Search

This article examines technical use of Fitbit during an intervention for pulmonary hypertension (PAH)-patients. Technical issues with the device led to data being unavailable(37.5%). During intervention objective daily physical activity (DPA) decreased and subjective DPA increased. This emphasizes that an assessment of DPA in PAH requires incorporating both objective and subjective measurements., Competing Interests: The authors declare no conflict of interest., (© 2024 The Authors. The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Several indices of right heart remodeling and function have been associated with survival in pulmonary arterial hypertension (PAH). Outcome analysis and physiological relationships between variables may help develop a consistent grading system. Patients with Group 1 PAH followed at Stanford Hospital who underwent right heart catheterization and echocardiography within 2 weeks were considered for inclusion. Echocardiographic variables included tricuspid annular plane systolic excursion (TAPSE), right ventricular (RV) fractional area change (RVFAC), free wall strain (RVFWS), RV dimensions, and right atrial volumes. The main outcome consisted of death or lung transplantation at 5 years. Mathematical relationships between variables were determined using weighted linear regression and severity thresholds for were calibrated to a 20% 1-year mortality risk. PAH patients ( n  = 223) had mean (SD) age of 48.1 (14.1) years, most were female (78%), with a mean pulmonary arterial pressure of 51.6 (13.8) mmHg and pulmonary vascular resistance index of 22.5(6.3) WU/m 2 . Measures of right heart size and function were strongly related to each other particularly RVFWS and RVFAC ( R 2  = 0.82, p  < 0.001), whereas the relationship between TAPSE and RVFWS was weaker ( R 2  = 0.28, p  < 0.001). Death or lung transplantation at 5 years occurred in 78 patients (35%). Guided by outcome analysis, we ascertained a uniform set of parameter thresholds for grading the severity of right heart adaptation in PAH. Using these quantitative thresholds, we, then, validated the recently reported REVEAL-echo score (AUC 0.68, p  < 0.001). This study proposes a consistent echocardiographic grading system for right heart adaptation in PAH guided by outcome analysis., Competing Interests: Bettia Celestin, Shadi P. Bagherzadeh, Kenzo Ichimura, Everton J. Santana, Andrew John Sweatt and Pablo Amador Sanchez, have no conflicts to report. Francois Haddad has received funding from Janssen Inc. to conduct the research. Tobore Tobore is a senior director of Medical Affairs at Janssen. Anton Vonk Noordegraaf is supported by the Netherlands CardioVascular Research Initiative (CVON‐2012‐08 PHAEDRA, CVON‐2017‐10 DOLPHIN‐GENESIS) and the Netherlands Organization for Scientific Research (NWO‐VICI: 918.16.610). In addition, his institute received speakers money from Johnson & Johnson, MSD, Actelion, Bayer and Ferrer in the past 3 years. Finally, he served as a member of the scientific advisory board of Morphogen‐X, Ferrer, Gosammer Bio Services Inc, Altavant, MSD and Johnson & Johnson. The remaining authors declare no conflict of interest., (© 2024 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Right heart (RH) structure and function are major determinants of symptoms and prognosis in pulmonary arterial hypertension (PAH). RH imaging provides detailed information, but evidence and guidelines on the use of RH imaging in treatment decisions are limited. We conducted a Delphi study to gather expert opinion on the role of RH imaging in decision-making for treatment escalation in PAH. A panel of 17 physicians with expertise in PAH and RH imaging used three surveys in a modified Delphi process to reach consensus on the role of RH imaging in PAH. Survey 1 used open-ended questions to gather information. Survey 2 contained Likert scale and other questions intended to identify consensus on topics identified in Survey 1. Survey 3 contained Likert scale questions derived from Survey 2 and summary information on the results of Survey 2. The Delphi panel reached consensus that RH imaging is likely to improve the current risk stratification algorithms and help differentiate risk levels in patients at intermediate risk. Tricuspid annular plane systolic excursion, right ventricular fractional area change, right atrial area, tricuspid regurgitation, inferior venae cavae diameter, and pericardial effusion should be part of routine echocardiography in PAH. Cardiac magnetic resonance imaging is valuable but limited by cost and access. A pattern of abnormal RH imaging results should prompt consideration of hemodynamic evaluation and possible treatment escalation. RH imaging is an important tool for decisions about treatment escalation in PAH, but systematically collected evidence is needed to clarify its role., Competing Interests: Paul Forfia has served on a speaker's bureau and consulted for Bayer, Janssen, and United Therapeutics. Raymond Benza has received consulting fees from Bayer, Janssen, United Therapeutics, Acceleron, CERENO, Abbott, and Gossamer; and advisory board fees from Acceleron. Michele D'Alto has received consulting fees from Janssen, MSD, Dompè, Ferrer, and AOP. Teresa De Marco has received research funding from Acceleron; and has served as a consultant for Action/Janssen, United Therapeutics, BIAL, Merck, NXT, Aerovate, and Pulnovo. Jean M. Elwing has served as a consultant for United Therapeutics, Altavant, Aerovate, Bayer, Gossamer Bio, Acceleron, Janssen, Liquid, and Insmed; and has participated in clinical research funded by Janssen, United Therapeutics, Liquidia, Phase Bio, Gossamer Bio, Bayer, Acceleron, Altavant, and Aerovate. Robert Frantz has received consulting fees from Altavant, Gossamer Bio, Insmed, Liquidia, ShouTi, and Tenax; serves on DSMB for IQVIA; and has received research grants from Bayer and United Therapeutics. Francois Haddad has received research funding from Janssen. Ronald Oudiz has received research funding, advisory board honoraria, and speaker fees from United Therapeutics. Ioana R. Preston has received research funding from Acceleron/Merck, Janssen, United Therapeutics, and PhaseBio; and consulting fees from Acceleron/Merck, Janssen, United Therapeutics, Aerovate, Gossamer Bio, and Respira. Stephan Rosenkranz has received fees for lectures and/or consultations from Abbott, Acceleron, Actelion, Aerovate, Altavant, AOP Orphan, AstraZeneca, Bayer, Boehringer Ingelheim, Edwards, Ferrer, Gossamer, Janssen, MSD, United Therapeutics, and Vifor; and his institution has received research grants from Actelion, AstraZeneca, Bayer, and Janssen. John Ryan has received consulting fees and payment or honoraria from lectures, presentations, speakers' bureaus, manuscript writing, or education events from Bayer, Merck, United Therapeutics, Kiniksa, and Janssen PH. Robert Schilz has received research funding from Acceleron/Merck, United Therapeutics, Respira, and Bellerophon; consulting fees from Janssen, United Therapeutics, and Acceleron; and currently serves on speakers' bureaus for Bayer, Janssen, and United Therapeutics. Oksana A. Shlobin has received consulting fees from United Therapeutics and Janssen; has received honoraria from Medscape, Total CME, and Bayer; and has participated in a Data Safety Monitoring Board or Advisory Board for Janssen and Altavant. Jean‐Luc Vachiery has received consulting fees from Acceleron, Actelion Pharmaceuticals (now Janssen), Altavant, Bayer HealthCare, Boehringer Ingelheim, GlaxoSmithKline, Gossamer Bio, MSD, Novartis, and Shouti. Carmine Dario Vizza has received consulting fees from Acceleron, Janssen, Altavant, Bayer HealthCare, Ferrer, GlaxoSmithKline, Gossamer Bio, and MSD. Anton Vonk Noordegraaf has served as a member of the scientific advisory board of Morphogen‐X, Ferrer, Gosamer Bio, and Johnson & Johnson. The institute of Anton Vonk Noordegraaf has received consulting fees from a speakers' bureau for Johnson & Johnson, MSD, Actelion, Bayer, and Ferrer. Margaret R. Sketch and Meredith Broderick are employees and shareholders of United Therapeutics Corporation. Vallerie McLaughlin has received research funding from Acceleron, Janssen, Sonovie, and United Therapeutics; and consulting fees from Acceleron, Aerovate, Altavant, Bayer, Caremark LLC, CiVi Biopharma Inc., Corvista, Gossamer Bio, Janssen, Merck, and United Therapeutics., (© 2023 The Authors. Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Hyperventilation is common in pulmonary arterial hypertension and may be related to autonomic imbalance. Patients underwent exercise testing and hyperoxic breathing before and after bisoprolol treatment. We found that neither beta blocker treatment nor hyperoxic breathing in patients reduced hyperventilation at rest and during exercise, although it reduced heart rate., Competing Interests: The author(s) declare that there is no conflict of interest., (© The Author(s).)

