ST Elevation Myocardial Infarction (STEMI)William J. Mosley II, MDCardiovascular Disease Fellow(Updated from John Rapp with 2007 guidelines)

ACS-STEMINo ST elevationST elevationUnstableanginaNSTEMISTEMIStableangina

Outline

Class/EvidenceGeneral TherapyBeta-blockersReperfusionFacilitated PCIComplications

Applying Classification of Recommendations and Level of Evidence

Class I Benefit >>> Risk

Procedure/ Treatment SHOULD be performed/ administeredClass IIa Benefit >> Risk Additional studies with focused objectives needed

IT IS REASONABLE to perform procedure/administer treatmentClass IIb Benefit Risk Additional studies with broad objectives needed; Additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED Class III Risk Benefit No additional studies needed

Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL

Hospitalizations in the U.S. Due to Acute Coronary Syndromes (ACS)Acute Coronary Syndromes*1.57 Million Hospital Admissions - ACSUA/NSTEMISTEMI1.24 million Admissions per year.33 million Admissions per yearHeart Disease and Stroke Statistics 2007 Update. Circulation 2007; 115:69-171. *Primary and secondary diagnoses. About 0.57 million NSTEMI and 0.67 million UA.

General Therapy

General TherapyMONAMorphine (q 5-15 min CLASS I)Oxygen (pulse ox>90% CLASS I)Nitroglycerin (0.4 mg SL NTG x 3 for ischemic pain CLASS I)Aspirin

AspirinAspirin should be chewed by patients who have not taken aspirin before presentation with STEMI. The initial dose should be 162 mg (Level of Evidence: A) to 325 mg (Level of Evidence: C). Class I In a dose of 162 mg or more, aspirin produces a rapid clinical antithrombotic effect caused by immediate and near-total inhibition of thromboxane A2 production. (ISIS-2-->ASA led to 23% reduction in mortality): 1. Antithrombotic Trialists Collaboration. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002; 324: 7186.

2. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised trial of intravenous streptokinase, oral aspirin, both, or neither among 17187 cases of suspected acute myocardial infarction. Lancet 1988;ii:349-60.

Beta-Blockers

INCLUSION:>45,000 patients with suspected acute MI (ST change or LBBB) within 24 h of symptom onset

TREATMENT:Metoprolol 15 mg iv over 15 mins, then 200 mg oral daily vs matching placeboEXCLUSION:Shock, systolic BP

Effects of MetoprololLancet. 2005;366:1622. Death 13% P=0.0006 ReMI 22% P=0.0002 VF 15% P=0.002 Totality of Evidence (N = 52,411)COMMIT (N = 45,852)30% relative increase in *cardiogenic shock*Risk factors for cardiogenic shock :heart failure, age > 70 , systolic blood pressure < 120, sinus tachycardia > 110 or heart rate < 60, increased time since onset of STEMI symptoms

Recommendations - Class Ia (B)ORAL beta-blocker therapy SHOULD BE initiated in the first 24 hours for patients who DO NOT have any of the following: signs of heart failure,evidence of a low output state, increased risk for cardiogenic shock, orrelative contraindications to beta blockade1AVB > 0.24 sec, 2nd- or 3rd-degree heart blockreactive airway disease ** There is no study evaluating oral beta blockers alone

Beta-Blockers*Risk factors for cardiogenic shock :heart failure, age > 70 , systolic blood pressure < 120, sinus tachycardia > 110 or heart rate < 60, increased time since onset of STEMI symptoms

Recommendations - Class IIa (B)It is reasonable to administer an IV BETA BLOCKER at the time of presentation to STEMI patients who are HYPERTENSIVE and who do not have any of the following: signs of heart failure,evidence of a low output state, increased risk for cardiogenic shock, orrelative contraindications to beta blockade1AVB > 0.24 sec, 2nd- or 3rd-degree heart blockreactive airway disease

Beta-Blockers*Risk factors for cardiogenic shock :heart failure, age > 70 , systolic blood pressure < 120, sinus tachycardia > 110 or heart rate < 60, increased time since onset of STEMI symptoms

Recommendations - Class III (A)IV beta blockers SHOULD NOT be administered to STEMI patients who have any of the following: signs of heart failureevidence of a low output stateincreased risk* for cardiogenic shockrelative contraindications to beta blockade1AVB > 0.24 sec, 2nd- or 3rd-degree heart blockreactive airway disease

