Pulmonary hypertension


Pulmonary hypertension PH or PHTN is an increase of blood pressure in the arteries of the lungs6 Symptoms include shortness of breath, syncope, tiredness, chest pain, swelling of the legs, and a fast heartbeat62 The condition may make it difficult to exercise6 Onset is typically gradual7

The cause is often unknown1 Risk factors include a family history, prior blood clots in the lungs, HIV/AIDS, sickle cell disease, cocaine use, COPD, sleep apnea, living at high altitudes, and problems with the mitral valve43 The underlying mechanism typically involves inflammation of the arteries in the lungs4 Diagnosis involves first ruling out other potential causes1

There is no cure6 Treatment depends on the type of disease5 A number of supportive measures such as oxygen therapy, diuretics, and medications to inhibit clotting may be used1 Medications specifically for the condition include epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, macitentan, and sildenafil1 A lung transplant maybe an option in certain cases5

While the exact frequency of the condition is unknown, it is estimated that about 1,000 new cases occur a year in the United States32 Females are more often affected than males2 Onset is typically between 20 and 60 years of age3 It was first identified by Ernst von Romberg in 189181

Contents

  • 1 Signs and symptoms
  • 2 Causes
    • 21 Classification
  • 3 Pathogenesis
    • 31 Molecular pathology
      • 311 Nitric oxide-soluble guanylate cyclase pathway
      • 312 Endothelin
      • 313 Prostacyclin
      • 314 Other pathways
  • 4 Diagnosis
    • 41 Physical examination
    • 42 Echocardiography
  • 5 Treatment
    • 51 Vasoactive substances
      • 511 Prostaglandins
      • 512 Endothelin receptor antagonists
      • 513 Phosphodiesterase type 5 inhibitors
      • 514 Activators of soluble guanylate cyclase
    • 52 Surgical
    • 53 Monitoring
  • 6 Prognosis
  • 7 Epidemiology
  • 8 Notable cases
  • 9 See also
  • 10 References
  • 11 Further reading
  • 12 External links

Signs and symptomsedit

The symptoms of pulmonary hypertension include the following:91011

  • Shortness of breath
  • Fatigue
  • Chest pain
  • Palpitations heartbeat rate increased
  • Pain right side of the abdomen
  • Poor appetite
  • Lightheadedness
  • Fainting or syncope
  • Swelling legs/ankles
  • Cyanosis

Less common signs/symptoms include non-productive cough and exercise-induced nausea and vomiting10 Coughing up of blood may occur in some patients, particularly those with specific subtypes of pulmonary hypertension such as heritable pulmonary arterial hypertension, Eisenmenger syndrome and chronic thromboembolic pulmonary hypertension12 Pulmonary venous hypertension typically presents with shortness of breath while lying flat or sleeping orthopnea or paroxysmal nocturnal dyspnea, while pulmonary arterial hypertension PAH typically does not13

Other typical signs of pulmonary hypertension include an accentuated pulmonary component of the second heart sound, a right ventricular third heart sound, and parasternal heave indicating a hypertrophied right atrium Signs of systemic congestion resulting from right-sided heart failure include jugular venous distension, ascites, and hepatojugular reflux101114 Evidence of tricuspid insufficiency and pulmonic regurgitation is also sought and, if present, is consistent with the presence of pulmonary hypertension101115

Causesedit

In terms of causes and classification,16 a 1973 meeting organized by the World Health Organization was the first to attempt classification of pulmonary hypertension A distinction was made between primary and secondary PH, and primary PH was divided in the "arterial plexiform", "veno-occlusive" and "thromboembolic" forms17 A second conference in 1998 at Évian-les-Bains also addressed the causes of secondary PH ie those due to other medical conditions,18 and the classification was refined further at the third, 19, fourth 20, and fifth 21 World Symposia on PAH based on new understandings of disease mechanisms The revised system developed at the fifth World Symposium on PAH in Nice was adapted further in subsequent European guidelines for the diagnosis and treatment of pulmonary hypertension, and provides the current framework for understanding pulmonary hypertension2223

Classificationedit

It can be one of seven different types2425 The Nice 2013 Updated Clinical Classification system with adaptations from the more recent European guidelines shown in italics can be summarized as follows: 2627

