circulatory support in cardiogenic shock Complementary role of percutaneous and surgical circulatory support in cardiogenic shock Introduction and objectives Holger Thiele Medical Clinic II (Cardiology/Angiology/Intensive Care) University of Lübeck, Germany

Disclosures Funding: German Research Foundation German Heart Research Foundation German Cardiac Society EU Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte Terumo Lilly Maquet Cardiovascular Teleflex Medical Consulting: Maquet Cardiovascular, Lilly Speaker Honoraria: Lilly, Astra Zeneca, Daiichi Sankyo, Boehringer Ingelheim, Maquet Cardiovascular, Medicines Company

In-hospital Mortality USIK 1995, USIC 2000, FAST-MI France National Registry 90 80 70 60 50 40 30 20 10 Shock No Shock 70 (62-77) 63 (56-70) Death after 30 days (%) 51 (44-59) 8.7 4.2 (7.5-10.0) 3.6 (3.4-5.1) (3.0-4.4) 1995 2000 2005 Aissaoui et al. Eur Heart J 2012; 33:2535–2543

Randomized Trials in Cardiogenic Shock Relative Risk 95% CI Relative Risk 95% CI Trial Revascularization (PCI/CABG) Follow-up n/N n/N SHOCK SMASH Total 1-year 30 days 76/152 22/32 103/184 83/149 18/23 117/172 0.80 (0.66;0.98) 0.87 (0.66;1.29) 0.82 (0.70;0.98) Early revascularization better Medical therapy better 0 0.25 0.5 0.75 1 1.5 2 2.5 3 Thiele et al. Eur Heart J 2010; 31,1828–1835

Class 1B → IIa B Class IC → IIb B Guidelines IABP in STEMI complicated by cardiogenic shock Class 1B → IIa B Class IC → IIb B Antman et al. Circulation 2004;110:82-292 O’Gara et al. Circulation. 2013;127:e362-e425 Van de Werf et al. Eur Heart J 2008;29:2909-2945 Steg et al. Eur Heart J.2012;33:2569-2619

Ethical Problems There are no controlled trials on parachute jumping Umbrellas protect from rain – randomized trials useless

Ethical Problems

Primary Study Endpoint (30-Day Mortality) 50 Control 41.3% 39.7% 40 IABP Mortality (%) 30 20 P=0.92; log-rank test Relative risk 0.96; 95% CI 0.79-1.17; P=0.69; Chi2-Test 10 5 10 15 20 25 30 Time after randomization (days) Thiele et al. NEJM 2012;367:1287-1296

Mortality 12-Month Follow-up P=0.94; log-rank test Relative risk 1.02; 95% CI 0.88-1.19 30-day 6-Month 12-Month Mortality Mortality Mortality 60% IABP 51.8% 48.7% Control 50% 41.3% 51.4% 49.2% Mortality 40% 39.7% 30% 20% 10% 0% 0 30 60 90 120 150 180 210 240 270 300 330 360 390 420 No. at risk Days after randomization IABP 301 181 171 165 161 159 154 152 149 147 146 144 136 45 21 Control 299 174 166 140 55 29 Thiele et al. Lancet 2013;382:1638-1645

Class IC → IIb B → III ESC Revascularization Guidelines 2014 IABP in cardiogenic shock Class IC → IIb B → III

Currently Available Percutaneous Devices IABP Impella TandemHeart Mini-ECLS (ECMO) 2.5 3.5 (CP) 5.0

ECMO for Transfer from Non-tertiary Centers 100 Mortality in patients> 62 years: 100% Mortality in patients with resuscitation: 100% Mortality in patients > 62 years: 100% Mortalität in patients with resuscitation: 100% 80 60 40 20 Total survival (%) No. at risk 87 1 27 2 18 3 10 4 5 Time after ECMO-Implantation (years) Beurtheret et al. Eur Heart J 2013;34:112-120

Cardiogenic Shock - Guidelines Steg et al. Eur Heart J.2012;33:2569-2619

Patient Inclusion in Cardiogenic Shock Trials Stop – no effect Stop – slow recruitment Stop slow recruitment 706 700 600 500 400 300 200 100 Surrogate endpoint 600 Underpowered 398 N Patients 302 55 80 57 45 SHOCK SMASH TRIUMPH TACTICS PRAGUE -7 IABP-SHOCK I IABP-SHOCK II CULPRIT-SHOCK

Thank you for your attention holger.thiele@uksh.de

Randomized Trials in Cardiogenic Shock Relative Risk 95% CI Relative Risk 95% CI Trial Revascularization (PCI/CABG) SHOCK Follow-up n/N n/N 1-year 76/152 83/149 0.80 (0.66;0.98) SMASH Total 30 days 22/32 103/184 18/23 117/172 0.87 (0.66;1.29) 0.82 (0.70;0.98) Early revascularization Medical treatment better better Catecholamines SOAP II (CS Subgroup) 28 days 64/145 50/135 Norepinephrine better 0.75 (0.55;0.93) Dopamine better Glycoprotein IIb/IIIa-Inhibitors PRAGUE-7 NO Synthase Inhibitors TRIUMPH SHOCK-2 Cotter et al Total In-hospital 15/40 13/40 1.15 (0.59;2.27) Up-stream Abciximab Standard treatment better better 30 days 97/201 24/59 4/15 125/275 76/180 7/20 10/15 93/215 1.14 (0.91;1.45) 1.16 (0.59;2.69) 0.40 (0.13;1.05) 1.05 (0.85;1.29) NO Synthase Inhibition Placebo better IABP IABP-SHOCK I IABP-SHOCK II Total better 30 Tage 7/19 119/300 126/319 6/21 123/298 129/319 1.28 (0.45;3.72) 0.96 (0.79;1.17) 0.98 (0.81;1.18) IABP better Standard treatment better 0 0.25 0.5 0.75 1 1.5 2 2.5 3 Updated Thiele et al. Eur Heart J 2010; 31:1828–1835

How to Prevent MODS? Optimal Timing MODS Prevention Optimal Support Optimal prevention/ Management of potential Device-complications (i.e. Device malfunction, Hemolysis, Infection)