Obesity modifies the energetic phenotype of dilated cardiomyopathy. (20th September 2021)

• Record Type: Journal Article
• Authors: Rayner, Jennifer J; Peterzan, Mark A; Clarke, William T; Rodgers, Christopher T; Neubauer, Stefan; Rider, Oliver J
• Is Part Of: European heart journal. Volume 43:Number 9(2022)
• Page Start: 868
• Page End: 877
• Publication Date: 2021-09-20
• Subjects: Heart failure -- Obesity -- Cardiac magnetic resonance imaging -- Magnetic resonance spectroscopy -- Cardiac energetics -- Weight loss; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehab663
• Languages: English
• ISSNs: 0195-668X

Abstract

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 31 P 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 k f 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. Graphical Abstract: