-
Comprehensive Physiology Jun 2021Pediatric pulmonary hypertension (PPH) is a multifactorial disease with diverse etiologies and presenting features. Pulmonary hypertension (PH), defined as elevated...
Pediatric pulmonary hypertension (PPH) is a multifactorial disease with diverse etiologies and presenting features. Pulmonary hypertension (PH), defined as elevated pulmonary artery pressure, is the presenting feature for several pulmonary vascular diseases. It is often a hidden component of other lung diseases, such as cystic fibrosis and bronchopulmonary dysplasia. Alterations in lung development and genetic conditions are an important contributor to pediatric pulmonary hypertensive disease, which is a distinct entity from adult PH. Many of the causes of pediatric PH have prenatal onset with altered lung development due to maternal and fetal conditions. Since lung growth is altered in several conditions that lead to PPH, therapy for PPH includes both pulmonary vasodilators and strategies to restore lung growth. These strategies include optimal alveolar recruitment, maintaining physiologic blood gas tension, nutritional support, and addressing contributing factors, such as airway disease and gastroesophageal reflux. The outcome for infants and children with PH is highly variable and largely dependent on the underlying cause. The best outcomes are for neonates with persistent pulmonary hypertension (PPHN) and reversible lung diseases, while some genetic conditions such as alveolar capillary dysplasia are lethal. © 2021 American Physiological Society. Compr Physiol 11:2135-2190, 2021.
Topics: Bronchopulmonary Dysplasia; Child; Female; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Lung; Persistent Fetal Circulation Syndrome; Pregnancy; Vasodilator Agents
PubMed: 34190343
DOI: 10.1002/cphy.c200023 -
Heart Failure Clinics Jul 2018Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct type of pulmonary hypertensive disease, characterized by incomplete or abnormal resolution of acute... (Review)
Review
Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct type of pulmonary hypertensive disease, characterized by incomplete or abnormal resolution of acute pulmonary embolism such that residual emboli become organized and fibrotic. CTEPH can occur in patients without a prior history of venous thromboembolism, and is diagnosed based on precapillary pulmonary hypertension on right heart catheterization with evidence of chronic emboli on ventilation/perfusion scan, chest imaging, or pulmonary angiogram. Pulmonary endarterectomy (PEA) is often curative, and results in improved survival. In patients for whom PEA is not feasible, medical therapy has been effective in improving hemodynamics and functional capacity.
Topics: Cardiac Catheterization; Chronic Disease; Endarterectomy; Hemodynamics; Humans; Hypertension, Pulmonary; Pulmonary Artery; Pulmonary Embolism
PubMed: 29966632
DOI: 10.1016/j.hfc.2018.02.009 -
Orphanet Journal of Rare Diseases Jul 2013Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of... (Review)
Review
Pulmonary arterial hypertension (PAH) is a chronic and progressive disease leading to right heart failure and ultimately death if untreated. The first classification of PH was proposed in 1973. In 2008, the fourth World Symposium on PH held in Dana Point (California, USA) revised previous classifications. Currently, PH is devided into five subgroups. Group 1 includes patients suffering from idiopathic or familial PAH with or without germline mutations. Patients with a diagnosis of PAH should systematically been screened regarding to underlying mutations of BMPR2 gene (bone morphogenetic protein receptor type 2) or more rarely of ACVRL1 (activine receptor-like kinase type 1), ENG (endogline) or Smad8 genes. Pulmonary veno occusive disease and pulmonary capillary hemagiomatosis are individualized and designated as clinical group 1'. Group 2 'Pulmonary hypertension due to left heart diseases' is divided into three sub-groups: systolic dysfonction, diastolic dysfonction and valvular dysfonction. Group 3 'Pulmonary hypertension due to respiratory diseases' includes a heterogenous subgroup of respiratory diseases like PH due to pulmonary fibrosis, COPD, lung emphysema or interstitial lung disease for exemple. Group 4 includes chronic thromboembolic pulmonary hypertension without any distinction of proximal or distal forms. Group 5 regroup PH patients with unclear multifactorial mechanisms. Invasive hemodynamic assessment with right heart catheterization is requested to confirm the definite diagnosis of PH showing a resting mean pulmonary artery pressure (mPAP) of ≥ 25 mmHg and a normal pulmonary capillary wedge pressure (PCWP) of ≤ 15 mmHg. The assessment of PCWP may allow the distinction between pre-capillary and post-capillary PH (PCWP > 15 mmHg). Echocardiography is an important tool in the management of patients with underlying suspicion of PH. The European Society of Cardiology and the European Respiratory Society (ESC-ERS) guidelines specify its role, essentially in the screening proposing criteria for estimating the presence of PH mainly based on tricuspid regurgitation peak velocity and systolic artery pressure (sPAP). The therapy of PAH consists of non-specific drugs including oral anticoagulation and diuretics as well as PAH specific therapy. Diuretics are one of the most important treatment in the setting of PH because right heart failure leads to fluid retention, hepatic congestion, ascites and peripheral edema. Current recommendations propose oral anticoagulation aiming for targeting an International Normalized Ratio (INR) between 1.5-2.5. Target INR for patients displaying chronic thromboembolic PH is between 2-3. Better understanding in pathophysiological mechanisms of PH over the past quarter of a century has led to the development of medical therapeutics, even though no cure for PAH exists. Several specific therapeutic agents were developed for the medical management of PAH including prostanoids (epoprostenol, trepoprostenil, iloprost), endothelin receptor antagonists (bosentan, ambrisentan) and phosphodiesterase type 5 inhibitors (sildenafil, tadalafil). This review discusses the current state of art regarding to epidemiologic aspects of PH, diagnostic approaches and the current classification of PH. In addition, currently available specific PAH therapy is discussed as well as future treatments.
