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Biomedical subjects

Stuart J Connolly

Publications and source records attributed to Stuart J Connolly.

At least 37 records · Page 2Linked to original sources
PubMed2004

Prophylactic use of an implantable cardioverter-defibrillator after acute myocardial infarction.

BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy has been shown to improve survival in patients with various heart conditions who are at high risk for ventricular arrhythmias. Whether benefit occurs in patients early after myocardial infarction is unknown. METHODS: We conducted the Defibrillator in Acute Myocardial Infarction Trial, a randomized, open-label comparison of ICD therapy (in 332 patients) and no ICD therapy (in 342 patients) 6 to 40 days after a myocardial infarction. We enrolled patients who had reduced left ventricular function (left ventricular ejection fraction, 0.35 or less) and impaired cardiac autonomic function (manifested as depressed heart-rate variability or an elevated average 24-hour heart rate on Holter monitoring). The primary outcome was mortality from any cause. Death from arrhythmia was a predefined secondary outcome. RESULTS: During a mean (+/-SD) follow-up period of 30+/-13 months, there was no difference in overall mortality between the two treatment groups: of the 120 patients who died, 62 were in the ICD group and 58 in the control group (hazard ratio for death in the ICD group, 1.08; 95 percent confidence interval, 0.76 to 1.55; P=0.66). There were 12 deaths due to arrhythmia in the ICD group, as compared with 29 in the control group (hazard ratio in the ICD group, 0.42; 95 percent confidence interval, 0.22 to 0.83; P=0.009). In contrast, there were 50 deaths from nonarrhythmic causes in the ICD group and 29 in the control group (hazard ratio in the ICD group, 1.75; 95 percent confidence interval, 1.11 to 2.76; P=0.02). CONCLUSIONS: Prophylactic ICD therapy does not reduce overall mortality in high-risk patients who have recently had a myocardial infarction. Although ICD therapy was associated with a reduction in the rate of death due to arrhythmia, that was offset by an increase in the rate of death from nonarrhythmic causes.

Adult↗
PubMed2004

Prognostic differences between atrial fibrillation and atrial flutter.

This report presents the outcome of a cohort of 94 patients with atrial fibrillation from the Canadian Registry of Atrial Fibrillation, in which we paid particular attention to the probability of stroke and death. We also evaluated warfarin use over time and compared left atrial dimensions in patients with atrial flutter with those with atrial fibrillation.

Aged↗
PubMed2004

Canadian Trial of Physiological Pacing: Effects of physiological pacing during long-term follow-up.

BACKGROUND: The Canadian Trial of Physiological Pacing (CTOPP) reported that the risk of stroke or cardiovascular death was similar between patients receiving ventricular versus physiological pacemakers at the end of the original follow-up period of 3 years. However, the occurrence of atrial fibrillation was significantly less frequent with physiological pacemakers. To assess a potential delayed benefit of physiological pacing, follow-up of patients in this study was extended to 6 years. METHODS AND RESULTS: A total of 1474 patients requiring a pacemaker for symptomatic bradycardia were randomized to receive ventricular and 1094 to physiological pacemakers. The primary outcome was stroke or cardiovascular death. The study was completed in July 1998, and follow-up was extended to July 2001. At a mean follow-up of 6.4 years, there was no difference between treatment groups in the primary outcome of cardiovascular death or stroke. There was no significant difference in total mortality or stroke between groups. There was a significantly lower rate of development of atrial fibrillation in the physiological group, with a relative risk reduction of 20.1% (CI, 5.4 to 32.5; P=0.009). CONCLUSIONS: The CTOPP extended study does not show a difference in cardiovascular death or stroke, or in total mortality, or in stroke between patients implanted with ventricular or physiological pacemakers over a mean follow-up of >6 years. However, there is a persistent significant reduction in the development of atrial fibrillation with physiological pacing.

Atrial Fibrillation↗
PubMed2004

The management of patients with carotid sinus syndrome: is pacing the answer?

