Coronary artery disease may affect cirrhotic patients regardless of age and etiology of the underlying liver disease. Early identification of coronary artery disease is important to be able to achieve the best posttransplant outcomes and survival. The coronary artery calcium score can be used as a screening tool to supplement the results of cardiac stress tests to identify a subgroup of patients who may benefit from further investigation with coronary arterio­gram. Arteriogram is an invasive test and may cause renal compromise and risk of bleeding associated with coagulopathy. The present retro­spective study showed that coronary artery calcium score > 250 Agatston units may help select the subgroup of patients who will benefit from further investigation with cardiac catheterization, and determining this score may limit the risks of catheterization.

Key words : Atherosclerosis, Cardiac catheterization, End-stage liver disease, Cardiac disease screening, Arteriogram alternative

Introduction

Cardiac evaluation is an integral part of evaluating a liver transplant candidate and is an important component of the preoperative evaluation before liver transplant.^1,2 Early identification of coronary artery disease (CAD) is important to enable the achievement of better posttransplant outcomes and higher survival rates. However, identification of occult CAD in asymptomatic candidates is a challenge.³ Cardiac stress tests and transthoracic echocardiography are integral parts of the evaluation but have lower sensitivity and specificity than arteriogram. In some transplant programs, pretransplant troponin levels have been used to supplement cardiac stress testing, but the troponin level does not have wide application because its contribution is not well established.^4,5 Cardiac catheterization remains the best option for investigating the presence and extent of CAD.³

The application of cardiac catheterization as a standard investigative tool to search for occult CAD in liver transplant candidates has been limited by the risk of renal compromise and the invasiveness of the procedure, especially when other risk factors are present such as diabetes mellitus, hypertension, obesity, nonalcoholic steatohepatitis (NASH), and smoking. Recently, there has been some literature published suggesting that the coronary artery calcium (CAC) score may be highly predictive of coronary heart disease event risk across all age groups, and its use as a risk-stratification tool has been suggested.^6,7 In addition, preliminary experience with application of CAC score in a liver transplant program has been reported.⁸

The purpose of this study was to identify a cutoff CAC score as a screening method that would predict advanced CAD in patients undergoing evaluation for liver transplant, in the absence of known history of CAD. Advanced CAD was defined as coronary artery obstruction ≥ 50% identified during a coronary arteriogram. The secondary purpose was to investigate the role of specific liver disease as a risk factor for advanced CAD in liver transplant candidates.

Materials and Methods

We investigated the role of CAC score in predicting the presence of CAD in patients aged > 40 years undergoing evaluation for liver transplant and who had ≥ 1 of the following major cardiac risk factors: diabetes mellitus, hypertension, extensive smoking history, body mass index > 35 kg/m², and diagnosis of NASH. The CAC score was reported as a noninvasive screening tool for coronary heart disease, and the only potential risk was exposure to radiation from the computed tomography scan.7 After Institutional Review Board approval, the electronic medical records of patients at the Johns Hopkins Liver Transplant Program between January 1, 2011, and May 1, 2013, were retrospectively reviewed.

The computerized tomography (CT) scan of the heart was obtained in the radiology department, without the administration of intravenous contrast, for quantification of calcification in the coronary arteries, reported as the Agatston score. A reported score of 0 signified no calcium load in the coronary arteries and no evidence of CAD.

Results

There were a total of 175 patients. The CAC score was obtained on 66 patients who had a history of diabetes mellitus, hypertension, smoking, or NASH. There were 40 males and 26 females (mean age, 57.8 ± 0.7 y). At the time of evaluation, the mean Model for End-Stage Liver Disease (MELD) score was 15.2 ± 6.8, and mean CAC score was 379.6 ± 639.8. There were 3 main diagnoses as the primary cause hepatic failure: patients who had hepatitis C virus cirrhosis (33 patients), alcoholic cirrhosis (14 patients), or NASH (12 patients); the other 7 patients had alternate causes of cirrhosis including hepatitis B virus, autoimmune liver disease, primary sclerosing cholangitis, and primary biliary cirrhosis (Figure 1). After the patient had a discussion with an experienced transplant cardiologist, cardiac catheterization was performed by a single experienced interventional cardiologist in 20 patients (30%).

