CON: Noninvasive Imaging Is the Preferred Strategy for Cardiovascular Risk Stratification in This Patient

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Abbreviations

CAD

coronary artery disease

CCS

coronary calcium score

CCTA

coronary computed tomography angiography

CT

computed tomography

CVD

cardiovascular disease

DSE

dobutamine stress echocardiography

LT

liver transplant

METs

metabolic equivalents

Key Points

• The purpose of pretransplant cardiac risk stratification is to rule out obstructive coronary artery disease (CAD).

• Pharmacological stress tests have well‐known limitations in patients who suffer from cirrhosis.

• Noninvasive coronary computed tomography (CT) angiography (CCTA) has no such limitations and has >99% negative predictive value in “ruling out” CAD in different clinical contexts.

• If cardiologists are comfortable “ruling out” CAD using CCTA in patients with active chest pain, then it is appropriate for an asymptomatic pre–liver transplant (pre‐LT) patient.

Why is it Important to Risk‐Stratify The Cardiac Risk Factors For a Pre‐LT Patient?

Cardiovascular disease (CVD) remains a leading cause of post‐LT mortality in the modern era. ¹ , ² Retrospective analysis of approximately 55,000 patients found CVD to be the leading cause of mortality in the first 30 days posttransplant, accounting for 40.2% of deaths. ¹ It is well recognized that the demands of a LT surgery warrant a robust pretransplant cardiac evaluation that can rule out significant CAD. The 2013 joint American Association for the Study of Liver Diseases/American Society for Transplantation practice guidelines recommend noninvasive testing as a screening mechanism, with “subsequent cardiac catheterization if CAD cannot be confidently excluded.” ³ , ⁴ In an average‐risk patient with chronic hepatitis C, one can expect a slightly higher prevalence of CAD as compared with uninfected control subjects. ⁵ Even so, the overall risk for obstructive CAD, as measured by invasive coronary angiography, is small. A single‐center study regarding universal invasive catheterization of 228 patients undergoing LT evaluation demonstrated that more than 80% of patients with HCV have either no CAD or nonsevere CAD. ⁶ This is in contrast with nonalcoholic steatohepatitis, which carries a risk for clinically significant CAD independent of traditional cardiovascular risk factors and metabolic syndrome. ⁷ Taking these facts into account, one can surmise that the risk for CAD in the pretransplant population is real and must be adequately excluded. An appropriate noninvasive diagnostic tool should rule out obstructive CAD with sufficient sensitivity, while simultaneously minimizing procedural risks to the frail and clinically tenuous transplant candidate. This now leaves us with the question: Which test in our armament can best fulfill this role?

Pitfalls of the Old Guard in Noninvasive Cardiac Assessment

Dobutamine stress echocardiography (DSE) has been routinely used to risk‐stratify low‐ and intermediate‐risk individuals prior to transplantation. However, DSE has important limitations that raise questions about the broad utilization of this particular diagnostic tool. Although DSE is safe and widely available, the results are reliable only if a patient can achieve 85% of the maximum heart rate. In patients with end‐stage liver disease, the ability to reach this target can be limited by beta‐blocking agents, peripheral vasodilatation, and chronotropic incompetence. Data from a recent systemic review highlighted that only 70% of patients undergoing DES as part of LT evaluation were able to achieve the goal heart rate, resulting in a significant proportion of inconclusive tests. ⁸

CCTA is a Game‐Changer

The advent of CCTA has changed the diagnostic landscape in cardiology. CCTA is obtained much the same way a traditional CT of the chest is obtained: noninvasively with intravenous contrast administration. Although first described in the 1970s, recent validation studies have now brought this technology to the forefront. A landmark multicenter, multivendor study prospectively enrolled 360 symptomatic patients with acute and stable anginal syndromes to undergo simultaneous CCTA and invasive coronary angiography. CCTA had a sensitivity of 99% and a negative predictive value of 97% in ruling out obstructive coronary disease ⁹ (Fig. 1). More than 15 trials in symptomatic patients have been published, with pooled analyses demonstrating a 99% negative predictive value on per‐patient, per‐coronary artery, and per‐coronary artery segment analysis. ¹⁰

FIG 1.

A thick maximum‐intensity projected CTCA image (A) shows the anatomy of the right coronary artery. A curved multiplanar reformatted image (B) discloses a significant coronary stenosis (arrow) in the mid‐right coronary artery and distally an intermediate coronary stenosis (arrowhead), which were both corroborated by conventional coronary angiography (C). Reprinted with permission from Journal of the American College of Cardiology. ⁹ Copyright 2008, American College of Cardiology.

There are far fewer studies in LT candidates. In a single‐center study of 85 LT candidates, 30 underwent both CCTA and invasive coronary angiography. CCTA had a negative predictive value of 100% and a sensitivity of 100% for detection of obstructive (>50%) stenosis. An additional data point, the coronary calcium score (CCS), also proved to have excellent test characteristics, with a CCS >400 indicating statistically significant associated with CAD on angiography (P = 0.02). ¹¹ A separate study demonstrated than an elevated CCS >400 was associated with increased risk for posttransplant cardiovascular complications. ¹² To date, no prospective head‐to‐head studies compare invasive coronary angiography with CCTA in the pre‐LT patient. ¹³ However, if CCTA can reliably rule out significant CAD in patients with high pretest probability of CAD (i.e., a patient with angina), one can postulate an even better negative predictive value in an asymptomatic patient, ¹⁴ such as a pre‐LT patient.

Invasive Coronary Angiography is…Well, Invasive

Invasive coronary catheterization and angiography have well‐known risks, including bleeding, pseudoaneurysm formation, infection, cholesterol emboli, heparin‐induced thrombocytopenia, risks from conscious sedation, arrythmias, and even death. ¹⁵ A single‐center study evaluating the safety of cardiac catheterization in ≥100 patients with cirrhosis undergoing transplant evaluation demonstrated a 3‐fold increase in the risk for major bleeding, 4‐fold increase in packed red blood cell transfusions, a 10‐fold increase in fresh frozen plasma administration, and a 6% risk for complicated pseudoaneurysms compared with 0% in age‐, sex‐, and body mass index–matched controls without cirrhosis. ¹⁶ Moreover, blood products, often given to patients with end‐stage liver disease prior to elective procedures, are not without risk. Plasma products are likely futile, increase portal pressures, and are associated with a higher risk for transfusion‐related acute lung injury in patients with cirrhosis. ¹⁷ , ¹⁸

Conclusions

CCTA offers a noninvasive, highly sensitive approach to rule out CAD in low‐ and intermediate‐risk individuals undergoing LT evaluation (Fig. 2). This modality allows for effective and safe assessment of CAD and, by proxy, cardiac risk estimation without the limitations that plague stress echocardiography. Moreover, CCTA avoids the unnecessary risks and costs associated with invasive coronary angiography.

FIG 2.

Proposed algorithm for cardiac risk stratification in a potential liver transplant candidate.