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*CHAIRMAN QMMC INTERNAL MEDICINE CHAIRMAN CLINICAL CARDIOLOGY DIVIISION, PHILIPPINE HEART CENTER
Kurt Glenn C. Jacoba*, MD, MHSA FPCP, FPCC, FPSCCII, FACC, FAHA
ST-elevation MI
15-20%
Chase SL, et.al.: Pharmacological Considerations In Acute Coronary Syndrome (ACS): An Expert Debate. Pharmacy and Therapeutics Vol 32(3):Suppl 1; March 2007
Endothelium
A Model of Risk Stratification Based on a Representative Panel of Molecular and Genetic Factors
Platelet Fn Inflammatory State Atherosclerotic Plaque Gene Profile Adipocyte Products
vWF Circulating EPCs Endothelial Cells CD40/CD40L P-Selectin CRP/CD40 MPO IL-18 MMPs/?PAPP-A FLAP/LTA4 Adinopectin TNF- VEGF PAI-1 IL-6
ACS
Endothelial Dysfunction
Endothelial + Dysfunction
Inflammation
vWF = Von Wille-brand factor fn = platelet function EPC = endothelial progenitor C-reactive protein CRP = cell
MPO = myeloperoxidase IL = interleukin TNF- = tumor necrosis factor alpha FLAP = 5-lipoxygenase activating proteinendothelial growth factor MMP = matrix metalloproteinases VEGF = vascular pathway PAPP-A = pregnancy-associated LTA4 = leukotriene A4 pathway plasminogen activator inhibitor PAI-1 = plasma protein A
Anwaruddin, S et al, Redefining Risk in Acute Coronary Syndromes Using Molecular Medicine. J Am Coll Cardiol 2007; 49:279-89
25%
75%
Antman EM, et al.: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). 2004.
Factors that lead to ACS ENVIRONMENTAL FACTORS Occupation, income, lifestyle Medical care availability
NATURAL HISTORY OF ACUTE CORONARY SYNDROME ASYMPTOMATIC Natural Course of ACS PHASE 50 years Death STEMI Non-STEMI Unstable angina Elevated/ Not elevated markers of myocardial necrosis Acute cardiac ischaemia with or w/o ST segment elevation Thrombus formation with or w/o embolisation
HOST FACTORS Age men: >45y women: >55 y Familial disposition History of Coronary Artery Disease Genetic predisposition Concomittant medical illness
Plaque disruption
Early Pathogenesis
Convalescence or death
PREPATHOGENESIS PERIOD
PERIOD OF PATHOGENESIS
PERIOD OF PATHOGENESIS
EARLY DIAGNOSIS & TREATMENT DISABILITY LIMITATION REHABILITATION
Medical Therapy
Mechanopharmacolgical Lifestyle modification approaches Thrombolytics Percutaneous Coronary Intervention Coronary Artery Bypass Graft
Primary Prevention
Secondary Prevention
Tertiary
NSTEMI
STEMI
Partial occlusion, Complete occlusion sufficient to cause tissue damage & mild myocardial necrosis ST depression +/- T wave inversion No Q wave Elevated ST-elevation New LBBB Q wave Elevated
ECG
Non-specific
Cardiac markers
Normal
Anderson JL, et al.. ACC/AHA 2007 guidelines for the management of patients with unstable angina/nonST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/NonST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, American College of Physicians, Society for Academic Emergency Medicine, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2007;50:e1157.
Anderson JL, et al.. ACC/AHA 2007 guidelines for the management of patients with unstable angina/nonST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/NonST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, American College of Physicians, Society for Academic Emergency Medicine, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2007;50:e1157.
Conservative
CABG = coronary artery bypass graft surgery; GRACE = Global Registry of Acute Coronary Events; HF = heart failure; LVEF = left ventricular ejection fraction; PCI = percutaneous coronary intervention; TIMI = Thrombolysis In Myocardial Infarction; TnI = troponin I; TnT = troponin T
Anderson JL, et al.. ACC/AHA 2007 guidelines for the management of patients with unstable angina/nonST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/NonST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, American College of Physicians, Society for Academic Emergency Medicine, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2007;50:e1157.
Algorithm for the management of patients with unstable angina or non-ST elevation myocardial infarction.
UA/NSTEMI ASA, enoxaparin or heparin, -block., nitrates, clopidogrel Risk stratify Low risk
Lower risk Stress test High risk Not high risk Negative
High/Intermediate risk Coronary arteriography LMCD, 3VD + LV dysfunction or diabetes mellitus CABG 1 or 2 VD, suitable for PCI IIb/IIIa inhibitors PCI Discharge on ASA, clopidogrel, statin, ACE-I Normal Consider alternative diagnosis
Superior Yield of the New strategy of Enoxaparin, Revasculariation and Glycoprotein IIb/IIIa inhibitors
Relative Risk of Outcomes With Early Invasive Versus Conservative Therapy in UA/NSTEMI
FRISC-II = FRagmin and fast Revascularization during InStability in Coronary artery disease ICTUS = Invasive versus Conservative Treatment in Unstable coronary Syndromes ISAR-COOL = Intracoronary Stenting with Antithrombotic Regimen COOLing-off study RITA-3 = Third Randomized Intervention Treatment of Angina trial TIMI-18 = Thrombolysis In Myocardial Infarction-18 TRUCS = Treatment of Refractory Unstable angina in geographically isolated areas without Cardiac Surgery VINO = Value of first day angiography/angioplasty in evolving Non-ST segment elevation myocardial infarction
Relative Risk of All-Cause Mortality for Early Invasive Therapy Compared With Conservative Therapy at a mean follow-up of 2 years
Relative Risk of Recurrent Nonfatal Myocardial Infarction for Early Invasive Therapy Compared With Conservative Therapy at a mean follow-up of 2 years
Relative Risk of Recurrent Unstable Angina Resulting in Hospitalization for Early Invasive Therapy Compared With Conservative Therapy at a mean follow-up of 13 months
Weaver WD and Block P: Is There a Conservative Strategy for NSTEMI? American College of Cardiology. February 2006.
