Validation of Becton Dickinson Barricor™ tubes for use with Abbott Alinity™ and Siemens Atellica® highly sensitive cardiac troponin I measuring systems.

BACKGROUND: BD Barricor™ tubes have been proposed to decrease laboratory turnaround time (TAT). We analytically validated and then clinically verified these tubes for use with Abbott Alinity™ and Siemens Atellica® highly sensitive cardiac troponin I (hs-cTnI) assays. METHODS: hs-cTnI measurements were undertaken in paired Barricor™ and in-use PSTII™ tubes on both systems. 359 matched samples with hs-cTnI levels between 3 and 15,000 ng/L (Atellica® values) were used to assess the hemolysis rate and make method comparisons. 599 paired patient samples were collected on emergency department (ED) admission to compare the performance of the rapid acute myocardial infarction (AMI) rule-out strategy based on hs-cTnI concentrations lower than recommended thresholds (<4 ng/L Alinity™; <5 ng/L Atellica®) when different tubes and systems were employed. RESULTS: No between-tube differences in hemolysis rate were seen when free hemoglobin concentrations in plasma samples were ≥0.25 g/L, even if PSTII™ showed a significant increase of hemolysis rate vs. Barricor™ (31% vs. 22%, p=0.007) when a lower cut-off for hemolysis (≥0.11 g/L) was employed on the Atellica® detection system. The alternate use of these tubes did not influence the hs-cTnI results obtained from either of the two assays, which remained markedly biased (~40%) irrespective of the tube used. The expected optimal ability of very low hs-cTnI values on ED admission for ruling out AMI was confirmed by using both systems regardless of the tube type. CONCLUSIONS: Barricor™ and PSTII™ tubes can provide analytically equivalent hs-cTnI results when used on either Alinity™ or Atellica® hs-cTnI assays.

A Case of Reverse Takotsubo Cardiomyopathy After Administering a Local Anesthetic Containing Epinephrine.

Takotsubo cardiomyopathy (TCM) is a rare syndrome characterized by acute and transient distinctive wall motion abnormalities accompanied by other defined objective findings. There are many variants of TCM, including the reverse (or basal) subtype. While the pathogenesis is not fully understood, both endogenous and exogenous catecholamines have been implicated. This case report describes a 30-year-old active-duty military female who developed reverse TCM immediately following local anesthetic with epinephrine administration in preparation for an elective septorhinoplasty. She developed electrocardiogram (ECG) changes, temporary hemodynamic instability, and cardiac troponin elevation. Transthoracic echocardiogram (TTE) demonstrated significantly reduced systolic and diastolic function, with akinesis of the basal segments and normal wall motion of the apical segments, consistent with a reverse Takotsubo pattern. Coronary computed tomography (CT) angiography showed normal coronary arteries. Repeat TTE was performed two days after the initial event and showed near-complete resolution of the wall motion abnormalities. Fourteen days later, TTE showed normalization of cardiac function. While there is a favorable prognosis for most patients with this diagnosis, there does remain the potential for significant adverse outcomes, risk of recurrence, and a non-negligible mortality rate. It is widely known that physical and emotional triggers can precipitate TCM through the release of catecholamines. This case, in addition to numerous other case reports, provides further documentation and support that exogenous epinephrine administration is also associated with the development of TCM. Clinicians should consider the diagnosis of Takotsubo cardiomyopathy if hemodynamic or ECG changes arise following epinephrine administration.

SARS-CoV-2 Infection-Dependent Modulation in Vital Components of the Serum Profile of Severely SARS-CoV-2 Infected Patients.

