Definition Criteria.. e/o myocardialnecrosis in a clinical setting consistent with myocardial ischaemia. • Detection ofrise &/or fall of cardiac biomarkers (preferably troponin)with at least one value >99th percentile of the URL together with e/o myocardial ischaemiawith at least one of the following: • Symptoms of ischaemia;•ECG changes indicative of new ischaemia(new STE ornew LBBB)• Dvpt ofpathological Q waves in the ECG;• Imaging e/o new loss of viable myocardium or new RWMA• For PCI/ CABG with normal baseline troponin values, elevations>99th percentile URL are s/o peri-procedural myocardial necrosis. By convention, increasesof biomarkers >3 x 99th percentile URL have beendesignated as defining PCI-related MI. •Increases of biomarkers>5 x 99th percentile URL plus either new pathologicalQ waves or new LBBB, or angiographically documented new graftor native coronary artery occlusion, or imaging evidence ofnew loss of viable myocardium ……….CABG-related MI. • Pathological findingsof an acute myocardial infarction.
Chronology of the interface between the patient and the clinician through the progression of plaque formation and the onset of complications of STEMI. Ischemic Discomfort Acute Coronary Syndrome No ST Elevation ST Elevation
Prehospital Chest Pain Evaluation and Treatment • Prehospital EMS providers …162 to 325 mg of aspirin (chewed) to chest pain patients suspected of having STEMI unless contraindicated or already taken by the patient…non–enteric-coated formulations. • Previously on NTG take I tab S/L Not improving after 5 mts Seek medical help
Prehospital Issues Prehospital 12-lead ECG by ACLS….Class IIa (B) Prehospitalfibrinolysis….Class IIa (B) Prehospital destination protocols • Patients with STEMI who have cardiogenic shock and are <75 yrs old should be brought immediately or secondarily transferred to facilities capable of cardiac catheterization and rapid revascularization within 18 hrs of shock (Class I) • Patients with STEMI who have contraindications to fibrinolytic therapy should be brought immediately or secondarily transferred promptly (primary-receiving hospital door-to-departure time less than 30 min.) to facilities capable of cardiac catheterization and rapid revascularization
Fibrinolysis Noninvasive Risk Stratification Late Hospital Care and Secondary Prevention Not PCI Capable Ischemia driven Rescue PCI Capable PCI or CABG Primary PCI
Initial Recognition and Management in the Emergency Department Examine • 1. Airway, Breathing, Circulation (ABC) • 2. Vital signs, general observation • 3. Presence or absence of jugular venous distension • 4. Pulmonary auscultation for rales • 5. Cardiac auscultation for murmurs and gallops • 6. Presence or absence of stroke • 7. Presence or absence of pulses • 8. Presence or absence of systemic hypoperfusion (cool, clammy, pale, ashen)
Laboratory examinations should be performed as part of the management of STEMI patients, but should not delay the implementation of reperfusion therapy. • Serum biomarkers for cardiac damage • Complete blood count (CBC) with platelets • International normalized ratio (INR) • Activated partial thromboplastin time (aPTT) • Electrolytes and magnesium • Blood urea nitrogen (BUN) • Creatinine • Glucose • Complete Lipid Profile
Supplemental oxygen should be administered to patients with arterial oxygen desaturation (SaO2 < 90%)…Class I (B) • It is reasonable to administer supplemental oxygen to all patients with uncomplicated STEMI during the first 6 hours…Class II a NTG : Patients with ongoing ischemic discomfort should receive sublingual NTG (0.4 mg) every 5 minutes for a total of 3 doses, after which an assessment should be made about the need for intravenous NTG. Class I (C) IV NTG is indicated for relief of ongoing ischemic discomfort that responds to nitrate therapy, control of hypertension, or management of pulmonary congestion. Class I Class III • systolic pressure < 90 mm Hg or ≥ to 30 mm Hg below baseline • severe bradycardia (< 50 bpm) • tachycardia (> 100 bpm) or • suspected RV infarction. • who have received a phosphodiesterase inhibitor for erectile dysfunction within the last 24 hours (48 hours for tadalafil).
