BMC Cardiovascular Disorders

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: The Cohorts for Heart and Aging Research in Genomic Epidemiology - Atrial Fibrillation (CHARGE-AF) score is a validated tool for estimating 5-year risk of atrial fibrillation (AF). We aimed to evaluate the utility of repeated CHARGE-AF scores for improving AF risk prediction. Methods: We analyzed participants from the Atherosclerosis Risk in Communities (ARIC) study with complete data from the first four clinic visits (9-year period) and with no prevalent AF by visit 4 (analysis baseline; N = 10,188). CHARGE-AF scores were calculated for each visit using clinical and demographic variables. Incident AF was determined from electrocardiograms, hospital discharge codes, and death certificates over a median follow-up of 19.5 years. Four Cox regression models were assessed: model 1 included only the visit 4 CHARGE-AF score, and subsequent models added prior CHARGE-AF scores in stepwise fashion. C-statistics were used to evaluate model discrimination, and comparison of observed versus predicted risk was employed to evaluate calibration. Secondary analysis restricted follow-up to five years. Results: During follow-up, 2,519 participants developed AF (14.2 cases per 1,000 person-years). The mean age of participants at start of follow-up was 62.8 (standard deviation 5.6) years. In the primary analysis, each 1% increase in the visit 4 CHARGE-AF score was associated with incident AF (Model 1 HR = 1.14, 95% CI 1.13-1.15). Addition of scores from prior visits did not significantly improve model discrimination (C-statistic: 0.702-0.703 for all models). Sex modified the association between a 1% increase in CHARGE-AF score and incident AF, with a stronger association among females (Model 1 HR = 1.21, 95% CI: 1.19-1.22) than among males (HR for model 1 = 1.12, 95% CI: 1.11-1.13). Similar patterns were observed in the secondary (5-year restricted) analysis. Conclusions: A single measurement of the CHARGE-AF score provided strong predictive value for incident AF, with the addition of prior scores offering limited incremental benefit. These findings suggest that, in clinical settings with longitudinal data, the most recent assessment is sufficient for AF risk prediction.

Background: Short and long sleep duration have been linked to atrial fibrillation (AF), but their influence on arrhythmia recurrence after catheter ablation is uncertain. We evaluated the association between nocturnal sleep duration and the risk of recurrent arrhythmias in patients undergoing catheter ablation for AF in the PREDIMAR trial. Methods: The PREDIMAR study is a multicentre, randomized, controlled, single-blind trial evaluating a Mediterranean diet enriched with extra-virgin olive oil for preventing arrhythmia recurrence after catheter ablation for AF. Nocturnal sleep duration was categorized as adequate (6?8 h/day) or inadequate (<6 h/day or >8 h/day). Multivariable Cox regression models estimated the association between sleep duration and the risk of recurrent atrial flutter (AFL) or AF. Results: Among 720 participants, we observed 226 incident cases of AF relapse and 107 cases of AFL. Inadequate nocturnal sleep duration was associated with a significantly higher risk of AFL recurrence compared with adequate sleep (adjusted HR = 1.87; 95% CI 1.18?2.96). No significant association was observed for AF recurrence (HR = 0.99; 95% CI 0.70?1.41). The association with AFL recurrence was particularly evident in patients with persistent AF at baseline before ablation (adjusted HR = 3.42; 95% CI 1.47?7.97), whereas no significant relationship was observed in those with baseline paroxysmal AF. Conclusions: Inadequate nocturnal sleep duration (<6 h/day or >8 h/day) may increase the risk of AFL recurrence following AF ablation. These findings highlight the relevance of sleep habits as a modifiable behavioural factor potentially influencing post-ablation outcomes.

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.

