Induced myocardial ischemia in candidates to liver transplantation without evidence of heart disease

Figures & data

Figure 1. Protocol to assess preoperatory cardiological risk in patients underwent liver transplantation. The number of patients allocated to single tests has been reported in brackets. CAD: coronary artery disease; CAG: coronary angiography; CCTA: coronary computed tomography angiography; CV-RF: cardiovascular risk factors; DM: diabetes mellitus; ECG: electrocardiogram; LT: liver transplantation; PCI: percutaneous coronary intervention; SE: stress echocardiography.

Table 1. Characteristics of the overall population.

Characteristics	Total (n = 283)	NO CAG (n = 242)	CAG NEG (n = 14)	CAG NCC (n = 19)	CAG PCI (n = 8)
Age, years (mean ± SD)	57 ± 10	56 ± 10	61 ± 6	61 ± 5	63 ± 4
BMI, kg/m^2 (mean ± SD)	25.52 ± 4.46	25.28 ± 4.51	26.91 ± 4.38	26.89 ± 3.67	26.42 ± 4.40
EF, % (mean ± SD)	62 ± 4	63 ± 4	62 ± 5	61 ± 5	63 ± 3
MELD (mean ± SD)	14.4 ± 8.8	14.2 ± 8.9	17.5 ± 8.2	14.2 ± 5.3	13.2 ± 10.9
Women, n (%)	74 (26.1)	67 (26.7)	5 (35.7)	2 (10.5)	0 (0)
Transplanted, n (%)	163 (57.6)	140 (57.9)	7 (50.0)	10 (52.6)	6 (75.0)
Etiology
HBV, n (%)	29 (10.2)	26 (10.7)	1 (7.1)	2 (10.5)	0 (0)
HCV, n (%)	106 (37.5)	93 (38.4)	5 (35.7)	6 (31.6)	2 (25.0)
ETOH, n (%)	68 (24.0)	57 (23.6)	1 (7.1)	7 (36.8)	3 (37.5)
NASH, n (%)	18 (6.4)	10 (4.1)	5 (35.7)	1 (5.3)	2 (25.0)
Other, n (%)	62 (21.9)	56 (23.1)	2 (14.3)	3 (15.8)	1 (12.5)
Risk factors
Diabetes, n (%)	91 (32.2)	68 (28.1)	8 (57.1)	11 (57.9)	4 (50.0)
Familiar history of CAD, n (%)	19 (6.7)	13 (5.4)	1 (7.1)	4 (21.1)	1 (12.5)
Active smoking, n (%)	83 (29.3)	71 (29.3)	3 (21.4)	7 (36.8)	2 (25.0)
Hypertension, n (%)	97 (34.3)	71 (29.3)	8 (57.1)	12 (63.2)	6 (75.0)
Dyslipidaemia, n (%)	13 (4.6)	6 (2.5)	2 (14.3)	3 (15.8)	2 (25.0)
≥2 RF, n (%)	81 (28.6)	56 (23.1)	8 (57.1)	11 (57.9)	6 (75.0)

CAG: coronary angiography; NEG: negative for coronary disease; NCC: non-critical coronaropathy; PCI: percutaneous coronary intervention; BMI: body mass index; EF: ejection fraction; MELD: model for end-stage liver disease; HBV: hepatitis B virus; HCV: hepatitis C virus; ETOH: ethanol (alcoholic liver disease); NASH: non-alcoholic steatohepatitis; OTHER include autoimmune hepatitis, Budd–Chiari syndrome, primary biliary cirrhosis and Wilson’s disease; RF: risk factors; SD: standard deviation.

Values are expressed as medians (interquartile ranges) for continuous variables and numbers (percentages) for categorical variables, referred to total population. Chi-square test for multiple variables showed no significant differences between the four evaluated groups.

Table 2. Indications to coronary angiography according to the non-invasive tests.

	SE +		CCTA +		TOT
	N	%	N	%	N	%
CAG NEG	14	4.9%	0	0%	14	4.9%
CAG NCC	12	4.2%	7	2.5%	19	6.7%
CAG PCI	4	1.4%	4	1.4%	8	2.8%
TOT	30	10.6%	11	3.9%	41	14.5%

SE +: stress echocardiography positive test results; CCTA +: coronary computed tomography angiography positive test results; CAG: coronary angiography; NEG: negative for coronary disease; NCC: non-critical coronaropathy; PCI: percutaneous coronary intervention; TOT: total.

Values are expressed as absolute numbers and percentages referred to total population.

Table 3. Sensitivity, specificity, positive predictive value and negative predictive value relative to non-invasive tests in patients who underwent liver transplantation.

