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The Journal of Pediatrics Jan 2023To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric...
OBJECTIVE
To characterize distinct comorbidities, outcomes, and treatment patterns in children with Down syndrome and pulmonary hypertension in a large, multicenter pediatric pulmonary hypertension registry.
STUDY DESIGN
We analyzed data from the Pediatric Pulmonary Hypertension Network (PPHNet) Registry, comparing demographic and clinical characteristics of children with Down syndrome and children without Down syndrome. We examined factors associated with pulmonary hypertension resolution and a composite outcome of pulmonary hypertension severity in the cohort with Down syndrome.
RESULTS
Of 1475 pediatric patients with pulmonary hypertension, 158 (11%) had Down syndrome. The median age at diagnosis of pulmonary hypertension in patients with Down syndrome was 0.49 year (IQR, 0.21-1.77 years), similar to that in patients without Down syndrome. There was no difference in rates of cardiac catheterization and prescribed pulmonary hypertension medications in children with Down syndrome and those without Down syndrome. Comorbidities in Down syndrome included congenital heart disease (95%; repaired in 68%), sleep apnea (56%), prematurity (49%), recurrent respiratory exacerbations (35%), gastroesophageal reflux (38%), and aspiration (31%). Pulmonary hypertension resolved in 43% after 3 years, associated with a diagnosis of pulmonary hypertension at age <6 months (54% vs 29%; P = .002) and a pretricuspid shunt (65% vs 38%; P = .02). Five-year transplantation-free survival was 88% (95% CI, 80%-97%). Tracheostomy (hazard ratio [HR], 3.29; 95% CI, 1.61-6.69) and reflux medication use (HR, 2.08; 95% CI, 1.11-3.90) were independently associated with a composite outcome of severe pulmonary hypertension.
CONCLUSIONS
Despite high rates of cardiac and respiratory comorbidities that influence the severity of pulmonary hypertension, children with Down syndrome-associated pulmonary hypertension generally have a survival rate similar to that of children with non-Down syndrome-associated pulmonary hypertension. Resolution of pulmonary hypertension is common but reduced in children with complicated respiratory comorbidities.
Topics: Child; Humans; Infant; Hypertension, Pulmonary; Retrospective Studies; Down Syndrome; Heart Defects, Congenital; Registries; Gastroesophageal Reflux
PubMed: 36027975
DOI: 10.1016/j.jpeds.2022.08.027 -
BMJ Open Respiratory Research Jun 2022Pulmonary hypertension (PH) is a progressive disease of the pulmonary vasculature, which is characterised by premature morbidity and mortality. The aim of this study is...
INTRODUCTION
Pulmonary hypertension (PH) is a progressive disease of the pulmonary vasculature, which is characterised by premature morbidity and mortality. The aim of this study is to define the characteristics of PH in the national PH unit (NPHU) in Ireland between 2010 and 2020.
METHODS
Cases of PH which were referred to the NPHU between 2010 and 2020 were included. PH was defined as a mean pulmonary artery pressure ≥25 mm Hg at right heart catheterisation.
RESULTS
Four hundred and fifteen cases of PH were identified during the study period. Group 1 pulmonary arterial hypertension (PAH) accounted for 39% (n=163) of cases, with a calculated annual incidence of 3.11 per million population (95% CI 1.53 to 4.70). The leading PAH subgroup was connective tissue disease-associated PAH (CTD-PAH), which was responsible for 49% of PAH referrals. This was followed by idiopathic PAH, with an estimated annual incidence of 0.63 cases per million population. The mean age at PAH diagnosis was 56±15 years and 86% (n=111) received double-combination or triple-combination therapy within the first 12 months of diagnosis. The 1-year, 3-year and 5-year transplant-free survival for PAH was 89%, 75% and 65%. This was significantly lower for individuals with CTD-PAH relative to other PAH subgroups (p<0.05).
DISCUSSION
This study describes the incidence and outcomes of PH in Ireland. While the outcomes are comparable to other centres, the incidence of PAH and specific subgroups appears low, suggesting that improved disease awareness and case recognition are required. Furthermore, the survival of individuals with CTD-PAH is poor and requires additional exploration.
Topics: Connective Tissue Diseases; Humans; Hypertension, Pulmonary; Incidence; Ireland
PubMed: 35768152
DOI: 10.1136/bmjresp-2022-001272 -
Methodist DeBakey Cardiovascular Journal 2021Chronic thromboembolic pulmonary hypertension (CTEPH) is a common long-term complication of pulmonary embolism characterized by thromboembolic obstruction of the...
