Cardiac Troponin Research Articles

Diagnostic potential of relative changes in high-sensitivity troponin levels during intracoronary acetylcholine provocation testing

Abstract Background Intracoronary acetylcholine (ACh) provocation testing is useful for the diagnosis of vasospastic angina (VSA). However, the positive or negative diagnosis of ACh testing is often challenging when lacking typical anginal symptoms and electrocardiographic changes during provocation tests. We hypothesized that relative changes in cardiac troponin levels during ACh provocation testing may be suggestive of myocardial ischemia and would be helpful for the VSA diagnosis. Purpose To evaluate the diagnostic potential of relative changes in high sensitivity troponin I (hs-TnI) levels during intracoronary ACh provocation test. Methods This preliminary study included a total of 29 patients undergoing invasive coronary angiography with or without ACh provocation tests. Patients were divided into three groups; no ACh provocation tests (i.e. angiography alone), negative ACh tests, and positive ACh tests. Blood samples were obtained twice, before and after angiography, through the arterial sheath to evaluate hs-TnI. The primary measure was relative changes in hs-TnI (i.e. Δhs-TnI). Positive ACh provocation test was defined as total or subtotal coronary occlusion accompanied by chest pain and/or ischemic electrocardiographic changes. Results Of the 29 patients, 10 (34.5%) underwent coronary angiography alone, while ACh provocation testing was performed in 19 (65.5%) patients, of whom 7 (36.8%) and 12 (63.2%) had negative and positive ACh test results. Overall, the mean time interval between the blood sample collections was 76 minutes. Levels of hs-TnI before angiography did not differ significantly in the no, negative, and positive ACh test groups (5.3 [2.8, 8.6] vs. 2.9 [1.3, 8.8] vs. 3.3 [1.6, 8.5] pg/ml, p=0.76), while Δhs-TnI was highest in the positive ACh test group, followed by the negative and no ACh test groups (4.2 [0.5, 8.1] vs. 0.8 [0.4, 4.6] vs. −0.3 [−0.6, 0.3], p=0.002) (Figure). Conclusions In patients undergoing intracoronary ACh testing for the VSA diagnosis, a relative increase in Δhs-TnI during angiography was observed than in those who did not undergo the provocation tests, particularly when the ACh test diagnosis was positive. Our findings suggest that Δhs-TnI has the potential to aid in the positive or negative diagnosis of ACh provocation testing.

Relation of plasma neuropeptide-Y with myocardial function and infarct severity in acute ST-elevation myocardial infarction

Abstract Background Acute myocardial infarction is associated with high levels of cardiac sympathetic stimulation, which leads to the release of the co-transmitter neuropeptide-Y (NPY). NPY acts as a potent vasoconstrictor and an association with increased risk for heart failure and microvascular dysfunction after acute ST-elevation myocardial infarction (STEMI) has been suggested. Purpose This study aims to comprehensively evaluate the association of plasma NPY with myocardial function and infarct severity, visualized by cardiac magnetic resonance (CMR) imaging, in STEMI patients revascularized by primary percutaneous coronary intervention (PCI). Methods In this observational study, we included 260 STEMI patients treated with primary PCI. Plasma NPY concentrations were measured by an immunoassay 24h after PCI from peripheral venous blood samples. Left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), infarct size (IS) and microvascular obstruction (MVO) were determined using CMR imaging 4 days and 4 months after PCI. Results Median plasma concentrations of NPY were 70 [interquartile range (IQR): 35-115] pg/ml. NPY levels above median were significantly associated with lower LVEF (48% vs. 52%, p=0.004), decreased GLS (-8.8% vs. -12.6%, p<0.001) and larger IS (17% vs. 13%, p=0.041) in the acute phase after infarction as well as in the chronic stage (LVEF: 50% vs. 52%, p=0.030, GLS: -10.5 vs. -12.9, p<0.001, IS: 13% vs. 10%, p=0.011). In addition, NPY levels were significantly related to presence of MVO (58% vs. 52%, p=0.041). Moreover, in multivariable linear regression analysis, NPY remained significantly associated with all investigated CMR parameters (LVEF: p<0.001, GLS: p<0.001, IS: p=0.003, MVO: p=0.042) independent of other established clinical variables including high-sensitivity cardiac troponin T, pre-interventional TIMI flow 0 and left anterior descending artery as culprit lesion location. Conclusion High plasma levels of NPY, measured 24h after STEMI, were independently associated with lower LVEF, decreased GLS, larger IS as well as presence of MVO, indicating plasma NPY as a valuable biomarker for optimized risk stratification.

