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 J.; Konik, Ewa; DuBrock, Hilary M.; Borlaug, Barry A.; Frantz, Robert P.; Jenkins, Sarah M.; Redfield, Margaret M.

doi:10.1161/circulationaha.117.031608

Cited by 261 publications

(200 citation statements)

References 40 publications

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“…; Guazzi & Naeije, ; Fayyaz et al . ). Particularly noteworthy, using urokinase plasminogen activator receptor (uPAR) as an anatomical venous marker, a recent study found that intima, media and adventitia in veins and arteries were significantly remodelled to similar degrees in patients with PH‐LHD and in rats with aortic banding (Hunt et al .…”

Section: Definitions Classification Of Subtypes and Diagnostic Factomentioning

confidence: 97%

“…; Fayyaz et al . ). In a recent study, venous and small vessel intimal thickening were found to be more severe than arterial intimal thickening in patients with PH‐HFpEF (Fayyaz et al .…”

Section: Definitions Classification Of Subtypes and Diagnostic Factomentioning

confidence: 97%

“…In a recent study, venous and small vessel intimal thickening were found to be more severe than arterial intimal thickening in patients with PH‐HFpEF (Fayyaz et al . ). Collectively, the above attributes describe the patients with CpcPH‐HFpEF – patients whose PH involves remodelling of alveolar–capillary and pre‐capillary small pulmonary arteries in addition to the passive increase in pulmonary artery pressure.…”

Section: Definitions Classification Of Subtypes and Diagnostic Factomentioning

confidence: 97%

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Insights into the pulmonary vascular complications of heart failure with preserved ejection fraction

Lai

Wang

Gladwin

2018

The Journal of Physiology

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Pulmonary hypertension in the setting of heart failure with preserved ejection fraction (PH-HFpEF) is a growing public health problem that is increasing in prevalence. While PH-HFpEF is defined by a high mean pulmonary artery pressure, high left ventricular end-diastolic pressure and a normal ejection fraction, some HFpEF patients develop PH in the presence of pulmonary Yen-Chun (Charly) Lai is an Assistant Professor at Indiana University. Her lab focuses primarily on investigating pathogenesis and development of alternative therapies for effective treatment of cardiopulmonary diseases, with the particular emphasis of metabolic syndrome, pulmonary hypertension and heart failure with preserved ejection fraction. Mark Gladwin is a Jack D. Myers Professor and Chair at University of Pittsburgh. He is recognized internationally as an expert in pulmonary hypertension, having described the pathobiology and clinical characteristics of pulmonary hypertension in patients with sickle cell disease and other chronic hereditary and acquired haemolytic diseases. He served on the Dana Point Pulmonary Hypertension Classification Committee and co-authored the report. He served on the NHLBI advisory committee to develop the 'Strategic Plan for Lung Vascular Research' . He has authored more than 10 textbook chapters on pulmonary vascular disease and has published over 100 papers on the topic of pulmonary hypertension alone. vascular remodelling with a high transpulmonary pressure gradient or pulmonary vascular resistance. Ageing, increased left atrial pressure and stiffness, mitral regurgitation, as well as features of metabolic syndrome, which include obesity, diabetes and hypertension, are recognized as risk factors for PH-HFpEF. Qualitative studies have documented that patients with PH-HFpEF develop more severe symptoms than those with HFpEF and are associated with more significant exercise intolerance, frequent hospitalizations, right heart failure and reduced survival. Currently, there are no effective therapies for PH-HFpEF, although a number of candidate drugs are being evaluated, including soluble guanylate cyclase stimulators, phosphodiesterase type 5 inhibitors, sodium nitrite and endothelin receptor antagonists. In this review we attempt to provide an updated overview of recent findings pertaining to the pulmonary vascular complications in HFpEF in terms of clinical definitions, epidemiology and pathophysiology. Mechanisms leading to pulmonary vascular remodelling in HFpEF, a summary of pre-clinical models of HFpEF and PH-HFpEF, and new candidate therapeutic strategies for the treatment of PH-HFpEF are summarized. Abstract figure legendPrevalence and pathophysiology of pulmonary hypertension (PH) in patients with heart failure with preserved ejection fraction (HFpEF). LA, left atrium; LV, left ventricle; LVEDP, left ventricular end-diastolic pressure; PA, pulmonary artery/arterial; PV, pulmonary vein; PVR, pulmonary vascular resistance; RV, right ventricle. Definitions, classification of subtypes and diagnostic factors of...

