State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure Treatment

Pulmonary hypertension (PH) is broadly defined as a mean pulmonary arterial pressure (mPAP) exceeding 20 mm Hg at rest. Pulmonary arterial hypertension (PAH) is a specific subset of PH characterized by a normal pulmonary arterial wedge pressure (PAWP), combined with elevated mPAP and increased pulmo...

Full description

Saved in:
Bibliographic Details
Main Authors: Melika Shafeghat, Yasmin Raza, Roberta Catania, Amir Ali Rahsepar, Blair Tilkens, Michael J. Cuttica, Benjamin H. Freed, Jingbo Dai, You-Yang Zhao, James C. Carr
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/13/7/1773
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849407454594465792
author Melika Shafeghat
Yasmin Raza
Roberta Catania
Amir Ali Rahsepar
Blair Tilkens
Michael J. Cuttica
Benjamin H. Freed
Jingbo Dai
You-Yang Zhao
James C. Carr
author_facet Melika Shafeghat
Yasmin Raza
Roberta Catania
Amir Ali Rahsepar
Blair Tilkens
Michael J. Cuttica
Benjamin H. Freed
Jingbo Dai
You-Yang Zhao
James C. Carr
author_sort Melika Shafeghat
collection DOAJ
description Pulmonary hypertension (PH) is broadly defined as a mean pulmonary arterial pressure (mPAP) exceeding 20 mm Hg at rest. Pulmonary arterial hypertension (PAH) is a specific subset of PH characterized by a normal pulmonary arterial wedge pressure (PAWP), combined with elevated mPAP and increased pulmonary vascular resistance (PVR), without other causes of pre-capillary hypertension such as lung diseases or chronic thromboembolic pulmonary hypertension. The majority of PAH cases are idiopathic; other common etiologies include connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. To a lesser extent, genetic and familial forms of PAH can also occur. The pathophysiology of PAH involves the following four primary pathways: nitric oxide, endothelin-1, prostacyclin, and activin/bone morphogenetic protein (BMP). Dysregulation of these pathways leads to a progressive vasculopathy marked by vasoconstriction, vascular proliferation, elevated right heart afterload, and ultimately right-sided heart failure. Diagnosing PAH is challenging and often occurs at advanced stages. The gold standard for diagnosis remains invasive right heart catheterization. Along with invasive hemodynamic measurements, several noninvasive imaging modalities such as echocardiography and ventilation-perfusion scanning are key adjunct techniques. Also, recent advancements in cardiac magnetic resonance (CMR) have opened a new era for PAH management. Additionally, CMR and echocardiography not only enable diagnosis but also aid in evaluating disease severity and monitoring treatment responses. Current PAH treatments focus on targeting molecular pathways, reducing inflammation, and inhibiting right-sided heart failure. Integrating imaging with basic science techniques is crucial for enhanced patient diagnosis, and precision medicine is emerging as a key strategy in PAH management. Additionally, the incorporation of artificial intelligence into both molecular and imaging approaches holds significant potential. There is a growing need to integrate new imaging modalities with high resolution and reduced radiation exposure into clinical practice. In this review, we discuss the molecular pathways involved in PAH, the imaging modalities utilized for diagnosis and monitoring, and current targeted therapies. Advances in molecular understanding and imaging technologies, coupled with precision medicine, could hold promise in improving patient outcomes and revolutionizing the management of PAH patients.
format Article
id doaj-art-9eb476ad894340449b41b5689cb1e2f8
institution Kabale University
issn 2227-9059
language English
publishDate 2025-07-01
publisher MDPI AG
record_format Article
series Biomedicines
spelling doaj-art-9eb476ad894340449b41b5689cb1e2f82025-08-20T03:36:03ZengMDPI AGBiomedicines2227-90592025-07-01137177310.3390/biomedicines13071773State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure TreatmentMelika Shafeghat0Yasmin Raza1Roberta Catania2Amir Ali Rahsepar3Blair Tilkens4Michael J. Cuttica5Benjamin H. Freed6Jingbo Dai7You-Yang Zhao8James C. Carr9Radiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USACardiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USARadiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USARadiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USACardiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USAPulmonary and Clinical Care, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USACardiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USAProgram for Lung and Vascular Biology, and Section for Injury Repair and Regeneration Research, Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USAProgram for