Serum Troponin Research Articles

Evaluation of serum gamma-glutamyl transferase among patients with coronary artery disease in Erbil city

Background and objective: The leading cause of morbidity and mortality globally is coronary artery disease (CAD). One of the recent new parameters for evaluating CAD is Serum GGT, which has been shown to be a predictor of coronary artery status irrespective of the traditional cardiovascular risk variables. This study aimed to evaluate and assess the correlation between serum GGT and other variables among patients with CAD in comparison with healthy subjects. Methods: A case-control prospective study. Subjects were grouped into Group I (CAD patients-117 individuals) and Group II (healthy Subjects-83 individuals) based on their Coronary Angiographic profile at surgical specialty Hospital-Cardiac Center-Erbil/Iraq. Parameters of S. GGT, S. total cholesterol, S.HDL-C, S.LDL-C, S. VLDL-C, and S.TG, S. (25)OH vitamin D, serum troponin T, S.CK-MB, and CRP were assessed for both groups. Results: The study population included 58% of male and 42% of female participants, with an age range of 30-77, with a mean of 56.13± 10.5 years old. The Pearson’s correlation coefficient of serum GGT with other variables showed that the relation between serum GGT with VLDL-C, CRP, and Triglyceride among CAD patients was found to be a weakly positive correlation and statistically significant (r=0.3, P = 0.004), (r=0.2, P = 0.031), and (r=0.3, P = 0.007) respectively. Conclusion: The present study showed that S.GGT as a new potential biochemical marker for preclinical atherosclerosis, would be a useful and important marker for assessing and evaluating risk factors of coronary artery disease and to further evaluations for CAD.

Emergency Department Cardiac Risk Stratification With High-Sensitivity vs Conventional Troponin HEART Pathway

Patients presenting to the emergency department with chest pain are routinely risk stratified for major adverse cardiac events using the HEART (History, Electrocardiogram, Age, Risk factors, and Troponin) score pathway, which incorporates clinical features, risk factors, electrocardiography findings, and initial serum troponin testing. A new HEART pathway incorporating high-sensitivity troponin level may improve risk stratification among patients with possible acute myocardial infarction (AMI). To compare health outcomes and resource use among emergency department patients undergoing cardiac risk stratification with a HEART pathway using conventional vs high-sensitivity serum troponin. This multicenter pre-post cohort study was conducted between January 1 and September 6, 2021, at 16 Kaiser Permanente Southern California hospitals during uptake of a high-sensitivity serum troponin assay and included 17 384 adult patients who presented to an emergency department with chest pain and were risk stratified with a HEART pathway based on conventional troponin or high-sensitivity troponin. A HEART pathway incorporating either conventional or high-sensitivity serum troponin was used to stratify study groups for risk of major adverse cardiac events within 30 days. The primary outcome was detection of AMI in the emergency department and within 30 days. Of the 17 384 patients (median age, 58 years [IQR, 45-69 years]; 9767 women [56.2%]), 12 440 (71.6%) were risk stratified with a HEART pathway based on conventional troponin, and 4944 (28.4%) were risk stratified with a HEART pathway based on high-sensitivity troponin. Detection of AMI within 30 days was higher for the high-sensitivity troponin group than the conventional troponin group (288 [5.8%] vs 545 [4.4%]; P < .001), while the 30-day all-cause mortality rate was unchanged (16 [0.3%] vs 50 [0.4%]; P = .50). In the emergency department, 228 of 4944 patients (4.6%) in the high-sensitivity troponin group received a diagnosis of AMI compared with 251 of 12 440 patients (2.0%) in the conventional troponin group (P < .001). Among those who did not receive a diagnosis of AMI in the emergency department, an additional 60 patients (1.2%) in the high-sensitivity troponin group and 294 (2.4%) in the conventional troponin group (P < .001) received a diagnosis within 30 days. Patients in the high-sensitivity troponin group had lower rates of health care use compared with the conventional troponin group, including admission (605 [12.2%] vs 1862 [15.0%]; P < .001), stress testing within 7 days (506 [10.2%] vs 1591 [12.8%]; P < .001), and coronary revascularization within 30 days (51 [1.0%] vs 244 [2.0%]; P < .001). This multicenter pre-post cohort study suggests that a new HEART pathway incorporating high-sensitivity troponin may improve detection of AMI and decrease resource use among emergency department patients with chest pain.

Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment.

Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or MGUS." Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy. N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T(or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5-year survivals are 82%, 62%, 34%, and 20%, respectively. All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥VGPR. In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine. Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to deplete deposited fibrils are underway.

