Management of Acute Pulmonary Embolism Judith Hurdman Consultant Respiratory Physician Judith.hurdman@sth.nhs.uk
Overview Risk Stratification Who can be managed as an outpatient? To thrombolyse or not to thrombolyse? Follow up & Anticoagulation
Nomenclature of Risk Stratification High Risk Intermediate Risk Low Risk Massive Submassive Low Risk
Stratifying Risk
Risk-adjusted management algorithm Konstantinides et al. Eur Heart J 2014; pii: ehu283
When a PE is diagnosed, what further information is necessary to risk stratify this patient?
Strategies for management of acute PE require an individual assessment clinical status to estimate PE related early mortality risk Clinical features Indicators of cardiorespiratory health Co-morbidities PESI score Biomarkers reflecting RV dysfunction BNP RV dysfunction on echocardiogram Increased RV size on CT scan Biomarkers reflecting myocardial injury Troponin Risk of further events USS of legs Atrial or ventricular thrombi on CT scan or echocardiogram
N=15,531 PE Severity Index
Original and simplified pulmonary embolism severity index (PESI)
Risk of mortality at 30 days by PESI score
Combining ESC and PESI: 2014 ESC guidelines Konstantinides et al. Eur Heart J 2014; pii: ehu283
RV:LV Ratio on transverse CT section good predictive value for adverse outcome in acute PE N=13162 Meta-analysis 49 studies Meinel FG et al Am J Med 2015;128(7):747-59
Measurement of RV / LV ratio Normal RV / LV ratio 1 RV / LV ratio >1-1.5 = moderate RV dilatation RV / LV ratio > 1.5 = severe RV dilatation John G et al. Biomed Res Int. 2014
High lactate predicts adverse outcome in 496 normotensive patients Vanni S et al. Thorax 2015;70:333-338
Case 1 51 year old male with pleuritic chest pain for 2days Sats 95% on air, pulse 90bpm, BP 132/84 No past medical history
Case 1 CTPA confirms PE with RV:LV ratio 0.8 indicating the absence of RV dysfunction
Case 1 management plan Patient has low risk PESI score = 51 age + 10 Male = 61 Simplified PESI = 0 Suitable for ambulatory care with LMWH or DOAC Is any further information required?
Features suggesting inpatient management required Haemodynamic instability Active or high risk bleeding PE while anticoagulated Co-existing major DVT Severe chest pain Renal or liver failure Social factors/difficulty with follow up Zontag et al J of throm & Haemostasis 2011:9(8) 1500-7 Davies et al erj 2007;30(4):708-14
What if his RV:LV ratio was 1.05?
Mild increase in RV:LV ratio in otherwise low risk patient does not preclude ambulatory care In patients who are low-risk on PESI score but mildly elevated RV:LV ratio on CT, check High sensitivity troponin
Outpatient management of low risk PE Outpatient management of low risk patients is safe and associated with good patient satisfaction Clinical risk tools and exclusion criteria identify patients suitable for outpatient management Piran et al Thrombosis Research 2013 32;515-9 Davies, CWH et al ERJ 2007 30(4);708-14 Zontag et al ERJ 2013 42; 134-44
Thrombolysis
Case 2 88 year lady PMH Hypothyroidism, OA Found on floor by pharmacist delivering meds Ambulance called - BP 80/54 in A&E Sats 92% on 35% oxygen Troponin 54
CTPA confirmed extensive PE with RV strain RV / LV ratio 1.7 indicating the presence of RV dysfunction
Key factors contributing to haemodynamic collapse in acute pulmonary embolism Konstantinides et al. Eur Heart J 2014; pii: ehu283
Case 2 BP 80/54 Requires reperfusion therapy Thrombolyse if no contra-indications If contraindications Refer for surgical embolectomy Refer for catheter-based therapy Conservative management
Contraindications to thrombolysis Contraindications to thrombolysis that are considered absolute in MI may become relative in a patient with immediately life threatening PE
Streptokinase & heparin versus heparin alone in high risk pulmonary embolism: a randomized controlled trial 8 high risk PE 4 heparin 4 heparin and streptokinase Heparin group: all died Streptokinase group: all survived Jerjes-Sanchez C et al. J Thromb Thrombolysis 1995;2:227
Thrombolysis in PE: prompt haemodynamic benefits Echocardiography: paradoxical septal motion rtpa + Heparin Heparin alone S Konstantinides, Am J Cardiol 1998;82:966-970
But her BP has recovered, what now? Arrived in A&E BP 80/54 but after IV fluids BP 115/74 Hypotension is defined as systolic BP <90 or drop of 40mmHg for >15minutes, requirement for inotropes or clinical signs of shock Use other features to decide whether to thrombolyse patient currently an intermediate high risk PE.
