Renal Denervation Improves Cardiac Function

March 01, 2012

March 1, 2012 (Salzburg, Austria) — As well lowering blood pressure in those with resistant hypertension, it seems that renal sympathetic artery denervation also reduces left ventricular hypertrophy (LVH) and improves cardiac function in these patients [1].

In March 6, 2012 issue of the Journal of the American College of Cardiology, Dr Mathias C Brandt (Paracelsus Medical University, Salzburg, Austria) and colleagues report the encouraging new results of an echocardiographic substudy of the Symplicity II trial — which was reported 18 months ago at the AHA meeting and in the Lancet and showed that renal denervation produced significant reductions in blood pressure without any major complications in more than 100 patients with severely resistant hypertension.

In an editorial accompanying the new Brandt et al paper [2], Drs Michael R Zile (Medical University of South Carolina, Charleston) and William C Little (Wake Forest University School of Medicine, Winston-Salem, NC) say renal denervation and other autonomic modulation strategies "hold enormous promise for the treatment of patients with hypertensive heart disease."

Renal denervation reduces LV mass, improves diastolic function

Renal sympathetic efferent and afferent nerves are crucial for the initiation and maintenance of systemic hypertension and lie within and immediately adjacent to the wall of the renal artery. The concept of denervation of the renal sympathetic nerve to try to reduce BP is old and was attempted, unsuccessfully, by surgical means some years ago.

The nerves are accessible using an interventional approach through the femoral artery; the procedure in this trial was performed bilaterally using radiofrequency ablation with the Symplicity catheter (Ardian, Palo Alto, CA) by either an interventional cardiologist or interventional radiologist and took around 40 minutes, with four or five sites at each renal sympathetic nerve ablated in a rotational manner to cover the full circumference. The procedure requires an overnight stay in hospital and is painful, so analgesia is employed.

We demonstrate for the first time, to our knowledge, that selective denervation of the renal sympathetic nerves reduces LV mass and improves diastolic function in patients with resistant hypertension.

In the echocardiographic substudy, 46 patients who underwent bilateral renal denervation were assessed by transthoracic echocardiography performed at baseline, after one month, and after six months. There were 18 patients who served as controls.

Besides reduction of systolic and diastolic BP, renal denervation was associated with a decrease in LV mass by 13% one month after treatment and by 17% six months after. By contrast, LV mass tended to increase in the control group.

Renal denervation was also associated with an improvement in LV diastolic function; again, in contrast, these measures of diastolic function became more abnormal in the control group. This effect was further substantiated by a 39% reduction in pro-B-type natriuretic peptide in those who underwent renal denervation, compared with only an 8% reduction in the control group.

"We demonstrate for the first time, to our knowledge, that selective denervation of the renal sympathetic nerves, in addition to lowering peripheral BP, significantly reduces LV mass and improves diastolic function in patients with resistant hypertension," say Brandt et al.

Extrapolating from drug trials, "the effect on cardiac remodeling documented in our study suggests a prognostic benefit of renal denervation in patients with refractory hypertension, which should be evaluated in future trials," they conclude.

In their editorial, Zile and Little agree: "It is anticipated that LVH regression induced by renal artery denervation will also be associated with a reduction in mortal and morbid events; however, to date, this remains an unproven hypothesis."

Other autonomic modulation studies are ongoing

The editorialists also describe other ongoing trials testing renal artery denervation with devices from Biosense Webster and St Jude, as well as the Symplicity studies. Other companies conducting trials with similar devices include Vessix Vascular [3] and ReCor [4].

And they detail other novel strategies to modulate the sympathetic nervous system that are being developed for the treatment of hypertensive heart disease and heart failure, including baroreceptor activation therapy, spinal-cord stimulation, and vagal-nerve stimulation.

Brandt received scientific support from Ardian. Disclosures for the coauthors are listed in the paper. Zile receives grant support from the Department of Veterans Affairs Merit Review Program and the National Heart, Lung, and Blood Institute; consulting fees from Medtronic, CVRx Gilead, Novartis Pharmaceuticals, Sanofi-Aventis, and Up-To-Date and has received them in the past from Boston Scientific, St. Jude Medical, Bristol-Myers Squibb, Merck, Pfizer, Johnson & Johnson, and the American Board of Internal Medicine. Little receives consulting fees from Medtronic, CVRx, BioControl Medical, Gilead, Amylin, Corassist, Ono Pharmaceuticals, and the American Board of Internal Medicine and has received them in the past from Boston Scientific; and receives grant funding from the National Heart, Lung, and Blood Institute.

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