Effect of humanine on the Notch signaling pathway in myocardial infarction.

By applying humanin (HN) before myocardial infarction (MI), its protection in myocardial injury and the possible roles of its cellular mechanism in the Notch pathway were investigated. The study was carried out at Fırat University Experimental Research Center (12/24/2018-12/23/2019). Spraque-Dawley rats were divided into 10 groups: I (control) (n = 6), II (HN 6 h) (n = 6), III (HN 24 h) (n = 6), IV (HN day 7) (n = 6), V (MI 6 h) (n = 7), VI (MI 24 h) (n = 7), VII (MI day 7) (n = 7), VIII (MI+HN 6 h) (n = 7), IX (MI+HN 24 h) (n = 7), and X (MI+HN day 7) (n = 7). To create MI, 200 mg/kg of isoproterenol (ISO) was administered to the rats subcutaneously. Moreover, 252 μg/kg of HN was given intraperitoneally (ip) to the rats on its own and before MI. Molecular parameters Notch1, Notch2, Hes1, Hes2, Jagged1, Jagged2, DLL1, and DLL4 were examined using polymerase chain reaction in the heart tissue, Notch1, Hes1, and DLL4 were examined using western blot, while heart tissue was taken for histochemical examinations. The mRNA expression levels of the Notch signaling members (Notch1, Notch2, Hes1, Hes2, Jagged1, Jagged2, DLL1, and DLL4) tended to decrease after MI. The Notch signaling members increased more significantly, especially toward day 7 after HN application before MI. In the western blot anylyses, the Notch1, Hes1, and DLL4 protein levels increased significantly toward day 7 in the groups given HN before MI. Moreover, the serum AST, LDH, CK-MB, and troponin I levels tended to decrease with the application of HN before MI and there was a significant decrease in edema, hemorrhage, and mononuclear cells in the heart tissue at 24 h post-MI and fibrosis on day 7 post-MI. HN administration before MI has a cardioprotective effect on rats via the Notch signaling pathway.

COVID-19 Associated Myocarditis: A Monocentric Series of 33 Cases

Introduction: Myocarditis is defined by an inflammatory myocardial infiltrate with necrosis of non-ischemic origin in three forms: fulminant, acute and chronic. Diagnosis is guided by clinical presentation, ECG, echocardiography and biology, and confirmed by MRI and myocardial biopsy. The prognosis depends on clinical manifestations, echocardiographic features and serum troponin levels. Management is based on the treatment of heart failure (HF). For two years, the world has been experiencing a pandemic related to SARS-CoV2 that can affect the heart with ischemic or non-ischemic lesions (myocarditis, most often fulminant) whose treatment is non-specific. Trials with corticosteroids and immunosuppressant drugs have yielded discordant results.&#x0D; Objective: To describe the evolutionary modalities of COVID-19 associated myocarditis and identify factors of poor ejection fraction recovery under HF treatment.&#x0D; Method: This observational, retrospective, single-center study, in 2021, included patients with non-fulminant COVID-19 associated myocarditis suspected at echocardiography and biology and confirmed on MRI. Patients with previous HF and reduced left ventricular ejection fraction (LVEF) were excluded (n=06). Patients were divided into two groups according to LVEF three months later (LVEF&gt;50% v. LVEF&lt;50%) and compared to identify factors predicting a poor LVEF recovery.&#x0D; Results: 33 patients (19♂/14♀) aged between 30–61 years with acute non-fulminant COVID-19 associated myocarditis were included. All had ECG repolarization abnormalities. The mean LVEF at baseline was 44.3% +/- 6.3 (30–52%) with an average troponin level 480 times normal (20–2,100). Beta-blocker and RASB treatment was initiated in all patients, spironolactone (37.5 mg) in 13 patients with LVEF &lt;40% and furosemide if congestive signs (17 patients/51.5%). Clinical, electrical, biological and echocardiographic monitoring was performed at one and three months. Eight patients developed uncomplicated pericardial effusion. A significant improvement in LVEF&gt;50% was observed in 29 patients. One patient with LVEF of 38% presented with incessant ventricular tachyarrhythmia that necessitated an ICD. Three patients kept LVEF&lt;50%. Sex, congestive signs, ECG and coronary angiogram abnormalities do not seem to influence the LVEF evolution (p at 0.62, 1.00, 1.00, 0.56, 0.50, and 0.23, respectively). Age &gt;60 years, troponins &gt;1,200 times normal, pericardial effusion and a combined criterion of the three seem to be a good predictor of poor LVEF evolution (p at 0.07, 0.02, 0.035 and 0.01, respectively).&#x0D; Discussion: The absence of fulminant forms in our series explains the absence of mortality at three months (&gt;30% in the literature). Acute non-fulminant COVID-19 associated myocarditis has a good prognosis with LVEF recovery in 87.88%. The factors of poor LVEF recovery are the age &gt;60 years, troponins &gt;1,200 times normal, pericardial effusion, and the combined criterion of the three (p respectively at 0.07, 0.02, 0.035, 0.01). The routine prescription of corticosteroids in the COVID-19 protocol made it impossible to analyze its impact on COVID-19 associated myocarditis.&#x0D; Interpretation: Cardiac manifestations are not uncommon during COVID-19; they can be ischemic or non-ischemic. There is no specific therapy for non-fulminant COVID-19 associated myocarditis and the evolution seems favorable. Patients with predictive factors of poor progress should have longer follow-ups.&#x0D; Informed consent: All participants gave their informed consent to participate in this study and share the results

