Bernard Thibault

Rhythm control versus rate control for atrial fibrillation and heart failure.

BACKGROUND It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied. METHODS We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes. RESULTS A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P=0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup. CONCLUSIONS In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. (ClinicalTrials.gov number, NCT00597077.)

Amiodarone to Prevent Recurrence of Atrial Fibrillation

Background The restoration and maintenance of sinus rhythm is a desirable goal in patients with atrial fibrillation, because the prevention of recurrences can improve cardiac function and relieve symptoms. Uncontrolled studies have suggested that amiodarone in low doses may be more effective and safer than other agents in preventing recurrence, but this agent has not been tested in a large, randomized trial. Methods We undertook a prospective, multicenter trial to test the hypothesis that low doses of amiodarone would be more efficacious in preventing recurrent atrial fibrillation than therapy with sotalol or propafenone. We randomly assigned patients who had had at least one episode of atrial fibrillation within the previous six months to amiodarone or to sotalol or propafenone, given in an open-label fashion. The patients in the group assigned to sotalol or propafenone underwent a second randomization to determine whether they would receive sotalol or propafenone first; if the first drug was unsuccessfu...

Efficacy and safety of cryoballoon ablation for atrial fibrillation: A systematic review of published studies

Further-more, the procedure is complex, time consuming, andhighly dependent on operator competency given the diffi-culties associated with creating contiguous curvilinear le-sions with focal ablation. As such, considerable effort hasbeen directed toward deriving more effective and saferapproaches.Balloon-based ablation systems potentially offer a sim-pler and faster means of achieving pulmonary vein isolation(PVI) that, theoretically, is less reliant on operator dexterity.Concurrently, cryothermal energy offers advantages overRF energy, including increased catheter stability, less endo-thelial disruption with lower thromboembolic risk, and min-imal tissue contraction with healing, an observation thoughtto result in less esophageal damage and PVS.

Feasibility of cardiac cryoablation using a transvenous steerable electrode catheter

We investigated the feasibility of using cryogenic technology in an electrode catheter for percutaneous ablation of cardiac tissue. Despite its high success rate, radiofrequency catheter ablation has important limitations especially with regards to the treatment of ventricular arrhythmias associated with a chronic scar. Arrhythmia surgery experience has shown that freezing with a hand held probe can permanently ablate the arrhythmogenic substrate of ventricular tachycardia associated with an old scar. Moreover, cryosurgery also allows for reversible “ice mapping,” in which the area likely responsible for the arrhythmia can be evaluated by suppressing its electrophysiologic properties prior to the creation of an irreversible state. A new steerable cryoablation catheter using Halocarbon 502 as a refrigerant was utilized in six dogs. Serial cryoapplications were performed in the right and left ventricles. In two dogs, we attempted reversible ice mapping of the AV node. Pathological evaluation of the lesions was done acutely in all the animals. Forty-two cryoapplications were delivered at a mean temperature of −45 ± 9.8°C. No lesion was found at pathological evaluation for 16 cryoapplications which did not achieve a temperature of less (colder) than −30°C. The remaining applications resulted in 26 lesions which were hemorrhagic and sharply demarcated from normal myocardium. Histological evaluation revealed contraction band necrosis. Reversible ice mapping of the AV node was successfully achieved in two animals. Cryoablation is feasible using an electrode catheter with multiple electrodes. This technology has the potential to allow for reversible ice mapping to confirm a successful ablation target before definitive ablation.

Ventricular Tachycardia Ablation versus Escalation of Antiarrhythmic Drugs

BACKGROUND Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain. METHODS We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock. RESULTS Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group. CONCLUSIONS In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH ClinicalTrials.gov number, NCT00905853.).

Transvenous Catheter Ice Mapping and Cryoablation of the Atrioventricular Node in Dogs

While radiofrequency catheter ablation is very effective, it does not allow for prediction of success prior to full delivery of the energy. We investigated the use of cryoablation using a new catheter on the AV node to determine (1) if a successful site might be identified prior to the ablation itself, and (2) the parameters of cryoablation of the AV node using a new cryocatheter. In eight dogs, the cryoablation catheter was advanced to the AV node to produce transient high degree AV block by lowering the temperature to a minimum of −40°C (ice mapping). Transient high degree AV node block was obtained in seven of eight animals at a mean temperature of −39.9 ± 11.6°C. No significant pathological modification was found in all animals but one and, in all cases, electrophysiological parameters of the A V node measured before, 20 minutes, 60 minutes, and up to 56 days after cryoapplication were not significantly different. In the 12 other dogs, after ice mapping, cryoablation of the A V node was attempted with a single freeze‐thaw cycle in 6 dogs (group 1) and a double freeze‐thaw cycle in the other 6 dogs (group II). Chronic complete AV block was obtained in only one animal in group I compared to all animals in group II. Ablation of the A V node is effective with a double freeze‐thaw cycle using a percutaneous catheter cryoablation system. Ice mapping of the area allows for identification of the targeted site.

Maintenance of sinus rhythm and survival in patients with heart failure and atrial fibrillation.

