KEY FINDINGS: sNFL was elevated in patients with AF compared with matched controls without AF. Ongoing AF rhythm was associated with even higher levels of sNFL than in patients with a diagnosis of AF but currently not in AF rhythm. Anticoagulation treatment did not affect sNFL levels.
BACKGROUND: Atrial fibrillation (AF) is associated with stroke and MRI features of cerebral tissue damage but its impact on levels of serum neurofilament light chain (sNFL), an established biochemical marker of neuroaxonal damage, is unknown.
DETAILS: In this observational study, sNFL was analyzed in 280 patients with AF and 280 controls without AF matched for age, sex, and diabetes status within the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. None of the patients had a history of previous stroke or transient ischemic attack. Patients with a diagnosis of AF were divided into two groups based on if they were in AF rhythm at the time of blood sampling (AF ECG+, n=74), or not (AF ECG-, n=206). Multiple linear regression analysis was performed to adjust for clinical risk factors. In patients with AF, the levels of sNFL were 15% (AF ECG+) and 10% (AF ECG-) higher than in the control group after adjustment for clinical risk factors, P=0.047 and 0.04, respectively. There was no association between anticoagulation treatment and sNFL levels.
Copyright © The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell
Source: Sjolin, K., Aulin, J., Wallentin, L., et al. (2022). Serum Neurofilament Light Chain in Patients With Atrial Fibrillation. Journal of the American Heart Association. 2022; 11(4): e025910. Published: July 15, 2022. DOI: 10.1161/JAHA.122.025910.
Fluoropyrimidine Chemotherapy: Mortality and Cardiovascular Risk in Gastrointestinal Cancer
[Posted 4/Jul/2025]
AUDIENCE: Oncologists, Cardiologists, Cardio-Oncologists, and Researchers involved in the treatment of gastrointestinal cancers.
KEY FINDINGS:
BACKGROUND: Fluoropyrimidine chemotherapy is a primary first-line treatment for many gastrointestinal cancers. However, concerns regarding its cardiotoxicity often lead to the use of alternative treatments in patients with pre-existing cardiovascular disease. This study aimed to quantitatively assess the risks of all-cause mortality and acute cardiovascular events associated with fluoropyrimidine treatment to inform clinical decision-making.
DETAILS: This observational cohort study utilized a target trial emulation framework with linked national cancer, cardiac, and hospitalization registry data from the Virtual Cardio-Oncology Research Initiative. The study included 103,110 adult patients (mean age 69.7 years, 59% male) diagnosed with tumors eligible for first-line fluoropyrimidine-based chemotherapy. Researchers compared all-cause mortality and a composite of hospitalization for acute cardiovascular events (including acute coronary syndrome, heart failure, cardiac arrhythmia, cardiac intervention, cardiac arrest, and cardiac death) between patients receiving fluoropyrimidine-based chemotherapy and those undergoing alternative management. The findings indicate that the improved overall survival with fluoropyrimidines in patients with gastrointestinal cancer is a significant benefit that should encourage oncologists to avoid undue clinical conservatism, particularly when treating patients with co-existing cardiovascular disease.
Copyright © Authors. All rights reserved.
Source: Abiodun, A. T., Ju, C., Welch, C. A., et al. Fluoropyrimidine Chemotherapy and the Risk of Death and Cardiovascular Events in Patients With Gastrointestinal Cancer. J Am Coll Cardiol CardioOnc.. 2025; 7(4): 345-356. Published: June, 2025. DOI: 10.1016/j.jaccao.2025.01.019.
A Cohort Study From the EINSTEIN-Jr Phase 3 Trial
[Posted 18/May/2025]
AUDIENCE: Hematology, Pediatric
KEY FINDINGS: Incidences of recurrent venous thromboembolism and bleeding during extended-phase anticoagulant treatment were low and similar to those observed during acute-phase treatment and adult studies on extended-phase anticoagulant treatment, providing valuable information for clinical practice on extended anticoagulation in children.
BACKGROUND: Extended-phase anticoagulation of venous thromboembolism in children is not well documented nor systematically reported. Previously, we reported on recurrent venous thromboembolism and bleeding during acute-phase anticoagulation in EINSTEIN-Jr, a randomised controlled study in 500 children with venous thromboembolism comparing rivaroxaban to standard anticoagulants. The aim of the present study was to evaluate the efficacy and safety of extended-phase anticoagulant therapy in children and to characterise factors associated with the decision to extend anticoagulation.
