Cardiac risk stratification
in ACS
Dr sadanand indi

Introduction
• Acute coronary syndrome (ACS) encompasses unstable angina, ST-
elevation MI (STEMI), and non-ST elevation ACS (NSTE ACS)
• Angina pectoris is defined as chest discomfort attributed to myocardial
ischemia. The Canadian Cardiovascular Society angina classification is a
symptom severity scale used to assess and grade physical limitation due to
symptoms.
• Studies have shown greater angina severity at the time of diagnosis to be
associated with higher mortality rates

Role of Clinical Decision Pathways
Multiple clinical decision pathways (CDPs) have been proposed over the past
decade to guide the diagnosis and management of ACS.
• The History, ECG, Age, Risk factors Troponin (HEART) score
• Vancouver Chest Pain Rule
• Manchester Acute Coronary Syndromes (MACS) rule
• Emergency Department Assessment of Chest Pain Score
• And Accelerated Diagnostic Protocol to Assess Patients With Chest Pain
Symptoms (ADAPT) are commonly known decision rules that incorporate
scoring systems that are used in the ED to risk stratify patients presenting
with chest pain

• A major challenge is identify the patients who have acute coronary syndrome (ACS)
or other life-threatening conditions among the large number who have more
benign conditions(noncardiac)
• The objectives of this Expert Consensus Decision Pathway are to provide
STRUCTURE around the evaluation of chest pain in the ED
• Patients classified as low risk (rule out) using hs-cTn–based CDPs supported by this
document can generally be discharged directly from the ED
• patients with substantially elevated initial hs-cTn values or those who have
significant dynamic changes over 1 to 3 hours are assigned to the abnormal/high-
risk category

• Chest pain should be considered stable when symptoms are
chronic and associated with precipitants such as exertion or
emotional stress.
• Clinical assessment should include the chest pain description and
associated symptoms, onset, duration, location, radiation, and
precipitating and relieving factors.
• A detailed assessment of cardiovascular risk factors and medical,
family, and social history should complement the assessment of
presenting symptoms

Initial ECG Interpretation
• The ECG is critical for the initial assessment and management of patients with
potential ACS and therefore should be performed and interpreted within 10
minutes of arrival at the ED

• Electrocardiogram Findings Suggestive of Ischemia
FINDING CRITERIA
STEMI equivalents
Posterior STEMICriteria:▪Horizontal ST-segment depression in V1-V3
• ▪Dominant R-wave (R/S ratio >1) in V2
• ▪Upright T waves in anterior leads
• ▪Prominent and broad R-wave (>30 ms)
• Confirmed by:▪ST-segment elevation of ≤0.5 mm in at least 1 of
leads V7-V9∗
De Winter Sign▪Tall, prominent, symmetrical T waves arising from
upsloping ST-segment depression >1 mm at the J-point in the
precordial leads
• ▪0.5-1 mm ST-segment elevation may be seen in lead aVR
• Hyperacute T wavesBroad, asymmetric, peaked T waves may be
seen early in STEMI

Left bundle branch block or ventricular paced rhythm
Sgarbossa Criteria A total score ≥3 points is required:
▪Concordant ST-segment elevation ≥1 mm in leads with a positive QRS
complex (5 points)
▪Concordant ST-segment depression ≥1 mm in leads V1-V3 (3 points)
▪Discordant ST-segment elevation ≥5 mm in leads with a negative QRS complex
(2 points)
Left bundle branch block or ventricular paced rhythm with Smith modified
Sgarbossa Criteria Positive if any of the following are present:
▪Concordant ST-segment elevation of 1 mm in leads with a positive QRS
complex
▪Concordant ST-segment depression of 1 mm in V1-V3
▪ST-segment elevation at the J-point, relative to the QRS onset, is at least 1 mm
and has an amplitude of at least 25% of the preceding S-wave

ECG findings consistent with acute/subacute myocardial ischemia
Avr- ST-segment elevation
Most often caused by diffuse subendocardial ischemia and usually
occurs in the setting of significant left main coronary artery or
multivessel coronary artery disease
▪ ST-segment elevation in aVR ≤1 mm
▪ Multilead ST-segment depression in leads I, II, Val, and/or V4-V6
▪ Absence of contiguous ST-segment elevation in other leads
• ST-segment depression,Horizontal or downsloping ST-segment
depression ≥0.5 mm at the J-point in 2 or more contiguous leads is
suggestive of myocardial Ischemia