BackgroundCardiac fibrosis is a central driver of adverse remodeling in heart failure with reduced ejection fraction (HFrEF), yet therapies directly targeting these pathways remain less established. We investigated the role of a pharmaceutical-grade synthetic (s) cannabidiol in HFrEF using an invitro and in vivo strategy. MethodsHFrEF was induced in 12-week-old C57BL/6J mice using angiotensin II, L-NAME, and salt exposure. A 5-week (w) s-cannabidiol course was administered either concomitantly (beginning at week 0) during disease induction or after disease induction (beginning at week 4). Echocardiography, cardiac morphological characterization was performed at 5 and 9 weeks of the experiment. Cardiac tissue was processed for RNA extraction. Standard statistical and informatics methodology was used to compare groups. ResultsAt 5 weeks, mice in the concomitant s-cannabidiol group had reduced cardiomyocyte hypertrophy and fibrosis area with better isovolumetric relaxation time, ejection fraction, and fractional shortening compared to HFrEF mice. In the treatment after disease induction model, at 9 weeks, s-cannabidiol treated mice maintained therapeutic effect compared to 5w HFrEF mice but also had enhanced structural and functional recovery compared to mice that recovered naturally. Bulk RNA-sequencing analysis demonstrated a significant transcriptional change in HFrEF compared to controls, with s-cannabidiol partially shifting the cardiac transcriptome away from the failing state and attenuates the HF-enriched transcriptional programs of oxidative stress, inflammatory signaling, hypoxia, apoptosis, p53/MYC/mTORC1/E2F remodeling, and EMT/fibrotic remodeling, while enriching lipid/peroxisomal metabolic pathways. In an invitro HUVEC model of Endothelial to Mesenchymal Transition (EndMT), s-cannabidiol inhibited the transition and also reversed established EndMT, with these effects attenuated by pharmacologic inhibition of CB2 and PPAR{gamma}, but not CB1 receptors. Conclusionss-cannabidiol attenuates adverse remodeling in experimental HFrEF, promotes recovery after injury, and is associated with suppression of EndMT-related programs mediated through CB2/PPAR{gamma}-linked endothelial signaling.

Background: Black individuals have a lower incidence of atrial fibrillation (AF) than White individuals despite a higher burden of many traditional cardiovascular risk factors. Differences in left atrial (LA) structure and function by race could partly explain the observed pattern of AF risk. Methods: This analysis included 4,576 (978 Black and 3,598 White) participants from the Atherosclerosis Risk in Communities (ARIC) study, followed between 2011 and 2021. The association of selected echocardiographic measures of LA structure and function with AF incidence was evaluated with race-specific Cox proportional hazards models with adjustment for sociodemographic and clinical covariates. Additional analyses assessed whether LA measures attenuated the association between race and incident AF. Results: The analysis included 778 AF cases (113 in Black and 665 in White participants, mean age 75 years). Larger LA size and worse LA function were associated with higher AF risk in both Black and White individuals, with most associations of similar magnitude in both groups, except for a slightly stronger association of LA reservoir strain in Black than White participants (Black: hazard ratio (HR) 0.89, 95% CI 0.86-0.92 per 1% increase; White: HR 0.94, 95% CI 0.92-0.95, p for interaction = 0.01). In the overall sample, White participants showed higher AF risk compared to Black participants (HR 1.59, 95% CI 1.24-2.03). Adjustment for most individual LA measures did not attenuate the association between race and AF risk. Conclusion: Larger LA size and worse LA function were associated with incident AF in both Black and White ARIC participants. However, these measures did not explain the lower AF incidence observed among Black participants. LA remodeling appears to be an important predictor of AF risk, but it is not the primary explanation for the Black-White AF paradox.

Background: The PREVENT (Predicting Risk of CVD EVENTs) equations estimate the risk of incident cardiovascular disease (CVD) in primary prevention patients. We hypothesized that risk factors incorporated in the equations may be relevant to prognosis in heart failure (HF) and investigated the association between estimated CVD risk and clinical outcomes in patients with preserved ejection fraction (HFpEF). Methods: We estimated the 10-year CVD risk using the PREVENT equations in 278 patients hospitalized for acutely decompensated HFpEF (median 75 years, 51.4% male). We divided them into four groups according to the quartiles of estimated CVD risk and followed them to observe major adverse cardiovascular events (MACE), a composite of all-cause death, HF hospitalization, and stroke. Results: MACE occurred in 125 patients (45.0%) over a median follow-up of 1,050 days. The estimated CVD risk classification was an independent predictor for MACE (p=0.02) in the multivariable Cox proportional hazard model. There was a difference in MACE-free survival across the four quartile groups (p<0.001 by log-rank test), and the lowest CVD risk group had significantly lower MACE incidence than other groups. The estimated CVD risk provided incremental prognostic value beyond N-terminal pro-B type natriuretic peptide (C-index: 0.626 vs, P=0.009). The predictive value of the estimated CVD risk for MACE at 1 year was comparable to that of the MAGGIC score (AUC 0.676 vs. 0.639, p=0.42). Conclusions: The 10-year CVD risk estimated by the PREVENT equations had a moderate predictive value for MACE in patients hospitalized for HFpEF.

