DuBrock, Hilary M

Patients with advanced chronic liver disease can develop specific pulmonary complications related or unrelated to pre-existing lung disease. The three major pulmonary complications in this patient population include hepatopulmonary syndrome (HPS), portopulmonary hypertension (PoPH), and hepatic hydrothorax (HH). These entities are most often revealed by increasing dyspnea together with signs of portal hypertension. The prevalence of these complications remains underestimated due to the lack of routine screening of the cirrhotic population. The pathophysiology of HH is better understood than that of HPS and PoPH. The clinical features, diagnosis, and therapeutic options of these pulmonary complications are extensively discussed in this chapter. Liver transplantation may offer a curative therapy in highly-selected cases and MELD exception points allow priority access to liver transplantation, thus avoiding potential deterioration while awaiting transplant and providing a better post liver transplant survival. The complexity of managing these pulmonary complications requires a multidisciplinary team approach, especially when liver transplantation is indicated.

AbstractPulmonary hypertension (PH) associated with chronic kidney disease (CKD) (PH‐CKD) affects approximately 20%–40% of CKD patients and is associated with increased morbidity and mortality. PH and CKD are both pathophysiologically associated with nitric oxide (NO) deficiency. The NO pathway, an important therapeutic domain in pulmonary arterial hypertension (PAH), is an intriguing but unexplored target in PH‐CKD. We sought to improve understanding of the clinical significance of the NO pathway in patients with PH‐CKD by assessing the hemodynamic response to inhaled NO (iNO) during right heart catheterization (RHC). In this retrospective cohort study, patients with diagnosis codes of PH and stage IV/V CKD or end‐stage renal disease and estimated glomerular filtration rate < 60 mL/min/body surface area who underwent RHC and hemodynamic drug study between July 2011 and June 2021 were eligible. Patients with mean pulmonary artery pressure (mPAP) > 20 mmHg and pulmonary vascular resistance (PVR) > 3 Wood units were included. The final cohort included 37 patients (45.9% female, mean age 72.5 ± 9.7 years). A total of 56.7% of the cohort (21/37) had precapillary PH, while 43.2% (16/37) had combined precapillary postcapillary PH (Cpc‐PH). Median survival was 3.1 years after RHC. iNO was associated with a significant decrease in both mPAP and PVR. Hemodynamic changes in mPAP and PVR were similar in precapillary and Cpc‐PH groups. Among a small subset (n = 14) who were subsequently treated with PAH‐targeted therapy, treatment response was mixed and did not reveal significant benefit. Further studies are warranted to better define the potential role of PAH therapy in PH‐CKD.

AbstractChronic lung disease (CLD) is the second leading cause of pulmonary hypertension (PH) and is associated with significant morbidity and mortality. Although PH associated with CLD (PH‐CLD) leads to impaired health‐related quality of life (HRQOL), there are no validated tools to assess HRQOL in PH‐CLD. The Pulmonary Arterial Hypertension–Symptoms and Impact Questionnaire (PAH‐SYMPACT) is an HRQOL instrument aimed at assessing the symptoms and impact of PH on overall function and well‐being. We performed a single‐center prospective cohort study using PAH‐SYMPACT scores to compare symptoms, exercise capacity and HRQOL in patients with PAH and PH‐CLD. One hundred and twenty‐five patients (99 patients with idiopathic/heritable PAH and 26 with PH‐CLD) completed the PAH‐SYMPACT questionnaire which consists of 22 questions that assess HRQOL across four domains: cardiopulmonary (CP) symptoms, cardiovascular (CV) symptoms, physical impact (PI), and cognitive/emotional (CE) impact. Higher scores indicate worse HRQOL. We compared patients with PAH and PH‐CLD using a Wilcoxon rank sum or chi‐squared test as appropriate. Multivariate linear regression analysis was used to assess the relationship between PH classification and SYMPACT scores. Compared to PAH, patients with PH‐CLD were older, more likely to use oxygen and had worse functional class and exercise capacity. While there was no significant difference between the two groups in CP, CV, or CE domain scores, patients with PH‐CLD had significantly worse PI scores by univariate (1.79 vs. 1.13, p < 0.001) and multivariate analysis (1.61 vs. 1.17, p = 0.02) and overall worse SYMPACT scores (1.19 vs. 0.91, p = 0.03). In conclusion, patients with PH‐CLD have worse HRQOL as assessed by the PAH‐SYMPACT questionnaire versus patients with PAH. Although PAH‐SYMPACT has not been validated in PH‐CLD, the results of this study can guide clinicians in understanding the symptoms and impact of PH‐CLD relative to PAH.

