Elevated Cardiac Biomarkers Research Articles

Fulminant myocarditis induced by SARS-CoV-2 infection without severe lung involvement: insights into COVID-19 pathogenesis

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often leads to pulmonary complications. Cardiovascular sequelae, including myocarditis and heart failure, have also been reported. Here, the study presents two fulminant myocarditis cases infected by SARS-CoV-2 exhibiting remarkable elevation of cardiac biomarkers without significant pulmonary injury, as determined by imaging examinations. Immunohistochemical staining reveals the viral antigen within cardiomyocytes, indicating that SARS-CoV-2 could directly infect the myocardium. The full viral genomes from respiratory, anal, and myocardial specimens are obtained via next-generation sequencing. Phylogenetic analyses of the whole genome and spike gene indicate that viruses in the myocardium/pericardial effusion and anal swabs are closely related and cluster together yet diverge from those in the respiratory samples. In addition, unique mutations are found in the anal/myocardial strains compared to the respiratory strains, suggesting tissue-specific virus mutation and adaptation. These findings indicate genetically distinct SARS-CoV-2 variants have infiltrated and disseminated within myocardial tissues, independent of pulmonary injury, and point to different infection routes between the myocardium and respiratory tract, with myocardial infections potentially arising from intestinal infection. These findings highlight the potential for systemic SARS-CoV-2 infection and the importance of a thorough multi-organ assessment in patients for a comprehensive understanding of the pathogenesis of COVID-19.

Rida Herbal Bitters Improve Cardiovascular Function in High-fat Diet/Streptozotocin-induced Diabetic Rats

Background: Effective medication to manage diabetes mellitus-related organ complications with minimal adverse drug toxicity is still in pursuit by scientists worldwide. This study investigated the cardio-protective of Rida herbal bitter (RHB) in a high-fat diet/streptozotocin (STZ)-induced diabetic rats. Methods: Thirty-two matured male Wistar rats (250 ± 20g) were used. The animals were fed with high-fat diet (HFD) for 6 weeks before diabetes induction. A single dose of (35 mg/kgb.wt) freshly prepared STZ was injected intraperitoneally to induce diabetes. The animals were allocated into four groups, 8rats/group. Group I: control; Group II: HFD/STZ-induced diabetic rats; Groups III & IV: HFD/STZ-induced diabetic rats treated with 0.3 ml RHB & 200 mg/kgb.wt metformin respectively. At the end of the experiment, the animals were sacrificed, blood was sample collected via cardiac puncture and the heart was excised and homogenized. The blood samples and cardiac homogenates tissue were centrifuged to retrieve clear supernatant plasma for biochemical assay. Results: Diabetic rats exhibited significant (p < 0.05) elevated blood glucose, insulin, glycated hemoglobin (HbA1c), cardiac biomarkers, lipid profile, malondialdehyde (MDA), pro-inflammatory cytokines, food, and water intake levels with a reduction in body weight, cardiac antioxidant activity, and total protein. RHB administration significantly (p < 0.05) diminished the blood glucose, insulin, HbA1c, cardiac biomarkers, MDA, pro-inflammatory cytokines, lipid profile, food, and water intake, and improved the body weight cardiac antioxidant activity, and total protein. Conclusion: Rida herbal bitter possesses a cardio-protective effect from this study and could be a better alternative medication for managing diabetes and its related cardiovascular complications.

Fixed combination of rivaroxaban and Aspirin: Tablet formulation and analytical method validation

Rivaroxaban and aspirin are commonly used antithrombotic agents in combination to prevent coronary artery disease (CAD) and atherothrombotic events in adult patients after acute coronary syndrome (ACS) with elevated cardiac biomarkers, or with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) in high-risk patients. The recommended dosage is 2.5 mg rivaroxaban twice daily in combination with 75–100 mg aspirin once daily. This study aimed to develop a fixed-dose combination tablet of rivaroxaban (2.5 mg) and aspirin (50 mg) to enhance medication adherence and decrease pill burden.Compatibility studies were conducted on the active ingredients to develop the product formula. The formula and the manufacturing procedure were chosen based on the risk assessment for each active substance, wet granulation with both actives intragranular was found to have faster dissolution than direct mix formulae. Furthermore, a validated reverse-phase HPLC stability indicator method was developed to detect APIs and their possible degradants.

Comparison between Off-Pump and On-Pump Beating Heart Coronary Artery Bypass Grafting.