Abstract Background: Most animal models of HCM are mouse-based, but the thin interventricular septum in mice makes it difficult to clearly distinguish pathological hypertrophy, which introduces substantial errors and constrains basic HCM research. Cats develop HCM spontaneously, and the common MYBPC3-A31P variant in cats is homologous to human mutations in both genetics and pathology, with a larger body size that makes them suitable as large-animal models. This study examines how heterozygosity or homozygosity for the p.A31P mutation (c.91G>C) in the MYBPC3 gene affects the phenotype and severity of HCM in affected cats, with the aim of establishing an ideal large-animal model for clinical risk stratification and precision diagnosis and treatment of human HCM. Methods: Forty-nine Maine Coon cats were enrolled and stratified into homozygous mutant (HOM, n=8), heterozygous mutant (HET, n=26), and wild-type (WT, n=15) groups. All cats underwent echocardiography, blood pressure measurement, physiological assessment, hematological and biochemical analyses, and cross-species sequence conservation analysis. Results: No significant differences in baseline characteristics including age and body weight were observed among groups (P>0.05). HOM cats exhibited significantly higher left ventricular outflow tract pressure gradients and greater basal septal thickness compared to WT cats (P<0.05), with HET cats showing intermediate values. Analysis of hematological and serum biochemical parameters revealed no evidence of systemic inflammation or hepatic injury. Sequence conservation analysis confirmed that the A31 residue is highly conserved across mammalian species. Conclusions: This study provides a phenotypic characterization of Maine Coon cats carrying the MYBPC3-A31P mutation, revealing marked gene-dose effects on cardiac structure and function, with homozygous individuals exhibiting more severe phenotypic features. This model serves as a large-animal translational platform that not only clarifies genotype-phenotype correlations but also supports risk stratification and precision therapeutic strategies in human HCM. Its spontaneous nature and genetic homology to human disease make it particularly valuable for bridging preclinical findings to clinical application.

Abstract Background: Heart Failure is a complex clinical syndrome of growing public health concern in sub-Saharan Africa, yet the data from Sierra Leone are absent. The aim of the study is to characterise the clinical profile, etiological and temporal trends of hospitalised HF patients at Choithrams Memorial Hospital (CMH), Freetown, Sierra Leone, to confirm specific management strategies. Methods: This single-center, retrospective observational cohort study analysed data on HF patients (>18years) admitted at the CMH between January 2021 to 31 December 2025. The clinical definition of HF was based on the Framingham criteria and the European Society of Cardiology (ESC) guidelines , including standard echocardiographic parameters. All variables, including patients demographics, HF. phenotype, aetiology, medical history and hospital outcomes were extracted from the digital record. Non-parameteric tests, multivariable logistic regression to identify variables associated with etiology, Wilcoxon rank-sum test to compare groups and Kruskal-Wallis test to analyse trends over time were utilised. Result: A total of 765 patients were included in the study, with a median age of 53 years (IQR 42-61) and male predominance of 55.3%. Patients with recurrent HF (60.9%) were more common than those with de novo HF (39.1%), were older (54 years vs 53 years), had a higher comorbidity burden (34% vs 4%, p < 0.001), and presented with a cold-wet hemodynamic profile (18.4% vs 8.4%, p < 0.001). HFrEF (61.3%) was the most predominant phenotype, though HFpEF increased with age. Dilated Cardiomyopathy (37.0%), Hypertensive Heart Disease (31.2%) and Valvular Heart Failure (17.1%) were the leading etiologies, while ischemic heart disease (6.3%) was relatively uncommon. A majority of the patients were referred (77.9%), and 50.8% presented with NYHA IV. The strongest independent predictor for HF was hypertensive heart disease [AOR = 17.81; C.I 95%: (3.13-48.76), p <0.001]. An analysis of the trends in etiologies and demographics over the five-year period demonstrated no significant changes (all p-values > 0.05 for age, sex, aetiology, and most comorbidities). Conclusion: HF affects the younger adult population in Sierra Leone and is mainly caused by DCM and HHD. The late case presentations, the high prevalence of recurrent HF, and the associated high burden of comorbidities emphasize an urgent need to develop and implement improved strategies for the prevention, early detection, and long-term management of HF within Sierra Leone's healthcare system.

