Transcript CHEST PAIN/ACUTE MI

CHEST PAIN/ACUTE MI
Sati Adlakha
Cardiovascular Disease Fellow
July 22nd, 2009
Disclosures
• None
Objectives
• Review the pathophysiology of angina
• Review the differential diagnosis of chest
pain
• Review current medical strategies at
reducing morbidity and mortality in ACS
• Review current invasive techniques for
reducing morbidity and mortality in ACS
CHEST PAIN
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Musculoskeletal pain
Coronary heart disease
Aortic dissection
Valvular heart disease
Pericarditis
Myocarditis
Stress-induced cardiomyopathy
Cardiac syndrome X
CHEST PAIN
• Gastroesophageal reflux disease
• Esophageal rupture, mediastinitis, and
foreign bodies
• Medication-induced esophagitis
• Acute pulmonary thromboembolism
• Pneumonia
• Psychogenic
• Coronary inflammation
MECHANISM OF ANGINA
Ischemia
Acidemia, Loss of the normal ATP sodiumpotassium pump, Loss of myocardial
membrane integrity, and the release of
chemical substances
lactate, serotonin, bradykinin, histamine,
reactive oxygen species, and adenosine
Platelets (serotonin, thromboxane A2, and 5hydroxytyrptamine)
Angina
A1 adenosine receptor
sympathetic afferent
sympathetic ganglia
(C7-T4)
Ascending spinothoracic pathways to the
medial and lateral thalamus
Cortex
ANGINA
PATHOPHYSIOLOGY OF ANGINA
Heart rate
Preload
Myocardial oxygen demand
Afterload
Contractility
ANGINA
Oxygen carrying capacity of the blood
Myocardial oxygen supply
oxygen unloading from hemoglobin
coronary artery blood flow
Coronary Blood Flow
Coronary artery diameter and tone
Collateral blood flow
Coronary Perfusion pressure
Heart rate (Diastolic filling period)
Conditions provoking or exacerbating ischemia
Increased oxygen
demand
Decreased oxygen supply
Non-cardiac
Anemia
Hyperthermia
Non-cardiac
Hypoxemia
Pneumonia
Hyperthyroidism
Asthma
Sympathomimetic toxicity (eg,
cocaine use)
Chronic obstructive pulmonary disease
Hypertension
Interstitial pulmonary fibrosis
Anxiety
Obstructive sleep apnea
Arteriovenous fistulae
Sickle cell disease
Pulmonary hypertension
Sympathomimetic toxicity (eg, cocaine use)
Cardiac
Hypertrophic cardiomyopathy
Aortic stenosis
Dilated cardiomyopathy
Hyperviscosity
Polycythemia
Leukemia
Thrombocytosis
Hypergammaglobulinemia
Tachycardia
Cardiac
Ventricular
Aortic stenosis
Supraventricular
Hypertrophic cardiomyopathy
Reproduced with permission from: ACC/AHA/ACP Guidelines for the Management of Patients with
Chronic Stable Angina. J Am Coll Cardiol 1999; 33:2092. Copyright ©1999 American College of Cardiology.
The Normal Artery
• Composed of three layers:
– Adventitia
– Media
– Intima
Hospitalizations in the U.S. Due to
ACS
Acute Coronary
Syndromes*
1.57 Million Hospital Admissions - ACS
UA/NSTEMI†
STEMI
1.24 million
0.33 million
Admissions per year
Admissions per year
*Primary and secondary diagnoses. †About 0.57 million NSTEMI and 0.67 million UA.
Heart Disease and Stroke Statistics – 2007 Update. Circulation 2007; 115:69–171.
Acute Coronary Syndrome
Thrombus
occluding
Lumen
Plaque:
Lipid core
Pathophysiology of STEMI
vs. NSTEMI/UA
• STEMI:
– Complete coronary occlusion
– So-called “red clot” – erythrocyte- and fibrinrich
• NSTEMI/UA:
– Incomplete coronary occlusion
– So-called “white clot” – platelet-rich
Ischemic Discomfort
Acute Coronary Syndrome
Presentation
Working Dx
ECG
Cardiac
Biomarker
Final Dx
No ST Elevation
ST Elevation
Non-ST ACS
UA
NSTEMI
Unstable
Angina
Myocardial Infarction
NQMI
Qw MI
Libby P. Circulation 2001;104:365, Hamm CW, Bertrand M, Braunwald E, Lancet 2001; 358:1533-1538; Davies MJ. Heart 2000; 83:361-366.
Anderson JL, et al. J Am Coll Cardiol. 2007;50:e1-e157, Figure 1. Reprinted with permission.
Classifications
• Characterization of chest pain symptoms:
Canadian Cardiovascular Society (CCS)
Angina Classification
Stable vs. Unstable Angina
Characteristics of Unstable Angina:
Timing of Release of Various Biomarkers
After Acute Myocardial Infarction
Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3 rd ed. Rochester, MN:
Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:773–80.
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5.
UA/NSTEMI
STEMI
Oxygen/Nitrates
• Given to patients with O2 levels less than
90%
• Nitrates are contraindicated in
hypotension, RV infarct, Severe AS and
after erectile dysfunction meds.
BETA BLOCKERS
Chadda, K, Goldstein, S, Byington, R, et al, Circulation 1986;73:503.
