Manouchehr Khoshbaten¹, Sahar Parkhideh^1*and Mehrnoush Toufan²

¹Department of Internal Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran ²Department of Cardiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran   Corresponding Author Email: parkhideh.tums@gmail.com

DOI : https://dx.doi.org/10.13005/bpj/822

Abstract

Non-alcoholic fatty liver disease, as an independent risk factor for development of cardiovascular events plays an increasingly prominent role worldwide. In this study, we evaluated systolic and diastolic functional parameters of left ventricles in NAFLD patients. 30 normotensive, non-diabetic, non-obese NAFLD patients and 30 controls underwent laboratory examinations, liver ultrasound and finally a complete echocardiographic study including conventional, 4D and speckle tracking echocardiography. NAFLD patients had increased LAVI (30.47± 7.71 vs 25.1± 4.03, p=0.001) and DT (192.47±1 42.4 vs 163.13± 17.1, p=0.001) compared to the controls. E/A ratio was 1.12±0.24 in NAFLD patients and 1.27±0.18 in healthy individuals, p=0.01. LVEF% was 54.81±6.72 on 2DE and 55.83±8.03 on 4DE among patient group; and also 57.43±7.3 on 2DE, and 59.75±7.4 on 4DE among control group (p=0.79 and 0.59 respectively). GPSS was significantly lower in patient group in comparison with healthy individuals (18.96±2.31 vs 20.27±1.72, p=0.016), using speckle tracking technique. NAFLD patients have systolic and diastolic LV dysfunction even in the absence of hypertension, obesity and diabetes.

Keywords

Non-alcoholic; echocardiography; ventricles

Download this article as: 

Copy the following to cite this article: Khoshbaten M, Parkhideh S, Toufan M. Comparison of Left Ventricular Function Between Patients With Non- Alcoholic Fatty Liver Disease and Healthy Individuals. Biomed Pharmacol J 2015;8(2)

Copy the following to cite this URL: Khoshbaten M, Parkhideh S, Toufan M. Comparison of Left Ventricular Function Between Patients With Non- Alcoholic Fatty Liver Disease and Healthy Individuals. Biomed Pharmacol J 2015;8(2). Available from: http://biomedpharmajournal.org/?p=1925

Introduction

NAFLD affects approximately 30% of normal population [1-2] and this prevalence appears to be rising with obesity epidemic (3-4). Nowadays, strong body of evidence shows that cardiovascular disease is leading cause of death in patients with NAFLD.  Although a relationship between NAFLD and atherosclerosis risk factors has been established, NAFLD, per se, has a direct impact on developing atherosclerosis [5-9].

Until now, only few studies have been conducted on anatomical and functional disturbances of the heart in NAFLD patients [10-13].

In this study we investigated alterations in LV structures and function with newer techniques like speckle tracking and 4D echocardiography to determine systolic and diastolic function in non-diabetic, normotensive, non-obese NAFLD patients.

Method and Materials

The current study was carried out on 30 ultrasound-diagnosed NAFLD patients and 30 healthy controls with completely normal sonographic findings. Patients on antihypertensive medications and those who had BP≥ 130/80 on three consecutive measurements at 5 minute intervals were excluded from the study. Patients who meet the following criteria were also excluded from the study: NAFLD cases with BMI higher than 30, a history of or laboratory findings consistent with diabetes mellitus, known cases of coronary artery and valvular heart disease, patients with history of liver disease, persons with excess alcohol intake (>200 g weekly), patients under the age 19 and those aged 50 and over.

Hepatic ultrasonography was performed in all participants by a single radiologist, who was blinded to subjects’ details.  NAFLD was diagnosed based on ultrasonographic Hamagichi’s criteria (score≥2), and participants with a score of zero were included in the control group [14].

In both groups anthropometric data were measured and recorded. All study participant underwent phlebotomy after a 12-hour fast and blood samples were analyzed for FBS, Chol, TG, LDL, HDL, AST, ALT, ALP, HB and PLT.

A Comprehensive echocardiogram study, including conventional, 4D and speckle tracking echocardiography was performed in all study subjects by one operator, who was blinded for the clinical, laboratory and ultrasound results of the participants.

The following indexes were recorded from conventional 2D echocardiography: Ejection fraction (EF %), left ventricular internal systolic diameter (LVISD), left ventricular internal diastolic diameter (LVIDD), deceleration time (DT), E/A ratio and left atrial volume (LAV). Biplane area-length method was used to calculate LA volume.  Left atrial volume index (LAVI) was calculated by dividing LA volume by body surface area. LV mass was calculated using the ASE formula and indexed to body surface area to obtain the LV mass index (LVMI). Left ventricular systolic function was assessed by measurement of global longitudinal peak systolic strain (GPSS) using two dimensional speckle tracking echocardiography.

Ethical committee of Tabriz University of Medical Sciences approved this project.

