Background: Hypertension (HTN) is an important risk factor for Atrial Fibrillation (AF). Effective blood pressure control with anti-HTN drugs has been shown to be beneficial in decreasing the incidence of AF. Preliminary data shows renal nerve denervation (RDN) to be effective for drug refractory hypertension. The authors sought to determine whether RDN can be used as an additive strategy along with pulmonary vein isolation (PVI) in improving freedom from AF in patients with drug refractory HTN.

Methods: A prospective randomized single blind study was conducted in 27 patients with 14 randomized to PVI alone (control) group and 13 to the PVI and RDN (study) group. All patients had a history of symptomatic AF refractory to 2 or more antiarrhythmic agents and drug-resistant HTN (systolic blood pressure >160 mm Hg despite triple drug therapy). Patients underwent PVI without any additional substrate modification. RDN was performed by creating up to 6 lesions 2 minutes each longitudinally and rotationally extending from distal main renal artery bifurcation to the ostium with 8 to 10 watts of power. Patients were followed at three, six, nine, and 12 months to assess for freedom from atrial arrhythmias and blood pressure changes.

Results: A large proportion (69%) had persistent AF without significant differences in the baseline characteristics between both groups. Immediate reduction in blood pressure (> 15mm) was noted following ablation in bilateral renal arteries with a mean of 4.4 RF applications. Procedural and fluoroscopic times were slightly longer in the study group without statistical significance. At 12 month follow up study group had significantly higher freedom from atrial arrhythmias than the control group (69% vs. 29%, p<0.03). A similar benefit was seen in BP reductions in the study group (mean SBP ∆25±5 and DBP ∆10±2, p=0.001). There was evidence of reverse cardiac remodeling in the study group with statistically significant reductions in the posterior, septal wall thickness and LV mass. There were no complications reported with no evidence of renal artery stenosis in either group with GFR remaining unchanged.

Conclusion:
RDN performed concomitantly with PVI reduces AF recurrence rate and BP in patients with drug refractory hypertension.

Commentary/Perspective:
Modification of renal sympathetic connections through RDN seems to reduce BP in patients with drug resistant HTN.¹ RDN not only affects regional sympathetic system but seems to have a broader impact on the Renin Angiotensin Activation System potentially resulting in a multisystem upstream benefit. RAAS seems to play an important role in the pathogenesis of AF through elevated BP resulting in the initiation (sympathetically mediated triggered activity) and maintenance (atrial stretch/dilatation and inflammatory changes).² An intervention that results in sustained suppression of the RAAS may result in abatement of the pro-arrhythmic milieu responsible for AF. Along these lines, a prior canine study showed RDN reduced episodes of AF during rapid atrial pacing.³

As an extension of this concept, Pokushalov et al performed the first-in-human proof-of-concept study demonstrating the positive effects of RDN in AF patients with drug refractory hypertension.⁴ While the results are very promising, further large randomized trials are necessary to evaluate the validity of this innovative approach. Despite the fact that the majority of patients had persistent AF, RDN still resulted in improved arrhythmia outcomes, highlighting the role of HTN and RAAS activation in substrate-mediated AF. The antifibrillatory effect was also associated with reverse cardiac remodeling. This study marks the beginning of a new chapter in AF therapy. A larger ongoing HFIB study by Reddy et al will examine the reproducibility of the outcomes seen in this feasibility study.

References

1. Schlaich MP, Sobotka PA, Krum H, Lambert E, Esler MD. Renal sympathetic-nerve ablation for uncontrolled hypertension. N Engl J Med 2009;361:932– 4.
2. Atrial fibrillation: hypertension as a causative agent, risk factor for complications, and potential therapeutic target. Healey JS, Connolly SJ. Am J Cardiol. 2003 May 22;91(10A):9G-14G
3. Zhao Q, Yu S, Zou M, Dai Z, Wang X, Xiao J, Huang C.Effect of renal sympathetic denervation on the inducibility of atrial fibrillation during rapid atrial pacing. J Interv Card Electrophysiol. 2012 Nov;35(2):119-25
4. Pokushalov E, Romanov A, Corbucci G, Artyomenko S, Baranova V, Turov A, Shirokova N, Karaskov A, Mittal S, Steinberg JS.A Randomized Comparison of Pulmonary Vein Isolation With Versus Without Concomitant Renal Artery Denervation in Patients With Refractory Symptomatic Atrial Fibrillation and Resistant Hypertension. J Am Coll Cardiol 2012;60:1163–70.

Keywords: Atrial Fibrillation, Denervation, Hypertension, Renal Artery, Renin

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