Approach to Interventional Management of Pulmonary Embolism and the Role of the Multidisciplinary Team Approach Kenneth Rosenfield, MD, MHCDS on behalf of MGH PERT collaborators With credits also to: Richard N. Channick, M.D. Michael R. Jaff, M.D. Christopher Kabrhel, M.D. The MGH PERT Team

Kenneth Rosenfield, MD, MHCDS Conflicts of Interest Research or Fellowship Support Abbott Vascular Atrium NIH InspireMD Lutonix-Bard Board Member VIVA Physicians (Not For Profit 501(c) 3 Organization) www.vivapvd.com Consultant Abbott Vascular Capture Vascular Cardinal Health Contego CRUZAR Systems Endospan Eximo InspireMD MD Insider Micell Shockwave Silk Road Surmodics Valcare Equity CardioMEMs Contego Embolitech Icon Janacare MD Insider Micell PQ Bypass Primacea Shockwave Vortex

PE (and DVT): A national crisis! Severely under-recognized and undertreated Significant immediate and long-term sequelae High recurrence rate Treatments available that reduce mortality, morbidity and sequelae Kearon C et al. Chest 2008; 133: 454S-545S.

Pulmonary Embolus: Why Worry?? Consequences By Clinical Presentation mortality 66-95% 22-53% 8-13% 1-4% 25% 30% Cardiac Arrest: 10-20% Massive PE (SBP <90 mmHg): 4-6% Submassive PE (stable hemodynamics with RV dysfunction): 23-40% Submassive PE (stable hemodynamics w/o RV dysfunction) Recurrent PE Untreated How many other diseases have such terrible implications??? Adapted from Fengler Am J of Emergency Medicine, 2009 27,84-95

Have we made much progress since 1969?

Massive vs. Submassive PE SBP<90mmHg or decrease > 40 mmHg from baseline for > 15 min Inotropic support Pulselessness Persistent bradycardia (HR < 40 bpm) Submassive PE SBP≥90mmHg RV dysfunction RV dilatation ECHO or CT (RV/LV diameter > 0.9) • BNP > 90 pg/mL • EKG changes • Myocardial necrosis: Troponin I > 0.4 ng/mL Troponin T > 0.1 ng/mL Jaff et al, Circulation 2011;123:1788

REMARKABLY LITTLE PROGRESS IN 30 YEARS PE Outcomes – Massive and Submassive “…good justification to treat!” Kucher et al, Circulation 2006 – ICOPER Registry 2454 consecutive patients with PE 108 patients with massive PE (SBP<90) Recurrent PE at 90 days Submassive PE: 7.6% Massive PE: 12.6% Mortality 52.4%* 14.7% *2/3 from recurrent PE REMARKABLY LITTLE PROGRESS IN 30 YEARS ICOPER Study - Kucher et al Massive PE Circulation 2006.

“Treatment gap” in PE <5% of patients with PE receive “advanced therapy”, including those with clear indications (hypotension, RV dysfunction, biomarkers, etc.) Many more are eligible than receive Reasons Failure to recognize potential benefit and integrate data in “real-time” Fear of complications Inability to respond rapidly (“systems” issues) “Paralysis” in decision-making

Real World Case #1 66 year-old man with no signif past medical history noted dyspnea on exertion 5-6 days prior to presentation. Symptoms progressed – shortness of breath walking 20 feet Outside hospital  PE-protocol CT  extensive bilateral saddle PE Started on heparin and transferred to a tertiary referral hospital TTE at second hospital: large clot in right atrium  confusion about best therapy Patient transferred to MGH 66 year-old male with no significant past medical history who presents with a pulmonary embolism and clot in transit. He reports developing shortness of breath and DOE 5-6 days prior to presentations. Because of symptoms progression, he went to Winchester Hospital ED where a PE protocol CT showed bilateral PEs extendings to segmental and subsegmental branches of all lobes. He was started on heparin gtt and transferred to Tufts medical center. A TTE there showed RV dilated and hypokinetic, septal flattening, reduced LVEF of 35% and a clot in the RA passing across the TV. Troponin-T: 0.4 ng/ml NT-proBNP: 1975 pg/ml

PE-Protocol CT:

Who makes the decision and on what basis? Transthoracic Echocardiogram: Still Images Thrombus Across Pulmonic Valve What would you do next? Who makes the decision and on what basis?

