Measurement Of Cardiac Biomarkers Research Articles

Multidisciplinary strategies for cardiotoxicity management in ambulatory care: exploring practices, insights, and prospects for advancement

Abstract Background The management of cardiotoxicity, a significant concern in chemotherapy patients, necessitates a multidisciplinary approach. This study investigates the variability in cardiotoxicity management in outpatient settings across different medical specialties, which may lead to inconsistencies in patient care. Methods An extensive questionnaire-based study was conducted to assess the current practices and viewpoints of cardiologists, oncologists, and gynecologists in the management of cardiotoxicity among patients receiving outpatient chemotherapy in Germany. The survey engaged 1,329 medical professionals through an online platform, with a participation rate of 9.9%, amounting to 132 respondents. Results Respondents reported managing a combined total of 1,905 chemotherapy patients monthly, with individual patient loads ranging from 1 to 200. Notably, only a fraction of these patients – 37% under oncologist care and 48% under gynecologist care – underwent routine cardiological examinations. As shown in Figure 1, the three most common causes of cardiological presentations in patients undergoing chemotherapy were due to acute patient complaints (65.2%), before the start of chemotherapy (91.3%), and after the end of chemotherapy (78.3%). Furthermore, 37% of healthcare providers reported incorporating chemotherapy-induced cardiovascular toxicity risk assessments in their clinical routines. Medical history, ECG, and echocardiography were the most frequent examinations. Notably, 91.3% did not include cardiac biomarker measurements in their follow-up procedures (Figure 2). More than half of the participants (56%) expressed a need for simplified cardio-oncology guidelines. The majority of participants (84% and 83%, respectively) requested tools to assist in cardiovascular toxicity risk assessment and the implementation of appropriate therapeutic measures for patients undergoing chemotherapy. Conclusions The study draws attention to significant interdisciplinary care gaps in managing cardiotoxicity, which may contribute to an increased risk of undiagnosed cardiovascular complications in chemotherapy patients. The evident variability in cardiotoxicity management practices among different medical specialties underscores the critical need for heightened awareness and enhanced collaborative efforts. The implementation of comprehensive interdisciplinary clinical pathways and the establishment of a dedicated cardio-oncology network could potentially address these challenges, particularly in supporting primary care physicians.Figure 1Figure 2

Quantitative measurement of acute myocardial infarction cardiac biomarkers by “All-in-One” immune microfluidic chip for early diagnosis of myocardial infarction

Acute myocardial infarction (AMI) is a life-threatening condition with a narrow treatment window, necessitating rapid and accurate diagnostic methods. We present an “all-in-one” convenient and rapid immunoassay system that combines microfluidic technology with a colloidal gold immunoassay. A degassing-driven chip replaces a bulky external pump, resulting in a user-friendly and easy-to-operate immunoassay system. The chip comprises four units: an inlet reservoir, an immunoreaction channel, a waste pool, and an immunocomplex collection chamber, allowing single-channel flow for rapid and accurate AMI biomarker detection. In this study, we focused on cardiac troponin I (cTnI). With a minimal sample of just 4 μL and a total detection time of under 3 min, the chip enabled a quantitative visual analysis of cTnI concentration within a range of 0.5 ∼ 60.0 ng mL−1. This all-in-one integrated microfluidic chip with colloidal gold immunoassay offers a promising solution for rapid AMI diagnosis. The system's portability, small sample requirement, and quantitative visual detection capabilities make it a valuable tool for AMI diagnostics.

High Responses Rates with Single Agent Belantamab Mafodotin in Relapsed Systemic AL Amyloidosis

