Cardiac conduction disease (CCD), which causes altered electrical impulse propagation in the heart, is a life-threatening condition with high morbidity and mortality. It exhibits genetic and clinical heterogeneity with diverse pathomechanisms, but in most cases, it disrupts the synchronous activity of impulse-generating nodes and impulse-conduction underlying the normal heartbeat. In this study, we investigated a consanguineous Pakistani family comprised of four patients with CCD. We applied whole exome sequencing (WES) and co-segregation analysis, which identified a novel homozygous missense mutation (c.1531T>C;(p.Ser511Pro)) in the highly conserved kinase domain of the cardiac troponin I-interacting kinase (TNNI3K) encoding gene. The behaviors of mutant and native TNNI3K were compared by performing all-atom long-term molecular dynamics simulations, which revealed changes at the protein surface and in the hydrogen bond network. Furthermore, intra and intermolecular interaction analyses revealed that p.Ser511Pro causes structural variation in the ATP-binding pocket and the homodimer interface. These findings suggest p.Ser511Pro to be a pathogenic variant. Our study provides insights into how the variant perturbs the TNNI3K structure-function relationship, leading to a disease state. This is the first report of a recessive mutation in TNNI3K and the first mutation in this gene identified in the Pakistani population.

No abstract

Arrhythmogenic right ventricular cardiomyopathy caused by a homozygous frameshift variant (c.2358delA) in DSG2.

Objective: To determine the frequency of ventricular arrhythmias in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) at a tertiary care hospital in Karachi, Pakistan. Material and Methods: This descriptive case series study was done at the National Institute of Cardiovascular Disease, Karachi. All patients of either gender having an age between 18 and 70 years of diagnosis with STEMI undergoing primary PCI were included. All the patients were kept under observation for 72 hours in the hospital, and ventricular arrhythmias such as Accelerated Idioventricular Rhythm (AIVR), Frequent PVCs (premature ventricular contractions), Non-Sustained Ventricular Tachycardia, Sustained Ventricular Tachycardia, and Ventricular Fibrillation were recorded. Results: The mean age of the patients was 54.72 ±10.75 years. The majority of the patients, 75.2%, were males and 24.8% were females. The frequency of ventricular arrhythmia was found in 89 (25.9%) of the patients. Among 89 patients with ventricular arrythmia, AIVR was found in 30 (33.71%), frequent PVCs in 18 (20.22%), non-sustained ventricular tachycardia in 23 (25.84%), sustained ventricular tachycardia and ventricular fibrillation in 9 (10.11%) each. Conclusion: As per the study conclusion, the ventricular arrhythmias was observed to be considerably higher among patients undergoing primary PCI for ST-STEMI. Keywords: Ventricular arrhythmias, PCI, ST-segment elevation MI

Objective: To determine the frequency of angiographically significant coronary artery disease (CAD) in patients undergoing valve replacement surgery and referred for Coronary angiography. Study Design: Cross Sectional Descriptive Study. Study Setting& duration: From 14th February 2016 to 14th August 2016 in the Department of Cardiology, Tabba Heart Institute, Karachi. Material and Methods: Total 127 patients of both genders with age 40-75 years undergone referred for coronary angiography and as a pre requisite of required valve replacement surgery were included and significant findings were noted. The history of comorbid, family history of premature CAD, smoking and basal metabolic index were noted. Results: There were 58.3% male and 41.7% female patients. Average age was 54.60±8.91 years. Mean BMI was 28.64±4.62 Kg/m2. 75.6% patients were obese. Angiographically significant CAD was observed positive in 27.6% patients. Significant association was found with hypertension and premature family history of CAD. The prevalence was high in patients with MVR followed in patients with AVR. Conclusion: The overall prevalence of angiographically significant coronary artery disease was 27.6%.in cases going through valve replacement is substantial. The prevalence was high in patients with MVR followed in patients with AVR. Keywords: CAD, Angiography, Significant Coronary Artery Disease, Valve Replacement Surgery