Wajid Hussain

A Randomized Trial to Assess Catheter Ablation Versus Rate Control in the Management of Persistent Atrial Fibrillation in Heart Failure

OBJECTIVES This study sought to compare catheter ablation with rate control for persistent atrial fibrillation (AF) in heart failure (HF). BACKGROUND The optimal therapy for AF in HF is unclear. Drug-based rhythm control has not proved clinically beneficial. Catheter ablation improves cardiac function in patients with HF, but impact on physiological performance has not been formally evaluated in a randomized trial. METHODS In a randomized, open-label, blinded-endpoint clinical trial, adults with symptomatic HF, radionuclide left ventricular ejection fraction (EF) ≤35%, and persistent AF were assigned to undergo catheter ablation or rate control. Primary outcome was 12-month change in peak oxygen consumption. Secondary endpoints were quality of life, B-type natriuretic peptide, 6-min walk distance, and EF. Results were analyzed by intention-to-treat. RESULTS Fifty-two patients (age 63 ± 9 years, EF 24 ± 8%) were randomized, 26 each to ablation and rate control. At 12 months, 88% of ablation patients maintained sinus rhythm (single-procedure success 68%). Under rate control, rate criteria were achieved in 96%. The primary endpoint, peak oxygen consumption, significantly increased in the ablation arm compared with rate control (difference +3.07 ml/kg/min, 95% confidence interval: 0.56 to 5.59, p = 0.018). The change was not evident at 3 months (+0.79 ml/kg/min, 95% confidence interval: -1.01 to 2.60, p = 0.38). Ablation improved Minnesota score (p = 0.019) and B-type natriuretic peptide (p = 0.045) and showed nonsignificant trends toward improved 6-min walk distance (p = 0.095) and EF (p = 0.055). CONCLUSIONS This first randomized trial of ablation versus rate control to focus on objective exercise performance in AF and HF shows significant benefit from ablation, a strategy that also improves symptoms and neurohormonal status. The effects develop over 12 months, consistent with progressive amelioration of the HF syndrome. (A Randomised Trial to Assess Catheter Ablation Versus Rate Control in the Management of Persistent Atrial Fibrillation in Chronic Heart Failure; NCT00878384).

Remodeling of Gap Junctional Channel Function in Epicardial Border Zone of Healing Canine Infarcts

Abstract— The epicardial border zone (EBZ) of canine infarcts has increased anisotropy because of transverse conduction slowing. It remains unknown whether changes in gap junctional conductance (Gj) accompany the increased anisotropy. Ventricular cell pairs were isolated from EBZ and normal hearts (NZ). Dual patch clamp was used to quantify Gj. At a transjunctional voltage (Vj) of +10 mV, side-to-side Gj of EBZ pairs (9.2±3.4 nS, n=16) was reduced compared with NZ side-to-side Gj (109.4±23.6 nS, n=14, P <0.001). Gj of end-to-end coupled cells was not reduced in EBZ. Steady-state Gj of both NZ and EBZ showed voltage dependence, described by a two-way Boltzmann function. Half-maximal activation voltage in EBZ was shifted to higher Vj in positive and negative directions. Immunoconfocal planimetry and quantification showed no change in connexin43 per unit cell volume or surface area in EBZ. Decreased side-to-side coupling occurs in EBZ myocytes, independent of reduced connexin43 expression, and is hypothesized to contribute to increased anisotropy and reentrant arrhythmias.

