Hygriv B. Rao

Biatrial and Three-Dimensional Mapping of Spontaneous Atrial Arrhythmias in Patients with Refractory Atrial Fibrillation

Introduction: While atrial fibrillation (AF) initiation in the pulmonary veins has been well‐studied, simultaneous biatrial and three‐dimensional noncontact mapping (NCM) has not been performed. We hypothesized that these two techniques would provide novel information on triggers, initiation, and evolution of spontaneous AF and permit study of different AF populations.

Catheter ablation of bundle branch reentrant ventricular tachycardia

Bundle branch reentrant ventricular tachycardia (BBR-VT) is a form of macroreentrant tachycardia involving the bundle of His, both bundle branches, and the ventricular myocardium in the circuit. It generally occurs in the background of dilated cardiomyopathy, prior valve surgery, or other cardiac disease with an underlying His-Purkinje system (HPS) disease. Clinically, BBR-VT usually results in marked hemodynamic compromise and often presents with syncope, presyncope, or sudden cardiac arrest. When a ventricular tachycardia is induced, the presence of His deflections preceding every ventricular deflection should alert one to the possibility of this entity. It is important to show that oscillations in the H-H cycle length results in variations in V-V cycle length. Entrainment of the tachycardia from atrium and right ventricular apex and characteristics of postpacing intervals can be used to differentiate this arrhythmia from intramyocardial reentry and supraventricular tachycardia with aberrancy. Right bundle branch ablation usually cures the tachycardia, and recurrence is uncommon. The underlying cardiac disease and ventricular dysfunction dictate the prognosis and choice of device therapy in these patients.

Mutational analysis of SCN5A gene in long QT syndrome

The SCN5A gene encodes for the INa channel implicated in long QT syndrome type-3 (LQTS-type-3). Clinical symptoms of this type are lethal as most patients had a sudden death during sleep. Screening of SCN5A in South Indian cohort by PCR-SSCP analyses revealed five polymorphisms — A29A (exon-2), H558R (exon-12), E1061E and S1074R (exon-17) and IVS25 + 65G > A (exon-25) respectively. In-silico and statistical analyses were performed on all the polymorphisms. Exon-2 of SCN5A gene revealed A282G polymorphism (rs6599230), resulting in alanine for alanine (A29A) silent substitution in the N-terminus of SCN5A protein. Exon-12 showed A1868G polymorphism (H558R — rs1805124) and its ‘AA’ genotype and ‘A’ allele frequency were found to be higher in LQTS patients pointing towards its role in LQTS etiology. Two polymorphisms A3378G (E1061E) and the novel C3417A (S1074R) were identified as compound heterozygotes/genetic compounds in exon-17 of SCN5A located in the DIIS6–DIIIS1 domain of the SCN5A transmembrane protein. IVS25 + 65G > A was identified in intron-25 of SCN5A. The ‘G’ allele was identified as the risk allele. Variations were identified in in-silico analyses which revealed that these genetic compounds may lead to downstream signaling variations causing aberrations in sodium channel functions leading to prolonged QTc. The compound heterozygotes of SCN5A gene polymorphisms revealed a significant association which may be deleterious/lethal leading to an aberrant sodium ion channel causing prolonged QTc.

Intra-Cardiac Echocardiography Guided Cardioversion to Help Interventional Procedures (ICE-CHIP) Study: Study Design and Methods

The ICE CHIP study is a sequential Phase I and Phase II pilot study comparing the cardiac imaging capabilities of intracardiac echocardiography (ICE) with with transesophageal echocardiography (TEE) followed by a randomized comparison of ICE guided cardioversion with a conventional cardioversion strategy in patients with atrial fibrillation. It is a prospective open label randomized multi-center investigation performed in two phases designed to initially compare two distinct imaging modalities (Phase 1) and subsequently two different strategies (ICE guided Cardioversion and Conventional) in the management of AF in patients undergoing invasive cardiac procedures in whom electrical cardioversion is indicated (Phase 2). This study will examines two hypotheses in AF patients undergoing invasive cardiac procedures: (1) ICE has comparable efficacy to TEE in visualization of left atrial pathology including thrombi or interatrial septal defects. This will be evaluated during the Phase I component of the study. (2) ICE can identify low risk patients in whom immediate cardioversion during the procedure is safe and comparably effective to electrical cardioversion performed based on a conventional strategy of a minimum of 3 weeks of preceding anticoagulation therapy. Phase 1 will enroll 100 patients at 12 centers, who will undergo a clinically indicated TEE procedure and cardiac catheterization procedure. Each patient will be imaged by TEE & ICE and a core echo laboratory will perform a blinded comparison of the two imaging modalities. In Phase 2, a total of 300 patients (3:2 randomization) will be enrolled in the study at up to 15 investigational sites in USA and Europe. The composite incidence rate of major cardiac and bleeding complications (stroke, TIA, peripheral embolism, major hemorrhagic event) will be compared between the two treatment groups over the duration of the study.

