Circulation Research

Background Hypertension is a major modifiable risk factor for atrial fibrillation (AF), yet blood pressure (BP) control remains suboptimal in older U.S. adults. Objectives This study evaluated how improve systolic BP (SBP) control could affect incident AF, downstream AF ablation demand, Medicare savings, and hospital revenue. Methods A population-based modelling framework was developed to estimate mortality and incident AF hazards across SBP strata: <120, 120-139, 140-159, and ?160 mm/Hg. AF incidence in the SBP <120 mmHg group was set at 2.2 per 1,000 person-year, with hazard ratios of 1.17, 1.42 and 1.64 applied to higher SBP strata. We assumed 25% of incident AF patients would undergo ablation, with a 7.2% complication rate. AF prevalence was projected to increase by 4.6% annually over 10 years. Medicare savings and hospital revenue foregone were estimated under varying procedure cost and contribution-margin assumptions. Results Higher SBP was associated with greater hazards of death and incident AF. Improved SBP control reduced projected AF incidence and ablation demand. Over 10 years, cumulative Medicare savings were projected at $8.7B-$10.9B across the full modelled population. However, reduced ablation volume translated into hospital revenue foregone, ranging from $75M to $377M in the first year, and approximately $1.03B-$5.2B cumulatively over 10 years. Conclusions Improved SBP control may reduce AF incidence, prevent avoidable invasive ablation procedures, relieve pressure on surgical waitlists, and generate substantial Medicare savings. However, these benefits may reduce hospital procedural revenue, highlighting a misalignment between prevention-oriented care and fee-for-service reimbursement incentives.

The apnea-hypopnea index (AHI), the conventional metric of obstructive sleep apnea (OSA) severity, is typically studied using scalar summaries of sleep architecture, such as the total time spent in each sleep stage. Although clinically interpretable, these summaries fail to capture the temporal organization of overnight sleep-stage sequences and may obscure stage-specific associations with OSA severity. Modeling the complete sleep-stage trajectory provides substantially richer temporal information; however, because total sleep duration varies across individuals, sleep-stage trajectories are observed over subject-specific domains, limiting the applicability of conventional functional regression methods that assume a common observation interval. We therefore applied Variable-Domain Functional Regression (VDFR) to overnight polysomnographic data from the APPLES study (n= 1,103), treating the epoch-by-epoch sleep-stage sequence as a continuous, variable-length functional predictor of AHI. We compared three levels of sleep-stage granularity: five stages (Wakefulness, N1, N2, N3, REM), three stages (Wakefulness, Non-REM, REM), and binary staging (Wakefulness vs. Sleep). Functional sleep-stage terms were significant across all staging granularities and model structures (all p-values [&le;]0.001). Wake, N1, and N2 were positively associated with AHI, whereas N3 and REM were negatively associated, with REM exhibiting the strongest association. These effects were attenuated under coarser staging representations, highlighting the importance of preserving fine-grained sleep architecture. To our knowledge, this is the first application of VDFR to overnight polysomnographic data in OSA, showing that accommodating subject-specific sleep durations enables the identification of stage-specific temporal associations with AHI severity that are attenuated or obscured by coarser staging and conventional scalar analyses.

Background and aims: Sex differences in ethnic minority risk of coronary heart disease (CHD) are often overlooked. Here we aim to explore sex-by-ethnicity differences in CHD outcomes and the contribution of risk factors. Methods: Incident CHD events were identified for Europeans, and South Asian and African/African Caribbean first generation migrants in the UK-based Southall and Brent Revisited (SABRE) cohort. Cardiovascular risk factors were assessed at baseline (1988-91). Cox proportional hazards models quantified group differences in CHD incidence and risk factor contribution. Population attributable fractions (PAFs) described risk factor contribution to group differences. Results: Among 4,754 participants followed for 40.8 years, 1,710 CHD first events occurred. Cumulative incidence of CHD was highest in South Asian males (65% by age 90) and females (55%), compared with 52% in European males and 24-31% in other groups. Sex differences in CHD incidence were pronounced in Europeans (female versus male HR=0.45, 95% CI [0.37,0.55]) but attenuated in South Asians (0.68 [0.56,0.82]) and African/African Caribbeans (0.79 [0.57,1.10]). CHD risk was higher in South Asian compared to European men (1.80 [1.63,1.99]). This ethnic difference was greater in females (2.44 [1.88,3.17]). PAFs for diabetes (PAF=18.0%, 95% CI [6.2,29.8]), hypercholesterolemia (44.2% [20.4,68.1]), and hypertriglyceridemia (22.4% [7.9,37.0]) made a greater contribution to the risk of CHD in South Asian females compared to all other groups. Conclusions: Ethnic minority female participants do not have the same protection from CHD as Europeans. Greater cardiometabolic burden may drive this elevated CHD risk and loss of female protection.

