Abstract
Objective
Liver disease (LD) is considered a risk factor for inferior outcomes in general and cardiac surgery, yet current cardiac surgery risk estimators exclude LD, and literature on the topic remains scant. We sought to evaluate whether the presence of advanced LD is associated with inferior outcomes following cardiac surgery.
Methods
This single-center, retrospective, observational study included 285 patients diagnosed with LD who underwent cardiac surgery in 2010 to 2020. The cohort contained 3 groups, Child-Turcotte-Pugh (CTP) class A (n = 219), CTP early-class B (n = 34), and CTP advanced-class B (n = 32). A model for end-stage liver disease score of 12.7 points (determined using a receiver-operating characteristic curve analysis on 30-day mortality) dichotomized class B into early- and advanced-groups. Univariate and multivariate logistic regression analyses were performed to identify predictors of 30-day mortality.
Results
Patients in CTP advanced-class B had the longest length of stay (14 days), highest incidence of prolonged ventilation (46.9%), renal failure (21.9%), 30-day mortality (18.8%), and in-hospital mortality (18.8%). Incidence of ≥1 postoperative complication was higher in CTP advanced-class B (59.4%), compared with CTP class A (37.9%) and CTP early-class B (38.2%). Multivariate logistic regression analysis demonstrated that female sex (odds ratio, 3.01; 95% CI, 1.07-8.77; P = .037) and peripheral vascular disease (odds ratio, 4.01; 95% CI, 1.33-12.2; P = .013) were independent predictors of 30-day mortality in patients with advanced LD.
Conclusions
Severity of LD influences perioperative outcomes following cardiac surgery. Our data suggest that patients in CTP class A and selected patients in CTP class B (model for end-stage liver disease score <12.7) can undergo surgery with acceptable risk.
Key Words: cardiac surgery, liver disease, cirrhosis, CTP, MELD, outcomes
Graphical abstract
Co-existence of cardiac and liver dysfunction.
Central Message.
Patients with cirrhosis in CTP class A and patients in CTP class B with a MELD score <12.7 may be candidates for cardiac surgery with an acceptable risk of postoperative morbidity and mortality.
Perspective.
An enhanced stratification of preoperative liver function may further inform postoperative outcomes and should be included in risk assessment for cardiac surgery.
Advanced liver disease (LD) is a major preoperative risk factor in abdominal surgery, with a direct correlation between the severity of LD, as determined by the Child-Turcotte-Pugh (CTP) classification or the model for end-stage liver disease (MELD) score, and surgical outcomes. However, it is not accounted for in risk estimators for cardiac surgery, and literature on the topic remains scarce.1 It is well documented that there is overlapping involvement of the heart and liver in multiple systemic disorders, such as inflammation, infections, and substance abuse disorder.2,3 Mortality of patients with cirrhosis after cardiac surgery is rarely due to impairment of cardiac function.4 Rather, morbidity and mortality in these cases tend to be a result of complications related to underlying LD, such as coagulopathy, increased susceptibility to bacterial infections, portal hypertension, and thrombocytopenia.5, 6, 7 The eligibility of patients with cirrhosis for major cardiac surgery has increased due to dramatic advancements in medical management and life expectancy of patients with advanced LD,8,9 including medical therapy for portal hypertension and viral hepatitis, endoscopic treatment of esophageal varices, and availability of transjugular intrahepatic portosystemic shunt.8 This study aims to assess whether the presence of advanced LD is associated with inferior surgical outcomes following cardiac surgery.
Materials and Methods
Study Design and Inclusion Criteria
We performed a single-center, retrospective cohort study including all adult patients with LD who underwent coronary artery bypass graft (CABG), aortic valve replacement, mitral valve replacement, or mitral valve repair at Yale-New Haven Hospital between 2010 and 2020. During this period, a total of 9098 open heart procedures were performed. The prevalence of patients with LD was 4.68% (426 patients). This includes the small number of patients who underwent reoperation. Patients were excluded if they were younger than age 18 years, or if the severity of LD could not be assessed by retrospective chart review.
Patient Cohort and Data Collection
Preoperative, operative, and postoperative data were collected from the Society of Thoracic Surgeons database and Yale-New Haven Hospital electronic health records. The Institutional Review Board of Yale approved the study protocol and publication of data according to institutional review board No, 2,000,020,356 (initial approval March 2, 2017, initial effective March 2, 2017, effective January 17, 2023). The patients provided informed written consent for the publication of the study data. A total of 285 patients were included in the final study population. Patients were stratified into three groups by severity of LD based on classification and values of the validated severity scores, CTP, and MELD. A receiver-operating characteristic curve analysis was used to identify a cutoff value of the MELD score to dichotomize CTP class B into 2 groups.
