scholarly journals Iron Deficiency in Pulmonary Arterial Hypertension: A Deep Dive into the Mechanisms

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 477
Author(s):  
Marceau Quatredeniers ◽  
Pedro Mendes-Ferreira ◽  
Diana Santos-Ribeiro ◽  
Morad K. Nakhleh ◽  
Maria-Rosa Ghigna ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Iron Deficiency ◽  
Arterial Hypertension ◽  
Iron Homeostasis ◽  
Pulmonary Arteries ◽  
Right Heart Failure ◽  
Deep Dive ◽  
Iron Deficient ◽  
Pulmonary Arterial ◽  
Progressive Occlusion

Pulmonary arterial hypertension (PAH) is a severe cardiovascular disease that is caused by the progressive occlusion of the distal pulmonary arteries, eventually leading to right heart failure and death. Almost 40% of patients with PAH are iron deficient. Although widely studied, the mechanisms linking between PAH and iron deficiency remain unclear. Here we review the mechanisms regulating iron homeostasis and the preclinical and clinical data available on iron deficiency in PAH. Then we discuss the potential implications of iron deficiency on the development and management of PAH.

Development of prognostic tools in pulmonary arterial hypertension: Lessons from modern day registries

2012 ◽  
Vol 108 (12) ◽  
pp. 1049-1060 ◽  
Author(s):  
Mardi Gomberg-Maitland ◽  
Adaani Frost ◽  
Robert Frantz ◽  
Marc Humbert ◽  
Michael McGoon ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Predictive Factors ◽  
Prognostic Model ◽  
Survival Rates ◽  
Pulmonary Arteries ◽  
Right Heart Failure ◽  
National Registry ◽  
The Body ◽  
Pulmonary Arterial

SummaryPulmonary arterial hypertension (PAH) is characterised by increased pressure in the pulmonary arteries leading to right-sided ventricular failure, and death. Identification of factors that affect patient survival is important to improve patient management and outcomes. The first registry to evaluate survival and develop a prognostic model was the National Institutes of Health (NIH) registry in 1981. Importantly this prognostic model is based on data collected prior to availability of PAH-targeted therapies and does not reflect survival rates for treated patients. Since the 1980s, however, four modern registries of PAH now exist which compensate for the NIH equations shortcomings and include the French National registry, Pulmonary Hypertension Connection registry, the Mayo registry, and the Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL). The similarities and difference in these registries are highlighted in this review and although similar in many respects, the four registries vary in patient population, including the numbers of newly and previously diagnosed patients, as well as the era of observation, period of survival, and timing of assessment of potential predictive factors. Despite this, the predictive factors identified in each registry and described in detail within the body of this manuscript share surprising homology in that disease aetiology, patient gender and factors reflective of right heart failure are integral in depicting survival. Future modifications of modern prognostic equations should be an ongoing goal of the PAH community in order to provide increased accuracy with identification of novel risk factors and prediction of disease course.

scholarly journals Steps forward in the treatment of pulmonary arterial hypertension: latest developments and clinical opportunities

2017 ◽  
Vol 8 (2-3) ◽  
pp. 47-64 ◽  
Author(s):  
Jessica B. Badlam ◽  
Todd M. Bull
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Soluble Guanylate Cyclase ◽  
Pulmonary Arteries ◽  
Right Heart Failure ◽  
Response To Treatment ◽  
Pulmonary Vasculature ◽  
Pulmonary Arterial ◽  
Efficacy Parameters

Pulmonary arterial hypertension (PAH) is a chronic disease that results in narrowing of the small pre-capillary pulmonary arteries leading to elevation of pulmonary artery pressure and pulmonary vascular resistance, subsequent right ventricular failure, and if unchecked, death. Advances in the treatment of PAH over the last two decades have markedly improved survival. These improvements reflect a combination of changes in treatments, improved patient care strategies, and varying disease phenotypes in the PAH population. Currently approved therapies for PAH are directed at the recognized abnormalities within the pulmonary vasculature and include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclin pathway agents. Most of these drugs have been approved on the basis of short-term trials that mainly demonstrated improvements in exercise capacity. More recently, long-term, event-driven trials of novel drugs have been performed, demonstrating new efficacy parameters. There have also been exciting advances in the understanding of right heart failure pathophysiology in PAH that have the potential to inspire the development of right ventricular targeted therapy and continued discoveries in the heterogeneity of disease and response to treatment has great potential for developing more ‘personalized’ therapeutic options. In this article, we review the current available data regarding the management of PAH, with an emphasis on the pharmacologic therapies and discussion of novel therapeutic directions for the treatment of this fatal disease.

scholarly journals EXPRESS: Iron Deficiency in Pulmonary Arterial Hypertension: Perspectives

2021 ◽  
pp. 204589402110213
Author(s):  
Marceau Quatredeniers ◽  
David Montani ◽  
Alain Cohen-Solal ◽  
Frédéric Perros
Keyword(s):  
Heart Failure ◽  
Pulmonary Arterial Hypertension ◽  
Iron Deficiency ◽  
Arterial Hypertension ◽  
Iron Supplementation ◽  
Right Heart Failure ◽  
First Line ◽  
Right Heart ◽  
Left Heart Failure ◽  
Pulmonary Arterial

In left heart failure, iron supplementation (IS) is a first line treatment option, regardless of anemia. Pulmonary arterial hypertension (PAH), a rare disease leading to right heart failure, is also associated with iron deficiency. While it is a very debated topic, recent evidence demonstrate that restoration of iron stores results in improved right ventricular function and exercise tolerance. Hence, IS may also be considered as an option in the treatment of PAH.

