Diffuse right ventricular fibrosis in heart failure with preserved ejection fraction and pulmonary hypertension

Ravi B. Patel; Emily Li; Brandon C. Benefield; Stanley A. Swat; Vincenzo B. Polsinelli; James C. Carr; Sanjiv J. Shah; Michael Markl; Jeremy D. Collins; Benjamin H. Freed

doi:10.1002/ehf2.12565

Diffuse right ventricular fibrosis in heart failure with preserved ejection fraction and pulmonary hypertension

Ravi B. Patel, Emily Li, Brandon C. Benefield, Stanley A. Swat, Vincenzo B. Polsinelli, James C. Carr, Sanjiv J. Shah, Michael Markl, Jeremy D. Collins, Benjamin H. Freed^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

Aims: While right ventricular (RV) dysfunction is associated with worse prognosis in co-morbid pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), the mechanisms driving RV dysfunction are unclear. We evaluated the extent and clinical correlates of diffuse RV myocardial fibrosis in PH-HFpEF, as measured by cardiovascular magnetic resonance-derived extracellular volume (ECV). Methods and results: We prospectively enrolled participants with PH-HFpEF (n = 14), pulmonary arterial hypertension (PAH; n = 13), and controls (n = 8). All participants underwent high-resolution cardiovascular magnetic resonance, and case subjects (PH-HFpEF and PAH) additionally underwent right heart catheterization. T1 mapping was performed using high-resolution modified look-locker inversion recovery with a 1 × 1 mm² in-plane resolution. RV free wall T1 values were quantified, and ECV was calculated. Participants with PH-HFpEF were older and carried higher rates of hypertension and obstructive sleep apnoea than those with PAH. While RV ECV was similar between PH-HFpEF and PAH (33.1 ± 8.0 vs. 34.0 ± 4.5%; P = 0.57), total pulmonary resistance was lower in PH-HFpEF compared with PAH [PH-HFpEF: 5.68 WU (4.70, 7.66 WU) vs. PAH: 8.59 WU (8.14, 12.57 WU); P = 0.01]. RV ECV in PH-HFpEF was associated with worse indices of RV structure (RV end-diastolic volume: r = 0.67, P = 0.01) and RV function (RV free wall strain: r = 0.59, P = 0.03) but was not associated with RV afterload (total pulmonary resistance: r = 0.08, P = 0.79). Conversely, there was a strong correlation between RV ECV and RV afterload in PAH (r = 0.57, P = 0.04). Conclusions: Diffuse RV fibrosis, as measured by ECV, is present in PH-HFpEF and is associated with adverse RV structural and functional remodelling but not degree of pulmonary vasculopathy. In PH-HFpEF, diffuse RV fibrosis may occur out of proportion to the degree of RV afterload.

Original language	English (US)
Pages (from-to)	253-263
Number of pages	11
Journal	ESC Heart Failure
Volume	7
Issue number	1
DOIs	https://doi.org/10.1002/ehf2.12565
State	Published - Feb 1 2020

Keywords

Cardiac magnetic resonance
Fibrosis
Heart failure with preserved ejection fraction
Pulmonary hypertension
Right ventricle

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1002/ehf2.12565

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@article{72b4ae0c9727496dad3a4a30529b3700,

title = "Diffuse right ventricular fibrosis in heart failure with preserved ejection fraction and pulmonary hypertension",

abstract = "Aims: While right ventricular (RV) dysfunction is associated with worse prognosis in co-morbid pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), the mechanisms driving RV dysfunction are unclear. We evaluated the extent and clinical correlates of diffuse RV myocardial fibrosis in PH-HFpEF, as measured by cardiovascular magnetic resonance-derived extracellular volume (ECV). Methods and results: We prospectively enrolled participants with PH-HFpEF (n = 14), pulmonary arterial hypertension (PAH; n = 13), and controls (n = 8). All participants underwent high-resolution cardiovascular magnetic resonance, and case subjects (PH-HFpEF and PAH) additionally underwent right heart catheterization. T1 mapping was performed using high-resolution modified look-locker inversion recovery with a 1 × 1 mm2 in-plane resolution. RV free wall T1 values were quantified, and ECV was calculated. Participants with PH-HFpEF were older and carried higher rates of hypertension and obstructive sleep apnoea than those with PAH. While RV ECV was similar between PH-HFpEF and PAH (33.1 ± 8.0 vs. 34.0 ± 4.5%; P = 0.57), total pulmonary resistance was lower in PH-HFpEF compared with PAH [PH-HFpEF: 5.68 WU (4.70, 7.66 WU) vs. PAH: 8.59 WU (8.14, 12.57 WU); P = 0.01]. RV ECV in PH-HFpEF was associated with worse indices of RV structure (RV end-diastolic volume: r = 0.67, P = 0.01) and RV function (RV free wall strain: r = 0.59, P = 0.03) but was not associated with RV afterload (total pulmonary resistance: r = 0.08, P = 0.79). Conversely, there was a strong correlation between RV ECV and RV afterload in PAH (r = 0.57, P = 0.04). Conclusions: Diffuse RV fibrosis, as measured by ECV, is present in PH-HFpEF and is associated with adverse RV structural and functional remodelling but not degree of pulmonary vasculopathy. In PH-HFpEF, diffuse RV fibrosis may occur out of proportion to the degree of RV afterload.",

