Christopher S. Simpson

Pacemaker or Defibrillator Surgery without Interruption of Anticoagulation

BACKGROUND Many patients requiring pacemaker or implantable cardioverter-defibrillator (ICD) surgery are taking warfarin. For patients at high risk for thromboembolic events, guidelines recommend bridging therapy with heparin; however, case series suggest that it may be safe to perform surgery without interrupting warfarin treatment. There have been few results from clinical trials to support the safety and efficacy of this approach. METHODS We randomly assigned patients with an annual risk of thromboembolic events of 5% or more to continued warfarin treatment or to bridging therapy with heparin. The primary outcome was clinically significant device-pocket hematoma, which was defined as device-pocket hematoma that necessitated prolonged hospitalization, interruption of anticoagulation therapy, or further surgery (e.g., hematoma evacuation). RESULTS The data and safety monitoring board recommended termination of the trial after the second prespecified interim analysis. Clinically significant device-pocket hematoma occurred in 12 of 343 patients (3.5%) in the continued-warfarin group, as compared with 54 of 338 (16.0%) in the heparin-bridging group (relative risk, 0.19; 95% confidence interval, 0.10 to 0.36; P<0.001). Major surgical and thromboembolic complications were rare and did not differ significantly between the study groups. They included one episode of cardiac tamponade and one myocardial infarction in the heparin-bridging group and one stroke and one transient ischemic attack in the continued-warfarin group. CONCLUSIONS As compared with bridging therapy with heparin, a strategy of continued warfarin treatment at the time of pacemaker or ICD surgery markedly reduced the incidence of clinically significant device-pocket hematoma. (Funded by the Canadian Institutes of Health Research and the Ministry of Health and Long-Term Care of Ontario; BRUISE CONTROL ClinicalTrials.gov number, NCT00800137.).

Evaluation of Early Complications Related to De Novo Cardioverter Defibrillator Implantation : Insights From the Ontario ICD Database

OBJECTIVES This study examined the predictors of early complications after defibrillator implantation. BACKGROUND Although implantable cardioverter-defibrillators are widely used, predictors of procedural complications and the consequences of these events have not been determined. METHODS In a prospective, multicenter, population-based clinical outcomes registry of all newly implanted defibrillator patients at 18 centers in Ontario, Canada, we examined 45-day complications and all-cause mortality from February 2007 to May 2009. Complications were determined longitudinally and were categorized as direct implant-related or indirect events. RESULTS Among 3,340 patients (mean age 63.8 +/- 12.5 years, 78.5% men), major complications occurred in 4.1% of de novo procedures. Compared with those undergoing a single-chamber device, implantation of a cardiac resynchronization defibrillator (adjusted hazard ratio [HR]: 2.17, 95% confidence interval [CI]: 1.38 to 3.43, p < 0.001) or dual-chamber device (adjusted HR: 1.82, 95% CI: 1.19 to 2.79, p = 0.006) was associated with increased risk of major complications. Major complications were increased in women (adjusted HR: 1.49, 95% CI: 1.02 to 2.16, p = 0.037) and when left ventricular end-systolic dimension exceeded 45 mm (adjusted HR: 1.54, 95% CI: 1.08 to 2.20, p = 0.018). Major complications (excluding death) occurring early after defibrillator implantation were associated with increased adjusted risk of subsequent death up to 180 days after defibrillator implant (adjusted HR: 3.70, 95% CI: 1.64 to 8.33, p = 0.002). Direct implant-related complications were associated with increased risk of early death (adjusted HR: 24.89, p = 0.01), whereas indirect clinical complications conferred increased risk of near-term death (adjusted HR: 12.35, p < 0.001) after defibrillator implantation. CONCLUSIONS Complications after de novo defibrillator implantation were strongly associated with device type. Major complications were associated with increased risk of mortality.