Analgesia • Morphine sulfate (2 to 4 mg intravenously with increments of 2 to 8 mg intravenously repeated at 5 to 15 minute intervals) is the analgesic of choice for management of pain associated with STEMI. [Class I] • NSAIDS should be discontinued immediately at the time ofSTEMI ..d/t Increased risk of cardiovascular events[A substudy analysis from the ExTRACTTIMI-25 trial ….increased risk of death, reinfarction,heart failure, or shock among patients on NSAIDswithin 7 days of enrollment].
Aspirin • Aspirin 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).. maintenance dose of 75 to 162 mg) should be given indefinitely after STEMI to all patients without a true aspirin allergy.
Thienopyridines In patients for whom PCI is planned, clopidogrel should be started and continued: • ≥ 1 month after bare-metal stent • ≥ 3 months after sirolimus-eluting stent • ≥ 6 months after paclitaxel-eluting stent • Up to 12 months in absence of high risk for bleeding. • CABG planned ?... the drug should be withheld for at least 5 days, and preferably for 7 days, unless the urgency for revascularization outweighs the risk of excessive bleeding. • Probably indicated in patients receiving fibrinolytic therapy who are unable to take aspirin because of hypersensitivity or GI intolerance.
Beta Blockers • Oralβ blockers should be given promptly to those pts without a C/I, irrespective of concomitant fibrinolytic therapy or PCI..Class 1 (A) • It is reasonable to administer IV β -blockers promptly to STEMI patients without C/I, esp if a tachyarrhythmia or SHT is present Class IIa (B) …. [COMMIT/CCS-2……. end points were not significantlyreduced by metoprolol. For every 1000 ptstreated…5 fewerepisodes of reinfarction & VF,but 11 more episodes of cardiogenic shock. The excess of CS was seen chiefly from Days 0 to 1 after hospitalization,whereas the reductions in reinfarction and VF appeared from Day 2 onward .. • avg relative increasein CS..30%, with higher rates for those >70 yrs, or SBP <120 mm Hg, or presenting HR >110 bpm,or with Killip class >1. • Pts withsinus tachycardia or AF should have LV function rapidly evaluated before IVBBs. From Day 2 onward, when beneficialeffects on reinfarction and VF are seen,administration of 200 CR oral metoprololdaily appears to be safe in stable patients. It is prudentto initiate with 50 mg orally every 6 hours,transitioning to a dose equivalent to 200 mg /d orallyor the maximum tolerated dose.]
GlycoproteinIIb/IIIa Inhibitors • It is reasonable to start abciximab as early as possible before primary PCI (with or without stenting) in patients with STEMI. • Tirofiban or eptifibatide may be considered before primary PCI (with or without stenting) in patients with STEMI.
Reperfusion • Most imp…minimize total ischemic time [time from onset of symptoms to initiation of reperfusiontherapy]….[timely use of some reperfusion therapy is likely more important than the choice of therapy]. • TIME IS MYOCARDIUM…time - dependent “ wave - front ” of myocardial necrosis beginning at the subendocardium and moving towards the epicardial surface. • goal ..rapid Rx… keep total ischemic time within 120 minutes (ideally within 60 minutes) … door-to- needlewithin 30 mtsor that door-to-balloonwithin 90 mts. • Fibrinolytics VS PCI
Fibrinolytics…plasminogen activators, • directly or indirectly converts the proenzyme plasminogen to plasmin [cleaving the arginine 560 - valine 561 bond]. • Plasmin degrades several proteins, including ﬁbrin, ﬁbrinogen, prothrombin, and factors V and VII.
tPA…recomb DNA tech .. five domains: finger, epidermal growth factor, kringle 1 and kringle 2, and serum protease[resp for enzymatic activity] .. inhibited by circulating PAI - I, so rapidly cleared (half - life about 5 minutes). So needs bolus/infusion regimens (over 1 – 3 hours)..The accelerated dose regimen over 90 minutes produces more rapid thrombolysis than the standard 3-hour infusion of t-PA.
rPA…non - glycosylated, single chain deletion variant consisting only of the kringle 2 and proteinase (plasmin cleavage site) domains of human tPA.TNK – tPA…mutant of t-PA with specific amino acid substitutions in the kringle 1 domain and protease domain ...decrease plasma clearance, increase fibrin specificity, and reduce sensitivity to PAI-1.
