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

BackgroundThe optimal timing and efficacy of pharmacological rhythm control in patients with preoperative atrial fibrillation (AF) undergoing cardiopulmonary bypass (CPB) surgery remain unclear. We aimed to evaluate the effectiveness of intravenous amiodarone administration during rewarming on early cardioversion and short-term outcomes, and to develop a predictive model for postoperative AF recurrence. MethodsThis retrospective cohort study included adult patients with preoperative atrial fibrillation who underwent cardiac surgery with CPB. Patients receiving a 150 mg intravenous bolus of amiodarone via the oxygenator at systemic rewarming initiation (nasopharyngeal temperature [&ge;]32{degrees}C) during aortic cross-clamping (ACC) were defined as the amiodarone group (A group, n=423), and were compared with the non-intervention group (NI group, n=191). The primary outcome was sustained sinus rhythm within 12 hours post-cardioversion. Secondary outcomes included myocardial injury (measured by cardiac troponin I, cTnI), inflammatory response (neutrophil count, NEUT), renal function (blood urea nitrogen, BUN), use of inotropic support (milrinone, MIL) and renal replacement therapy (hemodialysis, HD), length of hospital stay (LOHS), and other short-term clinical endpoints. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline imbalances. A multivariable logistic regression model was developed and validated to predict early AF recurrence. ResultsOf 614 patients, 423 were in the A group and 191 in the NI group. After IPTW adjustment, the A group had a significantly higher rate of sustained sinus rhythm (52.5% vs. 7.8%, P<0.001). They also exhibited lower levels of cTnI, NEUT, and BUN, reduced use of MIL and HD, and shorter LOHS, along with other favorable outcomes. NT-proBNP was transiently higher in the A group. The final prediction model--incorporating age, left atrial anteroposterior diameter (LAAD), left ventricular end-diastolic diameter (LVED), right ventricular anteroposterior diameter (RVAD), serum calcium, and comorbidity grade--showed strong discrimination (AUC: 0.866 in the training cohort, 0.795 in the validation cohort). ConclusionAmiodarone administration during rewarming improves early rhythm stability and short-term clinical outcomes in patients with preoperative AF undergoing CPB surgery. A validated risk prediction model identifies patients at high risk for recurrence, supporting individualized perioperative management strategies.

BackgroundGenetic testing is now recommended for select patients with early-onset atrial fibrillation (AF). Hemochromatosis is an autosomal recessive syndrome that occurs in patients who carry two pathogenic or likely-pathogenic (P/LP) variants in HFE. HFE is included on some genetic testing panels used for patients with AF. Hemochromatosis causes cardiomyopathy due to iron overload in the ventricle; however, it is unknown whether AF can be an early manifestation that is identified by genetic testing. MethodsA total of 347 patients were referred to a dedicated AF precision medicine clinic. The clinical diagnostic evaluation included an H&P, 12-lead ECG, ambulatory ECG monitoring, and cardiac imaging (cardiac MRI and/or TTE). Genetic testing was performed using CLIA-approved laboratories: Labcorp/Invitae, GeneDx, or Vanderbilt University Medical Center. HFE was included on the cardiomyopathy panel used by 2 of the 3 laboratories. ResultsHFE was tested in 165 participants (median age 46 years [IQR 35-55], 115 [70%] male, 149 [90%] White). Six participants (4%) had two pathogenic variants in HFE. All of them were C282Y/H63D compound heterozygotes. Forty-one participants (25%) were heterozygous carriers of one pathogenic HFE variant. Among the 6 participants with 2 pathogenic HFE variants, the median ferritin level was 346 mcg/L [IQR 262, 496] (normal <300 mcg/L males, <200 mcg/L females). Three participants (50%) met laboratory criteria for iron overload. One individual had isolated ferritin elevation with normal transferrin saturation. All 6 underwent cardiac MRI as part of the genetic evaluation for early onset AF, and there was no evidence of cardiac siderosis based on cardiac T1 mapping median 990 ms [IQR 968-1024] (normal 960-1030 ms). Dedicated sequences to evaluate for iron overload demonstrated short hepatic T2* in one individual, indicating presence of hepatic iron overload (9 ms, normal >11.4 ms; liver iron concentration 3.4 mg/g, normal <2 mg/g). Three out of 6 participants were referred for a hematology evaluation and 2 out of 6 were started on therapeutic phlebotomy. ConclusionGenetic testing can identify patients with early-onset AF who are genetically susceptible to hemochromatosis, have evidence of iron overload, and receive early intervention with therapeutic phlebotomy. These results suggest HFE should be sequenced as part of genetic testing for early-onset AF, but larger sample sizes are needed to confirm these results.

