Martin S. Green

Canadian Implantable Defibrillator Study (CIDS) A Randomized Trial of the Implantable Cardioverter Defibrillator Against Amiodarone

BACKGROUND Patients surviving ventricular fibrillation (VF) or sustained ventricular tachycardia (VT) are at a high risk of death due to a recurrence of arrhythmia. The implantable cardioverter defibrillator (ICD) terminates VT or VF, but it is not known whether this device prolongs life in these patients compared with medical therapy with amiodarone. METHODS AND RESULTS A total of 659 patients with resuscitated VF or VT or with unmonitored syncope were randomly assigned to treatment with the ICD or with amiodarone. The primary outcome measure was all-cause mortality, and the secondary outcome was arrhythmic death. A total of 328 patients were randomized to receive an ICD. A thoracotomy was done in 33, no ICD was implanted in 18, and the rest had a nonthoracotomy ICD. All 331 patients randomized to amiodarone received it initially. At 5 years, 85.4% of patients assigned to amiodarone were still receiving it at a mean dose of 255 mg/day, 28.1% of ICD patients were also receiving amiodarone, and 21.4% of amiodarone patients had received an ICD. A nonsignificant reduction in the risk of death was observed with the ICD, from 10.2% per year to 8.3% per year (19.7% relative risk reduction; 95% confidence interval, -7.7% to 40%; P=0.142). A nonsignificant reduction in the risk of arrhythmic death was observed, from 4.5% per year to 3.0% per year (32.8% relative risk reduction; 95% confidence interval, -7.2% to 57.8%; P=0.094). CONCLUSIONS A 20% relative risk reduction occurred in all-cause mortality and a 33% reduction occurred in arrhythmic mortality with ICD therapy compared with amiodarone; this reduction did not reach statistical significance.

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...

Identification of A gene responsible for familial wolff-parkinson-white syndrome

Background The Wolff–Parkinson–White syndrome, with a prevalence in Western countries of 1.5 to 3.1 per 1000 persons, causes considerable morbidity and may cause sudden death. We identified two families in which the Wolff–Parkinson–White syndrome segregated as an autosomal dominant disorder. Methods We studied 70 members of the two families (57 in Family 1 and 13 in Family 2). The subjects underwent 12-lead electrocardiography and two-dimensional echocardiography. Genotyping mapped the gene responsible to 7q34–q36, a locus previously identified to be responsible for an inherited form of Wolff–Parkinson–White syndrome. Candidate genes were identified, sequenced, and analyzed in normal and affected family members to identify the disease-causing gene. Results A total of 31 members (23 from Family 1 and 8 from Family 2) had the Wolff–Parkinson–White syndrome. Affected members of both families had ventricular preexcitation with conduction abnormalities and cardiac hypertrophy. The maximal combined two-point lo...

Significance of ventricular arrhythmias initiated by programmed ventricular stimulation: the importance of the type of ventricular arrhythmia induced and the number of premature stimuli required.

An increasing number of premature ventricular stimuli are being used during programmed stimulation of the heart in the investigation of patients with documented or suspected ventricular arrhythmias. To analyze the significance of the different types of ventricular arrhythmias that are initiated, we evaluated in a prospective study the effect of from one to four ventricular premature stimuli in 52 patients without (non-VT group) and 50 patients with (prior-VT group) documented ventricular tachycardia or ventricular fibrillation. More than half of the patients in the prior-VT group had coronary heart disease. In the majority of patients of the non-VT group the heart was normal. In 44 of the 50 patients in the prior-VT group the clinically documented ventricular arrhythmia was initiated by programmed ventricular stimulation of the heart. In 88% of these 44 patients, one or two ventricular premature beats were required to initiate the clinical arrhythmia. A ventricular arrhythmia could be initiated in 31 of the 52 patients in the non-VT group. The ventricular arrhythmias included nonsustained monomorphic ventricular tachycardia (two patients), six to 25 complexes of sustained polymorphic ventricular tachycardia (24 patients), and ventricular fibrillation (five patients). In 70% of patients in the non-VT group three or four ventricular premature beats were required to initiate the ventricular arrhythmia. Our results indicate that not only the number of extrastimuli required to initiate ventricular arrhythmias but also the type of ventricular arrhythmia initiated differed between the two groups of patients. Nonsustained polymorphic ventricular tachycardia and ventricular fibrillation are nonspecific responses to aggressive stimulation protocols.

