Development and recognition of cardiopulmonary complications in a child with cirrhosis: The heart in chronic liver disease

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Abbreviations

ESLD

end‐stage liver disease

HPS

hepatopulmonary syndrome

QTc

corrected QT

End‐stage liver disease (ESLD) in children is often associated with cardiovascular abnormalities that can lead to hemodynamic instability before or after transplantation. These changes may be secondary to myocardial dysfunction, pulmonary and/or systemic vascular abnormalities, and cardiac conduction defects. These cardiac complications are important determinants of morbidity and mortality while on the organ waiting list, during transplantation, and after the procedure, so careful diagnostic workup and tailored treatment must be performed.

Myocardial Disease

The prevalence of cardiomyopathy in patients with ESLD is higher than in the general population. Cardiac phenotypes in patients with cirrhosis may range from normal to dilated, restrictive, or hypertrophic cardiomyopathy appearance. Patients with apparently normal myocardial structure and function may manifest significant dysfunction only after dramatic change in their preload or afterload that can occur during the peritransplantation period.

Restrictive/Hypertrophic Cardiomyopathy

The etiology of restrictive cardiomyopathy in ESLD is usually secondary to ongoing systemic processes such as infiltration of iron/protein or the result of fibrosis from immunomediated myocarditis. Hepatitis C is the most common infectious etiology of immunomediated disease.1 The prognosis for infiltrative processes (e.g., hemochromatosis or amyloidosis) is less favorable compared with other cardiac phenotypes, as the disease typically progresses despite transplantation. Suspicion for infiltrative diseases may necessitate myocardial biopsy with immunohistochemistry or advanced imaging for diagnostic purposes. Iron chelation therapy in cases of iron deposition may be necessary and useful until there is a reversal of myocardial disease and transfusion requirements are lessened. Under those circumstances, cardiac magnetic resonance imaging can be used to quantify the extent of the infiltrate and follow progress as the patient is chelated.2

Dilated Cardiomyopathy

Findings consistent with dilated cardiomyopathy may be seen in patients with ESLD and may resolve with transplantation. A direct relationship between the severity of liver disease (increasing Model for End‐Stage Liver Disease scores) and increasing dilation of the left atrium and ventricle has been shown in adults.3

Cirrhotic Cardiomyopathy

Some patients with cirrhosis may have subtle defects in myocardial structure and function that are difficult to detect or may be underappreciated by routine imaging and examination. However, with careful clinical examination, they are often found to have marked vasodilation, consistent with low systemic vascular resistance. In addition, they may have subtle evidence of left atrial and ventricular dilation. These patients may not tolerate the profound change in afterload that occurs with reperfusion of the new organ, which may lead acutely to inadequate cardiac output, acidosis, and end organ dysfunction. This myocardial disease or cardiomyopathy has been coined “cirrhotic cardiomyopathy” and is important to detect in children with ESLD. This “phenotype” is characterized by increased cardiac contractility, peripheral vasodilation, impaired diastolic relaxation, repolarization abnormalities, and decreased response to catecholamines.4 In adults, 7%‐15% of deaths that occur after liver transplantation are due to perioperative cardiovascular collapse.5 This outcome does also occur in children, but the incidence is unknown. In a pediatric study of 40 subjects with biliary atresia, pediatric intensive care and length of hospital stay were longer after liver transplantation in patients with abnormal echocardiogram findings on preoperative screening.6 Given the paucity of pediatric data, we perform cardiac screening on all children with liver disease. This includes primary screening with careful clinical, echocardiographic, and electrocardiographic examination and, at the discretion of the cardiologist and hepatologist, invasive hemodynamic evaluation. Indications for invasive testing in these patients include evidence of low systemic vascular resistance, abnormal echocardiographic findings, and/or end organ insufficiency (Table 1). A thorough pretransplantation evaluation guides the anesthesia team and posttransplantation care, allowing individualized medical management.

Table 1.

Indications for Cardiac Catheterization in Children with ESLD

1. Clinical evidence of myocardial disease

a. Echocardiographic findings of ventricular dysfunction or left ventricular/atrial dilation

b. Deteriorating end organ function

c. Evidence of low systemic vascular resistance by physical examination

d. Concern for elevated central venous pressure

i. Evidence by echocardiogram, direct measurement, or clinical examination

ii. Unexplained ascites or peripheral edema

2. Clinical evidence of portopulmonary hypertension

a. Tricuspid regurgitation jet >3 m/s

b. Estimated RV pressure >50%

c. Other echocardiographic signs of pulmonary hypertension

3. Clinical evidence of hepatopulmonary syndrome that is unable to be delineated by echocardiographic studies

Cardiac Repolarization Abnormalities

Children with chronic liver disease can develop repolarization abnormalities independent of myocardial issues. Prolongation of the corrected QT (QTc) interval on an electrocardiogram is the most common finding, and the prevalence increases in parallel to the severity of cirrhosis. The adult literature reports that up to 60% of ESLD patients have an abnormal QTc. The prevalence of QTc prolongation may be less in pediatric age patients (40 of 88 [45.5%]). However, this finding was associated with a high rate of mortality.7 Clinicians should be aware and follow the interval on serial electrocardiograms, because it represents the substrate of severe ventricular arrhythmias. Efforts should be made to maintain electrolyte hemostasis and to avoid the initiation of medications that further prolong the QTc in these children. There is some role of acute and chronic B‐blockade to shorten the QT interval in some patients.

Hepatopulmonary Syndrome

Hepatopulmonary syndrome (HPS) is a triad of liver disease, pulmonary vascular dilation, and impaired oxygenation resulting from intrapulmonary right‐to‐left shunting through arteriovenous malformations. The prevalence of HPS in children with ESLD has been shown to be as high as 19% as diagnosed by noninvasive imaging.8 The clinical findings associated with this triad include progressive cyanosis, exertional dyspnea, and digital clubbing. A screening echocardiogram with injection of agitated saline through a peripheral vein should be performed if there is a concern about this phenomenon. The test is considered positive if the left atrium became opacified within 3–5 cardiac cycles (Fig. 1). Although HPS is a serious complication in liver disease, it is usually reversible in all patients after transplantation.8

Figure 1.

(A) Echocardiographic image of the apical four‐chamber view. LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle. (B) The same image orientation shows agitated saline injected through a peripheral vein and entering the right atrium (arrows). (C) The same image orientation after four cardiac cycles shows dense opacification from agitated saline in both the left atrium and left ventricle (arrows), indicative of a positive bubble echo study.

Portopulmonary Hypertension

Portopulmonary hypertension is a complication of ESLD in children that is rare but potentially lethal. Transplant programs remain cautious about organ replacement in these patients secondary to the increased mortality rate during the perioperative period. With advancements in medical therapy of pulmonary hypertension, portopulmonary hypertension is not an absolute contraindication to transplantation. Screening echocardiograms for evidence of high pulmonary artery pressures should be performed in children prior to the development of ESLD. If the child has echocardiographic signs of pulmonary vascular disease, such as a tricuspid regurgitation jet >3 m/s, an estimated right ventricular pressure >50% systemic, or other subtle evidence of high right ventricular pressure, invasive hemodynamic screening with pulmonary vasodilator testing should be performed.