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Pulmonary hypertension

Defined as a mean pulmonary artery pressure that exceeds 20-25 mm Hg at rest or 30 mm Hg with exercise.

Pulmonary hypertension is defined as a mean PAP of at least 20 mm Hg (3300 Pa) at rest, and PAH is defined as precapillary pulmonary hypertension (i.e. mean PAP ≥ 20 mm Hg with pulmonary arterial occlusion pressure [PAOP] ≤ 15 mm Hg and pulmonary vascular resistance [PVR] > 3 Wood Units).

PAOP and PVR cannot be measured directly with echocardiography. 

Echocardiographic assessment 4PH has a sensitivity and specificity of approximately 85% and 70%, respectively.

Therefore, diagnosis of PAH requires right-sided cardiac catheterization. 

Routine lung biopsy is discouraged in patients with PAH.

A Swan-Ganz catheter can also measure the cardiac output.

Measuring cardiac output can be used to calculate the cardiac index.

The cardiac index is more important in measuring disease severity than the pulmonary arterial pressure.

Pulmonary arterial pressure is confirmed by right sided heart catheterization.

Refers to a condition of increased blood pressure within the arteries of the lungs, due to increased pulmonary vascular resistance.

Usual onset is at 20 to 60 years of age.

An uncommon process with an incidence of about 2.0 cases per 1 million and the prevalence of 10.6 cases per 1 million adults.

Can affect both children and adults. 

Is most common in women age 75 years or older and black individuals.

Prior to of PAH specific therapy five-year survival was 34%.

Risk factors include:

Family history, pulmonary embolism, HIV/AIDS, sickle cell disease, cocaine use, COPD, sleep apnea, living at high altitudes, and mitral valve abnormalities.

Frequency about 1,000 new cases a year in US, and females are more often affected than males.

PH affects approximately 1% of the global population and up to 10% of individuals older than 65 years.

Heritable PAH (pulmonary arterial hypertension) affects approximately 6 to 10% of people with PH.

Variants in the bone morphogenetic protein receptor 2 gene (BMPR2) accounts for nearly 75% of heritable PAH and has an autosomal dominant/incomplete penetrance pattern of inheritance.

BMPR2 variants  are present approximately 25% of patients initially diagnosed with idiopathic PAH.

 

Onset is typically between 20 and 60 years of age.

PH affects at least 50% of patients with heart failure.

Estimated prevalence 10.6 per 1 million adults in the US.o

Regardless of court cause PH is almost always associated with progressive symptoms and increased mortality.

The cause often  remains unknown.

Symptoms include: shortness of breath, syncope, tiredness, chest pain, swelling of the legs, fast heartbeat, palpations, poor exercise tolerance, fatigue, right-sided abdominal pain, poor appetite, lightheadedness, fainting or syncope, cyanosis, non-productive cough and exercise-induced nausea and vomiting.

Symptoms may be nonspecific and have an insidious onset.

Dyspnea is the first symptom in 60%, although 98% report dyspnea at the time of diagnosis.

Less common signs/symptoms include non-productive cough, exercise-induced nausea and vomiting, and hemoptysis.

With advanced disease, symptoms occur with minimal exertion or at rest.

Physical examination is subtle in early disease, findings include: a loud second heart sound, a right sided third heart sound, tricuspid regurgitation murmur, increased jugular venous distention, right ventricular heave and late findings include lower extremity edema, abdominal distention, and ascites.

Delay in diagnosis is often present, and patients may have symptoms for more than two years before diagnosis.

Younger age and coexistence of common respiratory disorders such as asthma, and  obstructive sleep apnea increase the diagnostic delay.

Prognosis is associated with disease severity at presentation.

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 not.

Pulmonary hypertension may make it difficult to exercise, and its onset is typically gradual.

Hemoptysis may occur with specific subtypes of pulmonary hypertension: heritable pulmonary arterial hypertension, Eisenmenger syndrome and chronic thromboembolic pulmonary hypertension.