  • WHO Group I - Pulmonary arterial hypertension PAH
    • Idiopathic PAH
    • Heritable
      • BMPR2
      • ALK1, SMAD9, caveolin 1, KCNK3
      • Unknown
    • Drug- and toxin-induced eg, methamphetamine use
    • Associated with
      • Connective tissue disease
      • HIV infection
      • Portal hypertension
      • Congenital heart diseases
      • Schistosomiasis
  • WHO Group I' - Pulmonary veno-occlusive disease PVOD and/or pulmonary capillary hemangiomatosis PCH
    • Idiopathic
    • Heritable
      • EIF2AK4
      • Other mutations
    • Drugs, toxins and radiation induced
    • Assosciated with:
      • Connective tissue dsease
      • HIV infection
  • WHO Group I" - Persistent pulmonary hyptertension of the newborn
  • WHO Group II - Pulmonary hypertension owing to left heart disease
    • Left ventricular Systolic dysfunction
    • Left ventricular Diastolic dysfunction
    • Valvular heart disease
    • Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies
    • Congetial/acquired pulmonary veins stenosis
  • WHO Group III - Pulmonary hypertension due to lung disease and/or hypoxia
    • Chronic obstructive pulmonary disease COPD
    • Interstitial lung disease
    • Other pulmonary diseases with mixed restrictive and obstructive pattern
    • Sleep-disordered breathing
    • Alveolar hypoventilation disorders
    • Chronic exposure to high altitude
    • Developmental abnormalities
  • WHO Group IV - Chronic thromboembolic pulmonary hypertension CTEPH and other pulmonary artery obstructions
    • CTEPH
    • Other pulmonary artery obstructions
      • Angiosarcoma
      • Other intravscular tumors
      • Arteritis
      • Congenital pulmonary arteries stenosis
      • Parasites hydatidosis
  • WHO Group V - Pulmonary hypertension with unclear multifactorial mechanisms
    • Hematologic diseases: chronic hemolytic anemia including sickle cell disease
    • Systemic diseases: sarcoidosis, pulmonary Langerhans cell histiocytosis: lymphangioleiomyomatosis, neurofibromatosis, vasculitis
    • Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid diseases
    • Others: pulmonary tumoral thrombotic microangiopathy, fibrosing mediastinitis, chronic kidney failure, segmental pulmonary hyptertension pulonary hypertension in one or more lobes of one or both lungs

Pathogenesisedit

Right ventricle on left side

The pathogenesis of pulmonary arterial hypertension WHO Group I involves the narrowing of blood vessels connected to and within the lungs This makes it harder for the heart to pump blood through the lungs, much as it is harder to make water flow through a narrow pipe as opposed to a wide one Over time, the affected blood vessels become stiffer and thicker, in a process known as fibrosis The mechanisms involved in this narrowing process include vasoconstriction, thrombosis, and vascular remodeling excessive cellular proliferation, fibrosis, and reduced apoptosis/programmed cell death in the vessel walls, caused by inflammation, disordered metabolism and dysregulation of certain growth factors 2829 Over time, vascular remodeling causes the affected blood vessels to become progressively stiffer and thicker This further increases the blood pressure within the lungs and impairs their blood flow In common with other types of pulmonary hypertension, these changes result in an increased workload for the right side of the heart3031 The right ventricle is normally part of a low pressure system, with systolic ventricular pressures that are lower than those that the left ventricle normally encounters As such, the right ventricle cannot cope as well with higher pressures, and although right ventricular adaptations hypertrophy and increased contractility of the heart muscle initially help to preserve stroke volume, ultimately these compensatory mechanisms are insufficient; the right ventricular muscle cannot get enough oxygen to meet its needs and right heart failure follows323334 As the blood flowing through the lungs decreases, the left side of the heart receives less blood This blood may also carry less oxygen than normal Therefore, it becomes harder and harder for the left side of the heart to pump to supply sufficient oxygen to the rest of the body, especially during physical activity353637

In PVOD WHO Group 1', pulmonary blood vessel narrowing occurs preferentially though not exclusively in post-capillary venous blood vessels38 PVOD shares several characteristics with PAH, but there are also some important differences, for example differences in prognosis and response to medical therapy

Persistent pulmonary hypertension of the newborn occurs when the circulatory system of a newborn baby fails to adapt to life outside the womb; it is characterized by high resistance to blood flow through the lungs, right-to-left cardiac shunting and severe hypoxemia39