Serial troponin sampling over 60-minutes allows early distinction between myocardial infarction and chronic myocardial injury in patients presenting to emergency departments

Abstract Background High-sensitivity cardiac troponins (hs-cTn) are key clinical biomarkers in the assessment and diagnosis of patients with suspected acute coronary syndromes presenting to Emergency Departments (ED). These tests facilitate rapid triage through 0h/1h blood sampling regimens. Most patients will not have myocardial infarction (MI) diagnosed, having either hs-cTn levels below the upper reference limit (URL) or stable elevations. The latter group of complex, often multimorbid, patients is termed chronic myocardial injury (CMI) according to the 4th Universal Definition of MI (4thUDMI). These patients have long-term morbidity and mortality rates higher than those with type 1 MI. Early distinction of CMI from MI remains challenging with debate regarding optimal hs-cTnT delta cut-offs; both 3ng/L and 5ng/L over one-hour have been proposed. Methods and Results We prospectively collected 0-, 30- and 60-minutes (+/- 5 min) hs-cTnT samples from 185 patients presenting to Liverpool Hospital ED (Sydney, Australia) between March and August 2023. Diagnoses were adjudicated according to the 4thUDMI as follows: 16 (8.6%) MI ruled-in, 66 (35.7%) CMI and 103 (55.7%) MI ruled-out. Linear regression was used to calculate individual hs-cTnT slopes for each patient. Between CMI and MI, each 1 ng/L/hour increase in the slope of hs-cTnT resulted in a two-fold (95% CI: 1.5 to 2.9) greater likelihood of MI being diagnosed (P < 0.001). A stable hs-cTnT trajectory was observed in CMI, which ranged between 0 and 3 ng/L/hour in all patients with an initial hs-cTnT level ≤ 50 ng/L. Chronic myocardial injury patients with an initial hs-cTnT level > 50ng/L (n=12), exhibited more kinetic slopes ranging up to 8ng/L/hour (P <0.001). Unexpectedly, three MI patients had a non-linear slope, of whom two patients would not have displayed a significant rise had the additional 30-minute sample not been collected. These outlying patients presented at 9-12 hours and over 12 hours from symptom onset. Conclusion This study offers a novel characterisation of CMI, which has not previously been investigated in an unselected ED cohort using three serial samples over one hour. It validates a hs-cTnT delta of 3ng/L/hour in the recent ESC guidelines. However, there is a need for greater characterisation of short-term hs-cTn variability for more personalised MI risk stratification and to guide more targeted observation and further investigation of CMI patients.

Cardiac biomarkers can detect and track subclinical HIV-associated myocardial disease in newly diagnosed people living with HIV

Abstract Background Cardiovascular disease (CVD) in people living with HIV (PLWH) remains poorly understood, and the profile of disease differs between high-income and low- and middle-income settings[1]. Subclinical cardiovascular abnormalities may be present at the time of HIV diagnosis and serve as potential substrate for future CVD[2]. Biochemical markers are fundamental in cardiac evaluation, and various novel assays have recently been discovered. Purpose To assess the presence and evolution of subclinical myocardial disease, we prospectively assessed the hearts of newly diagnosed PLWH and matched, HIV-uninfected controls using cardiac biomarkers and correlated our findings with cardiovascular magnetic resonance imaging (CMR). Methods Newly diagnosed, antiretroviral treatment (ART) naïve PLWH were recruited along with HIV uninfected, age- and sex-matched controls in the Western Cape Province of South Africa. All participants underwent measurement of high-sensitivity cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), soluble ST2 (sST2), Galectin-3, and a CMR study with multiparametric mapping. The HIV group started ART and was re-evaluated 9 months later. The cardiac biomarkers and their correlation with CMR parameters were evaluated in, and between groups. Results Compared with controls (n=22), hs-cTnT (4.0 ng/l vs 5.1 ng/l; p=0.004) , NT-proBNP (23.2 ng/l vs 40.8 ng/l; p=0.02), and Galectin-3 (6.8 ng/ml vs 9.0 ng/ml; p=0.002) were all significantly higher in the ART naïve group (n=73). After 9 months of ART, hs-cTnT (5.1 ng/l vs 4.3 ng/l; p=0.02) and NT-proBNP (40.8 ng/l vs 28.5 ng/l; p=0.03) both decreased significantly, and a trend of decrease was seen in sST2 (16.5 ng/ml vs 14.8 ng/l; p=0.08). Galectin-3 did not demonstrate decrease over time (9.0 ng/ml vs 8.8 ng/ml; p=0.6). The cardiac biomarkers that showed the best correlation with CMR measurements native T1, T2, and ECV, were NT-proBNP (rs≥0.4, p<0.001) and Galectin-3 (rs≥0.3, p<0.01). Conclusion Our cardiac biomarker data supports the presence of subclinical myocardial injury, remodelling, and fibrosis at HIV diagnosis and ART had a positive influence on these blood markers. It remains unclear if the underlying pathological processes were fully addressed by ART. The elevation of Galectin-3 despite ART may be indicative of ongoing cardiac remodelling that may incur future risk of CVD, and necessitates further study. The ability of cardiac biomarkers to detect and track tissue abnormalities diagnosed with CMR, showed promise. With additional research, this could lead to improvements in screening and monitoring myocardial abnormalities, even in CMR-limited settings.

