The purpose of this prospective randomized study is to determine whether patients on cardiac resynchronization therapy with concomitant long-standing persistent or permanent atrial fibrillation would benefit from a strategy to restore and maintain sinus rhythm (rhythm control strategy) in comparison to a rate control strategy in terms of higher biventricular paced beats percentage.
Due to a lack of sufficient data the present guidelines on treatment of patients with atrial fibrillation (AF) and cardiac resynchronization therapy (CRT) devices are of low scientific evidence. The efficacy of CRT in AF patients is limited by the percentage of the effective biventricular paced beats (BiVp%), which should exceed 95%-98% - a goal which is seldom obtained by means of pharmacological rate control strategy. The only treatment strategy which effect is scientifically established is an atrioventricular junction ablation (AVJA) but the use of this method is limited. On the other hand, about 10% of patients with persistent forms of AF experience a spontaneous sinus rhythm (SR) resumption after CRT implantation. Moreover, SR resumption and it's maintenance by means of single external electrical cardioversion in AF patients has been proven feasible. A strategy of rhythm control in AF patients on CRT could provide high BiVp% and improve the efficacy of CRT in this group of patients. To show superiority of the rhythm control strategy over the rate control strategy a sample size of 60 patients was calculated based on following assumptions: two-tailed test, a type I error of 0.05, a power of 80%, efficacy (mean BiVp%) of rate control strategy 90%, efficacy (mean BiVp%)of rhythm control strategy 98% and 8% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to presumed lack of statistical power the secondary end points and safety endpoints will be considered exploratory.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
The pharmacological treatment in the rhythm control strategy consist of amiodarone given orally including the loading dose up to 600mg daily - for the first 4 weeks. Then, a maintenance dose of 200mg/daily is prescribed. The use of other anti-arrhythmic agents is possible unless they are contraindicated. The introduction of amiodarone must not be performed unless the patient is treated effectively with oral anticoagulants for 3 weeks at least. Discontinuation of amiodarone results neither in withdrawal from the study nor in change of the treatment arm.
The first EEC is performed after the loading dose of amiodarone has been administered. A maximal number of shocks during one cardioversion is 3. The amount of the energy delivered during shocks is left at discretion of a physician performing the EEC. The EEC must be performed in accordance with the present guidelines on EEC and post-procedural care and the state of art. If atrial fibrillation reoccur, the patient should undergo a next EEC as soon as possible but preserving the safety time margins (i.e. effective anticoagulation period). The maximal no. of EEC procedures is 3. If sinus rhythm resumption or its maintenance is impossible or AF reoccur after the 3rd EEC, a strategy of rhythm control is discontinued and a rate control strategy is implemented.
Institute of Cardiology, II Dept. of Coronary Heart Disease
Warsaw, Poland
RECRUITINGBiVp%
Percentage of effective biventricular paced beats during 1st year (mean percentage from baseline to the control visit in 12th month) .
Time frame: 1 year
6MWT distance
6 minute walk test distance (in meters)measured at 1 year from baseline
Time frame: 1 year
peak VO2
Peak oxygen uptake (peak VO2) measured by means of cardiopulmonary exercise test at 1 year from baseline
Time frame: 1 year
NYHA class
Heart failure (HF) symptoms escalation measured in New York Heart Association (NYHA) classes at 1 year from baseline
Time frame: 1 year
Ejection fraction
Ejection fraction (EF) \[%\] assessed in ECHO at 1 year from baseline
Time frame: 1 year
LVEDD reduction from baseline at 1 year
Change from baseline in left ventricle end-diastolic diameter (LVEDD) in ECHO at 1 year
Time frame: baseline and 1 year
LVEDV reduction from baseline at 1 year
Change from baseline in left ventricle end-diastolic volume (LVEDV) in ECHO at 1 year
Time frame: baseline and 1 year
LVESD reduction from baseline at 1 year
Change from baseline in left ventricle end-systolic diameter (LVESD) in ECHO at 1 year
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The pharmacotherapy should be consistent with current guidelines. It should include negative chronotropic and negative dromotropic agents such as beta-blockers, digitalis and amiodarone (the use of other, less popular agents, is also possible). The choice of the agents as well as their dosages are left at discretion of the treating physician. The goal of the therapy is to obtain BiVp% \>95%
The procedure of atrioventricular junction ablation is dedicated to the patients in the rate control group in who the rate control is unsatisfactory. An AVJA procedure is not obligatory. The decision to perform an AVJA should be discussed with the patient and should be made collectively by the therapeutic team.
