A multiperspective on the broad dissemination of research findings to past research participants and the community-at-large.

Dissemination of research findings to past research participants and the community-at-large is a critical element to improving health outcomes, yet it is often overlooked by researchers. Few studies have explored how to provide study findings to the community, and no studies have investigated how community members can be involved in this process. This study explored views on the broad dissemination of research findings to community members and the role of the community in the dissemination process. We conducted a comparative analysis from the perspective of researchers, community members, and program officers (POs) from national health research funding agencies. Semistructured interviews were conducted with community members (African American, N = 10; Latino, N = 10), academic researchers (N = 10), and POs (N = 5). Thematic analysis was utilized in which codes and themes were created. One cross-cutting theme was identified, Views on Disseminating Research Findings to Communities. There were three additional themes identified among community members, five among researchers, and four among POs. All groups perceived the value of dissemination to communities as meaningful and ethical. Groups differed in their perceptions of prioritization of dissemination audiences. This study highlighted consensus on the value of broad dissemination to the community-at-large and identified areas of insufficiency in the translational research continuum that could be expanded or improved to ensure targeted groups receive the intended benefits of positive research findings. The long-term benefit of disseminating findings to the community-at-large is increased acceptability of interventions and reduced mistrust in research and researchers.

Prognostic importance of defibrillator shocks in patients with heart failure.

BACKGROUND: Patients with heart failure who receive an implantable cardioverter-defibrillator (ICD) for primary prevention (i.e., prevention of a first life-threatening arrhythmic event) may later receive therapeutic shocks from the ICD. Information about long-term prognosis after ICD therapy in such patients is limited. METHODS: Of 829 patients with heart failure who were randomly assigned to ICD therapy, we implanted the ICD in 811. ICD shocks that followed the onset of ventricular tachycardia or ventricular fibrillation were considered to be appropriate. All other ICD shocks were considered to be inappropriate. RESULTS: Over a median follow-up period of 45.5 months, 269 patients (33.2%) received at least one ICD shock, with 128 patients receiving only appropriate shocks, 87 receiving only inappropriate shocks, and 54 receiving both types of shock. In a Cox proportional-hazards model adjusted for baseline prognostic factors, an appropriate ICD shock, as compared with no appropriate shock, was associated with a significant increase in the subsequent risk of death from all causes (hazard ratio, 5.68; 95% confidence interval [CI], 3.97 to 8.12; P<0.001). An inappropriate ICD shock, as compared with no inappropriate shock, was also associated with a significant increase in the risk of death (hazard ratio, 1.98; 95% CI, 1.29 to 3.05; P=0.002). For patients who survived longer than 24 hours after an appropriate ICD shock, the risk of death remained elevated (hazard ratio, 2.99; 95% CI, 2.04 to 4.37; P<0.001). The most common cause of death among patients who received any ICD shock was progressive heart failure. CONCLUSIONS: Among patients with heart failure in whom an ICD is implanted for primary prevention, those who receive shocks for any arrhythmia have a substantially higher risk of death than similar patients who do not receive such shocks.

Impact of implantable cardioverter-defibrillator, amiodarone, and placebo on the mode of death in stable patients with heart failure: analysis from the sudden cardiac death in heart failure trial.

BACKGROUND: The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter-defibrillator (ICD) therapy reduces all-cause mortality in patients with New York Heart Association class II/III heart failure and a left ventricular ejection fraction < or =35% on optimal medical therapy. Whether ICD therapy reduced sudden death caused by ventricular tachyarrhythmias without affecting heart failure deaths in this population is unknown. METHODS AND RESULTS: SCD-HeFT randomized 2521 subjects to placebo, amiodarone, or shock-only, single-lead ICD therapy. Over a median follow-up of 45.5 months, a total of 666 deaths occurred, which were reviewed by an Events Committee and initially categorized as cardiac or noncardiac. Cardiac deaths were further adjudicated as resulting from sudden death presumed to be ventricular tachyarrhythmic, bradyarrhythmia, heart failure, or other cardiac causes. ICD therapy significantly reduced cardiac mortality compared with placebo (adjusted hazard ratio, 0.76; 95% confidence interval, 0.60 to 0.95) and tachyarrhythmia mortality (adjusted hazard ratio, 0.40; 95% confidence interval, 0.27 to 0.59) and had no impact on mortality resulting from heart failure or noncardiac causes. The cardiac and tachyarrhythmia mortality reductions were evident in subjects with New York Heart Association class II but not in subjects with class III heart failure. The reduction in tachyarrhythmia mortality with ICD therapy was similar in subjects with ischemic and nonischemic disease. Compared with placebo, amiodarone had no significant effect on any mode of death. CONCLUSIONS: ICD therapy reduced cardiac mortality and sudden death presumed to be ventricular tachyarrhythmic in SCD-HeFT and had no effect on heart failure mortality. Amiodarone had no effect on all-cause mortality or its cause-specific components, except an increase in non-cardiac mortality in class III patients. [corrected] CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000609.

