scholarly journals Association between MDR1 gene polymorphism and clinical course of pediatric pulmonary arterial hypertension

2018 ◽  
Vol 26 (3) ◽  
pp. 305-312
Author(s):  
Iolanda Muntean ◽  
Carmen Şuteu ◽  
Rodica Togănel ◽  
Claudia Bănescu
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Progressive Disease ◽  
Pediatric Patients ◽  
Clinical Course ◽  
Heart Defects ◽  
Mdr1 Gene ◽  
Pulmonary Arterial ◽  
Mdr1 Polymorphism ◽  
Clinical Worsening

Abstract Pulmonary arterial hypertension (PAH) is a progressive disease with a complex pathogenesis. The polymorphism of the gene of multidrug resistance-1 (MDR1) has been associated with many diseases including PAH. Objective. In this study we aimed to investigate the relevance of the MDR1 polymorphism to pediatric PAH clinical course. Methods. A total of 40 pediatric patients with PAH (secondary to congenital heart defects or idiopathic) and 40 control subjects were enrolled. Patients with PAH were divided into 2 groups, according to their evolution: 28 patients who remained clinically stable at 12-months (non-worsening group) and 12 patients who presented clinical worsening at 12-months (worsening group). Genomic DNA was genotyped for MDR1 gene polymorphisms as follows: C1236T, G2677T and C3435T. Results. There were no significant differences between PAH children groups (clinical worsening and non-worsening) nor between PAH children and controls in terms of frequency distribution of the three studied genotypes or alleles. Conclusions. The MDR1 polymorphism could not be correlated with the clinical evolution of pediatric PAH patients in our study.

scholarly journals Where the congenital heart disease meets the pulmonary arterial hypertension, FLNA matters: a case report and literature review

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaoxian Deng ◽  
Shanshan Li ◽  
Qiu Qiu ◽  
Bowen Jin ◽  
Menghuan Yan ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Congenital Heart ◽  
Pediatric Patients ◽  
De Novo ◽  
Wide Spectrum ◽  
Heart Defects ◽  
Pulmonary Arterial

Abstract Background Pediatric patients with genetic disorders have a higher incidence of pulmonary arterial hypertension (PAH) regardless of their heart defects. Filamin A (FLNA) mutation is recently recognized to be associated with pediatric pulmonary disorders, however, the clinical courses of PAH related to the mutation were reported in limited cases. Here, we presented a case and pooled data for better understanding of the correlation between FLNA mutation and pediatric PAH. Case presentation The patient was a 8-month-old female with repeated episodes of pneumonia. Physical examination revealed cleft lip, cleft palate and developmental retardation. Imaging examination showed a small atrial septal defect (ASD), central pulmonary artery enlargement, left upper lobe of lung atelectasis, and pulmonary infiltration. Genetic test showed she carried a de novo pathogenic variant of FLNA gene (c.5417-1G > A, p.-). Oral medications didn’t slow the progression of PAH in the patient, and she died two years later. Conclusions FLNA mutation causes rare but progressive PAH in addition to a wide spectrum of congenital heart disease and other comorbidities in pediatric patients. We highly recommend genetic testing for pediatric patients when suspected with PAH. Given the high mortality in this group, lung transplantation may offer a better outcome.

SITAXSENTAN IMPROVES TIME TO CLINICAL WORSENING IN PATIENTS WITH PULMONARY ARTERIAL HYPERTENSION

CHEST Journal ◽  
2005 ◽  
Vol 128 (4) ◽  
pp. 160S ◽  
Author(s):  
David Badesch ◽  
Nazzareno Galie ◽  
David Langleben ◽  
Robert Naeije ◽  
Gerald Simonneau ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pulmonary Arterial ◽  
Clinical Worsening

scholarly journals Oral treprostinil in transition or as add-on therapy in pediatric pulmonary arterial hypertension

2019 ◽  
Vol 9 (3) ◽  
pp. 204589401985647 ◽  
Author(s):  
D. Dunbar Ivy ◽  
Jeffrey A. Feinstein ◽  
Delphine Yung ◽  
Mary P. Mullen ◽  
Edward C. Kirkpatrick ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Pediatric Patients ◽  
Cardiopulmonary Exercise Testing ◽  
Functional Class ◽  
World Health ◽  
Walk Distance ◽  
Pulmonary Arterial ◽  
Health Organization

Treprostinil, a prostacyclin analogue, is approved for the treatment of pulmonary arterial hypertension (PAH) in adults. Transition from parenteral to oral treprostinil has been successfully accomplished in adults with PAH but not in children. In this multicenter study, pediatric patients treated with parenteral (Cohort 1) or inhaled (Cohort 2) treprostinil were transitioned to oral treprostinil. Prostacyclin-naïve individuals on background oral PAH therapy received oral treprostinil as add-on therapy (Cohort 3). Successful transition was oral treprostinil dose maintenance through week 24. Patients were monitored for adverse events (AEs), 6-min walk distance (6MWD), PAH symptoms, World Health Organization (WHO) Functional Class (FC), cardiac magnetic resonance imaging (cMRI), cardiopulmonary exercise testing (CPET), and quality of life through 24 weeks. A total of 32 patients were enrolled in the study; 23 (72%) were girls (mean age = 12.2 years). All patients were on background oral PAH therapy. Overall, patients (96.9%) maintained transition to oral treprostinil; one patient (Cohort 1) transitioned to oral treprostinil, then back to parenteral after experiencing syncope and WHO FC change from II to III. Cohorts 1, 2, and 3 received a final mean oral treprostinil dose of 5.6, 3.3, and 4.5 mg t.i.d., respectively. All cohorts had variable changes in 6MWD, cMRI, and CPET. Overall, 12 serious AEs were reported. All patients had drug-related AEs including headache (81%), diarrhea (69%), nausea (66%), vomiting (66%), and flushing (56%). Pediatric patients maintained transition to oral treprostinil with preservation of exercise capacity and WHO FC. Prostanoid-related AEs were most common and similar to those reported in adults.

