Increase In Cardiac Troponin Research Articles

High-sensitivity cardiac troponin I and risk of dementia: 25-year longitudinal study in the Whitehall II cohort.

We hypothesise that subclinical myocardial injury during midlife, indexed by increases in cardiac troponin I, is associated with accelerated cognitive decline, smaller structural brain volume, and higher risk of dementia. Longitudinal cohort study. Civil service departments in London (Whitehall II study). 5985 participants aged 45-69 had cardiac troponin I measured by high-sensitivity assay at baseline (1997-99) for prospective cohort analyses. A nested case-control sample of 3475 participants (695 dementia cases and 2780 matched controls) was used for backward cardiac troponin I trajectory analysis. 641 participants provided magnetic resonance imaging (MRI) scans for brain volume analysis. Incident dementia cases were ascertained from national hospital episode statistics, mental health and mortality registers until 2023. Cognitive testing was performed at six waves over 25 years (1997-99, 2002-04, 2007-09, 2012-13, 2015-16, 2019-22). Brain volume metrics were derived from structural MRI scans (2012-16). For prospective cohort analyses, 606 (10.1%) incident cases of dementia were recorded over a median follow-up of 24.8 years. Doubling of cardiac troponin was associated with 11% higher risk of dementia (HR=1.11, 95% CI: 1.04 to 1.19). Participants with increased cardiac troponin at baseline had a faster decline of cognitive function with age. Compared to participants with concentrations below the limit of quantitation (<2.5 ng/L), those in the upper third (>5.2 ng/L) had similar global cognitive z score at age 60, but had 0.10 (95% CI: 0.02 to 0.18) standard deviations lower score at age 80, and 0.19 (0.03 to 0.35) standard deviations lower score at age 90. Participants with dementia had increased cardiac troponin concentrations compared with those without dementia between 7 and 25 years before diagnosis. Compared to those with low cardiac troponin level (<2.5 ng/L at baseline) those with concentrations >5.2 ng/L had lower grey matter volume and higher hippocampal atrophy 15 years later, equivalent to ageing effects of 2.7 and 3 years, respectively. Subclinical myocardial injury at midlife was associated with higher dementia risk in later life. A systematic review of observational studies suggests higher cardiac troponin concentrations are associated with poorer cognitive function and increased dementia risk. Formal meta-analysis was not performed due to the small number of available studies.Existing studies assessed cardiac troponin once and had relatively short follow-up time. Evidence is lacking on the time course of cardiac troponin level before diagnosis in dementia cases compared with controls. People with increased cardiac troponin I concentrations in mid-life had faster cognitive decline and were more likely to develop dementia over 25 years of follow-up. Backward trajectory analysis using three measurements using a high-sensitivity assay showed that people with dementia had higher cardiac troponin levels as early as 25 years before dementia diagnosis compared with those without dementia. People in the magnetic resonance imaging subcohort with higher cardiac troponin I concentrations at baseline had lower grey matter volume and hippocampal atrophy 15 years later.Subclinical myocardial injury in midlife, by indicating long-term risk of dementia, is unlikely to be due to preclinical changes before dementia onset and may lie on the causal pathway to dementia.

Quercetin and its potential therapeutic effects on aluminum phosphide-induced cardiotoxicity in rats: Role of NOX4, FOXO1, ERK1/2, and NF-κB

Acute Aluminum phosphide (AlP) poisoning poses a serious global issue, yet the exact mechanisms behind AlP-induced cardiotoxicity are still not well understood. Moreover, there is no specific antidote available for AlP toxicity. Nevertheless, Quercetin (QE) has emerged as a promising therapeutic candidate in various contexts. Accordingly, our study aimed to evaluate the QE potential therapeutic effects against AlP-induced cardiotoxicity and the mechanisms underlying such effects. Rats were assigned into four groups: Group I (control group), Group II (vehicle (corn oil) group), Group III (AlP group) received a single dose of AlP (10 mg/kg body weight) dissolved in corn oil by oral gavage, and Group IV (AlP + QE group) received a single dose of QE (400 mg/kg body weight) dissolved in saline, one hour after AlP administration. AlP-induced cardiotoxicity was evidenced by the increase in cardiac troponin I (cTnI) as well as the hemodynamic, ECG, and histopathological abnormalities. The AlP group denoted a decrease of the antioxidant enzymes; catalase and SOD and an increase of the lipid peroxidation marker; MDA. This was associated with a notable increase in inflammatory cytokines (TNFα, IL-6, and IL1β), in addition to a significant upregulation of the expression of NOX4, FOXO1, ERK1/2, and NF-κB. Moreover, Caspase3, and BAX showed strong immunopositive expression, while Bcl-2 showed mild immunoexpression. On the other hand, treatment with QE showed an improvement in the cardiotoxic effects of AlP, as indicated by significant enhancements in biomarkers, functional assessments, and histopathological findings. These results suggest that QE may be a promising candidate for treating AlP-induced cardiotoxicity, attributed to its antioxidant, anti-inflammatory, and anti-apoptotic properties, particularly emphasizing the roles of NOX4, FOXO1, ERK1/2, and NF-κB.

