Vasoreactivity Test With Nitrate-Hydralazine by Linking Gas Exchange and Hemodynamics in PH-HFpEF

Q: What are the key findings of this study?

Resting pulmonary arterial compliance strongly correlated with peak predicted VO2, and nitrate-hydralazine testing identified vasoreactivity in 5 of 7 PH-HFpEF patients.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) and precapillary PH (n=177). Intervention: Oral hydralazine and sublingual nitroglycerin vasoreactivity testing (prospective arm) and resting pulmonary arterial compliance (PAC) assessment (retrospective arm) vs. Baseline pre-vasodilator state (prospective arm) or pulmonary vascular resistance (PVR) and noncardiac dyspnea (retrospective arm). Primary outcome: Association of resting pulmonary arterial compliance (PAC) with percentage predicted peak VO2 and acute post-vasodilator changes in rest PAC and oxygen-uptake efficiency slope (OUES) (p=<0.01).

Q: What does this research mean for the field?

Resting pulmonary arterial compliance strongly correlates with peak predicted VO2 in pulmonary hypertension with preserved ejection fraction, and a combined nitrate-hydralazine challenge reveals distinct vasoreactive phenotypes by integrating compliance and oxygen-uptake efficiency. Novelty: ClaimNovelty.METHODOLOGICAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To identify hemodynamic correlates of abnormal gas exchange and develop a vasoreactivity testing protocol integrating hemodynamics and gas exchange in PH-HFpEF.

Ahmed El Shaer; Anas Abed; Mariana Garcia‐Arango; Wei Tu; Margaret Cochrane; Aria Kenarsary; A Salinas Gallegos; Zahra Mahmood; Muhammad Usman; Umbish Dino; Abdul Wahab Arif; Babak Tehrani; James Runo; Farhan Raza

doi:10.1016/j.yjcafi.2025.09.008

October 9, 2025Journal of Cardiac Failure - IntersectionsOpen Access

Vasoreactivity Test With Nitrate-Hydralazine by Linking Gas Exchange and Hemodynamics in PH-HFpEF

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Key result

Higher resting pulmonary arterial compliance is linked to ~3% greater exercise capacity per unit in PH-HFpEF.

P<0.01
n=177

Figures

Why the study?

Does resting pulmonary arterial compliance (PAC) correlate better with gas-exchange abnormalities than pulmonary vascular resistance (PVR) in pulmonary hypertension phenotypes, and can acute vasodilation with oral hydralazine and sublingual nitroglycerin identify vasoreactivity by improving PAC and oxygen-uptake efficiency slope (OUES) in PH-HFpEF?

Key Points

To identify hemodynamic correlates of abnormal gas exchange and develop a vasoreactivity testing protocol integrating hemodynamics and gas exchange in PH-HFpEF.
Retrospective cohort analysis of participants undergoing invasive cardiopulmonary exercise testing (iCPET; N=170), categorized into PH-HFpEF (n=91), precapillary PH (n=54), and noncardiac dyspnea (n=25).
Prospective pilot study in 7 participants with PH-HFpEF who underwent repeat iCPET following vasodilator administration with 20 mg oral hydralazine and 0.4 mg sublingual nitroglycerin.
In univariate regression, resting pulmonary arterial compliance (PAC) positively correlated with predicted peak VO2 in PH-HFpEF (P < 0.01) and precapillary PH (P < 0.01), with a 1.0 mL/mmHg increase in resting PAC linked to an increase in predicted peak VO2 by 2.6% and 6.6%, respectively, whereas resting PVR had no significant correlation (P > 0.05).
Resting PAC negatively correlated with VE/VCO2 slope in PH-HFpEF (P = 0.03) and precapillary PH (P = 0.02), while resting PVR showed no significant relationship.
In the pilot cohort (N=7), 5 participants exhibited vasoreactivity, showing resting PAC increases (range: +0.3 to +2.7 vs -1.0 to -1.4 in nonvasoreactive) and oxygen-uptake efficiency slope increases (range: +0.07 to +0.52 vs -0.08 to -0.11 in nonvasoreactive).

Study Design

Type

Cohort (n=177)

Structured PICO

Does resting pulmonary arterial compliance (PAC) correlate better with gas-exchange abnormalities than pulmonary vascular resistance (PVR) in pulmonary hypertension phenotypes, and can acute vasodilation with oral hydralazine and sublingual nitroglycerin identify vasoreactivity by improving PAC and oxygen-uptake efficiency slope (OUES) in PH-HFpEF?

