Background:Atrial fibrillation (AF) clinical trials are essential for informing evidence-based care, yet many trials are discontinued or remain unpublished. This contributes to research inefficiency and reduced transparency. This study evaluated characteristics associated with discontinuation and non-publication of AF clinical trials registered on ClinicalTrials.gov. Methods:We performed a retrospective analysis of interventional AF trials registered between 1999 and 2025 on ClinicalTrials.gov. Trials were categorized as completed or discontinued, and as published or unpublished. Trial characteristics were extracted, and multivariable logistic regression was used to identify predictors of discontinuation and non-publication. Results:Among 538 AF trials, 423 trials (78.6 percent) were completed and 115 trials (21.4 percent) were discontinued. Only 153 trials (36.2 percent) were published. The estimated median time from primary completion to publication was 18.0 months (95% confidence interval, 14.0-21.0 months). Trials enrolling 100 participants or more had significantly lower odds of both discontinuation and non-publication. Multicenter trials showed higher odds of discontinuation but lower odds of non-publication. The other characteristics studied were not significant predictors. Conclusions:A substantial proportion of AF trials are discontinued or remain unpublished, revealing ongoing gaps in research transparency. Larger sample sizes support higher completion and publication rates, while a multicenter design increases discontinuation risk but improves dissemination. These findings underscore the need for strategies that strengthen trial feasibility and reporting practices.
Objective To quantitatively measure gender-specific anatomical structures of the right atrial appendage (RAA) and right atrium (RA) in atrial fibrillation (AF) patients, and explore their clinical significance for post-radiofrequency ablation (RFA) recurrence using 256-slice spiral Computed Tomography (CT). Method This study included 321 AF patients (184 males and 137 females) undergoing RFA for the first time. All patients underwent a 256-slice spiral CT examination before surgery. The volume of the RA, RAA, and left atrium (LA); RAA height; short diameter, long diameter, area, and circumference of RAA base; RA anteroposterior diameter, tricuspid annulus diameter, crista terminalis, and cavo-tricuspid isthmus (CTI) were measured, and clinical data were collected. Results After body surface area normalization, the RA volume and RA anteroposterior diameter in female patients with AF showed more significant structural remodeling than those in male patients. Both male and female patients with recurrent AF showed larger RAA and RA structural parameters. In females, short diameter of RAA base, crista terminalis thickness and persistent AF were independent recurrence predictors post-RFA, while short diameter of RAA base and AF duration were independent predictors in males (all P < 0.05). ROC analysis showed that short diameter of RAA base served as the strongest predictor of AF recurrence in both genders. The optimal cutoff values were 26.95 mm for females (sensitivity = 0.696, specificity = 0.824, AUC = 0.811, P = 0.000) and 25.55 mm for males (sensitivity = 0.700, specificity = 0.746, AUC = 0.786, P = 0.000). Conclusion The short diameter of the RAA base had the highest predictive value for postoperative recurrence in both male and female patients.
Background:Cardio-ankle vascular index (CAVI) is an important indicator to evaluate arteriosclerosis. This study was to explore the changes and related factors of CAVI in the elderly population, providing a certain basis for the prevention and control of cardiovascular and cerebrovascular diseases. Methods:1117 subjects (M/F 488/629) were divided into three groups according to age: group 1: subjects with age 60-69 years; group 2: subjects with age 70-79 years; group 3: subjects with age≧80 years. CAVI value was recorded by using the VaseraVS-1000 vascular screening system. Results:There were significant differences about body mass index (BMI), CAVI, systolic blood pressure (SBP), diastolic blood pressure(DBP), pulse pressure, creatinine, fasting plasma glucose (FPG), total cholesterol, high-density lipoprotein cholesterol (HDL-C) and uric acid between these three groups. CAVI value was increasing year by year, with the increasing incidence of hypertension, coronary artery disease and stroke. General Linear Model analysis showed that age, incidence of diabetes mellitus, BMI, DBP and HDL-C were independent associating factors of CAVI in elderly subjects (β = 0.048, p < 0.001; β = 0.349, p = 0.012; β = -0.060, p = 0.001; β = 0.023, p = 0.001; β = -0.530, p = 0.020; respectively). Conclusions:CAVI was increasing with ageing. The influencing factors of CAVI varied among different age groups. Subjects aged 60-69 were needed to pay close attention to blood pressure and subjects aged 70-79 were needed to focus on diabetes meillitus, providing a theoretical basis for intervening in different targets in different age groups, to reduce or delay the progression of arteriosclerosis.