Abstract 4137609: Lentiviral shRNA Library Screen Using Human Pluripotent Stem Cell-derived Cardiomyocytes Identified Mediators of Protection via MAP4K4 Inhibition against Doxorubicin-induced Cardiotoxicity

Background: Doxorubicin (Dox) is a common component in chemotherapy for a wide range of tumors, but the cardiotoxicity has restricted its use. There is an unmet need for novel therapeutics of Dox-induced cardiotoxicity (DIC). We previously identified the protein kinase MAP4K4 as a mediator of DIC. Notably, we showed that blocking MAP4K4 activity via DMX-5804 protected against Dox-induced cell death and dysfunction in human iPSCs derived cardiomyocytes (hiPSC-CMs). As a powerful tool to study the protective mechanism, pooled library screen performs high-throughput phenotypic examination, but its potential on hiPSC-CMs is poorly explored. Hypothesis: A pooled lentiviral shRNA library screen in hiPSC-CMs treated with Dox ± DMX-5804 could identify mediators of protection against DIC. Methods: To maximize the chances to uncover key factors mediating DMX-5804 protection, we performed a high-throughput loss-of-function screen. A pooled library of 1731 lentiviral shRNAs was generated. hiPSC-CMs were transduced, then treated with Dox ± DMX-5804. Cardiac troponin I ELISA was used to examine myocyte injury. Genomic DNA was isolated, followed by amplification and sequencing of the integrated shRNAs. Log2 fold change was calculated and transformed into Z score to identify significantly shifted shRNAs. Results: To build the shRNA library we included 1) genes identified via transcriptomic analysis of hiPSC-CMs treated with Dox ± DMX-5804; 2) genes in the MAP4K4 signaling cascade; 3) previously defined pro-death or pro-survival genes in DIC. To ensure single gene silenced per cell, we used a low MOI of 0.5. After transduction, cells were treated with Dox ± DMX-5804. Confirming the cardiotoxicity and protection, Dox induced a 2-fold increase of cardiac troponin I release and DMX-5804 significantly reversed it. Next, we recovered and sequenced the integrated shRNAs, and quantified the frequency of each. We identified 146 significantly enriched or depleted shRNAs (|Z score| &gt; 2). When comparing Dox treated group to vehicle or DMX-5804 protected group, shRNA enrichment indicates pro-death function of the targeted gene. Conversely, pro-survival genes can be inferred from shRNA depletion. Amongst the 5 most consistently targeted genes, we identified SIRT6 and GATA4 which are known pro-survival in DIC, suggesting the screen is potent to define key genes. Conclusion: We performed a proof-of-concept pooled library screen in human cardiomyocytes and identified mediators of protection against DIC.

Interprétation d’une valeur élevée de troponine en dehors des syndromes coronariens aigus

AbstractApart from acute coronary syndrome, increased troponin represents 40 % of requests. In acute myocardial infarction (AMI), the increase in cardiac troponin is linked to cardiomyocyte necrosis. But any reversible or irreversible cardiomyocyte injury can be accompanied with an increase in cardiac troponin. It is important to know how to distinguish causes without any real deleterious ­impact, such as intense physical exercise, from the numerous pathological causes where the high value of cardiac troponin constitutes a prognostic factor : renal failure, pulmonary embolism, sepsis, non-cardiac surgery. The increase in cardiac troponin T alone in various muscular disorders seems more and more frequent and leads us to question the necessity of having the dosage of both cardiac troponin T and cardiac troponin l.

