Calambur Narasimhan

A Leadless Intracardiac Transcatheter Pacing System

BACKGROUND A leadless intracardiac transcatheter pacing system has been designed to avoid the need for a pacemaker pocket and transvenous lead. METHODS In a prospective multicenter study without controls, a transcatheter pacemaker was implanted in patients who had guideline-based indications for ventricular pacing. The analysis of the primary end points began when 300 patients reached 6 months of follow-up. The primary safety end point was freedom from system-related or procedure-related major complications. The primary efficacy end point was the percentage of patients with low and stable pacing capture thresholds at 6 months (≤2.0 V at a pulse width of 0.24 msec and an increase of ≤1.5 V from the time of implantation). The safety and efficacy end points were evaluated against performance goals (based on historical data) of 83% and 80%, respectively. We also performed a post hoc analysis in which the rates of major complications were compared with those in a control cohort of 2667 patients with transvenous pacemakers from six previously published studies. RESULTS The device was successfully implanted in 719 of 725 patients (99.2%). The Kaplan-Meier estimate of the rate of the primary safety end point was 96.0% (95% confidence interval [CI], 93.9 to 97.3; P<0.001 for the comparison with the safety performance goal of 83%); there were 28 major complications in 25 of 725 patients, and no dislodgements. The rate of the primary efficacy end point was 98.3% (95% CI, 96.1 to 99.5; P<0.001 for the comparison with the efficacy performance goal of 80%) among 292 of 297 patients with paired 6-month data. Although there were 28 major complications in 25 patients, patients with transcatheter pacemakers had significantly fewer major complications than did the control patients (hazard ratio, 0.49; 95% CI, 0.33 to 0.75; P=0.001). CONCLUSIONS In this historical comparison study, the transcatheter pacemaker met the prespecified safety and efficacy goals; it had a safety profile similar to that of a transvenous system while providing low and stable pacing thresholds. (Funded by Medtronic; Micra Transcatheter Pacing Study ClinicalTrials.gov number, NCT02004873.).

A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia

Heart failure is a leading cause of mortality in South Asians. However, its genetic etiology remains largely unknown. Cardiomyopathies due to sarcomeric mutations are a major monogenic cause for heart failure (MIM600958). Here, we describe a deletion of 25 bp in the gene encoding cardiac myosin binding protein C (MYBPC3) that is associated with heritable cardiomyopathies and an increased risk of heart failure in Indian populations (initial study OR = 5.3 (95% CI = 2.3–13), P = 2 × 10−6; replication study OR = 8.59 (3.19–25.05), P = 3 × 10−8; combined OR = 6.99 (3.68–13.57), P = 4 × 10−11) and that disrupts cardiomyocyte structure in vitro. Its prevalence was found to be high (∼4%) in populations of Indian subcontinental ancestry. The finding of a common risk factor implicated in South Asian subjects with cardiomyopathy will help in identifying and counseling individuals predisposed to cardiac diseases in this region.

Neuraxial modulation for refractory ventricular arrhythmias: value of thoracic epidural anesthesia and surgical left cardiac sympathetic denervation.

Background— Reducing sympathetic output to the heart from the neuraxis can protect against ventricular arrhythmias. The purpose of this study was to assess the value of thoracic epidural anesthesia (TEA) and left cardiac sympathetic denervation (LCSD) in the management of ventricular arrhythmias in patients with structural heart disease. Methods and Results— Clinical data of 14 patients (25 to 75 years old, mean±SD of 54.2±16.6 years; 13 men) who underwent TEA, LCSD, or both to control ventricular tachycardia (VT) refractory to medical therapy and catheter ablation were reviewed. Twelve patients were in VT storm, and 2 experienced recurrent VT despite maximal medical therapy and catheter ablation procedures. The total number of therapies per patient before either procedure ranged from 5 to 202 (median of 24; 25th and 75th percentile, 5 and 56). Eight patients underwent TEA, and 9 underwent LCSD (3 patients had both procedures). No major procedural complications occurred. After initiation of TEA, 6 patients had a large (≥80%) decrease in VT burden. After LCSD, 3 patients had no further VT, 2 had recurrent VT that either resolved within 24 hours or responded to catheter ablation, and 4 continued to have recurrent VT. Nine of 14 patients survived to hospital discharge (2 TEA alone, 3 TEA/LCSD combined, and 4 LCSD alone), 1 of the TEA alone patients underwent an urgent cardiac transplantation. Conclusions— Initiation of TEA and LCSD in patients with refractory VT was associated with a subsequent decrease in arrhythmia burden in 6 (75%) of 8 patients (68% confidence interval 51% to 91%) and 5 (56%) of 9 patients (68% confidence interval 34% to 75%), respectively. These data suggest that TEA and LCSD may be effective additions to the management of refractory ventricular arrhythmias in structural heart disease when other treatment modalities have failed or may serve as a bridge to more definitive therapy.

