4/22/2016 Updated. AllinaHealthSystem. Cardiogenic Shock: Definition. No Disclosures. Cardiogenic Shock: Declining (But Still High) Case Fatality Rate
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1 4/22/216 Updated Definition End-organ hypoperfusion secondary to cardiac failure Advanced Cardiopulmonary Support for the Critically Ill Adult April 22, 216 Cardiogenic Shock Michael A. Samara, MD FACC Advanced Heart Failure, Cardiac Transplant & Mechanical Circulatory Support No Disclosures Hemodynamics Persistent hypotension Systolic BP < 8-9 mmhg or MAP 3 mmhg below baseline Cardiac Index < 1.8 L/min/m 2 without support < 2. L/min/m 2 with support Elevated Filling Pressures LVEDP > 18 mmhg RVEDP > 1-15 mmhg Clinical Signs/Symptoms Poor urine output Altered mentation Cool periphery Abdominal pain/n/v Lactic acidosis and HCO 3 Pulmonary congestion Incidence/Etiologies AMI Isolated RV Failure 3.4% Ventricular Septal Rupture 4.6% Severe MR 8.3% JACC 2 35: % of STEMIs 2-3% of NSTEMIs Tamponade/ rupture 1.7% Other 7.5% Predominant LV Failure 74.5% Other Etiologies Postcardiotomy shock Fulminant myocarditis Tako-tsubo Cardiomyopathy 4.2% of cases complicated by CS Acute valvular regurgitation Endocarditis Trauma Aortic dissection Decompensated severe aortic/mitral stenosis Primary graft failure Pulmonary embolism Drug overdose Toxic cardiomyopathy of sepsis Declining (But Still High) Case Fatality Rate Case Fatality Rate (%) SHOCK PRESENT SHOCK ABSENT Adapted from Werdan et al. leuropean Heart Journal (214) 35, Goldberg et al. Circulation 29;119: SHOCK Trial TRIUMPH Study IABP SHOCK II A Spectrum of Disease Not Just Deranged Hemodynamics % Mortality Pre-shock Mild Shock Severe Shock Profound Refractory Shock 3% 7.5% 21% 42% 8% No inotropes Low-dose Moderate-dose High-dose (1) High-dose (2) High-dose (3) Inotropic Support HIGH DOSE: Epinephrine > 1 mcg/min; Dopamine > 1 mcg/kg/min; Dobutamine > 1 mcg/kg/min; Milrinone >.5 mcg/kg/min Samuels LE. J Card Surg 1999;14: Adapted from Hochman et al, Circulation. 23;17: &Hollenberg et al, Ann Intern Med. 1999;131:47 59.
2 4/22/216 Updated Distribution of LV Systolic Function Prognostic Biomarkers EPHESUS CAPRICORN RECENT MI VALIANT DINAMIT SHOCK Trial* MADIT II RALES HF COMET COPERNICUS CHARM REMATCH Ejection Fraction % *on support with IABP or inotropic therapy Ramanathan K, et al. J Am Coll Cardiol. 24;43:241A. Area Under the Curve Biomarker (Selejan et al, 212)* (Prodzinsky et al, 21) RAGE expression on monocytes.943, p <.1* SAPS score.873, p <.1* APACHE score.85, p <.1 Soluble RAGE in plasma.815, p =.4* Interleukin-6 in plasma.769, p =.11* Cardiac power index.742, p =.25* Cardiac index.771, p =.88 Werdan et al. Crit Care Med. 212;4: BNP.52, p =.987 CRP.55, p =.963* Markers of inflammation and MSOF are predictors of survival than the best hemodynamic variables. Not predictive of survival beyond 96 hours Prondzinsky et al. Crit Care Med 21;38: Selejan, et al. Crit Care Med 212;4: Randomized Trials in Cardiogenic Shock Randomized Trials in Cardiogenic Shock Trial Follow-up n/n n/n Revascularization SHOCK 1-year 76/152 83/149 SMACH 3 days 22/32 18/23 13/ /172 Relative Risk Relative-Risk.8 (.66;.98).87 (.66;1.29).82 (.7;.98) Early Medical treatment revascularization Better Catecholamines SOAP II (CS Subgroup) 28 days 64/145 5/ (.55;.93) Norepinephrine Dopamine Glycoprotein IIb/IIIa Inhib In-hospital 15/4 13/ (.59;2.27) PRAGUE-7 Up-stream Standard treatment abciximab NO Synthase Inhibitors TRIUMPH 3 days 97/21 76/ (.91;1.45) SHOCK-2 3 days 24/59 7/ (.59;2.69) Cotter et al 3 days 4/15 1/15.4 (.13;1.5) 125/275 93/ (.85;1.29) NO Synthase Placebo Inhibition IABP IABP-SHOCK I 3 days 7/19 