Pathogenesis in pulmonary hypertension due to left heart disease WHO Group II is completely different in that constriction or damage to the pulmonary blood vessels is not the issue Instead, the left heart fails to pump blood efficiently, leading to pooling of blood in the lungs and back pressure within the pulmonary system This causes pulmonary edema and pleural effusions40 In the absence of pulmonary blood vessel narrowing, the increased back pressure is described as ‘isolated post-capillary pulmonary hypertension’ older terms include ‘passive’ or ‘proportionate’ pulmonary hypertension or ‘pulmonary venous hypertension’ However, in some patients, the raised pressure in the pulmonary vessels triggers a superimposed component of vessel narrowing, which further increases the workload of the right side of the heart This is referred to as ‘post-capillary pulmonary hypertension with a pre-capillary component’ or ‘combined post-capillary and pre-capillary pulmonary hypertension’ older terms include ‘reactive’ or ‘out-of-proportion’ pulmonary hypertension41 42 43

In pulmonary hypertension due to lung diseases and/or hypoxia WHO Group 3, low levels of oxygen in the alveoli due to respiratory disease or living at high altitude cause constriction of the pulmonary arteries This phenomenon is called hypoxic pulmonary vasoconstriction and it is initially a protective response designed to stop too much blood flowing to areas of the lung that are damaged and do not contain oxygen When the alveolar hypoxia is widespread and prolonged, this hypoxia-mediated vasoconstriction occurs across a large portion of the pulmonary vascular bed and leads to an increase in pulmonary arterial pressure, with thickening of the pulmonary vessel walls contributing to the development of sustained pulmonary hypertension44454647

In CTEPH WHO Group 4, the initiating event is thought to be blockage or narrowing of the pulmonary blood vessels with unresolved blood clots; these clots can lead to increased pressure and shear stress in the rest of the pulmonary circulation, precipitating structural changes in the vessel walls remodeling similar to those observed in other types of severe pulmonary hypertension This combination of vessel occlusion and vascular remodeling once again increases the resistance to blood flow and so the pressure within the system rises4849

Molecular pathologyedit

Three major signaling pathways involved in the pathogenesis of pulmonary arterial hypertension

The molecular mechanism of pulmonary arterial hypertension PAH is not known yet, but it is believed that the endothelial dysfunction results in a decrease in the synthesis of endothelium-derived vasodilators such as nitric oxide and prostacyclin50 Moreover, there is a stimulation of the synthesis of vasoconstrictors such as thromboxane and vascular endothelial growth factor VEGF These results in a severe vasoconstriction and smooth muscle and adventitial hypertrophy characteristic of patients with PAH51

Nitric oxide-soluble guanylate cyclase pathwayedit

In normal conditions, the nitric oxide synthase produces nitric oxide from L-arginine in presence of oxygen52

This nitric oxide diffuses into neighboring cells including vascular smooth muscle cells and platelets, where it increases the activity of the enzyme soluble guanylate cyclase, leading to increased formation of cyclic guanosine monophosphate cGMP from guanosine triphosphate GTP53 The cGMP then activates cGMP-dependent kinase or PKG protein kinase G Activated PKG promotes vasorelaxation via a reduction of intracellular calcium levels, alters the expression of genes involved in smooth muscle cell contraction, migration and differentiation, and inhibits platelet activation54 Nitric oxide–soluble guanylate cyclase signaling also leads to anti-inflammatory effects55 Phosphodiesterase type 5 PDE5, which is abundant in the pulmonary tissue, hydrolyzes the cyclic bond of cGMP Consequently, the concentration of cGMP and thus PKG activity decreases56 57

Endothelinedit

Endothelin-1 is a peptide comprising 21 amino acids that is produced in endothelial cells It acts on the endothelin receptors ETA and ETB in various cell types including vascular smooth muscle cells and fibroblasts, leading to vasoconstriction, hypertrophy, proliferation, inflammation, and fibrosis It also acts on ETB receptors in endothelial cells; this leads to the release of both vasoconstrictors and vasodilators from those cells, and clears endothelin-1 from the system58 59

Prostacyclinedit

Prostacyclin is synthesized from arachidonic acid in endothelial cells In vascular smooth muscle cells, prostacyclin binds mainly to the prostaglandin I receptor This sends a signal to increase adenylate cyclase activity, which leads to increased synthesis of cyclic adenosine monophosphate cAMP This in turn leads to increased cAMP-dependent protein kinase or PKA protein kinase A activity, ultimately promoting vasodilation and inhibiting cell proliferation Prostacyclin signaling also leads to anti-thrombotic, anti-fibrotic, and anti-inflammatory effects Levels of cAMP which mediates most of the biological effects of prostacyclin are reduced by phosphodiesterases 3 and 46061 The vasoconstrictor thromboxane is also synthesized from arachidonic acid In PAH, the balance is shifted away from synthesis of prostacyclin towards synthesis of thromboxane62

