Pretransplantation Evaluation: Cardiac

Coronary Artery Disease

Patients with cirrhosis were once considered to be at low risk for CAD because of the associated low blood pressure, low cholesterol levels, and coagulopathic state. However, improvements in donor organ management, surgical techniques, and immunosuppression have improved patients’ survival, and cardiac complications have emerged as a prominent cause of morbidity and mortality early and late after liver transplantation. Traditional risk factors for CAD in the general population include men above 45 years of age, women above 55 years of age, hypertension, cigarette smoking, elevated cholesterol levels, family history of premature CAD, and diabetes. In liver transplant candidates, diabetes, age above 50 years, and cirrhosis caused by nonalcoholic steatohepatitis are predictive of postoperative ischemic complications. Hypertension and hyperlipidemia are also associated with worse outcomes after transplantation.

Although the exact incidence of significant CAD in patients undergoing liver transplantation is not clear, studies indicate that anywhere from 2.5% to 27% of asymptomatic patients with cirrhosis have CAD. Furthermore, there are clearly poor outcomes in patients with preexisting CAD who undergo liver transplantation. In a study of 32 patients the 3-year cardiovascular mortality was 50%, although more recent studies indicate lower 3- and 5-year mortality rates of 22% to 26%, perhaps related to better patient selection and postoperative management.

What is not clear, however, is how treatment of CAD affects outcomes after liver transplantation. Medication optimization is essential, with aspirin, statin, β-blocker, and angiotensin-converting enzyme (ACE) inhibitor therapy as tolerated based on the patient’s platelet count, transaminase levels, blood pressure, and renal function. As for coronary revascularization, this does not confer benefit in the general population of patients with chronic stable angina or in patients undergoing noncardiac surgery but may be feasible in liver transplant candidates.

There are also no clear guidelines to determine when CAD is an absolute contraindication to liver transplantation. At most centers, CAD not amenable to percutaneous or surgical revascularization would preclude liver transplantation. Similarly, patients who cannot tolerate percutaneous coronary intervention with its required antiplatelet therapy because of thrombocytopenia, coagulopathy, or significant risk for bleeding esophageal varices would be denied liver transplantation. Liver transplant candidates requiring surgical revascularization with coronary artery bypass grafting who have Child-Turcotte-Pugh class B or C cirrhosis may also be denied given the high perioperative mortality from cardiac surgery, although revascularization at the time of liver transplantation is an option that is now being considered at some centers.

Heart Failure

The most common cause of left ventricular systolic dysfunction is CAD. Other common causes include atrial fibrillation, aortic stenosis, illicit cardiotoxic drugs (cocaine, methamphetamine), medical cardiotoxic drugs (doxorubicin [Adriamycin]), as well as primary myocardial disorders such as myocarditis or peripartum cardiomyopathy. Heart failure can also occur in the setting of normal left ventricular function. In this case the cause is most often long-standing hypertension and diabetes mellitus but can be a result of infiltrative (such as sarcoidosis, amyloidosis, or hemochromatosis), hypertrophic, or constrictive cardiomyopathies. There are causes of heart failure specifically related to liver disease. Alcohol has a direct myocardial depressant effect and may cause a dilated cardiomyopathy, which can be reversible on cessation of alcohol use. Hemochromatosis not only results in cirrhosis from hepatic iron deposition but may cause an infiltrative cardiomyopathy as well.

There is also an entity termed cirrhotic cardiomyopathy . In this condition patients have normal cardiac function on resting echocardiogram because cardiac workload is reduced by the peripheral vasodilation related to liver failure, but when subjected to stress, these patients will develop heart failure and reduced left ventricular systolic function. There are specific abnormalities that may be detected in asymptomatic liver transplant candidates, including baseline increased cardiac output, a diminished contractile response to stress, impaired diastolic relaxation, and electrophysiological abnormalities such as a prolonged QT interval and chronotropic incompetence. However, there is no single diagnostic test to identify cirrhotic cardiomyopathy, and the entity is most helpful in retrospect because it provides insight into why some patients develop evidence of heart failure after transplant. Studies indicate that patients who survive the initial posttransplant period will have normalization of cardiac function over the ensuing months, and thus efforts should be directed at postoperative stabilization of blood pressure and volume status.

The incidence of heart failure in liver transplant recipients in retrospective studies ranges from 7% to 31%. However, identifying which patients may be at risk and identifying what level of pretransplant left ventricular dysfunction should preclude liver transplantation are not clear. For liver transplant candidates with known left ventricular dysfunction, optimization of medical therapy with diuretics, ACE inhibitors, β-blockers, and aldosterone antagonists is essential, as long as tolerated based on renal function and blood pressure. A general recommendation is to avoid liver transplantation in patients with an ejection fraction on echocardiogram at or below 40%. In extreme cases, heart-liver transplantation may be performed in patients with end-stage heart and liver disease and has been successful in case reports.

Arrhythmias

Patients with preexisting arrhythmias are generally not precluded from liver transplantation. The most common arrhythmias that occur in candidates for and recipients of liver transplantation are atrial fibrillation, other supraventricular tachycardias, and QT prolongation. Atrial fibrillation is an irregular narrow-complex tachycardia that may be paroxysmal (spontaneous return to normal sinus rhythm), persistent (return to normal sinus rhythm after chemical or electrical cardioversion), or chronic (chemical or electrical cardioversion is unsuccessful). Patients may have no symptoms or feel palpitations, chest discomfort, shortness of breath, and light-headedness related to the rapid and irregular ventricular response. The most common causes of atrial fibrillation are older age, hypertension, and CAD. Management strategies include rhythm control to maintain normal sinus rhythm or rate control to prevent rapid ventricular response and anticoagulation to prevent stroke. Other supraventricular tachycardias, such as regular narrow-complex tachycardia with reentrant electrical pathways often involving the atrioventricular node, may also be present in patients with end-stage liver disease. These tachycardias are paroxysmal and usually well controlled with atrioventricular-nodal blocking agents such as β-blockers, calcium channel blockers, or digoxin or radiofrequency ablation.

QT prolongation is often seen in patients with cirrhosis, most often associated with advanced age, alcoholic cirrhosis, and higher Child-Turcotte-Pugh class. A prolonged QT interval places patients at increased risk for ventricular arrhythmias, although there is no association between a prolonged QT interval and mortality. Management includes correction of reversible causes, including hypokalemia, hypomagnesemia, and hypocalcemia; and avoidance of medications that prolong the QT interval, including many antiarrhythmics, antipsychotics, macrolide and fluoroquinolone antibiotics, and azole antifungal medications.

Preexisting dysrhythmias such as atrial fibrillation or supraventricular tachycardia may be aggravated by the increased adrenergic state present after surgery. This is further aggravated by perioperative volume, electrolyte, and acid-base imbalances. These circumstances could lead to hypotension, making postoperative management more difficult. Patients with preexisting prolonged QT interval may be at particular risk for polypharmacy, and the electrocardiogram (ECG) should be closely monitored postoperatively. In general, atrial fibrillation should be treated with rate control as the blood pressure allows, and intravenous amiodarone may be particularly useful in cardioversion to normal sinus rhythm (as long as the QT interval remains acceptable). Electrical cardioversion is reserved for patients with hemodynamic instability, because patients may simply revert back to atrial fibrillation because of the ongoing postoperative stress driving the arrhythmia.