of Ser49Gly and Arg389Gly polymorphisms on the cardiovascular responses to metoprolol in a South Indian population. Materials and Methods: Forty-one genetically prescreened healthy male volunteers participated in the study. They were divided on the basis of genotype of each polymorphism: Ser49Ser, Ser49Gly, and Gly49Gly and Arg389Arg, Arg389Gly, and Gly389Gly. They were also grouped into combination genotypes viz, S49S R389R, S49G R389R, G49G R389R, S49S R389G, S49S G389G, and S49G R389G. They were subjected to treadmill exercise testing, and cardiovascular parameters were measured before and after metoprolol administration. Metoprolol concentration was determined by reversed phase high-performance liquid chromatography method. Results: The diastolic blood pressure (DBP) was significantly lower in S49S/G389G group when compared to S49S/A389A group. The cardiac parameters were significantly increased in all the genotype groups during treadmill exercise test done for a period of 9 minutes. During predrug treadmill exercise at the end of third and sixth minute, Gly49Gly showed a higher increase in heart rate and volume of oxygen consumption compared to Ser49Ser. Same group showed a higher increase of volume of oxygen consumption at the end of ninth minute of exercise compared to the Ser49Ser. Systolic and diastolic blood pressures were not different between Ser49Gly polymorphisms. However, there was no statistical difference between the genotype groups of both polymorphisms at any stage of post-drug treadmill exercise. The analysis of combination of genotypes showed no significant difference during predrug and postdrug exercise testing. Conclusion: The increase in cardiac responses to treadmill test was influenced by Ser49Gly polymorphism. Nevertheless, the above polymorphisms did not alter the beta-blocker response during treadmill exercise in South Indian population.

A Randomized Controlled Trial to Study the Effect of Yoga Therapy on Cardiac Function and N Terminal Pro BNP in Heart Failure

AIMS The purpose of this study was to evaluate whether yoga training in addition to standard medical therapy can improve cardiac function and reduce N terminal pro B-type natriuretic peptide (NT pro BNP) in heart failure (HF). METHODS 130 patients were recruited and randomized into two groups: Control Group (CG) (n = 65), Yoga Group (YG). In YG, 44 patients and in CG, 48 patients completed the study. Cardiac function using left ventricular ejection fraction (LVEF), myocardial performance index (Tei index), and NT pro BNP, a biomarker of HF, was assessed at baseline and after 12 weeks. RESULT Improvement in LVEF, Tei index, and NT pro BNP were statistically significant in both the groups. Furthermore, when the changes in before and after 12 weeks were in percentage, LVEF increased 36.88% in the YG and 16.9% in the CG, Tei index was reduced 27.87% in the YG and 2.79% in the CG, NT pro BNP was reduced 63.75% in the YG and 10.77% in the CG. The between group comparisons from pre to post 12 weeks were significant for YG improvements (LVEF, P < 0.01, Tei index, P < 0.01, NT pro BNP, P < 0.01). CONCLUSION These results indicate that the addition of yoga therapy to standard medical therapy for HF patients has a markedly better effect on cardiac function and reduced myocardial stress measured using NT pro BNP in patients with stable HF.

“Pseudo PJRT”—Fast‐Slow AV Nodal Reentrant Tachycardia Presenting with Tachycardia‐Induced Cardiomyopathy

A 52‐year‐old woman presented with left ventricular (LV) dysfunction and incessant narrow complex tachycardia. Electrocardiogram and clinical picture were suggestive of a permanent form of junctional reciprocating tachycardia, but electrophysiology study showed the tachycardia to be a fast‐slow form of atrioventricular nodal reentrant tachycardia (AVNRT). Slow pathway ablation terminated the tachycardia and the LV dysfunction resolved completely at follow‐up. Fast‐slow AVNRT has not been reported to present in incessant form, and the mechanism in this patient was absent retrograde fast pathway conduction resulting in easy initiation and maintenance of tachycardia.

Results of Radiofrequency Ablation of Permanent Atrial Fibrillation of > 2 Years Duration and Left Atrial Size >5 cm Using 2-mm Irrigated Tip Ablation Catheter and Targeting Areas of Complex Fractionated Atrial Electrograms

Complex fractionated atrial electrograms (CFAEs) have shown promise as target sites for ablation of atrial fibrillation (AF); however, the data are limited with regard to patients with a large left atrium (LA) (>5 cm), and/or a permanent AF duration of >2 years. We tested the hypothesis that ablation of user-defined, computer-generated CFAE and pulmonary vein isolation, without additional lines would help long-term maintenance of sinus rhythm (SR). A total of 21 patients, 9 men and 12 women, aged 32 to 78 years (mean 44 +/- 3.3) were selected. All had chronic AF for >2 years (range 2 to 20; mean 3.8) and a LA of 5.3 to 11.3 cm (mean 6.4 cm). The underlying structural heart disease was rheumatic mitral valve disease in 18, aortic stenosis in 1, and hypertension in 2. Mapping and ablation was done using the NAVx Ensite system and a 2-mm-tip IBI Therapy Cool Path ablation catheter. The target included circumferential pulmonary vein ablation and elimination of areas in the LA and proximal coronary sinus showing CFAEs. During ablation, 3 patients converted to SR. In 15 others, significant organization of the atrial activity occurred. They then underwent successful electrical cardioversion. Three patients showed no change in atrial activity nor had electrical cardioversion. No procedural complications occurred. Patients took oral amiodarone for 3 months after the procedure. At 3 to 12 months (mean 9.8) of follow-up, 3 patients who were in AF at the end of the ablation procedure continued to be in AF. Of the rest, all but 3 were able to maintain SR without antiarrhythmic drugs. In conclusion, ablation using a 2-mm tip irrigation catheter, targeting user-defined CFAEs and pulmonary vein isolation facilitated maintenance of SR in most patients with a LA >5 cm and an AF duration of >2 years.

