MANAGEMENT OF CARDIOGENIC SHOCK

CASE PRESENTATION 37 year old Dutch female No known coronary artery disease risk factors 1 week post partum at time of presentation (G3P3) after an uncomplicated normal delivery Sudden onset of severe retrosternal chest pain at 0115 hours Arrived at Emergency Department 0134 hours

CASE - ECG

CASE - CXR

CASE - PROGRESS Diagnosed acute anterolateral ST elevation MI and Killip Class 2 CVL activated and brought for primary PCI Arrived in CVL 0143 hours Vital signs: BP 104/76, HR 94/min, SpO2 98%

CASE - CORONARY ANGIOGRAM Left Main Occlusion

CASE - CORONARY ANGIOGRAM Co-dominant RCA with no collaterals

CASE - PROGRESS Diagnosed acute anterolateral ST elevation MI and Killip Class 2 CVL activated and brought for primary PCI Arrived in CVL 0143 hours Vital signs: BP 104/76, HR 94/min, SpO2 98% After the initial diagnostic angiogram, the patient became progressively breathless and BP was 80/60 mmhg and HR 120/min STEMI secondary to peri-partum left main dissection with cardiogenic shock

SHOCK: CLASSIFICATION Shock is a state of acute circulatory failure leading to inadequate tissue perfusion and resulted in end organ injury The simplest way to classify shock is: Pump failure cardiogenic shock Tubing malfunction- distributive shock- sepsis, anaphylaxis, spinal shock Fluid loss hypovolemic shock Cardiogenic shock is when the heart is unable to supply enough blood to the body; the primary problem is within the heart itself

CARDIOGENIC SHOCK: DEFINITION Evidence of hypoperfusion: cold clammy skin; impaired mentation, oliguria 1. Cardiac index < 1.8 l/min/m 2 2. Systolic BP < 90 mmhg 3. PAWP > 20 mmhg 4. Urine output < 0.5 ml/kg/hr 5. Systemic vasc resistance > 2000 dynes-sec/ cm 5 The failure to define cardiogenic shock consistently or to confirm hemodynamically the presence of elevated PAWP and low cardiac index have confused the clinician and confounded the literature

CARDIOGENIC SHOCK: ETIOLOGY AMI with subsequent LV dysfunction remains the most common cause of cardiogenic shock

CARDIOGENIC SHOCK: INCIDENCE AND TIMING IN AMI

CARDIOGENIC SHOCK: PROGNOSIS Babaer et al JAMA 2005;1294:448

CARDIOGENIC SHOCK: PATHOPHYSIOLOGY

CARDIOGENIC SHOCK: PATHOPHYSIOLOGY Cardiogenic Shock Spiral Thiele et al EHJ 2010;31:1828-35

CARDIOGENIC SHOCK: PATHOPHYSIOLOGY Stunned myocardium Infarcted myocardium

MANAGEMENT OF CARDIOGENIC SHOCK Specific measures Vasopressors/Ino-dilators Reperfusion Therapy Thrombolysis PCI CABG Intra-Aortic Balloon Pump (IABP) Extra-Corporal Membrane Oxygenation (ECMO) Ventricular Assist Device (Impella, Tandem Heart, LVAD)

CARDIOGENIC SHOCK: SPECIFIC MEASURES & VASOPRESSORS 1. Maximize volume (RAP 10-14 mm Hg, PAWP 18-20 mm Hg) 2. Maximize oxygenation (e.g., ventilator) 3. Correct electrolyte and acid-base imbalances 4. Control rhythm (e.g., pacemaker, cardioversion) 5. Sympathomimetic amines (e.g., dobutamine, dopamine, norepinephrine) 6. Phosphodiesterase inhibitors (e.g., milrinone) 7. Calcium sensitizer (e.g. levosimendan)

