1. Management of Acute Shock and Right Ventricular Failure Nader Moazami, MD Department of Thoracic and Cardiovascular Surgery and Biomedical Engineering, Cleveland Clinic

2. Disclosures NONE NONE

3. CARDIOGENIC SHOCK Scope of the Problem Diverse etiology − − 7-10% Acute MI − − Cardiac Arrest − − Post-cardiotomy 0.2-0.5% − − Decompensated CHF − − Acute fulminant myocarditis − − Acute Cardiac Allograft Rejection

4. CARDIOGENIC SHOCK Definition Arterial hypotension (systolic arterial blood pressure below 90 mmHg or mean arterial blood pressure below 70 mmHg for 30 minutes or longer with or without therapy); PCWP >18 mmHg (in patients with a pulmonary artery catheter) or an acute decrease of the left ventricular ejection fraction below 40% Need for a continuous infusion of inotropic drugs IABP C. Torgerson, et al Crit Care. 2009; 13(5): R157

5. N ptsyr AMI (%) % shock on all AMI % shock at admission on all shock Mortalit y pts in shock (%) NRMI-2426,23394- 97 STEMI 52 NSTEMI 48 8.1 4.9 2874 % BLITZ-11,959 Ott 01 STEMI 65 NSTEMI 35 62970 GISSI-111,80684- 85 STEMI 90 NSTEMI 10 8.52870 ISIS-341,29989- 91 STEMI 77 NSTEMI 23 7.0-- GUSTO-141,02190- 93 STEMI 7.21156 GUSTO-2b12,08494- 95 STEMI 34 NSTEMI 66 4.2 2.5 0000 63 73 GUSTO-315,05995- 97 STEMI 5.410.162 GRACE8,95199- 01 STEMI 66 NSTEMI 34 6.72659 6.2 Incidence and mortality cardiogenic shock with AMI

6. N ptsyr AMI (%) % shock on all AMI % shock at admission on all shock Mortalit y pts in shock (%) NRMI-2426,23394- 97 STEMI 52 NSTEMI 48 8.1 4.9 2874 % BLITZ-11,959 Ott 01 STEMI 65 NSTEMI 35 62970 GISSI-111,80684- 85 STEMI 90 NSTEMI 10 8.52870 ISIS-341,29989- 91 STEMI 77 NSTEMI 23 7.0-- GUSTO-141,02190- 93 STEMI 7.21156 GUSTO-2b12,08494- 95 STEMI 34 NSTEMI 66 4.2 2.5 0000 63 73 GUSTO-315,05995- 97 STEMI 5.410.162 GRACE8,95199- 01 STEMI 66 NSTEMI 34 6.72659 6.2 Incidence and mortality cardiogenic shock with AMI

7. A. Babaev, et al. JAMA 2005;294:448-454 Trends in Management and Outcomes of Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock

8. A. Babaev, et al. JAMA 2005;294:448-454 Trends in Management and Outcomes of Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock

10. SHOCK II Trial

11. Limitations of Conventional Therapy IABP decreases LV workload and increase C.O. by 10-15% Need for high dose inotropic support increases myocardial oxygen demand Mortality for cardiogenic shock remains >50% Could more powerful mechanical support improve outcomes?

12. Emerging Role of Early Mechanical Circulatory Support − Hemodynamic stabilization − Normalization of end organ perfusion − Potential for Cardiac recovery and weaning − Time for evaluation of other options Transplant Long-term Mechanical Therapy (Destination Therapy)

13. Early intervention increases the probability of survival: Timing is Critical In Acute Settings, Cardiac Function is RECOVERABLE

14. LV “Recovery” Goals To decompress the ventricle(s). Wean toxic levels of inotropes. Allow ATP stores to return. Allow cytokines to be metabolized. Preserve end organ function.

15. Impella study – Flameng et al 2000 Massive Myocardial damage Up to 5-times Reduction in infarct size over base line without offloading Infarct with offloading Infarct LAD occlusion model Potential reduction in infarct size

16. Increasing Use of ECMO Paden ML et al ELSO Registry. ASAIO J. 2013 May-Jun;59(3):202-10.

17. Why ECMO? Advantages − Rapid insertion (Fem artery, Fem Vein) − Ease of insertion − Low cost − Low maintenance Disadvantages − Loads the failing LV − Immobility − Truly short term rescue device

18. Impella 2.5 Technology Clinical Adoption in US FDA Clearance in June’08 1000+ patients treated 1000+ patients treated 300+ US Centers 2 Trials Open USpella Registry 18

19. 19 Impella ® 5.0 Miniaturized Blood Pump Technology 21 Fr micro-axial pump (requires 22-24 Fr Sheath) High-Flow Circulatory Support Delivers up to 5 L/min blood flow support Directly Unloads Left Ventricle Actively unloads up to 5 L/min from LV Peripheral Placement Single peripheral insertion point Femoral Artery Cut-down/ Axillary artery approach HCS-P110-062609

