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Cardiac Resynchronization in Atrial Fibrillation Trial - a Pilot Study

Phase 4
Conditions
Atrial Fibrillation
Heart Failure
Interventions
Drug: Pharmacotherapy to slow and control ventricular rate
Procedure: External electrical cardioversion (EEC)
Procedure: Atrioventricular junction ablation (AVJA)
Registration Number
NCT01850277
Lead Sponsor
National Institute of Cardiology, Warsaw, Poland
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
60
Inclusion Criteria
  • Permanent or long-standing persistent atrial fibrillation (definitions according to the latest European Society of Cardiology guidelines on AF)
  • At least 3 months after a procedure of a CRT device implantation
  • A CRT device with a presence of a right atrial electrode
  • Age: ≥18 years old
  • Effectively biventricular paced captured beats <95%
  • Effective therapy with oral anticoagulants for at least 3 months
  • Written informed consent
Exclusion Criteria
  • Reversible causes of AF
  • Significant valve disease
  • Advanced A-V block (including: AVJA)
  • Contraindications to amiodarone (hyperthyroidism, not compensated hypothyroidism, drug intolerance, QT>460ms for men, QT>450 for women)
  • Long-QT syndrome
  • Decompensation of the heart failure within 48 hours before the qualification
  • Cardiac transplantation in 6 months
  • Life expectancy less than 1 year
  • Chronic dialysis
  • LA diameter >6cm
  • Alcohol abuse
  • Pregnancy/lack of effective contraceptive therapy (in case of females in the reproductive age)
  • Participation in other clinical trial

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Rhythm controlExternal electrical cardioversion (EEC)In this group a strategy to restore and maintain SR, including amiodarone and an external electrical cardioversion (EEC), is implemented. A procedure of AF ablation is possible but not obligatory. At baseline, patients assigned to the group undergo a standard 12-lead ECG, a 6-minute walk test (6MWT), a cardiopulmonary exercise test(CPX), an echocardiography(ECHO), a standard device control; a serum thyroid -stimulating hormone (TSH) level is assessed and patients fill the Minnesota Living With Heart Failure Questionnaire (MLHFQ). Control visits are performed every 3 months including a 12-lead ECG measurement and a device control. On the visits in the 3rd and 12th month an ECHO, a CPX, a 6MWT are performed and a MLHFQ is filled; control TSH levels are assessed every 6 months.
Rate controlPharmacotherapy to slow and control ventricular rateIn the latter group a pharmacotherapy to slow and control ventricular rate by means of pharmacotherapy and an atrio-ventricular junction ablation (AVJA) is implemented. At baseline, each patient assigned to the rate control group undergoes a standard 12-lead ECG, a 6MWT, a CPX, an ECHO, a standard device control and a serum TSH level assessed. Moreover, the patient fills the Minnesota Living With Heart Failure Questionaire (MLHFQ). The control visits are performed for one year, every 3 months including a standard 12-lead ECG measurement and standard control of the device. On the visits in the 3rd and 12th month additionally an ECHO, a CPX, a 6MWT are performed and a MLHFQ is filled. The control TSH levels are assessed every 6 months.
Rate controlAtrioventricular junction ablation (AVJA)In the latter group a pharmacotherapy to slow and control ventricular rate by means of pharmacotherapy and an atrio-ventricular junction ablation (AVJA) is implemented. At baseline, each patient assigned to the rate control group undergoes a standard 12-lead ECG, a 6MWT, a CPX, an ECHO, a standard device control and a serum TSH level assessed. Moreover, the patient fills the Minnesota Living With Heart Failure Questionaire (MLHFQ). The control visits are performed for one year, every 3 months including a standard 12-lead ECG measurement and standard control of the device. On the visits in the 3rd and 12th month additionally an ECHO, a CPX, a 6MWT are performed and a MLHFQ is filled. The control TSH levels are assessed every 6 months.
Rhythm controlAmiodaroneIn this group a strategy to restore and maintain SR, including amiodarone and an external electrical cardioversion (EEC), is implemented. A procedure of AF ablation is possible but not obligatory. At baseline, patients assigned to the group undergo a standard 12-lead ECG, a 6-minute walk test (6MWT), a cardiopulmonary exercise test(CPX), an echocardiography(ECHO), a standard device control; a serum thyroid -stimulating hormone (TSH) level is assessed and patients fill the Minnesota Living With Heart Failure Questionnaire (MLHFQ). Control visits are performed every 3 months including a 12-lead ECG measurement and a device control. On the visits in the 3rd and 12th month an ECHO, a CPX, a 6MWT are performed and a MLHFQ is filled; control TSH levels are assessed every 6 months.
Primary Outcome Measures
NameTimeMethod
BiVp%1 year

