Homozygous frameshift variant in desmoglein 2 gene causes biventricular arrhythmogenic right ventricular cardiomyopathy.

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

A Novel Missense Mutation in TNNI3K Causes Recessively Inherited Cardiac Conduction Disease in a Consanguineous Pakistani Family.

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.

Localization Of Accessory Pathways In Wolff Parkinson White Syndrome Using R/S Ratios On Surface Ecgs.

BACKGROUND: This study was conducted to establish the accuracy of R/S ratios in localizing accessory pathways in Wolff Parkinson White Syndrome on surface ECGs. METHODS: This was a retrospective cross-sectional study from January 2002 till December 2016 conducted at National Institute of Cardiovascular diseases in Karachi, Pakistan. The sample included 157 patients with manifesting Wolff Parkinson White (WPW) Syndrome on a 12-lead surface ECG. As per the inclusion criteria, patients who had persistent or intermittent pre-excitation on surface ECG and had undergone electrophysiological study (EP) were included in the sample. Individuals with both successful and unsuccessful ablation procedures were included. RESULTS: The sample consisted of 62.4% males (n=98) and 37.6% females (n=59) with mean age being 35.36±12.44. Accessory pathways (APs) were identified on the left side in majority of the patients with 54.1% (n=85) while right sided pathways were seen in 42.1% (n=66). Moreover, the most common accessory pathway amongst the males was Left Anterior (LA) and Left Lateral (LL) with a percentage of 48%, followed by Right Posteroseptal (RPS) at 20.4%. As opposed to this, the most common pathways amongst the females turned out to be RPS at 33.9% followed by LL and LA at 32.2%. Furthermore, the test using ratios were most effective in identifying left sided APs with sensitivity 74.1% and was least sensitive in identifying right sided pathways (sensitivity=40.7%). However, it was highly specific in locating right sided pathways with specificity of 94.6% as opposed to 83.3% in the left side. Furthermore, mid-septum regions had a sensitivity and specificity of 66.7% and 69.6% respectively. CONCLUSIONS: This establishes the effectiveness of R/S ratios in determining the location of accessory pathway based on the surface ECG prior to the ablation procedure. Since the younger population is affected more commonly, prolonged exposure to ionizing radiation can cause long term complications therefore, by this means, the duration of exposure can be reduced.

Cardiac electrophysiologic procedures - A ten years' experience at National Institute of Cardiovascular Diseases, Karachi.

OBJECTIVE: To review 10 years of clinical practice of cardiac electrophysiology study and radiofrequency catheter ablation in the treatment of supraventricular tachycardia. METHODS: The retrospective chart review was conducted at the National Institute of Cardiovascular Diseases, Karachi, and comprised records of all patients who underwent electrophysiological study and / or radiofrequency catheter ablation from January2007 to December 2016. SPSS 21 was used for data analysis. RESULTS: Of the 627 patients, 335(53.4%) were females. The overall mean age was 40.99}13.59 years. The major indication for procedure was supraventricular tachycardia 376(59.97%). Final electrophysiological study diagnosis was typical slow fast atrioventricular nodal re-entrant tachycardia in 303(48.3%) patients. The overall success rate was 472(75.3%). Procedure-related complications were reported in 25(4%) patients, and there was 1(0.15%) mortality. CONCLUSIONS: Cardiac electrophysiology studies and radiofrequency catheter ablation were found to be an effective and safe method for diagnosis and treatment of supraventricular tachycardia.

Medication Adherence In Post Myocardial Infarction Patients.

BACKGROUND: Medication non-adherence after acute myocardial infarction is a global problem causing increased morbidity and mortality. This multifaceted problem has not been well studied in our part of the world. Our study aimed to determine the burden of medication non-adherence in post myocardial infarction patients. METHODS: This cross-sectional study was conducted at National Institute of Cardiovascular disease, Karachi, from December 2016 to June 2017. A total of 350 patients were included at the time of discharge after their first myocardial infarction (MI) of which follow up was completed for 315 patients. Baseline characteristics and discharged drug data were collected for each individual. Patients were called at 7th day, 1 and 3months post discharge and were assessed for the medication adherence using Morisky medication adherence scale. They were stratified accordingly into self-reported high, moderate and low groups. Chi- square test was used to determine significant relationship between variables. The level of significance was set at level of p-value ≤0.05. RESULTS: Among 315 patients, only 45% patients were adherent to prescribed drugs at 7th day follow up and the adherence further reduces to 19% at 3rd post MI month (p-value <0.001). High income, male gender, and presence of partner persistently showed significantly higher medication adherence. Factors like younger age, addiction and advance education showed higher adherence only in early follow up periods. However, presence of comorbidities, intervention and specific diagnosis had no significant impact. The most common stated reasons for non-adherence were forgetfulness and poor understanding of drugs. CONCLUSIONS: Adherence to prescribed medication in post myocardial infarction patients was found to be strikingly suboptimal, contributed by multiple factors. Modification of these factors would likely improve patient adherence to medication and eventually long-term outcome.

Cardiac electrophysiology studies and ablations for treatment of supraventricular arrhythmias--an initial experience from Karachi.

OBJECTIVES: To review the clinical experience, complications and outcome of Cardiac Electrophysiology Studies and Catheter Radiofrequency Ablation in treatment of supraventricular tachycardias in Karachi. METHODS: A retrospective review of records of all patients who underwent an electrophysiological study and radiofrequency ablation at National Institute of Cardiovascular Diseases and Aga Khan University Hospital from 2005 to 2007 was performed. Patient's demographics, disease and procedural data were collected and analyzed using SPSS.V.II. RESULTS: We enrolled 168 patients, 150 (89%) from National Institute of Cardiovascular Diseases and 18 (11%) from Aga Khan University Hospital. Sample had 86 (51%) male participants. The mean age was 43 +/- 15 years. Indications for procedure were recurrent supraventricular tachycardias (89.9%), Wolff Parkinson White Syndrome with atrial fibrillation (5.9%), syncope (2.4%), and wide QRS tachycardia (1.8%). Final diagnosis was Wolff Parkinson White Syndrome in 80 (48%) and Atriovetricular Nodal Reentrant Tachycardia in 88 (52%). The accessory pathway in Wolff Parkinson White Syndrome was located on left side in 61% of cases and on right side in 39% of cases. Overall acute success rate for Radio Frequency ablation was 90%. Success rate for ablation of accessory pathway in Wolff Parkinson White Syndrome was 85% while that for ablation of slow pathway in AV node re-entrant tachycardia was 95%. Complications occurred in one case. CONCLUSION: Electro Physiology Studies and Radiofrequency ablation proved to be a safe and effective method for diagnosis and treatment of supraventricular tachycardias in our patients.

Successful management of dislodged stents during percutaneous coronary intervention.

Stent dislodgement is a very rare but recognized and potentially serious complication of percutaneous coronary intervention (PCI). This case series describe the incidence and etiology of such cases at National Institute of Cardiovascular Diseases, Karachi during the year 2008 and the method of treatment of this complication.