ACUTE PULMONARY EMBOLISM

1. ACUTE PULMONARY EMBOLISM An Update On: Diagnosis & Treatment Coenie Koegelenberg Division of Pulmonology, Department of Medicine

2. Background ðIncidence according to two UK studies: ð1 in 1000 per year ðIncidence doubles for each 10-year ñ age ðPost mortem studies: ð Microemboli are found in 60 % of autopsies ð 30 % of all inpatient deaths (western world)

3. Background ðImmediate Mortality of untreated PE: 30% ðWith treatment: 2-8% ðInternational Co-operative PE Registry1: Three-Month Mortality = 17.5 % 1. Kniffin WD Jr, et al. The epidemiology of diagnosed pulmonary embolism and deep venous thrombosis in the elderly. Arch Intern Med 1994;154:861-866.

4. Background ðRudolf Karl Ludwig Virchow (1856) "Thrombose und Embolie" ðStasis ðHypercoagulability ðVascular injury ðStasis ðHypercoagulability ðVascular injury

5. Pathophysiology ðArterial obstruction ðRelease of vasogenic peptides ðNeurogenic broncho- & vasoconstriction

6. Pathophysiology ðIncrease in pulm vasc resistance ðIncreased alveolar dead space ðShunt / V/Q mismatch due to atelectasis & alveolar oedema ð Increased Raw ðDecreased lung compliance Hypoxaemia

7. Pathophysiology ðIncrease in pulm vasc resistance ðIncreased alveolar dead space ðShunt / V/Q mismatch due to atelectasis & alveolar oedema ð Increased Raw ðDecreased lung compliance RV Afterload

8. Pathophysiology • ðIncreased RV afterload • ðIncreased wall tension RV • ðDilatation RV è Tricuspid prolapse • ðRCA compressed è Ischaemia • ð Dysrythmias • ðRV Failure / Dysfunction

9. Pathophysiology Important prognostic Implications • ðRV Dysfunction • ðSeptal shift to left • ðUnderfilling of LV • ðFall is CO èò Blood pressure • ðLV myocardial ischaemia • ðCirculatory collapse ðDEATH

10. Pathophysiology ðAnalysis of the four major PE registries: ðRH hypokinesis ðNormal Systemic BP ðDoubling of mortality at 14 days & 3 times higher at one year ! ð Three large trails (incl. MAPPET1): Similar relationship RV dysf and mortality ðRV dysfunction = adverse outcome 1. Konstantinides S, et al. Comparison of alteplase versus heparin for resolution of major pulmonary embolism. Am J Cardiol. 1998;82:966-970 Mortality

11. Presentation ðAcute PE - Spectrum that ranges from: ðClinically unimportant / incidental ðMinor emboli ± infarction ðLarge pulmonary emboli ðMassive emboli

12. Presentation ðAcute PE - Spectrum that ranges from: ðClinically unimportant / incidental Haemoptysis ðMinor emboli ± infarction Pleuritic pain Pulmonary signs ðLarge pulmonary emboli Dyspnoea Ischaemic pain ðMassive emboli Collapse Cardiac signs

13. Presentation ðDiagnostic difficulties! ðSigns / symptoms non-specific ðOnly 25% of suspected cases actually have pulmonary emboli1,2 1. Lee AY, Hirsh J. Diagnosis and treatment of venous thromboembolism. Annu Rev Med. 2002;53:15-33. 2. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED).JAMA. 1990;263:2753-2759.

14. Presentation ðModified Wells score1 (“dichotomised”) 1. Wells PS, Anderson DR, Rodger M, et al. Derivation of a simple clinical model to categorize patients’ probability of pulmonary embolism: increasing the model’s utility with the SimpliRED D-dimer. Thromb Haemost. 2000;83:416-420. ≤ 4 PE “unlikely” > 4 PE “likely” Score

15. Special Investigations ðD-Dimer ðPatho-physiological background

16. Special Investigations • ðD-Dimer • ðQuantitative D-Dimer (ELISA) > 500 ng/ml • ðPresent in > 95 % of patients with PE • ðHigh sensitivity (>96 %) • ðLow specificity (AMI, pneumonia, etc) • ðHigh negative predictive value (99.0%) • ðUseful in excluding PE in outpatients • ðNot to be used to “diagnose” PE SA Labs < 0.25 mg/l

