• An evolving literature focused on the subset of patients at low-risk for complications (death, bleeding, recurrent VTE).. High Risk Jiminez, 2010[r]
(1)Division of PULMONARY &
CRITICAL CARE MEDICINE
Pulmonary Embolism:
Issues in Stratification, Prognosis and Management
Sean M Caples, D.O., M.Sc
(2)Learning Objectives
• Gain familiarity with various prognostication tools in acute PE
• Review controversies in management of intermediate risk PE
(3)• 66 M presents to ED with abdominal pain
• Similar to past diverticulitis (occasional sharp “10/10”)
• Last night, became SOB walking up stairs and passed out, recovered
(4)In ED hours Vital signs
• T 36.8C
• RR 18-26
• HR 86-95
• BP 124-148/66-82
Exam:
• Neg cardiopulm exam
(5)(6)(7)• What is the diagnosis and where should he be admitted?
1 Massive PE—ICU
2 Submassive PE—ICU Submassive PE—Ward Low-risk PE—Ward
(8)Massive—High Risk
– Sustained hypotension (SBP < 90) for at least 15m or on inotropes not due to another cause or
– Pulselessnes or
– Profound bradycardia (< 40)
– “Syncope” (perhaps)
– Distinct management pathway
• Acute resuscitation
• Primary reperfusion (lytics, surgery, percutaneous)
• ICU level care
• ECMO
(9)Submassive—Intermediate Risk
– Acute PE without hypotension but with either
• RV dysfnx
– Dilation
– Elev BNP
– ECG new RBBB or ischemia
• Myocardial necrosis
– Troponins
• Risk/Management uncertainties
(10)Low-Risk
– Doesn’t fit criteria for massive nor submassive
– Incidental, sub-segmentals
– Short-term mortality ~ 1%
(11)Most who make it through ED survive
Causes of Death in those 30+ days
• Recurrent PE
• CV collapse
• Bleeding
(12)Natural History
Most Deaths Occur Before Hospital
• European Union 2004:
– 34% with sudden death
• Olmsted County, MN
– Death at Day O: 23.5% (causal)
36.4% (+incidental) • Death at Day 30:
– another 5-10%
Heit, Arch Intern Med, 1999
Hospitalized patients Intermediate risk
(13)Focus on Submassive/ Intermediate Risk PE:
Risk Stratification
• Why?
• How?
(14)Submassive PE:
Why Stratify Risk?
• “Close monitoring” for early complications
• Optimize standard Tx (therapeutic heparin)
Smith, Morgenthaler et al, Chest, 2010
• Offer escalation in the case of deterioration
– Assuming we can detect it in time • ? Reduce long-term complications
(15)Risk Stratification • Demographics
• Comorbid illness
• Acute physiologic response markers
• Echocardiography
– RV dysfunction/failure has been seen in low risk sPESI
• Imaging
– Saddle embolism
• Biomarkers
– Troponin, BNP
(16)PESI
Pulmonary Embolism Severity Index
• 15K+ patients dismissals from 186 PA hospitals
– Data derived from dismissal coding (ICD-9)
• Primary outcome: 30-day mortality
• Prospective ext validation in 221 inpatients in France/Switz
• 11 variables predict risk
– Demographic (2)
– Comorbid disease (3)
– Acute clinical findings (6)
– Another lab values were indep associated but didn’t change modeling
• Didn’t include echocardiography, CT findings, biomarkers
(17)(18)Submassive/Intermediate Risk PE RV Enlargement/Dysfunction
• Traditionally considered a marker of higher risk
• ~20% mortality rates in older cohorts (1990’s)
Contemporary reassessment—
increasing use of portable echo and CT angio
more common and may not be a marker of high risk
• RV abnormalities are common in hemodynamically stable patients
– 63% by CT measurement
– 23% by echocardiography
(19)RV Assessment by Echo
• Subjectivity; operator dependent
• Shape defies reliable size assessment
• No agreement on best measure
– Tricuspid annular plane systolic excursion (TAPSE)
– McConnell’s sign—free wall down, apex contracts
• RV infarct mimics PE
(20)RV Assessment by CT
• Volumetric determination of RVV/LVV ratio is least user-dependent
• Septal bowing
• IVC reflux of dye
(21)Predictors of Early (30d) Mortality
(22)Submassive PE:
Why Stratify Risk?