Percentage of effective biventricular paced beats during 1st year (mean percentage from baseline to the control visit in 12th month) .

Secondary Outcome Measures
NameTimeMethod
peak VO23 months

Peak oxygen uptake (peak VO2) measured by means of cardiopulmonary exercise test at 3 months from baseline

NYHA class3 months

Heart failure (HF) symptoms escalation measured in New York Heart Association (NYHA) classes at 3 months from baseline

LVEDV reduction from baseline at 1 yearbaseline and 1 year

Change from baseline in left ventricle end-diastolic volume (LVEDV) in ECHO at 1 year

LVESV reduction froma baseline at 1 yearbaseline and 1 year

Change from baseline in left ventricle end-systolic volume (LVESV) in ECHO at 1 year

Ejection fraction3 months

Ejection fraction (EF) \[%\] assessed in ECHO at 3 months from baseline

LVEDD reduction from baseline at 1 yearbaseline and 1 year

Change from baseline in left ventricle end-diastolic diameter (LVEDD) in ECHO at 1 year

Side effects3 months

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.

Reduction of mitral regurgitation at 1 yearbaseline and 1 year

Change from baseline in mitral regurgitation measured in ECHO at 1 year

Heart failure exacerbationsup to 1 year

Number of heart failure exacerbations in the treatment arm in 1 year time from baseline

Ventricular arrhythmiaup to 3 months

Number of ventricular arrhythmias (VF/"Torsade de Pointes" VT/sVT/nsVT) during the first 3 months from basline

6MWT distance3 months

6 minute walk test distance (in meters) at 3 months from baseline

LVESD reduction from baseline at 1 yearbaseline and 1 year

Change from baseline in left ventricle end-systolic diameter (LVESD) in ECHO at 1 year

Mortalityup to 1 year

Numer of deaths assesed in 1 year follow-up

Cardiovascular hospitalizationsup to 1 year

Number of hospitalizations due to cardiovascular causes during a year follow-up

AF prevalence3 months

Measurement of the prevalence of atrial fibrillation (precentage of participants with AF) at 3 month from baseline

Reduction of LA diameter at 1 yearbaseline and 1 year

Change from baseline in left atrium diameter assessed in ECHO at 1 year

Stroke/TIAup to 3 months

Stroke or transient ischemic attack (TIA) during the first 3 months from baseline

CV mortalityup to 1 year

Death due to cardiovascular (CV) causes during a year follow-up

Quality of Life3 months

The quality of life measured with the Minnesota Living with Heart Failure Questionaire (MLHFQ) at 3 months from baseline

Electrotherapyup to 3 months

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

LVEDV reductionbaseline and 3 months

Change from baseline in left ventricle end-diastolic volume (LVEDV) reduction in ECHO at 3 months

Reduction of LA areabaseline and 3 month

Change from baseline in left atrium area assessed in ECHO at 3 months

LVEDD reductionbaseline and 3 months

Change from baseline in left ventricle end-diastolic diameter (LVEDD) reduction in ECHO at 3 months

Reduction of LA diameterbaseline and 3 months

Change from baseline in left atrium diameter assessed in ECHO at 3 months

Reduction of mitral regurgitationbaseline and 3 months

Change from baseline in mitral regurgitation measured in ECHO at 3 months

BiVp%3 months

Percentage of effective biventricular paced beats during first 3 months from baseline.

Trial Locations

Locations (1)

Institute of Cardiology, II Dept. of Coronary Heart Disease

🇵🇱

Warsaw, Poland

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