Beta-Blockers*Risk factors for cardiogenic shock :heart failure, age > 70 , systolic blood pressure < 120, sinus tachycardia > 110 or heart rate < 60, increased time since onset of STEMI symptoms

Reperfusion

Time is Muscle

Reperfusion STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within 90 min of first medical contact as a systems goal. Class Ia STEMI patients presenting to a hospital without PCI capability, and who cannot be transferred to a PCI center and undergo PCI within 90 min of first medical contact, should be treated with fibrinolytic therapy within 30 min of hospital presentation as a systems goal, unless fibrinolytic therapy is contraindicated. Class Ib

PCI vs Fibrinolysis for STEMI:Short-Term Clinical OutcomesPCI Frequency (%)P=.0002P=.0003P

Brief Review of Thrombolytic TrialsGISSI-1: Streptokinase 18% reduction in mortality at 21 dGUSTO-1: tPA. 15% reduction in 30-day mortality compared to StreptokinaseGUSTO-3: Reteplase had no benefit over tPA but is easier to use (double bolus)ASSENT: TNKase is similar to tPA but with less non-cerebral bleeding and better mortality with symptoms>4 hrs: Single bolus, fibrin selective, resistance to PAI-1*Overall risk of ICH is 0.7%; Strokes occurred in 1.4%

AnticoagulantsPatients undergoing reperfusion with fibrinolytics should receive anticoagulant therapy for a minimum of 48 hours (unfractionated heparin) or up to 8 days

Anticoagulant regimens with established efficacy include: UFH (LOE: C) Enoxaparin (LOE:A) Fondaparinux (LOE:B)

Summary of Observations from Trials of Anticoagulants for STEMIAntman EM, et al. J Am Coll Cardiol 2008. Published ahead of print on December 10, 2007. Available at http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001. Table 10.

AnticoagulantEfficacy (through 30 d)SafetyUse During PCIReviparinFibrinolysis: probably superiorto placebo.*

No reperfusion: probably superior to placebo.* risk of serious bleedsNo data on reviparin alone during PCI. Additional anticoagulant with anti-IIa activity, such as UFH or bivalirudin, recommended.FondaparinuxFibrinolysis: appears superior to control rx (placebo/UFH). Relative benefit vs placebo and UFH separately cannot be reliably determined from available data.*

Primary PCI: when used alone, no advantage over UFH and trend toward worse outcome.

No reperfusion: appears superior to control therapy (placebo/UFH). Relative benefit versus placebo and UFH separately cannot be reliably determined from available data.*Trend toward risk of serious bleeds risk of catheter thrombosis when fondaparinux used alone. Additional anticoagulant with anti-IIa activity, such as UFH or bivalirudin, recommended.

EnoxaparinFibrinolysis: appears superior to UFH risk of serious bleeds

Enoxaparin can be used to support PCI after fibrinolysis. No additional anticoagulant needed.

Facilitated PCI

Meta-analysis: Facilitated PCI vs Primary PCI

1.03(0.15-7.13)3.07(0.18-52.0)1.43(1.01-2.02) 1.03(0.49-2.17)MortalityReinfarctionMajor BleedingFac. PCI BetterPPCI BetterFac. PCI BetterPPCI BetterFac. PCI BetterPPCI BetterKeeley E, et al. Lancet 2006;367:579.0.11100.11100.11101.38 (1.01-1.87)1.71 (1.16 - 2.51)1.51 (1.10 - 2.08 )1.40 (0.49-3.98)

1.81 (1.19-2.77)

Lytic alone N=2953

IIb/IIIa alone N=1148

Lytic +IIb/IIIaN=399All (N=4500)

Rescue PCIIf evidence of cardiogenic shock, severe heart failure hemodynamically compromising ventricular arrhythmias.

If fibriolysis has failed Evaluate 90 minutes for a

Summary of Acute STEMI TreatmentStabilize, MONA/BB

ASA if MI is even considered.

The artery is CLOSED; time is muscle

PCI is preferred method of reperfusion

Cath lab (regardless of method of reperfusion) ifHemodynamic or electrical instabilityFailed Fibrinolysis

Case Presentation51 y.o. man with increasing shortness of breath and chest pain x 60minCame to ED because she can no longer walk up a flight of stairs or lay down flat.No N/V/Diaphoresis. No LH or dizzinessNo known history of cardiac or pulmonary disease.

