Pulmonary hypertension (PH) is defined by an elevated mean pulmonary arterial pressure (mPAP) > 20 mm Hg at rest. PH is divided into five groups based on the underlying causes: pulmonary arterial hypertension (PAH), left heart disease, chronic lung disease, pulmonary artery obstruction (e.g., due to chronic thromboembolic disease), and unclear multifactorial mechanisms. Over time, the increase in right ventricular pressure may result in structural changes (e.g., dilation or hypertrophy) or impaired function of the right ventricle, a cardiac condition known as cor pulmonale. While PH is often asymptomatic in the early stages, symptoms such as dyspnea on exertion, fatigue, cyanosis, and syncope appear in later stages. Echocardiograms are used as an initial noninvasive test to estimate pulmonary artery pressure and to evaluate for right ventricular dysfunction. Right heart catheterization provides a definite diagnosis by measuring mPAP but is not always required. Treatment mainly consists of managing the underlying cause of PH and preventing disease progression. Patients with PAH (i.e., ) usually benefit from treatment with calcium channel blockers and other pulmonary vasodilators, while their benefit is unclear for other groups. In most cases, evaluation by a PH specialist and referral to specialized centers is recommended. Acute decompensated pulmonary hypertension is a high-mortality complication that can occur and is very challenging to treat, typically requiring intensive care, and in some cases, ECMO and lung transplant. Some patients can develop acute or chronic cor pulmonale, which requires treatment of the underlying cause and, in some cases, acute stabilization.
Pulmonary hypertension (PH) 
- An elevated mean pulmonary arterial pressure (mPAP) > 20 mm Hg at rest (normal: 10–14 mm Hg) 
Precapillary pulmonary hypertension
- Pulmonary vascular remodeling leads to increased pulmonary vascular resistance.
- Caused by pulmonary arterial hypertension, chronic lung disease, chronic thromboembolism, or certain multifactorial mechanisms
- Right heart catheterization shows increased pulmonary vascular resistance (≥ 3 Wood units) and reduced pulmonary capillary wedge pressure (PCWP).
- Postcapillary pulmonary hypertension
- Precapillary pulmonary hypertension
- Pulmonary arterial hypertension (PAH): a type of precapillary pulmonary hypertension characterized by loss and obstructive remodeling of the pulmonary vascular bed that results in increased pulmonary arterial pressure (See “Etiology” for underlying causes) 
- PAH: more commonly affects female individuals
Epidemiological data refers to the US, unless otherwise specified.
Pulmonary arterial hypertension (Group 1 PH)
- Hereditary (e.g., BMPR2 loss-of-function mutation)
- Drug-induced 
- Associated conditions
Left heart disease (Group 2 PH)
- Congestive heart failure (CHF): e.g., HFrEF, HFpEF
- , e.g., aortic valve stenosis, mitral valve stenosis
- Other acquired or congenital heart diseases causing (e.g., , , , )
Chronic lung diseases (Group 3 PH)
- : e.g.,
- High altitude (e.g., high-altitude pulmonary hypertension)
- Others: e.g., developmental lung disorders, mixed obstructive and restrictive lung diseases
Pulmonary artery obstruction (Group 4 PH) 
Chronic thromboembolic pulmonary hypertension (CTEPH): Chronic thromboembolic occlusion of the pulmonary vessels
- Recurrent microthrombi narrow the cross-sectional area of pulmonary vessels.
- Affected individuals are at high risk for pulmonary embolism.
- Other causes of pulmonary artery (PA) obstruction: extrinsic compression by mediastinal tumors or masses, arteritis involving PAs, congenital PA stenoses, 
Unclear multifactorial mechanisms (Group 5 PH)
- Hematologic disorders (e.g., sickle cell disease, MPNs, chronic hemolytic anemias)
- Systemic disorders (e.g., sarcoidosis, neurofibromatosis, Langerhans cell histiocytosis)
- Metabolic disorders (e.g., metabolic syndrome, chronic kidney disease, Gaucher disease)
- Complex congenital heart disease 
Conditions at high risk of PH 
Periodic screening and monitoring for clinical features of PH is suggested for patients with any of the following:
- Family history of PAH
- Genetic screening positive in the patient or 1st-degree relative (e.g., for BMPR2)
- Exposure to drug or toxin known to cause PH (e.g., methamphetamine, fenfluramine)
- Mixed connective tissue diseases
- Portal hypertension
- Recent (e.g., within the last 3–6 months) surgical repair of a congenital
Increased pulmonary vascular resistance
- Occlusive vasculopathy (e.g., idiopathic pulmonary arterial hypertension, )
- Hypoxic pulmonary vasoconstriction: chronic hypoxic pulmonary vasoconstriction → airway smooth muscle hypertrophy (medial hypertrophy) and pulmonary vascular bed destruction → ↑ pulmonary vascular resistance (e.g., ,
- Increased pulmonary vessel pressure → right heart hypertrophy → right heart failure (cor pulmonale) and arrhythmias → death
- Inflammation (e.g., ) →↑ inflammatory cell infiltration of intima → thickened endothelial wall → intimal fibrosis
- PAH associated with endothelial dysfunction: ↑ endothelin and ↓ vasodilators (e.g., NO, prostacyclins) → vasoconstriction → arteriosclerosis, plexiform lesions 
- Increased pulmonary venous pressure: volume or pressure overload from left-sided heart disease (e.g. )
- Increased pulmonary blood flow
Patients with early PH may be asymptomatic.
