Liver cirrhosis and left ventricle diastolic dysfunction: Systematic review

Table 1 Included studies and patients’ characteristics

Author	Study type	Number of cases, n	Gender (male), n	Control, n	Etiology of cirrhosis, n			Means1 of Child-Pugh scores'	Child-Pugh classification, n			Means1 of MELD scores'
					V	A	O		A	B	C
Dadhich et al[31]	Cross sectional case control study	40	ND	20	26	10	4	7.5 ± 1.08 pre-ascitic group, 9.4 ± 2.11 ascitic group	4	22	14	ND
Lee et al[32]	Cohort study	70	55	0	16	47	7	ND	18	35		14.1 ± 5.9
Karagiannakis et al[33]	Cohort study	45	E33	0	19	22	4	6.43 ± 1.9	26	15	3	11.5 ± 4.2
Alexopoulou et al[34]	Cross-sectional observa-tional study	76	57	0	41	20	15	9.2 ± 2.7	11	28	37	17 ± 7
Farouk et al[15]	Cross-sectional study	35	22	16	35			ND	6	14	15	ND
Bhuin et al[16]	Descrip-tive study	70	32	0			70	ND	4	38	28	ND
Cesari et al[35]	Case series	117	106	46		57	60	8 ± 2	ND	ND	ND	12 ± 5
Ru ız-del- Arbol, et al[21]	Cross-sectional	80	67	0	32	35	13	8 ± 2 grade 0; 9 ± 2 grade 1; 10 ± 2 grade 2;	12	30	38	15 ± 6 grade 0; 16 ± 5 grade 1; 21 ± 6 grade 2;
Rimbas et al[36]	Cross-sectional observa-tional study	46	30	46	19	24	3	7 ± 2	23	16	7	13 ± 5
Hammami et al[25]	Cross-sectional study	80	42	80	42		38	ND	24	36	20	14.2 ± 4.98
Merli et al[37]	Cross-sectional observa-tional study	90	59	31	49	28	13	ND	48	26	16	11.9 ± 4.7
Merli et al[26]	Case series	74	44	26	41	21	12	ND	29	26	19	13 ± 5
Kazankov et al[38]	Cross-sectional observa-tional study	44	27	23	5	32	7	7.1 ± 2.2	20	12	8	12.3 ± 4.9
Nazar et al[22]	Case series	100	71	0	41	46	15	with LVDD 9 ± 2; no LVDD 8 ± 2.2	26	39	37	15 ± 7
Devauchelle et al[39]	Descrip-tive study	40	30	0	9	24	7	ND	13	9	18	16
Somani et al[24]	Cross-sectional observa-tional study	60	48	30	22	30	8	ND	8	26	26	15.2 ± 4.6 without LVDD;14.6 ± 4.3 with LVDD
Total		1067	723	318

¹Values are expressed as mean ± standard deviation. V: Viral; A: Alcoholic; O: Other; ND: No data.

Table 2 Risk of bias assessment in each study with ROBINS-I tool

Author	Bias due to confounding	Bias in selection of participants into the study	Bias in evaluation of LVDD and grading	Bias due to missing data	Bias in selection of the reported result	Bias in measurement of outcomes
Dadhich et al[31]	Moderate	Low	Low	No information	Low	Low
Lee et al[32]	Moderate	Moderate	Low	No information	Low	Low
Karagiannakis et al[33]	Moderate	Moderate	Low	Serious	Low	Low
Alexopoulou et al[34]	Moderate	Moderate	Low	No information	Low	Low
Farouk et al[15]	Moderate	Low	Low	No information	Low	Low
Bhuin et al[16]	Moderate	Moderate	Low	No information	Low	Low
Cesari et al[35]	Moderate	Serious	Low	Serious	Low	Low
Ru ız-del- Arbol, et al[21]	Low	Moderate	Low	No information	Low	Low
Rimbas et al[36]	Moderate	Moderate	Low	Seriuos	Moderate	Low
Hammami et al[25]	Moderate	Serious	Low	Low	Low	Moderate
Merli et al[37]	Moderate	Low	Low	Serious	Moderate	Moderate
Merli et al[26]	Moderate	Low	Low	Serious	Low	Low
Kazankov et al[38]	Serious	Moderate	Low	Serious	No information	Serious
Nazar et al[22]	Low	Moderate	Low	Serious	No information	Moderate
Devauchelle et al[39]	Critical	No information	Low	No information	Low	No information
Somani et al[24]	Low	Low	Low	No information	Low	Low

LVDD: Left ventricle diastolic dysfunction.

