BMC Cardiovascular Disorders

BackgroundInflammation plays a key role in atrial fibrillation (AF) pathogenesis. The empirical dietary inflammatory potential (EDIP) score predicts circulating inflammatory biomarkers and adverse cardiac outcomes, but its association with incident AF is unclear. This study aimed to examine the relationship between EDIP score and AF risk. MethodsParticipants from the Atherosclerosis Risk in Communities (ARIC) free of baseline AF who completed a validated food frequency questionnaire were included. Correlation of EDIP with inflammatory biomarkers (factor VIII, fibrinogen, von Willebrand factor, and C-reactive protein) was examined at baseline. Incident AF was ascertained using electrocardiograms, hospital records, and death certificates. Cox proportional hazards models estimated hazard ratios of AF across EDIP quantiles and per SD increase, adjusting for sociodemographic and cardiovascular risk factors. ResultsAmong 8,277 participants (54.1 years old, 51.3% women, 80% white), higher EDIP score correlated with circulating inflammatory biomarkers at baseline. Over a median 24.2 years of follow-up, 1,453 had incident AF (incident rate 8.6 per 1,000 person-years). Compared with the most anti-inflammatory diet (EDIP Q1), the most pro-inflammatory diet (EDIP Q5) was associated with increased AF risk (HR 1.21; 95% CI 1.03-1.43). Sex-stratified analyses showed a stronger association in men (HR 1.43; 95% CI 1.14-1.79), while no significant association was observed in women. ConclusionsPro-inflammatory dietary patterns are independently associated with higher AF risk in a middle-aged cohort. These findings would support incorporating dietary inflammatory load into AF risk stratification. Clinical Perspective What Is New?O_LIHigher Empirical Dietary Inflammatory Potential (EDIP) scores, indicating a more pro inflammatory diet, were associated with an increased long-term risk of atrial fibrillation (AF) in a large, biracial, community-based cohort followed for over two decades. C_LIO_LISex stratified analyses revealed a significant sex difference: higher EDIP scores were consistently associated with increased AF risk in men, whereas no significant association was observed in women, suggesting sex-specific susceptibility to EDIP. C_LIO_LIObesity modified the association between EDIP and AF, with the strongest risk observed among individuals with BMI [≥]30, while an inverse or attenuated association was seen among normal weight participants. C_LI What Are the Clinical Implications?O_LIDietary inflammatory load may serve as a meaningful and modifiable upstream AF risk factor, complementing conventional cardiovascular risk assessment, particularly in men and individuals with obesity. C_LIO_LIIncorporating dietary pattern assessment into routine AF risk stratification may help identify individuals who could benefit most from targeted lifestyle interventions. C_LIO_LIPublic health and clinical prevention strategies promoting anti-inflammatory dietary patterns (e.g., increased intake of fruits, vegetables, and whole grains; reduced intake of processed meats and refined carbohydrates) could meaningfully reduce AF incidence. C_LIO_LIRecognition of sex specific differences in AF pathways reinforces the need for personalized preventive strategies, as diet inflammation mechanisms appear to influence AF development more prominently in men. C_LI

BackgroundAdvances in wearable devices and machine-learning-based ECG analysis enable highly accurate detection of atrial fibrillation (AF) outside traditional clinical settings, leading to increasing identification of asymptomatic AF. However, the prognostic significance of AI-detected asymptomatic AF and its implications for downstream cardiovascular risk remain unclear. In contrast to clinically diagnosed AF, evidence guiding risk stratification and further evaluation in this population is limited. We therefore investigated the association between AI-detected asymptomatic AF and incident cardiovascular outcomes in a large population-based cohort. MethodsWe applied a validated open-source ECG-based deep learning model for atrial fibrillation detection (AI-AF) to 12-lead ECG recordings from participants in the UK Biobank. Participants with AI-detected AF on ECG and no prior clinical AF diagnosis were classified as asymptomatic AF (c). Kaplan-Meier curves and log-rank tests were used to compare the incidence of ischemic stroke and major adverse cardiovascular events (MACE: myocardial infarction, ischemic stroke, or cardiovascular death) across AF subgroups. Cox proportional hazards models were used to evaluate the association between AI-AF risk and incident MACE, adjusting for age, sex, current smoking, systolic blood pressure, total and HDL cholesterol, and prevalent type 2 diabetes. Follow-up was administratively censored at 6 years. ResultsThe study included 96,531 participants with mean [SD] age of 65 [8] years; 52% female; median follow-up [IQR] of 4.7 [1.6-7.2] years. ECG data were available for 64,029 participants and an additional 32,502 participants with clinically diagnosed atrial fibrillation (AF) without ECG recordings were included. Among participants without prior clinical AF and with available ECGs, 2,399 were classified as asympAF based on AI detection, while 58,879 were AF-free. Over 6 years of follow-up, the incidence of ischemic stroke was significantly higher in participants with asympAF compared with AF-free individuals (1.5% vs 0.52%, p = 7x10-7) and significantly lower than in participants with clinically diagnosed AF (1.5% vs 3.4%, p = 2x10-5). Similar patterns were observed for myocardial infarction and cardiovascular death. Using a more liberal AI-AF threshold corresponding to a 15% false-positive rate (asympAF15) yielded consistent findings: participants classified as asympAF15 had a 62% higher risk of incident MACE in adjusted Cox PH models (hazard ratio 1.6, 95% CI 1.2-2.2) over six years. ConclusionAI-detected asymptomatic AF identified individuals at elevated risk of ischemic stroke and major adverse cardiovascular events. As ischemic stroke is a hallmark complication of atrial fibrillation, these findings support the hypothesis that AI-ECG models may capture subclinical AF-related risk not detected by conventional clinical assessment. This approach may help extend the window for preventive interventions in populations without clinically diagnosed AF.

