Abstract
Data on coronary revascularization in patients with cirrhosis are scarce because it is often deferred in the setting of significant comorbidities and coagulopathies. It is unknown whether patients with cardiac cirrhosis have a worse prognosis. The National Inpatient Sample was surveyed to identify patients who underwent percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) for acute coronary syndrome (ACS) from 2016 to 2018. Those with and without liver cirrhosis were propensity score–matched and compared within the PCI and CABG cohorts. Primary outcome was in-hospital mortality. Patients with cirrhosis were further classified into cardiac and noncardiac cirrhosis and their in-hospital mortalities were compared. A total of 1,069,730 PCIs and 273,715 CABGs were performed for ACS, of which 0.6% and 0.7%, respectively, were performed in patients with cirrhosis. In both the PCI cohort (odds ratio = 1.56; 95% confidence interval, 1.10–2.25; P = 0.01) and the CABG cohort (odds ratio = 2.34; 95% confidence interval, 1.19–4.62; P = 0.01), cirrhosis was associated with higher in-hospital mortality. In-hospital mortality was greatest in cardiac cirrhosis (8.4% and 7.1%), followed by noncardiac cirrhosis (5.5% and 5.0%) and no cirrhosis (2.6% and 2.3%) in PCI and CABG cohorts, respectively. Higher in-hospital mortality and periprocedural morbidities should be considered when performing coronary revascularization in patients with cirrhosis.
KEYWORDS: Cirrhosis, coronary artery bypass grafting, liver, percutaneous coronary intervention, revascularization
Almost a half million adults (1.7%) in the United States have liver disease, and an even higher number (4.6%) have coronary artery disease.1,2 Patients with cirrhosis often have coexisting coronary artery disease, with a prevalence that is similar to or even higher than that of the general population.3,4 Moreover, patients with cirrhosis are at high risk for complications after coronary revascularization due to multiple underlying conditions such as kidney dysfunction, coagulopathy, thrombocytopenia, and varices.5–7
Previous studies have shown that patients with cirrhosis who undergo coronary revascularization have a higher morbidity and mortality profile, health care–associated costs, and rates of cardiac and noncardiac complications.8 Temporal trends showing escalating mortality rates after percutaneous coronary intervention (PCI) suggest that PCI is increasingly opted for in high-risk surgical candidates, including patients with cirrhosis, in whom coronary artery disease continues to be a leading cause of morbidity and mortality.9,10 However, data on coronary revascularization in this unique population is sparse, so we examined in-hospital outcomes in patients with cirrhosis, stratified by cardiac and noncardiac cirrhosis.
METHODS
This study was exempt from ethical review, because it used the National Inpatient Sample (NIS) from 2016 to 2018, which consists of deidentified data available to the public by the Healthcare Cost and Utilization Project.11 The NIS is the largest inpatient database in the USA containing information on each hospitalization. By sampling a fifth of discharges, the NIS represents yearly admissions occurring in the USA.
Among all admissions for the primary discharge diagnosis of acute coronary syndrome (ACS), those in whom PCI or coronary artery bypass grafting (CABG) was performed were stratified into those with or without cirrhosis. The International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) and ICD-10, Procedure Coding System (ICD-10-PCS) codes used in our study are shown in Supplementary Table 1. Only patients at least 18 years of age were included. Hospitalizations with missing information on demographics and outcomes were excluded. Hospitalizations in which both PCI and CABG were performed were also excluded from the study.
For every admission, patient age, sex, and race were extracted. Cardiovascular comorbidities were described for each group. Hospital characteristics pertaining to the hospital region, bed size, and urban location were catalogued. The primary outcome consisted of in-hospital mortality. Secondary outcomes included cardiac arrest, cardiogenic shock, hypovolemic shock, intracranial hemorrhage, gastrointestinal hemorrhage, blood transfusion, length of hospital stay, and total hospital charge.