Ablation of incessant orthodromic reciprocating tachycardia in a child with congenitally corrected transposition of great arteries and ebsteinoid malformation of left atrioventricular valve.

We report about a patient with congenitally corrected transposition of the great arteries and ebsteinoid malformation of left atrioventricular (AV) valve who presented with incessant orthodromic atrioventricular reciprocating tachycardia due to a left posteroseptal accessory pathway. Radiofrequency catheter ablation using trans-septal approach successfully eliminated the posteroseptal pathway across the morphologic tricuspid valve. This report highlights the importance of delineating the anatomy of the interatrial septum in complex congenital heart diseases for performing safe trans-septal puncture during ablation of accessory pathways.

Implantable defibrillators configured for hybrid therapy of persistent and permanent atrial fibrillation : Initial clinical experience with a novel lead system

Aim: Hybrid therapy strategies have combined antiarrhythmic drugs (AAD) with pacemakers, atrio-ventricular defibrillators (AV ICD) or atrial ablation individually. The feasibility combining AAD with dual site RA pacing (DAP) in an AV ICD has not been examined.Methods: We used an AV ICD with a novel lead configuration permitting DAP, antitachycardia pacing (ATP) or atrial shocks (ADF) in patients (pts) with refractory persistent or permanent AF. Hybrid therapy included linear RA ablation and/or focal ablation. Continuous DAP and automatic ATP with patient or physician activated ADF.Results: 24 pts, mean age 66 ± 10 yrs, with cardiac disease (22 pts), underwent insertion of an AVICD with dual RA leads. 20 patients had concomitant ablative procedures (RA only = 19, RA + LA = 1) and all pts continued previously ineffective AAD. During a follow-up of 2–36 months (mean 17 ± 8 mos), rhythm control was restored in all pts & maintained long-term in 19 (83%) pts. 8 pts used AF termination therapies successfully. Device datalogs showed no episodes of AF in 6 pts, asymptomatic brief arrhythmias in 4 pts, infrequent paroxysmal AF in 9 pts & persistent AF recurred in 5 pts. AV ICD detection algorithms reliably detected AF or AT in the DAP mode in all pts. Intermittent brief P wave double counting occurred during AT in selected pts. No pt received inappropriate ADF therapy.Conclusions: 1. DAP can be safely incorporated in an AVICD devices for use in an hybrid therapy strategy for AF pts. 2. These devices can be effective for both AF prevention & termination. 3. Long term rhythm control can be achieved and documented by device datalogs in persistent and permanent AF.

Atrial natriuretic peptide gene - a potential biomarker for long QT syndrome

This study highlights the possible implication of NPPA (natriuretic peptide precursor A) gene in the etiology of Long QT syndrome (LQTS) by population-based as well as familial study. Three SNPs of NPPA - C-664G, C1363A and T1766C were examined by molecular analyses in LQTS, controls and first degree relatives (FDRs). This study revealed a possible association of 1364 C>A SNP ‘C’ allele with LQTS (p = 0.0013). All three SNPs were in tight linkage disequilibrium. The familial study highlights the association of NPPA SNP with cLQTS and implicating it as a potential biomarker in South Indian population.

Use of secondary prevention drugs for cardiovascular disease in the community in high-income, middle-income, and low-income countries (the PURE Study): a prospective epidemiological survey

