ObjectiveTakotsubo syndrome (TTS) is an acute heart failure syndrome which resembles acute coronary syndrome (ACS) at presentation. Differentiation requires coronary angiography, but where this does not occur immediately, cardiac biomarkers may provide additional utility. We performed a meta-analysis to compare troponin and natriuretic peptides (NPs) in TTS and ACS to determine if differences in biomarker profile can aid diagnosis.MethodsWe searched five literature databases for studies reporting NPs (Brain NP (BNP)/NT-pro-BNP) or troponin I/T in TTS and ACS, identifying 28 studies for troponin/NPs (5618 and 1145 patients, respectively).ResultsTroponin was significantly lower in TTS than ACS (standardised mean difference (SMD) −0.86; 95% CI, −1.08 to −0.64; p<0.00001), with an absolute difference of 75 times the upper limit of normal (×ULN) higher in ACS than TTS. Conversely, NPs were significantly higher in TTS (SMD 0.62; 95% CI, 0.44 to 0.80; p<0.00001) and 5.8×ULN greater absolutely. Area under the curve (AUC) for troponin in ACS versus TTS was 0.82 (95% CI, 0.70 to 0.93), and 0.92 (95% CI, 0.80 to 1.00) for ST-segment elevation myocardial infarction versus TTS. For NPs, AUC was 0.69 (95% CI, 0.48 to 0.89). Combination of troponin and NPs with logistic regression did not improve AUC. Recursive Partitioning and Regression Tree analysis calculated a troponin threshold ≥26×ULN that identified 95% cases as ACS where and specificity for ACS were 85.71% and 53.57%, respectively, with 94.32% positive predictive value and 29.40% negative predictive value.ConclusionsTroponin is lower and NPs higher in TTS versus ACS. Troponin had greater power than NPs at discriminating TTS and ACS, and with troponin ≥26×ULN patients are far more likely to have ACS.

Treatment of chronic total occlusions (CTOs) by percutaneous coronary intervention (PCI) is technically challenging, with exponential difficulty in the presence of specific anatomical features. We present a complex case where procedural success was achieved by sequential PCIs to two separate CTOs in a 'two-in-one' procedure.

ObjectivesEnd-stage renal disease is associated with a high risk of cardiovascular disease. We compared the concentration and prognostic ability of high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI) and cardiac myosin-binding protein C (cMyC) among stable hemodialysis patients.MethodsPatients were sampled before and after hemodialysis. We measured hs-cTnI, hs-cTnT and cMyC and used Cox regressions to assess the association between quartiles of concentrations and all-cause mortality and a combination of cardiovascular events and all-cause mortality during follow-up.ResultsA total of 307 patients were included, 204 males, mean age 66 years (SD 14). Before dialysis, 299 (99 %) had a hs-cTnT concentration above the 99th percentile, compared to 188 (66 %) for cMyC and 35 (11 %) for hs-cTnI. Hs-cTnT (23 %, p<0.001) and hs-cTnI (15 %, p=0.049) but not cMyC (4 %, p=0.256) decreased during dialysis. Follow-up was a median of 924 days (492-957 days); patients in the 3rd and 4th quartiles of hs-cTnT (3rd:HR 3.0, 95 % CI 1.5-5.8, 4th:5.2, 2.7-9.8) and the 4th quartile of hs-cTnI (HR 3.8, 2.2-6.8) had an increased risk of mortality. Both were associated with an increased risk of the combined endpoint for patients in the 3rd and 4th quartiles. cMyC concentrations were not associated with risk of mortality or cardiovascular event.ConclusionsHs-cTnT was above the 99th percentile in almost all patients. This was less frequent for hs-cTnI and cMyC. High cTn levels were associated with a 3-5-fold higher mortality. This association was not present for cMyC. These findings are important for management of hemodialysis patients.

