Pulmonary
Hypertension
Pulmonary Hypertension
Incidence and Prevalence of Pulmonary Hypertension
- Pulmonary Hypertension (PH) is a major global health issue affecting all age groups
- Estimates suggest that around 1% of the global population has PH, increasing to 10% in those aged over 65 years
- Globally, left-sided heart and lung disease are the most common causes of PH

Very Common
PH associated with left heart disease [WHO Group 2]
Common
PH associated with lung disease [WHO Group 3]
Rare
- Pulmonary Arterial Hypertension [WHO Group 1]
- PH associated with pulmonary artery obstructions [WHO Group 4]
- PH with unclear and/or multifactorial mechanisms [WHO Group 5]
PH, Pulmonary Hypertension; WHO, World Health Organization.
Reference: Hoeper MM, et al. Lancet Respir Med. 2016;4(4):306–22.
Pulmonary Hypertension is categorized into five groups according to the World Health Organization [WHO] classification
Group 1
PAH
Incidence and prevalence are reported to be ~6 and 48–55 cases/million adults, respectively.1,2 Idiopathic PAH is the most common subtype (50–60% of all cases), followed by PAH associated with connective tissue disease, congenital heart disease, and portal hypertension.1,3
Group 2
PH associated with left-sided heart disease
The prevalence of PH increases with severity of left-sided valvular diseases and can be found in 60–70% of patients with severe and symptomatic mitral valve disease4 and in up to 50% of those with symptomatic aortic stenosis.1,5
Group 3
PH associated with lung disease and/or hypoxia
~1–5% of patients with advanced COPD have an mPAP > 35–40 mmHg.1,6,7 8–15% of patients with idiopathic pulmonary fibrosis have an mPAP ≥ 25 mmHg, with prevalence increasing in advanced (30–50%) and end-stage disease (60%).1,7
Group 4
PH associated with chronic pulmonary artery obstruction
Incidence and prevalence of Chronic Thromboembolic Pulmonary Hypertension are reported to be 2–6 and 26–38 cases/million adults, respectively.1,2,8,9
Group 5
PH with unclear and/or multifactorial mechanisms
As the causes of this disorder are often multifactorial and can be secondary to increased pre- and post-capillary pressure, the incidence and prevalence in most cases are unknown.1
COPD, Chronic Obstructive Pulmonary Disease; mPAP, Mean Pulmonary Arterial Pressure; PAH, Pulmonary Arterial Hypertension; PH, Pulmonary Hypertension. References: 1. Humbert M, et al. Eur Heart J. 2022;43(38):3618–731. 2. Leber L, et al. Pulm Circ. 2021;11:2045894020977300. 3. Lau EMT, et al. Nat Rev Cardiol. 2017;14:603–14. 4. Tichelbacker T, et al. Herz. 2019;44:491–501. 5. Weber L, et al. Eur J Heart Fail. 2019;21:172–81. 6. Hurdman J, et al. Eur Respir J. 2013;41:1292–301. 7. Nathan SD, et al. Eur Respir J. 2019;53:1801914. 8. Delcroix M, et al. Eur Respir J. 2021;57:2002828. 9. Kramm T, et al. Clin Res Cardiol. 2018;107:548–53.
What is Pulmonary Hypertension?
- PH is a disease of the lungs and heart where there is a pathologic increase in blood pressure in the pulmonary arteries. It is caused by several disorders and results in remodeling and narrowing of the pulmonary arteries, leading to right-heart failure1
- Loss of dilatory capacity and vasoconstriction of the pulmonary arteries occurs early in the course of PH
- Obstruction of the pulmonary artery, tightening and/or thickening of the artery wall (vascular remodeling) increase pulmonary blood pressure1-4
- The right side of the heart has to work harder to pump blood through the narrowed arteries1
- Eventually, the right heart becomes enlarged and consequently is less able to pump blood through the lungs, leading to right heart failure and death1-4
- Without treatment, the disease is characterized by high mortality rates
PH, Pulmonary Hypertension.
References: 1. Rosenkranz S. Clin Res Cardiol 2007;96:527–41. 2. Rosenblum WD. Cardiol Rev 2010;18:58–63. 3. Humbert M. Eur Respir Rev 2010;19:59–63.
4. Bousseau S. BMJ Medicine 2023;2:e000137.