Atrial tachyarrhythmias late after Fontan operation are related to increase in mortality and hospitalization

BACKGROUND Atrial tachyarrhythmias are a known complication late after Fontan operation. Limited information is available on their prognostic value. METHODS All patients with previous Fontan operation followed at our institution since 1999 were identified from the electronic database and included in this study. Demographic and clinical characteristics including history of atrial tachyarrhythmias were recorded at the earliest full clinical assessment and patients were followed thereafter for all-cause mortality and hospitalization. RESULTS A total of 98 patients, mean age 31.5 ± 8.9 years, 43.8% male, 31.6% with a total cavopulmonary connection (TCPC) were identified. A history of atrial tachyarrhythmia was present at baseline in 60.2% of patients who were older (33.0 ± 8.3 vs 29.1 ± 9.4 years, p=0.002), less likely to have a TCPC (13.5% vs 58.9%, p<0.001), and more symptomatic in terms of NYHA class (51.9% vs 26.7%, p=0.007) compared to arrhythmia-free patients. During a median follow-up of 6.7 years 18 patients died and 64 patients were hospitalized. Even after adjustment for baseline clinical characteristics, atrial tachyarrhythmia was an independent predictor of death (propensity score adjusted HR 9.35, 95% CI: 1.10-79.18, p=0.04, c-statistic 0.88) and composite of death or hospitalization (propensity score adjusted HR 5.00, 95% CI: 2.47-10.09, p<0.0001). CONCLUSIONS In adult patients with a Fontan-type operation, the presence of atrial tachyarrhythmias is associated with higher morbidity and mortality at mid-term follow-up. Whether early arrhythmia targeting intervention may improve clinical outcome needs to be studied in a prospective manner.

Relationship between contact force sensing technology and medium-term outcome of atrial fibrillation ablation: a multicenter study of 600 patients.

Contact force sensing (CFS) technology improves acute pulmonary vein isolation durability; however, its impact on the clinical outcome of ablating atrial fibrillation (AF) is unknown.

The Renin–Angiotensin System Mediates the Effects of Stretch on Conduction Velocity, Connexin43 Expression, and Redistribution in Intact Ventricle

Effect of Stretch on Conduction and Cx43. Introduction: In disease states such as heart failure, myocardial infarction, and hypertrophy, changes in the expression and location of Connexin43 (Cx43) occur (Cx43 remodeling), and may predispose to arrhythmias. Stretch may be an important stimulus to Cx43 remodeling; however, it has only been investigated in neonatal cell cultures, which have different physiological properties than adult myocytes. We hypothesized that localized stretch in vivo causes Cx43 remodeling, with associated changes in conduction, mediated by the renin–angiotensin system (RAS).

Biatrial linear ablation in sustained nonpermanent AF: Results of the substrate modification with ablation and antiarrhythmic drugs in nonpermanent atrial fibrillation (SMAN-PAF) trial

BACKGROUND More advanced atrial fibrillation (AF) is associated with lower success rates after pulmonary vein isolation (PVI), and the optimal ablation strategy is uncertain. OBJECTIVES To assess the impact of additional linear ablation (lines) compared to PVI alone. METHODS In this multicenter randomized controlled trial, 122 patients (mean age 61.9 ± 10.5 years; left atrial diameter 43 ± 6 mm) with persistent AF (PeAF) or sustained (>12 hours) paroxysmal AF (SusPAF) with risk factors for atrial substrate were included and followed up for 12 months. Patients were randomized to PVI-only or PVI + lines (left atrial roof line, mitral isthmus line, and tricuspid isthmus line) group. Holter monitoring was performed at 3, 6, and 12 months and according to symptoms. The primary outcome was atrial tachyarrhythmia recurrence lasting ≥30 seconds. RESULTS Baseline characteristics were comparable between groups; 61% had PeAF and 39% SusPAF. Successful PVI was achieved for 98% of pulmonary veins, and bidirectional block was obtained in 90% of lines. The primary end point occurred in 38% of the PVI + lines group and 32% of the PVI-only group (P = .50), which was consistent in both PeAF (36% vs 28%; P = .45) and SusPAF (42% vs 39%; P = .86). Compared with the PVI-only group, the PVI + lines group had higher procedure duration (209 ± 52 minutes vs 172 ± 44 minutes; P < .001), ablation time (4352 ± 1084 seconds vs 2503 ± 1061 seconds; P < .001), and radiation exposure (Dose-area product 3992 ± 6496 Gy·cm(2) vs 2106 ± 1679 Gy·cm(2); P = .03). Quality of life (disease-specific Atrial Fibrillation Effect on Quality of Life questionnaire and mental component scale of the Short Form 36 Health Survey) improved significantly during the study but did not differ between groups. CONCLUSION Adding lines to wide antral PVI in substrate-based AF requires significantly more ablation, increases procedure duration and radiation dose, but provides no additional clinical benefit.