Carotid sinus syndrome (CSS) is an under recognized cause of recurrent unexplained syncope and potentially of recurrent falls in the elderly. The mechanisms that lead to syncope in patients with CSS remain debated. However, evidence for both peripheral and central alterations have been recently reported. The diagnosis of CSS is challenging and a high clinical suspicion is usually needed to make the diagnosis. Clinical presentation may be typical and characterized by a clear association between accidental manipulation of the carotid sinus and the presentation of syncope. On the other hand, recurrent unexplained syncope and unexplained falls may be the clinical presentation of patients with CSS without a specific trigger. Carotid sinus hypersensitivity documented by carotid sinus massage (CSM) may be the only finding indicating the possibility of CSS as the cause of syncope. In older patients with recurrent unexplained syncope and a negative diagnostic work-up, carotid sinus massage both in the supine and upright positions is recommended. CSS may present primarily as a cardioinhibitory response or a true vasodepressor response. Therapy should address any underlying pathology if present, and be directed to either prevent cardioinhibition, vasodepression or both alterations. A variety of medical therapies have been used with unclear effects. No appropriately designed controlled clinical trials have been performed comparing pacing with medical therapy. Nonetheless, available information indicates that pacing may have a strong beneficial effect and prevents recurrence of syncope in patients with CSS. The present paper critically reviews the latest insights in the pathophysiology, diagnosis and management of CSS.

Cardiac Pacing, Artificial↗
PubMed2004

Diminishing proportional risk of sudden death with advancing age: implications for prevention of sudden death.

BACKGROUND: Advances in primary and secondary prevention of sudden death have led to a wide array of potentially beneficial therapies. Identification of patients most likely to benefit would be of use when considering costly interventions such as an implantable defibrillator. We sought to determine the effect of advancing age on the mode of death in the Amiodarone Trialists Metanalysis. METHODS AND RESULTS: Patients (n = 6252; age, 61.2+/-10.5 years; 83% men) were included in an analysis of predictors of sudden death (SD) and all-cause death (ACD), based on baseline variables at enrollment. Patients were divided into 5 age groups: < or =50 years, 51 to 60 years, 61 to 70 years, 71 to 80 years, and >80 years. During a mean of 16.8+/-10.3 months of follow-up, there were 1023 deaths, with an annual overall mortality rate of 11.7%. Both sudden death and nonsudden death rates increased with age, although the increase of nonsudden death with age was more dramatic. The overall proportion of death that was sudden (SD/ACD ratio) was 0.41, falling from 0.51 before age 50 years to 0.26 after age 80 years (P =.002 for trend). The SD/ACD ratio was not affected by sex, New York Heart Association Class, or left ventricular ejection fraction. CONCLUSIONS: Although the incidence of sudden death increases with age, the proportion of death that is sudden diminishes markedly. This finding may influence the yield of interventions targeted at prevention of sudden death.

Age Factors↗
PubMed2004

The association of left atrial size and occurrence of atrial fibrillation: a prospective cohort study from the Canadian Registry of Atrial Fibrillation.

BACKGROUND: The effect of left atrial (LA) dimension on the recurrence of atrial fibrillation (AF) has been examined in small studies. We evaluated the effect of LA dimension on the occurrence of AF using 2- and 4-year echocardiographic data in a large cohort of patients with new onset AF. METHODS: The Canadian Registry of AF (CARAF) enrolled subjects with AF at the first electrocardiographically confirmed diagnosis. Patients were classified at 2 and 4 years as no recurrent AF (No RAF), paroxysmal AF (PAF), or chronic AF (CAF) based on clinical symptoms and electrocardiographic documentation. The association between baseline, 2-, and 4-year LA dimensions with occurrence of AF as determined by echocardiography was evaluated using a multivariate analysis. RESULTS: The No RAF group (n = 176) had a significantly smaller LA dimension (36.9 +/- 6.8 mm) at baseline compared to the CAF group (n = 227) (42.8 +/- 7.5 mm, P <.0001). The No RAF and PAF (n = 153) groups did not have a significant change in LA dimension at 2 or 4 years. Only those with CAF had a significant increase in LA dimension at 2 and 4 years, +1.39 mm (95% CI 0.01-2.8) and +3.48 mm (95% CI 1.8-5.2), respectively. CONCLUSIONS: A larger baseline LA dimension is associated with progression to CAF. Patients with no or paroxysmal recurrence had no change in LA dimension over a 4-year period. These findings have implications in tailoring modes of therapy in patients with AF.