BackgroundAtrial adverse remodeling drives the maintenance and progression of atrial fibrillation (AF) through electrical and structural myocardial changes, often accompanied by inflammation. Circulating N-glycans are emerging as biomarkers in inflammatory diseases, yet their role in AF remains undefined. MethodsWe profiled the serum N-glycome of 138 patients with AF, non-AF arrhythmias, or sinus rhythm (SR) controls from peripheral venous (PV) and coronary sinus (CS) samples using hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry. Glycan traits associated with AF were identified via logistic regression adjusted for clinical risk factors. Multivariate glycan scores were derived from PV and CS datasets using LASSO regression. In a subset (N=37), plasma proteome profiling was performed with the Olink Reveal panel. ResultsSixty-two glycan peaks were detected; 27 in PV and 8 in CS serum differed significantly between AF and controls. PV and CS glycan scores accurately classified AF, with the PV score correlating with 11 plasma proteins linked to structural remodeling and thrombo-inflammatory processes. The most abundant glycan, A2G2S2 (peak 30), was associated with higher odds of AF after adjusting for confounders (OR 2.22 [95% CI: 1.40-3.75], P = 0.001). CS A2G2S2 correlated with C-reactive protein (R = 0.432, P = 0.0275) and was elevated in patients with left atrial enlargement (P = 0.0354), but unchanged in those with impaired left ventricular ejection fraction or hypertrophy. ConclusionIntegrated profiling of peripheral and cardiac serum identifies novel N-glycosylation signatures in AF. Specific cardiac and circulating N-glycan signatures, including A2G2S2, are associated with AF and reflect inflammation-driven atrial remodeling, highlighting potential mechanistic pathways and biomarker applications.

BackgroundThere are controversies about whether atrial fibrillation (AF) type, paroxysmal (PaAF) vs persistent (PeAF), affects stroke risk. The type of AF is still not included in most risk stratification tools. ObjectiveWe aim to assess differences in stroke outcomes between PaAF and PeAF patients in both low- and high-CHA2DS2-VASc groups. MethodsWe conducted an epidemiological study of all patients admitted to Tulane Medical Center with the diagnosis of AF from January 2010 to March 2020. Data were extracted from the regional US electronic medical records database, Research Action for Health Network (REACHnet), for all patients aged 18 years or older with a diagnosis of AF. Patients were divided into four groups: a low CHA2DS2-VASc score was defined as CHA2DS2-VASc < 2 in women and CHA2DS2-VASc < 1 in men. PeAF was defined as a patient with at least one episode of AF lasting 7 days or more. PaAF was defined as a patient with AF with no episode lasting more than 7 days. The outcome of the study was an ischemic stroke event or a transient ischemic attack that occurred after the diagnosis of AF. Kaplan-Meier curves and the log-rank test were used to compare the study outcomes across all four groups. Multivariable Cox regression was performed to adjust for the use of anticoagulants. ResultsA total of 1,079 patients were included in the study. 576 patients had PaAF and high CHA2DS2-VASc, 215 had PaAF and low CHA2DS2-VASc, 214 had PeAF and high CHA2DS2-VASc, and 74 patients were PeAF, and low CHA2DS2-VASc. Patients were followed up over 5 years. Based on the Log-rank test, there were significant differences among the four groups (p < 0.001). After adjusting for anticoagulants, patients with high CHA2DS2-VASc appeared to have more strokes on follow-up than patients with low CHA2DS2-VASc, independent of AF type and anticoagulation prescription. For the Cox model, when the PaAF High CHA2DS2-VASc group was used as the reference, both low CHA2DS2-VASc groups, PaAF (0.032 [0.012-0.081], p < 0.001) and PeAF (0.032 [0.008-0.135], p < 0.001), had a lower risk of stroke. However, there was no difference in stroke when the reference group was compared to high CHA2DS2-VASc, PeAF (1.169 [0.866 - 1.576], p=0.308). ConclusionIn our database, the CHA2DS2-VASc score remained superior to the type of AF when predicting stroke outcome. Type of AF did not affect stroke outcome even after adjusting for CHA2DS2-VASc and for anticoagulation prescription.

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.

