Search

Aims: Patients with heart failure usually have several other medical conditions that might alter the effects of interventions. We investigated whether the burden of comorbidity modified the clinical response to cardiac resynchronization therapy (CRT). Methods and results: Original patient‐level data from eight randomized trials exploring the effects of CRT versus no CRT were pooled (BLOCK‐HF, MIRACLE, MIRACLE‐ICD, MIRACLE‐ICD II, RAFT, COMPANION, MADIT‐CRT and REVERSE). A prior history of the following comorbidities was considered: episodic or persistent atrial fibrillation (n = 920), coronary artery disease (n = 3732), diabetes (n = 2171), and hypertension (n = 3353). Patients were classified into three groups based on the number of comorbidities: 0, 1–2, or ≥3. The outcomes of interest were time to all‐cause mortality and time to the composite outcome of heart failure hospitalization (HFH) or all‐cause mortality. Outcomes were evaluated within each comorbidity group using a Bayesian hierarchical Weibull survival regression model. Of 6324 patients, 970 (15%) had no comorbidities, 4052 (64%) had 1–2 and 1302 (21%) had ≥3 comorbidities. The adjusted hazard ratio (aHR) for CRT versus no CRT for all‐cause mortality in the overall cohort was 0.79 (95% credible interval [CI] 0.68–0.93) (p = 0.010); for no comorbidities the aHR was 0.54 (95% CI 0.34–0.86), for 1–2 comorbidities was 0.81 (95% CI 0.67–0.97) and for ≥3 comorbidities was 0.83 (95% CI 0.64–1.07) (no significant interaction between CRT and comorbidity burden: p = 0.13). For the endpoint of HFH or all‐cause mortality, the aHR for the overall cohort was 0.74 (95% CI 0.65–0.84) (p = 0.001), for no comorbidities was 0.69 (95% CI 0.50–0.94), for 1–2 comorbidities was 0.77 (95% CI 0.66–0.90) and for ≥3 comorbidities was 0.68 (95% CI 0.55–0.82) (no significant interaction between CRT and comorbidity burden: p = 0.081). Conclusion: In a meta‐analysis of patient‐level data from eight major trials, the totality of evidence suggests that CRT reduces HFH and/or all‐cause mortality even when several comorbid diseases are present. Clinical Trial Registration: NCT00271154, NCT00251251, NCT00267098, NCT00180271. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association of cardiac resynchronization therapy (CRT) on outcomes among participants with and without a history of atrial fibrillation (AF). Methods: Individual‐patient‐data from four randomized trials investigating CRT‐Defibrillators (COMPANION, MADIT‐CRT, REVERSE) or CRT‐Pacemakers (COMPANION, MIRACLE) were analyzed. Outcomes were time to a composite of heart failure hospitalization or all‐cause mortality or to all‐cause mortality alone. The association of CRT on outcomes for patients with and without a history of AF was assessed using a Bayesian‐Weibull survival regression model adjusting for baseline characteristics. Results: Of 3964 patients included, 586 (14.8%) had a history of AF; 2245 (66%) were randomized to CRT. Overall, CRT reduced the risk of the primary composite endpoint (hazard ratio [HR]: 0.69, 95% credible interval [CI]: 0.56–0.81). The effect was similar (posterior probability of no interaction = 0.26) in patients with (HR: 0.78, 95% CI: 0.55–1.10) and without a history of AF (HR: 0.67, 95% CI: 0.55–0.80). In these four trials, CRT did not reduce mortality overall (HR: 0.82, 95% CI: 0.66–1.01) without evidence of interaction (posterior probability of no interaction = 0.14) for patients with (HR: 1.09, 95% CI: 0.70–1.74) or without a history of AF (HR: 0.70, 95% CI: 0.60–0.97). Conclusion: The association of CRT on the composite endpoint or mortality was not statistically different for patients with or without a history of AF, but this could reflect inadequate power. Our results call for trials to confirm the benefit of CRT recipients with a history of AF. [ABSTRACT FROM AUTHOR]

Background No precise tools exist to predict appropriate shocks in patients with a primary prevention ICD. We sought to identify characteristics predictive of appropriate shocks in patients with a primary prevention implantable cardioverter defibrillator (ICD). Methods Using patient-level data from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), we identified patients with any appropriate shock. Clinical and demographic variables were included in a logistic regression model to predict appropriate shocks. Results There were 1,463 patients randomized to an ICD, and 285 (19%) had ≥1 appropriate shock over a median follow-up of 2.59 years. Compared with patients without appropriate ICD shocks, patients who received any appropriate shock tended to have more severe heart failure. In a multiple logistic regression model, predictors of appropriate shocks included NYHA class (NYHA II vs. I: OR 1.65, 95% CI 1.07-2.55; NYHA III vs. I: OR 1.74, 95% CI 1.10-2.76), lower LVEF (per 1% change) (OR 1.04, 95% CI 1.02-1.06), absence of beta-blocker therapy (OR 1.61, 95% CI 1.23-2.12), and single chamber ICD (OR 1.67, 95% CI 1.13-2.45). Conclusion In this meta-analysis of patient level data from MADIT-II and SCD-HeFT, higher NYHA class, lower LVEF, no beta-blocker therapy, and single chamber ICD (vs. dual chamber) were significant predictors of appropriate shocks. [ABSTRACT FROM AUTHOR]

