Cardiogenic Shock - FINAL

Cardiogenic Shock - FINAL - SCCM Online Critical Care...

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Unformatted text preview: SCCM Online Critical Care Course: SCCM Cardiogenic Shock, Acute Coronary Syndrome and Congestive Heart Failure Heart Fredric Ginsberg, MD Fredric Assistant Professor of Medicine, Robert Wood Johnson Medical School University of Medicine and Dentistry of New Jersey Joseph E. Parrillo, MD Professor of Medicine, Robert Wood Johnson Medical School University of Medicine and Dentistry of New Jersey Head, Division of Cardiovascular Disease and Critical Care Medicine Director, Cooper Heart Institute Director, Cardiovascular and Critical Care Services Cooper University Hospital Camden, New Jersey Cardiogenic Shock 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 < 90 mm Hg, cardiac index < 2.2 L/min/m2, PCWP > 15 mm Hg Parrillo, J. 2005 Causes of Cardiogenic Shock 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 Cardiogenic Shock Evolution Of The Disease Frequently, shock develops after presentation for myocardial infarction. - - SHOCK Registry • At presentation • Within 24 hours (median delay = 7 hours) GUSTO Trial • At presentation • After admission SHOCK Registry, Circulation. 1995;91:873-81. GUSTO J Amer Coll Cardiol. 1995;26:668-74 . 25% in shock 75% 11% in shock 89% Schematic Diagram of Stunned Myocardium Clamp Wall motion abnormality Wall motion abnormality during occlusion Coronary occlusion Coronary reperfusion Return of function Persistent wall motion abnormality (despite reperfusion and viable myocytes) Gradual return of function (hours to days) From Kloner RA. Am J Med. 1986;86:14. Hibernating Myocardium Wall motion abnormality Atherosclerotic narrowing Wall motion abnormality due to chronic ischemia without infarction From Kloner RA. Am J Med. 1986;86:14. Hibernating Myocardium Pre-operative Single vessel disease - Occluded L.A.D. CONTROL LVEDV = 128 EF = 0.37 POST NTG LVEDV = 101 EF = 0.51 End-Diastole End-Systole From Rahimtoola SH, et al. Circ. 1992;65:225. 8 Months Postoperative Patient Coronary Bypass Graft to L.A.D. LVEDV = 104 EF = 0.76 Ischemic Myocardium Cell death Significant residual stenosis Reperfusion Segments with myocardial stunning Segments with both stunning and hibernation Inotropic support No return of function Return of myocardial function Segments with hibernating myocardium Relief of ischemia Initial Approach: Management 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 Intra-aortic Balloon Counterpulsation 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 to allow for definitive therapy Early Revascularization in Acute Myocardial Early Infarction Complicated by Cardiogenic Shock Infarction Overall 30-Day Survival in the Study Proportion Alive 1.0 0.8 Revascularization (n =152) Survival = 53% 0.6 0.4 Medical therapy (n =150) Survival = 44% 0.2 p = 0.11 0.0 0 5 10 15 20 Days after Randomization Hochman JS, et al. N Engl J Med. 1999;341:625-34. 25 30 SHOCK Trial Mortality 100 80 P = 0.11 P = 0.027 P < 0.03 66.4 63.1 % 56 60 46.7 50.3 54.3 40 Revasc Med Rx 20 0 30 days 6 months 1 year ACC/AHA Class I Indication 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) National Registry of MI Early National Revascularization is Underutilized in Cardiogenic Shock Cardiogenic Despite ACC/AHA recommendation to treat patients < 75 years of age aggressively with early mechanical revascularization, in 2001, two years after the guidelines were published, only 41% of patients with cardiogenic shock complicating AMI were treated with primary PTCA and only 3.1% underwent early CABG. These data demonstrate significant underutilization of guideline recommended