LD Severity Score Definition
The preoperative severity of each patient's LD was determined using the CTP classification and MELD score. The CTP score was calculated using the following variables, with each variable being assigned 1 to 3 points: encephalopathy, ascites, total serum bilirubin level, serum albumin level, and prothrombin time-international normalized ratio (PT-INR). The resulting score yielded each patient's CTP classification (Table 1). Class A (5-6 points) indicates well-compensated LD, class B (7-9 points) indicates LD of moderate severity, and class C (10-15 points) indicates severe LD.10, 11, 12 The MELD score was calculated using the following formula: MELD = 11.2×loge (PT-INR) + 9.57×loge (creatinine [mg/dL]) + 3.78×loge (bilirubin [mg/dL]) + 6.43.13
Table 1.
Child-Turcotte-Pugh scoring
| Variable | 1 point | 2 points | 3 points |
|---|---|---|---|
| Encephalopathy | None | Grade 1-2 (or precipitant induced) | Grade 3-4 (or chronic) |
| Ascites | None | Mild/moderate (diuretic responsive) | Severe (diuretic refractory) |
| Total bilirubin (mg/dL) | <2 | 2-3 | >3 |
| Albumin (g/dL) | >3.5 | 2.8-3.5 | <2.8 |
| PT (sec prolonged) | <4 | 4-6 | >6 |
| or PT-INR | <1.7 | 1.7-2.3 | >2.3 |
PT, Prothrombin time; PT-INR, international normalized ratio of prothrombin time.
Outcomes
The primary outcomes of this study were 30-day and in-hospital all-cause mortality. Secondary outcomes were defined as per Society of Thoracic Surgeons guidelines for reporting mortality and morbidity after cardiac valve interventions.14 An additional outcome included a composite outcome of postoperative complications consisting of surgical site infection, stroke, sepsis, prolonged ventilation, renal failure, reoperation for bleeding, and readmission. Renal failure was defined as an increase in serum creatinine level 3.0-times greater than baseline, serum creatinine ≥4 mg/dL, or a new requirement for dialysis postoperatively.
Statistical Analysis
Following the assessment of normality, normally distributed continuous variables were compared using analysis of variance, and nonnormally distributed continuous variables were compared using the Kruskal-Wallis test. Categorical variables were compared using the χ2 test. Univariate and multivariate logistic regression were applied to predict the risk of 30-day mortality in those who underwent cardiac surgery, stratified by severity of LD. Variables with a P value < .2 in the univariate analysis and clinically significant variables for this group of patients were included in the multivariate analysis. Statistical analysis was performed by using R version 4.4 (R Foundation for Statistical Computing).
Results
The general and clinical demographics of the cohort are shown in Table 2. The cohort identified predominantly as male (68.1%) and White (67.0%). A cutoff value of the MELD score (ie, 12.7) was chosen as a result of the receiver-operating characteristic curve analysis on 30-day operative mortality and used to dichotomize CTP class B into early- and advanced-class B (Figure 1). The MELD value of 12.7 was found to be the optimal threshold of classification, maximizing the sum of sensitivity and specificity. A MELD score of 12.7 had a sensitivity of 79.9% and a specificity of 52.4% for 30-day mortality and an area under the curve of 0.6546. Patients in CTP class B had MELD scores ranging from 6.43 to 31.78, and a mean MELD score of 10.45. No patients were classified as CTP class C. Proportionately more patients in CTP class A had hypertension, dyslipidemia, diabetes, and chronic lung disease. Heart failure within 2 weeks as well as dialysis were most prevalent in CTP advanced-class B. CTP early-class B had the highest rate of infective endocarditis. Mild/moderate ascites was most common in CTP early-class B (44.1%) and encephalopathy was most common in CTP advanced-class B (15.6%). No patients developed hepatorenal syndrome. Approximately 52.7% of the cohort had liver disease that can be attributed to viral disease (Table 2).
Table 2.