BackgroundElevated resting heart rate (HR) and atrial cardiopathy are each linked to higher mortality risk, yet their interrelationship and joint prognostic value remain unclear. MethodsWe analyzed 7,326 adults (mean age 59 {+/-} 13 years) without cardiovascular disease from the Third National Health and Nutrition Examination Survey with available electrocardiograms. Atrial cardiopathy was defined by electrocardiogram as abnormal P-wave axis or deep terminal P-wave negativity in V1. Multivariable logistic regression assessed cross-sectional associations between HR categories and atrial cardiopathy. Cox proportional hazards models evaluated independent and joint associations of HR categories and atrial cardiopathy with all-cause mortality. ResultsAtrial cardiopathy was present in 1,833 participants (13.5%). After adjustment, sinus tachycardia ([≥]100 bpm) was associated with higher odds of atrial cardiopathy (OR 1.76, 95% CI 1.06-2.92), whereas sinus bradycardia ([≤]50 bpm) was associated with lower odds (OR 0.61, 95% CI 0.43-0.84). Each 10-bpm HR increase corresponded to 25% higher odds of atrial cardiopathy. Over a median 13.8-year follow-up, 2,415 deaths (33.0%) occurred. Sinus tachycardia (HR 3.58, 95% CI 2.61-4.91) and atrial cardiopathy (HR 1.27, 95% CI 1.16-1.39) were independently associated with mortality. Individuals with both conditions had the highest risk (HR 4.11, 95% CI 2.63-6.41). Associations varied by age and race. ConclusionsElevated resting HR is associated with higher odds of atrial cardiopathy, and their coexistence confers markedly increased mortality risk. Integrating resting HR into atrial cardiopathy metrics may enable granular population-level risk profiling.

BackgroundIn patients with atrial fibrillation (AF) and stable coronary artery disease beyond 1 year after percutaneous coronary intervention (PCI), oral anticoagulant monotherapy is guideline-recommended; however, its efficacy and safety in patients with complex PCI remain uncertain. MethodsWe conducted a post-hoc analysis of the randomized ADAPT AF-DES trial comparing NOAC monotherapy versus NOAC plus clopidogrel in AF patients [≥]12 months after second- or third-generation drug-eluting stent implantation. Complex PCI was defined by one of the following characteristics: [≥]3 stents, [≥]3 lesions, bifurcation with 2 stents, total stent length [≥]60 mm, left main PCI, or chronic total occlusion PCI. Net adverse clinical events (NACE), ischemic composite outcomes, and bleeding composite outcomes were evaluated according to PCI complexity. ResultsAmong 960 patients, 247 (25.7%) underwent complex PCI and 713 (74.3%) underwent noncomplex PCI. NOAC monotherapy was associated with a lower risk of NACE compared with combination therapy in both the complex PCI group (9.5% vs 21.5%; hazard ratio 0.42, 95% confidence interval 0.21-0.83; P=0.01) and the noncomplex PCI group (9.6% vs 15.7%; hazard ratio 0.59, 95% confidence interval 0.39-0.90; P=0.02), with no significant interaction. Ischemic outcomes did not differ significantly between treatment strategies regardless of PCI complexity, whereas bleeding outcomes were consistently lower with NOAC monotherapy in both complex and noncomplex PCI groups. ConclusionsIn this post hoc analysis of the randomized ADAPT AF-DES trial, the clinical benefits of NOAC monotherapy beyond 12 months after PCI--characterized by reduced bleeding without a significant increase in ischemic events--were consistent regardless of PCI complexity. While hypothesis-generating, these findings support a long-term antithrombotic strategy prioritizing bleeding reduction in patients with AF, irrespective of prior PCI complexity. Trial registrationURL: http://www.clinicaltrials.gov; Unique identifier: NCT04250116. Clinical perspectiveO_ST_ABSWhat is new?C_ST_ABSO_LIIn a randomized population of patients with AF and prior drug-eluting stent implantation, the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel were evaluated according to anatomic PCI complexity. C_LIO_LIAmong patients with prior complex PCI, NOAC monotherapy was not associated with an increased risk of ischemic events and was associated with a substantial reduction in bleeding. C_LI What are the clinical implications?O_LINOAC monotherapy beyond 1 year after PCI was supported in patients with AF, including those with prior complex PCI. C_LIO_LILong-term antithrombotic decisions may place greater emphasis on bleeding risk than PCI complexity. C_LIO_LIThe optimal duration of combination antithrombotic therapy after complex PCI in patients with AF remains to be determined. C_LI

