Heart

Background: Socioeconomic factors impact cardiovascular health. We investigated the association between patient education level and incident heart failure (HF), acute myocardial infarction (AMI), and stroke following a first hospitalization with atrial fibrillation (AF). Methods: In this nationwide retrospective cohort study using linked Swedish national registers, we included all patients receiving a diagnosis of AF while hospitalized in Sweden from 1995 through 2008; categorized education level as primary, secondary, or academic; and followed patients for up to five years. Outcomes were first hospitalization for HF, AMI, or stroke. Associations were assessed using sex-stratified Cox proportional hazards models adjusted for age, calendar year of AF diagnosis, and measures of comorbidity burden (Charlson Comorbidity Index) and thromboembolic risk (CHA2DS2VA score). Results: The cohort comprised 263,172 patients (mean age 72.5 {+/-} 10.4 years; 56.2% male). Compared with primary education, secondary and academic education attainment were associated with lower adjusted risk of HF and AMI in both females and males. For HF, adjusted hazard ratios (HR) were 0.96 (95% CI 0.93 - 1.00) for secondary and 0.82 (95% CI 0.77 - 0.87) for academic education for females and 0.93 (95% CI 0.90 - 0.96) and 0.76 (95% CI 0.72 - 0.80), respectively, for males. For AMI, adjusted HRs were 0.89 (95% CI 0.85 - 0.93) and 0.71 (95% CI 0.65 - 0.78) for females and 0.91 (95% CI 0.87 - 0.94) and 0.75 (95% CI 0.71 - 0.80) for males. For stroke, lower adjusted risk was observed only in the academic education group. Baseline comorbidity burden and thromboembolic risk were higher in lower education groups. Conclusions: Education level was inversely associated with risk of incident HF and AMI over five years, while the association with stroke risk was weaker. Documenting education level may help identify patients at increased risk who could benefit from careful monitoring and optimized preventive care.

Background Disparities between sexes in mortality and morbidity after coronary artery bypass grafting remain incompletely understood. Multi-arterial grafting demonstrates superior outcome compared to single arterial grafting, although the optimal type of a second arterial graft and possible sex-dependent differences in grafting strategy have not been elucidated. We aim to determine whether the right internal thoracic artery or the radial artery is the optimal second arterial graft. Methods We analyzed data from 14,196 patients undergoing primary isolated coronary artery bypass grafting with the left internal thoracic artery and either right internal thoracic artery or radial artery between 2013 and 2022 from the Netherlands Heart Registration. Patients were stratified by sex and type of second arterial graft. Inverse probability treatment weighting was used to balance baseline characteristics. The primary outcome was long-term mortality. Secondary outcomes included short-term complications and repeat revascularization. Results In both sexes, the choice of second arterial graft did not significantly impact long-term survival. Postoperative arrhythmias were more prevalent in both sexes following right internal thoracic artery use (p<0.001). The radial artery was associated with higher rate of repeat revascularization in men (p=0.044 at 5 years follow-up) and more cerebrovascular accidents in women (0.9% vs 0.2%, p=0.028). Conclusion The choice of second arterial graft did not affect long-term survival in either sex. The radial artery was associated with an increased risk of repeat revascularization in men and more cerebrovascular accidents in women. These results underscore the need for further research in the field of sex-specific considerations in operative strategy.

ObjectiveTo explore the interpretation of unexpected results from a randomized controlled trial (RCT). Study Design and SettingAdjunctive frequentist (power and type{square}M error) and Bayesian analyses were performed on a recently published RCT reporting a statistically significant relative risk reduction (p <0.01) for caffeinated coffee drinkers compared with abstinence on atrial fibrillation (AF) recurrence. Individual patient data for the Bayesian survival models were reconstructed from the RCT published material and priors informed by the RCT power calculations. ResultsThe original RCT design had limited power for realistic effect sizes, increasing susceptibility to type{square}M (magnitude) error. Bayesian analyses also tempered the benefit for caffeinated coffee implied by standard statistical analysis resulting in only modest probabilities of clinically meaningful risk reductions (e.g., hazard ratio < 0.9 of 88% or a risk difference > 2% of 82%). ConclusionsSupplemental frequentist and Bayesian approaches can provide robustness checks for unexpected RCT findings, providing contextualization, clarifying distinctions between statistical and clinical significance, and guiding replication needs. HighlightsO_LIRandomized controlled trial (RCT) results may be unexpected and challenge prior beliefs C_LIO_LISupplemental frequentist and Bayesian analyses can clarify interpretation of surprising findings C_LIO_LIPower and type{square}M error assessments help evaluate design adequacy for realistic effects C_LIO_LIBayesian posterior probabilities provide additional nuanced insights into contextulaization and clinical significance C_LI