COMMONLY USED VASOPRESSOR AGENTS Agent Dose Cardiac Peripheral Vascular Heart rate Contractility Vasoconstriction Vasodilation Dopaminergic Dopamine 1-4 mcg/kg/min 1+ 1+ 0 1+ 4+ 4-20 mcg/kg/min 2+ 2-3+ 2-3+ 0 2+ Dobutamine 2.5-15 mcg/kg/min 1-2+ 3-4+ 0 2+ 0 Noradrenaline 2-20 mcg/min 1+ 2+ 4+ 0 0 Isoprenaline 1-5 mcg/min 4+ 4+ 0 4+ 0 *vasodilation in renal, mesenteric, coronary, and cerebral vascular beds

INO-DILATORS Phosphodiesterase III inhibitors (PDIs), e.g. milrinone are inotropic agents with vasodilating properties The mechanism of action of PDIs is increasing intracellular camp levels by prevention of its breakdown The hemodynamic properties: Positive inotropic effect on the myocardium Peripheral vasodilation (decreased afterload) Reduction in pulmonary vascular resistance (decreased preload) Levosimendan acts by increasing the sensitivity of the cardiac myofilament to calcium A potent inotrope and also a vasodilator of the arterial, venous, and coronary circulation Should be used with caution as it can cause hypotension

SHOCK TRIAL: REVASC IN CARDIOGENIC SHOCK

SHOCK TRIAL: RESULTS Hochman et al. JAMA 2001;285:190-2

CARDIOGENIC SHOCK: PERCUTANEOUS VENTRICULAR ASSIST DEVICES (VAD)

CASE - IABP INSERTION Started on dopamine infusion Patient became restless with drop in O2 saturation and was subsequently mechanical ventilated Left femoral artery puncture with intra-aortic balloon pump (IABP) insertion after diagnostic angiogram Cardiac surgeon was called After discussion with surgeon, advised to proceed with PCI

IABP: MECHANISM OF ACTION Inflation (Diastole) Augmentation of diastolic pressure Increase coronary perfusion Increase myocardial O2 supply Deflation (Systole) Decrease cardiac work Decrease afterload Increase cardiac output

IABP: META-ANALYSIS IN STEMI WITH CS Sjauw et al. Eur Heart J. 2009; 30(4):459-468

IABP-SHOCK II TRIAL

IABP-SHOCK II: TRIAL FLOW AND TREATMENT

IABP SHOCK II: RESULTS IAPB had no impact on: 1. 30-day mortality (39.7% IABP vs. 42.3% control, p=0.92) independent of STEMI/NSTEMI 2. Renal function, serum lactate (microcirculation) and CRP increase (inflammatory) Thiele et al. NEJM 2012;367:1287-96

ISSUES WITH IABP SHOCK II Cross over of 10% More frequent use of LVAD devices (7.4 vs. 3.7%) More than 80% of IABP were insert after the PCI Inclusion criteria: No hemodynamic measurements Too strict? Too lenient? BP systolic < 90 mmhg for 30 min Required inotropes to maintain BP above 90 mmhg Signs of pulmonary congestion Signs of organ failure

CASE LAD AND LCX WIRING

CASE - LM/LAD STENTING BMS 4.5 x 32mm to LM/LAD

CASE - POST LAD STENTING BP 69/50, HR 182/min SpO2 96%

LCX STENTING

CASE - POST LCX STENTING

CASE - FINAL ANGIOGRAM BP 60/39, HR 160/min, SpO2 97%

PERCUTANEOUS VAD

TANDEMHEART CARDIAC ASSIST TECHNOLOGY

TANDEMHEART CENTRIFUGAL PUMP

TANDEM HEART IN CARDIOGENIC SHOCK

TANDEMHEART VS. IABP RANDOMIZED TRIAL IN CARDIOGENIC SHOCK Burkhoff et al. AHJ 2006;152:469

IMPELLA ABIOMED LP LD

IMPELLA AXIAL-FLOW PUMP

IABP=13 Impella LP 2.5 =12

46% both groups

IABP VS. PERCUTANEOUS VAD META-ANALYSIS - MORTALITY Kaplan-Meier curve for an individual patient based on a metaanalysis of the 3 randomized studies comparing percutaneous left ventricular assist devices (LVAD) versus intra-aortic balloon pump therapy

