C h a p t e r 3 Acute Myocardial Infarction - Management in First 3 Hours AB Mehta 1 BP Shivdasani 2 1 Director of Cardiology, Jaslok Hospital, Mumbai. 2 Clinical Associate, Jaslok Hospital, Mumbai. Introduction 50% of deaths due to Acute Myocardial Infarction (AMI) occur within one hour of symptom onset. 1 Therefore, rapid diagnosis and management is vital to reduce mortality. Out of Hospital Sudden Cardiac Arrest Majority are the result of fatal arrhythmias that can be treated with emergency Cardio-Pulmonary Resuscitation, defibrillation and prompt Advanced Cardiac Life Support. This requires patient education regarding symptoms, availability of trained Emergency medical services and rapid transport to a fully equipped cardiac hospital. 2,11 Recognition and Management Most patients seek medical care after 2 hours of symptom onset and even wait 12 hours or more. Pharmacologic therapy beyond 12 hours may offer little benefit. 2 Thus, prompt treatment is essential. Components of Delay to Treatment and Goals 3 1. Patient related (failure to recognize problem and delay in seeking help). Goal 15 minutes. 2. Pre hospital evaluation, treatment and transport time. Goal 30 minutes. 3. Diagnosis and initiation of treatment in hospital. Goal door to needle time for thrombolysis 30 minutes. 4. Time to reperfusion door to balloon time 90 minutes. High Risk Patients Include those with tachycardia ( 100 bpm), hypotension ( 100 mmhg), pulmonary edema (rales > one half way up) and shock. They should be managed in a tertiary hospital with early thrombolysis or Percutaneous Coronary Intervention(PCI). 4 Pre Hospital Thrombolysis A meta-analysis of trials showed a 17% relative improvement in outcome 5. However, it is administered only if transport time is >90 minutes or if a trained physician is present in the ambulance. 11 20 CME 2004
Diagnosis of AMI 1. History of Ischaemic type chest discomfort (lasting >20 minutes): Presentation in 70 to 80% of patients. 6 2. Changes in serially obtained ECG: ST segment elevation has sensitivity of 46% and specificity of 91% for diagnosing AMI 7. Mortality increases with number of leads showing ST elevation. 3. Rise and fall of cardiac markers: Elevated cardiac specific troponins ctni or ctnt identify patients who are at increase risk of death and those who benefit from treatment with GPII b/iiia inhibitors 8. Myoglobin may be detected after two hours of MI. CK-MB2 >1U/L or ratio of CK- MB2 to CK-MB1 of 1.5 has improved accuracy of diagnosing AMI within 1 st 6 hours.9 Routine Measures Oxygen Given to patients with overt pulmonary congestion, desaturation (SaO 2 <90%) and routinely to all patients with uncomplicated MI during 1 st 3 hours 11. It limits myocardial injury 10, reduces ST segment elevation and hypoxia due to excess lung water. Nitroglycerine (NTG) Given for 1 st 24-48 hours in patients with AMI + CHF, large anterior MI, persistent ischaemia or hypertension 11. It should be avoided in patients with hypotension (SBP < 100 mm Hg), bradycardia (<50 bpm) 12, tachycardia or RV infarct 11. Pre hospital sublingual NTG 5 mg every 5 minutes upto 3 doses. In hospital it is given as an infusion. Analgesia IV Morphine 4-8 mg relieves anxiety without causing myocardial depression. It reduces pain induced sympathetic activation which causes vasoconstriction and increased cardiac workload 11. Alternatively, pentazocine or buprenorphine may be used. Aspirin 160-325 mg of soluble Aspirin immediately after onset of symptoms. ISIS-2 study showed that Aspirin alone in AMI resulted in 35-day mortality reduction of 23%. When combined with Streptokinase (STK), mortality