Lo Coco, ValeriaValeriaLo CocoDi Mauro, MicheleMicheleDi MauroMariani, SilviaSilviaMarianiBidar, ElhamElhamBidarHryniewicz, KasiaKasiaHryniewiczLoforte, AntonioAntonioLoforteFux, ThomasThomasFuxHeuts, SamSamHeutsWiedemann, DominikDominikWiedemannKawcynsky, MichalMichalKawcynskyVerbelen, TomTomVerbelenBroman, Lars MikaelLars MikaelBromanKremer, JamilaJamilaKremerPozzi, MatteoMatteoPozziTakeda, KojiKojiTakedaBoeken, UdoUdoBoekenYIH-SHARNG CHENMasiello, PaoloPaoloMasielloVogel, Dominik J.Dominik J.VogelMaas, Jacinta J.Jacinta J.MaasBallotta, AndreaAndreaBallottaPappalardo, FedericoFedericoPappalardoGelsomino, SandroSandroGelsominoLorusso, RobertoRobertoLorussoMaessen, JosJosMaessenLohese, OpemaOpemaLohesePacini, DavideDavidePaciniSuarez, Sofia MartinSofia MartinSuarezBotta, LucaLucaBottaZimpfer, DanielDanielZimpferSchaefer, Anne-KristinAnne-KristinSchaeferSzalkiewicz, PhilippPhilippSzalkiewiczMeyns, BartBartMeynsDe Vos, MarieMarieDe VosVercaemst, LeenLeenVercaemstKarck, MatthiasMatthiasKarckMeyer, Anna L.Anna L.MeyerHoller, Ana J.Ana J.HollerJacquet-Lagrèze, MatthiasMatthiasJacquet-LagrèzeObadia, Jean FrancoisJean FrancoisObadiaFellahi, Jean LucJean LucFellahiWang, Amy S.Amy S.WangKalampokas, NikolaosNikolaosKalampokasLichtenberg, ArturArturLichtenbergAubin, HugHugAubinHuang, Chun-ChengChun-ChengHuangCHIH-HSIEN WANGHENG-WEN CHOUet al.2026-04-202026-04-202026-03https://scholars.lib.ntu.edu.tw/handle/123456789/737313Objective To evaluate whether dual-lumen (DL) versus single-lumen (SL) pulmonary artery cannulation improves outcomes in patients with refractory right ventricular failure (RVF) supported with extracorporeal life support and to identify which patients benefit most. Methods We conducted a multicenter retrospective cohort study using the international PLACE registry (2000-2020). Adults undergoing pulmonary artery cannulation for isolated RVF were included. Outcomes were in-hospital and 30-day mortality, bleeding, thromboembolic events, continuous renal-replacement therapy, and length of stay. Propensity score weighting was applied to adjust for baseline differences. Prespecified analyses tested effect modification by hypoxemia, renal function, platelet count, cannulation site, and oxygenator use. Mediation and clustering were used to explore physiological pathways and phenotypes. Results Among 345 patients, DL cannulation was associated with lower postoperative lactate and creatinine and with fewer bleeding events. In weighted multivariable models, DL reduced the risk of bleeding and the composite of bleeding or thromboembolism (weighted odds ratio, 0.50; 95% CI 0.32-0.77; P = .0017 and weighted odds ratio, 0.57; 95% CI 0.39-0.84; P = .004). Hypoxemia significantly strengthened the survival benefit of DL, whereas cannulation site and oxygenator use did not modify outcomes. Mediation analyses indicated that the effect of DL on survival was indirect, operating through early improvement in perfusion and renal function. Unsupervised clustering identified distinct postoperative biochemical phenotypes with markedly different prognoses; DL was associated with a shift toward favorable profiles. Conclusions In extracorporeal life support for RVF, DL pulmonary artery cannulation improves outcomes primarily by enhancing early organ function and reducing complications. Patients with baseline hypoxemia appear to benefit most, supporting a physiology-guided approach to cannulation strategy. © 2026 The Author(s).encausal mediationdual-lumen cannulationhypoxemiaright ventricular failurevenovenous ECMOjournal-article10.1016/j.xjon.2026.101699