Clinical impact of current evidence on cardiac troponin structure, function and release mechanisms - An up to date review.

High-Sensitive Troponin Testing and the “Runner's Syndrome”

The introduction of more sensitive cardiac troponin assays has led to increased recognition of myocardial injury in acute illnesses other than acute coronary syndrome. The Universal Definition of Myocardial Infarction recommends high-sensitivity cardiac troponin testing and classification of patients with myocardial injury based on pathogenesis, but the clinical implications of implementing this guideline are not well understood. In a stepped-wedge cluster randomized, controlled trial, we implemented a high-sensitivity cardiac troponin assay and the recommendations of the Universal Definition in 48 282 consecutive patients with suspected acute coronary syndrome. In a prespecified secondary analysis, we compared the primary outcome of myocardial infarction or cardiovascular death and secondary outcome of noncardiovascular death at 1 year across diagnostic categories. Implementation increased the diagnosis of type 1 myocardial infarction by 11% (510/4471), type 2 myocardial infarction by 22% (205/916), and acute and chronic myocardial injury by 36% (443/1233) and 43% (389/898), respectively. Compared with those without myocardial injury, the rate of the primary outcome was highest in those with type 1 myocardial infarction (cause-specific hazard ratio [HR] 5.64 [95% CI, 5.12-6.22]), but was similar across diagnostic categories, whereas noncardiovascular deaths were highest in those with acute myocardial injury (cause specific HR 2.65 [95% CI, 2.33-3.01]). Despite modest increases in antiplatelet therapy and coronary revascularization after implementation in patients with type 1 myocardial infarction, the primary outcome was unchanged (cause specific HR 1.00 [95% CI, 0.82-1.21]). Increased recognition of type 2 myocardial infarction and myocardial injury did not lead to changes in investigation, treatment or outcomes. Implementation of high-sensitivity cardiac troponin assays and the recommendations of the Universal Definition of Myocardial Infarction identified patients at high-risk of cardiovascular and noncardiovascular events but was not associated with consistent increases in treatment or improved outcomes. Trials of secondary prevention are urgently required to determine whether this risk is modifiable in patients without type 1 myocardial infarction. https://www.clinicaltrials.gov. Unique identifier: NCT01852123.

249High-sensitivity cardiac troponin and the universal definition of myocardial infarction: a randomised controlled trial

HomeCirculationVol. 144, No. 9Letter by Sandoval and Jaffe Regarding Article, “Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBLetter by Sandoval and Jaffe Regarding Article, “Temporal Release of High-Sensitivity Cardiac Troponin T and I and Copeptin After Brief Induced Coronary Artery Balloon Occlusion in Humans” Yader Sandoval, MD Allan S. JaffeMD Yader SandovalYader Sandoval Cardiovascular Department, Mayo Clinic, Rochester, MN. Search for more papers by this author and Allan S. JaffeAllan S. Jaffe Cardiovascular Department, Mayo Clinic, Rochester, MN. Search for more papers by this author Originally published30 Aug 2021https://doi.org/10.1161/CIRCULATIONAHA.121.054861Circulation. 2021;144:e168To the Editor:We have been intrigued by the observations of Árnadóttir and colleagues1 since we saw the abstract of their data at the 2018 European Society of Cardiology in Munich. They raise several interesting issues, most of which were discussed by the accompanying editorial comments, which were excellent. The results could scare clinicians about the clinical sensitivity of these assays. One issue of importance that helps ease some concerns that was not adequately addressed is the role of transient occlusion and reperfusion on the kinetics of cardiac troponin (cTn) release. Regardless of the mechanisms, there clearly is release of cTn after transient occlusion of a coronary artery. However, in this situation, the magnitude of the peak value is accentuated by the abrupt robust reperfusion that occurs due to reactive hyperemia, which, by washing out cTn, accentuates the magnitude of the changes. Clinicians understand this from observing the effects of reperfusion and physiologic studies confirm that in the human coronary circulation, flow can increase 4- to 5-fold.2 Although it was not done, had the authors continued to measure cTn, it is likely that the area under the time–concentration curve would be small despite such an apparent marked peak increase. This phenomenon is likely an important reason why atrial pacing3 and small doses of dobutamine4 even in normal patients cause detectable rises in high-sensitivity cTn as well when there are widely patent coronary arteries. It is also likely the reason that concentrations increase and come down so rapidly after exercise and with pulmonary embolism. On the other hand, when ischemic heart disease is present, the magnitude of release may be blunted because of less robust reperfusion but the area under the time–concentration curve will be much larger in that situation. Recognizing this important concept may alleviate some of the concerns clinicians may have.The universal definition of myocardial infarction mandates the need for objective evidence of myocardial ischemia (ECG changes, angiographic complications, or “imaging evidence of new loss of viable myocardium or new regional wall motion abnormality in a pattern consistent with an ischemic etiology”) in addition to biomarker criteria to diagnose a periprocedural myocardial infarction. As reported, these patients lacked those criteria and thus had myocardial injury but not myocardial infarction.5Disclosures Dr Sandoval has previously served on advisory boards for Roche Diagnostics and Abbott Diagnostics and has been a speaker for Abbott Diagnostics, both without personal financial compensation. Dr Jaffe consults for or has consulted for most of the major diagnostic companies, including Abbott, Beckman-Coulter, Siemens, Roche, Radiometer, ET Healthcare, Sphingotec, Amgen, and Novartis. These companies make the troponin assays used in the report commented on.Footnoteshttps://www.ahajournals.org/journal/circ