DETAILS: Children aged 17 years or younger, who were enrolled in the EINSTEIN-Jr trial (NCT02234843) from 107 paediatric hospitals in 28 countries, and who had previously completed a 3-month acute anticoagulation treatment phase (1-month in children <2 years with catheter-related venous thromboembolism) for acute venous thromboembolism within the trial were included in this cohort study. After completion of the preceding acute anticoagulation treatment phase, children could extend study treatment for up to 9 months (or up to 2 months for children <2 years with catheter-related venous thromboembolism). Study anticoagulants were bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20 mg equivalent dose or standard anticoagulants (heparin or vitamin K antagonist). The main outcomes were suspected recurrent venous thromboembolism (primary efficacy outcome) and clinically relevant bleeding (principal safety outcome), both confirmed or refuted by appropriate objective testing. Cumulative incidences of efficacy and safety outcomes are reported for children who received extended anticoagulation within the framework of the study. We also compared demographic and clinical characteristics of those administered any extended-phase anticoagulation (whether within or outside the framework of the study) with those not administered extended-phase anticoagulation, applying multivariable logistic regression. 248 (51%) children received extended-phase anticoagulation between Nov 14, 2014, and Jan 15, 2019, 214 within the study and 34 outside the framework of the study. During extended-phase anticoagulant treatment, recurrent venous thromboembolism occurred in three (1%) of the 214 children within the study (cumulative incidence 3.0%; 95% CI 0.9-9.8). Clinically relevant non-major bleeding occurred in four (2%) of 214 children (3.3%; 1.2-9.2). Fatal venous thromboembolism or major bleeding did not occur. Outcome rates were similar with rivaroxaban or standard anticoagulants. Symptomatic index venous thromboembolism (odds ratio 1.88; 95% CI 1.14-3.11), unprovoked venous thromboembolism or persistent risk factor (2.16; 1.46-3.19), and residual thrombosis on repeat imaging (3.79; 2.52-5.71) were associated with the decision to extend anticoagulation.
Copyright © Elsevier Ltd. All rights reserved.
Source: Male, C., Lensing, A. W. A., Chan, A. K. C., et al. Extended-Phase Anticoagulant Treatment of Acute Venous Thromboembolism in Children: A Cohort Study From the EINSTEIN-Jr Phase 3 Trial. The Lancet Haematology. 2025; 12(5):5, e357-e364. Published: April, 2025. DOI: PIIS2352-3026(25)00067-5.
KEY FINDINGS: The erythropoietin-erythroferrone-TfR1-hepcidin axis is activated in patients with heart failure as the disease advances and is further heightened by SGLT2 inhibitors, in parallel with their effect to enhance erythropoiesis and iron mobilization and use. These changes have important implications for understanding the mechanism of action of SGLT2 inhibitors and for monitoring the response to treatment.
BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors stimulate erythropoiesis, but the mechanisms and clinical relevance of the effect of SGLT2 inhibitors on systemic iron metabolism in patients with heart failure is not well understood. The authors sought to characterize a comprehensive suite of iron metabolism biomarkers—particularly the erythroblast signaling molecule, erythroferrone—in patients with heart failure before and after short- and long-term treatment with empagliflozin in patients with heart failure and a reduced or preserved ejection fraction.
DETAILS: Authors measured serum iron metabolism biomarkers at baseline, 12 weeks, and 52 weeks in 1,139 patients who were treated with placebo or empagliflozin in the EMPEROR (EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure) program, and characterized the inter-relationships of these biomarkers with clinical status and with the effect of empagliflozin on erythropoiesis and heart failure outcomes. Correlations among iron biomarkers indicated the presence of a functional erythropoietin-erythroferrone-transferrin-receptor-protein-1 (TfR1)-hepcidin axis. As heart failure advanced, patients showed higher levels of erythropoietin, erythroferrone, and TfR1 (P trend <0.01), and levels of these proteins predicted a heightened risk of cardiovascular death or heart failure hospitalization (all P < 0.01). Compared with placebo, at 12 weeks, empagliflozin increased hemoglobin by 0.6 to 0.9 g/dL (P < 0.001), an effect that was accompanied by further activation of the erythropoietin-erythroferrone-TfR1 axis and increased iron use. Empagliflozin increased serum levels of erythroferrone by >40% (along with increases in erythropoietin and TfR1), while simultaneously decreasing hepcidin levels and reducing serum iron concentrations and transferrin saturation (all P < 0.01). When treated with empagliflozin, patients with evidence of iron deficiency at baseline showed attenuation of the erythrocytic response (P trend = 0.04) but no diminution of the heart failure benefits.
Copyright © American College of Cardiology Foundation. All rights reserved.
Source: Ferreira, J. P., Anker, S. D., Butler, J., et al. (20245). Effect of Empagliflozin on the Mechanisms Driving Erythropoiesis and Iron Mobilization in Patients With Heart Failure: The EMPEROR Program. J Am Coll Cardiol.. 2025; 85(18): 1757-1770. Published: May, 2025. DOI: 10.1016/j.jacc.2025.03.503.