Background Exercise capacity varies among individuals with a Fontan circulation. Percent predicted peak oxygen consumption (%pVO2) may be influenced by ventricular morphology, Fontan subtype, and conduit characteristics, but data explaining variability in exercise capacity are limited. This study examined whether anatomical and surgical factors are associated with %pVO2 later in life. Methods Participants enrolled in the multicenter Single Ventricle Outcomes Network (SV-ONE) database who had cardiopulmonary exercise testing (CPET) data were included. Published reference equations were used to estimate %pVO2. Multivariable regression models evaluated associations between anthropometric, anatomical (diagnosis and dominant ventricle), and surgical (Fontan subtype, conduit size, and surgical era) factors and %pVO2. Restricted spline analyses assessed nonlinearity. Results 561 individuals with a Fontan circulation were included in the analysis; age 20 {+/-} 8 years, 54% male, mean %pVO2 was 63 {+/-} 16%. Sex and exercise modality were the strongest predictors of %pVO2, with females being 12% higher than males and treadmill 4.6% higher than a cycle. Age at CPET was a predictor of exercise capacity with %pVO2 decreasing by 0.8% per year. Ventricular morphology, diagnosis, and Fontan subtype did not have a statistical association with the primary outcome. In models restricted to patients with an extracardiac conduit (n = 330), conduit diameter and area were not associated with %pVO2, even after indexing to body surface area. Univariable nonlinear spline analyses suggested an optimal conduit size of 18 mm for %pVO2, but this was not significant after body size adjustments. Conclusion In this large multicenter cohort, surgical and anatomical features were not as important as sex, age, and body size as determinants of exercise performance in patients with a Fontan circulation. Reduced exercise capacity in this population appears to reflect progressive pathophysiological changes of the Fontan circulation rather than specific characteristics such as conduit size, ventricular morphology, or anatomy.

BACKGROUND: Guidelines recommend aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR) based on progressive changes in left ventricular (LV) function or size. We aimed to reassess the clinical relevance of current guideline recommendations pertaining to traditional echocardiographic measurements in routine practice. METHODS: Retrospective analysis of patients with severe AR who underwent serial echocardiographic follow-up over at least 18 months. The composite outcome was symptom-driven AVR, acute heart failure hospitalization, or death. We used a joint modelling approach to handle within-subject correlation and censoring. RESULTS: The cohort consisted of 140 patients, with a median follow?up of 93 months (interquartile range 58?130). LV end-systolic (LVESD) and fractional shortening (FS) showed a small but statistically significant longitudinal trend, while LVEDD did not. Changes in all three parameters in parallel joint models adjusted for age and gender were consistently associated with increased risk of the composite event. Each 1?mm increase in LVESD and LVEDD was associated with a 6% and 5% increase in risk, respectively; each 1% decrease in FS corresponded to a 12% increase in risk. Only 8 (5.7%) of patients were predicted to exceed the guideline-recommended LVEDD threshold of 65 mm over 10 years. Age at onset was also a significant risk factor, with each decade increasing risk by 65% for each of the three parallel joint models. CONCLUSIONS: LV parameters show modest changes over time, despite holding strong prognostic value in patients with severe AR. LVEDD, while associated with overall risk, does not predictably or significantly dilate over time in most patients. AVR decisions should be based on comprehensive clinical and volumetric assessment rather than waiting for simple linear progression to guideline cutoffs.

Background: Detection of disease progression is key to personalize treatment strategies in transthyretin cardiomyopathy (ATTR-CM), particularly with emerging therapies. Echocardiography can detect subtle longitudinal changes but is limited by operator dependence. This study evaluates agreement and reproducibility of fully automated, AI-assisted echocardiographic measurements under real-world conditions. Methods: This retrospective study included 62 patients with ATTR-CM undergoing 178 serial annual echocardiograms assessed by a reference cardiologist, a second cardiologist, a novice reader, and a fully automated AI algorithm (Us2.ai). Interrater agreement was assessed using Bland-Altman analysis and intraclass correlation coefficients (ICCs). Intrarater variability for human readers was derived from repeated blinded measurements, with limits of agreement (LoA = mean difference +/- 1.96 x SD) defining the smallest detectable change. AI repeatability was assessed using within-study pairwise differences. Results: AI showed moderate agreement with the reference cardiologist for IVSd and LVEDV (ICC 0.65 and 0.51), with biases of -1.9 mm and -39 mL, respectively. Interrater agreement between cardiologists was good (ICC 0.79 and 0.84) with minimal bias (-0.2 mm and +3 mL). Intrarater variability was moderate to excellent for both cardiologists (LoA 3.0 mm and 43 mL for the reference cardiologist; 2.7 mm and 31 mL for the second cardiologist). AI demonstrated comparable repeatability (LoA 3.6 mm and 37 mL), while the novice showed higher variability (5.1 mm and 61 mL). Conclusion: AI-based measurements demonstrated repeatability comparable to experienced cardiologists. Despite moderate agreement and systematic differences in volumetric assessments, their reproducibility supports automated analysis for longitudinal echocardiographic monitoring.