reduction was 42% 13. It reduces coronary re-occlusion and recurrent Ischaemic events after fibrinolysis 14. The tablet may be chewed or swallowed with equal benefit. Aspirin suppositories or intravenous form may be used in patients with severe nausea and vomiting or upper GI disorders. Other Anti-platelet Agents Clopidogrel, ticlopidine or dipyridamole are used if patient is allergic to aspirin or has aspirin resistence. Loading dose of 300mg clopidogrel or 500mg ticlopidine is given if PCI is contemplated. Atropine Recommended in patients with: 1) sinus bradycardia with low cardiac output and peripheral hypoperfusion. 2) acute inferior MI with type 1 second or third degree A-V block with hypotension, ischaemic discomfort or ventricular arrhythmia. 3) sustained bradycardia and hypotension after NTG. 4) ventricular asystole. Dose: 0.5 to 1mg I.V repeated every 3-5 minutes upto 2.5mg (0.04mg/kg). 11 Beta-blocker Analysis of 28 trials reveals absolute mortality reduction at 7 days from 4.3% to 3.7% 15. It should be used in setting of tachycardia (without CHF), hypertension or pain unresponsive to opiods or NTG. 11 ACE Inhibitors Given to patients with CHF or impaired LVEF in early phase.gissi-3 16 and ISIS-4 17 have shown that it reduces mortality at 4-6 weeks. Acute Myocardial Infarction - Management in First 3 Hours 21
Table 1 : Golden hour benefit period for thrombolysis: Time to lysis in hours 0-1 2-3 4-6 7-12 Lives saved/thousand 35 25 19 16 (FTT Collaborative Group. Lancet 1994; 343:311-322) Table 2 : Comparative Efficacy STK Anistreplase Alteplase Reteplase Dose 1.5MU in 30-60 min 30 mg in 5min 100mg in 90 min 10 u twice over 20 min 90min patency (%) 50 65 75 75 TIMI-3 flow % 32 43 54 64 Thrombolytic Therapy An overview of 9 trials have shown an 18% proportional reduction in 35-day mortality with thrombolytic therapy (9.6% fibrinolysis v/s 11.5% control). 18 Comparative Thrombolytic Efficacy The GISSI-2 19 and ISIS-3 20 studies showed that mortality rates at 4 to 5 weeks were similar. GISSI- 2: tissue plasminogen activator (tpa) 8.9% and STK 8.5%. ISIS-3: alteplase 10.3%, STK 10.6% and anistreplase 10.5%. Limitations of Thrombolysis 1)Reduced efficacy: GUSTO-1 study showed that TIMI grade 3 flow is seen in 32% with STK and 54% with tpa with corresponding mortality of 7.4% and 6.3%. 21 2)Reocclusion: Ohman et al in the TAMI study 22 showed post fibrinolysis re-occlusion rate of 12.4%.3) Re-infarction: occurs in 3-5%. 4) Recurrent ischaemia: in upto 34%. 5) No Tissue flow: occurs in about 30%. Thus, effective tissue flow is achieved in only about 25% of patients. 23 Adjunctive Anti-thrombotic Therapy Heparin: Does not improve clot lysis but enhances coronary patency after rtpa. 24 Low molecular weight heparin: In the ASSENT-3 trial, enoxaparin(30mg i.v bolus and 1mg/kg every 12 hours) for 7 days plus tenecteplase reduced in-hospital re-infarction or refractory ischaemia compared to heparin. 25 Direct thrombin inhibitors: Hirudin, bivalirudin and argatroban have not shown clear benefit over heparin following fibrinolysis. Combination therapy: fibrinolysis + GpIIb/IIIa Inhibitors Pooled analysis of TIMI-14 26, SPEED 27 and INRO-AMI 28 trials showed an improvement in TIMI Grade 3 flow from 56% with lytic therapy to 64% in patients with combination therapy (8% improvement with 0.4% mortality reduction). Percutaneous Coronary Interventions (PCI) Includes primary PCI, PCI + Pharmacologic reperfusion therapy-facilitated PCI and Rescue PCI after failed trombolysis. Primary PCI The DANAMI-2 investigators 29 found that routine transfer to a tertiary care hospital for primary PCI 22 CME 2004
