Jonathan D. Marmur, MD, FACC Professor of Medicine Director, Cardiac Catheterization and Interventional Cardiology. State University of New York

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STEMI Management 2007 Jonathan D. Marmur, MD, FACC Professor of Medicine i Director, Cardiac Catheterization and Interventional Cardiology Health Science Center at Brooklyn State University of New York 917-885-8854 8854 1

Pathophysiology of ACS ~ 2.0 MM patients admitted to CCU or telemetry annually 06MM 0.6 ST-segment elevation MI 14MM 1.4 Non-ST-segment elevation ACS

The EKG is based on the string galvanometer invented in 1901 in Leiden, The Netherlands Willem Einthoven In 1924, Einthoven was awarded the Nobel Prize in Medicine Einthoven W. Un nouveau galvanometre. Arch Neerl Sc Ex Nat 1901;6:625 ARCHIVES NEERLANDAISES DES SCIENCES EXACTES ET NATURELLES

NSTEMI vs STEMI

1980;303:897-902 Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction MA DeWood, J Spores, R Notske, LT Mouser, R Burroughs, MS Golden, and HT Lang To define the prevalence of total coronary occlusion in the hours after transmural myocardial infarction, we used coronary arteriography to study the degree of coronary obstruction in 322 patients admitted within 24 hours of infarction. Total coronary occlusion is frequent during the early hours of transmural infarction and decreases in frequency during the initial 24 hours, suggesting that coronary spasm or thrombus formation with subsequent recanalization or both may be important in the evolution of infarction.

ASA vs Placebo in ISIS-II: II: Odds of Vascular Death Astrological Gemini/Libra (n=1442) Birthsign All Others (n=7157) Odds ratio and 95% CI Play of chance Unrecognized randomization error True effect Prior MI Yes No Diabetic Yes No Sex Male Female Age <60 60-69 70+ Systolic BP <100 100-149 150-175 Heart Rate <60 60-99 100+ EKG BBB IMI AMI ST ALL PATIENTS (9.4 vs 11.8% mortality) 23% When in a trial with a clearly positive result many subgroups are considered, false negative results in some particular subgroups must be expected It is clear that the best estimate of the real effect is given by the overall results derived from all subgroups combined. Modified from: ISIS-2 Lancet 1988 Aug 13;2(8607):349-60 0.5 ASA better 1 Placebo better 1.5

Oral Anti-platelet Agents Sites of Action

Mo ortality (% %) 7 6 5 4 3 2 1 COMMIT: Effect of Clopidogrel on Death in Hospital Placebo + ASA: 1846 deaths (8.1%) Clopidogrel + ASA: 1728 deaths (7.5%) 7% (SE3) relative risk reduction (2P=.03) 0 0 7 14 21 28 Time (d Since Randomization [ 28 d) Adapted with permission from COMMIT Collaborative Group. Lancet. 2005;366:1607-1621.

CLARITY TIMI TIMI 28: Primary Endpoint Occluded Artery (or Death/MI Through Angio/HD) rtery or Death/MI (% %) 25 20 15 10 36% 21.7 Odds Reduction 15.0 Odds Ratio: 0.64 (95% CI, 0.53-0.76) P=.001 Oc ccluded A 5 0 n=1752 n=1739 Clopidogrel Placebo 0.4 0.6 0.8 1.0 1.2 1.6 Clopidogrel Better Placebo Better Sabatine MS et al N Engl J Med 2005;352:1179-1189

ST Elevation Myocardial Infarction (STEMI) 8 6 Relationship Between Time to Reperfusion and Mortality: GUSTO-IIb 6.4 p=0.001 30-day mortality (%) 4 3.7 4 2 1 0 < 60 61 75 76 90 > 91 N: 104 109 76 140 Time to PTCA (minutes) Berger et al. Circulation 1999;100:14