Background: Bicuspid aortic valve anatomy increases procedural complexity during transcatheter aortic valve implantation, yet outcome-oriented anatomic risk stratification for intraprocedural events remains limited. Aims: We aimed to develop and externally validate an anatomy-driven score to predict a composite intraprocedural endpoint, assessed at exit from the procedure room, in bicuspid transcatheter aortic valve implantation. Methods: Consecutive patients with bicuspid aortic valve undergoing transcatheter aortic valve implantation were analysed in a development cohort (N=793) and a multicentre external validation cohort (N=134). Candidate preprocedural computed tomography and echocardiographic variables were prespecified by expert consensus and refined using penalized regression with bootstrap stability selection within a domain-constrained framework. A five-indicator score (0 to 10 points) was derived from routine imaging metrics spanning the ascending aorta, aortic root, valve complex, annulus-outflow tract unit, and left ventricle, and tested using multivariable logistic regression. Results: The composite intraprocedural endpoint occurred in 101/793 (12.7%) patients in the development cohort, with stepwise increases across risk strata (7.2%, 13.3%, 30.6%; p<0.001). Each 1-point increase was independently associated with higher risk (odds ratio 1.32; 95% confidence interval 1.18-1.47). A similar gradient was observed in external validation (3.1%, 10.8%, 50.0%; p=0.012; odds ratio 1.55 per point), with a C-statistic of 0.725. Higher risk categories were associated with lower early safety and higher 30-day and 1-year mortality. Conclusions: An anatomy-driven score derived from routine preprocedural imaging demonstrates graded discrimination of intraprocedural risk and may inform procedural planning in bicuspid transcatheter aortic valve implantation.

Background: Neighborhood-level social determinants of health influence cardiovascular outcomes; however, their association with post-discharge healthcare utilization in heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. Methods: We conducted a retrospective cohort study of 6,702 adults hospitalized for HFpEF (2014 to 2022). Patients were assigned to one of four neighborhood environments (NEnv-1 to NEnv-4) using a validated clustering framework based on ZIP code-level socioeconomic variables. The primary outcome was time to first HF readmission, evaluated within prespecified post-discharge intervals (0-30 days, >30-90 days, and >90-365 days). Secondary outcomes included HF-related healthcare re-encounters and HF hospitalization burden (0, 1, or [&ge;]2 admissions). Cox proportional hazards and multinomial logistic regression models were used. Results: Neighborhood environment was independently associated with post-discharge outcomes with distinct temporal patterns. Early (0-30 days) HF readmission risk was higher in NEnv-3 (aHR, 1.63) and NEnv-4 (aHR, 1.76), with similar increases in HF-related re-encounters (aHR, 1.72 and 1.84) persisting through the >30-90-day interval. In contrast, NEnv-2 demonstrated a delayed-risk pattern, with the highest risk occurring in the >90-365-day interval (readmission aHR, 3.42; re-encounter aHR, 3.45). All non-reference environments were associated with a higher likelihood of at least one post-index HF admission (aOR range, 1.84-2.24). NEnv-4 uniquely demonstrated higher odds of recurrent hospitalization ([&ge;]2 vs. 1 admission; aOR, 1.64). Conclusions: Neighborhood environment is associated with distinct, time-dependent patterns of HF utilization in HFpEF, including early, delayed, and recurrent risks. Incorporating neighborhood context may help identify when patients with HFpEF are most vulnerable after discharge and guide the timing of post-discharge interventions.