Active surveillance for cardiac complications after major noncardiac surgery: implications on resource utilization and safety in high-risk patients

Abstract Background The 2022 ESC guidelines on cardiovascular assessment and management of patients undergoing noncardiac surgery recommend that high-risk patients should undergo active surveillance for cardiac complications, including perioperative myocardial infarction/injury (PMI), following major noncardiac surgery. Unfortunately, little is known about the resource use and safety of active surveillance compared to a control cohort (i.e. without active surveillance). Objective To quantify the impact of active surveillance for cardiac complications, by perioperative cardiac troponin (cTn) measurements and a systematic PMI work-up on working days, on resource usage and safety. Methods We did a retrospective comparison of non-randomised pre- vs post-implementation of an active surveillance program for cardiac complications in patients at elevated cardiovascular risk undergoing noncardiac surgery at two hospitals in Switzerland. The two cohorts' resource use and safety were compared. Resource use encompassed perioperative cTn measurements, ECGs, cardiac imaging, cardiology consultations as well as coronary angiography (CAG) and revascularisation procedures. Safety was assessed based on the number of "seemingly normal CAG" and complications arising from CAG and revascularisation procedures. Results A total of 13’147 patients, 10’346 in the active surveillance cohort and 2’805 in the standard-of-care (SOC) cohort, were eligible for this analysis. Patient characteristics between both cohorts were comparable (e.g. median age of 74 vs 73 and 44.8% vs 43% female, respectively). Patients in the active surveillance cohort underwent significantly more perioperative cTn measurements (86.4% vs 3.5%, respectively), postoperative ECGs (13.5% vs 5.7%), postoperative cardiac consultations (5.9% vs 2.4%), postoperative transthoracic echocardiogram (TTE) (7.5% vs 6.1%), postoperative myocardial perfusion imaging (MPI) (1.2% vs 0.6%), and postoperative CAG (0.8% vs 0.4%, all p <0.05). The increased resource use led to a substantial increase in detected cardiac complications within the first 48h after surgery: active surveillance 1’207 (12%) (95%CI 11%-12%) vs SOC 68 (2.4%) (95%CI 1.9%-3.1%). The active surveillance cohort generated an overall cardiac management cost of 236 Euros (95%CI 223–250) per patient vs 133 Euros (95%CI 110–160) per patient in the SOC cohort, resulting in an incremental cost for the active surveillance of 103 Euros (95%CI 110–160) per patient. Thereby the cost of detecting one additional cardiac complication within 48h was 989 Euros. Concerning safety, no significant differences in the number of "seemingly normal CAG" (6.4% vs 15%, p=0.1) and complications due to CAG and revascularisation (0.6% vs 5.1%, p=0.08) were observed. Conclusion The active surveillance for cardiac complications is safe when compared to a standard-of-care cohort while 989 Euros per additional detected cardiac complication seems reasonably priced.Resource-utilization tableOverview

The ghrelin receptor agonist AC01 improves cardiac function in non-human primates and in mice with heart failure by increasing cardiomyocyte contractility

Abstract Background Current therapy for Heart Failure (HF) includes neurohormonal antagonist and modulator drugs that improve remodelling, symptoms and clinical outcomes. However, these drugs do not target the underlying problem of reduced contractility. Improving cardiac contractility without harmful consequences is an unmet need in heart failure therapy. The human peptide hormone ghrelin increases cardiac output in HF patients and increases contractility in murine cardiomyocytes. Purpose We aim to study the cardiovascular effects of a novel oral small molecule ghrelin receptor agonist, AC01, in in vivo and ex vivo mouse models and in non-human primates. Methods HF mice (N=11) underwent pressure-volume loops analysis of cardiac functional and hemodynamic to assess the effects of intravenous AC01 (N=7) or placebo (N=4). Primary cardiomyocytes isolated from HF (N=3) and SHAM (N=5) mice, were treated with combinations of vehicle, AC01, ghrelin receptor antagonist (D-Lys-3-GHRP-6) and pertussis toxin (PTX, a Gαi signalling inhibitor). Live cell imaging was performed to assess cardiomyocyte fractional shortening and Ca2+ signalling, while biochemistry assays were employed to measure PKA activity, and phosphorylation of cardiac Troponin I (cTnI). Cynomolgus monkeys (N=6) were instrumented with devices to measure pulse contour, central aortic blood pressure and ECG devices. Cardiovascular effects of AC01 following single oral dosing were assessed through pulse contour hemodynamic modelling and analysis of autonomic system activation. Results In HF mice, AC01 significantly improved cardiac output (p< 0.01), stroke volume (p< 0.001), and ejection fraction (p< 0.001), and increased nominally the end-systolic pressure-volume curve relationship. In cardiomyocytes, AC01 dose-dependently improved fractional shortening (p< 0.01) without increasing Ca2+ transient amplitudes. AC01 reduced PKA activity (p< 0.05) and reduced phosphorylation of cTnI at Serine 23-24 (p< 0.01). These effects were blocked by pre-treatment with either D-Lys-3-GHRP-6 or PTX. In monkeys, oral AC01 sustainably increased cardiac output (p< 0.05) and stroke volume (p< 0.05) and reduced heart rate without altering central systolic blood pressure or causing tachycardia or arrhythmia. Conclusions AC01 improved CO, SV, and EF in HF mice by increasing contractility in a load-independent fashion. AC01 increased cardiomyocyte contractility without affecting Ca2+ transient amplitudes, through ghrelin receptor Gαi signalling, leading to reduced phosphorylation of cTnI. AC01 improved left ventricle systolic function in monkeys. AC01 is a first in class novel inotrope, which improves contractility in different species without harmful mobilization of Ca2+. AC01 should be explored for the treatment of patients with heart failure.graphical abstract