Background: COVID-19 modulates many serological biomarkers during the progress of disease severity. The study aimed to determine COVID-19 severity-associated perturbance in the serum profile. Methods: A retrospective study including COVID-19-positive individuals (n = 405) was accomplished. The serum profile of COVID-19 participants was mined from laboratory records. Severity-associated alteration in the serum profile was evaluated using Pearson correlation, regression, VCramer, Bayesian posterior VCramer, and bias factor using R-base-RStudio-version-3.3.0 with a significant cut-off of p < 0.05. Results: Significantly different mean ± standard deviation (SD) (highly versus moderately severe) of C-reactive protein (CRP), ferritin, neutrophil-lymphocyte ratio (NLR), D-dimer, platelets, prothrombin time (PT), partial prothrombin time (PTT), troponin 1, lactate dehydrogenase (LDH), aspartate-aminotransferase (AST), alanine aminotransferase (ALT), and AST/ALT ratio was observed (p < 0.001). Highly severe COVID-19 associated with CRP, ferritin, NLR, in D-dimer, PT, PTT, troponin 1, AST/ALT ratio, AST and ALT (adjusted odds ratio (AOR): 1.346, 1.05, 1.46, 1.33, 1.42, 1.23, 4.07, 3.9, 1.24, 1.45, p < 0.001). CRP with ferritin (r = 0.743), NLR (r = 0.77), white blood cells (WBC) (r = 0.8), troponin1 with LDH (r = 0.757), and D-dimer with platelets (r = -0.81) were highly correlated. X2pearson (p < 0.001), VCramer (0.71), Bayesian-VCramer (0.7), and bias-factor (-125) for troponin 1 indicate the strong association of troponin 1 level and with COVID-19 severity. X2pearson (p < 0.001), VCramer (1), Bayesian-VCramer (0.98), and bias-factor (-266.3) for NLR exhibited a very strong association of pathologic conditions with the high severity of the disease. Conclusion: These biomarkers of inflammation (CRP, Ferritin, NLR), coagulation disorders (D-dimer, PT, and PTT) cardiac abnormality (troponin 1), and liver injury (AST/ALT) could be crucial in low-medical resource settings as potential prognosticator/predictors of the COVID-19 severity and clinical outcomes. Moreover, the outcome of this study could be leveraged for the early prediction of disease severity during SARS-CoV or Middle East Respiratory Coronavirus (MERS-CoV) infection.

Markedly elevated high-sensitivity troponin and in-hospital mortality after cardiac surgery.

BACKGROUND: High-sensitivity troponin (hsTnI) is correlated with cardiac mortality; however, studies on the relationship of markedly elevated hsTnI with in-hospital mortality after cardiac surgery are sparse. Therefore, we aimed to define this relationship in order to help guide in-hospital, acute management of post-surgical patients. METHODS: We retrospectively analyzed all cardiac surgeries completed at our institution between January 2020 and June 2022 in which a peak hsTnI was noted to be >35× upper limit of normal (ULN = 34 ng/L). The primary outcome was in-hospital death. Subgroup analysis was performed to assess differences between coronary artery bypass grafting (CABG) and other cardiac surgeries. RESULTS: A total of 1382 cases met inclusion criteria. The patients' mean age was 64.8 years and 68.2 % were male. Median peak hsTnI after surgery was 4202 ng/L (interquartile ratio: 2427-7654). Univariate analysis of troponin level with mortality found that for every 1000 ng/L increase in hsTnI, odds of in-hospital death increased by 3.8 % (odds ratio [OR]: 1.038; 95 % confidence interval [CI] 1.027-1.050; p < 0.0001). In a multivariate model, troponin (OR 1.02; 95 % CI 1.01-1.04; p = 0.004) maintained a significant association with in-hospital death. CABG was associated with a lower risk of in-hospital death for any given hsTnI level up to 60,000 ng/L compared to other cardiac surgeries. CONCLUSION: Increasing hsTnI level is associated with increasing probability of in-hospital mortality and, therefore, serves as an additional, objective measure of risk to help guide in-hospital clinical management.

Detectable troponin below the 99th percentile predicts survival in patients undergoing coronary angiography.

Background: Cardiac troponin I (cTnI) above the 99th percentile is associated with an increased risk of major adverse events. Patients with detectable cTnI below the 99th percentile are a heterogeneous group with a less well-defined risk profile. The purpose of this study is to investigate the prognostic relevance of detectable cTnI below the 99th percentile in patients undergoing coronary angiography. Methods: The study included 14,776 consecutive patients (mean age of 65.4 ± 12.7 years, 71.3 % male) from the Essen Coronary Artery Disease (ECAD) registry. Patients with cTnI levels above the 99th percentile and patients with ST-segment elevation acute myocardial infarction were excluded. All-cause mortality was defined as the primary endpoint. Results: Detectable cTnI below the 99th percentile was present in 2811 (19.0 %) patients, while 11,965 (81.0 %) patients were below detection limit of the employed assay. The mean follow-up was 4.25 ± 3.76 years. All-cause mortality was 20.8 % for patients with detectable cTnI below the 99th percentile and 15.0 % for those without detectable cTnI. In a multivariable Cox regression analysis, detectable cTnI was independently associated with all-cause mortality with a hazard ratio of 1.60 (95 % CI 1.45-1.76; p < 0.001). There was a stepwise relationship with increasing all-cause mortality and tertiles of detectable cTnI levels with hazard ratios of 1.63 (95 % CI 1.39-1.90) for the first tertile to 2.02 (95 % CI 1.74-2.35) for the third tertile. Conclusions: Detectable cTnI below the 99th percentile is an independent predictor of mortality in patients undergoing coronary angiography with the risk of death growing progressively with increasing troponin levels.