Other pathwaysedit

The three pathways described above are all targeted by currently available medical therapies for PAH However, several other pathways have been identified that are also altered in PAH and are being investigated as potential targets for future therapies For example, the mitochondrial enzyme pyruvate dehydrogenase kinase PDK is pathologically activated in PAH, causing a metabolic shift from oxidative phosphorylation to glycolysis and leading to increased cell proliferation and impaired apoptosis6364 Expression of vasoactive intestinal peptide, a potent vasodilator with anti-inflammatory and immune-modulatory roles, is reduced in PAH, while expression of its receptor is increased6566 Plasma levels of serotonin, which promotes vasoconstriction, hypertrophy and proliferation, are increased in patients with PAH, although the role played by serotonin in the pathogenesis of PAH remains uncertain6768 The expression or activity of several growth factors including platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor is increased and contributes to vascular remodeling in PAH69 Focusing only on the pulmonary vasculature provides an incomplete picture of PAH; the ability of the right ventricle to adapt to the increased workload varies between patients and is an important determinant of survival The molecular pathology of PAH in the right ventricle is therefore also being investigated, and recent research has shifted to consider the cardiopulmonary unit as a single system rather than two separate systems Importantly, right ventricular remodeling is associated with increased apoptosis; this is in contrast to pulmonary vascular remodeling which involves inhibition of apoptosis70

Diagnosisedit

Phonocardiogram and jugular venous pulse tracing from a middle-aged man with pulmonary hypertension caused by cardiomyopathy The jugular venous pulse tracing demonstrates a prominent a wave without a c or v wave being observed The phonocardiograms fourth left interspace and cardiac apex show a murmur of tricuspid insufficiency and ventricular and atrial gallops Pulmonary artery catheter

In terms of the diagnosis of pulmonary hypertension, which can be of several types, a series of tests must be performed to distinguish pulmonary arterial hypertension from venous, hypoxic, thromboembolic, or miscellaneous varieties Further procedures are required to confirm the presence of pulmonary hypertension and exclude other possible diagnoses These generally include pulmonary function tests; blood tests to exclude HIV, autoimmune diseases, and liver disease; electrocardiography ECG; arterial blood gas measurements; X-rays of the chest followed by high-resolution CT scanning if interstitial lung disease is suspected; and ventilation-perfusion or V/Q scanning to exclude chronic thromboembolic pulmonary hypertension7172 Clinical improvement is often measured by a "six-minute walk test", ie the distance a patient can walk in six minutes Stability and improvement in this measurement correlate with better survival73

Diagnosis of PAH requires the presence of pulmonary hypertension Although pulmonary arterial pressure can be estimated on the basis of echocardiography,74 pressure measurements with a Swan-Ganz catheter through the right side of the heart provide the most definite assessment75 Diagnosis of PAH requires right-sided cardiac catheterization; a Swan-Ganz catheter can also measure the cardiac output, which is far more important in measuring disease severity than the pulmonary arterial pressure75 Normal pulmonary arterial pressure in a person living at sea level has a mean value of 8–20 mm Hg 1066–2666 Pa at rest Pulmonary hypertension is present when mean pulmonary artery pressure exceeds 25 mm Hg 3300 Pa at rest76

Physical examinationedit

Pulmonary artery hypertension and emphysema as seen on a CT scan with contrast

A physical examination is performed to look for typical signs of pulmonary hypertension described above,72 and a detailed family history is established to determine whether the disease might be heritable777879 A history of exposure to drugs such as benfluorex a fenfluramine derivative, dasatinib, cocaine, methamphetamine, ethanol leading to cirrhosis, and tobacco leading to emphysema is considered significant118081 Use of selective serotonin reuptake inhibitors during pregnancy particularly late pregnancy is associated with an increased risk of the baby developing persistent pulmonary hypertension of the newborn81

Echocardiographyedit

A meta-analysis of doppler echocardiography for predicting right heart catheterization reported a sensitivity and specificity of 88% and 56%, respectively82