	SE	CCTA
TOT	273	34
FP	26	7
TP	4	4
FN	4	0
TN	239	23
PPV	13.3%	36.4%
NPV	98.4%	100%
Sn	50.0%	100%
Sp	90.2%	76.7%

SE: stress echocardiography; CCTA: coronary computed tomography angiography; FP: false positives; TP: true positives; FN: false negatives; TN: true negatives; PPV: positive predictive value; NPV: negative predictive value; Sn: sensitivity; Sp: specificity.

Values are expressed as absolute numbers and percentages for categorical variables.

Figure 2. Kaplan–Meier’s curves relative to event-free survival in patients underwent liver transplantation. Patients were divided among the four CAG-related groups as follows: NO CAG: patients not subjected to coronary angiographies; CAG – NEG: negative coronary angiographies; CAG – NCC: non-critical coronaropathy; CAG – PCI: critical coronaropathy requiring revascularization. Censored patients are detailed by markings on the respective curves.

Table 4. Major adverse cardiac events (a) and all-cause mortality (b).

(a) MACE distribution
	Total (n = 163)	NO CAG (n = 140)	CAG NEG (n = 7)	CAG NCC (n = 10)	CAG PCI (n = 6)
CV death, n (%)	1 (0.6)	0 (0.0)	0 (0)	1 (0.1)	0 (0)
Hospitalization for coronary revascularization, n (%)	3 (1.8)	1 (0.7)	0 (0)	1 (10.0)	1 (16.7)
Hospitalizations for CV causes not related to coronary pathology, n (%)	1 (0.6)	0 (0)	1 (14.3)	0 (0)	0 (0)

MACE: major adverse cardiovascular event (cardiovascular death, hospitalization for coronary revascularization, hospitalizations for cardiovascular causes not related to coronary pathology); CAG: coronary angiography; NEG: negative for coronary disease; NCC: non-critical coronaropathy; PCI: percutaneous coronary intervention; CV: cardiovascular.

Values are expressed as absolute numbers and percentages referred to the LT population. No significant differences between these groups were found.

Table

(b) All-cause mortality
	Total (n = 163)	NO CAG (n = 140)	CAG NEG (n = 7)	CAG NCC (n = 10)	CAG PCI (n = 6)
Acute coronary events, n (%)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Acute non-coronary events, n (%)	1^a (0.6)	0 (0)	0 (0)	1^a (10.0)	0 (0)
Sepsis, n (%)	4 (2.4)	3 (2.1)	0 (0)	0 (0)	1 (16.7)
LT failure^b, n (%)	7 (4.3)	6 (4.3)	0 (0)	1 (10.0)	0 (0)
Other, n (%)	4 (2.4)	3 (2.1)	1 (14.3)	0 (0)	0 (0)
TOT, n (%)	16 (9.8)	12 (8.6)	1 (14.3)	2 (20.0)	1 (16.7)

CAG: coronary angiography; NEG: negative for coronary disease; NCC: non-critical coronaropathy; PCI: percutaneous coronary intervention.

Values are expressed as absolute numbers and percentages referred to the LT population. No significant differences between these groups were found.

^a Aortic dissection.

^b Recurrence of hepatocellular carcinoma (HCC), multi-organ failure (MOF), death on operating table (DOT) and graft failure.

Data availability statement

Data will be available at request.

Table

(b) All-cause mortality
	Total (n = 163)	NO CAG (n = 140)	CAG NEG (n = 7)	CAG NCC (n = 10)	CAG PCI (n = 6)
Acute coronary events, n (%)	0 (0)	0 (0)	0 (0)	0 (0)	0 (0)
Acute non-coronary events, n (%)	1^a (0.6)	0 (0)	0 (0)	1^a (10.0)	0 (0)
Sepsis, n (%)	4 (2.4)	3 (2.1)	0 (0)	0 (0)	1 (16.7)
LT failure^b, n (%)	7 (4.3)	6 (4.3)	0 (0)	1 (10.0)	0 (0)
Other, n (%)	4 (2.4)	3 (2.1)	1 (14.3)	0 (0)	0 (0)
TOT, n (%)	16 (9.8)	12 (8.6)	1 (14.3)	2 (20.0)	1 (16.7)

CAG: coronary angiography; NEG: negative for coronary disease; NCC: non-critical coronaropathy; PCI: percutaneous coronary intervention.

Values are expressed as absolute numbers and percentages referred to the LT population. No significant differences between these groups were found.

^a Aortic dissection.

^b Recurrence of hepatocellular carcinoma (HCC), multi-organ failure (MOF), death on operating table (DOT) and graft failure.