Background Functional mitral regurgitation results from interacting mechanisms whose relative contributions vary between atrial and ventricular subtypes and shift dynamically within each heartbeat, producing temporal patterns that static analyses cannot capture. Objectives To identify which structural determinants predict mitral regurgitation variability beat to beat using Granger causality within vector autoregression, focusing on papillary muscle dynamics across subtypes. Methods Frame-level echocardiographic time series from 41 patients (21 atrial, 20 ventricular; 1,959 frames) were z-score standardised within patient. Individual (lag 3) and pooled (lag 2) vector autoregression models tested whether left ventricular volume, left atrial volume, papillary muscle length, and annulus diameter Granger-predict mitral regurgitation area. Results Individual models revealed marked heterogeneity. In pooled analysis, left ventricular volume was the strongest Granger predictor at short lags (atrial p=0.011; ventricular p=0.006), while left atrial volume emerged at longer lags (lag 7: atrial p=0.043; ventricular p=0.011). Systolic papillary muscle length was not predictive. Full-cycle analysis revealed a subtype-specific dissociation: papillary muscle length Granger-predicted regurgitation only in the ventricular subtype (p=0.001), while regurgitation predicted papillary muscle displacement only in the atrial subtype (p<0.001). Left ventricular volume dominated within-beat prediction but lost cross-beat relevance in the ventricular subtype, while left atrial volume gained cross-beat predictive relevance in the atrial subtype. No structural determinant correlated with severity cross-sectionally. Conclusions Beat-to-beat vector autoregression and Granger modelling reveals heterogeneous, subtype-specific temporal patterns with distinct temporal windows of predictability for ventricular loading and papillary geometry. This framework may support patient-specific temporal phenotyping of functional mitral regurgitation.

Background The postmenopausal period is associated with a more adverse cardiometabolic risk factor profile as well as unfavourable cardiac remodelling patterns. However, it remains unclear whether and how the associations between risk factors and cardiac remodelling differ before and after menopause and in the corresponding age groups in men. Methods We used cross-sectional data from the baseline examination of the population-based German National Cohort (NAKO, age range 19-74 years). Cardiovascular resonance imaging (CMR) was performed on 3T MRI, and morphofunctional data of both ventricles were derived from standard short-axis cine balanced steady-state free precession. Associations between cardiometabolic risk factors and cardiac parameters were evaluated using adjusted multivariable linear regression, stratified by menopausal status in women and age group (<50 / [&ge;]50 years) in men. Results The final sample comprised 20,152 participants (40% women; mean age 47{+/-}12 years) from the NAKO MRI subsample. Cardiometabolic risk factor profiles differed across the stratified groups, with higher systolic blood pressure and less favourable lipid profiles in older participants. Ventricular volumes declined and concentric remodelling increased with age in both sexes, with a steeper age-related pattern observed in women than in men. Higher BMI in women was associated with higher left ventricular concentricity index (LVCI) in postmenopausal than in premenopausal women (0.097 vs. 0.047; p for difference = 0.016). Associations between triglycerides and ventricular volumes were strongest in premenopausal women and significantly stronger than in men younger than 50 years (e.g., right ventricular end-diastolic volume (RVEDV): -0.173 vs. -0.064, p for difference < 0.001). Sleep problems were more strongly associated with cardiac parameters in men, with significant sex differences in older men compared with postmenopausal women (e.g. left ventricular end-diastolic volume (LVEDV): -0.105 vs. 0.043, p for difference = 0.023). Conclusions Less favourable cardiac remodelling observed in postmenopausal women appeared to be associated with a higher burden of cardiometabolic risk factors rather than stronger associations between these risk factors and cardiac structure. Several associations showed sex- and age-specific patterns, including Body Mass Index (BMI), triglyceride levels, and sleep problems. These findings highlight the importance of controlling cardiometabolic risk factors across adulthood, and raising awareness for sex-specific differences.