COMPLICATIONS OF LV SUPPORT DEVICES

META-ANALYSIS OF THERAPY IN CARDIOGENIC SHOCK

CARDIOGENIC SHOCK: PATHOPHYSIOLOGY Cardiogenic Shock Spiral Thiele et al EHJ 2010;31:1828-35

ESC 2010 GUIDELINES ON MYOCARDIAL REVASCULARIZATION

CASE - ECMO INSERTION

DEFINITION FOR ECLS Short term devices of simplified Heart and/or Lung Bypass circuit Extracorporeal Membrane Oxygenation (ECMO) with veno-venous (VV) extracorporeal oxygenation for respiratory function substitution Extracorporeal life support technique (ECLS) with a veno-arterial (VA) circulation for both oxygenation and hemodynamic assistance Now more commonly used ECMO

VA ECMO Consists of: Cannulae Circuit tubing Centrifugal pump Oxygenator Heat exchanger All specially coated to reduce the risk of clot formation

N=27

N=81

N=21

N=33

N=134

CARDIOHELP SYSTEM MAQUET

LIFEBRIDGE B2T MEDIZINTECHNIK GMBH

CAPIOX EBS SYSTEM TERUMO

GUIDELINES ON MYOCARDIAL REVASCULARIZATION

NHCS EMCO EXPERIENCE PATIENTS AND INDICATIONS Number of patients supported on ECMO over the years: ECMO PATIENTS ECMO PATIENTS 28 55 46 48 44 40 54 Cardiac: 58% ECPR: 28% Respiratory: 19% Others: 5% 11 15 17 15 18 3 1 3 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 Main indication for post cardiotomy ECMO support: low cardiac output syndrome and/or ventricular arrhythmia Main indication for cardiogenic shock/ecpr ECMO support: acute myocardial infarct Steady increase in VV support for respiratory failure in the last few years

CASE - ECG POST PCI

CASE - TTE POST PCI

CASE - PROGRESS POST PCI No improvement of LVEF after PCI and remained in cardiogenic shock Unable to wean off ECMO Decision made for implantation of LVAD device as bridge to transplant HeartMate II LVAD was implanted D10 of admission

ESC 2010 GUIDELINES ON MYOCARDIAL REVASCULARIZATION

CASE - LVAD IMPLANTED

CASE - PROGRESS POST PCI Extubated 2 days post LVAD implantation No requirement for inotropic support Discharged and flown back to Holland 6 weeks post admission for heart transplant consideration

CASE PROGRESS 2 YEARS POST LVAD IMPLANTATION Doing well with LVAD Taken off transplant list No immediate plans for cardiac transplantation

52% 25% 8% 23%

HeartMate XVE vs HeartMate II

58% 24% RR 0.54 95% CI 0.34-0.86 P = 0.008

1 st gen pulsatile LVAD (Thoratec and Heartmate xve) 2 nd gen CF LVAD HeartMate II 3 rd gen CF LVAD HeartWare HVAD

HEARTMATE III

NHCS EXPERIENCE: CONTINUOUS-FLOW LVAD Total = 67 patients 16 14 12 7 1 4 10 8 6 4 2 4 3 10 4 7 9 3 5 10 HM3 HVAD HMII 0 2009 2010 2011 2012 2013 2014 2015 82

NHCS EXPERIENCE: CONTINUOUS-FLOW LVAD 5/09 TO 12/15 48 HeartMate II, 18 HVAD & 1 HM3 14 as Destination Therapy 53 Males & 14 Females Median age 50 years (14 70 years) Diagnosis (n=67): DCMP (29) Ischemic CMP (24) Chemo-induced (3) Viral (2) ACS (9) Crash & burn : 18

NHCS EXPERIENCE: CONTINUOUS-FLOW LVAD 5/09 TO 12/15 All discharged home with device except for 3 perioperative mortality ICU: 3 to 101 days Median 7 days Hospital Stay: 13 to 114 days Median 32 days Mean duration of support 722 days (1.98yrs) Longest support 2431 days (6.6yrs) Total follow-up period 132.4 patient years