Aged↗
PubMed2004

Atrial fibrillation: guiding lessons from epidemiology.

The epidemiology of AF is a challenging and surprising area of medical knowledge. The prevalence of AF may be not changing despite the common perception. It is possible that being earlier disease of the middle age, and because of changing etiology and successful treatment of underlying vascular conditions, AF is shifting to the elderly population. In this population, it becomes more clinically significant, and increasingly leads to disability and death. Screening procedures for silent AF likely are underimplemented and may change understanding of AF epidemiology significantly. Hypertension may be the most common primary etiology of AF, and the possibility of effective primary prevention of AF by strict control of hypertension needs to be evaluated adequately.

Adult↗
PubMed2003

Atrial fibrillation: hypertension as a causative agent, risk factor for complications, and potential therapeutic target.

Atrial fibrillation and hypertension are 2 prevalent, and often coexistent, conditions in the North American population. Their incidence increases with advancing age, and they are responsible for considerable morbidity and mortality. Although the relation between the 2 conditions has long been known, the treatment of hypertension is not currently a focus in the clinical management of atrial fibrillation. Hypertension is associated with left ventricular hypertrophy, impaired ventricular filling, left atrial enlargement, and slowing of atrial conduction velocity. These changes in cardiac structure and physiology favor the development of atrial fibrillation, and they increase the risk of thromboembolic complications. Conventional therapy of atrial fibrillation has focused on interventions to control heart rate and rhythm and the prevention of stroke through the use of anticoagulant medications. In patients with atrial fibrillation, aggressive treatment of hypertension may reverse the structural changes in the heart, reduce thromboembolic complications, and retard or prevent the occurrence of atrial fibrillation. Specific pharmacotherapy could potentially play a major role in the primary and secondary prevention of atrial fibrillation and its complications.

Antihypertensive Agents↗
PubMed2003

Pacemaker therapy for prevention of syncope in patients with recurrent severe vasovagal syncope: Second Vasovagal Pacemaker Study (VPS II): a randomized trial.

CONTEXT: Three previous small randomized trials have reported that pacemaker therapy is beneficial for patients with severe recurrent vasovagal syncope. However, because these trials were not double blind, they may have been biased in their assessment of outcomes and had a placebo effect of surgery. OBJECTIVE: To determine if pacing therapy reduces the risk of syncope in patients with vasovagal syncope. DESIGN, SETTING, AND PATIENTS: A randomized double-blind trial of pacemaker therapy in outpatients referred to syncope specialists at 15 centers from September 1998 to April 2002. In the year prior to randomization, patients had had a median of 4 episodes of syncope. Patients were followed up for up to 6 months. INTERVENTION: After implantation of a dual chamber pacemaker, 100 patients were randomly assigned to receive dual-chamber pacing (DDD) with rate drop response or to have only sensing without pacing (ODO). MAIN OUTCOME MEASURE: Time to first recurrence of syncope. RESULTS: No patients were lost to follow-up. Of the 52 patients randomized to ODO, 22 (42%) had recurrent syncope within 6 months compared with 16 (33%) of 48 patients in the DDD group. The cumulative risk of syncope at 6 months was 40% (95% confidence interval [CI], 25%-52%) for the ODO group and 31% (95% CI, 17%-43%) for the DDD group. The relative risk reduction in time to syncope with DDD pacing was 30% (95% CI, -33% to 63%; 1-sided P =.14). Lead dislodgement or repositioning occurred in 7 patients. One patient had vein thrombosis, another had pericardial tamponade leading to removal of the pacemaker system, and a third had infection involving the pacemaker generator. CONCLUSIONS: In this double-blind randomized trial, pacing therapy did not reduce the risk of recurrent syncope in patients with vasovagal syncope. Because of the weak evidence of efficacy of pacemaker therapy and the risk of complications, pacemaker therapy should not be recommended as first-line therapy for patients with recurrent vasovagal syncope.