Abstract Introduction Cardiac myosin-binding protein C (cMyC) is a novel protein biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients with cardiac disease. Understanding the physiological diurnal oscillation of cMyC and cardiac troponin is important for the interpretation of single and serial measurements within the biomarker-assisted triage and risk stratification algorithms. Purpose In this study, we aim to assess and compare the physiological diurnal oscillation of cMyC and cardiac troponin cTnT and cTnI. Method Twenty-six consecutive hourly blood samples were drawn between 08.30 am and 09.30 am (+1 day) from normotensive 24 individuals without a recent history of acute myocardial infarction, for the measurement of cMyC, cardiac troponin T (Roche hs-cTnT) and I (Abbott hs-cTnI). Fitted cosinor sine regression model (with R, version 3.6.1) was used to assess the presence and significance of circadian oscillation of the biomarker, and to estimate the respective amplitude and acrophase (the time of peak activity). Amplitude and acrophase were compared across the biomarkers that exhibited significant circadian rhythm. Results Mean age was 72±7. 79% of participants (n=19) were men. All participants were free from renal disease. On population-mean cosinor analysis, hs-cTnI exhibited random diurnal oscillation, whereas significant circadian rhythm was detected for cMyC and hs-cTnT (p=0.015 and <0.001, respectively) (Figure 1). The circadian rhythm of cMyC is characterised by gradually increasing concentrations from early afternoon until early morning (acrophase 03:03 am, 95% CI 01:54–04:26 am) compared to hs-cTnT concentrations which exhibits delayed increase and a later peak (acrophase, 08:01, 95% CI 07:10–08:51 am), p=0.028 for acrophase difference (Figure 1). Diurnal rhythm remained significant after correction for possible posture-induced changes in plasma volume. To allow direct comparison between amplitudes, the measurements of cMyC and hs-TnT were normalised to the respective 08:30 am value, re-fitted cosinor model did not show significant difference between the amplitudes (amplitude ng/L, 0.12, 95% CI 0.07–0.15 vs 0.11, 95% CI 0.08–0.12, for normalised cMyC vs hs-cTnT, respectively; p=0.67). Conclusion Significant circadian rhythm exists for cMyC and hs-cTnT, with 5-hours phase difference between the two biomarkers (cMyC ahead of hs-cTnT). The cause of this rhythmic variation is unknown, but the phase difference is consistent with the previously described disparity in the release of cMyC and cTnT after iatrogenic myocardial injury, raising the possibility of an underlying diurnal variation in myocardial vulnerability. Studies are required to assess the impact of this physiological phenomenon on the performance of the biomarkers within unadjused diagnostic algorithms Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): British Heart FoundationStichting de Weijerhorst

Chronic total occlusions (CTOs) represent the most complex subset of coronary artery disease and therefore careful planning of CTO percutaneous coronary recanalization (PCI) strategy is of paramount importance aiming to achieve procedural success, and improve patient's safety and post CTO PCI outcomes. Intravascular imaging has an essential role in facilitating CTO PCΙ. First, intravascular ultrasound (IVUS), due to its higher penetration depth compared to optical coherence tomography (OCT), and the additional capacity of real-time imaging without need for contrast injection is considered the preferred imaging modality for CTO PCI. Secondly, IVUS can be used to resolve proximal cap ambiguity, facilitate wire re-entry when dissection and re-entry strategies are applied and most importantly to guide stent deployment and optimization post implantation. The role of OCT during CTO PCI is currently limited to stent sizing and optimization, however, due to its high spatial resolution, OCT is ideal for detecting stent edge dissections and strut malapposition. In this review, we describe the use of intravascular imaging for lesion crossing, plaque characterization and wire tracking, extra- or intra-plaque, and stent sizing and optimization during CTO PCI and summarize the findings of the major studies in this field.