Background: Pulmonary arterial hypertension (PAH) is a serious disease with poor prognosis, especially in infants or preterm babies and there is still no optimal treatment for this disease. Noradrenalin (NE) is a vasoactive mediator which is released by sympathetic ganglion. According to previous studies, NE/1-adrenoreceptors is not only in regulating normal physiologic responses, but also in the pathogenesis of PAH. However, the mechanisms of NE in PAH are not fully understood. Methods: Human PASMC (PASMC) was used in this study. Cell viability assay and Wound healing assay were used to evaluate the proliferation and migration of PASMC. Immunoprecipitation and western blots analysis were used to investigate the mechanisms which involved in NE-induced PASMC proliferation. Results: We investigated that NE could induce human PASMC proliferation and migration. Furthermore, we first find that endothelin 1 (ET-1) signaling pathway plays an important role in NE-induced PASMC proliferation. ET1 is a critical molecular which is known for regulating cell growth and migration. We investigated that NE could increase NE-1 secretion, further enhancing ET-1 bind to its receptors. For further clarifying the downstream signals in NE/ET-1 induced PASMC proliferation, we detected the phosphorylation and expression levels of ERK and JNK. Conclusions: By combining the results from ours and previous studies, we believed that JNK/c-jun pathway may play an important role in NE-induced PASMC proliferation. Key Words: Noradrenaline; Pulmonary Arterial Hypertension; Pulmonary Artery Smooth Muscle Cells; Endothelin-1; JNK/c-Jun Signaling.

Background: Electrocardiographic (ECG) markers of atrial cardiopathy (AC) are associated with stroke mortality, but whether this association is modified by blood pressure (BP) is unknown. Methods: We analyzed 7,191 adults free of cardiovascular disease from the Third National Health and Nutrition Examination Survey who underwent baseline ECG. AC was defined by three ECG markers: prolonged P-wave duration 120 ms), abnormal P-wave axis (<0{degrees} or >75{degrees}), and deep terminal negativity of the P wave in V1 (<100 V). AC burden (per additional AC marker) and AC presence (1 vs. 0 markers) were examined in relation to stroke mortality using Cox proportional hazards models. Participants were stratified by BP as normal/elevated (<130/80 mmHg), stage 1-2 hypertension (130-159/80-99 mmHg), or severe hypertension (160/100 mmHg). Interaction by BP category was assessed. Results: During a median follow-up of 13.8 years, 183 stroke deaths occurred. In multivariable adjusted model, AC burden was associated with a 41% higher risk of stroke mortality (HR (95%CI): 1.41 (1.13-1.77)). This association was significantly modified by BP (interaction P=0.003). The HRs (95% CIs) per additional AC marker were 0.88 (0.52-1.49), 1.39 (1.03-1.88), and 2.94 (1.82-4.75) for normal/elevated BP, stage 1-2 hypertension, and severe hypertension, respectively. A similar pattern of associations was observed for AC presence, although the interaction with BP was not statistically significant. Conclusions: ECG-defined AC burden was independently associated with stroke mortality, with substantially stronger associations among individuals with severe hypertension, supporting BP as an important modifier of its prognostic significance.