therapy. Babaev A, et al. Circ. 2002;106(19):1811 (abstract). Pathophysiology of Cardiogenic Shock Observations from the SHOCK Trial and Registry that Challenge the Classic Paradigm Paradigm 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;107:2998-3002. Pathophysiology of Cardiogenic Shock 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 . The Overproduction of Nitric Oxide The May Cause Both Myocardial Depression and Inappropriate Vasodilatation. Vasodilatation. Thus, excess nitric oxide and peroxy nitrites may be a major contributor to cardiogenic shock complicating MI. cardiogenic LINCS: Conclusions Nitric oxide synthase inhibition can raise blood pressure in patients with persistent cardiogenic shock after percutaneous intervention. The mechanism of this effect is unknown, but may involve both an effect on coronary and other organ perfusion pressure, and potentially an improvement in cardiac function. Outcome data are not yet available. Cotter. Eur Heart J. 2003;24:1287-1295. Acute Coronary Syndromes: Definitions 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) Braunwald. Circulation 2002; 106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf Pathogenesis of Acute Coronary Syndromes Plaque rupture Platelet adhesion Platelet activation Partially occlusive arterial thrombosis & unstable angina Microembolization & non-STsegment elevation MI Totally occlusive arterial thrombosis & ST-segment elevation MI White HD. Am J Cardiol 1997;80 (4A):2B-10B. Structure of Thrombus Following Plaque Structure Disruption Disruption UA/NSTEMI: Partially-occlusive thrombus (primarily platelets) Intra-plaque thrombus (platelet-dominated) Plaque core UA = Unstable Angina NSTEMI = Non-ST-segment Elevation Myocardial Infarction STEMI = ST-segment Elevation Myocardial Infarction STEMI: Occlusive thrombus (platelets, red blood cells, and fibrin) Intra-plaque thrombus (platelet-dominated) SUDDEN DEATH White HD. Am J Cardiol 1997;80 (4A):2B-10B. Plaque core Diagnostic Algorithm for Acute Coronary Diagnostic Syndrome Management Syndrome &/or ST-segment elevation MI Therapeutic goal: rapidly break apart fibrin mesh to quickly restore blood flow Consider fibrinolytic therapy, if indicated, or primary percutaneous coronary intervention (PCI) Non-ST Elevation ACS* + Troponin or + CK-MB Non-ST Elevation MI 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 Braunwald E, et al. 2002. http://www.acc.org/clinical/guidelines/unstable/unstable.pdf . Risk of MI and Death During Treatment with Risk Low-Dose Aspirin and IV Heparin in Men with Unstable CAD Unstable 0.25 Placebo Probability of Death or MI 0.20 0.15 0.10 Aspirin 75 mg 0.05 Risk ratio 0.52 95% CL 0.37 - 0.72 0.00 0 3 6 Months Wallentin LC, et al. J Am Coll Cardiol, 1991;18:1587-93. 9 12 Low Molecular Weight Heparin (LMWH) vs. Low Unfractionated Haparin (UFH) in Non-ST elevation ACS: Effect on Death, MI, Recurrent Ischemia ACS: Day: Trial: s FRIC 6 s (Dalteparin; n = 1,482) 14 FRAXIS (nadroparin; n = 2,357) s (p= 0.032) 14 s (p= 0.029) 14 ESSENCE (enoxaparin; n = 3,171) TIMI 11B (enoxaparin; n = 3,910) .75 1.0 LMWH Better 1.5 UFH Better Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf Effects of Clopidogrel in Addition to Aspirin in Effects Patients with ACS without ST-Segment Elevation Patients % 14 12 Death, MI, or Stroke 11.4% Placebo + ASA 9.3% 10 8 Clopidogrel + ASA 6 4 20% RRR P < 0.001 N = 12,562 2 0 0 3 6 9 Months of Follow-Up N Engl J Med. 2001;345:494-502. 