Noninvasive cardiac-specific biomarkers for the diagnosis and prevention of vascular stenosis in cardiovascular disorder.

Background: The most frequent lesion in the blood vessels feeding the myocardium is vascular stenosis, a condition that develops slowly but can prove to be deadly in a long run. Non-invasive biomarkers could play a significant role in timely diagnosis, detection and management for vascular stenosis events associated with cardiovascular disorders. Aims: The study aimed to investigate high sensitivity troponin I (hs-TnI), cardiac troponin I (c-TnI) and high sensitivity C-reactive protein (hs-CRP) that may be used solely or in combination in detecting the extent of vascular stenosis in CVD patients. Methodology: 274 patients with dyspnea/orthopnea complaints visiting the cardiologists were enrolled in this study. Angiographic study was conducted on the enrolled patients to examine the extent of stenosis in the five prominent vessels (LDA, LCX, PDA/PLV, RCA, and OM) connected to the myocardium. Samples from all the cases suspected to be having coronary artery stenosis were collected, and subjected to biochemical evaluation of certain cardiac inflammatory biomarkers (c-TnI, hsTn-I and hs-CRP) to check their sensitivity with the level of vascular stenosis. The extent of mild and culprit stenosis was detected during angiographic examination and the same was reported in the form significant (≥50% stenosis in the vessels) and non-significant (<50% stenosis in the vessels) Carotid Stenosis. Ethical Clearance for the study was provided by Dr. Ram Manohar Lohia Institute of Medical Sciences Institutional Ethical Committee. Informed consent was obtained from all the participants enrolled in the study. Results: We observed that 85% of the total population enrolled in this study was suffering from hypertension followed by 62.40% detected with sporadic episodes of chest pain. Most of the subjects (42% of the total population) had stenosis in their LAD followed by 38% who had stenosis in their RCA. Almost 23% patients were reported to have stenosis in their LCX followed by OM (18% patients), PDA/PLV (13%) and only 10% patients had blockage problem in their diagonal. 24% of the subjects were found to have stenosis in a single vessel and hence were categorized in the Single Vessel Disease (SVD) group while 76% were having stenosis in two or more than two arteries (Multiple Vessel Disease). hs-TnI level was found to be correlated with the levels of stenosis and was higher in the MVD group as compared to the SVD group. Conclusion: hs-TnI could be used as a novel marker as it shows prominence in detecting the level of stenosis quite earlier as compared to c-TnI which gets detected only after a long duration in the CVD patients admitted for angiography. hs- CRP gets readily detected as inflammation marker in these patients and hence could be used in combination with hs-TnI to detect the risk of developing coronary artery disease.

Modeling the Impact of Biomarker-Guided Versus ASCVD Risk-Guided Drug Treatment in US Adults With Stage 1 Hypertension: The National Health and Nutrition Examination Survey, 1999 to 2004.

BACKGROUND: Guidelines recommend antihypertensive medication for adults with both stage 1 hypertension (systolic blood pressure, 130-139 mm Hg or diastolic blood pressure, 80-89 mm Hg) and 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥10%. Cardiac biomarkers could facilitate a more targeted approach to the treatment of stage 1 hypertension. METHODS: We studied 1999 to 2004 National Health and Nutrition Examination Survey participants aged ≥20 years with untreated stage 1 hypertension without heart failure or ASCVD. hs-cTnI (high-sensitivity cardiac troponin I) and hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) were measured in stored serum. We used the Pooled Cohort Equations to predict 10-year ASCVD risk. All participants had linked mortality follow-up through December 31, 2019. RESULTS: Overall, 17.5% of US adults (32.2 million) had untreated stage 1 hypertension. Among these 32.2 million persons, 15.7% had ASCVD risk ≥10%, 5.6% had elevated hs-cTnI, 4.7% had elevated hs-cTnT, and 9.5% had elevated NT-proBNP. Among adults aged 65 to 79 years with untreated stage 1 hypertension, 80.5% had ASCVD risk ≥10%, 13.0% had elevated hs-cTnI, 15.2% had elevated hs-cTnT, and 29.4% had elevated NT-proBNP. Less than half of the adults aged ≥80 years with untreated stage 1 hypertension had elevated biomarkers. The cardiovascular disease mortality rates among all adults with untreated stage 1 hypertension and with either ASCVD risk ≥10%, elevated hs-cTnI, elevated hs-cTnT, or elevated NT-proBNP were 7.51, 7.74, 8.75, and 5.87 per 1000 person-years, respectively. CONCLUSIONS: Cardiac biomarkers may be more selective for informing risk-based treatment decisions in stage 1 hypertension, particularly among adults aged ≥65 years.