Background:Coronary microvascular dysfunction (CMD) is increasingly recognized as a key contributor to angina and non-obstructive coronary arteries (ANOCA) and adverse cardiovascular outcomes. Despite its clinical importance, the molecular basis of CMD remains to be fully elucidated. CMD is known to be associated with systemic microvascular endothelial dysfunction. Methods:We examined serum levels of molecules crucial for endothelium-dependent vasodilation, especially nitric oxide (NO)- mediated responses and endothelium-dependent hyperpolarizing responses. These included caveolin-1 (Cav1), endothelial NO synthase (eNOS), and Cu,Zn-superoxide dismutase (Cu,Zn-SOD) in patients with ANOCA enrolled in the nationwide registry by the Japanese Association of CMD. Results:This multicenter study included 295 ANOCA patients (M/F 134/161, mean age 63.7 ± 13.9 years). All patients underwent coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) measurements for CMD diagnosis. Serum Cav1, eNOS, and Cu,Zn-SOD levels were quantified by enzyme-linked immunosorbent assay. CMD was identified in 43% of patients who showed significantly lower Cu,Zn-SOD levels than non-CMD patients (P = 0.001). In patients with abnormal IMR, Cu,Zn-SOD was particularly reduced, while those with both abnormal CFR and IMR had reduced Cav1. In contrast, eNOS levels did not differ significantly between groups. Multivariable logistic regression analysis revealed that Cu,Zn-SOD levels below the cut-off value (97.2 ng/ml) independently predicted CMD [odds ratio (95% confidence interval) 2.71 (1.56-4.74), P < 0.001]. Conclusions:Reduced Cu,Zn-SOD levels are associated with CMD, suggesting enhanced systemic oxidative stress. This reduction may impair the endothelium-derived hyperpolarizing factor pathway, thereby contributing to CMD pathophysiology.
Background:The prognostic role of endothelin-1 (ET-1) in patients with obstructive hypertrophic cardiomyopathy (oHCM) who underwent septal myectomy remains unclear. We aimed to assess its prognostic importance in patients undergoing septal myectomy. Methods:We recruited 1207 oHCM patients for this analysis. The participants were divided into three groups according to the tertile of big ET-1. Cox regression analyses were conducted to assess the prognostic value of big ET-1 on all-cause death and cardiovascular death. Results:The mean age of the participants was 49.9 ± 12.0 years, 713 (59%) study patients were male. female (adjusted coefficient 0.106, 95% CI: 0.053-0.158) and left atrial dimension (adjusted coefficient 0.005, 95%CI: 0.001-0.009) were significantly associated with big ET-1 levels. During mean 3.8 years follow-up, 35 patients died including 27 cardiovascular deaths. Multivariate Cox regression analyses showed that patients with highest tertile had the highest incidence of all-cause mortalities (adjusted HR = 3.483, 95% CI: 1.365-8.887, P = 0.009) and cardiovascular mortalities (adjusted HR = 8.328, 95%CI: 1.883-36.828, P = 0.005), compared to the referenced patients with lowest tertile. When Big ET-1 was evaluated as a continuous variable, data showed that the big ET-1 was correlated with higher risks of all-cause deaths (adjusted HR = 1.588, 95%CI: 1.148-2.196, P = 0.005) and cardiovascular deaths (adjusted HR = 1.757, 95%CI: 1.250-2.470, P = 0.001). Furthermore, interactions were detected in the subgroups of gender, and maximum wall thickness. Conclusion:Our study revealed that high level of plasma big ET-1 could predict worse clinical outcomes for oHCM patients undergoing myectomy.
