PULMONARY EMBOLISM PULMONARY HYPERTENSION COR ... 3. Pulmonary hypertension due to lung disease and/or

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  • PULMONARY EMBOLISM

    SIMONA TRUBAČOVÁ simona.trubačova@gmail.com

    PULMONARY HYPERTENSION COR PULMONALE

  • PULMONARY AND SYSTEMIC CIRCULATION

  • WHAT IS THE

    DIFFERENCE

    BETWEEN

    PULMONARY

    AND

    SYSTEMIC

    CIRCULATION?

    Cardiac output

    RV = LV

    (~ 5L/min)

  • pressure

    (25/8 mmHg

    mean PAP

    =12 – 16 mmHg)

    pressure

    (120/80 mmHg

    mean pressure

    = 100 mmHg)

    resistance

    (1/6 – 1/10

    systemic resistance)

    resistance

    compliance compliance

    PULMONARY

    CIRCULATION

    SYSTEMIC

    CIRCULATION

  • pulmonary circulation

    RESPONSE TO LOCAL HYPOXIA

    systemic circulation

    vasodilatation

    hypoxic pulmonary vasoconstriction

  • Pulmonary hypertension (PH) is defined as an

    increase in mean pulmonary arterial

    pressure (PAPm) ≥ 25 mmHg at rest assesed

    by right heart catheterisation.

    ▪ orphan disease (1case per 50 000 people)

    ▪ progressive disease – limited life expectancy

    PULMONARY HYPERTENSION

  • 1. PULMONARY

    ARTERIAL

    HYPERTENSION (PAH)

    2. PULMONARY HYPERTENSION DUE

    TO LEFT HEART DISEASE

    3. PULMONARY

    HYPERTENSION DUE

    TO LUNG DISEASE

    AND/OR HYPOXIA

    4. CHRONIC

    TROMBOEMBOLIC

    PULMONARY

    HYPERTENSION (CTPH)

    CLINICAL CLASSIFICATION OF

    PULMONARY HYPERTENSION

    5. PULMONARY HYPERTENSION WITH UNCLEAR MULTIFACT. MECHANISMS

  • CLINICAL CLASSIFICATION OF

    PULMONARY HYPERTENSION

    1. Pulmonary arterial hypertension

    1.1 Idiopathic PAH

    1.2 Heritable PAH 1.2.1 BMPR2

    1.2.2 ALK1, ENG, SMAD9, CAV1,

    KCNK3

    1.2.3 other mutations

    1.3 Drug & toxins induced

    1.4 Associated with 1.4.1 connective tissue disease

    1.4.2 HIV infection

    1.4.3 portal hypertension

    1.4.4 congenital heart disease

    1.4.5 schistosomiasis

  • 2. Pulmonary hypertension due to left heart

    disease

    2.1 systolic dysfunction

    2.2 diastolic dysfunction

    2.3 valvular disease

    2.4 congenital/aquired left heart inflow/outflow tract obstruction

    and congenital cardiomyopathies

    2.5 congenital/acquired pulmonary vein stenosis

    CLINICAL CLASSIFICATION OF

    PULMONARY HYPERTENSION

  • 3. Pulmonary hypertension due to lung

    disease and/or hypoxia

    3.1 chronic obstructive pulmonary disease

    3.2 interstitial lung disease

    3.3 other pulmonary diseases with mixed restrictive & obstructive

    pattern

    3.4 sleep-disordered breathing

    3.5 alveolar hypoventilation disorders

    3.6 chronic exposure to high altitude

    3.7 developmental lung diseases

    CLINICAL CLASSIFICATION OF

    PULMONARY HYPERTENSION

  • 4. Chronic tromboembolic pulmonary

    hypertension (CTPH)

    5. Pulmonary hypertension with unclear

    multifactorial mechanisms

    5.1 haematological disorders: chronic haemolytic anaemia

    5.2 systemic disorders, sarcoidosis

    5.3 metabolic disorders: glycogen storage disease, thyroid

    disorders

    5.4 other: segmental PH, chronic renal failure, fibrosis

    mediastinitis

    CLINICAL CLASSIFICATION OF

    PULMONARY HYPERTENSION

  • mean pulmonary artery

    pressure (PAPm) ≥ 25 mmHg

    hypertrophy & failure of RIGHT VENTRICLE

    1. PAH

    2. PH DUE TO LEFT HEART DISEASE

    3. PH DUE TO LUNG DISEASE AND/OR HYPOXIA

    4. CTEPH

    5. PH WITH UNCLEAR MULTIFACT. MECHANISMS

  • CLINICAL SIGNS & SYMPTOMS

    hemoptysis

    breathing

    shortness

    (dyspnoea)

    wheezing

    hepatomegaly

    ascites

    fatigue weakness

    syncope

    (loss of consciousness)

    peripheral

    edema

    ↑ jugular venous pressure

    chest pain

    (angina)