Topics: Heart Diseases; Humans; Hypertension, Pulmonary
PubMed: 23829793
DOI: 10.1186/1750-1172-8-97 -
Future Cardiology Jul 2018Pulmonary hypertension is defined as a mean pulmonary arterial pressure ≥25 mmHg. We focus on its relevance in congenital heart disease, reviewing pathophysiology,... (Review)
Review
Pulmonary hypertension is defined as a mean pulmonary arterial pressure ≥25 mmHg. We focus on its relevance in congenital heart disease, reviewing pathophysiology, diagnosis and management. Pulmonary hypertension is a relatively common complication of congenital heart disease, with adult prevalence between 5 and 10%. A multifactorial cause is recognized, relating to the size and nature of cardiac defect as well as environmental and genetic factors. More complex disease is increasingly recognized rather than pure Eisenmenger complex. Remodeling of the pulmonary vascular bed causes increased pulmonary vascular resistance diagnosed by a collection of investigations including echocardiography, exercise testing, cardiac catheterization, MRI and CT scanning. Management employs disease-modifying medications which are now used with increasing benefit.
Topics: Heart Defects, Congenital; Humans; Hypertension, Pulmonary
PubMed: 29792339
DOI: 10.2217/fca-2017-0065 -
Circulation. Heart Failure Jul 2023Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion of the total pulmonary hypertension population who bring... (Review)
Review
Patients with pulmonary hypertension associated with congenital heart disease make up an increasing proportion of the total pulmonary hypertension population who bring with them added complexity because of underlying anatomical and hemodynamic abnormalities. Currently, no consensus recommendations are available on how to best manage this group of patients for either the primary cardiologist or pulmonary hypertension subspecialist, including timing of referral. The purposes of this document are (1) to describe the various pulmonary hypertension groups and subgroups associated with congenital heart disease, (2) to describe imaging modalities used in patient evaluation, (3) to elucidate medical and surgical management considerations, (4) to highlight disparities within this population, and (5) to identify gaps and future research needs of patients with pulmonary hypertension associated with congenital heart disease.
Topics: United States; Humans; Hypertension, Pulmonary; American Heart Association; Heart Failure; Heart Defects, Congenital; Hemodynamics
PubMed: 37357777
DOI: 10.1161/HHF.0000000000000080 -
Pharmacology & Therapeutics Feb 2014Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of small pulmonary arteries that leads to elevated pulmonary arterial... (Review)
Review
Pulmonary arterial hypertension (PAH) is a rare disorder characterized by progressive obliteration of small pulmonary arteries that leads to elevated pulmonary arterial pressure and right heart failure. During the last decades, an improved understanding of the pathophysiology of the disease has resulted in the development of effective therapies targeting endothelial dysfunction (epoprostenol and derivatives, endothelin receptor antagonists and phosphodiesterase type 5 inhibitors). These drugs allow clinical, functional and hemodynamic improvement. Even though, no cure exists for PAH and prognosis remains poor. Recently, several additional pathways have been suggested to be involved in the pathogenesis of PAH, and may represent innovative therapies. In this summary, we review conventional therapy, pharmacological agents currently available for the treatment of PAH and the benefit/risk ratio of potential future therapies.
Topics: Animals; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary
PubMed: 24134901
DOI: 10.1016/j.pharmthera.2013.10.002 -
The European Respiratory Journal Jan 2019The function of the right ventricle determines the fate of patients with pulmonary hypertension. Since right heart failure is the consequence of increased afterload, a... (Review)
Review
The function of the right ventricle determines the fate of patients with pulmonary hypertension. Since right heart failure is the consequence of increased afterload, a full physiological description of the cardiopulmonary unit consisting of both the right ventricle and pulmonary vascular system is required to interpret clinical data correctly. Here, we provide such a description of the unit and its components, including the functional interactions between the right ventricle and its load. This physiological description is used to provide a framework for the interpretation of right heart catheterisation data as well as imaging data of the right ventricle obtained by echocardiography or magnetic resonance imaging. Finally, an update is provided on the latest insights in the pathobiology of right ventricular failure, including key pathways of molecular adaptation of the pressure overloaded right ventricle. Based on these outcomes, future directions for research are proposed.
