Renal denervation: Brightest hope since angioplasty?

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 - Medtronic Symplicity renal denervation system
The Symplicity renal denervation system uses a catheter to deliver low-level radiofrequency energy through the renal artery wall. A physician inserts the catheter into the femoral artery to access the renal artery. A generator is then activated to deliver the energy.
Source: Medtronic

Medical advances are announced at breakneck speed, many heralded as the greatest breakthrough since antibiotics or anesthesia. Although most don’t live up to the hype, some find a valuable if limited role in the clinician’s arsenal.

Renal sympathetic denervation is an emerging technique for treating drug-resistant hypertension, a significant problem globally. The therapy presents real hope, not only in offering a possible solution to the significant and stubborn problem of resistant hypertension, but potentially also in treating sleep apnea, heart failure and diabetes. Only extensive research and time will tell whether renal denervation is the best innovation since angioplasty or a niche therapy. Early indications are promising.

Hypertension is a huge health problem, affecting 72 million Americans (one in three adults) and 1 billion worldwide. The No. 1 killer globally, hypertension causes 7.1 million deaths associated with cardiovascular conditions such as heart disease and stroke. A 20 mm increase in mercury blood pressure doubles the risk of mortality, so lowering blood pressure is crucial.

Yet approximately one in three patients who are treated do not have their blood pressure under control, often despite taking two, three, four or more different antihypertensive medications. With no new hypertension drugs on the near horizon, clearly there is a need for new approaches to this extensive problem.

Renal denervation via Medtronic’s Symplicity radiofrequency ablation system is in clinical trials in the U.S., with the goal of winning FDA approval at completion. St. Jude Medical’s EnligHTN system also is in trials abroad. The rollout of renal denervation is further advanced overseas, where as many as 10,000 patients have undergone the procedure in Europe and Australia.

During trials of renal denervation, researchers observed benefits in treating comorbidities commonly found in patients with hypertension, such as diabetes, heart failure and sleep apnea. Very early research suggests that the benefits of renal denervation could be more far-reaching than lowering blood pressure. For this reason, the 2013 International Symposium on Endovascular Therapy (ISET) Town Hall meeting on Jan. 21 is “Sympathetic Denervation—The Next Great Endovascular Breakthrough?”

Whereas the central nervous system controls motor skills, the sympathetic nervous system controls body functions such as heart rate and blood pressure. In the 1930s, researchers desperate to control hypertension in certain patients tried various radical approaches involving the sympathetic nervous system, including surgically resecting renal artery nerves. The goal of greatly reducing blood pressure was achieved, but the procedure came with high perioperative complications, including death.

Fast-forward to the present, and the development of radiofrequency ablation to achieve the same goal has been shown successful and durable via the Symplicity HTN 1 and 2 trials. The current version of the trial includes a sham arm, and should be completed by the end of 2013. Recently reported EnligHTN 1 trial six-month results also showed benefit. Similar devices, including those that use alternate methods such as focused ultrasound, are in various stages of development.

Renal denervation has proven so successful in widespread use overseas that the European Society of Hypertension recommends it as routine practice for patients with resistant hypertension. Several European researchers are beginning to look at lowering the bar for the therapy and considering treating patients with less-severe levels of hypertension. Many people with hypertension also suffer from stress, anxiety and depression, and early reports suggest renal denervation can alleviate those symptoms.

Researchers also believe reducing sympathetic activity results in a number of additional benefits that may help in the treatment of diabetes, sleep apnea and heart failure. Medical experts recognize that sympathetic nervous system hyperactivity also plays a major role in heart failure. Early research on patients with advanced heart failure suggests renal denervation may be beneficial in treating heart failure by decreasing sympathetic tone. One small study showed employing renal denervation in heart failure patients with normal blood pressure raised left ventricular ejection fraction, reduced left ventricular end-systolic and end-diastolic volume index and cut serum levels of natriuretic peptide.

Obstructive sleep apnea affects up to 80 percent of patients with resistant hypertension. In fact, it is the most common condition associated with resistant hypertension. Researchers are exploring the possibility that obstructive sleep apnea is a consequence as well as a cause of increased sympathetic tone. A small study of 10 patients with resistant hypertension and obstructive sleep apnea suggests renal denervation improved both conditions.

Renal denervation reduces salt avidity by disrupting renal nerve activity, and researchers believe this might reduce total body fluid and peripharyngeal fluid accumulation, likely factors in sleep apnea. A variety of other systems and interactions may factor in, and the drop in blood pressure itself likely helps reduce episodes of obstructive sleep apnea. Sympathetic hyperactivity also is associated with insulin resistance and diabetes mellitus. Early work suggests renal denervation may regulate insulin sensitivity and improve glucose metabolism, and therefore holds promise in treating patients with diabetes.

Further, a cost analysis of the results of Symplicity HTN-2 found the procedure extremely cost effective. While a procedure is considered cost effective if it costs up to $50,000 per quality-adjusted life year (QALY), renal denervation costs $3,000 per procedure. If renal denervation continues to perform as it has so far, clinicians may well have an effective method of treating a number of chronically under-controlled and costly health problems. Perhaps, as was the case with angioplasty, the benefits and indications may exceed current aspirations.

For more on renal denervation and its potential cardiovascular applications, please read Newest Frontier in Cardiac Care: Kidneys” in the winter issue of Cardiovasular Business.

Dr. Katzen is course director for ISET and founder and medical director at Baptist Cardiac & Vascular Institute in Miami. The ISET meeting will be held from Jan. 19 to 23 in Miami Beach, Fla.