Introduction: Systemic AL amyloidosis, a rare incurable plasma cell disorder, has no approved treatments at relapse. Belantamab mafodotin is an antibody-drug conjugate which targets BCMA antigen approved for relapsed refractory myeloma. We report our results using belantamab mafodotin monotherapy for the treatment of patients with relapsed refractory AL amyloidosis including those traditionally excluded from clinical trials (eGFR<30 ml/min/1.73m 2 and cardiac Mayo stage IIIb disease). Methods: All patients treated with belantamab mafodotin monotherapy at standard dose (2.5 mg/kg) or dose reduction between April 2021 - July 2023. Standardised assessments including measurement of cardiac biomarkers, clonal parameters and imaging were performed and disease assessment was reported as per International Society of Amyloidosis consensus criteria. Results: Twenty-seven patients were included. The median age at was 65 years (range 41-76) and eight (30%) patients were aged >70 years. Eighteen (67%) had λ AL-type and nine (33%) κ AL-type. A median of two organs were involved at baseline (range 1-4) with renal and cardiac involvement in 20 (74%) and 15 (56%) respectively (3 each for Mayo stage IIIa and stage IIIb). The median time from AL amyloidosis diagnosis to first administration of belantamab mafodotin was 69 (range 5-174) months (~6 years) with a median of 3 prior lines of treatment (range 2-6). Prior drug class exposure included proteasome inhibitors (100%), immunomodulatory drugs (81%) and anti-CD38 antibody (81%) therapy. Ten patients (37%) had undergone prior melphalan-conditioned autologous stem cell transplantation. At the time of first belantamab mafodotin dose, the median involved free light chain concentration was 118mg/l (range 31-1778), eGFR was 40 ml/min (range 7 - 120) and a third (9/27) with an eGFR <30 ml/min/1.73m 2. NT-proBNP was 845 ng/l (range 99-70,000). At data cut-off, a median of 5 (range 1-11) doses of belantamab mafodotin were delivered. Of those with evaluable disease, best haematological overall response rate (partial response or better) was 80% (20/25) at a median time to best haematological response of 2 months (95% CI 1-4, range 1-17). Complete response (CR) or very good partial response (VGPR) was achieved in 64% (16/25). Two patients have only had 1 cycle and too early to perform response assessment. Reasons for treatment discontinuation (n=12) were: inadequate response/progression (n=7), keratopathy (n=1), grade 3 thrombocytopenia (n=1), physician choice (n=3: discontinued due to treatment for unrelated metastatic squamous cell carcinoma but remains in CR; facilitation of renal transplant; prior to BCMA-directed CAR-T in VGPR). At a median follow-up of 13 months follow-up (95% CI 4-18, range 1-27) from belantamab mafodotin initiation, 15 patients (56%) remain on therapy. Two patients died (1 due to progressive disease, 1 unrelated) and seven patients progressed and had subsequent line of therapy at a median time of 6 months (95% CI 2-4) in those that had a next line of therapy. Median treatment-free survival or death was 27 months (10-NR), and 1-year treatment-free survival/death was 69% (95% CI 41-86). Median overall survival (OS) is not reached. 1-year OS is 88% (95% CI 59-97). Bilateral microcystic corneal keratopathy, the most frequent adverse event, was seen in 19 (70%) patients (5%; 1/19 grade 4).Ocular adverse events improved in all patients after treatment delay. Only one patient required treatment cessation due to ocular toxicity (despite achieving PR after one dose). Thrombocytopenia was reported in 3 (11%) (grade 3: 1; grade 2: 1). Only two patients remained on the standard dose of 2.5mg/kg for >3 cycles. Nine patients had eGFR <30ml/min and 6/9 started at a dose of 1.25mg/kg with no unexpected side effects (1 patient had grade 3 keratopathy). One patient post-renal transplantation (on tacrolimus and mycophenolate) had no significant toxicity and achieved a CR after cycle 3. No treatment-related deaths, cardiac or renal toxicities observed in our cohort. Conclusion: Belantamab mafadotin has high efficacy and good tolerability in multiply relapsed AL amyloidosis including efficacy in patients otherwise excluded from clinical trials. Treatment-emergent adverse events (especially keratopathy) do not preclude delivery of drug with appropriate dose reductions.

Abstract 14391: Biomarkers, Proteomics, and Echocardiography Lend Insights into Cardiovascular Death in HFrEF: A VICTORIA Substudy

Background: Using data from the VICTORIA ECHO substudy in high-risk patients with heart failure with reduced ejection fraction (HFrEF), we evaluated the potential complementary role of cardiac function, biomarkers, and proteomics in association with cardiovascular death (CVD), a key component of the primary composite (HF hospitalization or CVD). Hypothesis: Measurement of cardiac biomarkers, proteins, and ECHO parameters may provide insights into the mechanism of CVD in HFrEF. Methods: At baseline, left ventricular ejection fraction (LVEF) and LV end-systolic volume index (LVESVI) on ECHO, 6 quantitative biomarkers, and 92 proteins (Olink CVD III panel) were assessed by blinded core labs. Adjusted (MAGGIC) associations and HRs (95% CIs) are presented. Proteomics associations were adjusted for false discovery rate. Results: Of 583 patients, 96 (16.5%) had CVD (21.6/100 pt-years) a median 8 months (IQR 6-11) from randomization. See Table for MAGGIC-adjusted HRs for LVEF, LVESVI, and biomarkers. NT-proBNP was most strongly associated with CVD (HR per doubling 1.53 [1.32-1.77]). Proteins significantly associated with CVD were cathepsin D (2.32 [1.62-3.32]), matrix metalloproteinase-2 (2.31 [1.45-3.68]), IL-2 receptor (1.74 [1.40-2.14]), transferrin receptor (1.64 [1.31-2.04]) and tumor necrosis superfamily (1.88 [1.41-2.50]) (Fig). Conclusions: After MAGGIC adjustment, a rise in LVESVI, but not LVEF, was associated with CVD. Upregulation of selected biomarkers/proteins related to myocardial wall stress, extracellular matrix turnover, inflammation, and oxidative stress were also associated with CVD and may serve as novel future therapeutic targets in HFrEF.

Measurement of Cardiac-Specific Biomarkers in the Emergency Department: New Insight in Risk Evaluation.