Outcomes and costs of left atrial appendage closure from randomized controlled trial and real-world experience relative to oral anticoagulation

AIMS The aim of this study was to analyse randomized controlled study and real-world outcomes of patients with non-valvular atrial fibrillation (NVAF) undergoing left atrial appendage closure (LAAC) with the Watchman device and to compare costs with available antithrombotic therapies. METHODS AND RESULTS Registry data of LAAC from two centres were prospectively collected from 110 patients with NVAF at risk of stroke, suitable and unsuitable for long-term anticoagulation (age 71.3 ± 9.2 years, CHADS2 2.8 ± 1.2, CHA2DS2-VASc 4.5 ± 1.6, and HAS-BLED 3.8 ± 1.1). Outcomes from PROTECT AF and registry study LAAC were compared with warfarin, dabigatran, rivaroxaban, apixaban, aspirin, and no treatment using a network meta-analysis. Costs were estimated over a 10-year horizon. Uncertainty was assessed using sensitivity analyses. The procedural success rate was 92% (103/112). Follow-up was 24.1 ± 4.6 months, during which annual rates of stroke, major bleeding, and all-cause mortality were 0.9% (2/223 patient-years), 0.9% (2/223 patient-years), and 1.8% (4/223 patient-years), respectively. Anticoagulant therapy was successfully stopped in 91.2% (93/102) of implanted patients by 12 months. Registry study LAAC stroke and major bleeding rates were significantly lower than PROTECT AF results: mean absolute difference of stroke, 0.89% (P = 0.02) and major bleeding, 5.48% (P < 0.001). Left atrial appendage closure achieved cost parity between 4.9 years vs. dabigatran 110 mg and 8.4 years vs. warfarin. At 10 years, LAAC was cost-saving against all therapies (range £1162-£7194). CONCLUSION Left atrial appendage closure in NVAF in a real-world setting may result in lower stroke and major bleeding rates than reported in LAAC clinical trials. Left atrial appendage closure in both settings achieves cost parity in a relatively short period of time and may offer substantial savings compared with current therapies. Savings are most pronounced among higher risk patients and those unsuitable for anticoagulation.

Permanent pacemaker implantation early and late after heart transplantation: Clinical indication, risk factors and prognostic implications

BACKGROUND Permanent pacemaker implantation (PPM) early after cardiac transplantation has been shown not to predict a worse outcome. However, the requirement for pacing late after transplantation and its prognostic implications are not fully known. We describe the clinical indications, risk factors and long-term outcome in patients who required pacing early and late after transplantation. METHODS The transplant database, medical records and pacing database/records were reviewed for all patients undergoing de novo orthotopic cardiac transplantation (n = 389) at our institution between January 1995 and May 2006. RESULTS A total of 48 patients (12.3%) received a pacemaker after transplantation. Of these patients, 30 were paced early, pre-hospital discharge (25 ± 19 days post-transplantation), and 18 patients had late pacing (3.0 ± 3.3 years post-transplantation). There were no differences in clinical characteristics, use of anti-arrhythmic drugs or length-of-stay post-transplantation between early and late groups. Early indications for pacing were more often sino-atrial (SA) disease (24 of 30, 80%), whereas atrio-ventricular (AV) disease was more likely to occur later (p = 0.03). Risk factors for PPM included use of biatrial anastomosis (p = 0.001) and donor age (p = 0.002). Prior rejection was a univariate but not multivariate (p = 0.09) predictor of the need for PPM. Development of cardiac allograft vasculopathy was not predictive. There was no significant difference in mortality between late and early PPM patients or between late PPM patients and the non-paced patients who survived transplantation and initial stay. CONCLUSIONS Patients who required PPM late after orthotopic cardiac transplantation had a prognosis comparable to those paced early and those who did not require PPM. The independent risk factors for PPM were biatrial anastomosis and increasing donor age. SA-nodal dysfunction as an indication for PPM was more prevalent early after transplantation, whereas atrioventricular (AV) disease more commonly presented late. The requirement for pacing late after transplantation was not associated with rejection or cardiac allograft vasculopathy.

