“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
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 37.90C, 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 S1 and S2 are heard without murmurs.
Lung fields are clear, distal pulses are normal and
no peripheral edema is present.
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.
Item 72 (Con’t)
•
Which of the following is the most
appropriate treatment?
A.
B.
C.
D.
Coronary artery bypass surgery
Intracoronary thrombolytic therapy
Medical therapy
Primary percutaneous coronary
intervention
STEMI Care and Time to
Treatment Goals
I IIa IIb III
A
2013 ACC/AHA
Guideline
• Primary PCI is the recommended method
of reperfusion when it can be performed in
a timely fashion by experienced operators.
JACC 2013;61:e1-63
STEMI Care and Time to
Treatment Goals
I IIa IIb III
A
2013 ACC/AHA
Guideline
• Reperfusion therapy should be
administered to all eligible patients with
STEMI with symptom onset within the prior
12 hours
JACC 2013;61:e1-63
STEMI Care and Time to
Treatment Goals
I IIa IIb III
B
2013 ACC/AHA
Guideline
• 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
JACC 2013;61:e1-63
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 S1 and S2
without an S3 and no murmurs. Lung fields are
clear.
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
V2 through V4 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.
MKSAP: Item 38
• Which of the following is the most
appropriate management?
A.
B.
C.
D.
Abciximab and thrombolytic therapy
Await the results of troponin and CK
Thrombolytic therapy
Transfer for primary PCI
STEMI Care and Time to
Treatment Goals
I IIa IIb III
B
2004 ACC/AHA
Guideline
• 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.
Circulation 2004;110:588-636
Door to Balloon Time for Transfer and Direct Arrival
Patients, National CV Data Registry (NCDR)
Am Heart J 2011;161:76-83
210
Time (Minutes)
180
Transfer PCI
150
120
Year
Target
Door to
Balloon
Time
Direct PCI
90
60
30
0
2005
QI
2005
Q3
2006
Q1
2006
Q3
2007
Q1
2007
Q3
Transfer and Direct PCI Door to Balloon Time
Percentage of Patients
Am Heart J 2011;161:76-83
50
90 minutes
40
Direct PCI = 79 min
(n=86,382)
63.4%
30
20
Transfer PCI = 149 min
(n=29,248)
10
9.7%
0
1
2
3
4
5
Door to Balloon Time (hours)
6
STEMI Care and Time to
Treatment Goals
I IIa IIb III
B
2013 ACCF/AHA
Guideline
• 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-PCIcapable hospital with a FMC-to-device
time goal of 120 minutes or less.
STEMI Patient, First Medical Contact
PCI Capable
Hospital
FMC* to
Device Time
≤90 mins
Cath Lab for
PCI
*FMC: First Medical
Contact
Door In Door
Out (DIDO)
≤30 mins
Non-PCI
Capable Hospital
FMC* to Device
Time ≤120 min
Transfer for
Primary PCI
JACC 2013;61:e1-63
Anticipated FMC*
to Device Time
≥120 min
Thrombolytic
Therapy within
30 mins
Acute Coronary Syndrome
Definition
A constellation of clinical symptoms
due to acute myocardial ischemia
Circulation 2011,123:e426-e579
Myocardial Infarction
Definition
Myocardial necrosis (or myocardial
cell death) due to prolonged
ischemia.
