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Flecainide in patients with arrhythmic mitral valve syndrome: A case series

Open AccessPublished:December 21, 2022DOI:https://doi.org/10.1016/j.hrthm.2022.12.024

      Keywords

      Arrhythmic symptoms are prevalent, and life-threatening ventricular arrhythmias (VA) are a feared complication in patients with arrhythmic mitral valve syndrome (AMVS).
      • Basso C.
      • Iliceto S.
      • Thiene G.
      • Perazzolo Marra M.
      Mitral valve prolapse, ventricular arrhythmias, and sudden death.
      There is no established medical therapy to suppress VA and relieve arrhythmic symptoms in these patients other than conventional beta-blocker therapy, which often is unsuccessful and not evaluated in randomized controlled trials. Catheter ablation can suppress VA in some patients but is limited because of the multifocal nature of premature ventricular complexes (PVC), papillary muscle origin, and VA recurrence despite initial successful procedures. Flecainide is a sodium channel blocker with an additional effect of reducing sodium-mediated calcium release, which gives flecainide efficacy for afterdepolarization-induced PVCs. Current hypotheses suggest that the curling motion of the myocardial wall or stretch of the papillary muscles by the prolapsing leaflets in AMVS may trigger PVCs by inducing calcium-mediated afterdepolarization. However, after the results of CAST (Cardiac Arrhythmia Suppression Trial),
      • Echt D.S.
      • Liebson P.R.
      • Mitchell L.B.
      • et al.
      Mortality and morbidity in patients receiving encainide, flecainide, or placebo.
      the use of flecainide has been limited to preventing atrial tachyarrhythmias and suppressing VA in patients without structural heart disease.
      We report our experience using additional flecainide in 7 patients with high-risk AMVS when VAs were refractory to beta-blocker therapy alone. PVCs originated from the inferior left ventricle in 6 patients and from the right ventricular outflow tract in 1 patient. Patients were followed and treated between June 2014 and February 2022 (median 27 months; range 11–89 months). The study complied with the Declaration of Helsinki and was approved by the Regional Committee for Medical Research Ethics (2015/596/REK nord). All study participants provided written informed consent.
      Before flecainide treatment was initiated, the cases were discussed by a multidisciplinary team. Patients were required to have a normal coronary angiogram, no other structural heart disease, and continuous arrhythmia monitoring with an implantable cardioverter-defibrillator (ICD) or implantable loop recorder (ILR). An ICD was inserted in 4 patients because of polymorphic ventricular tachycardia in 2 and aborted cardiac arrest in 2. Three patients were monitored using an ILR with remote monitoring. Exercise electrocardiogram (ECG) was recorded as part of routine follow-up.
      Flecainide was added at daily doses of 200 mg (n = 5) and 100 mg (n = 2) in combination with low-dose beta-blocker. On long-term cardiac monitoring, we observed 21 nonsustained ventricular tachycardias (NSVTs) during 90 patient-months on beta-blocker alone (median 4 NSVTs per patient; range 1–7) and 0 NSVTs during 250 patient-months with additional flecainide treatment (Figure 1). The 7 patients underwent 40 Holter monitor recordings during follow-up (19 off flecainide and 21 on flecainide). Combining treatment with flecainide and beta-blocker was associated with a lower PVC burden compared to beta-blockers alone (median 4.2% per 24 hours before flecainide vs 0.4% per 24 hours on flecainide) in a univariate linear mixed model regression with random effect on individual level (–3.4% per 24 hours on flecainide treatment; 95% confidence interval [CI] –5.0 to –1.8; P <.001). Flecainide treatment did not worsen VA burden in any of the patients, and no serious adverse effects were observed. Based on the 92 ECGs recorded during follow-up, flecainide therapy was associated with longer QRS duration in univariate linear mixed model regression with random effect on individual level (+6 ms on flecainide treatment; 95% CI 3–9; P = .001).
      Figure thumbnail gr1
      Figure 1Flecainide in arrhythmic mitral valve syndrome (arrhythmic mitral valve syndrome). CI = confidence interval; LGE = late gadolinium enhancement; NSVT = nonsustained ventricular tachycardia; PVC = premature ventricular complex; VT = ventricular tachycardia. (Servier Medical Art.)
      These results suggest that adding flecainide to beta-blocker therapy could be useful in treating VA in patients with high-risk AMVS. However, we report a limited number of patients with short-term follow-up, and the prognostic value of decreasing VA burden and NSVTs in patients with AMVS remains unknown. Thus, a randomized trial on the efficacy and safety of flecainide in these patients is needed (ClinicalTrials.gov Identifier: NCT05631730).
      It is challenging to translate the harmful effects of flecainide in CAST
      • Echt D.S.
      • Liebson P.R.
      • Mitchell L.B.
      • et al.
      Mortality and morbidity in patients receiving encainide, flecainide, or placebo.
      to patients with other structural heart diseases. Recent studies demonstrated the safety and efficacy of flecainide in patients with nonischemic structural heart disease.
      • Rolland T.
      • Badenco N.
      • Maupain C.
      • et al.
      Safety and efficacy of flecainide associated with beta-blockers in arrhythmogenic right ventricular cardiomyopathy.
      However, flecainide slows myocardial conduction velocity and facilitates reentry in patients with myocardial fibrosis, which is a recognized arrhythmic risk marker in patients with AMVS. This implies a potential risk of proarrhythmic events when flecainide is administered to these patients.
      In summary, we reported a reduction of VA after initiating flecainide and low-dose beta-blockers in patients with AMVS. This suggests that combining flecainide and beta-blocker could be useful in reducing VA burden in these patients, but randomized controlled trials are needed before clinical implementation.

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