ASA
• Research on Instability in Coronary Artery
Disease (RISC)
• Lancet. 1990;336:827-30
• Oral aspirin (75 mg/day) reduced the risk of MI
and death (57-69%) at 1 year
• Same data supported in 3 more randomized
trials
Antiplatelet Trialists’
Collaboration
•Meta-analysis of randomized trials of antiplatelet therapy for
prevention of death, MI, and stroke in high-risk patients
•195 trials and > 143,000 pts
•22% ↓ in odds of vascular death, MI, or stroke with antiplatelet
therapy across broad spectrum of clinical presentations that
included UA/NSTEMI
•Similar ↓ in odds of vascular events with ASA doses of 75-1500 mg
daily; < 75 mg benefit ↓; dose-dependent ↑ bleeding*
* Yusuf S, et al. N Engl J Med 2001;345:494–502 (bleeding analysis from CURE trial).
Antiplatelet Trialists’ Collaboration. BMJ 1994;308:81–106. Antithrombotics Trialists’ Collaboration. BMJ 2002; 324:71– 86.
ISIS - 2
Randomised trial of intravenous streptokinase, oral
aspirin, both, or neither among 17,187 cases of
suspected acute myocardial infarction: ISIS-2.
ISIS-2 (Second International Study of Infarct
Survival) Collaborative Group
Lancet 1988 Aug 13;2(8607):349-60
ASA
ISIS-2
• 804 deaths (9.4%) with aspirin vs. 1016
(11.8%) with placebo (23% odds
reduction; SD = 4; 2p <0.00001)
• Aspirin significantly reduced nonfatal
reinfarction (1.0% vs. 2.0% in the placebo
group) and nonfatal stroke (0.3% vs.
0.6%)
Clopidogrel
SYNERGY Primary Outcomes
1.0
14.5
14
14
12
10
UFH
Enoxaparin
8
6
Freedom from Death/MI
16
0.95
0.9
0.85
Enoxaparin
UFH
4
0.8
0
2
5
10
15
20
25
30
Days from Randomization
0
Death or MI
at 30 d
Absolute Risk Reduction
Hazard Ratio
95% CI
p
Kaplan Meier Curve
0.5
0.96
0.86–1.06
0.40
Reprinted with permission from Ferguson JJ, et al. JAMA 2004;292:45–54.
Primary End Point (ITT)
Death or Nonfatal MI
Primary End Point (%)
15
UFH
12
12.0%
17% RRR
9
9.9%
ENOX
Relative Risk
0.83 (0.77 to 0.90)
P<0.0001
6
3
Lost to follow up = 3
0
0
5
10
15
Days
20
25
30
Glycoprotein IIb/IIIa Inhibitors
• Consider in high risk patients
• (eptifibatide)
• Those undergoing an early invasive
therapy
• No benefit of starting prior to
revascularization in STEMI or with
thrombolytics
Variables Used in the TIMI Risk Score
•Age ≥ 65 years
•At least 3 risk factors for CAD
•Prior coronary stenosis of ≥ 50%
•ST-segment deviation on ECG presentation
•At least 2 anginal events in prior 24 hours
•Use of aspirin in prior 7 days
•Elevated serum cardiac biomarkers
The TIMI risk score is determined by the sum of the presence of the above 7 variables at admission. 1 point is given for each variable.
Primary coronary stenosis of 50% or more remained relatively insensitive to missing information and remained a significant predictor of
events. Antman EM, et al. JAMA 2000;284:835–42.
TIMI = Thrombolysis in Myocardial Infarction.
TIMI Risk Score
TIMI 11B and ESSENCE
TIMI
Risk
Score
All-Cause Mortality, New or Recurrent MI, or Severe
Recurrent Ischemia Requiring Urgent Revascularization
Through 14 Days After Randomization %
0-1
4.7
2
8.3
3
13.2
4
19.9
5
26.2
6-7
40.9
Reprinted with permission from Antman EM, et al. JAMA 2000;284:835–42. Copyright © 2000, American Medical Association. All Rights reserved.
The TIMI risk calculator is available at www.timi.org.
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Table 8.
TIMI = Thrombolysis in Myocardial Infarction.
GRACE Risk Score
Variable
Odds ratio
Older age
1.7 per 10 y
Killip class
2.0 per class
Systolic BP
1.4 per 20 mm Hg ↑
ST-segment deviation
2.4
Cardiac arrest during presentation
4.3
Serum creatinine level
1.2 per 1-mg/dL ↑
Positive initial cardiac biomarkers
1.6
Heart rate
1.3 per 30-beat/min ↑
The sum of scores is applied to a reference monogram to determine the corresponding all-cause mortality from hospital discharge to 6 months.
Eagle KA, et al. JAMA 2004;291:2727–33. The GRACE clinical application tool can be found at www.outcomes-umassmed.org/grace. Also see
Figure 4 in Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157.
GRACE = Global Registry of Acute Coronary Events.
Selection of Initial Treatment Strategy: Initial
Invasive Versus Conservative Strategy
Invasive
Recurrent angina/ischemia at rest with low-level activities despite
intensive medical therapy
Elevated cardiac biomarkers (TnT or TnI)
New/presumably new ST-segment depression
Signs/symptoms of heart failure or new/worsening mitral regurgitation
High-risk findings from noninvasive testing
Hemodynamic instability
Sustained ventricular tachycardia
PCI within 6 months
Prior CABG
High risk score (e.g., TIMI, GRACE)
Reduced left ventricular function (LVEF < 40%)
Conservative Low risk score (e.g., TIMI, GRACE)
Patient/physician presence in the absence of high-risk features
STEMI
• Thrombolytics vs PCI
• PCI has been found to be superior to lytics in
multiple trials
• PAMI
• Cadillac
• DANAMI-2
• STOPAMI
• STAT
Thrombolytics
Mortality Benefit