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.
At least 30 million people worldwide carry a diagnosis of atrial fibrillation (AF), and many more suffer from undiagnosed, subclinical, or 'silent' AF. Atrial fibrillation-related cardiovascular ...mortality and morbidity, including cardiovascular deaths, heart failure, stroke, and hospitalizations, remain unacceptably high, even when evidence-based therapies such as anticoagulation and rate control are used. Furthermore, it is still necessary to define how best to prevent AF, largely due to a lack of clinical measures that would allow identification of treatable causes of AF in any given patient. Hence, there are important unmet clinical and research needs in the evaluation and management of AF patients. The ensuing needs and opportunities for improving the quality of AF care were discussed during the fifth Atrial Fibrillation Network/European Heart Rhythm Association consensus conference in Nice, France, on 22 and 23 January 2015. Here, we report the outcome of this conference, with a focus on (i) learning from our 'neighbours' to improve AF care, (ii) patient-centred approaches to AF management, (iii) structured care of AF patients, (iv) improving the quality of AF treatment, and (v) personalization of AF management. This report ends with a list of priorities for research in AF patients.
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.
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.
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.
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.
See Editorial by Maas, A.H. and Westenbrink, B. D
Abstract 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.
NOWAK, B., et al.: Effect of the Atrial Blanking Time On the Detection of Atrial Fibrillation in Dual Chamber Pacing. Patients with paroxysmal atrial fibrillation (PAF) and dual chamber pacemakers ...frequently have short postventricular atrial blanking times and sensitive atrial sensing thresholds used to provide reliable detection and mode switching during AF. However, short atrial blanking times increase the risk of atrial sensing of ventricular far‐field signals. We evaluated if the length of the atrial blanking time influences the detection of AF. The study included ten patients with a VDDR (n = 7) or DDDR system (n = 3), who presented with AF at 18 follow‐up visits. Bipolar atrial sensing was programmed to the most sensitive value. Atrial blanking times were programmed from 100 to 200 ms in 25‐ms steps in each patient. Using marker annotation, the following parameters were measured at ten consecutive ventricular beats: VAF = the interval between ventricular stimulus and first sensing of AF; AFS = the number of atrial‐sensed events between two ventricular events; and XAF = the interpolated number of atrial‐sensed events during atrial blanking time. The intervals between ventricular events and between atrial‐sensed event markers showed no significant differences for the five blanking times tested. There was no significant influence of the atrial blanking time onto the measured parameters (least square means ± standard error) with VAF between 281 ± 12 and 300 ± 12 ms (P = NS), AFs between 3.4 ± 0.2 and 3.6 ± 0.2 beats (P = NS) and XAF between 1.84 ± 0.12 and 2.03 ± 0.12 beats (P = NS). At ventricular rates < 100/min, the atrial sensing of AF in dual chamber pacemakers demonstrated no evidence for deterioration by an increase of the atrial blanking time from 100 to 200 ms. Thus, the risk of ventricular far‐field sensing may be reduced without compromising atrial sensing.
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.
Maintenance of sinus rhythm is the main therapeutic goal in patients with atrial fibrillation. However, recurrences of atrial fibrillation and side effects of antiarrhythmic drugs offset the benefits ...of sinus rhythm. We hypothesized that ventricular rate control is not inferior to the maintenance of sinus rhythm for the treatment of atrial fibrillation.
We randomly assigned 522 patients who had persistent atrial fibrillation after a previous electrical cardioversion to receive treatment aimed at rate control or rhythm control. Patients in the rate-control group received oral anticoagulant drugs and rate-slowing medication. Patients in the rhythm-control group underwent serial cardioversions and received antiarrhythmic drugs and oral anticoagulant drugs. The end point was a composite of death from cardiovascular causes, heart failure, thromboembolic complications, bleeding, implantation of a pacemaker, and severe adverse effects of drugs.
After a mean (+/-SD) of 2.3+/-0.6 years, 39 percent of the 266 patients in the rhythm-control group had sinus rhythm, as compared with 10 percent of the 256 patients in the rate-control group. The primary end point occurred in 44 patients (17.2 percent) in the rate-control group and in 60 (22.6 percent) in the rhythm-control group. The 90 percent (two-sided) upper boundary of the absolute difference in the primary end point was 0.4 percent (the prespecified criterion for noninferiority was 10 percent or less). The distribution of the various components of the primary end point was similar in the rate-control and rhythm-control groups.
Rate control is not inferior to rhythm control for the prevention of death and morbidity from cardiovascular causes and may be appropriate therapy in patients with a recurrence of persistent atrial fibrillation after electrical cardioversion.
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