All statistical analyses were performed by SPSS for Windows, version 16.0. All variables are presented as means ± SD and differences between two groups were evaluated with the Student t test. A P value <0.05 was considered to be statistically significant.

Results

30 patients with NAFLD (mean age 39.97±6.84 years) and 30 controls (mean age 40.53±8.08 years) were included in the study. The demographic, anthropometric and biochemical characteristics of participants are shown in Table.1.

Table 1: Clinical and biochemical characteristics of the study population

Variables		NAFLD patients	Controls	P
Age(years)		39.97±6.84	40.53±8.08	0.71
Gender	Male	20(66.7%)	16(53.3%)	0.29
	Female	10(33.3%)	14(46.7%)
Height [cm]		170.93±54	172.03±10.57	0.87
Weight [kg]		79.90±10.5	74.4±7.08	0/02*
BMI [kg/m²]		27.33±2.41	24.95±1.74	<0.001 ⃰
WC [cm]		101.57±8.32	95.9±6.24	0/004*
AST [U/L]		33.74±16.01	26.5±7.27	0.02 ⃰
ALT [U/L]		57.38±37.41	37.4±13.91	0.008 ⃰
ALP [U/L]		181.23±37.55	170.87±44.25	0.33
Hb [g/L]		15.22±1.46	14.92±1.67	0.46
PLT /microL		267200±76794.57	258866±76176.17	0.670
FBS [mg/dl]		89.37±11.05	84.9±7.17	0.06
TG [mg/dl]		199.33±22.6	142.43±29.24	0.01 ⃰
Chol [mg/dl]		191.47±40.32	186.13±34.03	0.58
HDL [mg/dl]		43.73±7.81	45.16±6.78	0.45

⃰ Statistically significant

Age, gender, height, ALP, Hb, PLT, Chol and HDL were similar between two groups, and the differences were not significant. Individuals with NAFLD had significantly higher values for BMI (27.33±2.41 vs 24.95±1.74, p<0.001) as well as WC (101.57±8.32 vs 95.9±6.24, p=0.004). Accordingly, compared with control subjects, those with NAFLD also had higher AST, ALT and TG values (p= 0.02, 0.008 and 0.01 respectively). Although the difference in FBS values was remarkable between two groups, it was not statistically meaningful. The only variable independently associated with NAFLD in multivariate analyses was BMI (CI=95%, p=0.001).

The echocardiographic characteristics of participants are shown in Table.2.

Table 2: Echocardiographic characteristics of the study patients

Parameters	NAFLD patients	Controls	P
LAVI (ml/m²)	30.47±7.71	25.1±4.03	0/001*
DT (s)	192.47±42.4	163.13±17.01	0/001*
E/A Ratio	1.12±0.24	1.27±0.18	0/01*
IVS (cm)	0.99±0.15	0.89±0.13	0.01 ⃰
PW (cm)	0.94±0.18	0.85±0.12	0.01 ⃰
LVIDD (cm)	4.61±0.36	4.46±0.33	0.58
LVISD (cm)	3.18±0.33	3.08±0.3	0.68
EF% by 2DE	54.81±6.72	57.43±7.3	0.79
EF% by 4DE	55.83±8.03	59.75±5.4	0.59
LVEDV (ml)	88.96±19.1	82.57±14.34	0.63
LVESV (ml)	40.43±12.21	33.23±10.97	0.59
LVM (g)	162.84±43.06	118.9±32.98	<0.001 ⃰
LVMI (g/cm²)	83.99±20.83	65.23±11.28	<0.001 ⃰
GPSS	-18.96±2.31	-20.27±1.72	0.016 ⃰

*Statistically significant

Left atrial volume index (LAVI), Deceleration time (DT), and E/A ratio which all are representative parameters of diastolic function [15-16], were significantly different in two groups. NAFLD patients had increased LAVI (30.47± 7.71 vs 25.1± 4.03, p=0.001) and DT (192.47±1 42.4 vs 163.13± 17.1, p=0.001) compared to the controls. E/A ratio was 1.12±0.24 in NAFLD patients and 1.27±0.18 in healthy individuals, p=0.01.

Echocardiographic findings on LV geometry showed marked changes in NAFLD cases. Mean IVS was 0.99±0.15 in NAFLD group, and 0.89±0.13 in control group; LVPW was 0.94±0.18 and 0.85±0.12 respectively. No significant difference was observed for LVISD and LVIDD by conventional echocardiography.

Although LVESV and LVEDV measured by four-dimensional echocardiography [17-20], showed higher mean values among fatty liver patients, the difference was not remarkable (p=0.63 and 0.59). In the 4D study, LVM and LVMI showed significant increase in NAFLD patients (162.84±43.06 and 83.99±20.83 respectively).