Background: Cardiovascular diseases (CVD) are the leading cause of mortality worldwide. Historically, male sex was considered a cardiovascular risk factor however recent accumulating data suggest complex interaction between sex and CVD leading to specific inequalities affecting both males and females with specific cardiometabolic features. Methods: Data from a large nationwide screening cohort were used to assess the cardiometabolic burden among males vs females in Algeria. The prevalence and adjusted Odds Ratio (aOR) of major CVD diseases were compared across the study cohorts. Records of systolic (SBP) and diastolic blood pressure (DBP), as well as findings of clinical examination, ECG, and echocardiography were collected and reviewed for analysis. Results: A total of 21,522 patients were included among them 12,015 were females and 9,507 were males. The latter group had higher age (median age: 60 [51.00-68.00] vs 57 [49.00-65.00] years; p< 0.001), sitting DBP (83 [76.00-92.00] vs 80 [75.00-90.00]; p< 0.001), standing SBP (142 [130.00-160.00] vs 140 [124.00-154.00] mmHg; p< 0.001), smoking (22.1% vs 0.9%; p<0.001) and unknown diabetes (15.2% vs 13.2%; p< 0.001) rates. Moreover, females showed an overall worse cardiometabolic profile while males had a greater burden of ischemic heart disease, arrhythmia, conduction abnormalities, and left ventricular dysfunction. On multivariate analysis, female sex was correlated with higher aOR for known hypertension (aOR:1.55; 95%CI:1.40-1.72; p<0.001) and known dyslipidaemia (aOR: 1.23; 95%CI:1.09-1.39; p=0.001). On the other hand, female sex predicted lower risk of any CVD (aOR:0.84; 95%CI:0.72-0.98; p=0.028) and known cardiovascular disease (aOR: 0.79; 95%CI: 0.67-0.94; p=0.007). Conclusion: CVD affect males and females differently which reflects multifaceted biological, cardiometabolic, and sociodemographic disparities. These findings highlight the need to reduce the sex gap in the prevention and management of CVD. Keywords: Cardiovascular disease; Sex; Management disparities; Sex Gap; North Africa; Algeria

Background: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CTCA) has emerged as a novel non-invasive biomarker of coronary inflammation and cardiovascular risk. The degree to which PCAT reflects local or systemic inflammation remains uncertain. We hypothesized that the presence, location and extent of PCAT would be associated with transcoronary or transcardiac cytokine gradient. Methods: This prospective cohort study involved 31 adults with stable coronary artery disease who underwent clinically indicated CTCA within 90 days of invasive coronary angiography. Patients with acute coronary syndromes or unstable angina were excluded. Blood samples were obtained from peripheral vein, coronary sinus, aortic root, and right coronary artery at time of cardiac catheterization. Plasma interleukin-6 (IL-6) and interleukin-1{beta} (IL-1{beta}) concentrations from each site were used to calculate transcardiac and transcoronary cytokine gradients. PCAT attenuation was measured using semi-automatic software by readers blinded to clinical and biochemical endpoints. Results: Participants were predominantly male (76%), aged 66.6 {+/-} 9.4 years, with a high prevalence of hypercholesterolemia (76%), hypertension (73%), and diabetes (36%). Mean PCAT attenuation was -74.8 HU (RCA), -70.3 HU (LCx), and -73.6 HU (LAD). Regression analyses showed no significant associations between PCAT attenuation and IL-6 gradients across any coronary territory (all p >0.40; R2 {approx} 0), including in plaque-free subgroup analyses. IL-1{beta} was below the assay detection limit in 81% of participants; analyses using non-parametric testing and logistic no association with PCAT attenuation. RCA (OR 0.96, 95% CI 0.88-1.06, p=0.46), LCx (OR 1.00, 95% CI 0.91-1.09, p=0.94), LAD (OR 0.99, 95% CI 0.90-1.08, p=0.81). Conclusion: In a cohort with predominantly stable coronary disease, PCAT attenuation was not associated with intracardiac or intracoronary IL-6 or IL-1{beta} gradients, including in plaque-free vessels. These findings suggest that PCAT attenuation may not reflect active cytokine-mediated coronary inflammation in stable disease.

Background: Sex-related disparities in acute coronary syndrome (ACS) recognition and management remain a global health concern. We examined sex-based differences in clinical presentation, management, and outcomes among patients with chest pain attended by emergency medical services (EMS) across Brazil. Methods: We conducted a retrospective study using a registry from 14 Brazilian states between January 2020 and June 2024 within a private hospital network. Patients with chest pain were classified by cardiologists as unstable angina (UA), ST-elevation myocardial infarction (STEMI), or non-ST-elevation myocardial infarction (NSTEMI). Multivariable regression evaluated sex differences in diagnosis, treatment, and outcomes. Sensitivity analyses included state-clustered standard errors and E-values for unmeasured confounding. Results: Among 7,171 patients with confirmed ACS (68.2% male), median age was 63.0 years [IQR 20.0]; women were older than men (67.0 [20.0] vs 61.0 [19.0] years). Diagnoses were UA in 46.7%, STEMI in 18.8%, and NSTEMI in 34.6%. Overall, 91.7% received aspirin and 89.6% at least one additional antiplatelet agent. After adjustment, women had higher odds of chest pain classified as probably or possibly ischemic versus definitely ischemic (adjusted OR 1.51 [95% CI 1.33-1.72] and 1.60 [1.37-1.86], respectively) and lower odds of STEMI and NSTEMI relative to UA (adjusted OR 0.59 [0.51-0.68] and 0.74 [0.66-0.83], respectively). Door-to-ECG time was longer in women unadjusted ({beta}=1.53 minutes [0.24-2.82]) but not after adjustment ({beta}=1.04 [-0.27 to 2.36]). In-hospital mortality did not differ between sexes, with no evidence of excess short-term mortality in women. Conclusions: Within a private hospital network in Brazil, women with confirmed ACS were more often classified with less definitely ischemic chest pain and less frequently with STEMI or NSTEMI than men. Door-to-ECG differences did not persist after adjustment, and mortality did not differ by sex. These findings support sex-sensitive triage and diagnostic protocols to reduce inequities in ACS recognition and treatment.

