Liver TransplantationBackground. The causes and circumstances surrounding death are poorly studied in patients with portopulmonary hypertension (PoPH). We sought to determine the specific reasons for dying and characteristics surrounding this process in patients with PoPH. Methods. All deaths of patients with PoPH followed in the Cleveland Clinic Pulmonary Vascular Program were prospectively reviewed by the pulmonary hypertension team between 1996 and 2020. Results. A total of 69 patients with PoPH (age 56.0 ± 8.9 y), with 49% females, were included. Causes of death were available in 52 (75%) patients, of these PoPH either directly or indirectly contributed to death in 13 of 52 (25%) of patients, meanwhile 39 of 52 (75%) of the patients died because of progressive liver disease and its related complications. Decompensated liver disease was the leading cause of death in this cohort 20 of 52 (38%), whereas 19 of 52 (37%) died because of conditions associated with liver disease. About half, 36 of 69 (52%) of patients died in a healthcare environment and 23 of 36 (64%) during a hospitalization at Cleveland Clinic. A total of 59 of 69 (74%) of patients received pulmonary arterial hypertension (PAH)specific therapies. Six patients died after liver transplantation (in 3 death was related to PAH-related complications). Most of the patients in this cohort of PoPH patients were considered unsuitable for liver transplantation for a variety of reasons. Advanced healthcare directives were available in only 28% of patients. Conclusions. Most patients with PoPH died because of complications of their liver disease. PAH directly or indirectly contributed to death in a third of them. A quarter of them did not receive PAH-specific therapy before their death.
Background Idiopathic pulmonary arterial hypertension (IPAH) is a rapidly progressive disease with several treatment options. Long-term mortality remains high with great heterogeneity in treatment response. Even though most of the pathology of IPAH is observed in the lung, there is systemic involvement. Platelets from IPAH patients have characteristic metabolic shifts and defects in activation, therefore we investigated whether they could be used to identify other disease specific abnormalities. Methods We used proteomics to investigate protein expression changes in platelets from IPAH patients compared to healthy controls. Key abnormalities of nitric oxide pathway were tested in platelets from a larger cohort of unique IPAH patients. Results Platelets showed abnormalities in the prostacyclin and nitric oxide pathways, which are dysregulated in IPAH and hence targets of therapy. We detected reduced expression of G-protein as and increased expression of the regulatory subunits of the cAMP-dependent protein kinase (PKA) type II isoforms, supporting an overall decrease in the activation of the prostacyclin pathway. We noted reduced levels of the soluble guanylate cyclase (sGC) subunits and increased expression of the phosphodiesterase type 5A (PDE5A); conditions that affect the response to nitric oxide. Ensuing analysis of 38 unique patients with IPAH demonstrated considerable variation in the levels and specific activity of sGC, a finding with novel implications for personalized therapy. Interpretation Platelets have some of the characteristic vasoactive signal abnormalities seen in IPAH and may provide comprehensive ex-vivo mechanistic information to direct therapeutic decisions.
Background: It remains unknown whether the cutaneous microvascular responses are different between patients with scleroderma-associated pulmonary arterial hypertension (SSc-PAH) and SSc without pulmonary hypertension (PH). Methods: We included 59 patients with SSc between March 2013 and September 2019. We divided patients into 4 groups: (a) no PH by right heart catheterization (RHC) (n = 8), (b) no PH by noninvasive screening tests (n = 16), (c) treatment naïve PAH (n = 16), and (d) PAH under treatment (n = 19). Microvascular studies using laser Doppler flowmetry (LDF) were done immediately after RHC or at the time of an outpatient clinic visit (group b). Results: The median (IQR) age was 59 (54-68) years, and 90% were females. The responses to local thermal stimulation and postocclusive reactive hyperemia, acetylcholine, and sodium nitroprusside iontophoresis were similar among groups. The microvascular response to treprostinil was more pronounced in SSc patients without PH by screening tests (% change: 340 (214-781)) compared with SSc-PAH (naïve + treatment) (Perfusion Units (PU) % change: 153 (94-255) % [p = .01]). The response to A-350619 (a soluble guanylate cyclase (sGC) activator) was significantly higher in patients with SSc without PH by screening tests (PU % change: 168 (46-1,296)) than those with SSc-PAH (PU % change: 22 (15-57) % [p = .006]). The % change in PU with A350619 was directly associated with cardiac index and stroke volume index (R: 0.36, p = .03 and 0.39, p = .02, respectively). Conclusions: Patients with SSc-PAH have a lower cutaneous microvascular response to a prostacyclin analog treprostinil and the sGC activator A-350619 when compared with patients with SSc and no evidence of PH on screening tests, presumably
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.