is superior to in-hospital thrombolysis. A significant reduction in combined end point of death, reinfarction and stroke at 30 days was seen in primary PCI group (14.2% to 8.5%, p< 0.002). Primary PCI results in higher patency, less re-occlusion, improved LVEF and better clinical outcome. 30 It is indicated in patients ineligible for fibrinolytic therapy and treatment of choice in cardiogenic shock. 30 Facilitated PCI The SPEED trial 31 showed that PCI after combination therapy increased rate of TIMI 3 flow from 47% to 87%. In TIMI-14 32 study, those who received half dose alteplase and abciximab and early PCI had greater ST segment resolution compared to those with only combination therapy (57% v/s 24%) or with only fibrinolysis + PCI (54% v/s 8%). Rescue PCI Trials have shown clinical benefit if infarct related artery is recanalized by PTCA after failed thrombolysis.33 Role of IABP Used in patients with hemodynamic instability, persistent ischaemia or refractory arrhythmia often in conjunction with PCI. CABG It is performed when Angiography reveals unfavourable anatomy for PCI, failed PTCA or mechanical complications like VSD, papillary muscle rupture with MR or cardiac rupture. 30 Conclusion Successful management of AMI during the first 3 hours depends on early diagnosis, rapid triage and optimum combination of pharmacologic reperfusion and PCI. References 1. Herlitz J, Blohm M, Hartford M, et al. Delay time in suspected acute myocardial infarction and the importance of its modification. Clin. Cardiol 1989; 12: 370-374. 2. National Heart, Lung and blood Institute: Rapid identification and treatment of acute myocardial infarction. National Institutes of Health; 1993 & 1994: NIH publication Nos 93-3303 & 94-3302. 3. Cannon CP, Antman EM, Walls R, Braunwald E: Time as an adjunctive agent to thrombolytic therapy. J Thromb Thrombol. 1994; 1:27-34. 4. Weaver WD, Cerqueira M, Hallstrom AP, et al. Pre hospital initiated vs hospital initiated Thrombolytic therapy. The Myocardial Infarction Triage and Intervention Trial. JAMA 1993 ; 270: 1211-1216. 5. The European Myocardial Infarction Project Group. Pre-hospital thrombolytic therapy in patients with suspected acute myocardial infarction. NEJM 1993; 329:383-389. 6. Kannel W. Prevalence and clinical aspects of unrecognized myocardial infarction and sudden death. Circulation 1987; 75 (suppl II): II-4-II-5. 7. Rude RE, Poole WK, Muller JE, et al. Electrocardiography and clinical criteria for recognition of acute myocardial infarction based on analysis of 3697 pts. Am J Cardiol 1983; 52:936-942. 8. Ohman EM, Armstrong PW, Christenson RH, et al. Cardiac Troponin T levels for risk stratification in acute myocardial ischaemia. GUSTO IIA investigators. NEJM 1996; 335:1333-1341. 9. Puleo PR, Meyer D, Wathen C, et al. Use of a rapid assay of subforms of creatine Kinase MB to diagnose or rule out acute myocardial infarction. NEJM 1994; 331:561-566. 10. Maroko PR, Radvany P, Braunwald E, Reduction of infarct size by oxygen inhalation following acute coronary occlusion. Circulation 1975; 52:360-368. 11. Ryan et al. ACC/AHA guidelines on Management of Acute Myocardial Infarction 1999 update. J Am Coll Cardiol 1999; Sept 1: 1-91. 12. Come PC, Pitt B. Nitroglycerine induced severe hypotension and bradycardia in patients with AMI. Circulation 1976; 54:624-628. 13. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomised Trial of IV STK, oral aspirin, both or neither among 17187 cases of suspected AMI. Lancet 1988; 2:349-360. Acute Myocardial Infarction - Management in First 3 Hours 23
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