SCREEN LIVER TRANSPLANT CANDIDATES
Screening for portopulmonary hypertension should be mandatory in patients undergoing evaluation for liver transplantation. This condition increases the risk of perioperative death, so it is not acceptable to make the diagnosis in the operating room!5
Electrocardiographic abnormalities that may raise the suspicion of portopulmonary hypertension include right atrial or ventricular enlargement and a right bundle branch pattern.
Chest radiographic signs are enlarged central pulmonary arteries and cardiomegaly. These electrocardiographic and radiographic signs tend to reflect advanced pulmonary hypertension.
Pulmonary function testing is not generally helpful, but the diffusing capacity may be decreased.
B-type natriuretic peptide (BNP) measurement may be helpful. BNP is released from the ventricles when the ventricles become dilated (due to pressure or volume overload), as in left or right heart failure. BNP testing is clinically useful in monitoring the severity of disease and the efficacy of treatment in patients with pulmonary hypertension; its role in portopulmonary hypertension requires prospective study.23
Transthoracic Doppler echocardiography is an excellent screening test and should be performed in patients undergoing evaluation for liver transplantation to exclude pulmonary hypertension.1 Findings on echocardiography that suggest portopulmonary hypertension include elevation of right ventricular systolic pressure (RVSP), which is calculated from the peak tricuspid regurgitant velocity (TRV) using the modified Bernoulli equation and an estimate of right atrial pressure (RAP):
RVSP = 4(TRV)2 + RAP.
Right atrial pressure is estimated from the filling characteristics of the inferior vena cava.
Transthoracic Doppler echocardiography has a sensitivity of 97% and a specificity of 77% in diagnosing moderate to severe pulmonary hypertension in patients undergoing evaluation for liver transplantation.24 Using an RVSP cutoff of 40 mm Hg, the sensitivity of Doppler echocardiography is about 80%, specificity 96%, positive predictive value 60%, and negative predictive value 98%.25
At Mayo Clinic, patients with an estimated RVSP greater than 50 mm Hg undergo right heart catheterization (see below). Such patients should also have repeat echocardiography at 1-year intervals to monitor for increasing pulmonary artery pressures5; for those on the waiting list for liver transplantation, the interval should probably be every 6 to 12 months.
RIGHT HEART CATHETERIZATION CONFIRMS THE DIAGNOSIS
The diagnosis of portopulmonary hypertension is confirmed with right heart catheterization to accurately measure pulmonary artery pressures, pulmonary artery occlusion pressure (to exclude volume overload), cardiac output (to exclude high-output pulmonary hypertension), and pulmonary vascular resistance. One study in patients with decompensated cirrhosis and refractory ascites found that a right atrial pressure of 14 mm Hg or greater had a positive predictive value of 83% for pulmonary hypertension.6
Other, potentially treatable causes of pulmonary hypertension must be excluded before diagnosing portopulmonary hypertension. These include thromboembolic disease, interstitial lung disease, connective tissue disease, untreated obstructive sleep apnea, and elevated pulmonary artery pressures due to increased cardiac output.
Vasodilator studies are being done less frequently in patients with portopulmonary hypertension, as they generally cannot tolerate calcium channel blocker therapy. Calcium channel blocker therapy is usually started in patients with idiopathic pulmonary artery hypertension who exhibit a positive vasodilator response. A positive vasodilator response also does not predict survival with or without liver transplantation. Unlike those with idiopathic pulmonary artery hypertension, many patients with portopulmonary hypertension cannot tolerate calcium channel blockers, as some of these drugs can exacerbate edema and portal hypertension.
Treatment of mild portopulmonary hypertension (mean pulmonary artery pressure < 35 mm Hg) is debatable. In these cases many patients do not have any symptoms attributable to portopulmonary hypertension, but only symptoms of liver disease, and they have a good functional status. As a group, such patients have not been formally studied to date.
Anticoagulation is often contraindicated in portopulmonary hypertension because of gastroesophageal varices, thrombocytopenia, or other coagulation abnormalities related to liver disease. If contraindications to anticoagulation do not exist, it should be considered.
Diuretics are a mainstay in the treatment of portopulmonary hypertension, both for the pulmonary hypertension and for the liver disease, especially if ascites or peripheral edema is present.
Oxygen should be given to patients with hypoxemia to keep the saturation greater than 90%.
Beta-blockers: A dilemma
Beta-blockers are used in many patients with liver disease as both primary and secondary prophylaxis of variceal bleeding.
However, one study has shown that in patients with moderate to severe portopulmonary hypertension, beta-blockers are associated with significant worsening of exercise capacity and pulmonary hemodynamic measurements.26 After beta-blockers were withdrawn, the 6-minute walking distance increased in 9 of 10 patients, and cardiac output increased with no change in mean pulmonary artery pressure, resulting in a 19% decrease in pulmonary vascular resistance. The increases in cardiac output were related to a 25% increase in heart rate. Long-term follow-up was not reported, and it remains unclear whether rates of gastrointestinal bleeding may increase when beta-blockers are withdrawn.
Beta-blocker therapy in portopulmonary hypertension needs to be carefully considered and if at all possible should be avoided.