Reversal of Cardiomyopathy by Suppression of Frequent Premature Ventricular Complexes
Frequent monomorphic premature ventricular complexes (PVCs) may cause a cardiomyopathy (CMP) that is reversible by suppression of the ectopic focus. This study investigates whether PVC suppression therapy can improve cardiac function and clinical condition of patients with idiopathic or ischemic CMP and frequent monomorphic PVCs. For this purpose, patients will be randomized to either one of two treatment strategies: 1) conventional heart failure therapy plus PVC suppression therapy, consisting of RFCA as primary treatment and Amiodarone as secondary treatment in case of unsuccessful RFCA, or 2) conventional heart failure therapy without PVC suppression therapy.
Ventricular Premature Complexes
Systolic Heart Failure
Other: PVC suppression therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Reversal of Cardiomyopathy by Suppression of Frequent Premature Ventricular Complexes - A Prospective Randomized Clinical Trial|
- Change in left ventricular ejection fraction (LVEF) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
- Change in left ventricular end systolic diameter (LVESD) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
- Change in left ventricular end diastolic diameter (LVEDD) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
- Change in left ventricular end systolic volume (LVESV) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
- Change in left ventricular end diastolic volume (LVEDV) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
- Change in New York Heart Association (NYHA) functional class [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
- Change in 6 minute walking distance [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
- Change in quality of life (QOL) score [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
- Change in serum NT-proBNP level [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
- Change in premature ventricular complex (PVC) burden [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]
- Cost-effectiveness: costs from a health service perspective during 12 months follow-up and effectiveness measured as quality adjusted life years (QALY). [ Time Frame: Baseline and 12 months ] [ Designated as safety issue: No ]
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
|Experimental: Routine heart failure therapy plus PVC suppression therapy||
Other: PVC suppression therapy
Conventional heart failure therapy plus radiofrequency catheter ablation of PVCs as primary treatment and Amiodarone (tablets, loading dose of 600 mg per day for 4 weeks and 200 mg per day afterwards for at least 12 months) as secondary treatment in case of unsuccessful catheter ablation.
|No Intervention: Routine heart failure therapy|
Heart failure accounts for substantial morbidity and mortality in the western world. In addition, the financial burden associated with the disease is considerable. Prognosis is generally poor and quality of life is significantly reduced. The causes of heart failure are diverse. Identification of the underlying pathophysiological mechanism is essential, because a specific patient tailored therapy may help to improve the clinical status of the individual patient. In addition, some patients may have a potentially reversible cardiomyopathy (CMP). The present study will focus on the role of frequent premature ventricular contractions (PVCs) as a cause of left ventricular (LV) dysfunction. This is a potential reversible CMP generally unknown to the cardiological society.
Frequent ventricular ectopy in patients without structural heart disease is generally thought to be a benign finding with no prognostic significance. Suppression of PVCs with anti-arrhythmic drugs or catheter ablation is therefore usually only considered when PVCs are accompanied by disabling symptoms. However, recent data suggest that frequent monomorphic PVCs (symptomatic or asymptomatic) can cause a form of CMP that may be reversible by suppression of the ectopic focus. Furthermore, the high prevalence of frequent PVCs in patients with heart disease suggests that PVC-induced CMP may be a common phenomenon. Suppression of frequent monomorphic PVCs to improve LV systolic function may therefore emerge as a new and effective treatment strategy for patients with heart failure.
Beta-blockers are safe and effective anti-arrhythmic agents and are considered the first line therapy for suppression of PVCs. Most patients with HF are already taking a beta-blocker as part of standard therapy for their underlying disease. According to international guidelines, other AADs can be used if beta-blockers are ineffective, but they have potential adverse (arrhythmic) side-effects, especially in patients with diminished LV function, and may even be contra-indicated in this patient group. In patients with LV dysfunction and frequent monomorphic PVCs that are refractory to beta-blockers, long-term drug therapy and the potential adverse (arrhythmic) side-effects of AADs can be avoided by using catheter ablation as a first alternative treatment. RFCA is already a frequently applied, widely accepted, safe, effective and potentially curative treatment for symptomatic drug refractory PVCs. It has also been safely and effectively employed in patients with tachycardia-induced CMP and patients with PVC-induced CMP. A high acute success rate of 93% and a very low PVC recurrence rate of 3% have been reported. Although recent available data suggest that elimination of the PVC source by RFCA improves LV systolic function in HF patients, it is still applied in a limited fashion for this indication because the evidence supporting this is weak. The patient series published so far were not controlled and retrospective in nature. We intend to conduct a controlled, randomized, prospective study with careful documentation and long-term follow-up to evaluate the effect of PVC suppression therapy (with RFCA as primary treatment) on cardiac systolic function in patients with CMP and beta-blocker refractory frequent monomorphic PVCs. This could establish suppression of frequent monomorphic PVCs as a potential curative treatment strategy for patients with HF.
|Contact: Masih Mafi Rad, MDemail@example.com|
|Contact: Yuri Blaauw, MD, PhDfirstname.lastname@example.org|
|Maastricht University Medical Centre||Recruiting|
|Maastricht, Limburg, Netherlands, 6202 AZ|
|Contact: Masih Mafi Rad, MD +31-43-3871613 email@example.com|
|Contact: Yuri Blaauw, MD, PhD +31-43-3877095 firstname.lastname@example.org|
|Sub-Investigator: Masih Mafi Rad, MD|
|Principal Investigator:||Yuri Blaauw, MD, PhD||Maastricht University Medical Centre|
|Principal Investigator:||Harry JGM Crijns, MD, PhD||Maastricht University Medical Centre|