Treatmentedit

Treatment of pulmonary hypertension is determined by whether the PH is arterial, venous, hypoxic, thromboembolic, or miscellaneous The treatment is to optimize left ventricular function by the use of diuretics, digoxins, blood thinners, or to repair/replace the mitral valve or aortic valve85 Patients with left heart failure or hypoxemic lung diseases groups II or III pulmonary hypertension should not routinely be treated with vasoactive agents including prostanoids, phosphodiesterase inhibitors, or endothelin antagonists, as these are approved for the different condition called pulmonary arterial hypertension86 To make the distinction, doctors at a minimum will conduct cardiac catheterization of the right heart, echocardiography, chest CT, a six-minute walk test, and pulmonary function testing86 Using treatments for other kinds of pulmonary hypertension in patients with these conditions can harm the patient and wastes substantial medical resources86

High dose calcium channel blockers are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter Unfortunately, calcium channel blockers have been largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality15 The criteria for vasoreactivity have changed Only those patients whose mean pulmonary artery pressure falls by more than 10 mm Hg to less than 40 mm Hg with an unchanged or increased cardiac output when challenged with adenosine, epoprostenol, or nitric oxide are considered vasoreactive87 Of these, only half of the patients are responsive to calcium channel blockers in the long term88

A number of agents have recently been introduced for primary and secondary PAH The trials supporting the use of these agents have been relatively small, and the only measure consistently used to compare their effectivity is the "6 minute walk test" Many have no data on mortality benefit or time to progression89

Vasoactive substancesedit

Many pathways are involved in the abnormal proliferation and contraction of the smooth muscle cells of the pulmonary arteries in patients with pulmonary arterial hypertension Three of these pathways are important since they have been targeted with drugs — endothelin receptor antagonists, phosphodiesterase type 5 PDE-5 inhibitors, and prostacyclin derivatives90

Prostaglandinsedit

Prostacyclin prostaglandin I2 is commonly considered the most effective treatment for PAH Epoprostenol synthetic prostacyclin is given via continuous infusion that requires a semi-permanent central venous catheter This delivery system can cause sepsis and thrombosis Prostacyclin is unstable, and therefore has to be kept on ice during administration Since it has a half-life of 3 to 5 minutes, the infusion has to be continuous, and interruption can be fatal91 Other prostanoids have therefore been developed Treprostinil can be given intravenously or subcutaneously, but the subcutaneous form can be very painful An increased risk of sepsis with intravenous Remodulin has been reported by the CDC Iloprost is also used in Europe intravenously and has a longer half life Iloprost was the only inhaled form of prostacyclin approved for use in the US and Europe, until the inhaled form of treprostinil was approved by the FDA in July 2009medical citation needed

Endothelin receptor antagonistsedit

The dual ETA and ETB endothelin receptor antagonist bosentan was approved in 2001 Sitaxentan Thelin was approved for use in Canada, Australia, and the European Union,92 but not in the United States In 2010, Pfizer withdrew Thelin worldwide because of fatal liver complications A similar drug, ambrisentan is marketed as Letairis in the US by Gilead Sciences93

Phosphodiesterase type 5 inhibitorsedit

The US FDA approved sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 PDE5, for the treatment of PAH in 2005 It is marketed for PAH as Revatio In 2009, they also approved tadalafil, another PDE5 inhibitor, marketed under the name Adcirca94 PDE5 inhibitors are believed to increase pulmonary artery vasodilation, and inhibit vascular remodeling, thus lowering pulmonary arterial pressure and pulmonary vascular resistance95

Tadalafil is taken orally, as well as sildenafil, and it is rapidly absorbed serum levels are detectable at 20 minutes The T1/2 biological half-life hovers around 175 hours in healthy subjects96 Moreover, if we consider pharmacoeconomic implications, patients that take tadalafil would pay two-thirds of the cost of sildenafil therapy97 However, there are some adverse effects of this drug such as headache, diarrhea, nausea, back pain, dyspepsia, flushing and myalgia98

Activators of soluble guanylate cyclaseedit

Soluble guanylate cyclase sGC is the intracellular receptor for NO As of April 2009update, the sGC activators cinaciguat and riociguat were undergoing clinical trials for the treatment of PAH99

Surgicaledit

Atrial septostomy is a surgical procedure that creates a communication between the right and left atria It relieves pressure on the right side of the heart, but at the cost of lower oxygen levels in blood hypoxia Lung transplantation cures pulmonary arterial hypertension, but leaves the patient with the complications of transplantation, and a post-surgical median survival of just over five years100

