Management of Cardiogenic Shock in AMI Ramesh Daggubati, MD FACC FSCAI Director of the Cardiac Catheterization Laboratories Vidant Medical Center Co-Director of the Structural Heart Disease Service Line Director of the Interventional Cardiology Fellowship Program Brody School of Medicine East Carolina Heart Institute

Conflict Of Interest Consultant: Cardiac Assist, Abiomed, Abbott Vascular, Speaker’s Bureau: Astra Zeneca, Gilead, Medtronic

Cardiogenic Shock: United States AMI PCCS ADHF Admissions / Surgeries 785,000 528,000 1 million Shock Incidence 6% 1% 2% Refr IABP / Inotropes 40% 75% 80% Relative Incidence 1 : 40 1 : 150 1 : 60 Device Candidates ~18,000 ~4,000 ~16,000 AHA Heart Disease and Stroke Statistics-2011 Update

Cardiogenic Shock is a Spectrum Pre-Shock Shock Profound Shock No Hemodynamic Support Needs Partial Hemodynamic Support Needs Full Hemodynamic Support Three High Dose 2% 3% 7.5% 21% 42% 80% No Inotrope Low Moderate One High Two High Mortality Risk with Inotrope Dosing Adapted from Samuels LE et al , J Card Surg. 1999 Jul-Aug;14(4):288-93

Therapeutic Goal AMI Shock Stabilize the Patient Reperfuse Minimize Stunning - Stop myocardial injury - Restore normal myocardial metabolism - Prevent reperfusion injury - Enhance myocyte recovery

Current evidence from RCT in Cardiogenic Shock in the Era of PCI Small samples Different devices Not powered studies Thiele H et al. Eur Heart J 2010;31:1828-1835

Current Pharmacology & Devices Inotropes IABP ECMO Tandem-Heart Impella Surgical VAD Advantages Flow (L/min.) Coronary Perfusion LVEDP <0.5 ↑ 0.5 ↑↑ ↓ 4 - ↑↑↑↑ 3.5 ↓↓ 2.5 - 5.0 ↓↓↓ 6.0 ↓↓↓↓ Limitations Arrhythmia Stroke Limb ischemia Bleeding Cost +++ N.A $ ++ + ++++ $$$ + / ++ $$$$$

Inotropes: Energetic Data in AMI Shock Positive inotropic agent Energy-starved myocardium Theory Reality Alternative Positive inotropic agent on Ventricular Dysfunction Circulatory Support + Cardiac Function Drugs that increase systolic function typically increase energetic demand and result in adverse chronic outcomes What is the energetic cost of Circulatory Support Device? This cartoon explains a little bit the concept and rationale for inotropes usage…. In theory, if the slope represents the work load, you ll expect that giving stimuli to the muscle will improve the function…. Well in reality, that doesn’t help that much in case of ventricular dysfunction…. Unloading the heart with a circulatory support device will help provide enough output at NO energetic cost for the viable but suffering myocardium. Adapted from Katz AM. Cellular mechanisms in congestive heart failure. Am J Cardiol. 1988;62:8A.

Paradigm Shift in The Near Future: Percutaneous Cardiac Assist Devices Have Been Integrated in the 2011 PCI Guidelines Adapted from Percutaneous Cardiac Assist Device The purpose of this meeting is to make sure that you take full advantage of all of the services that are offered under the Partnership in Healthcare support Program. Some of the goals that I would like to achieve today is finding out Key contacts for each element so that when information is new or updated From this day forward….we would be able to contact you with that update. I Would also like to spend some time talking about the Six Sigma Performance Improvement Service that is part of this program.

Most Commonly Used Mechanical Devices in the CathLab IABP Impella TandemHeart

No Survival Benefit With IABP in AMI Cardiogenic Shock

IABP vs TandemHeart Cardiac Index 30-day Mortality Transfusion Post p=0.005 10 30 50 20 40 60 30-day Mortality (%) 1.4 1.8 2.2 1.6 2.0 2.4 Cardiac Index (l/min/m2) Pre p=0.4 p=0.8 2.3 45% 43% 1.7 1.7 1.5 9/20 9/21 n=20 n=21 IABP Tandem IABP Tandem IABP Tandem 40 60 80 50 70 90 Required Transfusion (%) 100 Transfusion Limb Ischemia 10 30 50 20 40 60 Limb Ischemia (%) 90% p=0.002 p=0.009 33% 0% 40% From hemodynamic point of view, a comapred to IABP, the tandem heart improves the CI, reduces significantly Wedge pressure, Central venous pressure and has a significant better impact on the perfusion of the tissues. 19/21 0/20 7/21 8/20 IABP Tandem IABP Tandem Thiele and al. Eur. Heart Journal 2005 Jul;26(13):1276-83