Analytical validation of the Mindray CL1200i analyzer high sensitivity cardiac troponin I assay: MERITnI study.

OBJECTIVES: This study performed an analytical validation study of the Mindray high-sensitivity cardiac troponin I (hs-cTnI) assay addressing limit of blank (LoB), limit of detection (LoD), precision, linearity, analytical specificity and sex-specific 99th percentile upper reference limits. METHODS: LoB, LoD, precision, linearity and analytical specificity were studied according to Clinical and Laboratory Standards Institute. We used one reagent lot and one CL1200i analyzer. Skeletal troponin I and T, cardiac troponin T, troponin C, actin, tropomyosin, myosin light chain, myoglobin and creatine kinase (CK-MB) were studied for cross-reactivity. Interference with biotin was examined. Lithium heparin samples (one freeze thaw cycle) from healthy males and females were measured to determine the 99th percentiles by using the non-parametric method. Analyses were performed before and after excluding subjects with clinical conditions and/or increased surrogate biomarkers. RESULTS: The Mindray hs-cTnI assay met criteria to be considered as a hs-cTn assay. LoB and LoD was <0.1 ng/L and 0.1 ng/L, respectively. Repeatability had a coefficient of variation 1.2-3.8 %, and within-laboratory imprecision 1.7-5.0 %. The measuring interval ranged from 1.1 to 28,180 ng/L. The analytical specificity was clinically acceptable for the interferents studied. After exclusions, the 99th percentile URLs obtained were 10 ng/L overall, 5 ng/L for females and 12 ng/L for males. CONCLUSIONS: Analytical observations of the Mindray hs-cTnI assay demonstrated excellent LoB, LoD, precision, linearity and analytical specificity, that were in alignment with the manufacturer's claims and regulatory guidelines for hs-cTnI. The assay is suitable for clinical investigation for patient-oriented studies.

The relationship between workload and exercise-induced cardiac troponin elevations is influenced by non-obstructive coronary atherosclerosis.

The relationship between exercise-induced troponin elevation and non-obstructive coronary artery disease (CAD) is unclear. This observational study assessed non-obstructive CAD's impact on exercise-induced cardiac Troponin I (cTnI) elevation in middle-aged recreational athletes. cTnI levels of 40 well-trained recreational athletes (73% males, 50 ± 9 years old) were assessed by a high-sensitive cTnI assay 24 h before, and at 3 and 24 h following two high-intensity exercises of different durations; a cardiopulmonary exercise test (CPET), and a 91-km mountain bike race. Workload was measured with power meters. Coronary computed tomography angiography was used to determine the presence or absence of non-obstructive (<50% obstruction) CAD. A total of 15 individuals had non-obstructive CAD (Atherosclerotic group), whereas 25 had no atherosclerosis (normal). There were higher post-exercise cTnI levels following the race compared with CPET, both at 3 h (77.0 (35.3-112.4) ng/L vs. 11.6 (6.4-22.5) ng/L, p < 0.001) and at 24 h (14.7 (6.7-16.3) vs. 5.0 (2.6-8.9) ng/L, p < 0.001). Absolute cTnI values did not differ among groups. Still, the association of cTnI response to power output was significantly stronger in the CAD versus Normal group both at 3 h post-exercise (Rho = 0.80, p < 0.001 vs. Rho = -0.20, p = 0.33) and 24-h post-exercise (Rho = 0.87, p < 0.001 vs. Rho = -0.13, p = 0.55). Exercise-induced cTnI elevation was strongly correlated with exercise workload in middle-aged athletes with non-obstructive CAD but not in individuals without CAD. This finding suggests that CAD influences the relationship between exercise workload and the cTnI response even without coronary artery obstruction.

Early myocardial injury in children on doxorubicin for cancer chemotherapy: a cross-sectional study in a tertiary referral centre in Kenya.