The aim of this article review is to analyze some models and clinical issues related to the implementation of accelerated diagnostic protocols based on specific cardiac biomarkers in patients admitted to the emergency department (ED) with symptoms compatible with acute cardiac disorders. Four specific clinical issues will be discussed in detail: (a) pathophysiological and clinical interpretations of circulating hs-cTnI and hs-cTnT levels; (b) the clinical relevance and estimation of the biological variation of biomarkers in patients admitted to the ED with acute and severe diseases; (c) the role and advantages of the point-of-care testing (POCT) methods for cardiac-specific biomarkers in pre-hospital and hospital clinical practice; and (d) the clinical role of specific cardiac biomarkers in patients with acute heart failure (AHF). In order to balance the risk between a hasty discharge versus the potential harms caused by a cardiac assessment in patients admitted to the ED with suspected acute cardiovascular disease, the measurement of specific cardiac biomarkers is essential for the early identification of the presence of myocardial dysfunction and/or injury and to significantly reduce the length and costs of hospitalization. Moreover, specific cardiac biomarkers (especially hs-cTnI and hs-cTnT) are useful predictors of mortality and major adverse cardiovascular events (MACE) in patients admitted to the ED with suspected acute cardiovascular disease. To guide the implementation of the most rapid algorithms for the diagnosis of Non-ST-Elevation Myocardial Infarction (NSTEMI) into routine clinical practice, clinical scientific societies and laboratory medicine societies should promote collaborative studies specifically designed for the evaluation of the analytical performance and, especially, the cost/benefit ratio resulting from the use of these clinical protocols and POCT methods in the ED clinical practice.

The Effect of Elective Ligation of the Arteriovenous Fistula on Cardiac and Renal Functions in Kidney Transplant Recipients.

Kidney transplantation (KTx) is considered as the best kidney replacement therapy and arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. The systematic ligation of a functioning AVF in stable kidney transplant recipients remains debatable. In this prospective study, we investigated the hemodynamic impact of the surgical closure of AVF in KTRs. Forty-three KTRs underwent an ambulatory blood pressure monitoring (24h-ABPM) before surgical closure of AVF (T0) and 12 months later (M12), as well as measurement of serum cardiac biomarkers (i.e., soluble suppression of tumorigenicity 2 (ST2), N-terminal pro b-type natriuretic peptide (NT-proBNP) and Galectin-3). Serum tests were also performed 6 months after AVF closure (M6). An echocardiographic exam was done at each time-point. All serum creatinine values were collected to compare the individual eGFR slopes before versus after AVF closure. The latest measure of the AVF flow (QAVF) prior to KTx was recorded. Diastolic blood pressure (DBP) significantly raised from T0 to M12: + 4.4±7.3 mmHg (p=0.0003) for 24h, + 3.8±7.4 mmHg (p=0.0018) during the day, and + 6.3±9.9 mmHg (p=0.0002) during the night, leading to an increased proportion of KTRs with ESH-defined arterial hypertension after AVF ligation. No change was observed for systolic BP. NT-proBNP significantly dropped between T0 and M6 (345 [190; 553] to 230 [118; 458] pg/mL, p=0.0001) and then remained stable from M6 to M12, while ST2 and Galectin-3 levels did not change from T0 to M12. We observed a significant decrease of left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV mass, interventricular septum diameter, left atrial (LA) volume, and tricuspid annular plane systolic excursion from T0 to M6, and then a stability from M6 to M12. LV ejection fraction and eGFR slope remained stable during the whole study. These observations remained unchanged after adjustment for QAVF. The closure of a patent AVF in KTRs is associated with elevation of DBP, drop of serum NT-proBNP levels, reduction of LV/LA dimensions, and stable eGFR slope.

PET/MRI Assessment of Acute Cardiac Inflammation 1 Month After Left-Sided Breast Cancer Radiation Therapy.

Our purpose was to investigate the utility of 18F-FDG PET/MRI and serial blood work to detect early inflammatory responses and cardiac functionality changes at 1 mo after radiation therapy (RT) in patients with left-sided breast cancer. Methods: Fifteen left-sided breast cancer patients who enrolled in the RICT-BREAST study underwent cardiac PET/MRI at baseline and 1 mo after standard RT. Eleven patients received deep-inspiration breath-hold RT, whereas the others received free-breathing RT. A list-mode 18F-FDG PET scan with glucose suppression was acquired. Myocardial inflammation was quantified by the change in 18F-FDG SUVmean (based on body weight) and analyzed on the basis of the myocardial tissue associated with the left anterior descending, left circumflex, or right coronary artery territories. MRI assessments, including left ventricular functional and extracellular volumes (ECVs), were extracted from T1 (before and during a constant infusion of gadolinium) and cine images, respectively, acquired simultaneously during the PET acquisition. Cardiac injury and inflammation biomarker measurements of high-sensitivity troponin T, high-sensitivity C-reactive protein, and erythrocyte sedimentation rate were measured at the 1-mo follow-up and compared with preirradiation values. Results: At the 1-mo follow-up, a significant increase (10%) in myocardial SUVmean in left anterior descending segments (P = 0.04) and ECVs in slices at the apex (6%) and base (5%) was detected (P ≤ 0.02). Further, a significant reduction in left ventricular stroke volume (-7%) was seen (P < 0.02). No significant changes in any circulating biomarkers were seen at follow-up. Conclusion: Myocardial 18F-FDG uptake and functional MRI, including stroke volume and ECVs, were sensitive to changes at 1 mo after breast cancer RT, with findings suggesting an acute cardiac inflammatory response to RT.

B-Type Natriuretic Peptide Can Distinguish Ischemic Stroke Subtypes Better than Other Cardiac Biomarkers.