Pulmonary venous hypertension typically presents with shortness of breath while lying flat or sleeping, while pulmonary arterial hypertension (PAH) typically does not.

Persistent pulmonary hypertension of the newborn occurs when the circulatory system of a newborn baby fails to adapt to life outside the womb, with high resistance to blood flow through the lungs, right-to-left cardiac shunting and severe hypoxemia.

Can occur as an isolated phenomenon or associated with cardiac, pulmonary and systemic disorders.

The underlying mechanism typically involves inflammation and subsequent remodeling of the arteries in the lungs.

Pulmonary vascular remodeling eventually includes the small precapillary arteries and arterioles being obliterated, leading to isolated reduction in diffusing capacity for carbon monoxide in patients with PH.

In normal conditions, the vascular endothelial nitric oxide synthase produces nitric oxide from L-arginine in the presence of oxygen.

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 (GTP).

The cGMP then activates cGMP-dependent kinase or PKG.

 Activated PKG promotes vasorelaxation, and inhibits platelet activation.

Nitric oxide–soluble guanylate cyclase signaling also leads to anti-inflammatory effects.

There is currently no cure for pulmonary hypertension.

Pulmonary hypertension evaluation includes cardiac catheterization of the right heart, echocardiography, chest CT, a six-minute walk test, and pulmonary function testing.

Pulmonary vascular disease is characterized by normal spirometry, normal lung volumes and a low DLCO due to destruction of the pulmonary vasculature.

Typical ECG abnormalities include right axis deviation, right ventricular hypertrophy, and right ventricular strain.

Plasma levels of N terminal pro-brain natriuretic peptide increase in patients with pulmonary arterial hypertension and right ventricular dysfunction.

Elevated NT-proBNP levels are associated with increased risk of death.

Untreated pulmonary hypertension typically progresses to right ventricular failure and death.

 

The underlying mechanism typically involves inflammation of the arteries in the lungs.

The pathogenesis of pulmonary arterial hypertension (WHO Group I) involves the narrowing of blood vessels connected to and within the lungs making it harder for the heart to pump blood through the lungs.

The affected blood vessels become stiffer and thicker, with fibrosis.

Vasoconstriction, thrombosis, vascular remodeling with excessive cellular proliferation, reduced apoptosis/programmed cell death in the vessel walls, associated with inflammation, disordered metabolism and dysregulation of certain growth factors.

The above vascular changes increases the blood pressure within the lungs and impairs  blood flow further, increasing workload for the right side of the heart.

The right ventricle normally is part of a low pressure system, with systolic ventricular pressures that are lower than those that the left ventricle.

The right ventricle cannot cope with higher pressures, and the right ventricular adaptations of hypertrophy, increased contractility of the heart muscle are insufficient.

Ultimately, the right ventricular muscle cannot get enough oxygen to meet its needs and right heart failure follows.

As the blood flowing through the lungs diminishes, the left side of the heart receives less blood, and may also carry less oxygen than normal. 

It becomes harder for the left side of the heart to pump to supply sufficient oxygen to the rest of the body, especially during physical activity.

Diagnosis requires ruling  out other potential causes.

Presently, no cure exists.

Treatment

Treatment  varies with the type of disease.

Treatment of pulmonary hypertension is determined by whether the PH is arterial, venous, hypoxic, or thromboembolic.

Therapy for  pulmonary arterial hypertension vasodilator treatment targets three pathways: stimulating nitric oxide-cyclic guanodinevmonophosphate biological pathway, increasing prostacyclin effects on receptors, and antagonizing the endothelin pathway.

Combination therapy that targets multiple pathways are superior to monotherapies.

PH is caused by left heart disease is treated to optimize left ventricular function by the use of medication or to repair/replace the mitral valve or aortic valve.

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.

These vasoactive agents are  approved for primary pulmonary arterial hypertension.

 

Supportive measures include: oxygen therapy, diuretics, and medications to inhibit clotting.

