Krowka, Michael J.

Background and Aims: Hepatopulmonary syndrome (HPS) and a hyperdynamic circulation are common complications of advanced liver disease, but the relationship between HPS and cardiac index (CI) is poorly understood. We sought to compare CI in patients with and without HPS and to assess the relationship between CI and symptoms, quality of life, gas exchange, and exercise capacity among liver transplantation (LT) candidates. We performed a cross-sectional analysis within the Pulmonary Vascular Complications of Liver Disease 2 study, a multicenter prospective cohort study of patients being evaluated for LT. We excluded patients with obstructive or restrictive lung disease, intracardiac shunting, and portopulmonary hypertension. We included 214 patients (81 with HPS and 133 controls without HPS). Compared with controls, patients with HPS had a higher CI (least square mean 3.2 L/min/m2, 95% CI 3.1–3.4 vs. 2.8 L/min/m2, 95% CI 2.7–3.0, p < 0.001) after adjustment for age, sex, Model for End-stage Liver Disease-Sodium (MELD-Na) score and beta-blocker use, and a lower systemic vascular resistance. Among all LT candidates, CI was correlated with oxygenation (Alveolar-arterial oxygen gradient r=0.27, p< 0.001), intrapulmonary vasodilatation severity (p < 0.001), and biomarkers of angiogenesis. Higher CI was independently associated with dyspnea and worse functional class and physical quality of life after adjusting for age, sex, MELD-Na, beta-blocker use, and HPS status. HPS was associated with a higher CI among LT candidates. Independent of HPS, higher CI was associated with increased dyspnea and worse functional class, quality of life, and arterial oxygenation.

A 6-minute walk test is a simple tool for assessing submaximal exercise capacity. We sought to determine whether a 6-minute walk distance (6MWD) predicts outcomes in patients with cirrhosis. The Pulmonary Vascular Complications of Liver Disease 2 study is a multicenter, prospective cohort study that enrolled adults with portal hypertension during liver transplantation evaluation. We excluded subjects with an incident or prevalent portopulmonary hypertension. The 6-minute walk test was performed using standardized methods. Cox proportional hazards modeling and multivariable linear regression analysis were performed to determine the relationship between baseline 6MWD and outcomes. The study sample included 352 subjects. The mean 6MWD was 391±101 m. For each 50-meter decrease in 6MWD, there was a 25% increase in the risk of death (HR 1.25, 95% CI [1.11, 1.41], p < 0.001) after adjustment for age, gender, body mass index, MELD-Na, and liver transplant as a time-varying covariate. In a multistate model, each 50-meter decrease in 6MWD was associated with an increased risk of death before the liver transplant ( p < 0.001) but not after the transplant. 6MWD was similar to MELD-Na in discriminating mortality. Each 50-meter decrease in 6MWD was associated with an increase in all-cause ( p < 0.001) and transplant-free hospitalizations ( p < 0.001) in multivariable models for time-to-recurrent events. Shorter 6MWD was associated with worse Short Form-36 physical ( p < 0.001) and mental component scores ( p = 0.05). In conclusion, shorter 6MWD is associated with an increased risk of death, hospitalizations, and worse quality of life in patients evaluated for liver transplantation. The 6-minute walk distance may be a useful adjunct for risk assessment in patients undergoing liver transplant evaluation.

Background. Model for end-stage liver disease (MELD) exception criteria for portopulmonary hypertension (POPH) were created to prioritize patients for liver transplant before POPH progression. Little is known about trends in POPH exception frequency, disease severity, pulmonary hypertension treatment patterns, or outcomes since the POPH MELD exception began. Methods. Using data from the Organ Procurement and Transplantation Network database, we describe the frequency of POPH MELD exceptions between 2006 and 2019, compare baseline patient characteristics, and characterize trends in liver disease and POPH severity‚ as well as POPH treatment and outcomes‚ over time. To facilitate comparison, we divided this 14-y period into 3 “eras” (2006–2010, 2011–2015, and 2016–2019). Results. Between 2006 and 2019, 504 unique POPH MELD exceptions were granted. Both liver disease severity and patient age have increased over time (P = 0.04 and P = 0.006, respectively). Posttreatment hemodynamic values (mean pulmonary arterial pressure and pulmonary vascular resistance) have significantly improved (P < 0.001 and P = 0.008, respectively). Treatment with endothelin receptor antagonists has become more prevalent, whereas use of parenteral therapy and monotherapy regimens has decreased (P < 0.001). Neither waitlist nor liver transplant mortality outcomes have significantly changed over the eras analyzed. Conclusions. In conclusion, 504 patients have received POPH MELD exceptions between 2006 and 2019. Since 2010, nearly all patients granted POPH MELD exceptions have met hemodynamic criteria for POPH. Over time, there has been a trend toward older age and higher MELD scores with significant changes in pulmonary arterial hypertension treatment patterns and an improvement in posttreatment hemodynamics without major change in outcomes.

AbstractPulmonary arterial hypertension (PAH) is a progressive pulmonary vascular disease that negatively impacts health‐related quality of life (HRQOL). The PAH‐symptoms and impact (PAH‐SYMPACT) questionnaire is a validated disease‐specific patient‐reported outcome (PRO) instrument that assesses a patient's symptoms and the impact of PAH and its treatment on well‐being. We performed a single‐center prospective cohort study of patients with PAH to determine the feasibility of assessing PROs in clinical practice and to determine the association between PAH‐SYMPACT domains and clinical characteristics and outcomes. One hundred and ten patients completed the 1‐day version of the PAH‐SYMPACT questionnaire which consists of 22 Likert‐scale questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive and emotional (CE) impact. Higher scores indicate worse HRQOL. Patients were predominantly female (n = 86, 78%) with a mean age of 57.8 ± 16.2 years. While several patient characteristics were associated with CP and PI domains, few were associated with CV and CE domains. PI and CE impact scores were associated with recent hospitalizations and mortality and CE impact score was independently associated with an increased risk of death after adjustment for disease severity (hazard ratio: 3.29, 95% confidence interval: 1.56–6.91, p = 0.002). In conclusion, the assessment of PROs in clinical practice using the PAH‐SYMPACT questionnaire is both feasible and valuable. PAH‐SYMPACT scores have independent prognostic value and are not adequately reflected by traditional measures of disease severity. These findings underscore the importance of assessing HRQOL in clinical practice.