Diagnostic Accuracy of High Sensitivity
Troponin I (hsTnI) in Predicting Acute Coronary Syndrome
Study Team
Dr. V.
Chitra Sree
Sr.
Consultant & HOD
Dept.,
of Biochemistry & Haematology
Dr.
Mullasari Ajit
Director
Institute
of Cardiovascular Disease
Background
Troponin
assays have been the biomarker of choice for Acute Coronary Syndrome (ACS) risk
stratification for the past two decades and have always been viewed as a bit of
the objective metric within ACS pathways. They are very specific for myocardial
injury.
The
European Society of Cardiology/American College of Cardiology/American Heart
Association/World Heart Federation (ESC/ACC/AHA/WHF) task force
consensus document recommends an assay-specific cut-off of the 99th percentile of a
normal healthy population in the clinical context of myocardial ischemia (i.e.
characteristic symptoms, ECG changes, imaging evidence) as the decision level,
in addition to a rise and fall pattern, for the diagnosis of AMI.
In order to reliably detect rise and fall,
assays with a coefficient of variation (CV) , of 10% at the 99th percentile are
considered to have optimal precision.
cTnI and
Myocardial Injury: Elevated cardiac troponin (cTn) values above the 99th
percentile Upper Limit of Normal (URL) indicate the presence of myocardial
injury, (detectable in the bloodstream 4-6 hours after an acute MI and remains
elevated for several days thereafter) which can be acute, with dynamic changes
in cTn levels (serial cTnI measurement ), or chronic, with persistently elevated
cTn levels.
Conditions
resulting in acute or chronic myocardial injury have elevated cTnI levels. Still, they are also seen in heart failure, myocarditis, cardiomyopathy, critical illness,
cardiotoxic chemotherapy, pulmonary embolism, pulmonary hypertension, stroke,
sepsis, and chronic kidney disease.
Introduction – hsTropI
The introduction of highly sensitive troponin assays and the application of robust kits into
clinical practice has substantially improved and facilitated early diagnosis of
MI. This improved sensitivity is inevitably associated with reduced
specificity, leading to elevated troponin levels in emergency departments.
We propose
to evaluate the clinical applicability of the hsTropI in conjunction with
serial changes within 2 hours in patients with suspected Acute coronary
syndrome (ACS) & compare the diagnostic performance of hsTropI with
contemporary TropI assay in this setting.
The Biochemistry
Integrated System is the random-access instrument designed to determine the
concentration of analytes in human specimens, most commonly serum, plasma,
urine, CSF, and other body fluids.
There are
both contemporary (Trop I ES assay) and high sensitive Troponin I (hsTrop I
assay) available which are based on
enhanced chemiluminescence method. When
compared to the Trop I ES assay, hsTrop I assays have been recommended by
ESC/ACC/AHA/WHF recently.
Aim
• To evaluate the diagnostic accuracy
of the cardiac marker, the high sensitivity Troponin I (hsTnI) in predicting acute
coronary syndrome of patients, presenting with symptoms suggestive of coronary
heart disease.
• To compare the diagnostic
performance of hsTropI with contemporary TropI assay in this setting.
Objectives
Primary
objective:
• To evaluate the sensitivity and
specificity of hsTnI in diagnosing Acute coronary syndrome in patients with
chest pain reporting to ER
Secondary objective:
Clinical Objective:
• To validate the Rule in / Rule out
algorithm for the early detection of Acute myocardial infarction (AMI) by
incorporating hsTnI in a clinical protocol, for assessing patients reporting to the emergency department of Cardiac tertiary care hospital by implementing a 0–2hr algorithm using hsTrop I assay
• To evaluate AUC (Area under curve)
with ROC for sensitivity vs specificity for the rule-in and rule-out of
diagnosis of Myocardial Infarction(MI)
• To evaluate the 99th
percentile cut-off (URL) of hsTnI to the population group of MMM for the
diagnosis of cardiac injury (Cardiac tertiary care hospital of South India)
• To evaluate the superiority of hsTnI
as an early cardiac marker in comparison to conventional Troponin I and Triage
Trop I POCT assay
• To study the significance of using
VITROS hs Trop I in cardiac diseases other than AMI such as congestive heart
failure, myocardial injury, myocarditis, etc.
