Pulmonary Embolism

Pulmonary embolism update

1. PULMONARY EMBOLISM DR. ASRAF HUSSAIN DM CARDIOLOGY RESIDENT (1 ST YEAR)

2. Definition Pulmonary thromboembolism : Thrombosis originating in venous system and embolizing to pulmonary arterial circulation.

3. INTRODUCTION PE contributes to 5 to 10% of deaths in hospitalized cases ( Alikhan et al.2004) Also accounts for 20-30% of deaths associated with pregnancy and delivery As per systemic review literature on the global disease burden (Western Europe,North America, Australia and Sothern latin America) Annual incidence of pulmonary embolism ranges between 0.75 to 2.69 per 1000 populations Incidence increased to between 2 to 7 per 1000 population of age above 70 years.

4. About 70% of cases of Acute PE are caused by pelvic or leg thromboses . DVT and PE are different presentations of the same underlying pathophysiological event i.e venous thromboembolism (VTE). One of the big three cardiovascular killer along with MI and stroke.

5. Predisposing factors Virchows triad for thrombogenesis Stasis: bed rest, inactivity, CHF, CVA within 3 mnth , air travel>6 h Injury to endothelium: trauma, surgery, prior DVT , inflammation Thrombophilia; protein c or s deficiency, prothrombin gene mutatuion ,, increased factor VIII, hyperhomocysteinemia , HIT, OCP, HRT, Tamoxifen , raloxifene Malignancy (12% of idiopathic DVT/PE) Inflammation White infarct and red infarct a myth in present day understanding

6. Obesity Hypertension Smoking Hypercholesterolemia White clot vs red clot???? Risk of arterial cardiovascular events doubles in VTE patients* * Becattini C et al, Incidence of arterial cardiovascular events after venous thromboembolism: a systemic review and meta analysis

7. PREDISPOSING FACTORS

8. Pathophysiology

9. Symptoms Dyspnea(sudden onset) most common Chest pain( pleuritic or atypical) Anxiety Cough and hemoptysis Dizziness or syncope (due to right heart failure)

10. Signs Tachypnea/tachycardia Hypoxia/cyanosis Low grade fever Cardiac :gallop rhythm,Jugular venous distension, loud P2, RV heave, widely split S2., TR. Haemoptysis Leg oedema , erythema, tenderness(signs of DVT) Systemic hypotension and cardiogenic shock.

11. Long term complications Recurrent VTE Post PE syndrome Chronic thromboembolic pulmonary hypertension Post thrombotic syndrome (venous insufficiency)

12. Assessment of clinical probability Clinical judgement lacks standardization , therefore clinical prediction rules have been developed Commonly used is the one offered by Wells et al. The revised Geneva rule is also simple and standardized

13. WELL’S SCORE CRITERIA FOR PE

14. Classification of pulmonary embolism category presentation Massive pulmonary embolism(5%-10%) Systolic blood pressure<90 mm hg or poor tissue perfusion or multisystem organ failure plus extensive thrombus, such as “saddle” PE or right or left main pulmonary artery thrombus Submassive pulmonary embolism(20%-25%) Haemodynamically stable but moderate or severe right ventricular dysfunction or enlargement, coupled with biomarker elevation indicative of right ventricular microinfarction and/or right ventricular pressure overload Small to moderate pulmonary embolism(70%) Normal haemodynamics and normal right ventricular size and function

15. Diagnostic tests labaratory Arterial blood gas: may reveal hypoxemia, hypocapnia and respiratory alkalosis Brain natriuretic peptide: BNP levels are greater in patient with PE compared to other patients: elevation of BNP level correlates with risk of subsequent complications and prolonged hospitalization. Troponin: serum troponin I and T are elevated in 30 to 50 % who have moderate to large pulmonary embolism.

16. D-DIMER TESTING Simultaneous activation of coagulation and fibrinolysis in presence of acute thrombosis causes elevated D-dimer levels Sensitivity of about 96% (Brown et al 2002). But low specificity. Negative predictive value of D-dimer testing is high and a normal D-dimer level renders acute PE or DVT unlikely Fibrin is also produced in various condtions such as cancer, inflammation, bleeding, trauma , surgery and necrosis, accordingly positive predictive value of elevated D-dimer level is low and D-dimer testing is not useful for confirmation of PE After age of 80 significance decreases

