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![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](https://image.slidesharecdn.com/hstrop-171207070115/85/High-sensitive-troponin-7-320.jpg)
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High sensitive troponin
High-sensitivity cardiac troponin (hs-ctn) assays provide improved diagnostic accuracy for acute myocardial infarction (AMI) by detecting troponin at lower concentrations than conventional assays. These assays can distinguish between acute and chronic troponin elevation, which is vital for accurate diagnosis and risk stratification in various cardiac and non-cardiac conditions. The introduction of hs-ctn testing enhances early rule-in and rule-out of AMI, supporting better clinical decision-making.
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High sensitive troponin
- 1. HIGH-SENSITIVITY CARDIAC TROPONIN DRMAHENDRA CARDIOLOGY, JIPMER
- 2. INTRODUCTION • A rapidand 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
- 3. CARDIAC BIOMARKERS Intern EmergMed (2017) 12:147–155
- 4. WHAT IS TROPONIN? •Troponin is a component of the contractile apparatus within skeletal and cardiac myocytes.
- 5. MECHANISMS TO EXPLAINTHE RELEASE • Normal cell turnover • Myocyte necrosis • Apoptosis or programmed cell death • Proteolytic fragmentation • Increased cell membrane permeability
- 6. OTHER CAUSES OFTROPONIN ELEVATION
- 7. ROLE OF CARDIACBIOMARKERS 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
- 8. NEED FOR HIGH-SENSITIVITYCARDIAC 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.
- 9. HIGH-SENSITIVITY CARDIAC TROPONIN 5thgeneration 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
- 11. DETECTION RANGE OFDIFFERENT TROPONIN ASSAYS
- 12. Characteristics of HsTroponin • 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.
- 13. MI and TROPONINRELEASE
- 16. USE OF HIGH-SENSITIVITYCARDIAC TROPONIN IN CLINICAL PRACTICE
- 17. ACUTE VERSUS CHRONICELEVATION 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
- 18. HIGH-SENSITIVITY CARDIAC TROPONINKINETICS 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
- 19. Lancet 2015; 386:2481–88
- 20. Intern Emerg Med(2017) 12:147–155
- 21. 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
- 23. • Stable coronaryartery 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
- 24. High-sensitivity cardiac troponinelevation 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
- 25. • Chronic heartfailure: 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.
- 26. CONCLUSIONS • The introductionof 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
- 27.
Editor's Notes
- #3 syndrome for the initiation of effective evidence-based medical management and revascularization prevents the mistaken discharge of patients with AMI with normal findings on initial ECG and also helps in early initiation of effective evidence- based therapy. prevents inadver- tent admission of patients without ACS and facilitates early discharge of patients and thereby decreases the unwarranted healthcare burden.10 . Patients with ST-segment elevation AMI can easily be diagnosed using an electrocardiogram (ECG) on admission, whereas the differential diagnosis of non-ST- segment elevation AMI (NSTEMI) and unstable angina pectoris is on the basis of cardiac troponin testing with serial sampling7
- #4 Timeline of the development of cardiac biomarkers for the diagnosis of acute myocardial infarction
- #5 troponin T attaches the troponin complex to the actin filament; troponin C acts as the calcium binding site; troponin I inhibits interaction with myosin heads in the absence of sufficient calcium ions. Troponin T and I isoforms are highly specific and sensitive to cardiac myocytes and, therefore, are known as cardiac troponins (cTn). 92–95% of troponin is attached to the actin thin filaments in the cardiac sarcomere, and the remaining 5–8% is free in the myocyte cytoplasm However, in patients with chronic renal failure, cTnI has greater specificity for myocar- dial injury than cTnT.
- #8 Current guidelines recommend serial measurements of troponin with a cut-off concentration at the 99th percentile to triage patients in the emergency department. Newer, high-sensitivity assays for troponin enable the detection of distinctly lower concentrations. Using these assays and very low cut-off concentrations, several rapid diagnostic strategies have been reported to improve diagnosis in acute cardiac care
- #9 5th generation hs-cTn T and I assays which can detect troponin at concentrations 10- to 100-fold lower than con- ventional assays hs-cTn assays detect troponin with higher sensi- tivity and precision at an earlier point of time [22], and allow detection and quantification in 50% to ideally 95% of healthy individuals In 2009, the first high-sensitivity assay for TnT (hs-TnT) was introduced (fifth-generation assays). The limit of detection was 2 ng/l and the 99th percentile was 14 ng/l2 The hs-TnT assay is a modification of the fourth- generation assay. It uses a mouse–human chimeric detection antibody, with an increased sample size, and decreased background noise owing to buffer opti- mization22 To label an assay as ‘high-sensitivity’, it should report troponin concentrations in a large proportion of the general population. A proportion of 50% has been dis- cussed, whereas an even higher proportion of up to 80% might be reasonable2
- #13 with analytical CV -10% at the 99th percentile concentration of the reference population (URL). thereby allowing for a more accurate calculation of the 99th percentile URL with its 99% confidence interval.