Summary of baseline characteristics
| Variable | Overall (N = 285) | CTP class A (n = 219) | CTP early- class B (n = 34) | CTP advanced-class B (n = 32) | P value∗ |
|---|---|---|---|---|---|
| Age (y) | 60 (52-66) | 61 (55-67) | 43 (30-56) | 60 (50-65) | <.001 |
| Male | 194 (68.1) | 156 (71.2) | 15 (44.1) | 23 (71.9) | .006 |
| Race | .448 | ||||
| White | 191 (67.0) | 147 (67.1) | 27 (79.4) | 17 (53.1) | |
| Black | 51 (17.9) | 39 (17.8) | 3 (8.8) | 9 (28.1) | |
| Hispanic | 22 (7.7) | 17 (7.8) | 2 (5.9) | 3 (9.4) | |
| Asian | 5 (1.8) | 5 (2.3) | 0 (0.0) | 0 (0.0) | |
| Other | 16 (5.6) | 11 (5.0) | 2 (5.9) | 3 (9.4) | |
| BMI | 27 (23-31) | 27 (24-32) | 24 (21-27) | 27 (22-33) | .002 |
| Ejection fraction (%) | 58 (50-63) | 58 (50-63) | 61 (57-64) | 57 (50-63) | .149 |
| Hypertension | 217 (76.1) | 179 (81.7) | 13 (38.2) | 25 (78.1) | <.001 |
| Pulmonary hypertension | 28 (9.8) | 21 (9.6) | 1 (2.9) | 6 (18.8) | .095 |
| Dyslipidemia | 159 (55.8) | 133 (60.7) | 8 (23.5) | 18 (56.3) | <.001 |
| Diabetes | 106 (37.2) | 91 (41.6) | 5 (14.7) | 10 (31.3) | .002 |
| Dialysis | 20 (7.0) | 11 (5.0) | 0 (0.0) | 9 (28.1) | <.001 |
| Cirrhosis | 95 (33.3) | 73 (33.3) | 8 (23.5) | 14 (43.8) | .502 |
| HF within 2 wk | 150 (52.6) | 107 (48.9) | 18 (52.9) | 25 (78.1) | .002 |
| Previous MI | 99 (34.7) | 81 (37.0) | 6 (17.6) | 12 (37.5) | .083 |
| Chronic lung disease | 81 (28.4) | 70 (32.0) | 7 (20.6) | 4 (12.5) | .015 |
| Infective endocarditis | 84 (29.5) | 43 (19.6) | 22 (75.9) | 19 (51.4) | <.001 |
| Intravenous drug use | 106 (37.2) | 70 (32.0) | 25 (73.5) | 11 (34.4) | <.001 |
| Peripheral vascular disease | 48 (16.8) | 31 (14.2) | 6 (17.6) | 11 (34.4) | .020 |
| Previous cardiac interventions | 105 (36.8) | 86 (39.3) | 9 (26.5) | 10 (31.3) | .076 |
| Medical therapy | |||||
| ACE inhibitors | 42 (14.7) | 42 (19.2) | 0 (0.0) | 0 (0.0) | .002 |
| Anticoagulant | 116 (40.7) | 86 (39.3) | 16 (47.1) | 14 (43.8) | .645 |
| Beta blocker | 158 (55.4) | 135 (61.6) | 10 (29.4) | 13 (40.6) | <.001 |
| Diuretics | 125 (43.9) | 86 (39.3) | 20 (58.8) | 19 (59.4) | .614 |
| Etiology of liver disease | .129 | ||||
| Viral | 150 (52.7) | 109 (49.8) | 22 (64.7) | 19 (59.4) | |
| Unknown | 56 (19.6) | 50 (22.8) | 4 (11.8) | 2 (6.3) | |
| Alcoholic | 24 (8.4) | 21 (9.6) | 1 (2.9) | 2 (6.3) | |
| >2 etiologies† | 19 (6.8) | 16 (7.4) | 2 (5.8) | 1 (3.1) | |
| Cardiogenic | 16 (5.6) | 9 (4.1) | 3 (8.8) | 4 (12.5) | |
| Other‡ | 20 (7.2) | 13 (6.5) | 2 (5.8) | 4 (12.5) | |
| Ascites | <.001 | ||||
| None | 247 (86.7) | 209 (95.4) | 18 (52.9) | 20 (62.5) | |
| Mild/moderate | 37 (13.0) | 10 (4.69) | 15 (44.1) | 12 (37.5) | |
| Severe | 1 (0.4) | 0 (0.0) | 1 (2.9) | 0 (0.0) | |
| Encephalopathy | <.001 | ||||
| None | 277 (97.2) | 218 (99.5) | 32 (94.1) | 27 (84.4) | |
| Grade 1-2 | 8 (2.8) | 1 (0.5) | 2 (5.9) | 5 (15.6) | |
| Grade 3-4 | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | |
| Laboratory values | |||||
| Creatinine (mg/dL) | 1.0 (0.8-1.4) | 1.0 (0.8-1.3) | 1.0 (0.7-1.3) | 1.9 (1.2-3.8) | <.001 |
| Albumin (g/dL) | 3.6 (3.1-4.0) | 3.8 (3.5-4.1) | 2.4 (2.2-3.0) | 3.0 (2.4-3.4) | <.001 |
| Bilirubin (mg/dL) | 0.5 (0.3-0.9) | 0.5 (0.3-0.8) | 0.5 (0.3-0.8) | 1.4 (0.5-2.2) | <.001 |
| INR | 1.1 (1.0-1.2) | 1.0 (1.0-1.1) | 1.1 (1.0-1.2) | 1.3 (1.2-1.6) | <.001 |
| Hemoglobin (g/dL) | 12 (9.4-13) | 12 (10-14) | 9.0 (8.4-10) | 9.2 (8.3-10) | <.001 |
| Platelets (109/L) | 195 (150-270) | 199 (150-260) | 208 (110-380) | 150 (110-230) | .041 |
| CTP score | 6 (5-6) | 5 (5-6) | 7 (7-7) | 7 (7-8) | <.001 |
| MELD score | 8.7 (7-12) | 7.9 (6.5-11) | 9.0 (7.8-11) | 18 (15-22) | <.001 |
Values are presented as median (interquartile range) or n (%). CTP, Child-Turcotte-Pugh; BMI, body mass index; HF, heart failure; MI, myocardial infarct; ACE, angiotensin-converting enzyme; INR, international normalized ratio; MELD, model for end-stage liver disease.