INTRODUCTION: Use of doxorubicin, an anthracycline chemotherapeutic agent has been associated with late-occurring cardiac toxicities. Detection of early-occurring cardiac effects of cancer chemotherapy is essential to prevent occurrence of adverse events including toxicity, myocardial dysfunction, and death. OBJECTIVE: To investigate the prevalence of elevated cardiac troponin T (cTnT) and associated factors of myocardial injury in children on doxorubicin cancer chemotherapy. METHODS: Design: A cross-sectional study. SETTING AND SUBJECTS: A hospital-based study conducted on children aged 1-month to 12.4-years who had a diagnosis of cancer and were admitted at Kenyatta National Hospital (KNH). INTERVENTIONS AND OUTCOMES: The patients underwent Echocardiography (ECHO) before their scheduled chemotherapy infusion. Twenty-four (24) hours after the chemotherapy infusion the patients had an evaluation of the serum cardiac troponin T (cTnT) and a repeat ECHO. Myocardial injury was defined as cTnT level > 0.014 ng/ml or a Fractional Shortening (FS) of < 29% on ECHO. RESULTS: One hundred (100) children were included in the final analysis. Thirty-two percent (32%) of the study population had an elevated cTnT. A cumulative doxorubicin dose of > 175 mg/m2 was significantly associated with and elevated cTnT (OR, 10.76; 95% CI, 1.18-97.92; p = 0.035). Diagnosis of nephroblastoma was also associated with an elevated cTnT (OR, 3.0; 95% CI, 1.23-7.26) but not statistically significant (p = 0.105). Nine percent (9%) of the participants had echocardiographic evidence of myocardial injury. CONCLUSION: When compared to echocardiography, elevated levels of cTnT showed a higher association with early-occurring chemotherapy-induced myocardial injury among children on cancer treatment at a tertiary teaching and referral hospital in Kenya.

Elevated Cardiac Troponin I Level associated to Cardiac Dysfunction in Burned Patients.

Severely burned patients often developed cardiac dysfunction and heart failure. The purpose of this retrospective study is to evaluate the role of Cardiac Troponin I (cTI) and its association to patients with burns. Patients deidentified data were collected from a national database in May 2023. Adult burn patients who had cTnI lab counted were enrolled in this study. Patients were grouped by the cTnI mean level within 72 hours including patients with elevated cTnI levels at >0.3 ng/mL (n= 2188 patients), and patients with non-elevated cTnI level (< 0.04 ng/mL) (n= 3200). The cohorts were further stratified by less than 20% TBSA mild burn population and >20% TBSA severe burn population to replicate the severity of burns. The 30-days incidences of acute myocardial infarction (MI), sepsis, and mortality were investigated after the cohorts were propensity matching balanced. The odds ratios (ORs) with 95%CI for MI were (9.829/7.081-13.645), sepsis (1.527/1.269-1.959) and mortality (2.586/2.110- 3.170) respectively (p<0.05). The groups that were further stratified into mild burn and severe burn had the following results: The mild burn ORs and 95% CI for MI was (6.237/3.986-9.785), sepsis (1.603/1.132-2.270), and mortality was (2.298/1.629-3.242). The severe burn cohort had ORs and 95% CI for MI (3.145/1.469-6.732), sepsis (0.993/0.555-1.777), mortality (2.934/1.924-4.475). In conclusion, the patients with earlier elevated cTnI level had worse outcomes of MI and mortality in both severe and mild burns.

Effects of preparticipating hypohydration on cardiac burden in recreational athletes.

The global temperature rise will have extensive consequences on our organ systems, but hypohydration caused by reduced water intake or increased water loss through sweating plays the most relevant role. Many studies have already demonstrated the association between hypohydration and impaired exercise performance, but data related to the cardiac burden of hypohydration are scarce. This study is a sub-investigation of our large, prospective, self-controlled trial on the effects of hypohydration on cardiopulmonary exercise capacity with previously published results. In the current sub-study, we analyzed the impact of hypohydration on cardiac burden in this cohort of fifty healthy, recreational athletes during cardiopulmonary exercise test.Therefore, each participant underwent cardiopulmonary exercise test with a standardized ramp protocol twice, once in hypohydrated state and once in euhydrated state as control, and the cardiac markers Troponin T, NT-pro-BNP and Chromogranin A were measured before and after the exercise test at each state. Mean age was 29.7 years and 34% of probands were female. Hypohydration led to a reduced body water, a significant decrease in oxygen uptake and lower levels of power output. Yet, Troponin T, NT-proBNP, Chromogranin A and lactate levels did not significantly differ between the two conditions.In this study cohort, decreased exercise capacity during hypohydration was more likely due to impaired cardiac output with diminished plasma volume rather than measurable cardiac stress from fluid deprivation. However, whether these data are generalizable to a diseased cohort is left unanswered and should be addressed in future randomized controlled trials.

The natural history of CVB3 myocarditis in C57BL/6J mice: an extended in-depth characterization.

