BMC Cardiovascular Disorders

Background Sedentary behavior (SB) has been associated with cardiovascular disease risk, independent of physical activity (PA) and sleep. However, the effect of replacing SB with PA or sleep on atrial fibrillation (AF) risk remains unclear. Methods We studied 86,096 participants from the United Kingdom Biobank (UKB) and 5,777 from the United States (US) REasons for Geographic And Racial Differences in Stroke (REGARDS) prospective cohort studies who were free of AF at baseline and had valid accelerometry data. The two cohorts were included to evaluate the consistency of associations across distinct populations in the UK and the US, two regions with a high burden of AF. Daily time spent in light PA (LPA), moderate to vigorous PA (MVPA), and SB were derived from accelerometer recordings; sleep was accelerometer-derived in UKB and self-reported in REGARDS. Incident AF was identified using ICD-10 codes (I48.x) listed as either a primary diagnosis, secondary diagnosis, or cause of death through hospital and death registry data linkage in UKB and in a follow-up visit through electrocardiogram and self-reported medical history in REGARDS. Isotemporal substitution models were used to examine replacing 30 minutes of SB with LPA or MVPA in both cohorts and with sleep in UKB on the outcome of incident AF. Results Among the UKB participants [57% female, mean age 56.0 (SD 7.8) years, 98% White race], 4,035 AF cases were identified during a median of 7.9 years of follow-up. Replacing 30 minutes of SB with PA was associated with a slightly lower risk of AF in the minimally adjusted models but the associations were attenuated after full adjustment (LPA: HR 0.99, 95% CI 0.95-1.02; MVPA: HR 1.00, 95% CI 0.99-1.02). The REGARDS participants had an average age of 63 (SD 8.3) years, 55% female, 31% Black and 69% White adults, with 486 AF cases identified. Fully adjusted substitution of 30 minutes of SB with MVPA was associated with lower AF odds (OR 0.80, 95% CI 0.63-1.01), whereas LPA showed no association. In UKB, replacing SB with sleep was not associated with AF risk. The magnitude of the association of MVPA substitution with AF appeared stronger among REGARDS participants aged [&ge;]65 years and those reporting <7 hours/day of sleep. Conclusion Replacing SB with moderate or higher intensity PA may decrease AF risk. In REGARDS, these substitutions appeared to benefit older individuals and those reporting shorter sleep duration. These findings highlight the potential benefit of reducing sedentarism to lower AF burden, warranting validation in future studies.

This study aims to investigate the cardioprotective effects of 4-Hydroxybenzaldehyde (4-HBA) against isoproterenol (ISO)-induced cardiac fibrosis and to elucidate the underlying mechanisms. In vivo, cardiac fibrosis was induced in C57BL/6 mice by subcutaneous injection of ISO, and the mice were treated with 4-HBA or a TGF-{beta} inhibitor. Assessments using echocardiography, histopathology, and Western blotting demonstrated that 4-HBA significantly alleviated ISO-induced cardiac dysfunction, reduced collagen deposition, and attenuated apoptosis in mice. Mechanistically, 4-HBA inhibited TGF-{beta} expression and Smad2/3 phosphorylation. In vitro, ISO was applied to cardiomyocytes (HL-1) and cardiac fibroblasts (MCFs), with or without 4-HBA or TGF-{beta} inhibitor intervention. The results showed that 4-HBA suppressed HL-1 apoptosis and fibroblast proliferation, and significantly reduced the expression of extracellular matrix genes, TGF-{beta} levels, and Smad2/3 phosphorylation in MCFs. These findings indicate that 4-HBA reduces myocardial injury while targeting the TGF-{beta}/Smad2/3 pathway to attenuate cardiac fibrosis, highlighting its potential as a therapeutic agent for fibrotic cardiomyopathy.This study aims to investigate the cardioprotective effects of 4-Hydroxybenzaldehyde (4-HBA) against isoproterenol (ISO)-induced cardiac fibrosis and to elucidate the underlying mechanisms. In vivo, cardiac fibrosis was induced in C57BL/6 mice by subcutaneous injection of ISO, and the mice were treated with 4-HBA or a TGF-{beta} inhibitor. Assessments using echocardiography, histopathology, and Western blotting demonstrated that 4-HBA significantly alleviated ISO-induced cardiac dysfunction, reduced collagen deposition, and attenuated apoptosis in mice. Mechanistically, 4-HBA inhibited TGF-{beta} expression and Smad2/3 phosphorylation. In vitro, ISO was applied to cardiomyocytes (HL-1) and cardiac fibroblasts (MCFs), with or without 4-HBA or TGF-{beta} inhibitor intervention. The results showed that 4-HBA suppressed HL-1 apoptosis and fibroblast proliferation, and significantly reduced the expression of extracellular matrix genes, TGF-{beta} levels, and Smad2/3 phosphorylation in MCFs. These findings indicate that 4-HBA reduces myocardial injury while targeting the TGF-{beta}/Smad2/3 pathway to attenuate cardiac fibrosis, highlighting its potential as a therapeutic agent for fibrotic cardiomyopathy.

