Baroreflex Sensitivity May Help Target Likely Responders to Renal Denervation

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Assessment of cardiac baroreflex sensitivity (BRS), one of the body’s mechanisms for maintaining blood pressure (BP), may help predict which patients with resistant hypertension will not respond to renal denervation therapy, according to data published online August 21, 2013, ahead of print in the Journal of the American College of Cardiology.

Axel Bauer, MD, of the University of Tübingen (Tübingen, Germany), and colleagues prospectively studied 50 patients with resistant hypertension who underwent BRS testing before receiving catheter-based renal denervation between October 2010 and September 2012.

Patients’ baseline ambulatory systolic BP of 157 ± 22 mmHg was reduced by 8 ± 19 mmHg (P = 0.003) at 6 months after denervation, while ambulatory diastolic BP of 89 ± 16 mmHg declined by 4 ± 12 mmHg (P = 0.022). At baseline, patients were taking 5.4 ± 1 antihypertensive medications. At 6 months postprocedure, there were no significant changes in the number or types of these drugs.

Only Half Respond to Denervation

In all, 26 patients (52%) were classified as renal denervation responders, defined as a reduction of mean systolic ambulatory BP of at least 10 mmHg 6 months postprocedure. Compared to nonresponders, responders had higher BMI (P = 0.013) and increased mean ambulatory BP (P = 0.001); other baseline characteristics were similar.

BRS values were lower in denervation responders than in nonresponders (0.16 ± 0.75 ms/mmHg vs. 1.54 ± 1.73 ms/mmHg, P < 0.001). Moreover, BRS highly correlated with reduced mean systolic BP at 6 months (r = -0.46; P < 0.001). Patients in the lowest tertile had the most notable reduction in systolic BP with treatment, 17± 20 mmHg, followed by 8 ± 13 mmHg for the middle tertile, while those in the highest tertile experienced a reduction of 0 ± 20 mmHg (P = 0.023).

According to receiver operating characteristic curve analysis, BRS was more strongly associated with denervation response (AUC 81.2%) than were baseline mean systolic BP (AUC 77.1%) or BMI (AUC 73.4%; P < 0.001 for both comparisons). In addition, multivariable analysis showed that adding BRS to BMI and systolic BP improved the predictability of denervation response (from C-statistic of 78.9% to 89.5%; P < 0.001).

“In conclusion, BRS assessment helps to identify patients who most likely benefit from [renal denervation] and, of equal importance, patients who do not,” the study authors conclude.

Importance of Patient Selection Underscored

In an e-mail communication with TCTMD, Dr. Bauer noted that while renal denervation is a novel approach to treating resistant hypertension, it is also invasive and might be potentially harmful. “Long-term sequelae of irreversible destruction of renal nerves are still unknown,” he said. “Therefore, selection of appropriate candidates . . . is of great importance.”

Dr. Bauer explained the rationale for assessing BRS. “We believe that impaired BRS in patients with resistant hypertension reflects increased sympathetic activity,” he said. Such patients may benefit the most from RDN, while the procedure might not be a good option in those with normal sympathetic tone, he observed, adding that nothing can be done to improve the likelihood of response in the latter group.

Not Ready for Prime Time?

In a telephone interview with TCTMD, Suzanne Oparil, MD, of the University of Alabama School of Medicine (Birmingham, AL), pointed to several study limitations.

BRS testing was limited to subjects in sinus rhythm and direct measures of sympathetic activity were not acquired, although this would be highly impractical in the clinic, Dr. Oparil acknowledged. Researchers also measured BRS just once before denervation and thus do not know whether the procedure improved impaired BRS. Moreover, cut-off values for BRS impairment need validation, and the technology required to measure BRS may not be widely available, she said.

Although BRS screening is interesting in the research setting, it “has limited practical clinical significance,” Dr. Oparil said. Importantly, she noted, it would not work unless patients have a regular sinus rhythm.

Dr. Bauer countered, however, that assessment of so-called spontaneous BRS can be completed noninvasively in 30 minutes. Certain equipment and software is required, such as a plethysmographic device to measure arterial BP on a beat-to-beat basis, and a technician needs to manually revise BP and ECG signals. However, industry development of smaller devices that allow for fully automated BRS testing may be possible, he said.

Practical Tool Clearly Needed

In an accompanying editorial, David E. Kandzari, MD, of Piedmont Heart Institute (Atlanta, GA), and Paul A. Sobotka, MD, of Ohio State University (Columbus, OH), write that “although the performance of BRS measurement is challenging, it is more practical than other methods to assess the sympathetic signature, including renal norepinephrine spillover sampling and recording of muscle sympathetic nerve activity.”

However, they add, the reproducibility and accuracy of testing is not well understood, and in the current study, “BRS was not uniformly predictive for all hypertensive patients nor did it predict the magnitude of blood pressure reduction.”

If renal denervation becomes widespread, clinicians will need a broadly applicable screening method to predict response, Dr. Oparil said, noting that the procedure’s failure rate ranges from 15% to 100% depending on how BP is measured. Whether failure is due to inadequacy of the intervention or to the patient being unresponsive is unknown, she said.

Study Details

Patients were aged 60.3 ± 13.8 years and had office-based systolic BP of 160 mmHg or higher and ambulatory BP of 130 mmHg or higher despite taking 3 or more antihypertensive drugs.

 


Sources:
1. Zuern CS, Eick C, Rizas KD, et al. Impaired cardiac baroreflex sensitivity predicts response to renal sympathetic denervation in patients with resistant hypertension. J Am Coll Cardiol. 2013;Epub ahead of print.

2. Kandzari DE, Sobotka PA. Ready for a marathon, not a sprint: Renal denervation therapy for treatment-resistant hypertension [editorial]. J Am Coll Cardiol. 2013;Epub ahead of print.

 

 

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Baroreflex Sensitivity May Help Target Likely Responders to Renal Denervation

Assessment of cardiac baroreflex sensitivity (BRS), one of the body’s mechanisms for maintaining blood pressure (BP), may help predict which patients with resistant hypertension will not respond to renal denervation therapy, according to data published online August 21, 2013, ahead
Disclosures
  • Dr. Bauer reports receiving support and honoraria from Medtronic Ardian.
  • Dr. Oparil reports no relevant conflicts of interest.
  • Dr. Kandzari reports receiving grant support and consulting honoraria from Boston Scientific and Medtronic CardioVascular.
  • Dr. Sobotka reports being an employee of CibiemHe, serving as a consultant to Abbott Investments, Ardelyx, Medtronic CardioVascular, and Rox, and receiving royalties from Medtronic CardioVascular.

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