Aims To evaluate the clinical feasibility of implementing the 2020 ESC 0/1 hr algorithm for rapid rule-out/rule-in of acute coronary syndrome (ACS).Methods and results Data were collected retrospectively from 5496 patients in 2020 and 7363 patients in 2021 who received cardiac troponin measurements through the ACS algorithm in acute care settings within a large tertiary cardiac centre in the United Kingdom. This period overlapped the introduction of the 2020 ESC 0/1 hr algorithm. After exclusion of haemolysis, 1905 patients underwent repeat troponin measurement within the study period in 2020 and 2658 in 2021. Median time to repeat was significantly reduced from 3 h 14 min for intermediate low risk patients (5-12 ng/L) in 2020 to 1 h 22 min in 2021, and from 3 h 30 min to 1 h 59 min in intermediate high-risk patients (12-51 ng/L). Less than 15% of patients requiring repeat testing had dynamic changes in troponin of sufficient magnitude to change their initial risk category. Of all patients, 58.1% of patients in 2020 were ultimately classified as 'low risk', 19.2% deemed 'ACS likely', and 22.7% as 'ACS possible', with similar distributions in 2021.Conclusion Whilst an efficient algorithm, our study demonstrates multi-faceted, practical limitations of achieving the 1 h target for the triage of patients with suspected ACS. Despite challenges predominantly of logistic nature, the algorithm enables rapid, streamlined, and efficient triage of large patient cohorts. Further work is required to streamline this process and achieve the targeted 1 h repeat in a resource-constrained healthcare environment, which would invariably require second blood draw before the result of first, as recommended by the ESC.

Percutaneous transluminal coronary angioplasty balloon fracture, retention, and embolization are rare complications of percutaneous coronary intervention. The incidence has historically been estimated at <0.8%, which is likely an underestimate given the increasing quantity and complexity of percutaneous procedures. We demonstrate how to avoid emergency surgery by using basic balloon trapping techniques and a snare in the more distal arterial bed.

Application of the hybrid algorithm for the treatment of coronary chronic total occlusions requires the operator to readily deploy complex techniques and advanced technologies to achieve successful revascularization. Patient-specific factors and limitations in torquability and material strength of low-profile equipment such as microcatheters can result in procedural complications due to device fracture. Using a mini-series of 2 cases to demonstrate the successful application of antegrade dissection re-entry techniques to overcome such challenges, we highlight procedural complexities and risk, and review prior approaches and literature.

Abstract Aims Cardiac myosin-binding protein C (cMyC) demonstrated high diagnostic accuracy for the early detection of non-ST-elevation myocardial infarction (NSTEMI). Its dynamic release kinetics may enable a 0/1h-decision algorithm that is even more effective than the ESC hs-cTnT/I 0/1 h rule-in/rule-out algorithm. Methods and results In a prospective international diagnostic study enrolling patients presenting with suspected NSTEMI to the emergency department, cMyC was measured at presentation and after 1 h in a blinded fashion. Modelled on the ESC hs-cTnT/I 0/1h-algorithms, we derived a 0/1h-cMyC-algorithm. Final diagnosis of NSTEMI was centrally adjudicated according to the 4th Universal Definition of Myocardial Infarction. Among 1495 patients, the prevalence of NSTEMI was 17%. The optimal derived 0/1h-algorithm ruled-out NSTEMI with cMyC 0 h concentration below 10 ng/L (irrespective of chest pain onset) or 0 h cMyC concentrations below 18 ng/L and 0/1 h increase <4 ng/L. Rule-in occurred with 0 h cMyC concentrations of at least 140 ng/L or 0/1 h increase ≥15 ng/L. In the validation cohort (n = 663), the 0/1h-cMyC-algorithm classified 347 patients (52.3%) as ‘rule-out’, 122 (18.4%) as ‘rule-in’, and 194 (29.3%) as ‘observe’. Negative predictive value for NSTEMI was 99.6% [95% confidence interval (CI) 98.9–100%]; positive predictive value 71.1% (95% CI 63.1–79%). Direct comparison with the ESC hs-cTnT/I 0/1h-algorithms demonstrated comparable safety and even higher triage efficacy using the 0h-sample alone (48.1% vs. 21.2% for ESC hs-cTnT-0/1 h and 29.9% for ESC hs-cTnI-0/1 h; P < 0.001). Conclusion The cMyC 0/1h-algorithm provided excellent safety and identified a greater proportion of patients suitable for direct rule-out or rule-in based on a single measurement than the ESC 0/1h-algorithm using hs-cTnT/I. Trial registration ClinicalTrials.gov number, NCT00470587.

