HIGH-SENSITIVITY CARDIAC TROPONIN

DR MAHENDRA

CARDIOLOGY, JIPMER

INTRODUCTION

• A rapid and accurate diagnosis is critical in patients with presumed ACS

• Clinical assessment, 12-lead ECG and cardiac troponin (cTn) I or T form the

diagnostic cornerstones

• Early rule-in of AMI

• An early rule-out of AMI

CARDIAC BIOMARKERS

Intern Emerg Med (2017) 12:147–155

WHAT IS TROPONIN? • Troponin is a component of the contractile apparatus within skeletal

and cardiac myocytes.

MECHANISMS TO EXPLAIN THE RELEASE

• Normal cell turnover

• Myocyte necrosis

• Apoptosis or programmed cell death

• Proteolytic fragmentation

• Increased cell membrane permeability

OTHER CAUSES OF TROPONIN ELEVATION

ROLE OF CARDIAC BIOMARKERS IN PATIENTS WITH NON DIAGNOSTIC ECGS

• A diagnosis of AMI is based on the detection of a rise and/or fall of cTn along with the

presence of characteristic symptoms, and/or ECG or imaging evidence of acute

myocardial ischemia.

• The cut-off value of cTn to diagnose MI is defined as a concentration exceeding the

99th percentile of a normal reference population (i.e. upper reference limit [URL])

using an assay with an imprecision (coefficient of variation, CV) ≤10% at the URL

NEED FOR HIGH-SENSITIVITY CARDIAC TROPONIN

The contemporary cTn assays cannot measure cTn levels at low concentrations

corresponding to the 99th percentile value of a normal reference population.

Thus, they lack the precision criteria to diagnose AMI

The high-sensitivity cardiac troponin (hs-cTn) assays were developed to meet

the requirements of analytical precision and overcome the short- comings

associated with contemporary cTn assays.

HIGH-SENSITIVITY CARDIAC TROPONIN

5th generation hs-cTn T and I assays which can detect troponin at

concentrations 10- to 100-fold lower than conventional assays

Hs-cTn assays detect troponin with higher sensitivity and precision at

an earlier point of time

DETECTION RANGE OF DIFFERENT TROPONIN ASSAYS

Characteristics of Hs Troponin

• Reported as nanograms per litre

• Cardiac troponin values below the lower limit of detection should not be

reported as numbers.

• High-sensitivity cardiac troponin assays have high precision at lower

concentration ranges

• High-sensitivity cardiac troponin assays enable detection of cTn in a significant

proportion of the reference population.

MI and TROPONIN RELEASE

USE OF HIGH-SENSITIVITY CARDIAC TROPONIN IN CLINICAL PRACTICE

ACUTE VERSUS CHRONIC ELEVATION OF TROPONIN RISE

• To maintain a high specificity, it is important to distinguish acute from chronic hs-

cTn elevation

• Acute cardiomyocyte injury causes a steep release of troponins, such as in AMI,

shock, myocarditis, pulmonary embolus, Tako-tsubo (stress-induced)

cardiomyopathy

• Chronic, stable elevations of hs- cTn at or above the 99th percentile without a

significant rise or fall are common in patients with structural heart disease

HIGH-SENSITIVITY CARDIAC TROPONIN KINETICS WITH SERIAL TESTING

• To differentiate acute from chronic troponin elevation and to maintain a high

specificity,

• Various rule-in and rule-out algorithms have been proposed using different

time points and cutoff values, including the question whether absolute or

relative hs-cTn changes

• Optimal cutoffs for (absolute and relative) changes and the earliest time

points of the second hs-cTn measurement will have to be determined for each

assay and clinical background

Lancet 2015; 386: 2481–88

Intern Emerg Med (2017) 12:147–155

Non AMI conditions

• Acute heart failure: Using a high-sensitivity assay, troponin was detectable in nearly all patients with

acute decompensation in the large RELAX-HF study.

• Pulmonary embolism: In patients with confirmed pulmonary embolism, elevated troponin

concentrations were reported in up to 50% of patients

• Sepsis: Elevated levels of hs-TnT were associated with adverse outcome, and changes (either

increase or decrease) in hs-TnT levels during the hospital stay were predictive of in-hospital mortality

• Stroke: In patients with stroke, elevated troponin concentrations have been reported and were

associated with mortality

• Stable coronary artery disease In BARI 2D study patients with

diabetes mellitus and stable coronary artery disease,elevated hs-TnT

level above the 99th percentile was reported in 39% of patients,

which was associated with increased rates of cardiovascular events

and death

• Chronic kidney disease. In the CRIC study, hs-TnT was detectable in

81% of patients with impaired renal function, but without previous

cardiovascular disease.

• Concentrations of hs-TnT were associated with incident heart failure

High-sensitivity cardiac troponin elevation in CKD

• Maintain high diagnostic accuracy in patients with renal dysfunction

when assay- specific higher optimal cutoff levels are used

• The high prevalence of persistently elevated more sensitive cTn levels

in patients with chronic kidney disease (CKD) cannot primarily be

explained by reduced renal clearance alone

• Chronic heart failure: Patients with chronic heart failure from the Val-

HeFT and the GISSI-HF studies, hs-TnT was measured at baseline and

after 3 or 4 months.

• Baseline hs-TnT level was a strong predictor of all-cause mortality, but

serial measurement had only a minor influence on risk discrimination.

CONCLUSIONS • The introduction of the hs-cTnT assay with lower cut-off levels for diagnosing AMI

in patients with acute chest pain is associated with enhanced overall diagnostic

accuracy

• A negative hs-cTnT test has a high negative predictive value, and may thus serve

as an exclusionary test early in the diagnostic process.

• Risk stratification for ACS

• The levels of hs-TnT can serve as a risk stratification in patients with stable CAD,

HF, and non-cardiac disease conditions

TANK U