Cardiogenic Shock: Risks and Benefits of Available Treatment - PowerPoint PPT Presentation

Cardiogenic Shock: Risks and Benefits of Available Treatment Options Arnold Seto, MD, MPA Chief, Cardiology Long Beach VA Medical Center Associate Clinical Professor University of CA, Irvine Disclosure: Getinge Speaker’s Bureau

Clinical Uses for Percutaneous Circulatory Support Cardiogenic Complex PCI Shock Support ( ± MI) Acute Coronary Syndrome (AMI) 2 ML-0800 Rev A/ MCV00091528 REVA

2 Key considerations for choosing an MCS device Early diagnosis and Risks Economic early MCS intervention vs benefits impact Which MCS device is What are the clinical What is the total appropriate for the stage considerations of the cost of care with of cardiogenic shock? selected device? the selected device? Which MCS device would be appropriate for ‘high - risk’ PCI? 3 ML-0800 Rev A/ MCV00091528 REVA

Cardiac Support Strategies Strategy Therapy / Device Mechanism Medical Increase Inotropes Management Contractility, HR Aortic Pressure Counterpulsation IABP Augmentation TandemHeart LA -> AO flow Extracorporeal Bypass Pump ECMO RA -> AO flow Impella 2.5 Implantable Impella cVAD Transvalvular LV -> AO flow Pump Impella 5.0 4 ML-0800 Rev A/ MCV00091528 REVA

Comparison of devices J Inv Cardiol 2015; 27: 148-54 5 ML-0800 Rev A/ MCV00091528 REVA

Hemodynamic support in AMI Cardiogenic Shock and Survival Estimated In-Hospital Mortality (%) Cardiac support increases CPO n==189 From SHOCK trial registry Cardiac Power Output (Watts) - Fincke et al. J AM Coll Cariol 2004 July; (44)2: 340-8 6 ML-0800 Rev A/ MCV00091528 REVA

6 Intra-Aortic Balloon • Aortic Counterpulsation (reduces afterload) • Single femoral artery access • 7-8 Fr • ~5 min set-up & insertion • Synchronous operation requires maintenance of ECG or pressure Systole waveform Diastole 7 ML-0800 Rev A/ MCV00091528 REVA

7  Diastolic pressure  CO  MAP  LV Wall Tension  PCWP  Oxygen Demand  LV Volume  or Coronary Blood Flow ➔ Onset systole Adjust timing deflate 8 ML-0800 Rev A/ MCV00091528 REVA

8 Effects of IABP • Decreased work • Afterload • Reduces wall stress • Decreases oxygen demand • Increases MAP • Increases peak diastolic pressure • Increases proximal coronary velocity • Does not increase flow across stenotic lesion • Augmented renal flow • Enhanced thrombolysis • Enhanced endothelium-derived NO release • Kahn JK, Almany SL in Practical Interventional Cardiology, 1997 • Richenbacher WE, Pierce WS in Heart Disease, Ed Braunwald E, 5th Edition, Saunders 1997. Fuchs RM et al, Circulation 1983;68:117-23 • Kern MJ et al, Circulation 1993;87:500-11. Kern MJ et al, JACC 1993;21:359-68 9 ML-0800 Rev A/ MCV00091528 REVA

9 Using the 50 cc IABP • 50 cc “IABP First” Strategy in AMICS (n = 31) 8 Fr Catheter → IABP with Survival to Discharge 61% • 20-30% More Displacement → IABP to VAD to Discharge 7% • 20-30% Greater Diastolic → IABP to Transplant to Discharge 3% Augmentation → Death 29% • 20-30% Greater Afterload 50 cc in AMICS – Responders and Non-Responders Pre- Post- Reduction P value n = IABP IABP Diast Aug (mm - 42 115 Hg) PASP (mm Hg) 55 45 87 < 0.01 PADP (mm Hg) 28 22 87 < 0.01 n = 16 mPAP (mm Hg) 38 29 87 < 0.01 n = 60 C.O. (l/min) 3.56 4.50 79 < 0.01 C.I. (l/min/m 2 ) 1.76 2.32 79 < 0.01 Baran, et al Cath Cardiovasc Intervent 2017; epub Cath Cardiovasc Intervent 2017; 90: e63-72 10 ML-0800 Rev A/ MCV00091528 REVA

Complications of MCS devices Int J Cardiol. 2015 Apr 1;184:36-46 . 11 ML-0800 Rev A/ MCV00091528 REVA

Vascular Complications: Size Matters 90 patients with Impella 74% with cardiogenic shock J Vasc Surg . 2015 Aug;62(2):417-23 . 12/90 pts with limb ischemia 12 ML-0800 Rev A/ MCV00091528 REVA

Major Bleeding 13 ML-0800 Rev A/ MCV00091528 REVA

Impella Hemolysis Incidence of Hemolysis in Patients with Cardiogenic Shock Treated with Impella Percutaneous Left Ventricular Assist Device Badiye, ASAIO Journal62(1):11-14, January/February 2016. Defined as LDH rise, Hgb drop, 62.5% of patients developed detectable hemolysis after 6 hrs. 17% transfused (n=40) Other studies show clinical rates of 7.5% (EUROSHOCK)-10.3% (USpella) 14 ML-0800 Rev A/ MCV00091528 REVA

14 87% of IABP placed after PCI 10% Cross-over in Control Arm – if 2/3 of these crossovers survived because of IABP, p = 0.04 NEJM 2012; 367: 1287- 96 15 ML-0800 Rev A/ MCV00091528 REVA

