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BMJ (Clinical Research Ed.) Mar 2018Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type... (Review)
Review
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells. Progress has been made in identifying the causes of PAH and approving new drug therapies. A cancer-like increase in cell proliferation and resistance to apoptosis reflects acquired abnormalities of mitochondrial metabolism and dynamics. Mutations in the type II bone morphogenetic protein receptor ( gene dramatically increase the risk of developing heritable PAH. Epigenetic dysregulation of DNA methylation, histone acetylation, and microRNAs also contributes to disease pathogenesis. Aberrant bone morphogenetic protein signaling and epigenetic dysregulation in PAH promote cell proliferation in part through induction of a Warburg mitochondrial-metabolic state of uncoupled glycolysis. Complex changes in cytokines (interleukins and tumor necrosis factor), cellular immunity (T lymphocytes, natural killer cells, macrophages), and autoantibodies suggest that PAH is, in part, an autoimmune, inflammatory disease. Obstructive pulmonary vascular remodeling in PAH increases right ventricular afterload causing right ventricular hypertrophy. In some patients, maladaptive changes in the right ventricle, including ischemia and fibrosis, reduce right ventricular function and cause right ventricular failure. Patients with PAH have dyspnea, reduced exercise capacity, exertional syncope, and premature death from right ventricular failure. PAH targeted therapies (prostaglandins, phosphodiesterase-5 inhibitors, endothelin receptor antagonists, and soluble guanylate cyclase stimulators), used alone or in combination, improve functional capacity and hemodynamics and reduce hospital admissions. However, these vasodilators do not target key features of PAH pathogenesis and have not been shown to reduce mortality, which remains about 50% at five years. This review summarizes the epidemiology, pathogenesis, diagnosis, and treatment of PAH.
Topics: Humans; Hypertension, Pulmonary; Pulmonary Artery; Ventricular Function, Right
PubMed: 29540357
DOI: 10.1136/bmj.j5492 -
The European Respiratory Journal Jan 2019Since the 1st World Symposium on Pulmonary Hypertension (WSPH) in 1973, pulmonary hypertension (PH) has been arbitrarily defined as mean pulmonary arterial pressure... (Review)
Review
Since the 1st World Symposium on Pulmonary Hypertension (WSPH) in 1973, pulmonary hypertension (PH) has been arbitrarily defined as mean pulmonary arterial pressure (mPAP) ≥25 mmHg at rest, measured by right heart catheterisation. Recent data from normal subjects has shown that normal mPAP was 14.0±3.3 mmHg. Two standard deviations above this mean value would suggest mPAP >20 mmHg as above the upper limit of normal (above the 97.5th percentile). This definition is no longer arbitrary, but based on a scientific approach. However, this abnormal elevation of mPAP is not sufficient to define pulmonary vascular disease as it can be due to an increase in cardiac output or pulmonary arterial wedge pressure. Thus, this 6th WSPH Task Force proposes to include pulmonary vascular resistance ≥3 Wood Units in the definition of all forms of pre-capillary PH associated with mPAP >20 mmHg. Prospective trials are required to determine whether this PH population might benefit from specific management.Regarding clinical classification, the main Task Force changes were the inclusion in group 1 of a subgroup "pulmonary arterial hypertension (PAH) long-term responders to calcium channel blockers", due to the specific prognostic and management of these patients, and a subgroup "PAH with overt features of venous/capillaries (pulmonary veno-occlusive disease/pulmonary capillary haemangiomatosis) involvement", due to evidence suggesting a continuum between arterial, capillary and vein involvement in PAH.
Topics: Consensus Development Conferences as Topic; Heart Diseases; Hemodynamics; Humans; Hypertension, Pulmonary
PubMed: 30545968
DOI: 10.1183/13993003.01913-2018 -
Journal of Veterinary Internal Medicine Mar 2020Pulmonary hypertension (PH), defined by increased pressure within the pulmonary vasculature, is a hemodynamic and pathophysiologic state present in a wide variety of...