17. Special Investigations ðD-Dimer ðQuantitative D-Dimer (ELISA) > 500 ng/ml ðNot useful in inpatients1: ð AUC of ROC Curves 0.8 for outpatients 0.5 for inpatients 1.Schreceqost JE, et al. Comparison of diagnostic accuracies in outpatients and hospitalized patients of D-dimer testing for the evaluation of suspected pulmonary embolism. Clin Chem. 2003;49(9):1483-90

18. Special Investigations • ðCombing Clinical Probability & D-Dimer • ðChristopher Study1 (n = 3,306) • ðDichotomized Wells score ≤ 4 • ðD-Dimer ≤ 500 ng/ml • ðNegative predictive value > 99.5% • ðUseful in excluding PE in outpatients ðSafe to withhold treatment 1. Van Belle A, et al. Effectiveness of Managing Suspected Pulmonary Embolism Using an Algorithm Combining Clinical Probability, D-Dimer Testing, and Computed Tomography. JAMA 2006;295(2):172-179

19. Special Investigations ðABG ðHypoxaemia ðHypocapnia ðNot specific or sensitive1 ðBiochemistry ðTroponin T/I ðBrain natriuretic peptide (BNP) ðSurrogate markers for RV dysfunction 1. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism: results of the Prospective Investigation of Pulmonary Embolism Diagnosis (PIOPED).JAMA. 1990;263:2753-2759.

20. Special Investigations ðECG ðSinus tachycardia ðNew onset / Paroxysmal AF/Afl/SVT ðRight heart strain: ðRight atrial enlargement ðPartial/complete RBBB ðRVH ðT-wave inversion ant chest leads (V1-V4) ðClassic: SI, QIII, TIII (rare) ðDifferential Diagnosis

21. Special Investigations ðCXR ðOften normal ðLinear atelectasis ðSmall effusions ðFocal oligaemia ðPeripheral wedge-shape densities ðPalla’s sign: enlarged right descending pulmonary artery

22. Special Investigations ðCXR ðOften normal ðLinear atelectasis ðSmall effusions ðFocal oligaemia ðPeripheral wedge-shape densities ðPalla’s sign: enlarged right descending pulmonary artery

23. Special Investigations ðCXR ðOften normal ðLinear atelectasis ðSmall effusions ðFocal oligaemia ðPeripheral wedge-shape densities ðPalla’s sign: enlarged right descending pulmonary artery

24. Special Investigations ðCXR ðOften normal ðLinear atelectasis ðSmall effusions ðFocal oligaemia ðPeripheral wedge-shape densities ðPalla’s sign: enlarged right descending pulmonary artery

25. Special Investigations ðEchocardiography ðRapidly gaining importance (risk stratify) ð40 % have abnormalities: ðRV pressure overload ðMcConnel sign: Regional RV dysfunction Apical wall motion remains normal Hypokinesis of free wall ðDif Diagnosis: AMI, Aortic dissection, Pericardial tamponade

26. Special Investigations ðEchocardiography

27. Special Investigations ðV/Q – Scan ðPerfusion: Tc-99M ðVentilation: Xenon ðUnderperfusion ~ V/Q mismatch

28. Special Investigations • ðV/Q – Scan • ðGreatest limiting factors: • ðStructural lung disease • ðAvailability • ð Often non-diagnostic (60%!)1 • ðStill useful: peripheral small/multiple PEs • 1. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute • pulmonary embolism: results of the Prospective Investigation of Pulmonary • Embolism Diagnosis (PIOPED).JAMA. 1990;263:2753-2759.

29. Special Investigations • ðV/Q – Scan • ðDiagnostic in the minority (41% in PIOPED) • High Probability PE Diagnosed • Intermediate Probability • Non-diagnostic • Low Probability • Normal Scan PE Excluded PTP

30. Special Investigations • ðHelical CT Pulmonary Angiography (CTPA) • ðFirst line / principal imaging!!! • ðHas superseded VQ scans • ðWidely available, performed rapidly • ðAlso provides alternative diagnoses • ðAttention to protocol… • Collimation, pitch, volume, field • Tube amperage • Contrast injection and timing

31. Special Investigations • ðHelical CT Pulmonary Angiography (CTPA) • ðMultidetector Row Helical CT Systems • Additional detectors • Rapid scanning vascular bed • (4 slice 3 x faster than SDCT) • Narrow collimation (1.25 mm) • Increased spatial resolution • ðMay combine with Helical CT Venography • (see later)