P

Population

177 total participants undergoing invasive cardiopulmonary exercise testing, comprising a retrospective cohort (n=170; 91 PH-HFpEF, 54 precapillary PH, 25 noncardiac dyspnea) and a prospective PH-HFpEF pilot cohort (n=7; median age 67 years, 71% female).

I

Intervention

Prospective pilot cohort: acute vasodilator challenge with 20 mg oral hydralazine and 0.4 mg sublingual nitroglycerin, followed by repeated iCPET (postvasodilator rest and 25 Watts exercise) after a 15-minute rest period. Retrospective cohort: iCPET on a recumbent ergometer to evaluate resting pulmonary arterial compliance (PAC) and pulmonary vascular resistance (PVR).

O

Outcome

Association of percentage predicted peak oxygen consumption (VO2) and ventilatory efficiency slope (VE/VCO2) with resting hemodynamic predictors (pulmonary vascular resistance [PVR] and pulmonary arterial compliance [PAC]) in the retrospective cohort; and acute postvasodilator changes in resting PAC and oxygen-uptake efficiency slope (OUES) to define vasoreactivity in the prospective cohort.surrogate

Main Result

p-value: p=<0.01

Resting pulmonary arterial compliance (PAC) is a stronger correlate of impaired gas exchange than pulmonary vascular resistance (PVR) in PH-HFpEF, and integrating PAC with oxygen-uptake efficiency slope (OUES) during a nitrate-hydralazine challenge offers a novel protocol to assess acute pulmonary vasoreactivity.

Limitations

Small sample size in the prospective pilot study (n = 7) precluded formal statistical analyses.
Peak VO2 achieved with a recumbent ergometer is lower than that achieved with treadmill CPET.
Fixed nitrate-hydralazine dosage may limit interpretation, as some participants may be vasoreactive only at higher dosages.
Small sample size in the pilot prospective study precluded formal statistical analyses
Peak VO2 achieved with a recumbent ergometer is lower than that achieved with treadmill CPET
Fixed nitrate-hydralazine dosage may limit interpretation as some participants may be vasoreactive at higher dosages

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Implication

PAC may aid PH-HFpEF phenotyping; hypothesis-generating for nitrate-hydralazine vasoreactivity testing before clinical adoption.

Abstract

Pulmonary vascular remodeling in pulmonary hypertension (PH) phenotypes leads to gas-exchange abnormalities, hemodynamic perturbations, and adverse clinical outcomes.1,2 The gas-exchange abnormalities, captured by peak oxygen consumption (VO2) and ventilatory efficiency slope (VE/VCO2), occur in PH phenotypes, such as heart failure with preserved ejection fraction (PH-HFpEF) and precapillary PH.1,2 Hemodynamically, patients with PH are assessed by pulmonary vascular resistance (PVR, which reflects steady load) and pulmonary arterial compliance (PAC, which reflects pulsatile load).

Discussion

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Cite This Study

Shaer et al. (2025) conducted a cohort in Pulmonary hypertension with heart failure with preserved ejection fraction (PH-HFpEF) and precapillary PH (n=177). Oral hydralazine and sublingual nitroglycerin vasoreactivity testing (prospective arm) and resting pulmonary arterial compliance (PAC) assessment (retrospective arm) vs. Baseline pre-vasodilator state (prospective arm) or pulmonary vascular resistance (PVR) and noncardiac dyspnea (retrospective arm) was evaluated on Association of resting pulmonary arterial compliance (PAC) with percentage predicted peak VO2 and acute post-vasodilator changes in rest PAC and oxygen-uptake efficiency slope (OUES) (p=<0.01). Resting pulmonary arterial compliance strongly correlated with peak predicted VO2, and nitrate-hydralazine testing identified vasoreactivity in 5 of 7 PH-HFpEF patients.

synapsesocial.com/papers/6a90368fc7b7d4543f89ddb9 https://doi.org/10.1016/j.yjcafi.2025.09.008

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Vasoreactivity Test With Nitrate-Hydralazine by Linking Gas Exchange and Hemodynamics in PH-HFpEF

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Vasoreactivity Test With Nitrate-Hydralazine by Linking Gas Exchange and Hemodynamics in PH-HFpEF

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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