Pearson χ2 test; Kruskal-Wallis test.
Includes the following combinations: alcoholic and cardiogenic, cardiogenic and viral, viral and alcoholic, viral and metabolic, viral and malignancy, and malignancy and autoimmune.
Includes the following etiologies, each with an absolute frequency of <4%: autoimmune, drug-induced hepatitis, malignancy, and metabolic.
Figure 1.
Receiver operator characteristic curve for the ability of the model for end-stage liver disease score to predict 30-day mortality. ROC, Receiver operating characteristics.
The most common operations were isolated CABG (30.2%) and isolated valvular surgery (22.8%). Off-pump CABG was performed for 10.5% of CTP class A, 0% of CTP early-class B, and 3.1% of CTP late-class B. Cardiopulmonary bypass time and crossclamp time was shortest in CTP early-class B (Table 3).
Table 3.
Summary of operative characteristics
| Variable | Overall (n = 285) | CTP class A (n = 219) | CTP early- class B (n = 34) | CTP advanced- class B (n = 32) | P value∗ |
|---|---|---|---|---|---|
| Type of surgery | <.001 | ||||
| Isolated valvular | 65 (22.8) | 47 (21.5) | 4 (11.8) | 14 (43.8) | |
| Isolated CABG | 86 (30.2) | 78 (35.6) | 3 (8.8) | 5 (15.6) | |
| Concomitant valvular | 10 (3.5) | 6 (2.7) | 2 (5.9) | 2 (6.3) | |
| CABG and valvular | 17 (6.0) | 15 (6.8) | 2 (5.9) | 0 (0.0) | |
| Other | 107 (37.5) | 73 (33.3) | 23 (67.6) | 11 (34.4) | |
| Clinical status | <.001 | ||||
| Elective | 110 (38.6) | 101 (46.1) | 5 (14.7) | 4 (12.5) | |
| Urgent | 160 (56.1) | 109 (49.8) | 27 (79.4) | 24 (75.0) | |
| CPB use | 261 (91.6) | 196 (89.5) | 34 (100) | 31 (96.9) | .006 |
| Perfusion time (min) | 110 (79-150) | 110 (83-150) | 98 (62-130) | 130 (100-180) | .279 |
| Crossclamp time (min) | 80 (59-110) | 81 (59-110) | 67 (53-110) | 87 (62-120) | .635 |
Values are presented as median (interquartile range) or n (%). CTP, Child-Turcotte-Pugh; CABG, coronary artery bypass graft; CPB, cardiopulmonary bypass.
Pearson χ2 test; Kruskal-Wallis test.
In regard to postoperative outcomes, there was a significant difference noted in the 3 groups with respect to the length of stay (LOS), the incidence of surgical site infection, prolonged ventilation, renal failure, and readmission rates. No significant difference was noted for stroke, sepsis, and reoperation for bleeding. There were 115 patients (40.4%) who had at least 1 postoperative complication. Further stratification of this composite outcome shows that patients in CTP class A (37.9%) and CTP early-class B (38.2%) had a similar incidence rate of complications, whereas patients in CTP advanced-class B (59.4%) had a higher incidence rate of any complications (Table 4). In total, 21 patients died within 30 days of surgery (Table 4). We found 18.8% of patients in CTP advanced-class B died compared with 5.9% of patients in both CTP class A and CTP early-class B (P = .033). Analysis of 30-day mortality using linear regression revealed that for every unit increase in MELD score, the odds ratio (OR) of death increased by a factor of 1.1107 (95% CI, 1.033-1.19; P = .029).
Table 4.