PH, Pulmonary Hypertension.
References: 1. Rosenkranz S. Clin Res Cardiol 2007;96:527–41. 2. Humbert M, et al. Eur Heart J. 2022;43(38):3618–731.
Hemodynamic Definitions of Pulmonary Hypertension
PH
mPAP > 20 mmHg
Pre-Capillary PH
mPAP > 20 mmHg
PAWP ≤ 15 mmHg
PVR > 2 WU
Isolated
Post-Capillary PH
mPAP > 20 mmHg
PAWP > 15 mmHg
PVR ≤ 2 WU
Combined Pre- and Post-Capillary PH
mPAP > 20 mmHg
PAWP > 15 mmHg
PVR > 2 WU
Exercise PH
mPAP/CO slope between rest and exercise
> 3 mmHg/L/min
CO, Cardiac Output; CpcPH, Combined Pre- and Post-Capillary Pulmonary Hypertension; IpcPH, Isolated Post-Capillary Pulmonary Hypertension; mPAP, Mean Pulmonary Arterial Pressure; PAWP, Pulmonary Arterial Wedge Pressure; PH, Pulmonary Hypertension; PVR, Pulmonary Vascular Resistance; WU, Wood Units.
Reference: Humbert M, et al. Eur Heart J. 2022;43(38):3618–731.
Clinical Classification of Pulmonary Hypertension
Pulmonary Hypertension is categorized into five groups according to the World Health Organization [WHO] classification
Group 1
PAH
Idiopathic (IPAH)
- Non-responders to vasoreactivity testing
- Acute responders to vasoreactivity testing
Heritable
Associated with drugs and toxins
Associated with:
- Connective tissue disease
- HIV infection
- Portal hypertension
- Congenital heart disease
- Schistosomiasis
PAH with features of venous/capillary (PVOD/PCH) involvement
Persistent PH of the newborn
Group 2
PH associated
with left-heart disease
Heart failure
- With preserved ejection fraction
- With reduced or moderately reduced ejection fraction
Valvular heart disease
Congenital/acquired cardiovascular conditions leading to post-capillary PH
Group 3
PH associated with
lung diseases and/or hypoxia
Obstructive lung disease or emphysema
Restrictive lung disease
Lung disease with mixed restrictive/obstructive pattern
Hypoventilation syndromes
Hypoxia without lung disease (e.g. high altitude)
Developmental lung disorder
Group 4
PH associated with pulmonary artery obstruction
CTEPH
Other pulmonary artery obstructions
Group 5
PH with unclear and/or multifactorial mechanisms
Hematologic disorders
Systemic disorders
Metabolic disorders
Chronic renal failure with or without hemodialysis
Pulmonary tumor thrombotic microangiopathy
Fibrosing mediastinitis
CTEPH, Chronic Thromboembolic Pulmonary Hypertension; HIV, Human Immunodeficiency Virus; IPAH, Idiopathic Pulmonary Arterial Hypertension; PAH, Pulmonary Arterial Hypertension; PCH, Pulmonary Capillary Hemangiomatosis; PH, Pulmonary Hypertension; PVOD, Pulmonary Veno-Occlusive Disease.
Reference: Humbert M, et al. Eur Heart J. 2022;43(38):3618–731.
Pulmonary Hypertension Diagnostic Workup
- A multi-step, pragmatic approach to diagnosis should be considered in patients with unexplained dyspnea or symptoms/signs raising suspicion of pulmonary hypertension (PH)
Suspicion
- Symptom assessment, medical and family history, physical examination (including blood pressure, heart rate, and pulse oximetry)
Detection
- Laboratory testing including brain natriuretic peptide/N-terminal probrain natriuretic peptide
- Resting electrocardiogram
- Non-invasive lung and cardiac testing, to include pulmonary function testing, echocardiography, VQ scan, and in some cases cardiopulmonary exercise testing
Confirmation
- Referral to PH center when an intermediate/high probability of PH is established, or in the presence of risk factors for Pulmonary Arterial Hypertension (PAH) or a history of pulmonary embolism
- Comprehensive workup to establish differential diagnoses and distinguish between PH etiologies
- Invasive hemodynamic assessment via right heart catheterization (RHC) is required to confirm a diagnosis of PAH
PAH, Pulmonary Arterial Hypertension; PH, Pulmonary Hypertension; RHC, Right Heart Catheterization; VQ, Ventilation/Perfusion Scan.
Reference: Humbert M, et al. Eur Heart J. 2022;43(38):3618–731.
The diagnosis of Group 1 PAH is a diagnosis of exclusion where other common causes of Pulmonary Hypertension such as underlying left heart and/or lung disease must be ruled out.
CTEPH, Chronic Thromboembolic Pulmonary Hypertension; PAH, Pulmonary Arterial Hypertension; PH, Pulmonary Hypertension.
Reference: Humbert M, et al. Eur Heart J. 2022;43(38):3618–731.
Diagnostic Assessments for Pulmonary Hypertension

CTEPH, Chronic Thromboembolic Pulmonary Hypertension; ECG, Electrocardiogram; PH, Pulmonary Hypertension.
Reference: Humbert M, et al. Eur Heart J. 2022;43(38):3618–731.
Gold Standard Diagnostic Assessment for Pulmonary Hypertension
- Right Heart Catheterization (RHC) is the gold standard for diagnosing and classifying PH as it accurately determines hemodynamic parameters1,2
- As RHC is a procedure requiring expertise and meticulous methodology, it is recommended to be performed at expert PH centers1,2
PH, Pulmonary Hypertension; RHC, Right Heart Catheterization.
References: 1. Humbert M, et al. Eur Heart J. 2022;43(38):3618–731. 2. Hoeper MM, et al. J Am Coll Cardiol. 2006;48:2546–52.
PH, Pulmonary Hypertension; RHC, Right Heart Catheterization.
References: 1. Humbert M, et al. Eur Heart J. 2022;43(38):3618–731. 2. Hoeper MM, et al. J Am Coll Cardiol. 2006;48:2546–52.

Treatment Goals for Pulmonary Hypertension
- The optimal therapy for a patient is an individualized decision, taking into account many factors including severity of illness, side effects, comorbid illness, treatment goals, and patient & clinician preference
- Treatment is focused on optimal management of underlying conditions that are causing pulmonary hypertension (e.g. optimization of underlying cardiac and lung conditions)
Reference: McLaughlin VV, et al. J Am Coll Cardiol. 2009;53:1573–619.