BACKGROUND The primary benefit to patients of being able to distinguish among subtypes of ischemic stroke (IS) is creation of a better treatment decision-making process. Current classification methods are complex and time-consuming, requiring hours to days. Blood-based cardiac biomarker measurements have the potential to improve mechanism classification of ischemic stroke. MATERIAL AND METHODS In this study, 223 patients with IS were selected as the case group and 75 healthy people who underwent physical examination at the same time were selected as the control group. The chemiluminescent immunoassay (CLIA) method established in this study was used to quantitatively detect plasma B-type natriuretic peptide (BNP) levels in subjects. All subjects were assessed for serum creatine kinase isoenzyme-MB (CK-MB), cardiac troponin I (cTnI), and myoglobin (MYO) after admission. We investigated the effectiveness of BNP and other cardiac biomarkers in the diagnosis of different subtypes of IS. RESULTS The levels of the 4 cardiac biomarkers were increased in IS patients. BNP could better diagnose different types of IS compared to other cardiac biomarkers, and BNP combined with other cardiac biomarkers was better than a single indicator in diagnosing IS. CONCLUSIONS Compared with other cardiac biomarkers, BNP is a better marker for the diagnosis of different subtypes of ischemic stroke. Routine screening for BNP in IS patients is recommended to improve the treatment decision-making process and minimize the time to thrombosis, thereby providing a more precise treatment for patients with different subtypes of stroke.

Effect of Training Load on Post-Exercise Cardiac Biomarkers in Healthy Children and Adolescents: A Systematic Review of the Existing Literature.

Postexercise release of cardiac biomarkers (cardiac troponins, cTn, and N-terminal pro b-type natriuretic peptide, NT-proBNP) is a well-known phenomenon in adults, although it remains unclear how it manifests in children. The aim of this review is to compare the pre-exercise with the post-exercise measurement of serum cardiac biomarkers, as well as to analyze their post-exercise release based on age, sex, and exercise intensity and duration. The terms troponin, football, swimmers, marathon, run, and exercise were used in a literature search at National Library of Medicine. The search was further refined by adding the keywords athletes, children, adolescents, and sport. Fifteen pediatric studies and four studies with a mixed population of adults and children totaled 19 studies for the final analysis. In addition to them, some adult studies have been included for comparison. The kinetics of the cTn and NT-proBNP response after exercise have been the subject of our interest. While the impact of sport type, age, and sex has not yet been fully characterized, the existing data points to considerable impacts of sport intensity and duration on post-exercise biomarkers elevation. Most of the findings came from endurance sports, but the evidence is sparse. Furthermore, there is only limited data on women and less on young adults, African Caribbeans, and professional athletes. Both amateur and competitive athletes can exhibit post-exercise release of both cTn and NT-proBNP. This is transient and lacks pathological significance, in contrast with adult population, in which exercise-induced increases in in these biomarker levels may not always be benign. While NT-proBNP release is still primarily driven by activity duration, cTnT release is additionally affected by exercise intensity. To define individual ranges of normality for postexercise cTn and NT-proBNP elevation, the role of several confounders (age, sex, sport type/intensity etc.) remains to be further elucidated.

Recent Advances in Cardiovascular Disease Biosensors and Monitoring Technologies.

Cardiovascular disease (CVD) causes significant mortality and remains the leading cause of death globally. Thus, to reduce mortality, early diagnosis by measurement of cardiac biomarkers and heartbeat signals presents fundamental importance. Traditional CVD examination requires bulky hospital instruments to conduct electrocardiography recording and immunoassay analysis, which are both time-consuming and inconvenient. Recently, development of biosensing technologies for rapid CVD marker screening attracted great attention. Thanks to the advancement in nanotechnology and bioelectronics, novel biosensor platforms are developed to achieve rapid detection, accurate quantification, and continuous monitoring throughout disease progression. A variety of sensing methodologies using chemical, electrochemical, optical, and electromechanical means are explored. This review first discusses the prevalence and common categories of CVD. Then, heartbeat signals and cardiac blood-based biomarkers that are widely employed in clinic, as well as their utilizations for disease prognosis, are summarized. Emerging CVD wearable and implantable biosensors and monitoring bioelectronics, allowing these cardiac markers to be continuously measured are introduced. Finally, comparisons of the pros and cons of these biosensing devices along with perspectives on future CVD biosensor research are presented.

Abstract P5-08-17: Monitoring for cardiotoxicity in early breast cancer: an Australian experience

