Ultrasound Renal Denervation Research Articles

Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient's global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.

Endovascular Ultrasound Renal Denervation to Treat Hypertension

Two initial sham-controlled trials demonstrated that ultrasound renal denervation decreases blood pressure (BP) in patients with mild to moderate hypertension and hypertension that is resistant to treatment. To study the efficacy and safety of ultrasound renal denervation without the confounding influence of antihypertensive medications in patients with hypertension. Sham-controlled, randomized clinical trial with patients and outcome assessors blinded to treatment assignment that was conducted between January 14, 2019, and March 25, 2022, at 37 centers in the US and 24 centers in Europe, with randomization stratified by center. Patients aged 18 years to 75 years with hypertension (seated office systolic BP [SBP] ≥140 mm Hg and diastolic BP [DBP] ≥90 mm Hg despite taking up to 2 antihypertensive medications) were eligible if they had an ambulatory SBP/DBP of 135/85 mm Hg or greater and an SBP/DBP less than 170/105 mm Hg after a 4-week washout of their medications. Patients with an estimated glomerular filtration rate of 40 mL/min/1.73 m2 or greater and with suitable renal artery anatomy were randomized 2:1 to undergo ultrasound renal denervation or a sham procedure. Patients were to abstain from antihypertensive medications until the 2-month follow-up unless prespecified BP criteria were exceeded and were associated with clinical symptoms. Ultrasound renal denervation vs a sham procedure. The primary efficacy outcome was the mean change in daytime ambulatory SBP at 2 months. The primary safety composite outcome of major adverse events included death, kidney failure, and major embolic, vascular, cardiovascular, cerebrovascular, and hypertensive events at 30 days and renal artery stenosis greater than 70% detected at 6 months. The secondary outcomes included mean change in 24-hour ambulatory SBP, home SBP, office SBP, and all DBP parameters at 2 months. Among 1038 eligible patients, 150 were randomized to ultrasound renal denervation and 74 to a sham procedure (mean age, 55 years [SD, 9.3 years]; 28.6% female; and 16.1% self-identified as Black or African American). The reduction in daytime ambulatory SBP was greater with ultrasound renal denervation (mean, -7.9 mm Hg [SD, 11.6 mm Hg]) vs the sham procedure (mean, -1.8 mm Hg [SD, 9.5 mm Hg]) (baseline-adjusted between-group difference, -6.3 mm Hg [95% CI, -9.3 to -3.2 mm Hg], P < .001), with a consistent effect of ultrasound renal denervation throughout the 24-hour circadian cycle. Among 7 secondary BP outcomes, 6 were significantly improved with ultrasound renal denervation vs the sham procedure. No major adverse events were reported in either group. In patients with hypertension, ultrasound renal denervation reduced daytime ambulatory SBP at 2 months in the absence of antihypertensive medications vs a sham procedure without postprocedural major adverse events. ClinicalTrials.gov Identifier: NCT03614260.

Patient-Level Pooled Analysis of Ultrasound Renal Denervation in the Sham-Controlled RADIANCE II, RADIANCE-HTN SOLO, and RADIANCE-HTN TRIO Trials