AimsCatheter ablation using radiofrequency (RF) or pulsed field (PF) energy is an effective treatment method for ventricular arrhythmia (VA). PF offers advantages in lesion formation in anatomically challenging regions. However, its acute effects on ventricular contractility during substrate modification require further elucidation. This study aimed to compare real-time hemodynamic changes associated with PF versus radiofrequency ablation in the left ventricle using stroke volume (SV) as a surrogate for myocardial response in regard to the safety of multiple lesion delivery within scarred myocardium. Methods and resultsWe conducted a prospective case series study of eight consecutive patients undergoing VA ablation using a dual-energy lattice-tip catheter (Sphere-9, Medtronic). Lesions were delivered to scarred regions identified via intracardiac echocardiography (ICE) and high-resolution 3D mapping. Hemodynamic monitoring was performed using a minimally invasive arterial waveform system (HemoSphere, Edwards Lifesciences). A total of 317 PFA and 41 RF lesions were delivered. PFA applications were associated with a transient SV reduction of 33.1{+/-}8.3 ml, with normalization post-delivery. RF lesions resulted in a minimal SV change ([≤]10% from baseline value). SV reduction following PFA was consistent across lesion locations. All patients achieved post-procedural non-inducibility of clinical VT. ConclusionPF causes transient but reversible reductions in LV stroke volume during lesion delivery, likely reflecting acute electroporation-induced myocyte stunning rather than irreversible dysfunction. RF lesions did not produce similar changes. These findings suggest a favorable safety profile for PF in ventricular substrate ablation, including in cases of multiple lesion sets, and support its use in regions of scarring. Further studies are warranted to validate these observations and assess long-term outcomes.

BackgroundAcute myocarditis is typically self-limiting and resolves spontaneously in most cases. However, ventricular arrhythmias (VA) complications, which may be life-threatening are associated with higher rates of in-hospital complications and mortality. Catheter ablation is occasionally required for acute myocarditis associated ventricular tachycardia (VT), but data on its procedural use and outcomes, in this setting, remain limited. We aimed to determine the prevalence of VA among patients hospitalized for acute myocarditis and to evaluate the subset who underwent in-hospital VT ablation, including their acute outcomes. MethodsRetrospective analyzed data from the National Inpatient Sample (NIS) database for U.S. hospitalizations with a diagnosis of myocarditis between 2016 and 2019. In-hospital outcomes were compared between patients with and without VA. Subgroup analysis examined patients with acute myocarditis associated VT stratified by whether VT ablation was performed. Patient demographics, comorbidities, procedures, and outcomes were identified using ICD-10-CM codes. ResultsAmong an estimated 17,845 hospitalizations for acute myocarditis, 8.4% (n=1,505) had VA (including 7.7% with VT). Patients with VA were more likely to have structural heart disease, renal disease, infectious etiologies, anemia, and atrial arrhythmias, despite lower prevalence of some traditional cardiac risk factors. VA was associated with markedly worse outcomes, including 5.5-fold higher in-hospital mortality (10% vs 1.6%; p<0.001). Multivariate analysis revealed that VA during admission for acute myocarditis was an independent significant risk factor for cardiac complications (aOR=4.8), total complications (aOR=4.2) and in hospital mortality (aOR=5.1) (p<0.001 for each analysis). Among patients with VT, catheter ablation was performed in 13.7% (n=190), more commonly with infectious etiologies. Ablated patients, compared to those without ablation, experienced significantly higher rates of in-hospital complications (73.7% vs 42.3%; p<0.001) and mortality (15.8% vs 6.7%; p<0.001). ConclusionsVA complicating acute myocarditis, portends significantly worse in-hospital outcomes. Although ablation was performed in approximately 1 in 7 patients with VT, those undergoing the procedure had less favorable acute results. Further prospective research is warranted to define optimal criteria for ablation and expected outcomes in this high-risk population.

BackgroundKetone bodies have shown potential to improve cardiac metabolism and function in patients with heart failure (HF). ObjectiveTo evaluate the effects of exogenous ketone-based interventions on cardiac function in patients with HF or related cardiometabolic risk factors. MethodsWe conducted a systematic review based on a search of MEDLINE, EMBASE, CINAHL, Cochrane Library, and Scopus from inception to January 2025. Eligible studies included randomized controlled trials evaluating exogenous ketones (oral ketones or ketone infusions) compared to placebo in adults with HF or patients with risk factors for HF including type 2 diabetes mellitus, hypertension, or coronary artery disease. Paired reviewers independently screened and identified hits at title-and-abstract and full-text levels to determine eligibility and extracted data from eligible studies. Random-effects meta-analysis was performed. Effects of interventions were summarized as mean differences (MD). Risk of bias was assessed using Cochrane RoB 2.0 tool. Certainty of evidence was evaluated using the GRADE (grading of recommendations assessment, development and evaluation) approach. ResultsOut of 565 unique records, 22 full-text articles were reviewed, and 8 studies met inclusion criteria. Exogenous ketone administration increased left ventricular ejection fraction (LVEF) (MD = 3.94, 95% CI 2.18-5.70, p = 0.001), cardiac output (CO) (MD = 1.11 L/min, 95% CI 0.55-1.67, p = 0.002), heart rate (4.85 bpm, 95% CI 2.24-7.46, p = 0.003), and stroke volume (SV) (MD = 10.21 mL, 95% CI 4.06-16.35, p = 0.005). Pulmonary capillary wedge pressure (PCWP) decreased (MD = -0.93 mmHg, 95% CI -1.44 to -0.43, p = 0.003), while mean arterial pressure showed no change (MD = -1.37 mmHg, 95% CI -3.53 to 0.79, p = 0.18). ConclusionsExogenous ketone-based therapies are associated with improvements in hemodynamic markers of cardiac function, including increases in LVEF, CO, and SV, along with a reduction in PCWP. These findings suggest that ketone supplementation may offer clinical benefits for patients with HF or vascular disease.