  • DIAGNOSTICS

    NON-SPECIFIC SYMPOMS

  • FUNCTIONAL CLASSIFICATION

  • SURVIVAL ACCORDING TO FUNCT. CLASS

    poor outcome relative to patients in lower FC

  • CHEST RADIOGRAPHY

    DIAGNOSTICS

    - central pulmonary arterial dilatation = PRUNING

    - loss of peripheral blood vessels

    - right atrium and right ventricle enlargement

  • ECHOCARDIOGRAPHY –

    RV

    LV

    LARA

    normal PH

    DIAGNOSTICS

    - estimation of pressure in a. pulmonalis

    - PH caused by valvular disease

    - evaluation of right ventricular size (enlargement, hypertrophy) function

  • Electrocardiogram

    Ventilation/perfusion lung scan (to diagnose PE)

    CT angiogram

    Serological testing HIV test (1. PAH)

    Genetic testing 1. HPAH

    Thrombophilia screening 4. CTPH

    Six-minute walk test the results correlate with the progression and prognosis of the

    disease

    DIAGNOSTICS

  • DIAGNOSTICS – final confirmation

    right heart catheterization with Swan – Ganz catheter

    Pulmonary Artery

    Wedge Pressure (PAWP)

    Mean Pulmonary Artery

    Pressure (mPAP)

  • Pre – capilary PH: PAPm ≥ 25 mmHg

    PAWP ≤ 15 mmHg

    Post – capilary PH: PAPm ≥ 25 mmHg

    PAWP >15 mmHg

    II. PH due to

    LHD

    III. PH due to respiratory

    disease

    I. PAH

    IV. CTEPH

    HAEMODYNAMIC DEFINITIONS OF

    PULMONARY HYPERTENSION

  • Epidemiology PAH (in Europe): incidence : 5-6 cases/million adults/year prevalence: 15 - 60 cases/million adults

    Idiopatic PAH 30-50% of all pacients with PAH (without known cause or associated factors)

    Heriteble PAH 75% heterozygous BMPR2 (type 2 receptor of bone morphogenic protein) mutation

    1. PULMONARY ARTERIAL HYPERTENSION

  • 1. PULMONARY ARTERIAL HYPERTENSION

    HPAH

    heterozygous mutation

    autosomal dominant disorder

    with penetrance ~ 20%

    What are the chances

    that child of affected

    parent (PH – BMPR2

    mutatoion) will be also

    affected by this heritable

    form of PH?

  • Drug & toxins induced PAH

    (amphetamines, appetite suppressants..)

    PAH associated with

    connective tissue disease HIV

    congenital heart disease portal hypertension

    (Eisenmenger‘s syndrome)

    schistosomiasis

    1. PULMONARY ARTERIAL HYPERTENSION

  • 1. PATHOGENESIS of PAH

    pulmonary vasculature injury:

    VOSOCONSTRICTION

    INFLAMATION

    TROMBOSISgenetic factors

    risk factors +

    associated conditions remodeling

    SMC proliferation

    ↑ pulmonary resistance

    & pressure

    PAH

  • most common form of PH in developed countries

    post – capilary form of PH

    development in response to the passive backward

    transmission of elevated left-sided filling pressures

    systolic dysfunction

    diastolic dysfunction

    valvular disease

    2. PULMONARY HYPERTENSION DUE TO

    LEFT HEART DISEASE

  • valvular disease

    2. PULMONARY HYPERTENSION DUE TO

    LEFT HEART DISEASE

  • chronic obstructive pulmonary disease

    interstitial pulmonary disease

    obstructive sleep apnea

    alveolar hypoxy

    hypoxic pulmonary vasoconstriction

    3. PULMONARY HYPERTENSION DUE TO

    LUNG DISEASE AND/OR HYPOXIA

  • 4. CHRONIC TROMBOEMBOLIC

    PULMONARY HYPERTENSION (CTPH)

    development due to chronic tromboembolic disease

    → non dissolvable trombus → fibrosis

    mechanical obstruction of pulmonary artery

  • to maintain patients in funcional class I - II

    GENERAL MEASURES infection prevention

    avoiding high altitude

    prevention of pregnancy

    physical activity & rehabilitation

    TREATMENT OF PRIMARY CAUSE of PH

    2. PH due to LHD (valve repairment) 3. PH due to respiratory disease (treatment of COPD, apnea)

    4. CTEPH (anticoagulation treatment)

    TREATMENT

  • SUPPORTIVE THERAPY:

    - diuretics

    - oral anticoagulants

    - oxygen administration

    SPECIFIC DRUG THERAPY

    CALCIUM CHANNEL BLOCKERS

    - small number of patients who demonstrate a favorable

    response to vasodilator testing

    TREATMENT

  • SPECIFIC DRUG THERAPY

    TREATMENT

    ENDOTHELIN RECEPTOR

    ANTAGONISTS

    endothelin = strong vasoconstrictor

    binding & blocking of Endothelin

    receptors - inducing vasodilation

  • SPECIFIC DRUG THERAPY

    TREATMENT

    PHOSPODIESTERASE TYPE 5

    INHIBITORS

    chronic PH – ↑ syntesis of PDE - 5

    PDE – 5 degredation of cGMP

    (2. messenger of NO vasadilation)

    GUANYLATE CYCLASE STIMULATORS

    inhibition of PDE – 5 → ↑ conc. cGMP

    direct stimulation of cGMP production

  • SPECIFIC DRUG THERAPY

    TREA