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
    Globe with 1% and a stethoscope around it
    Heart icon

    Very Common

    PH associated with left heart disease [WHO Group 2]

    Lungs icon

    Common

    PH associated with lung disease [WHO Group 3]

    Pulmonary artery icon

    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
    Pictorial representation of the pathophysiology of Pulmonary Hypertension

    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.

    Characteristics of Pulmonary Hypertension including definition, symptoms, criteria and diagnosis

    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)
    Step 1 icon

    Suspicion

    • Symptom assessment, medical and family history, physical examination (including blood pressure, heart rate, and pulse oximetry)
    Step 2 icon

    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
    Step 3 icon

    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.

    Diagnosis of unexplained dyspnea or symptoms/signs raising suspicion of pulmonary hypertension (PH) after which other common causes 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

    Diagnostic assessments of 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.

    Pictorial representation of Right Heart Catheterization (RHC), a gold standard diagnostic assessment for Pulmonary Hypertension

    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.

    Alt tag

    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.