Third Universal Definition of MI
Circulation 2012,126:2020-2035
Causes of Acute Coronary Syndrome
• Atherosclerosis
• Congenital
- Anomalous origin
- Anomalous course
- Single artery
• Compression
- Muscle bridges
- Aortic aneurysm
• Drugs
- Sumatriptan
• Embolic
- Vegetations
- Ergot alkaloids
- Cocaine
- Tumor
- Calcium
• Aortic dissection
• Vasospasm
• Trauma
• Arteritis
• Intimal proliferation
- Fibromuscular hyperplasia
- Radiation
3 Major Causes of ACS
• Atherosclerosis
• Atherosclerosis
• Atherosclerosis
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;126:2020-2035
MI Type 1
Plaque Rupture
Healed Plaque
Erosion
Progressive Narrowing of the Arterial Lumen
Vessel
Lumen
Atherosclerotic
Vessel
Lipid Core
Progressive Narrowing
(Time)
Clot
Thrombotic
Occlusion
Plaque Rupture and Atherothrombosis
Vessel
Lumen
Lipid Core
Atherosclerotic
Vessel
Plaque
Rupture
Thrombus
Platelet
Adhesion
Activation and
Aggregation
Thrombus
Formation
Thrombotic
Occlusion
MI
Stroke
Am J Med 1996;101:199-209
Vascular Death
Most MI’s Arise From Smaller Stenoses
Baseline Study
Circulation 1988;78:1157-1166
Most MI’s Arise From Smaller Stenoses
13 Days Later
Circulation 1988;78:1157-1166
Most MI’s Arise From Smaller Stenoses
Baseline Study
Circulation 1988;78:1157-1166
Most MI’s Arise From Smaller Stenoses
2 months later
Circulation 1988;78:1157-1166
Most MI’s Arise From Smaller Stenoses
Circulation 1995;92:657-671
80
MI Patients (%)
68%
Asymptomatic
60
Symptomatic
40
18%
20
0
< 50%
50-70%
Percentage Stenosis
14%
> 70%
Acute Coronary Syndrome
Circulation 2002;105:2000-2004
PCI With Stent
Systemic Medical Therapy to
Stabilize Plaque
• Aspirin
• Clopidogrel/Prasugrel/Ticagrelor
• Statins
• ACE Inhibitors/ARBs
• Beta Blockers
• Smoking Cessation
Multiple Plaques in ACS
Circulation 2002;106:804-808
MI Patients (%)
40
79% of patients had >1 plaque ruptured
29%
30
25%
21%
20
12.5%
10
7.5%
4.5%
0
Culprit Lesion 1
2
3
4
5
Number of Ruptured Plaques in Addition to
Culprit Lesion Detected by IVUS
The Asymptomatic Progression of CAD
Initial Presentation
62%
MEN (65.8 years)
46%
WOMEN (70.4 years)
0
10
20
Levy D, Textbook of CV
Medicine 1998
30
40
ACS or Sudden
Cardiac Death
50
60
AHA: Heart Disease and Stroke
Statistics-2006 Update
70
Ventricular Fibrillation
Ventricular Fibrillation and Survival
Proportion Surviving
1.0
0.8
0.6
0.4
0.2
0
1
2
3
Minutes
4
5
6
7
8
9 10
Ventricular Fibrillation
Deaths due to Acute MI
• In-hospital mortality had improved
significantly
– 1960’s – prior to introduction of CCUs, inhospital mortality averaged ~25-30%.
– 1980’s – CCU, pre-reperfusion era ~16%
– 1990 - 2000’s – era of fibrinolysis, coronary
interventions, those who participated in
clinical trials, one month mortality is ~4-6%
Eur HJ 2208;29:2909-2945
Mortality in Acute MI
Pre-Hospital
Pre-Hospital
21%
8%
52%
19%
24
In In-Hospital
24HrsHours
Hospital
48HrsHours
48
In In-Hospital
Hospital
30Days
Days
30
One-half of all deaths occur “in the field” within one hour after symptom onset
Acute Coronary Syndrome
• ST elevation myocardial infarction
• Non-ST elevation myocardial infarction
• Unstable Angina
Hospitalizations in the US due to ACS
Acute Coronary Syndromes
1.57 Million Hospital Admissions
79%
UA/NSTEMI
21%
STEMI
0.33 million admissions
1.24 million admissions
0.57 million NSTEMI
Heart Disease and Stroke Statistics 2007 Update
Circulation 2007;115:69-171
0.67 million UA
ACC/AHA 2009 Joint STEMI/PCI
Guidelines Focused Update
Rates of Acute MI, 1999 - 2008
Incidence Rate
(No. of cases/100,000 per person-year)
300
JACC 2013;61e7
MI
250
200
Non-STEMI
150
100
STEMI
50
0
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008
Year
Acute Coronary Syndrome
• Typical Symptoms:
–Central chest pain
– Chest discomfort
– Chest pressure
– Chest tightness
– Heaviness
– Cramping or burning sensation
– Indigestion or heartburn
Call
911
Acute Coronary Syndrome
Symptoms of Acute MI
Hospitalized
Recommended
Discouraged
Call 911
Ambulance Transport
Self Transport
JACC 2008;51:210-247
Percentage of Patients with ACS Calling 911
• National Registry of MI -2
Emergency Medical System
53%
• Survey of confirmed ACS patients in
20 US communities
Emergency Medical System
10-48% (23%)
Driven by someone else
60%
Drove themselves
16%
Circulation May, 2011 e440
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
– Third heart sound
– Basal rales
Acute Coronary Syndrome
Symptoms of Acute MI
Ambulance
Self Transport
12-Lead ECG
Hospital/ED
Obtained and Interpreted <10 mins
12 Lead-ECG
JACC 2008;51:210-247
Hospitalizations in the US due to ACS
Acute Coronary
Syndrome
1.57 Million Hospital Admissions
79%
UA/NSTEMI
21%
STEMI
1.24 million
0.33 million
Admissions per year
Admissions per year
Heart Disease and Stroke Statistics 2007 Update
Circulation 2007;115:69-171
ACC/AHA 2009 Joint STEMI/PCI
Guidelines Focused Update
Acute Coronary Syndromes
Pathophysiology
Large
Fissure
Lipid Pool
Occlusive thrombus
(ST Elevation MI)
Macrophages
Stress, tensile,
internal
Shear forces,
external
Atherosclerotic
plaque
Small
Fissure
Fissure
Plaque
rupture
Mural thrombus
(unstable angina/
non-ST elevation MI)
Thrombus
Fuster V et al. NEJM. 1992; 326: 310-318.