Wellen’s syndromeClinical syndrome characterized by:
▪Biphasic or deeply inverted and symmetric T waves in leads V2 and
V3 (may extend to V6)
Recent angina
• Absence of Q wave
• Inverted T wavesMay be seen in ischemia (subacute) or infarction
(may be fixed and associated with Q waves) in continuous leads,aVR
• V7 placed at left posterior axillary line in same plane as V6; V8 placed
at the tip of the left scapula; V9 placed in the left paraspinal region
in the same plane as V6.
• In the absence of ischemic ST-segment elevation, the ECG should be
examined for other changes that have been associated with
coronary artery occlusion ,when present, these should prompt
evaluation for emergent coronary angiography

Hs-cTn Assays
• The 2018 Fourth Universal Definition of MI defined biomarker evidence of acute
myocardial injury as an acute rise and/or fall in cTn values (≥20% change between
serial measurements), with at least 1 cTn value above the assay’s 99th percentile
URL
• Immediate disposition of approximately 25% to 50% of chest pain patients is
possible in those who have a single undetectable or very low hs-cTn value, provided
symptoms started ≥3 hours before the hs-cTn measurement (“0-hour rule out”).
This approach is not suitable for early presenters who have symptom onset <3
hours before presentation
• 0-hour rule-out threshold of <6 ng/L for hs-cTnT is reasonable in patients with a
nonischemic ECG and onset of symptoms ≥3 hours before cTn
measurement(Modified European Society of Cardiology 0/1-Hour CDP for Ruling
Out MI)
• Use of uniform 99th percentile URLs results in decreased sensitivity and negative
predictive value (NPV) in women, contributing to the existing sex bias in the
diagnosis and treatment of women with possible ACS

• Reichlin et al developed an algorithm incorporating both baseline hs-cTnT
values and changes in hs-cTnT between 0 and 1 hour to assign patients to
rule out, rule in, or observation zones. This approach has been replicated
with multiple hs-cTnI assays and externally validated

• The High-STEACS algorithm is another validated implementation approach for
hs-cTn. With this algorithm, MI is ruled out if the initial hs-cTnI is <5 ng/L; if hs-
cTnI is ≥5 ng/L (or the patient is an early presenter) but hs-cTnI is less than the
sex-specific 99th percentile URL, a second hs-cTnI measurement is performed 3
hours from the time of presentation

• Other potential biomarkers include heart-type fatty acid-binding protein
(H-FABP); biomarkers of systemic inflammation such as CRP; markers of LV
dysfunction, namely brain natriuretic peptide (BNP); and copeptin and
ischemia-modified albumin
Copeptin
• Copeptin is the C-terminal part of the arginine vasopressin (AVP)
precursor. Copeptin is a surrogate marker for AVP, which is elevated in
NSTE-ACS
• Copeptin levels rise rapidly at 0–4h and decline over 2–5 days.
• The combination of a negative copeptin and a negative troponin increased
the negative predictive value to 99%
H-FABP
• H-FABP is an intracellular protein involved in myocardial fatty acid
metabolism
• It is rapidly detectable following myocardial ischemia and infarction, but
has not been shown to have incremental diagnostic value in the diagnosis
of MI when combined with hs-cTn

• chest pain guideline recommends the incorporation of clinical risk scores in
the evaluation of patients with concern for ACS due to the insufficient
sensitivity and NPV of hsTnc assays alone for ruling out MI.
• One of the most commonly used scores is the HEART score, which uses readily-
available clinical data and the clinician’s interpretation of the history to risk-stratify
patients
• This “modified HEART score” is used for risk stratification among patients who
have been ruled out for MI based on cTn criteria
• A second commonly used risk score is EDACS, which also uses readily available
clinical information.
• This scoring system requires that the patient have a nonischemic ECG and serial
conventional cTn values ≤99th percentile over 2 hours
• The Global Registry of Acute Coronary Events and Thrombolysis in MI scores were
initially developed for risk stratification for managing NSTE-ACS, but have also
been studied for evaluating patients with acute chest pain. However, they have
inferior sensitivity and NPV to the HEART score and EDACS

UA/NSTEMI risk scores
1.Timi score
2.Grace score
3.Pursuit score
4.Frisco score
5.Gusto score

• GRACE 1.0 score has been extensively validated GRACE 1.0 predicts the in-
hospital and 6-month risk of death or MI using the variables
• The ESC and NICE guidelines recommend using this score to identify those
patients who will benefit from an invasive strategy
• The recently implemented GRACE 2.0 score implements revised GRACE
algorithms for predicting death and death or MI at 1 and 3 years
This nomogram retained
excellent discriminant
characteristics based on eight
variables and was used for the
calculation of risk

Limitations of the GRACE score
• Partial adoption
The GRACE risk score is only partially used in real-life clinical practice
TIMI SCORE
The TIMI risk score is a simple prognostication scheme that categorizes a
patient's risk of death and ischemic events and provides a basis for
therapeutic decision making.