32. Special Investigations • ðHelical CT Pulmonary Angiography (CTPA) • ðFindings of Acute PE • ðIntraluminal filling defect surrounded by contrast • ðAncillary findings that are suggestive: • Expanded unopicified vessels • Eccentric filling defects • Peripheral wedge-shaped consolidation • Oligaemia • Pleural effusion

33. Special Investigations ðHelical CT Pulmonary Angiography (CTPA)

34. Special Investigations ðHelical CT Pulmonary Angiography (CTPA)

35. Special Investigations ðHelical CT Pulmonary Angiography (CTPA)

36. Special Investigations ðHelical CT Pulmonary Angiography (CTPA)

37. Special Investigations ðHelical CT Pulmonary Angiography (CTPA)

38. Special Investigations ðHelical CT Pulmonary Angiography (CTPA)

39. Special Investigations ðHelical CT Pulmonary Angiography (CTPA) Saddle Embolism: pre- & post- thrombolysis

40. Special Investigations ðHelical CT Pulmonary Angiography (CTPA)

41. Special Investigations • ðHelical CT Pulmonary Angiography (CTPA) • ðPitfalls • Lymph nodes • Impacted bronchi • Pulmonary artery catheters • Pulmonary sarcomas • Technical: Respiratory motion • Improper contrast • Incorrect reconstruction algorithms

42. Special Investigations • ðHelical CT Pulmonary Angiography (CTPA) • ðDiagnostic accuracy • Large central emboli Sensitivity = 100% Specificity = 100% • Segmental (up to 5th) Sensitivity = 95-98% Specificity = 97% • Small subsegmental Sensitivity ? • Specificity ? • Relevance of small emboli? • Diagnostic accuracy equal to angiography! • Gold standard?

43. Special Investigations • ðHelical CT Pulmonary Angiography (CTPA) • ðBest evidence – PIOPED II Study1 • n = 1 090 (Outpatients) • Investigated the diagnostic accuracy of multidetector CTA alone and • combined CTA–CTV (CT Venography) • 1. Stein PD, et al. Multidetector Computer Tomography for Acute • Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327

44. Special Investigations • ðHelical CT Pulmonary Angiography (CTPA) • ðBest evidence – PIOPED II Study1 • Redefined the “reference standard” Abnormal VQ scan • Abnormal venous ultrasonography • Abnormal digital subtraction angiography • Subsequent events (F/U 3 and 6 months) • 1. Stein PD, et al. Multidetector Computer Tomography for Acute • Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327

45. Special Investigations • ðHelical CT Pulmonary Angiography (CTPA) • ðBest evidence – PIOPED II Study1 • CTA Sensitivity = 83% • Specificity = 96% • PPV = 96% • CTA-CTV Sensitivity = 90% • Specificity = 95% • NPV = 97% • 1. Stein PD, et al. Multidetector Computer Tomography for Acute • Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327

46. Special Investigations • ðHelical CT Pulmonary Angiography (CTPA) • ðBest evidence – PIOPED II Study1 • Both have a high PPV with concordant clinical assessment, but • Additional testing is necessary when clinical probability is inconsistent • 1. Stein PD, et al. Multidetector Computer Tomography for Acute • Pulmonary Embolism. N Engl J Med 2006;354(22):2317-2327

47. Special Investigations • ðPulmonary Angiography • ðGold Standard? Challenged in PIOPED II • ðCan detect emboli as small as 1 – 2 mm • ðDiagnostic: filling defects • ðSecondary signs: • ð‘Cut-off’ of vessels • ðSegmental oligaemia • ð Prolonged arterial phase, slow filling • ðTapering of vessels • ðAlt: Digital subtraction angiography

48. Special Investigations ðPulmonary Angiography

49. Special Investigations • ðPulmonary Angiography • ðMain Indications • ðDiagnostic dilemmas • ðPrior to catheter embolectomy • ðMortality: 0.5%1 • 1. The PIOPED Investigators. Value of the ventilation/perfusion scan in acute • pulmonary embolism: results of the Prospective Investigation of Pulmonary • Embolism Diagnosis (PIOPED).JAMA. 1990;263:2753-2759.

50. Special Investigations ðMRI ðLimited use ðGadolinium-enhanced MR angiography ðAnatomical features ðRV motion