Should you thrombolyse patients with intermediate high risk PE?
Risk-adjusted management algorithm Konstantinides et al. Eur Heart J 2014; pii: ehu283
RCTs in Intermediate Risk PE Chatterjee et al JAMA 2014;311:2414
PEITHO: primary efficacy outcome n=1006 Tenecteplase 30 50 mg Meyer et al N Engl J Med 2014;370:15
PEITHO: analysis of primary efficacy outcome Meyer et al N Engl J Med 2014;370:15
PEITHO: safety outcomes Meyer et al N Engl J Med 2014;370:15
PEITHO Trial showed no long term benefit in mortality or CTEPH rates
Effect of Age Meyer et al N Engl J Med 2014;370:15
Moderate pulmonary embolism treated with thrombolysis (MOPETT trial) n=121 Alteplase 50mg Sharifi M et al Am J Card 2012
Catheter directed therapy in intermediate high risk patients Lower risk of bleeding than systemic thrombolysis but likely higher than anticoagulation alone More effective at reducing PA pressure, RV strain and clot burden than anticoagulation alone but similar mortality rates Further studies needed regarding long term clinical benefits Consider in deteriorating patient where thrombolysis has failed or is contraindicated Interventional procedures guidance [IPG524]NICE 2015
Suggested to withhold routine thrombolysis in Intermediate High Risk PE Monitor closely - HDU/CCU Consider thrombolysis: Clinical worsening +ve DVT High/rising lactate Clinical impression If young age Need better tools to identify which patients to reperfuse Goldhaber SZ JACC 2017 69(12) 1545-8 Thrombolysis Dose weight adjusted dose consider half dose for >75 years
Follow up & anticoagulation
Sheffield PE Follow up Pathway Anticoagulation specialist nurse review after discharge Screen for malignancy Educate & counsel MDT discussion Review in PE clinic with haematology and respiratory consultant at 3/12 if appropriate Assess recovery and need for further investigation Advise on duration of anticoagulation Condliffe, RA Thromb J 2016 Dec; 14:47
Can we predict who is at high risk of recurrent VTE based on presentation? 570 patients with first episode VTE Split into 4 groups Group A: surgery within 6 weeks (86 patients) Group C: idiopathic (193) Group D: other transient risk factor for VTE (279) Eg cocp, lower limb fracture, concurrent illness Baglin et al, Lancet 2003
Duration of anticoagulation? PE following a surgical intervention 3-6 months PE with a transient risk factor 3-6 months but increased risk of recurrence compared to post surgical Idiopathic 6 months minimum, consider long term Life threatening idiopathic: consider long term anticoagulation Recurrent idiopathic: long term or until risks outweigh benefits If require long term anticoagulation, consider low dose DOAC. Review risk assessment annually Agnelli et al New Engl J Med 2013;368:699 Wells, PS Chest 2016 150(5) 1059-68
A small number of patient who are breathless after a PE have CTEPH Klok FA et al Blood Reviews 2014
A normal Q scan excludes CTEPH Q scanning is an excellent screening test for CTEPH The diagnosis may be missed on CT by nonspecialists 48
In Conclusion Risk assessment involves physiological parameters together with markers of RV dysfunction and RV ischaemia Outpatient management is safe in low risk patients even with mild RV dilatation on CT if troponin is negative The role of thrombolysis and CDT in intermediate high risk PE is unclear Increased age is a significant risk factor for bleeding with thrombolysis A combined respiratory/haematology PE clinic allows optimal assessment of need for further cardiorespiratory/haematological investigation and of optimal duration of anticoagulation Patients with SOB following previous VTE need evaluation for Chronic thromboembolic disease and CTEPH
Guidelines BTS Guideline Outpatient management of PE published soon