Renal Denervation for the Treatment of Hypertension: A Scientific Statement From the American Heart Association

Authors, Journal, Affiliations, Type, DOI

• Authors: Jennifer L. Cluett (Chair), Olivia Blazek, Angela L. Brown, Cara East, Keith C. Ferdinand, Naomi D.L. Fisher, Cassandra D. Ford, Karen A. Griffin, Carlos I. Mena-Hurtado, Harini Sarathy, Wanpen Vongpatanasin, Raymond R. Townsend (Vice Chair); on behalf of the AHA Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on the Kidney in Cardiovascular Disease; and Council on Peripheral Vascular Disease
• Journal: Hypertension, October 2024; 81:e135–e148
• Type: AHA Scientific Statement (consensus)
• DOI: 10.1161/HYP.0000000000000240

Overview

Renal denervation (RDN) is a catheter-based procedure that ablates the renal sympathetic nerves to reduce blood pressure via suppression of sympathetic activation. Following FDA approval of two RDN systems in November 2023 (Medtronic Symplicity Spyral and Recor Medical Paradise), this AHA Scientific Statement synthesises evidence from 22+ sham-controlled RCTs, providing guidance on efficacy, patient selection, safety, and shared decision-making. RDN produces modest but consistent reductions in 24-hour systolic BP (4–10 mmHg vs sham), equivalent to one additional antihypertensive medication, with a favourable safety profile including no evidence of kidney function impairment. Individual response varies and predictors of response remain incompletely identified, necessitating careful patient selection and multidisciplinary team involvement.

Keywords

AHA Scientific Statements, blood pressure, catheters, denervation, hypertension, kidney, patient care team

Key Takeaways

Background and Mechanism

• Hypertension affects ~120 million US adults; only 23% achieve BP control (<130/80 mmHg); ≈45% of uncontrolled adults have BP ≥140/90 mmHg
• The sympathetic nervous system contributes to hypertension through renal sympathetic nerve activity; effects depend on level of activation:
  • Low: renin release
  • Moderate: sodium reabsorption (antinatriuresis)
  • High: increased renal vascular resistance
• RDN provides a non-pharmacological method to suppress sympathetic outflow as an adjunct to lifestyle/medication

RDN Devices (3 main systems FDA-approved or studied)

Efficacy: Drug-Naive / Washout Patients (6 RCTs)

• SPYRAL OFF-MED pilot and Pivotal: Spyral system reduced 24h SBP by 4.7–5.5 mmHg vs sham (p<0.01)
• RADIANCE-HTN SOLO and RADIANCE II: Paradise system reduced daytime ambulatory SBP by 6.3 mmHg vs sham (p<0.01); consistent office BP reduction of 5.5 mmHg
• REDUCE HTN: REINFORCE (Vessix bipolar RF): No difference vs sham
• TARGET BP OFF-MED (Peregrine): No difference at 8 weeks; lower medication burden at 12 months
• Summary: Majority of trials positive; BP reduction comparable to 1 additional antihypertensive drug; primary endpoints at 2–3 months only (safety concern without medications)

Efficacy: Patients on 1–5 Antihypertensives

• SPYRAL ON-MED pilot: RDN superior by 7.4 mmHg 24h SBP
• SPYRAL ON-MED Expansion: No significant difference — larger-than-expected sham arm reduction (4.5 mmHg) attributed to protocol-violating medication intensification in sham arm (29.9% vs 17.3%)
• TARGET BP I (Peregrine): Modest but significant 3.2 mmHg reduction at 3 months (p=0.049)
• Results more variable due to medication protocol heterogeneity

Efficacy: Resistant Hypertension (RH)

• RH prevalence: ≈19.7% of treated hypertensive adults (10.3 million); 2× CVD risk vs responsive hypertension
• 10 sham-controlled RCTs; early trials with Symplicity Flex (unipolar) showed no difference (SYMPLICITY HTN-3, Desch, ReSET) — attributed to incomplete denervation and medication intensification in sham arms
• DENERHTN: Flex system reduced daytime SBP by 5.9 mmHg with standardised background triple therapy (p=0.03)
• RADIANCE-HTN TRIO: Paradise system reduced daytime SBP by 4.5 mmHg with standardised triple-pill therapy (p=0.02)
• RADIOSOUND-HTN: Ultrasound > radiofrequency in head-to-head comparison (only such trial)
• Unipolar RF (DENERVHTA, Prague-15): RDN efficacy inferior or equivalent to adding spironolactone as 4th agent
• Global SYMPLICITY Registry (3-year): sustained reduction in office SBP 16.5±28.6 mmHg and 24h ambulatory SBP 8.0±20.0 mmHg — but no sham control

