Understanding the Importance of Ventricular Unloading in Management - PowerPoint PPT Presentation

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 Heart Failure Programs Executive Director, The Cardiovascular Center for Research & Innovation

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 Charlton Award Tufts Medical Center RO1HL139785, RO1H133215

First, Let’s Define What LOAD means Load refers to any variable that increases myocardial oxygen consumption (demand) Heart Rate Coronary Occlusion LV Wall Stress (P/2rh) Collateral Blood Flow LV Systolic Pressure Multivessel Disease LV Diastolic Pressure Microvasc Dysfunction LV Stroke Work Systemic Hypotension Myocardial Myocardial Oxygen Supply Oxygen Demand

Second, Why is LOAD BAD in Acute MI? LVEDP (>18mmHg) is associated with increased incidence of heart failure in STEMI Kirtane and Gibson 2004 J Thromb Thromb

Second, Why is LOAD BAD in Acute MI? 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? LVEDP (>24mmHg) is associated with increased mortality in STEMI Planer and Stone 2011 Am J Card

Second, Why is LOAD BAD in Acute MI? Systolic BP-to-LVEDP Ratio and In-hospital Mortality SBP LVEDP < 4 Sola and Yeung 2017 CCI

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

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 Cardiogenic Shock Pressure Volume How about UNLOADING in AMI/Shock?

Now , Let’s Define UNLOADING in Shock Unloading refers to a reduction in myocardial oxygen consumption (demand) while maintaining systemic perfusion Heart Rate Coronary Occlusion LV Wall Stress (P/2rh) Collateral Blood Flow LV Systolic Pressure Multivessel Disease LV Diastolic Pressure Microvasc Dysfunction LV Stroke Work Systemic Hypotension Myocardial Myocardial Oxygen Supply Oxygen Demand

Finally, Show me the RCTs Studying Unloading Devices (Acute MCS) Trials In Acute MI and Shock IABP Shock II Negative Trial (IABP in AMI) IMPRESS Trial Negative Trial (IABP vs CP in AMI-Shock) VA-ECMO RCTs Do Not Exist Impella RCTs Do Not Exist

Here are the Problems No Algorithm + No Shock Stratification INSERT ANY DEVICE HERE AMI-Shock Management is Not Simple

Tufts Cardiogenic Shock Algorithm Hemo-Metabolic Shock has a Poor Prognosis Hemodynamically driven decision making Treat Shock Before Metabolic Failure Begins The Door to Support Time Morine & Kapur et al. Shock Working Group

Cardiogenic Shock Trials Should be Testing Algorithms not a Specific Pump

Success in Cardiogenic Shock Requires Early Initiation of Acute MCS O’Neill W. JIC 2013

Unloading Mechanistic Impact 1 Reduced LV Wall Stress & Myocardial O2 Consumption Courtesy of D. Burkhoff

VA-ECMO Before Reperfusion Does Not Reduce Infarct Size : Must Unload the LV IRI Impella ECMO Swain L, Qiao X, Reyet L, and Kapur NK et al 2019

Unloading Mechanistic Impact 2 Unloading Increases Perfusion without Reperfusion D. Burkhoff

Unloading Improves Myocardial Perfusion Without the Need for Reperfusion Collateral Flow Index (CFI) No Pump Impella P aorta VA-ECMO Pump Activated (LAD Occluded) P occl CFI Seiler and Meier et al. JACC 1998; Lee and Park et al. JACC 2000 Annamalali, Briceno and Kapur NK et al. 2019

Unloading Improves Myocardial Perfusion Without the Need for Reperfusion Unloading Shrinks the Area at Risk Annamalali, Briceno and Kapur NK et al. 2019

Unloading Protects the Heart and Sets the Stage for Myocardial Recovery Primary Reperfusion Primary Unloading Esposito, Zhang, Qiao and Kapur NK et al. JACC 2018

Unloading and Delaying Reperfusion Protects Complex One in the Mitochondrial Power Plant Ischemia Unload Reperfusion Beta-blockers and Afterload reduction Reperfusion Alone Primary Unloading Swain & Kapur 2019

Unloading and Delaying Reperfusion Impacts Fundamental Myocardial Biology Ischemia Unload Reperfusion Swain & Kapur et al 2019

Door To Unload: STEMI Pilot Trial: Study Design Anterior STEMI Referred for Primary PCI Electrocardiographic Confirmation Informed Consent and Enrollment Patient preparation, draping, anti-coagulation, anti-platelet therapy, ultrasound Time is Muscle guided femoral access, vascular angiogram, left ventriculography, 14 French sheath insertion, then Randomization to U-IR or U-DR Impella CP Insertion + Activation U-IR Group U-DR Group Radial (or femoral access), coronary 30 minutes of Unloading angiography, coronary wiring and Radial (or femoral access), coronary angioplasty angiography, coronary wiring and angioplasty Explant Impella CP after a minimum of 3 hours support Independent Data Safety Monitor, Electrocardiographic, Angiographic, and Cardiac Magnetic Resonance Imaging Core Labs Kapur NK and O’Neill W et al Circulation 2018

A New Era for Cardiovascular Therapeutics A Focus on Ventricular Unloading Kapur NK and O’Neill W et al Circulation 2018

Successful enrollment & protocol completion Zero Bailout PCI in the U-DR Group Impella to PCI Time (mins) 40 U-DR 34 mins 30 30 minutes of unloading Average 20 U-IR 10 11 mins Average 0 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 Kapur NK and O’Neill W et al Circulation 2018

The Potential to Change the Game Exists Kapur NK et al J Card Transl Res 2019

Unloading Diminishes the Impact of Ischemic Duration Among Large Anterior STEMIs 64 mins of Symptom Treatment Timeline (minutes) Onset ischemia Unload PCI U-IR 163 11 174 mins U-DR 193 34 227 mins Unload PCI Time is Muscle (Tarantini 2005) Infarct / AAR Standard Infarct vs Time Slope Unloaded Infarct vs Time Slope Expected 59.9% * p = 0.04 44.1% Observed Expected w/ no delay (163 mins) Expected w/ 60 min delay (223 mins) N=16 N=14 Observed w/ Unload + 60 min delay (227 mins) U-IR U-DR STE>6 Group

Our Collective Focus: The Door to Unload Pivotal Trial Aim: LV Unloading as an approach to limit infarct size and reduce heart failure after STEMI Pivotal RANDOMIZED SAFETY & FEASIBILITY PRECLINICAL CONTROLLED TRIAL HUMAN STUDY Multicenter, RCT • Test primary Goal: Establish safety & feasibility: hypothesis in Anterior STEMI • • Successful enrollment and Study mechanism protocol completion (Feasibility) • DTU + 30 min Delay Determine optimal timing of unloading • No increase in infarct versus • associated with 30 minute Examine late DTB: Standard of Care delay (Safety) functional effect and remodeling • No increase in major adverse Anticipated Launch in cardiovascular or cerebral 2019 events (MACCE Safety)

Education, Training, and Implementation of Best Practices to Achieve Safety

Thank you nkapur@tuftsmedicalcenter.org To Learn More about Acute Mechanical Circulatory Support December 2019 Paris, France Interventional Heart Failure August 2019, Paris, France