PULMONARY EMBOLISM

SIMONA TRUBAČOVÁsimona.trubačova@gmail.com

PULMONARY HYPERTENSIONCOR 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

compliancecompliance

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

fatigueweakness

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/yearprevalence: 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 MEASURESinfection 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

TREATMENT

PROSTACYCLIN ANALOGUES

PH – dysregulation of prostacyclin pathway

↓ production of prostacyclin

Prostacyclin – vasodilator

inhibitor of platelet

aggregation

antiproliferative activities

SURGICAL THERAPY:

pulmonary endarterectomy

removal of bloodclots from

pulmonary artery

(3. CTPH)

balloon atrial septosomy

hole created in atrial septum

to decrease pressure overload

of right heart

lung transplantation/

heart&lung transplantation

TREATMENT

Pulmonary embolism (PE) is on occlusion or partial

occlusion of the pulmonary artery or its branch by

an embolus

– mostly (in 95% of cases) from deep vein

thrombosis

PULMONARY EMBOLISM

Venous ThromboEmbolism (VTE)

DEEP VEIN TROMBOSIS (DVT) PULMONARY EMBOLISM (PE)

Annual incidence of VENOUS THROMBOEMBOLISM

[DEEP VEIN TROMBOSIS + PULMONARY EMBOLISM]

100 – 200 cases/100 000/year

3. most common cause of

cardiovascular disease

(after hypertension &

Ischemic heart disease)

most common preventable

cause of death in

hospitalized patients

flow stasis

immobilization

hospitalization

obesity

blood coagulation

major surgery/trauma

hormonal contraceptives

pregnancy

cancer

vessel injury

atherosclerosis infection

hypertension implants

trauma

VIRCHOW‘S TRIAD

PULMONARY EMBOLISM

MASSIVE PE

ACUTE SMALL PE

CHRONIC RECCURENT PE

RV dilatation

↑ RV afterload

tricuspid

insufficiency and

regurgitation

septal bowing

↓ LV cardiac output

↓ coronary blood flow

PATOPHYSIOLOGY of massive PE

occlusion of > 50 % pul. bed

↑ pulmonary artery pressure

release of vasoactive substances (serotonine, tromboxane A2 )

vasocontraction of non-obstructed pul. bed

DYSPNOE sudden onset

or intermittent

CHEST PAIN angina - ↓ coronary blood supply

pleuritic pain -

pulmonary infarction

COUGH

HEMOPTYSIS pulmonary infarction

CLINICAL SIGNS & SYMPTOMS

↓ peripheral blood supply

TACHYCARDIA compesation to ↓ cardiac

output

SYNCOPE

CYANOSIS

HYPOTENSION AND SHOCK

CLINICAL SIGNS & SYMPTOMS

DIAGNOSTICS

DIAGNOSTICS

D-DIMER TESTING

- final products of fibrin degradation

- ↑ concentration in plasma in the

presence of acute trombosis

(because of simultaneous coagulation

and fibrinolysis)

- non-specific test to exclude PE

DIAGNOSTICS

OTHER ASSESSMENT TOOLS

chest radiography

electrocardiogram

ventilation V/perfusion lung scan Q

DIAGNOSTICS

ventilationperfusion

MASSIVE PE with SHOCK/HYPOTENSION

- Anti-shock measures

- thrombolytic treatment (streptokinase, urokinase, tissue plasminogen activator)

- anticoagulation treatment

- pulmonary thrombectomy

– removal of thrombus

TREATMENT

PE with small embolus

- anticoagulation treatment

- heparin – inhibition of coagulation factor X & prothrombin

- vitamin K antagonist – synthesis of coagulation factor

II,VII,IX,X

PREVENTION:

- early mobilization post surgery

- inferior vena cava filter

- compression of the lower extremities

TREATMENT

Small proportion of PE caused by EXOTIC EMBOLI:

air trauma of large neck veins,

surgery

manipulation with the central venous

catheter

fat fractures, orthopedic surgeries

amniotic fluid

tumors

foreign body

parasites and eggs

NONTROMBOTIC PULMONARY EMBOLISM

Cor pulmonale is defined as an alteration in the structure and function of the right ventricle (hypertrophy, dilatation, failure) caused by a primary disorder of the respiratory system

but not respiratory disorder due to left heart disease

COR PULMONALE

acute

RV dilatation

chronic

RV hypertrophy

Cor pulmonale

massive pulmonary

embolism

acute respiratory distress

syndrome (ARDS)

CLASSIFICATION

pulmonary hypertension

chronic obstructive pulmonary disease

interstitial lung disease

sleep apnea

obesity

exposure to high altitude

PATHOGENESIS

RV afterload

RV hypertrophy

RV decompensation

RV failure

↑ pulmonary

resistance & pressure

- 10 % of all cases of heart failure

- 50 % of patients with chronic obstructive pulmonary

disease right heart failure

- 3 – 5 years from symptoms manifestation

mortality rate 50 – 70 % patients

- late detection – with manifestation of heart failure

EPIDEMIOLOGY

dyspnea

fatigue

cyanosis

chest pain

edema of lower limbs

ascites

hepatomegaly

splenomegaly

CLINICAL SIGNS & SYMPTOMS

ECHOCARDIOGRAPHY hypertrophy of right ventricle

ELECTROCARDIOGRAPHY P pulmonale

heart axis deviation

CHEST RADIOGRAPHY changes in heart shadow

DIAGNOSTICS

- therapy of primary cause

pulmonary hypertension

pulmonary embolism

chronic obstructive pulmonary disease

- oxygen

- diuretics

- supportive care of patiens with right heart failure

TREATMENT