Transcript Acute Myocardial Infarction

Acute Myocardial Infarction
Willis E. Godin, D.O.
South Jersey Heart Group
Lourdes Cardiology Services
Acute Coronary Syndrome
(ACS)

Refers to the array of clinical signs and
symptoms produced by acute
myocardial ischemia
 Unstable angina
 Non-ST-segment-elevation
 ST-segment-elevation MI

MI
Each condition shares common
pathophysiologic origins related to the
instability and rupture of artherosclerotic
vulnerable plaques
Unstable angina and NSTEMI
Differentiated one from the other by
primarily by their severity
 Whether the ischemia is prolonged
enough to lead to structural myocardial
damage and to the release of
detectable markers of myocardial injury

 Troponin
I (TnI)
 Troponin T (TnT)
 Creatine kinase (CK)-MB
Coronary heart disease
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Major cause of morbidity and death in the
United States
Affecting approximately 16 million Americans
Someone in the US experiences a coronary
event every 25 seconds, and someone dies
from a coronary event every minute.
More than 1.4 million hospitalizations for ACS
in the US each year
Direct and indirect costs of CHD are
estimated to be more than $165 billion in
2009 alone
Pathophysiology

Unstable angina and NSTEMI result
from a disparity between myocardial
oxygen delivery and demand, which
usually presents as angina occurring
with limited physical activity or at rest (a
crescendo pattern).
Demand-and-delivery mismatch
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Associated with UA/NSTEMI
Can occur because of dynamic obstruction
from:
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Intense arterial spasm
Progressive, severe, flow-limiting atherosclerosis
due to intimal hyperplasia or to lipid, calcium, and
thrombus deposition, or to fibrointimal hyperplasia
after PCI
 Coronary artery dissection
 Conditions that alter myocardial oxygen demand
or supply, such as intense emotion, tachycardia,
or uncontrolled systemic hypertension (secondary
MI)
Pathophysiology
The most frequent mechanism of
ischemia during limited physical activity
or at rest is a primary reduction of the
myocardial oxygen supply due to
rupture or ulceration of a vulnerable
atherosclerotic plaque
 Results in endothelial injury and
associated thrombosis and dynamic
vasoconstriction
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Pathophysiology

Plaque fissure or rupture exposes the highly
thrombogenic subendothelium to circulating
platelets and white blood cells, which in turn
activates the coagulation cascade
 The resultant platelet adhesion and
aggregation at the site of plaque disruption
leads to transient thrombosis or subtotal
coronary artery occlusion with dynamic
vasoconstriction
 Activated platelets release powerful
promoters of vasoconstriction and platelet
aggregation, including thromboxane A2,
serotonin, adenosine diphosphate, and
platelet-activating factor
Plaque Rupture
Can occur in mildly or severely
stenosed coronary arteries
 Often occurs in arteries where the
atherosclerotic lesions previously had
caused only mild-to-moderate
obstruction

Duration of ischemia

The duration of ischemia caused by the
platelet-fibrin thrombi and severe dynamic
vasoconstriction determines the overall
clinical picture.
 If ischemia is neither severe nor prolonged
(usually <20min) and oftern occurs at rest,
patients are given a diagnosis of UA
 If ischemia lasts longer than 30 minutes and
is associated with elevated cardiac markers,
the diagnosis of MI is made
 Further classification as STEMI or NSTEMI is
made on the basis of electrocardiographic
findings.
Pathophysiology

Patients with UA/NSTEMI remain at high risk
for a new infarction and its sequelae,
including sudden cardiac death, until the
endothelial injury is repaired
 UA, NSTEMI, and STEMI represent a
pathophysiologic continuum
 This concept has led to the development of
effective pharmacologic therapies that, used
in conjunction with careful and rapid riskassessment strategies and catheter-based
therapies, improve outcomes in UA/NSTEMI
patients.
Atherosclerosis

Progressive in nature
 Chronic inflammatory and multifocal disease
involving medium- and large-sized arteries
 May begin in the subendothelium as early as
in the 1st decade of life
 Usually develops in lesion-prone vascular
areas that exhibit underlying endothelial
dysfunction as a response to chronic,
multifactorial injury to the arterial wall
Endothelial injury
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Flow shear stress
Hypertension
Immune-complex deposition and complement
activation
Smoking
Diabetes mellitus
Aging
Substance abuse
Infection
Mechanical injury (coronary angioplasty, stent
placement, heart transplantation)
Endothelial Dysfunction
A process regarded as a precursor to
the development of vascular disease
 Characterized by disruption of vesselwall homeostasis, which is signified by
decreased vasodilation, increased
vasoconstriction, increased oxidative
stress and inflammation, deregulation of
thrombosis and fibrinolysis, abnormal
smooth-muscle-cell proliferation, and a
deficient repair mechanism.