Abstract Objectives Cardiac myosin-binding protein C (cMyC) is a novel biomarker of myocardial injury, with a promising role in the triage and risk stratification of patients presenting with acute cardiac disease. In this study, we assess the weekly biological variation of cMyC, to examine its potential in monitoring chronic myocardial injury, and to suggest analytical quality specification for routine use of the test in clinical practice. Methods Thirty healthy volunteers were included. Non-fasting samples were obtained once a week for ten consecutive weeks. Samples were tested in duplicate on the Erenna® platform by EMD Millipore Corporation. Outlying measurements and subjects were identified and excluded systematically, and homogeneity of analytical and within-subject variances was achieved before calculating the biological variability (CVI and CVG), reference change values (RCV) and index of individuality (II). Results Mean age was 38 (range, 21–64) years, and 16 participants were women (53%). The biological variation, RCV and II with 95% confidence interval (CI) were: CVA (%) 19.5 (17.8–21.6), CVI (%) 17.8 (14.8–21.0), CVG (%) 66.9 (50.4–109.9), RCV (%) 106.7 (96.6–120.1)/−51.6 (−54.6 to −49.1) and II 0.42 (0.29–0.56). There was a trend for women to have lower CVG. The calculated RCVs were comparable between genders. Conclusions cMyC exhibits acceptable RCV and low II suggesting that it could be suitable for disease monitoring, risk stratification and prognostication if measured serially. Analytical quality specifications based on biological variation are similar to those for cardiac troponin and should be achievable at clinically relevant concentrations.

HomeJournal of the American Heart AssociationVol. 10, No. 13Cardiac Biomarker Kinetics and Their Association With Magnetic Resonance Measures of Cardiomyocyte Integrity Following a Marathon Run: Implications for Postexercise Biomarker Testing Open AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citations ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toOpen AccessLetterPDF/EPUBCardiac Biomarker Kinetics and Their Association With Magnetic Resonance Measures of Cardiomyocyte Integrity Following a Marathon Run: Implications for Postexercise Biomarker Testing Vincent L. Aengevaeren, MD, PhD, Roland R. J. van Kimmenade, MD, PhD, Jordi Ordóñez‐Llanos, MD, PhD, Álvaro García‐Osuna, PhD, Thomas E. Kaier, MD, PhD, Michael Marber, MD, PhD, Martijn Froeling, PhD, Sandra van den Berg‐Faay, MSc, Melissa T. Hooijmans, PhD, Jithsa R. Monte, MD, Maria T. E. Hopman, MD, PhD, Gustav J. Strijkers, PhD, Aart J. Nederveen, PhD, Adrianus J. Bakermans, PhD and Thijs M. H. Eijsvogels, PhD Vincent L. AengevaerenVincent L. Aengevaeren Department of Physiology, , Radboud Institute for Health Sciences, Radboud University Medical Center, , Nijmegen, , The Netherlands Department of Cardiology, , Radboud Institute for Health Sciences, Radboud University Medical Center, , Nijmegen, , The Netherlands , Roland R. J. van KimmenadeRoland R. J. van Kimmenade Department of Cardiology, , Radboud Institute for Health Sciences, Radboud University Medical Center, , Nijmegen, , The Netherlands , Jordi Ordóñez‐LlanosJordi Ordóñez‐Llanos https://orcid.org/0000-0003-4896-5832 Department of Clinical Biochemistry, , IIB‐Hospital de Sant Pau, , Barcelona, , Spain , Álvaro García‐OsunaÁlvaro García‐Osuna https://orcid.org/0000-0002-6682-0226 Department of Clinical Biochemistry, , IIB‐Hospital de Sant Pau, , Barcelona, , Spain , Thomas E. KaierThomas E. Kaier https://orcid.org/0000-0002-4669-2095 The Rayne Institute, , St Thomas' Hospital, , King's College London British Heart Foundation