A BREIF REVIEW

Dr. R.NIRANJAN REDDY MD.,DM

Definition of Atherosclerosis & ACS

Etiology and pathogenesis

UA, NSTEMI, and STEMI

Patient approach & Risk stratification

Management


ATHEROSCLEROSIS DEFINITION
Atherosclerosis
A progressive inflammatory disorder of the arterial wall
that is characterised by focal lipid rich deposits of
atheroma that remain clinically silent
until they become large enough to impair tissue
perfusion,or
until ulceration and disruption of the lesion result in
thrombotic occlusion or distal embolisation of the vessel.

AHA CLASSIFICATION OF
ATHEROSCLEROSIS
DEFINITIONS
CAD is a continuum of disease.

Stable angina -> unstable angina -> AMI -> sudden cardiac death


Acute coronary syndrome encompasses Unstable angina, NSTEMI,
STEMI


Stable angina transient episodic chest pain due to myocardial
ischaemia,comes during exertion, reproducible , frequency constant over
time, usually relieved with rest or NTG.


Canadian Cardiovascular Association Classification of Angina
CLASS 1
NO PAIN WITH ORDINARY PHYSICAL ACTIVITY
CLASS 2
SLIGHT LIMITATION OF PHYSICAL ACTIVITY
PAIN OCCURS WITH WALKING, CLIMBING
STAIRS,STRESS
CLASS 3
SEVERE LIMITATION OF DAILY ACTIVITY PAIN
OCCURS ON MINIMAL EXERTION
CLASS 4
UNABLE TO CONDUCT ANY ACTIVITY WITHOUT
PAIN, PAIN AT REST
Definition Of ACS
A constellation of symptoms related to obstruction of
coronary arteries with chest pain being the most common
symptom in addition to nausea,vomiting, diaphoresis etc.
Chest pain concerned for ACS is often radiating to the left
arm or angle of the jaw, pressure-like in character, and
associated with nausea and sweating. Chest pain is often
categorized into typical and atypical angina.

UNSTABLE ANGINA

Angina pectoris (or equivalent type of ischemic
discomfort) with at least one of three features:
(1) occurring at rest (or minimal exertion) and usually
lasting >20 minutes (if not interrupted by the
administration of a nitrate or an analgesic);
(2) being severe and usually described as frank pain; or
(3) occurring with a crescendo pattern (i.e., pain that
awakens the patient from sleep or that is more severe,
prolonged, or frequent than previously).






UNSTABLE ANGINA
65% of patients with unstable angina have evidence of
myocardial necrosis on the basis of elevated cardiac
serum markers, such as cardiac-specific troponin T or I
and creatine kinase isoenzyme (CK)MB, and thus
have a diagnosis of NSTEMI.
ECG normal or ST depression(>0.5mm), T wave
changes

ACUTE MYOCARDIAL INFARCTION
ACC DEFINITION rise and fall in cardiac enzymes with one or more
of the following:
Ischaemic type chest pain/symptoms
ECG changes ST changes, pathological Q waves
Coronary artery intervention data
Pathological findings of an acute MI

NSTEMI = UNSTABLE ANGINA SYMPTOMS/FINDINGS +
POSITIVE CARDIAC ENZYMES


STEMI = ST ELEVATION ON ECG + SYMPTOMS
Classification of MI
Type 1spontaneous MI related to ischaemia due to a primary
coronary event such as plaque fissuring, erosion or rupture, or
dissection
Type 2myocardial infarction secondary to ischaemia due
either to increased oxygen demand or to decreased supply (e.g.
coronary spasm or embolism, anaemia, arrhythmias,
hypertension, or hypotension)
Type 3sudden unexpected cardiac death, including cardiac
arrest, with symptoms suggestive of myocardial ischemia,
accompanied by new ST elevation, or new left bundle branch
block, or definite new thrombus by coronary angiography
(death before blood samples obtained) or in the lag phase of
cardiac biomarkers
Type 4MI associated with PCI
Type 5MI associated with CABG

STEMI: ECG
ST elevations, hyper acute T waves; followed by T wave inversions,
Q waves.,
Clinically significant ST segment elevations:
> than 1 mm (0.1 mV) in at least two anatomical contiguous leads
or 2 mm (0.2 mV) in two contiguous precordial leads (V2 and V3)







Note: LBBB and pacemakers can interfere with diagnosis of MI on
EKG

NSTEMI:

ST depressions (0.5 mm at least) or T wave inversions ( 1.0
mm at least) without Q waves in 2 contiguous leads with
prominent R wave or R/S ratio >1.
Isolated T wave inversions:
can correlate with increased risk for MI
may represent Wellens syndrome:
critical LAD stenosis
>2mm inversions in anterior precordial leads
Troponin is primarily used for diagnosing MI because
it has good sensitivity and specificity.
CK-MB is more useful in certain situations such as post
reperfusion MI or if troponin test is not available
Other conditions can cause elevation in troponin such
as renal failure or heart failure
The increasing troponin trend is the important thing
to look for in diagnosing MI. Order Troponin together
with ECG when doing serial testing to rule out ACS.

pathophysiologic processes contributing to
the development of UA/NSTEMI
1. plaque rupture or erosion with superimposed nonocclusive
thrombus (this causes by far the most UA/NSTEMI);
2. dynamic obstruction due to
a. spasm of an epicardial coronary artery, as in Prinzmetal variant
b. constriction of the small, intramural muscular coronary arteries, that is,
the coronary resistance vessels
c. local vasoconstrictors, such as thromboxane A2, released from platelets;
d. dysfunction of the coronary endothelium; and
e. adrenergic stimuli including cold and cocaine;
3. severe coronary luminal narrowing caused by progressive coronary
atherosclerosis or postpercutaneous coronary intervention
restenosis;
4. inflammation; and
5. secondary unstable angina, that is, severe myocardial ischemia related
to increased myocardial oxygen demand or decreased oxygen supply (e.g.,
tachycardia, fever, hypotension, or anemia).
Individual patients may have several of these processes coexisting as the
cause of UA/NSTEMI. Several serum markers can serve as effective tools in
identifying these pathophysiologic processes.



Pathophysiology of ACS
APPROACH TO THE PATIENT WIYH
ACUTE ONSET CHESTPAIN
Identifying those with chest pain suggestive of IHD/ACS.
Thorough history required:
Character of pain
Onset and duration
Location and radiation
Aggravating and relieving factors
Autonomic symptoms

TYPICAL VS ATYPICAL HISTORY
Failure to recognise symptoms other than chest pain -> approx 2 hr delay
in seeking medical attention
TOOLS USED IN RISK STRATIFICATION
HISTORY

ECG

BIOCHEMICAL MARKERS

2D ECHO


Thrombolysis In Myocardial Ischemia (TIMI) risk score for unstable
angina or nonST elevation myocardial infarction (UA/NSTEMI).

Use of the TIMI risk score
for UA/NSTEMI to predict
the benefit of an early
invasive strategy.
The TIMI risk score was
applied in the Treat Angina
with Aggrastat and determine
Cost of Therapy with an
Invasive or Conservative
Strategy (TACTICS)TIMI 18
trial.
As shown, 75% of patients had
a risk score of 3 or higher, and
a significant benefit of an
invasive strategy was observed
in these patients ELECTROCARDIOGRAPH
Y
ECG should be obtained within 10 minutes after
presentation in patients with ongoing chest discomfort , to
identify patients who might benefit from immediate
reperfusion therapy (mechanical or pharmacologic)
The ECG provides critical information for both diagnosis
and prognosis.
New persistent or transient ST-segment abnormalities
(0.05 mV) that develop during a symptomatic episode at
rest and resolve when the symptoms resolve strongly
suggest acute ischemia and severe coronary disease.



Nonspecific ST-segment and T wave abnormalities --
defined as lesser amounts of ST-segment deviation or T
wave inversion of 0.2 mV or less, and are less helpful for
risk stratification.
A completely normal ECG does not exclude the
possibility of ACS;
the risk of acute MI is about 4% among patients with a
history of coronary artery disease and 2% among
patients with no such history.
However, patients with a normal or near-normal ECG
have a better prognosis than patients with clearly
abnormal ECGs at presentation.

Diffuse ST-segment elevation and PR-segment depression
suggest pericarditis.
Right axis deviation, right bundle branch block, T wave
inversions in leads V1 to V4, and an S wave in lead I and Q
wave and T wave inversion in lead III suggest pulmonary
embolism (S I Q3 T3 PATTERN).
The availability of a prior ECG improves diagnostic
accuracy and reduces the rate of admission for patients
with abnormal baseline tracings.
Serial electrocardiographic tracings improve the clinicians
ability to diagnose acute MI, particularly if combined with
serial measurement of cardiac biomarkers.
Posterior leads can be useful for identifying ischemia in
the territory supplied by the left circumflex coronary
artery, which is otherwise relatively silent
electrocardiographically.