Gly460Trp polymorphism of the ADD1 gene and essential hypertension in an Indian population: A meta-analysis on hypertension risk

BACKGROUND: Essential hypertension is a complex genetic trait. Genetic variant of alpha adducin (ADD1) gene have been implicated as a risk factor for hypertension. Given its clinical significance, we investigated the association between ADD1 Gly460Trp gene polymorphism and essential hypertension in an Indian population. Further, a meta-analysis was carried out to estimate the risk of hypertension. METHODS: In the current study, 432 hypertensive cases and 461 healthy controls were genotyped for the Gly460Trp ADD1 gene polymorphism. Genotyping was determined by real time PCR using Taqman assay. Multiple logistic regression analysis was used to detect the association between Gly460Trp polymorphism and hypertension. RESULTS: No significant association was found in the genotype and allele distribution of Gly460Trp polymorphism with hypertension in our study. A total of 15 case-control studies were included in the meta-analysis. There was no evidence of the association of Gly460Trp polymorphism with hypertension in general or in any of the sub group. CONCLUSIONS: We found that the Gly460Trp polymorphism is not a risk factor for essential hypertension in a south Indian Tamilian population. However, the role of ADD1 polymorphism may not be excluded by a negative association study. Further, large and rigorous case-control studies that investigate gene–gene–environment interactions may generate more conclusive claims about the molecular genetics of hypertension.

GENETIC VARIANTS OF β1-ADRENOCEPTOR GENE POLYMORPHISMS (SER49GLY AND ARG389GLY) AND ESSENTIAL HYPERTENSION IN A SOUTH INDIAN TAMIL POPULATION

1 Essential hypertension is a complex polygenic disorder, the pathogenesis of which is dependent on an interplay between genetic and environmental factors. Various studies suggest an association between β1‐adrenoceptor gene polymorphisms (Ser49Gly and Arg389Gly) and cardiovascular disorders, including hypertension, cardiomyopathy and congestive heart failure. 2 The genetic profile of the β1‐adrenoceptor gene has not yet been documented for any Indian population. Thus, the aim of the present study was to investigate the association between β1‐adrenoceptor gene polymorphisms and essential hypertension in a south Indian Tamil population. 3 The present case‐control study included 438 patients with essential hypertensives and 444 healthy volunteers from the Tamil population. Genotyping was performed using real‐time polymerase chain reaction. 4 Genotype and allele frequencies of Ser49Gly and Arg389Gly polymorphism were compared between hypertensive patients and healthy volunteers. The homozygous variant genotype Gly49Gly of the Ser49Gly polymorphism was higher in hypertensive patients compared with controls (12.3 vs 7.4%, respectively). After adjusting for confounding variables (odds ratio (OR) 2.0; 95% confidence interval (CI) 1.2–2.9; P < 0.01) by multilogistic regression analysis, the gene was found to be associated with hypertension. A significant interaction was observed in hypertensive patients carrying the Ser49Gly/Gly49Gly × Arg389Gly/Gly389Gly genotypes (OR 1.9; 95% CI 1.1 2.7). 5 In conclusion, the Ser49Gly polymorphism is associated with essential hypertension in a south Indian Tamil population. The results of the present study deviate from those of previous studies, implying that marked interethnic difference exist in β1‐adrenoceptor gene polymorphisms.

Reuse of pacemakers, defibrillators and cardiac resynchronisation devices

Objective Access to pacemakers remains poor among many patients in low/middle-income countries. Reuse of explanted pacemakers is a possible solution, but is still not widespread because of concerns regarding outcomes, especially infection. Our objective was to study early outcomes with implants using reused devices and compare them with those with implants using new devices. Methods We studied all patients who underwent implantation of a new or reused pacemaker, cardiac resynchronisation therapy (CRT) device or implantable cardioverter defibrillator (ICD) in the last 5 years at a single institution. We analysed outcomes related to infection, device malfunction and device-related death within 6 months after initial implantation. Results During the study period, 887 patients underwent device implant, including 127 CRT devices or ICDs. Of these, 260 devices (29.3%) were reused and the others were new. At 6 months, there were three device-related infections in implants using a new device. There were no infections among patients receiving a reused device. There were no device malfunctions or device-related deaths in either group. Conclusions We found no difference in rate of infection or device malfunction among patients getting a reused device as compared with those with a new device. This study reinforces the safety of reusing devices for implant including CRT and ICDs.