Centre, , London, , United Kingdom , Michael MarberMichael Marber The Rayne Institute, , St Thomas' Hospital, , King's College London British Heart Foundation Centre, , London, , United Kingdom , Martijn FroelingMartijn Froeling https://orcid.org/0000-0003-3841-0497 Department of Radiology, , University Medical Center Utrecht, , Utrecht, , The Netherlands , Sandra van den Berg‐FaaySandra van den Berg‐Faay Department of Radiology and Nuclear Medicine, , Amsterdam University Medical Centers, University of Amsterdam, , Amsterdam, , The Netherlands , Melissa T. HooijmansMelissa T. Hooijmans Biomedical Engineering and Physics, , Amsterdam University Medical Centers, University of Amsterdam, , Amsterdam, , The Netherlands , Jithsa R. MonteJithsa R. Monte https://orcid.org/0000-0002-6337-7660 Department of Radiology and Nuclear Medicine, , Amsterdam University Medical Centers, University of Amsterdam, , Amsterdam, , The Netherlands , Maria T. E. HopmanMaria T. E. Hopman Department of Physiology, , Radboud Institute for Health Sciences, Radboud University Medical Center, , Nijmegen, , The Netherlands , Gustav J. StrijkersGustav J. Strijkers https://orcid.org/0000-0001-6700-5058 Biomedical Engineering and Physics, , Amsterdam University Medical Centers, University of Amsterdam, , Amsterdam, , The Netherlands , Aart J. NederveenAart J. Nederveen Department of Radiology and Nuclear Medicine, , Amsterdam University Medical Centers, University of Amsterdam, , Amsterdam, , The Netherlands , Adrianus J. BakermansAdrianus J. Bakermans https://orcid.org/0000-0001-9291-9441 Department of Radiology and Nuclear Medicine, , Amsterdam University Medical Centers, University of Amsterdam, , Amsterdam, , The Netherlands and Thijs M. H. EijsvogelsThijs M. H. Eijsvogels * Correspondence to: Thijs M. H. Eijsvogels, PhD, Department of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands. E‐mail: E-mail Address: [email protected] https://orcid.org/0000-0003-0747-4471 Department of Physiology, , Radboud Institute for Health Sciences, Radboud University Medical Center, , Nijmegen, , The Netherlands Originally published26 Jun 2021https://doi.org/10.1161/JAHA.120.020039Journal of the American Heart Association. 2021;10:e020039Habitual physical activity reduces cardiovascular risk, yet exercise can acutely increase a variety of myocardial injury biomarker concentrations.1 Their kinetics and release mechanisms remain incompletely understood. We recently demonstrated that marathon running transiently increases contemporary cTnI (cardiac troponin I) concentrations and concomitantly results in compromised myocardial tissue integrity.2 Specifically, elevated postmarathon cTnI concentrations correlated with increased mean myocardial tissue water diffusivity (MD). An increased myocardial MD may point to increased cell membrane permeability as a mechanism for exercise‐induced cardiac biomarker elevations through leakage from the cytosolic pool into the circulation. We assessed the kinetics of exercise‐induced changes in novel and conventional cardiac biomarkers following a marathon run and related them to MD as measure of cardiomyocyte integrity.We recruited 12 men aged ≥45 years competing in the 2017 Amsterdam Marathon. Blood samples were collected at the following 6 time points: 1 week (baseline) and 1 hour premarathon, directly (±1 hour) postmarathon, at the time of magnetic resonance imaging examination postmarathon (4±2 hours postmarathon), 1 to 2 days postmarathon, and 2 weeks postmarathon (recovery). In this post hoc analysis, we measured cTnI by conventional (cTnI; Siemens ADVIA Centaur TnI‐Ultra) and single‐molecule counting assays (SMC‐cTnI; Singulex Clarity cTnI system), hs‐cTnT (high‐sensitivity troponin T; Roche Cobas), cMyC (cardiac myosin–binding protein C; EMD Merck Millipore), sST2 (soluble suppression of tumorigenicity 2; Critical Diagnostics Presage ST2 Assay), and BNP (B‐type natriuretic peptide; Siemens Centaur). Furthermore, magnetic resonance imaging was performed at baseline, 4±2 hours after finishing the marathon (postmarathon), and at recovery.2 Cardiomyocyte integrity was assessed using diffusion‐weighted magnetic resonance imaging to estimate myocardial MD. The Medical Ethical Committee of the Amsterdam University Medical Centers approved the study. Participants provided written informed consent. Data are presented as mean±SD, median [interquartile range] or frequency (%). The data that support the findings of this study are available from the corresponding author upon reasonable request.A total of 11 men (age 51 [50–56] years; BMI, 23.6±1.1 kg/m2) finished the marathon in 3:43 (3:28–4:34) hours:minutes at 89±5% of their predicted maximum heart rate. Kinetics of exercise‐induced biomarker elevations differed across biomarkers (Figure). Contemporary cTnI increased postmarathon and exceeded the upper reference limit (URL) in 7 participants (64%) and returned to baseline values at recovery (Figure). SMC‐cTnI and hs‐cTnT had similar kinetics with 8 (73%) and 11 (100%) participants exceeding the URL, respectively. Despite similar release kinetics, postmarathon values of cTnI did not significantly correlate with cTnT (cTnI r=0.50, P=0.12; SMC‐cTnI r=0.42, P=0.20). cMyC increased postmarathon in all participants without exceeding the URL at any time point. One marathon runner (9%) had an elevated sST2 concentration at baseline, whereas all runners had concentrations above the cut point postmarathon. sST2 did not correlate with any of the other cardiac biomarkers (P≥0.10). BNP concentrations showed no effect of exercise (P=0.27).MD increased postmarathon (1.54±0.08 to 1.67±0.18 mm2/s; P=0.04) and returned to baseline values within 2 weeks (1.56±0.09 mm2/s).2 Postmarathon values of MD correlated with cTnI (r=0.66, P=0.03) and SMC‐cTnI (r=0.71, P=0.02), whereas associations with hs‐cTnT (r=0.55, P=0.08) and cMyC (r=0.56, P=0.07) did not reach statistical significance. No association of MD with sST2 or with BNP was found.We only evaluated male runners to preclude any sex‐specific variability of cardiac effects within our cohort. Because of logistical constraints of performing elaborate cardiac magnetic resonance imaging exams (duration of ±1 hour) directly (<6 hours) postmarathon, we could not include more than 12 individuals using 2 identical magnetic resonance systems simultaneously. As such, the statistical power of this study was limited.In this field study, marked transient elevations in novel and conventional cardiac biomarkers were observed following a marathon run, with the highest concentrations at 4±2 hours postrace in all biomarkers except BNP, which unexpectedly did not increase. The magnitude and statistical significance of the association between MD and biomarkers was variable, but largely uniform for myocardial injury markers such as cTnI, SMC‐cTnI, hs‐cTnT, and cMyC. The lack of association between sST2 and MD or other biomarkers postmarathon suggests a different exercise‐induced mechanism of release, which could be explained by leakage from the cell (ie, cTn [cardiac troponin]/cMyC) versus upregulated production (sST2). Although our observations favor a physiological rather than pathological response, the magnitude of cardiac biomarker elevations may still be a surrogate for cardiac vulnerability given their predictive