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Biomedical subjects

S J Connolly

Publications and source records attributed to S J Connolly.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antiarrhythmic effects of azimilide in atrial fibrillation: efficacy and dose-response. Azimilide Supraventricular Arrhythmia Program 3 (SVA-3) Investigators.

OBJECTIVES: The purpose of this study was to assess the effectiveness of azimilide, a class III antiarrhythmic drug, in reducing the frequency of symptomatic arrhythmia recurrences in patients with atrial fibrillation, atrial flutter or both. BACKGROUND: Atrial fibrillation is an increasingly common disorder of the heart rhythm, and most patients with this problem are identified because they have symptoms associated with their arrhythmia. New antiarrhythmic therapies are needed to treat patients with this problem. METHODS: A total of 384 patients with a history of atrial fibrillation, atrial flutter or both were randomly assigned to receive once daily doses of placebo or azimilide; recurrent symptomatic arrhythmias were documented using transtelephonic electrocardiogram (ECG) recording. Azimilide 50 mg, 100 mg or 125 mg was tested; the primary efficacy analysis compared the time to first symptomatic recurrence in the combined azimilide 100 mg and 125 mg dose groups with that in the placebo group using the log-rank test. RESULTS: In the primary efficacy analysis, the time to first symptomatic arrhythmia recurrence was significantly prolonged in the combined azimilide 100 mg and 125 mg daily dose group compared with the placebo group (chi-square 7.96, p = 0.005); the hazard ratio (placebo: azimilide) for this comparison was 1.58 (95% confidence interval [CI] = 1.15, 2.16). In comparisons between individual doses and placebo, the hazard ratio for the 50 mg daily dose was 1.17 (95% CI = 0.83, 1.66; p = 0.37); for the 100 mg group, dose was 1.38 (95% CI = 0.96, 1.98; p = 0.08), and for the 125 mg group, dose was 1.83 (95% CI = 1.24, 2.70; p = 0.002). CONCLUSIONS: Azimilide significantly lengthened the symptomatic arrhythmia-free interval in patients with a history of atrial fibrillation, atrial flutter or both.

Aged↗
PubMed2000

Meta-analysis of the implantable cardioverter defibrillator secondary prevention trials. AVID, CASH and CIDS studies. Antiarrhythmics vs Implantable Defibrillator study. Cardiac Arrest Study Hamburg . Canadian Implantable Defibrillator Study.

AIMS: Three randomized trials of implantable cardioverter defibrillator (ICD) therapy vs medical treatment for the prevention of death in survivors of ventricular fibrillation or sustained ventricular tachycardia have been reported with what might appear to be different results. The present analysis was performed to obtain the most precise estimate of the efficacy of the ICD, compared to amiodarone, for prolonging survival in patients with malignant ventricular arrhythmia. METHODS AND RESULTS: Individual patient data from the Antiarrhythmics vs Implantable Defibrillator (AVID) study, the Cardiac Arrest Study Hamburg (CASH) and the Canadian Implantable Defibrillator Study (CIDS) were merged into a master database according to a pre-specified protocol. Proportional hazard modelling of individual patient data was used to estimate hazard ratios and to investigate subgroup interactions. Fixed effect meta-analysis techniques were also used to evaluate treatment effects and to assess heterogeneity across studies. The classic fixed effects meta-analysis showed that the estimates of ICD benefit from the three studies were consistent with each other (P heterogeneity=0.306). It also showed a significant reduction in death from any cause with the ICD; with a summary hazard ratio (ICD:amiodarone) of 0.72 (95% confidence interval 0.60, 0.87;P=0.0006). For the outcome of arrhythmic death, the hazard ratio was 0.50 (95% confidence interval 0.37, 0.67;P<0.0001). Survival was extended by a mean of 4.4 months by the ICD over a follow-up period of 6 years. Patients with left ventricular ejection fraction < or = 35% derived significantly more benefit from ICD therapy than those with better preserved left ventricular function. Patients treated before the availability of non-thoracotomy ICD implants derived significantly less benefit from ICD therapy than those treated in the non-thoracotomy era. CONCLUSION: Results from the three trials of the ICD vs amiodarone are consistent with each other. There is a 28% reduction in the relative risk of death with the ICD that is due almost entirely to a 50% reduction in arrhythmic death.

Amiodarone↗
PubMed2000

The defibrillator in acute myocardial infarction trial (DINAMIT): study protocol.