KEY FINDINGS: The use of cPOCUS by non-expert physicians after a short training course appears to be an accurate complementary tool for LVEF assessment in daily practice. Its diffusion in primary care could optimize patient management, without replacing specialist assessment.
BACKGROUND: Heart failure (HF) is the most frequent cardiovascular pathology in primary care. Echocardiography is the gold standard for diagnosis, follow-up, and prognosis of HF. Point-of-care ultrasound (POCUS) is of growing interest in daily practice. This study aimed to systematically review the literature to evaluate left ventricular ejection fraction (LVEF) assessment of unselected patients in primary care by non-expert physicians with cardiac POCUS (cPOCUS).
DETAILS: Authors searched in Medline, Embase, and Pubmed up to January 2024 for interventional and non-interventional studies assessing LVEF with cPOCUS in unselected patients with suspected or diagnosed HF in hospital or outpatient settings, performed by non-expert physicians. Forty-two studies were included, involving 6598 patients, of whom 60.2% were outpatients. LVEF was assessed by 351 non-expert physicians after an initial ultrasound training course. The LVEF was mainly assessed by visual estimation (90.2%). The most frequent views were parasternal long/short axis, and apical 4-chamber. The median time of cPOCUS was 8 minutes. A strong agreement was found (κ = 0.72 [0.63; 0.83]) compared to experts when using different types of ultrasound devices (hand-held and standard), and agreement was excellent (κ = 0.84 [0.71; 0.89]) with the same device. Training course combined a median of 4.5 hours for theory and 25 cPOCUS for practice.
Copyright © Oxford University Press. All rights reserved.
Source: Allimant, P., Guillo, L., Fierling, T., et al. (20245). Point-of-Care Ultrasound to Assess Left Ventricular Ejection Fraction in Heart Failure in Unselected Patients in Primary Care: A Systematic Review. Family Practice. 2025; 42(2): cmae040. Published: April, 2025. DOI: 10.1093/fampra/cmae040.
KEY FINDINGS: In this large national cohort, women who experienced any of 5 major adverse pregnancy outcomes had increased risk for HF up to 46 years later. Women with adverse pregnancy outcomes need early preventive actions and long-term clinical care to reduce the risk of HF.
BACKGROUND: Adverse pregnancy outcomes, such as preterm delivery and hypertensive disorders of pregnancy, may be associated with higher future risks of heart failure (HF). However, the comparative effects of different adverse pregnancy outcomes on long-term risk of HF, and their potential causality, are unclear. The authors sought to examine 5 major adverse pregnancy outcomes in relation to long-term risk of HF in a large population-based cohort.
DETAILS: A national cohort study was conducted of all 2,201,638 women with a singleton delivery in Sweden in 1973-2015, followed up for HF identified from nationwide outpatient and inpatient diagnoses through 2018. Cox regression was used to compute HRs for HF associated with preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, while adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. In 48 million person-years of follow-up, 667,774 women (30%) experienced an adverse pregnancy outcome, and 19,922 women (0.9%) were diagnosed with HF (median age, 61 years). All 5 adverse pregnancy outcomes were independently associated with long-term increased risk of HF. With up to 46 years of follow-up after delivery, adjusted HRs for HF associated with specific adverse pregnancy outcomes were: gestational diabetes, 2.19 (95% CI: 1.95-2.45); preterm delivery, 1.68 (95% CI: 1.61-1.75); other hypertensive disorders, 1.68 (95% CI: 1.48-1.90); preeclampsia, 1.59 (95% CI: 1.53-1.66); and small for gestational age, 1.35 (95% CI: 1.31-1.40). All HRs remained significantly elevated (1.3- to 3.0-fold) even 30 to 46 years after delivery. These findings were only partially explained by shared familial factors. Women with multiple adverse pregnancy outcomes had further increases in risk (eg, up to 46 years after delivery, adjusted HRs associated with 1, 2, or ≥3 adverse pregnancy outcomes were 1.51 [95% CI: 1.47-1.56], 2.31 [95% CI: 2.19-2.45], and 3.18 [95% CI: 2.85-3.56], respectively).
Copyright © American College of Cardiology Foundation. All rights reserved.
Source: Crump, C., Crump, J., and Crump, K. (20245). Adverse Pregnancy Outcomes and Long-Term Risk of Heart Failure in Women: National Cohort and Co-Sibling Study. J Am Coll Cardiol HF.. 2025; 3(4): 589–598. Published: April, 2025. DOI: 10.1016/j.jchf.2024.11.004.
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