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QUARTERLY FOCUS ISSUE: HEART FAILURE: CLINICAL RESEARCH

The Development of Heart Failure in Patients With Diabetes Mellitus and Pre-Clinical Diastolic Dysfunction

A Population-Based Study

Aaron M. From, MD^_*, Christopher G. Scott, MS and Horng H. Chen, MBBCh^_*,_*

^_* Department of Medicine, Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester, Minnesota
Division of Biostatistics, Mayo Clinic and Foundation, Rochester, Minnesota

Manuscript received July 24, 2009; revised manuscript received December 2, 2009, accepted December 7, 2009.

^_* Reprint requests and correspondence: Dr. Horng H. Chen, Division of Cardiovascular Diseases, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905 (Email: chen.horng{at}mayo.edu).

Objectives: The purpose of this study was to evaluate the outcomes of pre-clinical diastolic dysfunction in diabetic patients.

Background: Studies have reported a high prevalence of pre-clinical diastolic dysfunction among patients with diabetes mellitus.

Methods: We identified all diabetic patients with a tissue Doppler imaging assessment of diastolic function in Olmsted County, Minnesota, from 2001 to 2007. Diastolic dysfunction was defined as a passive transmitral left ventricular (LV) inflow velocity to tissue Doppler imaging velocity of the medial mitral annulus during passive filling (E/e') ratio >15. The main outcome was the development of heart failure (HF). Secondary outcomes were the development of atrial fibrillation and death.

Results: Overall, 1,760 diabetic patients with a tissue Doppler echocardiographic assessment of diastolic function were identified; 411 (23%) patients had diastolic dysfunction. Using multivariable Cox's proportional hazard modeling, we determined that for every 1-U increase in the passive transmitral LV inflow velocity to tissue Doppler imaging velocity of the medial mitral annulus during passive filling (E/e') ratio, the hazard ratio (HR) of HF increased by 3% (HR: 1.03; 95% confidence interval [CI]: 1.01 to 1.06; p = 0.006) and that diastolic dysfunction was associated with the subsequent development of HF after adjustment for age, sex, body mass index, hypertension, coronary disease, and echocardiographic parameters (HR: 1.61; 95% CI: 1.17 to 2.20; p = 0.003). The cumulative probability of the development of HF at 5 years for diabetic patients with diastolic dysfunction was 36.9% compared with 16.8% for patients without diastolic dysfunction (p < 0.001). Furthermore, diabetic patients with diastolic dysfunction had a significantly higher mortality rate compared with those without diastolic dysfunction.

Conclusions: We demonstrated that an increase in the passive transmitral LV inflow velocity to tissue Doppler imaging velocity of the medial mitral annulus during passive filling (E/e') ratio in diabetic patients is associated with the subsequent development of HF and increased mortality independent of hypertension, coronary disease, or other echocardiographic parameters.

Key Words: diabetes mellitus • diabetic cardiomyopathy • diastolic dysfunction • heart failure

Abbreviations and Acronyms   CI = confidence interval   DM = diabetes mellitus   E = passive transmitral left ventricular inflow velocity   e' = tissue Doppler imaging velocity of the medial mitral annulus during passive filling   HF = heart failure   HR = hazard ratio   LV = left ventricular

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