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1.  High prevalence of Arginine to Glutamine Substitution at 98, 141 and 162 positions in Troponin I (TNNI3) associated with hypertrophic cardiomyopathy among Indians 
BMC Medical Genetics  2012;13:69.
Background
Troponin I (TNNI3) is the inhibitory subunit of the thin filament regulatory complex Troponin, which confers calcium-sensitivity to striated muscle actomyosin ATPase activity. Mutations (2-7%) in this gene had been reported in hypertrophic cardiomyopathy patients (HCM). However, the frequencies of mutations and associated clinical presentation have not been established in cardiomyopathy patients of Indian origin, hence we have undertaken this study.
Methods
We have sequenced all the exons, including the exon-intron boundaries of TNNI3 gene in 101 hypertrophic cardiomyopathy patients (HCM), along with 160 healthy controls, inhabited in the same geographical region of southern India.
Results
Our study revealed a total of 16 mutations. Interestingly, we have observed Arginine to Glutamine (R to Q) mutation at 3 positions 98, 141 and 162, exclusively in HCM patients with family history of sudden cardiac death. The novel R98Q was observed in a severe hypertrophic obstructive cardiomyopathy patient (HOCM). The R141Q mutation was observed in two familial cases of severe asymmetric septal hypertrophy (ASH++). The R162Q mutation was observed in a ASH++ patient with mean septal thickness of 29 mm, and have also consists of allelic heterogeneity by means of having one more synonymous (E179E) mutation at g.4797: G → A: in the same exon 7, which replaces a very frequent codon (GAG: 85%) with a rare codon (GAA: 14%). Screening for R162Q mutation in all the available family members revealed its presence in 9 individuals, including 7 with allelic heterogeneity (R162Q and E179E) of which 4 were severely affected. We also found 2 novel SNPs, (g.2653; G → A and g.4003 C → T) exclusively in HCM, and in silico analysis of these SNPs have predicted to cause defect in recognition/binding sites for proteins responsible for proper splicing.
Conclusion
Our study has provided valuable information regarding the prevalence of TNNI3 mutations in Indian HCM patients and its risk assessment, these will help in genetic counseling and to adopt appropriate treatment strategies.
doi:10.1186/1471-2350-13-69
PMCID: PMC3495047  PMID: 22876777
TNNI3-Troponin I; Cardiomyopathy; SNPs; HCM; Indians; Mutations
2.  Three dimensional epicardial mapping and ablation of recurrent non-ischaemic ventricular tachycardia 
Indian Heart Journal  2012;64(3):324-328.
Radiofrequency ablation is a therapeutic option for recurrent ventricular tachycardia (VT) in both ischaemic and non-ischaemic subsets. Usually this is attempted by mapping endocardially; however, in some situations epicardial approach may be needed to access the VT circuit. We report two cases in which epicardial approach was used to successfully ablate the VT, when endocardial ablation was ineffective.
doi:10.1016/S0019-4832(12)60092-3
PMCID: PMC3860767  PMID: 22664820
Electroanatomic mapping; Epicardial approach; Substrate based mapping; Ventricular tachycardia (VT)
3.  Neuraxial Modulation for Refractory Ventricular Arrhythmias: Value of Thoracic Epidural Anesthesia and Surgical Left Cardiac Sympathetic Denervation 
Circulation  2010;121(21):2255-2262.
Background
Reducing sympathetic output to the heart from the neuraxis can protect against ventricular arrhythmias. The purpose of this study was to assess the value of thoracic epidural anesthesia (TEA) and left cardiac sympathetic denervation (LCSD) in the management of ventricular arrhythmias in patients with structural heart disease (SHD).
Methods and Results
Clinical data of 14 patients (age 25-75 years, 54.2±16.6 yrs,(mean±SD) 13 males) who underwent TEA, LCSD, or both, to control ventricular tachycardia (VT) refractory to medical therapy and catheter ablation were reviewed.12 patients were in VT storm and 2 patients experienced recurrent VT despite maximal medical therapy and catheter ablation procedures. Total number of therapies per patient prior to either procedure ranged from 5 to 202 (median of 24, 25th and 75th percentile of 5 and 56). Eight patients underwent TEA and 9 patients underwent LCSD (3 patients had both procedures). No major procedural complications occurred. After initiation of TEA, 6 patients had a large (≥80%) decrease in VT burden. Post LCSD, 3 patients had no further VT, 2 patients had recurrent VT which either resolved within 24 hours or responded to catheter ablation, and 4 patients continued to have recurrent VT. Nine out of 14 patients survived to hospital discharge (1 TEA alone, 3 TEA/LCSD combined, 4 LCSD alone), one of whom underwent an urgent cardiac transplantation (TEA alone).
