Catheter Based Renal Sympathetic Denervation - A New Treatment for Resistant Hypertension

The Joint National Committee 7 defines resistant hypertension (RHTN) as:"a failure to achieve goal BP (<140/90 mm Hg for the overall population and <130/80 mm Hg for those with diabetes mellitus or chronic kidney disease) when a patient adheres to maximum tolerated doses of 3 antihypertensive drugs including a diuretic". In the AHA Scientific Statement: Resistent Hypertension: Diagnosis, Evaluation, and Treatment , Calhoun and colleagues define it as “high blood pressure (BP) requiring >4 antihypertensive medications, whether controlled or uncontrolled”. [see an earlier post here]

Using the AHA definition of RHTN, estimates are that ≈ 9% of patients have RHTN, although clinical trials suggest the prevalence of RHTN may be 20-30%. So far, the treatment of RHTN includes, the identification and reversal of lifestyle factors contributing to treatment resistance; the diagnosis and appropriate treatment of secondary causes of hypertension; and the use of effective multidrug regimens.

A paper published May 17 in JASN Hering and co-workers adds renal denervation as a new dimension to the treatment of RHTN. In an article in heart.org, renal denervation is "poised to depose transcatheter aortic-valve implantation (TAVI) as the hottest thing in interventional cardiology."

Hering et al performed renal denervation in 15 patients with hypertension and CKD. They enrolled patients with an eGFR of < 45 ml/min per 1.73 m².  Blood pressure at baseline, on average, was 174/91 mmHg despite taking numerous antihypertensive drugs. With denervation, blood pressure readings dropped considerably at one, three, six, and 12 months after the procedure (-34/-14, -25/-11, -32/-15, and -33/-19 mmHg, respectively). They report that renal denervation did not worsen patients' kidney function, indicating that at least on the basis of this study it is safe even when CKD is present.

According to the the heart.org article over 20 companies are working on renal denervation technology. The leading system "Symplicity" is from Medtronic. In the SYMPLICITY HTN 2 trials 84% of patients had a >10 mmHg drop in systolic BP from baseline.

It's worth briefly recalling that the initial report of catheter-based renal sympathetic denervation for RHTN was published by Henry Krum and colleagues in the Lancet in 2009. This was a "first-in-man" non-randomized study of 45 patients with RHTN (SBP>160 mmHg on >3 anti-HTN drugs including a diuretic with an eGFR by MDRD of >45 ml/min/1.73m2). The mean BP at baseline was 177/101 mmHg and office Bps after the procedure were reduced by −14/−10, −21/−10, −22/−11, −24/−11, and −27/−17 mm Hg at 1, 3, 6, 9, and 12 months, respectively.

Subsequent reports summarized in a powerpoint on the web - Symplicity HTN-1 and Symplicity HTN-2 have enlarged the sample size and increased the follow-up. The data continue to be very promising. In the Symplicity HTN-1 study that Sievert et al presented at the European Society of Cardiology in 2010, patients tolerated the procedure very well both in the short and long-term. In their hands, the median procedure time is 38 minutes with an average of 4 ablations per renal artery. Intravenous narcotics and analgesics are used to manage the pain during the delivery of the radio frequency energy. They report no major complications. Only 4 of 153 in Symplicity HTN-1 had minor complications - one renal artery dissection during catheter delivery prior to the ablation and in three there were access complications. Long-term complications were also minimal both structurally to the renal artery and in terms of renal function. 

Symplicity HTN-2 published in the Lancet,  was a relatively small RCT of 106 patients who were randomly allocated to renal denervation (n=52) or control (n=54). "Office-based blood pressure measurements in the renal denervation group reduced by 32/12 mm Hg (SD 23/11, baseline of 178/96 mm Hg, p<0·0001), whereas they did not differ from baseline in the control group (change of 1/0 mm Hg [21/10], baseline of 178/97 mm Hg, p=0·77 systolic and p=0·83 diastolic). Between-group differences in blood pressure at 6 months were 33/11 mm Hg (p<0·0001). At 6 months, 41 (84%) of 49 patients who underwent renal denervation had a reduction in systolic blood pressure of 10 mm Hg or more, compared with 18 (35%) of 51 controls (p<0·0001). We noted no serious procedure-related or device-related complications and occurrence of adverse events did not differ between groups; one patient who had renal denervation had possible progression of an underlying atherosclerotic lesion, but required no treatment."

Bottom-line: Renal denervation is emerging to be a very promising option for management of resistant hypertension. Fasten your seat-belts!