DuBrock, Hilary M.

Background. The role of liver transplantation (LT) in the management of portopulmonary hypertension (POPH) is poorly understood. The aim of this study was to better understand provider attitudes and practice patterns regarding the management of patients with POPH and to assess the concordance between clinical practice and current guidelines. Methods. We performed a multicenter survey study of hepatologists and pulmonary hypertension (PH) physicians at US LT centers that performed >50 transplants per year. Survey responses are summarized as number (%). Associations were assessed using a Wilcoxon-rank sum, chi-square, or Fisher exact test, as appropriate. Results. Seventy-four providers from 35 centers were included. There was marked variability regarding screening practices, management, and attitudes. Forty-two percent responded that POPH nearly always or often improves with LT, and 15.5% reported that POPH rarely or never improves. In contrast to current guidelines, 50.7% agreed that treated POPH should be an indication for LT in patients with compensated cirrhosis. Hepatologists were more likely than PH physicians to agree that POPH should be an indication for LT (P = 0.02). Forty-nine percent of respondents thought that the current POPH Model for End-stage Liver Disease exception criteria should be modified, and management of patients with an elevated mean pulmonary arterial pressure and normal pulmonary vascular resistance differed from current policies. Conclusions. There is marked variability in provider attitudes and practice patterns regarding the management of POPH. This study highlights the need for prospective studies to inform practice and for improved implementation of practice guidelines in order to standardize care.

Abstract Abstract Background: Pulmonary hypertension (PH) is a significant preoperative risk factor. We aimed to determine predictors of perioperative morbidity and mortality after noncardiac surgery for patients with precapillary PH. Methods: We conducted a retrospective cohort study of adults with pulmonary hypertension having surgery at a single large medical referral center. The PH and surgical databases were reviewed from 2010 to 2017. Patients were excluded if PH was attributable to left-sided heart disease or they had undergone cardiac or transplant operations. To assess whether PH-specific diagnostic or cardiopulmonary testing parameters were predictive of perioperative complications, analyses were performed using generalized estimating equations. Results: Of 196 patients with PH undergoing noncardiac operations, 53 (27%) experienced 1 or more complications, including 5 deaths (3%) within 30 days. After adjustment for age and PH type, there were more complications in those undergoing moderate-to-high vs low-risk procedures (odds ratio [OR], 4.17 [95% CI, 2.07 to 8.40]; P<0.001). After adjustment for age, surgical risk, and PH type, the risk for complications was higher for patients with worse functional status (OR, 2.39 [95% CI, 1.19 to 4.78]; P=0.01 for class 3/4 vs class 1/2) and elevated serum N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) (OR, 2.28 [95% CI, 1.05 to 4.96]; P=0.04 for ≥300 vs. <300 pg/mL). From an analysis that included covariates for age, surgical risk, and functional status, elevated serum NT-proBNP levels remained associated with increased risk (OR, 2.23 [95% CI, 1.05 to 4.76]; P=0.04). Conclusions: Patients with PH undergoing noncardiac surgery with general anesthesia have a high frequency of perioperative complications. Specific clinical (functional status), diagnostic (serum NT-proBNP), and intraoperative factors (higher-risk surgery) are predictive of worse outcomes.

Background: We hypothesized that pulmonary venous hypertension in heart failure (HF) leads to predominate remodeling of pulmonary veins and that the severity of venous remodeling is associated with the severity of pulmonary hypertension (PH) in HF. Methods: Patients with HF (n=108; 53 preserved and 55 reduced ejection fraction) with PH (HF-PH; pulmonary artery systolic pressure [PASP] ≥40 mm Hg) were compared to normal controls (n=12) and patients with primary pulmonary veno-occlusive disease (PVOD; n=17). In lung specimens from autopsy (control, HF-PH, and 7 PVOD) or surgery (10 PVOD), quantitative histomorphometry was performed in all analyzable arteries (n=4949), veins (n=7630), and small indeterminate vessels (IV; n=2168) to define percent medial thickness (arteries) and percent intimal thickness (%IT) (arteries, veins, and IV) relative to external diameter. Results: The average arterial percent medial thickness (control, 6.9; HF-PH, 11.0; PVOD, 15.0), arterial %IT (control, 4.9; HF-PH, 14.9; PVOD, 31.1), venous %IT (control, 14.0; HF-PH, 24.9; PVOD, 43.9), and IV %IT (control, 10.6; HF-PH, 25.8; PVOD, 50.0) in HF-PH were higher than controls ( P <0.0001 for all) but lower than PVOD ( P ≤0.005 for all). PASP (mm Hg) was lower in HF-PH (median, 59 [interquartile range, 50–70]) than in PVOD (median, 91 [interquartile range, 82–103]). PASP correlated with arterial percent medial thickness ( r =0.41) and arterial %IT ( r =0.35) but more strongly with venous %IT ( r =0.49) and IV %IT ( r =0.55) ( P <0.0001 for all). Associations between PASP and venous or IV %IT remained significant after adjusting for arterial percent medial thickness and %IT and did not vary by HF type. In patients with right heart catheterization (30 HF-PH, 14 PVOD), similar associations between the transpulmonary gradient and pulmonary vascular remodeling existed, with numerically stronger associations for venous and IV %IT. Although the PASP was slightly higher in patients with HF-PH with right ventricular dysfunction, pulmonary vascular remodeling was not more severe. Pulmonary vascular remodeling severity was associated with reductions in the diffusing capacity of the lungs. Conclusions: In HF, PH is associated with global pulmonary vascular remodeling, but the severity of PH correlates most strongly with venous and small IV intimal thickening, similar to the pattern observed in PVOD. These findings expand our understanding of the pathobiology of PH in HF.