Association Between Stroke Severity and Serum Troponin in Acute Stroke.

Serum troponin is often elevated in patients with acute stroke and its mechanism is unknown. In a retrospective single-center cohort study, we evaluated the association between stroke severity and serum troponin in 187 patients with acute stroke using multivariable modified Poisson models. A one-point increase in the National Institutes of Health Stroke Scale (measure of stroke severity) was associated with a marginally higher serum troponin level in adjusted models (aIRR 1.03; 1.01-1.05, P = 0.001). The modest, yet potentially independent, association between stroke severity and serum troponins could suggest a neurogenic basis for a cardiac injury in patients with acute stroke.

Trajectories of postoperative serum troponin concentrations following pediatric heart transplantation

IntroductionTroponin is a readily measured serum biomarker of myocardial injury and death, but has not been well studied after pediatric heart transplants. The objective of this analysis is to describe the distribution and clinical determinants of serum troponin measured in the first week after pediatric heart transplantation. MethodsWe included all patients who underwent heart transplantation at Seattle Children’s Hospital between January 1, 2012 and December 31, 2016. During this period, serum Troponin-I (TnI) was measured daily in the first week after heart transplant. We described the distribution of serum TnT collected in this period. We examined the relationship between peak TnI with known pre- peri-operative risk factors for myocardial injury including etiology of heart failure, ischemia time, and donor to recipient characteristics. Logistic regression models were used to test the association between peak TnI with incidence of death or rejection and formation of donor specific antibodies within 1 year. Adjusted models included age, HF etiology, crossmatch status, and panel reactive antibodies. ResultsDuring the study period, 86 transplants were performed on 83 unique individuals. Serum TnI peaked at a median of 0.9 days after transplantation. In adjusted models, higher peak TnI was associated with death and/or rejection within 1-year post-transplant (Odds Ratio [95% confidence interval]: 1.10 [1.02, 1.19]). Higher peak TnI was not associated with de-novo DSA formation in adjusted models (OR [95%CI]: 1.01 [0.94, 1.09]). Post-transplant length of stay in the intensive care unit was positively correlated with peak TnI (r=0.36, p<0.001). ConclusionsThis study provides a description of serum TnI in the first week after pediatric heart transplant; a population for whom existing data is sparse. Post-transplant TnI reflects pre- and peri-operative factors such as ischemia time. This suggests TnI may have utility as a readily measurable biomarker of transplant-related myocardial injury. Our results serve as a basis to test the prognostic significance of higher post-transplant TnI in future studies.

Serial troponin-I and long-term outcomes in subjects with suspected acute coronary syndrome.

It is unclear how serial high-sensitivity troponin-I (hsTnI) concentrations affect long-term prognosis in individuals with suspected acute coronary syndrome (ACS). Subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent) separated by 1-7 h, during a first-time hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019, were identified through Danish national registries. Individuals were stratified per their hsTnI concentration pattern (normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (<20%, >20-50%, or >50% in either direction). We calculated absolute and relative mortality risks standardized to the distributions of risk factors for the entire study population. A total of 20 609 individuals were included of whom 2.3% had died at 30 days, and an additional 4.7% had died at 365 days. The standardized risk of death was highest among persons with a persistently elevated hsTnI concentration (0-30 days: 8.0%, 31-365 days: 11.1%) and lowest among those with two normal hsTnI concentrations (0-30 days: 0.5%, 31-365 days: 2.6%). In neither case did relative hsTnI concentration changes between measurements clearly affect mortality risk. Among persons with a rising hsTnI concentration pattern, 30-day mortality was higher in subjects with a >50% rise compared with those with a less pronounced rise (2.2% vs. <0.1%). Among individuals with suspected ACS, those with a persistently elevated hsTnI concentration consistently had the highest risk of death. In subjects with two normal hsTnI concentrations, mortality was very low and not affected by the magnitude of change between measurements.

