8/2/2019

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MANAGEMENT OF INTERMEDIATE &

HIGH-RISK PULMONARY EMBOLUS: THE UVA EXPERIENCE

Department of Medicine Grand RoundsAugust 2, 2019

Andrew D. Mihalek, MDAssistant Professor of Medicine

Division of Pulmonary & CC Medicine

Aditya Sharma, MDAssociate Professor of Medicine

Division of Cardiovascular Medicine

Financial Disclosure(s)

Dr. Andrew Mihalek participates in industry-sponsored clinical trials

Complexa, Inc

Corvia Medical, Inc

United Therapeutics

(None of these hold relevance to today’s conversation)

Dr. Aditya Sharma participates in industry-sponsored medical device trials

Portola, Inc

Vascular Medcure, Inc

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Session Objectives

Distinguish high-risk pulmonary embolus from intermediate-risk and low-risk pulmonary embolus

Review various treatment options for high and intermediate-high risk pulmonary embolus

Review, discuss, and dissect in-house data generated from the initiation of the Pulmonary Embolism Response Team at UVA

Our Personal Disclosures

Cardiovascular Disease Emergency Medicine

Pulmonary & CCMInterventional Radiology

Cardiovascular Surgery

PharmacologyHematology

Diagnostic Radiology

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Clot Propagation Equates to Propagation of Fear

“Clot Burden” Not Supported by Real World Clinical Experience

Jain et al. Am J Cardiol. 2017: Nonsaddle PE more likely to present with hypotension (46% vs. 33%, p = 0.02)

Nonsaddle had a higher 90 day mortality (26% vs. 13%, p = 0.02)

Conclusion: “Clot location not associated with patient outcomes”

Alkinj et al. Mayo Clin Proc. 2017: Saddle PE more likely to present with hypotension (31% vs. 21%, p = 0.01)

No difference in length of stay (5 vs. 4 days, p = 0.09)

No difference in hospital mortality (4 vs. 5 %, p = 0.81)

Conclusion: “No difference in short term outcomes”

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PE Risk Stratification

ESC/ERS Consensus. European Heart J 2014

2014 ESC PE Risk Stratification Guidelines

ESC/ERS Consensus. European Heart J 2014

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Techniques for PE Risk Stratification

Jaff et al. Circ 2011Quiroz et al. Circ 2004

“Massive” PE “Submassive” PE “Minor” PE

• Sustained Hypotension• Systolic BP < 90mmHg• 40mm Hg from baseline

• Inotropic Support

• Pulselessness

• Bradycardia• HR < 40bpm

• Normotensive

• Right Ventricle Dysfunction

• Myocardial Necrosis

• Normotensive

• No RV Dysfunction

• No myocardial necrosis

High-Risk PE Intermediate-Risk PE Low-RiskPE

Do Intermediate-Risk Patients Warrant Aggressive Care?

Konstantinides et al. NEJM. 2002Meyer et al. NEJM. 2014

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Are There Better Treatment Options for Intermediate-Risk Patients?

Diversity of Therapeutic Options for Pulmonary Embolus in 2019

Intermediate Risk

Pulmonary Embolism

IVC Filter

Systemic Lysis

Catheter-Directed

lysis

Mechanical Thrombectomy

ECMO

Surgical Therapies

• No clear recommendations from professional groups

• No strong RCTs

• High mortality in this group despite anticoagulation

• Complex clinical scenarios

Real-Life Conundrums

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Mission for PE Response Team program

Improve mortality and morbidity associated with intermediate and high-risk PE

Provide “state of the art” care utilizing multidisciplinary team approach in a rapid fashion

Rapid Response Team

(STEMI)

Multidisciplinary approach (Tumor board)

PERT

Who do you need in a PE Response Team?

CORE CLINICAL GROUP

Urgent evaluation: 24 / 7 x 365 days

Potential Benefits: Rapid multi-disciplinary medical decision making in complex scenarios in light of limited robust data and vague guideline recommendations Increase possibility of hybrid process requiring multidisciplinary team approach Increases accountability among specialties

Medical teamVascular MedicineCardiology

Pulmonary Critical Care

Interventional teamInterventional cardiologyInterventional radiology

Vascular surgery

Surgical teamCardiothoracic surgery

Vascular surgery.