Abstract 17034: The AKT/AMPK/FOXO3 Axis in Pulmonary Arterial Hypertension

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yann Grobs ◽  
Charlotte romanet ◽  
Valerie Nadeau ◽  
Junichi Omura ◽  
Mark Orcholski ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Vascular Remodeling ◽  
Pulmonary Arteries ◽  
Right Heart Failure ◽  
Metabolic Reprogramming ◽  
Nuclear Exclusion ◽  
Pulmonary Arterial

Like cancer, pulmonary arterial hypertension (PAH) is characterized by exaggerated proliferation and resistance to apoptosis related to metabolic alterations (Warburg effect) of pulmonary smooth muscle cells (PASMCs). These anomalies result in a progressive narrowing of the pulmonary arteries, increasing pulmonary resistance and leading to right heart failure and premature death. In cancer cells, unphosphorylated and nuclear FOXO3 has been extensively studied as a crucial protein that functions as a tumor suppressor by regulating expression of genes involved in apoptosis and cell cycle arrest. These functions combined with other FOXO3 attributes, including its key role in communicating mitochondrial-nuclear signals, make the FOXO3 a suitable candidate for controlling the cancer-like phenotype of PAH-PASMCs. Interestingly, AKT and AMPK known to be implicated in PAH exert antagonistic effects on FOXO3; AKT promoting its nuclear exclusion while AMPK favors its nuclear and mitochondrial accumulation. The thus made the hypothesis that FOXO3’s nuclear exclusion (secondary to AKT/AMPK imbalance) promotes metabolic reprogramming towards glycolysis leading to enhanced proliferation/resistance to apoptosis of PAH-PASMCs and vascular remodeling. Using Western blot and immunofluorescence in isolated PASMCs from both PAH and control patients (n=10), we found that nuclear and mitochondrial exclusion of FOXO3 due to its phosphorylation is a feature of PAH-PASMCs. In vitro, we demonstrated that nuclear localization of FOXO3 using an adenovirus expressing a constitutively active, non-phosphorylable form of FOXO3 or trifluoperazine (TFP) resulted in reduced PAH-PASMC proliferation (Ki67 labeling, p<0,0005) and resistance to apoptosis (Annexin V assay, p<0,05). These effects were accompanied by increased expression of P27 and SOD2 and diminished expression of Survivin (p<0,05). In vivo, we showed that FOXO3 activation using TPF improved established PAH in the monocrotaline rats (reduced RVSP and increased Sv and CO, by right catheterization, p<0,01, n=29) without any sign of toxicity. We showed that FOXO3 is implicated in pulmonary vascular remodeling. Pharmacological activation of FOXO3 may represent a novel avenue to improve PAH.

Iron deficiency in pulmonary arterial hypertension: a matter of definition!

Pneumologie ◽  
2016 ◽  
Vol 70 (05) ◽  
Author(s):  
E Rieger ◽  
T Sonnweber ◽  
K Cima ◽  
G Weiss ◽  
J Löffler-Ragg
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Iron Deficiency ◽  
Arterial Hypertension ◽  
Pulmonary Arterial

scholarly journals Study of the effect of Occlutech Atrial Flow Regulator on symptoms, hemodynamics, and echocardiographic parameters in advanced pulmonary arterial hypertension

2021 ◽  
Vol 11 (1) ◽  
pp. 204589402198996
Author(s):  
Kothandam Sivakumar ◽  
Gopalavilasam R. Rohitraj ◽  
Monica Rajendran ◽  
Nithya Thivianathan
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
High Risk ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Right Atrial ◽  
Echocardiographic Parameters ◽  
Procedural Complications ◽  
Pulmonary Arterial ◽  
Flow Regulator ◽  
Risk Predictors

Optimal sized balloon atrial septostomy improves hemodynamics in advanced pulmonary arterial hypertension. Occlutech Atrial Flow Regulator is designed to provide an atrial septal fenestration diameter titrated according to the age and right atrial pressures. This observational study analyzed symptoms, exercise distance, oxygen saturations, hemodynamics and echocardiographic parameters after Atrial Flow Regulator implantation in patients with syncope or right-heart failure. Patients with high-risk predictors of mortality during septostomy were scrutinized. Thirty-nine patients (9 children) with syncope (34/39) or right-heart failure (27/39) underwent Atrial Flow Regulator implantation without procedural complications. Six-minute walk distance increased from 310 ± 158.2 to 376.4 ± 182.6 m, none developed syncope. Oxygen saturations reduced from 96.4 ± 6.4% to 92 ± 4.9% at rest and further to 80.3 ± 5.9% on exercise. Right atrial pressures reduced from 9.4 ± 5 (2–27) mmHg to 6.9 ± 2.6 (1–12) mmHg, while cardiac index increased from 2.4 ± 0.8 (0.98–4.3) to 3 ± 1 (1.1–5.3) L/min/m2 and systemic oxygen transport increased from 546.1 ± 157.9 (256.2–910.5) to 637.2 ± 191.1 (301.3–1020.2) ml/min. Echocardiographic improvement included significant reduction of pericardial effusion and inferior caval congestion at a median follow-up of 37 months. Overall survival improved except two early and one late deaths in high-risk patients. Five of seven patients with advanced disease and key hemodynamic predictors of mortality survived. Acute hemodynamic benefits in pulmonary arterial hypertension after Atrial Flow Regulator were improved cardiac output, systemic oxygen transport, and reduced right atrial pressures. Improvement of symptoms especially syncope, exercise duration, and right ventricular systolic function as well as device patency were sustained on mid-term follow-up. Implantation was safe in all including young children without procedural complications. Mortality was noted only in patients who had high-risk predictors and patients at advanced stage of the disease.

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