Background:Fractional flow reserve (FFR) is widely used to guide percutaneous coronary intervention (PCI) as a surrogate of inducible myocardial ischemia (IMI). However, the relationship between very low FFR, electrically manifest ischemia, and subsequent symptomatic benefit remains incompletely understood. Methods:We investigated stress-induced ischemic electrocardiographic changes in 79 patients with FFR ≤ 0.60, comparing acute coronary syndrome (ACS) and stable coronary artery disease (CAD), and its association with post-PCI symptom improvement. IMI was defined by ischemic ST-segment changes during adenosine stress testing. Pressure-derived physiologic indices, including the instantaneous wave-free ratio (iFR) and resting Pd/Pa, were measured, and angina-related symptoms were assessed using the Seattle Angina Questionnaire. Results:IMI was present in all patients with ACS but was absent in 40 % of patients with stable CAD (p < 0.001). Despite similar angiographic severity and mean FFR values, iFR and resting Pd/Pa were significantly lower in ACS. In multivariate analyses, ACS and lower iFR or resting Pd/Pa independently predicted IMI. Although angina symptoms improved overall after PCI, the greatest improvement occurred in patients with ACS or IMI. Conclusions:At extremely low FFR values (≤0.60), substantial discordance exists between pressure-derived physiology and IMI, which is closely related to clinical presentation and symptomatic benefit after PCI.
Hemodynamic factors are essential in influencing cellular behaviors and facilitating the restoration of tissue structure and function through mechanotransduction pathways. This review explores the pivotal role of hemodynamics in the development of myocardial tissue and the remodeling processes involved in tissue regeneration. We systematically analyze the regulatory effects of hemodynamic conditions during embryonic heart development, adult cardiac regeneration, and pathological remodeling processes. The review summarizes the latest research findings and potential therapeutic strategies aimed at harnessing hemodynamic influences for the treatment of cardiovascular diseases. By shedding light on these mechanisms, we aim to provide a theoretical foundation to inform future therapeutic approaches in cardiovascular medicine.
Background:Accurate assessment of thrombus risk in atrial fibrillation (AF) requires the integration of structural and metabolic factors, which are insufficiently addressed by current clinical risk scores. We developed a model that added LAA morphology and metabolic markers, and compared it with the CHA2DS2‑VA score. Methods:This retrospective cohort study included 418 participants (262 AF patients without thrombus and 156 AF patients with thrombus). Data on medical history, contrast‑enhanced computed tomography with three‑dimensional reconstruction, and metabolic profiling were retrospectively collected. Results:The final model comprised six independent predictors: non‑paroxysmal AF, CHA2DS2‑VA score ≥ 2, anticoagulation use, AF duration, LAA orifice ellipticity index (LAA OEI), and lipoprotein(a) (Lp(a)). The model demonstrated excellent discrimination (AUC = 0.861, 95% CI 0.829-0.892) and good calibration (Hosmer‑Lemeshow test p = 0.462). It significantly outperformed the CHA2DS2‑VA score (AUC = 0.643; ΔAUC = 0.2186; p < 0.0001), with a net reclassification improvement of 0.844 (p < 0.001) and an integrated discrimination improvement of 0.311 (p < 0.001). Conclusions:Integrating LAA OEI and Lp(a) with clinical factors improves thrombus risk stratification in patients with AF compared with the CHA2DS2‑VA score alone.
