Clinical features of subclinical left ventricular systolic dysfunction in patients with diabetes mellitus

Mochizuki et al. Cardiovascular Diabetology Clinical features of subclinical left ventricular systolic dysfunction in patients with diabetes mellitus Yasuhide Mochizuki 0 Hidekazu Tanaka 0 Kensuke Matsumoto 0 Hiroyuki Sano 0 Hiromi Toki 0 Hiroyuki Shimoura 0 Junichi Ooka 0 Takuma Sawa 0 Yoshiki Motoji 0 Keiko Ryo 0 Yushi Hirota 1 Wataru Ogawa 1 Ken-ichi Hirata 0 0 Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine , 7-5-2, Kusunoki-choChuo-ku, Kobe 650-0017 , Japan 1 Division of Diabetes and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe , Japan Background: Left ventricular (LV) longitudinal systolic dysfunction has been identified even in asymptomatic patients with diabetes mellitus (DM) and preserved LV ejection fraction (LVEF). However, its relevant clinical features have not been fully evaluated. Methods: We studied 144 asymptomatic DM patients without coronary artery disease. Their mean age was 57 15 years, 79 (55%) were female, and mean LVEF was 66 4% (all 50%). Global longitudinal strain (GLS) was determined as the average peak strain of 18 segments from the three standard apical views, and was expressed as an absolute value. With the pre-defined cutoff for subclinical LV systolic dysfunction in DM patients with preserved LVEF set at GLS < 18%, this dysfunction was detected in 53 patients (37%). Results: Multivariate logistic regression analysis revealed that type 2 DM, hypertriglyceridemia, overweight/obesity, nephropathy and neuropathy were independently associated with GLS < 18%, with nephropathy being the highest risk factor (OR: 5.26; 95% CI 2.111-13.12, p < 0.001). For sequential logistic regression models, a model based on clinical variables including gender, type 2 DM and DM duration (2 = 24.1) was improved by addition of overweight/obesity and hypertriglyceridemia (2 = 45.6, p < 0.001), and further improved by addition of nephropathy and neuropathy (2 = 70.2, p < 0.001) as variables. Furthermore, albuminuria significantly correlated with GLS (r = 0.51, p < 0.001), and a multivariate regression model showed it to be the factor most closely associated with GLS ( = 0.33, p < 0.001). Conclusions: Diabetic complications, hypertriglyceridemia and overweight/obesity were closely associated with early stage of LV systolic longitudinal myocardial dysfunction in asymptomatic DM patients with preserved LVEF. Our findings can be clinically noticeable for the management of DM patients. Diabetes mellitus; Nephropathy; Albuminuria; Echocardiography; Two-dimensional speckle-tracking strain; Global longitudinal strain - Background Diabetes mellitus (DM) is considered a major contributor of the development of heart failure (HF) despite absence of coronary artery disease and hypertension even in patients with preserved left ventricular (LV) ejection fraction (EF). This condition is known as diabetic cardiomyopathy [1-3]. Although the pathogenesis of diabetic cardiomyopathy is believed to be multifactorial but with the exact cause remaining unknown, a number of mechanisms such as hyperglycemia and hyperinsulinemia have been reported to play an important role in its etiology. These changes are observed as changes in free acid metabolism, increased apoptosis, activation of the reninangiotensin system, abnormalities in copper metabolism, autonomic neuropathy, stem cell defect, and increased oxidative stress among others. All these underlying pathogenetic conditions change the cardiac structure and may lead to cardiac fibrosis [1,4]. Diabetic cardiomyopathy is currently defined as a diastolic dysfunction, and several studies of DM patients have identified LV diastolic dysfunction as the earliest functional alteration in the course of diabetic cardiomyopathy [5-9], and also established it as an important prognostic parameter [6]. On the other hand, LV longitudinal myocardial systolic dysfunction has been identified in DM patients with preserved LVEF without overt coronary artery disease or HF [10-16]. In addition, recent investigations have found that LV longitudinal myocardial systolic dysfunction, rather than LV diastolic dysfunction, should be considered the first marker of a preclinical form of diabetic cardiomyopathy in DM patients with preserved LVEF without overt HF [14,17]. However, which characteristics of DM patients are associated with impaired LV systolic longitudinal myocardial function is not fully understood. Accordingly, our objective was to evaluate the factors associated with the clinical features of impaired LV longitudinal myocardial systolic function in asymptomatic DM patients with preserved LVEF. Methods Study populations A series of 150 consecutive DM patients including type 1 and type 2 DM who were admitted to Kobe University Hospital between July 2013 and November 2014 were prospectively recruited for this study. The diagnosis of DM and its type were established according to the World Health Organization criteria [18]. We excluded patients with (1) ischemic heart disease; (2) LVEF < 50%; (3) a previous history of open-heart surgery; (4) severe types of renal dysfunction defined as glomerular filtration rate (GFR) <30 mL/min/1.73 m2; (5) hypertension >180/ 100 mmHg uncontrollable despite medical therapy; (6) significant valvular heart disease; (7) atrial fibrillation; and (8) left or right bundle branch block. All patients underwent exercise stress testing such as treadmill exercise or stress myocardial perfusion scintigraphy within at least 2 weeks after admission, and none of the patients showed an ischemic response. Six initially eligible patients (4%) were excluded from all subsequent analyses because of suboptimal images from poor echocardiographic windows. As a result, the final study group consisted of 144 patients. The study protocol was approved by the ethics committee of our institution and all patients gave informed consent before participation. Echocardiographic examination All echocardiographic studies were performed using a commercially available echocardiographic system within at least 2 weeks after admission (Vivid E9; GE-Vingmed, Horten, Norway). Digital routine grayscale two-dimensional cine loops from three consecutive heartbeats were obtained at end-expiratory apnea from the standard parasternal longaxis view and three apical views at depths of 1214 cm and mean frame rates of 67 8 frames/sec. Sector width was optimized to allow for complete myocardial visualization while maximizing the frame rate. Digital data were transferred to dedicated software (EchoPAC version113; GE Vingmed) for subsequent offline analysis. Standard LV measurements were obtained in accordance with the current guidelines of the American Society of Echocardiography/European Association of Cardiovascular Imaging [19]. LV volumes and LVEF were calculated using the modified biplane Simpsons method, which was also employed to calculate left a (...truncated)