Although coronary artery bypass grafting (CABG) is performed via three different techniques, conventional, on-pump beating heart CABG (ONBHCAB), or off-pump CABG (OPCAB), data are limited to compare ONBHCAB with OPCAB. We retrospectively investigated the postoperative cardiac biomarkers, creatine kinase-MB (CK-MB), and troponin I (cTnI), and early and late outcomes in 806 patients undergoing isolated ONBHCAB or OPCAB between February 2008 and September 2022. To eliminate the bias between different groups, propensity score matching was conducted to validate the findings. After matching, the number of each study group totaled 270 patients. In both complete and matched cohorts, early outcomes, including morbidities and mortalities, were similar. However, cTnI and CK-MB levels were significantly higher after ONBHCAB than after OPCAB with median peak cTnI of 9.85 versus 4.60 ng/mL and median peak CK-MB of 48.45 versus 17.10 ng/mL in the matched cohort, which were quite low, below the threshold for values defining perioperative myocardial infarction. At follow-up of 73 ± 45 months, the overall actuarial survival rates were similar between the ONBHCAB and OPCAB patients (86 vs. 87% at 5 years and 64 vs. 68% at 10 years, respectively, in the matched cohort). ONBHCAB may be a comparable alternative to OPCAB with similar early and late outcomes, despite higher elevation of postoperative cardiac biomarkers. ONBHCAB provides more efficient hemodynamic support, providing a better surgical visual field, than OPCAB while reducing the risk of incomplete revascularization.

Periprocedural myocardial infarction and injury.

Periprocedural myocardial infarction (PMI) and injury, pertinent to both cardiac and non-cardiac procedures, have gained increasing recognition in clinical practice. Over time, diverse definitions for diagnosing PMI have been developed and validated among patient populations undergoing coronary revascularization. However, this variety in definitions presents considerable challenges in clinical settings and complicates both the design and interpretation of clinical trials. The necessity to accurately diagnose PMI has spurred significant interest in establishing universally accepted and prognostically meaningful thresholds for cardiac biomarkers elevation and supportive ancillary criteria. In fact, elevations in cardiac biomarkers in line with the 4th Universal Definition of Myocardial Infarction, have been extensively confirmed to be associated with increased mortality and cardiovascular events. In the context of non-coronary cardiac procedures, such as Transcatheter Aortic Valve Implantation, there is a growing acknowledgment of both the high incidence rates and the adverse impact of PMI on patient outcomes. Similarly, emerging research underscores the significance of PMI and injury in non-cardiac surgery, highlighting the urgent need for effective prevention and risk management strategies in this domain.

Characterizing diabetic cardiomyopathy: baseline results from the ARISE-HF trial

BackgroundDiabetic cardiomyopathy (DbCM) is a form of Stage B heart failure (HF) at high risk for progression to overt disease. Using baseline characteristics of study participants from the Aldose Reductase Inhibition for Stabilization of Exercise Capacity in Heart Failure (ARISE-HF) Trial we sought to characterize clinical characteristics of individuals with findings consistent with DbCM.MethodsAmong study participants meeting inclusion criteria, clinical characteristics, laboratory testing, imaging, Kansas City Cardiomyopathy Questionnaire (KCCQ), Physical Activity Scale of the Elderly (PASE) and cardiopulmonary exercise testing (CPET) results were tabulated. Cluster phenogroups were identified.ResultsAmong 691 study participants (mean age 67.4 years; 50% were female), mean duration of type 2 diabetes mellitus (T2DM) was 14.5 years. The median (Q1, Q3) N-terminal pro-B type natriuretic peptide and high sensitivity cardiac troponin T were 71 (35, 135) ng/L and 9 [6, 12] ng/L. The most common echocardiographic abnormalities were reduced global longitudinal strain in 25.3% and impaired diastolic relaxation in 17.7%. Despite rather well-preserved KCCQ scores the average PASE score was markedly impaired at 155 accompanied by an average maximal oxygen consumption of 15.7 mL/Kg/minute on CPET. In K-means clustering, 4 phenogroups were identified including a higher-risk group with more advanced age, greater elevation of cardiac biomarkers, and more prevalent evidence for diastolic dysfunction and left ventricular hypertrophy.ConclusionsBaseline data from the ARISE-HF Trial provide clinical characterization of individuals with T2DM and features of stage B HF, and may help clarify the diagnosis of DbCM.Trial RegistrationARISE-HF, NCT04083339.

Clinical characteristics and risk factors of cardiac involvement in pediatric immunoglobulin A vasculitis: A 7-year retrospective study from a single tertiary medical center.