6/ (.45;3.72) IABP-SHOCK II 3 days 119/3 123/ (.79;1.17) 126/ / (.81;1.18) IABP Standard treatment Trial Follow-up n/n n/n Revascularization SHOCK 1-year 76/152 83/149 SMACH 3 days 22/32 18/23 13/ /172 Relative Risk Relative-Risk.8 (.66;.98).87 (.66;1.29).82 (.7;.98) Early Medical treatment revascularization Better Catecholamines SOAP II (CS Subgroup) 28 days 64/145 5/ (.55;.93) Norepinephrine Dopamine Clinical Trials are Extremely Challenging to Perform Thiele et al. Eur Heart J 21; 31: Thiele et al. Eur Heart J 21; 31: Inotropic Therapy: A Necessary Evil Increased mortality Milrinone 1,2 Enoximone 3 Imazodan 4 Vesnarinone 5 Dobutamine 6,7 Xamoterol 8 Ibopamine 9 Increased risk of admission 1 Arrhythmia Milrinone 1,11 Dobutamine 12 Dopamine 13 Tachyphylaxis 15 Neurohormonal activation 16 IABP in the Guidelines Class I B Antman et al. Circulation 24;11: O Gara et al. Circulation. 213;127:e362-e425 Class I C Van de Werf et al. Eur Heart J 28;29: Steg et al. Eur Heart J.212;33: Packer M, et al. New Engl J Med 1991; 325: DiBianco R, et al. New Engl J Med 1989; 32: Uretsky BF, et al. Circulation 199; 82: Goldberg AD, et al. Circulation 199; 82: Suppl III: III Cohn JN, et al. New Engl J Med 1998; 339: Dies F, et al. Circulation 1986;74: Suppl II: II O Connor CM, et al. Am Heart J 1999; 138: Xamoterol in Heart Failure Group. Lancet 199; 336: Hampton JR, et al. Lancet 1997; 349: Kleiman NS, et al. J Am Coll Cardiol 2; 36; Thackray S, et al. Eur J Heart Fail 2; 2: Burger AJ, et al. Am J Cardiol 21 Jul 1;88(1): Chiolero, et al, Cardiovasc Surgeon 1991; 39: Colucci WS. J Card Fail 21;7(1): B. Hoffman and R. Lefkowitz. Goodman and Gilman, Eds, 9 th. Edition Aronson D, et al. J Card Fail 21; 7 (No. 3 Suppl 2): Gorodeski et al. Circ Heart Fail. 29;2:
3 4/22/216 Updated Short-term Survival with IABP Long-term Survival with IABP P=.94; log-rank test Relative risk 1.2 ( ) 6-Month Mortality 12-Month Mortality Mortality (%) 3 2 Mortality (%) Time after Randomization (Days) N Engl J Med 212; 367: Days after Randomization N Engl J Med 212; 367: IABP in the Guidelines What About More Robust Mechanical Support? 5 Class I B IIa B Antman et al. Circulation 24;11: O Gara et al. Circulation. 213;127:e362-e425 Class I C III A Van de Werf et al. Eur Heart J 28;29: Steg et al. Eur Heart J.212;33: IIa B (Mechanical Complications) Mortality (%) ?? N Engl J Med 212; 367: Time after Randomization (Days) Tailored Approach to Temporary MCS in Refractory Failure CARDIO- PULMONARY CARDIAC PULMONARY Pulmonary + RV RA-LA ECMO Keys Pulmonary to Support: + VA ECMO LV/BiV 1.) Rapid initiation + local expertise 2.) Robust RV Failure and stable prvad circulatory support BiV Failure prvad/plvad VV ECMO 3.) Ability to achieve cardiac unloading? LV Failure plvad 4.) A healthy respect for complications & patient selection Tandem PVAD Tandem PVAD Impella Tandem PVAD Whatever the Modality of Support Earlier Is Probably Better Survival (%) Follow-up (days) W. O Neill for the USPELLA Investigators TCT 21 Impella 2.5 Use for AMI Before PCI After PCI
4 4/22/216 Updated Pressure-Volume (PV) Loop: Stroke Work Hemodynamic Effects and Ventricular Unloading with pvads LV Pressure (mmhg) AV closes MV opens STROKE WORK Pressure-Volume Area STROKE VOLUME Smaller PV Area EDV-ESV Less Stroke Work AV opens PV Area Stroke Work Myocardial oxygen consumption MV closes LV A LA A LV Volume (ml) Burkhoff, D. (215) Where next in cardiogenic shock owing to myocardial infarction? Nat. Rev. Cardiol. doi:1.138/nrcardio Hemodynamic Effects and Ventricular Unloading with pvads Meta-Analysis of IABP vs. Temporary Left Ventricular Assist Devices: Hemodynamics Cardiac Index Mean Arterial Pressure LV A LA A LVAD IABP P heterogeneity=.22 mean ± SD mean± SD I 2 =34.