Ultrasound renal denervation (uRDN) was shown to lower blood pressure (BP) in patients with uncontrolled hypertension (HTN). Establishing the magnitude and consistency of the uRDN effect across the HTN spectrum is clinically important. To characterize the effectiveness and safety of uRDN vs a sham procedure from individual patient-level pooled data across uRDN trials including either patients with mild to moderate HTN on a background of no medications or with HTN resistant to standardized triple-combination therapy. A Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN SOLO and TRIO) and A Study of the ReCor Medical Paradise System in Stage II Hypertension (RADIANCE II) trials. Trials with similar designs, standardized operational implementation (medication standardization and blinding of both patients and physicians to treatment assignment), and follow-up. Pooled analysis using individual patient-level data using linear regression models to compare uRDN with sham across the trials. The primary outcome was baseline-adjusted change in 2-month daytime ambulatory systolic BP (dASBP) between groups. A total of 506 patients were randomized in the 3 studies (uRDN, 293; sham, 213; mean [SD] age, 54.1 [9.3]; 354 male [70.0%]). After a 1-month medication stabilization period, dASBP was similar between the groups (mean [SD], uRDN, 150.3 [9.2] mm Hg; sham, 150.8 [10.5] mm Hg). At 2 months, dASBP decreased by 8.5 mm Hg to mean (SD) 141.8 (13.8) mm Hg among patients treated with uRDN and by 2.9 mm Hg to 147.9 (14.6) mm Hg among patients treated with a sham procedure (mean difference, -5.9; 95% CI, -8.1 to -3.8 mm Hg; P < .001 in favor of uRDN). BP decreases from baseline with uRDN vs sham were consistent across trials and across BP parameters (office SBP: -10.4 mm Hg vs -3.4 mm Hg; mean difference, -6.4 mm Hg; 95% CI, -9.1 to -3.6 mm Hg; home SBP: -8.4 mm Hg vs -1.4 mm Hg; mean difference, -6.8 mm Hg; 95% CI, -8.7 to -4.9 mm Hg, respectively). The BP reductions with uRDN vs sham were consistent across prespecified subgroups. Independent predictors of a larger BP response to uRDN were higher baseline BP and heart rate and the presence of orthostatic hypertension. No differences in early safety end points were observed between groups. Results of this patient-level pooled analysis suggest that BP reductions with uRDN were consistent across HTN severity in sham-controlled trials designed with a 2-month primary end point to standardize medications across randomized groups. ClinicalTrials.gov Identifier: NCT02649426 and NCT03614260.

Renal denervation in the management of hypertension in adults. A clinical consensus statement of the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI).

Since the publication of the 2018 European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines for the Management of Arterial Hypertension, several high-quality studies, including randomised, sham-controlled trials on catheter-based renal denervation (RDN) were published, confirming both the blood pressure (BP)-lowering efficacy and safety of radiofrequency and ultrasound RDN in a broad range of patients with hypertension, including resistant hypertension. A clinical consensus document by the ESC Council on Hypertension and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on RDN in the management of hypertension was considered necessary to inform clinical practice. This expert group proposes that RDN is an adjunct treatment option in uncontrolled resistant hypertension, confirmed by ambulatory BP measurements, despite best efforts at lifestyle and pharmacological interventions. RDN may also be used in patients who are unable to tolerate antihypertensive medications in the long term. A shared decision-making process is a key feature and preferably includes a patient who is well informed on the benefits and limitations of the procedure. The decision-making process should take (i) the patient's global cardiovascular (CV) risk and/or (ii) the presence of hypertension-mediated organ damage or CV complications into account. Multidisciplinary hypertension teams involving hypertension experts and interventionalists evaluate the indication and facilitate the RDN procedure. Interventionalists require expertise in renal interventions and specific training in RDN procedures. Centres performing these procedures require the skills and resources to deal with potential complications. Future research is needed to address open questions and investigate the impact of BP-lowering with RDN on clinical outcomes and potential clinical indications beyond hypertension.