Pulmonary hypertension (PH), defined by increased pressure within the pulmonary vasculature, is a hemodynamic and pathophysiologic state present in a wide variety of cardiovascular, respiratory, and systemic diseases. The purpose of this consensus statement is to provide a multidisciplinary approach to guidelines for the diagnosis, classification, treatment, and monitoring of PH in dogs. Comprehensive evaluation including consideration of signalment, clinical signs, echocardiographic parameters, and results of other diagnostic tests supports the diagnosis of PH and allows identification of associated underlying conditions. Dogs with PH can be classified into the following 6 groups: group 1, pulmonary arterial hypertension; group 2, left heart disease; group 3, respiratory disease/hypoxia; group 4, pulmonary emboli/pulmonary thrombi/pulmonary thromboemboli; group 5, parasitic disease (Dirofilaria and Angiostrongylus); and group 6, disorders that are multifactorial or with unclear mechanisms. The approach to treatment of PH focuses on strategies to decrease the risk of progression, complications, or both, recommendations to target underlying diseases or factors contributing to PH, and PH-specific treatments. Dogs with PH should be monitored for improvement, static condition, or progression, and any identified underlying disorder should be addressed and monitored simultaneously.
Topics: Animals; Dog Diseases; Dogs; Hypertension, Pulmonary; Practice Guidelines as Topic; Societies, Scientific; Veterinary Medicine
PubMed: 32065428
DOI: 10.1111/jvim.15725 -
Clinics in Perinatology Aug 2021Persistent pulmonary hypertension of the newborn (PPHN) is a disorder of circulatory transition resulting in high pulmonary vascular resistance with extrapulmonary... (Review)
Review
Persistent pulmonary hypertension of the newborn (PPHN) is a disorder of circulatory transition resulting in high pulmonary vascular resistance with extrapulmonary right-to-left shunts causing hypoxemia. There has been substantial gain in understanding of pathophysiology of PPHN over the past 2 decades, and biochemical pathways responsible for abnormal vasoconstriction of pulmonary vasculature are now better understood. Easy availability of bedside echocardiography helps in establishing early definitive diagnosis, understanding the pathophysiology and hemodynamic abnormalities, monitoring the disease process, and response to therapeutic intervention. There also has been significant advancement in specific management of PPHN targeted at deranged biochemical pathways and hemodynamic instability.
Topics: Administration, Inhalation; Echocardiography; Hemodynamics; Humans; Hypertension, Pulmonary; Infant, Newborn; Nitric Oxide; Persistent Fetal Circulation Syndrome; Vascular Resistance
PubMed: 34353582
DOI: 10.1016/j.clp.2021.05.009 -
Mayo Clinic Proceedings Sep 2020Pulmonary hypertension (PH) is classified into 5 clinical subgroups: pulmonary arterial hypertension (PAH), PH due to left-sided heart disease, PH due to chronic lung... (Review)
Review
Pulmonary hypertension (PH) is classified into 5 clinical subgroups: pulmonary arterial hypertension (PAH), PH due to left-sided heart disease, PH due to chronic lung disease, chronic thromboembolic PH (CTEPH), and PH with an unclear and/or multifactorial mechanisms. A range of underlying conditions can lead to these disorders. Overall, PH affects approximately 1% of the global population, and over half of patients with heart failure may be affected. Cardiologists are therefore likely to encounter PH in their practice. Routine tests in patients with symptoms and physical findings suggestive of PH include electrocardiography, chest radiography, and pulmonary function tests. Transthoracic echocardiography is used to estimate the probability of PH. All patients with suspected or confirmed PH, without confirmed left-sided heart or lung diseases, should have a ventilation-perfusion scan to exclude CTEPH. Right-sided heart catheterization is essential for accurate diagnosis and classification. All patients with PAH or CTEPH must be referred to a specialist center. Surgical pulmonary endarterectomy is the treatment of choice for eligible patients with CTEPH. Targeted treatments (phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin analogues, and prostacyclin receptor agonists) are licensed for patients with PAH. The soluble guanylate cyclase stimulator riociguat is the only licensed targeted therapy for patients with inoperable or persistent/recurrent CTEPH. Management of PH resulting from left-sided heart disease primarily involves treatment of the underlying condition.