Categorical and continuous variables were described as percentages and means with standard deviations, respectively. Baseline characteristics were compared using chi-square test for categorical variables and analysis of variance for continuous variables. To assess the impact of liver cirrhosis, greedy nearest neighbor propensity score matching based on all demographics, comorbidities, and hospital characteristics was performed separately in ACS hospitalizations for PCI and CABG with and without liver cirrhosis. Post-match absolute standardized differences below 10% were deemed to reflect sufficient balance between the two arms. Odds ratios (ORs) and mean differences were calculated for categorical and continuous outcomes, respectively. Multivariable logistic regression, adjusted for all demographics, comorbidities, and hospital characteristics, generated adjusted odds ratios (aORs) comparing in-hospital mortality of cardiac and noncardiac cirrhosis. A P value <0.05 was considered statistically significant. Predictors of in-hospital mortality were assessed using multivariable logistic regression. Data extraction, cleaning, and analyses were performed using SAS v9.4, and propensity score matching was conducted using the “MatchIt” and “optmatch” packages in R v4.0.2.
RESULTS
A total of 1,343,445 hospitalizations for coronary revascularization occurred with the primary discharge diagnosis of ACS (Figure 1). The majority consisted of PCI (70.6%), and a little over a quarter consisted of CABG (29.4%). A total of 8615 patients with liver cirrhosis underwent coronary revascularization, 77.2% by PCI and 22.8% by CABG. Baseline comorbidities varied widely for no cirrhosis, noncardiac cirrhosis, and cardiac cirrhosis in both PCI and CABG groups (Table 1).
Figure 1.
Flow diagram showing the patient selection process of this study.
Table 1.
Baseline characteristics of hospitalizations in which coronary revascularization was performed for ACS
| PCI for ACS (N = 1,069,730) |
CABG for ACS (N = 273,715) |
|||||||
|---|---|---|---|---|---|---|---|---|
| No cirrhosis | Noncardiac cirrhosis | Cardiac cirrhosis | P value | No cirrhosis | Noncardiac cirrhosis | Cardiac cirrhosis | P value | |
| N (sample) | 212,616 | 1079 | 251 | 54,530 | 327 | 66 | ||
| N (weighted) | 1,063,080 | 5,95 | 1255 | 271,750 | 1635 | 330 | ||
| Age (mean) (years) | 64.5% | 65.0% | 66.2% | 0.031 | 65.5% | 63.6% | 63.2% | 0.001 |
| Male | 67.5% | 69.1% | 62.2% | 0.108 | 74.0% | 74.6% | 74.2% | 0.963 |
| Female | 32.5% | 30.9% | 37.8% | 26.0% | 25.4% | 25.8% | ||