Effects on coronary arterial patency • Granger et al…14124 angiographic observations from 58 studies. Without ﬁbrinolytic therapy, spontaneous perfusion …15% and 21% at 60 and 90 minutes after study entry, respectively, remains unchanged at 1 day, then gradually increases to about 60% by 3 weeks. All ﬁbrinolytic regimens improve early patency rates. • patency rates at > 3 hours were similar for all regimens, and reocclusion rates were higher after tPA than non - ﬁbrin speciﬁc (systemically active) agents (13% vs 8%) (P =0.002). • The GUSTO angiographic study …. early but not late patency rates accurately predict mortality differences among AMI therapies. • Studies showing mortality benefit with FT • GISSI…1st definitive mortality trial..11806 pts….SK vs standard rx.Aspirin not given.Inhosp mortality [10.7 vs 13%...P 0.0002]…also showed time dependant benefit • ISIS-2…17187 pts … SK vs Asp vs both vs placebo…35 d mort reduced by 23% by asp .. 25 % by SK42 % by both..all P <0.00001 • ASSET study…tPA vs heparin..30 d mort 7.2 vs 9.8 % P 0.0011
Fibrinolytic Therapy Trialists Collaborative Group …. database from nine controlled trials…58600 pts of whom 6177 (10.7%) died, 564 (1.0%) had strokes, and 436 had major non - cerebral bleeds. The 45000 patients who presented with STE or BBB had an absolute mortality reduction of 30 per 1000 for Rx within the ﬁrst 6 hours, 20/1000 for hrs 7 – 12, and a statistically uncertain reduction of 13 per 1000 beyond 12 hours. • These data led to the national guidelines ( Class I, Level A ) that all STEMI patients should undergo rapid evaluation for reperfusion therapy and have a reperfusion strategy implemented promptly after contact with the medical system.
Those with BBB & Ant STE benefit the most with FT. • Those with normal ECGs or with ST depression alone showed no beneﬁt and adverse trends (7 and 14 more deaths per 1000, respectively). • The magnitude of mortality reductions in FTT was dependent on time to therapy from symptom onset. • For those with STE or BBB, the absolute beneﬁt was 39 (0 –1 h), 30( >1–3 h), 27( >3-6 h), 21(>6–12 h) & 7 (>12–24h) lives saved /1000 treated
mortality in each subgroup of ﬁbrinolytic treated (black bars) versus placebo - treated
Very early therapy can even abort a myocardial infarction. Role of ﬁbrinolytic therapy in the prehospital setting. So the ACC/AHA guidelines have given a indication ( Class IIa, Level A) for the establishment of a prehospitalﬁbrinolysis protocol in settings in which physicians are present in the ambulance or well - organized EMS systems with full - time paramedics who have 12 - lead ECGs in the ﬁeld with transmission capability, paramedic initial and ongoing training in ECG interpretation and STEMI treatment, on - line medical command, a medical director with training/experience in STEMI management, and an ongoing continuous quality improvement program.
The beneﬁt of ﬁbrinolysisafter 6 hours is less certain • LATE study….5711 pts …MI 6 - 24 hours …tPA (100 mg over 3h) or placebo. A 26% relative mortality reduction (8.9% vs 11.9%, P= 0.02) was observed for those treated within 12 hours. The 12 – 24 hour subgroup showed a non - signiﬁcant trend to beneﬁt (8.7% vs 9.2% mortality rate). • The South American EMERAS collaborative group ….4534 pts with IV SK or placebo within 24 hours after suspected AMI and found a non - signiﬁcant trend towards a mortality beneﬁt b/n 7 &12 hrs (SK 11.7%, placebo 13.2%). This provides the rationale for recommending FT 7-12 hrs group with persistent symptoms and ECG changes.