Topics: Cardiac Catheterization; Electrocardiography; Female; Humans; Hypertension, Pulmonary; Male; Risk Factors
PubMed: 32861339
DOI: 10.1016/j.mayocp.2020.04.039 -
European Respiratory Review : An... Mar 2016In 2015, more than 800 papers were published in the field of pulmonary hypertension. A Clinical Year in Review article cannot possibly incorporate all this work and... (Review)
Review
In 2015, more than 800 papers were published in the field of pulmonary hypertension. A Clinical Year in Review article cannot possibly incorporate all this work and needs to be selective. The recently published European guidelines for the diagnosis and treatment of pulmonary hypertension contain an inclusive summary of all published clinical studies conducted until very recently. Here, we provide an overview of papers published after the finalisation of the guideline. In addition, we summarise recent advances in pulmonary vasculature science. The selection we made from the enormous amount of published work undoubtedly reflects our personal views and may not include all papers with a significant impact in the near or more distant future. The focus of this paper is on the diagnosis of pulmonary arterial hypertension, understanding the success of combination therapy on the right ventricle and scientific breakthroughs.
Topics: Animals; Humans; Hypertension, Pulmonary; Risk Factors; Treatment Outcome
PubMed: 26929415
DOI: 10.1183/16000617.0096-2015 -
Deutsches Arzteblatt International Feb 2017About 1% of adults suffer from pulmonary hypertension (PH). The various types of PH differ widely with respect to their incidence, clinical significance, and treatment. (Review)
Review
BACKGROUND
About 1% of adults suffer from pulmonary hypertension (PH). The various types of PH differ widely with respect to their incidence, clinical significance, and treatment.
METHODS
Selective review of the literature in association with a consensus conference.
RESULTS
Pulmonary hypertension is divided into five major categories. Those that are of particular clinical relevance are pulmonary arterial hypertension, chronic thromboembolic pulmonary hypertension, and pulmonary hypertension due to left heart and lung diseases. Ten drugs from five different substance classes are now available for the treatment of PH and are often given in combination. The treatment strategy is determined by risk stratification based on the severity of disease, along with the clinical phenotype and possible accompanying illnesses. The preferred treatment for chronic thromboembolic pulmonary hypertension is surgical pulmonary endarterectomy; inoperable patients are treated with drugs and endovascular interventions. PH due to left heart and lung diseases generally calls for specific treatment of pulmonary hypertension only if there is severe right-heart strain.
CONCLUSION
The diagnosis and treatment of severe forms of PH, in particular, pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension, are complex and are best carried out in close cooperation between the local physician and specialized centers.
Topics: Adult; Chronic Disease; Endarterectomy; Humans; Hypertension, Pulmonary; Pulmonary Embolism
PubMed: 28241922
DOI: 10.3238/arztebl.2017.0073 -
The American Journal of Managed Care Mar 2021Group 1 pulmonary hypertension (or pulmonary arterial hypertension) is a rare, highly complex, and progressive disorder that is incurable and ultimately can lead to... (Review)
Review
Group 1 pulmonary hypertension (or pulmonary arterial hypertension) is a rare, highly complex, and progressive disorder that is incurable and ultimately can lead to premature death. PAH causes significant physical, social, work, and emotional burdens among affected patients and their caregivers. Early diagnosis and initiation of treatment is required for best outcomes; however, the clinical presentation of PAH is nonspecific and frequently overlaps with several other conditions, often leading to a delay in diagnosis or misdiagnosis. In the past decades, increased understanding of the pathobiology of PAH has led to changes in its definition. Additionally, contemporary PAH registries have shown greater survival rates among patients with PAH and have allowed for the development of risk calculator tools that are now used to drive therapeutic goals. To date, multiple PAH-specific therapies have been developed, and all currently target one of 3 pathways that contribute to the endothelial dysfunction pathogenesis of PAH (prostacyclin, endothelin, and nitric oxide pathways). Because PAH is classified into 7 subgroups, it is essential that individuals are grouped appropriately for the efficacy of treatment and avoidance of harm. As health-related quality of life for PAH is multifactorial, it is important that patients are involved in the clinical decision-making process and have access to multidisciplinary care. The purpose of this review is to update healthcare professionals on the management of PAH with the most current information on epidemiology, pathophysiology, clinical presentation, and diagnostic considerations.
Topics: Epoprostenol; Humans; Hypertension, Pulmonary; Prostaglandins I; Pulmonary Arterial Hypertension; Quality of Life
PubMed: 33710842
DOI: 10.37765/ajmc.2021.88609 -
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 -
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