1. Diagnosis and management of pulmonary thromboembolism DR.VIVEKANANTHAN D.A.,FRCA.,EDIC.,FFICM.,

2. OVERVIEW  Diagnosis – tests available and diagnostic strategies used  Prognostic assessment  Management- therapeutic strategies and methods available  Special circumstances

3. Pulmonary thromboembolism  Venous Thromboembolism (VTE) spectrum- DVT & PE  Major morbidity and mortality  Not uncommon  Diagnosis could be Elusive

4. Risk factors

5. pathophysiology

6. Diagnosis- Symptoms galore! Pollack et.al 2011

7. pitfall amongst symptoms and signs  30% patients with Confirmed PE do not have predisposing factors  40% patients with confirmed PE do not have hypoxaemia  20% patients with confirmed PE have normal alveolar arterial oxygen gradient  40% patients with confirmed PE have sinus tachycardia on ECG rather than classical ECG changes  59% of fatal PE were undiagnosed during life time

8. Acute PE- Initial diagnostic strategy  With shock and without shock-  High risk PE  Moderate and low risk PE

9. Diagnosis -Assessing clinical probability  Wells rule  Geneva rule  Three group category -Low, intermediate, high risk grouping  Two group category- PE likely, PE unlikely grouping

10. WELLS RULE

11. GENEVA RULE

12. Diagnosis- D-dimer  Positive predictive value is low  Negative predictive value is high  ELISA derived assay Vs latex derived assay reliability  Usefulness- can exclude PE in up to 30% of patients suspected with low or intermediate risk PE- (class I recommendation)  Age adjusted D-dimer cut off value improved specificity by 10%, if not specificity decreases with age

13. Diagnosis- CT pulmonary angiogram  83% sensitivity and 96% specificity –PIOPED II trial  Negative predictive value for CTPA is >89-96% in intermediate and low risk group  Segmental clot presence confirms PE -(class I recommendation)  CT venography combined with CTPA increases sensitivity from 83 to 90%, however specificity remains the same  Incidental CT diagnosis of PE is 1%  Sub segmental PE incidence is 4.5% with lower clinical significance

14. Diagnosis- ventilation perfusion scintigraphy  V/Q scan- technicium99  Well validated test  Safe, less allergic, <50% radiation exposure  Special groups of patients will benefit from it  Results are grouped into three- normal, high probability and non diagnostic scan

15. Diagnosis- other imaging techniques  SPECT imaging-  Pulmonary angiogram-  DSA-  MRI-

16. Diagnosis- Echocardiography  RV free wall contractility depressed as against the apex- “Mc Connell sign”  Disturbed RV ejection fraction- “60-60 sign”  RV dilatation – found in 25% of all cases of PE  Negative predictive value is only 40-50% due to other confounders  Not an investigation for low risk, non shocked patients

17. Diagnosis- compression venous ultrasonography  90% sensitivity and 95% specificity for symptomatic DVT  >70 % of PE patients have DVT  Proximal DVT in PE suspected patients is good enough to start anticoagulation- (class I recommendation)  Incomplete compressibility is a validated criterion for DVT diagnosis  Flow measurements are unreliable

18. Diagnostic strategy  Patients suspected to have PE, presenting  With shock  Without shock

19. Suspected PE with shock

20. Suspected PE without shock

21. PE exclusion -validated parameters

22. Treatment of PE- Overview  Haemodynamic, ventilatory support  Anti coagulation  Thrombolysis  Surgical embolectomy, percutaneous techniques, use of IVC filter

23. Treatment- resuscitation and supportive care  RV failure- main cause for mortality  adrenaline helps in RV failure  Modest fluid challenge helps improve cardiac index- caution needed  Effects of PEEP during ventilation needs careful titration  Levosimendan and nitric oxide might be useful

24. Treatment- anticoagulation  To prevent early death and recurrent VTE  Initial parenteral anticoagulation for 7-10 days necessary- heparin, LMWH, fondaparinux  vit.K antagonist after the initial phase for up to 3 months duration is essential  Duration of anticoagulation- unprovoked PE ( 3 months) unprovoked relapse of PE ( indefinite)- (class I recommendation)  Newer anticoagulants can be started earlier- rivaroxaban, apixaban

25. Treatment- choice of anticoagulant  UFH- shorter duration of action, suitable for pt. with renal impairment, obesity, APPT monitoring needed  LMWH- twice daily or single dose administration, caution with renal impairment, HIT possibility, anti Xa level monitoring possible  Fondaparinux- once daily s/c inj., results comparable to that of UFH, no reported HIT like effects, accumulates in renal failure

