Metformin Use and Mortality in Ambulatory Patients With Diabetes and Heart Failure

Introduction: Preclinical Diastolic Dysfunction (PDD) has been broadly defined as subjects with left ventricular diastolic dysfunction, without diagnosis of congestive heart failure (HF), and with normal systolic function. The clinical profile and natural history of PDD remain poorly defined. Our objectives were to determine the clinical profile, mortality, and progression to the development of HF in patients with a normal ejection fraction (EF) and with moderate or severe diastolic dysfunction (as determined by Doppler criteria) but without a diagnosis of HF in Olmsted County, Minnesota (MN) during 2004-2005. Methods: Using the resources of the Rochester Epidemiology Project, all residents of Olmsted County, MN who underwent echocardiography between 1/1/2004 and 12/31/2005 and had echocardiographic evidence of Grade II-IV diastolic dysfunction (DD) and EF $ 50% were identified. Patients with a diagnosis of HF prior to and within 30 days of the echocardiogram were excluded as were patients with severe mitral or aortic valve regurgitation. A total of 388 patients met the inclusion criteria and a detailed review of the medical record was conducted with followup clinical data collected until 06/30/2009. The primary end point was the development of HF. Our secondary end points were all-cause mortality, cardiac hospitalization, and development of atrial fibrillation. Results: The mean age of the cohort of PDD subjects was 67 6 12 years with a female (57%) predominance. Prevalence of hypertension was 87%, coronary artery disease was 52%, previous myocardial infarction was 24%, renal dysfunction (estimated GFR !60) was 34%, hyperlipidemia was 76%, and type II diabetes mellitus was 30%. Mean follow up was 3.9 years. The 3-year cumulative probabilities of development of HF, cardiac hospitalization, development of atrial fibrillation, and mortality were 11.6%, 4.6%, 14.5%, and 10.1% respectively. In multivariable Cox’s proportional hazard regression analysis we determined that age, renal dysfunction and right ventricular systolic pressure were associated with the subsequent development of HF; while age and BMI were associated with death. Conclusion: This population-based study provides a comprehensive clinical profile, prognosis, and predictors of outcome of patients with preclinical diastolic dysfunction. Importantly, there was a moderate degree of progression to development of HF, cardiac hospitalization, development of atrial fibrillation, and death over 3 years.