Clinical implications of idiopathic pulmonary arterial hypertension phenotypes defined by cluster analysis.


Journal

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation
ISSN: 1557-3117
Titre abrégé: J Heart Lung Transplant
Pays: United States
ID NLM: 9102703

Informations de publication

Date de publication:
04 2020
Historique:
received: 14 07 2019
revised: 22 11 2019
accepted: 29 12 2019
pubmed: 18 2 2020
medline: 7 1 2021
entrez: 17 2 2020
Statut: ppublish

Résumé

>Despite advances in drug development, life expectancy in idiopathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient outcome is still unfavorable. The aim of this study was to apply cluster analysis to improve phenotyping of patients with IPAH and analyze long-term clinical outcome of derived clusters. Patients with IPAH from 2 referral centers (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Patients were classified according to cluster analysis and followed for clinical worsening occurrence. The cluster analysis identified 4 IPAH phenotypes. Cluster 1 was characterized by young patients, mild pulmonary hypertension (PH), mild right ventricular (RV) dilation and high oxygen (O Cluster analysis of clinical variables identified 4 distinct phenotypes of IPAH. Our findings underscore the high degree of disease heterogeneity that exists within patients with IPAH and the need for advanced clinical testing to define phenotypes to improve treatment strategy decision-making. CONDENSED ABSTRACT Idiopathic pulmonary arterial hypertension (IPAH) characterization is based on criteria that may not adequately capture disease heterogeneity. The aim of this study was to apply cluster analysis to improve phenotyping of IPAH. Patients with IPAH (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Within the umbrella category of IPAH, it was the combination of mean pulmonary arterial pressure, right ventricular size, and oxygen pulse that further stratified patients into novel IPAH phenotypes that significantly associate with clinical worsening. These findings underscore the need for novel multidimensional IPAH phenotyping for improved patient care and trial quality.

Sections du résumé

BACKGROUND
>Despite advances in drug development, life expectancy in idiopathic pulmonary arterial hypertension (IPAH) remains unacceptable. Contemporary IPAH characterization is based on criteria that may not adequately capture disease heterogeneity and may be proposed as a possible explanation for why patient outcome is still unfavorable. The aim of this study was to apply cluster analysis to improve phenotyping of patients with IPAH and analyze long-term clinical outcome of derived clusters.
METHODS
Patients with IPAH from 2 referral centers (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Patients were classified according to cluster analysis and followed for clinical worsening occurrence.
RESULTS
The cluster analysis identified 4 IPAH phenotypes. Cluster 1 was characterized by young patients, mild pulmonary hypertension (PH), mild right ventricular (RV) dilation and high oxygen (O
CONCLUSIONS
Cluster analysis of clinical variables identified 4 distinct phenotypes of IPAH. Our findings underscore the high degree of disease heterogeneity that exists within patients with IPAH and the need for advanced clinical testing to define phenotypes to improve treatment strategy decision-making. CONDENSED ABSTRACT Idiopathic pulmonary arterial hypertension (IPAH) characterization is based on criteria that may not adequately capture disease heterogeneity. The aim of this study was to apply cluster analysis to improve phenotyping of IPAH. Patients with IPAH (n = 252) were evaluated with clinical, hemodynamic, and echocardiographic assessment and cardiopulmonary exercise test. Within the umbrella category of IPAH, it was the combination of mean pulmonary arterial pressure, right ventricular size, and oxygen pulse that further stratified patients into novel IPAH phenotypes that significantly associate with clinical worsening. These findings underscore the need for novel multidimensional IPAH phenotyping for improved patient care and trial quality.

Identifiants

pubmed: 32061507
pii: S1053-2498(20)30015-2
doi: 10.1016/j.healun.2019.12.012
pii:
doi:

Types de publication

Journal Article Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

310-320

Informations de copyright

Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Références

Hum Pathol. 2003 Aug;34(8):743-8
pubmed: 14506633
Cell Death Differ. 2012 Jan;19(1):75-86
pubmed: 22075985
Genes Dev. 2013 Aug 1;27(15):1640-9
pubmed: 23913919
Cell Death Dis. 2018 Sep 5;9(9):904
pubmed: 30185776

Auteurs

Roberto Badagliacca (R)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy. Electronic address: roberto.badagliacca@uniroma1.it.

Franz Rischard (F)

Department of Medicine, Divisions of Pulmonary and Critical Care, University of Arizona, Tucson, Arizona; Department of Medicine, Divisions of Cardiology, University of Arizona, Tucson, Arizona.

Silvia Papa (S)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Saad Kubba (S)

Department of Medicine, Divisions of Translational and Regenerative Medicine, University of Arizona, Tucson, Arizona.

Rebecca Vanderpool (R)

Department of Medicine, Divisions of Cardiology, University of Arizona, Tucson, Arizona.

Jason X-J Yuan (JX)

Department of Medicine, Divisions of Cardiology, University of Arizona, Tucson, Arizona.

Joe G N Garcia (JGN)

Department of Medicine, Divisions of Pulmonary and Critical Care, University of Arizona, Tucson, Arizona.

Sophia Airhart (S)

Department of Medicine, Divisions of Translational and Regenerative Medicine, University of Arizona, Tucson, Arizona.

Roberto Poscia (R)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Beatrice Pezzuto (B)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Giovanna Manzi (G)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Cristiano Miotti (C)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Federico Luongo (F)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Gianmarco Scoccia (G)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Susanna Sciomer (S)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Roberto Torre (R)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Francesco Fedele (F)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

Carmine Dario Vizza (CD)

Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy.

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