Introduction: Smoking cessation after acute coronary syndrome (ACS) is a Class I recommendation, yet prescription pharmacotherapy use remains low and its real-world cardiovascular effectiveness when added to nicotine replacement therapy (NRT) is poorly characterized. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (67 healthcare organizations). Adults hospitalized with ACS who received NRT within one month, serving as a proxy for active smoking status, were identified. Two co-primary propensity-matched (1:1, 50 covariates, caliper 0.10 SD) comparisons evaluated bupropion + NRT and varenicline + NRT individually versus NRT alone; a supportive analysis evaluated combined pharmacotherapy versus NRT alone. All-cause mortality was the primary endpoint. Secondary outcomes included MACE, heart failure exacerbations, major bleeding, TIA/stroke, emergency rehospitalizations, and cardiac rehabilitation utilization, assessed at 6 months and 1 year via Kaplan-Meier analysis. Hazard ratios (HRs) greater than 1.0 indicate higher hazard in the NRT-only group. Results: After matching, the combined analysis comprised 8,574 pairs, the bupropion analysis 4,654 pairs, and the varenicline analysis 2,126 pairs. At 1 year, the combined pharmacotherapy group had significantly lower all-cause mortality (HR 1.26, 95% CI 1.16-1.37), MACE (HR 1.16, 95% CI 1.12-1.21), heart failure exacerbations (HR 1.16, 95% CI 1.08-1.25), major bleeding (HR 1.18, 95% CI 1.08-1.28), and greater cardiac rehabilitation utilization (HR 0.82, 95% CI 0.74-0.92; all p < 0.001). TIA/stroke did not differ significantly. Six-month results were consistent. Both varenicline and bupropion individually showed lower mortality and MACE. A urinary tract infection falsification endpoint showed no between-group differences, supporting matching validity. The pharmacotherapy group had higher rates of new-onset depression, driven predominantly by bupropion recipients. Conclusions: In this propensity-matched real-world analysis, adding prescription smoking cessation pharmacotherapy to NRT after ACS was associated with lower mortality and fewer adverse cardiovascular events, supporting broader integration into post-ACS care pathways.

Background: Cardiovascular diseases (CVD) are more common in lower occupational classes, but the mediating role of health behaviours remains unclear. This study aimed to quantify the extent to which health behaviours mediate the association between occupational class and CVD, evaluate their relative contributions to CVD risk, and assess occupational class differences in the effects of health behaviours. Methods: Municipal employees from Helsinki, aged 40-60 at baseline, were followed from 2000-2002 (response rate 67%) to 2022. CVD events were identified from national registers, including hospitalizations, long-term sickness absence, disability pensions, and mortality. Counterfactual mediation analysis using additive survival regression was used to assess the contribution of health behaviours - excessive alcohol consumption, smoking, unhealthy diet, and insufficient physical activity - to the association of occupational class and CVD. Occupational class differences in the effects of health behaviours were assessed with Cox regression. Results: During follow-up, 50% of participants in the low occupational class and 46% in the high occupational class had a CVD event. All unhealthy behaviours except heavy alcohol use were more common in the low occupational class. Health behaviours explained approximately 40% of the excess risk of CVD when moving from high occupational class to low occupational class. Insufficient physical activity (HR 1.44, 95% CI 1.35-1.54) was the strongest predictor of CVD. Unhealthy diet was more strongly associated with CVD in the high occupational class. Conclusion: Health behaviours explained a part of occupational class inequalities in CVD, but most of the inequality remained unexplained, highlighting broader social determinants.

