Cardiogenic Shock, Acute Coronary Syndrome, Congestive Heart Failure, and Arrhythmias Dalhousie Critical Care Lecture Series

ICU Inadequate tissue perfusion resulting from cardiac dysfunction Clinical definition - decreased cardiac output and tissue hypoxia in the presence of adequate intravascular volume Hemodynamic definition - sustained systolic BP 15 mm Hg Parrillo, J Cardiogenic Shock

ICU Acute MI Pump failure Mechanical complications Right ventricular infarction Other conditions End-stage cardiomyopathy Myocarditis (fulminant myocarditis) Myocardial contusion Prolonged cardiopulmonary bypass Septic shock with myocardial depression Valvular disease Causes of Cardiogenic Shock

ICU Evolution Of The Disease Frequently, shock develops after presentation for myocardial infarction. - SHOCK Registry At presentation 25% in shock Within 24 hours 75% (median delay = 7 hours) - GUSTO Trial At presentation11% in shock After admission89% SHOCK Registry, Circulation. 1995;91: GUSTO J Amer Coll Cardiol. 1995;26: Cardiogenic Shock

ICU Wall motion abnormality during occlusion Wall motion abnormality From Kloner RA. Am J Med. 1986;86:14. Gradual return of function (hours to days) Persistent wall motion abnormality (despite reperfusion and viable myocytes) Coronary occlusion Coronary reperfusion Return of function Clamp Schematic Diagram of Stunned Myocardium

ICU Cell death Significant residual stenosis Reperfusion Segments with myocardial stunning Segments with both stunning and hibernation Segments with hibernating myocardium Relief of ischemia Inotropic support No return of function Return of myocardial function Ischemic Myocardium

ICU Assure oxygenation Intubation and ventilation if needed Venous access Pain relief Continuous EKG monitoring Hemodynamic support Fluid challenge if no pulmonary edema Vasopressors for hypotension - Dopamine -Norepinephrine - Dobutamine - Milrinone Initial Approach: Management

ICU Dopamine Dopaminergic, Beta, Alpha: ranges ? Dopa: 1-5 ug/kg/min ? Renal flow Beta: 5-10 ug/kg/min Inoptropy/chronotropy Alpha: >10 ug/kg/min Vasoconstriction Major use: increasing HR, ?bp

ICU Dobutamine Beta (little alpha) Inotropic/chronotropic 2-20 ug/kg/min Major use: Systolic dysfunction Caveat: can/will decrease MAP Often used in conjunction with levophed

ICU Epinepherine Alpha and Beta 0.01 – 1.0 ug/kg/min Major Use: when you need A&B Like using dobutamine and levophed mixed together

ICU Milrinone Used as an inotrope Mechanism of Action Phosphodiesterase inhibitor decrease the rate of cyclic AMP degradation increase in cyclic AMP concentration leads to enhanced calcium influx into the cell, a rise in cell calcium concentration, and increased contractility Side Effects can also cause vasodilatation but tends to have less chronotropy than dobutamine Onset of action 5-15 minutes Duration Half life of approximately 2 hours (so its gonna last a while Dose Loading dose: 50 mcg/kg administered over 10 minutes followed by mcg/kg/minute

ICU Norepinepherine Alpha and Beta ug/kg/min Major Use: when you need A&B ? Drug of choice for septic shock Good and bad for use in cardiogenic shock May increase blood pressure May decrease CO by increasing afterload Will increase cardiac strain

ICU Use of Inotropes BP is not a reliable indicator of CO CO = SV X HR MAP=SVR X CO if SVR is increased as CO drops then MAP will stay the same Need to titrate to the CO Swan ganz CO measure U/O Lactate ScVO2

ICU Use of Vasopressors Often used in conjunction with inotropes counteract the vasodilation that occurs Titrated to MAP

ICU Intra-aortic Balloon Counterpulsation

ICU The only thing that reduces afterload and augments diastolic perfusion pressure Beneficial effects occur without increase in oxygen demand No improvement in blood flow distal to critical coronary stenosis No improvement in survival when used alone May be essential support mechanism as a bridge to definitive therapy Intra-aortic Balloon Counterpulsation