BackgroundScreening for atherosclerosis focuses on identifying Standard Modifiable Risk Factors (SMuRFs), including diabetes, hypertension, hyperlipidaemia, and smoking. PurposeTo compare the extracardiac thoracoabdominal atherosclerotic plaque burden, as measured by computed tomography angiography (CTA), among heart transplant candidates with ischemic or non-ischemic cardiomyopathy (ICM, NICM), and evaluate potential associations between plaque burden and SMuRFs. MethodsThis retrospective study identified heart transplant candidates with ICM or NICM matched for age and sex, undergoing thoracoabdominal CTA. Patients were classified as with SMuRFs or SMuRF-less. Extracardiac thoracoabdominal non-calcified and calcified atherosclerotic plaque was classified as present or absent across 78 arterial segments per patient. ResultsAmong included patients (n=167, median [interquartile range] age 58 [53-63] years, 16% female, 51% NICM), 40 patients (24%) were SMuRF-less (ICM: 16/82 (20%), NICM: 24/85 (28%), age 56 [50-67] years). Overall, out of 13,026 arterial segments analysed, 1,746 (13%) were affected by atherosclerotic plaque (9 [4-15] segments per patient). ICM had a higher total plaque burden than NICM (11 [7-18] vs 6 [3-11] segments per patient, p<0.001). SMuRF-less patients showed no difference in non-calcified, calcified, or total plaque burden compared to patients with SMuRFs, among all patients (ICM+NICM, p>0.17) and within the ICM and NICM groups, respectively (p>0.30). ConclusionsThe burden of extracardiac thoracoabdominal atherosclerotic plaque is higher among heart transplant candidates with ICM. However, it does not differ between SMuRF-less or those with SMuRFs, regardless of underlying ICM or NICM. The prevalence of SMuRFs is not an effective marker to determine the need to screen for extracardiac atherosclerotic plaque among heart transplant candidates. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=134 SRC="FIGDIR/small/26347056v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1aff6b1org.highwire.dtl.DTLVardef@16cfb07org.highwire.dtl.DTLVardef@1d4894corg.highwire.dtl.DTLVardef@81e9d3_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundHeart failure (HF) is an increasingly common complication among patients with type 2 diabetes (T2D), yet its early detection remains challenging, especially in those with concomitant chronic kidney disease (CKD). NT-proBNP is a key biomarker for diagnosing and prognosticating HF, but its reference thresholds are influenced by renal function, age, and ethnicity. Current guideline cutoffs, largely derived from Western populations, may not apply to Asian patients. MethodsThis retrospective cohort study included 10,587 adults with T2D who underwent NT-proBNP testing between 2006 and 2021 at the National Taiwan University Hospital. Patients with prior HF were excluded. Generalized additive models identified NT-proBNP thresholds associated with HF hospitalization, and Kaplan-Meier analysis validated outcome separation. Subgroup analyses were stratified by age, sex, body mass index (BMI), and estimated glomerular filtration rate (eGFR). ResultsDuring a mean follow-up of 3.5 years, 1,892 (17.9%) patients were hospitalized for HF. NT-proBNP levels of 179 pg/mL (outpatient) and 728 pg/mL (emergency) marked inflection points for rising event risk (log-rank p < 0.0001). Age-specific analyses showed progressive increases in optimal thresholds: from 85 (<50 years old), 150 (50-74 years old) and 290 pg/mL ([&ge;]75 years old) in outpatients, and from 310, 600 and 1,165 pg/mL, respectively, in emergency settings. In the BMI-stratified analysis, NT-proBNP thresholds demonstrated an inverse relation with BMI. Considering renal function, the optimal cutoffs were 100, 310, and 935 pg/mL for eGFR > 60, 30-60, and < 30 mL/min/1.73 m{superscript 2}, respectively; in the emergency cohort, the corresponding thresholds were 290, 835, and 3,905 pg/mL. ConclusionsThis large Asian cohort defines setting- and renal function-specific NT-proBNP thresholds for predicting HF hospitalization in patients with T2D. The lower optimal cutoffs compared with Western guidelines highlight the need for ethnicity-adjusted diagnostic criteria to improve early identification and risk stratification of HF in clinical practice. What is new?O_LIIn a large real-world Asian cohort of patients with type 2 diabetes, we identified setting-specific NT-proBNP thresholds (179 pg/mL outpatient; 728 pg/mL emergency) associated with heart failure hospitalization risk. C_LIO_LIAge-, BMI-, and kidney function-stratified cutoffs revealed substantial heterogeneity in optimal NT-proBNP thresholds. C_LIO_LICompared with guideline-recommended values, Asian-specific thresholds were consistently lower ([~]30-40%), supporting ethnic differences in natriuretic peptide biology. C_LIO_LIA generalized additive model (GAM) captured nonlinear biomarker-risk relationships, enabling data-driven and clinically interpretable cutoff identification. C_LI What are the clinical implications?O_LIUse of ethnicity- and context-specific NT-proBNP thresholds may improve early detection of heart failure in Asian patients with type 2 diabetes. C_LIO_LIIncorporating kidney function and BMI into NT-proBNP interpretation enhances risk stratification, particularly in patients with CKD. C_LIO_LIReliance on Western guideline cutoffs may underestimate heart failure risk in Asian populations. C_LIO_LIThese findings support a precision medicine approach to biomarker interpretation and highlight the need for population-specific guideline refinement. C_LI