15 Improved hemodynamics has not translated into improved outcomes with newer devices ISAR-Shock RCT (n=26) IABP Impella Hemodynamic Values Before and After Device Implantation CI at baseline (I/min/m 2 ) 1.7 1.7 The cardiac power index was higher for Impella at 30 minutes only (0.49 ± 0.46 l/min/m 2 ) vs IABP (0.11 ± 0.31 CI with support 2.25 2.23 l/min/m 2 ); there were no significant differences at any other time points LVEF at baseline 28% 27% LVEF at discharge 45% 35% PCWP at baseline (mmHg) 22 22 PCWP after 20 19 implementation SVR at baseline (dynes-s- 1,546 1,617 cm-5) CI=cardiac index; LVEF=left ventricular ejection fraction; PCWP=pulmonary capillary wedge pressure; SVR=systemic vascular resistance. SVR after implementation 1,333 1,457 30-day mortality 46% 46% No difference in 30-day mortality J Am Coll Cardiol. 2008;52(19):1584-8 . 16 ML-0800 Rev A/ MCV00091528 REVA

16 Randomized Data – IABP vs PVAD in AMICS ISAR-SHOCK n = 26 IMPRESS n = 48 TandemHeart Investigators n = 33 IABP vs Impella CP IABP (n=14) vs TandemHeart (n=19) 6 Month Mortality 50% IABP vs Impella 2.5 30 Day Mortality 46% 30 Day Mortality 36% vs 46% Equivalent in Both Arms Equivalent in Both Arms Equivalent in Both Arms Transfusion, Bleeding Higher with PVAD Burkhoff D, et al. Am Heart J 2006;152:469 Seyfarth M, et al. J Am Coll Cardiol 2008;52:1584 Ouweneel D, et al. J Am Coll Cardiol 2017;69:358 Ouweneel D, et al. J Am Coll Cardiol 2017;69:278 Cheng J, et al. Eur Heart J 2009;30:2102 Meta-Analysis 2009 Meta-Analysis 2017 17 ML-0800 Rev A/ MCV00091528 REVA

17 The RCTs are Too Small, Too Underpowered to Look at Clinical Outcomes… Serum Lactate Levels Impress Trial, IABP vs Impella CP N=48 ISAR-SHOCK, IABP vs Impella 2.5 N=25 Seyfarth M, et al. J Am Coll Cardiol 2008;52:1584 Ouweneel D, et al. J Am Coll Cardiol 2017;69:358 18 ML-0800 Rev A/ MCV00091528 REVA

18 Matched Data: Impella vs IABP-Shock II Schrage et al. Circulation 2019; 139:1249-1258 19 ML-0800 Rev A/ MCV00091528 REVA

19 Matched Data: Impella vs IABP-Shock II 48.5% vs 46.4%, p=0.64 Schrage et al. Circulation 2019; 139:1249-1258 20 ML-0800 Rev A/ MCV00091528 REVA

20 Matched Data: Impella vs IABP-Shock II cohort • No difference in mortality • No subgroups with benefit • Higher rate of complications  Severe or life-threatening bleed (8.5% vs 3.0%, p<0.01)  Peripheral vascular complications (9.8% vs 3.8%, p=0.01)  Sepsis (35.3% vs 19.4%, p0.01) Schrage et al. Circulation 2019; 139:1249-1258 21 ML-0800 Rev A/ MCV00091528 REVA

21 Value? Resource Impact? • Patient Level versus Practice Level Decisions • Significant Impact of Novel Devices • Tiered Approach to Device Choice J Inv Cardiol 2015; 27: 148-54 22 ML-0800 Rev A/ MCV00091528 REVA

22 With more complications come higher risk of mortality and greater costs 1 • In a retrospective study of patients (n=1,816) receiving transcatheter intervention with large-bore catheters (PVAD), showed incidence of bleeding was 25.8% with 27.6% of those patients having more than one transfusion 1 • Receiving more than one transfusion was associated with increased in-hospital mortality. The mortality risk, hospital stay, and costs increased as the number of transfusions increased 1 Patients with bleeding complications were hospitalized 3 X as long as Cost patients without bleeding complications and costs were 2 X higher Number of transfusions 1. Redfors B, Watson BM, McAndrew T, et al. Mortality, length of stay, and cost implications of procedural bleeding after percutaneous interventions using large-bore catheters. JAMA Cardiol . 2017;2(7):798-802. 23 ML-0800 Rev A/ MCV00091528 REVA

23 IABP delivers clear cost advantages in the treatment of cardiogenic shock INCREASED associated costs Hospital cost of PCI with with newer devices, including 1 : cardiogenic shock was more than 2X • Increased use of blood products for PVADs vs IABP 1 and associated lab costs • Higher use of the OR due $74,457 to longer length of stay DECREASED associated $36,584 costs with IABP , including 1 : • Shorter intensive care (ICU) and hospital length of stay (LOS) • ICU: 7.11 vs. 8.74 days Tandem Heart/ IABP • Hospital: 8.5 vs. 10.70 days Impella ( evaluation of 2010 and 2011 Medicare MEDPAR data) J Invasive Cardiol . 2015 Mar;27(3):148-54 24 ML-0800 Rev A/ MCV00091528 REVA

24 Technology Assessment 25 ML-0800 Rev A/ MCV00091528 REVA

25 Impella, a uniquely American device? Sales 2017 91% of Impella devices were sold in the USA US Outside US Abiomed 2017 Annual Report 26 ML-0800 Rev A/ MCV00091528 REVA