Ejection fraction assessment and survival: an analysis of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

BACKGROUND: Ejection fraction (EF) is an important method of mortality prediction among cardiac patients, and has been used to identify the highest risk patients for enrollment in the defibrillator primary prevention trials. Evidence suggests that measures of EF by different imaging modalities may not be equivalent. In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), the type of imaging modality for EF assessment was not mandated. METHODS: Baseline assessment of EF was performed using either echocardiography, radionuclide angiography (RNA), or contrast angiography. Multivariable analysis using a Cox proportional hazards model was used to examine whether the modality of assessing EF affected the likelihood of survival. RESULTS: Among the 2,521 patients enrolled in SCD-HeFT, EF was measured by RNA in 616 (24%), echocardiography in 1,469 (58%), and contrast angiography in 436 (17%). Mean EF as measured by RNA was 25.1% +/- 6.9%; by echocardiography, 23.8 +/- 6.9%; and by angiography, 21.9 +/- 6.9%. These measures were significantly different (P < .001), and each pairwise comparison differed significantly (P < .001 for each). Multivariable analysis showed no significant difference in survival between patients enrolled based on RNA versus echocardiography (HR 1.06, 95% CI 0.88-1.28), RNA versus angiography (HR 1.25, 95% CI 0.97-1.62), or echocardiography versus angiography (HR 1.18, 95% CI 0.94-1.48). CONCLUSIONS: Among patients enrolled in SCD-HeFT, the distribution of ejection fractions measured by radionuclide angiography differed from those measured by echocardiography or contrast angiograms. Survival did not differ according to modality of EF assessment.

Primary prevention with defibrillator therapy in women: results from the Sudden Cardiac Death in Heart Failure Trial.

INTRODUCTION: The Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) demonstrated that implantable cardioverter defibrillator (ICD) therapy reduced overall mortality in patients with class II or III heart failure and left ventricular ejection fraction (LVEF)

Where patients with mild to moderate heart failure die: results from the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).

BACKGROUND: Common locations of death in patients with congestive heart failure (CHF) are unknown. In the SCD-HeFT, mortality of patients with CHF was assessed after randomization to an implantable cardioverter/defibrillator (ICD), amiodarone, or placebo. The aim of this study was to evaluate the location of deaths in SCD-HeFT. METHODS: Among SCD-HeFT patients whose location of death was identified, we used logistic regression to assess the relationship of randomized treatment arm and other baseline predictors with the location of death. Cause of death was adjudicated by a therapy-blinded events committee. RESULTS: In SCD-HeFT, 666 (26%) of 2521 patients died. Of the 604 (91%) for whom location of death was known, 58% died in hospital and 29% died at home. Patients randomized to receive an ICD were less likely to die at home than patients randomized to placebo (P = .002). Fewer patients randomized to ICDs died; even fewer randomized to ICDs died at home. Age, sex, etiology of heart failure, left ventricular ejection fraction, and New York Heart Association functional class were not associated with location of death. Sudden cardiac death represented 52% of all out-of-hospital deaths but in hospital deaths exceeded out-of-hospital deaths. CONCLUSION: Deaths in SCD-HeFT, a well-treated CHF population, were most often in hospital. ICDs were associated with lower total and sudden death rates at home and in hospital. Development of methods to identify which patients will not respond to optimal treatment, including an ICD, remain a challenge.

Unexpected deviation in circadian variation of ventricular arrhythmias: the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial).

OBJECTIVES: This study sought to determine whether circadian patterns in ventricular arrhythmias (VAs) occur in a current primary prevention defibrillator (implantable cardioverter-defibrillator [ICD]) population. BACKGROUND: Cardiovascular events, including VAs, demonstrate biorhythmic periodicity. METHODS: We tested for deviation from the previously described occurrences of a morning peak, early morning nadir, and peak on Mondays in ICD therapies using generalized estimating equations and Student t tests. All hypothesis tests were performed in the entire cohort of patients with VAs as well as pre-specified subgroups. RESULTS: Of 811 patients with an ICD, 186 subjects experienced 714 ICD therapy episodes for life-threatening VA. There was no morning (6 am to 12 pm) peak in therapies for the entire cohort or any subgroups. The overall cohort and several subgroups had a typical early morning (12 am to 6 am) nadir in therapies, with significantly less than 25% of therapies occurring during this 6-h block (all p < 0.05). A significant peak in therapies on Mondays occurred only in patients not on beta-blocker therapy (22% of events for the week, p = 0.029). CONCLUSIONS: In the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) population, the distribution of life-threatening VA failed to show a typical early morning peak or increased VA events on Mondays. A typical early morning nadir was seen in the entire cohort. An increased rate of events on Mondays was found in the subgroup of subjects not on beta-blocker therapy. These findings may indicate suppression of the neurohormonal triggers for VA by current heart failure therapy, particularly the use of beta-blockers in heart failure.

No benefit of a dual coil over a single coil ICD lead: evidence from the Sudden Cardiac Death in Heart Failure Trial.