12 Platelet Glycoprotein IIb/IIIa Inhibition for Non-ST Platelet elevation ACS Primary Endpoint Results from the 5 Major Trials Major Primary Endpoint % 20 15 17.9 Placebo GP IIb/IIIa 15.7 14.2 12.9 10 11.7 10.3 12.8 11.8 5.6 5 0 3.8 P = 0.04 P = 0.04 P = 0.01 P= PURSUIT 30 days PRISM 48 hrs P = 0.004 P = 0.48 P = 0.33 PRISM PLUS 7 days PARAGON A 30 days PARAGON B 30 days Hospital Care Anti-Thrombotic Therapy I IIa IIb III Immediate aspirin Clopidogrel, if aspirin contraindicated Aspirin + clopidogrel for up to one month, if medical therapy or PCI is planned Heparin (IV unfractionated, LMW) with antiplatelet agents listed above Enoxaparin preferred over UFH unless CABG is planned within 24 hours Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf Hospital Care Clopidogrel Therapy I IIa IIb III Aspirin + clopidogrel, for up to 1 month * Aspirin + clopidogrel, for up to 9 months * Withhold clopidogrel for 5 - 7 days for CABG Guidelines do not specify initial approach to using Guidelines clopidogrel when coronary anatomy is unknown clopidogrel * For patients managed with an early conservative strategy, and those who are planned to undergo early PCI Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.p df Hospital Care Platelet GP IIb/IIIa Inhibitors (1) I IIa IIb III Any GP IIb/IIIa inhibitor + ASA/Heparin for all patients, if cath/PCI planned Eptifibatide or tirofiban + ASA/Heparin for highrisk * patients in whom early cath/PCI is not planned Any GP IIb/IIIa inhibitor for patients already on ASA + Heparin + clopidogrel, if cath/PCI is planned * High-risk: Age >75; prolonged, ongoing CP; hemodynamic instability; rest CP w/ ST ∆ ; VT; positive cardiac markers Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf Hospital Care Platelet GP IIb/IIIa Inhibitors (2) I IIa IIb III Eptifibatide or tirofiban + ASA/Heparin for patients without continuing ischemia in whom PCI is not planned Abciximab for patients in whom PCI is not planned Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf Hospital Care Anti-ischemic Therapy (1) I IIa IIb III β-blocker (IV→oral) if not contraindicated Non-dihydropyridine Ca2+ antagonist if βblocker contraindicated and no LV dysfunction, for recurrent ischemia ACE inhibitor if ↑ BP persists with NTG+ βblocker, for pts with CHF or diabetes Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf Hospital Care Anti-ischemic Therapy (2) I IIa IIb III ACE inhibitor for all ACS pts Extended-release Ca2+ blocker instead of βblocker Immediate-release Ca2+ blocker with β-blocker Long-acting Ca2+ blocker for recurrent ischemia, if no contraindications and NTG + βblocker used fully Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf ST-segment Depression Predicts Higher Risk of Mortality in ACS % Cumulative Mortality at 6 Months 10% ST-segment depression 8.9% 8% ST-segment elevation 6.8% 6% 4% T-wave inversion 3.4% 2% 30 60 90 120 150 Days from randomization Savonitto S. J Am Med Assoc. 1999; 281: 707-711. 180 TIMI Risk Score for UA/NSTEMI 7 Independent Predictors of Higher Risk 1. Age > 65 years 2. > 3 CAD risk factors (elevated cholesterol, + family Hx, hypertension, diabetes, cigarette smoking) 3. Prior CAD (coronary stenosis > 50%) 4. ASA in last 7 days 5. > 2 anginal events < 24 hours 6. ST deviation 7. Elevated cardiac markers (CK - MB or troponin) Antman, et al. JAMA. 2000;284:835-842. TIMI UA Risk Score: Primary Endpoint at 6 months Death/MI/ACS Rehosp (%) CONS 35 INV OR = 0.75 CI (0.57, 1.00) 30 25 30.6 20.3 20 19.5 16.1 11.8 12.8 Low 15 OR = 0.55 CI (0.33, 0.91) 0-2 10 5 0 Intermed. 3-4 High 5-7 TIMI Risk Score % of Pts: 25% 60% 15% Troponin and ST-Segment Shift Predict Benefit of Invasive Treatment Strategy Cannon. J Invas Cardiol. 2003;15:22B. ACC/AHA Guideline Update for the Management ACC/AHA of Patients with Unstable Angina and Non-STof Segment Elevation MI Class I An early invasive strategy in patients with a high-risk indicator: 1. 2. 