Physical ExamVital Signs: HR 120; BP 90/60; RR 28.General: Alert and oriented x 3. Mild respiratory distress.HEENT: NC, no trauma.Neck: Supple, no lymphadenopathy.Heart: Regular S1 and S2. 2/6 early SEM along L sternal border (no significant radiation). No carotid bruits. ? JVD.Lungs: Tachypnic. Rales 1/3 up the back bilaterally. Otherwise clear.Abdomen: Obese. BenignExtremities: Warm. No C/C. Trace edema.

EKG

Chest X-Ray

TreatmentMONA - Morphine, Oxygen, Aspirin

No nitrates because hypotensive

No beta-blocker b/c in heart failure

Primary PCI LAD occlusion

Complications of Myocardial InfarctionArrhythmiasVentricular Septal PerforationIschemic Mitral Regurgitation, Papillary Muscle RuptureVentricular Free Wall RuptureSystemic Embolism Ventricular AneurysmPericarditisCardiogenic Shock (another lecture)

Ventricular Arrhythmias60-110 BPM; Up to 20% STEMI patients have thisUsually a result of reperfusion; no specific therapy needed if HD stable. Otherwise, atropine or even atrial pacing may increase sinus rate to overdrive pace the AIVRRoutine post-MI management with B-blockers, ACE, etc.

PVCsExtremely common, along with short runs of NSVTAmiodarone wont increase mortality, other antiarrhythmics (other than B-blockers) do. B-blockers, electrolytesBest if no antiarrhythmics are used

Not So Benign RhythmIschemic VT is often polymorphic; HR>100-110 BPMHigher risk with more LV damage and in first 2 days after MITreat: DCCV, cath lab (if needed), electrolyte correction, amiodarone, lidocaine, B-Blockers

If That Didnt Make You NervousPrimary VF: Sudden event with no warning--10% STEMI patients before lytics. MUCH MUCH less nowSecondary VF: Occurring in setting HF or shockLate VF: >48 hrs after MI-->Increased risk with IVCD, anterior wall MI, persistent SVT early in course, and RV infarction requiring pacing***Have to worry about structural complication (free wall rupture)/ischemiaTreat: Non-synced DCCV, electrolyte correction

Why get worked up about electrolytes?Nordrehaug JE, van der Lippe G: Hypokalemia and ventricular fibrillation in acute myocardial infarction. Br Heart J 50:525, 1983.NOTE: Pre-lytic study

Sinus Bradycardia/Junctional Escape Rhythm4-5% of STEMI patients have a bradyarrhythmiaSinus node ischemia--Blood supply to SA node is: 65% RCA, 25% LCX, 10% dual supply. Most commonly seen in Inferior/posterior MIs. Often induced by vagal reaction that may be protective

Atrioventricular BlockFirst-Degree: Usually the RCA and does not require treatment. Hold the B-blocker for PR>240 ms

Second-Degree: Usually RCA disease and does not require treatment unless HR less than 50 and arrhythmia or symptoms. Otherwise, atropine or pace

Third-Degree: Can be from any location of infarct. Can be preceded by Mobitz II BlockPace for symptoms and for hemodynamic support. Usually not needed in inferior MIs as block is transient (pace for HR

Post-MI VSD~2% of acute MIs prior to reperfusion era~0.2% in GUSTO-I streptokinase trialWithout reperfusion, usually occurs within first weekDay 1--Large intramural hematomas that dissectDay 3-5--Coagulation necrosis24 hr or less if receive lysis--Lytics reduce infarct size but may promote hemorrhagic dissection of myocardium

Symptoms, Exam, and DiagnosisChest pain, dyspnea

PE: Harsh, holosystolic murmur along sternal border radiating to base/apex/R parasternum; thrill in 1/2 patients; S3; Loud P2; TR.

Compared to acute MR, murmur is loud. Up to 20% of patients may have MR as well though

CCU ManagementIABPVentilationDiuresis/HF ManagementInotropes (can increase shunt)Nitroprusside if tolerated (can cause hypotension)Mortality with conservative management is HIGH (24%, 46%, 67-82% at 24 hrs, 1 wk, and 2 months, respectively)Ultimately, mechanical closure needed (surgery vs. percutaneous)-TIMING is questionable but clinical status should not preclude this

Acute Mitral RegurgitationCaused by papillary muscle ischemia or rupture (less likely). Rupture is usually partial since total is essentially incompatible with lifeUsually in setting of inferior MI involving the posteromedial papillary muscle (single PDA blood supply as opposed to anterolateral)Rupture usually occurs 3-5 days post-MI and in 1% of MIs and requires emergent operative repair (50% mortality in 24 hrs)Accounts for 7% of cardiogenic shock and 5% of mortality associated with acute MIArea of infarction does NOT have to be large