Postoperative outcomes
| Variable | Overall (N = 285) | CTP class A (n = 219) | CTP early- class B (n = 34) | CTP advanced- class B (n = 32) | P value∗ |
|---|---|---|---|---|---|
| Hospital LOS (d) | 8 (5-13) | 7 (5-11) | 11 (7-15) | 14 (9-28) | <.001 |
| Surgical site infection | 10 (3.5) | 9 (4.1) | 1 (2.9) | 0 (0.0) | .029 |
| Stroke | 7 (2.5) | 5 (2.3) | 2 (5.9) | 0 (0.0) | .286 |
| Sepsis | 9 (3.2) | 7 (3.2) | 1 (2.9) | 1 (3.1) | .997 |
| Prolonged ventilation | 59 (20.7) | 37 (16.9) | 7 (20.6) | 15 (46.9) | <.001 |
| Renal failure | 18 (6.3) | 11 (5.0) | 0 (0.0) | 7 (21.9) | <.001 |
| Reoperation for bleeding | 8 (2.8) | 5 (2.3) | 1 (2.9) | 2 (6.3) | .646 |
| Readmission | 51 (17.9) | 41 (18.7) | 7 (20.6) | 3 (9.4) | .007 |
| Composite outcome | .066 | ||||
| Yes | 115 (40.4) | 83 (37.9) | 13 (38.2) | 19 (59.4) | |
| No | 170 (59.6) | 136 (62.1) | 21 (61.8) | 13 (40.6) | |
| Discharge status | .033 | ||||
| Alive | 264 (92.6) | 206 (94.1) | 32 (94.1) | 26 (81.3) | |
| Dead | 21 (7.4) | 13 (5.9) | 2 (5.9) | 6 (18.8) | |
| 30-d status | .033 | ||||
| Alive | 264 (92.6) | 206 (94.1) | 32 (94.1) | 26 (81.3) | |
| Dead | 21 (7.4) | 13 (5.9) | 2 (5.9) | 6 (18.8) |
Values are presented as median (interquartile range) or n (%). CTP, Child-Turcotte-Pugh; LOS, length of stay.
Pearson χ2 test; Kruskal-Wallis test.
Univariate analysis of the whole cohort identified the following variables with significant association with 30-day mortality: sex, heart failure within 2 weeks, infective endocarditis, CTP score, MELD score, peripheral vascular disease, and cerebrovascular disease (Table 5). Upon examining the independent effect of those variables on 30-day mortality using multivariate analysis, independent predictors for 30-day mortality were found to be female sex (OR, 3.01; 95% CI, 1.07-8.77; P = .037), and peripheral vascular disease (OR, 4.01; 95% CI, 1.33-12.2; P = .013) (Table 6). Neither the CTP score (OR, 0.98; 95% CI, 0.56-1.64; P = .927) nor the MELD score (OR, 1.08; CI, 0.98-1.18; P = .126) were independent predictors for 30-day mortality.
Table 5.
Univariate logistic regression analysis for 30-day mortality status
| Variable | Odds ratio | 95% CI | P value |
|---|---|---|---|
| Age | 0.99 | 0.96-1.02 | .516 |
| Female | 2.05 | 0.83-5.06 | .115 |
| BMI | 0.98 | 0.91-1.04 | .555 |
| Dyslipidemia | 1.13 | 0.45-3.11 | .799 |
| Diabetes | 1.13 | 0.43-2.83 | .798 |
| Dialysis | 0.64 | 0.03-3.37 | .677 |
| Hypertension | 0.60 | 0.24-1.65 | .294 |
| Cirrhosis | 1.54 | 0.61-3.79 | .345 |
| Heart failure within 2 weeks | 3.08 | 1.17-9.64 | .033 |
| Infective endocarditis | 2.33 | 0.94-5.76 | .064 |
| Sleep apnea | 0.29 | 0.02-1.46 | .235 |
| CTP score | 1.73 | 1.17-2.53 | .004 |
| MELD score | 1.11 | 1.03-1.20 | .003 |
| Immunosuppressive | 0.64 | 0.10-2.34 | .561 |
| Peripheral vascular disease | 4.70 | 1.79-12.1 | .001 |
| Cerebrovascular disease | 3.59 | 1.38-9.15 | .007 |
BMI, Body mass index; CTP, Child-Turcotte Pugh; MELD, model for end-stage liver disease.
Table 6.
Multivariate logistic regression analysis for 30-day mortality status
| Variable | Odds ratio | 95% CI | P value |
|---|---|---|---|
| Female | 3.01 | 1.07-8.77 | .037 |
| Hypertension | 0.51 | 0.16-1.70 | .265 |
| Cirrhosis | 1.43 | 0.47-4.24 | .517 |
| Heart failure within 2 wk | 2.47 | 0.82-8.55 | .124 |
| Infective endocarditis | 1.80 | 0.61-5.35 | .286 |
| CTP score | 0.98 | 0.56-1.64 | .927 |
| MELD score | 1.08 | 0.98-1.18 | .126 |
| Peripheral vascular disease | 4.01 | 1.33-12.2 | .013 |
| Cerebrovascular disease | 2.49 | 0.83-7.25 | .094 |
CTP, Child-Turcotte Pugh; MELD, model for end-stage liver disease.