Background Structural heart disease (SHD) drives heart failure and cardiovascular mortality but remains underdiagnosed, and echocardiography is limited as a population-level screening tool. Objectives We evaluated whether a composite artificial intelligence-enabled electrocardiogram (AI-ECG), combining independently developed models for left ventricular systolic (LVSD) and diastolic dysfunction (LVDD), identifies prevalent and predicts incident SHD across diverse populations. Methods In this multinational cohort study, detection was assessed cross-sectionally in a Korean clinical cohort (Incheon Sejong Hospital) and a US dataset (Columbia University Irving Medical Center), and incident risk was assessed in the Korean cohort and the UK Biobank among individuals without baseline SHD or heart failure. Adults with paired ECG and echocardiography were analyzed for detection, with the composite defined as positive on either model. SHD comprised reduced left ventricular ejection fraction, moderate or severe valvular disease, left ventricular hypertrophy, or pulmonary hypertension. Detection was assessed by sensitivity and specificity, and incident risk by Cox models and the C statistic. Results Among 46,082 and 36,286 participants in the two detection cohorts, the composite detected SHD with sensitivity of 71.8% and 76.1% and specificity of 88.3% and 70.1%, with positivity across all phenotypes. Among at-risk individuals, composite positivity was associated with incident SHD (hazard ratios, 3.75 and 2.75), with C statistics of 0.69 to 0.78. Conclusions A composite AI-ECG identified prevalent and predicted incident SHD across multinational cohorts, capturing signals beyond its training targets and supporting its potential as a scalable cardiovascular screening tool; whether ECG-based risk stratification improves outcomes requires prospective evaluation.

We conducted a scaling evaluation of unlabeled pretraining for electrocardiogram foundation model performance. One-dimensional vision transformer masked autoencoders were pretrained across increasing ECG volumes and fine-tuned for rhythm, morphology, diagnostic, and structural heart disease tasks. Models pretrained below 400,000 ECGs failed to consistently exceed controls without self-supervised pre-training, whereas 600,000 to 800,000 ECGs improved AUROC across tasks, suggesting a minimum threshold for effective ECG representation learning.

Background: Prior analyses have demonstrated an inverse association between transcatheter aortic valve replacement (TAVR) procedural volume and short-term outcomes. However, less is known regarding the relationship between procedural volume and 1-year outcomes in the contemporary TAVR era. Objectives: To evaluate the association between annual hospital and operator TAVR procedural volumes and 1-year clinical outcomes in a contemporary national cohort. Methods: Clinical records from the Society of Thoracic Surgeons (STS)/American College of Cardiology (ACC) Transcatheter Valve Therapies (TVT) Registry for patients undergoing commercial TAVR between January 2020 and December 2022 were linked to Centers for Medicare & Medicaid Services administrative claims. Annualized hospital and operator TAVR volumes were modeled continuously and categorized into tertiles. Primary outcomes included 1-year all-cause mortality, stroke, the composite of mortality or stroke, and all-cause readmissions. Hierarchical risk-adjusted models accounting for patient clustering within sites were used to evaluate associations between procedural volume and outcomes. Results: Among 215,335 patients undergoing TAVR at 788 hospitals by 3,444 operators between 2020 and 2022, median annual hospital and operator volumes were 74 (IQR: 43-115) and 16 (IQR: 10-32), respectively. Volume was then categorized into tertiles (low, medium and high). Compared with high-volume hospitals ([&ge;]102/year), low-volume hospitals ([&le;]52/year) had higher adjusted rates of 1-year all-cause mortality (Odds Ratio (OR): 1.10 [95% CI: 1.05-1.16]), stroke (OR: 1.10 [95% CI: 1.01-1.19]), mortality or stroke (OR: 1.10 [95% CI: 1.05-1.15]), and all-cause readmissions (OR: 1.05 [95% CI: 1.00-1.09]). Compared with high-volume operators ([&ge;]25/year), low-volume operators ([&le;]11/year) had higher adjusted rates of stroke (OR: 1.16 [95% CI: 1.05-1.28]) and mortality or stroke (OR: 1.09 [95% CI: 1.03-1.15]) but not other endpoints. Conclusions: In a large, contemporary national TAVR registry, lower annual hospital ([&le;] 52/year) and operator ([&le;] 11/year) procedural volumes were independently associated with worse 1-year clinical outcomes. These findings suggest that procedural experience continues to influence outcomes despite maturation of contemporary TAVR practice.