- Common clinical features
- Less common clinical features
- Physical examination
Due to overlapping clinical features, PH is often diagnosed during the evaluation of more common differential diagnoses and etiologies of dyspnea, chest pain, and fatigue (e.g., COPD, CHF, cardiomyopathy, PE, OSA), or identified during screening echocardiography or cardiac catheterization (e.g., preoperative assessment).
- Screen and monitor patients with for suggestive clinical features. 
- If clinical suspicion is high for PH, perform (TTE) to noninvasively identify markers of elevated pulmonary artery pressure.
- If TTE suggests PH and the etiology is not yet known, begin evaluation for the most common underlying causes.
- If the etiology remains unclear, TTE is equivocal, and/or severe PH is identified (see “Severity assessment”):
Transthoracic echocardiography (TTE) 
For clinical purposes, noninvasive estimates of mPAP and its surrogate markers, (PASP) and right ventricular systolic pressure (RVSP), are typically accurate enough to make a diagnosis of PH and guide therapy. 
- Indication: first-line study in all patients with suspected PH 
Findings: A combination of findings can be used to estimate , RVSP, and . 
- ↑ Tricuspid regurgitation velocity (TRV)
- Right ventricular pressure overload
Right ventricular failure
- Dilation and hypokinesis of the right ventricle
- Right atrial dilation
- Underfilled left heart chambers
- Evidence of underlying cardiovascular disease
Right heart catheterization 
- Findings: mPAP > 20 mm Hg at rest is considered diagnostic for PH. 
- Typically shows nonspecific changes secondary to increased right ventricular workload
- May also show signs of underlying etiology, e.g., ischemic heart disease
- Right heart hypertrophy
- Enlarged central pulmonary arteries
- Reduction in number and size of vessels of the peripheral pulmonary vasculature (referred to as pulmonary vascular pruning)
- Signs of the underlying cause (e.g., nodular opacities in heart disease) , in , pulmonary venous congestion in left
Investigations of the underlying cause
Consider adding the following based on clinical suspicion of the underlying etiology:
- Left heart disease: NT-proBNP (See also “Diagnostics” in “CHF” and “Mitral regurgitation.”)
- Chronic lung disease (See also "Diagnostics" in “COPD,” “ILD,” and “OSA.”)
- Chronic pulmonary thromboembolism: V/Q scan (See also “ PE diagnostics.”)
Others: Consider if etiology remains unclear after investigations for left-heart disease, chronic lung disease, and CTEPH. 
- Drug-induced: e.g., urine drug screen
- liver chemistries, consider ultrasound liver. : Send
- Infection (based on risk factors): e.g., screen for HIV and schistosomiasis.
- Connective tissue disease (most commonly systemic sclerosis): e.g., antinuclear antibodies, anticentromere antibodies, anti-Scl-70 and anti-RNA polymerase III
- Sarcoidosis: e.g., inflammatory markers, serum calcium, ACE levels
- Hereditary: e.g., genetic testing
- Treat urgently, if present.
- Determine functional severity and screen for high-risk features; consult PAH specialist and strongly consider admission to PAH specialty center if present.
- Tailor treatment according to (see “Long-term management”).
Therapy should be initiated early before irreversible changes in the pulmonary vessels occur.
WHO functional class for PH (WHO-FC) 
- WHO-FC I: No limitations in physical activity; no significant symptoms during most regular ADLs and IADLs
- WHO-FC II: Slightly limited physical activity; no rest symptoms, but some symptoms during IADLs
- WHO-FC III: Noticeably limited physical activity; consistent symptoms during basic ADLs
- WHO-FC IV: Severely limited physical activity; frequent and/or progressive symptoms with almost any activity or even at rest
High-risk features 
- Assess for shock (e.g., or ).
- Consult a PH specialist.
- Admit to ICU and start continuous monitoring.
- Identify and treat any precipitating factors.
- Missed or interrupted medical treatment, e.g., IV prostacyclin pump failure
Respiratory support 
- ; consider > 90%HFNC for patients with high oxygen demand. 
- If possible, avoid intubation and (PPV).
- Extreme caution and specialist consultation is advised if mechanical ventilation is unavoidable. 
