1. Atypical Presentations Patients older than 75: frequently no chest pain ECG in evolution (nonspecific ECG changes) Diabetic patients: commonly no chest pain Stuttering chest pain Previous AMI Atypical symptoms

2. Modality ModalityAdvantagesDisadvantages EchocardiographyPortable Rapid Noninvasive Highly sensitive Expensive Limited availability Ischemia vs infarction Radionuclide studyNoninvasive Highly sensitive High negative predictive value Slow performance Expensive Ischemia vs infarction Low specificity Cardiac catheterization Defines coronary anatomy and physiology Testing delays Expensive Invasive Adjunctive Imaging Modalities

3. Variable Overall Population (n=40,830) Deaths (n=28,151) Adjusted  2, P value Older age (median) Lower systolic BP (median) Elevated HR (median) Anterior AMI (% of patients) Higher Killip class (% of patients) II III IV 62 y72 y717, 0.0001 130 mm Hg120 mm Hg550, 0.0001 74 bpm80 bpm275 (2 df ), 0.0001 39%56%143 (2 df ), 0.0001 13% 1% 25% 6% 350 (3 df ), 0.0001. Adapted from Lee KL, et al. Circulation. 1995;91:1659-1668. Independent Risk Factors Predictive of 30-Day Mortality: GUSTO-I Experience BP, blood pressure; HR, heart rate; bpm, beats per minute; df, degree of freedom.

4. Summary: Identifying Candidates for Reperfusion Therapy ECG indicators for immediate reperfusion –ST-segment elevation –LBBB –RBBB with ST-segment elevation Highly specific enzyme markers of myocardial necrosis –CK-MB isoforms –Troponins I and T

5. Adapted from Barron HV, et al. Circulation. 1998;97:1150-1156. Relative Risk LBBB, left bundle-branch block CP, chest pain at presentation CHF, congestive heart failure MI, myocardial infarction revasc, revascularization Prehosp., prehospital Sx, symptoms LBBB No CP Age >75 Prior CHF Prior MI Prior stroke Killip 3 Killip 2 Diabetes Female Prior revasc Anterior MI Current smoker Prehosp. ECG S  <3 h Less LikelyMore Likely Reperfusion Therapy Predictors for Underuse of Reperfusion Therapy

6. Barron HV, et al. Circulation. 1998;97:1150-1156. NRMI-2 Data on Underuse of Reperfusion Therapy in Eligible Candidates Patient characteristics associated with underuse were: –Age > 75 years –LBBB –Later arrival in the ED (3 to 6 hours) after symptom onset –Absence of chest pain Approximately 25% of eligible patients did not receive reperfusion therapy

7. From Symptom Onset to Randomization (hours) Absolute benefit per 1,000 patients with ST-segment elevation or LBBB allocated fibrinolytictherapy (  1 SD) Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Lancet. 1994;343:311-322. 7,000 9,000 12,000 14,000 3,000 0 10 20 30 40 06121824 Absolute Reduction in 35-Day Mortality Versus Delay From Symptom Onset to Randomization in Patients With ST-Segment Elevation or LBBB

8. Expanding Treatment in Elderly Patients Highest risk for complications, but potentially have the most to gain from treatment Understudied in randomized trials Heterogeneous group, multiple risk factors at play, potential for interactions High mortality Numerous comorbidities Tend to present late

9. FTT Collaborative Group. Lancet. 1994;343:311-322. 11 SD 3 (5 to 17) =0.0002 18 SD 4 (10 to 25) <0.00001 27 SD 5 (16 to 37) <0.00001 10 SD 13 (-16 to 36) NS Age (years) Benefit per 1000: 95% CI: 2 P: Mortality and the Use of FibrinolyticsAccording to Age Mortality and the Use of Fibrinolytics According to Age Percent Dead in Days 0-35

10. RR, risk reduction. Wilcox R, et al. Presented at 14th Annual Congress of the European Society of Cardiology; September 1992; Barcelona, Spain. Treated at 6-12 h P=0.02 Treated at  12-24 h P=0.60 Treated at 6-24 h P=0.07 RR = 14% RR = 26% RR = 5% Symptom Onset to Treatment (hours) 35-Day Mortality (%) Treatment of Patients Who Present Late

11. Summary: Reperfusion Underutilization Approximately 25% of eligible patients do not receive reperfusion therapy for AMI Predictors of underutilization –Absence of chest pain –Age >75 years –Presentation >3 hours after symptom onset