Key Points
- 1.
Cardiomyopathy and ischemic coronary artery disease are the most common cardiac conditions in liver transplant candidates.
- 2.
There are no clear recommendations for the assessment of cardiac status before liver transplantation, but each patient must be individually evaluated.
- 3.
Indications for liver transplant have shifted, which has resulted in more patients with underlying cardiac disease presenting for liver transplantation.
- 4.
Pulmonary hypertension and hepatopulmonary syndrome are two conditions that can impact liver transplantation.
- 5.
Intraoperative hemodynamic instability is greatest while the hepatic vein is occluded and during reperfusion.
- 6.
Postreperfusion management focuses on warming the patient, treating coagulopathies, maintaining acid–base balance, and optimizing oxygen delivery via transfusion and the management of hemodynamics.
Cardiac Condition in Liver Disease
Liver transplant places extreme metabolic and physiologic demands on the heart, which is why knowledge of the patient’s baseline cardiac status is imperative. Among cardiac conditions, cardiomyopathy and coronary artery disease (CAD) are most prevalent in this cohort. Estimates indicate that more than 50% of liver transplant recipients will have heart failure (HF) posttransplant, and cardiovascular disease is the third leading cause of death; however, it is unclear which patients should be excluded from liver transplantation based on their initial cardiac status.
Preoperative Cardiac Assessment
Because symptoms related to overt liver disease are often similar to those that are present in cardiac conditions (e.g., shortness of breath, lightheadedness, peripheral edema), preoperative assessment of the patient is challenging. Couple this with the fact that liver transplant candidates are subject to pulmonary hypertension and hepatopulmonary syndrome (HPS), and preoperative cardiac assessments become even more important. Although many tests can help determine the cardiac status of these patients, there are no definitive recommendations. Echocardiography and electrocardiography are routinely performed at most institutions; however, there is variability among centers regarding additional cardiac workup and CAD screening.
The comorbidities that accompany liver disease lead to myriad issues that affect the cardiovascular system, including increased inflammatory mediators, impaired repolarization, reduced vascular resistance, bradycardia, and myocardial depression. If liver disease is secondary to alcohol, the myocardium often thickens because of myocardial toxicity, which results in poor left ventricular function. As more and more patients are being transplanted for nonalcoholic fatty liver disease (NAFLD), there has been an associated increase in cardiac complications postoperatively. The increase in postoperative complications may be attributable to higher rates of CAD in the NAFLD patient population because NAFLD is a component of the metabolic syndrome. The increase in the average age of liver transplant recipients also brings with it greater risk of coronary atherosclerosis ( Table 17.1 ).
| Comorbidity | Effect |
|---|---|
| Alcoholism | Left ventricular dysfunction and disruption of myofibrillary system |
| Advanced age | Increased prevalence of atherosclerosis |
| Nonalcoholic fatty liver disease | Associated with metabolic syndrome and cardiac disease |
| Hemochromatosis | Deposits iron into myocardium: conduction abnormalities and heart failure |
| Familial amyloid polyneuropathy | Induces heart disease caused by amyloid deposition: cardiomyopathy and conduction disturbances |
The Child-Pugh score is widely used to assess prognosis in liver cirrhosis. For reference, the Child-Pugh score is a model frequently used to predict perioperative risk in patients with cirrhosis. It takes into account serum bilirubin, ascites, albumin, and prothrombin time (PT), as well as the extent of hepatic encephalopathy. The higher the cumulative score (class C being higher than class A), the greater the surgical risk and worse overall prognosis.
Alternatively, the Model for End-stage Liver Disease (MELD) score is occasionally used for risk stratification. Although this scoring system was originally designed to predict death after transjugular intrahepatic portosystemic shunt (TIPS), its use has expanded considerably. The MELD score uses serum bilirubin, creatinine, and international normalized ratio (INR), and the MELDna adds serum sodium to the calculation. Higher cumulative scores correlate with worse disease and greater surgical risk. The MELD score is widely used to rank the priority of liver transplantation candidates.
Pulmonary Hypertension and Circulatory Syndromes
Liver disease often causes direct effects on the circulatory system, with the three most common conditions being pulmonary hypertension, HPS, and hepatorenal syndrome (HRS).
Pulmonary Hypertension
Because liver transplant patients are five times more likely to have pulmonary hypertension, an echocardiogram before surgery is strongly suggested. Although liver transplant recipients are more likely to have pulmonary hypertension, the severity of pulmonary hypertension does not correlate with the severity of the liver disease.
There are no definitive recommendations on the time frame within which an echocardiogram should be obtained, but because the underlying disease can change quickly, it is best to have one done close to surgery. If the preoperative echocardiogram was not completed in a time frame that encompasses the patient’s current disease state, it should be repeated.
Although the pathophysiology of pulmonary hypertension in liver disease is not fully understood, the contributing factors include neurohumoral activation, vasoconstriction within the pulmonary arteries, genetic predisposition, a hyperdynamic arterial circulatory system, and increased pressure within the venous system ( Box 17.1 ). A patient is considered to have pulmonary hypertension when the pulmonary artery systolic pressure (PASP) by echocardiography is greater than 30 mm Hg. Severity is based on the PASP with mild pulmonary hypertension being 31 to 44 mm Hg, moderate 45 to 59 mm Hg, and severe greater than 60 mm Hg. It is well documented that there is a decrease in survival for patients displaying severe pulmonary hypertension. Therefore a widely accepted absolute contraindication to liver transplantation is a PASP greater than 50 mm Hg.