Myocardite aiguë secondaire à une maladie de Basedow : à propos d'un cas

The relationships between the thyroid and the heart are close and complex. In rare cases, hyperthyroidism induced by Graves' disease can be complicated by an acute myocarditis, which may be life-threatening. We report the case of a 41-year-old woman with Graves' disease not controlled by antithyroid drugs, hospitalized for odynophagia, palpitations due to atrial fibrillation, diffuse ST elevation on ECG and an increase in cardiac troponin. Coronary angiography was normal, cardiac MRI confirmed acute myocarditis. The evolution was favorable after a phase marked by supraventricular and ventricular rhythm disorders. The diagnostic and therapeutic challenge of this association are discussed, with a review of the literature.

Physical Exercise Increases Cardiac Troponin (cTn) Levels as a Marker of Myocardial Infarction: A Systematic Review

Objectives. This study aimed to analyze an indication of physical exercise on the increase of cardiac troponin (cTn) levels as a marker of myocardial infarction from the physiological perspective. Materials and methods. A search of journal databases including MEDLINE-Pubmed, Web of Science, Scopus, and Science Direct was used in this systematic review study. The inclusion criteria were papers that addressed cardiac troponin (cTn), physical activity, and myocardial infarction, and were published within the last five years. Using the databases Science Direct, Pubmed, and Web of Science, 83 recognized publications were found. For this systematic review, finally ten publications that fulfilled the requirements for inclusion were chosen and examined. This study evaluated standard operating procedures using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Results. This systematic review reports that physical exercise has been found to increase cardiac troponin (cTn) levels as a marker of myocardial infarction, but this increase is triggered by the body’s physiological response during exercise and is not considered as a pathological response. Conclusions. According to the findings of the study, physical exercise has been proven to elevate the risk of heart muscle damage by triggering an increase in cardiac troponin (cTn). However, this feature occurs in a physiological state and represents an exercise adaptation process. An analysis of the relevant articles reveals that this increase in cardiac troponin (cTn) has not been shown to have a negative influence on developing cardiovascular disease.

Evaluating the Rates of Mortality and Cardiac Catheterization Using High-Sensitivity Troponin and Conventional Troponin Assays.

Non-ST segment elevation myocardial infarction (NSTEMI) is an acute coronary syndrome event where myocardial ischemia is present, with an increase of cardiac troponins without an elevation of the ST segment.One of the fundamental measures used to diagnose or rule out acute coronary syndrome (ACS) is troponin levels in the blood.Troponin is a broad term used for the category of muscle contraction regulatory proteins and is commonly measured during ACS evaluation. Troponin I is only released by cardiac tissue, while some assay measurements will also pick up troponin released by skeletal muscle injury. This retrospective observational study was performed investigating troponin assays and how they relate to patient's outcomes. The troponin assays used in this Miami hospital where the database of patients was collected between 2018 and 2023 were troponin I (cTnI), the conventional troponin assay, and the newer high-sensitivity troponin I assay (hs-cTn). In this observational study patients who received an admitting diagnosis of NSTEMI corroborated by an independent cardiologist had their respective troponin assay levels included. Patients found to have ECG changes significant for non-ischemic pathologies, or echocardiogram findings suggestive of myocardial dysfunction not clinically correlated to an ACS were excluded from the study. A total of 75 patients were included in this study and the mean age was 75.97 ±14.72 years, with a presentation of chest pain, dyspnea and general weakness recorded in 59% (n = 45) of patients. The median time between troponin samples was 6.63 hours across both assays and hs-cTn showed a 4.99% increase in variation between samples while cTnI had a decrease of 2.53%. The study objective is to support whether there is a difference in rates of cardiac catheterization or mortality based on the type of troponin testing. There was no significant association found between, the type of troponin assay used during hospital admission, and the outcomes of catheterization and death (p > 0.009).

The current paradigm of cardiac troponin increase among athletes.

