Chronic thromboembolic pulmonary hypertension is not associated with iron overload

Xi, Qunying; Liu, Zhihong; Liu, Weihua; Zhao, Zhihui; Luo, Qin; Huang, Zhiwei

doi:10.1016/j.carpath.2014.09.006

Cited by 6 publications

(4 citation statements)

References 33 publications

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“…2, 8, 9, and 10). The changes in microvascular morphology were not accompanied by an overt pulmonary inflammatory response at this stage, as only IL-6 showed a trend toward an increase, consistent with the increase in IL-6 in patients with CTEPH (49,57,58), whereas IFN-␥, TNF-␣, and TGF-␤ were unaltered. Although the existence of pulmonary microvascular remodeling is known since 1993 (42), the consequences of this remodeling for pulmonary microvascular function have not been investigated to date.…”

Section: Discussionsupporting

confidence: 74%

Pulmonary microvascular remodeling in chronic thrombo-embolic pulmonary hypertension

Stam

Duin

Uitterdijk

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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Pulmonary vascular remodeling in pulmonary arterial hypertension involves perturbations in the nitric oxide (NO) and endothelin-1 (ET-1) pathways. However, the implications of pulmonary vascular remodeling and these pathways remain unclear in chronic thrombo-embolic pulmonary hypertension (CTEPH). The objective of the present study was to characterize changes in microvascular morphology and function, focussing on the ET-1 and NO pathways, in a CTEPH swine model. Swine were chronically instrumented and received up to five pulmonary embolizations by microsphere infusion, whereas endothelial dysfunction was induced by daily administration of the endothelial NO synthase inhibitor Nω-nitro-l-arginine methyl ester until 2 wk before the end of study. Swine were subjected to exercise, and the pulmonary vasculature was investigated by hemodynamic, histological, quantitative PCR, and myograph experiments. In swine with CTEPH, the increased right-ventricular afterload, decreased cardiac index, and mild ventilation-perfusion-mismatch were exacerbated during exercise. Pulmonary microvascular remodeling was evidenced by increased muscularization, which was accompanied by an increased maximal vasoconstriction. Although ET-1-induced vasoconstriction was increased in CTEPH pulmonary small arteries, the ET-1 sensitivity was decreased. Moreover, the contribution of the ETA receptor to ET-1 vasoconstriction was increased, whereas the contribution of the ETB receptor was decreased and the contribution of Rho-kinase was lost. A reduction in endogenous NO production was compensated in part by a decreased phosphodiesterase 5 (PDE5) activity resulting in an apparent increased NO sensitivity in CTEPH pulmonary small arteries. These findings suggest that pulmonary microvascular remodeling with a reduced activity of PDE5 and Rho-kinase may contribute to the lack of therapeutic efficacy of PDE5 inhibitors and Rho-kinase inhibitors in CTEPH.

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Section: Discussionsupporting

confidence: 74%

Pulmonary microvascular remodeling in chronic thrombo-embolic pulmonary hypertension

Stam

Duin

Uitterdijk

et al. 2018

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…We enrolled twenty-five consecutive patients with CTEPH who underwent BPA procedures in the Center for Pulmonary Vascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from May 11, 2018 to January 4, 2019. The diagnosis criteria of CTEPH, as we previously described, was established as follows: 1) existing precapillary PH defined as mean pulmonary arterial pressure (mPAP) ≥ 25 mmHg and pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg at rest confirmed by right heart catheterization (RHC); 2) evidence of thromboembolic occlusion of the proximal or distal pulmonary vasculature detected by imaging techniques such as computed tomography, magnetic resonance imaging, ventilation/perfusion scintigraphy or pulmonary angiography; 3) the above conditions should be obtained after at least 3 months of effective anticoagulation therapy [22, 23]. Inclusion criteria for BPA procedures: all CTEPH patients who are not suitable or contraindicated for PEA after operability assessment by our multidisciplinary team including PEA surgeons, PH experts, BPA interventionists and radiologists; Those with age more than 80 years old, severe liver or kidney dysfunction, iodinated contrast agents allergy, oxygen saturation in peripheral blood < 80%, existence of foreign body such as tumor and thrombus in catheter path, severe bleeding and coagulation disorders, life-threatening hypotension and cardiac arrhythmias, and different types of tumors were excluded.…”

Section: Methodsmentioning

confidence: 99%

Improved hemodynamics and cardiopulmonary function in patients with inoperable chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty

et al. 2019

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BackgroundBalloon pulmonary angioplasty (BPA) has been demonstrated to improve cardiac function and exercise capacity in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH), but its instant impact on cardiopulmonary function has seldom been evaluated. This study aims to determine the safety and efficacy of BPA and its immediate and lasting effects on cardiopulmonary function among CTEPH patients.MethodsFrom May 2018 to January 2019, patients with inoperable CTEPH who underwent BPA sessions were consecutively enrolled. Hemodynamics were measured by right heart catheterization, selective pulmonary angiography and BPA were successively conducted. Hemodynamic variables, WHO functional class (WHO-FC), 6-min walk distance (6MWD) and serum NT-proBNP were evaluated before and after BPA sessions during hospitalization. Pulmonary function testing (PFT) and cardiopulmonary exercise testing (CPET) were performed within 1–3 days pre and post BPA to evaluate the effect of BPA on cardiopulmonary function.ResultsTwenty-five patients with inoperable CTEPH who underwent a total of forty BPA sessions were consecutively enrolled. A total of 183 segmental or subsegmental vessels (4.6 ± 1.9 vessels per session) in 137 segments (3.4 ± 1.6 segments per session) were dilated. No procedure-related complications occurred. Instant hemodynamics, WHO-FC, 6MWD and NT-proBNP were all significantly improved after a single BPA session. Significant improvement in cardiopulmonary function was also evident as assessed by PFT indexes (forced vital capacity, forced expiratory volume in the first second, maximal voluntary ventilation) and CPET parameters (peak work rate, peak VO2, oxygen uptake efficiency slope). Further analysis among ten CTEPH patients receiving multiple BPA sessions (2–4 sessions) indicated BPA resulted in lasting improvements in hemodynamics and cardiopulmonary function.ConclusionsBPA, a safe and effective approach, can bring instant improvements after a single session and lasting benefits after multiple sessions to hemodynamics and cardiopulmonary function for patients with inoperable CTEPH.

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“…This prevalence estimate is similar to what is described in the general population[1] and was similar to the prevalence of iron deficiency in the JHS cohort at 5.0% (by ferritin level). Similarly, another study in chronic thromboembolic pulmonary hypertension patients found no difference in iron parameters between patients with chronic thromboembolic pulmonary hypertension and controls[25]. In a study examining zinc-protoporphyrin to heme ratio as a marker of iron deficiency or altered iron metabolism, a high zinc-protoporphyrin to heme ratio was noted in idiopathic pulmonary arterial hypertension patients, and this ratio was related to disease severity, but a similarly high ratio was not observed in associated pulmonary arterial hypertension of various causes[26].…”

Section: Discussionmentioning

confidence: 97%

Relationship of Iron Deficiency and Serum Ferritin Levels with Pulmonary Hypertension: The Jackson Heart Study

et al. 2016

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PurposeIron deficiency is prevalent in idiopathic pulmonary arterial hypertension (IPAH), but whether iron deficiency or ferritin levels are associated with pulmonary hypertension (PH) in the general population is unknown.MethodsWe performed a cross-sectional analysis of data on iron deficiency (exposure), and PH (pulmonary artery systolic pressure>40mmHg on echocardiogram) (outcome) on subjects with complete data on exposures and outcomes as well as covariates (n = 2,800) enrolled in the Jackson Heart Study, a longitudinal prospective observational cohort study of heart disease in African-Americans from Jackson, Mississippi. Iron deficiency was defined as a serum ferritin level < 15ng/mL (females); < 30ng/mL (males). We determined crude prevalence ratios (PRs) for PH in iron deficient versus non-iron deficient groups using modified Poisson regression modeling. We also analyzed the prevalence of PH by sex-specific quartiles of ferritin (Females ≤ 47ng/mL; > 47ng/mL– 95ng/mL; > 95ng/mL– 171ng/mL; > 171ng/mL; Males ≤ 110ng/mL; > 110ng/mL– 182ng/mL; > 182ng/mL– 294ng/mL; > 294ng/mL), using the same modeling technique with the lowest quartile as the referent.ResultsMedian pulmonary artery systolic pressure was 27mmHg (interquartile range 23-31mmHg) in the study cohort. 147 subjects (5.2%) had PH and 140 (5.0%) had iron deficiency. However, of the 147 subjects with PH, only 4 were also iron deficient. The crude PH PR was 0.5 (95% CI 0.2–1.4) in iron-deficiency compared to non-deficient. In analysis by quartiles of ferritin, adjusting for age and sex, there was no evidence of association with PH in quartiles 2 (PR 1.1, 95% CI 0.7–1.6), 3 (PR 0.8, 95% CI 0.5–1.3), or 4 (PR 0.8, 95% CI 0.5–1.2) compared with quartile 1 (referent group, PR 1). Further analyses of the relationship between PH and ferritin as a log-transformed continuous variable or by quartiles of serum iron showed similar results.ConclusionsIn the Jackson Heart Study, the prevalence of PH was similar in iron-deficient and non-iron deficient subjects. There was no evidence of association between ferritin (or serum iron) levels and PH.Clinical ImplicationsIron deficiency has been associated with IPAH, a rare disorder. However, in a large community-based sample of African-Americans, there was no evidence that iron deficiency or low iron levels were associated with PH.

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Chronic thromboembolic pulmonary hypertension is not associated with iron overload

Cited by 6 publications

References 33 publications

Pulmonary microvascular remodeling in chronic thrombo-embolic pulmonary hypertension

Pulmonary microvascular remodeling in chronic thrombo-embolic pulmonary hypertension

Improved hemodynamics and cardiopulmonary function in patients with inoperable chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty

Relationship of Iron Deficiency and Serum Ferritin Levels with Pulmonary Hypertension: The Jackson Heart Study

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