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PERT team: It Takes a Village to Treat a PE Patient

PERTCore clinical group

1. Medical Team

2. Interventional Team

3. Surgical Team

Clinical Members

Direct Patient Care

1. Emergency Medicine

2. Internal Medicine3. Pharmacy

4. Hematology

5. Nursing

Monitoring

1. QI Management

2. Research & Outcomes

3. Safety Reporting

A champion invested in PERT in each group is vital

Acute Massive or Submassive Patient in the Emergency Department, on Inpatient Service, or in Intensive Care

Acute PE ALERT Activation

x42012

PE ALERT Evaluation by On‐Call Physician

Multidisciplinary Conference

Discussion and Consensus

Vascular Medicine

Interventional Radiology

PulmonaryCritical Care

Echocardiography

Cardiothoracic Surgery

Cardiology

Options and Recommendations Presented to the Patient, Family, and Care Team

ACTION

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ICU available with systemic lysis

No interventional or surgical programs

Academic Tertiary Center with all members of the PE Response Team

PERT Center of ExcellenceAll clinical teams with 24 x 7 coverage with all procedures available as well as research and quality improvement programs IVC filter

Catheter directed therapySurgical embolectomy

ICU available with systemic lysis and catheter directed therapies

No surgical programs or advanced mechanical thrombectomy procedures

Mechanical thrombectomySurgical embolectomy

High Risk PECardiac ArrestIntermediate

Risk PE

Intermediate Risk PE

Low Risk PE

Systemic Lysisor

ECMO orRV Assist Device

Contraindicationto Systemic Lysis

Systemic Lysis

Surgical Thrombectomy

Catheter Directed Therapy +/- ECMO

Vs.Anticoagulation Alone

Anti-Coagulation +/-IVC Filter

Catheter Directed Lysis

Contra-Indications to Catheter

Directed Therapy

Intermediate-High

Risk PE

Acute PE

Surgical Candidate

YES

YES NO

NO

YES NO

YES NO

YES NO

Anticoagulation

Intermediate-Low

Risk PE

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• PE on call• Vascular

Medicine • Pulmonary • Cardiology

• Interventionaliston call

• Surgeon on call

• PESI• Echocardiogram• Cardiac

biomarkers • Lactate • PE stratification-

• Anticoagulation• Endovascular • Surgical • RV support

devices

• Hematology• High risk OB• Neurosurgery • Oncology

• Clinics• Vascular Medicine • Hematology• Pulmonary

Hypertension clinic

• IVC filter removal• CTEPH evaluation • Duration and choice of

anticoagulation

PERT Program Process

PE Diagnosis Practice Bias Treatment

Involvement of

Consultants

Discharge to Home

Has it changed outcomes?

Department of Medicine Grand RoundsAugust 2, 2019

PATIENT CARE UNDER THE PE RESPONSE TEAM AT UVA

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“Demographics” of Our Program at UVA

Lukasz Myc, MD

Alex Kadl, MD

“Go live” date: April 1, 2017

120 calls from Apr 2017- Oct 2018 Intermediate-High Risk Calls: 40

High-Risk Calls: 26

CDT hrombolysis/Thrombectomy: 22

Systemic Lysis: 5

ECMO/Surgical Thrombectomy: 5

Institutionalization of PE Response Team Has Improved Mortality at UVA

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PE Alert Team at UVA Services Very Critically Ill Patient Population

Therapeutic Results from UVA PE Response Team

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Use of a PE Response Team for High & Intermediate-Risk Patients Does Not Effect the Bottom Line

Benefits of a PE Response Team at UVA

Sicker patients serviced with better outcomes

Intermediate & high-risk PE patients are serviced without increased in hospital stay or cost

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Benefits of a PE Response Team at UVA(Extends Past the Data)

Customer Satisfaction (Providers): Program is an extraordinary resource for all service lines

Customer Satisfaction (Patients): Provides confidence in delivery of complicated quality care Protocolized out patient follow-up program

Customer Satisfaction (Outside Institutions): Established UVA as a clear leader in providing quaternary care for the region

Customer Satisfaction (Ancillary Staff): Open communication between service lines Standardization of bedside patient care needs

Customer Satisfaction (Hospital Leadership): Utilizing resources that already exist to promote care at UVA on a national stage Providing mentorship and research opportunities to trainees

Future Directions for the UVA Program

System-based approach to guideline-based risk stratification of pulmonary embolism

Large research & quality improvement opportunities: Standardization of RV strain grading

Identifying better risk stratification process Specific patient population needs?

