Flecainide in Idiopathic Premature Ventricular Contractions and Related Cardiomyopathy

Recruiting

• Conditions: Premature Ventricular Beats; Premature Ventricular Complexes; Premature Ventricular Contraction (PVC); Arrhythmia Ventricular; Ventricular Dysfunction, Left; Cardiomyopathies; Ventricular Dysfunction; Cardiomyopathies, Secondary
• Interventions: Drug: Flecainide (monotherapy)

• Registration Number: NCT06949748
• Lead Sponsor: University of Athens

Brief Summary

The UNIFLECA study is a prospective, single-arm, observational cohort evaluating the efficacy, safety, and tolerability of flecainide (in the form of Sanocard) in adults with frequent idiopathic premature ventricular contractions (PVCs) and suspected PVC-induced cardiomyopathy (PVCi-CMP). Frequent PVCs-defined as a burden \>5% on two separate 24-hour Holter recordings-are increasingly recognized as a cause of reversible systolic dysfunction in patients without structural heart disease.

Participants undergo a comprehensive baseline evaluation including echocardiography, occasionally cardiac MRI, and coronary angiography or equivalent testing to confirm the absence of structural abnormalities. Patients are enrolled only if they are ineligible or unwilling to undergo catheter ablation, and have no contraindications to flecainide.

Flecainide therapy is initiated at a starting dose of 100 mg/day and titrated up to 200 mg/day, guided by ECG findings, symptom response, and QRS duration. Regular follow-up occurs at three-month intervals over three years, with periodic 24-hour Holter monitoring and assessment of symptoms, LVEF, and adverse events.

The primary outcome is the reduction in PVC burden. Secondary outcomes include improvement in LVEF, symptom relief (measured by structured questionnaires), adverse effects, and long-term treatment adherence. The study aims to generate real-world data on the non-invasive management of PVCs with flecainide and explore its role as an alternative to ablation in carefully selected patients.

Detailed Description

The UNIFLECA study is a prospective, single-arm, non-randomized observational cohort designed to evaluate the long-term efficacy and safety of flecainide (in the form of Sanocard) in adult patients with frequent idiopathic premature ventricular contractions (PVCs) and suspected PVC-induced cardiomyopathy (PVCi-CMP). Despite being considered benign in structurally normal hearts, a persistently high PVC burden-particularly above 10%-is increasingly recognized as a cause of reversible left ventricular dysfunction and a potential trigger for cardiomyopathy. This condition is frequently underdiagnosed and may lead to unnecessary treatments or delayed intervention.

The study targets a unique population: symptomatic patients with idiopathic PVCs who have structurally normal hearts and have either declined catheter ablation or are ineligible for invasive procedures. Each patient undergoes comprehensive baseline cardiac evaluation, including transthoracic echocardiography, cardiac magnetic resonance imaging (CMR) to exclude late gadolinium enhancement or myocardial scar, and coronary angiography or non-invasive equivalent to rule out ischemic heart disease. Two 24-hour Holter ECG recordings, taken at least 30 days apart, are used to confirm persistent high PVC burden (\>5%).

Flecainide, a Class IC antiarrhythmic agent with sodium channel-blocking properties, is administered as monotherapy. The initial dose is 100 mg/day and may be titrated up to 200 mg/day based on clinical response, patient tolerability, and QRS interval monitoring. Beta-blockers are discontinued unless used for unrelated comorbidities such as hypertension. Patients are monitored with serial 12-lead ECGs, Holter recordings, and echocardiograms at baseline and every three months over a total follow-up period of three years.

The primary endpoint is the percentage reduction in PVC burden as measured by 24-hour Holter ECG. Secondary endpoints include (1) improvement in left ventricular ejection fraction (LVEF), (2) symptom relief as assessed by structured patient questionnaires focusing on palpitations, bradysphygmia, fatigue, dizziness, and exercise intolerance, (3) incidence of adverse events including proarrhythmia, conduction disturbances, and neurological side effects, and (4) adherence to long-term flecainide therapy, including need for dose modifications or drug discontinuation.

This investigator-initiated study is being conducted across tertiary arrhythmia centers in Greece. It aims to fill a significant evidence gap in the long-term pharmacologic management of idiopathic PVCs and PVCi-CMP. Preliminary results indicate significant PVC burden reduction and symptomatic improvement, supporting the potential utility of flecainide as an effective non-invasive therapeutic option in appropriately selected patients. Data from this study will contribute to optimizing treatment strategies for idiopathic ventricular arrhythmias in the absence of structural heart disease, supporting the use of personalized medicine and risk stratification.

Study Timeline

• Status Verified: 2024-04
• Study Start: 2024-04-26
• Study First Submitted: 2025-04-22
• Study First Submitted QC: 2025-04-22
• Last Update Submitted: 2025-04-22
• Study First Posted: 2025-04-29
• Last Update Posted: 2025-04-29
• Primary Completion: 2027-07-01
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

• Frequent idiopathic PVCs (burden >5% on multiple 24-hour Holter ECG recordings)
• Normal cardiac structure and function on echocardiography
• No late gadolinium enhancement or myocardial scar on cardiac MRI
• Normal coronary angiography (excluding ischemic cardiomyopathy)
• Normal serum electrolytes and renal function
• Willingness to comply with follow-up schedule and drug titration

Exclusion Criteria

• Structural heart disease
• Ischemic heart disease (confirmed by angiography)
• History of sustained ventricular arrhythmias
• Left ventricular ejection fraction (LVEF) <40% at baseline
• Brugada syndrome, long QT syndrome, or other channelopathies
• Contraindications to class IC agents
• Use of concurrent antiarrhythmics or proarrhythmic drugs

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
High PVC Burden Cohort	Flecainide (monotherapy)	Persistent, high PVC Burden (\>5%) in 24h Holter Monitoring

Primary Outcome Measures

Name	Time	Method
PVC Burden Reduction	3 years	Change in 24-hour Holter-measured PVC burden from baseline to 3 years. Unit of Measure: Percent (%)

Secondary Outcome Measures

Name	Time	Method
Symptom improvement (Questionnaire Score)	3 years	• Structured patient-reported symptom score (palpitations, fatigue, etc.). • Unit: Score on scale (e.g., 0-10)
Treatment Adherence and Dose Adjustments	3 years	* Rate of dose changes or discontinuation due to side effects.; * Unit: Number of participants
Change in Left Ventricular Ejection Fraction (LVEF)	3 years	* Measured by echocardiography.; * Unit: Percent (%)
Safety and tolerability of flecainide	3 years	* Incidence of adverse effects (e.g., proarrhythmia, dizziness).; * Unit: Number of participants with event

Trial Locations

Locations (6)

Cardiology Clinic, University Hospital of Patras; 🇬🇷 Patras, Achaia, Greece

1st Cardiology Clinic, National and Kapodistrian University of Athens; 🇬🇷 Athens, Attika, Greece

Cardilogy Clinic, University of Crete; 🇬🇷 Heraklion, Greece

2nd Cardiology Clinic, University of Ioannina; 🇬🇷 Ioannina, Greece

2nd Cardiology Clinic, Aristotle University of Thessaloniki; 🇬🇷 Thessaloniki, Greece

3rd Cardiology Clinic, Aristotle University of Thessaloniki; 🇬🇷 Thessaloniki, Greece