Tandem Heart for LV and RV support

AMI, AS, Left main and Cardiogenic shock patient

ISAR-SHOCK RANDOMIZED TRIAL: IMPELLA 2.5 vs. IABP in AMI Cardiogenic Shock Primary Endpoint: Increase in Cardiac Index From Baseline (measured after 20 min of support) 0.75 1.50 P<0.01 P<0.01 0.60 1.25 0.45 0.75 1.10 Cardiac Index Increase (L/min/m2) 0.53 Cardiac Output (L/min) 0.30 0.50 0.15 0.25 0.11 0.20 Impella IABP Impella IABP Seyfarth et al. JACC 2007

Study Not Powered for Mortality 30 day - Survival % 100 Impella (n=13) 80 60 IABP (n=13) 54 % 40 Study Not Powered for Mortality 20 Log-rank P = 0.97 5 10 15 20 25 30 Days After Randomization Seyfarth et al. JACC 2007

Managing Right Side Failure IMPELLA RP Flow: 4.0 l/mn Access: Femoral vein Diameter pump: 21F Length cannula: + 140.0mm Diameter cannula: 7.0mm Placement: monorail guide wire Sensor: afterload sensitive Flow monitoring: pressure sensor Outflow in PA Inflow in IVC IMPELLA RP is Not an FDA approved device

Percutaneous VA ECMO: Advantages Rapid deployment (no need for Cath Lab or OR suit Acceptable pump flow (3-6 l/min) RV support Pulmonary support Permits cooling Allows for inter-hospital transfer Provides time to achieve organ recovery and assess patient Inexpensive and available Of those patients affected 5-15% have advanced heart failure and it’s difficult to determine when patients will progress to the advanced heart failure classification

Problems LV Unloading, pulmonary edema and Clot formation Arterial/venous laceration/dissection LV Unloading, pulmonary edema and Clot formation Stroke Ischemic limb Air embolism Cannula dislodgement Thromboembolism Infection Atrial perforation

LV Decompression on VA ECMO IABP Atrial Septostomy and or TH Impella Left atrial cannulation PA Cannulation Of those patients affected 5-15% have advanced heart failure and it’s difficult to determine when patients will progress to the advanced heart failure classification

Support With ECMO: Lacks Evidence Poor outcomes with high complication rates in Adult Cardiac Patients even with last generation ECMO 100% bleeding, high rate of hemolysis, low survival rate in Shock

Of those patients affected 5-15% have advanced heart failure and it’s difficult to determine when patients will progress to the advanced heart failure classification

When Support Should Be Initiated?

When Support Should Be Initiated?

Impact of IABP-Timing in CS Design Total mortality DESIGN: Single center observational study in 102 patients (Jan. 2005-Dez. 2010). OBJECTIVE: To evaluate the impact of IABP timing (before or after PCI) in STEMI complicated by cardiogenic shock. ENDPOINTS: Total mortality, MACCE, renal failure Schwarz et al. (submitted for publication)

Peri-PCI Support Strategy vs. Outcomes Emergent Support Strategy (N=154) IABP Pre-PCI (N=53) No support Pre-PCI (N=38) Impella Pre-PCI (N=63) P=0.01 PCI Survival to discharge N=49 N=29 N=44 Impella Post PCI Continue O’Neill et al. Euro PCR 2012 (updated)

ECHI Shock Protocol

Predictor of Cardiogenic shock Finke et al JACC 2004; 44:340 Finke et al JACC 2004; 44:340 Finke et al JACC 2004; 44:340 Finke et al JACC 2004; 44:340 Finke et al JACC 2004; 44:340

ECHI CS protocol reduces mortality

RECENT DATA Out of 124 patients, 30 patients treated without a device had 50% mortality. 55/78 patients with IABP for CS from 1/12 to 6/13, 68% survival. 22 patients in refractory shock had 50% mortality.

2013 ACC/AHA STEMI Guidelines: Treatment of Cardiogenic Shock IIa IIb III B The use of intra-aortic balloon pump counterpulsation can be useful for patients with cardiogenic shock after STEMI who do not quickly stabilize with pharmacological. I IIa IIb III Alternative LV assist devices for circulatory support may be considered in patients with refractory cardiogenic shock. O’Gara PT, et al. Circulation 2013

Conclusions Management of Cardiogenic shock remains a challenge despite the progress made in reperfusion techniques and pharmacotherapy Without clear supporting evidence, hemodynamic support with IABP remains controversial and is being challenged The newly developed percutaneous left ventricular assist devices provide better hemodynamic support compared IABP As the technology continues to evolve and the experience matures, paradigm shifts and new protocol will emerge for the management of cardiogenic shock with circulatory support Stronger clinical evidence is required to define the selection criteria to identify the patients who would benefit the most from these new technologies