Immunoglobulin A vasculitis(IgAV) is the most common form of systemic vasculitis affecting children. To date, cardiac involvement in pediatric IgAV has not been fully investigated and its prevalence may be underestimated. This study aims to reveal the clinical and laboratory characteristics of cardiac involvement in pediatric IgAV and further determine its risk factors. A total of 1451 children with IgAV were recruited between January 2016 and December 2022. According to the severity of cardiac involvement, the patients were divided into the myocarditis/suspected myocarditis group, cardiac abnormalities group, and non-cardiac involvement group. Demographic, clinical, and laboratory characteristics were retrospectively extracted from the individual data collected in the medical records. Among the 1451 pediatric IgAV patients, 179 (12.3%) were identified with cardiac involvement, including 154 (10.6%) with cardiac abnormalities and 25 (1.7%) with myocarditis/suspected myocarditis. Cardiac involvement in pediatric IgAV mainly manifested as elevated cardiac biomarker levels (n = 162), electrocardiogram abnormalities (n = 46), and echocardiogram/chest X-ray abnormalities (n = 15); however, cardiac-related symptoms were only observed in 15.1% of patients with cardiac involvement. Multivariate analysis demonstrated that interval from disease onset to diagnosis > 7days (OR, 2.157; 95% CI, 1.523-3.057; p < 0.001), IgAV with multi-organ involvement (OR, 1.806; 95% CI, 1.242-2.627; p = 0.002), and elevated D-dimer levels (OR, 1.939; 95% CI, 1.259-2.985; p < 0.001) were independent risk factors for cardiac involvement in pediatric IgAV. The length of hospital stay was significantly longer in the myocarditis/suspected myocarditis group compared with the other two groups (p < 0.05). Conclusion:This study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV. What is Known: • Immunoglobulin A vasculitis (IgAV) is the most common form of systemic vasculitis affecting children and adolescents, which exhibits diverse clinical manifestations. Cases of severe IgAV complicated by cardiac involvement have been anecdotally reported. What is New: • The present study suggests that cardiac involvements in pediatric IgAV is non-negligible, and cardiac involvement is associated with interval from disease onset to diagnosis > 7days, IgAV with multi-organ involvement, and elevated D-dimer levels. Severe cardiac involvement may affect the prognosis of pediatric IgAV.

Left ventricular hypertrophy phenotype to predict incident atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis

Background and aimLeft ventricular hypertrophy (LVH) has been shown to be associated with the occurrence of atrial fibrillation (AF). However, the predictive value of the LVH phenotype for incident AF remains uncertain. This study aimed to investigate the predictive value of LVH phenotype for incident AF. Methods and resultsThis study utilized the Multi-Ethnic Study of Atherosclerosis (MESA) data. LVH was defined by cardiac magnetic resonance measured LV mass index. Isolated LVH was determined as LVH without elevated cardiac biomarker and malignant LVH was determined as LVH with at least 1 elevated biomarker. Receiver-operating characteristic (ROC) analysis was performed to calculate areas under the curves (AUC) for predicting AF. A total of 4983 community-dwelling participants were included, with a mean age of 61.5 years. 279 (5.6 %) had isolated LVH, and 222 (4.5 %) had malignant LVH. During a median follow-up of 8.5 years, 272 incident AF was observed. Compared to participants without LVH and elevated cardiac biomarkers, those with isolated LVH (HR, 1.82; 95 % CI, 1.03–3.20) and malignant LVH (HR, 4.13; 95 % CI, 2.77–6.16) had a higher risk of incident AF. Malignant LVH carried a 1.5-fold increased risk of AF compared to isolated LVH (HR: 2.48, 95 % CI: 1.30–4.73). Including the LVH phenotype in the CHARGE-AF model improved model discrimination (AUC increase: 0.03, p < 0.001). ConclusionsThe risks of AF incidence varied across LVH phenotypes. Malignant LVH carried the highest risk among LVH phenotypes. LVH phenotype provides incremental predictive value over the variables included in the CHARGE-AF model.