BACKGROUND: Dual coil implantable cardioverter-defibrillator (ICD) leads with a superior vena cava (SVC) electrode have been considered standard of care despite sparse data suggesting improved ICD defibrillation efficacy. SVC coils increase lead complexity, cost, risk of lead failure, and lead removal. OBJECTIVE: To compare all-cause mortality, sudden cardiac death, implant defibrillation threshold (DFT) test energies, appropriate shock rates, and first shock efficacy for ventricular tachyarrhythmias for dual coil vs single coil leads in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). METHODS: In SCD-HeFT, 811 patients with heart failure received a single lead transvenous ICD (Medtronic model 7223) and underwent protocol-driven DFT testing. The selection of a dual vs single coil right ventricular (RV) lead was at the physician's discretion. DFT data were available in 717 patients. RESULTS: Dual coil leads were used in 563 and single coil in 246 patients. After 45.5-month follow-up, overall mortality was similar (19.4% for dual coil vs 21.5% for single coil; adjusted hazard ratio 0.95; 95% confidence interval 0.68-1.34; P = .78). Sudden cardiac death was also similar (3.6% for dual coil vs 3.7% for single coil; P = .96). First shock efficacy was 82.2% vs 91.9% (dual coil vs single coil; unadjusted odds ratio 0.41; 95% confidence interval 0.15-1.13; P = .085). Mean DFT was 12.1 ± 4.7 J vs 12.8 ± 4.8 J (dual coil vs single coil; P = .087). CONCLUSIONS: In the SCD-HeFT, the addition of an SVC coil for left-sided implants was not associated with improved outcome measures. We advocate returning to single coil RV ICD leads as the standard of care to decrease chronic lead complications.

Thyroid function in heart failure and impact on mortality.

OBJECTIVES: The aim of this study was to investigate whether patients with systolic heart failure (HF) and abnormal thyroid function are at increased risk for death. BACKGROUND: Thyroid hormone homeostasis is vital to the optimal functioning of the cardiovascular system, but an independent prognostic effect of thyroid abnormalities in patients with HF has not been established. METHODS: In SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial), which randomized patients with ischemic or nonischemic HF to placebo or amiodarone or implantable cardioverter-defibrillator therapy, thyroid-stimulating hormone (TSH) was measured at baseline and at 6-month intervals throughout the 5-year study. RESULTS: Of 2,225 patients, the majority (87%) had normal TSH levels (0.3 to 5.0 µU/ml) at baseline, 12% had values suggestive of hypothyroidism, and 1% had values consistent with hyperthyroidism. Compared with euthyroid patients, those hypothyroid at baseline were older and included more women and Caucasians (all p values <0.05). Over the median follow-up period of 45.5 months, among patients euthyroid at baseline, 89 developed abnormally low TSH levels, and 341 developed abnormally high values. Patients randomized to amiodarone (median dose 300 mg) had an elevated risk for developing abnormal TSH levels compared with implantable cardioverter-defibrillator therapy or placebo (p < 0.0001). Patients with baseline or new-onset abnormal thyroid function had a higher mortality than those with normal thyroid function, even after controlling for other known mortality predictors (hazard ratio: 1.58; 95% confidence interval: 1.29 to 1.94; p < 0.0001 for hypothyroid; hazard ratio: 1.85; 95% confidence interval: 1.21 to 2.83; p = 0.0048 for hyperthyroid). Implantable cardioverter-defibrillator benefit did not vary with thyroid function. CONCLUSIONS: Abnormal thyroid function in patients with symptomatic HF and ejection fractions ≤35% is associated with significantly increased risk for death, even after controlling for known mortality predictors.

No benefit from defibrillation threshold testing in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial).

OBJECTIVES: This study investigated whether defibrillation threshold (DFT) testing during implantable cardioverter-defibrillator (ICD) implantation predicts clinical outcomes. BACKGROUND: Defibrillation testing is often performed during insertion of ICDs to confirm shock efficacy. There are no prospective data to suggest that this procedure improves outcomes when modern ICDs are implanted for primary prevention of sudden death. METHODS: The analysis included the 811 patients who were randomized to the ICD arm of the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) and had the device implanted. The DFT testing protocol in SCD-HeFT was designed to limit shock testing in a primary prevention heart failure population. RESULTS: Baseline DFT data were available for 717 patients (88.4%). All 717 patients had a DFT of < or =30 J, the maximum output of the device in this study. The DFT was < or =20 J in 97.8% of patients. There was no survival difference between patients with a lower DFT (< or =10 J, n = 547) and a higher DFT (>10 J, n = 170) (p = 0.41). First shock efficacy was 83.0% for the first clinical ventricular tachyarrhythmia event; there were no differences in shock efficacies when the cohort was subdivided by baseline DFT. CONCLUSIONS: Low baseline DFTs were obtained in patients with stable, optimally treated heart failure during ICD implantation for primary prevention of sudden death. First shock efficacy for ventricular tachyarrhythmias was high regardless of baseline DFT testing results. Baseline DFT testing did not predict long-term mortality or shock efficacy in this study.