BackgroundBlood pressure (BP) is routinely measured during healthcare visits. A standardized measurement is essential to ensure accurate values, particularly in outpatient settings, where patient preparation, environment, and technique can significantly influence results. MethodsA quasi-experimental study was conducted in adult outpatients. Demographic, anthropometric, and clinical data were collected through interviews and physical examination. BP was measured using a validated automated oscillometric device under four non-randomized predefined sequences. The standardized method followed international guideline recommendations, whereas the other three incorporated common errors observed in clinical practice (unsupported body position on the examination table, patient speaking, or legs crossed). Systolic and diastolic BP values were compared using the Friedman test and paired Wilcoxon tests with Holm adjustment. Effect sizes were expressed as median paired differences with interquartile ranges. Analyses were performed using R and Stata. ResultsA total of 295 participants were included (61% women; median age 56 years), with hypertension as the most frequent comorbidity (33%). Significant differences were observed across the four measurement models (p < 0.001). Compared with the standardized method, systolic BP was higher by +8 mmHg (M2), +2.5 mmHg (M3), and +4 mmHg (M4), while diastolic BP increased by +7 mmHg, +2 mmHg, and +2 mmHg, respectively. Clinically relevant differences (|{Delta}| [&ge;] 5 mmHg) occurred in up to 81% of systolic and 79% of diastolic measurements with M2. ConclusionsNon-adherence to guideline-recommended BP measurement protocols leads to BP overestimation and misclassification of hypertension status, which may affect therapeutic decision-making and the use of pharmacological treatments.

Background-Blockers (ABs) are the most commonly prescribed medications for benign prostatic hyperplasia (BPH), a highly prevalent condition. Although the ALLHAT raised concerns about cardiovascular (CV) safety of nonselective ABs for the treatment of hypertension, the comparative CV risk profile of selective 1A-adrenergic receptor (1A-AR) antagonists for BPH remains unclear. MethodsWe conducted a retrospective cohort study using the TriNetX federated research network (158 million patients across 113 healthcare organizations). Males aged 55 to 90 years with BPH who initiated ABs or 5-ARIs between October 1, 2015, and database lock were included. Three propensity score-matched analyses were conducted: (1) selective 1A-AR antagonists versus 5-ARIs (n=48,096 per group); (2) nonselective ABs versus 5-ARIs (n=33,232 per group); and (3) 1A-selective versus nonselective ABs (n=54,872 per group). Exposures were new use of selective 1A-AR antagonists, nonselective ABs, or 5-ARIs with evidence of adherence. Main outcomes and measures were heart failure (HF) hospitalization, acute MI, stroke, any hospitalization, major adverse CV events (MACE), and composite MACE plus HF at 1, 3, and 5 years. ResultsIn the 1A-selective AB versus 5-ARI analysis, 1A-selective ABs were associated with increased risk at 1 year of HF (hazard ratio [HR], 1.48 [95% CI, 1.39-1.57]), MI (HR, 1.41 [95% CI, 1.28-1.54]), and stroke (HR, 1.36 [95% CI, 1.22-1.50]). Similar patterns were observed for nonselective ABs versus 5-ARIs: HF (HR, 1.46), MI (HR, 1.29), stroke (HR, 1.32). At 5 years, CV risks remained elevated: HF (HR, 1.50 for selective ABs; HR, 1.52 for nonselective ABs), MI (HR, 1.41; HR, 1.30), and stroke (HR, 1.37; HR, 1.29). Head-to-head comparison of selective versus nonselective ABs showed similar CV outcomes (HF HR, 1.10 at 1 year). ConclusionsBoth 1A-selective and nonselective ABs were associated with increased CV event risk compared with 5-ARIs that persisted through 5 years of follow-up. These findings, which were robust across sensitivity analyses and specific to clinically important CV endpoints, may inform shared decision-making for BPH pharmacotherapy.