Study of Correlation of Complete Blood Count indices with the serum Troponin I level, ECG, Echocardiogram and Coronary Angiography extent of Myocardial Infarction at the time of admission.

Study of Correlation of Complete Blood Count indices with the serum Troponin I level, ECG, Echocardiogram and Coronary Angiography extent of Myocardial Infarction at the time of admission.

Relation between high-sensitivity troponin I serum levels and myocardial ischemia in patients with suspected chronic coronary syndrome: The RESET-MI study

BackgroundPrevious studies showed that exercise may increase cardiac troponin serum levels; whether the occurrence of myocardial ischemia influences the changes of exercise-induced troponin raise, however, remains debatable. MethodsWe prospectively enrolled consecutive patients undergoing for the first time an elective stress myocardial perfusion scintigraphy (MPS) because of clinical suspicion of obstructive coronary artery disease (CAD). Patients were divided into 3 groups based on the evidence and degree of stress-induced myocardial ischemia at MPS: 1) group 1, no myocardial ischemia (≤4 %); 2) group 2, mild myocardial ischemia (5–10 %); 3) group 3, moderate-to-severe myocardial ischemia (≥10 %). High-sensitivity cardiac troponin I (cTnI) was measured immediately before (T0) and 1 hour (T1) and 4 h (T2) after the stress test. ResultsOne hundred-seven patients (71 males; age 65.6 ± 9.4 years) were enrolled in the study. Serum hs-cTnI concentrations (logarithmic values) significantly increased after MPS, compared to baseline, in the whole population, from 1.47±1.26 ng/L at T0, to 1.68±1.12 ng/L at T1 (p<0.001) and 2.15±1.02 ng/L at T2 (p<0.001 vs. both T0 and T1). The increase in hs-cTnI did not significantly differ between the 3 groups (p = 0.44). The heart rate achieved during the test was the strongest determinant of cTnI increase (p < 0.001) after the stress test. ConclusionsIn patients with suspected CAD, stress MPS induces an increase of cTnI that is independent of the induction and extension/severity of myocardial ischemia and is mainly related to myocardial work, as indicated by the heart rate achieved during the test.

Serum asprosin levels are increased in patients with periodontitis and ST-segment elevation myocardial infarction and correlated with periodontal parameters: A case-control study.

The study aims to investigate whether patients with ST-elevation myocardial infarction (STEMI)-related periodontitis will experience any changes in asprosin levels. Periodontitis is a common, chronic infection of the periodontium that is epidemiologically associated with cardiovascular disease. Although asprosin, a hormone released from adipose tissue, is a protective role in cardiovascular diseases, its effectiveness in periodontitis is unknown. The study was conducted on a total of 120 patients, divided into four groups; the group of healthy control (n = 35), the group of periodontitis (n = 35), the group of periodontitis+STEMI (n = 25), and the group of STEMI (n = 25). In each patient, age, serum asprosin, CRP, troponin-I, and clinical periodontal parameters [plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL)] were evaluated. The results were analyzed statistically. Serum asprosin, CRP, and troponin-I levels were statistically higher in the STEMI+periodontitis group compared to the other groups. In addition, as a result of the study, it was observed that there was a correlation between serum asprosin levels, clinical periodontal parameters, and CRP levels. The results of this study show that STEMI and periodontitis are associated with high asprosin levels. Since the risk of periodontitis is high in STEMI patients, periodontitis should also be considered when evaluating asprosin levels in STEMI patients.

Evaluation of some heart enzymes and Iron levels in β-thalassemia patients in Thi-Qar City, Iraq

Beta thalassemia is one of the most common hereditary diseases in the world caused by a deficiency of globin chains. Heart disease is one of the main complications of this disease as a result of excess iron deposition in the cardiac tissues. Total of 100 patients of 2-18 years diagnosed with ß-TM were employed in the current study and admitted to Thi-Qar Center of Hereditary Blood Diseases in Thi-Qar city, Iraq, and 80 healthy participants, matched by age, and geographical area were adopted as control group. The current study included evaluating of serum Troponin I (c.TnI), Creatine kinase-MB isoenzyme (CK-MB), Apelin, aspartate aminotransferase (AST), and Lactate Dehydrogenase enzyme (LDH) of studied groups. The finding revealed a significant increase (p&lt;0.01) of c.TnI, CK-MB, AST, and LDH levels as well as a significant decrease (p&lt;0.01) in apelin level in all patients with ß-TM compared to the control group. Pearson's correlation coefficient (r) was also found between the biochemical parameters studied for ß-TM patients with ferritin level, were found a significant correlation (p&lt;0.01) between ferritin level with CK-MB, LDH, and AST levels while there was no significant correlation (P&gt;0.01) through apelin and c.TnI levels. The finding showed a clinical predictor to damage cardiac tissues in the near term, which portends the use of more efficient treatment protocols to remove excess iron from ß-TM patients.