Diagnosis & Risk Stratification
Early risk stratification is vital in the
timely diagnosis and treatment of ACS
 Assessment of patients with suspected
ACS should include:
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 Clinical
history
 Physical examination
 12 lead ECG
 Biochemical marker measurement
 Noninvasive risk stratification
Clinical History
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A thorough clinical history is of utmost
importance in the initial evaluation and
treatment of patients with suspected ACS
 Typical symptoms of ACS include chest pain
or discomfort that may or may not radiate to
the arm, back, neck, jaw, or epigastrium
 Women and elderly patients are more likely to
present with atypical features, such as
shortness of breath, weakness, diaphoresis,
nausea, and lightheadness
Physical Examination
Findings of patients with suspected
ACS are often normal
 Attention must be paid to the presence
of complications of ACS:
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 Acute
LV failure
 Hypotension
 S3 gallop
 New or worsening mitral regurgitation
 Pulmonary edema
Electrocardiography
Plays an important role in initial
assessment, emergency treatment,
prognostication, and subsequent
decision-making regarding the definitive
treatment of patients with suspected
ACS
 High specificity for diagnosing STEMI
 Remains test of 1st choice
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Electrocardiography
Complete (>90%) occlusion of the
coronary arteries alters the electrical
potentials of the epicardial surface and
usually manifests itself as ST-segment
elevation in 2 or more adjacent leads
 ST-segment depression associated with
UA/NSTEMI is transient and dynamic.
Its appearance is usually flat or downsloping
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Biochemical markers
When ischemia is prolonged enough to
produce myocardial necrosis, the
integrity of the myocytic membrane is
lost
 Cardiac enzymes and other substances
then leak into the peripheral blood, and
their elevated levels in the bloodstream
are indicative of acute myocardial
infarction (AMI)
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Biochemical markers
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Cardiac troponins: gold standard of
biomarkers for establishing a diagnosis
of AMI
 Previously,
elevated levels of CK and its
cardiac-specific isoform CK-MB were used
to make a diagnosis of AMI
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Any elevation in the circulating levels of
these biomarkers may provide a clinical
distinction between UA and NSTEMI
Cardiac Troponins
Excellent independent markers of shortterm and long-term prognoses
 Risk of death within the first 42 days is
directly proportional to cardiac troponin
levels, and the prognostic information is
independent of other clinical and
electrocardiographic risk factors
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Cardiac Troponins
Detectable in the serum 4-12 hours
after onset of myocardial necrosis
 Peak 12-48 hours from symptom onset
 Serial sampling, including the
acquisition of a baseline sample and a
follow-up sample 8-12 hours after
symptom onset, is recommended
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Risk Stratification
Clinical features, ECG, and cardiac
troponin levels are fairly insensitive for
immediately ruling out ACS
 It is important to reliably stratify patients
who are at high or low risk of an MI and
who are likely to have adverse events in
the near future
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 TIMI score
 PURSUIT score
 GRACE score
TIMI risk score
TIMI IIB trial
 Primary endpoint was the composite of
all-cause death, new or recurrent MI, or
severe recurrent ischemia that prompts
urgent revascularization by day 14
 Simple 7-point score that can be
calculated easily at the bedside
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Treatment strategies
Initial treatment: Invasive vs.
Conservative
 Despite the debate, it is now widely
accepted that the initial medical therapy
for patients with suspected ACS should
include relieving the ischemia and
preventing further myocardial damage
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Treatment strategies
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How clinicians go about this is largely
dictated by the initial risk assessment and
continued patient monitoring in a controlled
environment
 Hemodynamically unstable patients with
refractory ischemic pain are monitored in a
critical care environment and are taken to the
cardiac catheterization laboratory as soon as
possible
 Most patients’ conditions stabilize after a brief
period of medical therapy at which time they
can be further triaged according to ACS
guidelines
Nitrates
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Endothelium-independent vasodilatory effects