Systematic Assessment of Patients With Unexplained Cardiac Arrest Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER)

Background— Cardiac arrest without evident cardiac disease may be caused by subclinical genetic conditions. Provocative testing to unmask a phenotype is often necessary to detect primary electrical disease, direct genetic testing, and perform family screening. Methods and Results— Patients with apparently unexplained cardiac arrest and no evident cardiac disease (normal cardiac function on echocardiogram, no evidence of coronary artery disease, and a normal ECG) underwent systematic evaluation that included cardiac magnetic resonance imaging, signal-averaged ECG, exercise testing, drug challenge, and selective electrophysiological testing. Diagnostic criteria were based on accepted criteria or provocation of the characteristic clinical features for long-QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization, arrhythmogenic right ventricular cardiomyopathy, coronary spasm, and myocarditis. Sixty-three patients in 9 centers were enrolled (age 43.0±13.4 years, 29 women). A diagnosis was obtained in 35 patients (56%): Long-QT syndrome in 8, catecholaminergic polymorphic ventricular tachycardia in 8, arrhythmogenic right ventricular cardiomyopathy in 6, early repolarization in 5, coronary spasm in 4, Brugada syndrome in 3, and myocarditis in 1. Targeted genetic testing demonstrated evidence of causative mutations in 9 (47%) of 19 patients. Screening of 64 family members of these patients identified 15 affected individuals who were treated (24%). The remaining 28 patients (44%) were considered to have idiopathic ventricular fibrillation. Conclusions— Systematic clinical testing, including drug provocation and advanced imaging, results in unmasking of the cause of apparently unexplained cardiac arrest in >50% of patients. This approach assists in directing genetic testing to diagnose genetically mediated arrhythmia syndromes, which results in successful family screening.

Complications associated with defibrillation threshold testing: The Canadian experience

BACKGROUND Defibrillation threshold (DFT) testing has traditionally been a routine part of implantable cardioverter-defibrillator (ICD) implantation, despite a lack of compelling evidence that it predicts or improves outcomes. In the past, when devices were much less reliable, DFT testing seemed prudent; however, modern ICD systems have such a high rate of successful defibrillation that many electrophysiologists now question whether DFT testing is still worthwhile, particularly since DFT testing may now be the highest acute risk component of ICD implantation. OBJECTIVE The purpose of this study was to systematically document complications directly attributable to intraoperative DFT testing. METHODS We obtained data on DFT-related complications from all 21 adult ICD implant centers in Canada, covering the period from January 1, 2000, to September 30, 2006. RESULTS There were a total of 19,067 ICD implants in Canada during the study period. There were three DFT testing-related deaths, five DFT testing-related strokes, and 27 episodes that required prolonged resuscitation. Two patients had significant clinical sequelae after prolonged resuscitation. CONCLUSIONS The risk of severe complications from intraoperative DFT testing appears small, even allowing for the underestimation of its true rate with the current study methodology. These slight but measurable risks must be considered when assessing the risk-benefit ratio of the procedure. Additional data from ongoing prospective ICD registries and/or clinical trials are required.

Prevalence and Characteristics of Early Repolarization in the CASPER Registry Cardiac Arrest Survivors With Preserved Ejection Fraction Registry