Symptoms, Exam, DiagnosisSymptoms: Those of heart failure

PE: May or may not hear loud systolic murmur (need a gradient)

CCU ManagementMechanical ventilation if neededIABP--especially for hypotensionPCI if papillary m. ischemia (not rupture)Afterload reduction (nitroprusside if possible) to MAP of 70-80 mm HgSince mortality is 90% with medical therapy alone, surgery is the major therapy of choicePerioperative mortality 20-25%Overall surgical mortality is even higher

Free Wall Rupture~10% of patients who die in hospital from STEMIMost commonly between 1 and 4 days (up to 3 weeks)Caused by tear or dissecting hematomaMore common with fibrinolysis compared to PCIMore common in patients without previous infarction

Symptoms, Exam, DiagnosisAcute symptoms include sudden chest pain (esp with cough, strain) and sudden death

Subacute symptoms: Pericarditis-like symptoms (chest pain, nausea, vomiting)

Exam (think HF and tamponade): JVD, pulsus, diminished heart sounds, rub, possibly a new murmur

TreatmentPericardiocentesis if timeSurgical repair is the only treatmentMortality is reasonable if patient gets to the OR in time90% mortality withoutsurgery

Summary of Acute STEMI ComplicationsMuch more rare in the reperfusion eraLook for them especially in delayed presentationArrhythmias are most common complication and may require emergent treatmentVSDs, papillary muscle rupture, and free wall ruptures carry a VERY high mortality and require emergent surgical consultationSupport mechanically until patient receives operation

Other ReferencesCrawford PA, ed. The Washington Manual Subspecialty Consult Series: Cardiology Subspecialty Consult. Philadelphia: Lippincott Williams and Wilkins, 2004.Griffin BP, Topol EJ, eds. Manual of Cardiovascular Medicine, 2nd ed. Philadelphia: Lippincott Williams and Wilkins, 2004Zipes, Libby, Bonow, Braunwald, eds. Braunwalds Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed. Philadelphia: Elsevier Saunders, 2005

Questions?

ISIS-1 Between mid-1981 and Jan 1, 1985, 16 027 patients entering 245 coronary care units at a mean of 5.0 h after the onset of suspected acute myocardial infarction were randomised either to a control group or to a group receiving atenolol (5-10 mg iv immediately, followed by 100 mg/day orally for 7 days). MIAMI - The MIAMI trial randomized 5778 patients to blind treatment with iv metoprolol or placebo Treatment with intravenous metoprolol (15 mg) or placebo was started shortly after the patient's arrival in hospital within 24 h of the onset of symptoms, and then oral treatment (200 mg daily) was continued for the study period (15 days). 1985

*Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock): age > 70 years, systolic blood pressure < 120 mmHg, sinus tachycardia > 110 or heart rate < 60, increased time since onset of symptoms of STEMI.

*Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock): age > 70 years, systolic blood pressure < 120 mmHg, sinus tachycardia > 110 or heart rate < 60, increased time since onset of symptoms of STEMI.

*Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the risk of developing cardiogenic shock): age > 70 years, systolic blood pressure < 120 mmHg, sinus tachycardia > 110 or heart rate < 60, increased time since onset of symptoms of STEMI.

Note medical contact is defined as the time of EMS arrival on scene after the patient calls EMS/9-1-1 or the time of arrival at the emergency department door (whether PCI-capable or nonPCI-capable hospital) when the patient self-transports.Metaanalysis of 23 trials, which together randomly assigned 7739 thrombolytic-eligible patients with ST-segment elevation AMI to primary PTCA (n=3872) or thrombolytic therapy (n=3867). Streptokinase was used in eight trials (n=1837), and fibrin-specific agents in 15 (n=5902). Most patients who received thrombolytic therapy (76%, n=2939) received a fibrin-specific agent. Reduction in Mortality* See 2007 STEMI Focused Update for further discussion and subgroup analysis (Antman EM, et al. J Am Coll Cardiol 2008. Published ahead of print on December 10, 2007. Available at http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001). Definitions of significant bleeds varied among the trials. The original references should be consulted for details. Facilitated PCI (PCI with additional therapy) with fibrinolytics shows clear increase mortality. Primary PCI vs Facilitated with GPIIb/IIIa shows no difference.