Pulmonary embolism,
pulmonary hypertension,
cor pulmonale chronicum
KEY POINTS
• 1/1000/year
• early treatment is highly effective, but is underdiagnosed, therefore, remains a major health
problem
• diagnostic strategy should be based on clinical
evaluation (probability assessment)
• value of PPV and NPV are high when
concordant with clinical assessment
• additional tetsting is neccessery when test
result is inconsistent with clinical probability
Epidemiology
• USA: 117 %000VTE - 48 %000 DVT
- 69 %000 PE
(Arch Intern Med 1998; 158:585-593)
• NyE: 183 %000 VTE - 124 %000 DVT
- 60 %000 PE
(Thromb Haemost 2000; 83:657-660)
PE and DVT mortality
Goldhaber SZ, NEJM, 1998
Pathogenesis of VTE
1. Venous stasis – immobility (hospitalization-DVT), CHF, gravidity,
obesity, elderly patients
2. Intima injury– surgery (orthopedic, obstetrical), trauma
venous lines, venography
3. Abnormalities of coagulation – fibrinolysis
- malignancy
- lupus anticoagulant
- thrombophilias: AT III, protein S-, protein C deficiency
- mutation (Factor VLeiden)
- myeloproliferativ disorders, policythaemia
- nephrosis sy
- gravidity, contraceptive pills
- colitis ulcerosa
Fedullo PF, Tapson VF
NEJM 2003
Symptomes of PE
1.
2.
3.
4.
5.
6.
7.
Dyspnoe with sudden onset
Pleural chest pain
Cough
Hemoptoe
Sweat
Non-pleural chest pain
Syncope
84%
74%
53%
30%
27%
14%
13%
Physical findings
1. Tachypnoe (>16/min)
2. Crackles, local wheeze
3. PII !
4. Tachycardia (>100/min)
5. Fever
6. Sweating
7. Phlebitis
8. Anasarca
9. Cyanosis
10. Pleural friction rub, fluid
92%
58%
53%
44%
43%
36%
32%
24%
19%
11%
Fedullo PF, Tapson VF
NEJM 2003
Geneva score
Surgery in 6 months
2
Previous PE or DVT
2
Old age
2
Hypocapnia
2
Hypoxaemia
2
Tachycardia
2
Atelectasia
2
High hemidiaphragm
2
Low <=4
Medium 5-8
High >=9
Goldhaber SZ,
NEJM, 1998
Clinical classification
Hemodynamics (mmHg):
RA
1. Acute, massive
2. Acute, minor
3. Chronic, reccurant
(CTEPH)
12
5
6
RV
PA
45/0-12 45/20
30/0-5 30/15
90/0-6 90/50
Acute, massiv PE
• >50% obstruction (mechanic + humoral
+ neurogenic)
• Heavy, retrosternal pain, panic
• Pallor, cyanosis, sweating, strongs dyspnoe,
tachycardia
• Right heart failure, distended jugular veins
Diff dg: AMI, dissecant aortic aneurysm,
cardiac tamponade, pulmonary edema, ptx, shock
Acute, minor PE
•
•
•
•
•
Haemoptysis
Pleural chest pain
Mild dyspnoe
PaO2 normal
Fever, tachycardia
Diff dg: pleurisy, pneumonia, bronchial cc
Chronic, reccurant PE (CTEPH)
•
•
•
•
Reccurant episodes for months - years
Progression of effort dyspnea
Cyanosis
Angina-like chest pain (decreased
myocardial perfusion pressure)
• Tachycardia, PII !, systolic ejection
click
• Death: progression of right heart
failure
Diff dg: COPD, CHF, hyperventilation sy
Chest X-ray and ECG
X-ray
Wide PA
Elevated diaphragm
Pleural fluid
Wide RA vagy RV
Infiltrate
Atelectasia
Local oligemia
%
50
44
23
17
16
13
6
ECG
ST depression
Sinus tachycardia
Negative T in V2-3
SV arrhythmia
SI,QIII,negativ TIII
RBBB
P-pulmonale
%
50
44
23
17
16
13
6
Acute, massive PE
rsR’
CTEPH
ABG
•
•
•
•
PaO2 
PaCO2 
pH  !
