kabrhel - pe at both ends of the severity...

9/19/17

1

Pulmonary Embolism at Both Ends of the Severity Spectrum

ChristopherKabrhelMDMPHDirector,CenterforVascularEmergencies

DepartmentofEmergencyMedicineMassachuse>sGeneralHospital

HarvardMedicalSchoolBoston,Massachuse>s,USA

Disclosures

Rela%onship En%ty

Consultant DiagnosEcaStago,Genentech,SiemensHealthCare,PortolaPharmaceuEcals

AdvisoryBoard Pfizer,JanssenPharmaceuEcals,Portola,Boehringer-Ingelheim

GrantRecipient NIH,DiagnosEcaStago,SiemensHealthcare,JanssenPharmaceuEcals

Silent PE

500,000

Deaths

60,000

Post-thrombotic Syndrome

800,000

Pulmonary Hypertension

30,000

DVT

1-2 Million

PE

5-600,000

Hirsh J and Hoak J. American Heart Association. 1996. Heit J et al. Blood. 2005;106: Abstract 910.

Anderson FA et al. Am J Hematol. 2007;82:777-82.

VTE Incidence

Becattini C, Thromb Haemost. 2008

A Spectrum of Severity

HighRisk

LowRisk

PE Treatment

HighRisk

LowRisk

PE Treatment

9/19/17

2

An?coagulant Op?ons for Ini?al Treatment

An%coagulant Ini%aldose Restric%on

Peak

Unfrac%onatedheparin 18U/kgthen80U/kg/hr,IV Heparininducedthrombocytopenia 1hour

Enoxaparin 1mg/Kgsubcutaneously CreaEnineclearance<30ml/min 3hours

Dalteparin 200U/kgsubcutaneously CreaEnineclearance<30ml/min 4hours

Fondaparinux 5-10mgsubcutaneously CreaEnineclearance<30ml/min 3hours

Rivaroxaban 15mgorallyBIDwithfood Crea%nineclearance<30ml/min 2-4hours

Apixiban 10mgorallyBIDwithorwithoutfood

Crea%nineclearance<30ml/min 3-4hours

SPEED-D

Outcomes Primary outcome: Any patient who: • Received advanced cardiac life support • Developed a new cardiac dysrhythmia • Developed hypoxia (SaO2<90%) or required respiratory support (>2L NC) • Developed hypotension (Systolic Blood Pressure <90mmHg) • Was treated with vasopressors • Underwent thrombolysis or thrombectomy • Developed recurrent PE • Died Secondary “Severe” Outcome: Any patient who: • Received advanced cardiac life support • Developed ventricular tachycardia or fibrillation • Required positive pressure ventilation or endotracheal intubation • Was treated with vasopressors • Underwent thrombolysis or thrombectomy • Died

Kabrhel, Thorax, 2014

•  Primaryoutcome:–  AnyclinicaldeterioraEonorneedforhospital-

basedintervenEon(5day,30day).

•  Secondaryoutcomes:–  “Serious”clinicaldeterioraEonorneedfor“major”

hospital-basedintervenEon(5day,30day).–  All-cause30-daymortality.

Outcomes

• MedianLOS 3days

• Composite: 99(33%)•  Severe: 28(9%)•  30-Dayall-causemortality 12(4%)

•  10Cancer,2ChronicLungDisease


Most PE patients (67%) suffer no clinical deterioration and require no hospital-based intervention.

Outpa?ent Treatment of PE

Aujesky, Lancet, 2011

344PaEentsPESI<85Excluded:

SaO2<90%SBP<100mmHgCPneedingopiatesAcEvebleedingHighBleedingRisk

Strokewithin10daysGIbleedingwithin14daysPlatelets<75,000

RenalFailure,CrCl<30ml/minWeight>150kgHITTherapeuEcAnEcoagulaEonatEmeofPEBarrierstoOutpaEentTreatmentPregnancyPE>23hoursold

FIGURE: Outpatient Treatment By ED Volume

0

10

20

30

40

50

0 100 200 300 400

Out

patie

nt t

reat

men

t ra

te

Number of PE visits

PE

0

20

40

60

80

100

0 100 200 300 400

Out

patie

nt t

reat

men

t ra

te

Number of DVT visits

DVT

DVT: 197,000 visits / 691 hospitals 42.3% treated as outpatients

PE: 154,000 visits / 444 hospitals 4.8% treated as outpatients.