Utility of preoperative troponin I to predict mortality in adult liver transplant recipients: Revisiting pretransplant cardiac risk in the current MELD-allocation era.

Preoperative risk assessment in liver transplant (LT) candidates, particularly related to cardiac risk, is an area of intense interest for transplant clinicians. Various cardiac testing methods are employed by transplant centers to characterize cardiac risk. Serum troponin is an established method for the detection of myocardial injury in a wide variety of clinical settings. Preoperative troponin screening has been reported to predict postoperative cardiac events and mortality in various surgical patient populations, however, the utility of preoperative troponin to predict posttransplant outcomes in current LT candidate populations requires further investigation. We performed a prospective blinded study in a cohort of 275 consecutive LT recipients at a single transplant center to determine if preoperative serum troponin I (TnI) was predictive for postoperative 1-year mortality. Abnormal preoperative TnI levels (>.1ng/mL) were found in 38 patients (14%). One-year mortality occurred in 19 patients (7%). There was no significant difference in mortality between patients with normal and abnormal troponin levels. Additionally, we found that there was no significant difference in early postoperative major adverse cardiac events between patient groups. Contrary to previous reports, elevated preoperative TnI was not significantly predictive of posttransplant mortality in LT recipients at our institution.

Cardiovascular Follow-up of Patients Treated for MIS-C.

To assess the prevalence of residual cardiovascular pathology by cardiac MRI (CMR), ambulatory rhythm monitoring, and cardiopulmonary exercise testing (CPET) in patients ∼6 months after multisystem inflammatory disease in children (MIS-C). Patients seen for MIS-C follow-up were referred for CMR, ambulatory rhythm monitoring, and CPET ∼6 months after illness. Patients were included if they had ≥1 follow-up study performed by the time of data collection. MIS-C was diagnosed on the basis of the Centers for Disease Control and Prevention criteria. Myocardial injury during acute illness was defined as serum Troponin-I level >0.05 ng/mL or diminished left ventricular systolic function on echocardiogram. Sixty-nine of 153 patients seen for MIS-C follow-up had ≥1 follow-up cardiac study between October 2020-June 2022. Thirty-seven (54%) had evidence of myocardial injury during acute illness. Of these, 12 of 26 (46%) had ≥1 abnormality on CMR, 4 of 33 (12%) had abnormal ambulatory rhythm monitor results, and 18 of 22 (82%) had reduced functional capacity on CPET. Of the 37 patients without apparent myocardial injury, 11 of 21 (52%) had ≥1 abnormality on CMR, 1 of 24 (4%) had an abnormal ambulatory rhythm monitor result, and 11 of 15 (73%) had reduced functional capacity on CPET. The prevalence of abnormal findings was not statistically significantly different between groups. The high prevalence of abnormal findings on follow-up cardiac studies and lack of significant difference between patients with and without apparent myocardial injury during hospitalization suggests that all patients treated for MIS-C warrant cardiology follow-up.

EFFECT OF TAXIFOLIN ON DOXORUBICIN-INDUCED OXIDATIVE CARDIAC DAMAGE IN RATS: A BIOCHEMICAL AND HISTOPATHOLOGICAL EVALUATION

