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“Acute Coronary Syndrome” July 24, 2013. Item 72 A 78 year old man is evaluated in the ED with chest pain. The patient reports that the pain, which is.

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Presentation on theme: "“Acute Coronary Syndrome” July 24, 2013. Item 72 A 78 year old man is evaluated in the ED with chest pain. The patient reports that the pain, which is."— Presentation transcript:

1 “Acute Coronary Syndrome” July 24, 2013

2 Item 72 A 78 year old man is evaluated in the ED with chest pain. The patient reports that the pain, which is present in the left substernal area, began at rest, and has been present for 12 hours. He reports no similar episodes of chest pain. Medical history is significant for hypertension and a 30-pack year history of ongoing tobacco use. His only medication is nifedipine. On PE, temperature is C, BP 130/80 mm Hg, pulse rate is 72/minute and respiration rate is 12/min. BMI is 28. A normal carotid upstroke without carotid bruits is noted, jugular venous pulsations are normal and S 1 and S 2 are heard without murmurs. Lung fields are clear, distal pulses are normal and no peripheral edema is present.

3 Item 72 (Con’t) Serum creatinine kinase level is 500 units/L and troponin I level is 26 ng/mL. Lab findings are otherwise normal. EKG shows sinus rhythm at 70/min; 2 mm ST-segment elevation in leads II, III and aVF; and 1 mm ST segment depression in leads V2 and V3. He is taken to the cardiac cath lab and found to have single vessel coronary disease with severe stenosis of the proximal left anterior descending coronary artery.

4 Item 72 (Con’t) Which of the following is the most appropriate treatment? A.Coronary artery bypass surgery B.Intracoronary thrombolytic therapy C.Medical therapy D.Primary percutaneous coronary intervention

5 STEMI Care and Time to Treatment Goals Primary PCI is the recommended method of reperfusion when it can be performed in a timely fashion by experienced operators. I A IIaIIbIII 2013 ACC/AHA Guideline JACC 2013;61:e1-63

6 STEMI Care and Time to Treatment Goals Reperfusion therapy should be administered to all eligible patients with STEMI with symptom onset within the prior 12 hours I A IIaIIbIII 2013 ACC/AHA Guideline JACC 2013;61:e1-63

7 STEMI Care and Time to Treatment Goals Reperfusion therapy is reasonable for patients with STEMI within the prior 12 to 24 hours who have clinical and/or ECG evidence of ongoing ischemia. Primary PCI is the preferred strategy in this population I B IIaIIbIII 2013 ACC/AHA Guideline JACC 2013;61:e1-63

8 Item 38: MKSAP A 54 year old man is evaluated in the ED for acute coronary syndrome that began 30 minutes ago. He has type 2 diabetes mellitus and hypertension. He reports no history of bleeding or stroke. He has a remote history of peptic ulcer disease for which he takes no medications. Medications are lisinopril and glipizide. On physical exam, he is afebrile, BP is 160/90 mm Hg, pulse rate is 80 and respiration 12/min. CV examination reveals a normal S 1 and S 2 without an S 3 and no murmurs. Lung fields are clear.

9 MKSAP: Item 38 Serum troponin and creatinine kinase levels are pending. Hematocrit is 42% and platelet count is 220,000/  L EKG shows 3 mm ST segment elevation in leads V 2 through V 4 and a 1 mm ST segment depression in leads II, III and aVF. A chest radiograph is normal. There is no cardiac cath lab present at the hospital and it would take approximately 1.5 hours to transfer the patient to the closest facility that performs PCI.  -blockers, unfractionated heparin, clopidogrel and aspirin are initiated.