Hemodynamic support 
Consult a PH specialist to guide therapy and tailor treatment to individual needs.
General treatment goals
- Targeting euvolemia
- RV afterload reduction: e.g., with (prescribed by a PH specialist) 
- Optimizing cardiac output and peripheral perfusion: typically with a combination of dobutamine) and other vasopressors (e.g, norepinephrine) (e.g.,
- Refractory right heart failure: Consider as a bridge to urgent lung or heart-lung transplant. 
Patients with an IV prostacyclin pump (e.g., epoprostenol) 
- Consult the patient's PAH specialist immediately for any mechanical issues (e.g., suspected device failure or problems with tube patency).
- Do not stop the infusion or adjust dosage or flow rates without guidance from the treating specialist.
Management of acute decompensated PH is extremely challenging and should take place in a specialized center whenever possible. Consult a PAH specialist immediately for any issues with IV prostacyclin pumps. 
Consider individualized treatment based on the underlying condition and patient characteristics under the guidance of an appropriate specialist (e.g., cardiology, pulmonology). Calcium channel blockers and other pulmonary vasodilators are the mainstay of treatment for (i.e., PAH), while treatment of the underlying cause is the primary focus for the other WHO PH groups.
Supportive care 
- Oxygen therapy for patients with COPD and a PaO2 < 60 mm Hg
- Diuretics for volume overload
- Psychosocial support
- Exercise training 
- Avoidance of the following, whenever possible: 
- Pregnancy: Offer . 
- High altitude
- Nonessential surgeries
- Consider referral to palliative care for patients with advanced PH and distressing symptoms.
Patients who have a normal oxygen saturation at rest may desaturate with exercise or while sleeping; perform exercise and nocturnal oximetry and treat accordingly.
Group 1 PH: PAH 
- : A test performed during right heart catheterization to identify responsiveness to calcium channel blocker (CCB) therapy; mPAP is measured after administration of a vasodilator (e.g., inhaled nitric oxide) 
- Calcium channel blockers: First-line pulmonary vasodilator therapy for patients with PAH and positive and no or other contraindications to CCBs 
- Other pulmonary vasodilator therapies: typically second-line agents, the choice of which depends on symptom severity (e.g., WHO-FC) and should be guided by a PAH specialist. 
|Overview of specific pulmonary vasodilator agents|
|Agents||Clinical applications||Mechanism of action||Adverse effects||Contraindications||Interactions|
Endothelin receptor antagonists (e.g., bosentan, macitentan, ambrisentan) 
|Phosphodiesterase-5 inhibitors (e.g., sildenafil)|
|Prostacyclin analogs (iloprost, treprostinil)|| |
|Synthetic prostacyclin (epoprostenol) || |
- Surgical therapy for refractory PAH
heart disease : Left-sided
- Treat systemic hypertension (see “ ”).
- Provide as needed.
- Consider replacement or repair of damaged valves (see “Aortic valve stenosis”, “Aortic regurgitation, “Mitral valve stenosis”, and “Mitral regurgitation”).
- Aggressively treat any atrial fibrillation (see “Management of Afib with RVR” and “Management of Afib in CHF”).
- Treat comorbidities, e.g., diabetes, obesity, .
lung disease : Chronic
- Start .
- Optimize treatment of underlying COPD or interstitial lung disease.
- Consider lung transplantation.
: PA obstruction
- Pulmonary endarterectomy is the first-line treatment.
- Consider balloon pulmonary angioplasty if the patient is ineligible for pulmonary endarterectomy or if PH persists or recurs.
- Consider certain pulmonary vasodilators in select cases.
- Treat associated hypoxia and heart failure.
- Lifelong anticoagulation
- Extrinsic compression (rare): Consider treatment tailored to the individual extrinsic etiology. 
Altered structure (i.e., hypertrophy, dilation) or impaired function of the right ventricle due to pulmonary hypertension resulting from a primary disorder of the respiratory or pulmonary artery system
Acute cor pulmonale 
- Pathophysiology: a sudden increase in right ventricular afterload results in right ventricular dilation and dysfunction
- Etiology: : includes acute massive pulmonary embolism (most common) and ARDS 
- Clinical features: acute onset, chest pain, shortness of breath, hypotension, tachycardia, syncope, symptoms of deep vein thrombosis
Chronic cor pulmonale 
- Pathophysiology: Increased right ventricular afterload leads to progressive right ventricular hypertrophy that over time results in right ventricular dilation and dysfunction.
- Etiology: caused by diseases of the lung parenchyma and pulmonary vasculature or disorders of chronic hypoxia
- Similar to clinical features of pulmonary hypertension.
- Echocardiogram shows right ventricular dilation, hypertrophy, or dysfunction.
- Further workup depends on the suspected underlying cause; see “Diagnostics” of “Pulmonary hypertension.”
- For patients with suspected acute cor pulmonale, urgently perform .