BACKGROUND: The implantable cardioverter/defibrillator (ICD) has been shown to be superior to antiarrhythmic drug therapy for the secondary prevention of sudden cardiac death. Its role in the primary prevention of sudden death after myocardial infarction is unknown. Methods and Results The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT) is a randomized, open-label, parallel-group comparison of ICD therapy versus no ICD therapy in selected survivors of acute myocardial infarction. It will test the hypothesis that reduction of sudden arrhythmogenic death by means of the ICD will result in reduction of overall mortality rates in patients at high risk after acute myocardial infarction. Accordingly, this international multicenter study aims to enroll patients shortly after their infarction (day 6 to day 40) who have reduced left ventricular function (left ventricular ejection fraction </=0. 35) and impairment of cardiac autonomic function shown by depressed heart rate variability (standard deviation of normal-to-normal R-R intervals </=70 ms) or elevated average 24-hour heart rate (mean 24-hour R-R interval </=750 ms, assessed by Holter monitoring). Patients will be followed for approximately 3 years on average with subsequent data analysis based on the intent-to-treat principle. Primary outcome is all-cause death. The trial is expected to be completed in 2003. CONCLUSIONS: DINAMIT is the first prospective study to evaluate the benefit of ICD therapy for the primary prevention of sudden cardiac death in patients at high risk after acute myocardial infarction.

Defibrillators, Implantable↗
PubMed1999

Meta-analysis of antiarrhythmic drug trials.

During the past 15 years, the efficacy of antiarrhythmic drugs has been investigated for reducing premature death in patients at high risk of arrhythmia. Whereas the benefits of beta-blocker therapy are well established, a reduction in mortality with other antiarrhythmic drugs remains unproved and in some cases, there is evidence of increased mortality with class I and some class III agents. A limitation of individual clinical trials is inadequate sample size to detect significant differences between interventions. Meta-analysis, by combining results from multiple clinical trials, provides a technique to overcome sample size limitations and assess the benefits and limitations of an intervention. Thirteen randomized clinical trials evaluated the role of prophylactic amiodarone in patients at risk of death from cardiac arrhythmias. Whereas 3 of these studies reported a reduction in mortality, several others revealed no benefits of amiodarone. Because neither trial was designed to detect reductions in total mortality, it remained unclear whether the beneficial effect of amiodarone on arrhythmic death and resuscitated ventricular fibrillation translated into a beneficial effect on total mortality. To address this, a meta-analysis was performed from the 13 trials of amiodarone in patients after an acute myocardial infarction or with congestive heart failure. The results showed a significant reduction in mortality and in arrhythmic death with amiodarone.

Anti-Arrhythmia Agents↗
PubMed1999

Atrial pacing periablation for prevention of paroxysmal atrial fibrillation.

BACKGROUND: This study tested the hypothesis that rate-adaptive atrial pacing would prevent paroxysmal atrial fibrillation (PAF) in patients with frequent PAF in the absence of symptomatic bradycardia. METHODS AND RESULTS: Patients (n=97) with antiarrhythmic drug-refractory PAF received a Medtronic Thera DR pacemaker 3 months before planned AV node ablation. Patients were randomized to no pacing (n=48) or to atrial rate-adaptive pacing (n=49). After a 2-week stabilization period, patients were followed up for an additional 10 weeks. The time to first recurrence of sustained PAF, the interval between successive episodes of PAF, and the frequency of PAF were compared between the 2 groups in intention-to-treat analysis. Time to first episode of sustained PAF was similar in the no-pacing (4.2 days; 95% CI, 1.8 to 9.5) and the atrial-pacing (1.9 days; 95% CI, 0.8 to 4.6; P=NS) groups. PAF burden was lower in the no-pacing (0.24 h/d; 95% CI, 0.10 to 0.56) than in the atrial-pacing (0.67 h/d; 95% CI, 0.30 to 1.52; P=0.08) group. Paired crossover analysis in 11 patients revealed that time to first PAF was shorter during atrial pacing (1.6 days; 95% CI, 0.6 to 4.9) than with no pacing (6.0 days; 95% CI, 2.4 to 15.0; P=0.13), and PAF burden was greater during atrial pacing (1.00 h/d; 95% CI, 0.35 to 2.91) than with no pacing (0.32 h/d; 95% CI, 0.09 to 1.13; P<0.016). CONCLUSIONS: Atrial rate-adaptive pacing does not prevent PAF over the short term in patients with antiarrhythmic drug-resistant PAF without symptomatic bradycardia.

Adult↗
PubMed1999

Amiodarone interaction with beta-blockers: analysis of the merged EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) databases. The EMIAT and CAMIAT Investigators.