capacity for adverse outcomes.3Notably, although cMyC yields high diagnostic accuracy for acute myocardial infarction,4 cMyC concentrations postmarathon did not exceed the URL at any time point. This difference between cTn and cMyC concentrations following exercise may relate to the higher molecular mass of cMyC complexes (≈140 kDa) and fragments (≈40 kDa) compared with cTn complexes (cTnI ≈29 kDa, cTnT ≈37 kDa) and fragments (10–30 kDa), suggesting that cMyC may be less likely to leak from the cell into the circulation. Because postexercise cTn elevations can be challenging to interpret in the clinical setting because of concentrations exceeding the URL in the absence of signs of myocardial ischemia, a parallel assessment of cMyC might aid in discerning whether cTn elevations are physiological or pathological in endurance athletes.Sources of FundingThis work was supported by grants from the Medical Research Council (London, UK; G1000737), Guy's and St Thomas' Charity (London, UK; R060701, R100404), British Heart Foundation (Birmingham, London; TG/15/1/31518, FS/15/13/31320), and the UK Department of Health through the National Institute for Health Research Biomedical Research Centre award to Guy's & St Thomas' National Health Service Foundation Trust. Dr Aengevaeren was financially supported by a grant from the Radboud Institute for Health Sciences. Dr Bakermans is supported by a Veni grant from The Netherlands Organisation for Scientific Research (project number 91617155). Kaier is funded through an NIHR clinical lectureship (CL‐2019‐17‐006).DisclosuresEMD Merck Millipore (Hayward, CA) was contracted to undertake the analyses of cardiac myosin–binding protein C on a fee‐for‐service basis and holds no commercial interest. Dr Marber is named as an inventor on a patent held by King's College London for the detection of cardiac myosin–binding protein C as a biomarker of myocardial injury. The remaining authors have no disclosures to report.Download figureDownload PowerPointFigure 1. Cardiac biomarker kinetics following a marathon run.cTnI measured using a conventional assay (upper reference limit [URL], 40 ng/L; limit of detection [LOD], 6 ng/L; A), SMC‐cTnI (URL, 8.97 ng/L; LOD, 0.12 ng/L; B), hs‐cTnT (URL, 14 ng/L; LOD, 3 ng/L; C), cMyC (URL, 87 ng/L; LOD, 0.4 ng/L; D), sST2 (standard analysis cut point, 35 µg/L; LOD, 1.8 µg/L; E), and BNP (clinical cut point, 35 pg/mL; LOD, 2 pg/mL; F) measured at 6 time points surrounding a marathon run. Data for each individual participant are shown in gray, with group median values (n = 11) indicated by the red lines. Horizontal dashed lines indicate the URLs and/or clinical cut points. BNP indicates B‐type natriuretic peptide; cMyC, cardiac myosin–binding protein C; cTnI, cardiac troponin I; hs‐cTnT, high‐sensitivity troponin T; MRI, magnetic resonance imaging; SMC, single‐molecule counting assay; and sST2, soluble suppression of tumorigenicity 2.Footnotes* Correspondence to: Thijs M. H. Eijsvogels, PhD, Department of Physiology, Radboud Institute for Health Sciences, Radboud University Medical Center, P. O. Box 9101, 6500 HB Nijmegen, The Netherlands. E‐mail: thijs.[email protected]nlFor Sources of Funding and Disclosures, see page 3.REFERENCES1 Eijsvogels TM, Fernandez AB, Thompson PD. Are there deleterious cardiac effects of acute and chronic endurance exercise?Physiol Rev. 2016; 96:99–125. DOI: 10.1152/physrev.00029.2014.CrossrefMedlineGoogle Scholar2 Aengevaeren VL, Froeling M, Hooijmans MT, Monte JR, van den Berg‐Faay S, Hopman MTE, Strijkers GJ, Nederveen AJ, Bakermans AJ, Eijsvogels TMH. Myocardial injury and compromised cardiomyocyte integrity following a marathon run. JACC Cardiovasc Imaging. 