Right ventricular (RV) function and autonomic dysfunction are important determinants of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). Although successful in animal studies, effects of beta-blocker therapy on RV function in clinical trials were disappointing. To understand this discrepancy, we studied whether beta-blocker therapy changes RV sympathetic activity. Idiopathic PAH (IPAH) patients received beta-blocker therapy (uptitrated to a maximal tolerated dose) and underwent cardiac magnetic resonance imaging, right heart catheterization, and a [ 11 C]-hydroxyephedrine positron emission tomography ([ 11 C]HED PET) scan at baseline to determine, respectively, RV ejection fraction (RVEF), RV pressures, and sympathetic activity. [ 11 C]HED, a norepinephrine analogue, allows determination of sympathetic innervation of the RV. [ 11 C]HED retention index reflects norepinephrine transporter activity. As a consequence of excessive catecholamine levels in the synaptic cleft, this transporter may be downregulated. Therefore, low [ 11 C]HED retention index indicates high sympathetic activity. 13 IPAH patients underwent [ 11 C]HED PET scans at baseline and after bisoprolol treatment. Although heart rate was reduced, systemic modulation of autonomic activity by bisoprolol did not affect local RV sympathetic nerve activity, RV function, or RV wall tension. In PAH patients, RV [ 11 C]HED retention index was lower compared to LV tracer uptake (p<0.01) and was related to systolic wall tension (R 2  = 0.4731, p<0.01) and RV function (R 2  = 0.44, p = 0.01). In RV failure, the tolerated dosage of bisoprolol did not result in an improvement of RV function nor in a reduction in RV sympathetic activity., (© The Author(s) 2020.)