3. 4. Recurrent angina/ischemia despite intensive anti-ischemic rx Elevated troponin-T or troponin-I New or presumably new ST-segment depression 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 Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.p df 2002 ACC/AHA Guidelines for the Management of High-risk NSTE ACS At presentation ST-segment depression &/or elevated cardiac troponin Need to immediately arrest thrombus progression Need to eliminate occlusive ruptured plaque Start immediate Aspirin Heparin or low-molecular-weight heparin GP IIb-IIIa inhibitor Send for catheterization & revascularization within 24-48 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 Adapted from Braunwald E, et al. 2002. http://www.acc.org/clinical/guidelines/unstable/unstable.pdf . Ongoing Evaluation in an Early Conservative Strategy Early medical management Recurrent Symptoms/ischemia Heart failure Serious arrhythmia Patient stabilizes Evaluate LV function EF < .40 EF ≥ .40 Stress Test Not low risk Immediate angiography Low risk Follow on Medical Rx Braunwald E, et al. 2002. http://www.acc.org/clinical/guidelines/unstable/unstable.pdf . ACC/AHA Guidelines for Unstable Angina and NonST-Segment Elevation MI Acute Ischemia Pathway 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 Immediate angiography 12-24 hour angiography Early conservative strategy Patient stabilizes Recurrent symptoms/ischemia Heart failure Serious arrhythmia Evaluate LV Function EF < .40 EF > .40 Stress Test Not low risk Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf Low risk Follow on Medical Rx ACC/AHA Guidelines for the Management of ACC/AHA Patients with Unstable Angina and Non-STPatients Segment Elevation MI Class I indications for revascularization with PCI or CABG 1. CABG for ≥ 50% stenosis of the left main coronary artery 2. CABG for 3 vessel CAD 3. CABG for 2 vessel CAD including proximal LAD stenosis & EF < 50% 4. PCI or CABG for 1 or 2 vessel CAD, no proximal LAD, large area of viability, high-risk noninvasive test 5. PCI for patients with multivessel CAD, normal EF, no diabetes 6. IV platelet GP IIb/IIIa inhibitor in ACS patients undergoing PCI Braunwald. Circulation 2002; 106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf ACC/AHA Guidelines for the Management of ACC/AHA Patients with Unstable Angina and Non-STPatients Segment Elevation MI Class IIa indications for revascularization with PCI or CABG 1. Repeat CABG for patients with multiple saphenous vein graft stenoses, especially if LAD graft 2. PCI for focal saphenous vein graft lesions or multiple lesions if poor surgical candidate 3. PCI or CABG for patients with 1 or 2 vessel CAD, not proximal LAD, but moderate area of viability and ischemia 4. PCI or CABG for patients with 1 vessel CAD with proximal LAD 5. CABG with Internal Mammary artery for patients with multivessel CAD and diabetes Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf Recommendations for Revascularization Cardiac Catheterization Coronary Artery Disease NO Left Main Disease YES Discharge from Protocol CABG NO 1 or 2 Vessel Disease 3 Vessel Disease or 2 Vessel Disease with proximal LAD involvement PCI or CABG, if eligible Left Ventricular Dysfunction or Treated Diabetes NO PCI or CABG Smith et al. ACC/AHA PCI Guidelines. J Am Coll Cardiol 2001:2239-lxvi. YES CABG ACC/AHA REVISED GUIDELINES UA/NSTEMI UA/NSTEMI ASA, Heparin/Enox., β block., Nitrates, Clopidogrel ¦ block., RISK STRATIFY High Risk * High Low Risk * Recurrent ischemia; Trop; ST; LV failure/dysf.; hemodynamic instability; VT; prior CABG Enoxeparin. Preferred to UFH (IIa) ¦ If coronary arteriography >24 hours Braunwald E, et al. Circ. 2002;106:1893. ACC/AHA REVISED