Introduction:Estrogen protects vascular function, likely via adrenergic modulation. Previous studies of estrogen and beta-adrenoceptor (β-AR) interactions relied on non-coronary or animal models, limiting relevance to human coronary endothelium. This study aimed to characterize estrogen receptor (ER) and β-AR expression in human coronary artery endothelial cells (HCAECs), evaluate inter-donor variability, and determine whether ER stimulation alters β-AR gene expression. Methods:HCAECs from female donors were analyzed for expression of ERs (ERα, ERβ, GPER), and β-ARs (β1-, β2-, β3-AR) at mRNA and protein levels using RT-qPCR, western blotting, and immunofluorescence, with assessment of inter-donor variability. To investigate estrogen-β-AR interactions, cells were treated with 1 and 10 nM 17β-estradiol or 10 nM selective ER agonists; PPT (Propylpyrazoletriol, ERα), DPN (Diarylpropionitrile, ERβ), G-1 (G protein-coupled estrogen receptor, GPER) for 4, 12, and 24 h, and β-AR mRNA expression was measured. Results:Immunofluorescence revealed presence of all three ERs and β-ARs in the HCAECs. ERα had the lowest mRNA expression, while GPER was the most abundant, with donor-dependent variability. ERβ and GPER proteins were slightly higher than ERα. β3-AR exhibited the lowest mRNA, β2-AR was the highest, and donor-specific differences were observed. Stimulation with 17β-estradiol or selective ER agonists did not alter β-AR mRNA expression. Conclusion:These findings demonstrate donor variability in ER and β-AR expression in HCAECs, limiting generalization. Under the tested conditions estrogen and ER agonists did not alter β-AR mRNA levels, suggesting that short-term ER stimulation is unlikely to regulate β-AR expression at the transcriptional level within this experimental setting.
Introduction Obesity-related HFpEF is linked to worse quality of life and health outcomes; however, the association of obesity with real-world healthcare resource utilization (HCRU) and economic burden in HFpEF is unknown. This study assessed the association between BMI and HCRU- and cost-related outcomes among patients with HFpEF. Methods This claims-based study utilized the Optum Market Clarity database to identify adult commercial, Medicare, and Medicaid patients with HFpEF based on EF ≥ 50% and ≥ 1 diagnosis of HF from Oct 01, 2016 to Mar 31, 2023. Baseline clinical characteristics, post-index rehospitalization rates, and per-patient-per-year HCRU and cost data were described. Associations between BMI and HCRU and cost outcomes was examined using generalized linear models adjusted for baseline characteristics. Results A total of 95,070 patients were included; 14.4% were with normal weight, 26.1% with overweight, 23.8% Class 1 obesity, 15.9% Class 2 obesity, and 19.9% Class 3 obesity. Across cohorts, patients with Class 2 and Class 3 obesity had high rates of all-cause and HF-related rehospitalizations. Patients with Class 2 and Class 3 obesity had higher rates of HF-related hospitalization/ER visits (both p < 0.001), compared to the overweight cohort, when adjusted for baseline covariates. Across comparisons, patients with Class 3 obesity had numerically higher HF-related costs compared with the overweight cohort. Conclusions This study demonstrated that patients with HFpEF and Class 3 obesity incurred higher healthcare costs, more frequent all-cause and HF-related acute care encounters, in general, and increased readmissions rates, compared to patients in other BMI groups.
Heart failure in older adults increasingly occurs in the context of frailty, multimorbidity, and declining physiological reserve. In this population, therapeutic efficacy demonstrated in selected clinical trial populations does not automatically translate into meaningful clinical benefit. This discrepancy may create tension between guideline-driven care and goal-concordant prescribing.This narrative review proposes a conceptual framework to distinguish therapeutic efficacy from clinical relevance in ageing heart failure populations. Using tafamidis for transthyretin cardiac amyloidosis and apixaban for atrial fibrillation as illustrative paradigms, we examine how frailty severity, competing risks, life expectancy, and therapy-specific time-to-benefit influence the likelihood that a treatment will provide meaningful benefit for an individual patient.Disease-modifying therapies with delayed benefit may lose proportionality when lag-time-to-benefit exceeds the patient’s anticipated window of preserved survival or functional autonomy. In contrast, preventive strategies that rapidly reduce autonomy-threatening events may retain broader clinical relevance across vulnerability strata, although individualized reassessment remains essential.We introduce the concept of temporal therapeutic mismatch, defined as a situation in which expected therapeutic benefit occurs beyond the patient’s remaining functional trajectory or life expectancy. A pragmatic framework integrating frailty severity, estimated life expectancy, competing risks, therapy-specific time-to-benefit, and patient-defined goals is proposed to support proportional prescribing.In ageing cardiovascular populations, high-quality care requires moving beyond efficacy alone toward frailty-informed clinical relevance. Structured reassessment—including consideration of non-initiation or deprescribing when appropriate—represents a key component of patient-centered cardiovascular care.
