Obesity modifies the energetic phenotype of dilated cardiomyopathy

Jennifer J Rayner, Mark A Peterzan, William T Clarke, Christopher T Rodgers, Stefan Neubauer, Oliver J Rider, Jennifer J Rayner, Mark A Peterzan, William T Clarke, Christopher T Rodgers, Stefan Neubauer, Oliver J Rider

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 (DCMNW), and 27 with DCM and obesity (DCMOB), were compared to 26 normal weight controls (CTLNW). All underwent cardiac magnetic resonance imaging and 31P spectroscopy to assess function and energetics. Nineteen DCMOB underwent repeat assessment after a dietary weight loss intervention. Adenosine triphosphate (ATP) delivery through creatine kinase (CK flux) was 55% lower in DCMNW than in CTLNW (P = 0.004), correlating with left ventricular ejection fraction (LVEF, r = 0.4, P = 0.015). In contrast, despite similar LVEF (DCMOB 41 ± 7%, DCMNW 38 ± 6%, P = 0.14), CK flux was two-fold higher in DCMOB (P < 0.001), due to higher rate through CK [median kf 0.21 (0.14) vs. 0.11 (0.12) s-1, P = 0.002]. During increased workload, the CTLNW heart increased CK flux by 97% (P < 0.001). In contrast, CK flux was unchanged in DCMNW and fell in DCMOB (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.

Keywords: Cardiac energetics; Cardiac magnetic resonance imaging; Heart failure; Magnetic resonance spectroscopy; Obesity; Weight loss.

© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

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; kf, pseudo-first order forward rate constant; PCr/ATP, phosphocreatine to adenosine triphosphate ratio.
Figure 1
Figure 1
The relationship between cardiac energetics and left ventricular systolic function in normal weight participants (white circles indicate controls, grey circles dilated cardiomyopathy). CTLNW, normal weight controls, DCMNW, normal weight participants with dilated cardiomyopathy; LVEF, left ventricular ejection fraction; ns, non-significant; PCr/ATP, phosphocreatine to adenosine triphosphate ratio. *p<0.05; ****p<0.001.
Figure 2
Figure 2
Comparison of myocardial energetics in obese and normal weight individuals with dilated cardiomyopathy (light grey circles indicate normal weight dilated cardiomyopathy, dark grey circles obese dilated cardiomyopathy). DCMNW, normal weight participants with dilated cardiomyopathy; DCMOB, DCM and obesity; ns, non-significant; PCr/ATP, phosphocreatine to adenosine triphosphate ratio. **p<0.01.
Figure 3
Figure 3
Cardiac energetics and function during increased workload; a comparison of normal hearts and dilated cardiomyopathy in obese and normal weight volunteers. CK, creatine kinase; CTLNW, normal weight controls, DCMNW, normal weight participants with dilated cardiomyopathy; DCMOB, DCM and obesity; LVEF, left ventricular ejection fraction; ns, non-significant; PCr/ATP, phosphocreatine to adenosine triphosphate ratio. *p<0.05; ***p<0.005; ****p<0.001.
Figure 4
Figure 4
The effect of weight loss on left ventricular systolic function and myocardial adenosine triphosphate delivery rate. LVEF, left ventricular ejection fraction. *p

Figure 5

The effect of weight loss…

Figure 5

The effect of weight loss on stress cardiac energetics in obese patients with…

Figure 5
The effect of weight loss on stress cardiac energetics in obese patients with dilated cardiomyopathy. CK, creatine kinase; ns, non-significant; PCr/ATP, phosphocreatine to adenosine triphosphate ratio. **p
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Figure 5
Figure 5
The effect of weight loss on stress cardiac energetics in obese patients with dilated cardiomyopathy. CK, creatine kinase; ns, non-significant; PCr/ATP, phosphocreatine to adenosine triphosphate ratio. **p

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