10 MKSAP: Item 38 Which of the following is the most appropriate management? A.Abciximab and thrombolytic therapy B.Await the results of troponin and CK C.Thrombolytic therapy D.Transfer for primary PCI

11 STEMI Care and Time to Treatment Goals If the symptom duration is within 3 hours and the expected door to balloon time minus the expected door to needle time is: – Within 1 hour, primary PCI is preferred – Greater than 1 hour, fibrinolytic therapy is generally preferred. I B IIaIIbIII 2004 ACC/AHA Guideline Circulation 2004;110:

12 Door to Balloon Time for Transfer and Direct Arrival Patients, National CV Data Registry (NCDR) Time (Minutes) Year QI Am Heart J 2011;161: Q Q Q Q Q3 Transfer PCI Direct PCI Target Door to Balloon Time

13 Transfer and Direct PCI Door to Balloon Time Percentage of Patients Door to Balloon Time (hours) minutes Direct PCI = 79 min Transfer PCI = 149 min 9.7% 63.4% (n=86,382) (n=29,248) Am Heart J 2011;161:76-83

14 STEMI Care and Time to Treatment Goals Immediate transfer to a PCI-capable hospital for primary PCI is recommended strategy for STEMI patients who initially arrive at or are transported to a non-PCI- capable hospital with a FMC-to-device time goal of 120 minutes or less. I B IIaIIbIII 2013 ACCF/AHA Guideline

15 STEMI Patient, First Medical Contact PCI Capable Hospital FMC* to Device Time ≤90 mins Non-PCI Capable Hospital *FMC: First Medical Contact Anticipated FMC* to Device Time ≥120 min Thrombolytic Therapy within 30 mins FMC* to Device Time ≤120 min Cath Lab for PCI Door In Door Out (DIDO) ≤30 mins Transfer for Primary PCI JACC 2013;61:e1-63

16 Acute Coronary Syndrome Definition A constellation of clinical symptoms due to acute myocardial ischemia Circulation 2011,123:e426-e579

17 Myocardial Infarction Definition Myocardial necrosis (or myocardial cell death) due to prolonged ischemia. Circulation 2012,126: Third Universal Definition of MI

18 Causes of Acute Coronary Syndrome Congenital Embolic Vasospasm Trauma Compression - Muscle bridges - Aortic aneurysm Drugs - Sumatriptan - Ergot alkaloids - Cocaine Arteritis Aortic dissection Intimal proliferation - Fibromuscular hyperplasia - Radiation Atherosclerosis - Anomalous origin - Anomalous course - Single artery - Vegetations - Tumor - Calcium

19 3 Major Causes of ACS Atherosclerosis Atherosclerosis Atherosclerosis

20 Types of Myocardial Infarction Type 1: Spontaneous MI due to plaque rupture, ulceration, fissuring, erosion, etc. Type 2: MI secondary to an ischemic imbalance Type 3: MI resulting in death and biomarkers are unavailable Type 4a: MI related to PCI Type 4b: MI related to stent thrombosis Type 5: MI related to CABG Circulation 2012;126:

21 MI Type 1

22 Plaque Rupture

23 Healed Plaque

24 Erosion

25

26 Atherosclerotic Vessel Thrombotic Occlusion Progressive Narrowing of the Arterial Lumen Lipid Core Vessel Lumen Progressive Narrowing (Time) Clot

27 Atherosclerotic Vessel Plaque Rupture Platelet Adhesion Activation and Aggregation Thrombus Formation Thrombotic Occlusion MI Stroke Vascular Death Plaque Rupture and Atherothrombosis Lipid Core Vessel Lumen Am J Med 1996;101: Thrombus

28 Circulation 1988;78: Baseline Study Most MI’s Arise From Smaller Stenoses

29 Circulation 1988;78: Days Later Most MI’s Arise From Smaller Stenoses

30 Circulation 1988;78: Baseline Study Most MI’s Arise From Smaller Stenoses

31 Circulation 1988;78: months later Most MI’s Arise From Smaller Stenoses

32 MI Patients (%) < 50%50-70% > 70% Percentage Stenosis 68% 18% 14% Circulation 1995;92: Symptomatic Asymptomatic

33 Acute Coronary Syndrome Circulation 2002;105: PCI With Stent Systemic Medical Therapy to Stabilize Plaque Aspirin Clopidogrel/Prasugrel/Ticagrelor Statins ACE Inhibitors/ARBs Beta Blockers Smoking Cessation

34 Multiple Plaques in ACS MI Patients (%) Culprit Lesion2 3 Number of Ruptured Plaques in Addition to Culprit Lesion Detected by IVUS 21% 25% 12.5% Circulation 2002;106: % 7.5% 4.5% 45 79% of patients had >1 plaque ruptured