Introduction Pulmonary hypertension (PH) is associated with an increased risk of atrial fibrillation (AF), and AF onset in PH may signal advanced disease. While catheter ablation (CA) offers clinical benefits, post-ablation recurrence remains a challenge. We evaluated whether systolic pulmonary artery pressure (sPAP) predicts AF recurrence following pulmonary vein isolation (PVI). Methods Data from the prospective, multicenter Israeli Catheter Ablation Registry (ICAR) included 485 patients undergoing PVI between January 2019 and December 2021, all with echocardiographic sPAP measurements. Patients were stratified into two groups based on sPAP values: high-probability PH (sPAP > 45 mmHg) and low/intermediate probability PH (sPAP ≤ 45 mmHg). AF recurrence within 12 months was assessed, along with subgroup analyses and evaluation of procedural complications. Results Patients with high-probability PH were older (69.05 ± 8.75 vs. 64.34 ± 11.27 years; p < 0.01) and had more comorbidities. Cryoballoon ablation was utilized in 387 patients (79.8%). High-probability PH patients had significantly higher 12-month AF recurrence rates (30.4% vs. 17.2%; p = 0.029), despite similar acute procedural success and overall periprocedural complication rates. A Cox proportional hazards model identified sPAP > 45 mmHg as an independent predictor of recurrence (adjusted HR 2.55; p < 0.01), while spline analysis demonstrated a dose-dependent relationship between rising sPAP values and recurrence. Conclusion This study emphasizes the importance of PH, evaluated through echocardiographic sPAP values, in predicting post-PVI AF recurrence. These findings support incorporating echocardiographic sPAP into pre-procedural risk assessment to guide customized post-ablation monitoring.
Background:Oral P2Y12 inhibitors (P2Y12i) may have reduced efficacy in critically ill patients undergoing Impella-supported PCI. The intravenous P2Y12i cangrelor offers rapid and reversible platelet inhibition, but its role in this setting remains unclear. Objective:Comparison of outcomes in patients undergoing Impella-supported PCI receiving oral P2Y12i only versus loading with cangrelor. Methods:We analyzed consecutive patients managed at a Swiss tertiary cardiology facility who underwent Impella-supported PCI. Patients received either (1) oral P2Y12i or (2) cangrelor followed by oral P2Y12i. Periprocedural major bleeding (BARC ≥ 3) within 48 h, in-hospital major adverse cardiovascular events (MACE) and 6-month MACE were analyzed. Results:Among 295 patients, 201 received oral P2Y12i and 94 received cangrelor. Patients in the oral P2Y12i group were less likely to present with STEMI (55.7% versus 67.0%) or cardiogenic shock (55.2% versus 72.3%), whereas high-risk protected PCI was more frequent (17.9% versus 6.4%) compared to cangrelor group. No significant differences were observed in major bleeding, in-hospital MACE and 6-month MACE. Major bleeding was numerically lower in the oral P2Y12i group (26.4% versus 33.0%, p = 0.2). Early stent thrombosis rates were relatively low and not significantly different (1.0% versus 2.1%, p = 0.6). Presentation with cardiogenic shock was associated with a higher risk for post-PCI major bleeding (OR 7.09, 95%CI 2.97-18.49) and 6-month MACE (HR 2.01, 95% CI 1.01-3.97). Conclusion:In Impella-supported PCI, cangrelor was associated with no statistically significant differences in outcomes compared to oral P2Y12i, with consistent results after adjustment. Given the observational design, these findings require confirmation in randomized trials.