Davies MJ et al. Circulation. 1990; 82 (Suppl II): II-38, II-46.
TIMI Flow Grade
TIMI 0
Complete Occlusion
TIMI 1
Penetration of obstruction by
contrast but no distal perfusion
TIMI 2
Perfusion of entire artery but
delayed flow
TIMI 3
Full perfusion, normal flow
Myocardial Ischemia
Blood Supply
TIMI 0 Flow
Oxygen Demand
Heart Rate
Blood Pressure
Inotropicity
ST elevation = coronary artery is completely occluded
= TIMI 0 blood flow
ST Elevation MI
Circulation 1992;85;2311-2315
100
Benefit (%)
80
60
“Time is Muscle”
40
20
0
1
2
3
Hours
4
5
6
7
8
9 10
11 12
The 12-Lead ECG
The 12-lead ECG is the only modality that
can best identify the presence of a
completely occluded coronary artery
Diagnostic and Therapeutic Pathways in Patients
With and Without ST-Segment Elevation
Acute Coronary Syndrome
ECG
ST Elevation
Thrombolysis, PCI
No ST Elevation
Aspirin, clopidogrel,
UFH or LMWH, 2B/3A
antagonists
-blockers, nitrates
Hamm CW et al. Lancet. 2001;358:1533-1538.
2002 ACC/AHA UA/NSTEMI Guideline Update. Available at: www.acc.org
Normal ECG
Acute Coronary Syndrome
ST Elevation MI
Acute Coronary Syndrome
ASA
Chest Pain
Aspirin
• Give ASA as soon as possible unless there is GI
bleed or patient is allergic to aspirin
• Dose 162 - 325 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;50:652-726
Acute Coronary Syndrome
ASA
Chest Pain
NTG
Arrival in ED
ECG within 10 minutes
ST Elevation
NTG
NTG
NTG
ST Segment Elevation
Baseline ECG
ST Segment Elevation
After NTG
ST Segment Elevation
Baseline ECG
After NTG
ST Segment Elevation
Baseline
ST Segment Elevation
After NTG
ST Segment Elevation
Baseline
After NTG
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;50:652-726
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 <90 mm Hg or there is a drop of
>30 mm Hg below baseline BP
– Bradycardia of <50 beats per minute
– Tachycardia of >100 beats per minute
– Suspected right ventricular MI
JACC 2007;50:652-726
ST Elevation MI
ASA
Chest Pain
NTG
ECG within 10 minutes
ST Elevation
Self-Transport:
Door to Needle
<30 mins
EMS Transport:
<30 mins
Thrombolytic Therapy
NTG
NTG
NTG
Self-Transport:
Door to Balloon
<90 mins
EMS transport:
<90 mins
Primary PCI
Acute Inferior MI
Thrombolytic Therapy
Post Thrombolytic Therapy
One Hour Later
Initial ECG
Thrombolysis: One Hour Later
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
Contraindications to Thrombolysis
Relative Contraindications
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
•
•
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
Lives Saved per Thousand
Thrombolytic Therapy and Mortality
According to Admission ECG
Lancet 1994;343:311-322
60
50
49%
40
37%
30
20
8%
10
-14%
0
-10
BBB
Anterior ST
Elevation
Inferior ST
Elevation
Admission ECG
ST Depression
ST Elevation Criteria for STEMI
• ≥1 mm any 2 adjacent standard leads
• In V2 and V3:
– 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;53:982-991
Fibrinolytic Agents
Patency Rate
90 min TIMI 2 or 3
Fibrin-specific
● Tenecteplase (TNK-tPA)
85%
● Reteplase (rPA)
84%
● Alteplase (tPA)
73-84%
Non-fibrin-specific
