The clinical presentation of POPH is increasing fatigue, dyspnea on exertion, syncope, and occasional chest pain, and sudden death. In two series of patients with POPH the 4-year and 5-year survivals were 4 % and 14 %, respectively [11, 12]. The most common physical findings are an accentuated pulmonary component of the second heart sound and a systolic murmur. Therefore, on routine clinical assessment these patients are difficult to diagnose, although signs of right ventricular failure may be present. The electrocardiogram may reveal right heart strain. The chest X-ray may show right heart enlargement and failure with dilatation of the pulmonary arteries.

POPH may be precipitated by the increase in cardiac output that may follow a transjugular intrahepatic shunt formation (TIPS) [13].

The most important screening tool is the transthoracic echocardiograph. All patients presenting for liver transplantation should be screened for POPH by transthoracic echocardiography . The right ventricular systolic pressure (RVSP) is estimated based on the velocity of tricuspid regurgitation (TR) using the modified Bernoulli equation RVSP mm Hg = 4 × (TR m/s)² + right atrial pressure. The tricuspid regurgitant jet flow may not be present in all patients negating this diagnostic tool. In this case a careful assessment of right ventricular function should be made, preferably by transesophageal echocardiography and an estimation of PVR made. One test reporting a sensitivity and negative predictive value of 100 % utilizes the ratio of peak tricuspid regurgitant velocity (TRV) to right ventricular outflow tract velocity time (VTI_RVOT) [14]. To confirm the diagnosis an RHC should be performed to clearly characterize the pulmonary hemodynamics.

Assessing right ventricular performance still remains a challenge. The right ventricle (RV) is a complex structure that cannot be approximated by a simple geometric form. It functions in a low-impedance system; therefore it is sensitive to pressure overload. Along with contractility and loading conditions, ventricular interactions play an important part in right ventricular function and failure. Right ventricular dysfunction or failure may result in liver graft congestion and failure and may result in total loss of the newly implanted liver graft and also the recipient. Therefore careful evaluation of the right heart must be made in the pretransplant workup of these patients and a careful assessment of the severity of the POPH must also be made. Most institutions will make an RSVP of >50 mmHg a necessity for an RHC. However, it is not the absolute number of the RVSP or the MPAP that should be the trigger but the function of the RV must be included in this decision. Careful examination by TEE must be made for systolic and diastolic dysfunction of the RV. The RV faced with an increasing pressure overload adapts through hypertrophy and dilatation but eventually will fail. The diagnostic features of RV dysfunction are an E/A ratio <1, a prolonged deceleration time >200 ms, a prolonged isovolumetric relaxation time >80 ms, enlarged right chambers, abnormal pattern of contractility, and a prolonged ratio of pre-ejection period to LV ejection time >0.44 s [15]. Figure 33.5 shows transthoracic echocardiographic images of a patient with portopulmonary hypertension [16].

The typical patient with liver cirrhosis has a hyperdynamic circulation with a low systemic vascular resistance that may mask a significant cirrhotic cardiomyopathy, which can lead to a false sense of security when managing these patients. Most patients with liver cirrhosis will have some manifestations of a cardiomyopathy even if it is just a prolonged QT interval on the electrocardiogram or a downregulation of the beta receptors [17]. This must be taken into consideration when assessing the right heart function in a patient with POPH.

The key questions that need to be answered are the following: (1) Is it safe for patient and graft to transplant with POPH? (2) Will the POPH resolve after liver transplantation?

Those patients that have been assessed to have good RV function and proceed to transplantation still have the potential rigors of a major procedure to undergo and the potential to withstand a 300 % increase in cardiac output after liver graft reperfusion (Fig. 33.6) [20].

There is no reliable way to protect the RV and the liver graft if this scenario occurs. Inhaled nitric oxide may be effective in some patients in reversing or moderating this acute rise in pulmonary artery pressure [24]. Consideration for extracorporeal right heart bypass should be given to assist in unloading the RV [25]. Right ventricular assist devices are unlikely to be successful when the RV failure is the result of afterload resistance. Pumping blood into the pulmonary artery will result in increasing pulmonary artery pressure and lung injury [26].

Initially the prostacyclins were administered to reduce PVR. However, these drugs had to be given by long-term intravenous therapy (epoprostenol) or by inhalation (inhaled iloprost) [21–23]. Then oral preparations of phosphodiesterase inhibitors, namely sildenafil, became available with promising results [27, 28]. Now two newer drugs, bosentan and ambrisentan, that are endothelin receptor antagonists have been shown to be effective in selected patients [29, 30]. Despite these therapies there are case reports of patients wherein the pulmonary hypertension has progressed after a successful liver transplantation [31]. Perhaps these patients were misdiagnosed with POPH and really had primary pulmonary hypertension in the face of portal hypertension and liver disease.

Candidates with POPH will be eligible for an MELD exception. Diagnosis should include initial MPAP and PVR levels, documentation of treatment, and post-treatment MPAP < 35 mmHg and PVR < 400 dyn s/cm⁵. Transpulmonary gradient should be required for initial diagnosis to correct for volume overload [32].

In 1884 Flückiger [33] described a female patient with cyanosis finger clubbing and liver cirrhosis. The association between cyanosis and liver disease continued to be observed and a new syndrome termed the hepatopulmonary syndrome was coined to reflect the arterial hypoxemia which occurs in about one-third of patients with liver cirrhosis in the absence of detectable cardiorespiratory disease (Fig. 33.7).

The hepatopulmonary syndrome (HPS) is defined as the triad of liver disease and/or portal hypertension together with an increased alveolar-arterial gradient on room air, together with intrapulmonary microvascular vasodilatation [34, 35]. The intrapulmonary vascular dilatations result in a positive contrast echocardiogram, with echogenic material formed from agitated saline when injected intravenously passing from the right side of the heart to the left side with a 4–6-beat delay (Fig. 33.8) [34]. If the contrast crosses over to the left side faster than this then a septal defect should be considered.

The impairment in oxygenation that occurs with HPS in some patients may be found to worsen upon standing. This is termed orthodeoxia and is a strong indicator of HPS [36, 37]. It is the result of preferential perfusion of the lung bases in a standing patient. Some patients with HPS also exhibit platypnea which is shortness of breath that is made worse by sitting up from the lying posture. This is the opposite of most other pulmonary conditions in which the patient breathes better on sitting up. Criteria defining HPS are outlined in Table 33.4 [34, 38]. Figure 33.9 shows albumin uptake in the lung, brain, and kidneys in a patient with hepatopulmonary syndrome [34].