Diagnostic accuracy of High Sensitivity Troponin I (hsTnI) in predicting Acute coronary syndrome

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 Integratedanalyzer

•       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, …)