● Streptokinase
60-68%
(No longer marketed in the US)
JACC 2013;61e78-140
ST Elevation MI
ASA
Chest Pain
NTG
ECG within 10 minutes
ST Elevation
Self-Transport:
Door to Needle
<30 mins
EMS Transport:
<30 mins
Thrombolytic Therapy
NTG
NTG
NTG
Self-Transport:
Door to Balloon
≤90 mins
EMS transport:
≤90 mins
Primary PCI
AMI: Post PCI
ST Segment Elevation
Admission
Post PCI
STEMI PCI: National CV Data Registry
In hospital mortality of 43,801 patients with STEMI
undergoing PCI: JACC 2009;54:2205-2241
P <0.001
Mortality
10
8.4%
7.0%
5.6%
5
4.3%
3%
3.5%
30
mins
60
mins
90
mins
120
mins
150
mins
180
mins
Delay in Reperfusion in Minutes
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
PCI Vs Thrombolytic Therapy:
Short Term Outcomes
25
P<0.0001
PCI
Frequency (%)
20
Thrombolytic Therapy
P<0.0001
15
P=0.0002
10
P=0.0003 P<0.0001
P=0.0004
5
0
Death
Death Non-fatal Recurrent Total
Excluding
Ischemia Stroke
MI
SHOCK
Lancet 2003;361:13-20
data
Death, nonfatal reinfarction or
stroke
PCI Vs Thrombolytic Therapy:
Long Term Outcomes
50
P<0.0001
PTCA
Frequency (%)
40
Thrombolytic Therapy
P<0.0001
30
P=0.0019
20
P=0.0053 P<0.0001
Data Not
Available
10
0
Death
Death
Excluding
SHOCK
data
*
*
Non-fatal Recurrent Total
MI
Lancet
Death, nonfatal reIschemia Stroke
infarction or
2003;361:13-20 stroke
Options for Transport of Patients With STEMI and Initial
Reperfusion Treatment
Hospital fibrinolysis:
Door-to-Needle
within 30 min.
Not PCI
capable
Onset of
symptoms of
STEMI
9-1-1
EMS
Dispatch
• Encourage 12-lead ECGs.
• Consider prehospital fibrinolytic if
capable and EMS-to-needle within
30 min.
GOALS
5
min.
Patient
8
min.
EMS
InterHospital
Transfer
EMS on-scene
PCI
capable
EMS Transport
Prehospital fibrinolysis
EMS transport
EMS-to-needle EMS-to-balloon within 90 min.
within 30 min.
Dispatch
1 min.
Golden Hour = first 60 min.
Patient self-transport
Hospital door-to-balloon
within 90 min.
Total ischemic time: within 120 min.
Antman EM, et al. J Am Coll Cardiol 2008. Published ahead of print on December 10, 2007. Available at
http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001.
Coronary Angioplasty VS Fibrinolytic Therapy in Acute
Myocardial Infarction
Fibrinolysis
Door-to-Needle or
FMC to Needle
< 30 mins
Not PCI
capable
EMS Transport
PCI
Door-to-Balloon or FMC
to Balloon ≤ 90 mins
PCI
capable
Coronary Angioplasty VS Fibrinolytic Therapy in Acute
Myocardial Infarction
DIDO
2004 STEMI
Guideline
30 mins
PCI
Not PCI
capable
Door-to-Balloon or FMC
to Balloon ≤ 90 mins
EMS Transport
PCI
Door-to-Balloon or FMC
to Balloon ≤ 90 mins
PCI
capable
2013 STEMI
Guideline
PCI
Door-to-Balloon or FMC
to Balloon ≤ 120 mins
One Year Cardiac Mortality (%)
Mortality and Ejection Fraction
50
< 20%
N = 799
40
Mean EF = 46%
30
20
20-39%
10
40-59%
> 60%
0
0
10
20
30
40
50
60
70
Radionuclide Ejection Fraction (%)
80
STEMI: Standard Therapy
• Thrombolytic Agent or PCI
• Aspirin
• Heparin
• Clopidogrel
• Beta Blockers within 24 hours
• ACE Inhibitors or ARB’s within 24 hours
• Aldosterone antagonists for EF ≤40%
• Statins before hospital discharge