BackgroundGuideline-directed medical therapy (GDMT) has been shown to improve mortality and/or symptoms in heart failure with reduced ejection fraction (HFrEF). Medical devices also play an important role in improved quality of life and overall symptom relief for HFrEF patients. Baroreflex Activation Therapy (BAT) increases parasympathetic nervous system activity by stimulating the carotid baroreceptors, thereby reducing symptoms. Herein, we analyzed the effects of BAT on hospitalization, atrial arrhythmia (AA), and ventricular arrhythmia (VA) rates. MethodsA retrospective cohort study was conducted consisting of HFrEF patients treated with BAT at Keck Hospital of USC between 11/2014 and 11/2022. We compared median pre-BAT hospitalization, AA, and VA rates to post-BAT rates at both 6- and 12-months using Wilcoxon Signed Rank tests. ResultsAmong 31 patients on BAT, 38.7% met criteria for receiving all four GDMT classes for at least 12 months prior to BAT. Among these, 91.7% had an implantable cardioverter defibrillator (ICD) implanted for [&ge;]12 months pre- and post-BAT. Average pre- vs. post-BAT all-cause hospitalization rates were significantly different only at 12 months [1.3 {+/-} 1.4 vs 0.3 {+/-} 0.9, respectively (p=0.05)]. Borderline significant pre-post comparisons were noted including decreased VA rate at both 6 and 12 months and increased AA rate at 12-months (p=0.06 for all). ConclusionIn HFrEF patients on full GDMT, BAT was associated with a significant reduction in hospitalization rates at 12 months. There were no significant changes in AA or VA rates.

BackgroundSodium glucose co-transport inhibitors (SGLT2i), although established heart failure (HF) therapy in acquired heart disease, are not well-studied in adult congenital heart disease (ACHD). We aimed to conduct a systematic review and meta-analysis of SGLT2i therapy in moderate or severe complexity ACHD. MethodsFive databases (Pubmed, Medline, Embase, SCOPUS, and Cochrane) were searched for peer-reviewed journal articles describing SGLT2i HF therapy in moderate or severe complexity ACHD. Outcomes included adverse clinical events, biochemical markers of HF (N-terminal pro-brain natriuretic peptide [NT-proBNP] or BNP), and imaging markers of cardiac function (global longitudinal strain [GLS] and fractional area change [FAC]). Forest plots demonstrated mean study effects as individual and pooled estimates. The impact of heterogeneity on the overall variance was evaluated. ResultsThe systematic review included 10 studies (n=174 patients, 60% male). SGLT2i therapy was associated with a statistically significant improvement in GLS (mean difference -1.6 [-2.4,-0.9]) but not FAC (mean difference +1.86 [-6.2,+9.9]); there was no significant post therapy change in NT-proBNP or BNP (mean difference -240 pg/mL [-516,45] and -52 pg/mL [-129,26], respectively). Heterogeneity for the pooled effects for GLS and FAC was low (I2=0%), although moderate to high for NT-proBNP and BNP (I2=47% and I2=90%, respectively). Data were insufficient for evaluation of SGLT2i impact on clinical outcomes. ConclusionsPooled results across studies suggest that SGLT2i therapy can improve GLS among people with ACHD-HF, however the clinical implications of this observation warrant further study. Randomized controlled trials are now needed to evaluate the impact of SGLT2i therapy in ACHD.