Grouped into five categories-Group 1 includes primary pulmonary hypertension and benefits the most from specific pulmonary hypertension therapy.

Group one is characterized by loss in obstructive remodeling of the pulmonary vascular bed, mean pulmonary artery pressure of 20 mmHg or greater, pulmonary artery wedge upressure of 15 mmHg or less, and pulmonary vascular resistance of three Wood units or greater.

Chronic elevation of pulmonary vascular resistance can result in progressive right ventricular dysfunction and right ventricular failure.

In the presence of right ventricular failure, right atrial pressure may increase and cardiac index may decrease.

In the US heart disease is the most common cause of pulmonary hypertension.

Group I (pulmonary arterial hypertension) is further subdivided into Group I’ and Group I” classes.

WHO Group I – Pulmonary arterial hypertension (PAH)

Idiopathic

Heritable (BMPR2, ALK1, SMAD9, caveolin 1, KCNK3 mutations)

Mutations associated with this conditions these include bone morphogenetic protein receptor type 2 (BMPR2) and eukaryotic translation initiation factor 2 alpha kinase 4 gene (EIF2AK4).

Drug- and toxin-induced (methamphetamine, amphetamine, or cocaine use)

Associated conditions:Connective tissue disease, HIV infection, Portal hypertension, Congenital heart diseases, Schistosomiasis

WHO Group I’ – Pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis (PCH)

Idiopathic

Heritable (EIF2AK4 mutations)

Drugs, toxins and radiation-induced; methamphetamine, dasatinib or fenfluramine.

Methamphetamine is associated with a more severe cramping disease and rapid progression.

Dasatinib PH  resolves with stopping of the drug.

 

WHO Group I– Persistent pulmonary hypertension of the newborn

Group 2 involves pulmonary hypertension secondary to left heart disease including systolic, diastolic, and valve malfunction.

For Group 2 the current hemodynamic definition combines a mean pulmonary artery pressure of 25 mmHg, a pulmonary wedge pressure of 15 mmHg or greater, and normal or reduced cardiac output.

WHO Group II – Pulmonary hypertension secondary to left heart disease.

In WHO Group II pulmonary hypertension due to left heart disease damage to the pulmonary blood vessels is not the issue, but the left heart fails to pump blood efficiently.

This results in the pooling of blood in the lungs and back pressure within the pulmonary system, resulting in pulmonary edema and pleural effusions.

Left ventricular systolic dysfunction

Left ventricular diastolic dysfunction

Valvular heart disease

Congenital/acquired left heart inflow/

outflow tract obstruction and congenital cardiomyopathy

Congenital/acquired pulmonary venous stenosi

Group 3 includes pulmonary hypertension secondary to lung disease or hypoxia.

WHO Group III – Pulmonary hypertension due to lung disease, chronic hypoxia.

 pulmonary hypertension due to lung diseases and/or hypoxia (WHO Group III), of high altitude, low levels of oxygen in the alveoli cause constriction of the pulmonary arteries: 

This 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 alveolar hypoxia becomes widespread and prolonged, 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 hypertension.

Prolonged hypoxia induces the transcription factor HIF1A, which directly activates downstream growth factor signaling that causes irreversible proliferation and remodeling of pulmonary arterial endothelial cells, leading to chronic pulmonary arterial hypertension.

Chronic obstructive pulmonary disease (COPD)

Interstitial lung disease

Mixed restrictive and obstructive pattern pulmonary diseases

Sleep-disordered breathing

Alveolar hypoventilation disorders

Chronic exposure to high altitude

Developmental abnormalities

Group 4 comprises patients with chronic thromboembolic pulmonary hypertension.

WHO Group IV – chronic arterial obstruction

In chronic thrombotic embolitic pulmonary hypertension (WHO Group IV), the initiating event is thought to be blockage or narrowing of the pulmonary blood vessels with unresolved blood clots.