Lung and Vascular Biology, and Section for Injury Repair and Regeneration Research, Stanley Manne Children’s Research Institute, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL 60611, USARadiology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USAPulmonary hypertension (PH) is broadly defined as a mean pulmonary arterial pressure (mPAP) exceeding 20 mm Hg at rest. Pulmonary arterial hypertension (PAH) is a specific subset of PH characterized by a normal pulmonary arterial wedge pressure (PAWP), combined with elevated mPAP and increased pulmonary vascular resistance (PVR), without other causes of pre-capillary hypertension such as lung diseases or chronic thromboembolic pulmonary hypertension. The majority of PAH cases are idiopathic; other common etiologies include connective tissue disease-associated PAH, congenital heart disease, and portopulmonary hypertension. To a lesser extent, genetic and familial forms of PAH can also occur. The pathophysiology of PAH involves the following four primary pathways: nitric oxide, endothelin-1, prostacyclin, and activin/bone morphogenetic protein (BMP). Dysregulation of these pathways leads to a progressive vasculopathy marked by vasoconstriction, vascular proliferation, elevated right heart afterload, and ultimately right-sided heart failure. Diagnosing PAH is challenging and often occurs at advanced stages. The gold standard for diagnosis remains invasive right heart catheterization. Along with invasive hemodynamic measurements, several noninvasive imaging modalities such as echocardiography and ventilation-perfusion scanning are key adjunct techniques. Also, recent advancements in cardiac magnetic resonance (CMR) have opened a new era for PAH management. Additionally, CMR and echocardiography not only enable diagnosis but also aid in evaluating disease severity and monitoring treatment responses. Current PAH treatments focus on targeting molecular pathways, reducing inflammation, and inhibiting right-sided heart failure. Integrating imaging with basic science techniques is crucial for enhanced patient diagnosis, and precision medicine is emerging as a key strategy in PAH management. Additionally, the incorporation of artificial intelligence into both molecular and imaging approaches holds significant potential. There is a growing need to integrate new imaging modalities with high resolution and reduced radiation exposure into clinical practice. In this review, we discuss the molecular pathways involved in PAH, the imaging modalities utilized for diagnosis and monitoring, and current targeted therapies. Advances in molecular understanding and imaging technologies, coupled with precision medicine, could hold promise in improving patient outcomes and revolutionizing the management of PAH patients.https://www.mdpi.com/2227-9059/13/7/1773pulmonary arterial hypertensionheart failureBMPR2magnetic resonance imaging
spellingShingle Melika Shafeghat
Yasmin Raza
Roberta Catania
Amir Ali Rahsepar
Blair Tilkens
Michael J. Cuttica
Benjamin H. Freed
Jingbo Dai
You-Yang Zhao
James C. Carr
State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure Treatment
Biomedicines
pulmonary arterial hypertension
heart failure
BMPR2
magnetic resonance imaging
title State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure Treatment
title_full State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure Treatment
title_fullStr State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure Treatment
title_full_unstemmed State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure Treatment
title_short State of the Art in Pulmonary Arterial Hypertension: Molecular Basis, Imaging Modalities, and Right Heart Failure Treatment
title_sort state of the art in pulmonary arterial hypertension molecular basis imaging modalities and right heart failure treatment
topic pulmonary arterial hypertension
heart failure
BMPR2
magnetic resonance imaging
url https://www.mdpi.com/2227-9059/13/7/1773
work_keys_str_mv AT melikashafeghat stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment
AT yasminraza stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment
AT robertacatania stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment
AT amiralirahsepar stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment
AT blairtilkens stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment
AT michaeljcuttica stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment
AT benjaminhfreed stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment
AT jingbodai stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment
AT youyangzhao stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment
AT jamesccarr stateoftheartinpulmonaryarterialhypertensionmolecularbasisimagingmodalitiesandrightheartfailuretreatment