Effects of Dapagliflozin on Body Composition and Its Relation to Hemodynamics in Heart Failure with Preserved Ejection Fraction: The CAMEO-DAPA Randomized Clinical Trial

Excess visceral fat contributes to heart failure with preserved ejection fraction (HFpEF). Sodium-glucose cotransporter-2 inhibitors improve hemodynamics, reduce symptoms, and lower hospitalization risks, but their effects on body composition and its relationship with hemodynamics in HFpEF remain unclear.

Naser JA, discussed results at a session at the European Society of Cardiology (ESC) congress 2024 on 30^th August-2^nd September in London, UK that evaluated the effect of dapagliflozin on body and blood composition and examined the potential correlation of such changes on cardiac hemodynamics. The single-center, double-blind, randomized, placebo-controlled study, showed that 24 weeks of dapagliflozin reduced resting and exercise pulmonary capillary wedge pressures (PCWP) in patients with HFpEF. This prespecified secondary analysis reports the effects of dapagliflozin on body composition using dual energy x-ray absorptiometry (DEXA), blood composition (radiolabeled iodinated albumin), and cardiac hemodynamics using high-fidelity micromanometers. Analysis was performed based on the intention-to-treat. Relative change was calculated by dividing the absolute change on the baseline value. Overall, 37 patients (67 years, 65% women, 70% with obesity, 27% overweight) completed the trial. As compared with baseline, dapagliflozin decreased total body fat compared with placebo [mean (SD) absolute change: -2.29 (2.94) kg vs -0.32 (1.84) in placebo, p=0.03; relative change: -4.6% (5.4) vs -0.8% (4.3), p=0.02], Figure 1. This was primarily due to greater loss of upper body trunk fat [absolute change: -1.53 (1.70) kg vs +0.31 (0.99) in placebo, p<.001; relative change: -5.2% (5.6) vs +1.1% (4.1), p<.001], Figure 1. Reductions in trunk fat were correlated with decreases in PCWP (r=0.41, p=0.03), Figure 2. Total body fat-free mass (FFM) tended to decrease in the dapagliflozin group [absolute change: -0.63 (1.85) kg vs +0.34 (1.76), p=0.12]; reductions in leg, android, and gynoid FFM were all greater than placebo (p<0.05). Dapagliflozin reduced plasma volume [absolute change: -170 (343) ml vs +112 (346), p=0.02] compared with placebo, and the decrease in plasma volume was correlated with the reduction in FFM (r=0.47, p=0.006). Treatment with dapagliflozin had no effect on resting metabolic rate but was associated with modest reduction in bone mineral content [-16 (47) g vs +26 (61), p=0.03].

In HFpEF patients, dapagliflozin reduces trunk fat, suggesting an impact on visceral adipose tissue and improved hemodynamics. It also decreases fat-free mass, likely due to reduced body water and slight bone mineral content loss