Background: Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality following heart transplantation (HT). Reduced cardiovascular mortality and morbidity have been reported in non-HT patients treated with metformin. Given the high prevalence of type 2 diabetes mellitus (T2DM) in HT patients, we investigated the association between metformin therapy and cardiovascular outcomes after HT. Methods: The study population comprised 103 DM patients who had undergone HT between 1994 and 2018 and were prospectively followed-up. We excluded from the study patients with type 1 diabetes mellitus. Fifty-five HT patients (53%) in the cohort were treated with metformin. Clinical data were recorded on prospectively designed forms. The primary outcomes included CAV, survival, and the combined end-point of CAV or cardiovascular mortality. Results: Kaplan-Meier survival analysis showed that the CAV rate at 20 years of follow-up was lower in DM patients treated with metformin than in those who were not (30 vs. 65%; log-rank p = 0.044). Similarly, the combined risk of CAV or cardiovascular mortality was lower in the metformin-treated patients than in those not receiving metformin (32 vs. 68%; log rank p = 0.01). Consistently, multivariate analysis adjusted for age and comorbidities showed that metformin therapy was independently associated with a significant 90% reduction (95% confidence interval 0.02-0.46, p = 0.003) in the risk for the development of CAV, and a 91% reduction (95% confidence interval 0.02-0.42; p = 0.003) in the risk for CAV or cardiovascular mortality. Conclusions: In diabetic HT patients, metformin therapy is independently associated with a significant reduction in the long-term risk for CAV and the combined end-point of CAV or cardiovascular mortality after HT.

Purpose: To evaluate the role of diabetes mellitus in the incidence, risk factors, and outcomes of AKI (acute kidney injury) in patients admitted with ACS (acute coronary syndrome). Methods: We performed a comparative evaluation of ACS patients with vs. without DM who developed AKI enrolled in the biennial ACS Israeli Surveys (ACSIS) between 2000 and 2018. AKI was defined as an absolute increase in serum creatinine (³0.5 mg/dL) or above 1.5 mg/dL or new renal replacement therapy upon admission with ACS. Outcomes included 30-day major adverse cardiovascular events (MACE) and 1-year all-cause mortality. Results: The current study included a total of 16,879 patients, median age 64 (IQR 54–74), 77% males, 36% with DM. The incidence of AKI was significantly higher among patients with vs. without DM (8.4% vs. 4.7%, p < 0.001). The rates of 30-day MACE (40.8% vs. 13.4%, p < 0.001) and 1-year mortality (43.7% vs. 10%, p < 0.001) were significantly greater among diabetic patients who developed vs. those who did not develop AKI respectively, yet very similar among patients that developed AKI with vs. without DM (30-day MACE 40.8% vs. 40.3%, p = 0.9 1-year mortality 43.7 vs. 44.8%, p = 0.8, respectively). Multivariate analyses adjusted to potential confounders, showed similar independent predictors of AKI among patients with and without DM, comprising; older age, chronic kidney disease, congestive heart failure, and peripheral arterial disease. Conclusions: Although patients with DM are at much greater risk for AKI when admitted with ACS, the independent predictors of AKI and the worse patient outcomes when AKI occurs, are similar irrespective to DM status.

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