Background and AimsDespite advances in reperfusion and medical therapy, survivors of acute myocardial infarction (AMI) remain at risk for adverse left ventricular remodeling (LVR), a precursor to heart failure. Building on prior work outlining 12-month biomarker trajectories linked to early ventricular dysfunction, we aimed to assess whether these circulating biomarkers predict long-term adverse LVR. MethodsWe prospectively enrolled 155 patients experiencing their first AMI. Clinical, biochemical, and echocardiographic data were obtained at pre-percutaneous coronary intervention (pre-PCI), 24 h post-PCI, discharge (day 3), 6 months, and 12 months. Adverse LVR was defined as an increase of [&ge;]15 % in left ventricular end-systolic volume at 12 months. ResultsAdverse LVR occurred in 34 % of patients and was associated with cardiometabolic dysregulation (higher glucose, triglycerides, BMI, HOMA-IR; lower HDL-C). Among the six baseline biomarkers, only insulin-like growth factor-binding protein 2 (IGFBP-2) differed significantly between groups (p = 0.021) and remained independently associated in multivariable analysis (p = 0.036). Inclusion of IGFBP-2 increased the predictive models area under the receiver-operating characteristic curve from 0.735 to 0.801. ConclusionsIGFBP-2 is an independent predictor of adverse LVR following AMI, highlighting the interplay between metabolic dysfunction and maladaptive remodeling. Incorporating IGFBP-2 into clinical risk models could improve stratification and guide precision therapies for high-risk patients.

BackgroundLeft atrial (LA) remodeling, a hallmark of chronically elevated LA pressure, is characterized by enlargement and functional impairment. While global and reservoir LA functions are well described, the role of LA booster function and its failure remains poorly defined. ObjectivesTo characterize LA booster function using cardiac computed tomography angiography (CCTA) and to evaluate the relationship between LA preload, booster performance, remodeling, and clinical outcomes. MethodsWe retrospectively analyzed 975 patients who underwent spiral CCTA between 2010 and 2018. Phasic LA and LV volumes were obtained, from which LA reservoir and booster functions were derived. LA performance curve was constructed by plotting LA pre-A volume (preload) against LA booster stroke volume. Clinical outcomes (heart failure, stroke, or cardiovascular death) were analyzed based on the LA performance curve. ResultsLA pre-A volume strongly correlated with LA end-systolic volume (r=0.92, p<0.001). The LA booster stroke volume displayed an inverted U-shaped relation to LA pre-A volume (linear coefficient 0.64, P<0.0001; squared coefficient-0.0029, P<0.0001). The atrial booster function curve reached its vertex at 107 mL (95% CI 90 to 113 mL), indicating that the booster pump response for the increased preload is exhausted at this point. Booster dysfunction was associated with impaired reservoir function (r=0.77, p<0.001) and reduced LA systolic flow rates (-0.79, P<0.001). Patients with increased LA pre-A volume but reduced booster volume ("LA failure") exhibited the highest event rate of the combined endpoint of heart failure, stroke or cardiovascular mortality (43.2%, 95% CI 33.6-54.2%). ConclusionsLA enlargement predominantly serves to increase LA pre-A volume to sustain booster function. LA contractile dysfunction affects global LA function via a concomitant reduction in LA reservoir volume. LA failure can be defined as reduced booster contraction despite elevated preload, portending poor clinical outcomes.

IntroductionAtrial fibrillation (AF), a common arrhythmia, is associated with impaired quality of life (QoL) and increased stroke risk and mortality. Clinical guidelines recommend leveraging digital technologies to support patient education and AF self-management. Conversational artificial intelligence (AI) technologies may support patient engagement with self-management by enabling human-like conversations. This study aims to evaluate the effectiveness of a conversational AI intervention (Conversational HeAlth supporT in Atrial Fibrillation Self-Management - CHAT-AF-S) in improving QoL in patients with AF. Methods and analysisCHAT-AF-S is a 3-month randomised controlled trial with 1:1 allocation and embedded process evaluation. We will randomise 480 adults (18 years of age and older) with documented AF to the CHAT-AF-S intervention or usual care. Primary outcome is the Atrial Fibrillation Effect on QualiTy-of-life (AFEQT) overall score. We will follow intention-to-treat principles and data analysts will be blinded. Intervention participants will be invited to complete a user experience survey and take part in an interview to explore the feasibility, acceptability, perceived utility, and barriers and enablers to implementing the intervention. Qualitative data will be analysed thematically. Ethics and disseminationEthics approval was obtained from the Western Sydney Local Health District Human Ethics Research Committee (2023/ETH00765). Written and informed consent will be obtained from all study participants before commencing any study procedures. Results will be disseminated via peer-reviewed publications and presentations at international conferences. Declaration of InterestsAll investigators report nil conflicts of interest. Data AvailabilityThe data that supports this project are available from the corresponding author upon reasonable request. Trial registrationAustralian New Zealand Clinical Trials Registry ACTRN12623000850673 https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=386249