17. New D-dimer cut-off value: –< 50 years-old 500 ng/mL –> 50 years-old Patient age X 10 (e.g. 78-year-old patient, cut-off 780 ng/mL) Age-adjusted cut-off would increase the diagnostic yield of D-dimer by 10% (from 25 to 35% of all patients tested)

18. Diagnostic Tests ECG Sinus Tachycardia Atrial fibrillation P pulmonale RV strain patterns suggest severe PE Inverted T waves V1-V4 Incomplete RBBB S1Q3T3 (first described by McGinn and White in JAMA in 1935) has sensitivity of 54% and specificity of 62% (Ferrari et al 1997)

19. Rauniyar b, Adhikari cm at gnhc

20. S1Q3T3 and T wave changes

21. Diagnostic Tests CXR Chest radiograph findings in patient with pulmonary embolism Result Cardiomegaly Normal study Atelectasis Elevated Hemidiaphragm Pulmonary Artery Enlargement Pleural Effusion Parenchymal Pulmonary Infiltrate

22. Chest X-ray Eponyms of PE 29 Westermark's sign Focal , demarcated oligaemia Hampton’s Hump A triangular or rounded pleural-based infiltrate with the apex toward the hilum, usually located adjacent to the hilum. Palla’s sign prominent right descending pulmonary artery

23. Figure 1. Chest radiograph demonstrating focal oligemia in the right lung (area between white arrowheads) and a prominent right descending pulmonary artery (black arrow). Shiva Sreenivasan et al. Circulation. 2007;115:e211 Copyright © American Heart Association, Inc. All rights reserved.

24. MELTING SIGN (rapid clearing in contrast to pneumonic consolidation) FLEISHNER’S SIGN (prominent central artery secondary to PHTN or large PE)

25. ECHOCARDIOGRAPHY Acute PE may lead to RV pressure overload and dysfunction, which can be detected by echocardiography Disturbed RV ejection pattern (so-called ‘60–60 sign’) or on depressed contractility of the RV free wall compared with the RV apex (‘McConnell sign’) Echocardiographic examination is not recommended as part of the diagnostic work-up in haemodynamically stable, normotensive patients with suspected (not high-risk) PE This is in contrast to suspected high-risk PE, in which the absence of echocardiographic signs of RV overload or dysfunction practically excludes PE as the cause of haemodynamic instability Mobile right heart thrombi are detected by transthoracic or transoesophageal echocardiography (or by CT angiography)

26. LUNG ULTRASOUND Subpleural parenchymal consolidations in up to 75% of the patients

27. DIAGNOSTIC TESTS CT Angiography Studies have shown sensitivity of close to 95% with an experienced observer One of the most commonly cited benefits of CTA is its ability to detect alternative pulmonary abnormalities that may explain the patient's symptoms and sign It allows adequate visualization of the pulmonary arteries down to at least the segmental level. Contrast enhanced MDCT-PA is currently the preferred method of diagnosis.

28. RV to LV dimensional ratio of 0.9 or greater IVS septal bowing towards LV Reflux of contrast medium into inferior venacavae

29. Diagnostic tests PULMONARY ANGIOGRAPHY Definite diagnostic test or gold standard in diagnosis of PE (less preferred) A filling defect or abrupt cutoff of a small vessel is indicative of embolus A negative pulmonary angiogram excludes clinically relevant PE

30. V/Q SCAN Normal V/Q sensitivity 99% (r/o PE) High prob. V/Q specificity 96% (r/I PE) Lung scan results are frequently classified according to the criteria established in the PIOPED study: normal or near-normal, low, intermediate (non-diagnostic), and high probability of PE

31. DIAGNOSTIC TESTS MAGNETIC RESONANCE ANGIOGRAPHY The use of MRA for diagnosis of PE is limited by respiratory and cardiac motion artefact

32. Diagnostic tests LOWER LIMB ULTRASONOGRAPHY Proximal DVT in a patient with clinical suspicion of PE confirms PE Distal DVT further testing should be considered to confirm PE Almost 50% patients with symptomatic DVT have asymptomatic PE.