Time frame: baseline and 1 year
LVESV reduction froma baseline at 1 year
Change from baseline in left ventricle end-systolic volume (LVESV) in ECHO at 1 year
Time frame: baseline and 1 year
Reduction of LA diameter at 1 year
Change from baseline in left atrium diameter assessed in ECHO at 1 year
Time frame: baseline and 1 year
Reduction of mitral regurgitation at 1 year
Change from baseline in mitral regurgitation measured in ECHO at 1 year
Time frame: baseline and 1 year
Heart failure exacerbations
Number of heart failure exacerbations in the treatment arm in 1 year time from baseline
Time frame: up to 1 year
Mortality
Numer of deaths assesed in 1 year follow-up
Time frame: up to 1 year
Stroke/TIA
Stroke or transient ischemic attack (TIA) during a year follow-up
Time frame: up to 1 year
CV mortality
Death due to cardiovascular (CV) causes during a year follow-up
Time frame: up to 1 year
Cardiovascular hospitalizations
Number of hospitalizations due to cardiovascular causes during a year follow-up
Time frame: up to 1 year
Quality of Life
The quality of life measured with the Minnesota Living with Heart Failure Questionaire (MLHFQ) at 1 year from baseline
Time frame: 1 year
AF prevalence
Measurement of the prevalence of atrial fibrillation (precentage of participants with AF) at 1 year from baseline
Time frame: 1 year
Ventricular arrhythmia
Number of ventricular arrhythmias (VF/"Torsade de Pointes" VT/sVT/nsVT) during the first year from basline
Time frame: up to 1 year
Electrotherapy
The number of high-energy interventions ("shocks") including separately: adequate shocks, inadequate shocks, electrical storm applies only to the patients with CRT-D device during the first year from baseline
Time frame: up to 1 year
Side effects
Overall number of side effects cases and complications cases of the treatment strategies related to: the device, the pharmacotherapy, the electrotherapy during the first year from baseline.
Time frame: 1 year
6MWT distance
6 minute walk test distance (in meters) at 3 months from baseline
Time frame: 3 months
peak VO2
Peak oxygen uptake (peak VO2) measured by means of cardiopulmonary exercise test at 3 months from baseline
Time frame: 3 months
NYHA class
Heart failure (HF) symptoms escalation measured in New York Heart Association (NYHA) classes at 3 months from baseline
Time frame: 3 months
Ejection fraction
Ejection fraction (EF) \[%\] assessed in ECHO at 3 months from baseline
Time frame: 3 months
LVEDD reduction
Change from baseline in left ventricle end-diastolic diameter (LVEDD) reduction in ECHO at 3 months
Time frame: baseline and 3 months
LVEDV reduction
Change from baseline in left ventricle end-diastolic volume (LVEDV) reduction in ECHO at 3 months
Time frame: baseline and 3 months
Reduction of LA area
Change from baseline in left atrium area assessed in ECHO at 1 year
Time frame: baseline and 1 year
Reduction of LA diameter
Change from baseline in left atrium diameter assessed in ECHO at 3 months
Time frame: baseline and 3 months
Reduction of mitral regurgitation
Change from baseline in mitral regurgitation measured in ECHO at 3 months
Time frame: baseline and 3 months
Stroke/TIA
Stroke or transient ischemic attack (TIA) during the first 3 months from baseline
Time frame: up to 3 months
Quality of Life
The quality of life measured with the Minnesota Living with Heart Failure Questionaire (MLHFQ) at 3 months from baseline
Time frame: 3 months
BiVp%
Percentage of effective biventricular paced beats during first 3 months from baseline.
Time frame: 3 months
AF prevalence
Measurement of the prevalence of atrial fibrillation (precentage of participants with AF) at 3 month from baseline
Time frame: 3 months
Electrotherapy
The number of high-energy interventions ("shocks") including separately: adequate shocks, inadequate shocks, electrical storm applies only to the patients with CRT-D device during first 3 months from baseline
Time frame: up to 3 months
Ventricular arrhythmia
Number of ventricular arrhythmias (VF/"Torsade de Pointes" VT/sVT/nsVT) during the first 3 months from basline
Time frame: up to 3 months
Side effects
Overall number of cases of side effects and complications of the treatment strategies related to: device, pharmacotherapy, electrotherapy during the first 3 months from baseline.
Time frame: 3 months
Reduction of LA area
Change from baseline in left atrium area assessed in ECHO at 3 months
Time frame: baseline and 3 month