Survival in portopulmonary hypertension: Mayo Clinic experience categorized by treatment subgroups.

To determine the natural history of portopulmonary hypertension (POPH), a retrospective screening-right heart catheterization-survival analysis of patients was performed. We categorized patients by three treatment subgroups: (1) no therapy for pulmonary hypertension (PH) or liver transplantation (LT), (2) therapy for PH alone and (3) therapy for PH followed by LT. Seventy-four patients were identified between 1994 and 2007. Nineteen patients received no therapy for PH and no LT representing the natural history of POPH. Five-year survival was 14%, and 54% had died within 1 year of diagnosis. Five-year survival in 43 patients receiving therapy for PH but no LT was 45%, and 12% had died within 1 year of diagnosis. Twelve patients underwent LT and 5-year survival for the nine receiving therapy for PH was 67% versus 25% in the three who were not pretreated with prostacyclin therapy. The survival of untreated patients with POPH was poor. Subgroups of patients selected to medical treatment with or without LT had better long-term survival. Mortality did not correlate with baseline hemodynamic variables, type of liver disease or severity of hepatic dysfunction. Medical therapy for POPH should be considered in all patients with POPH, but the treatment effects and impact on those considered for LT still requires well-designed, prospective study before practice guidelines can be suggested.

Unexplained pulmonary hypertension in chronic myeloproliferative disorders.

AIM: To investigate the potential association between the chronic myeloid disorders (CMDs), including the chronic myeloproliferative disorders, and pulmonary hypertension (PH). METHODS: Retrospective chart review of patients who had received diagnoses of both CMD and PH. Patients with a known cause of PH were excluded. The diagnosis of a CMD was based on established criteria. The diagnosis of PH was based on echocardiographic data or right heart catheterization data. RESULTS: Twenty-six patients satisfied the criteria for both a CMD and PH. Twelve patients had myeloid metaplasia with myelofibrosis (MMM), 5 patients had essential thrombocythemia (ET), 6 patients had polycythemia vera, 2 patients had a myelodysplastic syndrome, and 1 patient had chronic myeloid leukemia. Twenty-two patients (92%) received treatment for their CMDs, which included therapy with hydroxyurea (18 patients), anagrelide (7 patients), and busulfan (3 patients). PH was diagnosed a median of 8 years after recognition of the CMD (range, 0 to 26 years). The median right ventricular systolic pressure (RVsys) was 71 mm Hg (range, 32 to 105 mm Hg). RVsys correlated with the platelet count in patients with MMM (r = 0.30) and ET (r = 0.6) and with the hemoglobin levels in patients with PV (r = 0.77). Treatment of CMD did not seem to affect the severity of the pulmonary artery pressures as measured by serial echocardiography. With a median survival time of 18 months after the diagnosis of PH, the cause of death in the majority of the patients was cardiopulmonary. CONCLUSIONS: The current study suggests a higher than expected incidence of PH in patients with MMM, PV, and ET. Prognosis in such a setting is poor and may not be influenced by aggressive treatment of the underlying hematologic disorder.

Hepatopulmonary syndrome: a prospective study of relationships between severity of liver disease, PaO(2) response to 100% oxygen, and brain uptake after (99m)Tc MAA lung scanning.

BACKGROUND: Because of the spectrum of intrapulmonary vascular dilation that characterizes hepatopulmonary syndrome (HPS), PaO(2) while breathing 100% oxygen varies. Abnormal extrapulmonary uptake of (99m)Tc macroaggregated albumin (MAA) after lung perfusion is common. GOAL: To describe relationships between (1) severity of liver disease measured by the Child-Pugh (CP) classification; (2) PaO(2) while breathing room air (RA) and 100% oxygen on 100% oxygen; and (3) extrapulmonary (brain) uptake of (99m)Tc MAA after lung scanning. METHODS AND PATIENTS: We prospectively measured PaO(2) on RA, PaO(2) on 100% oxygen, and brain uptake after lung perfusion of (99m)Tc MAA in 25 consecutive HPS patients. RESULTS: Mean PaO(2) on RA, PaO(2) on 100% oxygen, PaCO(2) on RA, and (99m)Tc MAA brain uptake were similar when categorized by CP classification. Brain uptake was abnormal (> or = 6%) in 24 patients (96%). Brain uptake was 29 +/- 20% (mean +/- SD) and correlated inversely with PaO(2) on RA (r = -0.57; p<0.05) and PaO(2) on 100% oxygen (r = -0.41; p<0.05). Seven patients (28%) had additional nonvascular pulmonary abnormalities and lower PaO(2) on 100% oxygen (215+/-133 mm Hg vs 391+/-137 mm Hg; p<0.007). Eight patients (32%) died. Mortality in patients without coexistent pulmonary abnormalities was associated with greater brain uptake of (99m)Tc MAA (48+/-18% vs 25+/-20%; p<0.04) and lower PaO(2) on RA (40+/-7 mm Hg vs 57+/-11 mm Hg; p<0.001). CONCLUSION: The degree of hypoxemia associated with HPS was not related to the CP severity of liver disease. HPS patients with additional nonvascular pulmonary abnormalities exhibited lower PaO(2) on 100% oxygen. Mortality was associated with lower PaO(2) on RA, and with greater brain uptake of (99m)Tc MAA.