| White | 75.9% | 72.9% | 67.7% | 0.001 | 77.1% | 74.0% | 63.6% | 0.015 |
| Non-White | 24.1% | 27.1% | 32.3% | 22.9% | 26.0% | 36.4% | ||
| Smoking | 52.5% | 57.8% | 50.6% | 0.002 | 51.8% | 57.8% | 59.1% | 0.049 |
| Hypertension | 69.9% | 69.3% | 57.8% | <0.001 | 75.1% | 69.1% | 66.7% | 0.013 |
| Diabetes mellitus | 38.6% | 56.6% | 41.8% | <0.001 | 48.7% | 60.6% | 53.0% | <0.001 |
| Hyperlipidemia | 72.1% | 58.9% | 66.9% | <0.001 | 79.1% | 69.7% | 78.8% | <0.001 |
| Obesity | 20.0% | 18.1% | 17.1% | 0.147 | 28.5% | 25.1% | 25.8% | 0.350 |
| Heart failure | 24.0% | 40.6% | 78.5% | <0.001 | 29.7% | 36.4% | 66.7% | <0.001 |
| Valvular heart disease | 7.0% | 11.8% | 13.9% | <0.001 | 12.6% | 17.7% | 25.8% | <0.001 |
| Atrial fibrillation | 13.0% | 16.3% | 31.1% | <0.001 | 32.1% | 33.6% | 48.0% | 0.029 |
| Pulmonary embolism | 0.2% | 0.3% | 0% | 0.715 | 0.4% | 0.3% | 3.0% | 0.005 |
| Peripheral artery disease | 2.2% | 3.1% | 3.2% | 0.069 | 4.7% | 3.7% | 6.1% | 0.590 |
| Cerebrovascular disease | 4.1% | 5.7% | 6.8% | 0.005 | 11.1% | 11.9% | 10.6% | 0.888 |
| Previous PCI | 1.5%% | 2.0% | 1.2% | 0.504 | 1.4% | 1.8% | 3.0% | 0.430 |
| Previous CABG | 9.1% | 10.4% | 4.8% | 0.021 | 2.1% | 2.8% | 1.5% | 0.674 |
| Pacemaker | 2.2% | 2.8% | 4.4% | 0.046 | 1.5% | 1.5% | 1.5% | 0.995 |
| Chronic pulmonary disease | 18.0% | 30.8% | 22.7% | <0.001 | 23.0% | 32.1% | 30.3% | <0.001 |
| Pulmonary hypertension | 3.2% | 8.6% | 12.4% | <0.001 | 4.4% | 6.1% | 16.7% | <0.001 |
| Renal failure | 17.1% | 30.2% | 35.5% | <0.001 | 20.9% | 24.2% | 19.7% | 0.334 |
| Deficiency anemia | 2.4% | 8.4% | 7.6% | <0.001 | 3.4% | 8.6% | 4.6% | <0.001 |
| Malnutrition | 1.2% | 3.6% | 4.8% | <0.001 | 3.2% | 8.3% | 7.6% | <0.001 |
| Hospital characteristics | ||||||||
| Hospital region | 0.003 | 0.142 | ||||||
| Northeast | 17.2% | 17.6% | 14.3% | 15.6% | 15.0% | 7.6% | ||
| Midwest | 22.8% | 20.9% | 20.7% | 20.9% | 24.4% | 19.7% | ||
| South | 42.3% | 42.4% | 37.5% | 46.6% | 45.3% | 45.4% | ||
| West | 17.7% | 19.2% | 27.5% | 16.9% | 15.3% | 27.3% | ||
| Hospital bed size | <0.001 | 0.859 | ||||||
| Small | 14.4% | 12.1% | 10.0% | 11.1% | 11.6% | 7.6% | ||
| Medium | 30.0% | 27.9% | 23.5% | 27.6% | 26.6% | 25.7% | ||
| Large | 55.6% | 60.0% | 66.5% | 61.3% | 61.8% | 66.7% | ||
| Urban location | <0.001 | 0.770 | ||||||
| Rural | 5.8% | 3.8% | 3.6% | 2.9% | 2.8% | 1.5% | ||
| Urban nonteaching | 23.5% | 19.0% | 17.1% | 18.3% | 15.9% | 19.7% | ||
| Urban teaching | 70.7% | 77.2% | 79.3% | 78.8% | 81.3% | 78.8% | ||
ACS indicates acute coronary syndrome; PCI, percutaneous coronary intervention; CABG, coronary artery bypass graft.
