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AHA 2022: Identification of Novel Right Ventricular Function Phenotypes in Pulmonary Arterial Hypertension Using Unbiased K-Means Clustering.

Vanderpool, R., Janowski, A., Fauvel, C., Liu, Z., Lin, S., Correa-Jaque, P., Webb, A., Kanwar, M., Kraisangka, J., Mathur, P., Perer, A., Everett, A., Visovatti, S., and Benza, R.L. “Identification of Novel Right Ventricular Function Phenotypes in Pulmonary Arterial Hypertension Using Unbiased K-Means Clustering”

Introduction: Survival in pulmonary arterial hypertension (PAH) is associated with right ventricular (RV) function rather than pulmonary vascular resistance (PVR). At present, RV function is not incorporated in current risk assessment models and studies evaluating RV function are generally limited to single-center studies. The aim was to identify novel RV function phenotypes using unbiased k-means clustering in patients with PAH.

Methods: Baseline clinical and hemodynamic data in patients with PAH were harmonized data from 5 PAH clinical trials (COMPASS3: n=98, EARLY: n=176, GRIPHON: n=720, MAESTRO: n=44, and SERAPHIN: n=728). Pearson correlation analysis was used to select variables that reduce the co-linearity (|r| < 0.7) between hemodynamic variables used in the models. K-means clustering methods were applied to advanced RV hemodynamics including end-systolic pressure (ESP), arterial elastance (Ea), single-beat end-diastolic elastance (Eed), Pulse pressure (PP), stroke volume (SV) and RV stroke work (RVSW). Survival analysis was used to compare all-cause mortality among each cluster group.

Results: Participants in the harmonized dataset (n=1766) had a mean PAP of 53 ± 17 mmHg, a cardiac output of 4.3±1.4 L/min, a wedge pressure of 9±4 mmHg and a PVR of 11.8±7.4 WU. K-means clustering identified four distinct RV cluster phenotypes that range from mild to severe RV dysfunction (Fig. A). Participants in RV cluster 1 (RV C1) have severe RV dysfunction with increased pressure/afterload, decreased cardiac function, and increased diastolic stiffness compared to RV cluster 4 (RV C4). (Fig. A) RV C1 had decreased six-minute walk distance compared to other clusters. RVC1 and RVC2 had increased risk of mortality compared to RV C4 (Fig. B).

Conclusion: Applying K-means clustering to harmonized hemodynamic data from PAH clinical trial data identified 4 unique RV function phenotypes with different clinical outcomes.

DOI: https://doi.org/10.1161/circ.146.suppl_1.15151