Multidisciplinary Approach to Cardiac and Pulmonary Vascular Disease Risk Assessment in Liver Transplantation

An Evaluation of the Evidence and Consensus Recommendations

Lisa B. VanWagner; Matthew E. Harinstein; James R. Runo; Christopher Darling; Marina Serper; Shelley Hall; Jon A. Kobashigawa; Laura L. Hammel


American Journal of Transplantation. 2018;18(1):30-42. 

In This Article

Heart Failure and Cardiomyopathy

Mortality from heart failure (HF) after LT is estimated to be as high as 15%,[62,63] and there is clinical or radiographic evidence of pulmonary edema in as many as 56% of patients within the first postoperative week.[20,64] In a large recent analysis of over 32 000 LT recipients in the United States, HF contributed to nearly 25% of hospital admissions within 90 days of transplant.[3] HF in ESLD may manifest with either reduction (HFrEF) or preservation (HFpEF) of left ventricular ejection fraction. To date, there are no studies that have systematically assessed differences in outcomes among LT candidates with HFrEF versus HFpEF. Patients with ESLD may also present with right HF typically as a result of underlying portopulmonary hypertension (PoPH, see below).

Cirrhotic cardiomyopathy is characterized by blunted inotropic and chronotropic responsiveness to stress, and/or altered diastolic relaxation with electrophysiological abnormalities in the absence of other known cardiac disease among patients with cirrhosis.[65,66] It is estimated that 40%-50% of patients with ESLD have cirrhotic cardiomyopathy, but nearly all patients with ESLD will display at least 1 feature of the condition, the most common of which is diastolic dysfunction.[66,67] Rate-corrected QT interval (QTc) of >440 ms is the electrophysiologic hallmark of cirrhotic cardiomyopathy and is present in 30%-60% of patients with this condition.[68] Although strong evidence exists that successful LT reverses the features of cirrhotic cardiomyopathy,[69,70] immediate perioperative stresses may precipitate myocardial dysfunction resulting in clinical heart failure.[71,72]

Specific indications for LT, including alcohol-induced (ETOH) liver disease, hepatitis C virus (HCV), amyloidosis, hemochromatosis, and NASH, are associated with increased risk for cardiomyopathy. ETOH cardiomyopathy is the main cause of secondary nonischemic dilated cardiomyopathy in the Western world and is often asymptomatic.[73,74] Patients consuming >90 g of alcohol a day (approximately 7–8 standard drinks per day) for >5 years are at risk for the development of ETOH cardiomyopathy and overt HF.[74] HCV can lead to chronic inflammation of the myocardium and, later, dilated cardiomyopathy attributable to myocyte necrosis.[75] Amyloidosis is associated with diastolic HF due to restrictive cardiomyopathy.[76] Iron overload is associated with iron deposition in the myocardium and conducting system that can lead to arrhythmias and HF. Patients with hemochromatosis have a 14-fold increase in mortality due to heart disease compared to an age- and sex-matched population,[77] and increased mortality after LT compared to other etiologies.[78] NASH has been associated with several markers of subclinical myocardial dysfunction with a propensity towards development of symptomatic diastolic dysfunction in both children and adults.[79–81] NASH is independently associated with increased left atrial volume, a powerful predictor of morbidity and mortality in HF.[82]

Echocardiography is the primary screening modality among LT candidates for the presence of HF and risk markers for the development of HF.[83] In cirrhotic cardiomyopathy, baseline resting echocardiography may reveal diastolic dysfunction, which can predispose to HF with preserved ejection, and DSE may reveal inducible systolic dysfunction.[62,84] Patients with HF resulting from either systolic or diastolic dysfunction have impaired aerobic capacity and thus CPET may be useful to identify candidates who are at increased risk for poor outcomes.[31–34] The presence of preoperative left ventricular dysfunction is not an absolute contraindication to LT per se, but is a risk factor for perioperative cardiovascular complications.[2,3] There is no well-documented EF cut-off for which LT alone is considered prohibitive. Based on practice patterns, most centers restrict LT to those with EF>40%, though LT with EF<40% has been reported at high-volume centers (Table 1).

DSE may also reveal inducible left ventricular outflow tract obstruction (LVOTO), defined as an outflow tract gradient of >36 mm Hg, in up to 43% of patients with ESLD.[85] LVOTO increases the risk of intraoperative hypotension, but has not been shown to increase postoperative mortality.[85] In rare cases, LT candidates may have LVOTO secondary to concomitant hypertrophic cardiomyopathy.[86] Intraoperative transthoracic echocardiography can play a critical role for continuous monitoring of ventricular volumes and dynamic LVOTO, guiding the use of volume resuscitation and vasopressor therapy.[4,83]

Conventional T2-weighted magnetic resonance sequences on cardiac magnetic resonance imaging can be used to assess the presence of iron or amyloid deposition in the myocardium.[87] The definitive diagnosis is made by subendocardial biopsy but is unreliable as severity can vary considerably among various cardiac sites.[87,88] Abnormalities detected on any of the above diagnostic modalities require a multidisciplinary approach as to the pathogenesis of findings, further testing, and initiation of HF therapies according to American College of Cardiology/American Heart Association clinical practice guidelines.[89,90]