BACKGROUND: Investigations with in vitro and animal models suggest an interaction between amiodarone and beta-blockers. The objective of this work was to explore if an interaction with beta-blocker treatment plays a role in the decrease of cardiac arrhythmic deaths with amiodarone in patients recovered from an acute myocardial infarction. METHODS AND RESULTS: A pooled database from 2 similar randomized clinical trials, the European Amiodarone Myocardial Infarction Trial (EMIAT) and the Canadian Amiodarone Myocardial Infarction Trial (CAMIAT), was used. Four groups of post-myocardial infarction patients were defined: beta-blockers and amiodarone used, beta-blockers used alone, amiodarone used alone, and neither used. All analyses were done on an intention-to-treat basis. Unadjusted and adjusted relative risks for all-cause mortality, cardiac death, arrhythmic cardiac death, nonarrhythmic cardiac death, arrhythmic death, or resuscitated cardiac arrest were lower for patients receiving beta-blockers and amiodarone than for those without beta-blockers, with or without amiodarone. The interaction was statistically significant for cardiac death and arrhythmic death or resuscitated cardiac arrest (P=0.05 and 0.03, respectively). Findings were consistent across subgroups. CONCLUSIONS: These findings are based on a post hoc analysis. However, they confirm prior results from in vitro and animal experiments suggesting an interaction between beta-blockers and amiodarone. In practice, not only is the adjunct of amiodarone to beta-blockers not hazardous, but beta-blocker therapy should be continued if possible in patients in whom amiodarone is indicated.

Adrenergic beta-Antagonists↗
PubMed1999

The North American Vasovagal Pacemaker Study (VPS). A randomized trial of permanent cardiac pacing for the prevention of vasovagal syncope.

OBJECTIVES: This study was done to evaluate pacemaker therapy for severe recurrent vasovagal syncope. BACKGROUND: Nonrandomized studies have suggested that permanent pacing might help control the symptoms of recurrent vasovagal syncope. The study goal was to evaluate the effect of permanent pacemaker implantation on syncope in patients with frequently recurrent vasovagal syncope. METHODS: Patients with > or = 6 lifetime episodes of syncope and with a tilt-table test that induced syncope or presyncope, as well as a relative bradycardia, were randomized to receive a dual-chamber pacemaker or not. The pacemaker prevented bradycardia and provided high-rate pacing if a predetermined drop in heart rate occurred (rate-drop response). The primary outcome was the first recurrence of syncope. Patients also completed a detailed diary recording presyncopal episodes. RESULTS: A total of 284 patients was originally planned and a pilot study of 60 patients was initiated. At the planned first formal interim analysis of efficacy of the pilot study, an unanticipated large treatment effect was observed which fulfilled the prespecified criteria for early termination of the study. At that time, there were 54 patients enrolled, randomized evenly to no pacemaker or to pacemaker. In the no-pacemaker and pacemaker groups the mean ages were 40 and 46 years; 74% and 70% patients, respectively, were female. The baseline tilt-table test showed a slowest heart <60/min or longest heart period >1000 ms in 60% of no-pacemaker patients and 72% of pacemaker patients. There was a marked reduction in the postrandomization risk of syncope in pacemaker patients (relative risk reduction 85.4%, 95% confidence interval 59.7% to 94.7%; 2p=0.000022). CONCLUSIONS: Dual-chamber pacing with rate-drop response reduces the likelihood of syncope in patients with recurrent vasovagal syncope.

Adult↗
PubMed1998

The Canadian Registry of Atrial Fibrillation: a noninterventional follow-up of patients after the first diagnosis of atrial fibrillation.

The Canadian Registry of Atrial Fibrillation (CARAF) is a nondirected, follow-up study of 1,086 patients who are enrolled at 6 centers across Canada at the time of initial electrocardiographically documented diagnosis of atrial fibrillation (AF). Enrollment commenced in 1991 with an intended 10-year follow-up. Comprehensive baseline data, including clinical history, laboratory, and echocardiographic variables were collected. The patients were treated by their own referring physicians and CARAF did not direct their care. Detailed follow-up was performed at 3 months, 1 year, then yearly, with echocardiograms repeated every 2 years. Several studies, which evaluated patient populations, predictors of events, and cardiac structure and functioning, have been performed and are ongoing. Thyroid function was evaluated at baseline, and, of 707 patients evaluated, only 6 patients were found to be hyperthyroid. Symptoms during AF were evaluated and a profile of the types of symptoms and the predictors of symptoms was compiled. Antiarrhythmic drug use is being followed. Sotalol and propafenone were the most commonly used medications, with the use of antiarrhythmic drugs increasing with recurrence of AF. The use of anticoagulants was assessed. The overall use of warfarin was relatively low, but its use increased dramatically with the presence of various risk factors including congestive heart failure, hypertension, and previous stroke. The one risk factor that did not result in increased use of warfarin was hypertension. Therefore, CARAF was able to identify that hypertension appears to be under-recognized and undertreated in its risk for thromboembolic events. CARAF is just now reaching maturity, with the majority of patients having > or=4 years of follow-up. Therefore, extensive investigations are currently under way that will evaluate the baseline characteristics and utilize these as predictors of recurrence of AF, progression to chronicity, and the occurrence of major events such as stroke and death. A very large cohort of patients with serial echocardiograms over 4 years will permit an understanding of the progression of structural and valvular disease. Therefore, CARAF offers a unique opportunity for comprehensive, nondirected follow-up of patients from their initial diagnosis of AF.

