JACC Cardiovasc Interv. 2020 Apr 27;13(8):989-999. doi: 10.1016/j. jcin.2019.12.027.


Intravascular ultrasound pulmonary artery denervation to treat pulmonary arterial hypertension (TROPHY1): Multicenter, early feasibility study


Alexander M K Rothman, Jean-Luc Vachiery, Luke S Howard, Ghada W Mikhail, Irene M Lang, Michael Jonas, David G Kiely, Dalit Shav, Or Shabtay, Avital Avriel, Gregory D Lewis, Erika B Rosenzweig, Ajay J Kirtane, Nick H Kim, Ehtisham Mahmud, Vallerie V McLaughlain, Stanley Chetcuti, Martin B Leon, Ori Ben-Yehuda, Lewis J Rubin


Objectives: The aim of this study was to investigate whether therapeutic intravascular ultrasound pulmonary artery denervation (PDN) is safe and reduces pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH) on a minimum of dual oral therapy.


Background: Early studies have suggested that PDN can reduce PVR in patients with PAH.


Methods: TROPHY1 (Treatment of Pulmonary Hypertension 1) was a multicenter, international, open-label trial undertaken at eight specialist centers. Patients 18–75 years of age with PAH were eligible if taking dual oral or triple nonparenteral therapy and not responsive to acute vasodilator testing. Eligible patients underwent PDN (TIVUS System). The primary safety endpoint was procedure-related adverse events at 30 days. Secondary endpoints included procedure-related adverse events, disease worsening and death to 12 months, and efficacy endpoints that included change in pulmonary hemodynamic status, 6-min walk distance, and quality of life from baseline to 4 or 6 months. Patients were to remain on disease-specific medication for the duration of the study.


Results: Twenty-three patients underwent PDN, with no procedure-related serious adverse events reported. The reduction in PVR at 4- or 6-month follow-up was 94 ± 151 dyn·s·cm-5


Lancet. 2020 May 2;395(10234):1444-1451. doi: 10.1016/S0140- 6736(20)30554-7. Epub 2020 Mar 29.


Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): A multicentre, randomised, sham-controlled trial


Michael Böhm, Kazuomi Kario, David E Kandzari, Felix Mahfoud, Michael A Weber, Roland E Schmieder, Konstantinos Tsioufis, Stuart Pocock, Dimitris Konstantinidis, James W Choi, Cara East, David P Lee, Adrian Ma, Sebastian Ewen, Debbie L Cohen, Robert Wilensky, Chandan M Devireddy, Janice Lea, Axel Schmid, Joachim Weil, Tolga Agdirlioglu, Denise Reedus, Brian K Jefferson, David Reyes, Richard D’Souza, Andrew S P Sharp, Faisal Sharif, Martin Fahy, Vanessa DeBruin, Sidney A Cohen, Sandeep Brar, Raymond R Townsend, SPYRAL HTN- OFF MED Pivotal Investigators


Background: Catheter-based renal denervation has significantly reduced blood pressure in previous studies. Following a positive pilot trial, the SPYRAL HTN-OFF MED (SPYRAL Pivotal) trial was designed to assess the efficacy of renal denervation in the absence of antihypertensive medications.


Methods: In this international, prospective, single-blinded, sham-controlled trial, done at 44 study sites in Australia, Austria, Canada, Germany, Greece, Ireland, Japan, the U.K. and the United States, hypertensive patients with office systolic blood pressure of 150 mm Hg to less than 180 mm Hg were randomly assigned 1:1 to either a renal denervation or sham procedure. The primary efficacy endpoint was baseline- adjusted change in 24-h systolic blood pressure and the secondary efficacy endpoint was baseline-adjusted change in office systolic blood pressure from baseline to 3 months after the procedure. We used a Bayesian design with an informative prior, so the primary analysis combines evidence from the pilot and Pivotal trials. The primary efficacy and safety analyses were done in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT02439749.


(p = 0.001) or 17.8%, which was associated with a 42


± 63 m (p = 0.02) increase in 6-min walk distance and a 671 ± 1,555 step (p = 0.04) increase in daily activity.


Conclusions: In this multicenter early feasibility study, PDN with an intravascular ultrasound catheter was performed without procedure-related adverse events and was associated with a reduction in PVR and increases in 6-min walk distance and daily activity in patients with PAH on background dual or triple therapy.


Findings: From June 25, 2015, to Oct. 15, 2019, 331 patients were randomly assigned to either renal denervation (n=166) or a sham procedure (n=165). The primary and secondary efficacy endpoints were met, with posterior probability of superiority more than 0·999 for both. The treatment difference between the two groups for 24-h systolic blood pressure was -3·9 mm Hg (Bayesian 95% credible interval -6·2 to -1·6) and for office systolic blood pressure the difference was -6·5 mm Hg (-9·6 to -3·5). No major device-related or procedural-related safety events occurred up to 3 months.


Interpretation: SPYRAL Pivotal showed the superiority of catheter-based renal denervation compared with a sham procedure to safely lower blood pressure in the absence of antihypertensive medications.


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