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Non-alcoholic fatty liver disease association with structural heart, systolic and diastolic dysfunction: a meta-analysis
  While a spectrum of hepatic complications is associated with NAFLD such as hepatocellular carcinoma and cirrhosis [4], cardiovascular disease remains the leading cause of death in NAFLD.
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Jie Ning Yong1 · Cheng Han Ng1 · Chloe Wen Min Lee1 · Yu Yi Chan1 · Ansel Shao Pin Tang1 · Margaret Teng1,2,3 · Darren Jun Hao Tan1 · Wen Hui Lim1 · Jingxuan Quek1 · Jieling Xiao1 · Yip Han Chin1 · Roger Foo1,4 · Mark Chan1,4 · Weiqin Lin1,4 · Mazen Noureddin5 · Mohammad Shadab Siddiqui6 · Mark D. Muthiah1,2,3 · Arun Sanyal6 ·
Nicholas W. S. Chew1,4

Several studies have documented a relationship between non-alcoholic fatty liver disease (NAFLD) and structural heart disease, particularly diastolic function. This meta-analysis will be the first to examine the echocardiographic-derived cardiac function and structural characteristics in NAFLD patients, and its association with liver disease severity and metabolic profile.
Medline and Embase were searched and pairwise meta-analysis was conducted in DerSimonian and Laird to obtain the odds ratio (OR) and mean difference (MD) for dichotomous and continuous variables, respectively, to compare the effects of NAFLD on the echocardiography parameters.
Forty-one articles involving 33,891 patients underwent echocardiography. NAFLD patients had worse systolic indices with lower ejection fraction (EF, MD: - 0.693; 95% CI: - 1.112 to - 0.274; p = 0.001), and worse diastolic indices with higher E/e’ (MD: 1.575; 95% CI: 0.924 to 2.227; p < 0.001) compared to non-NAFLD patients. NAFLD patients displayed increased left ventricular mass (LVM, MD: 34.484; 95% CI: 26.236 to 42.732; p < 0.001) and epicardial adipose thickness (EAT, MD: 0.1343; 95% CI: 0.055 to 0.214; p = 0.001). An increased severity of NAFLD was associated with worse diastolic indices (decreased E/A ratio, p = 0.007), but not with systolic indices.
NAFLD is associated with impaired systolic and diastolic function with changes in cardiac structure.
Concomitant metabolic risk factors and liver disease severity are independently associated with worsening systolic and diastolic function.
In conclusion, this meta-analysis describes the strong association between NAFLD and reduction in systolic and diastolic function, and adverse cardiac remodeling. Other components including concomitant metabolic factors, and liver disease severity appear to be important considerations when identifying patients with NAFLD at risk of developing cardiac dysfunction and heart failure.
While there is a strong association between NAFLD and structural heart disease and cardiomyopathy, this association is not well understood. Echocardiography remains one of the most readily available tools in the screening of cardiovascular disease and is recommended by the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD) for NAFLD [5, 6]. Recent evidence has found significant association between NAFLD and diastolic dysfunction [7], with the presence of diastolic dysfunction a known risk factor for cardiovascular-related morbidity and mortality [8]. However, conflicting evidence has been found between NAFLD and systolic dysfunction [9, 10]. Emerging evidence on other echocardiographic-derived structural features such as epicardial adipose thickness (EAT) have been shown to be thicker in NAFLD patients, with its thickness correlating with the severity of hepatic steatosis [11], thus potentially evoking unfavorable inflammatory responses in both hepatic and cardiac tissues. Moreover, left ventricular remodeling, with left ventricular mass (LVM) measurements as a surrogate may result from the systemic effects of increased afterload and neurohormonal activation in NAFLD patients.
While previous meta-analyses have investigated the association of NAFLD and adverse structural remodeling and cardiac dysfunction [10, 12], we hypothesize that there are several underlying determinants of adverse echocardiographic profile in NAFLD patients that have yet to be explored. More specifically, the severity of liver disease and metabolic profile may be a part of a complex interplay in adverse cardiac remodeling and function. Thus, in this comprehensive meta-analysis, we aimed to examine the systolic, diastolic, and structural echocardiographic characteristics in NAFLD patients.

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