Doxorubicin is a widely used anthracycline-derived broad-spectrum antitumoral antibiotic drug. However, cardiotoxicity due to doxorubicin treatment has warranted dose reduction or complete discontinuation in certain cases. The role of oxidative stress in the pathogenesis of doxorubicin-induced cardiotoxicity has been previously demonstrated. Against this background, this study aimed to investigate the protective effect of the potent antioxidant flavone taxifolin against possible oxidative heart damage biochemically and histopathologically induced by doxorubicin. Albino Wistar male rats were divided into three groups: healthy controls (HG), a group given doxorubicin alone (DG), and a group given taxifolin + doxorubicin (TDG). Taxifolin was administered orally at a dose of 50 mg/kg via gavage. Doxorubicin was injected intraperitoneally at a dose of 5 mg/kg. This procedure was repeated for 7 days. The results of the biochemical experiment showed that taxifolin significantly inhibited doxorubicin-induced malondialdehyde increases and glutathione decreases in heart tissues. In addition, taxifolin significantly suppressed the increases in cardiac damage markers, such as serum troponin I, creatine kinase, and creatine kinase-MB, induced by doxorubicin. Taxifolin treatment has also been histopathologically shown to alleviate doxorubicin-induced heart tissue damage. Accordingly, the results of the present study suggest that taxifolin may be useful in the treatment of doxorubicin-induced oxidative heart damage. Keywords: Antioxidant, cardiotoxicity, doxorubicin, flavonoid, taxifolin.

Mitochondrial function and oxidative stress in isolated peripheral blood mononuclear cells and trastuzumab-induced cardiotoxicity: a prospective longitudinal study

Abstract Introduction Trastuzumab, a monoclonal antibody against human epidermal growth factor receptor 2 (HER2), is believed to cause cardiotoxicity through mitochondrial dysfunction and oxidative stress. Although peripheral blood mononuclear cells (PBMCs) could represent systemic oxidative stress, they are also involved in trastuzumab-mediated antibody-dependent cell-mediated cytotoxicity. The usefulness of isolated PBMCs in the assessment of trastuzumab-induced cardiotoxicity remains uncertain. Purpose We aimed to determine the temporal changes of mitochondrial function and oxidative stress in isolated PBMCs, and cardiac function in breast cancer patients receiving sequential doxorubin and trastuzumab treatment. Methods Fourteen HER-2 positive breast cancer patients with apparently normal cardiac function at baseline were recruited from September 1, 2020 to August 31, 2022. After breast surgery, all patients received doxorubicin (60 mg/m²) and cyclophosphamide (600 mg/m²) every 3 weeks for 4 cycles, followed by trastuzumab (8 mg/kg loading then 6 mg/kg) every 3 weeks for 18 cycles. Adjuvant paclitaxel (175 mg/m²) every 3 weeks for 4 cycles was an additional treatment in patients with positive lymph node(s). Echocardiography and blood samples were collected at baseline, cycle 4 of doxorubicin chemotherapy, every 3 months during trastuzumab treatment and &amp;gt;1 month after treatment. Seahorse extracellular flux analyzer was used to determine mitochondrial oxygen consumption, and MitoSox/MitoTracker staining to determine oxidative stress in isolated PBMCs. Results Of 14 patients (mean age of 50.4 ±8.8 years), 2 had hypertension and 4 had hyperlipidemia. The serum troponin I levels were significantly increased during doxorubicin treatment, then gradually decreased afterward, while the serum NT-proBNP levels remained statistically unchanged (Figure 1A and B). The numerical reduction of ejection fraction was remarked during the treatment, however there was no clinical cardiac dysfunction (Figure 1C). Subclinical cardiac dysfunction, defined as a &amp;gt;15% relative reduction in global longitudinal strain (GLS), was observed in 9 of 14 patients during trastuzumab treatment (Figure 1D). Mitochondrial oxidative stress in isolated PBMCs, although unchanged during doxorubicin treatment, was gradually increased during trastuzumab treatment (Figure 2A and B). Mitochondrial proton leak was also increased, while oxygen consumption and ATP production remained unchanged (Figure 2C and D). After treatment completion, cardiac function, as well as mitochondrial oxidative stress, tended to improve. Interestingly, there was a strong positive correlation between mitochondrial oxidative stress at baseline and maximum GLS reduction during treatment (r=0.811, p=0.001). Conclusions Mitochondrial oxidative stress in isolated PBMCs could be a potential marker for the evaluation and prediction of trastuzumab-induced cardiotoxicity. Further studies are warranted.Figure 1Figure 2

Baseline predictors of final infarct size in patients with ST elevation myocardial infarction undergoing primary PCI

