ARTICLE: Congestion and Low Cardiac Output Hemodynamic Phenotype Drives Outcomes in Overweight and Obese HFpEF
AUTHORS: Vivek P Jani, Joban Vaishnav, Soumya Vungarala, Virginia S Hahn, Danielle Hopkins, Rishi Trivedi, Wendy Ying, David A Kass, Dhananjay Vaidya, Kavita Sharma
JOURNAL: JACC Heart Fail. 2025 Nov;13(11):102586. doi: 10.1016/j.jchf.2025.102586. Epub 2025 Sep 30.
Abstract
Background: Hemodynamic assessment of congestion and perfusion in overweight and obese patients with heart failure with preserved ejection fraction (HFpEF), and the respective impact of hemodynamic phenotypes on clinical outcomes has been limited to date.
Objectives: The authors characterized predominantly overweight and obese HFpEF patients by hemodynamic assessment of congestion and perfusion status and correlated these hemodynamic phenotypes with clinical outcomes.
Methods: A total of 227 patients referred to the Johns Hopkins HFpEF Clinic meeting clinical criteria for HFpEF and with right heart catheterization assessment were included. Hemodynamic-based groups were assigned as follows: dry-warm (pulmonary capillary wedge pressure [PCWP] <15 mm Hg, cardiac index >2.2 L/min/m2), wet-warm (PCWP ≥15 mm Hg, cardiac index >2.2 L/min/m2), dry-cold (PCWP <15 mm Hg, cardiac index ≤2.2 L/min/m2), and wet-cold (PCWP ≥15 mm Hg, cardiac index ≤2.2 L/min/m2).
Results: Compared to "warm" profile patients, HFpEF subjects classified as "cold" profile (dry-cold + wet-cold) accounted for 34% of the cohort and were more likely to be older (cold: 68 ± 11 years vs warm: 62 ± 12 years; P = 0.002), male (cold: 51% vs warm 66%; P = 0.04), have atrial fibrillation (P = 0.0007), with higher N-terminal pro-B-type natriuretic peptide (P = 0.03), and higher pulmonary vascular resistance indices. Of the 4 hemodynamic groups, wet-cold patients had the highest N-terminal pro-B-type natriuretic peptide levels (469 pg/mL [Q1-Q3: 257-1,389 pg/mL]; overall P = 0.0001), highest rate of atrial fibrillation (54%, overall P = 0.001), and were more likely to be on beta-blocker therapy (68%; P = 0.05). Kaplan-Meier survival analysis (median follow-up time: 39 months) revealed that HFpEF patients with low cardiac perfusion (thermodilution method and Fick method) had worse mortality even after accounting for potential overcorrection from body mass index.
Conclusions: In a predominantly overweight and obese HFpEF cohort meeting standard diagnostic criteria for clinical HFpEF, 34% had a depressed cardiac index on hemodynamic testing. Hemodynamic assessment may identify an under-recognized low-output hemodynamic phenotype in HFpEF, which in combination with congestion, is associated with worse clinical outcomes.
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