Topics: Adaptation, Physiological; Animals; Cardiac Catheterization; Echocardiography; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary; Pulmonary Circulation; Ventricular Dysfunction, Right; Ventricular Function, Right
PubMed: 30545976
DOI: 10.1183/13993003.01900-2018 -
European Respiratory Review : An... Sep 2021Pulmonary hypertension (PH) commonly affects patients with systemic sclerosis (SSc) and is associated with significant morbidity and increased mortality. PH is a... (Review)
Review
Pulmonary hypertension (PH) commonly affects patients with systemic sclerosis (SSc) and is associated with significant morbidity and increased mortality. PH is a heterogenous condition and several different forms can be associated with SSc, including pulmonary arterial hypertension (PAH) resulting from a pulmonary arterial vasculopathy, PH due to left heart disease and PH due to interstitial lung disease. The incidence of pulmonary veno-occlusive disease is also increased. Accurate and early diagnosis to allow optimal treatment is, therefore, essential. Recent changes to diagnostic haemodynamic criteria at the 6th World Symposium on Pulmonary Hypertension have resulted in therapeutic uncertainty regarding patients with borderline pulmonary haemodynamics. Furthermore, the optimal pulmonary vascular resistance threshold for diagnosing PAH and the role of exercise in identifying early disease require further elucidation. In this article we review the epidemiology, diagnosis, outcomes and treatment of the spectrum of pulmonary vascular phenotypes associated with SSc.
Topics: Humans; Hypertension, Pulmonary; Lung Diseases, Interstitial; Phenotype; Pulmonary Arterial Hypertension; Scleroderma, Systemic
PubMed: 34407977
DOI: 10.1183/16000617.0053-2021 -
Nature Reviews. Cardiology Jun 2011Our understanding of, and approach to, pulmonary arterial hypertension has undergone a paradigm shift in the past decade. Once a condition thought to be dominated by... (Review)
Review
Our understanding of, and approach to, pulmonary arterial hypertension has undergone a paradigm shift in the past decade. Once a condition thought to be dominated by increased vasoconstrictor tone and thrombosis, pulmonary arterial hypertension is now seen as a vasculopathy in which structural changes driven by excessive vascular cell growth and inflammation, with recruitment and infiltration of circulating cells, play a major role. Perturbations of a number of molecular mechanisms have been described, including pathways involving growth factors, cytokines, metabolic signaling, elastases, and proteases, that may underlie the pathogenesis of the disease. Elucidating their contribution to the pathophysiology of pulmonary arterial hypertension could offer new drug targets. The role of progenitor cells in vascular repair is also under active investigation. The right ventricular response to increased pressure load is recognized as critical to survival and the molecular mechanisms involved are attracting increasing interest. The challenge now is to integrate this new knowledge and explore how it can be used to categorize patients by molecular phenotype and tailor treatment more effectively.
Topics: Animals; Blood Coagulation; Cell Proliferation; Endothelial Cells; Familial Primary Pulmonary Hypertension; Hemodynamics; Humans; Hypertension, Pulmonary; Inflammation Mediators; Neovascularization, Physiologic; Signal Transduction
PubMed: 21691314
DOI: 10.1038/nrcardio.2011.87 -
Clinical Medicine (London, England) Sep 2023Pulmonary hypertension (PH) is common, with an estimated prevalence of approximately 1% that increases with age. Prompt and accurate diagnosis is key to institute timely... (Review)
Review
Pulmonary hypertension (PH) is common, with an estimated prevalence of approximately 1% that increases with age. Prompt and accurate diagnosis is key to institute timely and appropriate therapy to improve symptoms and prognosis. The international guidelines for the diagnosis and management of PH have recently been updated, with a lowering of the haemodynamic threshold for diagnosis to a mean pulmonary artery pressure >20 mmHg. New diagnostic algorithms and revised indications for screening in at-risk groups have been developed to facilitate early referral to specialist PH centres. This includes fast-track referral pathways for patients who are either clinically high-risk or are at-risk for pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH). This review summarises key changes in the PH guidelines for general physicians who are, most often, the first healthcare professionals to encounter these patients and consequently have a key role as referrers into specialist PH services.
Topics: Humans; Hypertension, Pulmonary; Prognosis; Physicians; Chronic Disease
PubMed: 37775164
DOI: 10.7861/clinmed.2023-23.5.Cardio4