PURSUIT SCORE
• The PURSUIT (Platelet glycoprotein IIb/IIIa in Unstable angina: Receptor
Suppression Using Integrilin Therapy) risk score was developed in a NSTEMI
ACS
• Established seven risk predictors for death and myocardial infarction (MI) in
patients with acute coronary syndromes.
• Five of these risk factors were then combined into a scoring system:
– Higher age
– Sex
– Canadian Cardiovascular Society (CCS) class of angina
– Signs of heart failure
– ST-segment depression on the index ECG
• Each of these elements is scored accordingly, resulting in a score ranging 1 -
18

UA/NSTEMI Score
1.HAS BLED
2.CRUSADE SCORE
3.ACUITY SCORE

HAS-BLED scoring system is similar to the GRACE and CRUSADE systems but
better than TIMI system to predict long-term survival outcomes in patients
with NSTEMI without atrial fibrillation

• The 2-Hour Accelerated Diagnostic Protocol to Assess Patients With Chest
Pain Symptoms Using Contemporary Troponins as the Only Biomarker
(ADAPT) pathway combines
1. a Thrombolysis In Myocardial Infarction score of 0
2.a nonischemic ECG and
3.0- and 2- hour cTn concentrations <99th percentile to identify patients at
low risk (30-day major adverse cardiac event risk <1%), but does so with
less efficacy than the HEART and EDACS pathways
• In summary, for patients presenting with symptoms of possible ACS with
serial conventional (ie, non–hs-cTn) cTn values less than the 99th
percentile URL and nonischemic ECGs, a low modified HEART score (≤3) or
EDACS (<16) can identify patients eligible for discharge without a
requirement for further diagnostic testing.

• Patients with intermediate- or high-risk scores, elevated cTn
concentrations, ischemic ECGs, or high suspicion for unstable
angina should undergo further diagnostic testing.
• EDACS and the modified HEART score are the best validated
strategies and identify the largest number of patients as low
risk using conventional cTn assays.

Noninvasive Cardiovascular Diagnostic Testing
Objectives of Secondary Testing: Focus on “Intermediate-Risk” Patients
• the primary role of subsequent noninvasive cardiac testing is for the evaluation
of patients classified as at intermediate risk according to the initial CDP
evaluation

• One should identify patients with previously known CAD, defined as a prior MI,
coronary revascularization procedure(s), or obstructive or nonobstructive CAD
on previous invasive coronary angiography or coronary CTA.Additionally, the
results of prior tests for CAD should influence subsequent test selection and
refine the initial risk assessment.
• Role of Rest Transthoracic Echocardiography
To assess for regional wall motion abnormalities, ventricular dysfunction, valvular
dysfunction, and pericardial effusion can provide valuable triage information in
intermediate-risk patients or those with ECG changes suggestive, but not
diagnostic of ischemia
• Coronary CTA
Coronary CTA is also effective as a “gatekeeper” to invasive coronary
angiography in patients with inconclusive ischemia tests
Noncontrast chest CT for CAC scanning is not currently recommended for
routine use as a stand-alone test (without coronary CTA) in patients with acute
chest pain due to its inability to assess coronary artery stenosis, noncalcified
plaque, and high-risk plaque features

• coronary CTA should be considered the preferred noninvasive test for patients
presenting to the ED with possible ACS who do not have known CAD
• Patients with obstructive coronary disease (≥50%) on CTA should generally be
admitted, treated with therapies for ACS, and undergo invasive coronary
angiography
Guideline-Directed Approach to Subsequent Diagnostic Testing in Patients
With Suspected ACS at Intermediate Clinical Risk

• CCTA provides anatomical information, coronary plaque burden, and coronary
plaque morphology
• CCTA provides anatomical information, coronary plaque burden, and coronary
plaque morphology
• The presence, severity (both obstructive and nonobstructive), and extent of
CAD provided by anatomical assessment are notable information for risk
discrimination
• Anatomical Assessment of Coronary Artery Disease by Coronary Computed
Tomographic Angiography
ICA has been a gold standard to identify anatomical significance of CAD but non
invasive method preffered is CCTA.
CCTA demonstrated excellent diagnostic performance, particularly high
sensitivity, and NPV with 95% and 99%, respectively.

