Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease

Table 3 Cardiac imaging studies relating -non-alcoholic fatty liver disease to structural and arrhythmogenic cardiac complications

	Ref.	Study characteristics	NAFLD diagnosis	Study measures	Main findings
Abnormalities in myocardial metabolism	Lautamaki et al[28], 2006	55 consecutive type 2 diabetic adults with known CHD	1H-MRS	Cardiac PET using [15O]-water and [18F]-2-fluoro-2-deoxy-D-glucose	Decreased coronary functional capacity and myocardial glucose uptake in NAFLD. These abnormalities were worse in those with higher intra-hepatic fat content
	Perseghin et al[7], 2008	Case-control: 21 nondiabetic, nonobese, normotensive, young men with NAFLD and 21 age- and BMI-matched male controls	1H-MRS	Cardiac 31P-MRS and MRI	Impaired LV energy metabolism in NAFLD, independently of age, BMI, blood pressure, lipids, fasting glucose. LV mass and function were not different between the groups
	Rijzewijk et al[74], 2008	Case-control: 38 uncomplicated type 2 diabetic men without CHD and 28 age, sex- and BMI-matched healthy controls	1H-MRS	Cardiac 1H-MRS and MRI	Myocardial fat content, which was much higher in diabetics than in control subjects, was positively associated with intra-hepatic fat content in both groups. Myocardial steatosis was a strong predictor of LV diastolic dysfunction
	Rijzewijk et al[75], 2010	61 uncomplicated type 2 diabetic men without CHD (32 of whom with high intra-hepatic triglyceride content)	1H-MRS	Cardiac MRI, 31P-MRS and cardiac PET using [15O]-water, [11C]-palmitate, and [18F]-2-fluoro-2-deoxy-D-glucose	Decreased myocardial perfusion, glucose uptake and impaired LV energy metabolism in NAFLD. Cardiac fatty acid metabolism, LV mass and function were not different between the two groups
Cardiac structure and function in adults	Goland et al[76], 2006	Case-control: 38 non-diabetic, normotensive NAFLD patients and 25 age- and sex-matched healthy controls	US and biopsy (29% of cases)	Echocardiography with TDI	Increased LV mass and increased prevalence of diastolic dysfunction in NAFLD. Reduced E’ wave only independent parameter associated with NAFLD on multivariate analysis
	Fallo et al[77], 2009	Case-control: newly-diagnosed untreated hypertensive patients (non-obese, non-diabetic): 48 NAFLD vs 38 controls	US	Echocardiography	Increased prevalence of diastolic dysfunction in NAFLD (according to its severity on ultrasound). LV mass was not different between the groups. Diastolic dysfunction and insulin resistance were independently associated with NAFLD
	Fotbolcu et al[78], 2010	Case-control: 35 nondiabetic, normotensive NAFLD patients and 30 age- and sex-matched healthy controls	US	Echocardiography with TDI	Increased LV mass and early impairment in systolic and diastolic function in NAFLD (no adjustment for potential confounders was made)
	Mantovani et al[79], 2011	116 consecutive older patients with hypertension and type 2 diabetes (53% of whom had NAFLD) without history of CHD and hepatic diseases	US	Echocardiography	Increased prevalence of LV hypertrophy in NAFLD. NAFLD was associated with LV hypertrophy independently of age, sex, BMI, systolic blood pressure, kidney function parameters and other diabetes-related variables
	Bonapace et al[8], 2012	50 consecutive type 2 diabetic patients without CHD and hepatic diseases (32 patients had NAFLD)	US	Echocardiography with TDI (speckle tracking analyses)	Impairment in LV diastolic function (including global longitudinal diastolic strain) in NAFLD, independently of age, sex, BMI, hypertension and other diabetes-related variables. These abnormalities were worse in those with severe NAFLD on ultrasonography. No differences in LV mass and systolic function between the groups
	Hallsworth et al[80], 2013	Case-control: 19 non-diabetic, overweight adults with NAFLD and 19 age-, sex- and BMI-matched healthy controls	1H-MRS	Cardiac MRI and 31P-MRS	Early impairment in systolic and diastolic function in NAFLD. Myocardial energy metabolism and LV mass were not altered in NAFLD
Cardiac structure and function in children or adolescents	Alp et al[81], 2013	Case-control: 400 obese children (93 with NAFLD) and 150 age- and sex-matched healthy controls	US	Echocardiography with TDI	Increased LV mass and early impairment in systolic and diastolic function in obese children with NAFLD independently of traditional cardiac risk factors. These abnormalities were worse in those with severe NAFLD on ultrasonography
	Singh et al[82], 2013	Case-control: 14 lean adolescents, 15 obese adolescents without NAFLD and 15 obese adolescents with NAFLD	1H-MRS	Echocardiography with TDI (speckle tracking analyses)	Decreased rates of LV global longitudinal systolic strain and early diastolic strain in obese adolescents with NAFLD independently of traditional cardiac risk factors. LV mass was not different between the groups
	Sert et al[83], 2013	Case-control: 108 obese adolescents and 68 healthy controls	US	Echocardiography with TDI (speckle tracking analyses)	Increased LV mass and impaired diastolic function and altered global systolic and diastolic myocardial performance in obese adolescents with NAFLD
	Pacifico et al[84], 2013	Case-control: 108 obese children (54 with NAFLD) and 18 lean healthy controls	MRI and biopsy (in 41 obese children)	Echocardiography with TDI	Early impairment in systolic and diastolic function in obese children with NAFLD independently of traditional cardiac risk factors. These abnormalities were more severe in those with NASH
Risk of atrial fibrillation	Sinner et al[87], 2013	Community-based cohort of 3744 adult individuals free of clinical HF (from the Framingham Heart Study original and Offspring cohorts)	Liver enzymes	Incidence of AF over up 10 yr of follow-up	Mildly elevated serum transaminases were associated with increased incidence of AF, independently of age, sex, BMI, systolic blood pressure, electrocardiographic PR interval, anti-hypertensive treatment, smoking, diabetes, valvular heart disease, alcohol consumption
	Targher et al[9], 2013	Hospital-based sample of 702 patients with type 2 diabetes without a history of hepatic diseases, or excessive alcohol intake (73% of them had NAFLD)	US	Prevalence of persistent or permanent AF	Increased prevalence of AF in those with NAFLD, independently of age, sex, systolic blood pressure, hemoglobin A1c, estimated glomerular filtration rate, total cholesterol, electrocardiographic left ventricular hypertrophy, chronic obstructive pulmonary disease, and prior history of heart failure, valvular heart disease or hyperthyroidism
	Targher et al[10], 2013	Random sample of 400 type 2 diabetic outpatients free from AF, moderate-to-severe heart valve disease and known causes of chronic liver diseases at baseline (70% of them had NAFLD)	US	Incidence of AF over 10 yr of follow-up	Increased incidence of AF in those with NAFLD, independently of age, sex, prior history of HF, BMI, systolic blood pressure, anti-hypertensive treatment, electrocardiographic LV hypertrophy, PR interval

BMI: Body mass index; CHD: Coronary heart disease; LV: Left ventricular; MRI: Magnetic resonance imaging; MRS: Magnetic resonance spectroscopy; TDI: Tissue doppler imaging; US: Ultrasonography; E’: Mitral annular tissue doppler early diastolic velocity; NAFLD: Non-alcoholic fatty liver disease; AF: Atrial fibrillation; HF: Heart failure.