BackgroundAtrial fibrillation and flutter (AF/AFL) represent a major global public health challenge, contributing significantly to stroke, heart failure, and cardiovascular mortality. While previous studies have documented a rising AF/AFL burden, comprehensive comparisons of long-term trends and forecasts across regions--particularly benchmarking China against Southeast Asia, Europe, and global averages--remain limited. This study aims to quantify the AF/AFL burden across these regions from 1990 to 2021 and project trends to 2050. MethodsUsing data from the Global Burden of Disease Study 2021, we analysed the burden of AF/AFL from 1990 to 2021 in China, Southeast Asia, Europe, and globally. We examined incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Advanced analytical methods, including Joinpoint regression, age-period-cohort modelling, decomposition analysis, Frontier analysis and Bayesian forecasting were employed to assess trends, drivers, and projections to 2050. FindingFrom 1990 to 2021, China experienced the most rapid increase in age-standardized incidence rate (ASIR) globally (AAPC +0.16%), with incident cases rising to 916,180, accounting for 20.43% of the global total. In contrast, Europe saw a slight decline in ASIR, while the global ASIR remained stable. China also recorded the largest increase in age-standardized prevalence rate (ASPR), whereas Europes ASPR declined. Despite rising incidence, China achieved the sharpest reduction in age-standardized mortality rate (ASMR; AAPC -0.45%), while Southeast Asias ASMR increased (AAPC +0.76%), and Europe maintained the highest ASMR globally. Frontier analysis highlighted Chinas rapid efficiency improvements in mortality reduction relative to its SDI, outperforming several high-income European countries. Projections to 2050 suggest Chinas ASIR and ASPR will continue to rise, whereas Europes are forecast to decline. Southeast Asia faces persistently increasing mortality, and global aggregates mask significant regional heterogeneity. ConclusionAF/AFL burdens are increasingly driven by population aging and metabolic risks, with heterogeneous mortality trends reflecting regional disparities in healthcare access and prevention. China s success in reducing mortality despite rising incidence highlights the impact of improved anticoagulation and stroke prevention, yet unchecked prevalence growth signals future complications. Southeast Asia s rising mortality underscores urgent needs for equitable resource allocation, while Europes stagnant burden reflects challenges in aging populations. Globally, prioritising primordial prevention--such as metabolic risk control--alongside targeted screening and gender-specific interventions, is critical to mitigating AF/AFL-related morbidity and mortality. Future efforts should integrate digital health technologies and address structural barriers to optimize care efficiency worldwide. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSPrior to undertaking this analysis, we systematically reviewed the existing epidemiological literature on atrial fibrillation and atrial flutter (AF/AFL), with a particular emphasis on global and regional comparative studies. Our searches covered PubMed, Embase, Web of Science, the Cochrane Library, and the Global Burden of Disease (GBD) repository from January 1990 to December 2023, without language restrictions. Key terms included "atrial fibrillation," "atrial flutter," "global burden," "epidemiology," "trend," and "GBD." We included studies providing representative estimates of AF/AFL burden and excluded small-sample or non-age-standardized reports. Previous analyses indicated a rising global AF/AFL burden, largely due to population aging and improved detection. However, comprehensive assessments capturing temporal dynamics, risk drivers, and forecasting across major world regions--especially benchmarking China, Southeast Asia, and Europe against global patterns--remained limited. Most studies focused on isolated regions or short spans, lacking integrative multidimensional approaches such as age-period-cohort modeling, decomposition, or Bayesian forecasting. Added value of this studyThis study provides a comprehensive and comparative assessment of the atrial fibrillation and atrial flutter (AF/AFL) burden across China, Southeast Asia, Europe, and globally from 1990 to 2021, utilizing the latest GBD 2021 data and advanced statistical methodologies, including Joinpoint regression, age-period-cohort modeling, Bayesian forecasting, decomposition analysis, and data envelopment frontier analysis. Our analysis reveals significant regional disparities against a backdrop of global stability: while the global age-standardized incidence rate (ASIR) remained stable (52{middle dot}51 in 1990 vs. 52{middle dot}12 in 2021), China experienced the most rapid increase worldwide (ASIR rising from 42{middle dot}63 to 44{middle dot}92), with a substantial number of new cases (916,180), accounting for 20{middle dot}43% of the global total (4,484,926 cases). In contrast, Europe recorded a slight decline in ASIR. China also demonstrated the most pronounced increase in prevalence globally, while Europes age-standardized prevalence rate (ASPR) declined and the global rate remained largely unchanged. Notably, China achieved a significant reduction in mortality (age-standardized mortality rate [ASMR] declining from 4{middle dot}93 to 4{middle dot}33) despite rising incidence, sharply contrasting with Southeast Asia, where ASMR increased from 2{middle dot}94 to 4{middle dot}06 (estimated annual percentage change +1{middle dot}07%)--trends potentially associated with structural challenges in Southeast Asia--while Europe maintained the highest ASMR globally (5{middle dot}10 in 2021) despite interventions. We further identified key drivers: population growth and aging accounted for the majority of the case increase in China, consistent with global demographic trends, while metabolic risk factors accelerated this trend. Gender and age analyses revealed a global pattern of later-life predominance in women and earlier onset in middle-aged groups, particularly pronounced in China. Our projections to 2050 indicate a continued rise in ASIR and ASPR in China, reinforcing its significant and growing contribution to the global AF/AFL burden, whereas other regions face divergent challenges--Southeast Asia is projected to experience persistently increasing mortality pressure, while Europe must address persistently high disability-adjusted life year (DALY) rates, masking mortality gains in an aging population. Implications of all the available evidenceThe collective evidence from this study and previous research underscores that AF/AFL remains a critical and growing public health challenge worldwide, characterized by heterogeneous patterns across regions when viewed against the global aggregate. Chinas success in reducing mortality within a rising incidence environment highlights the potential of enhanced clinical management and stroke prevention, yet its unchecked prevalence growth--especially among younger cohorts--signals a looming surge in complications absent strengthened primary prevention, a concern mirrored in many developing economies. Southeast Asias rising mortality underscores urgent needs for improved access to anticoagulation and rhythm control, while Europes stagnant burden reflects challenges in managing an aging population efficiently. These findings advocate for regionally tailored strategies that align with global frameworks but address local disparities--integrating primordial prevention (e.g., metabolic risk control) with early detection, gender-specific treatment, and equitable resource allocation. Future research should prioritize mechanistic studies of AF/AFL subtypes, real-world intervention assessments, and the integration of digital health technologies for scalable screening and management, thereby informing coordinated global actions to mitigate the evolving burden of AF/AFL.