BACKGROUND AND AIMS: Viral infections are the leading cause of myocarditis. Besides acute cardiac complications, late-stage sequelae such as myocardial fibrosis may develop, importantly impacting the prognosis. Coxsackievirus B3 (CVB)-induced myocarditis in mice is the most commonly used translational model to study viral myocarditis and has provided the majority of our current understanding of the disease pathophysiology. Nevertheless, the late stages of disease, encompassing fibrogenesis and arrhythmogenesis, have been underappreciated in viral myocarditis research to date. The present study investigated the natural history of CVB-induced myocarditis in C57BL/6J mice, expanding the focus beyond the acute phase of disease. In addition, we studied the impact of sex and inoculation dose on the disease course. METHODS AND RESULTS: C57BL/6J mice (12 weeks old; n=154) received a single intraperitoneal injection with CVB to induce viral myocarditis, or vehicle (PBS) as control. Male mice (n=92) were injected with 5 × 105 (regular dose)(RD) or 5 × 106 (high dose)(HD) plaque-forming units of CVB, whereas female mice received the RD only. Animals were sacrificed 1, 2, 4, 8 and 11 weeks after CVB or PBS injection. Virally inoculated mice developed viral disease with a temporary decline in general condition and weight loss, which was less pronounced in female animals (P<0.001). In male CVB mice, premature mortality occurred between days 8-23 after inoculation (RD: 21%, HD: 20%), whereas all female animals survived. Over the course of disease, cardiac inflammation progressively subsided, with faster resolution in female mice. There were no substantial group differences in the composition of the inflammatory cell infiltrates: predominance of cytotoxic T cells at day 7 and 14, and a switch from arginase1-reactive macrophages to iNOS-reactive macrophages from day 7 to 14 were the main findings. There was concomitant development and maturation of different patterns of myocardial fibrosis, with enhanced fibrogenesis in male mice. Virus was almost completely cleared from the heart by day 14. Serum biomarkers of cardiac damage and cardiac expression of remodeling genes were temporarily elevated during the acute phase of disease. Cardiac CTGF gene upregulation was less prolonged in female CVB animals. In vivo electrophysiology studies at weeks 8 and 11 demonstrated that under baseline conditions (i.e. in the absence of proarrhythmogenic drugs), ventricular arrhythmias could only be induced in CVB animals. The cumulative arrhythmia burden throughout the entire stimulation protocol was not significantly different between CVB and control groups. CONCLUSION: CVB inoculation in C57BL/6J mice represents a model of acute self-limiting viral myocarditis, with progression to different patterns of myocardial fibrosis. Sex, but not inoculation dose, seems to modulate the course of disease.

Cardiovascular adverse events associated with immune checkpoint inhibitors: A retrospective multicenter cohort study.

BACKGROUND: Over the past decade, immune checkpoint inhibitors (ICIs) have significantly transformed cancer treatment. However, ICIs inevitably may cause a spectrum of immune-related adverse events, among which cardiovascular toxicity, particularly myocarditis, while infrequent, has garnered increasing attention due to its high fatality rate. METHODS: We conducted a multicenter retrospective study to characterize ICI-associated cardiovascular adverse events. Logistic regression was performed to explore the risk factors for the development of myocarditis and severe myocarditis. Receiver operating characteristic curves were conducted to assess the diagnostic abilities of cardiac biomarkers to distinguish different cardiovascular toxicities, and the performance and calibration were evaluated using Hosmer-Lemeshow test. RESULTS: Forty-four patients were identified, including thirty-five myocarditis, five heart failure, three arrhythmias, and one myocardial infarction. Compared with other patients, myocarditis patients had higher cardiac troponin-I (cTnI) levels (p < 0.001), higher creatine kinase levels (p = 0.003), higher creatine kinase isoenzyme-MB (CK-MB) levels (p = 0.013), and shorter time to the incidence of adverse cardiovascular events (p = 0.022) after ICI treatment. Twenty-one patients (60%) were classified as severe myocarditis, and they presented higher cardiac troponin I (cTnI) levels (p = 0.013), higher N-terminal pro-B-type natriuretic peptide levels (p = 0.031), higher creatine kinase levels (p = 0.018), higher CK-MB levels (p = 0.026), and higher neutrophil to lymphocyte ratio (NLR) levels (p = 0.016) compared to non-severe myocarditis patients after ICI treatment. Multivariate logistic regression showed that CK-MB (adjusted odds ratio [OR]: 1.775, 95% confidence interval [CI]: 1.055-2.984, p = 0.031) was the independent risk factor of the development of ICI-associated myocarditis, and cTnI (adjusted OR: 1.021, 95% CI: 1.002-1.039, p = 0.03) and NLR (adjusted OR: 1.890, 95% CI: 1.026-3.483, p = 0.041) were the independent risk factors of ICI-associated severe myocarditis. The receiver operating characteristic curve showed an area under curve of 0.785 (95% CI: 0.642 to 0.928, p = 0.013) for CK-MB, 0.765 (95% CI: 0.601 to 0.929, p = 0.013) for cTnI, and 0.773 for NLR (95% CI: 0.597 to 0.948, p = 0.016). CONCLUSIONS: Elevated CK-MB after ICI treatment is the independent risk factor for the incidence of ICI-associated myocarditis, and elevated cTnI and NLR after ICI treatment are the independent risk factors for the development of ICI-associated severe myocarditis. CK-MB, cTnI, and NLR demonstrated a promising predictive utility for the identification of ICI-associated myocarditis and severe myocarditis.