Background There is a paucity of data regarding short-term outcomes and treatment responsiveness of myocardial T1 mapping via cardiac magnetic resonance (CMR) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) undergoing tafamidis therapy. Methods We retrospectively studied 60 wild-type ATTR-CM patients who underwent baseline CMR to measure native myocardial T1 value (T1native) and extracellular volume fraction (ECV), followed by tafamidis treatment. Cardiac biomarkers, including high-sensitivity cardiac troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were measured at baseline. We followed a one-year composite of worsening heart failure (WHF; hospitalization and/or intensification of diuretic therapy for heart failure). Additionally, 51 patients underwent follow-up CMR and measurements of cardiac biomarkers one-year after the initiation of tafamidis treatment. Results Patients with WHF (n = 12) exhibited significantly elevated baseline T1native and ECV than those without WHF, and their optimal cutoffs in predicting WHF were 1447 ms and 48.7 %, respectively. Multivariate analysis adjusted for Mayo or National Amyloidosis Center stages identified T1native of ≥ 1447 ms as an independent predictor of WHF, with hazard ratios of 15.2 and 9.3, respectively. A notable proportion of patients exhibited a reduction in T1native (39 %) and ECV (47 %) after one year of tafamidis treatment. Post-treatment changes in T1native were correlated positively with changes in NT-proBNP concentration (r = 0.40, p = 0.0036). Conclusions In wild-type ATTR-CM patients receiving tafamidis, elevated baseline T1 mapping parameters were associated with one-year WHF. T1 mapping parameters, particularly T1native, may offer imaging-based evidence of alterations in myocardial characteristics induced by tafamidis.
Background:Coronary artery disease (CAD) and aortic valve stenosis (AS) often coexist, with AS exacerbating myocardial ischemia and affecting prognosis. Aims:To investigate the prognostic impact of AS stratified by peak aortic jet velocity (AV-Vel) in patients undergoing PCI. Methods and results:We conducted retrospective multicenter observational study involving patients who underwent percutaneous coronary intervention (PCI) between April 2013 and March 2019. The patients were divided into non-AS group and AS group. The AS group was further categorized: 2.6 ≤ AV-Vel < 3.0 m/s, mild AS; 3.0 ≤ AV-Vel < 4.0 m/s, moderate AS; and AV-Vel ≥ 4.0 m/s, severe AS. The primary outcome was all-cause mortality, and the secondary outcome was major adverse cardiovascular events (MACE), defined as a composite of all-cause mortality, myocardial infarction, or stroke. Multivariable Cox proportional hazards analysis was performed over 5-year observation period, with landmark analyses conducted at 30 days after PCI and from day 31 after PCI to 5 years. In total, 9,690 patients were analyzed (AS group, n = 361). Over a median follow-up of 2.57 (IQR: 0.89-4.24) years, AS group exhibited higher rates of mortality (HR: 3.06; 95% CI: 2.41-3.90; p < 0.001) and MACE (HR: 2.45; 95%CI: 1.97-3.04; p < 0.001) compared with non-AS group. Subgroup analysis revealed that patients with moderate and severe AS had worse short-term mortality and MACE within 30 days after PCI than the non-AS group, while patients with mild to severe AS showed significantly worse long-term outcomes than the non-AS group. Conclusions:AV-Vel is independently associated with both short- and long-term outcomes in patients undergoing PCI.