Acute kidney injury in relation to high-sensitivity cardiac troponin T levels in the emergency department

Abstract Background The clinical implications of high-sensitivity cardiac troponin T (hs-cTnT) measurements in all-comers with AKI in the emergency department (ED) is largely unknown. Purpose To investigate the prevalence of myocardial injury, associations between serum-creatinine concentrations (SCC) and hs-cTnT kinetics, and the accuracy of established hs-cTnT-based myocardial infarction (MI) risk stratification algorithm criteria in patients with AKI. Methods This observational cohort study was based on patient visits to 7 EDs in Sweden from December 9, 2010 to August 31, 2017. All visits by patients ≥18 years fulfilling criteria for AKI with ≥1 hs-cTnT measurement and the exposure was dynamic change in SCC (ΔSCC) during the visits. Linear mixed models were used to estimate linear predictors of kinetic change in hs-cTnT (Δhs-cTnT). Logistic regression models were applied to calculate odds ratios (ORs) for Δhs-cTnT indicative of acute myocardial injury (Δhs-cTnT >20% and elevated hs-cTnT) in relation to ΔSCC among patients without MI, and to assess the diagnostic performance of hs-cTnT for MI in a subgroup of patients presenting with chest pain. Results A total of 15,211 visits by patients with AKI were included, of whom 1174 (8%) had an MI. Four of five (81%) patients without MI had myocardial injury (hs-cTnT >14 ng/l), and almost one of three (31%) had acute myocardial injury. These entities were common in both cardiac and non-cardiac conditions. The Δhs-cTnT in non-MI patients was 1.8-fold (β: 1.78, 95% CI: 1.62-1.96) in the highest quartile of ΔSCC and was paralleled by a 2-fold risk of acute myocardial injury (OR: 2.32, 95% CI: 2.08-2.59), compared with the lowest ΔSCC quartile. Using a 0 h hs-cTnT cut-off ≥52 ng/l assigned 627 (26%) patients to a high-risk group in whom the specificity and positive predictive value (PPV) for MI was low (78.5% (95% CI: 76.7-80.2) and 27.6% (95% CI: 24.1-31.3), respectively). Conclusions Hs-cTnT concentrations indicative of acute myocardial injury are frequently observed among all-comers with AKI in the ED and are associated with dynamic changes in SCC. These observations are accompanied by poor performance of recommended hs-cTnT-based algorithms for MI risk stratification in patients with chest pain.

Downregulation of CPEB3 exacerbates cardiac injury by inhibiting cardiomyocyte adaptive metabolic reprogramming after myocardial infarction

Abstract Background Adaptive metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis in hypoxia plays a protective role in cardiomyocyte survival by reducing reactive oxygen species (ROS) and increasing ATP. Cytoplasmic polyadenylation element binding protein 3 (CPEB3) influences protein translation by modulating 3' untranslated region (3'UTR) lengths through alternative polyadenylation (APA). However, the role of CPEB3 in cardiomyocyte after myocardial infarction (MI) remains unknown. Purpose This study aims to explore the function of CPEB3 in cardiomyocyte after MI. Methods Three GEO databases of mice MI (GSE110209, GSE114695 and GSE236374) were analyzed to identify CPEB3 dysregulation. Cardiomyocyte-specific CPEB3 knockout mice and CPEB3-knockdown neonatal mouse cardiomyocytes (NMCMs), RNA sequencing, flow cytometry, TUNEL staining, Seahorse, ROS and ATP measurements were used to investigate the impact of CPEB3. APA events analysis, RIP sequencing, CUT-TAG, 3’RACE, polysome profiling and dual luciferase report were performed to elucidate the mechanisms of CPEB3. Recombinant adeno-associated virus carrying cardiac troponin T promoter was used to evaluate the therapeutic efficacy of CPEB3 in mice with MI. Results CPEB3 expression was markedly reduced in the heart tissue after MI and in NMCMs after hypoxia. Cardiomyocyte-specific CPEB3 deletion aggravated cardiomyocyte apoptosis, enlarged infarct size, and exacerbated cardiac injury after MI. RNA sequencing revealed that CPEB3 deficiency predominantly inhibited glycolysis-related pathway, with a notable decrease in pyruvate dehydrogenase kinase 1 (PDK1) expression. In CPEB3-knockdown NMCMs, adaptive metabolic reprogramming from OXPHOS to glycolysis and ATP level were decreased in hypoxia, whereas ROS production was significantly enhanced, all of which resulted in apoptosis and were regulated by PDK1. Besides, PDK1 overexpression counteracted the effects of CPEB3 knockdown on metabolic pattern, ROS, ATP and apoptosis. Mechanistically, CPEB3 deficiency led to a shortened 3’UTR of the transcription factor forkhead box O3 (FOXO3), and a decline of FOXO3 protein level. CPEB3 protein was confirmed to directly bind to FOXO3 mRNA, and the translation efficiency of FOXO3 was decreased with CPEB3 knockdown. Furthermore, FOXO3 was found to activate the transcription of PDK1, and FOXO3 overexpression alleviated the decline of PDK1 and attenuated CPEB3 knockdown-induced apoptosis in hypoxia. Finally, cardiomyocyte-specific CPEB3 overexpression reduced cardiomyocyte apoptosis, suppressed myocardial fibrosis, and improved cardiac function by upregulating FOXO3 and PDK1 levels after MI. Conclusion CPEB3 could promote FOXO3 protein expression via APA of FOXO3 3’UTR, activate transcription of PDK1 and ultimately protect cardiomyocyte from apoptosis by restoring metabolic balance in hypoxia. CPEB3 may serve as a promising therapeutic target for cardiomyocyte apoptosis after MI.Schematic diagram

