Download Reduce Infarct Size

“Door to Unloading”
A New Paradigm in the Treatment of
Acute ST Elevation Myocardial Infarction
Howard A. Cohen, MD, FACC,FSCAI
Professor of Medicine
Director Temple Interventional Heart & Vascular Institute
Director Interventional Cardiology and Catheterization Laboratories
Percutaneous Left Ventricular Assist and
Reduction of Myocardial Infarct Size
A Paradigm Shift in the Treatment of STEMI?
Howard A. Cohen, MD, FACC,FSCAI
Professor of Medicine
Director Temple Interventional Heart & Vascular Institute
Director Interventional Cardiology and Catheterization Laboratories
DISCLOSURES
CardiacAssist, Inc
• Medical Director
• Stock options
Off-Label use
• Off-Label use of TandemHeart® in an FDA
approved trial
Time is Outcome: Primary PCI
One-Year Mortality (%)
6 RCTs of Primary PCI by Zwolle Group 1994-2001
P=0.001
RR=1.08 for each 30 min delay (P=0.04)
0
60
120
180
240
300
360
Symptom-to-balloon inflation (mins)
DeLuca G et al. Circulation 109:1223, 2004
CONSEQUENCES OF DELAY
• Higher mortality
– Gibler et al., 2002; Newby et al. 1996, Maynard et al., 1989
• Larger infarct size
– Liem et al., 1998
• Higher incidence of shock
– Newby et al., 1996
• Worse left ventricular function or heart
failure with associated increased disability
– Liem et al., 1998; Newby et al., 1996
Moser, Jan 2007
Trends in Door to Balloon Times and Mortality in Patients
Undergoing Primary PCI in STEMI
Flynn et al. Arch Intern Med.2010;170(20)1842-1849.
• Although national door-to-balloon times have improved significantly
for patients undergoing primary PCI for ST-segment elevation
myocardial infarction, in-hospital mortality has remained virtually
unchanged.
• These data suggest that additional strategies are needed to reduce
in-hospital mortality in this population
D to B Time and Mortality in the Overall Population
and High-Risk Subgroups, 2005 to 2009.
Age > 75
Overall
CGS
Anterior MI
Menees DS et al. N Engl J Med 2013;369:901-909
Mortality According to Door-to-Balloon Time
2005 to 2009.
Menees DS et al. N Engl J Med 2013;369:901-909
Unadjusted and Risk-Adjusted In-Hospital Mortality
from July 2005 through June 2009.
Menees DS et al. N Engl J Med 2013;369:901-909
D to B Times and 30-Day Unadjusted Mortality*
Menees DS et al. N Engl J Med 2013;369:901-909
Reducing Myocardial Infarct Size
• “Time is muscle”
• Decreasing door to balloon time (D2B) has
become the mantra in primary PCI, and is a major
QA/QI imperative of ACC/AHA and affects patient
flow and reimbursement
• Resultant improved survival up to a point, at least
in the short-term
• Can we further improve outcomes, particularly
with regard to preservation of LV function and
potentially long-term survival?
• Are there other factors to be considered?
Reperfusion Injury
• Myocardial reperfusion injury first postulated by
Jennings and co-workers in 1960
• Injury that occurs to the heart during reperfusion
causes four types of dysfunction
– Myocardial stunning- dysfunction post reperfusion
despite absence of irreversible damage
– No-reflow phenomenon – impedence of
microvascular flow after reperfusion
– Reperfusion arrhythmia
– Lethal reperfusion injury
Jennings et al 1960; Arch Pathol;70:68-78
Yellon DM and Hausenloy DJ 2007; N Engl J Med;357:1121-35
Importance of Other Factors





Lethal reperfusion injury (LRI)
Does LRI exist in man?
If LRI exists in man, can it be prevented?
Is it important how we restore flow?
Difficult to accurately assess
Contribution of Lethal Reperfusion Injury to Final MI Size
Yellon D and Hausenloy D. N Engl J Med 2007;357:1121-1135
Mediators of Lethal Reperfusion Injury
Inflammation
cytokines
Rapid Δ in pH
Calcium Overload
Reactive O2 species
PTP pore
LRI
Yellon D and Hausenloy D. N Engl J Med 2007;357:1121-1135
Limiting MI with LV Assist
Minimize Infarct Size =
(Early Support, Extent of Ventricle Unloading)
80%
70%
60%
Infarct size
% of total area
at risk
50%
40%
30%
20%
10%
0%
No Support
Partial Support
(2.5 l)
After Reperfusion
Full Support
(5.0 l)
After Reperfusion
Meyns, B. et al. J Am Coll Cardiol 2003;41:1087-1095
Full Support
(5.0 l)
After Ischemia &
Reperfusion
Limiting Myocardial Infarction
LA-FA BYPASS EFFECTIVENESS IN REDUCTION
OF EXPERIMENTAL AMI
Catinella et al. J of Thoracic & Cardiovasc
Surgery. 86(6):887-96, 1983
Methods for Limiting MI Expansion
During Reperfusion
Axelrod et al Circulation
76(supplV);28-32,1987
Calculating Total Pressure-Volume
Area
•
The area of the resulting triangle is equal to Potential Energy (PE)
SW
+
PE
=
PVA
Calculating Total Pressure-Volume
Area
•
The combined areas of SW and PE is equal to Pressure-Volume Area (PVA)
– Larger PVA = More Myocardial Oxygen Consumption (MVO2)
– Smaller PVA = Less Myocardial Oxygen Consumption (MVO2)
SW
+
PE
=
PVA
Calculating Total Pressure-Volume
Area
•
A rightward shift of the PV Loop, or an increase in End Systolic Volume, will cause
an increase in PE, even if the size of the PV loop remains the same.
SW
+
PE
=
PVA
Pressure Volume Loops in Animal Model
TandemHeart vs CP in Large Animal
Kapur et al. Circulation 2013;128:3278-336
Kapur et al. Circulation 2013;128:3278-336
Kapur et al. Circulation 2013;128:3278-336
Kapur et al. Circulation 2013;128:3278-336
TRIS TRIAL
TandemHeart to Reduce Infarct Size
• TandemHeart in Anterior SEMI
• LV unloading prior to reperfusion
• Primary efficacy EP – Myocardial salvage index
(Area at risk-infarct size/area at risk) by MRI
• Primary safety EP – MACCE at 30 days, 6
month and one year
• Initial trial sites: Temple University, Memorial
Hermann Texas, Henry Ford Hospital
• National PI Drs David Holmes and Biswajit Kar
TRIS TRIAL
Challenges
• Recruitment
• Maintaining safety
• True informed consent in a timely fashion
• Resource intensive – two cath lab attendings,
CCU nursing
TRIS TRIAL
Potential Benefits
• Decreased infarct size
• Improved LV function
• Improved long-term survival
• Decreased costs
– Decreased need for ICD
– Decreased CHF and need for re-hospitalizations
• Trial enrollment to begin imminently – stay
tuned!
THANK YOU