Outpa?ent Treatment

9/19/17

3

PhysicianConcerns

Survey of 135 emergency physicians about home treatment of low risk PE with NOACs.

Kahler ZP and Kline JA. Acad Emerg Med, 2014

PhysicianConcerns

Survey of 135 emergency physicians about home treatment of low risk PE with NOACs. Main concerns:

1.  Nofollow-up (85%)2.  Unfamiliaritywiththeprocess (40%)3.  PerceivedexpenseofaNOAC (33%)4.  Medicolegalliability(riskassessment) (25%)

Kahler ZP and Kline JA. Acad Emerg Med, 2014

Follow Up Follow Up

MGHOutpa%entVTEClinic:•  Staffedbyhematologyandvascularmedicine•  PaEentsfollowupwithinONEWEEKArrangingfollowupfromEDorObservaEonUnit:

•  Informprimarycarephysicianorappropriatespecialist•  IftreaEngwithaNOAC:

•  Calloremail(ajerhours)theOutpaEentVTEClinicscheduler•  Arrangeanappointmentwithhematologyorvascularmedicinewithinoneweek.

•  IftreaEngwithenoxaparin/warfarin:•  ArrangefollowupintheanEcoagulaEonclinicwithinoneweek.

Familiarity with the Process Familiarity with the Process

9/19/17

4

PerceivedCosts

Kahler ZP, Beam DM, Kline JA. Acad Emerg Med. 2015

PerceivedCosts

Kahler ZP, Beam DM, Kline JA. Acad Emerg Med. 2015

MedicolegalConcerns/RiskStraEficaEon MedicolegalConcerns/RiskStraEficaEon

PESI Age, in years ___ Male sex +10 Cancer +30 Heart failure +10 Chronic lung disease +10 Pulse ≥110 /min +20 SBP <100 mmHg +30 RR ≥30 /min +20 Temperature < 36 +20 Altered mental status +60 Sao2 < 90 +20 Low Risk <85

Simplified PESI Cancer +1 Cardiopulmonary disease +1 Pulse ≥110 /min +1 SBP <100 mmHg +1 Sao2 < 90% +1 Low Risk ≤1

Geneva Prediction Score Cancer +2 Heart failure +1 Previous DVT +1 SBP <100 mmHg +2 PaO2 <60 mmHg +1 DVT on US +1 Low Risk ≤2

Squizzato et al, J Thromb Haemost, 2012

22,127 patients, 21 cohorts Low 30 day all-cause mortality

Clinical Predic?on Rules

Severe

•  PESI (class I-II) •  Sensitivity .71 •  Specificity .50

•  sPESI (<1 point) •  Sensitivity .82 •  Specificity .36

•  Geneva (<2 points) •  Sensitivity .39 •  Specificity .78

30 Day Mortality •  PESI (classI-II)

•  Sensitivity 1.0 •  Specificity .51

•  sPESI (<1 point) •  Sensitivity 1.0 •  Specificity .36

•  Geneva (<2 points) •  Sensitivity .67 •  Specificity .78

Composite •  PESI (class I-II)

–  Sensitivity .70 –  Specificity .57

•  sPESI (<1 point) –  Sensitivity .81 –  Specificity .42

•  Geneva (<2 points) –  Sensitivity .37 –  Specificity .83


Predictor Composite Severe 30-day

Mortality Age 0.005 0.41 0.045 Race (white vs. nonwhite) 0.42 0.65 0.5 Highest HR 0.12 0.19 0.64 Lowest SBP <0.0001 <0.0001 0.16 Highest RR 0.0007 0.019 0.13 Lowest SaO2 <0.0001 0.011 0.084 Vital Signs Normal <0.0001 0.054 0.005 Coronary Artery Disease 0.0006 0.80 0.29 Lung Disease 0.091 0.059 0.014 Malignancy 0.25 0.40 0.0004 Malignancy (Active) 0.74 0.090 <0.001 Renal Insufficiency 0.31 0.76 0.16 Cerebrovascular Disease 0.008 0.37 0.34 D-dimer 0.31 0.48 0.077 Troponin 0.008 0.002 0.51 NT-proBNP 0.0002 <0.0001 0.22 PE Central 0.45 0.015 0.61 PE Multiple 0.14 0.90 0.54 Residual DVT 0.002 0.19 0.51 Right Heart Strain on Echo <0.0001 <0.0001 0.84