Abstract Background In patients with coronary artery disease, the presence and extent of myocardial scar determined from cardiac magnetic resonance (CMR) imaging have recognized associations with major adverse cardiac events. Therefore, in patients presenting with ST elevation myocardial infarction (STEMI), early prediction of final infarct size (IS) has important prognostic and therapeutic implications. Purpose We sought to determine the predictors of final IS from baseline clinical, laboratory, and CMR imaging variables in patients presenting with STEMI and undergoing successful primary PCI (pPCI). Methods After successful pPCI, 76 STEMI patients underwent baseline (within 48-hours) and 3-months follow-up CMR imaging. The baseline CMR study was used to measure left ventricular (LV) volumes, ejection fraction (EF), and global longitudinal strain (GLS), the latter calculated using feature tracking from cine images. Final IS was measured in the 3-months follow up study using signal intensity quantification by the full width at half maximum method from late gadolinium enhancement images and expressed as a percentage of the total LV mass. Serum ST2 was drawn within 48 hours of STEMI presentation. Maximum values of ECG ST elevation prior to pPCI and serum Troponin I during index hospitalization were measured. Non-collinear baseline variables deemed significantly associated with the final IS on univariable linear regression and captured in all patients were entered into a multivariable model, adjusting for age and sex. Results Mean age was 54.1±10.9 years, 64 patients (78%) being males. Mean LV EF was 43.5±9.8%. Univariable predictors of final IS included hypertension, baseline maximum troponin, ST2, maximum ST elevation, LV volumes and EF, GLS, total angiographic procedure time, the presence of multi-vessel CAD, use of thrombectomy, TIMI flow and myocardial blush grades at baseline and after wiring, and prescription of loop diuretics and potassium-sparing diuretics on discharge (Table 1). A final multivariable linear model was constructed including age, sex, maximum troponin, maximum ST elevation, ST2, LV EF and GLS. In this model, baseline LV EF, maximum troponin, and maximum ST elevation remained independently associated with the final IS. Respective beta coefficients [95% CI] were -0.63 [-1- (-0.26)], 0.22 [0.11-0.33], and 0.90 [0.22-1.58]; p=0.001, &amp;lt;0.001, and 0.01) (Table 2; adjusted R2=0.6, p&amp;lt;0.001). ST2 and GLS were no longer associated with the IS. Conclusion After successful pPCI, baseline LV EF, maximum troponin I, and maximum ST elevation were independent predictors of final IS. These simple markers can identify patients at high risk of final IS who might benefit from advanced therapeutics. Future studies are warranted to confirm the prognostic value of risk scores incorporating these markers. Advanced laboratory (ST2) and imaging (strain) markers were not independently associated with IS.

Sex differences in cardiac troponin trajectories over the life course

Abstract Background Cardiac troponin is a promising biomarker that may improve cardiovascular risk prediction. Previously, important differences have been demonstrated between cardiac troponin concentration in women and men. At this point, it is unknown whether changes in cardiac troponin concentration over the life course differ in women and men and whether this impacts cardiovascular risk prediction. Purpose Insights into sex-specific cardiac troponin trajectories and how these are influenced by risk factors are necessary to ensure approaches to the prevention of cardiovascular disease in women and men are equitable. Therefore, we examined whether age- and risk factor-related changes in cardiac troponin over the life course differ by sex and if the trajectory of cardiac troponin was informative in respect of cardiovascular outcomes in women and men in the general population. Methods In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Using linear mixed-effects models, the sex-specific trajectories of cardiac troponin were evaluated, and the relationship with conventional cardiovascular risk factors determined. Using multistate joint models, the association between sex-specific trajectories of cardiac troponin and a composite outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death was evaluated. Results In 2,142 women and 5,151 men (mean 58±7 and 57±7 years, respectively) there were 177 (8.3%) and 520 (10.1%) outcome events, respectively, during a median follow-up of 20.9 [25th to 75th percentile, 15.8 to 21.3] years. Cardiac troponin concentrations were persistently lower in women than in men (median baseline concentration: 2.4 [25th to 75th percentile, 1.7 to 3.6] ng/L versus 3.7 [25th to 75th percentile, 2.6 to 5.8] ng/L, respectively, P&amp;lt;0.001, Figure 1A), with women exhibiting a relatively larger increase with advancing age as compared with men (Pinteraction&amp;lt;0.001, Figure 1B). Apart from age, a significant and divergent interaction with sex was found for the association between cardiac troponin and body mass index (Pinteraction=0.008) and diabetes (Pinteraction=0.003). During follow-up, cardiac troponin concentrations were associated to the outcome in both women and men (adjusted HR per two-fold difference [95% CI], 1.34 [1.17-1.52] and 1.30 [1.21-1.40], respectively, Pinteraction=0.752). The slope of cardiac troponin was significantly associated with the outcome in women, but not in men (adjusted HR [95% CI], 2.70 [1.01-7.33] and 1.31 [0.62-2.75], respectively, Pinteraction=0.250). Conclusion Trajectories of cardiac troponin differ between women and men in the general population, with differing associations to conventional risk factors and cardiovascular outcomes. Our findings highlight the importance of a sex-specific approach when serial cardiac troponin testing is applied for cardiovascular risk prediction.

