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Coexistent diabetes is associated with the presence of adverse phenotypic features in patients with hypertrophic cardiomyopathy

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posted on 2022-07-05, 13:56 authored by Nicholas Jex, Amrit Chowdhary, Sharmaine Thirunavukarasu, Henry Procter, Anshuman Sengupta, Pavithra Natarajan, Sindhoora Kotha, Ana-Maria Poenar, Peter Swoboda, Hui Xue, Richard M Cubbon, Peter Kellman, John P Greenwood, Sven Plein, Stephen Page, Eylem Levelt

  

Objective- Type 2 diabetes mellitus (DM) is associated with worsened clinical outcomes in hypertrophic cardiomyopathy (HCM) patients. We sought to investigate if hypertrophic cardiomyopathy patients with type 2 diabetes mellitus comorbidity exhibit adverse cardiac alterations in myocardial energetics, function, perfusion, or tissue characteristics.

Research design and methods-  Fifty-five participants with concomitant HCM and DM (HCM-DM, n=20), isolated HCM (n=20), and healthy volunteers (HV, n=15) underwent 31phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance imaging. The HCM groups were matched for HCM phenotype. 

Results- ESC sudden cardiac death risk scores were comparable between the HCM groups (HCM:2.2±1.5%, HCM-DM:1.9±1.2%; p=NS) and sarcomeric mutations were equally common. HCM-DM had the highest NT-proBNP levels (HV:42ng/L[IQR:35-66], HCM:298ng/L[IQR:157-837], HCM-DM:726ng/L[IQR:213-8695]; p<0.0001). Left-ventricular ejection fraction, mass and wall thickness were similar between the HCM groups. HCM patients with DM comorbidity displayed a greater degree of fibrosis burden with higher scar percentage, and lower global longitudinal strain compared to the isolated HCM patients. PCr/ATP was significantly lower in the HCM-DM group than both the isolated HCM patients and the healthy controls (HV:2.17±0.49, HCM:1.93±0.38, HCM-DM:1.54±0.27; p=0.002). In a similar pattern, stress myocardial blood flow was significantly lower in the HCM-DM group than both the isolated HCM patients and the healthy controls (HV:2.06±0.42ml/min/g, HCM:1.74±0.44ml/min/g, HCM-DM:1.39±0.42ml/min/g; p=0.002).

Conclusions- We show for the first time that HCM patients with T2DM comorbidity display greater reductions in myocardial energetics, perfusion, contractile function and higher myocardial scar burden and serum NT-proBNP levels compared to patients with isolated HCM despite similar LV mass and wall thickness and presence of sarcomeric mutations. These adverse phenotypic features may be important components of the adverse clinical manifestation attributable to a combined presence of HCM and T2DM. 

Funding

The study was supported by the Wellcome Trust [grant number: 207726/Z/17/Z]. NJ receives support from Diabetes UK [grant number: 18/0005908, Diabetes UK PhD studentship]. EL is funded by a Wellcome Trust Clinical Career Development Fellowship [grant number: 221690/Z/20/Z]. AC receive support from the British Heart Foundation [grant number: FS/CRTF/20/24003]. Other authors have reported that they have no relationships relevant to the contents of this paper to disclose, and there are no conflicts of interests.

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