Table 3 Recorded echocardiographic parameters of left ventricle diastolic dysfunction

Author	DT	IVRT	E	A	E/A	E/e' = E/E'	e'(E')	e'(E') medial	e'(E') lateral
Dadhich et al[31]	+	+			+	+	+	+	+
Lee et al[32]	+	+			+	+	+	+	+
Karagiannakis et al[33]	+	+			+	+	+	+	+
Alexopoulou et al[34]	+		+	+	+	+	+
Farouk et al[15]	+		+	+	+	+	+
Bhuin et al[16]	+	+	+	+	+	+	+
Cesari et al[35]	+		+	+	+	+		+
Ruız-del-Arbol et al[21]	+	+			+	+	+	+	+
Rimbas et al[36]	+	+	+	+	+	+		+	+
Hammami et al[25]	+		+	+	+	+
Merli et al[37]	+	+			+	+			+
Merli et al[26]	+				+	+			+
Kazankov et al[38]	+				+	+			+
Nazar et al[22]	+				+		+	+
Devauchelle et al[39]					+	+	+	+	+
Somani et al[24]	+	+	+	+	+	+			+

DT: Deceleration time; IVRT: Isovolumetric relaxation time; E: Mitral inflow peak early filling velocity; A: Mitral inflow late diastolic filling velocity; E/A: Ratio of peak early filling and late diastolic filling velocities; E/e′ : Mitral valve E velocity divided by mitral annular e′ velocity; e′: Peak modal velocity in early diastole at the leading edge of spectral waveform, average from e′ medial and e′ lateral[26,27].

Table 4 Left ventricle diastolic dysfunction and its’ grades in analysed studies

Author	Diagnosis of LVDD in patients, n (%)	Grade 1, n	Grade 2, n	Grade 3, n	Diagnosis of LVDD in controls, n (%)	Year of LVDD guidelines used
Dadhich et al[31]	28 (70)	11	17			2009
Lee et al[32]	44 (62.8)	34	10			2009
Karagiannakis et al[33]	17 (37.7)	9	8			2009
Alexopoulou et al[34]	51 (67.1)	37	11	3		2009
Farouk et al[15]	9 (25.7)	9				2009
Bhuin et al[16]	57 (81.4)	29	28			2009
Cesari et al[35]	43 (37)	4	28	11	7 (16)	2009
Ru ız-del- Arbol, et al[21]	37 (46.2)	19	18			2009
Rimbas et al[36]	22 (47.8)	12	8	2		2016
Hammami et al[25]	41 (51.2)	19	11	11	8 (10)	2016
Merli et al[37]	36 (40)	24	12			2009
Merli et al[26]	47 (63.5)	37	10			2009
Kazankov et al[38]	24 (54.5)	11	12	1		2009
Nazar et al[22]	58 (58)	42	16			2009
Devauchelle et al[39]	14 (35)	11	3			2009
Somani et al[24]	18 (30)	15	3			2009
Total	546 (51.2)	323	195	28	15 (4.7)

LVDD: Left ventricle diastolic dysfunction.

Table 5 Difference in means of Child-Pugh scores between left ventricle diastolic dysfunction grades

Author	Number of cases, n	Difference in means of Child-Pugh scores between LVDD grades Yes/No/Not assessed	Mean Child-Pugh scores in patients without LVDD	Mean Child-Pugh scores in patients with LVDD	P value
Dadhich et al[31]	40	NA	NA	NA	-
Lee et al[32]	70	NA	NA	NA	-
Karagiannakis et al[33]	45	No	6.5 ± 2.1	6.4 ± 1.6	NS
Alexopoulou et al[34]	76	No	9 ± 2.8	9.2 ± 2.6	NS
Farouk et al[15]	35	NA	NA	NA	-
Bhuin et al[16]	70	NA	NA	NA	-
Cesari et al[35]	117	NA	NA	NA	-
Ru ız-del- Arbol, et al[21]	80	Yes	8 ± 2 (7-9)	10 ± 2 (9-11)	aP < 0.01
Rimbas et al[36]	46	Yes	7.1 ± 2	7.3 ± 2.1	aP < 0.01
Hammami et al[25]	80	NA		NA	-
Merli et al[37]	90	NA	NA	NA	-
Merli et al[26]	74	NA	NA	NA	-
Kazankov et al[38]	44	No	ND	ND	NS
Nazar et al[22]	100	NA	NA	NA	-
Devauchelle et al[39]	40	NA	NA	NA	-
Somani et al[24]	60	NA	NA	NA	-

^aLVDD grade 2 with respect to the values of LVDD grade 0. NA: Not assessed; ND: No data; NS: Not significant; LVDD: Left ventricle diastolic dysfunction.