Serum amyloid A-low-density-lipoprotein complex and cause-specific mortality in patients with suspected or known coronary artery disease: The ANOX Study

Abstract Background Serum amyloid A-low-density-lipoprotein (SAA-LDL) is a complex formed from the oxidative interaction between SAA and LDLs. A relatively small-scale study has shown that circulating SAA-LDL levels may serve as a prognostic marker in patients with stable coronary artery disease (CAD). However, the association between SAA-LDL and cause-specific mortality in patients with suspected or known CAD is unknown. Methods Serum SAA-LDL levels were measured in 2416 patients with suspected or known CAD undergoing elective coronary angiography. The outcomes were all-cause death, cardiovascular (CV) death, non-CV death, cancer death, and other non-CV death. Patients were followed up over a 3-year period. Results During the follow-up, 254 (10.5%) deaths occurred, including 88 (3.6%) CV deaths, 151 (6.3%) non-CV deaths, 66 (2.7%) cancer deaths, 85 (3.5%) other non-CV deaths, and 15 (0.6%) undetermined deaths. Stepwise regression analysis including baseline data on potential clinical confounders and established CV biomarkers (i.e., N-terminal pro-brain natriuretic peptide, high-sensitivity cardiac troponin I, and high-sensitivity C-reactive protein [hs-CRP]) revealed that the strongest independent determinant of SAA-LDL levels was hs-CRP (partial regression coefficient, 0.248; standard error, 0.010; p<0.001). After adjusting for potential clinical confounders and established CV biomarkers, the highest quartile of SAA-LDL levels (vs. the lowest quartile) was significantly associated with all-cause death (adjusted hazard ratio [aHR], 1.56; 95% confidence interval [CI], 1.05–2.34) and non-CV death (aHR, 1.76; 95% CI, 1.02–3.11), but not with CV death (aHR, 1.16; 95% CI, 0.62–2.20), cancer death (aHR, 1.68; 95% CI, 0.71–4.34), or other non-CV death (aHR, 1.65; 95% CI, 0.82–3.45) in the entire cohort. In patients with low hs-CRP levels (≤1.0 mg/L, n=1253), the highest quartile of SAA-LDL levels was significantly associated with all-cause death (aHR, 2.19; 95% CI, 1.11–4.57), non-CV death (aHR, 2.78; 95% CI, 1.05–8.79), and cancer death (aHR, 4.65; 95% CI, 1.12–31.9), but not with CV death (aHR, 1.22; 95% CI, 0.39–3.92) or other non-CV death (aHR, 1.68; 95% CI, 0.42–8.35). In contrast, the highest quartile of SAA-LDL levels was not significantly associated with all-cause death (aHR, 1.18; 95% CI, 0.72–1.96), CV death (aHR, 1.02; 95% CI, 0.45–2.31), non-CV death (aHR, 1.46; 95% CI, 0.75–2.91), cancer death (aHR, 1.35; 95% CI, 0.43–4.58), or other non-CV death (aHR, 1.38; 95% CI, 0.60–3.25) in patients with high hs-CRP levels (>1.0 mg/L, n=1163). Conclusions Elevated SAA-LDL levels were independently associated with all-cause and non-CV mortality, but unexpectedly not with CV mortality, in patients with suspected or known CAD. These associations were pronounced in patients with low hs-CRP levels (≤1.0 mg/L). The association between the SAA-LDL level and cancer mortality suggests its predictive utility in patients with low hs-CRP levels (≤1.0 mg/L).

Cardiac magnetic resonance T1 imaging for the diagnosis of cardiac amyloidosis among patients with symptomatic heart failure