AbstractPulmonary rehabilitation (PR) is a supervised exercise program for patients with chronic lung disease. Among patients with pulmonary hypertension (PH), PR has been shown to improve both quality of life and exercise capacity. The purpose of this study was to assess the prevalence of PR participation among PH patients, patient perspectives regarding PR, and to identify potential barriers to PR participation. We performed a cross‐sectional survey of patients with self‐reported PH who attended the Pulmonary Hypertension Association (PHA) conference in June 2022 in Atlanta, Georgia, and patients within the PHA listserv. A total of 429 participants completed the survey and were enrolled in the study. The average age of participants was 61 ± 14 years with 83% of participants identifying as female, 51% of patients self‐reported as having group 1 PH. Among patients who completed the survey, 41% had previously attended a PR program. Of those who had completed a PR program, 83% reported being satisfied or very satisfied with the program and 86% reported that they would recommend PR to other PH patients. After completion of a PR program, 76% of patients reported an improvement in their quality of life and 88% reported improvement in exercise capacity. Among the patients who had not previously participated in PR (n = 254), 63% reported an interest in participation while 64% cited a lack of discussion from their treatment team as the primary reason for the lack of PR participation. Limitations of the study include sampling and response bias. According to this cross‐sectional survey, the majority of PH patients who have participated in PR report improvement in both quality of life and exercise capacity and would recommend PR to other PH patients. The majority of PH patients who have not participated in PR were interested in participation and cited a lack of discussion with their treatment team as one of the primary reasons for the lack of participation. PR is associated with self‐reported improvements in quality of life and exercise capacity but remains underutilized among patients with PH.

Background: Patients with pulmonary hypertension (PH) who undergo endotracheal intubation have an increased risk of adverse outcomes, but little is known regarding prognostic factors and there is limited evidence to guide management. We sought to define characteristics, prognostic factors, and outcomes of critically ill patients with PH who underwent intubation. Study Design: We performed a single-center retrospective cohort study of critically ill patients with group 1, 3 or 4 PH who underwent intubation. Results: Eighty-one patients were included. Patients had a median age of 56 years (interquartile range 44-65) and were predominantly female (n = 53, 65%) and Caucasian (n = 71, 88%). Forty-five (56%) had group 1 PH while 25 (31%) had group 3 PH and 11 (14%) had group 4 PH. Patients were admitted to the hospital for right ventricular failure (n = 21, 25.6%), sepsis (n = 18, 22.2%), and respiratory failure (n = 19, 23.1%). Hypoxemic respiratory failure (n = 54, 66.7%) was the most common indication for intubation. In-hospital mortality was 30.9% and 1-year mortality was 48.2% . All patients (11 of 11, 100%) intubated electively for intensive care unit procedures survived to hospital discharge while only 1 of 6 (16.7%) intubated in the setting of a cardiac arrest survived. After adjusting for right ventricular systolic pressure, pre-intubation PaO 2 (odds ratio [OR] = 0.99, 95% confidence interval [CI] 0.97-1.00, P = .02) and postintubation PaO 2 (OR = 0.97 per 1mm Hg, 95% CI 0.95 to 0.99, P = .003), pH (OR = 0.49 per 0.1 increase, 95% CI 0.29 to 0.80, P = .005) and PaCO 2 (OR = 1.08 per 1mm Hg, 95% CI 1.02 to 1.14, P = .005) were significantly associated with in-hospital mortality. Results were similar when we excluded patients intubated electively or in the setting of cardiac arrest. Conclusions: Intubation in critically ill patients with PH is associated with significant in-hospital mortality and nearly 50% 1-year mortality. Potentially modifiable factors, such as peri-intubation gas exchange, are associated with an increased risk of death while other demographic and hemodynamic variables are not.

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.

AbstractWe present a novel description of Bezold–Jarisch Reflex (BJR) during cardiopulmonary exercise testing (CPET) in three young female patients with Group 1 pulmonary arterial hypertension (PAH). These three cases presented within 26 months, representing only 0.8% of 11,387 tests on patients with PAH undergoing CPET during this time frame.

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.

Abstract Patients with portopulmonary hypertension (POPH) have an increased cardiovascular and overall mortality risk when undergoing liver transplantation (LT). However, such risk is not captured in their Model for End‐Stage Liver Disease (MELD) laboratory score. POPH MELD exception criteria were established in 2006 with the aim of prioritizing these patients for LT prior to pulmonary hypertension (PH) progression and eventual right heart failure. The original criteria emphasized a posttreatment, pre‐LT mean pulmonary arterial pressure (mPAP) of <35 mm Hg and pulmonary vascular resistance (PVR) <400 dynes‐s‐cm−5 or <5 Wood units (WU). Since 2006, there have been important advances in the treatment of POPH with pulmonary arterial hypertension (PAH)–targeted therapies and newer evidence regarding LT outcomes and risk factors for perioperative mortality. Specifically, PVR rather than mPAP has been shown to be more strongly associated with outcomes, including mortality. In addition, among treated patients with POPH, mPAP may be persistently elevated related to an elevated cardiac output or other factors that do not necessarily reflect POPH disease severity. Thus, in February 2021, the Organ Procurement and Transplantation Network approved proposed modifications to POPH MELD exception criteria, now allowing either of the following posttreatment, pre‐LT hemodynamic profiles: mPAP less than 35 mm Hg and posttreatment PVR less than 400 dynes‐s‐cm−5 (or less than 5 WU) or mPAP greater than or equal to 35 mm Hg and less than 45 mm Hg and posttreatment PVR less than 240 dynes‐s‐cm−5 (or less than 3 WU). This article reviews the history of the POPH MELD exception criteria, describes the recent modifications to the exception criteria and the evidence supporting them, and highlights unanswered questions and areas for future research.