Pulmonary hemodynamics and perioperative cardiopulmonary-related mortality in patients with portopulmonary hypertension undergoing liver transplantation.

In the setting of moderate to severe pulmonary artery hypertension, orthotopic liver transplantation (OLT) may be complicated by pulmonary hemodynamic instability and cardiopulmonary mortality. We retrospectively studied the relationship between cardiopulmonary-related mortality and initial (untreated) pre-OLT pulmonary hemodynamics in 43 patients with portopulmonary hypertension who underwent attempted OLT. Thirty-six patients were reported in 18 peer-reviewed studies, and 7 patients underwent OLT at our institution since 1996. Transplantation procedure outcome, mean pulmonary artery pressure (MPAP), pulmonary vascular resistance (PVR), cardiac output, pulmonary capillary wedge pressure, and transpulmonary gradient (TPG) are summarized. Overall mortality was reported in 15 of 43 patients (35%). Fourteen of the 15 deaths (93%) were primarily related to cardiopulmonary dysfunction. Two deaths were intraoperative, 8 deaths occurred during the transplantation hospitalization, and 4 patients died of cardiopulmonary deterioration posthospitalization. In 4 patients, the transplantation procedure could not be successfully completed. Cardiopulmonary mortality was associated with greater pre-OLT MPAP (49 +/- 14 v 36 +/- 7 mm Hg; P <.005), PVR (441 +/- 173 v 261 +/- 156 dynes.s.cm(-5); P <.005), and TPG (37 +/- 13 v 22 +/- 10 mm Hg; P <.005). MPAP of 50 mm Hg or greater was associated with 100% cardiopulmonary mortality. In patients with an MPAP of 35 to less than 50 mm Hg and PVR of 250 dynes.s.cm(-5) or greater, the mortality rate was 50%. No mortality was reported in patients with a pre-OLT MPAP less than 35 mm Hg or TPG less than 15 mm Hg. Cardiopulmonary-related mortality in OLT patients with portopulmonary hypertension was frequent and associated with significantly increased pre-OLT MPAP, PVR, and TPG compared with survivors. Treated or untreated, we recommend intraoperative cancellation or advise against proceeding to OLT for an MPAP of 50 mm Hg or greater. Patients with an MPAP of 35 to less than 50 mm Hg and PVR of 250 dynes.s.cm(-5) or greater appear to be at high risk for cardiopulmonary-related mortality after OLT. A prospective study is needed to define optimal pretransplantation treatments and pulmonary hemodynamic criteria that minimize OLT mortality associated with portopulmonary hypertension.

Accuracy of Doppler echocardiography in the assessment of pulmonary hypertension in liver transplant candidates.

Pulmonary hypertension has been associated with poor outcome after liver transplantation. We assessed the diagnostic accuracy of Doppler echocardiography in detecting significant pulmonary hypertension. Seventy-four potential liver transplant candidates underwent Doppler echocardiography in which the systolic right ventricular pressure (RVsys) was used to estimate the systolic pulmonary artery pressure (PAsys). Group 1 included 39 consecutive patients with RVsys >/=50 mm Hg who underwent elective right heart catheterization. Group 2 consisted of 35 patients with RVsys <50 mm Hg in whom pulmonary artery pressures were measured at the beginning of the transplantation procedure. The accuracy of the estimates by Doppler echocardiography was assessed against measurements made by direct catheterization. Patients in groups 1 and 2 were comparable in their demographic and liver disease characteristics. There was a strong correlation between RVsys by Doppler echocardiography and PAsys by right heart catheterization (r =.78, P <.01). Of the 39 patients in group 1, 29 (72%) had at least moderate pulmonary hypertension (mean pulmonary artery pressure [MPAP] >/=35 mm Hg), including 12 (30%) with severe pulmonary hypertension (MPAP >/=50 mm Hg). Only 1 of the group 2 patients had MPAP >/=35 mm Hg. Thus, in the diagnosis of moderate to severe pulmonary hypertension, the sensitivity of echocardiography was 97% and specificity was 77%. Doppler echocardiography is an accurate screening test to detect moderate to severe pulmonary hypertension. We advise that liver transplant candidates with RVsys >/=50 mm Hg undergo right heart catheterization to fully characterize pulmonary hemodynamics.

Pulmonary hypertension: diagnostics and therapeutics.

Pulmonary hypertension (PH) may develop because of a spectrum of insults to the lungs; in some patients, there seems to be no cause. Noninvasive tests, such as standard chest radiography, electrocardiography, and transthoracic Doppler echocardiography, provide effective screening if PH is suspected. This synopsis focuses on these screening studies and the more common clinical problems, including primary cardiac abnormalities, obstructive sleep apnea, chronic pulmonary embolism, pulmonary parenchymal problems, connective tissue disorders, cirrhosis with portal hypertension, and use of appetite suppressants, that should be considered when PH exists. Treatment options for PH, including intravenous prostacyclin (epoprostenol), and investigational agents such as subcutaneous or oral prostacyclin analogues and oral endothelin receptor antagonists are described.

