Effects of Renal Artery Denervation on Ventricular Arrhythmias in a Postinfarct Model

Abstract

T he therapeutic potential of renal denervation (RDN) for cardiac arrhythmias was previously explored, yielding case reports and small case series that suggested RDN may be an effective adjunctive treatment in addition to medication and cardiac ablation for patients with ventricular tachycardia (VT) storm and atrial fibrillation.1-5 These promising results call for large-scale, well-controlled trials and detailed mechanistic evaluations. However, findings of the SYMPLICITY HTN-3 study (Renal Denervation in Patients With Uncontrolled Hypertension) have raised grave concerns over the benefits from RDN therapy for hypertension. 4 Hence, although RDN-based treatments are being developed for arrhythmias, it is important to reassess and confirm the antiarrhythmic potential of RDN in experiments designed to clearly demonstrate the impacts on cardiac electrophysiology. More importantly, the mechanistic basis of any antiarrhythmic effects should also be determined. See Editorial by Koruth and DukkipatiRDN has been shown to attenuate elevations in left ventricular end-diastolic pressure, suppress spontaneous premature beats, and reduce the incidence of ventricular fibrillation (VF) immediately post-acute coronary occlusion in pigs.6 RDN was also shown to reduce the incidence of ventricular arrhythmias (VAs) immediately after coronary occlusion in a similar acute canine model, in which RDN prolonged the ventricular effective refractory period (ERP) and the ventricular action potential duration, as well as decreased action potential duration dispersion. Although RDN is known to reduce renal sympathetic activity Background-The therapeutic potential of renal denervation (RDN) for arrhythmias has not been fully explored. Detailed mechanistic evaluation is in order. The objective of the present study was to determine the antiarrhythmic potential of RDN in a postinfarct animal model and to determine whether any benefits relate to RDN-induced reduction of sympathetic effectors on the myocardium. Methods and Results-Pigs implanted with single-chamber implantable cardioverter defibrillators to record ventricular arrhythmias (VAs) were subjected to percutaneous coronary occlusion to induce myocardial infarction. Two weeks later, a sham or real RDN treatment was performed bilaterally using the St Jude EnligHTN basket catheter. Parameters of ventricular remodeling and modulation of cardio-renal sympathetic axis were monitored for 3 weeks after myocardial infarction. Histological analysis of renal arteries yielded a mean neurofilament score of healthy nerves that was significantly lower in the real RDN group than in sham controls; damaged nerves were found only in the real RDN group. There was a 100% reduction in the rate of spontaneous VAs after real RDN and a 75% increase in the rate of spontaneous VAs after sham RDN (P=0.03). In the infarcted myocardium, presence of sympathetic nerves and tissue abundance of neuropeptide-Y, an indicator of sympathetic nerve activities, were significantly lower in the RDN group. Peak and mean sinus t...

Renal Denervation Effects on Myocardial Fibrosis and Ventricular Arrhythmias in Rats with Ischemic Cardiomyopathy

“…However, only a few studies have focused on the role of RDN against VAs in a model of MI-induced ischemic cardiomyopathy. Nicholas et al recently showed that RDN can reduce spontaneous VAs after MI, and this phenomenon may be associated with the downregulation of cardiac sympathetic activity [7]. In the present study, RDN indeed decreased the occurrence of VAs in ischemic heart disease, which was consistent with the findings of Jacksonet al [7].…”

“…RDN has also been reported to attenuate cardiac remodeling and preserve cardiac function in several studies [4,5]. In addition, with respect to VAs after MI, Linz et al reported that RDN suppressed VAs during acute ischemia events [6], while Nicholas et al recently demonstrated its role in reducing post-infarction VAs [7]. However, little is known of the mechanisms underlying these phenomena.…”

Danqi soft capsule prevents infarct border zone remodelling and reduces susceptibility to ventricular arrhythmias in post‐myocardial infarction rats

“…26 IBZ remodelling creates the substrate for re-entrant circuits and conduction dysfunction causing late post-MI VT. 3,29 Therapeutic strategies to homogenize infarct scarring, either by ablation or pharmacologically, are antiarrhythmic in the chronically infarcted heart. 30,31 In this study, more interstitial fibrosis, myocyte Interstitial fibrosis is the main pathological change in post-MI structural remodelling in the IBZ. 34 Excessive collagen, generated by activated fibroblasts, increases the stiffness of the myocardial wall and is linked to cardiac remodelling, thereby impeding normal electrical conduction function.…”

The autonomic nervous system and ventricular arrhythmias in myocardial infarction and heart failure

“…Ablation along the renal arteries affects both renal sympathetic afferent and efferent fibers that in turn seem to downregulate efferent sympathetic output to the heart and decreased VA threshold . RSD decreases spontaneous VAs in porcine models of ischemia rates of spontaneous VAs in porcine models of ischemia . In a canine study of myocardial ischemia, RSD led to decreased whole‐body and local tissue sympathetic activity and reversed neural remodeling in the heart and stellate ganglion .…”

“…52,93 RSD decreases spontaneous VAs in porcine models of ischemia rates of spontaneous VAs in porcine models of ischemia. [94][95][96] In a canine study of myocardial ischemia, RSD led to decreased whole-body and local tissue sympathetic activity and reversed neural remodeling in the heart and stellate ganglion. 97 This resulted in beneficial electrophysiological changes in border zones of infarcts, culminating in decreased VAs.…”