BackgroundThe Universal Definition of Myocardial Infarction recommends the 99th centile diagnostic threshold using a high-sensitivity cardiac troponin (hs-cTn) assay and classification of patients by the etiology of myocardial injury. Whether...

The frequency and characteristics of myocardial infarction (MI) subtypes per the Third Universal Definition of MI (TUDMI) classification system using high-sensitivity (hs) cardiac troponin assays with sex-specific cutoffs is not well known. We sought to describe the diagnostic characteristics of type 1 (T1MI) and type 2 (T2MI) MI using an hs-cardiac troponin I (hs-cTnI) assay with sex-specific cutoffs. A total of 310 consecutive patients with serial cTnI measurements obtained on clinical indication were studied with contemporary and hs-cTnI assays. Ninety-ninth percentile sex-specific upper reference limits (URLs) for the hs-cTnI assay were 16 ng/L for females and 34 ng/L for males. The TUDMI consensus recommendations were used to define and adjudicate MI based on each URL. A total of 127 (41%) patients had at least 1 hs-cTnI exceeding the sex-specific 99th percentiles, whereas 183 (59%) had hs-cTnI within the reference interval. Females had more myocardial injury related to supply/demand ischemia than males (39% vs 18%, P = 0.01), whereas males had more multifactorial or indeterminate injury (52% vs 33%, P = 0.05). By hs-cTnI, there were 32 (10%) acute MIs, among which 10 (3%) were T1MI and 22 (7%) were T2MI. T2MI represented 69% (22 out of 32) of all acute MIs, whereas T1MI represented 31% (10 out of 32). Ninety-five patients (31%) had an increased hs-cTnI above the 99th percentile but did not meet criteria for acute MI. The most common triggers for T2MI were tachyarrhythmias, hypotension/shock, and hypertension. By contemporary cTnI, more MIs (14 T1MI and 29 T2MI) were diagnosed. By contemporary cTnI, there were 43 MIs, 14 T1MI, and 29 T2MI. Fewer MI diagnoses were found with the hs-cTnI assay, contrary to the commonly accepted idea that hs-cTnI will lead to excessive false-positive diagnoses.

P1578Outcomes in patients with renal impairment and myocardial injury or infarction identified by high-sensitivity cardiac troponin testing: a secondary analysis of the High-STEACS trial