Developing blood biorepository database

Developing Quality and Outcome Markers for PE similar to STEMI & ACS programs

Identifying safer therapeutic options & processes

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Emerging Therapies: RV Support Devices

A general indication for ECMO : any respiratory or cardiac failure that is potentially reversible, has failed conventional therapies, and is associated with an otherwise high mortality

VA ECMO Hemodynamic support (generally considered for PE)

Semin Respir Crit Care Med 2017;38:66–72.

National trends and outcomes for extra-corporeal membrane oxygenation use in high-risk pulmonary embolism

Elbadawi, A. Vascular Medicine, 2019: 24(3), 230–233.

AHA Scientific Statement on management of PE published in 2011 did not include the use of ECMO, citing a lack of data.

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National Inpatient Sample Database

2005-2013: 77,809 hospitalizations with high risk PE

In-hospital mortality with ECMO use: 61.6%

Lower in-hospital mortality with ECMO use (OR = 0.34; 95% CI = 0.25 to 0.45, p < 0.001).

Independent predictors of increased mortality: age, female sex, obesity, congestive heart failure, and chronic pulmonary disease

Advanced therapies in conjunction with ECMO: 45 cases (20.4%) with surgical embolectomy

54 cases (24.9%) with thrombolysis

69 cases (31.7%) with IVC filter placementElbadawi, A. Vascular Medicine, 2019

ECMO as 1st line therapy in High-Risk PE

In ECMO group14/29 were only anticoagulatedSurvival better in ECMO group: (73% vs 96%; P =.02)

J Thorac Cardiovasc Surg 2018;156:672-81

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ECMO in High-Risk PE: Systematic Review & Meta-analysis Literature Search Strategy

Literature review until Feb 2019

Total 944 patients with high risk PE and ECMO

Mean age was 52.7 years old (18-86)

295 males (295/791), 37.3%

Mean duration of ECMO support was 4.41 (0.2-18) days

Results:

Survived index hospitalization: 517 patients

Pooled IV estimate survival to hospital discharge was 60% (95%CI =57% - 63%)

Pre- ECMO cardiac arrest (CA): 281 patients (reported in 19 studies)

Mortality for Patients with High-Risk PE Who Undergo ECMO vs. Patients Without ECMO

ECMO group: 34% more patients had pre-ECMO cardiac arrest compared to no ECMO group

Kaso et al. Unpublished

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Mortality Increased in Patients with Pre-ECMO CA

Outcomes may be better if ECMO considered sooner in high-risk PE patients rather than after cardiac arrest

Kaso et al. Unpublished

System-Based Improvement of Risk Stratification of Acute PE

Better Risk Stratification !!!UVA PE Research Data

45

31

44

16

81

64

51

39

99 99

82 81

Troponin BNP RV strain All three

Risk Stratification of PEPre-PERT Non-PERT PERT

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System-Based Improvement of Risk Stratification of Acute PE

Better Risk Stratification !!!UVA PE Research Data

Salient Points

Distinguish high-risk pulmonary embolus from intermediate-risk and low-risk pulmonary embolus Cardiovascular and hemodynamic effects of an acute pulmonary

embolus are the main determinant of patient outcomes from a PE Risk stratify all your PE patients

Review treatment options for intermediate-risk pulmonary embolus Liberal consideration for activating the Acute PE consult service

Discuss data generated from the initiation of the Acute Pulmonary Embolus service at UVA The UVA Acute Pulmonary Embolus is currently providing up-to-date

quality care some of the sickest patients in the hospital

Call x42012

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UVA

PE

Resp

onse

Tea

m: T

RULY

A T

EAM

EFF

ORT PE Officers:

Taison Bell

Michael Bergman

Kyle Enfield

Alexandra Kadl

Sarah Kilbourne

Younghoon Kwon

Numaan Malik

Sula Mazimba

Tessy Paul

Randy Ramcharitar

Diagnostic Radiology: Klaus Hagspiel

Patrick Norton

Vascular Medicine & Pulm/CCM Fellows

Echocardiography and Imaging Services

Emergency Operator Services

Cardiacthoracic Surgery: John Kern

Gorav Ailawadi

Nicholas Teman

Leora Yarboro

Interventional Radiology: Alan Matsumoto

John Angle

Ziv Haskal

Auh Whan Park

Daniel Sheeran

James Stone

Luke Wilkins

Emergency Medicine: David Burt

Hematology: Louise Man

Pharmacology: Angela Holian

Surabhi Palkimas