S-26-2: ULTRASOUND RENAL DENERVATION ACROSS THE HYPERTENSION SPECTRUM

In addition to lifestyle changes and pharmacotherapy, endovascular catheter-based renal denervation (RDN) has emerged as a BP-lowering treatment, but early trials reported inconsistent results. Subsequently, sham-controlled trials with more optimized study designs, improved catheter designs, procedural performance, and endpoint ascertainment were successfully conducted in patients with hypertension. Among these trials, the RADIANCE-HTN trial compared endovascular ultrasound renal denervation (uRDN) with a sham procedure in two separate cohorts. Within the first (SOLO) cohort of subjects with mild-to-moderate hypertension who were weaned off medications, a 6.3 mmHg greater reduction in daytime ambulatory SBP was demonstrated with uRDN vs. a sham procedure at two months. The BP- lowering effect of uRDN was maintained at six- and twelve months with less medications needed to achieve similar BP in the uRDN group compared with the sham group. In addition, the TRIO cohort of RADIANCE-HTN randomized 136 patients with hypertension resistant to three or more antihypertensive medications. Eligible patients were switched to a daily, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic, and if BP remained uncontrolled, were then randomized to uRDN or a sham procedure. At 2 months, the uRDN had a 4.5 mmHg greater decrease in daytime ambulatory SBP compared with sham. The BP-lowering effect of uRDN was sustained at 6 months with less prescribed medications, notably aldosterone antagonists, vs. sham. Adverse events were infrequent and similar between groups in the two cohorts. The maintenance of a BP-lowering effect of uRDN at 6 months mirror the results of the RADIANCE-HTN SOLO trial at 6 months and therefore, demonstrates persistent BP lowering efficacy of uRDN across a broad spectrum of patients with mild hypertension to severe and resistant hypertesion.

Resistant hypertension: integrated strategies between pharmacological treatment and renal denervation

The achievement of adequate blood pressure (BP) control and the management of resistant hypertension still represent two burning "unmet needs" in the field of cardiovascular diseases, thus originating a continuous search for more efficacious pharmacological and non-pharmacological strategies including radiofrequency and ultrasound renal denervation (RDN). The most recent guidelines recommend a combination therapy of two or more antihypertensive agents, preferably in a single-pill formulation, as first-line strategy to achieve an effective and early BP control also improving adherence to prescribed treatments. In the last few years several sham-controlled trials have confirmed both the BP-lowering efficacy and safety of RDN in a broad range of patients with hypertension, showing a significant reduction of office and ambulatory BP levels without a relevant increase of procedure-related adverse events such as renal artery stenosis and worsening renal function. These results have been recently confirmed by the analyses of 3-year follow-up data. According to these findings, RDN may represent a useful tool in addition to pharmacological treatment with more compelling indications for patients with resistant hypertension, those who are non-adherent or intolerant to multiple antihypertensive drugs or express a preference to undergo RDN. Further studies are necessary to explore the efficacy of RDN on prevention of hypertension-mediated organ damage and reduction of major cardiovascular events.

Effects of Renal Denervation vs Sham in Resistant Hypertension After Medication Escalation

Although early trials of endovascular renal denervation (RDN) for patients with resistant hypertension (RHTN) reported inconsistent results, ultrasound RDN (uRDN) was found to decrease blood pressure (BP) vs sham at 2 months in patients with RHTN taking stable background medications in the Study of the ReCor Medical Paradise System in Clinical Hypertension (RADIANCE-HTN TRIO) trial. To report the prespecified analysis of the persistence of the BP effects and safety of uRDN vs sham at 6 months in conjunction with escalating antihypertensive medications. This randomized, sham-controlled, clinical trial with outcome assessors and patients blinded to treatment assignment, enrolled patients from March 11, 2016, to March 13, 2020. This was an international, multicenter study conducted in the US and Europe. Participants with daytime ambulatory BP of 135/85 mm Hg or higher after 4 weeks of single-pill triple-combination treatment (angiotensin-receptor blocker, calcium channel blocker, and thiazide diuretic) with estimated glomerular filtration rate (eGFR) of 40 mL/min/1.73 m2 or greater were randomly assigned to uRDN or sham with medications unchanged through 2 months. From 2 to 5 months, if monthly home BP was 135/85 mm Hg or higher, standardized stepped-care antihypertensive treatment starting with aldosterone antagonists was initiated under blinding to treatment assignment. uRDN vs sham procedure in conjunction with added medications to target BP control. Six-month change in medications, change in daytime ambulatory systolic BP, change in home systolic BP adjusted for baseline BP and medications, and safety. A total of 65 of 69 participants in the uRDN group and 64 of 67 participants in the sham group (mean [SD] age, 52.4 [8.3] years; 104 male [80.6%]) with a mean (SD) eGFR of 81.5 (22.8) mL/min/1.73 m2 had 6-month daytime ambulatory BP measurements. Fewer medications were added in the uRDN group (mean [SD], 0.7 [1.0] medications) vs sham (mean [SD], 1.1 [1.1] medications; P = .045) and fewer patients in the uRDN group received aldosterone antagonists at 6 months (26 of 65 [40.0%] vs 39 of 64 [60.9%]; P = .02). Despite less intensive standardized stepped-care antihypertensive treatment, mean (SD) daytime ambulatory BP at 6 months was 138.3 (15.1) mm Hg with uRDN vs 139.0 (14.3) mm Hg with sham (additional decreases of -2.4 [16.6] vs -7.0 [16.7] mm Hg from month 2, respectively), whereas home SBP was lowered to a greater extent with uRDN by 4.3 mm Hg (95% CI, 0.5-8.1 mm Hg; P = .03) in a mixed model adjusting for baseline and number of medications. Adverse events were infrequent and similar between groups. In this study, in patients with RHTN initially randomly assigned to uRDN or a sham procedure and who had persistent elevation of BP at 2 months after the procedure, standardized stepped-care antihypertensive treatment escalation resulted in similar BP reduction in both groups at 6 months, with fewer additional medications required in the uRDN group. ClinicalTrials.gov Identifier: NCT02649426.

