Abstract Background and Aims Familial clustering of congenital heart defects (CHD) is well recognised, but variation across cardiac phenotypes and kinship remains incompletely understood. We examined lesion-specific familial aggregation by distinguishing occurrence of the same broad lesion category (concordant) from different lesion categories (discordant) and described lesion co-occurrence within individuals and families. Methods We conducted a nationwide population-based case–control study including 51,778 individuals with CHD and 522,543 matched controls born in Sweden 1987-2017, with relatives identified through national registers. Lesion categories included heterotaxy, complex CHD, conotruncal defects, atrioventricular septal defect (AVSD), anomalous pulmonary venous return, left- and right-sided obstructive lesions, septal defects, valve defects, patent ductus arteriosus in term infants, other specified CHD, and unspecified CHD. Logistic regression estimated adjusted odds ratios (ORs) for concordant and discordant aggregation by lesion category and kinship. Non-hierarchical analyses examined lesion co-occurrence. Results Among lesion categories with sufficient exposed individuals, concordant aggregation was consistently stronger than discordant. The strongest concordant associations were observed for AVSD (OR 17.40, 95% CI 7.77–38.99), valve defects (13.96, 7.83–24.87), conotruncal defects (11.12, 6.59–18.75), left- and right-sided obstructive lesions. Discordant associations were elevated but lower and relatively similar across lesion categories. Concordant aggregation was higher among mothers, full siblings, and offspring, and lower among fathers and half-siblings. Multiple lesions were recorded in 19% of cases, clustering mainly within the same broad categories. Conclusions Familial CHD history carries phenotype- and kinship-specific information beyond CHD presence in relatives, supporting structured interpretation by lesion category and biological relationship.
Abstract Aims To determine the relationship between B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) and body mass index in patients with chronic heart failure (HF). Methods Systematic review with narrative synthesis of original studies in adults with confirmed chronic HF that reported BNP or NT-proBNP stratified by BMI. Five databases were searched (June 2024); English-language full-text articles were included. Results We included 22 articles (21 studies; 24,460 patients, 36% female). Using each study’s own definitions, 11 articles (50%) enrolled patients with HF with reduced ejection fraction (HFrEF), 7 (32%) with preserved ejection fraction (HFpEF) and 4 (18%) a range of ejection fractions. Higher BMI was associated with lower BNP and/or NT-proBNP concentrations in 21 of 22 articles; one TOPCAT analysis reported a U-shaped relationship. Heterogeneity in BMI categories, HF definitions, assays and covariate adjustment precluded meta-analysis.. Conclusions This systematic review provides evidence for an inverse relationship between BMI and natriuretic peptides (NPs) in chronic heart failure suggesting that BMI is an important factor to consider when interpreting these natriuretic peptide concentrations. The clinical implication of these findings requires further investigation and may provide an opportunity to tailor approaches for risk stratification and treatment in this population.
Abstract Aims The causal relationship between childhood adiposity and adult arterial plaque burden remains to be established. Methods and results Two-sample Mendelian randomization (MR) was used to examine the associations of genetically predicted childhood body mass index (BMI) with coronary plaque burden (PB), coronary artery calcification (CAC), and carotid plaque (CP). Multivariable MR and mediation analyses were further performed to explore whether adult BMI, lipid traits, hypertension, or type 2 diabetes (T2D) mediated these associations. A genetically predicted 1-standard deviation increase in childhood BMI was associated with higher coronary PB (β = 0.326; 95% CI, 0.142–0.511) and CAC (β = 0.114; 95% CI, 0.032–0.196), but not CP (β = −0.095; 95% CI, −0.264 to 0.073). Multivariable analyses showed that these associations remained significant after adjustment for low-density lipoprotein cholesterol and T2D, but were attenuated after adjustment for adult BMI, high-density lipoprotein cholesterol, triglycerides (TG), or hypertension—each identified as a significant mediator, with TG accounting for the largest mediated proportion (15.6% for PB; 16.2% for CAC). Conclusions This MR study supports a causal role of childhood adiposity in adult coronary PB and CAC, mediated substantially through adult adiposity, dyslipidemia, and hypertension.
Abstract Background Left ventricular thrombus (LVT) is a serious thromboembolic complication of cardiac dysfunction. Vitamin K antagonists (VKAs) are the historical standard therapy, but have limitations. While direct oral anticoagulants (DOACs) offer practical advantages, their efficacy and safety in LVT remain uncertain. This meta-analysis aimed to compare the efficacy and safety of DOACs versus VKAs for the treatment of LVT. Methods We conducted a meta-analysis by systematically searching electronic databases from inception to December 2025. A random-effects model was used for all analyses. The primary outcome was LVT resolution. Secondary outcomes included ischemic stroke, non-cerebral systemic embolism (SE), the composite of stroke and SE, any bleeding, major bleeding, and mortality. Results A total of 35 studies (7 RCTs and 28 retrospective cohort studies), with 6,437 patients (DOACs n = 2,421, VKAs n = 4,016), were included in the analysis. DOACs showed a non-significant trend toward higher LVT resolution than VKAs (odds ratio [OR] 1.17; 95% confidence interval [CI] 0.99–1.39). DOACs were associated with a lower risk of stroke (OR 0.77, 95% CI 0.65–0.92), while SE rates remained comparable (OR 0.79, 95% CI 0.54–1.15). DOACs were associated with a significantly lower risk of major bleeding compared to VKAs (OR 0.62, 95% CI 0.48–0.79; p < 0.001). When analyses were limited to only randomized trials or post–acute coronary syndrome, efficacy and safety were similar across anticoagulants. Trial sequential analysis indicated indecisive results, highlighting the need for further clinical trials. Conclusions DOACs showed overall efficacy similar to VKAs for the treatment of LVT, with lower rates of major bleeding. Despite the large number of included studies, the current evidence base remains inconclusive due to the predominance of observational studies, underscoring the need for additional large, well-designed clinical trials.
Abstract Aims We aimed to evaluate the real-world use of contemporary international ECG interpretation criteria in athletes, and to compare practices, clinical decision-making, and perceived barriers between specialist and nonspecialist professionals across Europe. Methods and results Two sets of structured questionnaires were developed and distributed to either sports cardiologists or nonspecialist professionals. Knowledge of international guidelines, experience in ECG interpretation, and confidence levels in clinical decision-making across various clinical scenarios were evaluated. An open-ended questionnaire was also developed to explore aspects of ECG interpretation, medicolegal issues, relevant legal frameworks across European countries, and personal thoughts on possible future revisions to the documents. The questionnaires were revised and edited by expert sports cardiologists, affiliated with EAPC. Data were analysed both quantitatively and qualitatively. A total of 242 participants across Europe were included; 66% were male and 57% worked in public hospitals. Nonspecialists demonstrated uncertainty in standard definitions, classification systems, and key applications of ECG criteria. These findings highlight variability in preparticipation screening (PPS) practices and areas of uncertainty in clinical decision-making, alongside concerns regarding access to specialist services. Notably, 25% of specialists favoured a flexible interpretative approach beyond current standard criteria. The majority supported the need for updated guidance and improved description of specific ECG indices, including ventricular ectopy (83%), QRS fragmentation (83%), and low-amplitude QRS complexes (78%), alongside recognition of the potential role of artificial intelligence–based models. Gaps in knowledge, training, and practice were identified, and both groups emphasized medicolegal and pathway challenges. Conclusion This international survey provides a contemporary real-world overview of ECG interpretation and PPS practice in athletes across Europe and revealed substantial heterogeneity in access to services, training, interpretation uncertainty, referral pathways, and medico-legal frameworks.