Efficacy in Special Populations

• CKD: Smaller office SBP reduction but similar ambulatory BP reduction vs non-CKD (Global SYMPLICITY Registry); majority of RCTs excluded eGFR <30–45 mL/min/1.73m²; smaller studies show safety and efficacy in lower eGFR
• Diabetes (T2DM): Subgroup analysis of RADIANCE cohorts: no significant interaction between T2DM and BP response
• Overall response rate: 60–70% of patients achieve ≥5 mmHg meaningful SBP reduction; 24% achieve target daytime/home BP <135/85 mmHg vs 12% sham (with lower medication burden)

Patient Selection

Who to consider for RDN:

• True resistant hypertension (BP above goal on ≥3 drugs including diuretic)
• Uncontrolled BP despite medication intolerance, non-adherence, or inability to escalate
• Must confirm with 24h ABPM or appropriate home BP (exclude white-coat hypertension)

Absolute contraindications:

• Pregnancy
• Fibromuscular dysplasia
• Stented renal artery
• Renal artery aneurysm
• Significant renal artery stenosis (>50%)
• Known kidney or adrenal tumour

Limited data groups (not contraindicated, use with caution):

• Stage 1 hypertension
• Isolated systolic hypertension
• Stage 4–5 CKD
• Single kidney
• Kidney transplant recipients

Mandatory pre-RDN workup:

• Serum creatinine + urinalysis (eGFR assessment)
• Screen for primary aldosteronism (all candidates)
• Consider Cushing, phaeochromocytoma, thyroid, hyperparathyroidism, RAS, fibromuscular dysplasia, aortic coarctation based on clinical suspicion

Predictors of response (inconsistent evidence):

• Higher baseline BP (most consistent predictor of greater response)
• Orthostatic hypertension (pooled RADIANCE analysis: greater BP reduction post-RDN)
• Markers of increased sympathetic activity (heart rate variability, renin) — proposed but not validated

Safety

• Performed via femoral artery approach; procedure ≈1 hour
• Procedural risks same as standard femoral arterial access (haemorrhage, infection, arterial dissection, thromboembolism, AV fistula, pseudoaneurysm, contrast, radiation)
• Serious adverse events <1% (renal artery dissection, access site complications, death)
• Most common adverse event: pain >2 days post-procedure (12%)
• No deleterious effect on kidney function including in moderate-to-severe CKD and systolic HF
• Renal artery stenosis (RAS) post-procedure: estimated incidence 0.2%/year (similar to natural rate in hypertensive patients); greatest risk within first 6 months
• 3-year Global SYMPLICITY Registry: no late safety concerns
• Reinnervation concern: Animal studies show partial/full reinnervation with persistent BP reduction — functional significance of reinnervation in humans unclear

Patient Preferences and Shared Decision-Making

• ~30% of medicated hypertensive patients interested in RDN across global surveys
• 35–40% interest among unmedicated patients with hypertension
• Predictors favouring RDN preference: younger age, male sex, higher BP, more medications, CV comorbidities, medication side effects, poor adherence
• Gap: Patients expect >10 mmHg SBP reduction (over 96% in China; 40% expect to stop all medications in Germany); actual outcomes are 5–10 mmHg
• Lower increments (~2–3 mmHg) more acceptable to US patients
• A 10 mmHg BP reduction → 10–20% CVD mortality/morbidity reduction; RDN's 5–10 mmHg reductions could confer similar benefits — but no CVD outcome trial yet completed

Limitations of the Document

• No CVD outcomes trial data — all endpoints are BP-based; hard outcomes unknown
• Majority of RCTs limited to 2–6 months follow-up; durability of effect uncertain
• No predictive biomarker or clinical feature reliably identifies responders (except high baseline BP)
• RCTs largely excluded eGFR <40–45 mL/min/1.73m² — limits generalisability to advanced CKD
• Early trials (Symplicity Flex monoelectrode) confounded by suboptimal denervation technique and protocol deviations (medication intensification in sham arms)
• Cost-effectiveness vs generic antihypertensives not established
• Real-world outcomes outside clinical trial context not yet known

Key Concepts Mentioned

• concepts/Renal-Denervation — central procedure covered in this source
• concepts/Cuffless-BP-Monitoring — BP monitoring context

Key Entities Mentioned

• entities/Hypertension — primary disease entity; RDN as adjunctive therapy
• Resistant Hypertension — primary target population (subtype of Hypertension entity)

Wiki Pages Updated

• Created: wiki/sources/rnd-aha-2024.md
• Updated: wiki/sourceindex.md
• Updated: wiki/wikiindex.md
• Created: wiki/concepts/Renal-Denervation.md (new)
• Updated: wiki/entities/Hypertension.md (RDN section expanded)