NHCS EXPERIENCE: CONTINUOUS-FLOW LVAD 5/09 TO 12/15 13 - bridged to transplant (20%) 1 transferred to country of origin for further follow up (1.5%) 1 bridged to recovery (1.5%) 9 mortality (13%): 3 peri-operative (4.5%) 43 on-going support (64%) - 22 on waitlist, 11 DT, 2 refused transplant, 8 recovering from recent surgery & need reassessment for Heart Transplant eligibility (at least 3 mths s/p LVAD)

NHCS EXPERIENCE: HEART TRANSPLANT PROGRAM First heart transplant: 6 Jul 1990 66 heart transplants (3 redo heart transplants) Sex: Male = 49, Female =14 Age: 14 to 65 years (mean age 46) Indications

NHCS HEART TRANSPLANT: NUMBER OF PATIENTS/YEAR 0 1 2 3 4 5 6 1 5 1 2 3 0 0 1 1 5 1 2 2 0 4 3 6 4 3 5 3 2 2 4 0 6 HOTA amendment in July 2004 to include beyond kidneys, to heart, liver & cornea

NHCS HEART TRANSPLANT: SURVIVAL RATE Local Data ISHLT (2013) 1 Year 78.2% 85.7% 5 year 66.1% 72.1% 10 years 56.4% 56.1%

WAITING LIST 23 Patients waiting time 105-1974 days (mean 757) 22 on LVAD support, 4 Female Age 14-60 years (mean 45) Support duration range 240-2155 days (median 995) 1 non-lvad support 16 yo with possible chemo induced DCMP Issues with heart transplant Lack of donor Asian culture and religions Cost insurance or government funding Strict selection criteria young, minimal comorbidities etc Long term immunosuppression infection, maglinancy

CAUSES OF DEATH AFTER TRANSPLANT 4 major causes: Acute allograft rejection Infections other than cytomegalovirus (CMV); CMV infection was responsible for less than 1 percent of deaths in the ISHLT registry Allograft vasculopathy Lymphoma and other malignancies First 30 days: Graft failure (primary and non-specific) 40%of deaths Multiple organ failure - 14% Non-CMV infection - 13% Between 31 days and one year: Non-CMV infection - 33% Graft failure (primary and non-specific) - 18% Acute rejection - 12 percent After 5 years: Allograft vasculopathy and late graft failure - 30% Malignancies 22% Non-CMV infection 10%

TREATMENT OF CS IS PREVENTION! Reduction of CS during hospitalization with increase rate of PCI Jeger et al. Ann Intern Med 2008;149:618-28

AMIS (SWITZERLAND) PLUS REGISTRY Cardiogenic Shock in ACS Patients, 1997-2006 1997 2006 P Value Overall 12.9% 5.5% 0.001 Shock Developing In-Hospital 10.6% 2.7% 0.001 Mortality from Cardiogenic Shock in ACS Patients, 1997-2006 1997 2006 P Value Overall Mortality from Shock 62.8% 47.7% 0.010 Mortality from Shock Developing In- Hospital 73.8% 46.6% 0.009 Mortality from Shock on Admission 60.9% 48.9% 0.094

In-hospital mortality TREATMENT OF CS IS PREVENTION! Reduction in mortality with early PCI Zeymer et al ESC Congress 2009

CONCLUSION Cardiogenic shock is associated with extremely poor prognosis and early revascularization improve prognosis as compared to initial medical care Severe LV dysfunction post STEMI may be due to stunning and mechanical support with VADs can bridge the heart to functional recovery However, current VAD (IABP, TandemHeart, Impella ) have not been shown to improve survival in clinical trials Use of VA-ECMO has been successful in many case series in patients with refractory cardiogenic shock but never been tested in clinical trial Selection of patients and devices for mechanical support is important because of complications, cost and futility Early PCI in STEMI may reduce incidence of cardiogenic shock

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