Abstract 4867: Myocardial Effects of Beta-Blocker Therapy in the Failing Diabetic Heart
Raised diastolic left ventricular (LV) stiffness importantly contributes to heart failure (HF) in diabetes mellitus (DM) and results from myocardial deposition of advanced glycation endproducts (AGEs), interstitial fibrosis, cardiomyocyte hypertrophy and elevated diastolic resting tension (Fpassive) of cardiomyocytes. The relative importance of these mechanisms for diastolic LV stiffness differs between HF with reduced LV ejection fraction (EF) (HFrEF) and HF with normal LV EF (HFnEF) as evident from more fibrosis in HFrEF and more hypertrophy and higher Fpassive in HFnEF. The present study therefore compared myocardial effects of β-blocker therapy in DM patients suffering of HFrEF (n=11) or of HFnEF (n=15). All patients had DM type 2 and were free of significant coronary artery disease. LV endomyocardial biopsies were used to assess AGEs deposition by carboxymethyllysine immunohistochemistry and collagen volume fraction (CVF) or cardiomyocyte diameter (MyD) by histomorphometry. Cardiomyocytes were also isolated from the biopsies, attached to a force transducer and stretched to 2.2 μm to measure Fpassive. AGEs deposition was expressed relative to an age and sex matched control group without DM. In both HFrEF and HFnEF groups, β-blocker therapy reduced DM-related myocardial AGEs deposition. In both HFrEF and HFnEF groups, β-blocker therapy also reduced MyD. In HFnEF, β-blocker therapy lowered CVF but raised Fpassive of cardiomyocytes.
Conclusion: Myocardial effects of β-blocker therapy were uniformly beneficial for diastolic LV stiffness in DM patients suffering of HFrEF but not in DM patients suffering of HFnEF. In DM, HF phenotype could therefore affect outcome of β-blocker therapy.