Objectives This study sought to understand the prevalence and clinical relevance of iron deficiency in patients with idiopathic pulmonary arterial hypertension (IPAH). Background Iron availability ...influences the pulmonary vascular response to hypoxia in humans and may be significant in the pathogenesis of IPAH. Methods Iron deficiency, defined by raised levels of soluble transferrin receptor (sTfR), was investigated in 98 patients with IPAH. Hepcidin and erythropoietin (EPO) levels were also measured. The effect of bone morphogenetic protein (BMP) receptor knockdown on BMP-6–stimulated hepcidin production was assessed in human hepatoma HepG2 cells. Relationships between sTfR and exercise capacity, functional class, and all-cause mortality were analyzed. Results Circulating sTfR levels were raised in 63% of IPAH patients, indicating significant iron deficiency. Consistent with this, iron, ferritin, and transferrin saturation levels were reduced and red cell distribution width increased, without overt anemia. Hepcidin correlated inversely with sTfR and positively with increasing ferritin. Hepcidin was inappropriately raised in IPAH independent of the inflammatory marker interleukin-6. EPO levels were also raised and correlated inversely with hepcidin. BMP receptor-type 2 ( BMPR2 ) knockdown in HepG2 cells increased BMP-6–stimulated hepcidin expression. sTfR increased with World Health Organization functional class (p < 0.05), correlated negatively with exercise capacity (p = 0.027), and values >28.1 nmol/l independently predicted survival (p = 0.011). Conclusions Iron deficiency is common in IPAH patients and associated with disease severity and poor clinical outcome. Inappropriately raised hepcidin levels, which impair iron absorption from the gut, may be a factor.
Idiopathic and heritable pulmonary arterial hypertension form a rare but molecularly heterogeneous disease group. We aimed to measure and validate differences in plasma concentrations of proteins ...that are associated with survival in patients with idiopathic or heritable pulmonary arterial hypertension to improve risk stratification.
In this observational cohort study, we enrolled patients with idiopathic or heritable pulmonary arterial hypertension from London (UK; cohorts 1 and 2), Giessen (Germany; cohort 3), and Paris (France; cohort 4). Blood samples were collected at routine clinical appointment visits, clinical data were collected within 30 days of blood sampling, and biochemical data were collected within 7 days of blood sampling. We used an aptamer-based assay of 1129 plasma proteins, and patient clinical details were concealed to the technicians. We identified a panel of prognostic proteins, confirmed with alternative targeted assays, which we evaluated against the established prognostic risk equation for pulmonary arterial hypertension derived from the REVEAL registry. All-cause mortality was the primary endpoint.
20 proteins differentiated survivors and non-survivors in 143 consecutive patients with idiopathic or heritable pulmonary arterial hypertension with 2 years' follow-up (cohort 1) and in a further 75 patients with 2·5 years' follow-up (cohort 2). Nine proteins were both prognostic independent of plasma NT-proBNP concentrations and confirmed by targeted assays. The functions of these proteins relate to myocardial stress, inflammation, pulmonary vascular cellular dysfunction and structural dysregulation, iron status, and coagulation. A cutoff-based score using the panel of nine proteins provided prognostic information independent of the REVEAL equation, improving the C statistic from area under the curve 0·83 (for REVEAL risk score, 95% CI 0·77–0·89; p<0·0001) to 0·91 (for panel and REVEAL 0·87–0·96; p<0·0001) and improving reclassification indices without detriment to calibration. Poor survival was preceded by an adverse change in panel score in paired samples from 43 incident patients with pulmonary arterial hypertension in cohort 3 (p=0·0133). The protein panel was validated in 93 patients with idiopathic or heritable pulmonary arterial hypertension in cohort 4, with 4·4 years' follow-up and improved risk estimates, providing complementary information to the clinical risk equation.
A combination of nine circulating proteins identifies patients with pulmonary arterial hypertension with a high risk of mortality, independent of existing clinical assessments, and might have a use in clinical management and the evaluation of new therapies.
National Institute for Health Research, Wellcome Trust, British Heart Foundation, Assistance Publique-Hôpitaux de Paris, Inserm, Université Paris-Sud, and Agence Nationale de la Recherche.
Variation in perioperative care across centers for infants undergoing the Norwood procedure Pasquali, Sara K., MD, MHS; Ohye, Richard G., MD; Lu, Minmin, MS ...
Journal of thoracic and cardiovascular surgery/The Journal of thoracic and cardiovascular surgery/The journal of thoracic and cardiovascular surgery,
10/2012, Letnik:
144, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Objectives In the Single Ventricle Reconstruction trial, infants undergoing the Norwood procedure were randomly allocated to undergo a right ventricle-to-pulmonary artery shunt or a modified ...Blalock-Taussig shunt. Apart from shunt type, subjects received the local standard of care. We evaluated variation in perioperative care during the Norwood hospitalization across 14 trial sites. Methods Data on preoperative, operative, and postoperative variables for 546 enrolled subjects who underwent the Norwood procedure were collected prospectively on standardized case report forms, and variation across the centers was described. Results Gestational age, birth weight, and proportion with hypoplastic left heart syndrome were similar across sites. In contrast, all recorded variables related to preoperative care varied across centers, including fetal diagnosis (range, 55%-85%), preoperative intubation (range, 29%-91%), and enteral feeding. Perioperative and operative factors were also variable across sites, including median total support time (range, 74-189 minutes) and other perfusion variables, arch reconstruction technique, intraoperative medication use, and use of modified ultrafiltration (range, 48%-100%). Additional variation across centers was seen in variables related to postoperative care, including proportion with an open sternum (range, 35%-100%), median intensive care unit stay (range, 9-44 days), type of feeding at discharge, and enrollment in a home monitoring program (range, 1%-100%; 5 sites did not have a program). Overall, in-hospital death or transplant occurred in 18% (range across sites, 7%-39%). Conclusions Perioperative care during the Norwood hospitalization varies across centers. Further analysis evaluating the underlying causes and relationship of this variation to outcome is needed to inform future studies and quality improvement efforts.
Abstract Purpose To compare the characteristics and prognosis of acute myocardial infarctions (AMIs) that were not the primary reason for hospitalization, and thus not primary discharge diagnosis, to ...AMIs that were the primary reason for hospitalization. Methods Primary discharge diagnoses for Reasons for Geographic and Racial Differences in Stroke study participants (black and white men and women age ≥45 years) with adjudicated AMIs were categorized as “AMI” or “other”. Cox models were used to compare mortality up to 5 years post-AMI between primary discharge diagnoses of AMI and other. Results Of 871 AMIs, primary discharge diagnosis was not AMI in 550 (63%). When primary discharge diagnosis was not AMI, average troponin elevations were smaller and heart failure was more common. Adjusted for participant and hospitalization characteristics, all-cause, coronary heart disease, and cardiovascular disease mortality after AMI were similar between groups (hazard ratios 95% confidence intervals: 1.08 0.80–1.47; 1.29 0.76–2.18; and 0.86 0.58–1.27, respectively). Conclusions Studies limited to individuals with primary discharge diagnosis of AMI may underestimate the burden of AMI and exclude a group with elevated risk of all-cause, coronary heart disease, and cardiovascular disease mortality.
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