Background. Maximal oxygen uptake (VO2max) is a leading marker of cardiorespiratory fitness and a strong predictor of all-cause mortality. Cardiopulmonary exercise testing (CPET) is the reference method but is resource-intensive, so consumer wearables estimate VO2max from passively collected signals; these estimates compress the fitness range, returning near-correct group averages while ranking individuals poorly. No peer-reviewed validation of a smart-ring VO2max estimate against CPET has been reported, and none in a South Asian cohort. Objective. To validate the Ultrahuman Ring AIR VO2max estimate against laboratory CPET, benchmark it against published prediction equations, and assess its generalization and construct validity. Methods. In a single-site paired ring-CPET cohort (N = 101; mean CPET peak VO2 43.3 mL{middle dot}kg-{superscript 1}{middle dot}min-{superscript 1}, SD 9.9), peak oxygen uptake was measured by treadmill or cycle-ergometer CPET, and the Ultrahuman Ring AIR estimate was computed from passively collected signals using a transparent ensemble based on published equations. Ensemble weights and calibration were selected on an 85-subject development set by an automated search minimizing a composite 5-fold cross-validated error criterion; the locked estimate was evaluated on a 16-subject held-out test set. The calibrated coefficients are proprietary. Agreement was quantified with mean absolute error (MAE), bias, Pearson r, regression slope and Lin's concordance correlation coefficient (CCC; bootstrap 95% CIs), and Bland-Altman limits of agreement. Separately, in 181,133 de-identified Ring users (no CPET reference), construct validity was assessed against ring-measured sleep, continuous glucose monitoring (n = 2,597), and a venous blood panel (n up to 15,203), adjusted for age, sex, and BMI, with lipoprotein(a) as a pre-specified negative control. Reporting followed TRIPOD and STARD. Results. With a self-reported fitness level provided, the estimate agreed with CPET peak VO2 at MAE 4.68 mL{middle dot}kg-{superscript 1}{middle dot}min-{superscript 1} (95% CI 3.93 to 5.49), Pearson r 0.79, CCC 0.79, and slope 0.71. The five published equations were worse on every metric (MAE 6.2 to 10.6, CCC 0.28 to 0.56, slope 0.32 to 0.42), each compressing the fitness range. On the held-out test set (n = 16), agreement held (r 0.84, slope 0.81, MAE essentially unchanged). Without the fitness input, full-cohort MAE was 5.16, still ahead of every published equation. At population scale, higher estimated fitness tracked a healthier profile on measurements the estimate does not use: better ring-measured sleep; higher continuous-glucose time in target range (79.6% versus 61.5%, top versus bottom decile; n = 222 and 399 of 2,597 users); and lower triglycerides, fasting glucose, and HOMA-IR (n up to 15,203 assayed per marker). These associations held after adjustment for age, sex, and BMI, whereas the pre-specified negative control lipoprotein(a) did not separate the deciles. Conclusions. The Ultrahuman Ring AIR VO2max estimate agreed with laboratory CPET substantially better than published prediction equations, held its agreement on held-out subjects, and ordered a large population along independent cardiometabolic gradients consistent with true fitness.

Aims Polymer-free drug-eluting stents were developed to enhance vascular biocompatibility and safety while maintaining antirestenotic efficacy. The TRANSEVER registry evaluated 12-month clinical outcomes of the polymer-free everolimus-eluting ISAR SUMMIT stent in a large, real-world population undergoing percutaneous coronary intervention. Methods This prospective, multicentre study enrolled patients with coronary artery disease undergoing PCI with the ISAR SUMMIT stent across 33 centres in India. The primary endpoint was target-lesion failure (TLF) at 12 months, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularisation. Secondary endpoints included the patient-oriented composite endpoint (POCE) of all-cause death, any myocardial infarction, stroke, revascularization, and definite/probable stent thrombosis. Results A total of 1,000 patients were enrolled, of whom 996 completed 12-month follow-up. The cohort presented with a high-risk profile, including an acute coronary syndrome (ACS) in 89.8% of the cases and diabetes mellitus in 44.4% of them. Procedural outcomes were excellent in terms of device success and final TIMI 3 flow (achieved in all treated lesions). At 12 months, TLF occurred in 15 patients (1.5%). Definite or probable stent thrombosis was observed in 8 patients (0.8%). POCE was observed in only 21 patients (2.1%). Conclusions In this large, contemporary real-world population with a very high proportion of patients presenting with ACS, the polymer-free everolimus-eluting ISAR SUMMIT stent demonstrated favourable 12-month clinical outcomes, with low rates of target lesion failure and stent thrombosis. These results suggest that this novel device is both safe and effective for routine clinical use.