keywords = "Cardiac magnetic resonance, Fibrosis, Heart failure with preserved ejection fraction, Pulmonary hypertension, Right ventricle",

author = "Patel, {Ravi B.} and Emily Li and Benefield, {Brandon C.} and Swat, {Stanley A.} and Polsinelli, {Vincenzo B.} and Carr, {James C.} and Shah, {Sanjiv J.} and Michael Markl and Collins, {Jeremy D.} and Freed, {Benjamin H.}",

note = "Funding Information: S.J.S. was supported by the National Institutes of Health Grants R01 HL105755, R01 HL127028, and R01 HL140731 and American Heart Association Grants 16SFRN28780016 and 15CVGPSD27260148 and has received research grants from Actelion, AstraZeneca, Corvia, and Novartis and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer‐Ingelheim, Cardiora, Eisai, Ironwood, Merck, Novartis, Sanofi, Tenax, and United Therapeutics. All the remaining authors have nothing to disclose. Funding Information: R.B.P. is supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant (T32HL069771). B.H.F. is supported by Northwestern University Eleanor Wood‐Prince Grant Initiative, Chicago, Illinois, and International Society for Heart & Lung Transplantation/Bayer Pulmonary Hypertension Research Award, Addison, Texas. Funding Information: R.B.P. is supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant (T32HL069771). B.H.F. is supported by Northwestern University Eleanor Wood-Prince Grant Initiative, Chicago, Illinois, and International Society for Heart & Lung Transplantation/Bayer Pulmonary Hypertension Research Award, Addison, Texas. The authors would like to thank Marisol Bello, Rebecca Ditch, and Rachel Davids for their assistance with scanning and blood draws as well as Caitlin Brady for her assistance in recruitment and scheduling. We are indebted to Bruce Spottiswoode, PhD, for his assistance in optimizing the HR-MOLLI sequence and Michael Cuttica, MD, for his help in recruiting subjects with PAH. Publisher Copyright: {\textcopyright} 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology",

year = "2020",

month = feb,

day = "1",

doi = "10.1002/ehf2.12565",

language = "English (US)",

volume = "7",

pages = "253--263",

journal = "ESC heart failure",

issn = "2055-5822",

publisher = "The Heart Failure Association of the European Society of Cardiology",

number = "1",

}

TY - JOUR

T1 - Diffuse right ventricular fibrosis in heart failure with preserved ejection fraction and pulmonary hypertension

AU - Patel, Ravi B.

AU - Li, Emily

AU - Benefield, Brandon C.

AU - Swat, Stanley A.

AU - Polsinelli, Vincenzo B.

AU - Carr, James C.

AU - Shah, Sanjiv J.

AU - Markl, Michael

AU - Collins, Jeremy D.

AU - Freed, Benjamin H.

N1 - Funding Information: S.J.S. was supported by the National Institutes of Health Grants R01 HL105755, R01 HL127028, and R01 HL140731 and American Heart Association Grants 16SFRN28780016 and 15CVGPSD27260148 and has received research grants from Actelion, AstraZeneca, Corvia, and Novartis and consulting fees from Actelion, Amgen, AstraZeneca, Bayer, Boehringer‐Ingelheim, Cardiora, Eisai, Ironwood, Merck, Novartis, Sanofi, Tenax, and United Therapeutics. All the remaining authors have nothing to disclose. Funding Information: R.B.P. is supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant (T32HL069771). B.H.F. is supported by Northwestern University Eleanor Wood‐Prince Grant Initiative, Chicago, Illinois, and International Society for Heart & Lung Transplantation/Bayer Pulmonary Hypertension Research Award, Addison, Texas. Funding Information: R.B.P. is supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant (T32HL069771). B.H.F. is supported by Northwestern University Eleanor Wood-Prince Grant Initiative, Chicago, Illinois, and International Society for Heart & Lung Transplantation/Bayer Pulmonary Hypertension Research Award, Addison, Texas. The authors would like to thank Marisol Bello, Rebecca Ditch, and Rachel Davids for their assistance with scanning and blood draws as well as Caitlin Brady for her assistance in recruitment and scheduling. We are indebted to Bruce Spottiswoode, PhD, for his assistance in optimizing the HR-MOLLI sequence and Michael Cuttica, MD, for his help in recruiting subjects with PAH. Publisher Copyright: © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology

PY - 2020/2/1

Y1 - 2020/2/1

N2 - Aims: While right ventricular (RV) dysfunction is associated with worse prognosis in co-morbid pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), the mechanisms driving RV dysfunction are unclear. We evaluated the extent and clinical correlates of diffuse RV myocardial fibrosis in PH-HFpEF, as measured by cardiovascular magnetic resonance-derived extracellular volume (ECV). Methods and results: We prospectively enrolled participants with PH-HFpEF (n = 14), pulmonary arterial hypertension (PAH; n = 13), and controls (n = 8). All participants underwent high-resolution cardiovascular magnetic resonance, and case subjects (PH-HFpEF and PAH) additionally underwent right heart catheterization. T1 mapping was performed using high-resolution modified look-locker inversion recovery with a 1 × 1 mm2 in-plane resolution. RV free wall T1 values were quantified, and ECV was calculated. Participants with PH-HFpEF were older and carried higher rates of hypertension and obstructive sleep apnoea than those with PAH. While RV ECV was similar between PH-HFpEF and PAH (33.1 ± 8.0 vs. 34.0 ± 4.5%; P = 0.57), total pulmonary resistance was lower in PH-HFpEF compared with PAH [PH-HFpEF: 5.68 WU (4.70, 7.66 WU) vs. PAH: 8.59 WU (8.14, 12.57 WU); P = 0.01]. RV ECV in PH-HFpEF was associated with worse indices of RV structure (RV end-diastolic volume: r = 0.67, P = 0.01) and RV function (RV free wall strain: r = 0.59, P = 0.03) but was not associated with RV afterload (total pulmonary resistance: r = 0.08, P = 0.79). Conversely, there was a strong correlation between RV ECV and RV afterload in PAH (r = 0.57, P = 0.04). Conclusions: Diffuse RV fibrosis, as measured by ECV, is present in PH-HFpEF and is associated with adverse RV structural and functional remodelling but not degree of pulmonary vasculopathy. In PH-HFpEF, diffuse RV fibrosis may occur out of proportion to the degree of RV afterload.

AB - Aims: While right ventricular (RV) dysfunction is associated with worse prognosis in co-morbid pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF), the mechanisms driving RV dysfunction are unclear. We evaluated the extent and clinical correlates of diffuse RV myocardial fibrosis in PH-HFpEF, as measured by cardiovascular magnetic resonance-derived extracellular volume (ECV). Methods and results: We prospectively enrolled participants with PH-HFpEF (n = 14), pulmonary arterial hypertension (PAH; n = 13), and controls (n = 8). All participants underwent high-resolution cardiovascular magnetic resonance, and case subjects (PH-HFpEF and PAH) additionally underwent right heart catheterization. T1 mapping was performed using high-resolution modified look-locker inversion recovery with a 1 × 1 mm2 in-plane resolution. RV free wall T1 values were quantified, and ECV was calculated. Participants with PH-HFpEF were older and carried higher rates of hypertension and obstructive sleep apnoea than those with PAH. While RV ECV was similar between PH-HFpEF and PAH (33.1 ± 8.0 vs. 34.0 ± 4.5%; P = 0.57), total pulmonary resistance was lower in PH-HFpEF compared with PAH [PH-HFpEF: 5.68 WU (4.70, 7.66 WU) vs. PAH: 8.59 WU (8.14, 12.57 WU); P = 0.01]. RV ECV in PH-HFpEF was associated with worse indices of RV structure (RV end-diastolic volume: r = 0.67, P = 0.01) and RV function (RV free wall strain: r = 0.59, P = 0.03) but was not associated with RV afterload (total pulmonary resistance: r = 0.08, P = 0.79). Conversely, there was a strong correlation between RV ECV and RV afterload in PAH (r = 0.57, P = 0.04). Conclusions: Diffuse RV fibrosis, as measured by ECV, is present in PH-HFpEF and is associated with adverse RV structural and functional remodelling but not degree of pulmonary vasculopathy. In PH-HFpEF, diffuse RV fibrosis may occur out of proportion to the degree of RV afterload.

KW - Cardiac magnetic resonance

KW - Fibrosis

KW - Heart failure with preserved ejection fraction

KW - Pulmonary hypertension

KW - Right ventricle

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Diffuse right ventricular fibrosis in heart failure with preserved ejection fraction and pulmonary hypertension

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