BackgroundPatients with repaired coarctation of the aorta (CoAo) remain at risk for left ventricular hypertrophy (LVH) even in the absence of hypertension. Alterations in wave reflection and the timing of reflected pressure waves may contribute to ventricular remodeling beyond pressure load alone. MethodsWe performed a cross-sectional analysis of patients with repaired CoAo. Office and ambulatory blood pressure (ABPM), non-invasive central hemodynamics, and echocardiographic indices of left ventricular structure were assessed. Linear and multivariable regression models evaluated associations with posterior wall thickness (PWTd) and interventricular septal thickness (IVSTd). Computational simulations were conducted to examine the impact of heart rate on ventricular remodeling. ResultsFifty-seven patients (median post-repair follow-up 11 years) were included. LVH prevalence was 15.2% (95% CI: 4.8-25.6). Although 42% met criteria for hypertension based on ABPM, no patients exhibited elevated central blood pressure. Adjusted augmentation index (AIX@75) was inversely associated with PWTd and remained independently associated after multivariable adjustment (R2 = 0.40, p < 0.01). Replacing AIX@75 by heart rate improved model performance (R2 = 0.44), with lower heart rate independently associated with greater PWTd. Simulation modeling showed that a 10% increase in heart rate reduced mean PWTd and decreased posterior wall hypertrophy prevalence from 30.9% to 2.4% (OR =0.10; 95% CI: 0.01-0.44). ConclusionsVentricular remodeling occurs despite normal central blood pressure in CoAo. A lower heart rate associates with increased ventricular mass. Heart rate-mediated modulation of wave reflection timing represents a potential mechanistic and therapeutic target.

Subclinical rheumatic valvular disease is a significant yet underdiagnosed contributor to the global rheumatic heart disease (RHD) burden. Early detection through population screening is essential to prevent its progression to severe RHD. Rhythm changes and prolongations of PR and QTc intervals in the ECG are described in the advanced RHD cases. However, these parameters were not yet studied in asymptomatic RHD. We aimed to investigate the potential of ECG biomarkers for screening RHD in asymptomatic schoolchildren. ECG tracings from 611 schoolchildren aged 10 to 20 years were selected from a cohort screened for RHD in four schools in an RHD-endemic region. Confirmatory diagnoses were based on echocardiographic findings, where 564 (F=326, M=238) were healthy, and 47 (F=28, M=19) were positive for RHD (24 borderline RHD and 23 definite RHD). Independent, blinded reviewers manually annotated the ECGs and PR interval (PR), P-wave dispersion (PWd), and the ratio between the P-wave duration and PR interval (Pw/PR) were analyzed. The mean age of the study cohort at diagnosis was 16.1 {+/-} 2.5 years, and 58% of the participants were females. Atrial fibrillation was seen in 8% (n=4), and prolonged PR in 2% (n=1) of RHD-positive cases. The mean {+/-} std for normals vs RHD is (PR, 138{+/-}19 vs 150{+/-}19), (Pw/PR, 0.75{+/-}0.06 vs 0.71{+/-}0.07), and (PWd, 49{+/-}14 vs 56{+/-}17). The PR (p<0.001), Pw/PR (p<0.001), and PWd (p=0.008) showed a significant difference between healthy and RHD-positive subjects. The PR was increased consistently with severity across age groups above and below 16 years. The PR, PWd, and Pw/PR can serve as non-invasive biomarkers for the screening of RHD in at-risk schoolchildren. Monitoring alterations in these markers at an early stage of RHD is crucial for enabling prompt management and follow-up. It is thus evident that ECG can support an intermittent ambulatory RHD screening in resource-limited settings.

We performed a systematic review and meta-analysis of randomized controlled trials evaluating glucagon-like peptide-1 receptor agonists (GLP-1 RAs) versus placebo in adults with heart failure (HF), searching PubMed, Cochrane CENTRAL, and ClinicalTrials.gov through February 2026. The primary outcome was the composite of cardiovascular death and first HF hospitalization. Random-effects meta-analysis used restricted maximum likelihood estimation with Hartung-Knapp-Sidik-Jonkman adjustment. We included 14 studies (6 dedicated HF trials and 8 cardiovascular outcomes trial HF subgroup analyses) encompassing 18,558 patients, of whom 2,499 were randomized in dedicated HF trials. The primary composite did not reach statistical significance (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.73-1.01; P=0.067; I2=47%). GLP-1 RAs significantly reduced all-cause mortality (HR 0.87, 95% CI 0.81-0.93; P<0.001; I2=0%), major adverse cardiovascular events (HR 0.83, 95% CI 0.73-0.95; P=0.019), and improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (+7.4 points, 95% CI 6.3-8.5) and 6-minute walk distance (+17.6 m, 95% CI 13.4-21.7). Excluding the FIGHT trial (acute HFrEF) yielded a significant primary composite (HR 0.83, P=0.011). The mortality signal was driven primarily by CVOT subgroups; the largest dedicated HFpEF trial (SUMMIT) showed numerically higher mortality (HR 1.25). The strongest evidence supports GLP-1 RAs in HFpEF with obesity. HighlightsO_LIPrimary composite of CV death + HHF was not significant (HR 0.86, P=0.067) C_LIO_LIGLP-1 RAs reduced all-cause mortality (HR 0.87) with no heterogeneity C_LIO_LIKCCQ-CSS improved by 7.4 points and 6MWD by 17.6 m in HFpEF trials C_LIO_LIMortality benefit driven by CVOT subgroups, not dedicated HF trials C_LIO_LIStrongest evidence supports GLP-1 RAs in HFpEF with obesity C_LI

