Establishing a

PE Response Team

Daniel Schimmel, MD MSAssistant Professor of Medicine

Northwestern Medicine

November 3, 2018

Pulmonary Embolism Management

Pulmonary Embolism Management

Pulmonary Embolism Management

Pulmonary Embolism Management

Pulmonary Embolism Management

PERT

Pulmonary Embolism Management

PERT

What is a PERT?

• A multidisciplinary response team

available to triage and treat patients with

submassive or massive pulmonary

embolism

• First publicly described in 2013 by

colleagues at the MGH

Why do we need a PERT?

• 3rd most common CV death in US

• Lack of robust clinical trial evidence

Why do we need PERT?

• 3rd most common CV death in US

• Lack of robust clinical trial evidence

• Differing practice guidelines for risk

stratification AND treatment

Becattini C, Agnelli G. Thromb Haemost. 2008; 100(5): 747–751Abrahams van-Doorn P. and Hartmann IJC. Imaging Insights. 2011; 2: 705-715Dalen JE. Chest. 2002; 122: 1801-17

Shock

High-intermediate

risk PE

Low-intermediate risk PE

Low risk PE

Asymptomatic

5

10

20

25

40

Estimated Prevalence (%) Mortality 13-30%

• In clinical practice, systemic thrombolysis is

withheld in up to two thirds of patients with

high-risk (massive) PE

Eur Heart J 2008: 29:2276-2315Am J Cardiol. 2006;97:127-9Circulation 2006;113:577-82

12

Massive PE and hesitation to treat

Systemic Thrombolysis Trials

• 2004 Meta-analysis of RCTs:

– 748 unselected patients showed no benefit

– subgroup 128 patients unstable

• combined endpoint, death and recurrent PE

• 9.4% vs 19% OR 0.45 95% CI 0.22-0.92

• NNT=10

Circulation. 2004 Aug 10;110(6):744-9

Thrombolytics and Mortality

Chatterjee et al; JAMA. 2014;311(23):2414-2421

• In randomized trials, systemic lytics

• 13% risk of major bleeding

• 1-2% risk of intracranial hemorrhage

• In practice, systemic lytics

• 20% risk of major bleeding

• 3-4% risk of intracranial hemorrhage

Massive PE and hesitation to treat

Eur Heart J 2008: 29:2276-2315Am J Cardiol. 2006;97:127-9Circulation 2006;113:577-82

15

To lyse or not to lyse…

Chatterjee et al; JAMA. 2014;311(23):2414-2421

When will I give systemic thrombolysis?

• Persistent hypotension or shock are only widely accepted indication1

– SBP < 90 mmHg or 40 mmHg from baseline

–Normotensive shock

– Low bleeding risk

1Chest. 2016;149(2):315-3522Circulation. 2000 Jun 20;101(24):2817-22.

Contemporary Trials

intermediate risk PE (submassive)

• Systemic lytic trials - ?expanded use

– PEITHO

– MOPPET

– TOPCOAT

• Catheter trials

– ULTIMA

– SEATTLE

– PERFECT

PEITHO Trial

• PEITHO trial

• Tenecteplase + heparin VS placebo + heparin

• Normotensive patients with RV dysfunction and biomarker elevation

• 1005 patients enrolled

N Engl J Med. 2014 Apr 10;370(15):1402-11

PEITHO Trial

N Engl J Med. 2014 Apr 10;370(15):1402-11

PEITHO Trial

N Engl J Med. 2014 Apr 10;370(15):1402-11

Stroke risk 2.4% vs 0.2%

Contemporary Trials

intermediate risk PE (submassive)

• Systemic lytic trials

– PEITHO

– MOPPET

– TOPCOAT

• Catheter trials

– ULTIMA

– SEATTLE

– PERFECT

No mortality benefit

More complete and rapid

RV and PASP improvement

Possible improved QOL

Expense of more bleeding,

including ICH

Who are the key stakeholders?

• Non-interventional colleagues

– ED, intensivists/pulmonology

– Internal medicine, hematology

• Interventional colleagues

– Cardiology, IR, vascular, CT surgery

– Interventional cardiology partners

• Administrative

– Infrastructure, cohesiveness of above

– Bed assignment, transfer coordinator

Why cardiology?

• BNP and Troponin

• Echo

• Anticoagulation

• Thrombolytic therapy

• Time sensitive endovascular procedures

• Mechanical support

• ECMO

Why pulmonology?

• Historic familiarity

• Interpretation of imaging and

parenchymal changes

• Evaluation for chronic forms of

pulmonary hypertension

• Strategies for managing acute hypoxic

respiratory failure

Why hematology?