These chronic clots can lead to increased pressure and shear stress in the rest of the pulmonary circulation, precipitating structural changes in the vessel walls similar to those observed in other types of severe pulmonary hypertension.

Chronic thromboembolic pulmonary hypertension 

Other pulmonary artery obstructions

Angiosarcoma or other tumor within the blood vessels

Arteritis

Congenital pulmonary artery stenosis

Parasitic infection 

Group 5 includes pulmonary hypertension with unclear, multifactorial causative 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 hypertension

The prevalence of pulmonary hypertension among patients with left heart disease ranges between 25-80%.

COPD and interstitial lung disease is associated commonly with pulmonary hypertension.

Patients with chronic lung disease-associated pulmonary hypertension have significantly worse prognosis than patients without such pulmonary hypertension.

Definition of chronic lung disease with hypertension occurs when mean arterial

pressure is equal or greater than 25 mmHg.

Chronic lung disease with severe pulmonary hypertension occurs when the mean arterial pressure is equal or greater than 35 mmHg or equal or greater than 25 mm Hg, but less than 35 mm Hg with low cardiac index of less than 2 L per minute.

Chronic lung disease-associated pulmonary hypertension includes: idiopathic pulmonary fibrosis, COPD, and sarcoidosis.

Associated with sustained elevated pulmonary vascular resistance, ultimately leading to right heart failure and death.

Nearly the entire cardiac output flows through the pulmonary circuit, yet primary vascular pressure and resistance are much less then the systemic circulation.

The pulmonary circulation adapts to cardiac output changes by distending or recruiting previously underperfused pulmonary capillaries.

Pulmonary vascular resistance decreases as pulmonary flow increases.

Pulmonary vascular resistance =pulmonary driving Pressure/Cardiac output

Unlike the systemic circulation with greater vaso motor activity, pulmonary circulation has limited ability to control regional pulmonary flow and is influenced by other active and passive factors.

Pulmonary arteries and arterials with muscular walls are extra-alveolar and regulate pulmonary vascular resistance via nervous, humeral, will gaseous mechanisms.

Pulmonary capillaries lie adjacent to alveolar walls and resistance of these alveolar vessels is influenced greatly by alveolar pressure and volume.

In normal pulmonary circulation, vessels devoid of activitive vasoconstriction play a pivotal role in regulating pulmonary vascular resistance and distributing pulmonary blood flow.

Molecular mechanism of pulmonary arterial hypertension (PAH) may involve endothelial dysfunction resulting in a decrease in the synthesis of endothelium-derived vasodilators such as nitric oxide and prostacyclin.

Prostacyclin, a potent pulmonary artery vasodilation, is endogenous reduced produced by endothelial cells.

cAMP levels mediate most of the biological effects of prostacyclin, and are reduced by phosphodiesterases 3 and 4.

The vasoconstrictor thromboxane is also synthesized from arachidonic acid, and with PAH, synthesis increases towards of thromboxane.

In addition there is a stimulation of the synthesis of vasoconstrictors such as thromboxane and vascular endothelial growth factor (VEGF).

These result in a severe vasoconstriction and vascular smooth muscle and adventitial hypertrophy characteristic of patients with PAH.

Hypoxic pulmonary vasoconstriction plays a major role in the active regulation of pulmonary vascular resistance and pulmonary blood flow.

Characterized by the presence of precapillary pulmonary hypertension in the absence of left-sided heart disease, lung disease, or chronic thromboembolism.

Can be idiopathic, inherited, associated with anorexigens, associated with systemic sclerosis, congenital heart disease, HIV, and portal hypertension.

Histopatholoogical findings of proliferation of medial smooth muscle cells and endothelial cells in the small pulmonary arteries.

May be idiopathic, inherited, or associated with congenital diseases, congenital diseases, and sickle cell disease.

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 apoptosis.

Plasma levels of serotonin promoting vasoconstriction, hypertrophy and proliferation, are increased in PAH.