Management Alternatives Acute PE Anticoagulant Mechanical Thrombolytic Therapy Systemic Catheter Directed IVC Filter MCS How do we decide which therapy to apply in a given patient ??? Percutaneous Fragmentation & Aspiration Surgical Embolectomy Ultrasound- Assisted Pharmaco- mechanical ~More likely with  severity

Therapeutic Alternatives in Acute PE Thrombolytic Therapy Systemic (full or half-dose) Catheter Directed (CDT) Pharmacomechanical Catheter-Directed Thrombolysis (P-CDT) Mechanical Surgical Thrombectomy Thrombo-aspiration Adjunct Rx Extracorporeal support (ECMO) RVAD IVC Filter Anticoagulation Unfractionated Heparin Continuous Intravenous Full-Dose Subcutaneous Low-Molecular-Weight Heparin Direct Thrombin Inhibitors Synthetic Pentasaccharide Xa Antagonist Warfarin

Available Guidelines “Management of submassive PE crosses the zone of equipoise, requiring the clinician to use clinical judgment.” “In most situations of uncertain benefit of a treatment…we took the position of primum non nocere….given the certain risks of bleeding and less-certain benefits, thrombolysis is likely to be harmful. Selected patients without hypotension may benefit…” No lytics: A: prior ICH, AVM, malignant intracranial, CVA in 3 months, aortic dissection, active bleeding, recent surgery (spine), closed head or facial trauma R: > 75, anticoag, pregnancy, noncompressible puncture, CPR > 10, bleed 2-4 weeks, HTN 180/110/uncontrolled, dementia, CVA > 3 months, major surgery 3 weeks 2C: Very weak recommendations; other alternatives may be equally reasonable Jaff: ACCP took a step back. Unclear why --- waiting for definitive trial, and “time was up” Circulation 2011;123:1788. Chest 2012;141:419S.

Decision-making Beyond the Guidelines Guidelines offer few class I recommendations and do not cover all scenarios Paucity of data available for highest-risk patients Novel devices and approaches now available Expert multidisciplinary consultation essential (STEMI, Stroke,TAVR teams) Timely decision-making and intervention crucial ! Circulation 2010;122:1124. Tex Heart Inst J 2013;40:5.

Which therapy to use??? Best treatment unknown No “standard approach” No “Appropriate Use Criteria” for intervention Strategies “all over the map”… MGH experience as example: Practice variation by medical service, location, size and threat to patient, etc. No standard algorithm or consistency in decision-making No single “team” or “clearing-house” No centralized locations for care or “centers of excellence” No systematic evaluation of results How do we decide whether to “intervene” and by what modality? Who decides? What is the endpoint?

Pulmonary Embolism Response Team A Multidisciplinary Effort to Improve Care and Outcomes in Patients with PE

PERT: Pulmonary Embolism Response Team Goals: Improve patient outcomes with a collaborative, multidisciplinary team-based urgent consult to treat massive and submassive PE Functionality Modeled on rapid-response concept Multidisciplinary team of experts: convened via electronic meeting Evaluate and offer full range of available treatments Chest 2013;144:1738

Pulmonary Embolism – previous paradigm …Chaos ED / ICU / Floor Team Pulmonary Vascular Medicine/Cardiology Cardiac Surgery

Pulmonary Embolism Response Team (PERT) Objectives Respond expeditiously to treat patients with massive and submassive PE Provide best therapeutic option(s) available for each patient Leverage the input of a multidisciplinary team of experts Coordinate care among services involved in care of PE Develop protocols for the full range of therapies available Collect data on clinical presentation, treatment efficacy, and outcomes (short and long-term) …Fill unmet need and gap in knowledge base…

PERT Program Flow Map Expeditious input and clinical judgment from multiple specialties to optimize therapy Handoff to therapeutic site ED PERT fellow: History Physical Labs EKG Echo CT-PE Low Risk A/C MGH floor Lytic Submassive Attending CDT OSH Massive Vortex ECMO Electronic Meeting Vascular Medicine Cardiac Surgery ICU/Pulmonary Hematology Rad,Echo ACTIVATE PERT MULTIDISCIPLINARY TEAM Surgery 22

