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Nov 20, 2023 284 likes •617 views

Understanding the Importance of Ventricular Unloading in Management of AMI and Cardiogenic Shock (Clinical Trial Results) Navin K. Kapur, MD, FACC, FSCAI, FAHA Associate Professor, Department of Medicine Interventional Cardiology & Advanced

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Navin K. Kapur, MD, FACC, FSCAI, FAHA Associate Professor, Department of Medicine Interventional Cardiology & Advanced Heart Failure Programs Executive Director, The Cardiovascular Center for Research & Innovation

Understanding the Importance of Ventricular Unloading in Management of AMI and Cardiogenic Shock (Clinical Trial Results)

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Rele levant Dis isclo losures

Research Funding & Speaker/Consulting Honoraria: Abiomed, Abbott, Boston Scientific, Maquet, Medtronic, MD Start, Cardiac Assist

Herbert J. Levine Foundation Tufts Medical Center

RO1HL139785, RO1H133215

Charlton Award Tufts Medical Center

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First, Let’s Define What LOAD means

Heart Rate LV Wall Stress (P/2rh) LV Systolic Pressure LV Diastolic Pressure LV Stroke Work Coronary Occlusion Collateral Blood Flow Multivessel Disease Microvasc Dysfunction Systemic Hypotension Myocardial Oxygen Supply Myocardial Oxygen Demand

Load refers to any variable that increases myocardial oxygen consumption (demand)

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LVEDP (>18mmHg) is associated with increased incidence of heart failure in STEMI

Second, Why is LOAD BAD in Acute MI?

Kirtane and Gibson 2004 J Thromb Thromb

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LVEDP (>18mmHg) is associated with reduced coronary flow and myocardial perfusion

Kirtane and Gibson 2004 J Thromb Thromb

Second, Why is LOAD BAD in Acute MI?

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LVEDP (>24mmHg) is associated with increased mortality in STEMI

Planer and Stone 2011 Am J Card

Second, Why is LOAD BAD in Acute MI?

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Systolic BP-to-LVEDP Ratio and In-hospital Mortality

Sola and Yeung 2017 CCI

Second, Why is LOAD BAD in Acute MI?

SBP LVEDP < 4

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LOAD is BAD in Acute MI, but it is WORSE in SHOCK Forrester-Diamond-Swan Classification (1977) Cardiac Index and PCWP are associated with mortality

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Second, Let’s Understand Why LOAD is BAD in Acute Myocardial Infarction

Acute Myocardial Infarction With or Without Shock is Associated with Increased LV Wall Stress

Volume Pressure

Cardiogenic Shock

How about UNLOADING in AMI/Shock?

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Now, Let’s Define UNLOADING in Shock

Heart Rate LV Wall Stress (P/2rh) LV Systolic Pressure LV Diastolic Pressure LV Stroke Work Coronary Occlusion Collateral Blood Flow Multivessel Disease Microvasc Dysfunction Systemic Hypotension Myocardial Oxygen Supply Myocardial Oxygen Demand

Unloading refers to a reduction in myocardial oxygen consumption (demand) while maintaining systemic perfusion

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Finally, Show me the RCTs Studying Unloading Devices (Acute MCS) Trials In Acute MI and Shock

IABP Shock II

(IABP in AMI)

IMPRESS Trial

(IABP vs CP in AMI-Shock)

Negative Trial Negative Trial VA-ECMO RCTs Do Not Exist Impella RCTs Do Not Exist

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Here are the Problems No Algorithm + No Shock Stratification AMI-Shock Management is Not Simple

INSERT ANY DEVICE HERE

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Morine & Kapur et al. Shock Working Group

The Door to Support Time

Treat Shock Before Metabolic Failure Begins

Tufts Cardiogenic Shock Algorithm Hemodynamically driven decision making

Hemo-Metabolic Shock has a Poor Prognosis

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Cardiogenic Shock Trials Should be Testing Algorithms not a Specific Pump

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O’Neill W. JIC 2013

Success in Cardiogenic Shock Requires Early Initiation of Acute MCS

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Courtesy of D. Burkhoff

Unloading Mechanistic Impact 1 Reduced LV Wall Stress & Myocardial O2 Consumption

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Swain L, Qiao X, Reyet L, and Kapur NK et al 2019

IRI Impella ECMO

VA-ECMO Before Reperfusion Does Not Reduce Infarct Size : Must Unload the LV

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Unloading Mechanistic Impact 2 Unloading Increases Perfusion without Reperfusion