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 ([&ge;]100 bpm) was associated with higher odds of atrial cardiopathy (OR 1.76, 95% CI 1.06-2.92), whereas sinus bradycardia ([&le;]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.

BackgroundCoronary artery tortuosity (CAT) is often viewed as a benign angiographic finding; however, emerging evidence suggests its potential hemodynamic significance, particularly in non-atherosclerotic cardiomyopathies such as Takotsubo syndrome (TS). ObjectivesThis study aimed to investigate the prevalence and hemodynamic implications of CAT in patients diagnosed with Takotsubo cardiomyopathy (TCM) and to evaluate the association between the severity of tortuosity and myocardial injury markers, recovery of ventricular function, and other clinical variables. MethodsA retrospective review of 100 patients with TCM from the Baptist Memorial Hospital network (2015-2025) was conducted. Tortuosity severity was quantified using angiographic criteria per Eleid et al. (2014). Associations between CAT and biochemical or echocardiographic parameters were evaluated using multiple linear regression and non-parametric tests. ResultsCAT was highly prevalent (85.1%) in this TCM cohort, with a mean tortuosity index of 3.26--significantly higher than in general angiography populations. No significant correlations were found between tortuosity severity and peak troponin levels (p = .588) or ejection fraction (EF) at presentation (p = .820). Full EF recovery (55-65%) at [&ge;]3 months occurred in 70.7% of patients and was not significantly associated with prior cardiomyopathy, coronary artery tortuosity index or baseline troponin levels. ConclusionsCAT appears markedly more prevalent among patients with TCM, although its severity does not correlate with biomarker elevation or EF recovery. These findings suggest that coronary tortuosity may contribute to the hemodynamic environment predisposing to TS, without directly determining the extent of myocardial dysfunction or recovery.

BackgroundHypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease associated with increased risks of heart failure, sudden cardiac death (SCD), and stroke. Over 1,400 pathogenic variants, primarily in MYH7 and MYBPC3, have been identified, yet the prognostic significance of genetics remains unclear. Recent studies suggest genotype-positive (G+) HCM is linked to earlier diagnosis, greater disease severity, and poorer outcomes, necessitating further research to clarify the relationship between genotype, disease progression, and clinical management. ObjectivesO_LIExamine the association between genetic mutations (MYBPC3, MYH7, TNNT2, TNNI3) and both clinical outcomes (AF, syncope, ventricular arrhythmias, SCD, stroke) and structural cardiac characteristics (left atrial/ventricular thickness, LVEF) in HCM patients. C_LIO_LIConduct a systematic review and meta-analysis to evaluate the prognostic significance of genotype-positive HCM, aiming to inform clinical risk stratification and management strategies. C_LI MethodsA systematic literature search in PubMed for English-language articles from 2000 onward using relevant Medical Subject Headings (MeSH) terms identified six studies meeting inclusion criteria. G+ HCM was defined as mutations in MYBPC3, MYH7, TNNT2, or TNNI3. Data analysis employed the Cochrane Database of Systematic Reviews, assessing outcomes via risk ratios and mean differences with random-effects models. Heterogeneity was evaluated using appropriate statistical methods. ResultsG+ HCM showed significantly increased risk of AF (RR 1.20, p = 0.02) and ventricular arrhythmias (RR 1.56, p = 0.04), with greater left atrial thickness (p = 0.004). No significant differences were found in syncope (p = 0.33), stroke (p = 0.98), or SCD (p = 0.22), left ventricular thickness (p = 0.13), or LVEF (p = 0.10) between G+ and G-patients. These findings underscore the impact of genetic mutations on arrhythmic risk and structural remodeling in HCM. ConclusionsGenetic mutations in MYBPC3, MYH7, TNNT2, and TNNI3 increase AF, ventricular arrhythmias, and left atrial remodeling risks in HCM patients, but do not significantly affect stroke, SCD, syncope, or left ventricular structure. Genetic status is crucial in risk assessment, necessitating close arrhythmia monitoring in G+ patients and further research to refine risk stratification and management strategies in HCM.