Baseline NT-proBNP levels as a predictor of short-and long-term prognosis in COVID-19 patients: a prospective observational study

BackgroundUp to 20% of COVID-19 patients can suffer COVID-19-related myocardial injury. Elevated cardiac biomarkers, such as hs-cTnT and NT-proBNP, have been related to worse short-term prognosis. However, data on NT-proBNP and long-term prognosis are scarce. We have evaluated the potential association of baseline age-adjusted NT-proBNP levels and outcomes at one-year follow-up in COVID-19 patients.MethodsThis was a single-center prospective study of 499 COVID-19 patients in whom NT-proBNP was assessed at hospital admission. NT-proBNP levels were age-adjusted and patients were classified as high or low NT-proBNP. Clinical and demographic characteristics, comorbidities, laboratory results, and in-hospital complications and mortality were compared between the two groups. Survivors of the acute phase of COVID-19 were followed up for one year from admission to detect readmissions and mortality.ResultsThe 68 patients with high NT-proBNP levels at hospital admission were older, with more cardiovascular risk factors, cardiovascular disease, comorbidities, myocardial injury, and higher levels of inflammatory markers than patients with low NT-proBNP levels. They also had more in-hospital complications and a higher acute-phase mortality rate (60.3% vs. 10.2%, p < 0.001). High NT-proBNP levels were an independent marker of death during hospitalization (HR 1.95; CI 1.07–3.52). At one-year follow-up, high NT-proBNP levels were independently associated with mortality (HR 2.69; CI 1.47–4.89). Among survivors of the acute phase of COVID-19, there were no differences in hospital readmissions between those with high vs. low NT-proBNP levels, but survivors with high baseline NT-proBNP levels showed a higher 1-year mortality rate (7.4% vs. 1.3%, p = 0.018).ConclusionsHigh age-adjusted NT-proBNP levels at the time of hospital admission for COVID-19 are associated with poor short and long-term prognosis. High NT-proBNP seems also to be related to worse prognosis in survivors of the acute phase of COVID-19. A closer follow-up on these patients may be crucial.

Cardiac troponin I release after transcatheter closure of atrial septal defects is associated with supraventricular arrhythmias on early follow-up.

Atrial septal defects (ASD) are prevalent congenital heart anomalies found in the adult population. Percutaneous ASD closure has become a routine clinical practice. Elevation of postprocedural transient cardiac biomarkers and exacerbation of supraventricular arrhythmias have been reported in the subject literature. To explore the relationship between cardiac troponin I (cTnI) elevation and supraventricular ectopy (SVE) following percutaneous closure of secundum atrial septal defect (ASD) in adult patients. 600 consecutive patients who underwent successful transcatheter ASD secundum closure were analyzed. Serum levels of cTnI were measured before and within 72 h of device implantation. 24-hour Holter monitoring was performed before the procedure, at 1 month, and at 6 months of follow-up. SVE burden increased 1 month after the procedure (median 1021.00; min.-max. 11.00-29 862.00) compared to baseline values (median 146.00; min.-max. 0-1865.00; p < 0.01). 61.7% of patients demonstrated a cTnI rise exceeding 50% of the upper reference limit within 24 h of the procedure. A statistically significant positive correlation between SVE burden 1 month after the procedure and periprocedural cTnI increase (p < 0.05, r = 0.41) was observed, while cTnI levels significantly correlated with procedure and fluoroscopy time (p < 0.001), device size (p < 0.001) and maximal ASD diameter (p < 0.001). A significant increase of cTnI is noted frequently after transcatheter ASD closure and seems to predict exacerbation in SVE burden on short-term follow up. The independent risk factors of cTnI rise are prolonged procedure duration and larger device sizes.

Characteristics and outcomes of patients with symptomatic chronic myocardial injury in a Tanzanian emergency department: A prospective observational study.

Chronic myocardial injury is a condition defined by stably elevated cardiac biomarkers without acute myocardial ischemia. Although studies from high-income countries have reported that chronic myocardial injury predicts adverse prognosis, there are no published data about the condition in sub-Saharan Africa. Between November 2020 and January 2023, adult patients with chest pain or shortness of breath were recruited from an emergency department in Moshi, Tanzania. Medical history and point-of-care troponin T (cTnT) assays were obtained from participants; those whose initial and three-hour repeat cTnT values were abnormally elevated but within 11% of each other were defined as having chronic myocardial injury. Mortality was assessed thirty days following enrollment. Of 568 enrolled participants, 81 (14.3%) had chronic myocardial injury, 73 (12.9%) had acute myocardial injury, and 412 (72.5%) had undetectable cTnT values. Of participants with chronic myocardial injury, the mean (± sd) age was 61.5 (± 17.2) years, and the most common comorbidities were CKD (n = 65, 80%) and hypertension (n = 60, 74%). After adjusting for CKD, thirty-day mortality rates (38% vs. 36%, aOR 1.03, 95% CI: 0.52-2.03, p = 0.931) were similar between participants with chronic myocardial injury and those with acute myocardial injury, but significantly greater (38% vs. 13.6%, aOR 3.63, 95% CI: 1.98-6.65, p<0.001) among participants with chronic myocardial injury than those with undetectable cTnT values. In Tanzania, chronic myocardial injury is a poor prognostic indicator associated with high risk of short-term mortality. Clinicians practicing in this region should triage patients with stably elevated cTn levels in light of their increased risk.

