Reversal of Cardiomyopathy by Suppression of Frequent Premature Ventricular Complexes

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Maastricht University Medical Center
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01566344
First received: March 27, 2012
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

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 Intervention
Heart Diseases
Cardiac Arrhythmias
Ventricular Premature Complexes
Systolic Heart Failure
Cardiomyopathies
Other: PVC suppression therapy

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • Change in left ventricular ejection fraction (LVEF) [ Time Frame: Baseline and 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 70
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)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. LVEF < 50% without identifiable cause (idiopathic) or post-infarction, > 6 months.
  2. Optimal conventional heart failure therapy > 3 months.
  3. 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.
  4. Greater than 18 years of age.
  5. Willing and capable of giving informed consent.

Exclusion Criteria:

  1. 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).
  2. Electrocardiographic PVC characteristics suggestive of a focal origin not accessible by percutaneous approach.
  3. Sustained supra-ventricular arrhythmia.
  4. 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.
  5. Signs of current myocardial ischemia on ECG (dynamic STT segments) or during exercise testing (significant ST segment depression/elevation).
  6. Myocardial infarction within the last 6 calender months prior to enrollment.
  7. PCI / CABG within the last 6 calender months prior to enrollment.
  8. Physical status not allowing electrophysiological study (e.g. pregnancy or severe peripheral artery disease)
  9. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01566344

Contacts
Contact: Masih Mafi Rad, MD +31-43-3871613 masih.mafirad@mumc.nl
Contact: Yuri Blaauw, MD, PhD +31-43-3877095 yuri.blaauw@mumc.nl

Locations
Netherlands
Maastricht University Medical Centre Recruiting
Maastricht, Limburg, Netherlands, 6202 AZ
Contact: Masih Mafi Rad, MD    +31-43-3871613    masih.mafirad@mumc.nl   
Contact: Yuri Blaauw, MD, PhD    +31-43-3877095    yuri.blaauw@mumc.nl   
Sub-Investigator: Masih Mafi Rad, MD         
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
  More Information

Publications:

Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01566344     History of Changes
Other Study ID Numbers: NL37355.068.11, METC 11-2-076
Study First Received: March 27, 2012
Last Updated: May 16, 2013
Health Authority: Netherlands: Medical Ethics Review Committee (METC)
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:
Premature Ventricular Complex
Cardiomyopathy
Left ventricular dysfunction
Catheter Ablation
Anti-Arrhythmic Agents
Randomized Clinical Trial

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiomyopathies
Arrhythmias, Cardiac
Heart Failure, Systolic
Ventricular Premature Complexes
Cardiovascular Diseases
Pathologic Processes
Cardiac Complexes, Premature

ClinicalTrials.gov processed this record on September 18, 2014