Durability of blood pressure reduction after ultrasound renal denervation: three-year follow-up of the treatment arm of the randomised RADIANCE-HTN SOLO trial.

While the blood pressure (BP)-lowering effect of renal denervation (RDN) has been established, long-term durability is a key prerequisite for a broader clinical implementation. Our aims were to assess the long-term durability of the office BP (OBP)-lowering efficacy, antihypertensive medication (AHM) use, and safety of ultrasound RDN (uRDN). Four weeks after withdrawal of AHM, patients with untreated daytime ambulatory BP ≥135/85 mmHg and <170/105 mmHg were randomised to uRDN (n=74) or sham (n=72) in the RADIANCE-HTN SOLO trial. Initiation of AHM was encouraged for home BP >135/85 mmHg following primary endpoint ascertainment at 2 months. Patients and physicians were unblinded at 6 months. Results: Fifty-one of 74 patients (age: 53.9±11 years; 67% men) originally randomised to uRDN completed the 36-month follow-up. Initial screening OBP upon study entry was 145/92±14/10 mmHg on a mean of 1.2 AHM (range: 0-2.0). Baseline OBP after AHM washout was 154/99±13/8 mmHg. At 36 months, patients were on an average of 1.3 AHM (range: 0-3.0) with 8 patients on no AHM. OBP decreased by 18/11±15/9 mmHg from baseline to 36 months (p<0.001 for both). Overall, OBP control (<140/90 mmHg) improved from 29.4% at screening to 45.1% at 36 months (p=0.059). For patients uncontrolled at screening (n=36), systolic OBP decreased by 10.8 mmHg (p<0.001) at 36 months on similar AHM (p=0.158). The safety and effectiveness of uRDN was durable to 36 months, with reduced OBP and improved OBP control despite a similar starting medication burden. No new uRDN-related long-term safety concerns were identified.