Background: Approximately 40 million individuals in the US have diabetes, and 6.5 million are also afflicted with congestive heart failure (CHF). This paper outlines the natural history of CHF in T2DM and compares CHF outcomes between patients with and without T2DM. Methods: We performed a retrospective analysis of prospectively collected data from 2,008 patients hospitalized for CHF exacerbation between December 2016 and June 2019. Propensity score matching was used to match diabetics and nondiabetics. Outcomes included survival and readmission rates at 28 d, 3 mo and 6 mo, as well as comparison of echocardiographic findings. Results: A total of 2,008 patients were included. After matching, 492 patients were included, with 244 diabetics and 248 nondiabetics. After matching, readmission rates within 28 days (p=0.625) were not different, but there was a trend for higher readmission rates among diabetics at 3 months (29.3% vs. 21.5%, p=0.049) and 6 months (44.3% vs 35.8%, p=0.053). Echocardiographic characteristics, including LVEF (p=0.135), LV EDV (p=0.707), maximum velocity of mitral valve E wave (p=0.407), maximum velocity of mitral valve A wave (p=0.050), E/A ratio (p=0.501) and tricuspid valve regurgitation pressure (p=0.668) were not different in the two groups. However, tricuspid valve regurgitation velocity was higher in diabetics (3.1 vs 2.9, p=0.003). Conclusions: Although diabetes poses an additional burden for patients with CHF, survival is similar in diabetics and nondiabetics. Nonetheless, readmission rates may be higher among diabetics. Tricuspid return velocity is higher in diabetics, suggesting early pulmonary vasculature remodeling.

Background: Obstructive hypertrophic cardiomyopathy (oHCM) causes substantial symptom burden and impaired functional capacity. Mavacamten has emerged as a targeted pharmacologic treatment, whereas alcohol septal ablation (ASA) is an established septal reduction therapy (SRT). Direct comparative real-world data remain limited. Methods: In this propensity-controlled observational study, longitudinal registry data from Heidelberg University Hospital were analyzed. Consecutive adults with oHCM, NYHA class ?II symptoms, and a maximum LVOT gradient ?50 mmHg treated with mavacamten or ASA were included. The cohort comprised 107 ASA- and 113 mavacamten-treated patients. Follow-up was performed at 6 and 12 months. The primary endpoint was a composite adverse clinical outcome including cardiovascular death, heart failure hospitalization, SRT, heart transplantation, ventricular assist device implantation, permanent pacemaker implantation for third-degree atrioventricular block, or decline in left ventricular ejection fraction to <40%. Results: Both treatments showed significant improvement in NYHA class and LVOT gradient reduction over 12 months. Mean LVOT gradient decreased from 100.3 to 44.2 mmHg after ASA and from 85.7 to 18.4 mmHg with mavacamten at 12 months (both p<0.001). Between-group differences were not significant at 6 months, whereas residual LVOT gradient was lower with mavacamten at 12 months (p=0.004). NT-proBNP declined in both groups and was lower with mavacamten at both follow-up visits (both p<0.001). Third-degree atrioventricular block occurred more frequently after ASA (6.5% vs 0%, p=0.002). The composite endpoint occurred in 13 ASA- (12.1%) and 4 mavacamten-treated patients (3.5%) (p=0.003), with higher 1-year event-free survival in the mavacamten group (HR 0.19; 95%-CI 0.06-0.60; p=0.001). Conclusions: In this real-world comparative study, both ASA and mavacamten improved symptoms and LVOT obstruction in oHCM. Mavacamten was associated with a more favorable short-term hemodynamic and safety profile at 12 months.