• Complicating coagulopathies

• Heparin induced thrombocytopenia

• Role for hypercoaguable testing

• Duration of anticoagulation

• Family screening

Why interventionalist?

• Reperfusion is key in patients who are

unstable

• Need at least one champion in the space

who knows the data well and is

experienced

• Operator volume correlates with

avoidance of bad outcomes

• Interventional Cardiology, Interventional

Radiology or Vascular

Extra credit: Cardiac surgeon

• Extra corporeal membrane oxygenation

(ECMO) may be required

• Surgical embolectomy for those

unresponsive to thrombolytics or with

lytic contraindications

• May not be at your hospital

– Establish a relationship with a referral center

What is your capacity?

• Fellows and advanced practice providers

• 24 hour coverage (Echo? Intervention?)

• Consult-> dx VS decision VS activate

• All PE vs intermediate to high risk

• Interventional partners

What infrastructure needed?

• Call system/IT

• Infusion catheters +/- ultrasound facilitated

• Fragmentation and Suction embolectomy

devices

• ECMO and mechanical support

• IVC filter responsibility

• Quality review and education

Low Risk

Intermediate Risk

High Risk

Obs vs D/C

Telemetry

ICU/TX Decisions

Pulmonary Embolism Risk Stratification

Yes NosPESI = 0 and no RV dysfxn

sPESI>0 or RV dysfxn

Anticoagulate. Consider early transition to

outpt therapyMortality <1%

SBP<90

sPESI ScoreRisk Stratify*:

Troponin, BNP, Echo

Reperfusion therapy +/-

support Mortality >15%

Anticoagulate, Strongly consider

reperfusion therapy

30 day PE related mortality 10-15%

Anticoagulate. Consider

reperfusion therapy

30 day PE related

mortality ~ 5-7%

Anticoagulate.30 day PE

related mortality ~2-3%

High Risk PEScore 5+

Interm-high risk acute PE

Score 0-2Low-intermed

risk PEVery low risk PE

*risk stratification modified from ESC 2014 Guidelines, BOVA score and modified FAST scores**If HR less than 100 and biomarkers negative, consider chronic thromboembolic HTN

ICU Admit

sPESI calculation (each 1 pt)

Age>80CancerChronic heart failureChronic lung diseaseHR>110SBP<100RA SpO2<90%

Heart rate >110 1 point(HR>SBP) 2 points

Syncope hx 1 pointSys BP 90-100 2 pointsBiomarker + 1 point2nd Biomarker 1 pointSevere RV dysfxn 2 points

(by CT or echo)

Score 3-4 Intermediate risk acute PE

ICU ICU Obs vs D/C

Shared

Decision

Treatment Potential

Harm

PE Risk

Treatment Potential

Gain

Catheter-directed lysis

Chen R. Endovascular Today July 2014

Unifuse sidehole catheter AngioJet - Powerpulse

Angiovac – large volume suction embolectomy EKOs - Ultrasound facilitated

Ultrasound facilitated lysis

Fibrin separation₸

Fibrin without Ultrasound

Fibrin With Ultrasound

Active drug deliveryby acoustic streaming

Mechanism of Action

Braaten et al. Thromb Haemost 1997; 78:1063-8.

Ultrasound delivered in:High frequency (2.2 Mhz)Low power (0.5 W per element)Pulses of varying waveforms

Ultrasound pulses

ULTIMA trial Systolic RV

dysfunction

37

0%

20%

40%

60%

80%

100%

Baseline 24 hrs 90 days

Syst

olic

RV

Dys

fun

ctio

n

Baseline 24 hrs 90 days

Severe

Moderate

Mild

Normal

USAT + Heparin Heparin

P<0.0001P<0.0001

P=0.003**

Kucher et al. Circulation 2013

ULTIMA Secondary endpoint analysis

Clinical outcomes at 90 days

EKOS + Heparin Heparin

p-valueN = 30 N = 29

Death 0 0% 1* 3% 0.49

Recurrent venous thromboembolism 0 0% 0 0% 1.00

Major bleeding 0 0% 0 0% 1.00

Minor bleeding 3** 10% 1§ 3% 0.61

* rehospitalization and death from advanced pancreatic cancer** two patients with transient mild hemoptysis without medical intervention,

one patient with groin hematoma requiring manual compression§ one patient with transient anal bleeding following endoscopic removal of colon polyp

Catheter-directed Studies• SEATTLE: single arm, prospective 150 patients high and

intermediate risk

– Mean ratio reduction of 0.42, mean PA pressure reduction 14.5 mmHg (p<0.0001)

• PERFECT: 101 patients prospective registry high and intermediate

– Success in 85.7% massive PE pts, 97.3 submassive PE pts, 89.1% showed improvement in RV strain on echo (p<0.0001)