35 The Asymptomatic Progression of CAD Initial Presentation Levy D, Textbook of CV Medicine 1998 WOMEN (70.4 years) MEN (65.8 years) ACS or Sudden Cardiac Death 46% 62% AHA: Heart Disease and Stroke Statistics-2006 Update

36 Ventricular Fibrillation

37 Ventricular Fibrillation and Survival Proportion Surviving Minutes

38 Ventricular Fibrillation

39 Deaths due to Acute MI In-hospital mortality had improved significantly –1960’s – prior to introduction of CCUs, in- hospital mortality averaged ~25-30%. –1980’s – CCU, pre-reperfusion era ~16% – ’s – era of fibrinolysis, coronary interventions, those who participated in clinical trials, one month mortality is ~4-6% Eur HJ 2208;29:

40 Mortality in Acute MI Pre-Hospital 52% 24 Hours In-Hospital 48 Hours In-Hospital 30 Days 21% 19% 8% One-half of all deaths occur “in the field” within one hour after symptom onset

41 Acute Coronary Syndrome ST elevation myocardial infarction Non-ST elevation myocardial infarction Unstable Angina

42 Hospitalizations in the US due to ACS Acute Coronary Syndromes 1.57 Million Hospital Admissions 0.33 million admissions1.24 million admissions Heart Disease and Stroke Statistics 2007 Update Circulation 2007;115: million UA 0.57 million NSTEMI 79% 21% STEMI UA/NSTEMI ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update

43 Rates of Acute MI, Incidence Rate (No. of cases/100,000 per person-year) Year JACC 2013;61e7 300 STEMI Non-STEMI MI

44 Acute Coronary Syndrome Typical Symptoms: –Central chest pain –Chest discomfort –Chest pressure –Chest tightness –Heaviness –Cramping or burning sensation –Indigestion or heartburn Call 911

45 Acute Coronary Syndrome Symptoms of Acute MI Call 911 Ambulance Transport Self Transport Recommended Discouraged Hospitalized JACC 2008;51:

46 Percentage of Patients with ACS Calling 911 National Registry of MI -2 53% Survey of confirmed ACS patients in 20 US communities Emergency Medical System10-48% (23%) Emergency Medical System Driven by someone else60% Drove themselves 16% Circulation May, 2011 e440

47 Acute Coronary Syndrome Physical signs: –No physical signs diagnostic of Acute MI –Activation of autonomic nervous system Pallor Sweating Hypotension or narrow pulse pressure Irregularities in heart rate, bradycardia, tachycardia –Basal rales –Third heart sound

48 Acute Coronary Syndrome Symptoms of Acute MI Ambulance JACC 2008;51: Self Transport 12 Lead-ECG Hospital/ED Obtained and Interpreted <10 mins 12-Lead ECG

49 Hospitalizations in the US due to ACS Acute Coronary Syndrome 1.57 Million Hospital Admissions UA/NSTEMI STEMI 1.24 million Admissions per year 0.33 million Admissions per year Heart Disease and Stroke Statistics 2007 Update Circulation 2007;115: % 21% ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update

50 Pathophysiology Fuster V et al. NEJM. 1992; 326: Davies MJ et al. Circulation. 1990; 82 (Suppl II): II-38, II-46. Lipid Lipid PoolMacrophages Stress, tensile, internal Shear forces, external Atherosclerotic plaque Fissure Plaque rupture Large Fissure Small Fissure Mural thrombus (unstable angina/ non-ST elevation MI) Occlusive thrombus (ST Elevation MI) Thrombus Acute Coronary Syndromes

51 TIMI Flow Grade TIMI 0 Complete Occlusion TIMI 1 TIMI 2 TIMI 3 Penetration of obstruction by contrast but no distal perfusion Perfusion of entire artery but delayed flow Full perfusion, normal flow

52 Myocardial Ischemia Heart Rate Oxygen Demand Blood Supply Blood PressureInotropicity ST elevation = coronary artery is completely occluded TIMI 0 Flow = TIMI 0 blood flow

53 ST Elevation MI Benefit (%) Hours “Time is Muscle” Circulation 1992;85;

54 The 12-Lead ECG The 12-lead ECG is the only modality that can best identify the presence of a completely occluded coronary artery