Background: A growing burden of cardiovascular risk factors has raised cardiovascular disease-related mortality in Sub-Saharan Africa (SSA), driving higher prevalence of heart failure with reduced ejection fraction (HFrEF) and its complication with atrial fibrillation (AF). No prospective study has examined AF's clinical impact on HFrEF in SSA. Aim: To determine AF prevalence in HFrEF, describe HFrEF-AF clinical characteristics, and determine AF's impact on mortality. Methods: In this prospective observational study at a tertiary hospital in Johannesburg, 136 HFrEF patients were enrolled and categorised as HFrEF- SR (sinus rhythm) or HFrEF-AF. Baseline clinical characteristics and biochemistry were recorded. Comprehensive echocardiography including left atrial strain by 2D speckle-tracking was performed. Median follow-up was 30.6 months. Results: AF was present in 28 patients (21%). The mean age was 58.7 {+/-} 14.9 years (52.9% male) and differed between groups (p < 0.001). Hypertensive heart disease was the leading cause of HFrEF (36%). Compared with SR, HFrEF-AF patients had poorer health status (KCCQ 27 [16-43] vs 45 [32-60], p < 0.001) and lower left atrial strain (26.2 {+/-} 11.3%, p < 0.001). Guideline-directed medical therapy was suboptimal in the AF group: anticoagulation use was higher than SR (60% vs 9.5%, p < 0.001) but overall inadequate; HFrEF-AF patients received lower median doses of carvedilol (15.6 mg vs 25 mg, p = 0.002) and enalapril (10 mg vs 20 mg, p = 0.004), and fewer received spironolactone (50% vs 75.3%, p = 0.013). Survival was significantly lower in HFrEF-AF (0.41 [0.22-0.61]) versus SR (0.73 [0.61-0.82], p < 0.001). Independent predictors of mortality included prior stroke, lower TAPSE and KCCQ, and higher E/e' and heart rate. Conclusion: AF is common among HFrEF patients in this SSA cohort (though lower than in high-income countries) and associates with worse clinical status, suboptimal therapy, and higher mortality.

Introduction Percutaneous coronary intervention (PCI) is a widely adopted strategy for managing coronary artery disease (CAD), leading to improved survival rates, particularly in developing countries. However, the increased survival of these patients imposes a substantial burden on long-term management, especially at the primary healthcare level. Recently, the hemoglobin-to-red cell distribution width ratio (HRR) has emerged as a potentially valuable prognostic biomarker for post-PCI patients. Despite its accessibility and cost-effectiveness, HRR has not been extensively investigated in resource-limited settings. Aim This study aimed to evaluate the prognostic value of the HRR in predicting 3-year major adverse cardiovascular events (MACE) among patients undergoing PCI who were managed at the primary healthcare level. Methods We conducted a multicenter prospective cohort study in Vietnam. A total of 626 post-PCI patients were ultimately included in the final analysis. The study commenced in October 2019 and concluded in October 2025. The association between HRR and 3-year MACE was evaluated using Cox proportional hazards regression models. Results The MACE incidence decreased progressively across the ascending HRR quartiles (p < 0.001). According to the unadjusted Cox model, each unit increase in HRR was associated with a lower risk of MACE (HR = 0.756; 95% CI, 0.703-0.814; p < 0.001). This association persisted after adjustment for age, sex, comorbidities (Model I: HR = 0.810; 95%CI: 0.750-0.878; p < 0.001). HRR outperformed its individual components, hemoglobin and red cell distribution width. Subgroup analyses confirmed the consistency of the association across clinically relevant strata. Calibration and decision-curve analyses further suggested acceptable risk estimation and potential clinical utility of HRR for 3-year MACE risk stratification. In the discriminative analysis for predicting 3-year MACE, the HRR had the highest area under the curve outperforming other inflammation-based indices. Conclusion A lower HRR was independently associated with a greater 3-year MACE risk in post-PCI patients. HRR outperforms commonly used leukocyte- and platelet-derived indices, highlighting its potential utility as a simple, cost-effective prognostic marker in resource-constrained healthcare settings.