ICU Overall 30-Day Survival in the Study Hochman JS, et al. N Engl J Med. 1999;341: Proportion Alive 0 Days after Randomization Revascularization (n =152) Medical therapy (n =150) Survival = 53% Survival = 44% p = 0.11 Early Revascularization in Acute Myocardial Infarction Complicated by Cardiogenic Shock

ICU % P = 0.11P = 0.027P < days 6 months 1 year Revasc Med Rx SHOCK Trial Mortality

ICU Patients with ST segment elevation MI who have cardiogenic shock and are less than 75 years of age should be brought immediately or secondarily transferred to facilities capable of cardiac catheterization and rapid revascularization (PCI or CABG) if it can be performed within 18 hours of onset of shock. (Level of Evidence: A) ACC/AHA Class I Indication

ICU Average LVEF is only moderately severely depressed (30%), with a wide range of EFs and LV sizes noted. Systemic vascular resistance (SVR) on vasopressors is not elevated on average (~ 1350), with a very wide range of SVRs measured. A clinically evident systemic inflammatory response syndrome is often present in patients with CS. Most survivors (85%) have NYHA functional Class I-II CHF status. Hochman JS. Circ.2003;107: Pathophysiology of Cardiogenic Shock Observations from the SHOCK Trial and Registry that Challenge the Classic Paradigm

ICU Cardiogenic shock IS NOT simply the result of severe depression of LV function due to extensive myocardial ischemia/injury. Depressed Myocardial Contractility combined with Inadequate Systemic Vasoconstriction resulting from a systemic inflammatory response to extensive myocardial ischemia/injury results in cardiogenic shock. Pathophysiology of Cardiogenic Shock

Thus, excess nitric oxide and peroxy nitrites may be a major contributor to cardiogenic shock complicating MI. The Overproduction of Nitric Oxide May Cause Both Myocardial Depression and Inappropriate Vasodilatation.

ICU Acute coronary syndrome: Constellation of clinical symptoms compatible with acute myocardial ischemia ST-segment elevation MI (STEMI) Non-ST-segment elevation MI (NSTEMI) Unstable angina Unstable angina: Angina at rest (usually > 20 minutes) New-onset of class III or IV angina Increasing angina (from class I or II to III or IV) Acute Coronary Syndromes: Definitions

ICU Plaque rupture Platelet adhesion Platelet activation Partially occlusive arterial thrombosis & unstable angina Microembolization & non-ST- segment elevation MI Totally occlusive arterial thrombosis & ST-segment elevation MI White HD. Am J Cardiol 1997;80 (4A):2B-10B. Pathogenesis of Acute Coronary Syndromes

ICU UA/NSTEMI: Partially-occlusive thrombus (primarily platelets) Intra-plaque thrombus (platelet-dominated) Plaque core STEMI: Occlusive thrombus (platelets, red blood cells, and fibrin) Intra-plaque thrombus (platelet-dominated) Plaque core SUDDEN DEATH UA = Unstable Angina NSTEMI = Non-ST-segment Elevation Myocardial Infarction STEMI = ST-segment Elevation Myocardial Infarction Structure of Thrombus Following Plaque Disruption White HD. Am J Cardiol 1997;80 (4A):2B-10B.