ACUTE IWMI
CHEST RADIOGRAPHY.
A chest X-RAY typically obtained in all patients
presenting with chest pain.
It is usually nondiagnostic in patients with ACS,
but can show pulmonary edema caused by
ischemia-induced diastolic or systolic dysfunction.
It is more useful for diagnosing or suggesting
-- may show a widened mediastinum or aortic knob
in aortic dissection.
-- The chest radiograph is usually normal in
pulmonary embolism,
-- but can show atelectasis, an elevated
hemidiaphragm, a pleural effusion or, more rarely,
Hamptons hump or Westermarks sign.
-- can reveal pneumonia or pneumothorax.

BIOCHEMICAL MARKERS OF MYOCARDIAL NECROSIS
CREATINE KINASE MB ISOENZYME.
Major limitation to CK-MB as a diagnostic biomarker is its relative lack of specificity
CK exist in 3 Isoenzyme forms (MM, BB, and MB).
Brain and kidney -- BB isoenzyme
Skeletal muscle -- MM, but also contains some MB (1% to 3%)
Cardiac muscle --- both MM and MB isoenzymes.
The MB isoenzymes of CK can also be present in small quantities in the small
intestine, tongue, diaphragm, uterus, and prostate.
Strenuous exercise, particularly in trained long-distance runners or professional
athletes, can cause elevation of both total CK and CK-MB.

Use of the CK-MB relative index (the ratio of CK-MB to total CK) partially addresses
this limitation for skeletal muscle as a source.
The amount of CK-MB is increased from skeletal muscle in patients with conditions
that cause chronic muscle destruction and regeneration, such as muscular
dystrophy, high-performance athletics (e.g., marathon running), or rhabdomyolysis
or muscular trauma.
One advantage of CK-MB--shorter half-life in the circulation
Useful for gauging the timing of an MI
A normal CK-MB with an elevated troponin level could represent a small MI or an
MI that occurred several days ago
For diagnosing reinfarction in a patient who has had an MI in the past week.






TROPONINS.
Different genes encode troponins I and T in cardiac muscle, slow skeletal
muscle, and fast skeletal muscle
Hence the assays for cardiac troponins are more specific than the assay for
CK-MB for myocardial injury
cardiac troponin is the preferred diagnostic biomarker.
The high specificity of cardiac troponins for myocardium make false-
positive elevations (i.e., an elevated cardiac troponin in the absence of
myocardial injury) exceedingly rare.
Elevations in the absence of other clinical data
consistent with an ACS usually represent true myocardial
damage from causes other than atherosclerotic coronary artery disease.
Such damage may occur with
Myocarditis, myocardial contusion, or cardioversion or defibrillation,
Left ventricular strain from congestive heart failure, hypertensive crisis,
or extreme exercise,
Right ventricular strain from pulmonary embolus, or other causes of
acute pulmonary hypertension.
Patients with renal disease, severe sepsis .






