Roberto Badagliacca1, Franz Rischard2, Silvia Papa3, Saad Kubba4, Rebecca Vanderpool5, Jason X-J Yuan5, Joe G N Garcia6, Sophia Airhart4, Roberto Poscia3, Beatrice Pezzuto3, Giovanna Manzi3, Cristiano Miotti3, Federico Luongo3, Gianmarco Scoccia3, Susanna Sciomer3, Roberto Torre3, Francesco Fedele3, Carmine Dario Vizza3. 1. Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy. Electronic address: roberto.badagliacca@uniroma1.it. 2. 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. 3. Department of Cardiovascular and Respiratory Science, Sapienza University of Rome, Rome, Italy. 4. Department of Medicine, Divisions of Translational and Regenerative Medicine, University of Arizona, Tucson, Arizona. 5. Department of Medicine, Divisions of Cardiology, University of Arizona, Tucson, Arizona. 6. Department of Medicine, Divisions of Pulmonary and Critical Care, University of Arizona, Tucson, Arizona.
Abstract
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 (O2) pulse; Cluster 2 by severe PH and RV dilation and high O2 pulse; and Cluster 3 by male patients, severe PH and RV dilation, and low O2 pulse. Cluster 4 patients were older and overweight, with mild PH and RV dilation and low O2 pulse. After a mean follow-up of 995 ± 623 days, 123 (48.8%) patients had clinical worsening. Cluster 1 patients presented the best prognosis, whereas Cluster 3 had the highest rates of clinical worsening. Compared with Cluster 1, risk of clinical worsening ranged from 4.12 (confidence interval [CI] 1.43-11.92; p = 0.009) for Cluster 4 to 7.38 (CI 2.80-19.40) for Cluster 2 and 13.8 (CI 5.60-34.0; p = 0.0001) for Cluster 3. 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.
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 (O2) pulse; Cluster 2 by severe PH and RV dilation and high O2 pulse; and Cluster 3 by male patients, severe PH and RV dilation, and low O2 pulse. Cluster 4 patients were older and overweight, with mild PH and RV dilation and low O2 pulse. After a mean follow-up of 995 ± 623 days, 123 (48.8%) patients had clinical worsening. Cluster 1 patients presented the best prognosis, whereas Cluster 3 had the highest rates of clinical worsening. Compared with Cluster 1, risk of clinical worsening ranged from 4.12 (confidence interval [CI] 1.43-11.92; p = 0.009) for Cluster 4 to 7.38 (CI 2.80-19.40) for Cluster 2 and 13.8 (CI 5.60-34.0; p = 0.0001) for Cluster 3. 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.
Authors: Teri J Franks; Pek Y Chong; Paul Chui; Jeffrey R Galvin; Raina M Lourens; Ann H Reid; Elena Selbs; Col Peter L McEvoy; Col Dennis L Hayden; Junya Fukuoka; Jeffery K Taubenberger; William D Travis Journal: Hum Pathol Date: 2003-08 Impact factor: 3.466
Authors: Rebecca R Vanderpool; Kendall S Hunter; Michael Insel; Joe G N Garcia; Edward J Bedrick; Ryan J Tedford; Franz P Rischard Journal: Chest Date: 2021-10-09 Impact factor: 10.262
Authors: Beate Stubbe; Hans-Jürgen Seyfarth; Janina Kleymann; Michael Halank; Hussam Al Ghorani; Anne Obst; Susanna Desole; Ralf Ewert; Christian F Opitz Journal: BMC Pulm Med Date: 2021-04-21 Impact factor: 3.317