Appropriate propensity score matching between cirrhosis and no cirrhosis was achieved in both hospitalizations for ACS in which PCI or CABG was performed (Supplementary Figures 1, 2; Supplementary Tables 1, 2). Among hospitalizations for ACS in which PCI was performed, those with and without liver cirrhosis were each allotted 6650 hospitalizations after propensity score matching. Liver cirrhosis was associated with increased in-hospital mortality (OR = 1.56; 95% confidence interval [CI], 1.10–2.25; P = 0.01), cardiogenic shock (OR = 1.49; 95% CI, 1.16–1.92; P < 0.01), gastrointestinal hemorrhage (OR = 2.58; 95% CI, 1.75–3.81; P < 0.01), need for blood transfusion (OR = 2.50; 95% CI, 1.71–3.65; P < 0.01), length of stay (mean difference = 1.10; 95% CI, 0.55–1.67; P < 0.01), and total hospital charge (mean difference = $17,468; 95% CI, $6838–$28,100) (Supplementary Table 4). Among hospitalizations for ACS in which CABG was performed, groups with and without liver cirrhosis were each allotted 1965 hospitalizations after propensity score matching. Liver cirrhosis was associated with increased odds of in-hospital mortality (OR = 2.34; 95% CI, 1.19–4.62; P = 0.01) and gastrointestinal hemorrhage (OR = 2.49; 95% CI, 1.04–5.99; P = 0.04) (Supplementary Table 5). Multivariable logistic regression showed that cardiac arrest, cardiogenic shock, intracranial hemorrhage, and gastrointestinal hemorrhage were each independent predictors of in-hospital mortality in both PCI and CABG groups with liver cirrhosis (Supplementary Figure 3).
In hospitalizations for ACS in which PCI was performed, in-hospital mortality was greatest in those with cardiac cirrhosis (8.4%), followed by noncardiac cirrhosis (5.5%) and no cirrhosis (2.6%) (Figure 2). Cardiac cirrhosis was associated with increased odds of in-hospital mortality compared to no cirrhosis (aOR = 1.96; 95% CI, 1.23–3.11; P < 0.01) but not to noncardiac cirrhosis (aOR = 1.24; 95% CI, 0.64–2.34; P = 0.51). Noncardiac cirrhosis was also associated with increased odds of in-hospital mortality compared to no cirrhosis (aOR = 1.61; 95% CI, 1.22–2.11; P < 0.01). Similar results were found within the CABG group (Table 2).
Figure 2.
In-hospital mortality for no cirrhosis (light gray), noncardiac cirrhosis (gray), and cardiac cirrhosis (black) in hospitalizations for percutaneous coronary intervention and coronary artery bypass graft in acute coronary syndrome.
Table 2.
Adjusted odds ratio of in-hospital mortality for noncirrhosis, noncardiac cirrhosis, and cardiac cirrhosis
| Percutaneous coronary intervention | Coronary artery bypass grafting | ||||
|---|---|---|---|---|---|
| No cirrhosis | 0.62 (0.47–0.82)* | 0.51 (0.32–0.81)* | No cirrhosis | 0.41 (0.25–0.66)* | 0.25 (0.11–0.58)* |
| 1.61 (1.22–2.11)* | Noncardiac cirrhosis | 0.81 (0.43–1.53) | 2.46 (1.53–3.97)* | Noncardiac cirrhosis | 0.69 (0.19–2.46) |
| 1.96 (1.23–3.11)* | 1.24 (0.65–2.34) | Cardiac cirrhosis | 4.06 (1.72–9.56)* | 1.46 (0.41–5.20) | Cardiac cirrhosis |
*P < 0.01.
DISCUSSION
Our results show that coronary revascularization for ACS, whether by PCI or CABG, was associated with higher odds of in-hospital mortality and periprocedural morbidities if a co-diagnosis of liver cirrhosis was present. Results were similar after stratifying into cardiac and noncardiac cirrhosis. Hospitalizations for both PCI and CABG were associated with higher odds of in-hospital mortality and gastrointestinal bleeding, whereas the former was also associated with higher odds of cardiogenic shock, blood transfusions, and longer length of hospital stay.
Our findings are consistent with those of previous studies reporting poorer outcomes in patients with liver cirrhosis undergoing coronary revascularization.6,12–14 For years, excessive postoperative mortalities and morbidities were reported in patients with cirrhosis who underwent cardiac surgery.12,13,15 Patients with cirrhosis performed even poorer than expected, because some cardiac surgical risk scores did not consider hepatic function.16 Therefore, these patients are typically referred for a less invasive PCI rather than an open-heart CABG if coronary revascularization is needed. Our analysis also revealed a greater than threefold number of hospitalizations in which PCI was performed compared to CABG in patients with liver cirrhosis.