- #15 The lower the level of hs-cTn, the higher the negative predictive value (NPV) for the presence of AMI. The higher the level of hs-cTn, the higher the positive predictive value (PPV) for the presence of AMI. Levels just above the 99th percentile have a low PPV for AM
- #16 Cohorts of patients, including those with suspected AMI, were used to investigate the diagnostic performance of various troponin assays and shorter time intervals (TABLE 2). These cohorts were heterogeneous in terms of prevalence of AMI (8–22%) and cardiovascular risk factors (for example, 9–25% had a history of AMI). The ADAPT study45 was the first cohort, and serial troponin measurement after only 2 h was investigated. The researchers used a hs-Tn cut-off level at the 99th percentile in combination with a nonischaemic ECG and a low risk score, based on history and symptoms. This approach resulted in a high NPV of 99.7% for the primary outcome (major adverse cardiac events (MACE) after 30 days; n the TRAPID-AMI study48, a hs-TnT assay with two different strategies was used To rule out AMI, a baseline cut-off concentration of 12 ng/l, which is close to the 99th percentile, and an absolute change of only 3 ng/l were used, which resulted in a high NPV of 99.1%. The rule-in of AMI was based on a high cut-off value of 52 ng/l, or a change of >5 ng/l, and had a high positive predictive value (PPV) of 77%. In the High-STEACS study53, this approach was prospectively tested using a hs-TnI assay. A hs-TnI cut-off value of 5 ng/l resulted in the ruling out of AMI in 61% of the study population, and a NPV of 99.6%. The first US testing of the use of a baseline hs-TnI measurement to rule out AMI involved the UTROPIA cohort; a cut-off value of 1.9 ng/l (the limit of detection) was associated with a NPV of 99.6%56.
- #18 In these cases, increased ventricular wall tension is thought to cause direct myofibrillar filament damage and an increase in programmed cell death, both of which contribute to hs-cTn release This has been observed in patients with left ventricular hypertrophy, valvular heart disease, stable congestive heart failure, pulmonary hypertension, stable angina or other forms of clinically stable cardiomyopathy.
- #19 clinical evaluation (pre-test probability) and serial testing of hs-cTn are warranted.
- #21 It is generally recommended to use the 3-h algorithm. In cases of high pre-test probability for NSTEMI and if chest pain onset [3 h, a 1-h algorithm has now been proposed with assay-specific hs-cTn cutoff levels Additional blood sampling after 3 h in patients with strong clinical suspicion of AMI but no significant rise or fall of hs-cTn may nevertheless still be warranted:
- #22 In a large study using an insensitive assay for troponin, 6% of patients with acute decompensated heart failure had elevated concentrations of troponin . Furthermore, troponin detection was associated with adverse outcomes in this popula- tion, and improved risk prediction when added to the established biomarker B-type natriuretic peptide. s well as increased wall stress, oxidative stress, inflammatory processes, and several other causes more related to the heart failure pathophysiology itself. Pulmonary embolism is one of the most important differential diagnoses in patients presenting with suspected AMI, and is often associated with chest pain or dyspnoea.
- #24 An elevated level of TnT or TnI was an independent predictor of heart failure and death. In patients with chronic kidney disease, troponin con- centrations are often elevated, which is mostly explained by an increased prevalence of cardiovascular disease, but also by reduced renal elimination of troponin from the blood . In patients receiv- ing haemodialysis, hs-TnT level was a powerful predictor of all-cause mortality, whereas all patients with a hs-TnT level <24 ng/l survived follow-up (median 46 months)1
- #25 The etiology of persistent troponin elevation in CKD remains incompletely explained and controversial. The underlying process appears to be multifactorial related to both increased subclinical cardiac damage (uremic toxicity, ischemic heart disease, heart failure or hypertensive heart disease) and decreased renal clear- ance in this population
- #26 In patients with stable heart fail- ure, troponin concentrations increased with worsening NYHA class and were associated with a worse outcome in these patients1
- #27 The gain in sensitivity may be particularly important in patients with a short dura- tion from symptom onset to admission. even at levels below the LoD of the previous generation of assays.