OBJECTIVES The goal of this study was to evaluate the relationship between the presence of sinus rhythm and outcomes in patients with a history of congestive heart failure (CHF) and atrial fibrillation (AF). BACKGROUND The value of sinus rhythm maintenance in patients with AF and heart failure (HF) is uncertain. METHODS A total of 1,376 patients with AF, ejection fraction < or =35%, and heart failure symptoms were randomized to a rhythm- or rate-control strategy. Detailed efficacy analyses were used to evaluate the independent effects of treatment strategy and the presence of sinus rhythm on cardiovascular outcomes. RESULTS Overall, 445 (32%) patients died and 402 (29%) experienced worsening HF. The rhythm-control strategy was not predictive of cardiovascular mortality (hazard ratio [HR]: 0.90, 95% confidence interval [CI]: 0.70 to 1.16; p = 0.41), all-cause death (HR: 0.86, 95% CI: 0.69 to 1.08; p = 0.19), or worsening HF (HR: 0.86, 95% CI: 0.68 to 1.10; p = 0.23). In analyses devised to isolate the effect of underlying rhythm, sinus rhythm was not associated with cardiovascular mortality [HR: 1.22, 95% CI: 0.80 to 1.87; p = 0.35), total mortality [HR: 1.11, 95% CI: 0.78 to 1.58; p = 0.57), or worsening HF [HR: 0.62, 95% CI: 0.37 to 1.02; p = 0.059). CONCLUSIONS A rhythm-control strategy or the presence of sinus rhythm are not associated with better outcomes in patients with AF and CHF.

Cardioverter defibrillator implantation without induction of ventricular fibrillation: A single-blind, non-inferiority, randomised controlled trial (SIMPLE)

BACKGROUND Defibrillation testing by induction and termination of ventricular fibrillation is widely done at the time of implantation of implantable cardioverter defibrillators (ICDs). We aimed to compare the efficacy and safety of ICD implantation without defibrillation testing versus the standard of ICD implantation with defibrillation testing. METHODS In this single-blind, randomised, multicentre, non-inferiority trial (Shockless IMPLant Evaluation [SIMPLE]), we recruited patients aged older than 18 years receiving their first ICD for standard indications at 85 hospitals in 18 countries worldwide. Exclusion criteria included pregnancy, awaiting transplantation, particpation in another randomised trial, unavailability for follow-up, or if it was expected that the ICD would have to be implanted on the right-hand side of the chest. Patients undergoing initial implantation of a Boston Scientific ICD were randomly assigned (1:1) using a computer-generated sequence to have either defibrillation testing (testing group) or not (no-testing group). We used random block sizes to conceal treatment allocation from the patients, and randomisation was stratified by clinical centre. Our primary efficacy analysis tested the intention-to-treat population for non-inferiority of no-testing versus testing by use of a composite outcome of arrhythmic death or failed appropriate shock (ie, a shock that did not terminate a spontaneous episode of ventricular tachycardia or fibrillation). The non-inferiority margin was a hazard ratio (HR) of 1·5 calculated from a proportional hazards model with no-testing versus testing as the only covariate; if the upper bound of the 95% CI was less than 1·5, we concluded that ICD insertion without testing was non-inferior to ICD with testing. We examined safety with two, 30 day, adverse event outcome clusters. The trial is registered with ClinicalTrials.gov, number NCT00800384. FINDINGS Between Jan 13, 2009, and April 4, 2011, of 2500 eligible patients, 1253 were randomly assigned to defibrillation testing and 1247 to no-testing, and followed up for a mean of 3·1 years (SD 1·0). The primary outcome of arrhythmic death or failed appropriate shock occurred in fewer patients (90 [7% per year]) in the no-testing group than patients who did receive it (104 [8% per year]; HR 0·86, 95% CI 0·65-1·14; pnon-inferiority <0·0001). The first safety composite outcome occurred in 69 (5·6%) of 1236 patients with no-testing and in 81 (6·5%) of 1242 patients with defibrillation testing, p=0·33. The second, pre-specified safety composite outcome, which included only events most likely to be directly caused by testing, occurred in 3·2% of patients with no-testing and in 4·5% with defibrillation testing, p=0·08. Heart failure needing intravenous treatment with inotropes or diuretics was the most common adverse event (in 20 [2%] of 1236 patients in the no-testing group vs 28 [2%] of 1242 patients in the testing group, p=0·25). INTERPRETATION Routine defibrillation testing at the time of ICD implantation is generally well tolerated, but does not improve shock efficacy or reduce arrhythmic death. FUNDING Boston Scientific and the Heart and Stroke Foundation (Ontario Provincial office).