GUIDELINES High Risk Cor. Arteriography LMCD, 3VD+LV Dys., or Diab. Mell. or CABG CABG 1 or 2VD, Suitable or for PCI for Clopidogrel, Clopidogrel, IIb/IIIa inhib. IIb/IIIa PCI Discharge on ASA, Clopidogrel, Statin, ACEI Braunwald E, et al. Circ. 2002;106:1893. Normal Consider Alternative Consider Diagnosis Diagnosis Discharge/Post-discharge Medications I IIa IIb III ASA, if not contraindicated Clopidogrel, when ASA contraindicated Aspirin + Clopidogrel, for up to 9 months β-blocker, if not contraindicated Lipid ↓ agents (statins) + diet ACE Inhibitor: CHF, EF < 40%, DM, or HTN Braunwald. Circulation 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf All-Cause Death or Major Cardiovascular All-Cause Events in All Randomized Subjects Events 30 Pravastatin 40 mg (26.3%) % with Event 25 20 Atorvastatin 80 mg (22.4%) 15 10 16% RR 5 (P = 0.005) 0 0 3 6 9 12 15 18 21 Months of follow up Cannon CP, et al. N Engl J Med. 2004;350:1495-1504. 24 27 30 Reductions in Major Cardiac End Points 2-Year Event Rates RR Atorva 80 Prava 40 All-cause Mortality CHD-related Death 28% 2.2% 3.2% 30% 1.1% 1.4% 13% 6.6% 7.4% 18% 8.3% 10.0% UA Requiring Hospitalization 14% 16.3% 18.8% Death/MI/Urgent Revascularization 29% 3.8% 5.1% 14% 1.5 19.7% 22.3% MI Death or MI Revasc >30 d 0.5 0.75 1.0 Atorvastatin 80 mg Better 1.25 Pravastatin 40 mg Better Cannon CP, et al. N Engl J Med. 2004;350:1495-1504. Risk Factor Modification I IIa IIb III Smoking Cessation Counseling Dietary Counseling and Modification Cardiac Rehabilitation Referral HTN Control (BP <130/85 mm Hg) Tight Glycemic Control in Diabetics Braunwald. Circulation. 2002;106:1893-2000. www.acc.org/clinical/guidelines/unstable/unstable.pdf Heart Failure Due to LV Systolic Dysfunction Approximately 5 million Americans have heart failure (male to female ratio 1:1) 550,000 new cases annually Hospital discharges 1,000,000 annually 80% of men and 70% of women under the age of 65 with HF will die within eight years Numbers based on 2000 data. American Heart Association. 2003 Heart and Stroke Statistical Update. Dallas, Tex: AHA; 2002. Neurohormonal Activation in Heart Failure Myocardial injury to the heart (CAD, HTN, CMP, valvular disease) Initial fall in LV performance, ↑ wall stress Activation of RAS and SNS Remodeling and progressive worsening of LV function Fibrosis, apoptosis, hypertrophy, cellular/ molecular alterations, myotoxicity Morbidity and mortality Arrhythmias Pump failure RAS, renin-angiotensin system; SNS, sympathetic nervous system. Peripheral vasoconstriction Hemodynamic alterations Heart failure symptoms Fatigue Activity altered Chest congestion Edema Shortness of breath LV Remodeling Post Anteroseptal MI 1 week 3 months EDV 137 mL ESV 80 mL EF 41% EDV 189 mL ESV 146 mL EF 23% Apical 4 Chamber View Drugs for Heart Failure “Enlightened Polypharmacy” 1. ACE-inhibitors 2. Beta-blockers 3. Angiotensin receptor blockers 4. Aldosterone antagonists 5. Loop diuretics 6. Nitrates with hydralazine 7. Digoxin 8. Nesiritide, inotropic agents ACE - Inhibitation and CHF Trials ACE SAVE - captopril, 1992. Post-MI (not CHF) with EF < 40%, f/u 42 mos, 2,231 pts. Mortality reduced from 25% to 20% N Engl J Med. 1992;327:669. SOLVD - enalapril, 1991. CHF pts, class II-III, EF < 35%, f/u 41 mos, 2,569 pts. Mortality reduced from 39% to 35% N Engl J Med. 1991;325:293. SOLVD - enalapril, 1992. Asymptomatic LV dysfunction, EF < 35%, f/u 37 mos, 4,228 pts. Non-significant reduction in mortality, significant reduction in CHF and hospitalization. N Engl J Med. 1992;327:685. ACE - I and CHF: Meta-analysis Captopril, enalapril, ramipril, quinapril, lisinopril 32 trials, 7,105 patients, FC II - III 2 mortality trials Combined - total