Chronic thromboembolic pulmonary hypertension (CTEPH) is a common long-term complication of pulmonary embolism characterized by thromboembolic obstruction of the pulmonary arteries, vascular arteriopathy, vascular remodeling, and ultimately pulmonary hypertension (PH). Although pulmonary endarterectomy (PEA) surgery is the standard of care, approximately 40% of patients in the international CTEPH registry were deemed inoperable. In addition to lifelong anticoagulation, the cornerstone of PH-specific medical management is riociguat, a soluble guanylate cyclase stimulator. Medical management should be started early in CTEPH patients and may be used as a bridge to PEA surgery or balloon pulmonary angiography. Medical management is indicated for inoperable CTEPH patients and patients who have recurrence of PH after PEA surgery.
Topics: Chronic Disease; Endarterectomy; Humans; Hypertension, Pulmonary; Pulmonary Artery; Pulmonary Embolism
PubMed: 34306521
DOI: 10.14797/ICHN7633 -
International Journal of Molecular... May 2023This Special Issue, "Molecular Research on Pulmonary Hypertension 3 [...].
This Special Issue, "Molecular Research on Pulmonary Hypertension 3 [...].
Topics: Humans; Hypertension, Pulmonary; Translational Research, Biomedical; Research
PubMed: 37239809
DOI: 10.3390/ijms24108462 -
American Journal of Physiology. Lung... May 2018Pulmonary hypertension describes a heterogeneous disease defined by increased pulmonary artery pressures, and progressive increase in pulmonary vascular resistance due... (Review)
Review
Pulmonary hypertension describes a heterogeneous disease defined by increased pulmonary artery pressures, and progressive increase in pulmonary vascular resistance due to pathologic remodeling of the pulmonary vasculature involving pulmonary endothelial cells, pericytes, and smooth muscle cells. This process occurs under various conditions, and although these populations vary, the clinical manifestations are the same: progressive dyspnea, increases in right ventricular (RV) afterload and dysfunction, RV-pulmonary artery uncoupling, and right-sided heart failure with systemic circulatory collapse. The overall estimated 5-yr survival rate is 72% in highly functioning patients, and as low as 28% for those presenting with advanced symptoms. Metabolic theories have been suggested as underlying the pathogenesis of pulmonary hypertension with growing evidence of the role of mitochondrial dysfunction involving the major proteins of the electron transport chain, redox-related enzymes, regulators of the proton gradient and calcium homeostasis, regulators of apoptosis, and mitophagy. There remain more studies needed to characterize mitochondrial dysfunction leading to impaired vascular relaxation, increase proliferation, and failure of regulatory mechanisms. The effects on endothelial cells and resulting interactions with their microenvironment remain uncharted territory for future discovery. Additionally, on the basis of observations that the "plexigenic lesions" of pulmonary hypertension resemble the unregulated proliferation of tumor cells, similarities between cancer pathobiology and pulmonary hypertension have been drawn, suggesting interactions between mitochondria and angiogenesis. Recently, mitochondria targeting has become feasible, which may yield new therapeutic strategies. We present a state-of-the-art review of the role of mitochondria in both the pathobiology of pulmonary hypertension and potential therapeutic targets in pulmonary vascular processes.
Topics: Animals; Humans; Hypertension, Pulmonary; Mitochondria; Mitochondrial Diseases
PubMed: 29345195
DOI: 10.1152/ajplung.00331.2017 -
Respiration; International Review of... 2017Among patients with sleep apnea the reported prevalence of precapillary pulmonary hypertension (PH) has varied largely, depending on patient selection, disease... (Review)
Review
Among patients with sleep apnea the reported prevalence of precapillary pulmonary hypertension (PH) has varied largely, depending on patient selection, disease definition, and associated conditions, in particular chronic pulmonary disease. However, in the absence of comorbidities, PH seems to be rare in patients with sleep apnea. Conversely, sleep-related breathing disorders have been commonly found in patients with PH and they have been associated with an impaired quality of life. Since sleep-related breathing disorders may affect the pulmonary circulation and vice versa, patients with sleep-related breathing disorders should be evaluated for risk factors, symptoms and clinical signs of PH and right ventricular heart failure and patients with PH should be evaluated for sleep apnea. Therapeutic options for patients with sleep apnea and PH may include supplemental oxygen, drugs and positive pressure ventilation. Both nocturnal oxygen administration and acetazolamide have been shown to improve sleep apnea in patients with PH. In addition, oxygen therapy also improved exercise performance. Further studies are needed to corroborate the efficacy of these and other treatments.