Growth factors, including:  platelet-derived growth factor, basic fibroblast growth factor, epidermal growth factor, and vascular endothelial growth factor are increased and contribute to vascular remodeling in PAH.

PAH is diagnosed after exclusion of other possible causes of pulmonary hypertension.

Pulmonary hypertension defined by some as tricuspid valve regurgitation jet velocity of at least 2.5 m per second on Doppler echocardiography.

Diagnosis is considered in any patient presenting with unexplained exertional dyspnea.

Signs of pulmonary hypertension on CT scan of the chest are:

Enlargement of the pulmonary trunk, a poor predictor of pulmonary hypertension in patients with interstitial lung disease.

A diameter of more than 27 mm for women and 29 mm for men is suggested as a cutoff.

A cutoff of 31.6 mm may be a more accurate in individuals without interstitial lung disease.

Increased ratio of the diameter of the main pulmonary artery to the ascending aorta: A ratio of 1.0 is suggested as a cutoff in adults.

Cutoff ~1.09 in children.

Increased diameter ratio of segmental arteries to bronchi in three or four lobes, in the presence of a dilated pulmonary trunk (≥29 mm), and absence of significant structural lung disease confers a specificity of 100% for pulmonary hypertension.

Mural calcification in central pulmonary arteries can be seen in patients with Eisenmenger’s syndrome.

Right heart catheterization with a Swan-Ganz catheter inserted through the right side of the heart provide the most definite assessment.

Right heart catheterization is required for definitive diagnosis of pulmonary arterial hypertension and to assess disease severity, which guides treatment.

Recommended diagnostic confirmation by right heart catheterization.

Echocardiography alone results in a substantial number of false positive diagnoses that are not confirmed on right heart catheterization.

The first recommended test is a transthoracic echocardiogram.

Echocardiography for predicting the results of right heart catheterization reported a sensitivity and specificity of 88% and 56%, respectively.

Doppler echocardiography can suggest the presence of pulmonary hypertension, but right heart catheterization is the gold standard for diagnosis of PAH.

Right heart catheterization can distinguish between precapillary pulmonary arterial hypertension, which is mainly caused by pulmonary hypertension, and postcapillary pulmonary hypertension, which is associated with left sided heart disease.

WHO classifies pulmonary hypertension into five groups:pulmonary arterial hypertension, pulmonary venous hypertension, hypertension due to hypoxemia, thromboembolic hypertension, and miscellaneous hypertensive disorders (Simonneau G).

Pulmonary arterial hypertension involves destruction and narrowing of the pulmonary artery due to an inherited or unknown cause, some drugs or toxins, and certain medical conditions including connective tissue diseases, HIV, liver cirrhosis, congenital heart disease, and schistosomiasis.

A history of exposure to drugs such as benfluorex, dasatinib, cocaine, methamphetamine, ethanol leading to cirrhosis, and tobacco leading to emphysema is considered significant.

The use of selective serotonin reuptake inhibitors during pregnancy is associated with an increased risk of  pulmonary hypertension of the newborn

Pulmonary hypertension due to heart disease involves increase pressure in blood vessels of the lungs from heart failure problems with heart valves.

Pulmonary hypertension due to lung disease caused by low oxygen levels such as by chronic obstructive pulmonary disease, or progressive lung scarring due to interstitial lung disease or other medical conditions such as sleep apnea.

Pulmonary hypertension due to blockage of blood vessels typically related to large blood clot‘s but may also be due to tumors with or externally compressing the pulmonary artery.

Pulmonary hypertension due to other causes including blood disorders such as sickle cell disease, sarcoidosis, chronic kidney disease, and complex congenital heart disease.

May occur because of obstruction to blood flow with an increased pulmonary vascular resistance, secondary to a high flow state with elevated cardiac output, or increased intravascular volume.

Along with cor pulmonale a complication of COPD.