mortality reduced 21.9% to 15.8%, and total mortality plus CHF hosp reduced 32.6% to 22.4%. Summary: 1. Improvement in risk of death or MI or CHF hospitalization 2. Class effect JAMA. 1995;273:1450. Beta Blockade: Rationale Catecholamine levels are increased in CHF Higher levels correlate with worse disease severity Catecholamines contribute to myocyte hypertrophy and necrosis (apoptosis) More ischemia, arrhythmia, vasoconstriction, and LV dilatation Metoprolol MERIT - HF: Metoprolol tartrate Preceded by two previous trials in CHF (MDC, RESOLVD) 3,991 pts, mean f/u 12mos, class II - III Mean EF 28% Results - stopped early as total mortality + all cause hospitalization was reduced 38% to 32% (p = .00012) and total mortality reduced 10.8% to 7.2 % (p < .0001) JAMA .2000;283:1295. CAPRICORN: Carvedilol in Post-MI patients with Reduced EF: All-cause Mortality Proportion Event-free 1.00 Carvedilol n = 975 0.90 Risk reduction ↓ 23% 0.80 Placebo n = 984 0.70 P = .031 0.60 Mortality rates: Placebo 15%; Carvedilol 12% 0 0 0.5 1 1.5 Years The CAPRICORN Investigators. Lancet. 2001;357:1385–1390. 2 2.5 COPERNICUS: Carvedilol in Class III - IV Heart Failure Inclusion - EF < 25%, class III - IV, euvolemic 2,289 pts, mean f/u 10.4 mos, stopped early Mortality 18.5% (placebo) vs. 11.4% with carvedilol 35% reduction (p < .00013) No difference in withdrawal rates Mortality curves diverge w/in three weeks, thus beneficial effects are not delayed and can occur at low dose N Engl J Med. 2001;344:1651. COPERNICUS All-cause Mortality 100 Carvedilol n = 1156 % Survival 90 Risk reduction ↓ 35% 80 (19%, 48%) P = .0014 Placebo n = 1133 70 60 Mortality rates: Placebo 19.7%; Carvedilol 12.8% 0 0 3 6 9 12 15 18 21 Months Packer M et al. N Engl J Med. 2001;344:1651–1658. Coreg (carvedilol) Prescribing Information. GlaxoSmithKline, Research Triangle Park, NC. Mar 2003. COMET First head-to-head mortality study comparing two betablocking agents in CHF - carvedilol vs. short-acting metoprolol titrate 3,029 pts, class II - III, EF < 35%, 80% male, 99% Caucasian Carvedilol compared to metoprolol reduced annual mortality from 10.0% to 8.3% and prolonged median survival by 1.4 years Lancet. 2003;362:7. Beta Blockers for CHF: Summary Ischemic or non-ischemic CMP All symptomatic CHF patients Class II - IV Hemodynamically stable and euvolemic Even in “compensated” patients as there is a high likelihood of symptom progression in 12 months Beneficial effects are in addition to effects of other therapies Angiotensin Receptor Blockers in CHF Trial Trial RESOLVD 1999 ELITE II 2000 ValHeft 2001 CHARM 2003 Drugs Baseline EF Candesartan vs Avg 27% enalapril Losartan vs. captopril Valsartan Candesartan Mortality vs. Mortality ACE-I Notes Notes 6.1 vs. 3.7 (p = NS) < 40% 17.7 vs. 15.9 (p = NS) < 40% 19.9 vs. 19.4 (p = NS) 33% decreased mortal if not on ACE-I Small decrease in mortality when added to ACE-I No increased mortality w/ beta-blocker Angiotensin Receptor Blockers in CHF: Summary ARBs should be used in patients intolerant of ACE inhibitors. ARBs can be added on in patients receiving ACEinhibitors and beta blockers with a small added benefit. Increased risk of hypotension, hyperkalemia, and renal insufficiency when added on to ACE-I and beta-blocker therapy. Aldosterone Blockers in CHF Study RALES 1999 EPHESUS 2003 Drug Patients spironolactone Class III and IV CHF eplerenone Post-MI w/ EF < 40% or diabetes Added therapy Mortality vs. placebo Hyperkalemia ACE-I, no beta-blocker Reduced from 46.3% to 35% (p < .001) 2% ACE-I and beta-blocker Reduced from 14.6% to 8.5% (p = .008) 5.5% Aldosterone Blockers: Summary Aldosterone blockers should be used in patients with chronic heart failure with