Wavefront Theory of Myocardial Loss 100 80 60 40 20 100 80 60 40 20 0 0 40 min 3h 6h 24h 96h 0 3h 6h 24h Duration of occlusion Time post-occlusion Reimer et al Circulation 1977;56:786-94

19 Randomized Trials of PCI vs Lysis N = 5,066 12% 10% 10.0% Lysis PCI vent rate E 8% 6% 4% 2% 0% p=.0019 76% 7.6% 6.7% p=.0053 4.8% 72% 7.2% p<.0001 2.9% Death Death (excl shock) Reinfarction Keeley, Grines; Lancet 2003

19 Randomized Trials of PCI vs Lysis N = 5,066 3% Lysis PCI 2.2% vent rate E 2% 1% 1.3% P<0.0001 p=0.0002 0.8% 0% 008% 0.08% Hemorrhagic stroke Total stroke Keeley, Grines; in press

DANAMI-2: Patient Flow ST- elevation MI (n=1,900) Randomize 100 mg accelerated t-pa PCI (+ stent)

DANAMI-2 DENMARK 5.4 mill. inhabitants t 5 PCI centers 24 referral hospitals 62% of the Danish population Transport distance up to 95 US miles (mean 35 miles) 100 US miles

DANAMI-2: Primary Results (%) Death / MI / Stroke 16% 12% 8% 4% 14% Combined P=0.0003 RRR 45% 8% Transfer Sites P=0.002 16% 16% 14% 12% 8% 4% RRR 40% 9% 12% 8% 4% Non-Transfer Sites P=0.048 12% RRR 45% 7% 0% 0% 0% Lytic Primary PCI Lytic Primary PCI Lytic Pi Primary PCI

2007;99:1384 1388 Mortality with PCI with different delays to therapy compared with immediate thrombolytic therapy. A patient s baseline mortality risk, assuming treatment with thrombolytic therapy at 30 minutes (x axis), is presented. A 70-year-old patient s expected mortality with PCI at different ECG-to-needle times for a given baseline risk (multiple solid lines) is displayed, with prediction intervals (gray areas). Patients at low risk (baseline mortality risk 5%) have similar mortality outcomes regardless of delay. When delay to therapy is short (e.g., ECG-to-needle time 90 minutes), the degree of benefit increases with increasing baseline risk. However, when delay to therapy is longer (e.g., ECG-to-needle time 150 minutes), increasing baseline risk is associated with a higher probability of harm. At an ECG-to-needle time of 130 minutes (representing a PCI-related delay of 100 minutes compared with thrombolysis), mortality outcomes are expected to be roughly similar with either form of reperfusion across the spectrum of baseline risk.

Monday, November 13, 2006, 12:01 a.m. CT The American College of Cardiology and Partners Launch National Alliance To Reduce Door-to-Balloon (D2B) Times D2B alliance aims to save time and lives CHICAGO - The American College of Cardiology (ACC), together with the American Heart Association (AHA) and other key national healthcare organizations, announces the launch of its latest quality campaign, Door to Balloon (D2B): An Alliance for Quality. A Guidelines Applied in Practice (GAP) Program, the D2B campaign is aimed at improving the timeliness of lifesaving therapy for patients with heart attacks at the nation s hospitals that perform emergency angioplasty. Previously published guidelines developed by the ACC and the AHA recommend that hospitals treating STEMI patients with percutaneous coronary intervention (PCI) should reliably achieve a door-to-balloon time of 90 minutes or less. However, accomplishing this level of performance is an organizational challenge and many patients are not treated within the guideline recommendation

Six Evidence-Based Strategies Adopted at SUNY Downstate Having ED physicians activate cath lab. Using a single call to activate the cath lab. Having the cath-lab team arrive and be ready within 20 to 30 minutes. Providing real-time data feedback Having commitment from management. Using a team-based approach spanning multiple departments. Percent of C ases 120 100 80 60 40 20 0 Door to Balloon Time Within Guidelines 100 75 43 0 Y 2004 Y 2005 Y 2006 Y 2007 <90 min as of 3rd Q 2006

