|Home | About | Journals | Submit | Contact Us | Français|
Ventricular arrhythmias in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) are precipitated by an increase in sympathetic activity, typically physical exercise. As such, beta blockade is the cornerstone of medical treatment. However, some patients are either intolerant or refractory to beta-blockers, and many continue to have arrhythmias despite catheter ablation. This report presents the case of an ARVD/C patient with severe ventricular arrhythmias refractory to beta-blockade, anti-arrhythmic drugs, and three endocardial/epicardial VT ablations, who was successfully treated with bilateral sympathectomy.
A previously healthy 16-year-old male triathlete presented with a sudden cardiac arrest while swimming. He was diagnosed with ARVD/C based on T-wave inversions V1-V4; 7216 premature ventricular complexes on 24-hr Holter monitoring; left bundle inferior axis ventricular tachycardia (VT); and subtricuspid dyskinesia with right ventricular ejection fraction 33% (Figure 1). Genetic testing revealed no pathogenic mutation in a 76-gene cardiomyopathy panel (including all 5 desmosomal genes), and he had no familial history of disease. He received a single-chamber ICD, and was discharged on sotalol. Five months after discharge, the patient received his first shock for VT at 233 bpm while dancing. He underwent an endocardial/epicardial VT ablation (Figure 2) and was non-inducible at the end of the procedure during programmed stimulation with and without isoproterenolol. He was discharged on long acting metoprolol. Flecainide was added when palpitations recurred soon after discharge. Five months later, he experienced a VT storm requiring 43 ICD shocks after climbing stairs. He received CPR and regained consciousness two days later. He underwent a second endocardial/epicardial ablation. A stress test prior to discharge was normal. Amiodarone was initiated for further arrhythmia control. VT recurred six months later when he received 8 appropriate ICD shocks while running. In the EP laboratory he developed spontaneous VT, which promptly terminated on deep sedation. Electroanatomic mapping showed minimal signs of scar progression. Open chest epicardial cryoablation was performed with no inducible VT five days post ablation. One month later, the patient experienced 6 ICD shocks during exercise, and a decision was made to perform bilateral sympathectomy. Using a video-assisted thoracoscopic surgery approach, the bilateral lower half of the stellate ganglia were removed together with the 2nd through 4th thoracic ganglia. The procedure was well tolerated and no complications occurred.
To assess the impact of sympathectomy, the patient underwent non-invasive neurophysiologic testing before and 8 weeks after sympathectomy while on the same medications (Figure 3). Following sympathectomy, diastolic blood pressure responses to sympathetic stressors were similar to pre-sympathectomy levels, while systolic blood pressure responses were attenuated, confirming denervation (Figure 3A). Similarly, resting heart rate was lower following sympathectomy, but augmented robustly to sympathetic stress to levels below pre-sympathectomy values (Figure 3B). Following sympathectomy, levels of finger pulse volume (FPV), the amplitude of the finger plethysmograph (Figure 3C), were higher, reflecting an overall decrease in sympathetic drive. Responses to sympathetic stress were however preserved. Interestingly, while FPV did not recover to baseline during the final rest period before sympathectomy, the FPV values returned to baseline after sympathectomy, showing restored capacity to attenuate sympathoexcitation when stress is withdrawn. As shown in Figure 3D, baseline skin conductance was also significantly attenuated by sympathectomy. Spectral analysis of heart rate variability (HRV) demonstrated an overall reduction in sympatho-vagal balance (LF/HF ratio) from 0.58 to 0.46 (Figure 3E), owing to a decrease in the low frequency (LF) sympathetic component (1.84x10−4 vs. 1.42 x10−4); but not the high frequency (HF) parasympathetic component (3.17x10−4 vs. 3.10 x10−4) (Figure 3F).
During 1-year follow-up after sympathectomy, the patient remains asymptomatic on metoprolol. His ventricular ectopy levels have significantly decreased and he remains free of ICD therapy (Figure 4).
Involvement of the sympathetic nervous system in ARVD/C has been suspected since the first reports of the disease1. The right ventricle and the proximal pulmonary artery are richly innervated by sympathetic nerves from the ventromedial cardiac nerves. High frequency stimulation in the pulmonary artery induces PVCs from the RVOT and these nerves have been implicated in the pathophysiology of idiopathic VT. Indeed, the VTs in our patient exhibit features suggestive of catecholamine-mediated focal VT. VTs were easily inducible by minimal exercise and isoproterenol infusion, had fast cycle lengths, and VT salvos on electrophysiology study had similar morphology but different cycle lengths, favoring a triggered over re-entrant mechanism. Of note, every prior ablation in this patient had been successful, and exercise stress testing and NIPS were normal after 2 of 3 ablation procedures. This questions the role of these tests in the setting of catecholamine-sensitive recurrent arrhythmias. The success of bilateral sympathectomy in controlling arrhythmias in our patient after three prior endocardial/epicardial ablations reveals that sympathectomy may achieve arrhythmia control after all other treatment options have been exhausted. Since bilateral sympathectomy involves the removal of post-ganglionic soma, intra-myocardial sympathetic neural regeneration does not occur, leading to a durable anti-arrhythmic effect. Unilateral sympathectomy may be less effective in the long term, as remodeling may occur in the contralateral ganglion2, and may include sprouting within the heart. Further, left and right sympathetic nerves have been demonstrated to innervate unique regions of the heart, with overlap3. As such, implementation of this technique early in the disease course may prevent recurrent VT storms and incapacitating psychosocial symptoms associated with ICD shocks. While this does not eliminate the need for an ICD, it may result in lower arrhythmia burden, lower medication dependence, and increased quality of life. Future studies in a large number of patients should confirm the role of cardiac sympathectomy in ARVD/C, and investigate its optimal timing and use in ARVD/C management.
Conflict of Interest Disclosures: None.