Cost-Effectiveness of Ultrasound Renal Denervation in Patients With Resistant Hypertension

Cost-Effectiveness of Ultrasound Renal Denervation in Patients With Resistant Hypertension

20 THE CLINICAL SAGA OF RENAL DENERVATION IN UNCONTROLLED HYPERTENSION: AN UPDATED META-ANALYSIS OF RANDOMIZED SHAM-CONTROLLED TRIALS

Background: Renal denervation (RDN) with catheter ablation has shown promising yet conflicting results in the management of uncontrolled hypertension. With the availability of recent randomized sham-controlled trials, we decided to perform an updated meta-analysis. Objective: To examine the utilization of renal denervation in patients with uncontrolled hypertension. Method: A systematic search in electronic databases was conducted. We included randomized sham-controlled trials comparing RDN and sham procedure in patients with uncontrolled hypertension. Included studies were evaluated for risk of bias. Our outcomes of interest were 24-hour ambulatory blood pressure (BP) and office BP. We performed fixed and random-effects meta-analysis using the inverse variance method to calculate the mean difference (MD) and 95% confidence interval (CI). Result: Final analysis included 10 studies with a total of 1,571 patients. With the median follow-up period of 6 months, RDN was associated with a significant decrease in 24-hour ambulatory BP (Systolic: MD -3.50 mmHg, 95% CI -4.75, -2.25, p&lt;0.00001, I2=0.00; Diastolic: MD -1.97 mmHg, 95% CI -2.74, -1.20, p&lt;0.00001, I2=0.31) compared to sham procedure. Similiarly, office BP was reduced significantly with RDN when compared to sham procedure (Systolic: MD -4.89 mmHg, 95% CI -7.67, -2.10, p=0.04, I2=0.51; Diastolic: MD -3.07 mmHg, 95% CI -4.14, -2.00, p&lt;0.00001. I2=0.38). Further subgroup analysis showed that radiofrequency RDN was associated with a significant reduction in both 24-hour ambulatory and office BP, while ultrasound RDN was not associated with such differences. Conclusion: This updated meta-analysis suggests that RDN is associated with statistically significant improvement in uncontrolled hypertension management.

Changes in blood pressure after crossover to ultrasound renal denervation in patients initially treated with sham in the RADIANCE-HTN SOLO trial.

The multicentre, randomised, sham-controlled RADIANCE-HTN SOLO trial reported the blood pressure (BP)-lowering efficacy and safety of ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 and 12 months) of antihypertensive medications in patients with mild-to-moderate hypertension. The aim of this report was to evaluate patients originally assigned to the sham group who crossed over to RDN. After the primary endpoint was met, patients in the sham arm who remained uncontrolled were allowed to cross over to receive RDN. All patients were unblinded and treated with standard of care medications at the time of crossover. Ambulatory BP was evaluated 2 and 6 months after crossover. Among 72 subjects of the sham arm, 33 underwent ultrasound RDN after an average follow-up of 23±6 months. Prior to crossover, patients had a daytime ambulatory BP of 144.1±10.1/89.9±8.4 mmHg and received 1.2±0.8 antihypertensive medications. Mean change in daytime ambulatory BP from pre-crossover to 2 and 6 months post RDN was -11.2±13.7/-7.1±8.9 mmHg (n=33; p<0.001; p<0.001) and -10.8±17.3/-7.8±11.6 mmHg (n=27; p=0.002; p<0.001). The number of antihypertensive medications did not change from pre-crossover baseline to 2 and 6 months. Eighteen of 33 (54.5%) patients had their daytime ambulatory BP controlled (<135/85 mmHg) at 2 months and 44.4% (12/27) at 6 months post RDN. No major procedure-related adverse events occurred. During unblinded long-term follow-up of the RADIANCE-HTN SOLO study, patients originally assigned to a sham procedure who remained uncontrolled had significant reductions in BP following crossover treatment with ultrasound RDN.