Treatment Delays Prehospital assessment ED care Those associated with the cath lab Transport

2007;99:1360 1363 We developed a protocol empowering paramedics to identify and directly triage patients with STEMI to a prealerted PCI hospital. This study assessed time to PCI and in-hospital mortality using this protocol compared with other patterns of arrival. Paramedics were educated in EKG criteria for STEMI. Medtronic LIFEPAK 12 defibrillators were used to obtain an initial EKG on all field patients with suspected MI. Paramedic identified patients with STEMI were transported directly to a PCI hospital ED, often bypassing closer, referring hospitals. The PCI ED triage personnel, upon receipt of the paramedic alert, activated t the cath lab team.

2007;99:1360 1363

Inclusion ST-segment elevation Myocardial infarction (MI), with any mention of location or combinations of locations (e.g., anterior, apical, basal, inferior, lateral, posterior, or combination), IF DESCRIBED AS ACUTE/EVOLVING (e.g., posteriorami ) Q wave AMI Q wave MI, IF DESCRIBED AS ACUTE/EVOLVING ST ST abnormality consistent with injury, infarct, or acute/evolving MI ST changes consistent t with injury, infarct, or acute/evolving MI ST consistent with injury, infarct, or acute/evolving MI ST-elevation (STE) ST-elevation myocardial infarction (STEMI) ST-segment noted as.10mv ST-segment noted as 1 mm Transmural AMI Transmural MI, IF DESCRIBED AS ACUTE/EVOLVING Left bundle branch block (LBBB) Intraventricular conduction delay of LBBB type Variable LBBB Exclusion ST-segment elevation Non Q wave MI (NQWMI) Non ST-elevation MI (NSTEMI) ST clearly described as confined to ONE lead ST described as minimal, <.10mV, <1 mm, non-diagnostic, or non-specific inall leads noted to have ST-elevation ST-elevation clearly described as confined to ONE lead ST-elevation described as minimal, <.10mV, < 1 mm, nondiagnostic, or nonspecific in ALL leads noted to have STelevation ST-elevation due to early repolarization ST-elevation due to left ventricular hypertrophy (LVH) ST-elevation due to normal variant ST-elevation with mention of pericarditis ST-elevation with mention of Pit Printzmetal/Printzmetal's tl/pit tl' variant ST-segment elevation, or any of the other ST-segment elevation inclusion terms, described using one of the negative modifiers or qualifiers listed in Appendix H, Table 2.6, Qualifiers and Modifiers Table ST-elevation elevation, or any of the other STsegment elevation inclusion terms, with mention of pacemaker/pacing (unless atrial only) Left bundle branch block (LBBB) Incomplete left bundle branch block (LBBB) Intraventricular conduction block Intraventricular conduction delay(ivcd) Left bundle branch block (LBBB), or any of the other left bundle branch block inclusion terms, described using one of the negative modifiers or qualifiers listed in Appendix H, Table 2.6, Qualifiers and Modifiers Table Left bundle branch block (LBBB), or any of the other left bundle branch block inclusion terms, with mention of pacemaker/pacing (unless atrial only)

Definitions Definition: A percutaneous coronary intervention (PCI) is considered non-primary when it is used for reasons that are not emergent in nature. Non-primary PCIs include elective, rescue, and salvage PCIs. In contrast, a primary PCI is the use of a percutaneous reperfusion procedure in the acute phase of ST-segment elevation MI (usually within 12 hours or less from the onset of ischemic symptoms) with the goal of restoring blood flow to the affected myocardium, thereby improving outcomes including reduced mortality rates.