BackgroundThe molecular drivers distinguishing valvular heart disease-associated atrial fibrillation (VHD-AF) from other AF etiologies remain poorly defined, with prior transcriptomic studies largely focused on non-valvular AF. MethodsWe performed RNA sequencing on peripheral blood mononuclear cells (PBMCs) from 15 patients with VHD-AF and 15 age- and sex-matched healthy controls. Bioinformatic analyses identified differentially expressed genes (DEGs), enriched pathways, and protein-protein interaction (PPI) networks. ResultsWe identified 3,308 DEGs (2,891 upregulated, 417 downregulated) in VHD-AF patients. Functional enrichment revealed two dominant mechanisms: (i) a pronounced systemic inflammatory response, with significant enrichment in cytokine-cytokine receptor interaction (P=1.2e-15) and TNF signaling pathways (P=3.4e-08); and (ii) a core epigenetic module centered on nucleosome assembly (P=8.9e-12) and histone-related genes. PPI network analysis identified a high-confidence hub module (Cluster 1) overwhelmingly composed of histone genes (e.g., H4C6, H3C13). ConclusionThis first PBMC transcriptomic map of VHD-AF reveals a convergent pathology of chronic inflammation and widespread epigenetic remodeling. The findings nominate TNF inhibition and histone-modifying agents as potential therapeutic strategies and position PBMC-derived signatures as minimally invasive biomarkers for this specific AF population.

The objective of this systematic review and meta-analysis was to identify the interventions used to manage intolerance in patients receiving statins for primary prevention of CVD and to determine the effectiveness of these interventions. This study was conducted according to the PRISMA checklist. The electronic databases MEDLINE (PubMed), SCOPUS, EMBASE, and CINAHL were searched for studies published until June 2025. Based on the NLA definition of statin intolerance, the outcomes were split into adverse effects caused by statins and statin discontinuation. In total, 1,238 studies were identified and screened. Nine studies were eligible for systematic review, and six studies were eligible for meta-analysis. The identified intervention strategies were adjuvant therapy, statin titration, replacing statins with other lipid-lowering agents and switching to different statin. The meta-analysis showed that the pooled risk ratio (RR) relative to control was 0.97 (95% CI, 0.86-1.08) in randomized controlled trials and 0.94 (95% CI, 0.63-1.42) in overall, with point estimates in favour of intervention arms. Moderate to substantial heterogeneity was observed, with I2 between 27% to 57%. Due to the smaller number of studies, no clear conclusions can be drawn regarding how the implemented interventions may affect statin discontinuation. This study showed no strong evidence that the implemented interventions reduced statin intolerance. PROSPERO registration numberCRD42024587573 HighlightsThis study found that the intervention strategies used to manage intolerance in patients receiving statins for the primary prevention of cardiovascular diseases were adjuvant therapy, statin titration, replacing statins with other lipid-lowering agents and switching to different statin. O_LIThis study showed no strong evidence that the implemented interventions reduced statin intolerance C_LIO_LIDue to the smaller number of studies, no clear conclusions can be drawn regarding how the implemented interventions may affect statin discontinuation C_LI

BackgroundLong-term electrocardiogram (ECG) monitoring with wearable devices enables large-scale characterisation of cardiac rhythms, but population-based evidence remains limited. The UK Biobank Cardiac Monitoring Study integrates 14-day patch-based ECG monitoring with accelerometry and detailed phenotypic and lifestyle data. Here, we report the acquisition protocol, data processing, and initial findings from 27,658 participants. MethodsParticipants in the UK Biobank imaging study were invited to undergo 14-day cardiac monitoring using a Zio XT (pilot phase; 2015-18) or BodyGuardian MINI (main phase; 2019- ongoing) monitor. ECGs were analysed by certified technicians and automated algorithms to identify atrial, ventricular, and conduction arrhythmias. In parallel, beat-to-beat RR intervals were derived using in-house algorithms, and physical activity from calibrated triaxial accelerometer data. Analyses assessed wear time, arrhythmia prevalence, circadian patterns, and repeatability. FindingsIn total, 27,658 participants (mean age 71 years; 49.9% women) were analysed, including 7,795 from the pilot phase and 21,141 from the main phase; 1,353 (4.9%) had repeat recordings. In the main phase, median wear time was 13.2 days (IQR 11.9-13.9), and undiagnosed atrial fibrillation (AF) was detected more frequently in men than women (3.2% vs 1.7%; p<0.001); 68% was paroxysmal, with 27.4% detected during week two. Ventricular tachycardia occurred in 12.1% (8.4% in women), with sustained episodes rare (0.4%) but observed. Arrhythmia timing varied markedly with activity, with AF peaking during nocturnal inactivity and ventricular ectopy increasing during activity, peaking at midday. Repeat assessments showed strong reproducibility of diurnal heart rate and activity profiles, with more modest arrhythmia consistency. InterpretationExtended ECG monitoring enables detection of subclinical arrhythmias and long-term physiological rhythms in older adults. Linkage to imaging, multi-omics, and clinical outcomes in UK Biobank will enable unprecedented evaluation of the natural history of asymptomatic rhythm disturbances and their impact on brain health. FundingBritish Heart Foundation and Wellcome Trust.