Abstract Background Breast cancer is the most commonly diagnosed cancer in Australia. Patient outcomes continue to improve with current 10 year survival of 86%. Given this, greater focus is needed to minimise potential long term toxicities of prescribed therapies. Anthracyclines and HER2 targeted therapies are commonly prescribed agents for high risk early breast cancers and are associated with acute and long term cardiotoxicity. Despite this, screening of cardiotoxicity in Australian patients receiving these therapies remains variable due to a lack of endorsed national screening guidelines. We conducted a retrospective review of screening procedures for cardiotoxicity in 2 major oncology centres in metropolitan Sydney and compared the findings to current international recommendations from ASCO/ESMO guidelines. Methods Patients were included if they received doxorubicin, epirubicin or trastuzumab with neoadjuvant or adjuvant intent during 2021. Baseline patient and tumour characteristics including cardiovascular risk factors were reviewed. Baseline ECG, transthoracic echocardiogram (TTE) or cardiac biomarkers (cardiac troponin or brain natriuretic peptide) were recorded, as well as frequency of serial monitoring and incidence of cardiotoxicity and cardiology referrals. Results 111 patients receiving initial curative therapy were included of which 45 received anthracycline therapy without trastuzumab. 66 received trastuzumab of which 34 also received anthracycline. 38 patients were aged greater than 60 and 31 had 2 or more cardiovascular risk factors. Of the patients receiving anthracycline only, 96% had a baseline TTE. All patients receiving trastuzumab only had a baseline TTE and of the 34 patients who received anthracycline and trastuzumab 3 did not undergo baseline TTE but underwent one prior to commencing trastuzumab. 3 patients total had a baseline ECG. No patients had baseline biomarkers measured. Only 5 patients had biomarkers measured at 1 year and all 5 had developed grade 1 heart failure on treatment. These 5 patients were referred for cardiology review and 2 required an interruption of trastuzumab. All patients receiving trastuzumab underwent 3 monthly TTEs on treatment. Of the 35 patients now more than 1 year post treatment completion, only 3 patients had a TTE at 12 months. No patients referred to cardiology have reached 12 months post treatment. Discussion International guidelines recommend screening to identify and treat early cardiotoxicity and prevent long term morbidity. ASCO and ESMO guidelines both recommend patients receiving anthracycline undertake a TTE at baseline and at 6-12 months after completing therapy. Both recommend 3 monthly TTEs for patients receiving trastuzumab. The ESMO guidelines recommend a baseline ECG and consideration of further TTE at 2 years post therapy. For high risk patients the ASCO guidelines discuss offering routine TTEs during treatment. The ESMO guidelines recommend measurement of cardiac biomarkers for patients receiving anthracycline prior to each cycle and routine monitoring can be considered for patients receiving anti HER2 therapy. The ASCO guidelines reserve use of cardiac biomarkers for patients who develop signs or symptoms of cardiac dysfunction. Our study demonstrates that while baseline cardiac assessment is well performed a personalised approach to cardiac monitoring during curative therapy is not. These were unexpected findings given both treatment units are located in well resourced areas of Sydney. An outcome of this study has been the development of a cardio-oncology group within our oncology and cardiology departments. This has led to the development of new clinical guidelines to screen and manage high risk breast cancer patients receiving cardiotoxic therapies. This has empowered patients, care coordinators and physicians to proactively manage cardiac risks from therapy and we hope these institutional guidelines will be adopted nationally. Citation Format: Brendan Kirwin, Lina Pugliano, Sally Baron Hay. Monitoring for cardiotoxicity in early breast cancer: an Australian experience [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 P5-08-17.

Cardiac Biomarkers in Sports Cardiology.

Sustained physical activity induces morphological and functional changes in the cardiovascular system. While mostly physiological, they can also become a trigger for major adverse cardiovascular events, the most severe of which are sudden cardiac arrest and sudden cardiac death. Therefore, any novel method which can help more accurately estimate the cardiovascular risk should be considered for further studying and future implementation in the standard protocols. The study of biomarkers is gaining more and more ground as they have already established their utility in diagnosing ischemic cardiac disease or in evaluating cardiac dysfunction in patients with heart failure. Nowadays, they are being implemented in the screening of apparently healthy individuals for the assessment of the cardiovascular risk. The aim of this paper is to gather published data regarding the measurements of cardiac biomarkers in athletes, i.e., troponins, myoglobin, CK-MB, NT-proBNP, and D-Dimers, and their potential use in the field of sports cardiology.

Assessing Acute Cardiac Inflammation after Left-Sided Breast Cancer Radiotherapy with Hybrid PET/MRI (RICT-BREAST)