Risk Stratification by Anatomical Assessment of Coronary Artery
Disease by Coronary Computed Tomographic Angiography
• Nonobstructive,obstructive CAD and nonextensive (≤4 segments)
and extensive (>4 segments) CAD
Functional Assessment of Coronary Artery Disease by Coronary
Computed Tomographic Angiography
• CT perfusion (CTP) can evaluate myocardial ischemia induced by
pharmacological stress
• FFRCT is a novel method provided by an advanced technique to
identify lesion-specific ischemia by invasive FFR

• a) Interpretation of FFRCT results in a 65-year-old woman with typical
angina. Agatston score, 333. Left: Coronary CT angiography curved
multiplanar reconstructions demonstrate a 50%–69% proximal left
anterior descending artery (LAD) stenosis (red arrow) and in the mid-LAD,
nonobstructive diffuse disease. The blue arrow indicates where the lesion-
specific FFRCT value was assessed. Right: In the FFRCT three-dimensional
model, the FFRCT value 16 mm distal to the stenosis was 0.85, indicating
that the lesion did not cause significant pressure loss. However, FFRCT was
significantly low (0.76) in the terminal vessel segments

• Assessment of Coronary Plaque Type and Vulnerability by
Coronary Computed Tomographic Angiography
-The coronary plaque with vulnerability is the so-called
vulnerable plaque.
-ICA without obstructive CAD does not always imply an excellent
prognostic value.
-The potential mechanism underlying why ICA misses the
coronary lesion associated with future cardiovascular events
may be because ICA cannot show the visualization of coronary
plaque type and/or vulnerability associated with plaque
rupture beyond stenosis.

• Coronary artery calcium (CAC) scanning is a diagnostic tool to
determine the presence and extent of calcified plaque in coronary
arteries by noncontrast CT and an examination for early detection
of CAD and improvement of risk stratification for individuals at
low-intermediate or intermediate CAD risk
• CACS is calculated by the sum of coronary calcified plaque lesions
with density greater than or equal to 130 Hounsfield units (HU)
having an area ≥1 mm2
• Serial assessments by noncontrast cardiac CT can only provide the
development of calcified plaque burden

OTHER NON-INVASIVE MODALITY
1.TREADMILL TEST
2.STRESS ECHO CARDIOGRAPHY
3.SPECT SCAN
4.PET SCAN

Ischemia Test Modality
ISCHEMIA TEST
MODALITY
STRENTHS LIMITATIONS PATIENTS
CONSIDERATIONS
FAVORING FOR
TEST
EXERCISE STRESS
TEST
LOW COST DECREASED
ACURACY
RARELY
RECOMMENDED AS
A STAND-ALONE
TEST
•WIDE AVAILABILTY
•ASSESSMENT OF
EXERCISE
SYMPTOMS,CAPACITY
REQUIRES ABILITY
TO EXCERCISE
NO IONISING
RADIATION

TEST MODALITY STRENTHS LIMITATIONS PATIENT
CONSIDERATIONS
STRESS
ECHOCARDIOGRAPY
WIDELY AVAILABLE DECREASED
SENSITIVITY
COMPARED OTHER
ANATOMICAL OR
FUNCTIONAL
MODALITY
•KNOWN GOOD
IMAGE QUALITY AND
ABILITY TO EXERCISE
•CONSIDER USE OF
AN ULTRASOUND-
ENHANCING AGENT
TO IMPROVE
ENDOCARDIAL
VISUALIZATION
HIGH DIAGNOSTIC
SPECIFICITY
DEPENDS ON GOOD
QUALITY IMAGES
KNOWN SEVERE OR
MODERATE
VALVULAR DISEASE
HIGH DIAGNOSTIC
SPECIFICITY
REQUIRES
DOBUTAMINE IF
PATIENT IS UNABLE
TO EXERCISE