Reasons for Delay System reasons for delay are not acceptable, regardless of any linkage to the timing of PCI/reperfusion. ο Equipment-related (e.g., unavailability, malfunction) ο Staff-related (e.g., waiting for cath lab staff) ο Participation in clinical trial (e.g., waiting for trials coordinator) ο Consultation with other clinician ο Cath lab unavailability (e.g., no open cath lab) The linkage between a non-system reason and the timing/delay of PCI/reperfusion/cath/transfer to cath lab must be made clear somewhere in the medical record. Abstractors should NOT make inferences from documentation of a sequence of events alone or otherwise attempt to interpret from documentation. Clinical judgment should not be used in abstraction.

Reasons for Delay Examples of ACCEPTABLE documentation: H Hold on PCI. Will do TEE to r/o aortic dissection. Patient waiting for family and clergy to arrive wishes to consult with them before PCI. Pt. presented to ER in full cardiac arrest. ACLS protocol instituted. Unable to do PCI until patient stable. He had to be defibrillated several times prior to transfer to cath lab. SVG Angiojet cath did not cross lesion. XMI catheter successfully crossed the stenosis. Flow reestablished after 30 min. delay. PCI delayed due to intermittent hypotensive episodes when crossing lesion. o Note: Initial patient/family refusal of PCI/reperfusion/cath/transfer to cath lab is an acceptable reason for delay and does NOT need to be linked to the timing/delay in PCI.

Reasons for Delay Examples of UNACCEPTABLE documentation: Patient is discussing PCI with family. (Effect on timing/delay of PCI not documented) Patient developed v fib and cardiorespiratory arrest. Defib x 2, intubated. To cath lab for PCI. (Linkage to timing/delay of PCI not clear Abstractor should not infer from sequence of events) ST-elevation on initial ECG resolved. Chest pain now recurring. To cath lab for PCI. (Linkage to timing/delay of PCI not clear requires clinical judgment) Cath contraindicated too high risk. (Effect on timing/delay of PCI not documented) d) PCI not indicated. (Effect on timing/delay of PCI not documented) During the Angiojet thrombectomy, the patient had bradycardia which required pacing. (Effect on timing/delay i of PCI not documented) d) If unable to determine whether a documented reason is system in nature, or if physician/apn/pa documentation does not establish a linkage between event(s)/condition(s) and the timing/delay in PCI/reperfusion/cath/transfer to cath lab, select No.

False Positive STEMI

True Positive STEMI

Reciprocal Changes Wall Affected Leads Showing ST Segment Elevation Leads Showing Reciprocal ST Segment Depression Septal V1, V2 None LAD Anterior V3, V4 None LAD Anteroseptal eosepa V1, V2, V3, V4 None LAD Anterolateral Extensive anterior (Sometimes called Anteroseptal with Lateral extension) V3, V4, V5, V6, I, avl V1,V2,V3, V2 V3 V4, V5, V6, I, avl II, III, avf II, III, avf Suspected Culprit Artery LAD, or CIRC Left Main Inferior II, III, avf I, avl RCA or CIRC Lateral I, avl, V5, V6 II, III, avf CIRC Posterior (Usually associated with Inferior or Lateral but can be isolated) Right Ventricular (Usually associated with Inferior) V7, V8, V9 V1,V2,V3, V4 PDA II, III, avf, V1, V4R http://en.wikipedia.org/wiki/myocardial_infarction I, avl RCA

IMI due to OM1 (old total RCA); patent LAD

IMI due to proximal RCA occlusion; patent LAD

Algorithm for EKG Identification of the Infarct Related Artery in Anterior MI Zimetbaum et al NEJM 2003;348:933-940

Algorithm for EKG Identification of the Infarct Related Artery in IMI Zimetbaum et al NEJM 2003;348:933-940

The Evolution of Optimal Myocardial Infarction Therapy 1955-2000 Eisenhower Year: 1955 2000 Cheney Therapy: Morphine Angioplasty/Stent Heparin Heparin Warfarin Aspirin Atropine Abciximab Clopidogrel pd β-blocker Statin Bd Bed Rest: 7 Weeks < 2 Days Expected Mortality: 30% < 5%