Population-level data on preclinical heart failure (HF) remain limited because most epidemiological studies focus on symptomatic HF. We therefore developed an administrative-data algorithm to classify HF stages across the national population and describe temporal trends, stage transitions, and mortality across the HF continuum. Methods Using a claims-based staging framework adapted from the Universal Definition of HF, we classified HF stages from ICD-10 codes, prescription records, and medical procedures. We applied this algorithm to the Czech population, linking the National Registry of Reimbursed Health Services to National mortality records from 2015 to 2024. Results In 2024, 27.8% of the Czech population met criteria for Stage A HF and 8.2% for Stage B. Over 10 years, the prevalence of both preclinical stages increased beyond what could be explained by population aging alone, with age-standardized prevalence rising by 9.5% for Stage A and 19.2% for Stage B. Age-standardized 1-year mortality showed a steep stepwise gradient, from 0.69% in Stage A to 1.69% in Stage B, 3.06% in Stage C, and 7.27% in Stage D. Among 52,172 individuals with incident clinical HF in 2024, more than 95% had previously met administrative criteria for Stage A or Stage B. Conclusion Administrative surveillance of the HF continuum using routinely collected healthcare data provides a scalable administrative framework for population-level monitoring of HF burden. In Czechia, both preclinical and clinical HF burdens increased over time beyond population aging alone, underscoring the need for earlier preventive strategies targeting preclinical disease.

BACKGROUND: Chronic coronary syndromes (CCS) remain under-characterized in Latin America, where clinical profiles may differ from high-income countries. OBJECTIVE: We aim to characterize the clinical presentation, coronary anatomic profile, and pharmacologic treatment patterns of adults living with CCS using data from the Mexican Chronic Coronary Syndrome Registry (RESINCCRO). METHODS: RESINCCRO is an observational, multicenter, cross-sectional registry conducted across ~50 centers in five regions from Mexico. We included adults ([&ge;]18 years) enrolled between September 2024 and March 2025 who met 2019 ESC CCS criteria. Coronary imaging data was collected from medical records into a standardized electronic case report form. RESULTS: We enrolled 3,029 adults (men [72.5%]; mean age 67.2 {+/-} 10.7 years). Cardiometabolic comorbidities were frequent: overweight/obesity (76%), arterial hypertension (69.0%), type 2 diabetes (44.0%), and chronic kidney disease (24.2%). Persistent angina/equivalents occurred in (23.9%), of which most had Canadian Cardiovascular Society class I - II (91.2%). The mean LVEF was of 53.7 {+/-} 12.0. Cardiac rehabilitation participation was (6.2%). Median LDL-C was 70 mg/dL (IQR 51 - 95) and LDL <55 mg/dL was only 26.1%, despite high prescription of lipid-lowering therapies, including statins (93.2%), ezetimibe (24.6%), and PCSK9 inhibitors (2.4%). 60.3% had obstructive epicardial disease. CONCLUSIONS: Mexican adults with CCS exhibit high cardiometabolic burden, frequent symptoms, suboptimal LDL-C goal attainment, low rehabilitation uptake, and a substantial obstructive phenotype. These findings highlight opportunities to intensify secondary prevention, adopt mechanism-directed evaluation and therapy, and expand cardiac rehabilitation to improve CCS care in Mexico.