This multicenter, randomized, double-blind, placebo-controlled study assessed ambrisentan or placebo in patients with inoperable chronic thromboembolic pulmonary hypertension. Futility of enrollment led to early termination. Trends of improvement in favor of ambrisentan versus placebo in the primary and some secondary endpoints were observed; adverse event profiles were similar between groups.

Levosimendan is an inotropic and vasodilator drug, which is known to improve cardiac function in animal models of right ventricular (RV) failure. The effects of levosimendan on oxygen consumption and myocardial efficiency in the failing RV is unknown. We investigated the effects of levosimendan on RV function, myocardial oxygen consumption, myocardial external efficiency (MEE), and myocardial metabolism in rats with RV hypertrophy and failure. RV hypertrophy and failure were induced by pulmonary trunk banding in rats. Rats were randomized to seven weeks of treatment with vehicle (n = 16) or levosimendan (3 mg/kg/day) (n = 13). Control animals without pulmonary banding received vehicle treatment (n = 11). RV MEE and RV metabolism were evaluated by echocardiography, 11 C-acetate positron emission tomography (PET), 18 F-FDG PET, and invasive pressure measurements. We found that levosimendan improved RV MEE (26 ± 3 vs. 14 ± 1%, P < 0.01) by increasing RV external work (0.62 ± 0.06 vs. 0.30 ± 0.03 mmHgċmL, P < 0.001) without affecting RV myocardial oxygen consumption ( P = 0.64). The improvement in RV MEE was not associated with a change in RV myocardial glucose uptake (1.3 ± 0.1 vs. 1.0 ± 0.1 µmol/g/min, P = 0.44). In conclusion, in the hypertrophic and failing RV of the rat, levosimendan improves RV function without increasing myocardial oxygen consumption leading to improved MEE. The improvement in RV MEE was not associated with a change in myocardial glucose uptake. This study emphasizes the potential therapeutic value of chronic levosimendan treatment RV failure. It extends previous observations on the effect profile of levosimendan and motivates clinical testing of levosimendan in RV failure.

Patients with idiopathic pulmonary arterial hypertension (IPAH) and a reduced diffusion capacity of the lung for carbon monoxide (DLCO) have a worse survival compared to IPAH patients with a preserved DLCO. Whether this poor survival can be explained by unresponsiveness to pulmonary hypertension (PH)-specific vasodilatory therapy is unknown. Therefore, the aim of this study was to evaluate the hemodynamic and cardiac response to PH-specific vasodilatory therapy in patients with IPAH and a reduced DLCO. Retrospectively, we studied treatment naïve hereditary and IPAH patients diagnosed between January 1990 and May 2015 at the VU University Medical Center. After exclusion of participants without available baseline DLCO measurement or right heart catheterization data and participants carrying a BMPR2 mutation, 166 participants could be included in this study. Subsequently, hemodynamics, cardiac function, exercise capacity, and oxygenation at baseline and after PH-specific vasodilatory therapy were compared between IPAH patients with a preserved DLCO (DLCO >62%), IPAH patients with a moderately reduced DLCO (DLCO 43-62%), and IPAH patients with a severely reduced DLCO (DLCO <43%). Baseline hemodynamics and right ventricular function were not different between groups. Baseline oxygenation was worse in patients with IPAH and a severely reduced DLCO. Hemodynamics and cardiac function improved in all groups after PH-specific vasodilatory therapy without worsening of oxygenation at rest or during exercise. Patients with IPAH and a severely reduced DLCO show a similar response to PH-specific vasodilatory therapy in terms of hemodynamics, cardiac function, and exercise capacity as patients with IPAH and a moderately reduced or preserved DLCO.

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by remodeling and vasoconstriction of the pulmonary vasculature, ultimately leading to right ventricular (RV) failure and death. Recent developments in echocardiography, cardiovascular magnetic resonance imaging, computed tomography, and positron emission tomography allow advanced, noninvasive, in vivo assessment of the RV and have contributed to the identification of risk factors, prognostic factors, and monitoring of therapeutic responses in patients with PAH. Although far from reaching its future potential, these techniques have not only provided global RV assessment but also allowed evaluation of changes in cellular and molecular tissue processes, such as metabolism, oxygen balance and ischemia, angiogenesis, and apoptosis. Integrated application of these techniques could provide full insights into the different pathophysiological aspects of a failing RV in the setting of PAH. Recent advances in hybrid imaging have implemented simultaneous measurements of myocardial and vascular interactions and will be one of the most important potential future developments.