Background Atrial fibrillation (AF) is associated with declines in physical function. While physical activity is linked to better physical function in the general population, its long-term impact in people with AF remains unclear. Investigating this relationship could provide insights and inform interventions for this population. Methods 624 participants with AF from the Atherosclerosis Risk in Communities (ARIC) cohort assessed in 2011-2013 were studied. Physical activity was assessed using the modified Baecke Physical Activity Questionnaire. Physical function was measured using the Short Physical Performance Battery (SPPB), grip strength, and 4-meter walk time up to 3 times over an 8-year period, with 4-meter walk speed as a secondary outcome evaluated in supplemental analyses. Confounder-adjusted linear mixed models were used to assess associations between physical activity and change in physical function trajectories over time. Results Participants had a mean age of 78.5 {+/-} 5.4 years, with 52.6% males and 13.8% Black. Median follow-up was 6.6 years. At baseline, greater sport-related leisure time, non-sport leisure time, and total moderate-to-vigorous physical activity (MVPA) were cross-sectionally associated with better physical function. However, physical activity measures were not significantly associated with temporal trajectories in physical function over time. Conclusions In participants with AF, greater habitual physical activity was significantly associated with better baseline physical function but not with future trajectories. Randomized trials are needed to examine whether interventions that improve habitual physical activity or MVPA can improve physical functioning in individuals with AF.

Background: Rates of atrial fibrillation (AF) are lower in Black compared to White Americans. Socioeconomic disadvantage and reduced healthcare access may contribute to lower observed AF incidence in Black populations due to underdiagnosis and underascertainment. Therefore, we evaluated the association of socioeconomic status and healthcare access with AF incidence in a cohort of Black Americans. Methods: 3,240 participants from the Jackson Heart Study, which recruited Black adults from the Jackson metropolitan area in 2000-2004, were followed up through 2016 for incident AF. Socioeconomic position (education and income) and healthcare access (insurance status, difficulty obtaining care, trust in providers, and satisfaction with care) were assessed at baseline. AF was ascertained from study electrocardiograms at baseline and exam 3 and self-reported physician diagnosis at annual follow-up surveys. Multivariable Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between exposure variables and AF incidence adjusting for potential confounders. Results: During a mean follow-up of 11.5 years, 817 incident AF cases were identified. Higher educational attainment and income were associated with a reduced risk of AF. Compared with participants who had less than a high school education, those who attended trade or vocational school or college had an 18% lower estimated hazard of AF (HR 0.82, 95% CI 0.67, 1.02). Likewise, participants in the highest income category had a 39% lower estimated hazard of AF (HR 0.61, 95% CI 0.47, 0.78) compared with those in the lowest. Easier access to healthcare and greater satisfaction with received healthcare were also associated with lower AF risk. Conclusion: Higher socioeconomic status and better healthcare access were associated with lower risk of AF in a cohort of Black Americans. These findings do not support a simple explanation in which socioeconomic disadvantage and poorer healthcare access lead to lower observed AF incidence through underascertainment within Black adults.

Abstract Background The SYNTAX score (SS) quantifies the severity and complexity of coronary artery lesions and serves as an independent predictor of major adverse cardiovascular events and mortality in patients with acute coronary syndrome (ACS). However, few studies have examined the association between SS and in-hospital cardiac arrest (IHCA) in this population. Therefore, this study aims to elucidate the relationship between SS and the incidence of IHCA in patients with ACS. Methods This study consecutively enrolled 3,224 patients undergoing percutaneous coronary intervention (PCI). Logistic regression and restricted cubic spline (RCS) analyses were employed to examine the association between SS and the incidence of IHCA. Participants were stratified into three groups based on SS: Group T1 (SS ? 10, N = 1,097), Group T2 (10 < SS ? 18, N = 1,089), and Group T3 (SS > 18, N = 1,038). The primary endpoint was the incidence of IHCA. Results The overall incidence of IHCA was 4% (N=147). After adjusting for covariates, SS was significantly associated with the incidence of IHCA in ACS patients treated with PCI (OR = 1.0400; 95% confidence interval (CI) = 1.0200?1.0700; p < 0.001). Compared with the T1 group, the T3 group exhibited an increased risk of IHCA (OR = 2.1800; 95% CI = 1.2900?3.6900; p = 0.0040). Subgroup analyses revealed that, after covariate adjustment, patients with ST-segment elevation myocardial infarction (STEMI) had an increased risk of IHCA (OR = 1.0700; 95% CI = 1.0300?1.1100; p < 0.001). Similarly, both patients with diabetes mellitus (DM) (OR = 1.0400; 95% CI = 1.000?1.0700; p = 0.0270) and those without DM (OR = 1.0600; 95% CI = 1.0200?1.1000; p = 0.0020) showed an increased risk. Furthermore, elderly patients (?60 years) (OR = 1.0300; 95% CI = 1.0100?1.0700; p = 0.0210) and non-elderly patients (<60 years) (OR = 1.0500; 95% CI = 1.000?1.1000; p = 0.0470) had an increased risk, as did male patients (OR = 1.0500; 95% CI = 1.0200?1.0700; p = 0.0020). RCS analysis indicated a dose-response relationship between IHCA incidence and SS (nonlinear p-value = 0.906), with the risk of IHCA increasing when SS exceeded 23.975. Incorporating SS into the baseline risk model improved the predictive value for IHCA incidence in ACS patients undergoing PCI (Net reclassification improvement [NRI]: 0.3537 [0.1906?0.5167], p < 0.001; Integrated discriminant improvement [IDI]: 0.0104 [0.0025?0.0183], p = 0.0097). Conclusions Among patients with ACS undergoing PCI, SS is significantly associated with the incidence of IHCA. Consequently, SS may serve as an effective predictor of IHCA in this population.