55 Diagnostic and Therapeutic Pathways in Patients With and Without ST-Segment Elevation Hamm CW et al. Lancet. 2001;358: ACC/AHA UA/NSTEMI Guideline Update. Available at: Acute Coronary Syndrome ECG ST Elevation Thrombolysis, PCI Aspirin, clopidogrel, UFH or LMWH, 2B/3A antagonists  -blockers, nitrates No ST Elevation

56 Normal ECG

57 Acute Coronary Syndrome ST Elevation MI

58 Acute Coronary Syndrome Chest Pain ASA

59 Aspirin Give ASA as soon as possible unless there is GI bleed or patient is allergic to aspirin Dose mg one dose Aspirin should be chewable or soluble If patient cannot take ASA due to nausea or GI disorder, use ASA suppositories Other than ASA, do not make the mistake of giving NSAID such as Motrin, Naprosyn, Celebrex, etc since NSAID increases mortality, re-infarction, myocardial rupture, CHF, and HBP JACC 2007;50:

60 Acute Coronary Syndrome ST Elevation NTG Chest Pain ECG within 10 minutes ASA NTG Arrival in ED

61 ST Segment Elevation Baseline ECG

62 ST Segment Elevation After NTG

63 ST Segment Elevation Baseline ECG After NTG

64 ST Segment Elevation Baseline

65 ST Segment Elevation After NTG

66 ST Segment Elevation After NTG Baseline

67 Nitroglycerin For relief of chest pain, give NTG up to 3 doses at 3-5 minute intervals until pain is relieved or blood pressure is low Dose of NTG is 0.4 mg sublingual tablet or spray JACC 2007;50:

68 Nitroglycerin Do not give if: –Taking PDE Inhibitors for erectile dysfunction sildenafil (Viagra, Revatio) 24 h taladafil (Cialis, Adcirca) 48 h vardenafil (Levitra) ? –Systolic BP 30 mm Hg below baseline BP –Bradycardia of <50 beats per minute –Tachycardia of >100 beats per minute –Suspected right ventricular MI JACC 2007;50:

69 ST Elevation MI ST Elevation NTG Primary PCI EMS transport: <90 mins Self-Transport: Door to Needle <30 mins EMS Transport: <30 mins Self-Transport: Door to Balloon <90 mins Chest Pain Thrombolytic Therapy ECG within 10 minutes ASA NTG

70 Acute Inferior MI Thrombolytic Therapy

71 Post Thrombolytic Therapy One Hour Later

72 Initial ECG Thrombolysis: One Hour Later

73 Thrombolysis No contraindication to thrombolysis Best results within 2 hours after onset of symptoms Hemodynamically stable: –Not in cardiogenic shock or CHF or with mechanical complications of AMI

74 Absolute Contraindications Any prior ICH Known structural cerebral vascular lesion (AVM) Known malignant intracranial neoplasm (primary/metastatic) Ischemic stroke within 3 months Suspected aortic dissection Active bleeding or bleeding diathesis (excluding menses) Closed head or facial trauma within 3 months Relative Contraindications History of chronic severe, poorly controlled hypertension Severe uncontrolled hypertension (SBP >180 mm Hg or DBP >110 mm Hg) History of prior ischemic stroke >3 mos, dementia or IC pathology Traumatic or prolonged (>10 mins) CPR or major surgery <3 weeks Recent (2-4 weeks) internal bleeding Pregnancy Active peptic ulcer Current use of anticoagulants Contraindications to Thrombolysis

75 Thrombolytic Therapy and Mortality According to Admission ECG Lives Saved per Thousand BBB Anterior ST Elevation Inferior ST Elevation 49% 37% 8% Lancet 1994;343: % ST Depression Admission ECG

76 ST Elevation Criteria for STEMI ≥1 mm any 2 adjacent standard leads In V 2 and V 3 : –Males <40 years of age ≥2.5 mm for males ≥40 years of age ≥2.0 mm for males –Females (any age) ≥1.5 mm ST elevation is measured at the J point JACC 2009;53:

