William D. Toff

Blood-pressure lowering in intermediate-risk persons without cardiovascular disease

BACKGROUND Antihypertensive therapy reduces the risk of cardiovascular events among high-risk persons and among those with a systolic blood pressure of 160 mm Hg or higher, but its role in persons at intermediate risk and with lower blood pressure is unclear. METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to receive either candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; the second coprimary outcome additionally included resuscitated cardiac arrest, heart failure, and revascularization. The median follow-up was 5.6 years. RESULTS The mean blood pressure of the participants at baseline was 138.1/81.9 mm Hg; the decrease in blood pressure was 6.0/3.0 mm Hg greater in the active-treatment group than in the placebo group. The first coprimary outcome occurred in 260 participants (4.1%) in the active-treatment group and in 279 (4.4%) in the placebo group (hazard ratio, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P=0.40); the second coprimary outcome occurred in 312 participants (4.9%) and 328 participants (5.2%), respectively (hazard ratio, 0.95; 95% CI, 0.81 to 1.11; P=0.51). In one of the three prespecified hypothesis-based subgroups, participants in the subgroup for the upper third of systolic blood pressure (>143.5 mm Hg) who were in the active-treatment group had significantly lower rates of the first and second coprimary outcomes than those in the placebo group; effects were neutral in the middle and lower thirds (P=0.02 and P=0.009, respectively, for trend in the two outcomes). CONCLUSIONS Therapy with candesartan at a dose of 16 mg per day plus hydrochlorothiazide at a dose of 12.5 mg per day was not associated with a lower rate of major cardiovascular events than placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).

Home use of automated external defibrillators for sudden cardiac arrest

BACKGROUND The most common location of out-of-hospital sudden cardiac arrest is the home, a situation in which emergency medical services are challenged to provide timely care. Consequently, home use of an automated external defibrillator (AED) might offer an opportunity to improve survival for patients at risk. METHODS We randomly assigned 7001 patients with previous anterior-wall myocardial infarction who were not candidates for an implantable cardioverter-defibrillator to receive one of two responses to sudden cardiac arrest occurring at home: either the control response (calling emergency medical services and performing cardiopulmonary resuscitation [CPR]) or the use of an AED, followed by calling emergency medical services and performing CPR. The primary outcome was death from any cause. RESULTS The median age of the patients was 62 years; 17% were women. The median follow-up was 37.3 months. Overall, 450 patients died: 228 of 3506 patients (6.5%) in the control group and 222 of 3495 patients (6.4%) in the AED group (hazard ratio, 0.97; 95% confidence interval, 0.81 to 1.17; P=0.77). Mortality did not differ significantly in major prespecified subgroups. Only 160 deaths (35.6%) were considered to be from sudden cardiac arrest from tachyarrhythmia. Of these deaths, 117 occurred at home; 58 at-home events were witnessed. AEDs were used in 32 patients. Of these patients, 14 received an appropriate shock, and 4 survived to hospital discharge. There were no documented inappropriate shocks. CONCLUSIONS For survivors of anterior-wall myocardial infarction who were not candidates for implantation of a cardioverter-defibrillator, access to a home AED did not significantly improve overall survival, as compared with reliance on conventional resuscitation methods. (ClinicalTrials.gov number, NCT00047411 [ClinicalTrials.gov].).

Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease.

BACKGROUND Previous trials have shown that the use of statins to lower cholesterol reduces the risk of cardiovascular events among persons without cardiovascular disease. Those trials have involved persons with elevated lipid levels or inflammatory markers and involved mainly white persons. It is unclear whether the benefits of statins can be extended to an intermediate-risk, ethnically diverse population without cardiovascular disease. METHODS In one comparison from a 2-by-2 factorial trial, we randomly assigned 12,705 participants in 21 countries who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included revascularization, heart failure, and resuscitated cardiac arrest. The median follow-up was 5.6 years. RESULTS The overall mean low-density lipoprotein cholesterol level was 26.5% lower in the rosuvastatin group than in the placebo group. The first coprimary outcome occurred in 235 participants (3.7%) in the rosuvastatin group and in 304 participants (4.8%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.64 to 0.91; P=0.002). The results for the second coprimary outcome were consistent with the results for the first (occurring in 277 participants [4.4%] in the rosuvastatin group and in 363 participants [5.7%] in the placebo group; hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P<0.001). The results were also consistent in subgroups defined according to cardiovascular risk at baseline, lipid level, C-reactive protein level, blood pressure, and race or ethnic group. In the rosuvastatin group, there was no excess of diabetes or cancers, but there was an excess of cataract surgery (in 3.8% of the participants, vs. 3.1% in the placebo group; P=0.02) and muscle symptoms (in 5.8% of the participants, vs. 4.7% in the placebo group; P=0.005). CONCLUSIONS Treatment with rosuvastatin at a dose of 10 mg per day resulted in a significantly lower risk of cardiovascular events than placebo in an intermediate-risk, ethnically diverse population without cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; HOPE-3 ClinicalTrials.gov number, NCT00468923.).