Risks of FT ICH is the most imp risk, occurring in about 0.5 – 1.0% ….risk of fatality (44 – 75%). MC with fibrin selective agents 7 predictors of ICH [GUSTO-1 group]….advanced age, lower weight, h/o cerebrovascular disease, h/o hypertension, higher SBP/DBP on presentation, and randomization to tPA (vs SK). In contrast, the incidence of non cerebral bleeding is higher with SK. Allergy, hypotension, and fever Anaphylaxis or bronchoconstriction is rare ( < 0.2 – 0.5%). SK may acutely release bradykinin, a vasodilator. The incidence of clinical hypotension after SK (11.8%) was greater than after tPA (7.1 %); Repeat thrombosis and its associated reinfarction is a known, potentially devastating risk after ﬁbrinolytic therapy.
Comparative ﬁbrinolytic trials : • ASSENT – 2………compared weight - adjusted TNK (as a 30 – 50 mg bolus over 5 – 10 seconds) and accelerated rt - PA. All patients received aspirin and heparin. 30 day mortality rates were virtually identical [6%].. A lower mortality rate with TNK - tPA was observed among patients presenting 4 hours after symptom onset (7.0% vs 9.2%), which may be due to either greater activity of the more ﬁbrin - speciﬁc TNK - tPA against older, ﬁbrin - rich clots or chance. • GISSI-2…..ISIS-3…..tPA vs SK….mortality rates at 35 days were similar • GUSTO…. The primary endpoint, 30 - day mortality, was lowest with accelerated tPA with IV heparin compared to SK with IV/SC heparin
FT in elderly : Analyses restricted to elderly patients with clear indications for ﬁbrinolytic therapy suggested similar or greater absolute beneﬁt vs younger patients. ? Safety concerns……..SK, which carries a lower risk of ICH, or PCI should be considered as preferred reperfusion strategies in the elderly.
Fibrinolysis • CLASS I • symptom onset within the prior 12 hours. [A] • symptom onset within the prior 12 hours and new or presumably new left bundle branch block (LBBB). [A] • CLASS II a • symptom onset within the prior 12 hours and 12-lead ECG findings consistent with a true posterior MI. [C] • symptoms of STEMI beginning in the prior 12 to 24 hours who have continuing ischemic symptoms and ST elevation > 0.1 mV in ≥ 2 contiguous precordial leads or ≥ 2 adjacent limb leads. [B] • CLASS III • initial symptoms of STEMI began more than 24 hours earlier • 12-lead ECG shows only ST-segment depression, except if a true posterior MI is suspected.
Assessment of Reperfusion after fibrinolysis It is reasonable [Class IIa] to monitor • the pattern of ST elevation,cardiac rhythm and clinical symptoms over the 60 to 180 mts after initiation of fibrinolytic therapy. Noninvasive findings s/o reperfusion include: • Relief of symptoms • Maintenance and restoration of hemodynamic and/or electrical instability • Reduction of ≥ 50% of the initial STE pattern on follow-up ECG 60 to 90 minutes after initiation of therapy.
PCI vsFibrinolysis for STEMI: • early randomized trials tended to favor direct balloon angioplasty over ﬁ brinolysis in certain settings. [PAMI…395 pts…with in 12 hrs …PCI vstPA … PCI reduced the composite outcome]. • In a meta analysis of 23 randomized STEMI trials comparing primary PCI with FT, signiﬁcant reductions in short - term (4 – 6 weeks) and long term (6 – 8 months) mortality, non - fatal MI, and stroke were seen. Regardless of whether the fibrinolytic was ﬁbrinspeciﬁc,primarypci showed similar benefit. • Greatest benefit with pci is seen in high risk settings as in Cardiog shock.. as shown in SHOCK trial…302 pts with CS….emergency revascularsnvs medical stabilisn….Significant mortality reduction is seen @ 6 months 50% vs 63 %... P 0.03. • As the delay for performing PCI increases, the mortality beneﬁt for primary PCI over ﬁbrinolysis decreases. Compared with a ﬁbrin - speciﬁclytic agent, a PCI strategy may not reduce mortality when a delay > 60 minutes is anticipated vs immediate FT [Nallamothu et al JACC 2003]
TYPE OF REPERFUSION THERAPY ? STEP 1….. Assess Time and Risk (a)Time Since Symptom Onset (b)Risk of STEMI….TIMI RISK SCORE…Mortality benefit with PCI is high in pts at highest mortality risk.So as the risk decreases the mort benefit also decreases such that mort adv vs FT wont be seen in pts with estimated 30 d mort rate b/w 2-3%.