<h3>Purpose/Objective(s)</h3> The goal of this study is to investigate the utility of hybrid ¹⁸FDG PET/MRI and serial blood work to detect early inflammatory response and cardiac functionality changes at one-month and one-year post radiation therapy (RT) in patients with left-sided breast cancer. <h3>Materials/Methods</h3> Fifteen left-sided breast cancer patients are currently enrolled in the RICT-BREAST study (NCT03748030). Serial imaging with hybrid ¹⁸FDG PET/MRI and blood work was obtained at baseline (before RT), at one-month post RT, and at one-year post RT. The hybrid ¹⁸FDG PET/MR imaging protocol consisted of a sixty-minute list-mode ¹⁸FDG PET scan with prior glucose suppression. Myocardial inflammation was quantified by calculating the change of mean ¹⁸FDG standard uptake (meanSUV_bw) at 40-60 minutes post injection and was grouped based on the supplied artery (left anterior descending (LAD), left circumflex (LC) or right coronary artery (RCA)). MRI assessments, including left ventricle (LV) functional and extracellular volume matrices (ECV), were extracted from T1 (pre and during-constant infusion of gadolinium) and cine images, respectively, and acquired simultaneously during PET acquisition. Cardiac disease and inflammation biomarker measurements of high-sensitivity troponin T (hs-TnT), C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were compared at each timepoint. <h3>Results</h3> Eleven patients received deep-inspiration breath-hold RT (DIBH-RT), while four patients received free-breathing RT (FB-RT), where 4D-CT simulation was performed to define cardiac motion encompassment. To date, all patients have received hybrid ¹⁸FDG PET/MRI cardiac imaging and bloodwork at baseline and at one month after RT. Two patients have received their one-year follow-up ¹⁸FDG PET/MRI scan and bloodwork. At 1-month follow-up, a significant increase (10%) of ¹⁸FDG/PET myocardial uptake (meanSUV_bw) was detected at LAD territories (p = 0.04). A significant increase in mean ECV, measured with T1-mapping, was observed in slices of the apex (6%) and base (5%) were also detected (p < 0.02). A significant reduction of mean LV stroke volume (-7%) was also identified (p < 0.02). Insignificant changes of all blood work measurements at 1-month follow-up were reported. There was no detectable difference in any cardiac measure between patients who received DIBH-RT and FB-RT. For the two patients who had their one-year follow-ups, an increase in hs-CRP and ESR levels were detected compared to baseline, whereas global reduction of FDG uptake was seen. One patient had an increase of hs-TnT (up to 19ng/L) with left ventricle remodeling reported in echocardiography and a global increase of ECV. <h3>Conclusion</h3> ¹⁸FDG/PET myocardial uptake and functional MR, including SV and ECV were sensitive to changes at 1-month after breast cancer RT with findings suggesting an acute inflammatory response in the heart. One-year median follow-up imaging and bloodwork has been acquired for 2 of 15 patients thus far.

Sequential assessment of cardiac function after CART therapy in accordance with the grade of CRS

Abstract Introduction As Chimeric Antigen Receptor T-cell (CAR-T) therapy gains its clinical advantage in the management of diffuse large B cell lymphoma (DLBCL), accumulating evidence shows that it often accompanies cardiac dysfunction. Previous retrospective studies indicated the potential involvement of cytokine release syndrome (CRS) in cardiac dysfunction after CAR-T therapy, but no prospective study has reported the time course of cardiac dysfunction. Moreover, the relationship between the severity of CRS and cardiac dysfunction after CAR-T therapy remains unclear. Purpose The objectives of this study are to prospectively examine the sequential changes in cardiac markers overtime after CAR-T therapy and to clarify the association between the grade of CRS and cardiac markers. Methods In this prospective observational study, 30 DLBCL patients who underwent CAR-T therapy from July 2020 to March 2022 were enrolled. Before and after the treatment, the level of cardiac biomarkers and echocardiographic index were sequentially collected. We classified all patients into two groups according to the severity of CRS after CAR-T therapy, namely low-CRS group (CRS &amp;lt;2) and high-CRS group (CRS ≥2). Cardiac biomarkers and echocardiographic parameters were further analyzed in both groups. Results The average age of participants was 59.6 years, and 9 patients (30%) were female. The average duration of DLBCL was 2.7 years. The CRS showed its peak severity on day 3. The number of patients in low- and high-CRS group was 13 and 17, respectively and tocilizumab was administrated for 46% and 71% of the patients in low- and high-CRS group, respectively. At the baseline before CAR-T therapy, there were no significant differences in cardiac parameters between the two groups. During the follow-up, sequential measurements of cardiac biomarkers revealed that high-CRS group showed significantly higher NT-proBNP level compared to that of low-CRS group (NT-proBNP; 90pg/ml vs. 623pg/ml, p=0.0001, respectively) and both had their peak on day 3, whereas troponin T level did not show any differences. Likewise, sequential measurements of echocardiographic parameters revealed that high-CRS group showed significantly increased E/A compared to low-CRS group on day 7 (E/A; 0.77 vs. 0.90, p=0.021, respectively), but not in the later phase. The parameters for systolic function including GLS and EF and parameters for diastolic function such as E/e' and LAVI did not alter among the two groups throughout the follow-up. Conclusion In the patients who underwent CAR-T therapy for DLBCL, the elevation of NT-proBNP level and increase in E/A was transiently observed within a week and correlated with the severity of CRS. Funding Acknowledgement Type of funding sources: None.

Cardiopulmonary Exercise Testing and Cardiac Biomarker Measurements in Young Football Players: A Pilot Study.

Constant and intense physical activity causes physiological adaptive changes in the human body, but it can also become a trigger for adverse events, such as sudden cardiac arrest or sudden cardiac death. Our main objective was to assess the use of combined cardiopulmonary exercise testing (CPET) and cardiac biomarker determinants in young professional athletes. We conducted a study which involved the full examination of 19 football players, all male, aged between 18 and 20 years old. They underwent standard clinical and paraclinical evaluation, a 12-lead electrocardiogram (ECG), and transthoracic echocardiography (TTE). Afterwards, a tailored CPET was performed and peripheral venous blood samples were taken before and 3 h after the test in order to determine five biomarker levels at rest and post-effort. The measured biomarkers were cardiac troponin I (cTnI), myoglobin (Myo), the MB isoenzyme of creatine-kinase (CK-MB), the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and D-dimers. While cTnI and NT-proBNP levels were undetectable both at rest and post-effort in all subjects, the variations in Myo, CK-MB and D-dimers showed significant correlations with CPET parameters. This highlights the potential use of combined CPET and biomarker determinants to evaluate professional athletes, and encourages further research on larger study groups.