Discussion
This study aimed to assess whether the presence of advanced LD was associated with inferior surgical outcomes after cardiac surgery. The results demonstrated that increased severity of LD was significantly associated with an increase in death at 30-days, death at discharge, LOS, prolonged pulmonary ventilation, and renal failure.
Baseline characteristics of the 3 groups differed significantly. CTP early-class B had a significantly lower median age of 43, compared with a median age of 61years and 60 years for CTP class A, and CTP advanced-class B, respectively. A possible explanation for this age difference is that the majority of CTP early-class B consisted primarily of young patients with a history of intravenous drug use (73.5%) with infective endocarditis (75.9%), rather than other pathologies with risk that increases with age. The CTP early-class B group also had the lowest prevalence and incidence of all comorbidities except for heart failure within 2 weeks, infective endocarditis, peripheral vascular disease, and previous cardiac interventions. Although there were no patients in CTP class C in this study, those patients are not categorically declined for surgery, they rarely undergo operation.15
Due to the increase in severity of systematic implications as LD progressed, the urgency and complexity of operations increased as well. The rate of urgent operations increased, and elective operations become less frequent. Additionally, both perfusion time and crossclamp time were on average the shortest for CTP early-class B, which could be explained by the predominance of infective tricuspid endocarditis. An increase in hospital LOS was also observed, as well as prolonged pulmonary ventilation (>24 hours) with increasing severity of LD. Renal failure was most prominent in CTP advanced-class B (21.9%), which is consistent with incidence reports in other studies.16 Patients with more advanced LD were readmitted less frequently in comparison to CTP class A patients, which could be due to the higher mortality rate in CTP advanced-class B group. For both 30-day and in-hospital mortality, the observed overall mortality rate was surprisingly low (7.4%). Both CTP class A and CTP early-class B had a 5.9% 30-day and in-hospital mortality rate, whereas the rate increased to an 18.8% 30-day and in-hospital mortality rate in CTP advanced-class B. The results of this study suggest an overall 30-day mortality rate 2- to 4-fold lower than previous reports in the literature.17, 18, 19 The most common causes of mortality in the overall cohort were cardiogenic shock (3.2%) and sepsis (2.5%), both of which are frequently associated with poor prognosis in patients with liver disease.20,21 Other causes of mortality included cardiac tamponade, heart failure, multiorgan failure, RVAD failure, and hemorrhage (0.4% each).
Similarities in the incidence of postoperative complications in CTP class A and CTP early-class B, along with the aforementioned mortality rate suggest that patients in CTP class A and CTP early-class B should be able to safely undergo cardiac surgery (Figure 2). The contrasting baseline characteristics of the CTP early-class B patient group in comparison to the other 2 groups requires further investigation. This included mostly young patients with drug-use infective endocarditis, which by itself is associated with unfavorable short-term outcomes.22
Figure 2.
Coexistence of cardiac and liver dysfunction. CTP, Child-Turcotte Pugh; MELD, model for end-stage liver disease.
Multivariate logistic regression showed that female sex (OR, 3.01; 95% CI, 1.07-8.77; P = .037), and peripheral vascular disease (OR, 4.01; 95% CI, 1.33-12.2; P = .013) were independent predictors for 30-day mortality. Previous literature has shown that men are twice as likely to die from LD and cirrhosis in comparison to women.23 In contrast, Johnston and colleagues24 reported that in patients without liver disease, women had a higher 30-day mortality rate after cardiac surgery. Sex-related differences in outcomes for cardiovascular and valvular pathologies are extensively studied and may be attributed to various factors such as a greater burden of comorbidities, delay in diagnosis, and treatment biases.24,25 Advanced LD is associated with the transformation of both intra- and extrahepatic vasculature.26 Additionally, abnormality of vascular endothelium contributes to multiple cardiovascular morbidities,27 which may explain the fact that peripheral vascular disease was an independent predictor of 30-day mortality in this study. In the univariate analysis, the CTP score (P = .004) and MELD score (P = .003) were significantly associated with 30-day mortality. However, neither variable was found to be an independent predictor of 30-day mortality in the multivariate analysis, presumably as a result of both varying baseline characteristics and cohort size.
Limitations
Despite a sizeable cohort, this was a single-center, retrospective observational study. This consisted of patients with LD deemed suitable to undergo cardiac surgery, therefore excluding patients with a more severe liver dysfunction deemed too high risk for operation. This introduces a selection bias including a lack of CTP class C, potentially underestimating the risk of perioperative complications and death. There was no control group, therefore limiting comparisons of overall mortality to patients without LD.