% 2.3±.6 1.8±.4.55 ( ) Thiele et al LVAD IABP P heterogeneity=.1 mean±sd mean± SD I 2 =55.9% 76±1 7± ( ) Thiele et al Burkhoff et al 2.2±.6 2.1±.2.16 ( ) Burkhoff et al 91±16 72± ( ) Seyfarth et al 2.2±.6 1.8±.7.36 ( ) Seyfarth et al 87±18 71± ( ) Pooled.35 (.9-.61) Pooled 12.8 ( ) Pulmonary Capillary Wedge Pressure LVAD IABP P heterogeneity=.1 mean± SD mean± SD I 2 =76.6% 16±5 22±7-5.6 (-9.2 to Thiele et al -2.1) Burkhoff et al 16±4 25±3-8.4 (-11.o to -5.8) Seyfarth et al 19±5 2±6-1. ( ) Pooled -5.3 (-9.4 to -1.2) Burkhoff, D. (215) Where next in cardiogenic shock owing to myocardial infarction? Nat. Rev. Cardiol. doi:1.138/nrcardio Cheng et al: Eur Heart J 29;3: Meta-Analysis of IABP vs. Temporary Left Ventricular Assist Devices: Mortality 3 Day Mortality LVAD IABP 3-day mortality P (heterogeneity=.83 (no.) (no.) relative risk I 2 =% Thiele et al 9/21 9/2.95 ( ) Burkhoff et al 9/19 5/ ( ) Seyfarth et al 6/13 6/13 1. ( ) Pooled 24/53 2/ ( ) Meta-Analysis of IABP vs. Temporary Left Ventricular Assist Devices: Complications Limb Ischemia LVAD IABP P heterogeneity=.38 LVAD IABP P heterogeneity=.73 (no.) (no.) I 2 =% (no.) (no.) I 2 =% / ( ) Keys to Support: Thiele et al 7/21 Thiele et al 19/21 8/ ( ) Burkhoff et al 4/19 2/ ( ) Burkhoff et al 8/19 2/ ( ) /13 3. ( ) Pooled 27/4 1/34 2/47 1.) Rapid initiation 2.59 ( ) + local expertise Seyfarth et al 1/ ( ) Pooled 12/ , LVAD IABP P heterogeneity=.1 (no.) (no.) I 2 =62.1 Thiele et al 17/21 1/ ( ) Burkhoff et al 4/19 5/14.59 ( ) Bleeding 2.) Robust and stable circulatory support 3.) Ability to achieve cardiac unloading? Sepsis 4.) A healthy respect for complications & patient selection Pooled 21/4 15/ ( ) Cheng et al: Eur Heart J 29;3: Cheng et al: Eur Heart J 29;3:
5 4/22/216 Updated Algorithmic Approach to Patients with Refractory Cardiogenic Shock How Long Does The Storm Last? Majority of Added Morbidity/Mortality occurs in the first 2 months following discharge. After this period, outcomes are comparable to patients without shock. Thiele et al, EAPCI 212; Kapitel 23 J Am Coll Cardiol. 216;67(7): doi:1.116/j.jacc The Majority of Cardiogenic Shock Survivors Enjoy Good Functional Status/QOL SHOCK Trial (Patients having undergone urgent revascularization) Summary % Class I/II Class III/IV Deceased Cardiogenic shock continues to be associated with high morbidity/mortality. While historically considered a complication of AMI, increasingly seen in other clinical contexts. There is a spectrum of disease severity with nearly uniform mortality in those with the most severe shock. 2 weeks Post-discharge 6 months Post-discharge 1 year Post-discharge Sleeper et al. J Am Coll Cardiol. 25;46: Summary Summary Markers of end-organ dysfunction and inflammation may be more predictive of survival than hemodynamic variables. Guideline recommendations for IABP support have been downgraded due to recent trial results. Whether alternative forms of mechanical support (Impella, Tandem Heart, etc.) achieve superior survival has yet to be conclusively demonstrated. In patients with adequate end-organ function (most critically neurologic function), temporary MCS may serve as a bridge to durable MCS/transplant. The majority of long-term survivors of cardiogenic shock have acceptable quality of life and functional status.
6 4/22/216 Updated Michael Samara, MD FACC
AllinaHealthSystem 1
: Definition End-organ hypoperfusion secondary to cardiac failure Venoarterial ECMO: Patient Selection Michael A. Samara, MD FACC Advanced Heart Failure, Cardiac Transplant & Mechanical Circulatory Support
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