With serial sampling up to 12 hours after presentation, cardiac
troponins offer a sensitivity higher than 95% and a specificity of 90%.
When using only a single sample at presentation, performance has
been substantially worse, with a sensitivity of only 70% to 75%.
Recently, however, sensitive assays have been developed that offer a
lower limit of detection, (approximately 0.001 to 0.01 ng/mL,
depending on the specific assay) and acceptable imprecision at low
levels that, importantly, are now below the 99th percentile in a
normal reference population (typically 0.01 to 0.07 ng/mL), thereby
improving the ability to detect myocardial injury.
Using such assays, the sensitivity for detecting myocardial infarction
using a single sample at presentation is approximately 90%, the
specificity approximately 90%, and the negative predictive value
approximately 97% to 99%.
Moreover, among patients presenting within 3 hours of the onset of
chest pain, the superior performance of high-sensitivity assays is even
more striking,a sensitivity of 80% to 85%, compared with
approximately 55% for older assays.
Algorithm for the initial diagnostic approach to a patient with
chest pain
UNSTABLE ANGINA /NSTEMI TREATMENT
Oral Antiplatelet Therapy Aspirin Initial dose of 162325 mg nonenteric
formulation followed by 75162 mg/d of an enteric or a nonenteric formulation
Clopidogrel Loading dose of 300-600 mg followed by 75 mg/d Prasugrel Pre-
PCI: Loading dose 60 mg followed by 10 mg/d
Intravenous Antiplatelet Therapy Abciximab 0.25 mg/kg bolus followed
by infusion of 0.125 g/kg per min (maximum 10 g/min) for 12 to 24 h
Eptifibatide 180 g/kg bolus followed by infusion of 2.0 g/kg per min for 72 to 96
h Tirofiban 0.4 g/kg per min for 30 min followed by infusion of 0.1 g/kg per
min for 48 to 96 h
Heparins
*
Unfractionated Heparin (UFH) Bolus 6070 U/kg (maximum
5000 U) IV followed by infusion of 1215 U/kg per h (initial maximum 1000
U/h) titrated to a PTT 5070 s Enoxaparin 1 mg/kg SC every 12 h; the first dose
may be preceded by a 30-mg IV bolus; renal adjustment to 1 mg/kg once daily if
creatine Cl < 30 cc/min Fondaparinux 2.5 mg SC qd Bivalirudin Initial bolus
intravenous bolus of 0.1 mg/kg and an infusion of 0.25 mg/kg per hour. Before
PCI, an additional intravenous bolus of 0.5 mg/kg was administered, and the
infusion was increased to 1.75 mg/kg per hour.
Class I Recommendations for Use of an Early
Invasive Strategy (PCI)
Class I (Level of Evidence: A)indications
Recurrent angina at rest/low-level activity despite Rx
Elevated TnT or TnI
New ST-segment depression
Angina/ischemia with CHF symptoms, rales, MR
Positive stress test
EF < 0.40
Decreased BP
Sustained VT
PCI < 6 months, prior CABG
High-risk score
STEMI Management
STEMI patients usually go straight to the cath lab from the
ED. Goal: door to balloon 90 minutes.
Initial management for STEMI:
Cardiac monitor
Supplemental O2
Nitrates
Beta blocker
Morphine
Clopidogrel
Aspirin
Good IV access
Call cardiologist immediately after seeing ECG OF MI

Major components of time delay between onset of infarction and
restoration of flow in the infarct-related artery.

Importance of time to
reperfusion in patients
receiving fibrinolytic
therapy for STEMI.

The data from 22 trials of
fibrinolytic therapy were pooled
and the findings stratified by the
six time categories shown in the
figure.
Because the lifesaving
effect of fibrinolysis is
maximal in the first
hour from onset of
symptoms, this has
been referred to as the
golden hour for
pharmacologic
reperfusion.

The kinetics of release of CK-MB and cardiac troponin in patients
who do not undergo reperfusion are shown in the solid blue and
pink curves as multiples of the upper reference limit (URL).
TIMI risk score for STEMI predicting 30-day mortality.

Classic shock paradigm is shown in pink. The influence of the inflammatory
response syndrome initiated by a large MI is illustrated in black coloured
arrows
Emergency management of complicated STEMI.

NSTE-ACS
STEMI
TROPONIN
SK
Landmark Practice Advances in Acute Coronary
Syndromes
SK+
ASPIRIN
r-tPA
TNK
Pre-H lysis
Morrison
PRIMARY PCI ABCIXIMAB
CLOPIDOGREL
REACT
BIVALIRUDIN
VIENNA REGISTRY
CARESS
ASPIRIN +
HEPARIN
1983-88
CLOPIDOGREL
UPSTREAM
GP IIb/IIIa
EARLY INVASIVE
ABCIXIMAB
IN CATH LAB
FONDAPARINUX
BIVALIRUDIN
ENOXAPARIN
1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008
Conclusions
ACS is the major cause of mortality
Care full histiry about chest pain onset characteristics
,associated symptoms,and risk stratification using history
and ECG ,Bio markers is needed for identifying high risk
patients who need early invasive strategy
Chestpain protocol implemention and avoiding time
delays in transport, trying to achieve ideal door to needle
and door to balloon time are essential in reducing the area
of infarct and preventing complications
Carefull serial monitoring of vitals and serial ECG are
essential things in managent of ACS patients
Main risk factors Diabetes ,HTN,Hyperlipidemia,
smoking,alchohol,obesity are to be managed effectively as
primary and secondary prevention measures.
THANK YOU ALL