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Pulmonary hypertension in patients with heart failure and preserved ejection fraction: differential diagnosis and management.

ABSTRACT: The most common cause of pulmonary hypertension (PH) due to left heart disease (LHD) was previously rheumatic mitral valve disease. However, with the disappearance of rheumatic fever and an aging population, nonvalvular LHD is now the most common cause of group 2 PH in the developed world. In this review, we examine the challenge of investigating patients who have PH and heart failure with preserved ejection fraction (HF-pEF), where differentiating between pulmonary arterial hypertension (PAH) and PH-LHD can be difficult, and also discuss the entity of combined precapillary and postcapillary PH. Given the proven efficacy of targeted therapy for the treatment of PAH, there is increasing interest in whether these treatments may benefit selected patients with PH associated with HF-pEF, and we review current trial data.

SUBMITTER: Hussain N

PROVIDER: S-EPMC4860544 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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Pulmonary hypertension in patients with heart failure and preserved ejection fraction: differential diagnosis and management.

Hussain Nehal N Charalampopoulos Athanasios A Ramjug Sheila S Condliffe Robin R Elliot Charlie A CA O'Toole Laurence L Swift Andrew A Kiely David G DG

Pulmonary circulation 20160301 1

The most common cause of pulmonary hypertension (PH) due to left heart disease (LHD) was previously rheumatic mitral valve disease. However, with the disappearance of rheumatic fever and an aging population, nonvalvular LHD is now the most common cause of group 2 PH in the developed world. In this review, we examine the challenge of investigating patients who have PH and heart failure with preserved ejection fraction (HF-pEF), where differentiating between pulmonary arterial hypertension (PAH) a ...[more]

PMID: 27162611

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Project description:BACKGROUND:We hypothesized that pulmonary venous hypertension in heart failure (HF) leads to predominate remodeling of pulmonary veins and that the severity of venous remodeling is associated with the severity of pulmonary hypertension (PH) in HF. METHODS:Patients with HF (n=108; 53 preserved and 55 reduced ejection fraction) with PH (HF-PH; pulmonary artery systolic pressure [PASP] ?40 mm?Hg) were compared to normal controls (n=12) and patients with primary pulmonary veno-occlusive disease (PVOD; n=17). In lung specimens from autopsy (control, HF-PH, and 7 PVOD) or surgery (10 PVOD), quantitative histomorphometry was performed in all analyzable arteries (n=4949), veins (n=7630), and small indeterminate vessels (IV; n=2168) to define percent medial thickness (arteries) and percent intimal thickness (%IT) (arteries, veins, and IV) relative to external diameter. RESULTS:The average arterial percent medial thickness (control, 6.9; HF-PH, 11.0; PVOD, 15.0), arterial %IT (control, 4.9; HF-PH, 14.9; PVOD, 31.1), venous %IT (control, 14.0; HF-PH, 24.9; PVOD, 43.9), and IV %IT (control, 10.6; HF-PH, 25.8; PVOD, 50.0) in HF-PH were higher than controls (P<0.0001 for all) but lower than PVOD (P?0.005 for all). PASP (mm?Hg) was lower in HF-PH (median, 59 [interquartile range, 50-70]) than in PVOD (median, 91 [interquartile range, 82-103]). PASP correlated with arterial percent medial thickness (r=0.41) and arterial %IT (r=0.35) but more strongly with venous %IT (r=0.49) and IV %IT (r=0.55) (P<0.0001 for all). Associations between PASP and venous or IV %IT remained significant after adjusting for arterial percent medial thickness and %IT and did not vary by HF type. In patients with right heart catheterization (30 HF-PH, 14 PVOD), similar associations between the transpulmonary gradient and pulmonary vascular remodeling existed, with numerically stronger associations for venous and IV %IT. Although the PASP was slightly higher in patients with HF-PH with right ventricular dysfunction, pulmonary vascular remodeling was not more severe. Pulmonary vascular remodeling severity was associated with reductions in the diffusing capacity of the lungs. CONCLUSIONS:In HF, PH is associated with global pulmonary vascular remodeling, but the severity of PH correlates most strongly with venous and small IV intimal thickening, similar to the pattern observed in PVOD. These findings expand our understanding of the pathobiology of PH in HF.

Project description:Importance:Heart failure with preserved ejection fraction (HFpEF) is highly prevalent, yet there are no specific therapies, possibly due to phenotypic heterogeneity. The development of pulmonary hypertension (PH) in patients with HFpEF is considered a high-risk phenotype in need of targeted therapies, but there have been limited hemodynamic and outcomes data. Objective:To identify the hemodynamic characteristics and outcomes of PH-HFpEF. Design, Setting, and Participants:Cohort study of participants who had a right heart catheterization from January 2005 to September 2012 (median [interquartile range] follow-up time, 1578 [554-2513] days) were analyzed. Hemodynamic catheterization data was linked to the clinical data repository of all inpatient and outpatient encounters across a health system. Single tertiary referral center for heart failure and PH within a large health care network using a common clinical data repository was studied. There were 19 262 procedures in 10 023 participants. Exposures:Participants were classified as having no PH, precapillary PH, or PH in the setting of left heart disease (reduced or preserved ejection fraction). Pulmonary hypertension associated with HFpEF was defined as mean pulmonary artery pressure of 25 mm Hg or more, pulmonary artery wedge pressure of 15 mm Hg or more, and left ventricular ejection fraction of 45% or more. Pulmonary hypertension severity was quantified by the hemodynamic parameters transpulmonary gradient, pulmonary vascular resistance, and diastolic pulmonary gradient. Main Outcomes and Measures:The primary outcome was time to all-cause mortality. Secondary outcomes were time to acute hospitalization and cardiovascular hospitalization. Results:The mean (SD) of all study individuals was 65 (38) years. Of 10 023 individuals, 2587 (25.8%) had PH-HFpEF. Mortality was 23.6% at 1 year and 48.2% at 5 years. Cardiac hospitalizations occurred in 28.1% at 1 year and 47.4% at 5 years. The frequency of precapillary PH using clinically defined cut-offs for transpulmonary gradient (>12 mm Hg), pulmonary vascular resistance (3 Woods units), and diastolic pulmonary gradient (≥7 mm Hg) were 12.6%, 8.8%, and 3.5%, respectively. Transpulmonary gradient, pulmonary vascular resistance, and diastolic pressure gradient were predictive of mortality and cardiac hospitalizations. Conclusions and Relevance:In a large cohort referred for invasive hemodynamic assessment, PH-HFpEF was common. Transpulmonary gradient, pulmonary vascular resistance, and diastolic pulmonary gradient are all associated with mortality and cardiac hospitalizations.

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Pulmonary hypertension in patients with heart failure and preserved ejection fraction: differential diagnosis and management.

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Pulmonary hypertension in patients with heart failure and preserved ejection fraction: differential diagnosis and management.

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