Complications Associated With Revision of Sprint Fidelis Leads Report From the Canadian Heart Rhythm Society Device Advisory Committee

Background— It has been observed that replacement of an implantable cardioverter-defibrillator generator in response to a device advisory may be associated with a substantial rate of complications, including death. The risk of lead revision in response to a lead advisory has not been determined previously. Methods and Results— Twenty-five implantable cardioverter-defibrillator implantation and follow-up centers from the Canadian Heart Rhythm Society Device Advisory Committee were surveyed to assess complication rates as a result of lead revisions due to the Sprint Fidelis advisory issued in October 2007. As of June 1, 2009, there had been 310 lead failures found in 6237 Sprint Fidelis leads in Canada (4.97%) over a follow-up of 40 months. There were 469 leads to be revised, 66% for confirmed fracture. Of the patients who underwent revision, 95% had a new lead inserted, whereas 4% had a pace/sense lead added. The lead was removed in 248 cases (53%), by simple traction in 61% and by laser lead extraction in 33%. Complications were encountered in 14.5% of the lead revisions; 7.25% of these were major, whereas 7.25% were minor. There were 2 deaths (0.43%). The overall risk of complications (19.8%) was greater in those who underwent lead removal at the time of revision than in those whose leads were abandoned (8.6%; P=0.0008). Conclusions— The overall rate of major complications that arose from lead revision due to the Sprint Fidelis advisory was significant. This must be taken into account when lead revision is planned in those patients who have not yet demonstrated an abnormality in lead performance.

Cardiac Resynchronization Therapy in Patients With Heart Failure and a QRS Complex <120 Milliseconds The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) Trial

Background— Although the benefits of cardiac resynchronization therapy are well established in selected patients with heart failure and a prolonged QRS duration, salutary effects in patients with narrow QRS complexes remain to be demonstrated. Methods and Results— The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial is a randomized, double-blind, 12-center study that was designed to compare the effects of active and inactive cardiac resynchronization therapy in patients with severe left ventricular dysfunction and a QRS duration <120 milliseconds. The trial was interrupted prematurely by the Data Safety and Monitoring Board because of futility and safety concerns after 85 patients were randomized. Changes in exercise duration after 12 months were no different in patients with and without active cardiac resynchronization therapy (−0.7 minutes [95% confidence interval (CI), −2.9 to 1.5] versus 0.8 minutes [95% CI, −1.2 to 2.9]; P=0.31]. Similarly, no significant differences were observed in left ventricular end-systolic volumes (−6.4 mL [95% CI, −18.8 to 5.9] versus 3.1 mL [95% CI, −9.2 to 15.5]; P=0.28) and ejection fraction (3.3% [95% CI, 0.7–6.0] versus 2.1% [95% CI, −0.5 to 4.8]; P=0.52). Moreover, cardiac resynchronization therapy was associated with a significant reduction in the 6-minute walk distance (−11.3 m [95% CI, −31.7 to 9.7] versus 25.3 m [95% CI, 6.1–44.5]; P=0.01), an increase in QRS duration (40.2 milliseconds [95% CI, 34.2–46.2] versus 3.4 milliseconds [95% CI, 0.6–6.2]; P<0.0001), and a nonsignificant trend toward an increase in heart failure–related hospitalizations (15 hospitalizations in 5 patients versus 4 hospitalizations in 4 patients). Conclusions— In patients with a left ventricular ejection fraction ⩽35%, symptoms of heart failure, and a QRS duration <120 milliseconds, cardiac resynchronization therapy did not improve clinical outcomes or left ventricular remodeling and was associated with potential harm. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00900549.Background —While the benefits of cardiac resynchronization therapy (CRT) are well established in selected patients with heart failure and a prolonged QRS duration, salutary effects in patients with narrow QRS complexes remain to be demonstrated. Methods and Results —The LESSER-EARTH trial is a randomized, double-blind, 12-center study that was designed to compare the effects of active versus inactive CRT therapy in patients with severe left ventricular dysfunction and a QRS duration <120 ms. The trial was prematurely interrupted by the Data Safety and Monitoring Board due to futility and safety concerns after 85 patients were randomized. Changes in exercise duration after 12 months were no different in patients with and without active CRT [-0.7 (-2.9, 1.5) minutes versus +0.8 (-1.2, 2.9) minutes, P =0.31]. Similarly, no significant differences were observed in left ventricular end-systolic volumes [-6.4 (-18.8, 5.9) mL versus +3.1 (-9.2, 15.5) mL, P =0.28] and ejection fraction [+3.3% (0.7%, 6.0%) versus +2.1% (-0.5%, 4.8%), P =0.52]. Moreover, CRT was associated with a significant reduction in the 6-minute walk distance [-11.3 (-31.7, 9.7) meters versus +25.3 (6.1, 44.5) meters, P =0.01], an increase in QRS duration [40.2 (34.2, 46.2) ms versus 3.4 (0.6, 6.2) ms, P <0.0001], and a non-significant trend towards an increase in heart failure-related hospitalizations (15 hospitalizations in 5 patients versus 4 hospitalizations in 4 patients). Conclusions —In patients with a left ventricular ejection fraction ≤35%, symptoms of heart failure, and a QRS duration <120 ms, CRT did not improve clinical outcomes or left ventricular remodelling, and was associated with potential harm. Clinical Trial Registration Information —ClinicalTrials.gov. Identifier: [NCT00900549][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00900549&atom=%2Fcirculationaha%2Fearly%2F2013%2F02%2F05%2FCIRCULATIONAHA.112.001239.atom