scholarly journals Circulating Plasma Metabolomic Profiles Differentiate Rodent Models of Pulmonary Hypertension and Idiopathic Pulmonary Arterial Hypertension Patients

2019 ◽  
Vol 32 (11) ◽  
pp. 1109-1117
Author(s):  
Jun-Han Zhao ◽  
Yang-Yang He ◽  
Shan-Shan Guo ◽  
Yi Yan ◽  
Zhe Wang ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Progressive Disease ◽  
Idiopathic Pulmonary Arterial Hypertension ◽  
Rodent Models ◽  
Preclinical Models ◽  
Metabolic Dysregulation ◽  
Pulmonary Arterial ◽  
Significant Pathway

Abstract BACKGROUND Pulmonary arterial hypertension (PAH) is a severe progressive disease with systemic metabolic dysregulation. Monocrotaline (MCT)-induced and hypoxia-induced pulmonary hypertension (PH) rodent models are the most widely used preclinical models, however, whether or not these preclinical models recapitulate metabolomic profiles of PAH patients remain unclear. METHODS In this study, a targeted metabolomics panel of 126 small molecule metabolites was conducted. We applied it to the plasma of the 2 preclinical rodent models of PH and 30 idiopathic pulmonary arterial hypertension (IPAH) patients as well as 30 healthy controls to comparatively assess the metabolomic profiles of PAH patients and rodent models. RESULTS Significantly different metabolomics profiling and pathways were shown among the 2 classical rodent models and IPAH patients. Pathway analysis demonstrated that methionine metabolism and urea cycle metabolism were the most significant pathway involved in the pathogenesis of hypoxia-induced PH model and MCT-induced model, respectively, and both of them were also observed in the dysregulated pathways in IPAH patients. CONCLUSIONS These 2 models may develop PAH through different metabolomic pathways and each of the 2 classical PH model resembles IPAH patients in certain aspects.

scholarly journals Assessment of the REPLACE study composite endpoint in riociguat-treated patients in the PATENT study

2020 ◽  
Vol 10 (4) ◽  
pp. 204589402097312
Author(s):  
Gérald Simonneau ◽  
Hossein-Ardeschir Ghofrani ◽  
Paul A. Corris ◽  
Stephan Rosenkranz ◽  
Ekkehard Grünig ◽  
...  
Keyword(s):  
Relative Risk ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Clinical Improvement ◽  
Composite Endpoint ◽  
World Health ◽  
Walking Distance ◽  
Pulmonary Arterial ◽  
Clinical Worsening

The goal of treatment in patients with pulmonary arterial hypertension is to achieve a low risk status, indicating a favorable long-term outcome. The REPLACE study investigated the efficacy of switching to riociguat in patients with pulmonary arterial hypertension and an insufficient response to phosphodiesterase-5 inhibitors. In this post hoc analysis, we applied the REPLACE composite endpoint of clinical improvement to the placebo-controlled PATENT-1 study of riociguat in pulmonary arterial hypertension and its long-term extension, PATENT-2. Clinical improvement was defined as ≥2 of the following in patients who completed the study without clinical worsening: ≥10% or ≥30 m improvement in 6-minute walking distance; World Health Organization functional class I or II; ≥30% decrease in N-terminal prohormone of brain natriuretic peptide. At PATENT-1 Week 12, patients treated with riociguat were more likely to achieve the composite endpoint vs. placebo ( P < 0.0001), with similar results in pretreated ( P = 0.0189) and treatment-naïve ( P < 0.0001) patients. Achievement of the composite endpoint at Week 12 was associated with a 45% reduction in relative risk of death and a 19% reduction in relative risk of clinical worsening in PATENT-2. Overall, these data suggest that use of the REPLACE composite endpoint in patients with pulmonary arterial hypertension is a valid assessment of response to treatment.

Management of Pulmonary Arterial Hypertension in the ICU

2019 ◽  
Vol 32 (3) ◽  
pp. 303-313 ◽  
Author(s):  
Heather Torbic
Keyword(s):  
Critical Illness ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Progressive Disease ◽  
Hemodynamic Instability ◽  
Organ Damage ◽  
Health Care Team ◽  
Acute Decompensation ◽  
Pulmonary Arterial ◽  
Rv Function

Patients with pulmonary arterial hypertension (PAH) who are admitted to the intensive care unit (ICU) pose a challenge to the multidisciplinary health-care team due to the complexity of the pathophysiology of their disease state and the medication considerations that must be made to appropriately manage them. PAH is a progressive disease with the majority of patients ultimately dying as a result of right ventricular (RV) failure. During an acute decompensation, patients must be appropriately managed to optimize volume status, RV function, cardiac output, and systemic perfusion, while treating the underlying cause of the exacerbation. During times of critical illness, the ability to administer medications approved for use in PAH can be impacted by end-organ damage, hemodynamic instability, new drug interactions, or available dosage forms. Balancing the multimodal treatment approach needed to manage an acute exacerbation and the pharmacokinetic and administration concerns impacting baseline PAH therapy as a result of critical illness requires an expert multiprofessional PAH team. The purpose of this review is to evaluate specific management considerations for critically ill patients with PAH in the ICU.

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