Reversal of Cardiomyopathy by Suppression of Frequent Premature Ventricular Complexes

Sponsor

Maastricht University Medical Center (Other)

Overall Status

Unknown status

CT.gov ID

NCT01566344

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Diseases Cardiac Arrhythmias Ventricular Premature Complexes Systolic Heart Failure Cardiomyopathies	Other: PVC suppression therapy	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Reversal of Cardiomyopathy by Suppression of Frequent Premature Ventricular Complexes - A Prospective Randomized Clinical Trial

Study Start Date :

May 1, 2012

Anticipated Primary Completion Date :

Sep 1, 2016

Anticipated Study Completion Date :

Dec 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Change in left ventricular ejection fraction (LVEF) [Baseline and 6 months]

Secondary Outcome Measures

Change in left ventricular end systolic diameter (LVESD) [Baseline and 6 months]
Change in left ventricular end diastolic diameter (LVEDD) [Baseline and 6 months]
Change in left ventricular end systolic volume (LVESV) [Baseline and 6 months]
Change in left ventricular end diastolic volume (LVEDV) [Baseline and 6 months]
Change in New York Heart Association (NYHA) functional class [Baseline and 6 months]
Change in 6 minute walking distance [Baseline and 6 months]
Change in quality of life (QOL) score [Baseline and 12 months]
Change in serum NT-proBNP level [Baseline and 6 months]
Change in premature ventricular complex (PVC) burden [Baseline and 6 months]
Cost-effectiveness: costs from a health service perspective during 12 months follow-up and effectiveness measured as quality adjusted life years (QALY). [Baseline and 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

LVEF < 50% without identifiable cause (idiopathic) or post-infarction, > 6 months.
Optimal conventional heart failure therapy > 3 months.
Frequent monomorphic PVCs on Holter monitoring.

Frequent = more than 15% of all QRS complexes are PVCs.
Monomorphic = more than 75% of PVCs have the same morphology.

Greater than 18 years of age.
Willing and capable of giving informed consent.

Exclusion Criteria:

Other causes of LV systolic dysfunction:

Significant valvular disease.
Untreated hypertension (blood pressure > 140 mmHg).
Primary CMP (HCM, ARVC, LVNC, myocarditis, stress, peripartum).
Secondary CMP (infiltrative, storage, toxic, neuromuscular/neurological, autoimmune).

Electrocardiographic PVC characteristics suggestive of a focal origin not accessible by percutaneous approach.
Sustained supra-ventricular arrhythmia.
Evidence of significant CAD (>70% stenosis of a coronary artery) on coronary angiogram (CAG) or coronary CT necessitating revascularization (PCI / CABG) in the foreseeable future.
Signs of current myocardial ischemia on ECG (dynamic STT segments) or during exercise testing (significant ST segment depression/elevation).
Myocardial infarction within the last 6 calender months prior to enrollment.
PCI / CABG within the last 6 calender months prior to enrollment.
Physical status not allowing electrophysiological study (e.g. pregnancy or severe peripheral artery disease)
Presence of any disease, other than the patient's cardiac disease, associated with a reduced likelihood of survival for the duration of the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maastricht University Medical Centre	Maastricht	Limburg	Netherlands	6202 AZ

Sponsors and Collaborators

Maastricht University Medical Center

Investigators

Principal Investigator: Yuri Blaauw, MD, PhD, Maastricht University Medical Centre
Principal Investigator: Harry JGM Crijns, MD, PhD, Maastricht University Medical Centre