Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction

Ahmed U. Fayyaz, William D. Edwards, Joseph Maleszewski, Ewa A. Konik, Hilary M. DuBrock, Barry A Borlaug, Robert Frantz, Sarah M. Jenkins, Margaret May Redfield

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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 H F. 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.

Original languageEnglish (US)
Pages (from-to)1796-1810
Number of pages15
JournalCirculation
Volume137
Issue number17
DOIs
StatePublished - Jan 1 2018

Fingerprint

Pulmonary Hypertension
Heart Failure
Lung
Pulmonary Artery
Blood Pressure
Tunica Intima
Vascular Remodeling
Arteries
Veins
Pulmonary Veno-Occlusive Disease
Right Ventricular Dysfunction
Lung Volume Measurements
Pulmonary Veins
Patient Rights
Cardiac Catheterization
Autopsy

Keywords

  • Diffusing capacity of the lungs for carbon monoxide
  • Heart failure
  • Heart failure with preserved ejection fraction
  • Pulmonary function
  • Pulmonary hypertension
  • Right ventricle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction. / Fayyaz, Ahmed U.; Edwards, William D.; Maleszewski, Joseph; Konik, Ewa A.; DuBrock, Hilary M.; Borlaug, Barry A; Frantz, Robert; Jenkins, Sarah M.; Redfield, Margaret May.

In: Circulation, Vol. 137, No. 17, 01.01.2018, p. 1796-1810.

Research output: Contribution to journalArticle

@article{d845ad2864ac46d5b8d2b3ea9b1f9749,
title = "Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction",
abstract = "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 H F. 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.",
keywords = "Diffusing capacity of the lungs for carbon monoxide, Heart failure, Heart failure with preserved ejection fraction, Pulmonary function, Pulmonary hypertension, Right ventricle",
author = "Fayyaz, {Ahmed U.} and Edwards, {William D.} and Joseph Maleszewski and Konik, {Ewa A.} and DuBrock, {Hilary M.} and Borlaug, {Barry A} and Robert Frantz and Jenkins, {Sarah M.} and Redfield, {Margaret May}",
year = "2018",
month = "1",
day = "1",
doi = "10.1161/CIRCULATIONAHA.117.031608",
language = "English (US)",
volume = "137",
pages = "1796--1810",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "17",

}

TY - JOUR

T1 - Global pulmonary vascular remodeling in pulmonary hypertension associated with heart failure and preserved or reduced ejection fraction

AU - Fayyaz, Ahmed U.

AU - Edwards, William D.

AU - Maleszewski, Joseph

AU - Konik, Ewa A.

AU - DuBrock, Hilary M.

AU - Borlaug, Barry A

AU - Frantz, Robert

AU - Jenkins, Sarah M.

AU - Redfield, Margaret May

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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 H F. 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.

AB - 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 H F. 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.

KW - Diffusing capacity of the lungs for carbon monoxide

KW - Heart failure

KW - Heart failure with preserved ejection fraction

KW - Pulmonary function

KW - Pulmonary hypertension

KW - Right ventricle

UR - http://www.scopus.com/inward/record.url?scp=85064251676&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064251676&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.117.031608

DO - 10.1161/CIRCULATIONAHA.117.031608

M3 - Article

C2 - 29246894

AN - SCOPUS:85064251676

VL - 137

SP - 1796

EP - 1810

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 17

ER -