Intermediate-high risk pulmonary embolism: When teamwork really matters

Pulmonary embolism is a common disease associated with significant morbidity and mortality. Existing validated risk stratification tools have enabled the rapid identification of patients with low versus high-risk pulmonary embolism. Intermediate-high risk pulmonary embolism is defined as pulmonary embolism with haemodynamic stability, evidence of right ventricular dysfunction and elevated cardiac biomarkers. The therapeutic management of intermediate-high risk pulmonary embolism in the acute setting is challenging as these patients are often unwell, but do not fulfil criteria for high-risk pulmonary embolism. Although current guidelines recommend prompt first-line treatment with systemic anticoagulation and monitoring for deterioration, alternative strategies are being increasingly considered in this cohort. These include systemic or catheter-directed thrombolysis, surgical embolectomy, and mechanical circulatory support. In this case series, we discuss three cases of intermediate-high risk pulmonary embolism with a focus on multidisciplinary decision making in clinical management. Following on from this, we provide a brief narrative review of the current literature and guidelines surrounding this topic, considering the risks and benefits of alternative therapy options on patient outcomes.

Recreational Exposure of Liquified Petroleum Gas: Case report and Review of the Literature

Introduction: LPG, a combination of aliphatic hydrocarbon gases, is utilized as a source of fuel for cooking appliances and vehicles. LPG mainly comprises butane (80%) and propane (20%), which are combustible gases, along with small concentrations of propylene and butylene. Mercaptans are included in the mixture to enable easy detection of any gas leakage due to their unpleasant smell. Because propane gas is heavier than air, it tends to settle at floor level. Due to the non-specific and diverse nature of its signs and symptoms, the timely and accurate diagnosis of LPG poisoning remains challenging. Due to easy access to LPG, there has been an increase incidence of its use for suicidal purposes and abuse. The current case report focuses on the effects of the abuse potential of LPG and its toxic effects. Case Report: In this case report, four individuals of same family (19 yrs, 23 yrs, 24 yrs, 25 yrs old brothers) who have abused LPG for recreational purpose under alcoholic intoxication and subsequently, of four of them three individuals showed acute toxic myocarditis with ECG changes and elevated cardiac biomarkers, hypoxia, neurological manifestations such as generalized weakness, unconsciousness. The fourth person was brought dead to casualty and it was determined that approximately 22% of the people who used inhalants died during their first use. Sudden deaths are usually caused by abuse of butane, propane, or butane/propane mixture and it is due to cardiac arrhythmia. Conclusion: The gas mixture of propane butane is among the most lethal inhalant substances. The substance abuse is increasing especially in adolescents and young adults. The public population must be educated about dangers of this gas abuse and its bad outcomes and should be recommended to stay away from it.

Prognostic value of elevated cardiac and inflammatory biomarkers in patients with severe COVID-19: a single-center, retrospective study: Erratum

Prognostic value of elevated cardiac and inflammatory biomarkers in patients with severe COVID-19: a single-center, retrospective study: Erratum

Abnormal Global Longitudinal Strain Correlates with Amyloidogenic Light Chain-Induced Cardiac Dysfunction via Direct Myocardial Toxicity in Patients without Significant Amyloid Fibril Deposition