Subclinical Cardiac Injury And Clinical Congestion

<h3>Introduction</h3> Clinical congestion is associated with worse outcomes in patients with heart failure (HF). The pathophysiological mediators of this association remain uncertain. <h3>Hypothesis</h3> Detailed phenotyping of patients with HF, including clinical examination and measurement of invasive hemodynamics and cardiac biomarkers, will provide insights into the pathophysiology of clinical congestion. <h3>Methods</h3> In a prospective cohort of patients with HF and reduced LVEF, a clinical examination followed the same day by right heart catheterization and blood sampling for biomarker measurement was performed. A clinical congestion score was created based on JVP (cm H20 <10 = 0, 10-14 =1, >14 =2 points), bendopnea (0-1), S3 (0-1) and peripheral edema (0-2). Congestion tier was defined as Absent, Mild (1 point) or Moderate-Severe (≥ 2 points). Biomarker elevation was defined as high-sensitivity troponin T ≥52 ng/L or NT-proBNP ≥1000 pg/mL. Elevated right atrial pressure (RAP) was ≥10 mmHg and pulmonary capillary wedge pressure (PCWP) ≥22 mmHg. Univariate and multivariable analyses tested the association of biomarkers, RAP, and PCWP with clinical congestion. <h3>Results</h3> Of 154 subjects, 65 (42%) had no congestion, 35 mild (23%) and 54 (35%) moderate-severe. Increasing congestion tier was associated with NT-proBNP, troponin, RAP and PCWP (P<0.001 for each). Increasing congestion tier was associated with the combined presence of elevated troponin, NT-proBNP and PCWP (Figure). Only 22% of those with absent congestion had more than one of these findings, whereas 76% of those with moderate-severe congestion had at least 2 of them (p<0.001). In multivariable regression, elevated troponin was associated with the presence of clinical congestion (OR 2.8, 1.1-7.3, p=0.03) independently of RAP, PCWP, and NT-proBNP levels. <h3>Conclusions</h3> Increased ventricular filling pressures, elevated natriuretic peptide levels, and subclinical myocardial injury frequently coexist in patients with clinical congestion. Elevated troponin was associated with clinical congestion independently of ventricular filling pressures and natriuretic peptide levels, suggesting that subclinical cardiac injury contributes to the pathophysiology of clinical congestion.

Prospective evaluation of the combined value of physical examination and biomarker variables in screening for preclinical dilated cardiomyopathy in Doberman Pinschers

IntroductionScreening to assess likelihood of preclinical dilated cardiomyopathy (PC-DCM) prior to advanced diagnostic tests in Doberman Pinschers (DP) is desirable. ObjectiveTo investigate the combined value of physical examination (PE), N-terminal pro B-type natriuretic peptide (NTproBNP) and cardiac troponin I (cTnI) for identifying PC-DCM in DP. Animals, materials and methodsAll dogs underwent: PE, echocardiogram, 3-min ECG and cardiac biomarker measurement. Asymptomatic DP (414) were classified based on 3-min ECG and echocardiogram as: No-DCM/MMVD or myxomatous mitral valve disease (MMVD), PC-DCM based on echocardiogram (PC-DCM-Echo), PC-DCM based on arrhythmias with a normal echocardiogram (PC-DCM-ECG), equivocal DCM (EQ-DCM), and MMVD. Receiver operator characteristic curves and prediction models were derived. ResultsHeart murmurs and arrhythmias were rare and gallop sounds were absent in No-DCM/MMVD DP. Dogs ≥ four years old and males had higher probabilities of PC-DCM-Echo. Prediction models incorporating PE variables with NTproBNP had an area under the curve (AUC) of 0.940 for distinguishing between PC-DCM-Echo and all other groups, which was similar to the AUC for NTproBNP (0.939) or cTnI (0.932) alone. Discrimination between No-DCM/MMVD and all other groups was similar for NTproBNP (0.781) and cTnI (0.742) as individual tests, however, models combining PE variables and NTproBNP increased the AUC to 0.812. An NTproBNP cut-off of ≥548 pmol/L, was 100% sensitive and 77.3% specific for detecting PC-DCM-Echo. ConclusionsBoth NTproBNP and cTnI had good utility as sole tests to discriminate PC-DCM-Echo DP from all others. Models differentiating No-DCM/MMVD DP from all other DP were improved by using PE and NTproBNP together.

Prognostic Implications of a Second Peak of High-Sensitivity Troponin T After Myocardial Infarction.