Background: Sleep disturbance has been associated with atrial fibrillation (AF), but prior studies have largely relied on sleep assessed at a single time point or examined specific sleep disorders. Whether changes in sleep disturbance over time predict AF and, conversely, whether AF predicts subsequent sleep disturbance within the same population is not well established. Methods: We conducted a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT), which enrolled adults with hypertension and increased cardiovascular risk without diabetes. Two prospective analytic cohorts were constructed to examine each direction of the association: 7,232 participants without baseline AF for the analysis of sleep disturbance and incident AF, and 6,079 participants without clinically significant sleep disturbance at baseline for the reciprocal analysis. Sleep disturbance was assessed repeatedly using a 0-3 patient-reported symptom score, with clinically significant sleep disturbance defined as a score [&ge;]2. AF was ascertained from protocol 12-lead ECGs. Time-dependent Cox models evaluated time-updated sleep disturbance in relation to incident AF and time-updated AF in relation to incident clinically significant sleep disturbance, with adjustment for demographic, lifestyle, and cardiovascular risk factors. Results: During a median follow-up of 3.3 years, 189 incident AF events occurred. Time-updated clinically significant sleep disturbance was associated with a 78% higher adjusted risk of incident AF (HR, 1.78; 95% CI, 1.27-2.51). Each 1-point increase in the time-updated sleep score was associated with a 26% higher risk of AF (HR, 1.26; 95% CI, 1.09-1.46). Compared with a sleep score of 0, the adjusted HRs were 1.20 (95% CI, 0.85-1.70), 2.05 (95% CI, 1.33-3.15), and 1.72 (95% CI, 1.03-2.88) for scores of 1, 2, and 3, respectively. In the reciprocal analysis, 1,422 incident clinically significant sleep-disturbance events occurred during a median follow-up of 3.2 years. Time-updated AF was associated with a 59% higher adjusted risk of incident clinically significant sleep disturbance (HR, 1.59; 95% CI, 1.16-2.16). Associations in both directions were consistent across prespecified subgroups, with no significant effect modification. Conclusion: In adults with hypertension, sleep disturbance and AF were prospectively and reciprocally associated when evaluated longitudinally. These findings support a bidirectional relationship between sleep disturbance and AF and highlight the potential clinical relevance of assessing sleep health in patients with or at risk for AF.

Background: Sleep-disordered breathing (SDB) is an established adverse prognostic factor in heart failure (HF). Sleep apnea-specific hypoxic burden (SASHB), which reflects the duration and depth of respiratory event-related oxygen desaturation, has shown stronger prognostic value than the apnea-hypopnea index (AHI) in general populations and patients with coronary artery disease. However, its clinical utility in patients hospitalized due to acute HF remains unclear. Objectives: This study evaluated the prognostic value of SASHB in patients hospitalized for acute HF and compared its performance with AHI for risk stratification and identification of patients who may benefit from positive airway pressure (PAP) therapy. Methods: This post hoc analysis included 230 patients from a prospective single-center observational cohort of adults hospitalized for acute HF. The primary analysis included 178 patients who did not receive PAP treatment. Associations of SASHB and AHI with the composite endpoint of cardiovascular death or rehospitalization for worsening HF were evaluated using Cox proportional hazards models. Model improvement after adding SASHB or AHI to a model including established clinical risk factors was assessed using changes in the C index and Brier score, reflecting changes in model discrimination and prediction error, respectively. In the full cohort, the interaction between PAP treatment and SDB metrics was evaluated using the g-formula. Results: During a median follow-up of 3.7 years, 58 of 178 patients (32.6%) reached the composite endpoint. Both SASHB and AHI were independently associated with the composite outcome after multivariable adjustment. However, only SASHB consistently predicted outcomes across analyses and improved model performance beyond established prognostic factors (bootstrap {Delta} C index, 0.020 [95% CI: 0.008 - 0.031]; bootstrap {Delta} Brier score, - 0.007 [95% CI: - 0.014 to - 0.001]), whereas AHI did not. In the analysis including PAP-treated patients, both SASHB and AHI showed interaction with PAP treatment. Conclusions: In patients hospitalized for acute HF, SASHB showed a consistent independent association with adverse clinical outcomes and provided additional prognostic information beyond AHI. SASHB may improve risk stratification and may help identify patients who are more likely to benefit from PAP therapy.