Background: Clinical genetic evaluation for patients with dilated cardiomyopathy (DCM) is minimally implemented and models of care are not defined. To understand current genetics care for DCM, a systematic needs assessment was conducted. Methods: Principal Investigators (PIs) of the DCM Consortium convened at the Summer Scientific Symposium in July 2025. An electronic needs assessment was collected from the 24 PIs in advance to define current care models by evaluating which Heart Failure Society of America-recommended genetic evaluation components are conducted, by whom, and time required. Descriptive statistics were generated to characterize model features. Focus group discussions explored barriers and facilitators to implementing genetic services. Results: Four care models emerged from the PI responses: 1 -- Traditional-Synchronous (25%, n=6, requiring the most time per patient), 2 -- Traditional-Asynchronous (33%, n=8), 3 -- Externally Sourced (17%, n=4), and 4 -- Physician/Advanced Practice Provider Conducted (25%, n=6, requiring the least time per patient). All models used genetic testing, whereas other components were implemented variably or not at all. Models 1 (15.7{+/-}4.1) and 2 (15.4{+/-}3.0) were rated more acceptable than Model 4 (9.8{+/-}2.9, 1 vs 4: p=0.027; 2 vs 4, p=0.023). Notably, 88% of PIs used genetic information for treatment decisions, including ICD placement (83%; n=20) or cardiac transplant (63%; n=15). Major facilitator themes from focus group discussions included having a genetic counselor on the HF team and developing authoritative standards directing provision of DCM genetic services. Barrier themes included operational challenges, limited personnel, clinician under-recognition, need for new service delivery models, and billing/reimbursement. Conclusions: DCM genetic care models and components were highly variable across the 24 sites of the DCM Consortium, even though all sites discussed similar factors that enable or hinder implementing genetic services for DCM. Understanding the basis of practice model variability may provide insight to yield more scalable care approaches.

Abstract Aims: While traditional anthropometric indices are established cardiovascular predictors, their prognostic value for incident infective endocarditis (IE) remains undefined. Methods: We included 386,859 participants (mean age 57.0 years; 52.9% female) from the UK Biobank between 2006 and 2010 with standardized baseline data on BMI, waist circumference (WC), waist-to-height ratio (WhtR), and the triglyceride-glucose (TyG) index.Multivariable Cox proportional hazard models with restricted cubic splines were used to estimate the hazard ratio (HR) of these indices, adjusting for demographic and clinical risk factors. Results: Over 16.87 median years (25th, 16.02; 75th, 17.60 percentile) of follow-up, there were a total of 1,124 incident IE events. During the follow-up period, 38,342 total deaths were recorded, of which 8,524 were cardiovascular disease (CVD)-related.Overall, compared to individuals with normal weight and baseline metabolic indices, those in the fourth quartile of WC, WHtR, and TyG index exhibited the highest risk of incident IE. Compared to other metabolic indices, WC (HR = 1.53, 95% CI 1.23?1.90,P < 0.001) and WHtR (HR = 1.46, 95% CI 1.20?1.78,P < 0.001) demonstrated higher relative increases in risk associated with IE. Furthermore, the risk of IE was significantly elevated among the younger population with abdominal obesity and concomitant diabetes. However, no significant increase in IE risk was observed among participants with pre-existing valvular heart disease (P = 0.796). Conclusion: Compared with BMI, higher WC and WHtR were robustly associated with increased risk of IE, even after adjusting for traditional risk factors. Furthermore, the risk of IE was markedly elevated among younger individuals with abdominal obesity and diabetes.

Background: Resting electrocardiogram (ECG) is not currently recommended as part of cardiovascular disease (CVD) risk assessment, although accumulating evidence suggests a potential role. Objective: To examine the association between ECG abnormalities and incident CVD events as assessed by the 2023 Predicting Risk of Cardiovascular Disease Events (PREVENT) equations. Design: Secondary data analysis from the REasons for Geographic And Racial Differences in Stroke (REGARDS) prospective cohort, including study participants without a baseline CVD. Exposure: ECG abnormalities were classified by Minnesota Code (MC) as normal, any minor, or major abnormality at baseline (2003-2007). Outcome: Participants were followed for expert adjudicated incident CVD events through December 31, 2021. Results: Among 19,173 participants (mean age at baseline of 63.7 years; 57.8% were female). According to the PREVENT risk equations, 39.4% were classified as <7.5% 10-year risk CVD risk, 44.6% as 7.5-20% risk, and 16.0% as >20% risk. Overall, 47.0% had normal ECG, 44.0% had any minor abnormality, and 9.0% had any major abnormality. During follow-up, CVD events occurred in 12.4% of participants with normal ECG, 17.0% of those with any minor abnormality, and 25.4% of those with any major abnormality. Compared to those without ECG abnormality, the adjusted HR for incident CVD were 1.19 (95% CI 1.10-1.29) for any minor abnormality, and 1.53 (1.36-1.72) for any major ECG abnormality. In the <7.5% risk group, 43.6% had at least one ECG abnormality; in this risk group compared to those without ECG abnormality, the HR for incident CVD associated with any major ECG abnormality, present in 5.0% of the <7.5% risk group, was 1.87 (95% CI 1.34-2.62), The HR for any minor ECG abnormalities, present in 38.6% was 1.13 ( 95% CI 0.93 - 1.37). Conclusion: ECG abnormalities were associated with risk of CVD events across PREVENT risk groups. A substantial proportion of low-risk participants (according to the PREVENT equation) had ECG abnormalities and associated elevated risk. This supports the potential for using ECG to identify a subgroup of low-risk patients who may benefit from more aggressive primary prevention especially with major ECG abnormalities. Addition of electrocardiographic evaluation to the PREVENT risk equations may improves cardiovascular risk discrimination.