(c)Risk of fibrinolysis…(Risk factors for ICH ….increased age, low body weight, and hypertension on admission)….when no PCI is available, FT should still be favored over no reperfusion until the risk of a life-threatening bleed exceeds 4 %. (d)Time to reach a skilled PCI lab • If presentation is < 3 hours and there is no delay to an invasive strategy, there is no preference for either strategy. • Fibrinolysis generally preferred • Early presentation ( ≤ 3 hours from symptom onset) and delay to invasive strategy • Invasive strategy not an option Cath lab occupied or not available Vascular access difficulties No access to skilled PCI lab 3. Delay to invasive strategy Prolonged transport Door-to-balloon more than 90 minutes > 1 hour vsfibrinolysis (fibrin-specific agent) now
Invasive strategy generally preferred • Skilled PCI lab available with surgical backup [Team experience greater than a total of 36 Primary PCI cases/yr & Operator experience > a total of 75 primary PCI cases/yr]. Door-to-balloon < 90 minutes (Door-to-Balloon) – (Door-to-Needle) is <1 hour • High Risk from STEMI Cardiogenic shock, Killip class ≥ 3 • Contraindications to fibrinolysis, including increased risk of bleeding (ICH) • Late presentation … > 3 hours from symptom onset • Diagnosis of STEMI is in doubt
Primary PCI…CLASS I [A] • Patient with STEMI (including posterior MI) or MI with new or presumably new LBBB • PCI of infarct artery within 12 hours of symptom onset • Balloon inflation within 90 minutes of presentation • Skilled personnel available (individual performs > 75 procedures per year) • Appropriate lab environment (lab performs > 200 PCIs/year of which at least 36 are primary PCI for STEMI) • Cardiac surgical backup available • CLASS I [B] • Medical contact–to-balloon or door-to-balloon should be within 90 minutes. • PCI preferred if > 3 hours from symptom onset • Severe CHF and/or pulmonary edema and onset of symptoms within 12 hrs.
CLASS II a [C] • onset of symptoms within the prior 12 to 24 hours and 1 or more of the following: • a. Severe CHF • b. Hemodynamic or electrical instability • c. Persistent ischemic symptoms.
Primary PCI in Cardiogenic shock • CLASS I …patients less than 75 years old with ST elevation or LBBB who develop shock within 36 hours of MI and are suitable for revascularization that can be performed within 18 hours of shock. • CLASS II a … Those >75 years with ST elevation or LBBB who develop shock within 36 hours of MI and are suitable for revascularization that can be performed within 18 hours of shock.
PCI After Fibrinolysis In patients whose anatomy is suitable, PCI should be performed for the following: ieCLASS I • Objective evidence of recurrent MI [C] • Moderate or severe spontaneous/provocable myocardial ischemia during recovery from STEMI [B] • Cardiogenic shock or hemodynamic instability [B] CLASS IIa ...routine PCI in patients with left ventricular ejection fraction (LVEF) ≤ 0.40, CHF, or serious ventricular arrhythmias. CLASS IIa ...documented clinical heart failure during the acute episode, even though subsequent evaluation shows preserved LV function (LVEF > 0.40). CLASS IIbRoutine PCI might be considered as part of an invasive strategy after fibrinolytic therapy. [B]
Direct stenting vs FT…..Schomig et al, Le May et al, Kastrati et al….superior outcome with stenting • Primary angioplasty vs primary stenting…meta analyses…no diff in mortality or renifarction..but MACE was reduced due to reduction in TVR with stenting • DES vs BMS…..DES signif reduce restenosis,TVR … • Trials showing the safety of DES …TYPHOON,PASSION,SESAMY,MULTISTRATEGY trials..