Background: Growth differentiation factor 15 (GDF-15) has emerged as a prognostic biomarker in patients with non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). Our study evaluated the temporal evolution of GDF-15 in the acute phase and its association with recurrent ischemic events. Methods: Serum samples were collected from patients with NSTE-ACS at admission and at 1 and 3 hours after admission. GDF-15 levels, along with other prognostic biomarkers, NT-proBNP and hs-cTnT, were measured. Spearman rank-correlation coefficients and linear regression models were used to identify the variables associated with GDF-15 levels at admission and with their temporal changes. Associations between GDF-15 and clinical outcomes were evaluated using Cox proportional hazards models. To assess incremental prognostic value, the areas under the curve (AUC) were calculated for each model. Results: GDF-15 levels showed a slight increasing trend within 3 hours of admission. The 1-hour change in GDF-15 was correlated with hs-cTnT changes. Increased 1-hour GDF-15 levels, compared with the admission levels, were associated with a higher risk of recurrent ischemic events during the 1-year follow-up (1.9% vs. 17.5%, P =0.019) and were an independent predictor after adjusting for established clinical variables and biomarkers (adjusted hazard ratio, 1.71 (1.28 to 228.75), P =0.03). Furthermore, serial measurements of GDF-15 provided additional prognostic information beyond traditional risk factors. Conclusions: Serial measurements of GDF-15 of NSTE-ACS patients provided independent and incremental prognostic value for predicting recurrent ischemic events. These findings support the potential utility of GDF-15 as a dynamic biomarker for early risk stratification in the acute management of NSTE-ACS.

Background: Electrocardiographic markers of atrial cardiomyopathy (AtCM) are associated with adverse cardiovascular outcomes. Whether AtCM further refines cardiovascular disease (CVD) mortality risk across increasing cardiometabolic risk factor (CMRF) burden is unclear. Methods: We analyzed 7,083 adults free of baseline CVD. AtCM was defined by the presence of [&ge;]1 ECG marker: prolonged P-wave duration [&ge;]120 ms in lead II, abnormal P-wave axis outside 0-75, or deep terminal negativity of the P wave in V1 <-100 V. CMRF burden was defined as the presence of 0, 1, or [&ge;]2 of hypertension, diabetes, and obesity. CVD mortality was ascertained through December 31, 2006. Results: Among 7,083 participants (mean age 58 years and 48% men), CVD mortality rates increased progressively across the six combined exposure groups. In a multivariable adjusted Cox proportional hazard analysis, AtCM identified higher-risk subgroups within each CMRF burden category, with risk increasing progressively across combined exposure groups and highest among participants with [&ge;]2 risk factors and AtCM (HR 2.25, 95% CI 1.75-2.87). In secondary analyses, a similar pattern was observed for individual CMRFs, with the combination of AtCM and hypertension, diabetes, or obesity conferring the highest risk compared with participants with neither condition (HR (95% CI): 1.58 (1.31-1.89); 2.08 (1.62-2.68); and 1.47 (1.19-1.82), respectively). Conclusions: ECG-defined AtCM refined CVD mortality risk across increasing CMRF burden. Individuals with both AtCM and multiple CMRFs had the highest risk. These findings support the potential role of ECG-based AtCM assessment as a scalable approach to improve cardiovascular risk stratification among individuals with CMRFs.

Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery and has been associated with an increased risk of thromboembolic events. However, cardiac surgical populations are heterogeneous, and the long-term thromboembolic implications of POAF may differ according to the index surgical procedure. This systematic review and meta-analysis evaluated the procedure-specific association between POAF and long-term thromboembolic outcomes after adult cardiac surgery, with particular emphasis on coronary artery bypass grafting (CABG) and isolated valve surgery. PubMed and Scopus were searched from database inception through August 3, 2026. Studies reporting long-term thromboembolic outcomes in patients with new-onset POAF compared with patients without POAF were evaluated, with eligible evidence classified according to the index surgical procedure. Four observational studies were included in the primary quantitative synthesis, with two studies contributing to the CABG analysis and two to the isolated valve-surgery analysis. Adjusted hazard ratios (HRs) were pooled separately by procedure using inverse-variance methods, and a formal between-subgroup interaction test was performed. Following CABG, POAF was associated with an increased long-term thromboembolic hazard (pooled HR 1.147, 95% CI 1.053-1.249; I^2=0%). A stronger association was observed following isolated valve surgery (pooled HR 1.362, 95% CI 1.181-1.573; I^2=0%). The between-subgroup interaction was statistically significant ({chi}^2=4.10, P=0.043), providing exploratory evidence that the magnitude of the association may differ according to surgical procedure. These findings suggest that the long-term thromboembolic implications of POAF may not be uniform across cardiac surgical populations. However, because only two studies contributed to each procedure subgroup and the available evidence was observational, the interaction should be considered hypothesis-generating. Further adequately powered studies with standardized outcome definitions and procedure-specific reporting are required to confirm these findings and determine their implications for long-term risk stratification and anticoagulation strategies.

BackgroundCardiovascular disease risk is higher in men than in women. Although sex differences in aortic wall adaptation following antihypertensive treatment have been reported in acute hypertension models, the response after gradually developing hypertension, which mimics human essential hypertension, remains unclear. This study investigated sex differences in aortic wall adaptation following acute blood pressure reduction after gradually developing hypertension. MethodSeventeen-week-old spontaneously hypertensive rats (SHRs) were assigned to the Hypertensive group or the antihypertensive (Reversal) group (N = 5/sex each). The Reversal group received the antihypertensive drug captopril for 4 weeks to maintain systolic blood pressure below 130 mmHg. Age-matched Wistar Kyoto rats (N = 3/sex) served as normotensive (Normal) group. After the experimental period, arterial wall thickness, circumferential wall stress, smooth muscle cell phenotype, and histological changes were evaluated. ResultsAntihypertensive treatment significantly reduced systolic blood pressure in both sexes. Both male and female SHRs exhibited elevated circumferential wall stress during the gradual development of hypertension. In females, antihypertensive treatment significantly reduced medial thickness compared with the Hypertensive group, whereas males showed no reduction. Circumferential wall stress in female Reversal group did not differ significantly from either the Hypertensive or Normal group, whereas males exhibited a significant reduction in circumferential wall stress compared with the Hypertensive group. Furthermore, the reduced collagen area fraction in the Hypertensive group returned to the normotensive levels only in females following antihypertensive treatment. ConclusionThese findings indicate that vascular remodeling induced by gradually developing hypertension is more effectively reversed by antihypertensive treatment in females than in males.

Background: The systemic immune-inflammation index (SII) is a routinely available blood-derived marker with potential prognostic relevance after coronary artery bypass grafting (CABG). We evaluated associations between preoperative SII and postoperative outcomes. Methods: PubMed, Embase, Scopus and Web of Science were searched to 1 October 2026, with supplementary searches through 14 October 2026. Peer-reviewed observational studies evaluating preoperative SII in adults undergoing CABG were eligible. Methodological quality was assessed using the Newcastle-Ottawa Scale. Compatible categorical associations and exploratory adjusted continuous mortality effects were pooled separately using restricted maximum-likelihood random-effects models; other findings were summarized descriptively. Results: Thirty-one reports were included, with an aggregate sample of 30,976 and possible cohort overlap; five contributed to meta-analysis. Two off-pump cohorts comprising 1,378 patients and 180 atrial-fibrillation events yielded an imprecise crude association with postoperative atrial fibrillation (OR 1.60, 95%CI 0.53-4.82; I2=68%). An exploratory crude synthesis indicated greater intra-aortic balloon pump use with higher SII (OR 2.45, 95%CI 1.16-5.18; I2=51%). Two cohorts with differing follow-up yielded an exploratory adjusted mortality HR of 1.11 (95% Wald CI 1.05-1.18) per study-specific SD increase in log-SII. In one 624-patient cohort, high SII was associated with postoperative acute kidney injury after adjustment (OR 3.35, 95% CI 2.25-4.97).Apparent atrial-fibrillation discrimination varied (AUC 0.587-0.946). Conclusions: Preoperative SII showed associations with selected adverse outcomes after CABG, supporting further evaluation as an accessible prognostic marker. Its incremental value beyond established clinical risk models requires validation. Keywords: Systemic immune-inflammation index; Coronary artery bypass grafting; Atrial fibrillation; Prognosis; Systematic review