Adult↗
PubMed2003

Asymptomatic or "silent" atrial fibrillation: frequency in untreated patients and patients receiving azimilide.

BACKGROUND: Asymptomatic, or "silent" atrial fibrillation could increase the risk of stroke. Little is known about the frequency of asymptomatic atrial fibrillation in patients who also have symptomatic atrial fibrillation; similarly, little is known about the effect of antiarrhythmic drug therapy on asymptomatic atrial fibrillation. METHODS AND RESULTS: Patients in sinus rhythm with a history of symptomatic atrial fibrillation or atrial flutter received placebo or azimilide (35 to 125 mg) once daily for 6 or 9 months in 4 similar double-blind trials. The end point was the first recurrence of a symptomatic ECG-documented supraventricular arrhythmia. Routine transtelephonic electrocardiograms, in the absence of symptoms, were recorded for 30 seconds every 2 weeks until patients completed follow-up or documented a symptomatic supraventricular arrhythmia. Of the 1380 patients, 489 received placebo. Among these patients receiving placebo, 303 transmitted at least one routine ECG while asymptomatic. Asymptomatic atrial fibrillation was recorded in 50 (17%) within 6 months and before recurrence of symptomatic supraventricular arrhythmia. In the 3 trials evaluating azimilide in therapeutic doses (100 and 125 mg), asymptomatic atrial fibrillation occurred in 49 of 382 (13%) receiving azimilide and 43 of 233 (18%) receiving placebo. Although drug effect on time to first asymptomatic event was not statistically significant (hazard ratio, 0.70; P=0.09), there was a 40% reduction in asymptomatic atrial fibrillation on azimilide compared with placebo (P=0.03) when repeated observations were considered. CONCLUSIONS: Asymptomatic atrial fibrillation is common in untreated patients with a history of symptomatic atrial fibrillation (and is likely underestimated by this analysis). Azimilide may reduce the occurrence of this silent arrhythmia.

Adult↗
PubMed2003

Symptoms at the time of arrhythmia recurrence in patients receiving azimilide for control of atrial fibrillation or flutter: results from randomized trials.

BACKGROUND: Azimilide is a new antiarrhythmic agent being developed for the management for atrial fibrillation and flutter (AF). Four randomized, placebo-controlled, double-blind trials have been performed that investigated the effect of azimilide on time to first recurrence of symptomatic AF. This paper examines the data collected during those studies regarding the symptoms reported by patients at the time of AF recurrence METHODS: At the time that patients reported their first documented symptomatic recurrence of arrhythmia, they were systematically asked whether or not they were experiencing any of the following 6 symptoms: palpitation, fatigue, chest pain, shortness of breath, dizziness, or sweating. Patients were required to answer yes or no. A symptom score was created varying from 0 to 6, in increasing order of number of symptoms reported. This was compared for patients receiving either of 2 doses of azimilide or placebo. The relationship between the number of symptoms, heart rate at time of arrhythmia recurrence and treatment was analyzed. RESULTS: In 2 separate studies, azimilide at a dose of 125 mg/day significantly reduced the number of symptoms at the time of arrhythmia recurrence compared to placebo. On the other hand, in 2 studies, the dose of 100 mg/day did not significantly reduce symptom burden. The individual symptoms significantly reduced by azimilide125 mg/day were fatigue, shortness of breath, chest pain and dizziness. Palpitations and sweating were not significantly reduced. Modeling of heart rate at the time of arrhythmia recurrence, symptoms and treatment indicated that a small reduction in heart rate with azimilide accounted for only a small part of the symptom reduction. There was another effect of azimilide: an average reduction of 0.38 symptoms (P <.01) that was independent of heart rate. CONCLUSION: Azimilide (125 mg/day) reduces the number of symptoms reported at the time of AF recurrence.

Anti-Arrhythmia Agents↗
PubMed2003

Atrial fibrillation after cardiac surgery: update on the evidence on the available prophylactic interventions.

Post-operative atrial fibrillation is very common. It is associated with increased length of ICU and hospital stay, and costs of post-operative care of patients after cardiac surgery. More then seventy trials on the pharmacological and non-pharmacological interventions were conducted since 1970's. Meta-analysis of these trials, together with detailed analysis of the largest of these trials suggested that conventional beta-blockers, sotalol, amiodarone and bi-atrial overdrive pacing are effective in prevention of post-operative atrial fibrillation. Amiodarone and bi-atrial pacing may decrease the length of hospital stay.

Adrenergic beta-Antagonists↗
PubMed2003

The Defibrillator in Acute Myocardial Infarction Trial (DINAMIT): rationale, design and specific aims.

The implantable defibrillator (ICD) effectively palliates arrhythmogenic events and thereby reduces total mortality in patients after a first episode of cardiac arrest. At present, four randomized controlled trials have addressed the issue of primary prevention by the ICD in patients with coronary artery disease and two small studies are available dealing with patients suffering from nonischemic cardiomyopathy. Importantly, none of the randomized studies in patients suffering from coronary artery disease has examined the potential role of the ICD in patients early after myocardial infarction. Within the next 12 months, important additional data is expected from several studies which have completed patient enrollment and follow-up. All studies are prospective randomized trials investigating the effects of ICD compared to optimal medical therapy. This paper summarizes the rationale, design and specific contributions of the Defibrillator in Myocardial infarction trial (DINAMIT) in comparison to other relevant studies on primary prevention of sudden cardiac death.

Death, Sudden, Cardiac↗
PubMed2003

Combined antiplatelet therapy in atrial fibrillation: review of the literature and future avenues.

Atrial fibrillation (AF), the most commonly encountered cardiac rhythm disorder, affects approximately 1% of the general population and is associated with serious complications, most notably ischemic stroke. AF-associated stroke occurs at an annual rate of 4.5%. Anticoagulation therapy with warfarin has been demonstrated in randomized controlled trials to reduce the risk for AF-related stroke by two thirds, but warfarin therapy is markedly underused in clinical practice because of its narrow therapeutic window and its implications on quality of life. This article reviews the present knowledge and potential future research avenues for the role of antiplatelet therapy in AF as an alternative to anticoagulation with warfarin for prevention of AF-associated stroke. Antiplatelet therapy recently has been shown to be protective against thrombotic events related to blood stasis. There is ample evidence from experimental and clinical studies that a combination of different antiplatelet agents may increase antithrombotic efficacy compared to monotherapy. Accordingly, a series of randomized controlled trials (ACTIVE [Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events]) has been designed to vigorously examine the role of combined antithrombotic therapy for prevention of vascular events, including stroke in high-risk AF patients. The ACTIVE program began patient enrollment in spring 2003.

Aspirin↗
PubMed2003

Prevention of vascular events in patients with atrial fibrillation: evidence, guidelines, and practice.

Atrial fibrillation (AF) is a common arrhythmia that is associated with an increased risk for vascular events, particularly stroke. Two different therapies have been extensively evaluated for prevention of vascular events in AF: oral anticoagulation (such as warfarin), and aspirin. Placebo-controlled trials of warfarin have been performed and summarized in a meta-analysis. There is clear evidence of a benefit, with a relative risk reduction in stroke of 67% and in total vascular events of 42%. Aspirin also has been studied and is effective, but with a more modest benefit (relative risk reduction of 22%). Several studies have compared warfarin and aspirin, and showed a clear benefit in favor of warfarin for reduction of vascular events and stroke. Compared to aspirin, the risk of major hemorrhage with oral anticoagulation is increased by 70% to 100%. Current practice guidelines recommend oral anticoagulation therapy for high-risk patients with AF, unless there is an increased risk for bleeding. Nonetheless, oral anticoagulation therapy with drugs such as warfarin is difficult for both patients and physicians because of the increased risk for bleeding and the need for ongoing monitoring of coagulation status. Many patients do not receive anticoagulation therapy despite its proven benefits.