Current methods (highly sensitive and ultra-sensitive) of cardiospecific troponins detection have enabled early diagnosis of myocardial infarction (MI) and selection of optimal treatment tactics for patients early from admission. The use of these methods in real clinical practice helps to choose the most optimal treatment tactics for patients in the early stages after admission, and this significantly improved the further prognosis of patients suffering from MI. However, there are a number of problems that arise when using highly sensitive or ultra-sensitive methods for determining cardiospecific troponins: frequent and unexplained increases in serum levels of cardiospecific troponins in a number of pathological conditions unrelated to MI; insufficient knowledge and understanding of the mechanisms of release and increase in the levels of cardiospecific troponins; poorly understood features and mechanisms of circulation and elimination of cardiospecific troponins; the presence of conflicting information about the influence of several factors (gender, age and circadian characteristics) on the levels of cardiospecific troponins in blood serum; undisclosed diagnostic potential of cardiospecific troponins in non-invasive human biological fluids. These problems cause great difficulties and increase the risk of errors in the differential diagnosis of MI, and also do not allow to fully unlock the diagnostic potential of cardiospecific troponins. In general, these problems are associated with a lack of understanding of the fundamental mechanisms of the metabolism of cardiospecific troponins. The main purpose of this narrative review is to summarize and provide detailed information about the metabolism of cardiospecific troponins and to discuss the potential impact of metabolic features on the diagnostic value of cardiospecific troponins and their diagnostic capabilities. This narrative review is based on the analysis of publications in the Medline, PubMed, and Embase databases. The terms "cardiac troponins", "troponin T", and "troponin I" in combination with "mechanisms of increase", "mechanisms of release", "circulation", "proteolytic cleavage", "elimination", "circadian rhythms", "saliva", and "urine" were used to search publications. It has been reported that the metabolic features (mechanisms of release, circulation, and elimination) of cardiospecific troponins may have an important influence on the diagnostic value of cardiospecific troponins in a number of physiological and pathological conditions that cause cardiomyocyte damage. The main mechanisms of cardiac troponin release are: cardiomyocyte apoptosis; myocardial cell regeneration and renewal; increased cell membrane permeability; release of troponins by vesicular transport; increased proteolytic degradation of cardiospecific troponin molecules within the cell which may facilitate their release from intact myocardial cells or in the initial phase of those pathological conditions that increase the activity of enzymes that degrade cardiospecific troponins. Besides, the formation of small fragments (troponin molecules) may facilitate their penetration into other body fluids such as urine and/or oral fluid which may provide researchers and practitioners with a new diagnostic opportunity. It should be noted that in addition to release mechanisms, cardiospecific troponin elimination mechanisms may play an important diagnostic role. The contribution of release and elimination mechanisms to different pathologies may differ significantly. Circadian rhythms of cardiospecific troponins may be associated with fluctuations in the activity of those organ systems which influence the mechanisms of cardiospecific troponin release or elimination. Such major systems include: neuroendocrine, urinary, and hemostasis. Cardiospecific troponins metabolism has an important influence on diagnostic value and diagnostic capabilities. Further study of the features of cardiac troponin metabolism (mechanisms of release, circulation and elimination) is required to improve diagnosis and differential diagnosis of diseases causing cardiomyocyte damage. The data on the influence of circadian rhythms of cardiospecific troponins on the diagnostic value and the possibility of determining cardiospecific troponins in body fluids that can be obtained by noninvasive methods are very interesting. However, so far this information and valuable capabilities have not been applied in clinical practice because of the paucity of studies conducted.

A Biomarker Model to Distinguish Types of Myocardial Infarction and Injury

Incidence and prediction of periprocedural myocardial infarction in elective PCI: the ALPHEUS-MI sub-study

Circadian rhythm of cardiac troponins. Does it really exist?

Biomarkers in the triage of chest pain: are we making progress?

Cardiac biomarkers of necrosis provide clinicians with important “messages” from the heart. They are released into the interstitium of the myocardium after loss of the integrity of cardiac myocyte membranes. The pattern of the rise and fall of an individual biomarker (ie, its release kinetics) depends on its intracellular location in the myocyte, molecular weight, and clearance from the interstitium of the myocardium and ultimately the circulation.1 Cardiac biomarkers play an integral role in the clinical diagnosis of myocardial infarction (MI). Referring to the spontaneous occurrence of MI in patients, the World Health Organization required that at least 2 of the following be present to fulfill the criteria for MI: a history of ischemia-type chest discomfort, evolutionary changes on serially obtained ECG tracings, and a rise and fall in serum cardiac markers.2 Article see p 10 See Editorial Circulation . 2008;118:609–611 See Article Circulation . 2008;118:632–638 Several dramatic advances have occurred in the biomarker component of the diagnosis of MI. Analytes with greater specificity for the myocardium were introduced into clinical medicine, with creatine kinase-MB replacing total creatine kinase and subsequently cardiac-specific troponins replacing creatine kinase-MB as the biomarker of choice for diagnosing MI.3 Assay technology improved as clinical chemists moved from enzymatic activity assays for CK to highly specific immunoassays that can detect progressively smaller concentrations of cardiac troponins in the peripheral circulation.4 Although ST-elevation MI (STEMI) is easily identified on the 12-lead ECG, we now recognize that many patients previously diagnosed with unstable angina are more properly diagnosed as having non–ST-elevation MI (NSTEMI) on the basis of the detection of elevated levels of cardiac troponins in their blood.5 Cardiac biomarkers are used as a rough guide to the extent of myocardial necrosis. The higher the peak biomarker level after STEMI, the larger the …

Long-term follow-up of patients with myocardial infarction and myocardial injury

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