Abstract Background Cardiac amyloidosis (CA) is a significant cause of heart failure in elderly patients. However, specific signs in cardiac imaging are lacking, hence bone scintigraphy in combination with screening for monoclonal protein, or myocardial biopsy is required for the diagnosis. Cardiac magnetic resonance (CMR) imaging with T1 mapping is a promising diagnostic tool, which may allow to differentiate causes of left ventricular (LV) hypertrophy, particularly CA. Purpose The aim of this study was to test the diagnostic accuracy of T1 mapping for the diagnosis of CA in elderly patients with symptomatic heart failure and red flags for CA. Methods We prospectively enrolled 120 patients aged above 60 years with symptomatic heart failure NYHA II-IV, LV ejection fraction ≥ 40%, increased LV wall thickness of ≥ 12 mm end-diastolic on echocardiography, and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥ 1,000 ng/L, high-sensitivity cardiac troponin T (hs-cTnT) ≥ 14 ng/L). All patients underwent standardized quantitative CMR with a 3.0T scanner. 99mTc-DPD bone scintigraphy, blood screening for monoclonal protein, and, where applicable, cardiac biopsy, were performed as reference methods in all patients. Primary endpoint was diagnostic accuracy of native T1 mapping for the diagnosis of CA. Results 112 patients were included in the final analysis. Median age was 81.0 years (interquartile range 74.0–85.0 years), and 45% were female. CA was diagnosed in 38 patients (34%), of which 32 suffered from a Transthyretin (ATTR) and 6 patients from light chain (AL) amyloidosis. The areas under the receiver operating characteristic curves for native T1 were 0.713, 0.772, 0.836 for global, septal short-axis (SAX), and septal 4-chamber (4Ch) view measurements. The corresponding value of extracellular volume fraction (ECV) was 0.904 (Figure 1). Based on these results, we developed a new diagnostic algorithm for the diagnosis of CA including T1 septal 4Ch and ECV, with a sensitivity and positive predictive value of both 92.9% and a specificity and negative predictive value of 95.8% (Figure 2). Thereby, contrast application can be avoided in 33% of patients. A definite diagnosis could be provided in 81%. Conclusion CMR with T1 imaging provides a high diagnostic accuracy to diagnose CA in patients with symptomatic heart failure at risk for CA. These data may help to identify underlying causes in heart failure which require specific treatment. An earlier diagnosis of CA may improve outcome of these patients.Figure 1Figure 2

Biomarkers in early and late period after radiofrequency and pulsed field catheter ablation of atrial fibrillation

Abstract Introduction Biomarkers are routinely used parameters for disease diagnosis, treatment control and risk stratification. In connection with atrial fibrillation (AF), the importance of GDF-15 (growth differentiation factor 15), NT-proBNP (N-terminal fragment brain natriuretic factor) and hs-TnT (high sensitivity cardiac troponin T) is discussed. Catheter ablation is an established treatment method in selected population with AF. However, biomarker response to radiofrequency catheter ablation (RFCA) and pulsed field ablation (PFA) of AF has not been precisely described. Purpose Purpose of the study was to describe early and late dynamics of GDF-15, hs-TnT and NT-proBNP in different ablation technologies. Methods We prospectively enrolled 48 patients (median (IQR) age 62 (55; 70) years, 30 males) undergoing RFCA, which we compared with 30 patients (median (IQR) age 64 (56; 71) years, 18 males) undergoing PFA. All patients underwent 6 sequential blood takes: before ablation (baseline), right after ablation (0h), 24 and 48 hours after procedure (24h and 48h), 90 and 180 days after procedure. Levels of GDF-15, hs-TnT and NT-proBNP were analyzed. Results Out of all patients, 19 (40 %) and 20 (67 %) patients had paroxysmal AF in RFCA and PFA group, respectively. Additional ablation lesions over pulmonary vein isolation were done in 26 (54 %) patients in RFCA group and 11 (43 %) patients in PFA group. Median procedural time was significantly longer in RFCA than in PFA group (155 (130; 190) vs. 80 (70; 90) min; p < 0.01). Early dynamics of GDF-15 and cardiac hs-TnT are visualised in Figure 1 and 2. GDF-15 level peak was registered 48 hours after ablation with median (IQR) 1183 (824; 1988) ng/l. Compared to baseline, GDF-15 values sustained elevated up to 90 days after ablation in both groups and decreased to baseline levels after 180 days. No significant differences were found in GDF-15 levels between patients treated with RFCA and PFA. Maximal values of hs-TnT were significantly higher in PFA group than in RFCA group (1001±589 vs. 458±202 ng/l; p < 0.001). We have recognised decrease of NT-proBNP between baseline and 90 days after procedure in both groups: 338 (112; 613) vs. 209 (101; 545) ng/l; p < 0.05. Conclusion Eventhough GDF-15 is considered as a nonspecific biomarker reflecting general condition of patient, the levels are significantly affected by catheter ablation of AF for several months irrespective to ablation technology. PFA is associated with advanced elevation of hs-TnT.Dynamics of GDF-15 (median; IQR)Dynamics of hs-TnT (median; IQR)

MicroRNAs and other biomarkers of atrial fibrillation in ischemic stroke patients.

This study aimed to evaluate the ability of selected microRNAs as biomarkers of atrial fibrillation (AF) in ischemic stroke patients in comparison with other established biochemical biomarkers. A prospective case-control study of consecutive ischemic stroke patients with AF admitted to a comprehensive stroke center was conducted. The control group consisted of patients with ischemic stroke with no AF detected on prolonged (at least 3 weeks) Holter ECG monitoring. As potential biomarkers of AF, we analyzed the plasma levels of microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) and 13 biochemical biomarkers at admission. The predictive accuracy of biomarkers was assessed by calculating the area under the receiver operating characteristic curve. The data of 117 patients were analyzed (61 with AF, 56 with no AF, 46% men, median age 73 years, median National Institutes of Health Stroke Scale 6). Biochemical biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and total triglycerides) were significantly associated with AF. NT-proBNP had the best diagnostic performance for AF with area under the receiver operating characteristic curve 0.92 (95%, CI 0.86-0.98); a cutoff value of >528 ng/L had a sensitivity of 79% and a specificity of 97%. None of the other biomarkers, including microRNAs, was associated with AF. Conventional biochemical biomarkers (NT-proBNP, high-sensitivity cardiac troponin I, fibrinogen, C-reactive protein, eGFR, and triglycerides), but not microRNAs (miR-21, miR-29b, miR-133b, miR-142-5p, miR-150, miR-499, and miR-223-3p) were significantly associated with AF in our ischemic stroke cohort.