Low Level of First Morning Urine Cardiac Troponin I: A Specific Hallmark of Aortic Stenosis Severity.

Background: It has recently been shown that cardiac-specific troponin I concentrations in first morning urine samples can be measured with commercially available tests. Due to their accumulation in the first morning urine, scientific papers indicate a potential predictive value for cardiovascular diseases. Therefore, the aim of this study was to compare the concentration of cardiac troponin I in the first morning urine in patients with severe aortic stenosis and the healthy population. Patients and Methods: Blood and first morning urine samples were collected from 34 healthy individuals (17 female) at University Hospital Merkur and 25 patients with severe aortic stenosis (14 female) before surgical treatment at University Hospital Dubrava. Cardiac troponin I and T values were determined using high-sensitivity assays using commercially available Abbott and Roche tests. Results: Patients with severe aortic stenosis had significantly lower troponin I concentrations in the first morning urine samples (0.3 ng/L (0.1-0.6)) as compared to the healthy population (15.2 ng/L (8.4-19.9)) (p < 0.001). There was no statistically significant difference in troponin T concentrations between healthy individuals and patients with severe aortic stenosis. In parallel, both I and T plasma troponin concentrations were significantly higher in patients with severe aortic stenosis. Conclusions: In patients with severe aortic stenosis, cardiac troponin I values in the first morning urine are significantly lower than in healthy subjects.

Early Cardiac Evaluation, Abnormal Test Results, and Associations with Outcomes in Patients with Acute Brain Injury Admitted to a Neurocritical Care Unit.

Background: to examine factors associated with cardiac evaluation and associations between cardiac test abnormalities and clinical outcomes in patients with acute brain injury (ABI) due to acute ischemic stroke (AIS), spontaneous subarachnoid hemorrhage (SAH), spontaneous intracerebral hemorrhage (sICH), and traumatic brain injury (TBI) requiring neurocritical care. Methods: In a cohort of patients ≥18 years, we examined the utilization of electrocardiography (ECG), beta-natriuretic peptide (BNP), cardiac troponin (cTnI), and transthoracic echocardiography (TTE). We investigated the association between cTnI, BNP, sex-adjusted prolonged QTc interval, low ejection fraction (EF < 40%), all-cause mortality, death by neurologic criteria (DNC), transition to comfort measures only (CMO), and hospital discharge to home using univariable and multivariable analysis (adjusted for age, sex, race/ethnicity, insurance carrier, pre-admission cardiac disorder, ABI type, admission Glasgow Coma Scale Score, mechanical ventilation, and intracranial pressure [ICP] monitoring). Results: The final sample comprised 11,822 patients: AIS (46.7%), sICH (18.5%), SAH (14.8%), and TBI (20.0%). A total of 63% (n = 7472) received cardiac workup, which increased over nine years (p < 0.001). A cardiac investigation was associated with increased age, male sex (aOR 1.16 [1.07, 1.27]), non-white ethnicity (aOR), non-commercial insurance (aOR 1.21 [1.09, 1.33]), pre-admission cardiac disorder (aOR 1.21 [1.09, 1.34]), mechanical ventilation (aOR1.78 [1.57, 2.02]) and ICP monitoring (aOR1.68 [1.49, 1.89]). Compared to AIS, sICH (aOR 0.25 [0.22, 0.29]), SAH (aOR 0.36 [0.30, 0.43]), and TBI (aOR 0.19 [0.17, 0.24]) patients were less likely to receive cardiac investigation. Patients with troponin 25th-50th quartile (aOR 1.65 [1.10-2.47]), troponin 50th-75th quartile (aOR 1.79 [1.22-2.63]), troponin >75th quartile (aOR 2.18 [1.49-3.17]), BNP 50th-75th quartile (aOR 2.86 [1.28-6.40]), BNP >75th quartile (aOR 4.54 [2.09-9.85]), prolonged QTc (aOR 3.41 [2.28; 5.30]), and EF < 40% (aOR 2.47 [1.07; 5.14]) were more likely to be DNC. Patients with troponin 50th-75th quartile (aOR 1.77 [1.14-2.73]), troponin >75th quartile (aOR 1.81 [1.18-2.78]), and prolonged QTc (aOR 1.71 [1.39; 2.12]) were more likely to be associated with a transition to CMO. Patients with prolonged QTc (aOR 0.66 [0.58; 0.76]) were less likely to be discharged home. Conclusions: This large, single-center study demonstrates low rates of cardiac evaluations in TBI, SAH, and sICH compared to AIS. However, there are strong associations between electrocardiography, biomarkers of cardiac injury and heart failure, and echocardiography findings on clinical outcomes in patients with ABI. Findings need validation in a multicenter cohort.