Introduction: Patients with advanced cardiac AL have high early mortality despite receiving effective plasma cell-directed therapies. Cardiac dysfunction is caused by direct myocardial toxicity from amyloidogenic light chains (LCs) and architectural distortion from amyloid fibril deposition. Diagnosis before significant fibril-induced cardiac dysfunction is critical for improving outcomes. While measuring cardiac biomarkers is standard for risk stratification of patients with newly diagnosed AL, serum concentrations can be impacted by fluid shifts and renal impairment, suggesting a need for complementary biomarkers. Our transcriptomic analysis highlighted dysregulation of myocardial contractility in cardiac cells exposed to amyloidogenic LCs, leading us to hypothesize that there could be clinically measurable differences in cardiac contractility (Ghosh et al., 2023). Global longitudinal strain (GLS) is a sensitive echocardiographic measure of myocardial contractility and may predict survival independent of serum cardiac biomarkers. Since LC-induced cardiac dysfunction via direct myocardial toxic effects is reversible with plasma cell-directed therapy and may represent an early cardiac insult in patients with cardiac AL, we identified and evaluated patients with LC-induced cardiac dysfunction and no clinical or echocardiographic evidence of significant cardiac amyloid fibril deposition to determine clinical features potentially associated with early cardiac AL. Methods: We analyzed the demographic, clinical, and echocardiographic features of patients with non-cardiac biopsy-proven AL amyloidosis and LC-induced cardiac dysfunction seen at the Boston University Amyloidosis Center between January 1, 2011 and March 31, 2023. Direct LC-induced cardiac dysfunction was defined as: (1) elevated cardiac biomarkers (BNP &amp;gt;176 pg/mL or NT-proBNP &amp;gt;899 pg/mL or troponin I &amp;gt;0.033 ng/mL, per institutional reference ranges); (2) normal echocardiographic interventricular septal thickness (&amp;lt;11 mm in males and &amp;lt;10 mm in females); (3) estimated glomerular filtration rate &amp;gt;60 mL/min/1.73m 2; (4) absence of late gadolinium enhancement on cardiac magnetic resonance imaging (if performed); and (5) negative endomyocardial biopsy (if performed). Echocardiographic variables, including left ventricular ejection fraction (LVEF) and GLS, were collected from the electronic health record or post-processed manually using TomTec 2D CPA. All statistical analyses were performed using GraphPad Prism version 8©. Overall survival (OS) was evaluated using the Kaplan-Meier estimator and log rank tests. Results: Twenty-nine patients met our criteria for direct LC-induced cardiac dysfunction. Median age at diagnosis was 65 years (range: 46-83), and 55% of patients (n=16) were male ( Table 1). LC isotype was lambda in 69% (n=20) and kappa in 31% (n=9) of patients. The difference in free light chains (dFLC) was &amp;gt;50 mg/L in 62% (n=18) of patients at diagnosis.Additionally, 76% (n=22) of patients met criteria for Boston University stage II cardiac disease with mildly elevated cardiac biomarkers (median BNP 237 pg/mL, median troponin I 0.053 ng/mL). Among 16 patients for whom a GLS measurement was available, 81% (13/16) had an abnormal GLS (normal &amp;lt; -18%). Median and mean GLS were -15.5% (-7 to -21.7) and -15.3% ± 4.5, respectively ( Figure 1). Median OS was 5.2 years for the entire cohort. Conclusion: We found that a subset of patients with AL amyloidosis demonstrate cardiac dysfunction without substantial clinical or echocardiographic evidence of amyloid deposition; this we postulate to be the result of direct myocardial toxic effects by amyloidogenic LCs. Early cardiac biomarker stage and abnormal GLS were commonly associated with LC-induced cardiac dysfunctionin these patients.

Differences in the prevalence of cardiovascular toxicity in a cohort of female breast cancer patients according to the different cardiotoxicity definitions

Abstract Background The definition of cancer therapy-related cardiac dysfunction (CTRCD) has evolved in the past ten years, as Cardio Oncology has consolidated as a new medical discipline. However, great heterogeneity is noted among the published criteria of the different types of cardiotoxicities by the different scientific societies. In order to mitigate this variability, a new definition of CTRCD has been recently proposed by the International Cardio-Oncology Society (IC-OS) and endorsed by the latest 2022 ESC Guidelines on cardio-oncology. CTRCD is now classified into different degrees of severity according to symptoms, left ventricular ejection fraction (LVEF) reduction guided by echocardiography and elevation of cardiac biomarkers. Purpose we aimed to assess the impact of the new consensus definition of CTRCD in the reclassification of cardiotoxicity in a breast cancer cohort of female patients receiving potentially cardiotoxic therapies (CT) attended in our third-level hospital. Methods we retrospectively analyzed and compared the incidence of the different subtypes of CTRCD in a cohort of female breast cancer patients evaluated in our hospital from 2018 to 2021 according to both the previous 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity and the latest 2021 ICOS definition. Results a cohort of 193 women with a breast cancer diagnosis and receiving CT was analyzed. Mean age was 58 ± 11 years and 57 % of the patients (110) had a least one cardiovascular risk factor, with no past history of cardiac disease. According to the previous ESC 2016 criteria, 16 patients (8.3%) had cardiac dysfunction associated with cancer treatment whereas with the 2021 IC-OS new definition, a total of 23 women (12%) would have been satisfied the CTRCD criteria. Of Those, 11 were asymptomatic and 7 had severe CTRCD. Overall, this would have translated into a 30% rise in the incidence of patients experiencing any type of cardiotoxicty (p &amp;lt; 0.0001). Conclusion(s) by using the new IC-OS criteria for CTRCD, a significant increase in the prevalence of cardiotoxicity was noted in our population, which may translate the higher sensitivity of the proposed criteria to detect clinical or subclinical cardiovascular damage derived from cancer treatment.