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 [&ge;]12 months after second- or third-generation drug-eluting stent implantation. Complex PCI was defined by one of the following characteristics: [&ge;]3 stents, [&ge;]3 lesions, bifurcation with 2 stents, total stent length [&ge;]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

Structured abstractO_ST_ABSBackgroundC_ST_ABSTransthyretin amyloid cardiomyopathy (ATTR-CM) has historically been underdiagnosed but has recently become increasingly recognized due to advances in diagnostic techniques and heightened clinical awareness. Despite this progress, treatment options remain limited, as current approved therapies are costly and not widely accessible. Given the benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors in broader heart failure (HF) populations, we aimed to evaluate their efficacy in reducing mortality and hospitalizations in ATTR-CM. ObjectivesTo determine whether SGLT2 inhibitors reduce all-cause mortality, CV mortality, and HF hospitalizations in ATTR-CM, offering a potential adjunctive therapy for this undertreated population. MethodsWe performed a systematic review and meta-analysis of SGLT2 inhibitors against SGLT2 inhibitors-naive patients with ATTR-CM. PubMed, Embase, Scopus and Cochrane databases were searched for trials published up to January 31, 2025. Data were extracted from published reports, and quality assessment was performed per Cochrane recommendations. Risk ratios (RRs) with 95% confidence interval (CI) were pooled across trials. Outcomes included all-cause mortality, CV mortality and HF hospitalization. ResultsOut of 177 database results, four observational studies and 5039 patients were included; 2489 (49.39%) received a SGLT2 inhibitor. All-cause mortality (RR 0.44; 95% CI 0.33-0.59; p<0.00001; I{superscript 2}=54%) and CV mortality (RR 0.30; 95% CI 0.16-0.55; p=0.0001; I{superscript 2}=25%) were significantly lower in patients treated with SGLT2 inhibitors compared with control. HF hospitalization (RR 0.68; 95% CI 0.33-1.41; p=0.30; I{superscript 2}=89%) showed a downward trend, yet this was not statistically significant. ConclusionsIn patients with ATTR-CM, SGLT2 inhibitors significantly reduce both all-cause and cardiovascular mortality compared to standard care, suggesting they may serve as a valuable adjunctive therapy for this undertreated population. Although HF hospitalization showed a nonsignificant downward trend, these findings underscore the need for large randomized trials to confirm and expand on these promising results.

BackgroundDespite the broad availability of antihypertensive drugs, approximately 40% of hypertensive patients fail to achieve the recommended blood pressure (BP) levels and may require alternative treatment(s). Currently, renal denervation is the only proven non-pharmacological device-based alternative treatment available but is a costly hospital-based invasive procedure that is unlikely to be widely available. Transcutaneous autonomic neuromodulation (tAN), if safe, acceptable and efficacious, can offer a non-invasive, inexpensive, self-administered device-based innovative adjunct or alternative to pharmacological therapy. MethodsSCRATCH-HTN is a double-blind, sham-controlled trial, with 63 participants randomised on a 2:1 basis to receive either tAN or sham-tAN treatment. Hypertensive patients on medications were included if they had elevated systo-diastolic BPs on daytime ambulatory BP monitoring (ABPM) (systolic BP (SBP) of [&ge;]135 and <170 mmHg and mean daytime diastolic BP (DBP) of [&ge;]85 and < 115 mmHg). Participants were trained to self-administer tAN therapy for 30 minutes every day for first 14 days, and then once a week for 10 weeks. The primary endpoint was the change in daytime ambulatory SBP from baseline to 3 months. Secondary endpoints included the change in 24-hour ambulatory and office SBP and DBP, BP variability, heart rate variability, quality of life, and sleep quality from baseline to end-of-treatment. Other exploratory outcomes included evaluation of impact on functional exercise (6-minute walk test), structural and functional changes in the heart, cognitive function and central blood pressures. In a subgroup of patients detailed autonomic functional assessment was conducted at the start and end of the study. ConclusionThe SCRATCH-HTN trial is a phase 2a study testing the safety, acceptability, and potential efficacy of tAN treatment for improving blood pressure control in patients with elevated BP despite medication. It also explores tANs effects on sleep, exercise tolerance, heart rate variability, central BP, cardiac structure, and autonomic function. If effective, it could offer a transformative approach to hypertension management. Registrationclinicaltrials.gov (NCT05179343).

