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CLINICAL RESEARCH: HEART FAILURE

Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction

A Community-Based Study

Carolyn S.P. Lam, MBBS^_*,, Véronique L. Roger, MD, MPH^_*, Richard J. Rodeheffer, MD^_*, Barry A. Borlaug, MD^_*, Felicity T. Enders, PhD and Margaret M. Redfield, MD^_*,_*

^_* Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
Yong Loo Lin School of Medicine, Singapore, Singapore
Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota

Manuscript received August 20, 2008; revised manuscript received November 17, 2008, accepted November 30, 2008.

^_* Reprint requests and correspondence: Dr. Margaret M. Redfield, 200 First Street SW, Rochester, Minnesota 55905 (Email: redfield.margaret{at}mayo.edu).

Objectives: This study sought to define the prevalence, severity, and significance of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) in the general community.

Background: Although HFpEF is known to cause PH, its development is highly variable. Community-based data are lacking, and the relative contribution of pulmonary venous versus pulmonary arterial hypertension (HTN) to PH in HFpEF is unknown. We hypothesized that PH would be a marker of symptomatic pulmonary congestion, distinguishing HFpEF from pre-clinical hypertensive heart disease.

Methods: This community-based study of 244 HFpEF patients (age 76 ± 13 years; 45% male) was followed up using Doppler echocardiography over 3 years. Control subjects were 719 adults with HTN without HF (age 66 ± 10 years; 44% male). Pulmonary artery systolic pressure (PASP) was derived from the tricuspid regurgitation velocity and PH defined as PASP >35 mm Hg. Pulmonary capillary wedge pressure (PCWP) was estimated from the ratio of early transmitral flow velocity to early mitral annular diastolic velocity.

Results: In HFpEF, PH was present in 83% and the median (25th, 75th percentile) PASP was 48 (37, 56) mm Hg. PASP increased with PCWP (r = 0.21; p < 0.007). Adjusting for PCWP, PASP was higher in HFpEF than HTN (p < 0.001). The PASP distinguished HFpEF from HTN with an area under the receiver-operating characteristic curve of 0.91 (p < 0.001) and strongly predicted mortality in HFpEF (hazard ratio: 1.3 per 10 mm Hg; p < 0.001).

Conclusions: PH is highly prevalent and often severe in HFpEF. Although pulmonary venous HTN contributes to PH, it does not fully account for the severity of PH in HFpEF, suggesting that a component of pulmonary arterial HTN also contributes. The potent effect of PASP on mortality lends support for therapies aimed at pulmonary arterial HTN in HFpEF.

Key Words: pulmonary hypertension • diastolic heart failure • heart failure with preserved ejection fraction

Abbreviations and Acronyms   AUC = area under the curve   COPD = chronic obstructive pulmonary disease   EF = ejection fraction   HF = heart failure   HFpEF = heart failure with preserved ejection fraction   HTN = hypertension   PASP = pulmonary artery systolic pressure   PCWP = pulmonary capillary wedge pressure   PH = pulmonary hypertension   TR = tricuspid regurgitation

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