There were 8 patients (40%) who had coronary obstruction < 50%. The other 12 patients (60%) had maximum obstruction ≥ 50% (range, 50%-90%). Mean total CAC score was 750.3 ± 714 Agatston units in patients with < 50% stenosis ). Mean total CAC score was 883.8 ± 659.7 Agatston units in patients with coronary obstruction reported as ≥ 50% noted at cardiac catheterization.

There was no statistical difference between the groups in extent of CAD and mean CAC score (P > .05). However, receiver operating characteristic curve analysis showed 91% sensitivity and 50% specificity at a calculated CAC score cutoff of 243 Agatson units for the identification of occult coronary artery disease (Figure 2).

In the 14 patients with alcoholic cirrhosis, 7 patients were catheterized and 3 patients had coronary obstruction ≥ 50%. In the 12 patients with NASH, 4 patients were catheterized and 2 patients had coronary obstruction ≥ 50%. In the 33 patients who had hepatitis C virus, 9 patients underwent cardiac catheterization and all 9 catheterized patients had coronary artery obstruction ≥ 50%

Discussion

Early identification of CAD is essential to be able to achieve better posttransplant outcomes and survival. The CAC score can be used as a screening tool to supplement traditional cardiac stress tests. The application of CAC scoring has been proposed to screen larger populations.⁷ According to our preliminary experience obtained from this retrospective analysis of the data, CAC score > 250 Agatston units can be helpful in identifying liver transplant candidates who would benefit from further investigation with cardiac catheterization. Catheterization still is considered the best test to investigate the presence of CAD, but it may be limited because of possible renal compromise. Application of the CAC score as a screening tool can potentially eliminate the risks of routine invasive cardiac catheterization. In addition, the CAC score may identify a subgroup of patients who may benefit from catheterization in an effort to identify advanced CAD, evidenced by coronary obstruction ≥ 50%. Renal function must be reviewed in detail prior to the decision to perform an arteriogram, especially in patients who have higher MELD score and elevated serum creatinine level. The risks and benefits of coronary catheterization should be discussed in a multidisciplinary way among transplant hepatologists, transplant surgeons, and cardiologists experienced with liver transplant patients, especially considering the planned liver transplant.

The underlying liver disease also should be taken into consideration. In this small cohort, there was a significant overrepresentation of hepatitis C virus in individuals with coronary obstruction ≥ 50%. This observation should be studied further in a larger cohort.

References:

1. Carey WD, Dumot JA, Pimentel RR, et al. The prevalence of coronary artery disease in liver transplant candidates over age 50. Transplantation. 1995;59(6):859-864.
2. Plotkin JS, Scott VL, Pinna A, Dobsch BP, De Wolf AM, Kang Y. Morbidity and mortality in patients with coronary artery disease undergoing orthotopic liver transplantation. Liver Transpl Surg. 1996; 2(6):426-430.
3. Wray C, Scovotti JC, Tobis J, et al. Liver transplantation outcome in patients with angiographically proven coronary artery disease: a multi-institutional study. Am J Transplant. 2013;13(1):184-191. doi: 10.1111/j.1600-6143.2012.04293.x.
4. Coss E, Watt KD, Pedersen R, Dierkhising R, Heimbach JK, Charlton MR. Predictors of cardiovascular events after liver transplantation: a role for pretransplant serum troponin levels. Liver Transpl. 2011; 17(1):23-31. doi: 10.1002/lt.22140.
5. Umphrey LG, Hurst RT, Eleid MF, et al. Preoperative dobutamine stress echocardiographic findings and subsequent short-term adverse cardiac events after orthotopic liver transplantation. Liver Transpl. 2008;14(6):886-892. doi: 10.1002/lt.21495.
6. Gerber TC, Kantor B. Refining coronary heart disease event prediction in young and old individuals by coronary artery calcification imaging with computed tomography. Mayo Clin Proc. 2014;89(10):1324-1327. doi: 10.1016/j.mayocp.2014.08.008.
7. Tota-Maharaj R, Blaha MJ, Blankstein R, et al. Association of coronary artery calcium and coronary heart disease events in young and elderly participants in the multi-ethnic study of atherosclerosis: a secondary analysis of a prospective, population-based cohort. Mayo Clin Proc. 2014;89(10):1350-1359. doi: 10.1016/j.mayocp.2014.05.017.
8. Kemmer N, Case J, Chandna S, Neff GW. The role of coronary calcium score in the risk assessment of liver transplant candidates. Transplant Proc. 2014;46(1):230-233. doi: 10.1016/j.transproceed. 2013.09.035.