Coexistent Diabetes Is Associated With the Presence of Adverse Phenotypic Features in Patients With Hypertrophic Cardiomyopathy

Abstract

OBJECTIVE Type 2 diabetes mellitus (T2DM) is associated with worsened clinical outcomes in hypertrophic cardiomyopathy (HCM) patients. We sought to investigate whether HCM patients with T2DM comorbidity exhibit adverse cardiac alterations in myocardial energetics, function, perfusion, or tissue characteristics. RESEARCH DESIGN AND METHODS A total of 55 participants with concomitant HCM and T2DM (HCM-DM) (n = 20) or isolated HCM (n = 20) and healthy volunteers (HV) (n = 15) underwent 31P-MRS and cardiovascular MRI. The HCM groups were matched for HCM phenotype. RESULTS Mean ± SD European Society of Cardiology sudden cardiac death risk scores were comparable between the HCM groups (HCM 2.2 ± 1.5%, HCM-DM 1.9 ± 1.2%; P = not significant), and sarcomeric mutations were equally common. HCM-DM patients had the highest median NT-proBNP levels (HV 42 ng/L [interquartile range 35–66], HCM 298 ng/L [157–837], HCM-DM 726 ng/L [213–8,695]; P < 0.0001). Left ventricular (LV) ejection fraction, mass, and wall thickness were similar between the HCM groups. HCM-DM patients displayed a greater degree of fibrosis burden with higher scar percentage and lower global longitudinal strain compared with HCM patients. PCr/ATP (the relative concentrations of phosphocreatine and ATP) was significantly lower in the HCM-DM group than in both HCM and HV (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 in both HCM and HV (HV 2.06 ± 0.42 mL/min/g, HCM 1.74 ± 0.44 mL/min/g, HCM-DM 1.39 ± 0.42 mL/min/g; P = 0.002). CONCLUSIONS We show for the first time that HCM-DM patients display greater reductions in myocardial energetics, perfusion, and contractile function and higher myocardial scar burden and serum NT-proBNP levels compared with 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.

Is Type 2 Diabetes Mellitus an Independent Risk Factor for Mortality in Hypertrophic Cardiomyopathy?

“…Our data reinforce data from previous studies demonstrating that T2DM was associated with poorer outcomes in patients with HCM [ 10 - 13 ]. For example, a study in 2022 by Lee et al [ 11 ] analyzed adverse outcome risk between HCM patients with and without T2DM using data from the Korean National Health Insurance Service database.…”

Association Between Type 2 Diabetes and Changes in Myocardial Structure, Contractile Function, Energetics, and Blood Flow Before and After Aortic Valve Replacement in Patients With Severe Aortic Stenosis

“…19 The LV short axis stack of images was first assessed visually for presence of late gadolinium hyperenhancement, followed by quantification when late gadolinium hyperenhancement was present, as previously described. 22 Late gadolinium hyperenhancement was defined as areas of signal intensity ≥5 SDs from normal myocardium and was expressed as the percentage of LV mass, quantified in a blinded fashion.…”

Roles of cMyBP-C phosphorylation on cardiac contractile dysfunction in db/db mice

“…In general terms, HFpEF is exacerbated by T2DM secondary to diabetic cardiomyopathy (T2DM-CM). T2DM-CM is initially characterized by cardiac hypertrophy, increased left ventricular stiffness, wall thickness, myocardial fibrosis, dysfunctional remodeling, end-diastolic dimension, and reduced diastolic relaxation, as well as later systolic dysfunction, and, eventually, overt heart failure [ 16 , 17 ]. All these features are present in the absence of coronary artery disease or hypertension and without changing global cardiac pumping [ 18 , 19 ].…”