Cardiovascular Outcomes With Atrial-Based Pacing Compared With Ventricular Pacing Meta-Analysis of Randomized Trials, Using Individual Patient Data

Background— Several randomized trials have compared atrial-based (dual-chamber or atrial) pacing with ventricular pacing in patients with bradycardia. No trial has shown a mortality reduction, and only 1 small trial suggested a reduction in stroke. The goal of this review was to determine whether atrial-based pacing prevents major cardiovascular events. Methods and Results— A systematic review was performed of publications since 1980. For inclusion, trials had to compare an atrial-based with a ventricular-based pacing mode; use a randomized, controlled, parallel design; and have data on mortality, stroke, heart failure, or atrial fibrillation. Individual patient data were obtained from 5 of the 8 identified studies, representing 95% of patients in the 8 trials, and a total of 35 000 patient-years of follow-up. There was no significant heterogeneity among the results of the individual trials. There was no significant reduction in mortality (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.87 to 1.03; P=0.19) or heart failure (HR, 0.89; 95% CI, 0.77 to 1.03; P=0.15) with atrial-based pacing. There was a significant reduction in atrial fibrillation (HR, 0.80; 95% CI, 0.72 to 0.89; P=0.00003) and a reduction in stroke that was of borderline significance (HR, 0.81; 95% CI, 0.67 to 0.99; P=0.035). There was no convincing evidence that any patient subgroup received special benefit from atrial-based pacing. Conclusions— Compared with ventricular pacing, the use of atrial-based pacing does not improve survival or reduce heart failure or cardiovascular death. However, atrial-based pacing reduces the incidence of atrial fibrillation and may modestly reduce stroke.

A comparison of single-lead atrial pacing with dual-chamber pacing in sick sinus syndrome

AIMS In patients with sick sinus syndrome, bradycardia can be treated with a single-lead pacemaker or a dual-chamber pacemaker. Previous trials have revealed that pacing modes preserving atrio-ventricular synchrony are superior to single-lead ventricular pacing, but it remains unclear if there is any difference between single-lead atrial pacing (AAIR) and dual-chamber pacing (DDDR). METHODS AND RESULTS We randomly assigned 1415 patients referred for first pacemaker implantation to AAIR (n = 707) or DDDR (n = 708) pacing and followed them for a mean of 5.4 ± 2.6 years. The primary outcome was death from any cause. Secondary outcomes included paroxysmal and chronic atrial fibrillation, stroke, heart failure, and need for pacemaker reoperation. In the AAIR group, 209 patients (29.6%) died during follow-up vs. 193 patients (27.3%) in the DDDR group, hazard ratio (HR) 1.06, 95% confidence interval (CI) 0.88-1.29, P = 0.53. Paroxysmal atrial fibrillation was observed in 201 patients (28.4%) in the AAIR group vs. 163 patients (23.0%) in the DDDR group, HR 1.27, 95% CI 1.03-1.56, P = 0.024. A total of 240 patients underwent one or more pacemaker reoperations during follow-up, 156 (22.1%) in the AAIR group vs. 84 (11.9%) in the DDDR group (HR 1.99, 95% CI 1.53-2.59, P < 0.001). The incidence of chronic atrial fibrillation, stroke, and heart failure did not differ between treatment groups. CONCLUSION In patients with sick sinus syndrome, there is no statistically significant difference in death from any cause between AAIR pacing and DDDR pacing. AAIR pacing is associated with a higher incidence of paroxysmal atrial fibrillation and a two-fold increased risk of pacemaker reoperation. These findings support the routine use of DDDR pacing in these patients. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT00236158.

Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease

BACKGROUND Elevated blood pressure and elevated low-density lipoprotein (LDL) cholesterol increase the risk of cardiovascular disease. Lowering both should reduce the risk of cardiovascular events substantially. METHODS In a trial with 2-by-2 factorial design, we randomly assigned 12,705 participants at intermediate risk who did not have cardiovascular disease to rosuvastatin (10 mg per day) or placebo and to candesartan (16 mg per day) plus hydrochlorothiazide (12.5 mg per day) or placebo. In the analyses reported here, we compared the 3180 participants assigned to combined therapy (with rosuvastatin and the two antihypertensive agents) with the 3168 participants assigned to dual placebo. The first coprimary outcome was the composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second coprimary outcome additionally included heart failure, cardiac arrest, or revascularization. The median follow-up was 5.6 years. RESULTS The decrease in the LDL cholesterol level was 33.7 mg per deciliter (0.87 mmol per liter) greater in the combined-therapy group than in the dual-placebo group, and the decrease in systolic blood pressure was 6.2 mm Hg greater with combined therapy than with dual placebo. The first coprimary outcome occurred in 113 participants (3.6%) in the combined-therapy group and in 157 (5.0%) in the dual-placebo group (hazard ratio, 0.71; 95% confidence interval [CI], 0.56 to 0.90; P=0.005). The second coprimary outcome occurred in 136 participants (4.3%) and 187 participants (5.9%), respectively (hazard ratio, 0.72; 95% CI, 0.57 to 0.89; P=0.003). Muscle weakness and dizziness were more common in the combined-therapy group than in the dual-placebo group, but the overall rate of discontinuation of the trial regimen was similar in the two groups. CONCLUSIONS The combination of rosuvastatin (10 mg per day), candesartan (16 mg per day), and hydrochlorothiazide (12.5 mg per day) was associated with a significantly lower rate of cardiovascular events than dual placebo among persons at intermediate risk who did not have cardiovascular disease. (Funded by the Canadian Institutes of Health Research and AstraZeneca; ClinicalTrials.gov number, NCT00468923.).

Long-term effect of cardiac resynchronisation in patients reporting mild symptoms of heart failure: a report from the CARE-HF study

Background: Cardiac resynchronisation therapy (CRT) improves symptoms and prognosis in patients with heart failure and cardiac dyssynchrony. Guidelines from the National Institute of Health and Clinical Excellence in the United Kingdom recommend CRT for patients with recent or persistent moderate or severe symptoms of heart failure. This analysis investigated whether the severity of symptoms was an important determinant of the prognostic benefits of CRT. Methods: In CARE-HF, patients with left ventricular ejection fraction ⩽35% and markers of cardiac dyssynchrony who were, in the investigators’ opinion, in New York Heart Association (NYHA) class III/IV were randomly assigned to pharmacological treatment alone or with addition of CRT. This analysis investigated whether the severity of symptoms reported by patients, using Likert Scales from the EuroHeart Failure Questionnaire and self-assessed NYHA class, influenced prognosis and the response to CRT. Results: Of 813 patients, 175 (21.5%) assessed themselves to be in NYHA class I or II. These patients also reported less severe symptoms and better quality of life than patients who assessed themselves to be in NYHA class III or IV. No statistical interaction was observed between the severity of symptoms assessed in several ways and the benefits of CRT on morbidity and mortality. Conclusions: The severity of symptoms was not an important determinant of the prognostic effects of CRT in patients with moderate or severe LVSD and markers of dyssynchrony in the CARE-HF study. This finding requires confirmation in an adequately powered prospective randomised controlled trial in patients with milder symptoms.

Are elderly patients at increased risk of complications following pacemaker implantation? A meta-analysis of randomized trials.

Background:  Patients over the age of 75 represent more than half the recipients of permanent pacemakers. It is not known if they have a different risk of complications than younger patients.

Left ventricular dysfunction resulting from frequent unifocal ventricular ectopics with resolution following radiofrequency ablation

A case is presented, in which asymptomatic but persistent right ventricular outflow tract (RVOT) ectopics resulted in left ventricular (LV) dilatation and systolic dysfunction. The patient underwent extensive investigation with no other cause for the cardiomyopathy being found. Successful ablation of the RVOT ectopic focus resulted in normalization of LV size and function. This case suggests that frequent ventricular ectopy should be considered as a potentially remediable cause of LV dysfunction.

Fitness to fly for passengers with cardiovascular disease.

Following this review of evidence and after due consideration, it is clear that there are few cardiovascular conditions that warrant the denial of fitness to fly as a passenger. Given the right aircraft, on-board equipment and appropriately qualified and experienced escort personnel, aircraft can act as flying intensive care units and carry extremely ill passengers.1 For those with cardiovascular disease who are not critically ill but who wish to fly on commercial aircraft, the aircraft environment does not pose a significant threat to their health. It is only when their underlying condition is associated with a significant risk of acute deterioration that reasonable restrictions should apply. For those at the more severe end of the spectrum of their specific cardiovascular condition, services exist to help make the journey more easily and safely. Most carriers and airport authorities provide assistance on the ground and in the air. Oxygen is available on most major carriers, although this is sometimes subject to a charge and at least 7 days notice is normally required.2 Passengers are advised to plan their arrival at the airport in plenty of time to avoid having to rush and to warn the carrier and/or airport authority of any requirements for assistance, including requirement for in-flight oxygen, well in advance of the date of departure. They are strongly advised to ensure they have an appropriate supply of their medication, a clear list of the medications and doses they take and a letter of explanation from their doctor regarding their condition, drugs, allergies and devices (eg, pacemaker). Physicians are advised to consider the stability of a passengers condition and apply the guidance herein. The authors have contributed to this document in good faith and consider it to be an honest conclusion of the review of evidence and assessment of the …