Elevated Troponins after COVID-19 Hospitalization and Long-Term COVID-19 Symptoms: Incidence, Prognosis, and Clinical Outcomes-Results from a Multi-Center International Prospective Registry (HOPE-2).

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

Clinical Implications of High-Sensitivity Troponin Elevation Levels in Non-ST-Segment Elevation Myocardial Infarction Patients: Beyond Diagnostics.

Standard troponin has long been pivotal in diagnosing coronary syndrome, especially Non-ST-Segment Elevation Myocardial Infarction (NSTEMI). The recent introduction of high-sensitivity troponin (hs-cTnI) has elevated it to the gold standard. Yet, its nuanced role in predicting angiographic lesions and clinical outcomes, notably in specific populations like obesity, remains underexplored. Aim: To evaluate the association between hs-cTnI magnitude in NSTEMI patients and angiographic findings, progression to acute heart failure, and its performance in obesity. Methods: Retrospective study of 208 NSTEMI patients at a large university center (2020-2023). Hs-cTnI values were assessed for angiographic severity, acute heart failure, and characteristics in the obese population. Data collected and diagnostic performance were evaluated using manufacturer-specified cutoffs. Results: 97.12% of patients had a single culprit vessel. Hs-cTnI elevation correlated with angiographic stenosis severity. Performance for detecting severe coronary disease was low, with no improvement using a higher cutoff. No association was found between hs-cTnI and the culprit vessel location. Hs-cTnI did not predict acute heart failure progression. In the obese population, hs-cTnI levels were higher, but acute heart failure occurred less frequently than in non-obese counterparts. Conclusions: In NSTEMI, hs-cTnI elevation is associated with significant stenosis, but not with location or acute heart failure. Obesity correlates with higher hs-cTnI levels but a reduced risk of acute heart failure during NSTEMI.

Interaction of heparin with human cardiac troponin complex and its influence on the immunodetection of troponins in human blood samples.

OBJECTIVES: Heparin is a highly charged polysaccharide used as an anticoagulant to prevent blood coagulation in patients with presumed myocardial infarction and to prepare heparin plasma samples for laboratory tests. There are conflicting data regarding the effects of heparin on the measurement of cardiac isoforms of troponin I (cTnI) and troponin T (cTnT), which are used for the immunodiagnosis of acute myocardial infarction. In this study, we investigated the influence of heparin on the immunodetection of human cardiac troponins. METHODS: Gel filtration (GF) techniques and sandwich fluoroimmunoassay were performed. The regions of сTnI and cTnT that are affected by heparin were investigated with a panel of anti-cTnI and anti-cTnT monoclonal antibodies, specific to different epitopes. RESULTS: Heparin was shown to bind to the human cardiac full-size ternary troponin complex (ITC-complex) and free cTnT, which increased their apparent molecular weights in GF studies. Heparin did not bind to the low molecular weight ITC-complex and to binary cTnI-troponin С complex. We did not detect any sites on cTnI in the ITC-complex that were specifically affected by heparin. In contrast, cTnT regions limited to approximately 69-99, 119-138 and 145-164 amino acid residues (aar) in the ITC-complex and a region that lies approximately between 236 and 255 aar of free cTnT were prone to heparin influence. CONCLUSIONS: Heparin binds to the ITC-complex via cTnT, interacting with several sites on the N-terminal and/or central parts of the cTnT molecule, which might influence the immunodetection of analytes in human blood.