77

78

79 Fibrinolytic Agents Fibrin-specific JACC 2013;61e ● Tenecteplase (TNK-tPA) ● Reteplase (rPA) ● Alteplase (tPA) Non-fibrin-specific ● Streptokinase Patency Rate 90 min TIMI 2 or 3 85% 84% 73-84% 60-68% (No longer marketed in the US)

80 ST Elevation MI ST Elevation NTG Primary PCI EMS transport: ≤90 mins Self-Transport: Door to Needle <30 mins EMS Transport: <30 mins Self-Transport: Door to Balloon ≤90 mins Chest Pain Thrombolytic Therapy ECG within 10 minutes ASA NTG

81

82 AMI: Post PCI

83 ST Segment Elevation Admission Post PCI

84 STEMI PCI: National CV Data Registry In hospital mortality of 43,801 patients with STEMI undergoing PCI: JACC 2009;54: mins 60 mins 3% 3.5% 4.3% 90 mins 120 mins 5.6% mins 7.0% 180 mins 8.4% Mortality Delay in Reperfusion in Minutes P <0.001

85 Primary PCI vs IV Thrombolytic Therapy for Acute MI: Review of 23 Randomized Trials 23 randomized clinical trials with 7739 patients with STEMI –Thrombolytic therapy = 3867 –Primary PCI = 3872 Results: Primary PCI was better than thrombolytic therapy at reducing short-term and long-term death, non-fatal reinfarction, stroke and combined endpoint of death, non-fatal reinfarction and stroke Conclusion: Primary PCI is more effective than thrombolytic therapy for the treatment of STEMI Lancet 2003;361:13-20

86 PCI Vs Thrombolytic Therapy: Short Term Outcomes Frequency (%) Death P= P= Death Excluding SHOCK data P< Non-fatal MI P< Recurrent Ischemia Thrombolytic Therapy PCI P= Total Stroke Death, non- fatal re- infarction or stroke P< Lancet 2003;361:13-20

87 PCI Vs Thrombolytic Therapy: Long Term Outcomes Frequency (%) Death P= P= Death Excluding SHOCK data P< Non-fatal MI P< Recurrent Ischemia Thrombolytic Therapy PTCA Data Not Available Total Stroke Death, non- fatal re- infarction or stroke P< Lancet 2003;361:13-20 **

88 Options for Transport of Patients With STEMI and Initial Reperfusion Treatment EMS Transport Onset of symptoms of STEMI EMS Dispatch EMS on-scene Encourage 12-lead ECGs. Consider prehospital fibrinolytic if capable and EMS-to-needle within 30 min. GOALS PCI capable Not PCI capable Hospital fibrinolysis: Door-to-Needle within 30 min. EMS Triage Plan Inter- Hospital Transfer Golden Hour = first 60 min.Total ischemic time: within 120 min. PatientEMS Prehospital fibrinolysis EMS-to-needle within 30 min. EMS transport. EMS-to-balloon within 90 min. Patient self-transport Hospital door-to-balloon within 90 min. Dispatch 1 min. 5 min. 8 min. Antman EM, et al. J Am Coll Cardiol Published ahead of print on December 10, Available at

89 PCI capable Fibrinolysis Door-to-Needle or FMC to Needle < 30 mins Coronary Angioplasty VS Fibrinolytic Therapy in Acute Myocardial Infarction EMS Transport PCI Door-to-Balloon or FMC to Balloon ≤ 90 mins Not PCI capable

90 PCI capable Not PCI capable Coronary Angioplasty VS Fibrinolytic Therapy in Acute Myocardial Infarction EMS Transport PCI Door-to-Balloon or FMC to Balloon ≤ 90 mins 2004 STEMI Guideline PCI Door-to-Balloon or FMC to Balloon ≤ 90 mins 2013 STEMI Guideline PCI Door-to-Balloon or FMC to Balloon ≤ 120 mins DIDO 30 mins

91 Mortality and Ejection Fraction One Year Cardiac Mortality (%) Radionuclide Ejection Fraction (%) < 20% N = 799 Mean EF = 46% > 60% 40-59% 20-39%

92 STEMI: Standard Therapy Thrombolytic Agent or PCI Aspirin Beta Blockers within 24 hours ACE Inhibitors or ARB’s within 24 hours Aldosterone antagonists for EF ≤40% Statins before hospital discharge Heparin Clopidogrel

93


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