Secondary
objective:
Analytical
Objective:
• Performance verification study by
evaluating Accuracy & Precision (as per CLSI guidelines EP15-A3);
• Linearity of hsTropI (CLSI
Guidelines EP 06 A)
• Upper Reference interval
verification (CLSI Guidelines EP28 A3c)
• To compare the diagnostic performance of
hsTropI with contemporary TropI assay in terms of accuracy & precision.
Methodology
• Study type: Prospective single-centre study
• Study Place: ICVD, MMM Hospital
• Study Period: 2 months (2024)
• Study Population: All patients
reporting to the ER with suspected Acute
coronary syndrome, who are assigned by clinical team for cardiac testing
protocol by POCT for diagnosis of ACS.
• Analysis Equipment – Vitros XT 7600
Integrated analyzer
• Kit / Reagent –
VITROS
Immunodiagnostic Products hs Troponin I / Troponin I (Calibrators &
Reagents)
• Analysis method - CLIA
(Chemiluminescence Immunoassay
• Quality Assurance - Desired quality
Controls will be run daily to ensure that the data for that day are acceptable (2
levels – Normal & Abnormal)
Sample
size: Sample size:
320 patients (Both male and female)
The sample
size was calculated based on the study by Cullen et al, hs-Troponin I Strategy
for Chest Pain (Validation of
High-Sensitivity Troponin I in a 2-Hour Diagnostic Strategy to Assess 30-Day
Outcomes in Emergency Department Patients With Possible Acute Coronary
Syndrome)
Calculation
of Sample size:
95%
confidence interval, 92% sensitivity,
93% Specificity, expected 10% dropout, 0.05 precision
Study Protocol
Selection
and testing of samples :
• In the Emergency Department, all the
patients presenting with acute angina or equivalent symptoms are evaluated for
ACS, by using Triage TnI POCT assay in conjunction with other clinical
investigations (ECG, ECHO).
• Time of onset of symptom is noted.
• Blood sample (Serum/plasma)
collected at zero hour testing (POCT) by standardized method shall be
parallelly tested using VITROS hsTn I assay in VITROS XT 7600 Integrated
system, along with the current TnI ES assay, without any delay for this study.
• For all the patient samples (zero
sample), which showed value above the 99th percentile URL limit (11
ng/L) as per kit insert signifying myocardial injury, the second sample shall
be collected at 2 hrs and tested for hsTnI assay and TnI ES assay. Based on the
delta algorithm, reports will be evaluated and communicated to the ER for required
clinical follow-up (Delta value > 20%).
• All patients will be followed up for
30 days by standardized telephone interview and review of hospital data through
MRD.
Data collection
• The goal of this study is to collect
data that will be utilized to validate the accuracy, precision, linearity, and
clinical performance of the hsTropI test
• Patient demographic details
• Clinical history
• Comorbidities
• Drug details
• ECG changes
• Imaging details
• Other blood investigations
• Details of clinical interventions
(Angio, Thrombolysis, other interventions, etc..)
• Clinical follow-up for 1 month with
hospital records.
Data Analysis
• Categorical variables will be
expressed as proportions and quantitative variables will be expressed as mean
and standard deviation
• Appropriate statistical tests of
significance will be applied and factors affecting outcome will be explored
• Receiver Operating characteristic
curves (ROC) will be constructed to assess the sensitivity and specificity
• Data will be entered in MS Excel and
analysis will be done using SPSS 21.0 version.
Inclusion Criteria:
• All walk-in patients between 18 and
85 years of age presenting with Acute angina or equivalent symptoms suggestive
of ACS who are evaluated and proceeded for cardiac triage by the clinical team of the Emergency Department of Madras Medical Mission
Exclusion Criteria:
• Less than 18 years of age
• History of Pregnancy,
• Patients with a history of
surgery/trauma in the previous 4 weeks
• Primary Endpoint
To assess
the probability of defining an algorithm incorporating hs Trop I to rule in and
rule out a diagnosis of Myocardial Infarction/ Cardiac injury in conjunction with
available clinical information
• Secondary Endpoint
To evaluate hsTnI as a
diagnostic marker of diagnosing the study outcome of patients belonging to the clinical category of Non-coronary chest pain, Unstable Angina pectoris, and
Acute MI. Assessing hsTnI as a risk predictor (positive and negative) for all
patients with one-month follow-up for cardiac and related critical clinical
outcomes if any (Cardiac failure, Pulmonary edema, …)
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