Objective To review the performance characteristics of the instruments most commonly used to measure clinical outcomes in juvenile idiopathic arthritis (JIA), including global assessments, articular indices, functional/disability assessments, and quality of life measures. Methods As part of an Agency for Healthcare Research and Quality comparative effectiveness review of antirheumatic drugs, we explored the characteristics of commonly used outcome measures for JIA. English-language studies of children with JIA were identified from Medline and Embase. Two independent reviewers screened titles and abstracts, with subsequent full-text review of studies selected based on predetermined criteria. Results We included 35 publications describing 34 unique studies and involving 14,831 patients. The Childhood Health Assessment Questionnaire (C-HAQ) was the most extensively studied instrument and had high reliability, but only moderate correlations with other indices of disease activity and poor responsiveness to change in disease status. The physician global assessment of disease activity (PGA) and articular indices had the strongest association with disease activity and were the most responsive to change. Measures of psychosocial function and quality of life were moderately associated with measures of disease activity, but were less responsive to changes in disease status. Conclusion In children with JIA, no single instrument was superior in reliability or validity or in describing the impact of JIA. Although the C-HAQ has been extensively evaluated, the PGA and articular indices appear to have the highest responsiveness to change and, therefore, the highest potential for detecting important differences in treatment response. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pathologic and genetic data suggest that epithelial ovarian cancer may consist of indolent and aggressive phenotypes. The objective of the current study was to estimate the impact of a 2-phenotype paradigm of epithelial ovarian cancer on the mortality reduction achievable using available screening technologies. METHODS: The authors modified a Markov model of ovarian cancer natural history (the 1-phenotype model) to incorporate aggressive and indolent phenotypes (the 2-phenotype model) based on histopathologic criteria. Stage distribution, incidence, and mortality were calibrated to data from the Surveillance, Epidemiology, and End Results Program of the US National Cancer Institute. For validation, a Monte Carlo microsimulation (1000,000 events) of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) multimodality prevalence screen was performed. Mortality reduction and positive predictive value (PPV) were estimated for annual screening. RESULTS: In validation against UKCTOCS data, the model-predicted percentage of screen-detected cancers diagnosed at stage I and II was 41% compared with 47% (UKCTOCS data), and the model-predicted PPV of screening was 27% compared with 35% (UKCTOCS data). The model-estimated PPV of a strategy of annual population-based screening in the United States at ages 50 to 85 years was 14%. The mortality reduction using annual postmenopausal screening was 14.7% (1-phenotype model) and 10.9% (2-phenotype model). Mortality reduction was lower with the 2-phenotype model than with the 1-phenotype model regardless of screening frequency or test sensitivity; 68% of cancer deaths are accounted for by the aggressive phenotype. CONCLUSIONS: The current analysis suggested that reductions in ovarian cancer mortality using available screening technologies on an annual basis are likely to be modest. A model that incorporated 2 clinical phenotypes of ovarian carcinoma into its natural history predicted an even smaller potential reduction in mortality because of the more frequent diagnosis of indolent cancers at early stages. [ABSTRACT FROM AUTHOR]

Implantable cardioverter defibrillator (ICD) therapy improves survival of patients with systolic heart failure. We assessed whether physicians' recommendation for ICD therapy varies as a function of patient age, gender, race, and physician's specialty. We surveyed a random sample (n = 9969) of U.S. physicians who are active members of the American College of Cardiology (ACC). We asked participants about their likelihood to recommend ICD therapy in 4 clinical scenarios that randomly varied patient age, gender, race, and ICD indication (guideline Class I, Class IIa, Class III, and Class I in a noncompliant patient). Responses were received from 1210 physicians (response rate 12%), of whom 1127 met the study inclusion criteria. Responders and nonresponders had similar demographics. In responding to hypothetical clinical scenarios, physicians were less likely to recommend an ICD to older patients (≥80 vs 50 years) (P < 0.01) but were unaffected by gender or race for all class indications. Compared with nonelectrophysiologists (EPs), EPs were significantly more likely to recommend an ICD for a Class I indication (92.4% vs 81.4%; P < 0.01), but they were not more likely to offer an ICD for a Class III indication (0.4% vs 0.6%; P = 0.95). Based on survey responses, physicians were equally willing to offer an ICD to men and women and to whites and blacks, but were less likely to offer an ICD to an older patient even when indicated by practice guidelines. Electrophysiologists (EPs) more often adhered to practice guideline recommendations on ICD therapy compared with non-EPs. [ABSTRACT FROM AUTHOR]

