Catheter-based radio frequency (RF) renal denervation for resistant hypertension showed benefit at three years in a prospective registry-based study, but an analysis did not identify the best candidates for the procedure.
Reduction in 24-hour systolic BP at 3 years was −8.9 ± 20.1 mm Hg for the overall cohort. For high-risk subgroups (all P < 0.0001 compared with baseline), it was:
- −10.4 ± 21.0 mm Hg in patients with resistant hypertension.
- −8.6 ± 18.7 mm Hg in isolated patients with isolated systolic hypertension.
- −8.7 ± 17.4 mm Hg in patients >65 years.
- −10.2 ± 17.9 mm Hg in patients with diabetes.
- −10.1 ± 20.3 mm Hg in chronic kidney disease.
- −10.0 ± 19.1 mm Hg in atrial fibrillation (Afib).
“BP reduction after renal denervation was similar in patients with and without baseline conditions associated with increased sympathetic activity and irrespective of atherosclerosis cardiovascular disease (ASCVD) risk,” wrote Felix Mahfoud, MD, of Saarland University Hospital in Germany, and coauthors, in Journal of the American College of Cardiology.
The study, based on the Global Symplicity Registry (GSR) data, “modestly extends previous reports by presenting post hoc analyses of several ’risk subgroups’ in the registry: these were defined by age older or younger than 65 years, presence or absence of diabetes mellitus, isolated systolic hypertension, associated chronic kidney disease (defined as estimated glomerular filtration rate <60 ml/min/1.73 m2), and predilection to atrial fibrillation,” wrote Stephen Textor, MD, of the Mayo Clinic in Rochester, Minnesota, in an accompanying editorial.
“Each of these represented a limited subset due to incomplete data, making multivariate analysis impractical,” he added.
Adrenergic signaling, which includes renal afferent and efferent pathways, plays a key role in regulation of blood pressure and sodium homeostasis. Over the last 10 years, interest in RF renal denervation for disorders involving sympathetic adrenergic activity has led to multiple denervation systems and to studying the approach in obstructive apnea, arrhythmias, and glucose intolerance.
For hypertension, trials of the Symplicity system include:
- Symplicity 1 (2009): n=50; proof of principle trial in which a subset of 45 participants with resistant hypertension treated with renal denervation had mean 6 month BP reduction of −22/−11 mm Hg versus a mean 6-month rise of of +14/+9 mm Hg in 5 untreated patients without serious adverse events.
- Symplicity 2 (2010): n=106 participants who had baseline systolic BP of 160 mm Hg or more despite at least 3 medications were randomized to continue previous treatment with or without renal denervation; at 6 months 84% in the denervation group had systolic BP reduced by 10 mm Hg or more versus 35% of controls.
- Symplicity 3 (2013): n=535; showed no significant difference in reduction of systolic blood pressure between treatment and control groups with no significant difference in safety.
“Initial reports have focused on short-term effects, reporting safety and efficacy outcomes for 2 to 6 months after the procedures,” noted Textor. “Major concerns remain focused on: 1) patient selection for optimal efficacy; 2) durability of BP and renal functional outcomes, particularly because experimental studies indicate that some renal reinnervation can occur; and 3) evaluating technical success of denervation.”
Mahoud and colleagues reviewed data from the prospective, single-arm, open-label, real-world Global Symplicity Registry. Registry inclusion criteria mandated that patients were acceptable candidates for renal denervation based on user instructions for the Medtronic renal denervation system, which must be performed with an initial use, market-released Medtronic renal denervation catheter. Median follow-up was 2.5 years.
Of 2,652 patients included in the analysis who were registered by March 2019, the authors had sufficient information to calculate atherosclerosis cardiovascular disease (ASCVD) risk scores for 1,485 (mean 19.8%).
Blood pressure reduction at 6, 12, 24, and 36 months showed similar reductions in office and in 24-hour measurements for patients with baseline ASCVD risk scores in tertiles of <10%, 10 to <20%, and 20% or more over 3 years.
Those with baseline ASCVD risk scores of 20% or more had higher 3-year rates of death (8.4%), cardiovascular (CV) death (4.5%), hospitalization for new-onset heart failure (5.3%) and Afib (6.3%), compared with patients with lower risk scores.
Adverse events at 3 years were similar between subgroups, although participants with diabetes had a higher rate of myocardial infarction (4.0% versus 1.6%), end-stage renal disease (2.8% versus 1.0%), and elevated creatinine levels (2.4% versus 0.8%).
Death and CV death rates at 3 years were higher for those with diabetes. Patients with Afib had higher rates of death than those without.
“Clinical events increased with increasing ASCVD risk score, and elevated rates were also seen in patients with Afib and diabetes, identifying these subgroups who might derive even greater clinical benefit from improved BP control using renal denervation,” the authors wrote.
Limitations of the analysis include absence of a control group. In addition, not all patients were available for 3-year follow-up.
“For individuals with treatment-resistant hypertension, some respond with spectacular and meaningful BP reductions that were previously unachievable,” Textor observed. “How to identify those individuals who are likely to have clinically important benefits remains uncertain— and cannot be inferred directly from these registry data.”
“The outcomes reported here suggest that age, diabetes, isolated systolic hypertension, chronic kidney disease, or other demographic data do not reliably demarcate the populations likely to respond to renal denervation,” he added. “Identifying the truly optimal candidates for renal denervation remains the unresolved ’holy grail’ for this technology.”
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Catheter-based radio frequency (RF) renal denervation for resistant hypertension showed benefit at three years in a prospective registry-based study, but an analysis did not identify the best candidates for the procedure.
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Outcomes reported here suggest that age, diabetes, isolated systolic hypertension, chronic kidney disease, or other demographic data do not reliably demarcate the populations likely to respond to renal denervation, according to the editorialist. Identifying the truly optimal candidates for renal denervation remains the unresolved “holy grail” for this technology.
Paul Smyth, MD, Contributing Writer, BreakingMED™
The Global SYMPLICITY Registry is funded by Medtronic.
Mahfoud is supported by Deutsche Gesellschaft für Kardiologie and Deutsche Forschungsgemeinschaft; and has received speaker honoraria from Medtronic and ReCor.
Textor reported no disclosures.
Cat ID: 6
Topic ID: 74,6,730,6,130,142,192,925
