Obesity modifies the energetic phenotype of dilated cardiomyopathy

Abstract

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.

Graphical Abstract

Graphical Abstract

Myocardial energetics are different in obese individuals with cardiomyopathy compared to normal weight with maintained resting adenosine triphosphate delivery. Weight loss reverses this difference and improves left ventricular systolic function. CK, creatine kinase; EF, ejection fraction; k _f , pseudo-first order forward rate constant; PCr/ATP, phosphocreatine to adenosine triphosphate ratio.