AimsEarly discharge after electrophysiological procedures has gained increasing attention. However, definition of patient- and procedure-related prerequisites for successful and safe discharge strategies after atrial tachycardia (AT) ablation remains unknown. We therefore evaluated patient characteristics, procedural features, and outcomes according to index length of stay (LOS) following AT ablation. Methods and resultsThe multicenter observational SATELLITE registry enrolled consecutive patients undergoing AT rhythm control. Patients were stratified by LOS ([&le;]1, 2 and >2 nights) after catheter ablation. Among 670 patients (67 [IQR 56-75] years, 54.9% male), LOS was [&le;]1 night in 13.9%, 2 nights in 41.9% and >2 nights in 44.2%. LOS was only modestly predictable from clinical characteristics including age, sex, atrial fibrillation and prior atrial ablation (AUC 0.73). Discrimination improved after inclusion of procedural variables and early post-procedural events (AUC 0.77; P=0.0300), consistent with an increase in left atrial procedures (26.5% vs. 76.0% vs. 80.8%; P<0.0001), acute minor complications (3.2% vs. 2.5% vs. 14.5%; P<0.0001) and early recurrences of atrial arrhythmia (2.2% vs. 6.8% vs. 21.3%; P<0.0001). During 2.8{+/-}3.0 years of follow-up, LOS did not predict long-term outcomes including subsequent cardiovascular hospitalization (HR 1.19, 95% CI 0.78-1.81; P=0.4175). ConclusionDespite multiple comorbidities, most patients undergoing AT ablation need up to 2 nights of hospitalization. However, prolonged hospital stays before successful and safe discharge are common and associated with acute minor complications and early recurrences of atrial arrhythmia rather than comorbidities. Accordingly, discharge timing largely reflects the immediate peri-procedural clinical course, therefore challenging purely logistics-driven planning. Key Learning PointsO_ST_ABSWhat is already knownC_ST_ABSO_LIEarly discharge after electrophysiological procedures has gained increasing attention. C_LIO_LIDefinition of patient- and procedure-related prerequisites for successful and safe discharge strategies after atrial tachycardia (AT) ablation remains unknown. C_LI What this study addsO_LIDespite multiple comorbidities, most patients undergoing AT ablation need up to 2 nights of hospitalization. C_LIO_LIProlonged hospital stays before successful and safe discharge are common and associated with acute minor complications and early recurrences of atrial arrhythmia rather than comorbidities. C_LIO_LIDischarge timing largely reflects the immediate peri-procedural clinical course, therefore challenging purely logistics-driven planning C_LI Structured Graphical AbstractO_LIDespite multiple comorbidities, most patients undergoing AT ablation need up to 2 nights of hospitalization. However, prolonged hospital stays before successful and safe discharge are common and associated with acute minor complications and early recurrences of atrial arrhythmia rather than comorbidities. Accordingly, discharge timing largely reflects the immediate peri-procedural clinical course, therefore challenging purely logistics-driven planning. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=130 SRC="FIGDIR/small/26345799v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@200309org.highwire.dtl.DTLVardef@1a745fcorg.highwire.dtl.DTLVardef@e3cd45org.highwire.dtl.DTLVardef@1b98c3e_HPS_FORMAT_FIGEXP M_FIG C_FIG

BackgroundWhile various reports described the characteristics and catheter ablation strategies for para-Hisian premature ventricular contraction (PVC), the patient population were limited in previous literatures and optimal approach remain unknown. This study sought to comprehensively assess the safety and outcomes of catheter ablation for para-Hisian PVC, with a particular focus on the safety and efficacy of ablation from aortic coronary cusps. MethodsA total of 122 para-Hisian PVC cases were retrospectively included in this study. The acute and clinical outcomes of ablation, especially the success rate, the rate of conduction system injury, and the ablation site (right side, left side His bundle (HB) region, and aortic coronary cusp), were analyzed. ResultsAcute procedural success was achieved in 89 patients (73%). However, long-term clinical success ([&ge;]80% reduction of PVC burden) was achieved only in 52% of acute-success cases. Cusp ablation was attempted in 35 patients (31%). Cusp ablation was performed significantly more often in clinical-success cases than clinical-failed cases (38% vs.7% P = 0.005), although ablation from multiple locations was still required. In 28 of 35 cases (80%) who underwent cusp ablation, cusp ablation affected PVC by eliminating, transiently suppressing, or changing morphology. Predictors of successful cusp ablation included earlier activation at the cusp and close anatomical proximity to the earliest site at the HB region. Conduction system injury occurred in 31 cases of the entire cohort, mainly during the HB-region ablation, with only one event during cusp ablation. ConclusionIn this large cohort of para-Hisian PVC ablation, an anatomical approach from the adjacent coronary cusp ablation can be considered as an effective and safe strategy. Early local activation and a close anatomical proximity between the earliest para-Hisian site and the coronary cusp region are predictors of ablation success with this approach. What is knownO_LICatheter ablation of para-Hisian premature ventricular contraction (PVC) is challenging due to the proximity to the His bundle (HB) and/or potentially intramural sources. C_LIO_LICatheter mapping and ablation from multiple sites, including aortic coronary cusps, have been reported as potential alternative approaches, however systematic analyses of the ablation outcome and safety for para-Hisian PVC remain scarce. C_LI What the study addsO_LIClinical-success rate of radiofrequency (RF) ablation for para-Hisian PVC was still suboptimal (52%). However, the cases undergoing cusp ablation were associated with a better success rate (85%) than those with direct ablation to the HB region alone (42%), indicating this approach may improve the outcome. C_LIO_LIThe anatomical features, including PVC earliest activation site above the HB or within short distance from the coronary cusp, may predict successful PVC elimination from the coronary cusp. C_LIO_LIConduction system injury, including minor forms, occurred in approximately 30% cases during the RF ablation near the HB region, while only one AH prolongation observed during cusp ablation, indicating superior safety of cusp ablation. 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 ([&le;]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.