The Correlation of Level of Surgical Risk with High Sensitivity Cardiac Troponin in Non-Cardiac Surgical Patients

The Correlation of Level of Surgical Risk with High Sensitivity Cardiac Troponin in Non-Cardiac Surgical Patients

A Systematic Review and Meta-analysis of Efficacy and Safety of Mavacamten for the Treatment of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common hereditary cardiomyopathy. Mavacamten, a first-in-class cardiac myosin inhibitor, is considered to be a specific drug for the treatment of HCM. This meta-analysis aimed to assess the efficacy and safety of mavacamten in patients with HCM. PubMed, Cochrane Library, Embase and Clinical Trials.gov databases were searched from inception to February 6, 2024 for randomized controlled trials (RCTs) which compared the efficacy and safety between mavacamten and placebo in treating HCM. Six RCTs involving 732 patients were included in this meta-analysis. This meta-analysis showed that mavacamten improved the New York Heart Association (NYHA) function class [risk ratios (RR): 2.21, 95% confidence interval (CI): 1.48 to 3.30, p = 0.00001], Clinical Summary Score of the Kansas City Cardiomyopathy Questionnaire (KCCQ-CSS) scores [mean difference (MD): 9.33, 95% CI: 7.09 to 11.57, p < 0.00001] and composite functional end point (RR: 1.86, 95% CI: 1.25 to 2.78, p = 0.002). Meanwhile, mavacamten decreased N-terminal pro-B-type natriuretic peptide (NT-proBNP) (MD: -492.28, 95% CI: -611.55 to -373.02, p < 0.00001), cardiac troponin I (cTnI) (MD: -14.58, 95% CI: -26.98 to -2.17, p = 0.02) and Valsalva left ventricular outflow tract (LVOT) gradient (MD: -57.96, 95% CI: -82.15 to -33.78, p < 0.00001). The results for the incidence of ≥1 total emergent adverse event (TEAE) and ≥1 serious adverse event (SAE) showed that there was no significant difference between both groups (RR: 1.9, 95% CI: 0.97 to 1.24, p = 0.16) (RR: 1.06, 95% CI: 0.46 to 2.44, p = 0.90). Mavacamten has great efficacy for the treatment of HCM. Meanwhile, mavacamten did not increase the incidence of adverse events or serious adverse events.

Temporal trends in concordance between ICD-coded and cardiac biomarker-classified hospitalisation rates for acute coronary syndromes: a linked hospital and biomarker data study

BackgroundSince 2000, the definition of myocardial infarction (MI) has evolved with reliance on cardiac troponin (cTn) tests. The implications of this change on trends of acute coronary syndrome (ACS) subtypes...

A multimodality score strategy for assessing the risk of immune checkpoint inhibitors related cardiotoxicity

This study aimed to find the association between four common clinical biomarkers and subsequent ICICT, developing a risk scoring strategy to assess the ICICT risk. Three terminals for ICICT were : Terminal 1, cancer therapy-related cardiomyopathies; Terminal 2, myocarditis or heart failure; and Terminal 3, myocarditis, heart failure, myocardial infarction, cerebral infarction, atrial fibrillation, or death. The thresholds were : N-terminal-pro-B-type-natriuretic-peptide ≥ 125 pg/mL, cardiac troponin T ≥ 6 ng/L, high-sensitivity C-reactive protein ≥ 3 mg/L, and coronary artery calcium score > 10 U. Each of the four abnormal biomarkers received 1 point. The links between biomarkers, score stage, and ICICT were analyzed. 375 patients with a mean follow-up of 1.91 years were included. All four biomarkers measured before immunotherapy were associated with a higher risk of developing ICICT. These scores were also associated with ICICT risk. The highest risk was the very high stage (score = 4) has 7.29, 8.83, and 7.02 folder higher risk compared to low risk group for Terminal 1–3, respectively. The cumulation of incidences also showed that the higher stages of score had an earlier onset and higher incidence of ICICT. 4 biomarkers and the scoring strategy enables clinicians to assess risk easily.

An Easy-to-Use Arrayed Brain–Heart Chip

Multi-organ chips are effective at emulating human tissue and organ functions and at replicating the interactions among tissues and organs. An arrayed brain–heart chip was introduced whose configuration comprises open culture chambers and closed biomimetic vascular channels distributed in a horizontal pattern, separated from each other by an endothelial barrier based on fibrin matrix. A 300 μm-high and 13.2 mm-long endothelial barrier surrounded each organoid culture chamber, thereby satisfying the material transport requirements. Numerical simulations were used to analyze the construction process of fibrin barriers in order to optimize the structural design and experimental manipulation, which exhibited a high degree of correlation with experiment results. In each interconnective unit, a cerebral organoid, a cardiac organoid, and endothelial cells were co-cultured stably for a minimum of one week. The permeability of the endothelial barrier and recirculating perfusion enabled cross talk between cerebral organoids and cardiac organoids, as well as between organoids and endothelial cells. This was corroborated by the presence of cardiac troponin I (cTnI) in the cerebral organoid culture chamber and the observation of cerebral organoid and endothelial cells invading the fibrin matrix after one week of co-culture. The arrayed chip was simple to manipulate, clearly visible under a microscope, and compatible with automated pipetting devices, and therefore had significant potential for application.