Background: Cardiogenic shock (CS) remains associated with high short-term mortality despite contemporary advances in care. The association between institutional cardiac capability and outcomes?particularly among transferred patients and after accounting for clinical instability?remains incompletely defined. Objectives: To evaluate the association between hierarchical hospital cardiac capability and in-hospital mortality using a latent measure of acute physiologic severity. Methods: Using the National Inpatient Sample (2016?2022), hospitals were classified into five hierarchical tiers ranging from non-PCI (Tier 1) to heart transplant/durable LVAD centers (Tier 5). Generalized structural equation modeling (GSEM) assessed the relationship between hospital tier and mortality. A latent "Acute Severity" construct?comprising cardiac arrest, acute kidney and liver injury, and mechanical ventilation?was incorporated to model the effects of clinical instability Results: Among an estimated 1,177,180 CS hospitalizations, most occurred at cardiac surgical and transplant/LVAD centers. Crude mortality declined stepwise from non-PCI hospitals (64.5%) to transplant/LVAD centers (36.5%). After adjustment, higher hospital tier was independently associated with lower mortality (Tier 2 OR 0.43 [95% CI 0.38?0.48]; Tier 3 OR 0.37 [0.32?0.43]; Tier 4 OR 0.33 [0.30?0.38]; Tier 5 OR 0.35 [0.31?0.40]). Although transfer-in status was associated with increased mortality (OR 1.39 [1.33?1.46]), this association was attenuated at cardiac surgical and transplant/LVAD centers, consistent with a mitigation of transfer associated risk. Conclusions: Higher hospital cardiac capability is independently associated with lower mortality in CS. Advanced centers are associated with mitigation transfer-associated risk, supporting regionalized hub-and-spoke systems with early referral to high-capability centers.

Background: The prevalence of heart failure (HF) is increasing worldwide, and rehospitalizations due to exacerbations remain a major clinical and economic burden. Beyond medical triggers, insufficient patient understanding and inadequate self-management often contribute to recurrent admissions. The Kurume-HEARTS program was developed to provide regular planned hospitalizations incorporating structured education, cardiac rehabilitation, and medication adjustment for patients with recurrent HF. Objective: To retrospectively evaluate the clinical and economic impact of the Kurume-HEARTS program. Methods: We enrolled consecutive patients with recurrent HF hospitalizations who underwent the program at Kurume University Hospital between January 2020 and October 2025. Outcomes compared planned versus unplanned hospitalizations within the same patients. Co-primary endpoints were total hospitalization cost and total length of stay per person-year. Secondary endpoints included per-hospitalization cost, length of stay, unplanned and planned admission frequency, and NT-proBNP levels at admission. Results: Of 31 screened patients, 20 with recurrent heart failure were included. During a median follow-up of 27.1 months, 135 hospitalizations occurred (69 unplanned and 66 program-based). Total hospitalization cost per person-year was significantly lower during the Kurume-HEARTS program than during unplanned hospitalizations, while length of stay per person-year tended to be shorter. Per-admission cost and length of stay were significantly lower with the program, without differences in admission frequency. NT-proBNP levels at admission were higher during unplanned hospitalizations, indicating greater clinical instability. Conclusions: The Kurume-HEARTS program can help reduce the cost and hospitalization length of unplanned admissions by enabling earlier intervention and structured inpatient management.