SPEED-D Study Outcomes

9/19/17

5

MGH Risk Stra?fica?on System MGH Outpa?ent Treatment n=163, 12 months

Diagnosis:•  PE 38(23%)•  PE&DVT 11(7%)•  DVT 113(70%)

Dischargedfrom:

•  ED 107(66%)•  Obs.Unit 56(34%)

Treatment:•  Rivaroxaban 103(63%)•  Enoxaparin/warfarin 49(30%)•  Apixaban 8(5%)•  Aspirin 3(2%)

ReturntoED:•  7days 9(6%)•  30days 21(13%)

Patient’s Words

“I believe [this medicine] is better than takin coumadin…being hospitalized

and having blood draws…”

Conclusions

• Outpa%enttreatmentofPEissafe• Riskstra%fica%onisthefirststep• Adefinedprotocolincreasesphysiciancomfort• ReliableoutpaEentfollowupiscri%cal• PaEentsexpresshighsa%sfac%on• Overallcostsarelower

LowRisk

PE Treatment

HighRisk

52.4%*

14.7%

A Spectrum of Severity

Kucher et al, Circulation 2006

9/19/17

6

EMPEROR Registry

1880PaEentswithconfirmedPE:•  Hypotension: 3%•  RVhypokinesisonTTE 12%•  Troponin(+): 23%•  BNP/NT-proBNP(+): 11%•  Aggregate 35%with≥1highriskmarker•  Fibrinolysis 2%(45/1880)overall

9%(3/58)hypotensivepa%ents

Pollack CV, J Am Coll Cardiol 2011

A Case…

A 36-year-old male…

•  History of Present Illness: •  Dyspnea and near syncope while sitting on toilet

•  Past Medical History •  3 weeks status post a knee arthroscopy for a meniscus tear

•  Physical Examination: •  EMS Vital Signs: HR 110, BP 80/55, RR 28, SaO2 85% on Room Air •  ED Vital Signs: HR 120, BP 132/72, RR 24, SaO2 93% on 6L NC •  General: Awake and alert. •  Chest: Clear bilaterally. •  Heart: Regular tachycardia at 120

NTpro-BNP: 12,000 Troponin T: 0.14

Echocardiogram

Plan?

9/19/17

7

37

Therapeutic Alternatives

•  Anticoagulation •  Unfractionated Heparin •  Low-Molecular-Weight Heparin •  Direct Thrombin Inhibitors •  Xa Antagonist •  Warfarin

•  Thrombolytic Therapy •  Systemic •  Catheter Directed •  Pharmacomechanical

/Catheter-Directed Thrombolysis (P/CDT)

•  Mechanical Removal •  Surgical Thrombectomy •  Thromboaspiration

•  Hemodynamic Support •  IV Fluids •  Vasopressors •  ECMO

•  Vena Cava Filter

High Risk PE

Thrombolysis vs. Heparin

•  TrialsincludinghemodynamicallyunstablepaEents•  SignificantdecreaseinrecurrentPEordeath

•  19%vs.9%

•  TrialsexcludinghemodynamicallyunstablepaEents•  NosignificantdifferenceinrecurrentPEordeath

•  5%vs.5%

Wan, Circulation, 2004

Intravenous Thrombolysis PEITHO

Meyer, NEJM, 2014

Tenecteplase(n=506)