33. Treatment Respiratory support: supplemental oxygen if hypoxemia exists Hemodynamic support: patient with PE and hypotension, hemodynamic support should be instituted Intravenous fluid administration Intravenous vasopressors: norepinephrine, dopamine or epinephrine may be effective Dobutamine increases myocardial contractility and causes vasodilatation and is ideal for cardiogenic shock

34. Treatment Thrombolytic treatment Thrombolysis restores pulmonary perfusion more rapidly than anticoagulation with UFH alone leading to a prompt reduction in pulmonary artery pressure and resistance, with a concomitant improvement in RV function The greatest benefit is observed when treatment is initiated within 48 hours after the onset of symptoms, but thrombolysis can still be effective in patients who have had symptoms for up to 14 days Fibrinolysis results in 47% reduction in all cause mortality, 60% decrease in recurrent PE at cost of 2.7 X risk of major bleeding and 4.6 X risk if ICH* -*Chatterjee S. Chakraborty et al Thrombolysis for PE and risk of all cause mortality, major bleeding and ICH: a meta analysis

35. Treatment Indication of thrombolysis Systemic thrombolysis should be considered only after acute PE has been confirmed Persistent hypotension ( systolic blood pressure of<90 mm hg or decrease in systolic BP by >/40mm Hg from baseline Severe hypoxemia Large perfusion defect on ventilation perfusion scans Extensive embolic burden on CT Right ventricular dysfunction Free floating right atrial or ventricular thrombus Patent foramen ovale

36. Advances in Catheter Based Therapy SEATTLE II trial with 24 mg t-PA Major bleeding in 10% with no ICH (vs 1% to 3% patients developing ICH in patients receiving systemic thrombolysis.) Promising modality INDIGO thrombectomy system- microaspiration without using fibrinolysis (US FDA approved 2019)

37. Treatment Initiation of anticoagulation therapy Anticoagulation is recommended, with the objective of preventing both early death and recurrent symptomatic or fatal VTE Consists of administering parenteral anticoagulation [unfractionated heparin (UFH), low molecular weight heparin (LMWH), or fondaparinux ] over the first 5–10 days Parenteral heparin should overlap with the initiation of a vitamin K antagonist (VKA); alternatively, it can be followed by administration of one of the new oral anticoagulants: dabigatran or edoxaban . rivaroxaban or apixaban Oral treatment with one of these agents should be started directly or after a 1–2 day administration of UFH, LMWH or fondaparinux In this latter case, acute-phase treatment consists of an increased dose of the oral anticoagulant over the first 3 weeks (for rivaroxaban ), or over the first 7 days (for apixaban )

38. Treatment Parenteral anticoagulation LMWH or fondaparinux are preferred over UFH for initial anticoagulation in PE, as they carry a lower risk of major bleeding and heparin-induced thrombocytopenia (HIT) UFH is recommended for patients in whom primary reperfusion is considered, as well as for those with serious renal impairment (creatinine clearance <30 mL/min), or severe obesity These recommendations are based on the short half-life of UFH, the ease of monitoring its anticoagulant effects, and its rapid reversal by protamine. The dosing of UFH is adjusted, based on the activated partial thromboplastin time ( aPTT )

39. Adjustment of UFH dose

40. Treatment Vitamin K antagonists Oral anticoagulants should be initiated as soon as possible, and preferably on the same day as the parenteral anticoagulant VKAs have been the ‘gold standard' in oral anticoagulation for more than 50 years and warfarin remain the predominant anticoagulants prescribed for PE Anticoagulation with UFH, LMWH, or fondaparinux should be continued for at least 5 days and until the international normalized ratio (INR) has been 2.0–3.0 for two consecutive days Warfarin can be started at a dose of 10 mg in younger (e.g. <60 years of age), otherwise healthy outpatients, and at a dose of 5 mg in older patients and in those who are hospitalized The daily dose is adjusted according to the INR over the next 5–7 days

41. NEW ORAL ANTICOAGULANTS

42. Treatment Surgical embolectomy The first successful surgical pulmonary embolectomy was performed in 1924( Kirschner a pupil of Trendelenburg in Germany), several decades before the introduction of medical treatment for PE. Reserved for patients with absolute contraindications to thrombolysis and in those in whom thrombolysis has failed to improve the hemodynamic status.

43. Percutaneous catheter embolectomy and fragmentation If surgical embolectomy not available.

44. Treatment Venous filters Venous filters ( Mobin Uddin Umbrella) are usually placed in the infrarenal portion of the inferior vena cava (IVC) Venous filters are indicated in patients with acute PE who have absolute contraindications to anticoagulant drugs, and in patients with objectively confirmed recurrent PE despite adequate anticoagulation treatment

45. ESC GUIDELINES 2019

46. Mechanical VTE Prophylaxis Intermittent pneumatic compression Graduated compression stockings Role in doubt

47. Medical prophylaxis

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