BackgroundAmong patients with ST segment elevation myocardial infarction (STEMI), higher concentrations of high sensitivity troponin T (hs-cTnT) are associated with larger MI size and predict a worse prognosis. In the 2467 patient CELEBRATE trial, a single subcutaneous injection of the short-acting glycoprotein IIb/IIIa receptor blocker antagonist zalunfiban at first medical contact significantly improved the primary outcome including clinical endpoints. In this study, we assessed the impact of zalunfiban on MI size and association with downstream outcomes remains unclear. MethodsIn a prespecified analysis, we studied results among study participants treated with two doses of zalunfiban who had core laboratory measurements concentrations of hs-cTnT. ResultsThe median concentration of hs-cTnT at presentation was 62 ng/L; at 24 hours it was 1962 ng/L. More elevated hs-cTnT concentrations at presentation were associated with less resolution of ST deviation after revascularization (P =0.006) and more frequent Q wave development (all P <0.001). At coronary angiography more elevated hs-cTnT at presentation was also associated with higher thrombus grade and worse epicardial and myocardial perfusion (all P <0.05). In multivariable analyses, higher hs-cTnT concentrations at 24 hours were associated with greater adjusted risk for all-cause death (odds ratio [OR] 1.83 per log unit increase; P=0.03), cardiovascular death (OR 1.83 per log unit increase; P=0.03), heart failure (OR 2.74 per log unit increase; P <0.001) or the composite of death (or cardiovascular death) and heart failure (P<0.001) by 30 days. At 24 hours, those treated with zalunfiban had lower hs-cTnT compared to placebo (1900 vs 2082 ng/L; P =0.04) and across multiples [&ge;]10 to [&ge;]1000 times elevation, treatment with zalunfiban resulted in smaller hs-cTnT determined MI size. ConclusionAmong patients with STEMI, higher concentrations of hs-cTnT are associated with worse angiographic and ECG measures of reperfusion. More elevated hs-cTnT predicted a higher risk for short-term death or heart failure. A single dose of zalunfiban at first medical contact reduced MI size, as judged by more study participants with lower hs-cTnT concentrations. These results provide a mechanistic basis for the improved clinical outcomes associated with zalunfiban treatment in the CELEBRATE Trial. Study registrationA Phase 3 Study of Zalunfiban in Subjects With ST-elevation MI (CELEBRATE); NCT04825743

BackgroundCatheter ablation is an established rhythm control therapy for atrial fibrillation. However, as the extent of ablation increases, the risk of complications may also rise. This has motivated strategies that achieve pulmonary vein isolation with less lesion creation while preserving safety and effectiveness. MethodsIn this prospective, multicenter, randomized non-inferiority trial, 130 patients undergoing first-time ablation for paroxysmal or non-paroxysmal atrial fibrillation were assigned 1:1 to a voltage-guided stepwise pulmonary vein isolation approach or conventional circumferential antral pulmonary vein isolation with voltage blinded to operators. The primary end point was recurrence of atrial tachyarrhythmia within 12 months after ablation. ResultsAt 12 months, recurrence occurred in 23/65 (35.4%) in the stepwise group versus 13/65 (20.0%) in the control group (risk difference 15.4 percentage points; 90% confidence interval, 2.7-28.1), and non-inferiority was not demonstrated (one-sided P=0.520). The treatment group had a higher risk of recurrent atrial tachyarrhythmia than the control group (hazard ratio, 2.05; 95% confidence interval, 1.04-4.06), with longer procedure times and more frequent acute pulmonary vein reconnection after the initial lesion set. The treatment group had fewer acute complications than the control group (1.5% versus 9.2%; P=0.115), and esophageal thermal injury was observed only in the control group (3 cases). ConclusionsVoltage-guided stepwise pulmonary vein isolation failed to demonstrate non-inferiority to conventional circumferential antral pulmonary vein isolation for 12-month atrial tachyarrhythmia recurrence. ClinicalTrials.gov ID: NCT07354737