BackgroundAfter an acute myocardial infarction (MI), repeated measurement of cardiac biomarkers is commonly performed, although not recommended in current guidelines. There is only limited data on the kinetics of troponin in this phase. For high-sensitivity cardiac troponin T (hs-cTnT), but not high-sensitivity cardiac troponin I (hs-cTnI), late increases in terms of a second peak have been described. Their impact on the prognosis of patients with MI remains unclear.MethodsWe included 2,305 patients presenting to the emergency department with symptoms suggestive of MI. Five hundred and seven were diagnosed with MI. Hs-cTnT, creatine kinase (CK) and the MB fraction of CK (CK-MB) were measured at admission, after 1 and 3 h and thereafter as indicated by the treating physician. A mixed-model approach was applied for modeling the biomarker kinetics. All patients were followed up to assess a composite endpoint of mortality, recurrent MI, revascularization and rehospitalization and to investigate the effect of a second hs-cTnT peak on prognosis.ResultsOut of 507 patients with MI, 192 had a sufficient amount of hs-cTnT measurements after the index MI. In 111 (57.8%) patients a second hs-cTnT peak was found after 4.48 days. For CK and CK-MB a second peak could not be identified. Regarding the composite endpoint there was no significant difference between patients with and without a second hs-cTnT peak.ConclusionIn our analyses, a second peak of hs-cTnT after an acute MI was common, but not associated with poorer outcome. Thus, the clinical value of hs-cTnT for monitoring myocardial ischemia might be limited in this phase and other biomarkers might be more suitable.Trial Registration: www.ClinicalTrials.gov, identifier: NCT02355457, Date of registration: February 4, 2015.

STUDY OF TROPONIN-I LEVELS IN COVID-19 PATIENTS

BACKGROUND AND OBJECTIVES: Elevated Troponin-I levels either due to direct or indirect cardiac injury can present as asymptomatic to fulminant myocarditis and circulatory shock in COVID-19 patients. Our objective is to evaluate the Troponin-I levels in covid patients. AIM: To evaluate the possible myocardial involvement in covid-19 patients with the help of Troponin-I levels as an indicator of cardiac injury and its prognostic implication and significance as it is associated with increased mortality in patients with COVID-19. METHORDS: This was a both a prospective and retrospective cohort study done from 1st January 2021 to 1st July 2021. A total of 240 admitted patients were included and whose Troponin-I levels were evaluated and in a comparative analysis was performed for the demography, clinical features, biochemical markers and their outcome with their Troponin-I levels. RESULTS: Out of 250 covid-19 positive hospitalized patients, 15patients have elevated Troponin-I levels. Among these 15 patients 60% had preexisting co morbidities like hypertension, diabetes and history of cardiac disease. Patients with elevated troponin level had mean age of 61.1years, length of stay was &gt;14 days in 60% patients. In 46% patients Troponin-I levels were more than 200ng/L. These patients had a higher need for intensive care with mortality of 73%. CONCLUSION: Etiology of myocardial involvement is multifactorial. Our study also concluded that elevated troponin levels in patients with covid19 have high morality. Therefore, the measurement of cardiac biomarkers, including Troponin-I and brain natriuretic peptide (BNP), should be performed on admission.

Abstract 9828: Active Surveillance of Cardiotoxicity with Cardiac Biomarkers During Chimeric Antigen Receptor T-Cell Therapy

Introduction: Chimeric Antigen receptor T- Cell (CAR-T) immunotherapy has been a breakthrough for various hematological malignancies. Cardiotoxicites such as heart failure, arrhythmia and acute coronary syndrome occur in approximately 1/3 of patients who develop cytokine release syndrome (CRS) following CAR-T. High grade CRS (Grade ≥ 2) and elevated troponin level are associated with increased risk of cardiotoxicity. It is unclear whether active cardiotoxicity surveillance with serial cardiac biomarker measurements during CAR-T would allow early detection of cardiotoxicity. Methods: This was retrospective cohort study involving patients diagnosed with non-Hodgkin lymphoma treated with CAR-T therapy (Axicabtagene ciloleucel- Yescarta, tisagenlecleucel- Kymriah, Brexucabtagene autoleucel- Tecartus). Baseline cardiac workup with electrocardiogram (ECG), transthoracic echocardiogram (TTE), troponin (Reference &lt;0.03ng/mL), B-natriuretic peptide (BNP, &lt;100pg/mL) were uniformly performed in all participants. Follow up ECG, Troponin and BNP were obtained at day 5 after CAR-T and at development of CRS Grade ≥2. When clinically indicated, cardiac MRI with gadolinium contrast was performed. Cardiac MRI diagnosis of myocarditis was based on Lake Louise Criteria. Results: A total of 47patients undergoing CAR-T therapy were studied. Baseline comorbidities were not predictive of CRS or cardiac events. There were 39 patients with low grade CRS (82.9%) and 8 patients (17.0%) with grade 2 CRS. Five patients had elevated troponin I levels (Grade 1 CRS - 3; Grade 2 CRS - 2). Cardiac MRIs were performed in three patients (two normal studies, one with mild myocarditis). Five patients (10.6%) had an adverse cardiac event (Myocarditis with heart failure - 1; new-onset atrial fibrillation - 3; Type 2 myocardial infarction -1). Conclusion: Adverse cardiac events are a relatively common occurrence in patients receiving CART therapy. Active surveillance for cardiotoxicity using cardiac biomarkers in CAR-T patients may play an adjunctive role in the early identification of adverse cardiac events. Larger studies are needed to adjudicate the use of such screening measures in these high-risk patients.