Administration, Oral↗
PubMed2003

Double-blind, placebo-controlled, randomized trial of prophylactic metoprolol for reduction of hospital length of stay after heart surgery: the beta-Blocker Length Of Stay (BLOS) study.

BACKGROUND: Atrial fibrillation (AF) is a common complication of heart surgery. Previous studies have shown that there is an association between postoperative AF and prolongation of hospital length of stay. No previous trials have been primarily directed at demonstrating that the use of drugs that prevent AF would shorten length of stay and reduce the costs of postoperative care. METHODS: A randomized, double-blind, placebo-controlled trial of metoprolol was performed in patients immediately after nonemergent heart surgery. Metoprolol was given orally at a dose of 100 mg per day after the patient's arrival in the intensive care unit until hospital discharge or 14 days, whichever was sooner. This dose was increased to 150 mg per day after the enrollment of 411 patients. The primary outcome measure of the study was hospital length of stay from admission to intensive care unit until hospital discharge. There were 1000 patients enrolled, evenly distributed to the metoprolol and placebo groups. RESULTS: There was a 20% reduction in the risk of AF developing with metoprolol, from 39% of patients to 31% of patients (P =.01). There was no effect of treatment on hospital length of stay, which was 152 +/- 61 hours for placebo and 155 +/- 90 hours for metoprolol (P = 0.79). The cost of postoperative care in the 2 treatment groups was similar. CONCLUSION: Prophylactic metoprolol reduces the risk of AF after heart surgery. It does not reduce hospital length of stay. Although it is cost effective for the reduction of AF, it did not reduce the overall cost of care.

Adrenergic beta-Antagonists↗
PubMed2003

Effect of pacing mode on health-related quality of life in the Canadian Trial of Physiologic Pacing.

BACKGROUND: Both "physiologic" (dual-chamber or atrial only) or ventricular-pacing-only permanent pacemakers provide chronotropic competence, with unknown health-related quality of life (QOL) differences between these options. The QOL studies within the Canadian Trial of Physiologic Pacing were performed to assess whether QOL differences exist in patients randomized to these 2 pacing modes. METHODS: Two QOL protocols were performed: 1) a substudy of 269 patients with detailed QOL measures (The Medical Outcomes Study, Short-Form [SF-36], the Pacemaker Syndrome Scale, an activity scale, and a pacemaker-specific scale) at baseline and 6 months after implantation; and 2) a parent study assessment of QOL in 1721 patients with a 12-item QOL instrument package (SF-6, "ladder of life," and pacemaker syndrome scale) given 6 months after implantation only. RESULTS: In the substudy, pacing was associated with an average significant (P <.05) 0.36 SD unit improvement in QOL across all domains (SF-36: 38 +/- 9 to 41 +/- 11 for physical scores, 47 +/- 11 to 52 +/- 9 for mental health scores, both P <.001). Similar improvements were seen with the pacemaker-specific scales. There were no significant differences in the absolute or relative improvement in QOL between assigned pacing modes. The parent study similarly showed no differences in QOL between pacing modalities. Presyncope occurred in 31% of patients in the physiological pacing group, compared with 38% of the patients in the ventricular pacing group (P <.01). No other symptoms were different between the 2 groups. Pacemaker dependency, defined as an escape heart rate <50 beats per minute, did not influence the lack of difference in QOL scores between the 2 assigned pacing modes. CONCLUSION: In this largest randomized assessment of QOL in patients with pacemakers, with the instruments used, there was no significant health-related QOL difference seen between "physiologic" pacing and ventricular pacing.

Aged↗