LVEF% was 54.81±6.72 on 2DE and 55.83±8.03 on 4DE among patient group; and also 57.43±7.3 on 2DE, and 59.75±7.4 on 4DE among control group. LVEF% was lower in patient group by both 2DE and 4DE, but the EF% reduction was not statistically significant (p=0.79 and 0.59).

GPSS was significantly lower in patient group in comparison with healthy individuals (18.96±2.31 vs 20.27±1.72, p=0.016), using speckle tracking technique [21-23].

Discussion

This study revealed significant systolic and diastolic dysfunction, as well as marked structural changes of left ventricle in non-diabetic, non-obese, normotensive NAFLD patients. In our study the patient average age was 39.97±6.84 years. In order to exclude age bias on cardiac function, the patients were selected within the age range 19 to 50. The mean age in Goland and Fotbolcu studies were 46.7±8 and 41.40±6.25 respectively [10, 13, 23].

Studies have shown that obesity per se contributes to cardiac systolic and diastolic dysfunction which seems to be mediated by several mechanisms [24, 25]; so in this study the obese adults (BMI≥30) were excluded. The mean BMI of patients in present study was 27.33±2.41 that was lower than that of 30.44±3.45 reported by Fotbolku et al. ¹⁰ Although we tried to exclude obese participants, the mean BMI was still higher in patient group when compared to controls, which may have played a role in significant diastolic dysfunction seen in NAFLD patients (27.33±2.41 vs 24.95±1.74, p<0.001). Most of previous echocardiographic studies shared the same problem [10, 13].

LVPW and IVS found to be significantly higher in patients with NAFLD as compared with healthy controls. Same results observed in Goland and Fotbolku studies [10, 13].

According to our echocardiographic measurements, diastolic indices, such as LAVI, E/A, DT, all were significantly different between two groups, representing LV diastolic dysfunction in NAFLD group. Goland et al and Fotbolku et al, also reported LV diastolic dysfunction in NAFLD patients [10, 13].

In our study as well Goland study, EF% was lower among the patients with NAFLD, but the analysis did neither reveal statistically significant results [13]. Conversely, EF% was insignificantly lower in healthy controls in Fotbolku study [10].

To date, only few studies have been conducted on structural and functional echocardiographic characteristics in NAFLD patients. One advantage of our study was using newer and more accurate technologies, i.e. speckle tracking and 4D echocardiography, to assess cardiac function [17-22]. We demonstrated that although both conventional and 4D echocardiography showed insignificant decrease in  EF% of NAFLD patients, speckle tracking echocardiography showed a significant reduction in global peak systolic strain in patients group (-18.96±2.31 vs -20.27±1.72, p=0.016). The reduction in strain has been shown to denote LV systolic dysfunction. Thus, EF% fails to show early subtle changes, and when decreased, it reflects irreversible heart damage. In this context we would need to conduct another study with larger sample size and minimizing the effects of confounding factors such as weight difference between case and control groups. Moreover, determination of optimal cut point for GPSS to screen subclinical ventricular dysfunction of NAFLD patients is necessary. Also the relation between severity of fatty liver and subsequent reduction of strain should be explored.

Conclusion

NAFLD patients have systolic and diastolic LV dysfunction even in the absence of hypertension, obesity and diabetes; and speckle tracking echocardiography is a new sensitive and non-invasive method provides useful information to detect early identification of cardiac dysfunction in asymptomatic NAFLD patients.