Background Systolic dysfunction, diastolic dysfunction, and clinically overt heart failure are frequently encountered after acute ischaemic stroke. We investigated whether these cardiac phenotypes, considered as distinct entities, are associated with readmission and death within two years after stroke in the prospective SICFAIL cohort. Methods Adults with acute ischaemic stroke were consecutively enrolled between 01/2014 and 02/2017. Cardiac function was assessed at baseline, and patients were followed annually by mail or telephone. The primary endpoint was the composite of all-cause readmission or death. Secondary analyses considered individual endpoints and cardiovascular readmissions. Associations were estimated using multivariable Cox proportional hazards models. Results Of 696 enrolled patients, 644 (92.5%) had interpretable echocardiographic data. During two-year follow-up, 206 of 554 patients (37.1%) with complete outcome information were rehospitalised, and 63 of 577 patients (11.4%) with available vital status data died. After adjustment, systolic dysfunction and clinically overt heart failure were independently associated with the composite endpoint (systolic dysfunction: hazard ratio [HR] 1.97 (95% confidence interval [CI], 1.34–2.91); clinically overt heart failure: HR 1.62, 95% CI 1.02–2.58). Systolic dysfunction also predicted cardiovascular readmissions (HR 2.27, 95% CI 1.22–4.21). Diastolic dysfunction was not associated with adverse outcomes. Conclusion In this cohort, systolic dysfunction and clinically overt heart failure at the time of ischaemic stroke independently predicted the composite of readmission or death over the subsequent two years, whereas isolated diastolic dysfunction was not prognostically informative. Routine echocardiographic assessment after stroke may therefore help identify patients who would benefit from intensified cardiac follow‑up and secondary prevention.
Background:Atrial Fibrillation (AF) may progress from paroxysmal AF (PAF) to more sustained forms, but predicting which patients progress remains a challenge. The RACE V study is a prospective, observational study aiming to characterize phenotypical differences between patients with and without AF progression. Based on interim data of the RACE V study, a clinical risk prediction model for AF progression in patients with PAF was previously developed. The aim of the current analysis is to assess its performance in the complete cohort over extended follow-up. Methods:In the RACE V study, 612 patients with PAF were extensively phenotyped and continuously monitored using implantable loop recorders to track AF recurrences. AF progression was the primary outcome, defined as (1) progression to persistent or permanent AF, or (2) AF burden increase > 3%, during complete follow-up. The risk score incorporates five clinical predictors at baseline: sex, PR interval duration, left atrial contractile function, waist circumference, and presence of mitral valve regurgitation. Prediction model performance was assessed using receiver operating characteristic (ROC) curve-derived area under the curve (AUC). Results:Patients had a median age 64 [57 - 70] years, and 42% were female. During a follow-up of 3.4 (2.8 - 3.7) years, 108 (5.2%/year) patients progressed. The risk prediction model demonstrated a C-statistic of 0.647 (95% CI: 0.590-0.707) in the full cohort, compared with 0.709 (95% CI: 0.617-0.801) in the interim cohort (DeLong's unpaired test, p = 0.656). Conclusions:The model may help clinicians identify patients at risk of progression, showing stable performance in the whole cohort over extended follow-up.
Background:Atrial fibrillation (AF) is an important late complication in patients with repaired tetralogy of Fallot (TOF); however, its clinical determinants and arrhythmogenic substrates remain uncertain. Identifying high-risk anatomical profiles is essential for optimal rhythm management and tailored ablation strategies. Methods:We retrospectively analyzed 137 consecutive patients with repaired TOF followed at the University of Tsukuba Hospital (2013-2024). Clinical characteristics, echocardiographic parameters, and procedural findings were compared between patients with and without AF. Logistic regression identified independent predictors. Catheter ablation approaches and outcomes were evaluated in patients who underwent AF ablation. Results:AF occurred in 14 patients (10.2%), frequently coexisting with atrial tachycardia (78.6%). Compared with patients without AF, those with AF were older, had undergone more repeat cardiac surgeries, and more commonly exhibited a persistent left superior vena cava (PLSVC), greater biatrial enlargement, and mildly reduced right ventricular function. On multivariable analysis, PLSVC remained statistically associated with AF (odds ratio 15.5, p = 0.002); however, this association was primarily driven by patients with combined AF and AT, as no PLSVC was observed in the small isolated AF subgroup. Among six patients who underwent catheter ablation, those without PLSVC were successfully treated with pulmonary vein isolation (PVI) alone, whereas two patients with PLSVC underwent right-sided ablation targeting the right atrium and coronary sinus, with no AF recurrence observed during follow-up. Conclusions:PLSVC was associated with more complex atrial tachyarrhythmias, particularly in patients with concomitant AF and AT. Recognizing this substrate may inform individualized ablation strategies beyond conventional PVI.
