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

Townsend, Raymond R.; Mahfoud, Felix; Kario, Kazuomi; Pocock, Stuart J.; Weber, Michael A.; Ewen, Sebastian; Tsioufis, Κonstantinos; Tousoulis, Dimitrios; Sharp, Andrew; Watkinson, Anthony; Schmieder, Roland E.; Schmid, Axel; Choi, James W.; East, Cara; Walton, A.; Hopper, Ingrid; Cohen, Debbie L.; Wilensky, Robert L.; Lee, David P.; Ma, Adrian; Devireddy, Chandan; Lea, Janice P.; Lurz, Philipp; Fengler, Karl; Davies, Justin E.; Chapman, Neil; Cohen, Sidney A.; DeBruin, Vanessa; Fahy, Martin; Jones, Denise; Rothman, Martin T.; Böhm, Michael; Aoki, Jiro; Batson, Bryan; Dangas, George; David, Shukri; Kandzari, David E.; Patel, Manesh R.; Patel, Kiritkumar; Singh, Jasvindar; Weber, Thomas; Weil, Joachim; Zeller, Thomas; Ziada, Khaled M.; Tanabe, Kengo; Wilkins, Robert B.; Contreras, Johanna; Steigerwalt, Susan; Reedus, Denise; Hoshide, Satoshi; Svetkey, Laura P.; Rao, Anjani; Brown, Angela L.; Suppan, Markus; Agdirlioglu, Tolga; Noory, Elias; Chasen, Craig

doi:10.1016/s0140-6736(17)32281-x

Cited by 602 publications

(491 citation statements)

References 35 publications

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“…Since then there have been considerable advances in our understanding of renal neural microanatomy and how best to achieve effective endovascular renal SNS ablation. Now that a recent proof of concept study has demonstrated convincingly that RDN is effective at lowering BP in moderate hypertension compared with sham, it has become more important than ever before to demonstrate procedural success 31. Our approach using the Valsalva maneuver is relatively straightforward and reproducible and illustrates convincingly that RDN can attenuate BP responses to the Valsalva maneuver, which was not the case with a sham procedure.…”

Section: Discussionmentioning

confidence: 77%

Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success

Saxena

Shour

Shah

et al. 2018

JAHA

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BackgroundRenal denervation has no validated marker of procedural success. We hypothesized that successful renal denervation would reduce renal sympathetic nerve signaling demonstrated by attenuation of α‐1‐adrenoceptor‐mediated autotransfusion during the Valsalva maneuver.Methods and ResultsIn this substudy of the Wave IV Study: Phase II Randomized Sham Controlled Study of Renal Denervation for Subjects With Uncontrolled Hypertension, we enrolled 23 subjects with resistant hypertension. They were randomized either to bilateral renal denervation using therapeutic levels of ultrasound energy (n=12) or sham application of diagnostic ultrasound (n=11). Within‐group changes in autonomic parameters, office and ambulatory blood pressure were compared between baseline and 6 months in a double‐blind manner. There was significant office blood pressure reduction in both treatment (16.1±27.3 mm Hg, P<0.05) and sham groups (27.9±15.0 mm Hg, P<0.01) because of which the study was discontinued prematurely. However, during the late phase II (Iii) of Valsalva maneuver, renal denervation resulted in substantial and significant reduction in mean arterial pressure (21.8±25.2 mm Hg, P<0.05) with no significant changes in the sham group. Moreover, there were significant reductions in heart rate in the actively treated group at rest (6.0±11.5 beats per minute, P<0.05) and during postural changes (supine 7.2±8.4 beats per minute, P<0.05, sit up 12.7±16.7 beats per minute, P<0.05), which were not observed in the sham group.ConclusionsBlood pressure reduction per se is not necessarily a marker of successful renal nerve ablation. Reduction in splanchnic autotransfusion following renal denervation has not been previously demonstrated and denotes attenuation of (renal) sympathetic efferent activity and could serve as a marker of procedural success.Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT02029885.

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Section: Discussionmentioning

confidence: 77%

Attenuation of Splanchnic Autotransfusion Following Noninvasive Ultrasound Renal Denervation: A Novel Marker of Procedural Success

Saxena

Shour

Shah

et al. 2018

JAHA

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“…These include baroreceptor activation therapy,17, 18, 19 renal denervation,7, 20 arteriovenous shunting,10, 21 carotid body resection or denervation,12, 22 and mechanical stimulation of the baroreceptors 23. Prior review articles have provided overviews and comparisons of these different approaches and will not be repeated here,24, 25 other than to say that treatment of isolated systolic hypertension (ie, patients with office diastolic blood pressure <90 mm Hg), which is characterized by increased vascular stiffness, has proved to be particularly challenging for some of these approaches, with such patients excluded from the recently complete SPYRAL HTN‐OFF MED study 19, 26.…”

Section: Discussionmentioning

confidence: 99%

Pacemaker‐Mediated Programmable Hypertension Control Therapy

Neužil

Merkely

Ērglis

et al. 2017

JAHA

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BackgroundMany patients requiring a pacemaker have persistent hypertension with systolic blood pressures above recommended levels. We evaluated a pacemaker‐based Programmable Hypertension Control (PHC) therapy that uses a sequence of variably timed shorter and longer atrioventricular intervals.Methods and ResultsPatients indicated for dual‐chamber pacing with office systolic blood pressure (oSBP) >150 mm Hg despite stable medical therapy were implanted with a Moderato™ pulse generator that delivers PHC therapy. Patients were followed for 1 month (Run‐In period) with conventional pacing; those with persistent oSBP >140 mm Hg were included in the study and had PHC therapy activated. The co‐primary efficacy end points were changes in 24‐hour ambulatory systolic blood pressure and oSBP between baseline and 3 months. Safety was assessed by tracking adverse events. Thirty‐five patients met the initial inclusion criteria and underwent Moderato implantation. At 1 month, oSBP was <140 mm Hg in 7 patients who were excluded. PHC was activated in the remaining 27 patients with baseline office blood pressure 166±11/80±10 mm Hg despite an average of 3.2 antihypertensive medications. During the Run‐In period, oSBP and 24‐hour ambulatory systolic blood pressure decreased by 8±13 and 5±12 mm Hg (P<0.002), respectively. Compared with pre‐PHC activation measurements, oSBP decreased by another 16±15 mm Hg and 24‐hour ambulatory systolic blood pressure decreased by an additional 10±13 mm Hg (both P<0.01) at 3 months. No device‐related serious adverse effects were noted.ConclusionsIn pacemaker patients with persistent hypertension despite medical therapy, oSBP and 24‐hour ambulatory systolic blood pressure are decreased by PHC therapy. Initial indications are that this therapy is a safe and promising therapy for such patients.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02282033.

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“…DETO2X-AMI confirmed that routine use of supplemental oxygen in patients with suspected AMI who did not have hypoxemia does not reduce 1-year all-cause death. 6 Up to one-third of adults have hypertension and many of them remain uncontrolled. Renal denervation (RDN) therapy targets the sympathetic nervous system.…”

Section: Risk Of Triggering Ami and Asian Dust Exposurementioning

confidence: 99%