Eisenmenger syndrome and pulmonary arterial hypertension (PAH) due to unrepaired congenital shunts, including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), remain life-threatening conditions despite advances in congenital heart disease (CHD) care. In this population, vasodilator-based therapies effective in other forms of PAH have shown limited benefit, and no disease-modifying treatment has been established. Sotatercept, an activin-signalling inhibitor, improved exercise capacity and haemodynamics in phase 2/3 PAH trials; however, patients with unrepaired CHD, including Eisenmenger syndrome, were excluded. The efficacy and safety of sotatercept in this population remain unknown.

The SuMILE trial is a prospective, exploratory, multicentre, open-label, randomised, controlled trial conducted at 11 Japanese tertiary centres. 36 adults with vasodilator-resistant PAH due to unrepaired ASD, VSD or PDA, including Eisenmenger syndrome, will be randomised 2:1 to sotatercept add-on therapy plus vasodilator-based PAH therapy versus vasodilator-based PAH therapy alone. Sotatercept will be administered subcutaneously every 3 weeks in accordance with label-approved dose-modification rules for haemoglobin and platelet changes. The primary endpoint is the change in 6-min walk distance from baseline to week 24. Key clinical events will be independently adjudicated. Secondary endpoints include all-cause mortality or lung transplantation; pulmonary hypertension-related hospitalisation or initiation of parenteral prostacyclin and changes in WHO functional class, N-terminal pro-brain natriuretic peptide and emPHasis-10. Exploratory endpoints include genotype, right heart catheterisation and cardiac MRI parameters. The primary analysis will use ANCOVA, adjusting for baseline 6-min walk distance and randomisation stratum in the intention-to-treat population.

The protocol has been reviewed and approved by the certified central review board (Kyushu University Hospital Clinical Ethics Review Board) and participating institutions. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, scientific conferences and trial registries.

Japan Registry of Clinical Trials no. 1071250069; ClinicalTrials.gov NCT07356778. Protocol version and date: V.1.3; 23 October 2025

This study describes the prototype testing and clinical validation of the Fit-Frailty App, a fully guided, interactive mobile health (mHealth) app to assess frailty and sarcopenia. This multi-dimensional tool is freely available on the App Store and considers medical history, physical performance, cognition, nutrition, daily function and psychosocial domains. To guide management, a total frailty score and clinical summary of underlying "risk flags" are provided. Our objectives were to examine usability, feasibility, criterion and construct validity.

Cross-sectional

Outpatient geriatric medicine clinic

Community-dwelling older adults, age 65 years or older

The primary outcome of the clinical validation study was criterion validity. A research nurse administered the Fit-Frailty App during a routine clinic appointment. Clinicians simultaneously completed a paper-based frailty index (FI) tool with similar items from a comprehensive geriatric assessment (FI-CGA). Total scores for both assessments were computed using the cumulative deficits frailty index scoring method. Intraclass and Pearson correlation coefficients and 95% CIs were calculated to examine criterion validity. Secondary outcomes were construct validity, feasibility (eg, completion rates, safety occurrences, resources) and usability (eg, ratings on ease of use, time to complete the app).

In the clinical validation study (n=75, mean age 79.2, SD=7.0, 53% female), the mean total Fit-Frailty App score was 0.33 (SD=0.13) with 73% of our sample considered frail or severely frail. The app presented comparable results to FI-CGA (moderate to good validity; ICC=0.65, 95%CI=0.50–0.76) with a strong association between the measures (r=0.74, 95%CI=0.62–0.83). In our prototype and clinical cohorts, the app had a 100% completion rate with no safety occurrences and had high usability ratings.

The Fit-Frailty App is a feasible and valid tool that can be used in research and clinical settings to comprehensively assess frailty and sarcopenia by non-geriatricians and could assist with developing targeted interventions.