Background: Progression of transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) can lead to worsening congestion requiring diuretic intensification (DI), heart failure (HF)-related hospitalizations (HFH), and death. Tafamidis was the only approved ATTR-CM therapy in the US from 2019 until the 2024 approval of acoramidis, which achieves near-complete ([&ge;]90%) TTR stabilization. As head-to-head trials are lacking, real-world comparative effectiveness (CE) data are needed to guide treatment selection. Objective: To evaluate real-world CE of acoramidis versus tafamidis in newly treated patients with ATTR-CM. Methods: Retrospective study using Komodo Healthcare Map (R) US claims data tokenized to Claritas. Patients newly initiating acoramidis or tafamidis between 12/11/2024 and 04/30/2025 with [&ge;]1 prescription claim (first defined as index date) and [&ge;]6 months of continuous enrollment preindex date were included and followed until disenrollment, death, treatment switch, or study end date (07/31/2025). Outcomes included DI (initiation or dose-equivalent escalation of oral loop diuretics, parenteral loop diuretic use, or addition of thiazide-like diuretic) and a composite of DI, HFH (inpatient admission with a HF-related ICD-10-CM diagnosis code in any position), and mortality. Propensity score weighting balanced baseline characteristics, disease severity, comorbidity burden, and baseline medication use. Time-to-event outcomes were assessed using weighted Cox proportional hazards models. Results: After weighting, acoramidis (n=170) and tafamidis (weighted sample size=448) patients were comparable at baseline (mean age, 78.6 vs 78.7 years; male, 80.0% vs 80.2%) with mean follow-up of 139 and 143 days, respectively. DI cumulative incidence curves separated early and remained divergent, with acoramidis significantly reducing the hazard of DI events by 43% compared with tafamidis (11.8% vs 20.5%; HR, 0.57; 95% CI, 0.35-0.92; P=0.021). Acoramidis also had a significantly lower risk of composite events, with a 34% reduction in hazard compared with tafamidis (17.6% vs 26.4%; HR, 0.66; 95% CI, 0.44-0.99; P=0.046). Conclusions: In this first real-world CE study of newly treated patients, acoramidis had significantly lower risk of DI events and composite events of DI, HFH, and mortality than tafamidis, potentially supporting improved clinical stability with acoramidis initiation. Additional evaluation with longer follow-up, larger cohorts, and/or prospective clinical outcomes is warranted.

Aims: Responses to remote pulmonary artery pressure data vary across programs. We evaluated SMART-HF, a structured pulmonary artery diastolic pressure (PAD)-guided workflow, in a community heart failure cohort. Methods: We retrospectively analysed adults with heart failure and an implanted pulmonary artery pressure sensor managed with SMART-HF. Pulmonary artery diastolic pressure (PAD) was calculated from prespecified 14-day windows at baseline, 90 days, and 6 months. Two hemodynamic management performance indices (HMPI) were prespecified: the 6-Month Delta HMPI (PAD reduction >2 mmHg from baseline) and the 90-Day Target HMPI (PAD [&le;]20 mmHg at 90 days). Exploratory analyses evaluated patients with baseline PAD >20 mmHg. Results: Of 37 patients, 36 had paired 90-day and 29 had paired 6-month windows. Mean PAD decreased from 18.3 +/- 7.0 to 16.1 +/- 6.3 mmHg at 90 days and from 18.8 +/- 6.8 to 15.5 +/- 5.8 mmHg at 6 months (both P < 0.001). The 90-Day Target HMPI was achieved in 26/36 (72.2%) and the 6-Month Delta HMPI in 19/29 (65.5%) [95% CI 45.7-82.1]. In the exploratory subgroup (baseline PAD >20 mmHg), mean PAD changes were -2.9 +/- 3.6 mmHg at 90 days (n = 19; P = 0.002) and -4.9 +/- 4.9 mmHg at 6 months (n = 15; P = 0.002). Conclusions: SMART-HF was associated with improved ambulatory pulmonary artery diastolic pressure control at 90 days and 6 months. Exploratory subgroup findings support further evaluation in patients with elevated baseline pulmonary artery diastolic pressure.

Aims: Dynamic left ventricular outflow tract obstruction (LVOTO) is a hemodynamically significant complication following transcatheter aortic valve replacement (TAVR) that remains difficult to predict with conventional transthoracic echocardiography (TTE). We examined whether a deep learning (DL) model developed for LVOTO detection in hypertrophic cardiomyopathy (HCM) could predict post-TAVR LVOTO from pre-TAVR TTE in patients with severe aortic stenosis (AS). Methods and Results: In this retrospective study of 302 consecutive patients undergoing TAVR for severe AS, a pre-trained DL model was applied to pre-TAVR TTE to generate a patient-level DL index of LVOTO (DLi-LVOTO; range 0-100). Post-TAVR LVOTO was defined as a peak pressure gradient [&ge;]30 mmHg on follow-up TTE. Logistic regression and receiver operating characteristic analyses assessed the association and discriminative performance of DLi-LVOTO. Pre-TAVR LVOTO was present in 32 patients (10.6%) and post-TAVR LVOTO in 35 (11.6%). Follow-up TTE was performed at a median of 47 days (IQR 37-63) after TAVR, with the majority of TTE (216 of 302, 71.5%) performed within 2 months. DLi-LVOTO was significantly higher in patients with LVOTO at both pre- and post-TAVR TTE (all p<0.001). In multivariable analysis, DLi-LVOTO remained independently associated with post-TAVR LVOTO even after adjusting for conventional TTE parameters and pre-TAVR LVOTO (adjusted OR 1.29, 95% CI 1.06-1.56 per 10-score increase, p=0.011), with an AUROC of 0.78 (95% CI 0.72-0.85). Among patients without pre-TAVR LVOTO, DLi-LVOTO retained independent predictive value (adjusted OR 1.56, 95% CI 1.19-2.06, p=0.001; AUROC 0.84, 95% CI 0.77-0.91). Conclusion: A DL model originally trained in HCM patients independently predicts post-TAVR LVOTO from pre-TAVR TTE, including in patients without pre-existing LVOTO, suggesting it captures hemodynamic features beyond conventional echocardiographic assessment.

