Long QT syndrome- a genetic insight

Long QT syndrome is a rare arrhythmogenic disorder characterized by a prolongation of the QT interval on Electrocardiogram (ECG) with a propensity to ventricular tachyarrhythmia, leading to syncope, cardiac arrest or sudden death. It is regarded as the “Rosetta Stone” for studying the genetic basis of ventricular arrhythmogenesis. It is caused mainly due to mutations in sodium and potassium channel genes or in the genes involved in the signal transduction pathway. Molecular, genetic and functional studies revealed the impliction of about 13 genes in this disorder. Studies have also revealed the variation in mutations in different ethnic groups, thus necessitating a complete genetic analysis in all the known ethnic groups of the world. This would help to develop personalized medicine, molecular diagnosis, risk stratification, establish a genotype-phenotype correlation, to find the epidemiological variables responsible for the etiology of the disease and identify the possible mode of inheritance

Clinical Picture Of Arrhythmogenic Right Ventricular Dysplasia / Cardiomyopathy Patients From Indian Origin

Objective: Among the inherited cardiomyopathies, Arrhythmogenic right ventricular dysplasia/cardiomyopathy is unique with a peculiar pathology of fibro-fatty replacement. Studies have been carried out all over the world and several groups have reported clinical heterogeneity in manifestation of ARVD/C related symptoms. Present study is an attempt to identify the clinical profile of ARVD/C patients from Asian Indian origin.Methods: 31 patients in the span of three years were diagnosed with ARVD/C. Diagnosis was based on proposed task force criteria.Results: The mean age at diagnosis was 32.9 ± 16.4 years with slight tilt in male to female ratio (1.46). About 80% cases had palpitations, syncope in 45.16% and dyspnea in 22.5%, whereas 16% of patients were asymptomatic. About 50% of patients revealed a family history of confirmed ARVD/C or sudden death of a family member without any known cause. ECG showed T-wave inversion in about 60% cases, prolongation of QRS was observed in 20% cases. RV dilatation was observed in 80% of patients and 66.7% showed systolic dysfunction. RV free wall motion abnormalities were found in 33% patients. Most of the early onset cases with less than 30 years of age showed family history indicative of ARVD/C. Familial study in three patients indicated early onset of condition in younger generations in two families. Conclusion: ARVD/C in India shows relatively early age at onset when compared with other Asian populations with more than half of patients showing the disease below the age of 30 years. History in most of the early onset cases revealed family history indicating strong genetic influence

Adrenal and extra-adrenal pheochromocytomas presenting as life-threatening ventricular arrhythmias: Report of three cases

Pheochromocytoma patients can rarely have prolonged QT interval in the ECG. We report three cases of pheochromocytoma in females presenting with ventricular arrhythmia; two had torsades de pointes and a third patient had frequent VPCs and nonsustained ventricular tachycardia. All the patients were treated with surgical removal of the tumor with complete relief of symptoms and normalization of QT interval

Thiamine mediated reversal of left ventricular dysfunction in patients with alcoholic cardiomyopathy

This study aimed to evaluate the effect of thiamine supplementation on left ventricular (LV) systolic function in patients of alcoholic cardiomyopathy(ACM) presenting with acute heart failure(HF). 11 newly diagnosed patients were included. They were treated with 3 days of intravenous(IV) therapy with thiamine followed by oral supplementation. LVEF was 30% at baseline which improved by 45% and 53% along with reduction in LV dimensions over 3 and 6 months respectively. The study suggests the benefit of thiamine supplementation on LVEF in ACM patients with HF

Hypermethylation and reduced expression of lipoprotein metabolism genes ABCG1, LIPC and PLTP in Obese and Diabetic subjects: Potential risk factors for Coronary artery disease

517-525Increased lipid levels in the body can cause a plethora of complications and the lipoprotein metabolism genes such as ATP binding cassette transporter G1 (ABCG1), hepatic lipase (LIPC) and phospholipid transfer protein (PLTP) have a key role in the efflux of cholesterol from peripheral tissues to the liver. Altered methylation and expression of these genes in obese individuals and patients with diabetes mellitus can increase the risk of coronary artery disease (CAD). Here, we investigated the relationship of promoter methylation and expression of these lipoprotein metabolism genes ABCG1, LIPC and PLTP with the risk of CAD in diabetes and obese subjects. The study group consisting of 574 subjects, including 207 angiographically confirmed CAD patients, 100 diabetic patients and 82 obesity subjects without CAD and 185 healthy controls. DNA methylation status of ABCG1, LIPC and PLTP gene loci was determined by methylation-specific PCR and gene expression was analysed by real-time PCR. In obese individuals, the hypermethylation of ABCG1 (OR = 3.83, 95% CI = 2.11–6.96, P =0.0001) and PLTP (OR = 1.88, 95% CI = 1.07–3.28, P = 0.02 versus control) and reduced expression of ABCG1 (0.4-fold) and PLTP (decreased by 0.0025-fold) were observed. Hypermethylation of ABCG1 (OR = 1.71, 95% CI = 1.14–2.55, P = 0.01) and LIPC (OR = 1.58, 95% CI = 1.06–2.36, P = 0.02) genes was significantly higher in CAD patients when compared to healthy controls, whereas reduced expression of these genes by 0.77- and 0.82-fold was observed. The hypermethylation of LIPC was observed in CAD subjects with higher cholesterol and LDL (low density lipoproteins) levels (OR = 2.2, 95% CI = 1.18–4.09, P = 0.01; OR = 2.08, 95% CI = 1.12–4.22, P = 0.02, respectively). CAD subjects with diabetes (n=118) showed hypermethylation of LIPC (OR = 2.1, 95% CI = 1.2–3.67, P = 0.01) and PLTP (OR = 2.01, 95% CI = 1.13–3.59, P = 0.01). Hypermethylation of ABCG1 (OR = 1.91, 95% CI = 1.09–3.36, P = 0.03) and LIPC (OR = 2.0, 95% CI = 1.12–3.55, P = 0.02) genes were associated with lifestyle habit such as cigarette smoking. The results suggest that obese individuals are at a risk of CAD through alteration of lipoprotein homeostasis. Lifestyle modifications such as reduction in BMI and cessation of cigarette smoking might reduce the risk of CAD