Yusuf S, Shofi qul Islam SQ, Chow CK, et al, Prospective Urban Rural Epidemiology (PURE) Study Investigators. Lancet 2011;378:1231–43. A large burden of cardiovascular disease exists in the low-income and middle-income countries, however the use of proven medications for secondary prevention these countries is unknown. Prospective Urban Rural Epidemiology (PURE) study was designed to study the use of proven effective secondary prevention drugs (antiplatelet drugs, β-blockers, angiotensin-converting-enzyme [ACE] inhibitors or angiotensin-receptor blockers [ARBs] and statins) in individuals with a history of coronary heart disease (CHD) or stroke. Individuals aged 35–70 years from rural and urban communities from countries of varied economies were recruited. Standardised questionnaires were administered by telephonic or personal interview to collect data on presence of cardiovascular disease and use of proven medications for secondary prevention and anti-hypertensive drugs. Totally 153,996 adults from 628 (348 urban and 280 rural) communities in 17 countries with incomes classified as high (three countries), upper middle (seven), lower middle (three), or low (four) were enrolled between January 2003 and December 2009. Around 5650 participants had a self-reported CHD event (median duration 5 years) and 2292 had stroke (median duration 4 years). Use of medications by patients with cardiovascular disease were antiplatelet drugs (25.3%), β-blockers (17.4%), ACE inhibitors or ARBs (19.5%), or statins (14.6%). Use was highest in high-income countries (antiplatelet drugs 62.0%, β-blockers 40.0%, ACE inhibitors or ARBs 49.8%, and statins 66.5%), lowest in low-income countries (8.8%, 9.7%, 5.2%, and 3.3%, respectively), and decreased in line with reduction of country economic status (P trend <0.0001 for every drug type). Fewest patients received no drugs in high-income countries (11.2%), compared with 45.1% in upper middle-income countries, 69.3% in lower middle-income countries, and 80.2% in low-income countries. Drug use was higher in urban than rural areas (antiplatelet drugs 28.7% urban vs 21.3% rural, β-blockers 23.5% vs 15.6%, ACE inhibitors or ARBs 22.8% vs 15.5%, and statins 19.9% vs 11.6%; all P < 0.0001), with greatest variation in poorest countries (P interaction <0.0001) for urban vs rural differences by country economic status). Two-third of the under usage of medications was related to the stage of economic development of the country and 1/3rd to individual factors which included younger people, lower level of education, female gender, smokers, non-hypertensive, non-diabetic, and non-obese individuals. Globally there a significant under usage of medications for secondary prophylaxis and this is more striking in low-income countries. Systematic programmes to ensure increased and appropriate use of proven drugs for secondary prevention are needed in most countries.

Genotype-phenotype correlation in long QT syndrome families.

Heterogeneity in clinical manifestations is a well-known feature in Long QT Syndrome (LQTS). The extent of this phenomenon became evident in families wherein both symptomatic and asymptomatic family members are reported. The study hence warrants genetic testing and/or screening of family members of LQTS probands for risk stratification and prediction. Of the 46 families screened, 18 probands revealed novel variations/compound heterozygosity in the gene/s screened. Families 1–4 revealed probands carrying novel variations in KCNQ1 gene along with compound heterozygosity of risk genotypes of the SCN5A, KCNE1 and NPPA gene/s polymorphisms screened. It was also observed that families- 5, 6 and 7 were typical cases of “anticipation” in which both mother and child were diagnosed with congenital LQTS (cLQTS). Families- 16 and 17 represented aLQTS probands with variations in IKs and INa encoding genes. First degree relatives (FDRs) carrying the same haplotype as the proband were also identified which may help in predictive testing and management of LQTS. Most of the probands exhibiting a family history were found to be genetic compounds which clearly points to the role of cardiac genes and their modifiers in a recessive fashion in LQTS manifestation.

Septal Pacing of Right Ventricle: Has The Last Word Been Said?

The deleterious effects of Right ventricular (RV) pacing on development of ventricular dyssynchrony leading to heart failure, genesis of atrial fibrillation and consequent increased mortality have been repeatedly demonstrated in numerous pacing studies. Trials with dual chamber pacemakers and defibrillators did not succeed in negating these effects, raising the question if it was RV pacing per se or RV apical pacing that was the culprit. Innovations in algorithms to reduce RV pacing were simultaneously supplemented by investigation into alternative sites of pacing to counter these undesirable outcomes. These included pacing of the His bundle, right ventricular outflow tract (RVOT), mid and apical septum. Dictated by the ability to achieve satisfactory lead stability and thresholds, the search has practically narrowed to septal pacing. Physiologically septal pacing results in earlier depolarization of the septum and a closer conduction sequence to normal. This would be expected to reduce LV activation time, prevent dyssynchrony and preserve LV function. RVOT remains the most investigated nonapical pacing site, though other septal sites theoretically can be expected to result in a similar benefit by achieving a narrow QRS and a physiological ventricular activation.