Box 17.1- •
Humoral substances: serotonin, interleukin-1, glucagon, or endothelin-1 enter through portosystemic collaterals, increasing pressure in the pulmonary arteries.
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Genetic predisposition: the gene for familial pulmonary hypertension has been localized to chromosome 2.
- •
Thromboembolism: thromboemboli from the portal venous system to the pulmonary circulation producing pulmonary arterial hypertension.
- •
Hyperdynamic circulation: increased blood flow causes sheer stress on the vascular wall, producing pulmonary hypertension.
It is strongly recommended that any patient with moderate to severe pulmonary hypertension by echocardiography undergo a right heart catheterization. If the right heart catheterization shows a mean pulmonary artery pressure (PAP) greater than 25 mm Hg and a pulmonary capillary wedge pressure 15 mm Hg or less, then the liver transplant can proceed. If the mean PAP is 35 to 45 mm Hg, the patient should be referred to a pulmonologist for management. If the patient has a good response to vasodilatory therapy, then the outcome after liver transplant is comparable to that of other candidates. Any patient who has a mean PAP greater than 45 mm Hg will require initial medical management and should not receive an immediate transplant ( Table 17.2 ).
| Severity | Mean Pulmonary Artery Pressure (mm Hg) | Pulmonary Capillary Wedge Pressure (mm Hg) | Action |
|---|---|---|---|
| Mild | >25 | <15 | Proceed with liver transplant |
| Moderate | 35–45 | <15 | Proceed with liver transplant; pulmonary pressures responds to vasodilator therapy |
| Severe | >45 | <15 | Medical management |
Hepatopulmonary Syndrome
Hepatopulmonary syndrome is defined by arterial hypoxemia that is attributable to pulmonary vasculature changes in the setting of advanced hepatic disease ( Box 17.2 ). The pathogenesis is unclear. It has been proposed that the damaged liver’s inability to clear mediators of pulmonary vasodilation such as nitric oxide, tumor necrosis factor-α, and heme-oxygenase–derived carbon monoxide all contribute to pulmonary capillary dilation with occasional direct arteriovenous (AV) connections.
Box 17.2- •
Presence of liver disease (with or without portal hypertension)
- •
Arterial hypoxemia
- •
Pulmonary vascular changes
Irrespective of the pathogenesis, there are three principal mechanisms of arterial hypoxemia in HPS: ventilation/perfusion (V/Q) mismatch, diffusion limitation, and less frequently, anatomic shunt. V/Q mismatch leads to the transit of deoxygenated mixed venous blood straight into the systemic circulation, which depresses arterial saturation (i.e., high venous admixture). Diffusion limitation is the result of enlarged alveolar capillaries, which leads to a reduction in alveolar surface area relative to capillary cross-sectional area. The driving pressure (i.e., partial pressure of oxygen from alveoli to blood) is inadequate to equilibrate with the blood in the center of the enlarged capillary. Unlike a true shunt, this form of hypoxemia responds to increasing fraction of inspired oxygen (F I O 2 ) because this will increase the driving pressure of oxygen from the alveoli to the capillary. The severity of HPS is based on the arterial partial pressure of oxygen. Finally, direct anatomic shunt from pulmonary artery (PA) capillaries to pulmonary venous capillaries is rare and like most forms of pure shunt is refractory to increasing F I O 2 ( Box 17.3 ).
Box 17.3- •
Mild: PaO 2 >80 mm Hg on room air
- •
Moderate: PaO 2 <80 mm Hg on room air
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Severe: PaO 2 between 50 and 60 mm Hg on room air
- •
Very severe: PaO 2 <50 mm Hg on room air or PaO 2 <300 mm Hg on F I O 2 of 1.0
F I O 2 , Fraction of inspired oxygen; PaO 2 , arterial partial pressure of oxygen.
The diagnosis of HPS is made via both clinical examination and diagnostic testing. Aside from dyspnea and hypoxemia in the setting of advanced hepatic disease, there are two unusual markers of HPS on clinical examination: platypnea and orthodeoxia. These are worsening dyspnea and arterial hypoxemia in the upright position, which improve by transitioning to the recumbent position. Clinically, this contrasts with most other causes of hypoxemia and dyspnea, which improve in the upright position. Mechanistically, this occurs because the majority of HPS-related vascular changes occur in the base of the lungs. Moving to the upright position forces a higher proportion of the cardiac output into these pathologic regions and worsens gas exchange.
Diagnostic testing for intrapulmonary AV shunt is done, in part, via echocardiography, again assuming this is completed in an appropriate time frame. During the echocardiogram, a bubble study can be completed to detect an intrapulmonary AV shunt, patent foramen ovale, or atrial septal defect ( Fig. 17.1 ). The late appearance of bubbles in the left atrium (e.g., 6–10 beats) is consistent with HPS and an AV shunt. In contrast, the early appearance of bubbles in the left atrium (e.g., within 2–3 beats) or a defect in the interatrial septum appreciated on two-dimensional imaging may be indicative of a patent foramen ovale or atrial septal defect.
