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Background The clinical utility and long-term effects of endothelin receptor antagonists (ERAs) in Fontan-palliated patients remain unclear and there are currently no approved therapies. A decline in peak VO2 between consecutive cardiopulmonary exercise tests (CPETs) is highly prognostic for death or transplant in adult Fontan patients, hence its use as a primary endpoint in clinical trials of ERAs in patients with Fontan circulation. Purpose The RUBATO trial aimed to assess the efficacy and safety of macitentan, an endothelin receptor antagonist, in Fontan-palliated patients over 52 weeks. Methods In the multicentre, double-blind, randomised, placebo-controlled, phase 3 RUBATO trial, Fontan-palliated patients were randomised 1:1 to macitentan 10 mg once-daily or placebo for 52 weeks. Eligible patients were aged ≥12 years, in New York Heart Association functional class II or III, had no limitations for CPET (including no pacemakers), had undergone lateral tunnel or extracardiac conduit Fontan (total cavopulmonary connection) >1 year before screening and showed no signs of Fontan failure or clinical deterioration within 3 months before screening. Primary efficacy endpoint was change in peak VO2 from baseline to week 16. Secondary endpoints were change in peak VO2 from baseline over 52 weeks and change in mean count per minute of daily physical activity from baseline to week 16 as measured by an accelerometer. Adverse events were also assessed. Results 137 patients were randomised to macitentan (n=68) or placebo (n=69). 92.7% of patients completed 52 weeks of double-blind treatment: 7 and 3 patients prematurely discontinued study treatment in macitentan and placebo arms, respectively. Patient baseline characteristics are shown in Table 1. At week 16, the mean (SD) change from baseline in peak VO2 was –0.16 (2.86) with macitentan vs –0.67 (2.66) mL/kg/min with placebo (median unbiased estimate of the difference between macitentan and placebo: 0.62 mL/kg/min [99% repeated confidence interval –0.62; 1.85], p=0.1930). No treatment effect was observed in the two secondary endpoints (Table 2): mean (SD) count per minute of daily physical activity decreased from baseline to week 16 by 3.02 (92.44) with macitentan and by 14.34 (117.56) with placebo (p=0.4512). The most common AEs were headache (10.3% vs 8.7% on placebo), nasopharyngitis (5.9% vs 4.3%), and pyrexia (5.9% vs 4.3%). AEs leading to treatment discontinuation were reported in 3 (4.4%) and 1 (1.4%) of macitentan and placebo patients. Conclusion The 52-week RUBATO trial provides an important addition to data on the clinical utility of ERAs in Fontan-palliated patients. The primary efficacy endpoint was not met and no treatment effect was observed for the two secondary endpoints. Macitentan was well tolerated; safety findings were consistent with the known safety profile of macitentan 10 mg. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson & Johnson.

Background Patients with a native or re CoA with an invasively meassured peak to peak gardient >20 mmHg have a guideline indication for intervention. The decision regarding transcatheter versus surgical intervention depends on a variety of factors including location and complexity of CoA, patient/parent preference and availability of a team capable to perform the intevention with a low rate of complications. The aim of the present analysis was to describe factors associated with risk for procedural complications during transcatheter interventions in CoA. Separate anlysis was done for complications at intervention site and at access site. Methods All consecutive patients undergoing catheter interventions for CoA from 1st of January 2000 to 31st of December 2016 were identified by each of the particpating nine centers. The nine centers perform all catheter interventions for CoA for a complete population coverage of 25 millions inhabitants. A common protocol was filled out from medical records. Exclusion criteria were weight less than 20 kg at the time of intervention or Norwood surgery for hypoplastic left heart surgery. Complications at the intervention site included aneurysm formation, dissection of the aorta, extravasation of the aorta or neurological impairment. Complications at the access site was defined as any complication that prolonged the hospital stay. Results 590 interventions were performed on 520 patients: two interventions n=76, three: n=11, four n=2 and one patient underwent five interventions. There was no mortality in relation to the procedure or during the hospitalisation. The age span of the patients was wide; 4–79 years old (median= 23). 51% had a native CoA, 42% post surgery re-CoA, 22% had had a previous catheter intervention. In 160 (27%) of the interventions balloon dilatation only was performed. Overall, procedural succes was 87%, n=513, 44 procedures (8%) were partially successful and 9 procedures (2%) were not successful. 512 (87%) had one day in hospital stay and 17 patients (6%) had a hospital stay longer than 3 days. In 11 procedures (1.9%) at least one complication occurred at the intervention site; (6 aneurysm formation, 3 neurological impairment, 3 dissection of aorta, 2 extra vasation of aorta), nine of them without prolonged hospital stay. In 25 procedures (4.2%) at least one complications at the access site was observed. Access site complications were associated with older age (mean 38 years (10–79)) Conclusions In a large, multicenter registry with complete follow-up, complications at the intervention site occurred in 1.9% and at the access site in 4.2% of interventions. Transcatheter intervention of CoA can be performed with low risk of complications. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): ALF-LUA, Gothenburg Heart and Lung Foundation