By Angela Gonzalez
Renal denervation has shown positive long-term effects lowering blood pressure in resistant hypertensive patients without significant adverse events, as reported by the Symplicity trials. Now, studies are exploring renal denervation as an adjunctive treatment in other diseases characterised by sympathetic overactivity such as ventricular arrhythmias, atrial fibrillation, metabolic syndrome and obstructive sleep apnoea. Cardiac Rhythm News spoke to leading physicians who are investigating this technology for the management of atrial fibrillation
Hypertension is an important risk factor for developing atrial fibrillation and is one of the few modifiable risk factors for the condition.”Increased sympathetic drive together with autonomic imbalance play an important role for the initiation and perpetuation of atrial fibrillation,” explained Dominik Linz, Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany.
Linz, who investigated the effect of renal denervation on atrial fibrillation in a pig model, also told Cardiac Rhythm News that: “Atrial fibrillation itself, as well as other pathophysiological conditions like congestive heart failure, leads to atrial autonomic remodelling characterised by sympathetic hyperinnervation.”
In his study (Hypertension, 2012; 60:172178) Linz identified several anti-arrhythmic effects of renal denervation. “In anaesthetised pigs with atrial fibrillation, induced by rapid atrial pacing, renal denervation provides sufficient rate control, which might reduce clinical symptoms in patients with atrial fibrillation,” Linz and his fellow authors concluded. Linz will be giving a talk on this topic at the AF Summit of the Heart Rhythm Symposium (HRS) 2013 (8 May, Denver, USA).
First-in-man study
The atrial anti-arrhythmic effects of renal denervation have not only been explored in animals. A prospective, randomised, double blind, first-in-man study (J Am Coll Cardiol [JACC] 2012; 60:1163-1170) undertaken by Evgeny Pokushalov, from the State Research Institute of Circulation Pathology, Novosibirsk, Russia, and others investigated the impact of renal denervation in patients with a history of refractory atrial fibrillation and drug-resistant hypertension who were referred for pulmonary vein isolation. Pokushalov said: “In this study, we hypothesised that renal artery denervation could have a salutary effect on atrial fibrillation patterns in patients with poorly controlled hypertension.” He explained that the mechanisms by which renal denervation could help were believed to fall into two non-mutually exclusive possibilities: by improving blood pressure control and by reducing central sympathetic cardiac stimulation. “The implication of the latter is very important, ie. that this technique has potential value in non-hypertensives,” he added.
Pokushalov et al enrolled 27 patients; 14 were randomised to pulmonary vein isolation only and 13 were randomised to pulmonary vein isolation with renal denervation with the Stimulator B-53 from Biotok. At the end of the follow-up (one year after procedure), the authors found significant reductions in systolic (from 181±7 to 156±5, p<0.001) and diastolic blood pressure (from 97±6 to 87±4, p<0.001) in patients treated with pulmonary vein isolation with renal denervation. There was no significant change in the group with pulmonary vein isolation only. Pokushalov et al also found that nine (69%) of the 13 patients in the pulmonary vein isolation with renal denervation group were atrial fibrillation free at one-year post ablation follow-up examination vs. 4 (29%) of the 14 patients treated with pulmonary vein isolation only. The authors concluded that renal artery denervation provided incremental atrial fibrillation suppression after pulmonary vein isolation in patients with symptomatic and refractory atrial fibrillation in the setting of drug-resistant hypertension.
In order to clarify the rationale behind the positive effect of renal denervation on atrial fibrillation, Pokushalov told Cardiac Rhythm News: “Optimised blood pressure control might play a considerable role at the substrate level of the atria in preventing the development or recurrence of atrial fibrillation. In addition, the ablation of afferent renal nervous input decreases central sympathetic output, which might attenuate autonomic triggers of atrial fibrillation in addition to improved blood pressure control and offer the potential for an anti-arrhythmic effect superior to medications.”
There were some limitations found in this study. Pokushalov acknowledged that the number of patients was limited. Also, he said, “Because our data refer to a follow-up period of one year after the ablation procedure, we cannot extrapolate our results to the long-term maintenance of sinus rhythm or blood pressure control.”
Ralph Verdino (Hospital of the University of Pennsylvania, Philadelphia, USA), wrote in the Journal of the American College of Cardiology in an accompanying editorial of Pokushalov et al’s study: “Although the study cohort is small and one can certainly question the comprehensiveness of documenting arrhythmia recurrence because continuous ambulatory monitoring was not used in this study, the findings nevertheless are impressive.” He told Cardiac Rhythm News: “Atrial fibrillation is a complex arrhythmia with many different medical conditions contributing to its genesis and maintenance. I wonder if better control of hypertension with procedures such as renal denervation may decrease the incidence of atrial fibrillation and obviate the need for catheter ablation in certain patients.” In the editorial, he also raised the questions: “Should renal artery denervation be part of ablation for all patients undergoing catheter ablation for the treatment of atrial fibrillation? Or should it be limited to those with hypertension? Also, should renal artery denervation be performed instead of pulmonary vein isolation? And have we been targeting the wrong organ?” To answer some of these questions, larger studies are currently underway, Verdino commented.
Pokushalov spoke to Cardiac Rhythm News on Verdino’s questions: “From my perspective, I think that renal denervation can be effective only in patients with drug-refractory hypertension. When we are discussing that renal denervation can work with atrial fibrillation in two directions the control of blood pressure and reduction central sympathetic stimulation I think pressure control plays a more significant impact, and decreasing sympathetic stimulation complements it. So I think pulmonary vein isolation and renal ablation will be effective only in atrial fibrillation patients with resistant hypertension. In patients with atrial fibrillation and without hypertension or non-resistant hypertension this combination will be comparable in effectiveness with just pulmonary vein isolation.”