D. Burkhoff

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Unloading Improves Myocardial Perfusion Without the Need for Reperfusion

CFI

Seiler and Meier et al. JACC 1998; Lee and Park et al. JACC 2000

Poccl

Collateral Flow Index (CFI)

Paorta

Pump Activated (LAD Occluded)

Annamalali, Briceno and Kapur NK et al. 2019

No Pump Impella VA-ECMO

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Annamalali, Briceno and Kapur NK et al. 2019

Unloading Improves Myocardial Perfusion Without the Need for Reperfusion Unloading Shrinks the Area at Risk

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Esposito, Zhang, Qiao and Kapur NK et al. JACC 2018

Primary Reperfusion Primary Unloading

Unloading Protects the Heart and Sets the Stage for Myocardial Recovery

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Reperfusion Ischemia Unload

Beta-blockers and Afterload reduction

Unloading and Delaying Reperfusion Protects Complex One in the Mitochondrial Power Plant

Swain & Kapur 2019

Reperfusion Alone Primary Unloading

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Reperfusion Ischemia Unload

Unloading and Delaying Reperfusion Impacts Fundamental Myocardial Biology

Swain & Kapur et al 2019

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Electrocardiographic Confirmation Informed Consent and Enrollment

Explant Impella CP after a minimum of 3 hours support

Anterior STEMI Referred for Primary PCI

Patient preparation, draping, anti-coagulation, anti-platelet therapy, ultrasound guided femoral access, vascular angiogram, left ventriculography, 14 French sheath insertion, then Randomization to U-IR or U-DR Impella CP Insertion + Activation

Time is Muscle

Door To Unload: STEMI Pilot Trial: Study Design

U-DR Group 30 minutes of Unloading U-IR Group Radial (or femoral access), coronary angiography, coronary wiring and angioplasty

Independent Data Safety Monitor, Electrocardiographic, Angiographic, and Cardiac Magnetic Resonance Imaging Core Labs

Radial (or femoral access), coronary angiography, coronary wiring and angioplasty

Kapur NK and O’Neill W et al Circulation 2018

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A New Era for Cardiovascular Therapeutics A Focus on Ventricular Unloading

Kapur NK and O’Neill W et al Circulation 2018

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10 20 30 40 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

Patients Enrolled Impella to PCI Time (mins) U-DR 34 mins Average U-IR 11 mins Average

30 minutes of unloading

Successful enrollment & protocol completion Zero Bailout PCI in the U-DR Group

Kapur NK and O’Neill W et al Circulation 2018

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The Potential to Change the Game Exists

Kapur NK et al J Card Transl Res 2019

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Unloading Diminishes the Impact of Ischemic Duration Among Large Anterior STEMIs

193 163

34 11 U-DR U-IR

Unload PCI Unload PCI

227 mins

59.9%

U-IR U-DR Infarct / AAR

Expected N=14 Observed

44.1%

N=16 p = 0.04

*

Symptom Onset

Treatment Timeline (minutes) 64 mins of ischemia

174 mins

STE>6 Group

Standard Infarct vs Time Slope

Expected w/ 60 min delay (223 mins) Observed w/ Unload + 60 min delay (227 mins) Expected w/ no delay (163 mins)

Time is Muscle (Tarantini 2005)

Unloaded Infarct vs Time Slope

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Our Collective Focus: The Door to Unload Pivotal Trial

Goal: Establish safety & feasibility:

Successful enrollment and

protocol completion (Feasibility)

No increase in infarct

associated with 30 minute delay (Safety)

No increase in major adverse

cardiovascular or cerebral events (MACCE Safety)

Aim: LV Unloading as an approach to limit infarct size and reduce heart failure after STEMI

SAFETY & FEASIBILITY HUMAN STUDY Pivotal RANDOMIZED CONTROLLED TRIAL PRECLINICAL

Test primary

hypothesis

Study mechanism
Determine optimal

timing of unloading

Examine late

functional effect and remodeling

Multicenter, RCT in Anterior STEMI DTU + 30 min Delay versus DTB: Standard of Care Anticipated Launch in 2019

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Education, Training, and Implementation

f Best Practices to Achieve Safety

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nkapur@tuftsmedicalcenter.org

Thank you

To Learn More about Acute Mechanical Circulatory Support

Interventional Heart Failure

December 2019 Paris, France

August 2019, Paris, France