OBJECTIVES We evaluated the prevalence and characteristics of early repolarization in patients in CASPER (Cardiac Arrest Survivors With Preserved Ejection Fraction Registry). BACKGROUND Early repolarization has been implicated in a syndrome of polymorphic ventricular tachycardia and fibrillation in patients without organic heart disease. METHODS One hundred patients with apparently unexplained cardiac arrest and preserved ejection fraction underwent extensive clinical and genetic testing to unmask subclinical electrical or structural disease. A blinded independent analysis of the 12-lead electrocardiogram (ECG) was performed. Early repolarization was defined as ≥0.1 mV QRS-ST junction (J-point) elevation with terminal QRS slurring or notching in at least 2 contiguous inferior and/or lateral leads. RESULTS One hundred cardiac arrest patients were enrolled (40 females, age 43 ± 14 years). Forty-four were diagnosed with an established cause for cardiac arrest. Significant early repolarization was found in 19 patients, including 6 with a primary diagnosis that explained their cardiac arrest (14%), compared with 23% of the 56 patients with idiopathic ventricular fibrillation (IVF) (p = 0.23). J-point elevation in IVF patients had higher amplitude (0.25 ± 0.11 mV vs. 0.13 ± 0.05 mV, p = 0.02) and wider distribution (4.3 ± 1.3 leads vs. 2.8 ± 0.8 leads; p = 0.01) than those with an established cause of cardiac arrest. J-wave amplitude was fluctuant on serial ECGs; at least 1 ECG failed to demonstrate early repolarization in 58% of patients. CONCLUSIONS Early repolarization is present in a significant proportion of causally diagnosed and idiopathic VF. It is often intermittent and more pronounced in IVF patients. (Registry of Unexplained Cardiac Arrest; NCT00292032).

Predictors of Short-Term Complications After Implantable Cardioverter-Defibrillator Replacement: Results From the Ontario ICD Database

Background— Complications after implantable cardioverter-defibrillator (ICD) replacement are often clinically devastating, particularly when infection or reoperation occurs. Identifying factors contributing to complications may permit identification of high-risk individuals that warrant incremental monitoring and therapy to attenuate risk. In addition, replacement may be a discretionary decision in the context of an advisory or borderline device performance and patient, device, and implanter factors that predict adverse outcome may assist in clinical decision-making. Methods and Results— In a prospective, multicenter, population-based registry of all ICD patients at 18 centers in Ontario, Canada, we examined 45-day complication and all-cause mortality rates from February 2007 to August 2009 in patients undergoing ICD generator replacement. Complications were determined longitudinally and were categorized as major or minor. ICD replacement was performed in 1081 of 5176 patients (20.8%) undergoing ICD implantation (age, 64.3±12.7 years; 78.5% men). In patients undergoing ICD replacement, 47 patients (4.3%) had a complication within 45 days, with 47 major complications in 28 patients (2.6%), most commonly infection (n=23), lead revision (n=35), electrical storm (n=14), and pulmonary edema (n=13). Minor complications occurred in 2.3% of patients, most commonly incisional infection (n=10) and pocket hematoma (n=10). On multivariable analysis, risk factors associated with major complications were Canadian Cardiovascular Society angina class (adjusted hazard ratio [HR], 3.70 for class 2 to 4 versus 0 to 1; P=0.027) and multiple previous procedures on the pocket (adjusted HR, 3.35 for >1 versus 1; P=0.058). Risk factors associated with any complication were the use of antiarrhythmic therapy (adjusted HR, 6.29; P=0.001), implanter volume (adjusted HR 10.4 for <60/y versus >120/y, P=0.026), and Canadian Cardiovascular Society angina class (adjusted HR, 3.00 for class 2 to 4 versus 0 to 1; P=0.031). In a Cox model with a time-dependent variable of major complication within 45 days after replacement, major complications after ICD replacement were associated with an increased risk of mortality at 45, 90, and 180 days (adjusted HR, 9.61, 12.69, and 6.41, respectively; P=0.002 to 0.039). Conclusions— Risk factors associated with complications after ICD replacement include the presence of angina, antiarrhythmic therapy, increased number of previous procedures, and low implanter volume. Major complications may be associated with increased risk of subsequent mortality.

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.