A typical sign of pulmonary hypertension is an accentuated pulmonary component of the second heart sound, a right ventricular third heart sound, and parasternal heave indicating a hypertrophied right ventricle. 

Findings of congestion resulting from right-sided heart failure include jugular venous distension, ascites, and hepatojugular reflux.

Evidence for tricuspid insufficiency and pulmonic regurgitation, if present, is consistent with the presence of pulmonary hypertension.

Manifests by symptoms of progressive-right sided heart failure.

Patients with PH may have symptoms resembling CAD, with chest pain and dyspnea.

Often leads to a substantial reduction in exercise tolerance.

Resting pulmonary artery pressure correlates with resting PaO2 in COPD.

Associated with sickle cell disease, thalassemia, hereditary spherocytosis, PNH, and other hereditary and chronic hemolytic states.

Occurs in 10-30% of patients with sickle cell disease and thalassemia.

Associated with germline mutations in BMPR2, ACVRL1.

pHTN is associated with increased mortality and readmission for heart failure in patients undergoing TMVr using the MitraClip system for severe mitral regurgitation.

Phosphodiesterase type 5 (PDE5) is abundant in the pulmonary tissue, hydrolyzes the cyclic bond of cGMP and PKG activity decreases.

Phosphodiesterase type 5 (PDE5) Inhibitors cause vessel dilation, particularly in the pulmonary vasculature and improves six minute walk distances.

Soluble guanylate cyclase stimulators such as oral riociguat enhances cyclic guanosine monophosphate production, causing vasodilation and increased six minute walk distances.

Endothelin-1  is a potent endogenous vasoconstrictor and is over expressed in the pulmonary vasculature of patients with pulmonary arterial hypertension.

Endothelin-1 is a peptide of  21 amino acids, that is produced in endothelial cells. 

Endothelin-1 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. 

Endothelin-1 acts on ETB receptors in endothelial cells, releasing  vasoconstrictors and vasodilators from those cells, and clears endothelin-1 from the system.

Endothelin-receptor antagonists, phosphodiesterase type 5 inhibitors and prostacyclin and its analogues approved for treatment.

Endothelin-1 receptor antagonists such as  bosetan and ambriseran  block the activity of endothelin-1 resulting in vasodilatation and improved six minute walk distances.

TREATMENT:

Medications specifically for the condition include epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, macitentan, and sildenafil.

 

A lung transplant may also be an option in certain cases.

Above agents shown to improve 6 minute distances walked in 12-16 weeks.

Macitentan, a dual endothelin-receptor antagonist, significantly reduces morbidity and mortality (Pulido T et al).

Calcium channel blockers are useful in only 5% of IPAH patients who are vasoreactive by Swan-Ganz catheter. 

Calcium channel blockers are largely misused, being prescribed to many patients with non-vasoreactive PAH, leading to excess morbidity and mortality.

Vasoactivity defined in 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 vasoreactive.

Targeting pathways involved in the abnormal proliferation and contraction of the smooth muscle cells of the pulmonary arteries in patients with pulmonary arterial hypertension, with vasoactive drugs: endothelin receptor antagonists, phosphodiesterase type 5 (PDE-5) inhibitors, and prostacyclin derivatives.

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. 

Treprostinil can be given intravenously or subcutaneously, but the subcutaneous form can be very painful. 

Iloprost and treprostinil are inhaled  forms of prostacyclin approved for use.

Combinations of pulmonary vasodilator therapies are more affective than single agents.

Evidence suggests that endothelin receptor antagonists improve exercise capacity and decrease symptoms severity.

Phosphodiesterase type 5 inhibitors:

Sildenafil, a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5), for the treatment of PAH, and tadalafil, another PDE5 inhibitor are believed to increase pulmonary artery vasodilation, and inhibit vascular remodeling, thus lowering pulmonary arterial pressure and pulmonary vascular resistance.

Adverse effects of tadalafil drug such as headache, diarrhea, nausea, back pain, dyspepsia, flushing and myalgia.