Placebo(n=499) Pvalue

n (%) n (%)Non-intracranialmajorbleeding 32 (6.3) 6 (1.5) <0.001

Severe 16 2

Moderate 16 4

Allstrokesbyday7 12 (2.4) 1 (0.2) 0.003

Hemorrhagic 10 1

Ischemic 2 0

Mechanical Fragmenta?on

Rotational Pigtail Catheter

Balloon Masceration

Mechanical Fragmenta?on

25paEents•  PigtailcatheterrotaEon/mechanicalfragmentaEon•  ThrombolysisandsucEon

Nakazawa, BJR, 2008

Rheoly?c Thrombectomy

• AngioJet®• Hydrolyzer®• Oasis®

Venturi Effect

9/19/17

8

Rheoly?c Thrombectomy

• Ahigh-pressuresalinejetwithinthedevicegeneratesalowpressuregradient(Bernoulli'sprinciple).

• Clotfragmentsaresuckedintosidechannelsofthecatheterbythevacuumcreated.

•  LocalinjecEonofthrombolyEcagentintothrombusbypulsespray.

AngioJet®

Platelet

Adenosine

Potassium

Adenosine

Bradykinin

BradycardiaComplete Heart Block

Catheter Directed Thrombolysis

•  ProximalinfusionofthrombolyEc•  MechanicalFragmentaEon•  UltrasonicacceleraEon

•  12-24hourtreatment

•  TheoreEcalbenefits:•  lowerdrugdose(10-20mgtPA)•  Drugactsfaster,clearingclotsooner•  MonitorPApressure

Scmitz-Rode CVIR 1998

EKOS®

ULTrasound Accelerated ThrombolysIs of

PulMonAry Embolism

•  Phase II, multicenter, open-label, randomized, controlled clinical trial

•  30 Heparin

•  29 Heparin + CDT

Kucher, Circulation, 2014

ULTIMA

RV:LVRa%o

Pre-Treatment 24Hours 90Days

CDT 1.28 0.99 0.95

Heparin 1.20 1.17 0.98

Kucher, Circulation, 2014

Pulmonary Embolism Response to Fragmenta?on, Embolectomy and Catheter Thrombolysis (PERFECT) Registry

•  101PaEents•  28MassivePE

•  73SubmassivePE

•  76CDT•  28mgtPA

Kuo CHEST, 2015

Echocardiographic Grade of RV Dysfunction

PA Pressure

9/19/17

9

PERFECT Registry

Kuo CHEST, 2015

SEATTLE II

Piazza, Circ Intervention, 2015

SEATTLE II

Piazza, Circ Intervention, 2015

Suc?on Thrombectomy

Weinberg et al, Cath and Cardiovasc Int, 2014

MGH Case Series

Weinberg et al, Cath and Cardiovasc Int, 2014

Alterna?ve Suc?on Devices

9/19/17

10

Open Surgical Embolectomy

Stein, Am J Med. 2012.

ECMO

MGH Case Series:•  10paEentswithmassivePEandhemodynamiccollapse

•  8/10(80%)Survivedto30days

Hospital Unit

Referring Hospital

Vascular MedicineCardiology

Interventional Radilogy

Cardiac or Vascular Surgery

ED/Floor TeamPulmonaryHematology

Severe PE Identified

Anticoagulation?IV Thrombolysis? Surgery?

Catheter?

Hospital Unit

Referring Hospital

Vascular MedicineCardiology

Interventional Radilogy

Cardiac or Vascular Surgery

ED/Floor TeamPulmonary

Hematology


Anticoagulation?IV Thrombolysis? Surgery?

Catheter?

Pulmonary Embolism Response Team (P.E.R.T)


MGH Unit Referring Hospital

Immediate Conference with:ED/Floor Team

PulmonaryVascular Medicine/Cardiology

Cardiac Surgery

PERT Team Activated

Disposition and Treatment Plan

Provias, Hospital Practice, 2014

Rapid Response

Response Triggering

PERT


9/19/17

11

•  CardiologyandVascularMedicine

•  CardiacandVascularSurgery•  ECMOteam

•  EmergencyMedicine•  Hematology

•  IntervenEonalRadiology•  PulmonaryandCriEcalCare

Rapid Response

Pre-Determined Response Team

PERT


PERT

Rapid Response

Response Mechanism


PERT

Immediate

Multidisciplinary Discussion

Plan?