TCT-369 Durability of Reduced Office-Measured Blood Pressure and Antihypertensive Medication Use After Ultrasound Renal Denervation: 24-Month Results From the RADIANCE-HTN SOLO Trial

TCT-369 Durability of Reduced Office-Measured Blood Pressure and Antihypertensive Medication Use After Ultrasound Renal Denervation: 24-Month Results From the RADIANCE-HTN SOLO Trial

Catheter-based ultrasound renal denervation in patients with resistant hypertension: the randomized, controlled REQUIRE trial

Renal denervation is a promising new non-pharmacological treatment for resistant hypertension. However, there is a lack of data from Asian patients. The REQUIRE trial investigated the blood pressure-lowering efficacy of renal denervation in treated patients with resistant hypertension from Japan and South Korea. Adults with resistant hypertension (seated office blood pressure ≥150/90 mmHg and 24-hour ambulatory systolic blood pressure ≥140 mmHg) with suitable renal artery anatomy were randomized to ultrasound renal denervation or a sham procedure. The primary endpoint was change from baseline in 24-hour ambulatory systolic blood pressure at 3 months. A total of 143 patients were included (72 renal denervation, 71 sham control). Reduction from baseline in 24-hour ambulatory systolic blood pressure at 3 months was not significantly different between the renal denervation (−6.6 mmHg) and sham control (−6.5 mmHg) groups (difference: −0.1, 95% confidence interval −5.5, 5.3; p = 0.971). Reductions from baseline in home and office systolic blood pressure (differences: –1.8 mmHg [p = 0.488] and −2.0 mmHg [p = 0.511], respectively), and medication load, did not differ significantly between the two groups. The procedure-/device-related major adverse events was not seen. This study did not show a significant difference in ambulatory blood pressure reductions between renal denervation and a sham procedure in treated patients with resistant hypertension. Although blood pressure reduction after renal denervation was similar to other sham-controlled studies, the sham group in this study showed much greater reduction. This unexpected blood pressure reduction in the sham control group highlights study design issues that will be addressed in a new trial.Clinical trial registrationNCT02918305 (http://www.clinicaltrials.gov).

Ultrasound renal denervation for hypertension: impact of the RADIANCE-HTN-TRIO trial on future management of resistant hypertension

A role for excess sympathetic nervous system activity in the pathogenesis of hypertension was already known in the 1930s, when Smithwick developed radical lumbodorsal splanchnicectomy for the management of untreatable, commonly fatal hypertension.1 This technique lowered blood pressure (BP) significantly, decreasing cardiac, renal, and cerebral morbidity, but was abandoned owing to severe adverse effects of nonselective interruption of autonomic function and the development of new oral pharmacologic agents with better safety profiles.

Plasma renin and aldosterone concentrations related to endovascular ultrasound renal denervation in the RADIANCE-HTN SOLO trial.

The RADIANCE-HTN SOLO trial demonstrated a greater reduction in daytime ambulatory SBP at 2 months by endovascular ultrasound renal denervation than sham procedure. We hypothesized that plasma renin and aldosterone concentrations would be associated with the SBP response to renal denervation. Hypertensive patients were randomized to renal denervation (n = 74) or sham (n = 72) after a 4-week washout of antihypertensive medications. In a 53-patient subset, 2-month and 6-month plasma renin and aldosterone concentration were measured. Dietary sodium was not controlled. Mean age of the 29 treatment and 24 sham patients was 54 years; 62% were men; 17% black. Daytime ambulatory SBP fell in the denervation but not the sham group at 2 months (-7.8 ± 10.7 vs. -0.1 ± 10.1 mmHg; P = 0.048). Baseline plasma renin and aldosterone concentrations were in the low-normal range, did not change significantly at 2 months in either group and did not predict response to renal denervation. At 6 months, after the addition of antihypertensive medications, there was a significant rise in renin in the sham but not the denervation group. Although renal denervation but not sham resulted in a decrease in daytime ambulatory SBP at 2 months, renin and aldosterone concentrations did neither predict the BP response to renal denervation; nor did they fall after denervation. A rise in renin at 6 months in the sham group likely represents confounding from antihypertensive medications. Whether the BP-lowering effect of renal denervation depends on reducing local intrarenal renin release requires further study.

Predictors of blood pressure response to ultrasound renal denervation in the RADIANCE-HTN SOLO study

The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN.

