Prophylactic Frequent Premature Ventricular complexeS sUPPression on Left ventriculaR Function impairmEnt in aSymptomatic patientS

Overview

The main objective of the study is to demonstrate that prophylactic treatment of patients with asymptomatic frequent (>10%) PVCs is superior to simple follow-up strategy with no therapy to prevent subsequent LV dysfunction at 24 months. The prophylactic treatment is based on drugs ± ablation (ablation can be performed if the PVC burden remain >10% after 2 lines of AAD treatment since the initiation of the study). The primary endpoint will be the development of LV dysfunction (PVC-iCMP) defined as a 15% relative LVEF decrease (and/or a LVEF <50%) within 2 years following randomization, on cardiac magnetic resonance imaging (cMRI) (or transthoracic echocardiography (TTE) when not possible).

Study Type

• Study Type: Interventional
• Study Design
  • Allocation: Randomized
  • Intervention Model: Parallel Assignment
  • Primary Purpose: Prevention
  • Masking: None (Open Label)
• Study Primary Completion Date: May 1, 2027

Detailed Description

Premature ventricular contractions (PVCs) are frequently encountered in clinical practice, in the setting of underlying heart disease as well as in "normal" hearts. Frequent PVCs have been shown to impact long term prognosis in patients with structurally normal hearts,[1] as well as in documented cardiomyopathy. In both settings, PVCs may cause symptoms and, in rare cases, sudden cardiac death. For about two decades, it has been accepted that frequent PVCs may also induce left ventricular (LV) dysfunction called PVC-induced cardiomyopathy (PVC-iCMP). Indeed, PVC suppression by using drugs or catheter ablation has been associated with full recovery of left ventricular dysfunction.[2-4] De facto, PVC-iCMP diagnosis as well as identification of predictors has always been established retrospectively. Therefore, risk stratification or simply knowing the exact incidence of the disease in exposed patients remain difficult. European and US guidelines recommend to treat symptomatic PVC patients regardless of the burden or their risk profile, as well as "frequent PVCs" associated with LV dysfunction (Experts tend to consider worthwhile treating for burden >10%, which was the lowest burden associated with PVC-iCMP). However, there is no clear recommendation for asymptomatic patients exposed to very frequent PVCs, at risk of developing cardiomyopathy. As no previous studies included such population, expert suggested that these patients should be at least closely followed. Consequently, management of such patients is widely heterogeneous. The hypothesis of this study is that prophylactic suppression of very frequent PVCs (>10%) will prevent or significantly reduce the incidence of PVC-iCMP.

Interventions

• Drug: Experimental group
  • medical treatment including drug administration ± catheter ablation (Ablation can be performed if the PVC burden remain >10% after 2 lines of AAD treatment).
• Drug: Control group
  • patients of this group have no therapeutic or no treatment modification such as drug therapy

Arms, Groups and Cohorts

• Experimental: Experimental group
  • Patients treated for PVCs with drug therapy and/or catheter ablation/ medical treatment including drug administration ± catheter ablation (Ablation can be performed if the PVC burden remain >10% after 2 lines of AAD treatment).
• Active Comparator: Control group
  • Patients with therapeutic abstention or no treatment modification such as drug therapy/ Therapeutic abstention or no modification of therapy

Clinical Trial Outcome Measures

Primary Measures

• occurence of Left ventricular dysfunction (PVC-iCMP)
  • Time Frame: 24 months
  • The primary endpoint will be the development of left ventricular dysfunction (PVC-iCMP) defined as a 15% relative LVEF decrease (and/or a LVEF <50%) within 2 years following randomization, on cardiac magnetic resonance imaging (cMRI) (or transthoracic echocardiography (TTE) when not possible).

Secondary Measures

• Rate of Death
  • Time Frame: 24 months
  • Death from any cause
• Rate of Cardiovascular Death
  • Time Frame: 24 months
  • measure of safety endpoint: Death cause of death
• Rate of Hospitalization for an adverse event
  • Time Frame: 24 months
  • occurence of adverse events (AE) and serious adverse events (SAE) within follow-up that may be linked or not to anti-arrhythmic drugs (AAD) or ablation procedure
• Percentage of patients with a PVC burden <10%
  • Time Frame: during 24 months follow up
  • measure of efficacy endpoints: PVC burden will be measured the second year following randomization
• LVEF variation
  • Time Frame: 24 months
  • LVEF variation(from baseline to M24)
• Nt-ProBNP relative variation
  • Time Frame: 24 months
  • Nt-ProBNP relative variation from baseline to M24

Participating in This Clinical Trial

Inclusion Criteria

Inclusion criteria (all must be present): 1. 18 ≤ Age ≤ 85 2. PVC burden ≥ to 10% regardless of current or preexisting antiarrhythmic drug intake (for instance, a patient under betablocker therapy because of his PVCs or hypertension can be included) 3. Asymptomatic status 4. Normal (>or= 55%) LVEF. Patients with underlying cardiomyopathy can be included as long as LV function remains preserved. 5. Signed informed consent Exclusion criteria (any of them): 1. Pregnant woman or Female of childbearing potential without effective method of birth control or nursing woman. 2. Patients that can't undergo MRI study 3. De novo requirement for antiarrhythmic drug prescription for another indication (e.g. atrial fibrillation…) 4. The physician already decided that the patient requires drug initiation or escalation; 5. Ischemic cardiomyopathy requiring revascularization (PCI or surgery) 6. History of LV dysfunction 7. Participation in another research involving the human person 8. Patient under legal protection 9. Non affiliation to a social security scheme

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: No

Investigator Details

• Lead Sponsor
  • Assistance Publique – Hôpitaux de Paris
• Provider of Information About this Clinical Study
  • Sponsor