Subclinical left ventricular myocardial dysfunction in non-obstructive coronary artery disease

Abstract

BackgroundThere is increasing evidence that accumulation of ectopic fat in the heart such as epicardial adipose tissue (EAT) contribute to cardiovascular disease and myocardial dysfunction. These ectopic fat play important physiological roles in the regulation of glucose metabolism and as an energy source. However, in pathological conditions, they are pro-inflammatory and secrete adipokines, which could accelerate atherosclerosis and cardiac remodeling. As these ectopic fats are well linked to conventional cardiovascular risk factors, previous studies have mainly investigated its association with coronary artery disease (CAD). The effects of EAT and non-obstructive coronary atherosclerosis on left ventricular (LV) myocardial function in those with preserved ejection fraction (EF) independent of otherconfounders such as diabetes and hypertension are unknown.AimsThe main aim of this research is to investigate the effect of EAT and non-obstructive coronary atherosclerosis on subclinical LV myocardial function using two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) in patients with preserved LV EF.MethodsIn the first study, 130 patients (53 p 9 years, 53.1% male) with non-obstructive CAD (defined as l50% coronary stenosis by cardiac contrasted-enhanced CT) and preserved LV EF were enrolled prospectively. EAT volume was measured by cardiac CT and multidirectional global strains were evaluated by 3D STE.In the second study, 96 patients (51 p 8.6 years, 56% male) without significant CAD, hypertension and diabetes were enrolled prospectively. The exclusion of patients with hypertension and diabetes eliminate other known confounders of LV strains. LV strains were evaluated by 2D and 3D STE.Multivariable analyses were performed to investigate independent determinants of 2D and 3D multidirectional strains in each study. Additional analyses were performed to compare the predictive value of 2D versus 3D global longitudinal strainnfor the presence of coronary atherosclerosis.ResultsIn the first study, EAT volume measured by cardiac computed tomography (CT) was independently associated with 3D global longitudinal strain (GLS, r = 0.601; p l 0.001), global circumferential strain (GCS, r = 0.375; p l 0.001), global radial strain (GRS, r = m0.546; p l 0.001), and global area strain (GAS, r = 0.558; p l 0.001). In multivariable analyses, EAT volume was the strongest predictor of 3D GLS (standardized b = 0.512; p l0.001), GCS (standardized b = 0.242; p = 0.006), GRS (standardized b = m0.422; p l 0.001), and GAS (standardized b = 0.428; p l 0.001). In contrast, other measures of obesity including BMI and waist/hip ratio were not independent determinants of 3D multidirectional global strain (all p g 0.05).In the second study, patients with non-obstructive CAD had lower 2D GLS (-18.5 p 2.2% vs. -20.1 p 1.9%, p l 0.001) and 3D GLS (-14.9 p 2.4% vs. -16.3 p 3.1%, p = 0.011) compared to those without any coronary atherosclerosis. In multivariable analyses model using 2D GLS, both age (odd ratio = 2.16, p = 0.011) and 2D GLS (odd ratio = 1.55, p =0.001) were independent determinants of non-obstructive coronary atherosclerosis. When 2D GLS was replaced with 3D GLS in similar analyses, both age (odd ratio = 2.23, p = 0.007) and 3D GLS (odd ratio =1.21, p = 0.027) were also independent determinants of coronary atherosclerosis. These associations were independent of obstructive CAD, diabetes and hypertension. 2D GLS was superior to 3D GLS in detecting coronary atherosclerosis using decision curve analysis despite having similar receiver operating characteristic curve derived area under the curves (2D GLS: 0.70 vs. 3D GLS: 0.65, p g 0.05).ConclusionsEAT and non-obstructive coronary atherosclerosis are independent determinants of subclinical myocardial dysfunction, independent of significant CAD, diabetes and hypertension. Future studies are needed to explore the potential role of reducing EAT volume and management of early coronary atherosclerosis in prevention of progression of myocardial dysfunction especially in patients with metabolic and diabetic heart disease.