on the coronary and peripheral vascular beds
Dilate venous capacitance vessels and
peripheral arterioles
Decrease preload and afterload
Lead to decrease in both myocardial wall
stress and oxygen demand
Relieve coronary spasm in atherosclerotic
vessels and increase oxygen delivery to the
subendocardial region that is supplied by the
severely narrowed coronary artery
Nitrates
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ISIS-4 and GISSI-3 studies
No survival benefit or decrease in recurrent
myocardial infarction
 Should be used in patients who have
refractory ischemic discomfort
 Contraindicated:
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Patients who have taken sildenafil, tadalafil, or
vardenafil in the previous 24 hours
Systemic hypotension
Marked tachycardia
Severe aortic stenosis
Right ventricular infarct
B-Adrenergic Blockers
Decrease sinus node rate and
atrioventricular node conduction
velocity, systolic blood pressure, and
contractile responses at rest and during
exercise
 Decrease myocardial oxygen demand
and increase the length of diastole
 Good anti-ischemic agents
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B-Blockers
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Recommended that ACS patients without
contraindications should receive their initial
dose of an oral B-blocker within the first 24
hours of medical therapy
 Overview of literature (1988) showed a 13%
relative reduction in the risk of progression
from UA to an MI
 Pooled analysis of 5 trials (2003) showed a
50% reduction in mortality at 30 days and 6
months
Calcium channel blockers
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Reduces myocardial contraction and
relaxation of vascular smooth muscle, which
increases coronary blood flow
 Decrease afterload and heart rate, while
relaxing the left ventricle and increasing
arterial compliance
 2 major classes:
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Dihydropyridine
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Nifedipine, amlodipine
Nondihydropyridine
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Verapamil, diltiazem
Calcium channel blockers
Not routinely given to AMI patients due
to lack of convincing evidence that they
actually reduce death
 CCBs can be used as 3rd-line antiischemic agents (after nitrates and Bblockers) in patients who have elevated
blood pressure or angina at rest
 Short acting nifedipine should be
avoided due to increased adverse
events
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Antiplatelet therapy
Acetylsalicylic acid (Aspirin)
 Thienopyridines
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 Ticlopidine
 Clopidogrel
 Prasugrel
Aspirin
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Causes irreversible acetylation of serine
529 of cyclooxygenase (COX-1) in
platelets and the endothelium, thereby
preventing thromboxane A2 (TXA2)
production and resultant platelet
aggregation
Aspirin
Reduces the risk of angina, death, or MI
by approximately 30% in patients with
CAD
 1994 - the Antiplatelet Trialists’
Collaboration meta-analysis of 174 trials
(70,000 pts)
 2002 - meta-analysis of 287 studies
(135,000 pts)
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Thienopyridines
Block P2Y12 receptor signaling to
prevent production of adenyl cyclase,
thereby inhibiting platelet activation
through adenosine diphosphate (ADP)
 Limit ADP-mediated conversion of
GPIIb/IIIa to its active form
 Mechanism of action is independent of
and complementary to that of aspirin
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Ticlopidine
1st-generation thienopyridine
 In combination with ASA, reduces rate
of vascular death and MI by 46% in
NSTEMI patients
 Used less frequently than the newer
thienopyridines because of its potential
for side effects:
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 Rash,
nausea, neutropenia,
thrombocytopenia
Clopidogrel
2nd-generation thienopyridine
 Most widely used and studied ADPreceptor-blocking agent
 CAPRIE study (1996) : 19,185 pts
 CURE trial (2001) : 12,562 pts
 CHARISMA trial (2006)
 PCI-CURE trial (2001)
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Clopidogrel
9% relative risk reduction in adverse
cardiovascular events (vascular death,
MI, or ischemic stroke) when compared
to aspirin - (CAPRIE)
 20% reduction in the primary composite
endpoint (cardiovascular death, MI, or
stroke) up to 12 months of f/u - (CURE)
 31% reduction in cardiovascular death
or MI in patients undergoing PCI - (PCICURE)
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Glycoprotein IIb/IIIa Inhibitors
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Platelets are activated through multiple
pathways, however, the “final common
pathway” of platelet activation and
aggregation invloves a conformational
change of the GPIIb/IIIa receptors from
a resting state to an active state
Glycoprotein IIb/IIIa Inhibitors
Abciximab
