Session 03 : Arrhythmia

Session 3: Arrhythmia
Chairpersons: Vanita Arora and K.Shivakumar

10:55-11:15 C. Narasimhan 
11:15-11:35 Bijal Vyas 
11:35-11:55 Sridhar Sivasubbu 
11:55-12:15 Praloy Chakraborty 
12:15-12:35 R Juneja 
Early postoperative arrhythmia
12:35-12:55 Rakesh Yadav 
Long QT syndrome

Approaches to arrhythmias with Heart Failure

posted Jan 25, 2017, 11:31 PM by sourav ghosh

C.Narasimhan
Director-Arrhythmia and Electrophysiology Service, Care Hospitals, Hyderabad, India

Patients with Heart Failure develop arrhythmias frequently. There are certain situations wherein Arrhythmias leads to development of Heart failure viz. tachycardiomyopathy. This review will address two common arrhythmias. a) atrial fibrillation and b) ventricular tachycardia and fibrillation.
Atrial fibrillation is a common in HF population and results in significant morbidity and mortality. It increases the risk of thromboembolic events and worsens heart failure. Effective rate control and use of anticoagulants in appropriately selected patients results in improved outcome. In patients persistent AF, a more definitive therapy involves catheter ablation of AF, or AV junction ablation and implantation of CRT.
Ventricular arrhythmias in heart failure are a prognostic marker for sudden death. There are certain situations where Ventricular arrhythmias are frequent like myocarditis, Lamin mutation etc. Optimal beta blocker therapy is useful to prevent sudden cardiac arrest in this population. Implantable cardioverter therapy and CRT-D are extremely useful to further minimize the risk of sudden cardiac death. 

Genotyping of Cardiac channelopathies: Indian data

posted Jan 25, 2017, 11:30 PM by sourav ghosh   [ updated Jan 26, 2017, 3:01 AM ]

Bijal Vyas
University School of Medical & Paramedical Sciences, Guru Gobind Singh Indraprastha University, New Delhi, India

Introduction: Cardiac channelopathies have a prevalence of about 1:2000-2500 in different populations worldwide. The common life threatening cardiac channelopathies, Long QT (LQTS type 1-13) and Brugada (BrS type 1-12) present with syncope/ palpitations/ seizures/ aborted cardiac arrest. They have incomplete penetrance and variable expressivity. The three common genes (KCNQ1, KCNH2 and SCN5A) account for 75% of all LQTS cases, and SCN5A in BrSaccounts for 25% of all cases.
Aim: To identify the causative variation in the associated genes responsible for causing cardiac channelopathies in Indian patients.
Materials & Methods: Fifty patients who fulfilled the inclusion criteria of the study were enrolled. Mutation analysis was performed in most probable candidate gene by direct sequencing. If a mutation was not identified, NGS was performed to identify mutations in other cardiac genes. Parents and siblings were screened if a mutation was identified in the proband. Novel mutations were evaluated for pathogenicity using bioinformatics and molecular modeling softwares.
Results: Mutations was identified in twenty-five patients by Sanger sequencing, twenty-two had LQTS and three were affected with BrS. Among the LQT syndromes, mutations were identified in nineteen in KCNQ1 (LQTS1), one in KCNH2 (LQTS2)and two in SCN5A (LQTS3). Among the LQTS1 patients, ten were identified with biallelic mutations. The three BrS patients had mutations in SCN5A, agene responsible for BrS1. Eleven of twenty-five mutations were novel. NGS identified mutation in twelve of the remaining twenty-five patients. Of which, ten had LQTS and two had BrS. Of these mutations, seven were novel. 
Conclusion: Genotyping is important for confirming type of LQTS/ BrS, which has implications for management, and identification of asymptomatic at risk individuals.

Role of N-methyl D-aspartate (NMDA) receptors in zebrafish heart development and function

posted Jan 25, 2017, 11:24 PM by sourav ghosh

Sridhar Sivasubbu
CSIR-Institute of Genomics & Integrative Biology, New Delhi, India

NMDA receptors (NMDAR) are a subtype of ionotropic glutamate receptors mediating calcium uptake upon their activation by co-agonists glutamate and glycine. NMDAR exhibit distinct patterns of developmental expression in the central nervous system. However their role in heart development and function remains elusive. We employed a gene trapping based insertional mutagenesis approach to isolate zebrafish mutant animals that displayed pronounced cardiac arrhythmia followed by chamber enlargement and cardiac hypertrophy. Owing to the phenotype of an enlarged heart, we have named this mutant as bigheart (bh). The mutation in bh, maps to an intron of the NMDAR gene family member that forms calcium permeable ion channels. Our investigation revealed the presence of a novel transcript within the intron of the NMDAR gene. We name this transcript as NMDAR Associated RNA Transcript (NMDAR-ART). We characterized the novel transcript and shown that the NMDAR-ART is a putative long non-coding RNA (lncRNA). bh mutant zebrafish embryos and adults exhibited calcium handling defects and differential expression of calcium handling genes as well as cardiac remodelling markers were also documented. In summary, we report the identification of a novel lncRNA transcript called NMDAR-ART that expresses in specific zebrafish heart chambers. We show that NMDAR-ART has a potential role in cardiac rhythm function by regulating calcium flux. We hypothesize that NMDAR-ART regulates key calcium handling genes for maintaining intracellular calcium homeostasis in the zebrafish heart.

Understanding Antiarrhythmics: from cell to bed side

posted Jan 25, 2017, 11:23 PM by sourav ghosh

Praloy Chakraborty
Associate Professor, Cardiology, Vardhman Mahavir Medical College and Safdarjang Hospital, New Delhi, India

Although antiarrhythmics have versatile mechanisms of action, they suppress arrhythmias either by preventing enhanced automaticity or by altering the electrophysiological properties of reentrant pathways. Inhibition of reentry occurs due to reduction of conduction velocity or due to increase in the refractory period. Sodium channel blockers(Class I agents) reduce the conduction velocityof fast conducting tissue(i.e Ventricular Myocardium, accessory pathways)where as calcium channel antagonists exerts action by slowing conduction through slow conducting tissue(i.e AV node). So, Sodium channel antagonists terminate accessory pathway dependent reentry (AVRT) as well as atrial and ventricular tachycardias whereas calcium channel antagonists terminate AV node dependant tachycardias. Calcium channel antagonists also inhibit after depolarization induced triggered activities. Repolarization blocking agents(Class III agents), by prolonging the action potential duration, increase the refractory period of reentry circuit and terminate large numbers of atrial and ventricular tachyarrhythmias.Beta blockers block multiples steps in arrhythmogenesis. Other AV nodal blocking agents block AV node directly or via vagomimetic action and terminate AV node dependent tachyarrhythmias.

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