P(A-a)O2 
Alveolar gas equation:
PA (mmHg) = (PB-47) x FIO2 – 1.2 x PaCO2
102
=
150
-
48
V/Q mismatch (3-compartment model)
West JB, 1998
D-dimer
Goldhaber SZ, NEJM, 1998
Blood chemistry
- D-dimer (ELISA): sensitive, but not specific
(AMI, pneumonia, CHF, cc, surgery)
> 500 ng/ml, in 90% of PE, (latex test 50%)
negative test: exclude PE
- LDH-3 
- Bi 
ECHO
After therapy
Acute, massive PE
Pulmonary hypertension by
Doppler
21/9 mmHg
62/24 mmHg
RA thrombus
Massiva PE, TTE
Goldhaber SZ, NEJM, 1998
Other diagnostic tests
• Vascular Doppler of the leg
• Inhalation-perfusion scintigraphy: V/Q
mismatch
• Helical CT: central - segmental – subsegmental
• Angiography (gold standard)
Ventilation-perfusion scintigraphy
Multiplex PE
Right upper lobe: „match”,
Both lower lobes: „mismatch”
Massive PE
Perfusion defect in emphysema
Alfa-1 AT deficiency
Homogenous
Smoker
PIOPED
JAMA, 1990
Clinical
probability
Scintigraphic probability
“non-diagnostic”
low
intermed.
high
Low
normal,
very low
2
4
16
56
Intermedier
6
16
28
88
High
0
40
66
96
Angio CT
Angio CT
Angio CT
Angiography
Angiography: massive PE
Acute: 45/20 mmHg
Subacute: 85/50 mmHg
CTPH
mPAP = 75 mmHg
Hemodynamic “ vitious circle”
Therapy
•Streptokinase
•Urokinase
•Alteplase
Treatment
• Sodium-heparin iv. bolus (5-10 000 U) followed by either
- continouos infusion or
- low molecular weight (ultrafractionated) heparin (LMWH) s.c.
• Coumarin for 6-12 months (if irreversible or unknown etiology:
lifeterm anticoagulation)
therapeutic level: INR: 2-3
• Ximelagatran, Dabigatran (and some more novel oral direct
thrombin or Xa f. inhibitors), for long-term prevention of VTE,
no need to monitor coagulation
New therapy
•
•
•
•
•
Oral thrombin inhibitor - dabigatran (Pradaxa)
Xa inhibitor - rivaroxaban (Xarelto)
No need to control coagulability
Side effect: bleeding
Disadvantage: no antidotum, expansive
Rare forms of PE
• Fat (trauma, surgery - diffuse alveolar
infiltrates)
• Septic (osteomyelitis, tricuspid valve
endocarditis)
• Air (canulla insertion, gynecological
intervention)
• Amniotic fluid (delivery)
Etiology of chronic cor pulmonale
• Airway or parenchymal disease
• Alveolar hypoventilation
• Pulmonary vascular disease (arteria, vena –
pulmonary veno-occlusive disease)
• Mediastinal compression (tumor, aneurysm)
• Chest deformity (e.g. kiphoscoliosis)
Classification of PAH
• Postcapillary
- LV systolic or diastolic dysfunction
- pericardial constriction
- LA disease (MS, MI, thrombus), veno-occlusive disease
• Precapillary
- iPAH
- airway or parenchyma disease (COPD, fibrosis, collagen
diseases, cancer, resection)
- embolism
- vasculitis (Wegener, Churg-Strauss sy, CREST-sy, SLE, PN)
- Eisenmenger-sy
- Alveolar hypoventilation (chest deformity, pleural callus, SAS,
neuromuscular diseases)
- other (pulmonal stenosis, high altitude, hemoglobinopathies)
Treatment of CCP
• Treatment of primer disease
• Oxygen supplementation
• Diuretics, vasodilators with caution –
preload !
• New vasodilators for iPAH (PD-5 inhibitors,
Pg analogs, endothelin antagonists)
• Venesection, in case of polyglobulia
• Anticoagulation