Background: Metabolic dysfunction, subclinical myocardial injury, and myocardial stress may contribute to atrial fibrillation (AF), but ther independent and cumulative associations with incident AF are unclear. Methods: We analyzed 7,261 Systolic Blood Pressure Intervention Trial (SPRINT) participants without prevalent AF, who had baseline fasting glucose, high-sensitivity cardiac troponin I (hs-cTnI), and N-terminal pro?B-type natriuretic peptide (NT-proBNP) measurements. By trial design, SPRINT excluded individuals with diabetes, prior stroke or recent symptomatic heart failure or left ventricular ejection fraction <35%. Prediabetes represented metabolic dysfunction, elevated hs-cTnI myocardial injury, and elevated NT-proBNP myocardial stress. Cox models assessed associations of individual domains and the number of abnormal domains (0?3) with incident AF. Secondary analyses examined the 8 mutually exclusive domain combinations. Results: During a median 3.76-year follow-up, 174 participants developed AF. In multivariable adjusted model, prediabetes, elevated hs-cTnI, and elevated NT-proBNP were associated with incident AF (HR, 1.48 [95% CI, 1.07?2.05], 1.84 [95% CI, 1.30?2.60], and 2.35 [95% CI, 1.56?3.55], respectively). AF risk increased progressively with increasing domain burden (P for trend <0.001); each additional abnormal domain was associated with an 82% higher AF risk (HR, 1.82 [95% CI, 1.50?2.22]). Participants with abnormalities in all 3 domains had the highest risk (HR, 6.11 [95% CI, 2.82?13.24]). Conclusions: Prediabetes, subclinical myocardial injury, and myocardial stress were independently associated with incident AF, with progressively greater risk as abnormalities accumulated. These findings support a multidomain framework in which complementary metabolic and cardiac abnormalities collectively characterize susceptibility to AF.

Conventional bibliometrics rely on lifetime citations, obscuring immediate shifts in cardiovascular research paradigms. To track emerging trends in atrial fibrillation management, we performed a comparative bibliometric analysis of the 50 highest-cited original research articles per year in OpenAlex topic T10065 across consecutive 2023 (Class of 2025) and 2024 (Class of 2026) publication cohorts. Articles were ranked using a fixed 18-month post-publication citation window, and extracted concepts were normalized into 719 canonical topics and 32 parent themes using large language model curation. Concept frequency tracking demonstrated a swift technological shift, with pulsed field ablation showing the largest topic frequency increase (+0.08, from 0.30 to 0.38) to become the leading canonical topic in 2024, displacing conventional thermal pulmonary vein isolation (-0.18, 0.40 to 0.22). Simultaneously, stroke prevention focus shifted toward refined predictive modeling, with increases in Risk Stratification and Predictive Models (+0.08, 0.30 to 0.38) and CHA2DS2-VASc scoring (+0.08, from 0.10 to 0.18). High-impact atrial fibrillation research is rapidly pivoting toward non-thermal ablation safety profiling and precision risk stratification, highlighting the utility of fixed-window concept mining for capturing real-time scientific evolution. Online explorer of the result is available at https://pri.pepkio.com.

Background and Objective: Heart rate variability (HRV) analysis provides a non-invasive method for quantifying autonomic modulation from electrocardiographic recordings. However, practical HRV analysis often depends on fragmented workflows, limited signal-quality review, and software tools optimized for either human or preclinical recordings, but not both. This study developed and evaluated HRV-GUI, a MATLAB-based graphical interface for electrocardiogram (ECG)-derived HRV analysis in translational biomedical research. Methods: The HRV-GUI integrates electrocardiographic and RR interval loading, human and rat analysis modes, preprocessing, segment selection, automated R-peak detection, manual peak correction, RR interval generation, multi-domain HRV computation, diagnostic visualization, result export, and session saving/loading. The software was evaluated using deterministic synthetic RR interval datasets, baseline recordings from healthy human controls and healthy rats, and a clinical use-case comparison between healthy controls and patients with diabetic gastroparesis. Results: The HRV-GUI produced expected outputs in synthetic RR validation tests, including constant RR sequences, alternating RR sequences, outlier-containing RR sequences, and low-frequency- or high-frequency-dominant sinusoidal RR modulation. The software generated physiologically plausible HRV profiles in both human and rat recordings. In the clinical use-case analysis, patients with diabetic gastroparesis showed higher heart rate and sympathetic index, together with lower respiratory sinus arrhythmia, absolute low- and high-frequency spectral power, standard deviation of normal-to-normal intervals (SDNN), root mean square of successive differences (RMSSD), percentage of successive RR intervals differing by more than 50 ms (pNN50), Poincare short-term variability (SD1), and Poincare long-term variability (SD2) compared with healthy controls. Conclusions: HRV-GUI provides an integrated biomedical software workflow for ECG-derived HRV analysis. The validation results support its use for controlled RR testing, human and rodent ECG recordings, and clinical autonomic assessment in diabetic gastroparesis.