Topics: Humans; Hypertension, Pulmonary; Prevalence; Sleep Apnea Syndromes
PubMed: 27884004
DOI: 10.1159/000452957 -
JACC. Cardiovascular Imaging Jun 2016Individual patient response to effective therapies for pulmonary hypertension (PAH) is variable and difficult to quantify. Consequently, management decisions regarding... (Review)
Review
Individual patient response to effective therapies for pulmonary hypertension (PAH) is variable and difficult to quantify. Consequently, management decisions regarding initiation and continuation of therapy are highly dependent on the results of investigations. Registry data show that changes in cardiac index, mean right atrial pressure, and mean pulmonary artery pressure have the greatest influence on survival. It is recognized that pulmonary artery pressure (PASP) responses to PAH-specific drugs are heterogeneous. However, follow-up testing is strongly focused on assessing changes in PASP and functional status (6-min walk). The goals of therapy, which should be highlighted in follow-up imaging, include not only reduction of PASP, decrease in pulmonary vascular resistance, and improvements in right ventricular function, cardiac output, and tricuspid regurgitation. This paper reviews the echocardiographic follow-up of pulmonary hypertension, and especially focuses on right ventricular function-a major determinant of outcome, for which reliable echocardiographic assessment has become more feasible.
Topics: Arterial Pressure; Echocardiography, Doppler; Hemodynamics; Humans; Hypertension, Pulmonary; Image Interpretation, Computer-Assisted; Predictive Value of Tests; Pulmonary Artery; Risk Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Function, Right
PubMed: 27282440
DOI: 10.1016/j.jcmg.2016.02.022 -
Methodist DeBakey Cardiovascular Journal 2021
Topics: Humans; Hypertension, Pulmonary
PubMed: 34326926
DOI: 10.14797/IAME5992 -
Archives of Cardiovascular Diseases 2017Pulmonary hypertension due to left heart disease, also known as group 2 pulmonary hypertension according to the European Society of Cardiology/European Respiratory... (Review)
Review
Pulmonary hypertension due to left heart disease, also known as group 2 pulmonary hypertension according to the European Society of Cardiology/European Respiratory Society classification, is the most common cause of pulmonary hypertension. In patients with left heart disease, the development of pulmonary hypertension favours right heart dysfunction, which has a major impact on disease severity and outcome. Over the past few years, this condition has been considered more frequently. However, epidemiological studies of group 2 pulmonary hypertension are less exhaustive than studies of other causes of pulmonary hypertension. In group 2 patients, pulmonary hypertension may be caused by an isolated increase in left-sided filling pressures or by a combination of this condition with increased pulmonary vascular resistance, with an abnormally high pressure gradient between arteries and pulmonary veins. A better understanding of the conditions underlying pulmonary hypertension is of key importance to establish a comprehensive diagnosis, leading to an adapted treatment to reduce heart failure morbidity and mortality. In this review, epidemiology, mechanisms and diagnostic approaches are reviewed; then, treatment options and future approaches are considered.
Topics: Heart Failure; Humans; Hypertension, Pulmonary; Predictive Value of Tests; Prognosis; Risk Factors; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right; Ventricular Pressure
PubMed: 28411107
DOI: 10.1016/j.acvd.2017.01.010 -
Innere Medizin (Heidelberg, Germany) Jun 2024Heritable pulmonary arterial hypertension (PAH) can be triggered by at least 18 genes. The most frequently altered gene is the bone morphogenetic protein receptor 2... (Review)
Review
Heritable pulmonary arterial hypertension (PAH) can be triggered by at least 18 genes. The most frequently altered gene is the bone morphogenetic protein receptor 2 (BMPR2). Further genes from the same pathway are also well known PAH-causing genes. Genetic testing can aid to confirm differential diagnoses such as a pulmonary veno-occlusive disease. It also enables the testing of healthy family members. In addition to the PAH patient population particularly served by genetic testing, this article touches on the mode of inheritance and provides insights into the first treatments soon on the market that rebalance the BMPR2 signaling pathway.
Topics: Humans; Bone Morphogenetic Protein Receptors, Type II; Genetic Testing; Pulmonary Arterial Hypertension; Hypertension, Pulmonary; Familial Primary Pulmonary Hypertension; Genetic Predisposition to Disease; Signal Transduction
PubMed: 38771375
DOI: 10.1007/s00108-024-01718-y