low EF (spironolactone) and in patients post-MI and heart failure with EF < 40% or diabetes mellitus (eplerenone) Contraindications - renal insufficiency (creat > 2.5 mg%) or hyperkalemia (over 5.0) Patients on aldosterone blockers must have renal function and electrolytes carefully and frequently monitored Digoxin and CHF: “Dig Trial” 1997, CHF with EF < 45%, NSR, class I - III 6,800 pts, 94% ACE - I, little beta-blocker, f/u 37 mos Total and CV mortality - no significant differences Decreased need for hospitalization for CHF, 2% hosp for dig toxicity Summary - use digoxin for symptomatic benefit, not mortality benefit N Engl J Med. 1997; 336:525. Vasodilators and CHF V-HeFT I - 1986: preceded use of ACE-I and beta blockers for CHF Placebo vs. prazosin vs. combined isosorbide dinitrate (avg. 136 mg) with hydralazine (avg. 270 mg) 642 pts, EF < 45% All cause mortality improvement only with ISDN + Hydralazine (p = .04) Recommend - use for pts unable to take ACE-I or ARBs. N Engl J Med. 1986;314:1547. Vasodilator Therapy: A-Heft Therapy with ISDN and hydralazine added on to standard CHF therapy 1,050 black patients; class III - IV heart failure, EF < 45% 76% on ACE-I/ARB, 74% on beta-blocker Mortality reduced from 10.2% to 6.2% at 10-month followup (p = 0.02) N Engl J Med. 2004;351:2049. A-Heft: Kaplan-Meier Estimates of Overall Survival Survival NESERITIDE (BNP) Inpatient intravenous infusion Arterial and venodilator Natriuresis and diuresis No tolerance or proarrhythmia Associated with hypotension Rapid fall in PCWP No adverse effect on mortality Intravenous Inotropic Agents ACC/AHA Guidelines (Circ. 2001;104:2996.) 1. For symptomatic systolic dysfunction (Stage C): Class III (i.e., NOT indicated) - Long term intermittent use of an infusion of a positive inotropic drug (level of evidence C) 2. For refractory end-stage CHF (Stage D): Class IIb - Continuous intravenous infusion of a positive inotropic agent for palliation of symptoms (level of evidence C) Class III (NOT indicated) - Routine intermittent infusions (level of evidence B) Search for Aggravating Medical Conditions Ischemia, arrhythmias, conduction abnormalities Worsening valve regurgitation Hypertension, bilateral renal artery stenosis Anemia, thyroid disease, infection, renal failure, obstructive sleep apnea, medication noncompliance Patients Refractory to Pharmacologic Therapy Resynchronization therapy to improve heart failure (biventricular pacemaker) Revascularization if documented ischemia ICD implant to reduce risk of sudden arrhythmic death Surgery - CABG, valve repair, transplant Selected References 1. Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. N Eng J Med. 1999;341:625-634. 2. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndrome without ST segment elevation. N Eng J Med. 2001;345:494-502. 3. Braunwald E, Antman EM, Beasley JW. ACC/AHA guideline update for the management of patients with unstable angina and non-ST segment elevation myocardial infarction-2002: summary article. A report of the ACC/AHA Task Force on Practice Guidelines. Circulation. 2002;106:1893-1900. Selected References 4. McMurray JJ, Ostergren J, Swedberg K, et al, CHARM Investigators and Committees. Effects of candesartan in patients with chronic heart failure and reduced left ventricular systolic function taking angiotensin converting enzyme inhibitors: the CHARM-added trial. Lancet. 2003;362:767-771. 5. Packer M, Coats AJ, Fowler MB, et al, Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Eng J Med. 2001;344:1651-1658. ...
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Cardiogenic Shock - FINAL - SCCM Online Critical Care...

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