Background and Aims: Data from randomized trials investigating different access closure strategies after transfemoral transcatheter aortic valve implantation (TF-TAVI) remain scarce. In this study, two vascular closure device (VCD) strategies to achieve haemostasis after TF-TAVI were compared. Methods: The ACCESS-TAVI (Comparison of Strategies for Vascular ACCESS Closure after Transcatheter Aortic Valve Implantation) is a prospective, multicentre trial in which patients undergoing TF-TAVI were randomly assigned to a strategy with a combined suture-/plug-based VCD strategy (suture/plug group) using one ProGlide™/ProStyle™ (Abbott Vascular) and one Angio-Seal® (Terumo) vs. a suture-based VCD strategy (suture-only group) using two ProGlides™/ProStyles™. The primary endpoint was a composite of major or minor access site-related vascular complications during index hospitalization according to Valve Academic Research Consortium 3 criteria. Key secondary endpoints included time to haemostasis, bleeding type ≥ 2, and all-cause mortality over 30 days. Results: Between September 2022 and April 2024, 454 patients were randomized. The primary endpoint occurred in 27% (62/230) in the suture/plug group and 54% (121/224) in the suture-only group [relative risk .55 (95% confidence interval: .44, .68); P < .001]. Time to haemostasis was significantly shorter in the suture/plug group compared with the suture-only group (108 ± 208 s vs. 206 ± 171 s; P < .001). At 30 days, bleeding type ≥ 2 occurred less often in the suture/plug group compared with the suture-only group [6.2% vs. 12.1%, relative risk .66 (.43, 1.02); P = .032], with no significant difference in mortality. Conclusions: With regard to the composite of major or minor access site-related vascular complications, a combined suture-/plug-based VCD strategy was superior to a suture-based VCD strategy for vascular access closure in patients undergoing TF-TAVI.

Background: The aim of the present work was to study the influence of body position on resting and exercise pulmonary hemodynamics in patients assessed for pulmonary hypertension (PH). Methods and Results: Data from 483 patients with suspected PH undergoing right heart catheterization for clinical indications (62% women, age 61±15 years, 246 precapillary PH, 48 postcapillary PH, 106 exercise PH, 83 no PH) were analyzed; 213 patients (main cohort, years 2016–2018) were examined at rest in upright (45°) and supine position, such as under upright exercise. Upright exercise hemodynamics were compared with 270 patients (historical cohort) undergoing supine exercise with the same protocol. Upright versus supine resting data revealed a lower mean pulmonary artery pressure 31±14 versus 32±13 mm Hg, pulmonary artery wedge pressure 11±4 versus 12±5 mm Hg, and cardiac index 2.9±0.7 versus 3.1±0.8 L/min per m ² , and higher pulmonary vascular resistance 4.1±3.1 versus 3.9±2.8 Wood P <0.001. Exercise data upright versus supine revealed higher work rates (53±26 versus 33±22 watt), and adjusting for differences in work rate and baseline values, higher end‐exercise mean pulmonary artery pressure (52±19 versus 45±16 mm Hg, P =0.001), similar pulmonary artery wedge pressure and cardiac index, higher pulmonary vascular resistance (5.4±3.7 versus 4.5±3.4 Wood units, P =0.002), and higher mean pulmonary artery pressure/cardiac output (7.9±4.7 versus 7.1±4.1 Wood units, P =0.001). Conclusions: Body position significantly affects resting and exercise pulmonary hemodynamics with a higher pulmonary vascular resistance of about 10% in upright versus supine position at rest and end‐exercise, and should be considered and reported when assessing PH.