Although it is known that exercise improves cardiovascular health and extends life expectancy, a significant number of people may also experience an elevation in cardiac troponin levels as a result of exercise. For many years, researchers have argued whether exercise-induced cardiac troponin rises are a consequence of a physiological or pathological reaction and whether they are clinically significant. Differences in cardiac troponin elevation and cardiac remodeling can be seen between athletes participating in different types of sports. When forecasting the exercise-induced cardiac troponin rise, there are many additional parameters to consider, as there is a large amount of interindividual heterogeneity in the degree of cardiac troponin elevation. Although it was previously believed that cardiac troponin increases in athletes represented a benign phenomenon, numerous recent studies disproved this notion by demonstrating that, in specific individuals, cardiac troponin increases may have clinical and prognostic repercussions. This review aims to examine the role of cardiac troponin in athletes and its role in various sporting contexts. This review also discusses potential prognostic and clinical implications, as well as future research methods, and provides a straightforward step-by-step algorithm to help clinicians interpret cardiac troponin rise in athletes in both ischemic and non-ischemic circumstances.

Early Detection and Prediction of Anthracycline-Induced Cardiotoxicity - A Prospective Cohort Study.

In the present study, we aimed to investigate whether early cardiac biomarker alterations and echocardiographic parameters, including left atrial (LA) strain, can predict anthracycline-induced cardiotoxicity (AIC) and thus develop a predictive risk score. The AIC registry is a prospective, observational cohort study designed to gather serial echocardiographic and biomarker data before and after anthracycline chemotherapy. Cardiotoxicity was defined as a reduction in left ventricular ejection fraction (LVEF) ≥10 percentage points from baseline and <55%. In total, 383 patients (93% women; median age, 57 [46-66] years) completed the 2-year follow-up; 42 (11.0%) patients developed cardiotoxicity (median time to onset, 292 [175-440] days). Increases in cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) and relative reductions in the left ventricular global longitudinal strain (LV GLS) and LA reservoir strain [LASr] at 3 months after anthracycline administration were independently associated with subsequent cardiotoxicity. A risk score containing 2 clinical variables (smoking and prior cardiovascular disease), 2 cardiac biomarkers at 3 months (TnT ≥0.019 ng/mL and BNP ≥31.1 pg/mL), 2 echocardiographic variables at 3 months (relative declines in LV GLS [≥6.5%], and LASr [≥7.5%]) was generated. Early decline in LASr was independently associated with subsequent cardiotoxicity. The AIC risk score may provide useful prognostication in patients receiving anthracyclines.

Effects of Energy Drinks and Flunitrazepam on Some Cardiac Biomarkers, and Oxidative Stress in Wistar Rats.

This study was conducted to investigate the effects of some energy drinks on cardiac biomarkers (tropin and creatinine phosphokinase) and oxidative stress in male Wistar rats. 45 Wistar rats were divided into 8 groups. Group 1 received distilled water; Group 2 received an energy drink (A) (3.75 mg/kg). Group 3 energy drink (A) (7.5 mg/kg) Group 4 received energy drink (B) (3.75 mg/kg). Group 5 energy drink (B) (7.5 mg/kg) Group 6 received flunitrazepam (0.03 ml/kg), Group 7 received 3.75 ml/kg of energy drink (A) and 0.03 ml/kg of flunitrazepam, and Group 8 received 3.75 ml/kg of energy drink (B) and 0.03 ml/kg of flunitrazepam. The result showed that in Group 2, there was a significant increase (p&lt;0.05) in cardiac troponin kinase and no significant change in bicarbonate. Group 3 showed a significant increase (p&lt;0.05) in the level of cardiac troponin, a significant increase (p&lt;0.05) in creatine kinase, and no significant change in bicarbonate. Group 4 showed a significant (p &gt; 0.05) decrease in cardiac troponin and creatine kinase and no significant change in bicarbonate. Group 5 showed a significant (p &gt; 0.05) decrease in cardiac troponin and creatine kinase and no significant change in bicarbonate when compared to the control group. Group 6 showed a significant (p&lt;0.05) increase in cardiac troponin and a decrease (p&gt;0.05) in creatine kinase, but no significant change in bicarbonate. Group 7 showed a significant decrease in cardiac troponin and creatine kinase and no significant change in bicarbonate level when compared to the control group. Group 8 showed a decrease in cardiac troponin and creatine kinase. It was concluded therefore that the consumption of energy drinks and Flunitrazepam led to an increase in oxidative stress and cellular damage.

Cardiac Troponin I and Electrocardiographic Evaluation in Hospitalized Cats with Systemic Inflammatory Response Syndrome.