Pulmonary thromboendarterectomy PTE is a surgical procedure that is used for chronic thromboembolic pulmonary hypertension It is the surgical removal of an organized thrombus clot along with the lining of the pulmonary artery; it is a very difficult, major procedure that is currently performed in a few select centers101

Monitoringedit

Established clinical practice guidelines dictate the frequency of pulmonary nodule evaluation and surveillance,86102 patients are normally monitored through commonly available tests such as:citation needed

  • Pulse oximetry
  • Arterial blood gas tests
  • Chest X-rays
  • Serial ECG tests
  • Serial echocardiography
  • Spirometry or more advanced lung function studies

Prognosisedit

Cor pulmonale

The prognosis of pulmonary arterial hypertension WHO Group I has an untreated median survival of 2–3 years from time of diagnosis, with the cause of death usually being right ventricular failure cor pulmonale103 A recent outcome study of those patients who had started treatment with bosentan Tracleer showed that 89% patients were alive at 2 years104 With new therapies, survival rates are increasing For 2,635 patients enrolled in The Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management REVEAL Registry from March 2006 to December 2009, 1-, 3-, 5-, and 7-year survival rates were 85%, 68%, 57%, and 49%, respectively For patients with idiopathic/familial PAH, survival rates were 91%, 74%, 65%, and 59%105 Levels of mortality are very high in pregnant women with severe pulmonary arterial hypertension WHO Group I Pregnancy is sometimes described as contraindicated in these women106107108

Epidemiologyedit

The epidemiology of IPAH is about 125-150 deaths per year in the US, and worldwide the incidence is similar to the US at 4 cases per million However, in parts of Europe France indications are 6 cases per million of IPAH Females have a higher incidence rate than males 2-9:1109

Other forms of PH are far more common In systemic scleroderma, the incidence has been estimated to be 8 to 12% of all patients;110 in rheumatoid arthritis it is rare111 However, in systemic lupus erythematosus it is 4 to 14%,112 and in sickle cell disease, it ranges from 20 to 40%113 Up to 4% of people who suffer a pulmonary embolism go on to develop chronic thromboembolic disease including pulmonary hypertension114 A small percentage of patients with COPD develop pulmonary hypertension with no other disease to explain the high pressure115 On the other hand, obesity-hypoventilation syndrome is very commonly associated with right heart failure due to pulmonary hypertension116

Notable casesedit

  • Elaine Kaufman, American restaurateur117
  • Priya Balachandran, TV producer 118
  • Ina Balin, American Broadway and TV actress119
  • Chloe Temtchine, American singer-songwriter120121
  • Natalie Cole, American singer122

See alsoedit

  • Pulmonary Hypertension Association
  • Cambridge Pulmonary Hypertension Outcome Review CAMPHOR

Referencesedit

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Further readingedit

  • Rubin LJ, Badesch DB 2005 "Evaluation and management of the patient with pulmonary arterial hypertension" Ann Intern Med 143 4: 282–92 PMID 16103472 doi:107326/0003-4819-143-4-200508160-00009 
  • Abman, SH; Hansmann, G; Archer, SL; Ivy, DD; Adatia, I; Chung, WK; Hanna, BD; Rosenzweig, EB; Raj, JU; Cornfield, D; Stenmark, KR; Steinhorn, R; Thébaud, B; Fineman, JR; Kuehne, T; Feinstein, JA; Friedberg, MK; Earing, M; Barst, RJ; Keller, RL; Kinsella, JP; Mullen, M; Deterding, R; Kulik, T; Mallory, G; Humpl, T; Wessel, DL 3 November 2015 "Pediatric Pulmonary Hypertension: Guidelines From the American Heart Association and American Thoracic Society" Circulation 132: 2037–99 PMID 26534956 doi:101161/CIR0000000000000329 

External linksedit

Classification
  • ICD-10: I270, I272
  • ICD-9-CM: 4160, 4168
  • OMIM: 178600
  • MeSH: D006976
  • DiseasesDB: 10998
External resources
  • MedlinePlus: 000112
  • eMedicine: radio/583 med/1962 Secondary pulmonary hypertension Pediatric primary pulmonary hypertension Persistent newborn pulmonary hypertension
  • Patient UK: Pulmonary hypertension



  • The Merck Manual Home Edition: Pulmonary Hypertension
  • Webcast: The Changing World of Pulmonary Arterial Hypertension Therapies - American College of CHEST Physicians


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