TRIAL
Treat angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Ischemia 18
NEJM 2001;344:1879-1887
2220
Value of first day angiography/angioplasty In evolving Non-ST segment elevation myocardial infarction, an Open multicenter randomized trial
European Heart Journal 2002;23:230-238
131
1810
TRIAL
2287
Endpoints
INV (%) 2.4 5.1 8.6 16.2 7.8 9.4 7.8 1.9
CONS (%) 2.5 5.7 10.0 18.1 14.1 12.1 10.1 2.9
Nonfatal MI 6-wk exercise tolerance test Total (primary end point) No. of patients rehospitalized within 6 wk
Positive After
FRISC II
or MI MI alone Death
TACTICS-TIMI 18
At 6 months Primary endpoint Death or nonfatal MI Death Fatal or nonfatal MI Rehospitalization for ACS At 6 months Primary endpoint (death/reinfarction) at 6 months Mortality in the first day angiography group Non-fatal Reinfarction At 4 months Death, MI, or refractory angina At 1 year
VINO
RITA-3
9.6
14.5
0.001
TRIAL
Endpoints
ICTUS
Rehospitalization
COURAGE
At 4.6 year Primary-event Composite of Death, MI and stroke Hospitalization for ACS MI
STEMI
Major components of time delay between onset of symptoms from ST-elevation MI and restoration of flow in the infarct artery.
Antman EM, et al.: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). 2004.
1 -1l 9 st l Ca ll fa Ca
EMS on-scene EMS Encourage12-lead ECGs Triage Consider prehospital fibrinolytic if Plan capableand EMS-to-needle within 30 min
Goals
Patient 5 min after symptom onset Dispatch 1 min EMS on scene Within 8 min
EMS transport
Prehospital fibrinolysis: EMS-to-Neddle within 30 min
Antman EM, et al.: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). 2004.
Fibrinolysis
Rescue
Receiving Hospital
PCI or CABG
Primary PCI
Antman EM, et al.: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). 2004.
2.
3.
4.
Braunwald E, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non ST-segment elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina).
Mild/moderate resting LV dysfunction (LVEF 0.35-0.49) Intermediate-risk treadmill score (-11 < score <5) Stress-induced moderate perfusion defect without LV dilation or increased lung intake (thallium-201) Limited stress echocardiographic ischemia with a wall motion abnomality only at higher doses of dobutamine
3.
Braunwald E, et al. ACC/AHA 2002 guideline update for the management of patients with unstable angina and non ST-segment elevation myocardial infarction: a report of the American College of Cardiology/ American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina).
Low-risk treadmill score (score 5) Normal or small myocardial perfusion defect at rest or with stress Normal stress echocardiographic wall motion or no change of limited resting wall motion abnormalities during stress
Absolute contraindications Prior intracranial hemorrhage Structural cerebral vascular lesion Malignant intracranial neoplasm Ischemic stroke w/in 3 mo. EXCEPT acute ischemic stroke w/in 3 h Suspected aortic dissection Active bleeding or bleeding diathesis Significant closed head or facial trauma w/in 3 mo.
4 9 3 7
-1 4
BBB ANT ST Elevation INF ST Elevation ST DEP
BBB=bundle-branch block; ANT ST Elevation=anterior ST-segment elevation; INF ST Elevation=Inferior STsegment elevation; ST DEP= ST-segment depression
Antman EM, et al.: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction). 2004.
High risk from STEMI Contraindications to fibrinolysis including risk of bleeding and ICH Late presentation Diagnosis of STEMI is in doubt
Provides a greater chance for restoring blood flow and stabilization of the infarct artery compared to thrombolysis The expanded latitude of temporal benefit may mitigate the logical constraints Stents enhance the durability of the procedure The promise for evolution of the science of microcirculatory and
Coronary Artery Bypass Graft Surgery Effective in relieving symptoms Improved survival in certain subsets Ability to achieve complete revascularization Wider applicability (anatomical Cost Morbidity
PCI VS CABG
TRIAL N Endpoints PCI (%) 73.8 90 42 26.7 CABG (%) 87.8 79 21 6.6 p Arterial Revascularization 1205 At 1 year Rate of event-free survival Therapy Study Rate of freedom from angina Use of antianginal medications At 3 years Repeat revascularization OCTOSTENT 280 At 1 year Event-free survival Total mortality Cardiac death 988 At median follow-up of 2 years Required additional revascularization Death or QWMI Death 450 First 30 days Major adverse cardiac events: Death, Q-wave MI, repeat revascularization or stroke Mean follow-up 18.5 months Survival rate Free from MI Repeat revascularization <0.001 <0.001 <0.001 0.0001
85.5 0 0 21 9 5
Stent or Surgery
ERACI II
3.6
12.3
0.002
Short-term clinical outcomes of patients in 23 randomized trials of primary angioplasty versus thrombolysis
20
15
For every 1,000 patients treated, PTCA compared with lytic therapy: 20 lives saved 43 re-MI prevented 13 ICH prevented
P = 0.0003
P < 0.0001
Percentage
10
P = 0.0003
P < 0.0001
Angioplasty Thrombolysis