References

1. Browning, J. D., Szczepaniak, L. S., Dobbins, R., Nuremberg, P., Horton, J. D., Cohen, J. C., … Hobbs, H. H. Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity. Hepatology, 2004; 40(6): 1387–1395. doi:10.1002/hep.20466
2. Bellentani, S., Scaglioni, F., Marino, M., Bedogni, G. Epidemiology of Non-Alcoholic Fatty Liver Disease. Dig Dis, 2010; 28(1): 155–161. doi:10.1159/000282080
3. Fabbrini, E., Sullivan, S., Klein, S. Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications. Hepatology, 2009; 51(2): 679–689. doi:10.1002/hep.23280
4. Fabbrini, E., Sullivan, S., Klein, S. Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications. Hepatology, 2009; 51(2): 679–689. doi:10.1002/hep.23280
5. Hamaguchi M, Kojima T, Takeda N, Nagata C, Takeda J, Sarui H, et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol, 2007; 13:1579-1584.
6. Domanski, J.P., Park, S.J., Harrison, S. A. Cardiovascular disease and nonalcoholic fatty liver disease: does histologic severity matter? J Clin Gastroenterol, 2012; 46(5):427-30.
7. Gaudio, E., Nobili, V., Franchitto, A., Onori, P., Carpino, G. Nonalcoholic fatty liver disease and atherosclerosis. Internal and Emergency Medicine, 2012; 7(S3), 297–305.
8. Al Rifai, M., Silverman, M.G., Nasir, K., Budoff, M.J., Blankstein, R., Szklo, M., Katz R., Blumenthal, R.S., Blaha, M.J. The association of nonalcoholic fatty liver disease, obesity, and metabolic syndrome, with systemic inflammation and subclinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis; 2015; 239(2):629-33.
9. Hamaguchi, M., Kojima, T., Takeda, N., Nagata, C., Takeda, J., Sarui, H., … Yoshikawa, T. (2007). Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol, 2007; 13(10):1579-84.
10. Fotbolcu, H., Yakar, T., Duman, D., Karaahmet, T., Tigen, K., Cevik, C., … Dindar, I. (2010). Impairment of the left ventricular systolic and diastolic function in patients with non-alcoholic fatty liver disease. Cardiol J, 2010; 17(5):457-63.
11. Kocabay, G., Karabay, C.Y., Colak, Y., Oduncu,V., Kalayci, A., Akgun, T., Guler, A., Kirma, C. Left atrial deformation parameters in patients with non-alcoholic fatty liver disease: a 2D speckle tracking imaging study. Clin Sci, 2014; 126(4):297-304.
12. Karabay, C.Y., Kocabay, G., Kalayci, A., Colak, Y., Oduncu, V., Akgun, T., Kalkan, S., Guler, A., Kirma, C. Impaired left ventricular mechanics in nonalcoholic fatty liver disease: a speckle-tracking echocardiography study. Eur J Gastroenterol Hepatol, 2014; 26(3):325-31.
13. Goland, S., Shimoni, S., Zornitzki, T., Knobler, H., Azoulai, O., Lutaty, G., Melzer, E., Orr, A., Caspi, A., Malnick, S.(2006). Cardiac abnormalities as a new manifestation of nonalcoholic fatty liver disease: echocardiographic and tissue Doppler imaging assessment. J Clin Gastroenterol, 2006; 40(10):949-55.
14. Mishra, P., Younossi, Z.M. Abdominal Ultrasound for Diagnosis of Nonalcoholic Fatty Liver Disease (NAFLD). The American Journal of Gastroenterology, 2007; 102: 2716–2717.
15. Cahill, J.M., Horan, M., Quigley, P., Maurer, B., McDonald, K. Doppler-echocardiographic indices of diastolic function in heart failure admissions with preserved left ventricular systolic function. Eur J Heart Fail, 2002; 4(4):473-8.
16. Mottram M. Assessment of diastolic function: what the general cardiologist needs to know. Heart, 2005; 91(5): 681–695.
17. Li XC, Yao GH, Zhang C, Zhang M, Zhang PF, Zhang W, Hu YY, Ji XP, Zhang Y. Quantification of regional volume and systolic function of the left ventricle by real-time three-dimensional echocardiography. Ultrasound Med Biol, 2008; 34(3):379-84.
18. Kleijn A., Kamp, O. Clinical application of three-dimensional echocardiography: past, present and future. Neth Heart J; 2009; 17(1): 18–24.
19. Correale, M., Ieva, R., Manuppelli, V., Rinaldi, A., Di Biase, M. Controversies in echocardiography: 2D vs 3D vs 4D. Minerva cardioangiologica, 2009; 57(4), 443-455.
20. Belohlavek, M., Foley, D.A., Gerber, T.C., Kinter, T.M., Greenleaf, J.F., Seward, J.B. Three- and four-dimensional cardiovascular ultrasound imaging: a new era for echocardiography. Mayo Clin Proc; 1993; 68(3):221-40.
21. Mondillo, S., Galderisi, M., Mele, D., Cameli, M., Lomoriello, V. S., Zacà, V., … Badano, L. Speckle-tracking echocardiography a new technique for assessing myocardial function. J Ultrasound Med; 2011; 30(1):71-83.
22. Szulik, M., Pappas, C.J., Jurcut, R., Magro, M., Peeters, E., Goetschalckx, K., Rademakers, F., Desmet, W., Voigt, J.U. Clinical validation of a novel speckle-tracking-based ejection fraction assessment method. J Am Soc Echocardiogr, 2011; 24(10):1092-100.
23. Cheng, S., Fernandes, V. R. S., Bluemke, D. A., McClelland, R. L., Kronmal, R. A., and Lima, J. A. C. Age-Related Left Ventricular Remodeling and Associated Risk for Cardiovascular Outcomes: The Multi-Ethnic Study of Atherosclerosis.Circ Cardiovasc Imaging; 2009; 2(3): 191–8.
24. Boden, G., Salehi, S. Why does obesity increase the risk for cardiovascular disease? Curr Pharm Des, 2013; 19(32):5678-83.
25. Hubert, H.B., Feinleib, M., McNamara, P. M., Castelli, W.P. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation, 1983; 67(5):968-77.

(Visited 344 times, 1 visits today)