Conclusions
Postoperative outcomes in cardiac surgery are influenced by increasing severity of preexisting LD (Figure 3). Our data suggest that select patients in CTP class A, as well as patients in CTP class B with a MELD score <12.7, may be able to undergo cardiac surgery with acceptable risks of postoperative morbidity and mortality (Video 1).
Figure 3.
Graphical abstract. CTP, Child-Turcotte Pugh; MELD, model for end-stage liver disease; OR, odds ratio; CI, confidence interval; ROC, receiver operating characteristics.
Webcast
You can watch a Webcast of this AATS meeting presentation by going to: https://www.aats.org/resources/outcomes-in-cardiac-surgery-patients-with-advanced-liver-disease.
Conflict of Interest Statement
Dr Amabile receives consulting fees from JOMDD. Dr Krane is a physician proctor and a member of the medical advisory board for JOMDD, a physician proctor for Peter Duschek, a medical consultant for EVOTEC and Moderna, and has received speakers' honoraria from Medtronic and Terumo. Dr Geirsson receives consulting fees for being a member of the Medtronic Strategic Surgical Advisory Board and from Edwards Lifesciences. All other authors reported no conflicts of interest.
The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they have a conflict of interest. The editors and reviewers of this manuscript have no conflicts of interest.
Footnotes
Institutional Review Board number: Yale IRB No. 2000020356 (initial approval March 2, 2017, initial effective March 2, 2017, effective January 17, 2023).
Supplementary data
Totally endoscopic, robotic-assisted mitral and tricuspid valve repair in a patient with liver disease. Video available at: https://www.jtcvs.org/article/S2666-2736(23)00180-8/fulltext.
References
- 1.Geissler H. Risk stratification in heart surgery: comparison of six score systems. Eur J Cardio Thorac Surg. 2000;17:400–406. doi: 10.1016/s1010-7940(00)00385-7. [DOI] [PubMed] [Google Scholar]
- 2.Møller S., Bernardi M. Interactions of the heart and the liver. Eur Heart J. 2013;34:2804–2811. doi: 10.1093/eurheartj/eht246. [DOI] [PubMed] [Google Scholar]
- 3.Xanthopoulos A., Starling R.C., Kitai T., Triposkiadis F. Heart failure and liver disease. J Am Coll Cardiol Heart Fail. 2019;7:87–97. doi: 10.1016/j.jchf.2018.10.007. [DOI] [PubMed] [Google Scholar]
- 4.Vanhuyse F., Maureira P., Portocarrero E., Laurent N., Lekehal M., Carteaux J.-P., et al. Cardiac surgery in cirrhotic patients: results and evaluation of risk factors. Eur J Cardio Thorac Surg. 2012;42:293–299. doi: 10.1093/ejcts/ezr320. [DOI] [PubMed] [Google Scholar]
- 5.Kujovich J.L. Coagulopathy in liver disease: a balancing act. Hematology. 2015;2015:243–249. doi: 10.1182/asheducation-2015.1.243. [DOI] [PubMed] [Google Scholar]
- 6.Noor M.T., Manoria P. Immune dysfunction in cirrhosis. J Clin Transl Hepatol. 2017;5:50–58. doi: 10.14218/JCTH.2016.00056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Peck-Radosavljevic M. Thrombocytopenia in chronic liver disease. Liver Int. 2017;37:778–793. doi: 10.1111/liv.13317. [DOI] [PubMed] [Google Scholar]
- 8.Schuppan D., Afdhal N.H. Liver cirrhosis. Lancet. 2008;371:838–851. doi: 10.1016/S0140-6736(08)60383-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Sørensen H.T., Thulstrup A.M., Mellemkjar L., Jepsen P., Christensen E., Olsen J.H., et al. Long-term survival and cause-specific mortality in patients with cirrhosis of the liver: a nationwide cohort study in Denmark. J Clin Epidemiol. 2003;56:88–93. doi: 10.1016/s0895-4356(02)00531-0. [DOI] [PubMed] [Google Scholar]
- 10.Child C.G., Turcotte J.G. Surgery and portal hypertension. Major Probl Clin Surg. 1964;1:1–85. [PubMed] [Google Scholar]
- 11.Morisaki A., Hosono M., Sasaki Y., Kubo S., Hirai H., Suehiro S., et al. Risk factor analysis in patients with liver cirrhosis undergoing cardiovascular operations. Ann Thorac Surg. 2010;89:811–817. doi: 10.1016/j.athoracsur.2009.12.021. [DOI] [PubMed] [Google Scholar]
- 12.Pugh R.N.H., Murray-Lyon I.M., Dawson J.L., Pietroni M.C., Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 2005;60:646–649. doi: 10.1002/bjs.1800600817. [DOI] [PubMed] [Google Scholar]