Several studies conducted on humans demonstrate the increase in cardiac troponins and the onset of arrhythmias in the course of systemic inflammatory response syndrome (SIRS). The aim of the current study was to assess the blood concentration of cardiac troponin I (cTnI) and electrocardiographic findings in SIRS-affected cats. Seventeen shorthair cats hospitalized with SIRS were enrolled (Group 1). SIRS diagnosis was performed based on the detection of at least two of the four criteria such as abnormal body temperature, abnormal heart rate (i.e., tachycardia or bradycardia), abnormal respiratory rate (i.e., tachypnea or bradypnea), and alterations of white blood cell number (i.e., leukocytes or band neutrophils). Ten cats screened for elective surgery such as neutering or dental procedures were evaluated as a control population (Group 2). They were considered healthy based on history, physical examination, hematological and biochemical profile, urinalysis, coprological exam, thyroxine assay, blood pressure measurement, and echocardiography. A physical examination, complete blood cell count, biochemistry test (including an electrolyte panel), electrocardiographic examination, and cTnI assay were carried out in each cat enrolled. Traumatic events, gastrointestinal, neoplastic, respiratory, and neurological disorders were identified as causes of SIRS in Group 1. In Group 1, a significantly higher concentration of cTnI than that in Group 2 was recorded (p = 0.004). In 37.5% of cats with SIRS, ventricular premature complexes occurring in couplets with multiform configuration were detected. Similarly, to humans, data herein reported would indicate possible cardiac damage present in cats with SIRS diagnosis.

Ruxolitinib ameliorated coxsackievirus B3-induced acute viral myocarditis by suppressing the JAK-STAT pathway

BackgroundAccumulating evidences have demonstrated that overwhelming inflammation occurs in the process of Coxsackievirus B3 (CVB3)-induced acute viral myocarditis (AVM). No specific therapy is available. More than an effective Janus-associated kinase (JAK) inhibiter, ruxolitinib exerts a critical role in the inflammatory diseases. In this study, we investigated the potential effect of ruxolitinib on CVB3-induced acute viral myocarditis. MethodIn vivo, BALB/c mice were intraperitoneally injected of CVB3, treated of a successive gavage of ruxolitinib for seven days, and subjected to a series of analysis. In vitro, primary bone marrow-derived macrophages (BMDMs) and cardiac fibroblasts were isolated, cultured, treated, harvested and finally detected. ResultsIn vivo, acute viral myocarditis was successfully induced by the injection of CVB3 characterized by impaired cardiac function, predominant infiltration of inflammatory cells, necroptosis of myocardium, great increase of cardiac troponin I (cTnI) and cytokine levels, replication of CVB3, and excessive activation of JAK-STAT pathways. Oral administration of ruxolitinib suppressed the activation of JAK-STAT pathway in a dosage-dependent way, lessened the infiltration of inflammatory cells and necroptosis of myocardium, reduced the levels of cTnI and cytokines, and finally alleviated CVB3-induced cardiac dysfunction, with the reduced production of type I interferon and no promising effect on the replication of CVB3. In vitro, the treatment of ruxolitinib inhibited the activation of JAK-STAT pathway and increase of multiple cytokines mRNA levels in BMDMs and had no protective effect against CVB3 replication in cardiac fibroblasts. ConclusionsOur study suggested that ruxolitinib ameliorated CVB3-induced AVM by inhibiting the activation of JAK-STAT pathway, infiltration of inflammatory cells and necroptosis of myocardium, which may provide a novel strategy for AVM therapy.

Evaluation of cardiopreventive effects of Ximenia americana (Linn.) and Pappea capensis (Eckl. and Zeyh.) leaf aqueous extracts in rat models with myocardial infarction