Initial anticoagulation therapy with direct oral anticoagulants in patients with intermediate-high-risk pulmonary embolism: from the COMMAND VTE Registry-2

Abstract Background Patients with intermediate-high-risk pulmonary embolism (PE) who have both right ventricular dysfunction and elevated cardiac biomarkers are at a high risk of early hemodynamic decompensation and circulatory collapse, and it might be reasonable to treat these patients with parenteral anticoagulation therapy before switching to oral anticoagulation therapy. Recently, initial direct oral anticoagulants (DOACs) therapy in patients with PE have been shown to be non-inferior compared with initial parenteral anticoagulation therapy followed by vitamin K antagonist, which might be also a potential alternative for patients with intermediate-high-risk PE. However, the effectiveness and safety of initial DOACs therapy in this patient population have not been well investigated. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic venous thromboembolism (VTE) patients among 31 Japanese medical centers in the DOAC era between January 2015 and August 2020. The current study population consisted of 515 patients with intermediate-high-risk PE who were normotensive and right ventricular dysfunction on echocardiography or computed tomography, accompanied by elevated troponin levels (troponin I &amp;gt;0.028 ng/mL or troponin T &amp;gt;0.014 ng/mL) or N-terminal pro-B-type natriuretic peptide (NT-proBNP)/B-type natriuretic peptide (BNP) levels (NT-proBNP ≥600 pg/mL or BNP ≥100 pg/mL). The patients were divided into 2 groups; patients with initial DOACs therapy (N=107) and those with initial parenteral anticoagulation therapy (N=408). Results Most of baseline characteristics were comparable between the 2 groups. The 1-year cumulative incidence of bleeding events was significantly lower in patients with initial DOACs therapy than in those with initial parenteral anticoagulation therapy (6.5% vs. 15.3%, P=0.007) (Figure 1A), whereas the 1-year cumulative incidence of VTE recurrence was comparable between the 2 groups (2.2% vs. 2.2%, P=0.62) (Figure 1B). The 1-year incidence of all-cause mortality was numerically lower in patients with initial DOACs therapy than in those with initial parenteral anticoagulation therapy without statistically significant difference (4.5% vs. 13.5%, P=0.06) (Figure 1C). Conclusions Initial DOACs therapy in patients with intermediate-high-risk PE showed no signal of worse outcomes compared with initial parenteral anticoagulation therapy, which could be a potential initial anticoagulation strategy in this patient population.Figure 1

Abstract 18264: Associations of High-Sensitivity Troponin and Natriuretic Peptide Levels With Cognitive Outcomes in SPRINT

Background: Subclinical elevations in high sensitivity cardiac troponin T (hsc-TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) identifies a high-risk subgroup with reduction in cardiovascular disease in response to intensive systolic blood pressure (SBP) lowering. However, it remains unknown if these markers also identify subgroups with greater improvement in cognitive outcomes from intensive SBP lowering. Methods: We measured hs-cTnT and NT-proBNP at baseline in Systolic Blood Pressure Intervention Trial (SPRINT). Adjudicated cognitive outcomes were classified as probable dementia (PD) and mild cognitive impairment (MCI). Combined cardiac biomarker categories were defined as elevated, intermediate, and non-elevated. The association of combined biomarker categories with risk of cognitive outcomes was assessed using multivariable Cox proportional hazards models. Heterogeneity in the effect of intensive versus standard SBP lowering on the risk of cognitive outcomes across combined biomarker categories was determined. Results: Of 8,111 SPRINT participants with measured biomarkers and at least one follow-up cognitive assessment, 830 (10.2%) experienced the composite outcome of PD or MCI. After multivariable adjustment, elevated vs. non-elevated cardiac biomarker levels were independently associated with increased risk of composite outcome [HR 95% CI: 1.56 (1.26 - 1.92)]. The effect of intensive SBP lowering on the composite outcome was strongest among participants with non-elevated cardiac biomarkers (see Table). Conclusion: Elevated cardiac biomarkers were associated with higher risk for cognitive impairment. The effect of intensive SBP lowering on preventing cognitive impairment was strongest among patients with non-elevated cardiac biomarkers. This suggests that intensive SBP lowering may be more effective in preventing cognitive impairment in individuals with favorable cardiac biomarker profiles.

