Cardiac resynchronization therapy in heart failure patients with less severe left ventricular dysfunction.

Cardiac resynchronization therapy is beneficial in heart failure patients with LVEF ≤35% and electrical dyssynchrony. However, its effects among patients with less severe LV dysfunction have not been established. Recent post-hoc analyses of landmark CRT trials suggest that CRT benefit may be present in patients with LVEF >35% and is associated with improvement in cardiac reverse remodelling, all-cause mortality, and need for heart failure hospitalizations. This review summarizes the currently available literature regarding the potential impact of CRT in patients with more modest reductions in LVEF.

Trials of implantable monitoring devices in heart failure: which design is optimal?

Implantable monitoring devices have been developed to detect early evidence of heart failure (HF) decompensation, with the hypothesis that early detection might enable clinicians to commence therapy sooner than would otherwise be possible, and potentially to reduce the rate of hospitalization. In addition to the usual challenges inherent to device trials (such as the difficulty of double-blinding and potential for bias), studies of implantable monitoring devices present unique difficulties because they involve assessment of therapeutic end points for diagnostic devices. Problems include the lack of uniform approaches to treatment in study protocols for device alerts or out-of-range values, and the requirement of levels of evidence traditionally associated with therapeutic devices to establish effectiveness and safety. In this Review, the approaches used to deal with these issues are discussed, including the use of objective primary end points with blinded adjudication, identical duration of follow-up and number of encounters for patients in active monitoring and control groups, and treatment recommendations between groups that are consistent with international guidelines. Remote monitoring devices hold promise for reducing the rate of hospitalization among patients with HF. However, optimization of regulatory approaches and clinical trial design is needed to facilitate further evaluation of the effectiveness of combining health information technology and medical devices.

Current challenges for clinical trials of cardiovascular medical devices.

Several features of cardiovascular devices raise considerations for clinical trial conduct. Prospective, randomized, controlled trials remain the highest quality evidence for safety and effectiveness assessments, but, for instance, blinding may be challenging. In order to avoid bias and not confound data interpretation, the use of objective endpoints and blinding patients, study staff, core labs, and clinical endpoint committees to treatment assignment are helpful approaches. Anticipation of potential bias should be considered and planned for prospectively in a cardiovascular device trial. Prospective, single-arm studies (often referred to as registry studies) can provide additional data in some cases. They are subject to selection bias even when carefully designed; thus, they are generally not acceptable as the sole basis for pre-market approval of high risk cardiovascular devices. However, they complement the evidence base and fill the gaps unanswered by randomized trials. Registry studies present device safety and effectiveness in day-to-day clinical practice settings and detect rare adverse events in the post-market period. No single research design will be appropriate for every cardiovascular device or target patient population. The type of trial, appropriate control group, and optimal length of follow-up will depend on the specific device, its potential clinical benefits, the target patient population and the existence (or lack) of effective therapies, and its anticipated risks. Continued efforts on the part of investigators, the device industry, and government regulators are needed to reach the optimal approach for evaluating the safety and performance of innovative devices for the treatment of cardiovascular disease.

Outcome parameters for trials in atrial fibrillation: executive summary.

Atrial fibrillation (AF), the most common atrial arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, 'upstream therapy') only prevent a part of this burden of disease. Several new treatment modalities are therefore under evaluation in controlled trials. Given the multifold clinical consequences of AF, trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these 'requirements' for outcome assessment in AF trials, further, more detailed outcome parameters are described. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF-related morbidity and mortality is desirable for any clinical trial in AF.

Outcome parameters for trials in atrial fibrillation: recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork and the European Heart Rhythm Association.

Atrial fibrillation (AF), the most common atrial arrhythmia, has a complex aetiology and causes relevant morbidity and mortality due to different mechanisms, including but not limited to stroke, heart failure, and tachy- or bradyarrhythmia. Current therapeutic options (rate control, rhythm control, antithrombotic therapy, 'upstream therapy') only prevent a part of this burden of disease. New treatment modalities are therefore currently under evaluation in clinical trials. Given the multifold clinical consequences of AF, controlled trials in AF patients should assess the effect of therapy in each of the main outcome domains. This paper describes an expert consensus of required outcome parameters in seven relevant outcome domains, namely death, stroke, symptoms and quality of life, rhythm, left ventricular function, cost, and emerging outcome parameters. In addition to these 'requirements' for outcome assessment in AF trials, further outcome parameters are described in each outcome domain. In addition to a careful selection of a relevant primary outcome parameter, coverage of outcomes in all major domains of AF-related morbidity and mortality is desirable for any clinical trial in AF.