BackgroundMyocardial infarction is a significant health issue in both wealthy and underdeveloped nations. Globally, it is the leading cause of deaths among cardiovascular diseases. In 2012, myocardial infarction-related deaths were about 14.1 million out of 17.5 million cardiovascular disease-related deaths. Clinical management of myocardial infarction remains a challenge because most conventional drugs provide symptomatic relief only. In addition, conventional remedies are associated with numerous advese effects and arguably, in many cases are quite expensive. Hence, herbal remedies, which are widely available, with comparatively fewer side effects, and are affordable, provide a more attractive therapeutic alternative. This study aimed at determining cardiopreventive effects of aqueous leaf extracts of X. americana and P. capensis. Phytochemical screening was done using liquid chromatography-mass spectrometry. Wistar albino rats were employed to test for cardiopreventive effects of the extracts and were randomized into 6 groups of 5 animals each. Groups I, II, and III were normal, negative, and positive controls, respectively, and rats were given normal saline, salbutamol (7.5 mg/Kg bw), and propranolol, respectively. Groups IV, V, and VI rats were treated with extracts dose levels 50, 100, and 150 mg/Kg bw, respectively. Biochemical analysis was done to determine effects of the extracts on levels of serum cardiac troponin T, creatine kinase-MB, lactate dehydrogenase-1, and lipid profiles. Levels of oxidative stress markers were determined in the heart tissue.ResultsThe LC–MS analysis revealed different phytocompounds in the extracts, including flavonoids, phenolic acids, glycosides and tannins, which are known to confer cardioprotective activities. The extracts significantly prevented increase in cardiac troponin T, creatine kinase-MB, lactate dehydrogenase-1, total cholesterol, triglycerides, LDL, and MDA levels, as well as a significant increase in superoxide dismutase, catalase, glutathione peroxidase, and HDL levels.ConclusionsThis study confirmed that Ximenia americana and Pappea capensis extracts have the potential to prevent myocardial infarction in rats. Generally, P. capensis extract showed better activity as compared to X. americana extract. The effects of the extracts could be attributable to the presence of various cardioactive phytocompounds. Therefore, these plants can be considered in the development of potent and safe cardiopreventive drugs.

C31 NEXT GENERATION MYOCARDITIS

Abstract A 75–year–old overweight man, affected by hypertension, diabetes mellitus and atrial fibrillation since 2020. After 3 unsuccessful attempts of electrical cardioversion it was opted for a strategy of rate control with beta blocker and anticoagulant therapy with Rivaroxaban 20 mg. Following episodes of rectal bleeding; adenocarcinoma of the colon was diagnosed. The patient underwent hemicolectomy and started therapy with Pembrolizumab. The anticoagulant was replaced with Edoxaban 60 mg. In August 2022, he was admitted to the emergency department for severe signs and symptoms of heart failure. On ECG, atrial fibrillation with a heart rate of 90 bpm and non–specific changes in ventricular repolarization. The echocardiogram showed a severe reduction of the ejection fraction (FE 30%), which was not present at previous controls. On blood tests, troponins were negative and BNP increased. The patient underwent coronarography which was negative for significant lesions, and heart failure therapy was prescribed. Three months later the patient came to our cardio–oncology outpatient clinic; we repeated the echocardiogram which showed a recovery of the ejection fraction to 45% and planned a cardiac MRI. Cardiac MRI (CMR) showed global left ventricular hypokinesia (FE 42%) and late subepicardial gadoline enhancement in the basal segment of the inferior wall and transmural in the basal segment of the lateral wall without signs of oedema. Report described as compatible with myocarditis. The case was discussed collegially with radiologists and oncologists, and it was decided to discontinue immunotherapy (ICI). Myocarditis is the most common cardiovascular adverse events of ICI therapy, although it has a very low incidence. Generally, myocarditis related to ICI therapy has a high mortality rate and requires discontinuation of ICI. In addition, CMR may have a lower sensitivity in this setting. There is also a possibility of developing left ventricular dysfunction without associated myocarditis in the absence of increase in cardiac troponin and active myocardial inflammation at CMR. Although our case has been defined as myocarditis, it presents some unclear aspects due in part to the early non–diagnosis as a complication of ICI therapy. Although cancer patients taking ICI has expanded considerably in recent years, the evidence on cardiovascular complications is scarce and unknown to the clinical cardiologist.

Abstract P4-01-17: Phase I/II study of pembrolizumab in combination with oral binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer

Abstract Background: Previous studies demonstrated that activation of the RAS/MAPK pathway is associated with reduced tumor-infiltrating lymphocytes and poor response to neoadjuvant chemotherapy in triple-negative breast cancer (TNBC). Further in vivo study showed that inhibition of the MAPK pathway with a MEK inhibitor is synergistic with immune checkpoint inhibitors (ICIs). Methods: Patients with unresectable locally advanced or metastatic TNBC with ≤ 3 prior lines of therapy were treated with pembrolizumab 200 mg every 3 weeks plus an oral MEK inhibitor binimetinib. Treatment was started with a 2-week run-in period with single-agent binimetinib. There were 2 dose levels in phase I, including dose level 0 (DL 0) with binimetinib at 45 mg orally twice daily continuously and dose level -1 (DL -1) at 30 mg twice daily. A standard 3+3 design was used in phase I to identify the recommended phase II dose (RP2D) and Simon’s two-stage Optimal design was used in phase II. Results: A total of 22 patients were enrolled. The median age was 58 years old (range 37-77). 14 (63.6%) patients had no prior systemic therapy in the metastatic setting and 8 (36.4%) patients had 1-2 prior lines of therapy. There were 4 patients treated in DL 0. Dose-limiting toxicity (DLT) was observed in 2 out of 4 patients in DL 0 with grade 3 ALT abnormality in one patient and grade 3 flank pain together with grade 3 nausea and vomiting &amp;gt; 48 hours despite anti-emetic therapy in the other patient. Binimetinib dose was reduced to DL -1. In the next 6 patients, there was 1 DLT observed with grade 3 AST/ALT abnormality. Thus, DL -1 was the RP2D, and an additional 12 patients were treated with DL -1 in phase II. Overall, 18 patients were treated in DL -1 and were included in phase II efficacy evaluation. 17 patients were evaluable for response. Objective responses were observed in 5 patients (29.41% 55.96) with 1 complete response (CR) and 4 partial responses (PR). The clinical benefit rate (CBR) was 35.29% (95% CI: 14.21 - 61.67) with 6 out of 17 having had CR, PR, or stable disease &amp;gt;= 24 weeks. Since previous studies showed poor responses to ICIs in patients with liver metastases due to macrophage-mediated T cell elimination, we further conduct exploratory analysis to evaluate responses among patients with and without liver metastases. Among all 5 patients with liver metastases, no response was observed. The objective response rate (ORR) in patients without liver metastases was 55.56% (95% CI: 21.20 - 86.30) and CBR was 66.67% (95% CI: 29.93-92.51), when excluding 3 patients who discontinued treatment due to adverse events prior to follow-up scans. Median progression-free survival in DL 0 was 2.4 (95%CI: 0.5-NE) and in DL -1 was 8.3 (95% CI: 3.9-NE) months. Median overall survival in DL 0 was 7 (95%CI: 0.5-NE) and in DL -1 was 33.2 (95% CI: 10.3-NE) months. Among patients who responded, 3 out of 5 (60%) had a duration of response greater than 12 months and ongoing even after stopping treatment (range: 5.4 - 32.0 months). Adverse events (AEs) were mostly grade 1-2 including anemia, CPK increase, fatigue, diarrhea, nausea, peripheral neuropathy, acneiform rash, AST increase, cardiac troponin increase, and constipation. Additional correlative studies are ongoing and will be presented at the meeting. Conclusions: Pembrolizumab in combination with binimetinib at 30 mg twice daily appears to be safe with manageable toxicities. Promising activity with durable responses was observed with this combination without chemotherapy, particularly in patients without liver metastases. Future studies are warranted to further evaluate the efficacy of this combination. Citation Format: Saranya Chumsri, Joseph J. Larson, Kathleen S. Tenner, Jun He, Mei-Yin Polley, Morgan T. weidner, Amanda N. Arnold, Dana Haley, Pooja Advani, Kostandinos Sideras, Alvaro Moreno-Aspitia, Edith A. Perez, Keith L. Knutson. Phase I/II study of pembrolizumab in combination with oral binimetinib in patients with unresectable locally advanced or metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-17.

Macrotroponin Complex as a Cause for Cardiac Troponin Increase after COVID-19 Vaccination and Infection.

Macrotroponin Complex as a Cause for Cardiac Troponin Increase after COVID-19 Vaccination and Infection.

Commentary on Macrotroponin Complex as a Cause for Cardiac Troponin Increase after COVID-19 Vaccination and Infection.

Commentary on Macrotroponin Complex as a Cause for Cardiac Troponin Increase after COVID-19 Vaccination and Infection.

Commentary on Macrotroponin Complex as a Cause for Cardiac Troponin Increase after COVID-19 Vaccination and Infection.

Commentary on Macrotroponin Complex as a Cause for Cardiac Troponin Increase after COVID-19 Vaccination and Infection.