Abstract 18365: Elevated Biomarkers of Subclinical Myocardial Injury and Inflammation Among Community-Dwelling Adults With Covid-19

Background: Subclinical cardiovascular impact of SARS-CoV-2 infection in mild-moderate cases is unclear. Hypothesis We hypothesized that positive anti-nucleocapsid/spike SARS-CoV-2 antibodies will be associated with elevated subclinical cardiac and inflammatory biomarkers. Methods: This study was nested within a randomized controlled trial among community-dwelling adults. We used logistic regression to estimate adjusted odds of positive anti-nucleocapsid/ spike protein antibodies and elevated cardiac and inflammatory biomarkers (high-sensitivity cardiac troponin [hs-TnI], N-terminal pro-B-type natriuretic peptide [NT-proBNP], Galectin-3 [Gal-3], and C-reactive protein, [CRP]). Results: Among 231 adults, mean (±SD) age was 50 (±17.6) years, 63% were female, 57% were Black persons. Overall, 11% had detectable hs-cTnI (&amp;ge;6 ng/L), 21% had elevated NT-proBNP (&amp;ge;125pg/dL), 42% had elevated Gal-3 (&amp;ge;18.5 ng/mL), 70% had elevated CRP (&amp;ge;0.9 mg/dL). CRP levels were significantly higher among persons with positive spike protein antibodies [positive: median, 1.9 (Interquartile range IQR, 4.1) vs. negative: median, 0.7 (IQR, 2.1); p=0.014]. Those with positive spike protein antibodies were 3.49 (95% CI, 1.33-9.15) times more likely to have elevated CRP than those who were negative. Cardiac/inflammatory biomarkers were slightly higher in persons with positive SARS-CoV-2 IgG antibody detecting nucleocapsid protein (virus-specific antibody) versus negative ( Figure ). Conclusions: In this sample, we observed elevated cardiac and inflammatory biomarkers indicative of myocardial injury. Further research on the durability of elevated cardiac biomarkers and their contributions to post-acute sequela of COVID-19 is needed.

Abstract 12716: Left Ventricular Hypertrophy Phenotype to Predict Incident Atrial Fibrillation: The Multi-Ethnic Study of Atherosclerosis

Introduction: Left ventricular hypertrophy (LVH) has been shown to be associated with the occurrence of atrial fibrillation (AF). However, due to the heterogeneous nature of LVH, the predictive value of the LVH phenotype for incident AF remains uncertain. Methods: We utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA). In this study, participants who underwent cardiac magnetic resonance imaging examination were included for analysis. LVH was defined as LV mass index ≥ 85.3 g/m 2 for females and ≥ 107.8 g/m 2 for males. Isolated LVH was determined as LVH without elevated cardiac biomarkers, and malignant LVH was determined as LVH with elevated hs-TnT level of ≥14 ng/L, or/and NT Pro-BNP level of ≥125 pg/mL. Results: A total of 4983 participants were included in the final analysis, with a mean age of 61.5 years. 272 (5.6%) had isolated LVH, and 222 (4.5%) had malignant LVH. During a median follow-up of 8.5 years, 272 cases of AF were observed. Compared to participants without LVH or elevated cardiac biomarkers, those with isolated LVH (HR, 1.82; 95% CI, 1.03-3.20) and malignant LVH (HR, 4.13; 95% CI, 2.77-6.16) had higher AF risks after adjusted for age, sex, race, body mass index, systolic blood pressure, antihypertensive medication use, smoking status, and diabetes. Malignant LVH carried a 1.5-fold increased risk (HR: 2.48, 95% CI: 1.30-4.73) of AF compared to isolated LVH (Panel A). Kaplan-Meier cumulative AF incidence curves showed that malignant LVH had a significantly higher incidence of AF than those in other phenotypes (Panel B). Including the LVH phenotype in the CHARGE-AF model improved model discrimination (areas under the curves[AUC] increase: 0.03, p&lt;0.001) (Panel C). Conclusions: The risks of AF incidence varied across LVH phenotypes, showing that malignant LVH carried a higher risk compared to other LVH phenotypes. LVH phenotype could provide additional predictive power for AF occurrence above the CHARGE-AF model.