Evaluation of a novel high-resolution mapping system for catheter ablation of ventricular arrhythmias.

BACKGROUND The mapping of ventricular arrhythmias in humans using a minibasket 64-electrode catheter paired with a novel automatic mapping system (Rhythmia) has not been evaluated. OBJECTIVE The purpose of this study was to evaluate the safety and efficacy of mapping ventricular arrhythmias and clinical outcomes after ablation using this system. METHODS Electroanatomic maps for ventricular arrhythmias were obtained during 20 consecutive procedures in 19 patients (12 with ventricular tachycardia [VT] and 2 with ventricular ectopy [VE]). High-density maps were acquired using automatic beat acceptance and automatic system annotation of electrograms. RESULTS Forty-seven electroanatomic maps (including 3 right ventricular and 9 epicardial maps) were obtained. Left ventricular endocardial mapping by transseptal (n = 13) and/or transaortic (n = 11) access was safe with no complications related to the minibasket catheter. VT substrate maps (n = 14; median 10,184 points) consistently demonstrated late potentials with high resolution. VT activation maps (n = 25; median 6401 points) obtained by automatic annotation included 7 complete maps (covering ≥90% of the tachycardia cycle length) in 5 patients in whom the entire VT circuit was accurately visualized. VE timing maps (n = 8) successfully localized the origin of VEs in all, with all accepted beats consistent with clinical VEs. Over a median follow-up of 10 months, no arrhythmia recurrence was noted in 75% after VT ablation and 86% after VE ablation. CONCLUSION In this first human experience for ventricular arrhythmias using this system, ultra-high-density maps were created rapidly and safely, with a reliable automatic annotation of VT and consistent recording of abnormal electrograms. Medium-term outcomes after ablation were encouraging. Further larger studies are needed to validate these findings.

Impact of stepwise ablation on the biatrial substrate in patients with persistent atrial fibrillation and heart failure.

Background—Ablation of persistent atrial fibrillation can be challenging, often involving not only pulmonary vein isolation (PVI) but also additional linear lesions and ablation of complex fractionated electrograms (CFE). We examined the impact of stepwise ablation on a human model of advanced atrial substrate of persistent atrial fibrillation in heart failure. Methods and Results—In 30 patients with persistent atrial fibrillation and left ventricular ejection fraction ⩽35%, high-density CFE maps were recorded biatrially at baseline, in the left atrium (LA) after PVI and linear lesions (roof and mitral isthmus), and biatrially after LA CFE ablation. Surface area of CFE (mean cycle length ⩽120 ms) remote to PVI and linear lesions, defined as CFE area, was reduced after PVI (18.3±12.03 to 10.2±7.1 cm2; P<0.001) and again after linear lesions (7.7±6.5 cm2; P=0.006). Complete mitral isthmus block predicted greater CFE reduction (P=0.02). Right atrial CFE area was reduced by LA ablation, from 25.9±14.1 to 12.9±11.8 cm2 (P<0.001). Estimated 1-year arrhythmia-free survival was 72% after a single procedure. Incomplete linear lesion block was an independent predictor of arrhythmia recurrence (hazard ratio, 4.69; 95% confidence interval, 1.05–21.06; P=0.04). Conclusions—Remote LA CFE area was progressively reduced following PVI and linear lesions, and LA ablation reduced right atrial CFE area. Reduction of CFE area at sites remote from ablation would suggest either regression of the advanced atrial substrate or that these CFE were functional phenomena. Nevertheless, in an advanced atrial fibrillation substrate, linear lesions after PVI diminished the target area for CFE ablation, and complete lesions resulted in a favorable clinical outcome.