- 13.Malinchoc M., Kamath P.S., Gordon F.D., Peine C.J., Rank J., Ter Borg P.C.J. A model to predict poor survival in patients undergoing transjugular intrahepatic portosystemic shunts. Hepatology. 2000;31:864–871. doi: 10.1053/he.2000.5852. [DOI] [PubMed] [Google Scholar]
- 14.Akins C.W., Miller D.C., Turina M.I., Kouchoukos N.T., Blackstone E.H., Grunkemeier G.L., et al. Guidelines for reporting mortality and morbidity after cardiac valve interventions. Ann Thorac Surg. 2008;85:1490–1495. doi: 10.1016/j.athoracsur.2007.12.082. [DOI] [PubMed] [Google Scholar]
- 15.Nicoll A. Surgical risk in patients with cirrhosis. J Gastroenterol Hepatol. 2012;27:1569–1575. doi: 10.1111/j.1440-1746.2012.07205.x. [DOI] [PubMed] [Google Scholar]
- 16.Thapa P., Kc S., Hamal A.B., Sharma D., Khadka S., Karki N., et al. Prevalence of acute kidney injury in patients with liver cirrhosis. J Nepal Med Assoc. 2020;58:554–559. doi: 10.31729/jnma.5147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Friedman L.S. Surgery in the patient with liver disease. Trans Am Clin Climatol Assoc. 2010;121:192–204. discussion 205. [PMC free article] [PubMed] [Google Scholar]
- 18.Lopez-Delgado J.C., Esteve F., Javierre C., Perez X., Torrado H., Carrio M.L., et al. Short-term independent mortality risk factors in patients with cirrhosis undergoing cardiac surgery. Interact Cardiovasc Thorac Surg. 2012;16:332–338. doi: 10.1093/icvts/ivs501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Thielmann M., Mechmet A., Neuhäuser M., Wendt D., Tossios P., Canbay A., et al. Risk prediction and outcomes in patients with liver cirrhosis undergoing open-heart surgery. Eur J Cardio Thorac Surg. 2010;38:592–599. doi: 10.1016/j.ejcts.2010.02.042. [DOI] [PubMed] [Google Scholar]
- 20.Chebl R.B., Tamim H., Sadat M., Qahtani S., Dabbagh T., Arabi Y.M. Outcomes of septic cirrhosis patients admitted to the intensive care unit: a retrospective cohort study. Medicine. 2021;100:e27593. doi: 10.1097/MD.0000000000027593. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Kasper P., Tacke F., Steffen H.M., Michels G. [Hepatic dysfunction in patients with cardiogenic shock] Med Klin Intensivmed Notfmed. 2019;114:665–676. doi: 10.1007/s00063-019-00618-6. [DOI] [PubMed] [Google Scholar]
- 22.Geirsson A., Schranz A., Jawitz O., Mori M., Feng L., Zwischenberger B.A., et al. The evolving burden of drug use associated infective endocarditis in the United States. Ann Thorac Surg. 2020;110:1185–1192. doi: 10.1016/j.athoracsur.2020.03.089. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Sagnelli E., Stroffolini T., Sagnelli C., Pirisi M., Babudieri S., Colloredo G., et al. Gender differences in chronic liver diseases in two cohorts of 2001 and 2014 in Italy. Infection. 2018;46:93–101. doi: 10.1007/s15010-017-1101-5. [DOI] [PubMed] [Google Scholar]
- 24.Johnston A., Mesana T.G., Lee D.S., Eddeen A.B., Sun L.Y. Sex differences in long-term survival after major cardiac surgery: a population-based cohort study. J Am Heart Assoc. 2019;8:e013260. doi: 10.1161/JAHA.119.013260. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Bansal A., Cremer P.C., Jaber W.A., Rampersad P., Menon V. Sex differences in the utilization and outcomes of cardiac valve replacement surgery for infective endocarditis: insights from the National Inpatient Sample. J Am Heart Assoc. 2021;10:e020095. doi: 10.1161/JAHA.120.020095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Iwakiri Y., Shah V., Rockey D.C. Vascular pathobiology in chronic liver disease and cirrhosis—current status and future directions. J Hepatol. 2014;61:912–924. doi: 10.1016/j.jhep.2014.05.047. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Sun H.-J., Wu Z.-Y., Nie X.-W., Bian J.-S. Role of endothelial dysfunction in cardiovascular diseases: the link between inflammation and hydrogen sulfide. Front Pharmacol. 2020;10:1568. doi: 10.3389/fphar.2019.01568. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Totally endoscopic, robotic-assisted mitral and tricuspid valve repair in a patient with liver disease. Video available at: https://www.jtcvs.org/article/S2666-2736(23)00180-8/fulltext.