Conclusion
Initiation of TEA and LCSD in patients with refractory VT was associated with a subsequent decrease in arrhythmia burden in 6 out of 8 (75%- CI 51% to 91%) and 5 out of 9 (56%- CI 34% to 75%) patients, respectively. These data suggest that TEA and LCSD may be effective additions to the management of refractory ventricular arrhythmias in SHD when other treatment modalities have failed and/or may serve as a bridge to more definitive therapy.
doi:10.1161/CIRCULATIONAHA.109.929703
PMCID: PMC2896716  PMID: 20479150
ventricular tachyarrhythmias; nervous system; sympathetic
4.  The MYH7 p.R787H mutation causes hypertrophic cardiomyopathy in two unrelated families 
BACKGROUND:
Familial hypertrophic cardiomyopathy (FHC) is a Mendelian disorder usually caused by mutations in any one of more than 12 genes, most of which encode sarcomere proteins. The disease exhibits extensive genetic heterogeneity, and it is important to identify mutations that result in adverse symptoms and/or lethality in affected individuals. An analysis of disease-causing mutations has been initiated in the Indian population to determine prevalent mutations.
METHODS:
FHC was detected using echocardiography and by analysis of clinical symptoms and family history. The disease-causing mutation was identified using polymerase chain reaction DNA sequencing.
RESULTS:
The p.R787H mutation was identified in the MYH7 gene in two FHC families. Sequence and structure analysis suggested impaired binding of the mutant protein to the myosin essential light chain.
CONCLUSIONS:
Although the mutation results in variable clinical symptoms in the affected individuals, probably owing to the effect of modifier genes and/or environmental factors, it does not appear to be a lethal mutation.
PMCID: PMC2907879  PMID: 20664766
Beta-cardiac myosin heavy chain 7 gene; Familial hypertrophic cardiomyopathy; Hypertrophy; Mutation
5.  Substrate Based Ablation of Ventricular Tachycardia Through An Epicardial Approach 
Ventricular tachycardia (VT) occurring late after myocardial infarction is often due to reentry circuit in the peri-infarct zone. The circuit is usually located in the sub-endocardium, though subepicardial substrates are known. Activation mapping during VT to identify target regions for ablation can be difficult if VT is non inducible or poorly tolerated. In the latter, a substrate based approach of mapping during sinus rhythm in conjunction with pace mapping helps to define the reentry circuit and select target sites for ablation in majority of patients with hemodynamically unstable VT. Percutaneous epicardial catheter ablation has been attempted as an approach where ablation by a conventional endocardial access has been unsuccessful. We report a case of post myocardial infarction scar VT which could be successfully ablated with a substrate based approach from the epicardial aspect.
PMCID: PMC2766586  PMID: 19898661
ventricular tachycardia; substrate based mapping; epicardial approach; electroanatomic mapping
6.  A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia 
Nature genetics  2009;41(2):187-191.
Heart failure is a leading cause of mortality in South Asians. However, its genetic etiology remains largely unknown1. Cardiomyopathies due to sarcomeric mutations are a major monogenic cause for heart failure (MIM600958). Here, we describe a deletion of 25 bp in the gene encoding cardiac myosin binding protein C (MYBPC3) that is associated with heritable cardiomyopathies and an increased risk of heart failure in Indian populations (initial study OR = 5.3 (95% CI = 2.3–13), P = 2 × 10−6; replication study OR = 8.59 (3.19–25.05), P = 3 × 10−8; combined OR = 6.99 (3.68–13.57), P = 4 × 10−11) and that disrupts cardiomyocyte structure in vitro. Its prevalence was found to be high (~4%) in populations of Indian subcontinental ancestry. The finding of a common risk factor implicated in South Asian subjects with cardiomyopathy will help in identifying and counseling individuals predisposed to cardiac diseases in this region.
doi:10.1038/ng.309
PMCID: PMC2697598  PMID: 19151713
7.  Successful Catheter Ablation of Persistent Electrical Storm late Post Myocardial Infarction by Targeting Purkinje Arborization Triggers 
Drug refractory ventricular tachycardia (VT) occurring as a storm after acute myocardial infarction has grave prognosis. We report a case of a middle-aged lady who presented with drug refractory VT that lead to persistent electrical storm two weeks after an anterior wall myocardial infarction. She underwent a successful catheter ablation of VT followed a few days later by implantation of an AICD. Catheter ablation of the VT could control the persistent electrical storm and the patient was free from a recurrence of VT at three month follow up.
PMCID: PMC2572020  PMID: 18982139
Electrical storm; Catheter ablation; Purkinje arborization triggers
8.  A p.R870H mutation in the beta-cardiac myosin heavy chain 7 gene causes familial hypertrophic cardiomyopathy in several members of an Indian family 
The Canadian Journal of Cardiology  2007;23(10):788-790.
Familial hypertrophic cardiomyopathy is an autosomal dominant genetic disorder characterized mainly by left ventricular hypertrophy and myocyte disarray; it is the most common cause of sudden death in otherwise healthy individuals. More than 270 mutations in genes encoding the cardiac sarcomere have been identified. Attempts to establish a genotype-phenotype correlation for each of the mutations have not been highly successful. It has been suggested that additional genetic loci, as well as nongenetic factors such as lifestyle, gender and age, may play a role in modulating the clinical presentation of the disease. The p.R870H mutation has been identified as the cause of familial hypertrophic cardiomyopathy in an Indian family. The results indicate that the disease phenotype varied among various affected members of the family, and the variation may be attributed to factors, such as gender and gene dosage.
PMCID: PMC2651383  PMID: 17703256
Angiotensin; Cardiomyopathy; Hypertrophy

Results 1-8 (8)