BackgroundEccentric cycling exercise (ECC) allows training at low metabolic costs and may therefore be valuable for patients with precapillary pulmonary hypertension (PH) due to pulmonary vascular disease (PVD). Research QuestionThe aim of this study was to compare the ventilatory and circulatory responses to ECC versus conventional cycling (CON) in patients with PVD. Study Design and MethodsThis was a randomized controlled crossover trial in which patients diagnosed with PVD, defined as either pulmonary arterial or chronic thromboembolic PH (PAH/CTEPH), performed CON and ECC cycling tests at identical submaximal work-rates, following stepwise incremental protocols. Oxygen uptake (V’O2) and additional cardiorespiratory responses were measured breath-by-breath by ergospirometry. Hemodynamic parameters such as systolic pulmonary artery pressure (sPAP) and tricuspid annular plain systolic excursion (TAPSE) were measured by echocardiography. Results33 patients (19 PAH, 14 CTEPH, 13 females, 50±15 years) were included. At identical work-rates during ECC compared to CON, V’O2 was significantly lower by - 200 ml/min (-40%, 95CI: -272 to -129, p<0.01), minute ventilation by -5.5 l/min (-30%, 95CI: -9.2 to -3.1, p<0.01), and sPAP by -12 mmHg (-20%, 95CI: -20 to -4 p<0.01). Right ventricular–arterial coupling, as measured by TAPSE/sPAP, was 0.11 mm/mmHg higher (+31%, 95CI: 0.04 to 0.18, p<0.01). No adverse events occurred. InterpretationThe current study supports the hypothesis that ECC is a feasible and well-tolerated exercise modality for PVD patients, with lower O2 demand and a reduced load on the right ventricle. Future studies should investigate whether ECC improves exercise capacity, muscle force and possibly hemodynamics during prolonged rehabilitation programs in patients with PVD.