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Background and Aims: The role of biomarkers in diagnosing pulmonary hypertension (PH) and distinguishing between pre- and post-capillary PH remains poorly understood. We aimed to identify biomarkers with a strong association with mean pulmonary arterial pressure, mPAP (PH diagnosis) and pulmonary vascular resistance, PVR (pre-capillary component), but not with pulmonary arterial wedge pressure, PAWP (post-capillary component)., Methods: Blood samples were collected in patients undergoing right heart catheterization within a prospective cross-sectional study. Biomarkers measured included BMP10, NT-proBNP, ANG2, ESM1/endocan, FGF23, GDF15, IGFBP7, IL6, MyBPC3, proC3, and proC6/endotrophin. Primary outcomes were mPAP, PVR, and PAWP, while secondary outcomes included PH diagnosis (mPAP > 20 mmHg) and elevated PVR (> 2 Wood units). Multivariable linear and logistic regression models were used to assess the relationship between biomarkers and outcomes., Results: Of the 127 patients included (age 66 ± 13 years, 54% female), 73% were diagnosed with PH. BMP10, NT-proBNP, ANG2, MyBPC3, and FGF23 showed a strong association with mPAP (p < 0.001). BMP10 and NT-proBNP were strongly associated with PVR (p < 0.001), while NT-proBNP and ANG2 were strongly associated with PAWP (p < 0.001). NT-proBNP had the strongest association with the diagnosis of PH (area under the curve = 0.76). BMP10 was the only biomarker associated with elevated PVR (OR 1.60, 95%CI 1.01-2.54, p = 0.04) but not with PAWP (p = 0.86)., Conclusions: Several biomarkers were strongly associated with mPAP, PAWP, and PVR. BMP10 was the only biomarker strongly associated with mPAP and PVR, but not with PAWP, thus reflecting the pre-capillary PH component. Measurement of BMP10 along with NT-proBNP may aid in diagnosing PH., (© 2024. The Author(s).)

Background: Stroke remains one of the most serious complications in atrial fibrillation (AF) patients and has been linked to disturbances of the autonomic nervous system., Objective: The purpose of this study was to test the hypothesis that impaired cardiac autonomic function might be associated with an enhanced stroke risk in AF patients., Methods: A total of 1922 AF patients who were in either sinus rhythm (SR group; n = 1121) or AF (AF group; n = 801) on a 5-minute resting electrocardiographic (ECG) recording were enrolled in the study. Heart rate variability triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-minute total power, and power in the high-frequency, low-frequency, and very-low-frequency ranges were calculated. Cox regression models were constructed to examine the association of heart rate variability (HRV) parameters with the composite endpoint of stroke or systemic embolism., Results: Mean age was 71 ± 8 years in the SR group and 75 ± 8 years in the AF group. Thirty-seven patients in the SR group (3.4%) and 60 patients in the AF group (8.0%) experienced a stroke or systemic embolism during follow-up of 5 years. In patients with SR, HRVI <15 was the strongest HRV parameter to be associated with stroke or systemic embolism (hazard ratio 3.04; 95% confidence interval 1.3-7.0; P = .009) after adjustment for multiple confounders. In the AF group, no HRV parameter was found to be associated with the composite endpoint., Conclusion: HRVI measured during SR on a single 5-minute ECG recording is independently associated with stroke or systemic embolism in AF patients. HRV analysis in SR may help to improve risk stratification in AF patients., Competing Interests: Disclosures Dr Beer reports grants from the Swiss National Foundation of Science, The Swiss Heart Foundation, and Bayer; and lecture fees from Sanofi Aventis and Amgen, to the institution outside the submitted work. Dr Blum has received research grants from the Swiss National Science Foundation and the Swiss Heart Foundation, all for work outside the submitted study. Dr Bonati has received an unrestricted research grant from AstraZeneca; consultancy or advisory board fees or speaker honoraria from Amgen, Bayer, Bristol-Myers Squibb, and Claret Medical; and travel grants from AstraZeneca and Bayer, outside the submitted work. Dr Conen received consultancy fees from Roche Diagnostics and Trimedics; and speaker fees from Servier and BMS/Pfizer, outside the submitted work. Dr Kühne received personal fees from Daiichi Sankyo and grants from the Swiss National Science Foundation, Swiss Heart Foundation, Foundation for CardioVascular Research Basel, Bayer, Pfizer, Boston Scientific, BMS, Biotronik, and Daiichi Sankyo, outside the submitted work. Dr Krisai has speaker fees from BMS/Pfizer, outside the submitted work. Dr Müller reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical, and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St. Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, Novartis, Zoll, and Bristol Myers Squibb; consultant fees from Biosense Webster, Medtronic, Abbott/St. Jude Medical, and Biotronik, outside the submitted work. Dr Moschovitis has received advisory board and/or speaker fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gebro Pharma, Novartis, and Vifor, outside the submitted work. Dr Osswald received research grants from the Swiss National Science Foundation and Swiss Heart Foundation, Foundation for CardioVascular Research Basel, and F. Hoffmann-La Roche Ltd.; and educational and speaker grants from F. Hoffmann-La Roche Ltd., Bayer, Novartis, Sanofi, AstraZeneca, Daiichi-Sankyo, and Pfizer, outside the submitted work. Dr Reichlin has recieved research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the sitem insel support funds; speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense-Webster, Biotronik, Boston-Scientific, Daiichi Sankyo, Farapulse, Medtronic, Pfizer-,BMS and Roche; and support for his institution’s fellowship program from Abbott/SJM, Biosense Webster, Biotronik, Boston Scientific, and Medtronic for work, outside the submitted study. Dr Zuern has received funding from the “Freiwillige Akademische Gesellschaft Basel”; and personal fees from Cardiomatics, outside the submitted work. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Direct-acting oral anticoagulants (DOACs) have, to a substantial degree, replaced vitamin K antagonists (VKA) as treatments for stroke prevention in atrial fibrillation (AF) patients. However, evidence on the real-world causal effects of switching patients from VKA to DOAC is lacking. We aimed to assess the empirical incremental cost-effectiveness of switching patients to DOAC compared with maintaining VKA treatment., Methods: The target trial approach was applied to the prospective observational Swiss-AF cohort, which enrolled 2415 AF patients from 2014 to 2017. Clinical data, healthcare resource utilisation and EQ-5D-based utilities representing quality of life were collected in yearly follow-ups. Health insurance claims were available for 1024 patients (42.4%). Overall survival, quality-of-life, costs from the Swiss statutory health insurance perspective and cost-effectiveness were estimated by emulating a target trial in which patients were randomly assigned to switch to DOAC or maintain VKA treatment., Results: 228 patients switching from VKA to DOAC compared with 563 patients maintaining VKA treatment had no overall survival advantage over a 5-year observation period (HR 0.99, 95% CI 0.45, 1.55). The estimated gain in quality-adjusted life years (QALYs) was 0.003 over the 5-year period at an incremental costs of CHF 23 033 (€ 20 940). The estimated incremental cost-effectiveness ratio was CHF 425 852 (€ 387 138) per QALY gained., Conclusions: Applying a causal inference method to real-world data, we could not demonstrate switching to DOACs to be cost-effective for AF patients with at least 1 year of VKA treatment. Our estimates align with results from a previous randomised trial., Competing Interests: Competing interests: JHB reports grant support from the Swiss National Foundation of Science, The Swiss Heart Foundation and the Stiftung Kardio; grant support, speakers and consultation fees to the institution from Bayer, Sanofi and Daichii Sankyo. EB reports grants from Swiss Cancer Research Foundation, Amgen, MSD, Novartis, Vifor, all outside the submitted work. MB is supported by grants from the Swiss National Science Foundation and the Swiss Heart Foundation. LB reports personal fees and non-financial support from Amgen, grants from AstraZeneca, personal fees and non-financial support from Bayer, personal fees from Bristol-Myers Squibb, personal fees from Claret Medical, grants from Swiss National Science Foundation, grants from University of Basel, grants from Swiss Heart Foundation, outside the submitted work. DC received consulting fees from Roche Diagnostics, and speaker fees from Servier and BMS/Pfizer, all outside of the current work. MK reports grants from Bayer, grants from Pfizer, grants from Boston Scientific, grants from BMS, grants from Biotronik, grants and personal fees from Daiichi Sankyo. GM has received advisory board and/or speaker’s fees from Astra Zeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Gebro Pharma, Novartis and Vifor, all outside of the submitted study. AM reports fellowship and training support from Biotronik, Boston Scientific, Medtronic, Abbott/St. Jude Medical and Biosense Webster; speaker honoraria from Biosense Webster, Medtronic, Abbott/St Jude Medical, AstraZeneca, Daiichi Sankyo, Biotronik, MicroPort, Novartis, and consultant honoraria for Biosense Webster, Medtronic, Abbott/St. Jude Medcal and Biotronik. SO received research grants from the Swiss National Science Foundation and from the Swiss Heart Foundation, research grants from Foundation for CardioVascular Research Basel, research grants from Roche, educational and speaker office grants from Roche, Bayer, Novartis, Sanofi AstraZeneca, Daiichi-Sankyo and Pfizer. TR has received research grants from the Swiss National Science Foundation, the Swiss Heart Foundation, and the sitem insel support fund, all for work outside the submitted study. Speaker/consulting honoraria or travel support from Abbott/SJM, Astra Zeneca, Brahms, Bayer, Biosense-Webster, Biotronik, Boston-Scientific, Daiichi Sankyo, Medtronic, Pfizer-BMS and Roche, all for work outside the submitted study. Support for his institution’s fellowship programme from Abbott/SJM, Biosense-Webster, Biotronik, Boston-Scientific and Medtronic for work outside the submitted study. MS reports grants from Swiss National Science Foundation, for the conduct of the study; grants from Amgen, grants from MSD, grants from Novartis, grants from Pfizer, grants from Roche, grants and personal fees from BMS and personal fees from Sandoz, all outside the submitted work. MS-B reports grants from the European Commission outside of the present work. CS has received speaker honoraria from Biosense Webster and Medtronic and research grants from Biosense Webster, Daiichi-Sankyo and Medtronic. The remaining authors have nothing to disclose., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)