IntroductionCirculating proteins may augment prognostic scores and provide mechanistic insights for cardiovascular disease. Their role for adding precision to predicting response to therapeutic exercise training is less certain. Older adults with HF frequently experience geriatric syndromes, which may influence response to a rehabilitation intervention (RI). We sought to determine if the functional benefits of a 12-week tailored, structured, and progressive multidomain physical RI program in older adults, following a HF admission, could be estimated by pre-intervention levels of proteins. MethodsHospitalized adults age [&ge;] 60 years with HF were randomized to 12-week multidimensional (aerobic, strength, balance, flexibility) physical therapist-led RI versus attention control (AC). Outcomes included change in the short physical performance battery (SPPB) and 6-minute walk distance (6MWD). At pre-intervention and 12-weeks, 92 circulating proteins associated with CVD and inflammation were measured. Using linear regression, LASSO and ensemble tree-based approaches for flexible feature selection, proteins were selected for stratification of treatment response. Decision trees were developed to incorporate a multi-protein approach to optimize stratification of treatment response (effect measure modifiers [EMM]) for both functional outcomes. Differences in 12-week temporal changes based on RI vs AC and mediation analysis were used to assess possible causal roles for these proteins. ResultsBaseline proteomic data was available in 243/349 participants (69.6%). For SPPB, 2 proteins (GP6, ST2), and for 6MWD, 3 proteins (ALCAM, Gal-4, PECAM-1) were selected as EMMs. For SPPB, a decision tree with ST2 followed by GP6 level identified a differential 12-week improvement in score for RI vs AC from -0.8 (95%CI -1.9, 0.2) to 2.1 (95%CI 1.5, 2.7). For 6MWD, the optimized decision tree was based only on ALCAM with a differential 12-week improvement in score for RI vs AC from 10m (95%CI -17m, 36m) to 85m (95%CI 56m, 113m). However, none of the EMM proteins were mediators of change for the functional outcomes. ConclusionsCirculating proteins related to CVD and inflammation (GP6, ST2, ALCAM) stratify a successful functional response to the REHAB-HF rehabilitation program in older adults following HF hospitalization. Further investigation is needed to identify proteins associated with a causal role for rehabilitation benefits.

Abstract Background: Coronary artery bypass grafting (CABG) is often preferred over percutaneous coronary intervention (PCI) in patients with diabetes mellitus (DM) and multivessel coronary artery disease (MVD), but whether it confers a long-term survival advantage remains unclear. Moreover, whether anatomic complexity modulates this relationship is unknown. Methods: We included 5,615 patients with diabetes and MVD revascularized with contemporary drug-eluting stents (PCI-DES; n=3,410) or CABG (n=2,205) in Alberta, Canada, between 2009 and 2019. The primary outcome was 5-year all-cause mortality. Secondary outcomes were 5-year major adverse cardiovascular events (MACE) and 10-year mortality and MACE in an earlier-era subcohort of 2,103 patients. Inverse probability of treatment weighting with Cox proportional hazards models was used. Interactions between revascularization, Duke Jeopardy Score (DJS), and clinical presentation (stable angina, unstable angina/NSTEMI, or STEMI) were examined. Results: Five-year all-cause mortality did not differ between PCI-DES and CABG (HR, 1.14; [95% CI,0.99-1.31]; P=0.08). However, PCI-DES was associated with a higher 5-year MACE (HR, 1.23; [95% CI,1.10-1.38]; P=0.0004), but lower 10-year all-cause mortality compared to CABG (HR,0.85; [95% CI,0.72-0.99]; P=0.04) with no difference in MACE (HR, 0.97; 95 % CI: 0.85-1.11; P=0.68). Anatomic complexity modified these findings, with lower 5-year mortality after CABG only at higher DJS (Pinteraction=0.003), and lower 10-year mortality after PCI-DES only at lower DJS (Pinteraction<0.0001). Conclusions: In patients with diabetes and MVD, 5-year all-cause mortality did not differ significantly between groups, although PCI-DES was associated with higher 5-year MACE rates. At 10 years, multivessel PCI-DES was associated with lower 10-year mortality and no difference in MACE. Effects were modified by anatomic complexity, favouring CABG at higher DJS and PCI-DES at lower DJS. Our findings should be factored in when contemplating a revascularization strategy in diabetes with MVD.