Atrial Fibrillation↗
PubMed1997

Definition of predicted effective antiarrhythmic drug therapy for ventricular tachyarrhythmias by the electrophysiologic study approach: randomized comparison of patient response criteria.

OBJECTIVES: We sought to compare efficacies of therapy for ventricular tachyarrhythmias selected by programmed stimulation using two different patient response efficacy criteria: <5 versus <16 repetitive ventricular responses. BACKGROUND: Therapy selection for ventricular tachyarrhythmias by programmed stimulation requires definition of a patient response that predicts long-term efficacy. Such definitions have not been previously compared prospectively. METHODS: Patients with sustained ventricular tachyarrhythmias were randomized to therapy selection using either the <5 or <16 repetitive response criterion of predicted effective therapy. The primary end point was sudden death or recurrence of ventricular tachyarrhythmia requiring intervention. RESULTS: Predicted effective drug therapy was found for 23 (34%) of 68 patients randomized to the <5 criterion and 29 (36%) of 81 patients randomized to the <16 criterion (p = NS). Definition of therapy required 3.0 +/- 1.6 drug trials (mean +/- SD) in patients randomized to the <5 criterion and 2.9 +/- 1.8 trials in patients randomized to the <16 criterion (p = NS). Patients randomized to the <5 criterion had a lower 2-year probability of the primary end point (0.20 +/- 0.05) than did patients randomized to the <16 criterion (0.33 +/- 0.05, one-tailed p = 0.004). The advantage of the <5 criterion was also seen in subgroup analyses involving patients with and without an initial drug efficacy prediction. CONCLUSIONS: The programmed stimulation approach to the selection of antiarrhythmic therapy for ventricular tachyarrhythmias using a patient response criterion of <5 repetitive ventricular responses results in a lower probability of recurrence of ventricular tachyarrhythmia than does use of a <16 repetitive response criterion.

Actuarial Analysis↗
PubMed1997

Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators.

BACKGROUND: Survivors of acute myocardial infarction with frequent or repetitive ventricular premature depolarisations (VPDs) have higher mortality 1-2 years after the event than those without VPDs. Although there is no therapy of proven efficacy for such patients, previous studies of amiodarone have been encouraging. CAMIAT was a randomised double-blind placebo-controlled trial designed to assess the effect of amiodarone on the risk of resuscitated ventricular fibrillation or arrhythmic death among survivors of myocardial infarction with frequent or repetitive VPDs (> or = 10 VPDs per h or > or = 1 run of ventricular tachycardia). METHODS: Patients from 36 Canadian hospitals were randomly assigned amiodarone or placebo; a loading dose of 10 mg/kg daily for 2 weeks, a maintenance dose of 300-400 mg daily for 3.5 months, 200-300 mg daily for 4 months, and 200 mg for 5-7 days per week for 16 months. Patients were followed up for 2 years. The primary outcome was the composite of resuscitated ventricular fibrillation or arrhythmic death. FINDINGS: We recruited 1202 patients (606 in the amiodarone group and 596 in the placebo group). The mean follow-up was 1.79 years (SD 0.44). In the efficacy analysis, resuscitated ventricular fibrillation or arrhythmic death occurred in 39 (6.9%) [corrected] patients in the placebo group and in 25 (4.5%) [corrected] in the amiodarone group (relative-risk reduction 48.5% [95% CI 4.5 to 72.2], p = 0.016). In the intention-to-treat analysis, primary outcome events occurred in 24 (6.9%) patients in the placebo group and in 15 (4.5%) in the amiodarone group (38.2% [95% CI -2.1 to 62.6], p = 0.029). The absolute-risk reductions were greatest among patients with congestive heart failure or a history of myocardial infarction. INTERPRETATION: Amiodarone reduces the incidence of ventricular fibrillation or arrhythmic death among survivors of acute myocardial infarction with frequent or repetitive VPDs. Treatment decisions for individual survivors should require an assessment of their baseline risk factors and judgments based on the synthesis of our findings with those of related trials.

Adult↗