Clin Res Cardiol 108, Suppl 2, October 2019

Successful treatment of multifocal premature ventricular contractions with sotalol in a patient with a rare SNC5A mutation

J. Vogler1, T. Fink1, V. Sciacca1, N. Große1, M. Sano1, S. Liosis1, B. Brüggemann1, C. Eitel1, C.-H. Heeger1, J. Erdmann2, R. R. Tilz1

1Medizinische Klinik II / Kardiologie, Angiologie, Intensivmedizin, Universitätsklinikum Schleswig-Holstein, Lübeck; 2Institut für Kardiogenetik, Universitätsklinikum Schleswig-Holstein, Lübeck;

Background: Mutations in SCN5A encoding the Na+ channel alpha subunit of the human cardiac voltage-gated sodium channel cause susceptibility to atrial and ventricular arrhythmias, familial heart block with or without sinus node dysfunction. Recently, mutations with a clinical phenotype of dilated cardiomyopathy with both atrial and ventricular arrhythmias and a so called “multifocal ectopic Purkinje-related premature contractions” syndrome have been described. Case: A 26-year old woman presented to our emergency department with recurrent ICD-shocks and dyspnea on exertion. Her 12-lead ECG showed frequent multiforme premature ventricular complexes (PVC) and non-sustained ventricular tachycardias (VTs) and only very few conducted sinus beats. The dominant PVCs morphology was reminiscent of fascicular (anterior and posterior fascicle) foci, but ECG showed also junctional beats and PVCs with broad QRS complexes suggesting a myocardial origin. Ventricular ectopy reached a daily burden of up to 20% ectopy without increase on physical exertion. ICD interrogation revealed multiple episodes of polymorphic VTs, mostly due to PVCs with R on T-phenomenon and 40 atrial high frequency episodes. On echocardiography, the left ventricle (LV) was dilated and LV ejection fraction was severely reduced. Reliable planimetry was not possible due to the high PVC burden suggesting a PVC related cardiomyopathy. The patient`s past medical history was remarkable: She had been resuscitated in Russia several times and had received a dual chamber ICD in Germany in June 2016 after another resuscitation due to ventricular fibrillation. PVC ablation had been performed four times during the last 3 years, but had been unsuccessful. An ajmaline test had been unremarkable. Genetic analysis had revealed a rare SNC5A mutation (c.2440C>T (p.R814W, rs199473161). The mutation has been described to produce a type of “gain of function” Na+ channel protein characterized by abnormal activation and deactivation kinetics resulting in slower onset of activation, but increased channel opening at hyperpolarized membrane voltages. The patient was on flecainide 50 mg bid at the time of admission. In the past she had been treated with mexiletine (inefficacious) and amiodarone which was stopped because of side effects. The patient’s older brother has been treated for frequent PVCs with a similar morphology than her PVCs and cardiomyopathy as well. His PVC burden decreased substantially going along with an improvement in LV function after treatment with Sotalol. Owing to the multifocality of the PVCs and the unsuccessful prior ablation attempts no further ablation was performed. The patient was treated with Sotalol starting with 240 mg per day. Although the PVCs were not clearly sympathically driven, she underwent bilateral cardiac sympathetic denervation (CSD). PVC burden, however, remained high after bilateral CSD. Sotalol was further increased thereafter to 480 mg per day which led to a reduction of the PVC burden to 1.5-3%. LV function almost completely recovered (50%). The patient remained free of sustained arrhythmias and ICD therapy. Conclusion: We present a case of PVC-induced cardiomyopathy with SCN5A “gain-of-function” mutation characterized by heart failure and recurrent malignant arrhythmias. Sotalol treatment resulted in reduction of PVC burden, arrhythmia suppression and concomitant recovery of LV function.

https://www.abstractserver.com/dgk2019/ht/abstracts//P695.htm