Atrial septostomy is a surgical procedure that creates a communication between the right and left atria, relieving pressure on the right side of the heart, but at the cost of hypoxia.

Lung transplantation has a post-surgical median survival of just over five years.

Pulmonary thromboendarterectomy (PTE) is a surgical procedure that is used for chronic thromboembolic pulmonary hypertension. 

Prominent right ventricle radiotracer uptake in myocardial perfusion SPECHT images suggests presence of pulmonary hypertension.

Pulmonary hypertension in interstitial lung disease: 

Precapillary pulmonary hypertension due to lung disease is classified as group 3, and the most common lung disease is associated with this group is pulmonary hypertension of COPD and interstitial lung disease.

 

Pulmonary hypertension has been reported in up to 86% of patients with ILVN is associated with reduced exercise capacity, greater need for supplemental oxygen therapy, decreased quality-of-life, and early death.

 

In patients with pulmonary hypertension due to interstitial lung disease, inhaled treprostinil improved exercise capacity from baseline, assessed with the use of a six minute walk test, as compared with placebo (Waxman A).

Supportive measures such as oxygen therapy, diuretics, and medications to inhibit blood clotting may be used.

Specific medications specifically used to treat pulmonary hypertension include:  epoprostenol, treprostinil, iloprost, bosentan, ambrisentan, macitentan, and sildenafil.

Lung transplantation may be an option in severe cases. 

Basic treatment: oxygen therapy, diuretics to decrease swelling, and antocoagulants to prevent blood clots, and exercise.

 

Pulmonary arterial hypertension can be treated with medications to dilate the pulmonary artery.

 

Lung transplant may be considered in severely affected patients.

 

Pulmonary hypertension due to lung disease is treated with medications for the underlying disease, and oxygen therapy.

 

Pulmonary hypertension due to blockage and blood vessels can be treated sometimes with surgical removal.

Treprostinil Is the stable analogue of prostacyclin,  which promotes direct basal dilatation of pulmonary and systemic arterial vascular beds and inhibits plate with aggregation.

The inhaled formulation of Treprostinil improves patients with group 1 pulmonary hypertension.

Sotatercept a fusion protein designed to trap activism  and growth differential factor 8 and 11 reduces pulmonary vascular resistance in patients with pulmonary hypertension (STELLAR trial).

Patients are normally monitored through commonly available tests:

Pulse oximetry

Arterial blood gas tests

Chest X-rays

Serial ECG tests

Serial echocardiography

Spirometry or more advanced lung function studies

6-minute walk test

PAH is considered a universally fatal illness.

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.

With new therapies, survival rates are increasing. 

Levels of mortality are very high in pregnant women with severe pulmonary arterial hypertension (WHO Group I). 

Pregnancy is relatively contraindicated in this group.

Connective tissue disease associated pulmonary arterial hypertension affects 15 to 25% of patients with pulmonary arterial hypertension most commonly: scleroderma, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, and Sgogren syndrome.

In systemic scleroderma, the incidence of PAH has been estimated to be 8 to 12% of all patients.

Patients with scleroderma associated pulmonary arterial hypertension have a worse prognosis compared with other forms of connective tissue associated pulmonary arterial hypertension and have a higher prevalence of pericardial effusion,  shorter six minute walk distance, worse digfusion lung capacity compared with those with idiopathic pulmonary arterial hypertension.

Patients with scleroderma who have pulmonary hypertension have a higher rate of mortality and those without pulmonary hypertension, 94% versus 56% at three years.

In systemic lupus erythematosus it is 4 to 14%, and in sickle cell disease, it ranges from 20 to 40%.

Up to 4% of people who suffer a pulmonary embolism go on to develop chronic thromboembolic disease including pulmonary hypertension.

Only a small percentage of patients with COPD develop pulmonary hypertension without other explanation.

Obesity-hypoventilation syndrome is very commonly associated with right heart failure due to pulmonary hypertension.

 

 

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