TY - JOUR
T1 - Advanced hemodynamic and cluster analysis for identifying novel RV function subphenotypes in patients with pulmonary hypertension
AU - Janowski, Alexandra M.
AU - Ravellette, Keeley S.
AU - Insel, Michael
AU - Garcia, Joe G.N.
AU - Rischard, Franz P.
AU - Vanderpool, Rebecca R.
N1 - Publisher Copyright:
© 2024 International Society for the Heart and Lung Transplantation
PY - 2024/5
Y1 - 2024/5
N2 - Background: Quantifying right ventricular (RV) function is important to describe the pathophysiology of in pulmonary hypertension (PH). Current phenotyping strategies in PH rely on few invasive hemodynamic parameters to quantify RV dysfunction severity. The aim of this study was to identify novel RV phenotypes using unsupervised clustering methods on advanced hemodynamic features of RV function. Methods: Participants were identified from the University of Arizona Pulmonary Hypertension Registry (n = 190). RV-pulmonary artery coupling (Ees/Ea), RV systolic (Ees), and diastolic function (Eed) were quantified from stored RV pressure waveforms. Consensus clustering analysis with bootstrapping was used to identify the optimal clustering method. Pearson correlation analysis was used to reduce collinearity between variables. RV cluster subphenotypes were characterized using clinical data and compared to pulmonary vascular resistance (PVR) quintiles. Results: Five distinct RV clusters (C1-C5) with distinct RV subphenotypes were identified using k-medoids with a Pearson distance matrix. Clusters 1 and 2 both have low diastolic stiffness (Eed) and afterload (Ea) but RV-PA coupling (Ees/Ea) is decreased in C2. Intermediate cluster (C3) has a similar Ees/Ea as C2 but with higher PA pressure and afterload. Clusters C4 and C5 have increased Eed and Ea but C5 has a significant decrease in Ees/Ea. Cardiac output was high in C3 distinct from the other clusters. In the PVR quintiles, contractility increased and stroke volume decreased as a function of increased afterload. World Symposium PH classifications were distributed across clusters and PVR quintiles. Conclusions: RV-centric phenotyping offers an opportunity for a more precise-medicine-based management approach.
AB - Background: Quantifying right ventricular (RV) function is important to describe the pathophysiology of in pulmonary hypertension (PH). Current phenotyping strategies in PH rely on few invasive hemodynamic parameters to quantify RV dysfunction severity. The aim of this study was to identify novel RV phenotypes using unsupervised clustering methods on advanced hemodynamic features of RV function. Methods: Participants were identified from the University of Arizona Pulmonary Hypertension Registry (n = 190). RV-pulmonary artery coupling (Ees/Ea), RV systolic (Ees), and diastolic function (Eed) were quantified from stored RV pressure waveforms. Consensus clustering analysis with bootstrapping was used to identify the optimal clustering method. Pearson correlation analysis was used to reduce collinearity between variables. RV cluster subphenotypes were characterized using clinical data and compared to pulmonary vascular resistance (PVR) quintiles. Results: Five distinct RV clusters (C1-C5) with distinct RV subphenotypes were identified using k-medoids with a Pearson distance matrix. Clusters 1 and 2 both have low diastolic stiffness (Eed) and afterload (Ea) but RV-PA coupling (Ees/Ea) is decreased in C2. Intermediate cluster (C3) has a similar Ees/Ea as C2 but with higher PA pressure and afterload. Clusters C4 and C5 have increased Eed and Ea but C5 has a significant decrease in Ees/Ea. Cardiac output was high in C3 distinct from the other clusters. In the PVR quintiles, contractility increased and stroke volume decreased as a function of increased afterload. World Symposium PH classifications were distributed across clusters and PVR quintiles. Conclusions: RV-centric phenotyping offers an opportunity for a more precise-medicine-based management approach.
KW - RV function
KW - RV subphenotypes
KW - cardiopulmonary hemodynamics
KW - machine learning
KW - pressure-volume loop
KW - pulmonary hypertension
KW - right heart failure
UR - http://www.scopus.com/inward/record.url?scp=85184246079&partnerID=8YFLogxK
U2 - 10.1016/j.healun.2023.12.009
DO - 10.1016/j.healun.2023.12.009
M3 - Article
C2 - 38141893
AN - SCOPUS:85184246079
SN - 1053-2498
VL - 43
SP - 755
EP - 770
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 5
ER -