Hormone replacement therapy (HRT) with oestrogen and progestogen is a common medical treatment for alleviating symptoms of menopause. Since 2015, its use has been increasing in the UK. Unscheduled bleeding can be a symptom of endometrial cancer, and guidelines state that women experiencing this should have an urgent referral for suspected endometrial cancer. However, unscheduled bleeding is also common in women taking HRT, particularly in the first few months after starting HRT or if there is a change in regimen. Current guidelines may result in women on HRT receiving referrals that are not necessary and undergoing unpleasant and invasive tests such as hysteroscopy. However, there is a lack of current information to guide recommendations. This protocol describes a cohort study in the ORCHID-e database of anonymised patient records from English primary care. We will use a cohort of women aged over 40 years starting on HRT with oestrogen and progestogen, age matched to women who have not started HRT. Exposure will be a prescription for oestrogen containing HRT with no previous prescription for oestrogen containing HRT in the previous year. Index date in each matched set will be the date of this prescription. Prescriptions for progestogen containing drugs will not be used to define the exposure, but this information will be extracted to describe the study population and for sensitivity analyses. Outcomes will be consultations for unscheduled bleeding, urgent referrals for suspected endometrial cancer, and diagnosis of endometrial cancer. Women will be followed up until they change exposure status or are otherwise censored. Women who start taking HRT in follow-up will re-enter the cohort in the exposed group. We will describe proportions of women with a code for consulting with unscheduled bleeding, proportions of those women referred for further investigation on the pathway for suspected endometrial cancer, and proportions diagnosed with endometrial cancer within one year of referral. We will investigate the diagnostic accuracy of unscheduled bleeding for endometrial cancer separately for women on HRT and those not on HRT. Analyses will be done by 6-month categories of time since index, age, calendar year, sociodemographic variables, risk factors for endometrial cancer, type of HRT.

Abstract Background: Poor sleep quality is associated with increased cardiovascular risk, although its relationship with left ventricle (LV) structure is poorly understood and ethnic differences in the relationship between sleep and LV structure have not been studied. We investigated the association between poor sleep quality and LV structure in a tri-ethnic cohort. Methods: A total of 1284 participants were analysed from the Southall and Brent Revisited (SABRE) study (age=49.9{+/-} 6.2y; male 75.9%, Europeans (EU)=615, South Asians (SA)=457, African/African-Caribbean (AC)=212). A composite sleep quality score was calculated, and LV structure was measured using echocardiography. Associations between sleep quality and LV mass indexed to height1.7 (LVMi), relative wall thickness (RWT) and LV end-diastolic volume indexed to height1.7 (LVEDVi) were estimated using multivariable linear regression with adjustment for demographic and lifestyle factors across three models. Analyses were performed in the whole cohort and stratified by ethnicity. Results: Compared with those who reported very good sleep quality, participants with poorer sleep quality had higher LVMi (4.8 (95% CI 1.4; 8.2)g/(m1.7*unit sleep score); p=0.006). When stratifying by ethnicity, the association between sleep quality and LVMi was unconvincing in EU (1.9(-3.5, 7.3)g/(m1.7*unit sleep score); p=0.493), whereas poor sleep was associated with higher LVMi in AC and SA participants (9.1(1.3;16.8)g/(m1.7*unit sleep score); p=0.023 and 5.8(0.5;11.0)g/(m1.7*unit sleep score); p=0.031 respectively). Conclusions: Poor sleep quality is associated with higher LVMi in older African/African-Caribbeans and South Asians, but not in Europeans. This may contribute to cardiovascular risk. Keywords: sleep, left ventricle, hypertrophy, remodelling