Gotomeeting.com Multidisciplinary Virtual Consultation Leverage low- and no-cost internal and commercially available tools Citrix® GoToMeeting web-based HD videoconferencing Allows exchange of screen control Tracks meeting date, time and length Group email distribution lists Group paging 11/14/13 61F China, HTN, thrombocytopenia Tachycardia to 130s before fluid now 108, SBP 94 (home 140s) -> 124, rr 32, SaO2 97 2L CT with bilateral thrombus burden R main-RUL, RLL, L main-LUL, LLL PERT due to VS, EKG with anterior TWI, PLT 90, and RLL ? infarct. Echo in real time while on call: RVSP 43, RV sl dilated 45, McConnell, no TIT She has relatively large thrombus burden and is still tachyneic and modeately tachycardic. THere is no firm rule or guideline, nor clinical indicator to tell us whether she will ultimately do better with lysis versus heparin alone. I do believe she could potentially benefit from low dose, limited infusion of tPA via EKOS into Rt main pulm artery. On other hand, she is slightly improved over past 12 hours. D/w DR. O'Donnell...we agree her usual BP is much higher and she is very dyspneic/tachypneic with almost any motion. If we can help her along by lysing some of her thrombus with very low dose lytic, we likely can minimize risk of bleeding while still giving her a "head start" with CDT Got EkOS – large mobile burden in bilateral segmental arteries. After 24h UFH switched to Coumadin and UFH. R popliteal DVT 98 BP: 140/97 : RR:24 O2: 95% RA ‎ ‎‎‎‎ Gotomeeting.com

Multidisciplinary Collaboration PERT Vascular Medicine and Intervention Pulmonary/ Critical Care Cardiac Surgery Cardiac and Thoracic Imaging Nursing Quality & Safety Vascular Surgery Echocardiography Cardiology Hematology/ Oncology Emergency Medicine

Back to our 66 y. o. man with Submassive PE and Back to our 66 y.o. man with Submassive PE and ?clot in transit…what to do? Multidisciplinary “gotomeeting” CT surgery, cardiology, vascular med, pulm critical care, hematology, ED, and anesthesiology  Decision made to proceed to catheterization laboratory for Vortex Angiovac Procedure under general anesthesia with TEE guidance Access: Percutaneous Subclavian vein – triple lumen Right femoral vein – 26 F Dry-seal sheath Left femoral vein – 17 F Venous Return Left femoral artery (in case ECMO required)

Transesophageal Echocardiogram

AngioVac“VORTEX” 18 F Suction Catheter 17 F Return Pump/Filter

Thrombus Extracted by Vortex AngioVac

Transesophageal Echocardiogram: Post Extraction

Pulmonary Angiography: Still Image

Post-VORTEX Plan to send to SICU for monitoring Sudden drop in BP to 60, requiring additional pressors Decision for thrombolysis of saddle PE’s Re-prepped and EKOS catheters placed bilaterally

EKOS Catheter Placement

Post-procedure Initial 12 hours 2mg bolus tPA, then 1mg/hr via each EKOS x 4 hrs, then 0.5mg/hr x 6 hours Total dose 21mg Remained hypotensive/shocky requiring Epi @ 2-5, Phenylephrine @ 5-15, +/-Vasopressin RV function poor 14 hours post-procedure – Prop. d/c’ed and awoke, extubated, pressors stopped. BP 140, HR 80, O2 sat 100% on 2 L Home day 4

Emerging Technologies - “game-changers”? Ultrasound facilitated lysis More rapid clot dissolution with lower dose of lytic agent? VORTEX Angiovac - En bloc thrombus aspiration Rapid removal of offending clot percutaneously Requires perfusionist & addl resources ECMO Ability to support patient hemodynamically “bridge” to definitive Rx Will these change the paradigm completely? How do we integrate these into existing treatments? Underscores need for integrated, TEAM approach to PE …with multi-disciplinary decision-making

PERT Activations October 2012 Launch through November 2015 333 Activations in 25 Months

PERT Activations October 2012 Launch to Present Male: 56% Female: 45% Age range: 10 – 98 yrs Median age: 62 yrs. Survival to discharge: 85% Interventions: 59.8% Anticoagulation only 9.1% Catheter-direct thrombolysis 4.2% Surgery 2.8% IV systemic lysis 2.4% Mechanical support/ECMO 21.0% IVC filters 0.7% Vortex

PERT Consortium- Launch Meeting Boston, MA May 21, 2015 25+ Interested Centers

Future of Vascular Intervention Pulmonary Embolus Management Summary PE still poorly understood; much to learn New era: heightened awareness and coordinated institutional approach to a complex, life-threatening problem OPTIMAL CARE WITH TEAM APPROACH!! PERT: a “model” program, demonstrating the power of interdisciplinary collaboration to streamline care, optimize outcomes for our patients, and enable development of better treatment paradigms for patients with PE PERT Consortium …Contact us if interested!! 39

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