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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)
Relevant Disclosures
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
First, Let’s Define What LOAD means
Heart RateLV Wall Stress (P/2rh)LV Systolic PressureLV Diastolic Pressure
LV Stroke Work
Coronary OcclusionCollateral Blood FlowMultivessel Disease
Microvasc DysfunctionSystemic Hypotension
Myocardial
Oxygen Supply
Myocardial
Oxygen Demand
Load refers to any variable that increases
myocardial oxygen consumption (demand)
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
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
Sola and Yeung 2017 CCI
Second, Why is LOAD BAD in Acute MI?
SBP
LVEDP< 4
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
Volume
Pre
ssure
Cardiogenic
Shock
How about UNLOADING in AMI/Shock?
Now, Let’s Define UNLOADING in Shock
Heart RateLV Wall Stress (P/2rh)LV Systolic PressureLV Diastolic Pressure
LV Stroke Work
Coronary OcclusionCollateral Blood FlowMultivessel Disease
Microvasc DysfunctionSystemic Hypotension
Myocardial
Oxygen Supply
Myocardial
Oxygen Demand
Unloading refers to a reduction in
myocardial oxygen consumption (demand)
while maintaining systemic perfusion
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
Here are the Problems
No Algorithm + No Shock Stratification
AMI-Shock Management is Not Simple
INSERT
ANY DEVICE
HERE
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 makingHemo-Metabolic Shock has a Poor Prognosis
Cardiogenic Shock Trials Should be
Testing Algorithms not a Specific Pump
O’Neill W. JIC 2013
Success in Cardiogenic Shock Requires
Early Initiation of Acute MCS
Courtesy of D. Burkhoff
Unloading Mechanistic Impact 1
Reduced LV Wall Stress & Myocardial O2 Consumption
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
Unloading Mechanistic Impact 2
Unloading Increases Perfusion without Reperfusion
D. Burkhoff
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)
PaortaPump Activated
(LAD Occluded)
Annamalali, Briceno and Kapur NK et al. 2019
No Pump
Impella
VA-ECMO
Annamalali, Briceno and Kapur NK et al. 2019
Unloading Improves Myocardial Perfusion
Without the Need for Reperfusion
Unloading Shrinks the Area at Risk
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
ReperfusionIschemia Unload
Beta-blockers and Afterload reduction
Unloading and Delaying Reperfusion Protects
Complex One in the Mitochondrial Power Plant
Swain & Kapur2019
Reperfusion Alone Primary Unloading
ReperfusionIschemia Unload
Unloading and Delaying Reperfusion Impacts
Fundamental Myocardial Biology
Swain & Kapur et al 2019
Electrocardiographic ConfirmationInformed 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
Tim
e is M
uscle
Door To Unload: STEMI Pilot Trial: Study Design
U-DR Group30 minutes of Unloading
U-IR GroupRadial (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
A New Era for Cardiovascular Therapeutics
A Focus on Ventricular Unloading
Kapur NK and O’Neill W et al Circulation 2018
0
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 P
CI T
ime (
min
s)
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
The Potential to Change the Game Exists
Kapur NK et al J Card Transl Res 2019
Unloading Diminishes the Impact of Ischemic DurationAmong 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
OnsetTreatment 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
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 TRIALPRECLINICAL
• 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
Education, Training, and Implementation of Best Practices to Achieve Safety
Thank you
To Learn More about
Acute Mechanical Circulatory Support
Interventional Heart Failure
December 2019
Paris, France
August 2019, Paris, France