Plan? ED Course

• PERTRecommendaEon:•  “WeagreedthatsucEonthrombectomywouldbereasonableapproachandthecathlabwasopened.”

9/19/17

12

ED Course

• PERTRecommendaEon:•  “WeagreedthatsucEonthrombectomywouldbereasonableapproachandthecathlabwasopened.”

• PaEentrequestedtourinatepriortoprocedure…

•  Tachycardic,hypotensive,diaphoreEc,pale•  OxygenaEondroppedtothelow90s•  Bradycardic,lostpulsesandwasunresponsive

Mul?disciplinary PERT Response

EmergencyMedicine:•  CPR/EndotrachealintubaEon•  IVepinephrinex3•  ReturnofspontaneouscirculaEon•  100mgIVtPA

CardiacSurgery:•  PlacedpaEentonECMOintheED

VascularMedicineandCardiacSurgery:•  ToOperaEngRoom•  SurgicalEmbolectomy•  “Vortex”onstandby

R

L

Mul?disciplinary PERT Response

Pulmonary/Cri%calCare:•  Admi>edthepaEenttoMedicalICU•  FiO2decreasedfrom100%to40%over24hours•  Pressorsweanedover24-48hrs•  RepeatCTPA:

•  ResidualsmallemboliinsegmentalandsubsegmentalbranchesofRLL•  RepeatEchocardiogram:

•  ImprovedRVfuncEon•  ExtubatedonDay5•  DischargedonDay14torehab

•  SPO2:96%onroomair•  FollowupinPulmonaryHypertensionClinic

Case Resolution

Clinic Note: Dear ____, “It was very nice to see you feeling so well….”

The MGH PERT Experience

9/19/17

13

MGH PERT Ac?va?ons n=394 (initial 30 months)

now, n≈700

•  Multidisciplinary virtual consults •  Average length: 25 mins. •  Range 5–15 physicians

•  Off-hours/weekends: 53%

Kabrhel, CHEST, 2016

MGH PERT Pa?ents


n. % PE LOCATION Intracardiac 28 8.9 Saddle 61 19.4 Main Pulmonary Artery 127 40.4 Lobar Pulmonary Artery 75 23.9 Segmental Pulmonary Artery 44 14 PE SEVERITY Right Heart Strain on Echocardiogram 178 56.7 Right Heart Strain on CT 133 42.4 Troponin >/= 0.1 ng/ml 101 32.2 NT-proBNP >/=500 pg/ml 187 59.6 DVT present 158 50.3 CLINICAL SEVERITY Endotracheally Intubated 45 14.3 Admitted to ICU 159 50.6

MGH PERT Pa?ents


MGH PERT Treatment


0

10

20

30

40

50

60

70

80

AnEcoags IVLysis CDT Vortex Surgery ECMO IVCFilter

Treatment(%)

ED

ICU

Inpt

MGH PERT Treatment

• BleedingcomplicaEon: 14%overall 8%day0-7 6%day8-30

• Bleedingajertreatment:•  IVtPA 6/14(43%)•  CDT 1/28(4%)•  AnEcoagulaEonalone 8/209(4%)

MGH PERT Bleeding


9/19/17

14

PERT Outcomes


Pulmonary Embolism Response Team Consortium

Pulmonary Embolism Response Team Consortium

Web: www.pertconsortium.org

@pertconsortium

Email: [email protected]

PERT Across the United States

Academic71%

Non-AcademicTeaching13%

Non-AcademicNon-

Teaching13%

Other3%

1-516%

6-1042%

11-2042%

SingleMD5%

Alwaysteam-based63%

Varies32%

Barnes, CHEST, 2016

Activations per Month

Hospital Type

Initial Response

Summary

• TreatmentsforPEareevolvingrapidly.• Low-riskPEpaEentscansafelybetreatedasoutpaEents.

• TherearenewtreatmentsfortreaEnghigh-riskPEpaEents.

• ThetreatmentofPEismulEdisciplinary.

Thank You [email protected]

kabrhel - pe at both ends of the severity...

Documents