Bioinformatics design of peptide binding to the human cardiac troponin I (cTnI) in biosensor development for myocardial infarction diagnosis.

Cardiovascular disease has reached a mortality rate of 470,000 patients each year. Myocardial infarction accounts for 49.2% of these deaths, and the cTnI protein is a crucial target in diagnosing myocardial infarction. A peptide-based bioreceptor design using a computational approach is a good candidate to be developed for a rapid, effective, and selective detection method for cTnI although it is still lacking in study. Hence, to address the scientific gap, we develop a new candidate peptide for the cTnI biosensor by bioinformatics method and present new computational approaches. The sequential point mutations were made to the selected peptide to increase its stability and affinity for cTnI. Next, molecular docking was performed to select the mutated peptide, and one of the best results was subjected to the molecular dynamics simulation. Finally, the results showed that the best peptide showed the lowest affinity and good stability among other mutated peptide designs for interacting with the cTnI protein. In addition, the peptide has been tested to have a higher specificity towards cTnI than its major isomer, sTnI, through molecular docking and molecular dynamics simulation. Therefore, the peptide is considered a good potential bioreceptor for diagnosing myocardial infarction diseases.

Development of the Pulmonary Embolism Progression (PEP) score for predicting short-term clinical deterioration in intermediate-risk pulmonary embolism: a single-center retrospective study.

Accurate risk stratification in acute intermediate-risk pulmonary embolism (PE) is essential. Current prediction scores lack the ability to forecast impending clinical decline. The Pulmonary Embolism Progression (PEP) score aims to predict short-term clinical deterioration (respiratory failure or hemodynamic instability within 72h) in patients with intermediate-risk PE. This single-center retrospective cohort study analyzed patients with intermediate PE. The outcome of interest was respiratory failure or hemodynamic instability within 72h. A multivariate logistic regression identified five predictive variables for the final PEP score: use of > 4L/min of supplemental oxygen above baseline, lactate > 2.0 mmol/L, high-sensitivity cardiac troponin T (hs-cTnT) > 40 ng/L, tricuspid annular plane systolic excursion (TAPSE) < 13mm, and the combination of central and subsegmental clot. The derivation cohort included 117 patients, and the validation cohort included 70 patients. The area under the receiver operating characteristic (AUROC) curve for the derivation cohort was 0.8671 (95% CI: 0.7946, 0.9292), and for the validation cohort, it was 0.9264 (95% CI: 0.8680, 0.9847). A PEP score of 4 points yielded the highest combination of sensitivity (93%) and specificity (65%). Each incremental point increase in the PEP score raised the probability of clinical deterioration by a factor of 1.933. The PEP score is a reliable tool for predicting the likelihood of clinical deterioration in intermediate-risk PE patients within 72h, potentially aiding in timely clinical decision-making and improving patient outcomes.

Clinical, laboratory, and echocardiographic characteristics of critical multisystem inflammatory syndrome in children: a retrospective, observational study

ObjectiveMultisystem inflammatory syndrome in children (MIS-C) is a critical childhood disease that is associated with coronavirus disease (COVID-19). We aimed to describe the clinical, laboratory, and echocardiographic characteristics and outcome of critical MIS-C cases in Egyptian children during the first wave of the COVID-19 pandemic.DesignA retrospective, observational study.SettingA single-center tertiary pediatric intensive care unit (PICU).In Ain Shams university hospitals Cairo EgyptMethodsChildren admitted to the PICU diagnosed with severe MIS-C as per the Centers for Disease Control’s definition from June 23, 2020, to August 22, 2020, were included.ResultsThe patient’s mean age was 7.45 (interquartile range [IQR], 4.23) years, and the cause of PICU admission was hypotension and shock. All patients had a fever for 4.8 (IQR, 2.5) days before shock developed. Overall, 68% had a gastrointestinal manifestation, and 55.6% had a rash. Thirty-five of 45 patients had ≥ 4 elevated inflammatory markers. The cardiac troponin I level was elevated in 35 of 45 patients. The most common cardiac condition was valvulitis (tricuspid regurgitation, 29/45; mitral valve regurgitation, 28/45; pulmonary valve regurgitation, 5/45; atrial valve regurgitation, 4/45). Twenty-one patients had an impaired ejection fraction < 50%, and 17 patients had coronary dilatation. Six patients had pericardial effusion, 1 patient had dilated pulmonary arteries, and 6 patients (13.3%) died of their associated comorbidities. The mean PICU length of stay among patients with no associated comorbidities was 7 days.ConclusionsCritical cases of MIS-C had a spectrum of different cardiac conditions, with valvulitis being the most common one. The worst outcome occurred in patients with comorbidities and infants.