Upregulation of mitochondrial fusion as potential cardioprotective strategies against trastuzumab-induced cardiotoxicity in rats

Abstract Background Trastuzumab (TRZ) is a commonly used chemotherapeutic drug for treating advanced malignancies that express human epidermal growth factor receptor type 2. However, TRZ has been linked with cardiotoxicity, which is an unfavourable clinical side effect of cancer treatment. Alterations in mitochondrial dynamic mechanisms, particularly reduced fusion, have been shown to be a key mechanistic insight into the progression of chemotherapy-induced cardiotoxicity. Despite the cardioprotective benefits of a mitochondrial fusion promoter (M1) that have been established in various cardiovascular settings, its ability to counteract the cardiotoxicity caused by TRZ remains unknown. Purpose To examine the effect of M1 treatment on mitochondrial fusion, myocardial oxidative stress, apoptosis, and cardiac injury biomarker in TRZ-induced cardiotoxicity rats. Methods Male Wistar rats (n=18) were divided into the TRZ group (4 mg/kg/day for 7 days, I.P., n=12) and the control group (CON, n=6). In the TRZ group, at the time of first TRZ injection all rats also received the intervention with either the vehicle injection (VEH, n=6) or M1 (M1, 2 mg/kg/day, n=6) via I.P. injection for 7 days. The left ventricular ejection fraction (LVEF) was measured using echocardiography, and troponin-I levels were determined using blood serum. Then, the cardiac tissue was processed to assess the levels of malondialdehyde (MDA) for oxidative stress, mitochondrial fusion, and apoptotic proteins. Results TRZ induced cardiotoxicity via downregulation of mitochondrial fusion along with upregulation of myocardial oxidative stress and apoptosis, as indicated by decreasing Mfn1 protein expression and increasing the levels of MDA and Bax to Bcl-2 ratio, respectively (Fig. 1A, B, C, and E). TRZ also showed markedly higher levels of serum Troponin-I (Fig. 1D) and impaired LV function (77% LVEF for TRZ vs. 89% LVEF for CON). M1 co-treatment promoted Mfn1-mediated mitochondrial fusion, resulting in a reduction in MDA-associated oxidative stress, apoptosis, Troponin-I, and cardiac dysfunction (16% improvement over the TRZ group) (Fig. 1A-E). Conclusion M1 effectively protected the heart against TRZ-induced cardiotoxicity by promoting mitochondrial fusion and preventing oxidative stress and apoptosis-mediated myocardial injury. These findings suggest that the pharmacological promotion of mitochondrial fusion could be a novel anti-cardiotoxicity strategy in TRZ-induced cardiotoxicity.

The diagnosis of acute myocarditis in emergency (DAME) score: improving diagnostics within the emergency department

Abstract Purpose The final diagnosis of myocarditis is challenging. The aim of our study was to provide the D.A.M.E. (Diagnosis of Acute Myocarditis in Emergency) Score for the fast identification of patients suffering from myocarditis at Emergency Department (ED). Methods This was a multicenter, retrospective study involving three centers. All medical records from January 2010 to December 2014 reporting a final discharge diagnosis of myocarditis were considered. One hundred-four patients (mean age: 40.2±16.5 years) were enrolled. Clinical, biochemical and instrumental data were gathered. Data were analysed by means of logistic regression model and factorial analysis. A validation cohort from a fourth center was enrolled. Results The final determinants of the DAME score were six: fever, chest pain, erythrocyte sedimentation rate (ESR) &amp;gt; 20 mm/h, C-reactive protein (hs-CRP) &amp;gt;3 mg/L, troponin serum levels &amp;gt;3 ng/L, and left ventricle ejection fraction &amp;lt; 50%. All of them received a specified score ranging from 0 to 4. A score &amp;gt; 4 was related to 75% probability of myocarditis; a final score ranging between 1 and 4 was related to 57% probability of myocarditis. ROC curve on the validation cohort (289 patients, 27 with myocarditis) demonstrated the best cut-off to be 7: AUC 0.958 (p&amp;lt; 0.001), sensibility: 100%, specificity: 85.11%, PPV: 40.9%, NPV: 100% (LR+: 6.72; LR-: 0.00). Logistic regression analysis revealed Odds Ratio equal to 2.83 (95% CI 1.90 - 4.20, p &amp;lt; 0.0001). Conclusions DAME score can offer a reliable tool in ED setting for the evaluation of patients suffering from suspected myocarditis.