Unusual diagnosis of feline cardiac lymphoma using cardiac needle biopsy

BackgroundCardiac tumors in cats are relatively rare, with lymphoma accounting for more than half of all cases. However, feline cardiac lymphoma is often diagnosed post-mortem, and it is difficult to diagnose while the cat is still alive. It is the first report of a direct, rather than estimative, diagnosis with cardiac needle biopsy of a living cat with cardiac lymphoma.Case presentationA 3-year-old domestic short-haired male cat experienced loss of energy and loss of appetite. Thoracic radiography and transthoracic echocardiography showed cardiomegaly with slight pleural effusion and cardiac tamponade due to pericardial effusion, respectively. In addition, partial hyperechoic and hypertrophy of the papillary muscle and myocardium were observed. Blood test showed an increase in cardiac troponin I levels. Pericardial fluid, removed by pericardiocentesis, was analyzed; however, the cause could not be determined. With the owner’s consent, pericardiectomy performed under thoracotomy revealed a discolored myocardium. Cardiac needle biopsy was performed with a 25G needle, and a large number of large atypical lymphocytes were collected; therefore, a direct diagnosis of cardiac lymphoma was made. Pathological examination of the pericardium diagnosed at a later date revealed T-cell large cell lymphoma. The cat underwent chemotherapy followed by temporary remission but died 60 days after the diagnosis. Postmortem, two-dimensional speckle-tracking echocardiography (data when alive) revealed an abnormal left ventricular myocardial deformation, which corresponded to the site of cardiac needle biopsy.ConclusionsThis rare case demonstrates that cardiac lymphoma should be added to the differential diagnosis in cats with myocardial hypertrophy and that the diagnosis can be made directly by thoracotomy and cardiac needle biopsy. In addition, the measurement of cardiac troponin I levels and local deformation analysis of the myocardium by two-dimensional speckle-tracking echocardiography may be useful in the diagnosis of cardiac tumors.

Incidence of acute myocardial injury and its association with left and right ventricular systolic dysfunction in critically ill COVID-19 patients

BackgroundPrevious studies have found an increase in cardiac troponins (cTns) and echocardiographic abnormalities in patients with COVID-19 and reported their association with poor clinical outcomes. Whether acute injury occurs during the course of critical care and if it is associated with cardiac function is unknown.The purpose of this study was to document the incidence of acute myocardial injury (AMInj) and echocardiographically defined left ventricular (LV) and right ventricular (RV) systolic dysfunction in consecutive patients admitted to an intensive care unit (ICU) for COVID-19. The relationship between AMInj and echocardiographic abnormalities during the first 14 days of ICU admission was studied. Finally, the association between echocardiographic findings, AMInj and clinical outcome was evaluated.MethodsSeventy-four consecutive patients (≥18 years) admitted to the ICU at Linköping University Hospital between 19 Mar 2020 and 31 Dec 2020 for COVID-19 were included. High-sensitivity troponin-T (hsTnT) was measured daily for up to 14 days. Transthoracic echocardiography was conducted within 72 h of ICU admission. Acute myocardial injury was defined as an increased hsTnT > 14ng/l and a > 20% absolute change with or without ischaemic symptoms. LV and RV systolic dysfunction was defined as at least 2 abnormal indicators of systolic function specified by consensus guidelines.ResultsIncreased hsTnT was observed in 59% of patients at ICU admission, and 82% developed AMInj with peak levels at 8 (3–13) days after ICU admission. AMInj was not statistically significantly associated with 30-day mortality but was associated with an increased duration of invasive mechanical ventilation (10 (3–13) vs. 5 days (0–9), p=0.001) as well as ICU length of stay (LOS) (19.5 (11–28) vs. 7 days (5–13), p=0.015). After adjustment for SAPS-3 and admission SOFA score, the effect of AMInj was significant only for the duration of mechanical ventilation (p=0.030).The incidence of LV and RV dysfunction was 28% and 22%, respectively. Only indices of LV and RV longitudinal contractility (mitral and tricuspid annular plane systolic excursion) were associated with AMInj. Echocardiographic parameters were not associated with clinical outcome.ConclusionsMyocardial injury is common in critically ill patients with COVID-19, with AMInj developing in more than 80% after ICU admission. In contrast, LV and RV dysfunction occurred in approximately one-quarter of patients. AMInj was associated with an increased need for mechanical ventilation and ICU LOS but neither AMInj nor ventricular dysfunction was significantly associated with mortality.