Slide 1

Pulmonary embolism, pulmonary hypertension, cor pulmonale chronicum

Slide 2

KEY POINTS 1/1000/year early treatment is highly effective, but is under- diagnosed, 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

Slide 3

Epidemiology USA: 117 % 000 VTE - 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)

Slide 4

PE and DVT mortality Goldhaber SZ, NEJM, 1998

Slide 5

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 V Leiden ) - myeloproliferativ disorders, policythaemia - nephrosis sy - gravidity, contraceptive pills - colitis ulcerosa

Slide 6

Fedullo PF, Tapson VF NEJM 2003

Slide 7

Symptomes of PE 1.Dyspnoe with sudden onset 84% 2.Pleural chest pain 74% 3.Cough 53% 4.Hemoptoe 30% 5.Sweat 27% 6.Non-pleural chest pain 14% 7.Syncope 13%

Slide 8

Physical findings 1.Tachypnoe (>16/min)92% 2.Crackles, local wheeze 58% 3.PII ! 53% 4.Tachycardia (>100/min)44% 5.Fever43% 6.Sweating 36% 7.Phlebitis32% 8.Anasarca 24% 9.Cyanosis19% 10.Pleural friction rub, fluid 11%

Slide 9

Fedullo PF, Tapson VF NEJM 2003

Slide 10

Geneva score Surgery in 6 months2 Previous PE or DVT2 Old age2 Hypocapnia2 Hypoxaemia2 Tachycardia2 Atelectasia2 High hemidiaphragm2 Low =9

Slide 11

Goldhaber SZ, NEJM, 1998

Slide 12

Clinical classification 1.Acute, massive 12 45/0-12 45/20 2.Acute, minor 5 30/0-5 30/15 3.Chronic, reccurant 6 90/0-6 90/50 (CTEPH) Hemodynamics (mmHg): RA RV PA

Slide 13

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

Slide 14

Acute, minor PE Haemoptysis Pleural chest pain Mild dyspnoe PaO 2 normal Fever, tachycardia Diff dg: pleurisy, pneumonia, bronchial cc

Slide 15

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

Slide 16

Chest X-ray and ECG X-ray%ECGECG% Wide PA50ST depression50 Elevated diaphragm44Sinus tachycardia44 Pleural fluid23 Negative T in V 2-3 23 Wide RA vagy RV17SV arrhythmia17 Infiltrate16S I,Q III,negativ T III 16 Atelectasia13RBBB13 Local oligemia6P-pulmonale6

Slide 17

Acute, massive PE rsR

Slide 18

CTEPH

Slide 19

ABG PaO 2 PaCO 2 pH ! P(A-a)O 2 Alveolar gas equation: P A (mmHg) = (P B -47) x F I O 2 1.2 x PaCO 2 102 = 150 - 48

Slide 20

West JB, 1998

Slide 21

D-dimer Goldhaber SZ, NEJM, 1998

Slide 22

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

Slide 23

Acute, massive PE After therapy ECHO

Slide 24

Pulmonary hypertension by Doppler 21/9 mmHg 62/24 mmHg

Slide 25

Slide 26

RA thrombus

Slide 27

Massiva PE, TTE Goldhaber SZ, NEJM, 1998

Slide 28

Other diagnostic tests Vascular Doppler of the leg Inhalation-perfusion scintigraphy: V/Q mismatch Helical CT: central - segmental subsegmental Angiography (gold standard)

Slide 29

Ventilation-perfusion scintigraphy

Slide 30

Multiplex PE Right upper lobe: match, Both lower lobes: mismatch

Slide 31

Massive PE

Slide 32

Perfusion defect in emphysema Alfa-1 AT deficiency HomogenousSmoker

Slide 33

Clinical probability Scintigraphic probability non-diagnostic normal, very low lowintermed.high Low241656 Intermedier6162888 High0406696 PIOPED JAMA, 1990

Slide 34

Angio CT

Slide 35

Slide 36

Slide 37

Angiography

Slide 38

Angiography: massive PE Acute: 45/20 mmHgSubacute: 85/50 mmHg

Slide 39

Slide 40

Slide 41

CTPH mPAP = 75 mmHg

Slide 42

Hemodynamic vitious circle

Slide 43

Therapy Streptokinase Urokinase Alteplase

Slide 44

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

Slide 45

New therapy Oral thrombin inhibitor - dabigatran (Pradaxa) Xa inhibitor - rivaroxaban (Xarelto) No need to control coagulability Side effect: bleeding Disadvantage: no antidotum, expansive

Slide 46

Rare forms of PE Fat (trauma, surgery - diffuse alveolar infiltrates) Septic (osteomyelitis, tricuspid valve endocarditis) Air (canulla insertion, gynecological intervention) Amniotic fluid (delivery)

Slide 47

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)

Slide 48

Classification of P A H 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)

Slide 49

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