20. USpella AMI Population 20 Baseline Characteristics Mean ± SD or % ShockNo Shock p-value 64 ± 16 92 % 69% (31%) 31 ± 14 50 % 91 % 65% / 23% / 12% 14% 2.2 ±.4 Age (yrs) Gender (Male in %) STEMI (NSTEMI) LVEF (%) Unprotected LM or LPC Multivessel Disease Revasc (PCI/CABG/None) Impella placement Pre-PCI Pump Flow (L/min) 74 ± 10 72 % 3% (97%) 33 ± 15 50 % 75 % 100% / 0 / 0 95% 2.2 ±.3 0.003 0.04 <0.001 0.6 0.9 0.2 0.002 0.001 0.9

21. Cardiac Index (l/min/m2) Wedge Pressure 0 1.6 1.8 2.0 2.2 2.4 2.6 On Impella PCWP (mmHg) 0 20 24 28 22 26 30 Pre Impella* 1.9±0.5 SVR (x 1000 dynes/sec x cm -5 ) 0 1.2 1.4 1.6 1.8 2.0 1.0 1.8±0.7 Impella Improves Hemodynamics in AMI Shock On Impella Pre Impella* On Impella Pre Impella* 2.5±0.6 28±8 20±10 p=0.02 p=0.001 p=0.01 Mean Arterial Pressure 62±19 87±16 p=0.003 *Pre-Impella measurements were recorded with optimal medical management measures (inotropes + IABP) 1.3±0.5 MAP (mmHg) 0 50 60 70 80 90 On Impella Pre Impella* 100

22. Survival to Discharge By Indication 0% 25% 50% 75% 100% AMI with No Shock AMI with Shock (n=36) 89% (n=26) 58% USpella 22

23. Removes oxygenated blood from the LA via a transeptal cannula Removes oxygenated blood from the LA via a transeptal cannula Returns blood to the femoral artery Returns blood to the femoral artery Continuous flow, centrifugal pump 4-5 LPM Continuous flow, centrifugal pump 4-5 LPM TandemHeart ® PTVA

24. TandemHeart ® PTVA Transseptal Cannulation

25. Highlights of Texas Heart Institute Experience Refractory Cardiogenic Shock Pre TandemHeart Post TandemHeart P value CI (lpm)0.7 +/- 0.52.79 +/- 0.97<0.0001 SVO2 (%)39 +/- 1066 +/- 8<0.0001 PCWP (mmHg) 29 +/- 914 +/- 5<0.0001 SBP (mmHg)79 +/- 20101 +/- 13<0.0001 Lactic acid (mg/dl) 64 +/- 5427 +/- 30<0.03 Creatinine (mg/dl) 2.3 +/- 1.31.5 +/- 0.7<0.02

26. Heartmate PHP

27. Cardiac Catheter Pump Low-profile percutaneous device delivered through 13F sheath Expands to 24F across aortic valve Designed to deliver over 4 lpm for up to 10 days Cardiac Catheter Pump Low-profile percutaneous device delivered through 13F sheath Expands to 24F across aortic valve Designed to deliver over 4 lpm for up to 10 days Target Applications Acute MI Cardiogenic Shock High-risk PCI Acutely decompensated heart failure

28. Treatment of RV Failure Pulmonary vasodilators (inhaled nitric oxide or prostacyclin)Pulmonary vasodilators (inhaled nitric oxide or prostacyclin) Inotropic drugs (milrinone, epinephrine)Inotropic drugs (milrinone, epinephrine) Avoidance of Hypoxia and HypercarbiaAvoidance of Hypoxia and Hypercarbia Adequate drainage of the pleural spacesAdequate drainage of the pleural spaces Maintain MAP>70 mmHg, CVP,15 mmHgMaintain MAP>70 mmHg, CVP,15 mmHg RVADRVAD  Temporary (short- to mid-term )

29. Current Short-Term RVAD Devices

30. New Devices for Temporary RVAD support

31. Old Concepts New Designs Impella RP IDE Study ongoing for RV failure − Within 48 hours post LVAD − Within 48 hours post surgery or post MI.

32. IMPELLA RP

33. Conclusion Increasing Use of Mechanical Pumps for LV and RV support Increasing Use of Mechanical Pumps for LV and RV support Majority will be percutaneously placed Majority will be percutaneously placed In addition to hemodynamic support ambulation will be possible In addition to hemodynamic support ambulation will be possible The biggest driver for use will be cost The biggest driver for use will be cost Value-based medicine will mandate stricter selective use in patients Value-based medicine will mandate stricter selective use in patients