TEST STRENTHS LIMITATIONS PATIENTS
CONSIDERATION
STRESS/REST SPECT RELATIVELY HIGH
DIAGNOSTIC
SENSITIVITY
INCREASED
ARTIFACTS
RESULTING IN
NONDIAGNOSTIC
RESULTS AND
DECREASED
DIAGNOSTIC
ACCURACY
COMPARED WITH
STRESS/REST PET
PREFERRED OVER
STRESS
ECHOCARDIOGRAPH
Y IN PATIENTS WHO
CANNOT EXERCISE
OR WHO DO NOT
HAVE SIGNIFICANT
BRONCHOSPASTIC
DISEASE
WIDELY AVAILABLE RADIATION
EXPOSURE
KNOWN CAD OR
HIGH CAC BURDEN
ON CHEST CT
IMAGING
ASSESSMENT OF
VENTRICULAR
FUNCTION

Test Strenths limitation Patient’s
consideration
STRESS/REST PET HIGH DIAGNOSTIC
ACCURACY
LOW RADIATION
EXPOSURE
COMPARED TO
SPECT SCAN
LIMITED
AVAILABILITY
KNOWN CAD OR
HIGH CAC BURDEN
ON CHEST CT
IMAGING
MEASURES
MYOCARDIAL BLOOD
FLOW AND FLOW
RESERVE
RELATIVELY HIGHER
COST
PREFFERED OVER
SPECT FOR HIGH
DOAGNOSTIC
ACCURACY
ASSESSMENT OF
VENTRICULAR
FUNCTION
LACK OF EXERCISE
ASSESSMENT

Test modality Strenths Limitations Patient’s
considerations
STRESS CMR HIGH DIAGNOSTIC
ACCURACY
LIMITED
AVAILABILITY
ACCURATE
ASSESSMENT OF
CHAMBER SIZES,
VENTRICULAR AND
VALVULAR FUNCTION
HIGHER COST
LACK EXERCISE
ASESSMENT
KNOWN CAD
AND/OR
CARDIOMYOPATHY
MEASUREMENT OF
MYOCARDIAL BLOOD
FLOW AND FLOW
RESERVE IS POSSIBLE
LONG SCAN
ACQUSITION TIME
KNOWN MODERATE
OR SEVERE
VALVULAR DISEASE
DIAGNOSIS OF PRIOR
INFARCTION, SCAR,
FIBROSIS
CLAUSTROPHOBIA KNOWN MODERATE
OR SEVERE
VALVULAR DISEASE
NO IONIZING
RADIATION
CONTRAINDICATED
IN PATIENTS WITH
SIGNIFICANT RENAL
DYSFUNCTION
NO SIGNIFICANT
RENAL DYSFUNCTION

Myocardial Injury Differential:
Defined as at Least 1 ng/L Above the 99th Percentile URL
Acute myocardial injury Chronic myocardial injury
Cardiovascular /non cardiovascular causes Cardiovascular /noncardiovascular causes
•Acute mi (type1-5)
•Hypertensive urgency/emergency
•Pulmonary embolism
•Acute aortic synrome
•After cardiac procedure ,after PCI
•Stresss cardiomyopathy
•Cardiac contusion
•Stable coronary syndrome
•Chronic heart failure
•Uncontrolled arrhythmia
•Hypertension
•Valvular heart disease
•Pulmonary hypertension
•cardiomyopathy

Classification, Evaluation, and Management of Myocardial Injury
• Myocardial injury is considered
-acute if there is a dynamic rise and/or fall of cTn concentrations exceeding
the analytical variation of the assay (>20% relative change), with at least 1
value above the 99th percentile, and
-chronic if the cTn level remains elevated but stable over serial measurements

Importance of Differentiating Subtypes of MI
• The differentiation of type 1 MI from the remaining subtypes of MI and
nonischemic myocardial injury is important for several reasons
• Treatment strategies for type 1 MI are defined by evidence from large
randomized controlled trials and outlined in clinical guidelines
• There are limited data on the appropriate management of patients with type 2
MI, and even less for patients with nonischemic myocardial injury
• If there is uncertainty regarding whether the diagnosis is a type 1 or 2 MI,
clinicians should generally manage the patient as presumed type 1 MI.

• Once the diagnosis of type 2 MI is made, clinicians should first
identify and treat the precipitant of acute supply/demand
mismatch.
• Initial management should focus on identification and treatment
of the underlying cause of myocardial injury.
• Notably, patients with acute myocardial injury have a high rate of
subsequent cardiovascular events,with approximately 15%
experiencing an MI or cardiovascular death at 1 year
• The risk is higher among patients with acute rather than chronic
myocardial injury.

APPROACH TO MYOCARDIAL
INJURY