Background:The PRAGUE-25 trial demonstrated catheter ablation (CA) superiority over lifestyle modification plus antiarrhythmic drugs (LFM + AAD) in obese patients with atrial fibrillation (AF). However, obese AF patients represent a heterogeneous population with varying pathophysiological substrates. We hypothesized that distinct patient phenotypes may exhibit differential treatment responses. Methods:This post-hoc analysis applied hierarchical cluster analysis (Ward's D2 method, Euclidean distance) to 122 PRAGUE-25 patients with complete data using six delta (12-month minus baseline) echocardiographic and metabolic variables (Δ-LAVI, Δ-LVEDD, Δ-NT-proBNP, Δ-triglycerides, Δ-leukocytes, Δ-platelets). Treatment effects within each phenotype were compared using Fisher's exact test and odds ratios with 95% confidence intervals. Results:Three distinct phenotypes were identified: Metabolic (n = 20, 16%), characterized by highest triglycerides with minimal structural remodeling; Intermediate Remodeling (n = 67, 55%), distinguished by largest LV chamber with lowest inflammatory burden; and Advanced Neurohormonal/Inflammatory (n = 35, 29%), exhibiting highest NT-proBNP with elevated inflammatory markers. While cluster membership did not predict overall AF freedom (χ2 = 3.45, p = 0.178), CA superiority was statistically significant only in the Intermediate phenotype (OR 3.98, 95% CI: 1.01-15.57, p = 0.047; AF freedom 88.5% CA vs 65.9% LFM + AAD). In the Metabolic and Advanced Neurohormonal/Inflammatory phenotypes (45% of patients), no statistically significant treatment difference was observed; however, wide confidence intervals preclude conclusions of treatment equivalence in these underpowered subgroups. These findings appear to be primarily driven by the Intermediate Remodeling phenotype. Conclusions:These hypothesis-generating findings suggest phenotype-dependent treatment response heterogeneity in obese atrial fibrillation. As cluster membership can only be determined retrospectively, prospective validation using baseline predictor models is required before clinical application.
Background:Non-obstructive hypertrophic cardiomyopathy (nHCM) remains a therapeutic challenge, with limited pharmacological options beyond symptomatic management. Mavacamten, a selective allosteric cardiac myosin inhibitor, has shown benefit in obstructive HCM, but its role in nHCM is uncertain. Methods:A systematic search of PubMed, Embase, CENTRAL, and ClinicalTrials.gov was conducted up to November 2025 for placebo-controlled randomized controlled trials (RCTs) enrolling patients with nHCM. Outcomes included Kansas City Cardiomyopathy Questionnaire (KCCQ) score, peak oxygen consumption (pVO2), New York Heart Association (NYHA) functional class, and treatment-emergent adverse events (TEAEs). Pooled mean differences (MDs) and risk ratios (RRs) were estimated using random- or fixed-effects models based on heterogeneity. Results:Two RCTs (n = 639) met inclusion criteria. Mavacamten showed a nonsignificant improvement in KCCQ (MD: 2.12; 95% CI: -0.98 to 5.22; I2 = 0%) and peak oxygen consumption (MD: 0.36 mL/kg/min; 95% CI: -0.20 to 0.92; I2 = 0%). No significant difference was observed in NYHA class improvement (RR: 1.15; 95% CI: 0.93 to 1.43; I2 = 0%). TEAE incidence was similar between groups (RR: 1.11; 95% CI: 0.34 to 3.58; I2 = 40.8%). Atrial fibrillation occurred more frequently with mavacamten (RR: 1.41; 95% CI: 1.28 to 1.56), whereas palpitations and dizziness did not differ significantly. Conclusions:Mavacamten does not significantly enhance symptoms, functional capacity, or health status in nHCM, though safety is comparable to placebo. Ongoing monitoring for arrhythmias and reduced ejection fraction is essential. Larger, longer-term studies are needed to clarify its role in this population.