Background. Information is lacking about everyday psychological states of individuals with a recent myocardial infarction (MI) and whether they influence outcomes. We investigated real world psychological experiences and their association with subsequent cardiovascular events in survivors of an MI. Methods. We studied 287 individuals [&le;] 60 years of age within 8 months from an MI. At the baseline visit, we assessed sociodemographic and clinical factors, and administered a battery of psychological scales of depression, anxiety, anger, perceived stress and social support. Participants underwent a 7-day home monitoring of mood and stress using ecological momentary assessments, and a momentary negative affect (MNA) score, integrating daily mean ratings of sadness, anxiety, anger, distress and loneliness, was calculated. Participants were followed for a median time of 28 months. The study endpoint was a composite index of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal MI, stroke or hospitalizations for heart failure. Cox proportional hazards models adjusted for sociodemographic and clinical factors. Results. The mean age of the sample was 51 years, and 43% of participants were women. Each standard deviation increase in MNA was significantly associated with a 60% increased risk of MACE (95% confidence interval (CI), 20% to 100%), irrespective of adjustment for sociodemographic factors and clinical characteristics. The association was similar in women and men. Momentary positive mood and momentary perceived stress were not associated with MACE. The MNA score showed a larger independent contribution to MACE compared to the combined battery of baseline psychological assessments and the association was independent of baseline history of depression. Conclusion. Among individuals after MI, moment-to-moment negative affect during one week of monitoring in daily life is a powerful predictor of subsequent cardiovascular events. A prospective evaluation of negative mood during everyday living could represent a novel strategy to uncover residual risk after MI.

Hypertrophic cardiomyopathy (HCM) is an inherited disease characterized by the thickening of the heart muscle. Mutations in genes encoding contractile proteins, such MYBPC3 and MYH7 account for over half of patients with familial HCM. MicroRNAs (miRNAs) are pivotal regulators of gene expression that may influence disease progression. Despite their potential significance, there is a scarcity of published data on miRNAs in HCM. Induced pluripotent stem cells (iPSCs) have emerged as valuable tools for modeling various cardiovascular diseases, including HCM. However, the miRNA expression profiles associated with HCM remain largely unexplored within iPSC models. Investigating the differential expression of miRNAs in HCM patients offers a promising avenue to identify potential therapeutic targets for individuals affected by this condition. In this study, we performed an unbiased screen using a microarray (NanoString Technologies) that contained 798 miRNAs to identify differentially expressed miRNAs in iPSC-cardiomyocytes (CM) and myocardial tissues derived from healthy donors and HCM patients with MYBPC3 and MYH7 mutations, identifying miR-9-5p as significantly downregulated in all HCM iPSC-CM and myectomy tissue compared to control. KEGG pathway analysis of gene targets using miRTarBase and g:Profiler revealed that miR-9-5p regulates genes in the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance pathway, which is involved in hypercontractility associated with HCM. Modulation of miR-9-5p expression in vitro using mimics significantly reduced cardiomyocyte size and contractility of MYBPC3 mutant iPSC-CMs whereas healthy control iPSC-CMs treated with antagomiRs exhibited hypertrophy. Our findings identify miR-9-5p as a regulator of cardiomyocyte hypertrophy and contractility, and suggest the miR-9-5p/EGFR tyrosine kinase inhibitor resistance axis as a potential therapeutic target to mitigate hypertrophy and hypercontractility exhibited in HCM.

Background: This study aimed to determine the prevalence of BBB, characterize associated clinical and echocardiographic phenotypes, and evaluate associations with incident cardiovascular diseases and all-cause mortality in the general population. Methods: We analyzed 12-lead electrocardiograms from 14,212 subjects from the Hamburg City Health Study (45-74 years). BBBs were defined using Minnesota Code criteria. We applied elastic net regularization to identify clinical associations, and multivariable Cox models for outcome analyses. The total cardiovascular outcome included all-cause mortality, incident heart failure, myocardial infarction, atrial fibrillation, pulmonary embolism, and stroke. Results: Complete left (cLBBB) and right (cRBBB) bundle branch blocks were prevalent in 0.8% and 2.3% of subjects, respectively. Subjects with complete BBB were generally older with a higher burden of cardiovascular risk factors and comorbidities, cLBBB additionally showed higher N-terminal pro-hormone of brain natriuretic peptide levels. The main predictor of BBB was age. Male sex was an additional predictor for cRBBB, while hypertension, hypercholesterolemia, and reduced left ventricular ejection fraction predicted cLBBB. Both, cLBBB and cRBBB were associated with a reduced left ventricular ejection fraction, increased septal wall thickness, and left atrial enlargement. cRBBB demonstrated right ventricular dilation, whereas cLBBB showed markedly impaired left atrial strain. In adjusted analyses, both BBBs were associated with the total cardiovascular outcome (cLBBB: hazard ratio [HR], 2.71; 95% confidence interval [CI], 1.68-4.39; p<0.001; cRBBB: HR, 1.52; 95% CI, 1.09-2.12; p=0.01). Although both were significantly associated with incident heart failure, myocardial infarction, and atrial fibrillation, cLBBB uniquely was associated with all-cause mortality, whereas cRBBB distinctly was associated with incident stroke. Conclusion: In the general population, BBB is a high-risk phenotype characterized by subclinical cardiac alterations and a markedly worse long-term outcome. These findings underscore the importance of early risk stratification. Proactive clinical management in otherwise asymptomatic individuals presenting with these conduction disturbances should be considered.