26. Treatment- oral anticoagulants  Warfarin –Vit K Antagonist(VKA) started as soon as possible, INR target of 2.0-3.0 is aimed  Pharmacogenetics' guided therapy is not found to be superior  Newer oral anticoagulants (NOAC)- dabigatran, rivaroxaban.,  NOAC- not inferior to UFH/ VKA regimen, possibly the bleeding risk is lesser – (class I recommendations for rivaroxaban apixaban and edoxaban)

27. Treatment- thrombolytic therapy  Restores pulmonary perfusion earlier than anticoagulation therapy  Two hours’ accelerated therapy preferred over 12-24 hour prolonged infusion therapy  >90% patients have clinical recovery within 36 hours of therapy, greatest benefit seen if therapy initiated within 48 hours of onset of symptoms  Normotensive patients with raised biochemical parameters and echocardiographic features of RV dysfunction, if thrombolysed, 7 day mortality and further complications were prevented (PEITHO trial)  Major bleeding risk- intra cranial and non intracranial bleeds- 2%

28. Treatment- surgical embolectomy  Surgical technique used since 1924  Indicated for failed thrombolytic therapy or where it is contraindicated amongst intermediate or high risk patients

29. Treatment- percutaneous catheter directed treatment  Thrombus fragmentation, rotational thrombectomy, suction thrombectomy, rheolytic thrombectomy techniques are available  Systemic Thrombolysis contraindicated patients are suitable for these techniques  RCT: Catheter directed clot thrombolysis technique has been found superior in reversing RV function within 48 hours as compared to systemic thrombolysis WITHOUT bleeding complications in intermediate risk group of patients

30. Treatment – IVC filter  Infra renal placement is usually done  IVC filters should be considered in patients with acute PE with absolute contraindications to anticoagulation. ( class II a recommendation)  IVC filters should be considered in case of recurrence of PE, despite therapeutic levels of anticoagulation. ( class II a recommendation)  Routine use of IVC filters in patients with PE is not recommended ( class I recommendation)

31. Special circumstances- pregnancy  D-Dimer is useful to avoid unnecessary irradiation  Venous compression ultrasonography is considered to avoid irradiation risk  Perfusion scintigraphy may be considered to rule out suspected PE when the chest x ray is normal  CT angiography considered only when chest x ray is abnormal  LMWH adjusted to weight is treatment of choice in pts without shock

32. Special circumstances- cancer and PE  Incidental PE on cancer screening is treated along the same guidelines for non cancer patients suspected to have PE  Negative D-dimer has similar negative diagnostic value  LMWH adjusted to body weight is used for 3-6 months  Extended anticoagulation with LMWH is considered until cancer is cured- (class II a recommendation)

33. Chronic thromboembolic pulmonary hypertension  Incidence of 1.5 % in patients diagnosed with earlier PE  Diagnostic criteria: findings after 3 months of effective anticoagulation:  1. mean pulmonary arterial pressure ≥25 mm Hg, with pulmonary arterial wedge pressure≤15 mm Hg  2. at least one (segmental) perfusion defect detected by perfusion lung scan or pulmonary artery obstruction seen by MDCT angiography or conventional pulmonary cine angiography V/Q scan is investigation of choice Pulmonary endarterectomy offered if operable, if not extended anticoagulation advised - (Class I recommendation)

34. Prognosis in PE  Simplified predicted severity in PE (sPSE score)- validated clinical score  Age >80, Cancer  Chronic cardiac, pulmonary disease  Heart rate >110, blood pressure <100, saturation <90%  0 points =1% mortality, >1 point= 10% risk of 30 day mortality- used for low and intermediate severity- ( class II a recommendation)  Patients to be assessed for presence of shock- carries higher mortality – (class I recommendation)  Lab tests and biomarkers- BNP, Pro BNP, troponin T, I ( class II a)

35. acknowledgment  http://www.escardio.org/guidelinessurveys/esc- guidelines/about/Pages/rules-writing.aspx http://www.escardio.org/guidelinessurveys/esc- guidelines/about/Pages/rules-writing.aspx  European society of cardiology guideline 2014  European heart Journal August 2014

36. Summary- Diagnosis and treatment of PE  Strong clinical suspicion is necessary to investigate and use the diagnostic strategies  Judicious use of investigations will avoid unnecessary burden in patient care delivery  Choice of therapy is vital in dictating better patient outcome

37. Thank you