ICU Therapeutic goal: rapidly break apart fibrin mesh to quickly restore blood flow ST-segment elevation MINon-ST Elevation ACS*Non-ST Elevation MI + T roponin or + CK-MB Consider fibrinolytic therapy, if indicated, or primary percutaneous coronary intervention (PCI) Therapeutic goal: prevent progression to complete occlusion of coronary artery and resultant MI or death Consider GP IIb-IIIa inhibitor + aspirin + heparin before early diagnostic catheterization &/or Braunwald E, et al Diagnostic Algorithm for Acute Coronary Syndrome Management

ICU Probability of Death or MI Placebo Aspirin 75 mg Risk ratio % CL Risk of MI and Death During Treatment with Low-Dose Aspirin and IV Heparin in Men with Unstable CAD Wallentin LC, et al. J Am Coll Cardiol, 1991;18: Months

ICU Trial: FRIC (Dalteparin; n = 1,482) FRAXIS (nadroparin; n = 2,357) ESSENCE (enoxaparin; n = 3,171) TIMI 11B (enoxaparin; n = 3,910) Trial: FRIC (Dalteparin; n = 1,482) FRAXIS (nadroparin; n = 2,357) ESSENCE (enoxaparin; n = 3,171) TIMI 11B (enoxaparin; n = 3,910) (p= 0.032) (p= 0.029) LMWHBetterLMWHBetter UFHBetterUFHBetter 6 14 Day: Braunwald. Circulation. 2002;106: Low Molecular Weight Heparin (LMWH) vs. Unfractionated Haparin (UFH) in Non-ST elevation ACS: Effect on Death, MI, Recurrent Ischemia

ICU Death, MI, or Stroke Clopidogrel + ASA 369 Placebo + ASA Months of Follow-Up 11.4% 9.3% 20% RRR P < N = 12, % % N Engl J Med. 2001;345: Effects of Clopidogrel in Addition to Aspirin in Patients with ACS without ST-Segment Elevation

ICU Primary Endpoint % Placebo GP IIb/IIIa PURSUIT 30 days PRISM 48 hrs PRISM PLUS 7 days P = 0.04 P = 0.01 P = PARAGON A 30 days P = 0.48 PARAGON B 30 days P = 0.33 Platelet Glycoprotein IIb/IIIa Inhibition for Non-ST elevation ACS Primary Endpoint Results from the 5 Major Trials

ICU % 8% 6% 4% 2% T-wave inversion 3.4% ST-segment elevation 6.8% ST-segment depression 8.9% Days from randomization % Cumulative Mortality at 6 Months Savonitto S. J Am Med Assoc. 1999; 281: ST-segment Depression Predicts Higher Risk of Mortality in ACS

ICU

Cannon. J Invas Cardiol. 2003;15:22B. Troponin and ST-Segment Shift Predict Benefit of Invasive Treatment Strategy

ICU Class I An early invasive strategy in patients with a high-risk indicator: 1.Recurrent angina/ischemia despite intensive anti-ischemic rx 2.Elevated troponin-T or troponin-I 3.New or presumably new ST-segment depression 4.Recurrent angina/ischemia with CHF sx, S3, pulmonary edema, worsening rales, or new or worsening MR 5.High-risk findings on noninvasive stress testing 6.Depressed LV systolic function (EF <40%) 7.Hemodynamic instability 8.Sustained ventricular tachycardia 9.PCI within 6 months 10.Prior CABG Either early invasive or early conservative strategy if not high risk ACC/AHA Guideline Update for the Management of Patients with Unstable Angina and Non-ST-Segment Elevation MI

ICU Start immediate  Aspirin  Heparin or low-molecular-weight heparin  GP IIb-IIIa inhibitor Adapted from Braunwald E, et al At presentation ST-segment depression &/or elevated cardiac troponin Need to immediately arrest thrombus progression Need to eliminate occlusive ruptured plaque Send for catheterization & revascularization within hours Cautionary information  No clopidogrel within 5-7 days prior to CABG surgery  No enoxaparin within 24 hours prior to CABG surgery  No abciximab, if PCI is not planned 2002 ACC/AHA Guidelines for the Management of High-risk NSTE ACS

ICU Recurrent Symptoms/ischemia Heart failure Serious arrhythmia Patient stabilizes EF .40 Stress Test Not low risk Follow on Medical Rx Evaluate LV function EF <.40 Low risk Early medical management Immediate angiography Braunwald E, et al Ongoing Evaluation in an Early Conservative Strategy