ICD Implant Timing. Background: The optimal timing of implantable cardioverter defibrillator (ICD) placement for the primary prevention of sudden cardiac death after myocardial infarction (MI) remains unknown. Methods and Results: We developed a Markov model to investigate the optimal timing of ICD implantation after MI (no ICD, ICD at 60 days, 6 months, and 1 year) in patients who meet current guidelines. Estimates of arrhythmic death (baseline risk 6%, range 1–20% per year), nonarrhythmic death, and ICD efficacy were based upon MADIT-II and other contemporary post-MI clinical trials. We used both deterministic and stochastic modeling processes in our analysis. After 10 years follow-up, the baseline probability of survival was higher in those treated with ICD implantation versus not (42% vs 30%, P < 0.001). Survival was highest with ICD implantation at 60 days versus 6 months versus 1 year: 42.4%, 42.3%, and 42.0% (P = 0.0028). ICD implantation at 60 days provided a mean incremental survival of 0.28 months and 0.84 months per patient (compared with implantation at 6 months and 1 year). In sensitivity analyses, patients’ competing risk for nonarrhythmic death was the primary determinant of benefit from ICD implantation. Overall, ICD implantation at 60 days resulted in the greatest life expectancy over a wide range of plausible nonarrhythmic and arrhythmic death rates. Conclusions: The benefits of early ICD implantation are modest when compared with delayed implantation at 6 months/1 year. Our results suggest that making sure a patient receives an ICD, when appropriate, may be more important than the timing of the implantation procedure. (J Cardiovasc Electrophysiol, Vol. pp. 791-798, July 2010) [ABSTRACT FROM AUTHOR]

ICD: Remote Monitoring Versus Clinic Interrogations. Introduction: Remote monitoring is increasingly becoming the new standard of care for implantable cardioverter defibrillator (ICD) follow-up. We sought to determine whether remote monitoring of ICDs improves patient outcomes compared with quarterly device interrogations in clinic. Methods and Results: In this single-center pilot clinical trial, adult patients with an ICD were randomly assigned to remote monitoring versus quarterly device interrogations in clinic. The primary endpoint was a composite of cardiovascular hospitalization, emergency room visit for a cardiac cause, and unscheduled visit to the electrophysiology clinic for a device-related issue at 1 year. We also examined health-related quality of life, costs, and patient satisfaction with their ICD care. Of 151 patients enrolled in this trial, 76 were randomized to remote monitoring and 75 to quarterly device interrogations in clinic. There was no significant difference in the primary endpoint (32% in the remote monitoring arm vs 34% in the control arm; P = 0.8), mortality, or cost between the 2 arms. Quality of life and patient satisfaction were significantly better in the control arm than in the remote monitoring arm at 6 months (83 [25th, 75th percentiles 70, 90] vs 75 [50, 85]; P = 0.002 and 88 [75, 100] vs 75 [75, 88]; P = 0.03, respectively), but not at 12 months. Conclusion: We showed no significant reduction in cardiac-related resource utilization with remote monitoring of ICDs. However, given the small number of patients in our study, the real clinical and health economics impact of remote monitoring needs to be verified by a large, multicenter, randomized clinical trial. (J Cardiovasc Electrophysiol, Vol. 21, pp. 545-550, May 2010) [ABSTRACT FROM AUTHOR]

AbstractCommonly used methods for guideline development and dissemination do not enable developers to tailor guidelines systematically to specific patient populations and update guidelines easily. We developed a web-based system, ALCHEMIST, that uses decision models and automatically creates evidence-based guidelines that can be disseminated, tailored and updated over the web. Our objective was to demonstrate the use of this system with clinical scenarios that provide challenges for guideline development. We used the ALCHEMIST system to develop guidelines for three clinical scenarios: (1) Chlamydia screening for adolescent women, (2) antiarrhythmic therapy for the prevention of sudden cardiac death; and (3) genetic testing for the BRCA breast-cancer mutation. ALCHEMIST uses information extracted directly from the decision model, combined with the additional information from the author of the decision model, to generate global guidelines. ALCHEMIST generated electronic web-based guidelines for each of the three scenarios. Using ALCHEMIST, we demonstrate that tailoring a guideline for a population at high-risk for Chlamydia changes the recommended policy for control of Chlamydia from contact tracing of reported cases to a population-based screening programme. We used ALCHEMIST to incorporate new evidence about the effectiveness of implantable cardioverter defibrillators (ICD) and demonstrate that the cost-effectiveness of use of ICDs improves from $74 400 per quality-adjusted life year (QALY) gained to $34 500 per QALY gained. Finally, we demonstrate how a clinician could use ALCHEMIST to incorporate a woman’s utilities for relevant health states and thereby develop patient-specific recommendations for BRCA testing; the patient-specific recommendation improved quality-adjusted life expectancy by 37 days. The ALCHEMIST system enables guideline developers to publish both a guideline and an interactive decision model on the web. This web-based tool enables... [ABSTRACT FROM AUTHOR]