Early performance of a miniaturized leadless cardiac pacemaker: the Micra Transcatheter Pacing Study

Aims Permanent cardiac pacing is the only effective treatment for symptomatic bradycardia, but complications associated with conventional transvenous pacing systems are commonly related to the pacing lead and pocket. We describe the early performance of a novel self-contained miniaturized pacemaker. Methods and results Patients having Class I or II indication for VVI pacing underwent implantation of a Micra transcatheter pacing system, from the femoral vein and fixated in the right ventricle using four protractible nitinol tines. Prespecified objectives were >85% freedom from unanticipated serious adverse device events (safety) and <2 V 3-month mean pacing capture threshold at 0.24 ms pulse width (efficacy). Patients were implanted (n = 140) from 23 centres in 11 countries (61% male, age 77.0 ± 10.2 years) for atrioventricular block (66%) or sinus node dysfunction (29%) indications. During mean follow-up of 1.9 ± 1.8 months, the safety endpoint was met with no unanticipated serious adverse device events. Thirty adverse events related to the system or procedure occurred, mostly due to transient dysrhythmias or femoral access complications. One pericardial effusion without tamponade occurred after 18 device deployments. In 60 patients followed to 3 months, mean pacing threshold was 0.51 ± 0.22 V, and no threshold was ≥2 V, meeting the efficacy endpoint (P < 0.001). Average R-wave was 16.1 ± 5.2 mV and impedance was 650.7 ± 130 ohms. Conclusion Early assessment shows the transcatheter pacemaker can safely and effectively be applied. Long-term safety and benefit of the pacemaker will further be evaluated in the trial. Clinical Trial Registration ClinicalTrials.gov ID NCT02004873.

Antithrombotic management in patients undergoing electrophysiological procedures: a European Heart Rhythm Association (EHRA) position document endorsed by the ESC Working Group Thrombosis, Heart Rhythm Society (HRS), and Asia Pacific Heart Rhythm Society (APHRS).

Since the advent of the non-vitamin K antagonist oral anticoagulant (NOAC) agents, which act as direct thrombin inhibitors or inhibitors of Factor Xa, clinicians are provided with valuable alternatives to vitamin K antagonists (VKAs). At the same time, electrophysiologists frequently perform more invasive procedures, increasingly involving the left chambers of the heart. Thus, they are constantly faced with the dilemma of balancing the risk for thromboembolic events and bleeding complications. These changes in the rapidly evolving field mandate an update of the European Heart Rhythm Association (EHRA) 2008 consensus document on this topic.1 The present document covers the antithrombotic management during different ablation procedures, implantation or exchange of cardiac implantable electronical devices (CIEDs), as well as the management of peri-interventional bleeding complications. The document is not a formal guideline and due to the lack of prospective randomized controlled trials (RCTs) for many of the clinical situations encountered, the recommendations are often ‘expert opinion’. The document strives to be practical for which reason we subdivided it in the three main topics: ablation procedure, CIED implantation or generator change, and issues of peri-interventional bleeding complications on concurrent antiplatelet therapy. For quick reference, every subchapter is followed by a short section on consensus recommendations. Many RCTs are ongoing in this field and it is hoped that this document will help to prompt further well-designed studies. ### Ablation of atrial fibrillation, left atrial arrhythmias and right sided atrial flutter In patients with symptomatic paroxysmal or even persistent atrial fibrillation (AF), catheter ablation is indicated when antiarrhythmic drugs have failed in controlling recurrences or even as a first-line therapy in selected patients.2–4 Patients with AF have an increased risk of thromboembolic events, which varies according to the presence of several risk factors.5,6 Apart from their intrinsic thromboembolic risks, ablation in these patients increases thromboembolic risk due to the introduction and manipulation …

Efficacy and safety of implantable cardiac defibrillators for treatment of ventricular arrhythmias in patients with cardiac sarcoidosis

AIMS Implantable cardiac defibrillator (ICD) implantation is a class IIA recommendation for patients with cardiac sarcoidosis (CS). However, little is known about the efficacy and safety of ICDs in this population. The goal of this multicentre retrospective data review was to evaluate the efficacy and safety of ICDs in patients with CS. METHODS AND RESULTS Electrophysiologists at academic medical centres were asked to identify consecutive patients with CS and an ICD. Clinical information, ICD therapy history, and device complications were collected for each patient. Data were collected on 235 patients from 13 institutions, 64.7% male with mean age 55.6 ± 11.1. Over a mean follow-up of 4.2 ± 4.0 years, 85 of 234 (36.2%) patients received an appropriate ICD therapy (shocks and/or anti-tachycardia pacing) and 67 of 226 (29.7%) received an appropriate shock. Fifty-seven of 235 patients (24.3%) received a total of 222 inappropriate shocks. Forty-six adverse events occurred in 41 of 235 patients (17.4%). Patients who received appropriate ICD therapies were more likely to be male (73.8 vs. 59.6%, P = 0.0330), have a history of syncope (40.5 vs. 22.5%, P = 0.0044), lower left ventricular ejection fraction (38.1 ± 15.2 vs. 48.8 ± 14.7%, P ≤ 0.0001), ventricular pacing on baseline electrocardiogram (16.1 vs. 2.1%, P = 0.0002), and a secondary prevention indication (60.7 vs. 24.5%, P < 0.0001) compared with those who did not receive appropriate ICD therapies. CONCLUSION Patients with CS and ICDs are at high risk for ventricular arrhythmias. This population also has high rates of inappropriate shocks and device complications.