Table 6 The difference in means of MELD scores between with and without left ventricle diastolic dysfunction groups

Author	MELD1 score in patients with LVDD	MELD1 score in patients without LVDD	P value
Lee et al[32]	13.9 ± 5.7	14.5 ± 6.4	NS
Karagiannakis et al[33]	11 ± 3.5	11.7 ± 4.6	NS
Alexopoulou et al[34]	15.5 ± 6.5	14.3 ± 5.7	NS
Nazar et al[22]	16 ± 8	14 ± 6	P = 0.07
Somani et al[24]	14.6 ± 4.3	15.2 ± 4.6	NS
Rimbas et al[36]	13 ± 6	13 ± 5	NS
Ru ız-del- Arbol, et al[21]	16 ± 53 and 21 ± 64	15 ± 6	aP < 0.005
Kazankov et al[38]	ND	ND	ND
Devauchelle et al[39]	14 (4)2	16 (11)2	NS

¹Values are expressed as mean ± standard deviation;

²Values are expressed as medians (interquartile range);

³MELD scores of grade 1 left ventricle diastolic (LVDD);

⁴MELD scores of grade 2 LVDD;

^aLVDD grade 2 with respect to the values of LVDD grade 0. LVDD: Left ventricle diastolic dysfunction; ND: No data; NS: Not significant.

Table 7 The presence of ascites association with left ventricle diastolic dysfunction

Author	Overall patients with LVDD, n (%)	LVDD in patients with ascites, n (%)	LVDD in patients without ascites, n (%)	P value
Dadhich et al[31]	28/70	16/80	12/60	P = 0.09
Lee et al[32]				NA
Karagiannakis et al[33]	17/37.8	9/40.9	8/34.8	NA
Alexopoulou et al[34]	51/67.1	14/93.3	37/60.7	P = 0.016
Farouk et al[15]				NA
Bhuin et al[16]	47/67.1	47/67.1	0
Cesari et al[35]	37/32.7	22/28.6	15/41.7	P < 0.005
Ru ız-del- Arbol et al[21]	37/46.3	31/57.4	6/23.1	aP < 0.01 and bP < 0.025
Rimbas et al[36]				NA
Hammami et al[25]	49/61.0	25/64.1	24/58.5	NA
Merli et al[37]				NA
Merli et al[26]				P = 0.04
Kazankov et al[38]				NA
Nazar et al[22]	58/58.0	47/63.5	11/42.3	P = 0.03
Devauchelle et al[39]				NA
Somani et al[24]				NA

^aLeft ventricle diastolic dysfunction (LVDD) grade 2 with respect to values of LVDD grade 0;

^bLVDD grade 2 with respect to values of LVDD grade 1. LVDD: Left ventricle diastolic dysfunction; NA: Not assessed.

Table 8 Older age association with the presence of left ventricle diastolic dysfunction

Author	Number of cases, n	Older age association with the presence of LVDD, Yes/No/Not assessed	Age (patients without LVDD)1	Age (patients with LVDD)1	P value
Dadhich et al[31]	40	No	ND	ND	NS
Lee et al[32]	70	Yes	47.8 ± 8.0	58.2 ± 9.9	P < 0.001
Karagiannakis et al[33]	45	Yes	53.8 ± 13	62.8 ± 9	P = 0.016
Alexopoulou et al[34]	76	Yes	53.4 ± 16.5	62.4 ± 12.7	P = 0.04
Farouk et al[15]	35	NA	NA	NA	-
Bhuin et al[16]	70	NA	NA	NA	-
Cesari et al[35]	117	Yes	ND	ND	P = 0.005
Ru ız-del- Arbol et al[21]	80	No	ND	ND	NS
Rimbas et al[36]	46	NA	NA	NA	-
Hammami et al[25]	80	NA	NA	NA	-
Merli et al[37]	90	NA	NA	NA	-
Merli et al[26]	74	NA	NA	NA	-
Kazankov et al[38]	44	No	ND	ND	NS
Nazar et al[22]	100	No	55 ± 10	57 ± 10	NS
Devauchelle et al[39]	40	No	57 (10)	59 (13)	NS
Somani et al[24]	60	No	50.5 ± 9.9	49.5 ± 8.5	NS

¹Values are expressed as mean ± standard deviation. LVDD: Left ventricle diastolic dysfunction; NA: Not assessed; NS: Not significant.