Hepatic hydrothorax: pathogenesis, diagnosis, and management.

Hepatic hydrothorax is defined as a pleural effusion in a patient with cirrhosis of the liver and no cardiopulmonary disease. The estimated prevalence of this often debilitating complication in patients with liver cirrhosis is 4% to 10%. Its pathophysiology involves movement of ascitic fluid from the peritoneal cavity into the pleural space through diaphragmatic defects. As a result patients are at increased risk of respiratory infection. Initial management consists of sodium restriction, diuretics, and thoracentesis. A transjugular intrahepatic portosystemic shunt may be required. Because most patients with hepatic hydrothorax have end-stage liver disease, a liver transplant should be considered if these options fail.

Progressive splenomegaly after epoprostenol therapy in portopulmonary hypertension.

Patients with end-stage liver failure, portal hypertension, and associated pulmonary artery hypertension (portopulmonary hypertension [PPHTN]) have a high mortality when undergoing liver transplantation. Successful transplantation in these patients may depend on efforts to reduce pulmonary artery pressure (PAP). To this end, a number of centers are using a continuous intravenous (IV) infusion of epoprostenol, which has been shown to improve symptoms, extend life span, and reduce PAP in patients with primary pulmonary hypertension. We report four cases in which treatment of patients with PPHTN with continuous IV epoprostenol was followed by the development of progressive splenomegaly, with worsening thrombocytopenia and leukopenia. This finding may limit the usefulness of epoprostenol in PPHTN and influence the timing of transplantation in such patients.

Inhaled nitric oxide reduces pulmonary artery pressures in portopulmonary hypertension.

Pulmonary artery hypertension in association with liver failure (portopulmonary hypertension [PPHTN]) is a significant barrier to liver transplantation because patients with this condition have a very high mortality when transplantation is undertaken. Inhaled nitric oxide (NO), a potent pulmonary vasodilator, reduces pulmonary artery pressure (PAP) in some patients with primary pulmonary hypertension, but its effect in patients with PPHTN is controversial. We investigated the hemodynamic effects of inhaled NO in 6 patients with PPHTN. Five of 6 patients responded to NO inhalation with decreases in PAP and pulmonary vascular resistance of greater than 10%; these decreases were statistically significant at NO concentrations of 10 and 30 ppm. Cardiac output did not significantly change. We conclude that inhalation of NO reduces PAPs in some patients with PPHTN.

Late recurrence and rapid evolution of severe hepatopulmonary syndrome after liver transplantation.

Recurrence of hepatopulmonary syndrome (HPS) after orthotopic liver transplantation (OLT) in an adult has never been reported. We describe a 23-year-old woman who initially underwent OLT because of debilitating and severe HPS associated with nonalcoholic steatohepatitis (NASH). Although the clinical resolution of HPS was well documented day 117 post-OLT, the reappearance of NASH was documented by liver biopsy. Severe hypoxemia because of recurrent HPS rapidly evolved beginning approximately day 700 post-OLT. Retransplantation was attempted, but the patient died post-OLT of sepsis and/or multiorgan failure.

Improvement in pulmonary hemodynamics during intravenous epoprostenol (prostacyclin): A study of 15 patients with moderate to severe portopulmonary hypertension.

Pulmonary hypertension associated with increased pulmonary vascular resistance (PVR) and occurring in the setting of portal hypertension is referred to as "portopulmonary hypertension." Intravenous epoprostenol (prostacyclin) is a potent pulmonary and systemic vasodilator with antithrombotic properties. It can decrease PVR and pulmonary artery pressure in patients with primary (idiopathic) pulmonary hypertension. Using right-heart catheterization, we evaluated the acute pulmonary hemodynamic effects of intravenous epoprostenol in patients with moderate to severe pulmonary hypertension (mean pulmonary artery pressure [MPAP] >/=35 mm Hg) associated with clinical manifestations of portal hypertension. Effects of long-term infusion of epoprostenol were also evaluated. We studied 15 consecutive patients with portopulmonary hypertension; 14 underwent acute administration of epoprostenol, and no significant side effects were noted. Ten patients received continuous epoprostenol (range, 8 days-30 months). Acute changes in PVR (-34% +/- 18%), MPAP (-16% +/- 10%), and cardiac output (CO) (+21 +/- 18%), were statistically significant (P <.01). Long-term use of epoprostenol further lowered PVR (-47% +/- 12% from baseline and -31% +/- 22% from the acute change; P <.05) in the 6 patients restudied by right-heart catheterization. Death occurred in 6 of 10 (60%) of those receiving long-term epoprostenol. In moderate to severe portopulmonary hypertension, intravenous epoprostenol resulted in a significant improvement (both acute and long-term) in PVR, MPAP, and CO. Potential adverse effects on portal hypertension and implications for orthotopic liver transplantation (OLT), however, require further study.