By Angela Gonzalez
A retrospective study, including the largest series of patients with refractory ventricular tachycardia undergoing cardiac sympathetic denervation for structural heart disease, has shown freedom from ventricular tachycardia/implantable cardioverter defibrillator (ICD) shock, heart transplant death of 50% at one year and freedom from sustained ventricular tachycardia/ICD shock of 58% at one year. The study also demonstrated a notable 88% reduction in burden of ICD shocks.
According to study authors Marmar Vaseghi (University of California, Los Angeles, USA) and others, cardiac sympathetic denervation has been shown to reduce ventricular tachycardia inducibility and ischaemia-driven ventricular arrhythmias in animal models of myocardial infarction and decrease the burden of ventricular tachycardia and ICD shocks in small series of patients with cardiomyopathy and recurrent ventricular tachycardia or ventricular tachycardia storm. However, “long-term outcomes in larger patient populations and predictors of ventricular recurrence and ICD shocks after cardiac sympathetic denervation are unknown,” write the authors in the Journal of the American College of Cardiology.
Hence, these researchers sought to investigate the benefits of cardiac sympathetic denervation in treatment of ventricular tachycardia using an international multicentre database named “The International Cardiac Sympathetic Denervation Collaboration”. This collaboration includes five international centres experienced in performing cardiac sympathetic denervation.
Vaseghi et al performed a retrospective analysis of 121 consecutive patients (age 55±13 years, 26% female, mean ejection fraction of 30±13%) with structural heart disease who underwent cardiac sympathetic denervation for recurrent ventricular tachycardia or ventricular tachycardia storm between April 2009 and April 2016. Structural heart disease was defined as left ventricular ejection fraction <55%, hypertrophic cardiomyopathy, or arrhythmogenic right ventricular cardiomyopathy. Ischaemic cardiomyopathy was defined by history of myocardial infarction or myocardial perfusion defect with correlating obstructive disease and coronary angiography. Ventricular tachycardia storm was defined as at least three episodes of ventricular tachycardia within 24 hours.
Left or bilateral cardiac sympathetic denervation by means of a video-assisted thoracoscopic surgery was performed in all patients and they were followed-up clinically and by ICD interrogations at regular intervals (median follow-up was 1.1 years). Eleven per cent of patients had New York Heart Association (NYHA) functional class I, 41% had class II, 40% had class III, and 8% had class IV heart failure. Thirty three (27%) of the patients had ischaemic cardiomyopathy and 86 (71%) had non-ischaemic cardiomyopathy. One hundred and twenty patients were being treated with antiarrhythmic drug therapy and 92% were being treated with beta-blocker therapy. A history of ventricular tachycardia storm before the procedure was present in 75% of patients and 64% had more than one ventricular tachycardia morphology noted before cardiac sympathetic denervation. Ventricular tachycardia ablation had been performed in 66% of the patients (median of two ablations) and cardiac sympathetic denervation was offered to 34% of patients instead of ventricular tachycardia ablation after failure of antiarrhythmic therapies, either because the patients also had polymorphic ventricular tachycardia, thought to be unresponsive to ventricular tachycardia ablation, or because of the high cost of ventricular tachycardia ablation at some centres.
The researchers found that one-year freedom from sustained ventricular tachycardia/ICD shock and ICD shock, heart transplant and death were 58% and 50%, respectively. Additionally, the burden of ICD shocks with cardiac sympathetic denervation was reduced from a mean of 18±30 (median 10) in the year before the study entry to 2.0±4.3 (median 0) at a median follow-up of 1.1 years. Therefore, Vaseghi et al note “cardiac sympathetic denervation reduced the number of ICD shocks by 88%.” This result is “noteworthy”, the authors comment, as “ICD shocks have been shown to increase morbidity and mortality and decrease quality of life.” Additionally, “ICD shocks appear to shift the mode of death towards increased nonarrhythmic mortality, potentially by worsening heart failure.” Importantly in the study, 99% of patients where on anti-arrhythmic drug therapy prior to the procedure, and after the procedure, this number was reduced to 32%.
The authors also comment that the patients referred for cardiac sympathetic denervation (75% of whom presented with ventricular tachycardia storm) had a cardiac transplant/mortality rate of 25% at one year.
Vaseghi et al also note that the findings of this study indicated that patients with advanced NYHA functional class, particularly class IV, “might not derive the same benefit” with cardiac sympathetic denervation. The results also demonstrated that cardiac sympathetic denervation should be considered “earlier, rather than later, in the disease course in patients with ventricular tachycardia and cardiomyopathy, before the development and progression of severe heart failure.” In addition, a bilateral procedure appears to be more beneficial than a left sided only procedure.
Finally, the researchers found that the benefit of cardiac sympathetic denervation in patients with ventricular tachycardia cycle lengths >400ms (<150 beats/min) is less clear. “The lack of benefit in patients with very long ventricular tachycardia cycle lengths is intriguing but might be related to an underlying substrate with extensive scar or a metabolically compromised heart, for which the autonomic-sympathetic nervous system is not the primary driver of arrhythmogenesis, and could represent a subgroup or patients who need orthotopic heart transplantation or mechanical support as destination therapy or bridge to transplant,” they write.
The authors acknowledge that this study represents outcomes of specialised centres experienced in performing cardiac sympathetic denervation. “Therefore, the results might not be directly applicable to centres that do not perform this procedure frequently,” they write.
Vaseghi et al conclude calling for the need for prospective randomised clinical trials to further study this intervention. The authors have currently initiated such a study (PREVENT VT ‒ Prophylactic cardiac sympathetic denervation for prevention of ventricular tachyarrhythmias).
In an accompanying editorial, Edward Gerstenfeld and Joshua Moss from the University of California-San Francisco, USA, praise the work of Vaseghi et al commenting: “We are indebted to the authors for additional insight into this unique therapy…Vaseghi et al have really set the standard for bringing a research concept to clinical practice. They performed extensive preclinical research in animal models that demonstrated the mechanisms whereby cardiac sympathetic denervation might reduce ventricular tachycardia…They then published small case series of cardiac sympathetic denervation in humans with refractory ventricular tachycardia and few interventional options…Now they have put together a multicentre retrospective study…We look forward to the results of prospective randomised studies from this group to further define the role of cardiac sympathetic denervation in treating patients with refractory ventricular tachycardia.”