2020; 13:1445–1447. DOI: 10.1016/j.jcmg.2019.12.020.CrossrefMedlineGoogle Scholar3 Aengevaeren VL, Hopman MTE, Thompson PD, Bakker EA, George KP, Thijssen DHJ, Eijsvogels TMH. Exercise‐induced cardiac troponin I increase and incident mortality and cardiovascular events. Circulation. 2019; 140:804–814. DOI: 10.1161/CIRCULATIONAHA.119.041627.LinkGoogle Scholar4 Kaier TE, Twerenbold R, Puelacher C, Marjot J, Imambaccus N, Boeddinghaus J, Nestelberger T, Badertscher P, Sabti Z, Giménez MR, et al. Direct comparison of cardiac myosin‐binding protein C with cardiac troponins for the early diagnosis of acute myocardial infarction. Circulation. 2017; 136:1495–1508. DOI: 10.1161/CIRCULATIONAHA.117.028084.LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetails July 6, 2021Vol 10, Issue 13Article InformationMetrics Download: 1,335 Copyright © 2021 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley BlackwellThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.https://doi.org/10.1161/JAHA.120.020039PMID: 34180243 Manuscript receivedMarch 20, 2021Manuscript acceptedMay 17, 2021Originally publishedJune 26, 2021 PDF download SubjectsBiomarkersExerciseMagnetic Resonance Imaging (MRI)

AimsCardiac myosin‐binding protein C (cMyC) seems to be even more sensitive in the quantification of cardiomyocyte injury vs. high‐sensitivity cardiac troponin, and may therefore have diagnostic and prognostic utility.Methods and resultsIn a prospective multicentre diagnostic study, cMyC, high‐sensitivity cardiac troponin T (hs‐cTnT), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) plasma concentrations were measured in blinded fashion in patients presenting to the emergency department with acute dyspnoea. Two independent cardiologists centrally adjudicated the final diagnosis. Diagnostic accuracy for acute heart failure (AHF) was quantified by the area under the receiver operating characteristic curve (AUC). All‐cause mortality within 360 days was the prognostic endpoint. Among 1083 patients eligible for diagnostic analysis, 51% had AHF. cMyC concentrations at presentation were higher among AHF patients vs. patients with other final diagnoses [72 (interquartile range, IQR 39–156) vs. 22 ng/L (IQR 12–42), P < 0.001)]. cMyC's AUC was high [0.81, 95% confidence interval (CI) 0.78–0.83], higher than hs‐cTnT's (0.79, 95% CI 0.76–0.82, P = 0.081) and lower than NT‐proBNP's (0.91, 95% CI 0.89–0.93, P < 0.001). Among 794 AHF patients eligible for prognostic analysis, 28% died within 360 days; cMyC plasma concentrations above the median indicated increased risk of death (hazard ratio 2.19, 95% CI 1.66–2.89; P < 0.001). cMyC's prognostic accuracy was comparable with NT‐proBNP's and hs‐cTnT's. cMyC did not independently predict all‐cause mortality when used in validated multivariable regression models. In novel multivariable regression models including medication, age, left ventricular ejection fraction, and discharge creatinine, cMyC remained an independent predictor of death and had no interactions with medical therapies at discharge.ConclusionCardiac myosin‐binding protein C may aid physicians in the rapid triage of patients with suspected AHF.

The 4th Universal Definition of Myocardial Infarction has stimulated considerable debate since its publication in 2018. The intention was to define the types of myocardial injury through the lens of their underpinning pathophysiology. In this review, we discuss how the 4th Universal Definition of Myocardial Infarction defines infarction and injury and the necessary pragmatic adjustments that appear in clinical guidelines to maximize triage of real-world patients.