Question addressed by the study: To investigate exercise performance and hypoxia-related health effects in patients with pulmonary hypertension (PH) during a high-altitude sojourn.Patients and methods: In a randomised crossover trial in stable (same therapy for >4 weeks) patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) with resting arterial oxygen tension (PaO₂) ≥7.3 kPa, we compared symptom-limited constant work-rate exercise test (CWRET) cycling time during a day-trip to 2500 mversus470 m. Further outcomes were symptoms, oxygenation and echocardiography. For safety, patients with sustained hypoxaemia at altitude (peripheral oxygen saturation 30 min or 15 min) received oxygen therapy.Results: 28 PAH/CTEPH patients (n=15/n=13); 13 females; mean±sdage 63±15 years were included. After >3 h at 2500 mversus470 m, CWRET-time was reduced to 17±11versus24±9 min (mean difference −6, 95% CI −10 to −3), corresponding to −27.6% (−41.1 to −14.1; p<0.001), but similar Borg dyspnoea scale. At altitude,PaO₂was significantly lower (7.3±0.8versus10.4±1.5 kPa; mean difference −3.2 kPa, 95% CI −3.6 to −2.8 kPa), whereas heart rate and tricuspid regurgitation pressure gradient (TRPG) were higher (86±18versus71±16 beats·min⁻¹, mean difference 15 beats·min⁻¹, 95% CI 7 to 23 beats·min⁻¹) and 56±25versus40±15 mmHg (mean difference 17 mmHg, 95% CI 9 to 24 mmHg), respectively, and remained so until end-exercise (all p<0.001). The TRPG/cardiac output slope during exercise was similar at both altitudes. Overall, three (11%) out of 28 patients received oxygen at 2500 m due to hypoxaemia.Conclusion: This randomised crossover study showed that the majority of PH patients tolerate a day-trip to 2500 m well. At highversuslow altitude, the mean exercise time was reduced, albeit with a high interindividual variability, and pulmonary artery pressure at rest and during exercise increased, but pressure–flow slope and dyspnoea were unchanged.

Platelets modulate the process of cancer metastasis. However, current knowledge on the direct interaction of platelets and tumor cells is mostly based on findings obtained in vitro. We addressed the role of the platelet fibrinogen receptor glycoprotein IIb (integrin αIIb) for experimental melanoma metastasis in vivo. Highly metastatic B16-D5 melanoma cells were injected intravenously into GPIIb-deficient (GPIIb^-/-) or wildtype (WT) mice. Acute accumulation of tumor cells in the pulmonary vasculature was assessed in real-time by confocal videofluorescence microscopy. Arrest of tumor cells was dramatically reduced in GPIIb^-/- mice as compared to WT. Importantly, we found that mainly multicellular aggregates accumulated in the pulmonary circulation of WT, instead B16-D5 aggregates were significantly smaller in GPIIb^-/- mice. While pulmonary arrest of melanoma was clearly dependent on GPIIb in this early phase of metastasis, we also addressed tumor progression 10 days after injection. Inversely, and unexpectedly, we found that melanoma metastasis was now increased in GPIIb^-/- mice. In contrast, GPIIb did not regulate local melanoma proliferation in a subcutaneous tumor model. Our data suggest that the platelet fibrinogen receptor has a differential role in the modulation of hematogenic melanoma metastasis. While platelets clearly support early steps in pulmonary metastasis via GPIIb-dependent formation of platelet-tumor-aggregates, at a later stage its absence is associated with an accelerated development of melanoma metastases.

Stable-treated patients with pulmonary vascular disease (PVD) defined as pulmonary arterial or distal chronic thromboembolic pulmonary hypertension (PAH/CTEPH) wish to participate in daily activities including travel to high altitude or by air, but may be at increased risk of adverse events at high altitude (AE_HA).^1,2 Thus, pulmonary hypertension (PH) guidelines recommend that symptomatic PVD patients should not travel >1500 m or fly without supplemental oxygen therapy (SOT),³ but evidence is scarce and ambiguous.⁴

Objective: To investigate the effect of a daylong exposure to high altitude on peak exercise capacity and safety in stable patients with pulmonary arterial and chronic thromboembolic pulmonary hypertension (PAH/CTEPH).Methods: In a randomised controlled cross-over trial, stable patients with PAH or distal CTEPH without resting hypoxemia at low altitude performed two incremental exercise tests to exhaustion, one after 3–5 h at high (2500 m) and one at low altitude (470 m).Results: In 27 patients with PAH/CTEPH (44% women, 61±14 y), maximal work-rate was 110±64 watts at 2500 m and 123±64 watts at 470 m (−11%, 95%CI: −16 to −11, p<0.001). SpO₂and PaO₂at end-exercise were 83±6%versus91±6% and 6.1±1.9 kPaversus8.6±1.9 kPa (−8%; −29%; both p<0.001) at 2500 mversus470 m, respectively. Maximal oxygen uptake at high altitude was 17.8±7.5 L·min⁻¹·kg⁻¹versus20±7.4 L·min⁻¹·kg⁻¹at low altitude (−11%, p<0.001). At end-exercise, the ventilatory equivalent for CO₂was 43±9 at 2500 mversus39±9 at 470 m (+9%, 95%CI: 2 to 6; p=0.002). No adverse events occurred during or after exercise.Conclusion: Among predominantly low-risk patients with stable PAH/CTEPH, cycling exercise during the first day at 2500 m was well tolerated, but peak exercise capacity, blood oxygenation and ventilatory efficiency were lower compared to 470 m.