Radiofrequency catheter ablation of ventricular arrhythmias in patients with hypertrophic cardiomyopathy: safety and feasibility

BACKGROUND Management of ventricular tachycardia (VT) in patients with hypertrophic cardiomyopathy (HCM) is challenging. OBJECTIVE The purpose of this study is to assess the value of radiofrequency catheter ablation (RFCA) for the treatment of the VTs in the setting of HCM. METHODS Twenty-two patients (18 with ICD) with HCM and multiple episodes of VTs resistant to medical therapy underwent RFCA with an open irrigation catheter. Epicardial access was obtained if required. All patients were followed for at least 1 year after RFCA. RESULTS Mean age was 50.4 +/- 15.3, and mean ejection fraction was 34.3% +/- 9.8%. RFCA was performed endocardially in all patients, while epicardial radiofrequency applications were needed in 13 patients. A previous endocardial ablation was unsuccessful in six patients. At 20 +/- 9 months of follow-up, elimination of VTs reached 73%. No major complication was observed during and after the procedures in all patients. CONCLUSION Catheter ablation of VTs in patients with hypertrophic cardiomyopathy refractory to medical therapy is safe, feasible, and successful in eliminating VT. Epicardial VT mapping and ablation should be considered as an important access option for the treatment of these patients to increase the success rate.

Molecular genetics of familial hypertrophic cardiomyopathy (FHC).

AbstractFamilial hypertrophic cardiomyopathy is an autosomal dominant disease with a wide range of clinical features from benign to severe, and is the most common cause of sudden death in otherwise healthy individuals. The two prominent clinical features are left ventricular hypertrophy and myocyte/myofibrillar disarray. The former is responsible for clinical symptoms such as breathlessness and angina, whereas the latter may lead to sudden cardiac death. The last decade has seen an enormous improvement in our understanding of the molecular genetics of this disorder. The clinical heterogeneity has been linked to genetic heterogeneity; mutations in nine genes encoding sarcomere proteins have been shown to be the molecular basis for the disorder. However, attempts to establish a genotype-phenotype correlation for each of the more than 100 mutations that have been identified have not been highly successful. Additional genetic loci, as well as nongenetic factors such as lifestyle, sex, and age, have also been shown to play a role in modulating the clinical presentation of the disease. How each mutation results in hypertrophy and/or myofibrillar disarray is unclear. The present review discusses the current status of the molecular genetic characterization of this important disorder.

The rationale and design of the Micra Transcatheter Pacing Study: Safety and efficacy of a novel miniaturized pacemaker

AIMS Recent advances in miniaturization technologies and battery chemistries have made it possible to develop a pacemaker small enough to implant within the heart while still aiming to provide similar battery longevity to conventional pacemakers. The Micra Transcatheter Pacing System is a miniaturized single-chamber pacemaker system that is delivered via catheter through the femoral vein. The pacemaker is implanted directly inside the right ventricle of the heart, eliminating the need for a device pocket and insertion of a pacing lead, thereby potentially avoiding some of the complications associated with traditional pacing systems. METHODS AND RESULTS The Micra Transcatheter Pacing Study is currently undergoing evaluation in a prospective, multi-site, single-arm study. Approximately 720 patients will be implanted at up to 70 centres around the world. The study is designed to have a continuously growing body of evidence and data analyses are planned at various time points. The primary safety and efficacy objectives at 6-month post-implant are to demonstrate that (i) the percentage of Micra patients free from major complications related to the Micra system or implant procedure is significantly higher than 83% and (ii) the percentage of Micra patients with both low and stable thresholds is significantly higher than 80%. The safety performance benchmark is based on a reference dataset of 977 subjects from 6 recent pacemaker studies. CONCLUSIONS The Micra Transcatheter Pacing Study will assess the safety and efficacy of a miniaturized, totally endocardial pacemaker in patients with an indication for implantation of a single-chamber ventricular pacemaker. CLINICALTRIALSGOV REGISTRATION ID NCT02004873.

Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry.

Our aim is to determine mortality and morbidity in Asian patients under clinical management for heart failure (HF). Specifically, we will define the incidence of, and risk factors for, sudden cardiac death, as well as the socio‐cultural factors influencing therapeutic choices in these patients.