ICU ST , positive cardiac markers, deep T-wave inversion, transient ST , or recurrent ischemia Aspirin, Beta Blockers, Nitrates, Antithrombin regimen, GP IIb-IIIa inhibitor, Monitoring (rhythm and ischemia) Early invasive strategy Early conservative strategy Immediate angiography hour angiography Recurrent symptoms/ischemia Heart failure Serious arrhythmia Patient stabilizes Evaluate LV Function EF <.40 EF >.40 Stress Test Not low riskLow risk Follow on Medical Rx Braunwald. Circulation. 2002;106: ACC/AHA Guidelines for Unstable Angina and Non-ST-Segment Elevation MI Acute Ischemia Pathway

ICU UA/NSTEMI High Risk * ASA, Heparin/Enox.,   block., Nitrates, Clopidogrel  RISK STRATIFY Low Risk Braunwald E, et al. Circ. 2002;106:1893. * Recurrent ischemia; Trop; ST; LV failure/dysf.; hemodynamic instability; VT; prior CABG  Enoxeparin. Preferred to UFH (IIa)  If coronary arteriography >24 hours ACC/AHA REVISED GUIDELINES

ICU Braunwald E, et al. Circ. 2002;106:1893. LMCD, 3VD+LV Dys., LMCD, 3VD+LV Dys., or Diab. Mell. CABG CABG High Risk Cor. Arteriography 1 or 2VD, Suitable for PCI Normal Clopidogrel, IIb/IIIa inhib. Consider Alternative Diagnosis Discharge on ASA, Clopidogrel, Statin, ACEI PCI ACC/AHA REVISED GUIDELINES

ICU I I IIa IIb III Braunwald. Circulation 2002;106: Discharge/Post-discharge Medications ASA, if not contraindicated Clopidogrel, when ASA contraindicated Aspirin + Clopidogrel, for up to 9 months  -blocker, if not contraindicated Lipid  agents (statins) + diet ACE Inhibitor: CHF, EF < 40%, DM, or HTN

ICU Tachydysrhythmias Regular Narrow complex Sinus Tachycardia Atrial Tachycardia Atrial Flutter AVNRT/AVRT Wide complex Ventricular tachycardia Pacer-mediated tachycardia SVT with pre-existing BBB SVT with rate-dependent BBB Irregular Narrow complex MAT Atrial Fibrillation Atrial Flutter with variable block Wide complex Torsade des Pointes Ventricular fibrillation

ICU Afib

Incidence of Afib

ICU Risk Factors for Afib MICU Electrolyte abnormalities High cardiac filling pressures Hypoxia Comorbid heart disease Sepsis MOF SICU Post-op hypotension Post-op sepsis Post-op pulmonary edema PA catheters Blunt thoracic trauma

ICU Morbidity of Afib in the ICU

ICU Management Stable vs. Unstable Unstable Electrical, synchronized cardioversion 100J Stable Rate vs rhythm control Rate control Digoxin B blocker Verapamil Rhythm control Diltiazam Amiodarone magnesium

ICU Rate vs Rhythm control In non ICU patients rate vs rhythm control seems to make no difference In the ICU patients may not tolerate lose of the atrial kick (up to 25% reduction in CO) Most patients with new onset afib in the ICU will require a trial of chemical cardioversion

ICU Chemical Cardioversion Amiodarone 300 mg bolus, then 1 g over 24 hr infusion 75% will convert in 24 hrs 5% incidence of hypotension Diltiazam 25 mg bolus, 20 mg/h infusion 70% conversion 30% hypotension

ICU Magnesium 86% conversion rate No side effects 37 mg/kg bolus followed by 25 mg/kg/hr for 24 hrs (approx 3 gm bolus then 2gm/hr for an 80kg patient) Benign neglect 56% cardioversion Chemical Cardioversion

ICU Aflutter

ICU SVT or Flutter? flutter

ICU

Vtach

ICU Vfib

ICU Vtach

ICU Hyperkalemia

ICU Hyperkalemia

ICU Summary Review ACLS guidelines