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Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved ejection fraction

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Abstract

Over 2.5 million patients in the USA suffer from heart failure with preserved ejection fraction (HFpEF), and pulmonary hypertension (PH) is present in the majority of these patients. PH represents an adverse prognostic factor in HFpEF and has been identified as a potential therapeutic target to improve symptoms and outcomes. The recognition and investigation of a subset of patients with superimposed pulmonary vascular disease (on top of pulmonary venous hypertension) has led to further subclassification of PH due to left heart disease (PH-LHD) into two categories: isolated post-capillary PH and combined post- and pre-capillary PH (CpcPH). In this review, we (1) describe the evolution of the diagnostic criteria of PH-LHD; (2) identify the diagnostic modalities that can be utilized for the identification of patients with CpcPH-HFpEF; (3) review the literature on the prevalence, clinical characteristics, and prognostic factors of CpcPH-HFpEF; (4) discuss recent and ongoing clinical trials investigating the effectiveness of selective pulmonary vasodilators in PH-LHD; and (5) propose future areas for further investigation of the etiology and pathophysiological mechanisms contributing to the development of CpcPH and highlight important considerations in the design of future trials to promote better characterization of this clinical entity. CpcPH-HFpEF is a distinct subset within HFpEF and one that may respond to targeted therapeutics.

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Abbreviations

CpcPH:

Combined post- and pre-capillary pulmonary hypertension

DPG:

Diastolic pulmonary gradient

HFpEF:

Heart failure with preserved ejection fraction

mPAP:

Mean pulmonary artery pressure

PADP:

Pulmonary artery diastolic pressure

PAH:

Pulmonary arterial hypertension

PASP:

Pulmonary artery systolic pressure

PCWP:

Pulmonary capillary wedge pressure

PH-LHD:

Pulmonary hypertension due to left heart disease

PH:

Pulmonary hypertension

PVR:

Pulmonary vascular resistance

RVOT:

Right ventricular outflow tract

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Acknowledgments

S.J.S. was supported by the American Heart Association, Dallas, TX (#0835488N) and the National Institutes of Health, Bethesda, MD (R01 HL107557, R01 HL127028), and D.D.D. was supported by the Sarnoff Cardiovascular Research Foundation, Great Falls, VA.

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  1. Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, 676 N. St. Clair St., Suite 600, Chicago, IL, 60611, USA

    Debra D. Dixon, Amar Trivedi & Sanjiv J. Shah

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  1. Debra D. Dixon
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  2. Amar Trivedi
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Correspondence to Sanjiv J. Shah.

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S.J.S. reports receiving a research grant from Actelion Pharmaceuticals Ltd., consulting fees from Novartis, Bayer, AstraZeneca, and Alnylam; and honoraria from the Pulmonary Hypertension Association, the American Society of Echocardiography, and the American Board of Internal Medicine. D.D.D. and A.T. have no disclosures to report.

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Dixon, D.D., Trivedi, A. & Shah, S.J. Combined post- and pre-capillary pulmonary hypertension in heart failure with preserved ejection fraction. Heart Fail Rev 21, 285–297 (2016). https://doi.org/10.1007/s10741-015-9523-6

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