• “Close monitoring” for early complications
• Optimize standard Tx (therapeutic heparin)
Smith, Morgenthaler et al, Chest, 2010
• Offer escalation in the case of deterioration
– Assuming it’s detected
• ? Reduce long-term complications
(23)• 1005 pts with RV dysfunction and elevated troponin but normotensive
• Randomized to heparin with or without tenecteplase (with option for cross-over)
• Primary outcome: death or hemodynamic
decompensation within 7d of randomization
(24)(25)(26)(27)• Hemorrhagic stroke: 2.0% vs 0.2%
• Low risk of death from any cause in the heparin group (1.8%)
• Only 3.4% received rescue thrombolysis for hemodyn decompensation
(28)JAMA 2014
• NNT 65, NNH 18
(29)Submassive PE:
Why Stratify Risk?
• “Close monitoring” for early complications
• Optimize standard Tx (therapeutic heparin)
Smith, Morgenthaler et al, Chest, 2010
• Offer escalation in the case of deterioration
– Assuming we see it coming
• ? Reduce long-term complications
(30)• 709 of the original 1,006 patients (28 of 76 sites)
• Followed median 38 mos
• No significant differences in long-term:
– Death since randomization (20 vs 18%; “low”)
– Functional limitation
– Suggestion of pulm HTN by echo parameters
(31)(32)76 yo woman
• To ED with acute pleuritic chest pain; h/o post-operative DVT yrs ago
• PMH: HTN, on lisinopril; OSA, non-adherent to CPAP
(33)• BP 108/76; HR 95
• O2 sat 90% RA
• Exam BMI 42; otherwise unremarkable
(34)Which of the following excludes this patient from ED dismissal to home for
treatment of PE?
1 Her age (76 yrs) RV enlargement
3 90% saturation on RA BMI 42
(35)ED-to-Home:
Rationale
• Influences:
– high in-patient census numbers
– resource and cost-containment
– The “incidental” PE detected on imaging performed for other indications
– Anecdotes of the patient that “didn’t need to be admitted”
– More patient-friendly home treatment (DOAC’s)
• An existing ED-to-Home pathway for DVT
(36)• 344 pts in 19 ED in Europe and US
• Low risk classification (PESI class I and II)
• Up to days SQ LMWH then oral A/C
• Recurrent VTE at 90d (1 vs 0)
• Death at 90d (1 vs 1)
• Young (late 40’s), low rates of Ca (1-2%)
(37)Risk Stratification: Tools
• Pulmonary Embolism Severity Index (PESI)
– 11 variables to predict risk via a numeric scale
– classes Aujesky, 2005
• sPESI (simplified PESI)
– variables
– Low risk vs High Risk Jiminez, 2010
(38)(39)• Ottawa Hospital
– 1,100 bed major teaching hospital
– 50% of PE’s treated as an outpatient, empirically selected
• Seen in Thrombo Clinic within 24 hrs (7 days/wk)
• 2010-15; symptomatic PE, CT confirmed or high-prob V/Q
• Chart review of 576 inpatients vs 506 outpatients (matched)
• Primary outcome: adverse events at 14 days
– Recurrent VTE, major bleeding, death
(40)(41)A few words about direct oral anticoagulants (DOACs)
• Not studied in those with BMI > 40
• Contraindicated in valvular disease/prosthesis, pregnancy, end-stage liver disease
• Other idiosyncracies; reimbursement issues
• Ask Mayo Expert