 Tirofiban
 eptifibatide
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Glycoprotein IIb/IIIa Inhibitors
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EPIC trial (1994) - 35% reduction in primary
composite endpoint (death, MI, recurrent
ischemia) in pts given abciximab vs placebo
 CAPTURE trial (1997) - 30% relative
reduction of death, MI, or recurrent ischemia
in pts given abciximab
 PRISM study (1998) - 32% reduction in
death, MI, or recurrent ischemia in pts given
tirofiban
 PURSUIT trial (1998) - 10% reduction in the
relative risk of death and MI in pts given
eptifibatide
Anticoagulants
Unfractionated heparin
 Low-molecular-weight heparin
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 Enoxaparin
 dalteparin
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Factor X inhibitors
 fondaparinux
Heparin
Anticoagulative effect by activating and
accelerating the proteolytic activity of
plasma cofactor antithrombin (AT)
 Close and frequent monitoring of the
activated partial thromboplastin time
(PTT) is necessary to ensure that a safe
therapeutic range is maintained
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Heparin (UFH and LMWH)
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FRISC trial (1997) - 63% relative risk
reduction in death or MI in pts given
dalteparin vs placebo
 ESSENCE trial (1997) - the risk of death, MI,
or recurrent angina was significantly lower in
pts given enoxaparin vs UFH (16.6% vs
19.8%)
 TIMI 11B trial (1999) - 14.3% risk reduction of
death, MI, or need of urgent revascularization
in pts given enoxaparin vs UFH
Early-Conservative and EarlyInvasive Strategies
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Coronary angiography aids in defining
the extent and location of CAD and in
directing the definitive care strategy
 PCI/stenting
 CABG
 Medical
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management
Angiography is an invasive procedure
and there is a small risk of serious
complications (~1 in 1,000 cases)
Early-Conservative and EarlyInvasive Strategies
In the early-invasive strategy, all
patients without contraindications
undergo coronary angiography with the
intent to perform revascularization
within 4 to 24 hours of hospital
admission.
 The early-conservative strategy consists
of aggressive medical therapy for
patients
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TIMI-IIIB trial
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Compared an early-invasive strategy to an
early-conservative strategy in UA/NSTEMI pts
(1994)
 Primary endpoint: composite of death, MI, or
abnormalities on a exercise stress test at 6
weeks
 No significant difference in the occurrence of
the composite endpoint between the groups.
 However, the average length of initial
hospitalization, the incidence of
rehospitalization within 6 weeks, and the
number of days of rehospitalization all were
significantly lower in the early-invasive group
VANQUISH trial
Compared an early-conservative
strategy to an early-invasive strategy
(1998)
 Combined endpoint of death and nonfatal MI occurred in 3.3% of pts in the
early-conservative group and 7.7% of
pts in the early-invasive group
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 (No
benefit of early-invasive strategy)
FRISC-II trial
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Compared an early-conservative strategy to
an early-invasive strategy (1999)
 Incidence of the composite endpoint of death
or MI was 9.4% in the early-invasive group
and 12.1% in the early-conservative group
 Furthermore, angina symptoms and hospital
readmissions were reduced by 50% with the
use of the early-invasive strategy
Conclusions
ACS is associated with high rates of
adverse cardiovascular events, despite
recent therapeutic advances
 Plaque composition and inflammation
are more important in the pathogenesis
of ACS than is the actual degree of
stenosis
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Conclusions
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The cornerstone of contemporary
treatment remains early risk
stratification and aggressive medical
therapy, supplemented by coronary
angiography in appropriately selected
patients
Conclusions
An early-invasive treatment strategy is
of most benefit to high-risk patients
 An early-conservative strategy is
recommended for low-risk patients
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Conclusions
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Adjunctive medical therapy with ASA,
clopidogrel, GPIIb/IIIa inhibitors, and either
LMWH or UFH, in the appropriate setting,
further reduces the risk of ischemic events
secondary to thrombosis
 Anticoagulation and short- and long-term
inhibition of platelet aggregation should be
achieved by appropriately evaluating the risk
of bleeding complications in each patient
 Our goal: enhance both short- and long-term
event-free survival