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Section: Definitions Classification Of Subtypes and Diagnostic Factomentioning

confidence: 97%

“…; Fayyaz et al . ). In a recent study, venous and small vessel intimal thickening were found to be more severe than arterial intimal thickening in patients with PH‐HFpEF (Fayyaz et al .…”

Section: Definitions Classification Of Subtypes and Diagnostic Factomentioning

confidence: 97%

Section: Definitions Classification Of Subtypes and Diagnostic Factomentioning

confidence: 97%

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Insights into the pulmonary vascular complications of heart failure with preserved ejection fraction

Lai

Wang

Gladwin

2018

The Journal of Physiology

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“…Post-capillary PH and mixed pre-post-capillary PH feature the involvement of post-capillary pulmonary vessels caused by parenchymal destruction, inflammatory processes and chronic elevation of post-capillary pressure as a consequence of impaired left heart function [23]. Additionally, hemolysis and decompartmentalisation of haemoglobin play a pivotal role in the emergence of PH in WHO group 5 patients suffering from haemoglobinopathies associated with hemolytic anaemia [24].…”

Section: Pulmonary Hypertensionmentioning

confidence: 99%

Anaemia, iron homeostasis and pulmonary hypertension: a review

et al. 2020

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Anaemia is a highly prevalent condition, which negatively impacts on patients' cardiovascular performance and quality of life. Anaemia is mainly caused by disturbances of iron homeostasis. While absolute iron deficiency mostly as a consequence of chronic blood loss or insufficient dietary iron absorption results in the emergence of iron deficiency anaemia, inflammation-driven iron retention in innate immune cells and blockade of iron absorption leads to the development of anaemia of chronic disease. Both, iron deficiency and anaemia have been linked to the clinical course of pulmonary hypertension. Various mechanistic links between iron homeostasis, anaemia, and pulmonary hypertension have been described and current treatment guidelines suggest regular iron status assessment and the implementation of iron supplementation strategies in these patients. The pathophysiology, diagnostic assessment as well as current and future treatment options concerning iron deficiency with or without anaemia in individuals suffering from pulmonary hypertension are discussed within this review.

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“…Thus, it remains uncertain whether VEGF-D mediated VEGFR-2 signalling impacts cardiac remodelling and/or facilitates favourable cardiac angiogenesis during HF. PH-LHD may ultimately lead to pulmonary vascular remodelling [6], which may be similar to, but not precisely the same as that observed in PAH patients [15,36]. In the context of in vivo research, a model of severe angio-obliterative PAH displayed that expressions of VEGF-D and VEGFR-3 were elevated in lung tissue and inhibition of VEGFR-3 signalling prevented angio-obliteration, but did not reverse already existing vascular remodelling [37].…”

Section: Tablementioning

confidence: 89%

Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics

Ahmed

Säleby

et al. 2020

Heart Vessels

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Receptor tyrosine kinases (RTKs) are implicated in cardiovascular growth and remodelling. We aimed to identify the plasma levels of RTKs and related proteins and their association with haemodynamic alterations in heart failure (HF) and related pulmonary hypertension (PH) following heart transplantation (HT). Using proximity extension assay, 28 RTKs and related proteins were analysed in plasma from 20 healthy controls and 26 HF patients before and 1-year after HT. In end-stage HF, out of 28 RTKs, plasma vascular endothelial growth factor-D (VEGF-D) and human epidermal growth factor-4 (HER4) were elevated compared to controls (p < 0.001), but decreased (p < 0.0001) and normalised after HT. Following HT, plasma changes (Δ) of VEGF-D correlated with Δmean pulmonary artery pressure (r s = 0.65, p = 0.00049), Δpulmonary artery wedge pressure (r s = 0.72, p < 0.0001), Δpulmonary arterial compliance (PAC) (r s = − 0.52, p = 0.0083) and Δpulmonary vascular resistance (PVR) (r s = 0.58, p = 0.0032). ΔHER4 correlated with Δmean right atrial pressure (r s = 0.51, p = 0.012), ΔNT-proBNP (r s = 0.48, p = 0.016) and Δcardiac index (r s = − 0.56, p = 0.0044). In HF patients following HT, normalisation of VEGF-D reflected reversal of passive pulmonary congestion and restored PAC and PVR; whereas the normalisation of HER4 reflected decreased volume overload and improved cardiac function. The precise function of these proteins, their potential clinical use and pathophysiological relation in HF and related PH remain to be elucidated.

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Global Pulmonary Vascular Remodeling in Pulmonary Hypertension Associated With Heart Failure and Preserved or Reduced Ejection Fraction

Abstract: 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.

Cited by 261 publications

References 40 publications

Insights into the pulmonary vascular complications of heart failure with preserved ejection fraction

Insights into the pulmonary vascular complications of heart failure with preserved ejection fraction

Anaemia, iron homeostasis and pulmonary hypertension: a review

Elevated plasma tyrosine kinases VEGF-D and HER4 in heart failure patients decrease after heart transplantation in association with improved haemodynamics

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