Facilitated PCI Facilitated PCI using regimens other than full-dose fibrinolytic therapy might be considered as a reperfusion strategy when all of thefollowing are present: a. Patients are at high risk, b. PCI is not immediately available within 90 minutes, and c. Bleeding risk is low (younger age, absence of poorly controlled hypertension, normal body weight). A planned reperfusion strategy using full-dosefibrinolytic therapy followed by immediate PCI is not recommended and may be harmful.
Intracoronary aspiration/ thrombectomy devices Signiﬁ cant clot burden may complicate acute STEMI management. Prospective clinical studies have shown that intracoronary thrombectomy and thrombus aspiration may improve TIMI - 3 ﬂ ow, hasten ST segment elevation resolution, and enhance myocardial tissue perfusion and reduce MI. TAPAS trial…pts randomized to initial aspiration thrombectomy vs standard PCI regardless of the presence or absence of angiographically visible thrombus. At 1yr follow - up, cardiac death was 3.6% (19 of 535) vs 6.7% (36 of 536) (P=0.020). One - year cardiac death or non - fatal reinfarction occurred in 5.6% (30 of 535) vs 9.9% (53 of 536) of patients in the conventional PCI group (P=0.009). So when performing primary PCI for STEMI, aspiration thrombectomy prior to balloon inﬂation should be performed whenever possible.
Embolization protection devices…. no beneﬁt has been found when applied to native vessels in the setting of STEMI • DEDICATION Trial….626 patients with STEMI and undergoing primary PCI were randomized to distal protection using the FilterWire or standard therapy. There was no signiﬁcant difference in the occurrence of the primary endpoint of complete ( = 70%) ST segment resolution (76% vs 72%, P= 0.29), no difference in maximum troponin - T (4.8 µ g/L and 5 µ g/L, P =0.87) or maximum CK- MB (185µ g/L and 184 µg/L, P= 0.99), and no difference in median LV wall motion index (1.70 vs 1.70, P=0.35). The rate of major adverse cardiac and cerebral events 1 month after PCI was 5.4% with distal protection and 3.2% with conventional treatment (P=0.17). • So when performing primary PCI for STEMI, use of distal protection devices during balloon inﬂation is not generally recommended ( Class III, Level A).
EMERGENCY CABG • Class Ia.Failed PCI with persistent pain or hemodynamicinstability b. Persistent or recurrentischemia refractoryto medical therapy ; have a significant areaof myocardium at risk,and are not candidates for PCI or fibrinolytictherapy. c. At thetime of surgical repair of postinfarctionVSR or MRd. Cardiogenic shock in pts <75 years old with STE/LBBB/PW MI whodevelopshock within 36 hrs of STEMI, have severe multivesselor leftmain disease, and are suitable for revascularizationthat canbe performed within 18 hrs of shock, unless furthersupportis futile because of the patient’s wishes or contraindications/unsuitabilityfor further invasive care. e.Life-threatening ventricular arrhythmiasin the presence of> 50% LMCA stenosis&/or TVD
Class IIa • Can be useful as primary reperfusion strategyin patients who have suitable anatomy, who are not candidatesfor fibrinolysis or PCI, and who are in the early hours (6 to12 hours) of an evolving STEMI, esp if severe multivesselor LMCA disease is present. • can be effective in selected pts 75 yearsor olderwith STE/LBBB/PW MI whodevelopshock within 36 hrs of STEMI, have severe multivesselor leftmain disease, and are suitable for revascularizationthat canbe performed within 18 hrs of shock. Class III • persistentangina and a small area of risk if they are hemodynamicallystable. • successfulepicardial reperfusionbut unsuccessful microvascular reperfusion.
ANCILLARY THERAPY TO REPERFUSION • Anticoagulants…. • more prolonged anticoagulanttherapy…..beneficial… (duration of index hospitalization) in pts receivingfibrinolytics, as seen in the comparisons of reviparin versusplacebo (CREATE), fondaparinux versus placebo (OASIS-6), and enoxaparin versus UFH (ExTRACT-TIMI 25). • The mechanismof benefit from a more prolonged regimen ….includes a longer exposure to anticoagulantsto prevent rethrombosis of the infarct artery and preventionof the rebound increase in events seen after abrupt discontinuationof UFH infusions. • Overall, UFH does not appear to improve early (60 – 90 mt) IRA patency.