However, our findings showed that even with PCI, patients with liver cirrhosis have a significantly higher odds of mortality and morbidities. Patients undergoing PCI are administered anticoagulants and sometimes glycoprotein IIb/IIIa inhibitors periprocedurally, exacerbating the bleeding risk in the setting of underlying deficiencies in coagulation factors, thrombocytopenia, and consumptive coagulopathy in liver cirrhosis.17 In addition, after a drug-eluting stent has been placed, dual antiplatelet therapy typically ensues for at least 1 to 3 months, which further increases the risk of bleeding and need for transfusion.18 The increased bleeding tendency in this vulnerable population was well demonstrated in a nationwide cohort study of 150,887 patients, which showed that dual antiplatelet therapy in patients with cirrhosis who underwent PCI for acute myocardial infarction was associated with a lower recurrence of myocardial infarction but an increased risk of gastrointestinal bleeding.19
Although more known for its bleeding complications, cirrhosis is also associated with increased thrombosis.20 The liver is responsible for producing not only factors I, II, V, VII, VIII, IX, X, XI, and XII but also proteins C and S.21 Previous studies have found progressively decreasing protein C, protein S, and antithrombin levels with worsening severity of Child-Pugh class, with one study noting a 60% decrease in protein C concentrations compared to the general population.22,23 As a result, patients with cirrhosis are also at a risk of thrombosis, as demonstrated by an estimated annual incidence of spontaneous portal vein thrombosis in 5% to 10% of patients.24 These phenomena lead to a dynamic disequilibrium between thrombophilia and hemophilia, posing a significant clinical challenge in managing cirrhosis.25 Management becomes especially difficult after PCI, because stent thrombosis needs to be prevented while minimizing bleeding risks.
In addition to these challenges, patients with cirrhosis also frequently have chronic kidney disease and metabolic disturbances.26 Previous studies have shown that patients with chronic kidney disease who undergo PCI have a higher risk of in-hospital mortality, nonfatal stroke, and nonfatal myocardial infarction.27 Electrolyte imbalances are also associated with poor prognosis after PCI, posing another challenge in treating patients with cirrhosis.28–30
Interestingly, our results showed higher in-hospital mortality rates with cardiac cirrhosis compared to noncardiac cirrhosis in both the PCI and CABG groups, albeit not statistically significant because of the smaller sample size and the lack of power. This can be explained by the concomitant cardiac dysfunction, severe enough to cause cirrhosis, adding to the morbidities associated with cirrhosis.31 Cardiac cirrhosis results from increased preload and back-pressure to the hepatic veins and sinusoids due to right-sided heart failure, leading to hepatic injury and eventual cirrhosis.32,33 Presence of both right-sided heart failure and resultant cardiac cirrhosis substantially increases the odds of in-hospital mortality after coronary revascularization.34
Our study should be interpreted in the setting of several limitations. The NIS, an administrative database, was used to compare clinical outcomes. However, previous studies using the NIS have been peer-reviewed and validated.5,35 ICD-10-CM codes were used to create clinical scenarios, which may result in misclassification bias. However, the Healthcare Cost and Utilization Project regularly conducts quality control assessments to maintain the accuracy of the database. Liver-specific disease severity measures, such as Child-Pugh class or Model for End-stage Liver Disease sodium scores, were unavailable in NIS. Therefore, propensity score matching based on a comprehensive list of baseline characteristics was performed to create a balance between case and control groups, with excellent post-match absolute standardized differences. We looked only at inpatient outcomes, so our findings do not apply after discharge. Data on medications and complexity of coronary artery anatomy were not available in the database.
Disclosure statement/Funding
The authors report no conflicts of interest.
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