• OPTALYSE PE: 4 arms comparing lytic dose and duration of ultrasound facilitated lytics – no significant difference Circulation. 2014 Jan;129(4):479-86

JACC Cardiovasc Interv. 2015 Aug 24;8(10):1382-92Chest. 2015 Sep;148(3):667-73

Contemporary Trials

intermediate risk PE (submassive)

• Systemic lytic trials

– PEITHO

– MOPPET

– TOPCOAT

• Catheter trials

– ULTIMA

– SEATTLE

– PERFECT

– OPTALYSE PE

– FLARE

No mortality data

More complete and rapid RV

and PASP improvement

More bleeding than heparin

Less major bleeding than

systemic lysis (however no direct comparison)

Contemporary Trials

intermediate risk PE (submassive)

• Systemic lytic trials

– PEITHO

– MOPPET

– TOPCOAT

• Catheter trials

– ULTIMA

– SEATTLE

– PERFECT

No mortality data

More complete and rapid RV

and PASP improvement

More bleeding than heparin,

but no ICH in recent data

No comparison systemic lysis

Contemporary Trials

intermediate risk PE (submassive)

• Systemic lytic trials

– PEITHO

– MOPPET

– TOPCOAT

• Catheter trials

– ULTIMA

– SEATTLE

– PERFECT

No mortality data

More complete and rapid RV

and PASP improvement

More bleeding than heparin,

but no ICH in recent data

No comparison systemic lysis

Submassive and massive PELanes of care

Hemodynamics

• ECMO

• Pressor/Inotrope

• RP Impella?

• None required

Reperfusion

• Systemic tPA

• Catheter directed lysis

• Suction embolectomy

• Surgical embolectomy

• Endogenous lysis

Prevention

• Anticoagulation

• IVC Filter

NMH PE Response Team

• ~ 4 years experience

• ~ 350 consults

• systemic and catheter directed cases

• Suction embolectomy

• emergent ECMO and surgical embolectomies

PERTCONSORTIUM.ORG

Life after acute PE

All PE patients

Reduced functional status 50%

Persistent thrombi 15-33%

Measurable limitation

10-30%

CTEPH

0.1-4%

Klok Blood Reviews 2014Matthews Pulm Circulation 2016

Web image from Quizlet.com

PE Response Team Follow-up

• Pulmonary HTN advanced practice nurse follows in hospital

• Standard discharge follow-up for submassive and massive PE to Pulmonary HTN/CLOT Clinic

PE Response Team Follow-up

• Pulmonary HTN advanced practice nurse follows in hospital

• Standard discharge follow-up for submassive and massive PE to Pulmonary HTN/CLOT Clinic

CTED and CTEPH

Chronic thromboembolic disease

CTEPH/Acute PE imitators• Syncope but otherwise looks well

• No troponin rise with large RV

• Elevated PASP above 50

• RV hypertrophy

• High residual burden after lysis

Becattini Chest 2006Klok Blood Reviews 2014

Things to look for on Angiography

1) Pouch defects

2) Pulmonary artery webs or bands

3) Abrupt narrowings

4) Complete obstruction at origin of vessel

5) Intimal irregularities

Fedullo et al. 2011 American Thoracic Society Journal

Things to look for on Angiography

1) Pouch defects

2) Pulmonary artery webs or bands

3) Abrupt narrowing

4) Complete obstruction at origin of vessel

5) Intimal irregularities

Fedullo et al. 2011 American Thoracic Society Journal

Things to look for on Angiography

1) Pouch defects

2) Pulmonary artery webs or bands

3) Abrupt narrowing

4) Complete obstruction at origin of vessel

5) Intimal irregularities

Fedullo et al. 2011 American Thoracic Society Journal

Hiroki Mizoguchi et al. Circ Cardiovasc

Interv. 2012;5:748-755

Controversies in

acute care and f/u

• How do we risk stratify?

• Does CDT add anything meaningful?

• When to recommend surgery?

Controversies in

acute care and f/u

• How do we risk stratify?

• Does CDT add anything meaningful?

• When to recommend surgery?

• How do we follow-up?

• Duration anticoagulation?

• Activity recommendations?

• CTEPH Evaluation?

Building a PE Response Team

dschimme@nm.org

Homework

• ESC guidelines 2014

• JACC March 2016; 67 –Management of PE

• JACC March 2016; 67 –Acute PE Interventional Approach

• Circulation 2016;133 – Multidisciplinary PERT

• CHEST Feb 2016;149 – Antithrombotic therapyfor VTE

• www.pertconsortium.org Dan Schimmeldschimme@nm.org