Obesity modifies the energetic phenotype of dilated cardiomyopathy.

Aims We sought to determine if myocardial energetics could distinguish obesity cardiomyopathy as a distinct entity from dilated cardiomyopathy. Methods and results Sixteen normal weight participants with dilated cardiomyopathy (DCM_NW), and 27 with DCM and obesity (DCM_OB), were compared to 26 normal weight controls (CTL_NW). All underwent cardiac magnetic resonance imaging and ³¹P spectroscopy to assess function and energetics. Nineteen DCM_OB underwent repeat assessment after a dietary weight loss intervention. Adenosine triphosphate (ATP) delivery through creatine kinase (CK flux) was 55% lower in DCM_NW than in CTL_NW (P = 0.004), correlating with left ventricular ejection fraction (LVEF, r = 0.4, P = 0.015). In contrast, despite similar LVEF (DCM_OB 41 ± 7%, DCM_NW 38 ± 6%, P = 0.14), CK flux was two-fold higher in DCM_OB (P < 0.001), due to higher rate through CK [median k _f 0.21 (0.14) vs. 0.11 (0.12) s⁻¹, P = 0.002]. During increased workload, the CTL_NW heart increased CK flux by 97% (P < 0.001). In contrast, CK flux was unchanged in DCM_NW and fell in DCM_OB (by >50%, P < 0.001). Intentional weight loss was associated with positive left ventricular remodelling, with reduced left ventricular end-diastolic volume (by 8%, P < 0.001) and a change in LVEF (40 ± 9% vs. 45 ± 10%, P = 0.002). This occurred alongside a fall in ATP delivery rate with weight loss (by 7%, P = 0.049). Conclusions In normal weight, DCM is associated with reduced resting ATP delivery. In obese DCM, ATP demand through CK is greater, suggesting reduced efficiency of energy utilization. Dietary weight loss is associated with significant improvement in myocardial contractility, and a fall in ATP delivery, suggesting improved metabolic efficiency. This highlights distinct energetic pathways in obesity cardiomyopathy, which are both different from dilated cardiomyopathy, and may be reversible with weight loss. [ABSTRACT FROM AUTHOR]