Right Ventricular Function and Pulmonary Coupling in Patients With Heart Failure and Preserved Ejection Fraction.

Background: Limited data exist to characterize novel measures of right ventricular (RV) function and the coupling to pulmonary circulation in patients with heart failure and preserved left ventricular ejection fraction (HFpEF).
Objectives: This study sought to assess the clinical implications of RV function, the association with N-terminal pro-B-type natriuretic peptide, and the risk for adverse events among patients with HFpEF.
Methods: This study analyzed measures of RV function by assessing absolute RV free wall longitudinal strain (RVFWLS) and its ratio to estimated pulmonary artery systolic pressure (PASP) (RVFWLS/PASP ratio) in 528 patients (mean age 74 ± 8 years, 56% female) with adequate echocardiographic images quality enrolled in the PARAGON-HF trial. Associations with baseline N-terminal pro-B-type natriuretic peptide and with total HF hospitalizations and cardiovascular death were assessed, after accounting for confounders.
Results: Overall, 311 patients (58%) had evidence of RV dysfunction, defined as absolute RVFWLS <20%, and among the 388 patients (73%) with normal tricuspid annular planar systolic excursion and RV fractional area change, more than one-half showed impaired RV function. Lower values of RVFWLS and RVFWLS/PASP ratios were significantly associated with higher circulating N-terminal pro-B-type natriuretic peptide. With a median follow-up of 2.8 years, there were 277 total HF hospitalizations and cardiovascular deaths. Both absolute RVFWLS (HR: 1.39; 95% CI: 1.05-1.83; P = 0.018) and RVFWLS/PASP ratio (HR: 1.43; 95% CI: 1.13-1.80; P = 0.002) were significantly associated with the composite outcome. Treatment effect of sacubitril/valsartan was not modified by measures of RV function.
Conclusions: Worsening RV function and its ratio to pulmonary pressure is common and significantly associated with an increased risk of HF hospitalizations and cardiovascular death in patients with HFpEF. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711).
Competing Interests: Funding Support and Author Disclosures The PARAGON-HF trial was funded by Novartis. Dr Abanda received institutional support from National Institutes of Health (5HL9804812) through the Harvard T.H. Chan School of Public Health. Dr A. Shah has received research support from Novartis, through Brigham and Women’s Hospital; and has received consulting fees from Philips Ultrasound and Bellerophon Therapeutics. Dr Cikes has received grants, personal fees, and nonfinancial support (travel support) from Novartis, GE Healthcare, Abbott, Roche Diagnostics, Bayer, Pfizer, Boehringer Ingelheim, Berlin-Chemie Menarini, Servier, Corvia, AstraZeneca, Sanofi Genzyme, Sandoz, Amgen, Orion Pharma, and Teva Pharmaceutical Industries. Dr Vaduganathan has received research grants from American Regent, Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Chiesi, Cytokinetics, Novo Nordisk, Relypsa, Roche Diagnostics, Sanofi, and Tricog Health; and participates in clinical trial committees for studies sponsored by AstraZeneca, Occlutech, Impulse Dynamics, Galmed, Bayer AG, and Novartis. Dr S. Shah has received research grants from the National Institutes of Health (R01 HL107577, R01 HL127028, R01 HL140731, and R01 HL149423), Actelion, AstraZeneca, Corvia, and Novartis; and has served as a consultant or an Advisory Board member for Abbott, Actelion, AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Cardiora, Coridea, CVRx, Eisai, Ionis, Ironwood, Merck, MyoKardia, Novartis, Pfizer, Sanofi, Shifamed, Tenax, and United Therapeutics. Dr Zile has received grants and personal fees from Novartis, CVRx, and Medtronic; and has received personal fees from Abbott, Boston Scientific, EBR, Endotronics, Ironwood, Merck, Myokardia, and V Wave. Dr Lam has received research support from Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, and Vifor Pharma; has served as consultant or on Advisory Boards, Steering Committees, or Executive Committees for Boston Scientific, Bayer, Roche Diagnostics, AstraZeneca, Medtronic, Vifor Pharma, Novartis, Amgen, Merck, Janssen Research and Development, Menarini, Boehringer Ingelheim, Novo Nordisk, Abbott Diagnostics, Corvia, Stealth Bio-Therapeutics, JanaCare, Biofourmis, Darma, Applied Therapeutics, MyoKardia, WebMD Global, Radcliffe Group, and Corpus; and is a cofounder of eKo.ai. Dr Pfeffer has received research grant support through Brigham and Women’s Hospital from Novartis; and has received consulting fees from Alnylam, AstraZeneca, Boehringer Ingelheim, Eli Lilly Alliance, Corvidia, DalCor, GlaxoSmithKline, National Heart, Lung, and Blood Institute CONNECTs (Master Protocol Committee), Novartis, Novo Nordisk, Peerbridge, and Sanofi; and has equity in DalCor. Dr McMurray has received payment paid to his employer, Glasgow University, from Novartis for his role as co–principal investigator of PARAGON-HF; has received grants paid to his employer from AstraZeneca, Theracos, and GlaxoSmithKline during the conduct of the study; and has received grants paid to his employer from Novartis, Amgen, Bristol Myers Squibb, Bayer, Abb-vie, Dal-Cor, Kidney Research UK, and Cardurion; and has received grants from the British Heart Foundation. Dr Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Sanofi Pasteur, and Theracos; and has consulted for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol Myers Squibb, Cardior, Corvia, Cytokinetics, Daiichi-Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, and Tenaya. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)