Outcome of the Fidelis implantable cardioverter-defibrillator lead advisory: A report from the Canadian Heart Rhythm Society Device Advisory Committee

BACKGROUND The Medtronic Sprint Fidelis family of leads has recently been the subject of a widespread advisory. Lead failure rates are estimated at 2.3% at 30 months, 2.6 times the failure rate of the reference Medtronic 6947 lead. OBJECTIVE The purpose of this study was to contact pediatric and adult implantable cardioverter-defibrillator (ICD) implant centers across Canada to determine the short-term response to the October 15, 2007 Medtronic Fidelis lead advisory. METHODS All centers completed an 11-part survey to assess the frequency and presentation of lead failure, operator characteristics, and centers response. RESULTS Lead failure was noted in 80 (1.29%) of 6,181 patients at 21.0 months, with inappropriate shocks experienced in 45 (56%) of the 80 patients (overall risk 0.73%). No deaths were attributed to lead failure. Sensing was the primary form of failure, seen in 60 leads (75%), with pacing failure in 10 (13%), and high-voltage failure in 15 (19%). Assessment of the previous routine ICD interrogation prior to the advisory or lead failure demonstrated evidence of altered lead performance in only 8 (10%) of the 80 leads. Inappropriate shocks typically were multiple (median 7, range 1-122), with a single shock seen in only 5 patients. Lead failure was noted in 18 of 23 centers, representing 89.8% of leads implanted, with at least one failure noted in 15 of 16 centers that implanted more than 200 leads. Forty-seven of the 135 operators in the 23 institutions implanted the 80 leads that subsequently failed. Only 16 operators were involved in more than a single lead that subsequently failed; seven operators participated in three or more leads that subsequently failed. Seven centers planned to replace leads in most pacing-dependent patients, and two centers planned to replace leads in patients unable to hear the alert tone. CONCLUSION This national experience suggests a Fidelis lead failure rate of 1.29% at 21 months, most often presenting with multiple inappropriate shocks without evidence of impending failure from routine lead follow-up. Lead failure did not appear to cluster around specific operators or around high-volume or low-volume implant centers.

Cardiac Resynchronization Therapy in Patients with Permanent Atrial Fibrillation: Results from the Resynchronization for Ambulatory Heart Failure Trial (RAFT)

Background—Cardiac resynchronization (CRT) prolongs survival in patients with systolic heart failure and QRS prolongation. However, most trials excluded patients with permanent atrial fibrillation. Methods and Results—The Resynchronization for Ambulatory Heart Failure Trial (RAFT) randomized patients to an implantable cardioverter defibrillator (ICD) or ICD+CRT, stratified by the presence of permanent atrial fibrillation. Patients with permanent atrial fibrillation were randomized to CRT-ICD (n=114) or ICD (n=115). Patients receiving a CRT-ICD were similar to those receiving an ICD: age (71.6±7.3 versus 70.4±7.7 years), left ventricular ejection fraction (22.9±5.3% versus 22.3±5.1%), and QRS duration (151.0±23.6 versus 153.4±24.7 ms). There was no difference in the primary outcome of death or heart failure hospitalization between those assigned to CRT-ICD versus ICD (hazard ratio, 0.96; 95% CI, 0.65–1.41; P=0.82). Cardiovascular death was similar between treatment arms (hazard ratio, 0.97; 95% CI, 0.55–1.71; P=0.91); however, there was a trend for fewer heart failure hospitalizations with CRT-ICD (hazard ratio, 0.58; 95% CI, 0.38–1.01; P=0.052). The change in 6-minute hall walk duration between baseline and 12 months was not different between treatment arms (CRT-ICD: 19±84 m versus ICD: 16±76 m; P=0.88). Patients treated with CRT-ICD showed a trend for a greater improvement in Minnesota Living with Heart Failure score between baseline and 6 months (CRT-ICD: 41±21 to 31±21; ICD: 33±20 to 28±20; P=0.057). Conclusions—Patients with permanent atrial fibrillation who are otherwise CRT candidates appear to gain minimal benefit from CRT-ICD compared with a standard ICD. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00251251.Background— Cardiac resynchronization (CRT) prolongs survival in patients with systolic heart failure and QRS prolongation. However, most trials excluded patients with permanent atrial fibrillation. Methods and Results— The Resynchronization for Ambulatory Heart Failure Trial (RAFT) randomized patients to an implantable cardioverter defibrillator (ICD) or ICD+CRT, stratified by the presence of permanent atrial fibrillation. Patients with permanent atrial fibrillation were randomized to CRT-ICD (n=114) or ICD (n=115). Patients receiving a CRT-ICD were similar to those receiving an ICD: age (71.6±7.3 versus 70.4±7.7 years), left ventricular ejection fraction (22.9±5.3% versus 22.3±5.1%), and QRS duration (151.0±23.6 versus 153.4±24.7 ms). There was no difference in the primary outcome of death or heart failure hospitalization between those assigned to CRT-ICD versus ICD (hazard ratio, 0.96; 95% CI, 0.65–1.41; P =0.82). Cardiovascular death was similar between treatment arms (hazard ratio, 0.97; 95% CI, 0.55–1.71; P =0.91); however, there was a trend for fewer heart failure hospitalizations with CRT-ICD (hazard ratio, 0.58; 95% CI, 0.38–1.01; P =0.052). The change in 6-minute hall walk duration between baseline and 12 months was not different between treatment arms (CRT-ICD: 19±84 m versus ICD: 16±76 m; P =0.88). Patients treated with CRT-ICD showed a trend for a greater improvement in Minnesota Living with Heart Failure score between baseline and 6 months (CRT-ICD: 41±21 to 31±21; ICD: 33±20 to 28±20; P =0.057). Conclusions— Patients with permanent atrial fibrillation who are otherwise CRT candidates appear to gain minimal benefit from CRT-ICD compared with a standard ICD. Clinical Trial Registration— URL: . Unique identifier: [NCT00251251][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00251251&atom=%2Fcirchf%2F5%2F5%2F566.atom

Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database.

BACKGROUND Sex differences in the use and outcomes of implantable cardioverter-defibrillators (ICDs) have not been fully studied. OBJECTIVE To examine potential sex differences in ICD implantation and device outcomes. DESIGN Health payer-mandated, prospective study of patients referred for ICD implantation, with comprehensive, longitudinal follow-up for complications, deaths, and device outcomes. SETTING 18 ICD implantation and follow-up centers in Ontario, Canada. PATIENTS 6021 patients (4733 men) referred for ICD implantation from February 2007 to July 2010. MEASUREMENTS Multivariate-adjusted ICD implantation rate, complications up to day 45, multivariate-adjusted complications, device outcomes (including appropriate shocks and therapies), and deaths occurring during 1-year follow-up. RESULTS Rates of ICD implantation were similar in men and women (relative risk, 0.99 [95% CI, 0.97 to 1.02]; P = 0.60). However, women were significantly more likely to experience major complications by 45 days (odds ratio, 1.78 [CI, 1.24 to 2.58]; P = 0.002) and 1 year (hazard ratio [HR], 1.91 [CI, 1.48 to 2.47]; P < 0.001) after implantation. Occurrence of any major or minor complication was also increased in women at both 45-day follow-up (odds ratio, 1.50 [CI, 1.12 to 2.00]; P = 0.006) and 1-year follow-up (HR, 1.55 [CI, 1.25 to 1.93]; P < 0.001). After implantation, women were less likely than men to receive appropriate ICD shock (HR, 0.69 [CI, 0.51 to 0.93]; P = 0.015) or appropriate therapy via shock or antitachycardia pacing (HR, 0.73 [CI, 0.59 to 0.90]; P = 0.003). Total mortality among defibrillator recipients did not differ between men and women (HR, 1.00 [CI, 0.64 to 1.55]; P = 0.99). LIMITATION The differential effects of sex on prereferral events were not examined. CONCLUSION Although ICD implantation rates were similar after referral to an electrophysiologist, women who underwent ICD implantation had greater risks for complications and were less likely to experience appropriate ICD-delivered therapies than men. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research and Ontario Ministry of Health and Long-Term Care.