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

https://doi.org/10.1016/j.jacc.2023.05.010Get rights and content

Abstract

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)

Section snippets

Patient population

PARAGON-HF was a multicenter, international, randomized, double-blind, event-driven trial testing the long-term efficacy and safety of sacubitril/valsartan compared with valsartan alone in patients with signs and symptoms of HF and LVEF ≥45%, as was previously described.9,11 Briefly, PARAGON-HF enrolled 4,822 patients who met the following key inclusion criteria: 1) age ≥50 years; 2) symptoms of HF requiring treatment with diuretic agents and with current NYHA functional class II-IV symptoms;

Study population

Comparison between PARAGON-HF patients not in the echocardiography cohort and those in the echocardiography cohort has been previously reported.10 Overall, 528 patients (mean age 74.3 ± 7.9 years, 56.4% female, 79.5% White) were included in this analysis. Compared to patients without available RV strain assessment, those included in the current analysis were older, more likely to be female, and had lower body mass index (Supplemental Table 1). Modest differences were observed in comorbidity

Discussion

In a contemporary large HFpEF population enrolled in PARAGON-HF, we found that up to 60% of the patients had evidence of RV dysfunction assessed by myocardial deformation imaging. Reduced RV free wall strain was identified in more than one-half of patients without evidence of RV impairment as assessed by traditional echocardiographic methods. Impaired RV free wall strain and its ratio to pulmonary circulation were associated with higher circulating NT-proBNP levels and with a higher risk of

Conclusions

In a large HFpEF population enrolled in the PARAGON-HF trial, impairment of RV function assessed by myocardial deformation imaging was identified in approximately 60% of the population, including those with normal conventional measures of RV function. RVFWLS and its ratio to pulmonary circulation were significantly associated with elevation in NT-proBNP and total hospitalizations for HF and CV death, regardless of LV systolic and diastolic function and NT-proBNP. These data suggest that RV

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,

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    • Cited by (5)

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    ∗

    Drs Inciardi and Abanda contributed equally to this work.

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    © 2023 by the American College of Cardiology Foundation. Published by Elsevier.