New-Onset Atrial Fibrillation

Background—Although sex differences in coronary artery disease have received considerable attention, few studies have dealt with sex differences in the most common sustained cardiac arrhythmia, atrial fibrillation (AF). Differences in presentation and clinical course may dictate different approaches to detection and management. We sought to examine sex-related differences in presentation, treatment, and outcome in patients presenting with new-onset AF. Methods and Results—The Canadian Registry of Atrial Fibrillation (CARAF) enrolled subjects at the time of first ECG-confirmed diagnosis of AF. Participants were followed at 3 months, at 1 year, and annually thereafter. Treatment was at the discretion of the patients’ physicians and was not directed by CARAF investigators. Baseline and follow-up data collection included a detailed medical history, clinical, ECG, and echocardiographic measures, medication history, and therapeutic interventions. Three hundred thirty-nine women and 560 men were followed for 4.1...

Canadian Implantable Defibrillator Study (CIDS): Study design and organization

The Canadian Implantable Defibrillator Study (CIDS) is an on-going randomized multicenter clinical trial that compares implantable cardioverter-defibrillator (ICD) therapy against amiodarone in patients with prior cardiac arrest or hemodynamically unstable ventricular tachycardia. Eligible patients are equally randomized to receive or not receive an ICD as initial management. Those not receiving an ICD receive amiodarone. All patients are seen in follow-up every 6 months. The primary outcome event cluster is arrhythmic death or any other death occurring within 30 days of therapy initiation. Secondary outcomes are all-cause mortality and nonfatal occurrences of ventricular tachycardia or fibrillation. The goal of the study is to recruit 400 patients over 4 years. All patients will be followed to the end of the year. This will result in an 80% chance of detecting a reduction in arrhythmic death of 58% by ICD if such a difference in truth exists. Recruitment began in October 1990 and 184 patients have been enrolled to date.

Arrhythmia characterization and long-term outcomes in catecholaminergic polymorphic ventricular tachycardia.

BACKGROUND Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by adrenergically induced ventricular tachycardia (VT) associated with syncope and sudden death. OBJECTIVE This study sought to characterize arrhythmias associated with CPVT with respect to provocation by exercise and drugs, electrocardiographic characteristics, and association with long-term outcomes; and to explore the relation between age and clinical presentation. METHODS Seventy patients from 16 families were evaluated with exercise and selective adrenaline challenge, and screened for RyR2 mutations. CPVT was diagnosed in probands with symptoms and stress- or adrenaline-provoked VT, or in asymptomatic relatives with provoked VT or RyR2 mutations. Patients were followed up for recurrent syncope, VT, and sudden death. RESULTS Twenty-seven patients including 16 probands were identified (median age 35 years, 67% female). Presentation was cardiac arrest in 33% and syncope in 56%, and 11% were asymptomatic. Polymorphic or bidirectional VT was provoked with exercise in 63% and adrenaline in 82%. The initiating beat of VT was late-coupled and wide (coupling interval 418 ± 42 ms; QRSd 131 ± 17 ms), and QRS morphology suggested an outflow tract origin in 59%. During follow-up of 6.2 ± 5.7 years, 2 patients died despite an implantable cardioverter-defibrillator (ICD), 4 patients received ICD therapy for VT, and 5 patients had inappropriate therapy for supraventricular tachycardia. Patients presenting with late-onset CPVT (age > 21; n = 10) were often female (80%) and less likely to have RyR2 (Ryanodine receptor type 2) mutations (33%), and fatal events were not observed during follow-up (4.1 ± 3.6 years). CONCLUSION Ventricular arrhythmia in CPVT is often initiated from the outflow tract region. Despite β-blocker therapy and selective ICD implantation, breakthrough arrhythmias occur and may be associated with adverse outcomes.

Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper.

The era of gene discovery and molecular medicine has had a significant impact on clinical practice. Knowledge of specific genetic findings causative for or associated with human disease may enhance diagnostic accuracy and influence treatment decisions. In cardiovascular disease, gene discovery for inherited arrhythmia syndromes has advanced most rapidly. The arrhythmia specialist is often confronted with the challenge of diagnosing and managing genetic arrhythmia syndromes. There is now a clear need for guidelines on the appropriate use of genetic testing for the most common genetic conditions associated with a risk of sudden cardiac death. This document represents the first ever published recommendations outlining the role of genetic testing in various clinical scenarios, the specific genes to be considered for testing, and the utility of test results in the management of patients and their families.

Relationship Between Pacemaker Dependency and the Effect of Pacing Mode on Cardiovascular Outcomes

Background—A recently completed trial, the Canadian Trial of Physiological Pacing (CTOPP), showed that physiological pacing did not significantly reduce mortality, stroke, or heart failure hospitalization, but it did show that atrial fibrillation occurred less frequently in patients with physiological pacing. Many pacemaker patients experience only transient bradyarrhythmias with an adequate unpaced heart rate (UHR) and are not pacemaker-dependent. The purpose of the present analysis was to determine if pacemaker-dependent patients have an increased benefit from physiological pacing compared with non–pacemaker-dependent patients. Methods and Results—Of 2568 patients included in the CTOPP trial, 2244 patients had a pacemaker dependency test performed at the first follow-up visit. The yearly event rate of cardiovascular death or stroke steadily increased with decreasing UHR in the ventricular pacing group, but it remained constant in the physiological pacing group. When the patients were subdivided to UHR ≤60 bpm or >60 bpm, there was an interaction between pacing mode treatment and UHR subgroup. The Kaplan-Meier plot confirmed a physiological pacing advantage only in the UHR ≤60 bpm subgroup. This differential effect was also present for the outcomes of cardiovascular death and total mortality. Conclusions—This study demonstrated that UHR at first follow-up has an important influence on how pacing mode selection affects cardiovascular death and total mortality. Pacemaker-dependent patients with low UHR will probably be paced frequently and will likely benefit from physiological pacing. In contrast, non–pacemaker-dependent patients will likely be paced infrequently and may not benefit from physiological pacing.

Value of QRS alteration in determining the site of origin of narrow QRS supraventricular tachycardia.

To determine the value of alternation of QRS morphology in determining the site of origin of sustained narrow QRS supraventricular tachycardia (SVT), we retrospectively studied 163 distinct tachycardias in 161 patients (ages 4 to 91 years) in whom the site of origin of SVT was proven by intracardiac electrophysiologic study. Sustained SVT was defined as lasting longer than 30 sec. Narrow QRS was defined as QRS width less than 0.12 sec. Atrial fibrillation and flutter were excluded. The presence or absence of QRS alternation was judged at least 10 sec after initiation of SVT. Circus movement tachycardia with anterograde AV node conduction and a retrograde accessory AV pathway was seen in 89 patients (58 with Wolff-Parkinson-White syndrome, 31 with concealed accessory pathway); intra-AV nodal reentrant tachycardia (AVNT) was present in 57 cases, and 17 tachycardias were atrial in origin. QRS alternation was present in 36 of 163 cases (22%). In only eight of these 36 did RR interval length alternation accompany alternation in QRS morphology. Thirty-three of 36 (92%) tachycardias with QRS alternation were circus movement tachycardias. Two were atrial in origin and one was AVNT. We conclude that the presence of QRS alternation during sustained narrow QRS SVT is highly indicative of a retrograde accessory AV pathway in the tachycardia circuit.