Ultrasound Renal Denervation Shows Modest Effects in Resistant Hypertension

Catheter-based renal denervation (RDN) has had mixed results in patients with hypertension. Recently, however, radiofrequency or ultrasound RDN has

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial

Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications. In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426. Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups. Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. ReCor Medical.

Blood pressure and renal denervation with ultrasound: another step forward

Among cardiovascular risk factors, arterial hypertension has the highest prevalence and is poorly controlled. 1 Stanaway JD Afshin A Gakidou E et al. Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018; 392: 1923-1994 Summary Full Text Full Text PDF PubMed Scopus (1438) Google Scholar The sympathetic nervous system targeting the kidney via efferent and afferent nerves, thereby contributing to hypertension and potentially other cardiovascular conditions, 2 Böhm M Linz D Ukena C Esler M Mahfoud F Renal denervation for the treatment of cardiovascular high risk-hypertension or beyond?. Circ Res. 2014; 115: 400-409 Crossref PubMed Scopus (62) Google Scholar can be modulated with different denervation technologies. 3 Lauder L Azizi M Kirtane AJ Böhm M Mahfoud F Device-based therapies for arterial hypertension. Nat Rev Cardiol. 2020; 17: 614-628 Crossref PubMed Scopus (17) Google Scholar Rigorously controlled clinical trials without 4 Böhm M Townsend RR Kario K et al. Rationale and design of two randomized sham-controlled trials of catheter-based renal denervation in subjects with uncontrolled hypertension in the absence (SPYRAL HTN-OFF MED Pivotal) and presence (SPYRAL HTN-ON MED Expansion) of antihypertensive medications: a novel approach using Bayesian design. Clin Res Cardiol. 2020; 109: 289-302 PubMed Google Scholar , 5 Böhm M Kario K Kandzari DE et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet. 2020; 395: 1444-1451 Summary Full Text Full Text PDF PubMed Scopus (102) Google Scholar , 6 Townsend RR Mahfoud F Kandzari DE et al. Catheter-based renal denervation in patients with uncontrolled hypertension in the absence of antihypertensive medications (SPYRAL HTN-OFF MED): a randomised, sham-controlled, proof-of-concept trial. Lancet. 2017; 390: 2160-2170 Summary Full Text Full Text PDF PubMed Scopus (374) Google Scholar and with 7 Kandzari DE Böhm M Mahfoud F et al. Effect of renal denervation on blood pressure in the presence of antihypertensive drugs: 6-month efficacy and safety results from the SPYRAL HTN-ON MED proof-of-concept randomised trial. Lancet. 2018; 391: 2346-2355 Summary Full Text Full Text PDF PubMed Scopus (302) Google Scholar antihypertensive medications have shown a significant reduction in blood pressure with high-frequency energy. Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trialCompared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension. Full-Text PDF

12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation.

This study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6months. The blood pressure (BP)-lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2months) and presence (6months) of antihypertensive medications were previously reported. Patients with daytime ambulatory BP≥135/85mmHg after 4weeks off medication were randomized to RDN (n=74) or sham (n=72) and maintained off medication for 2months. A standardized medication escalation protocol was instituted between 2 and 5months (blinded phase). Between 6 and 12months (unblinded phase), patients received antihypertensive medications at physicians' discretion. Outcomes at 12months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety. Sixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on≥2 medications (27.7% vs. 44.8%; p=0.041), the number of medications (0 vs. 1.4; p=0.015), and defined daily dose (1.4 vs. 2.2; p=0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (-16.5 ± 12.9mmHg) remained stable at 12months. The RDN versus sham adjusted difference at 12months was-2.3mmHg (95% confidence interval [CI]:-5.9 to 1.3mmHg; p=0.201) for dASBP,-6.3mmHg (95%CI:-11.1 to-1.5mmHg; p=0.010) for office SBP, and-3.4mmHg (95%CI:-6.9 to 0.1mmHg; p=0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography. Despite unblinding, the BP-lowering effect of RDN was maintained at 12months with fewer prescribed medications compared with sham.