Background: Apical sparing of left ventricular longitudinal strain (LS) is an echocardiographic clue to cardiac amyloidosis but may also occur in hypertensive heart disease (HHD). Objectives: To determine whether apical sparing in HHD is associated with regional left ventricular wall stress estimated according to Laplace's law. Methods: We retrospectively studied 1,559 patients with HHD, 47 with light-chain cardiac amyloidosis (ALCA), and 409 normotensive controls. Artificial intelligence-assisted echocardiography quantified segmental LS, wall thickness, and cavity radius at the basal, midventricular, and apical levels. Wall stress was estimated as mean blood pressure (MBP) x radius/(2 x wall thickness). Apical sparing was defined as a relative regional strain ratio (RRSR)[&ge;]1.0. Results: Apical sparing was present in 14 patients with HHD (0.9%), 13 with ALCA (27.7%), and no controls. Among HHD patients with apical sparing, RRSR decreased from 1.11{+/-}0.13 to 0.72{+/-}0.10 after antihypertensive treatment (P<0.001), accompanied by reduced wall stress and improved basal and midventricular LS, with resolution of apical sparing in all 14 patients. In the overall HHD cohort, changes in MBP and left ventricular mass index were independently associated with changes in RRSR. In an exploratory analysis of HHD patients with apical sparing, a reduction in basal wall stress was associated with a reduction in RRSR ({beta}=0.267 for {bigtriangleup}RRSRx100, 95% CI 0.023-0.511; P=0.036). In ALCA, favorable hematologic response was the only determinant of RRSR reduction. Conclusions: Apical sparing in HHD was uncommon but reversible and may represent a load-sensitive deformation pattern associated with regional wall stress, consistent with Laplace's law.

Background: The clinical benefit and safety of drug-coated devices in chronic limb-threatening ischemia remain debated, particularly after recent randomized evidence questioning paclitaxel-coated technologies. We evaluated wound healing, limb outcomes, and mortality after infrainguinal endovascular therapy with uncoated, paclitaxel-coated, and sirolimus-coated devices. Methods: Consecutive patients with chronic limb-threatening ischemia undergoing successful infrainguinal endovascular therapy in a prospective single-center service evaluation were analyzed. The primary exposure was use of any drug-coated device during the index procedure. Inverse probability of treatment weighting and multivariable Cox models were used to adjust for baseline differences. Exploratory analyses compared paclitaxel-coated, sirolimus-coated, and uncoated devices. Results: Among 341 patients, 244 (71.6%) received at least one drug-coated device. After weighting, drug-coated device use was associated with more frequent wound healing, whereas major amputation, clinically driven target lesion revascularization, major adverse limb events, and death did not differ significantly between groups. In weighted multivariable models, drug-coated device use remained associated with wound healing (HR, 1.86; 95% CI, 1.14?3.02), but not with mortality or major limb events. Exploratory drug-specific analyses suggested the highest wound-healing rates among patients treated with sirolimus-coated devices, while mortality was comparable between paclitaxel-coated and uncoated devices. Conclusion: In this real-world cohort of patients with chronic limb-threatening ischemia undergoing infrainguinal endovascular therapy, drug-coated device use was not associated with increased adjusted 1-year mortality and was associated with improved wound healing. Exploratory analyses suggested favourable wound-healing outcomes with sirolimus-coated balloons, with a lower observed mortality signal that warrants confirmation in larger comparative studies.

BACKGROUND In line with International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations for high-sensitivity cardiac troponin assays, analytical validation and reference limit assessments are required to confirm that an assay meets performance criteria. This study evaluated the analytical performance and established the 99th percentile upper reference limit (URL) for the SPINCHIP High-Sensitivity Cardiac Troponin I (SPINCHIP hs-cTnI) point-of-care assay. METHODS Analytical performance characteristics, including the limit of blank (LoB), limit of detection (LoD), and limit of quantification (LoQ), were assessed. Additionally, 1,053 plasma samples and 1,055 whole-blood samples were used to determine the URL. Imprecision around the 99th percentile URL was evaluated as part of the analytical validation. High-sensitivity criteria were assessed by confirming measurable cTnI in [&ge;]50% of healthy individuals (n=432 plasma; n=431 whole blood) and achieving imprecision <10% at the 99th percentile (plasma, n=960; whole blood, n=480). RESULTS SPINCHIP hs-cTnI demonstrated a LoB of 0.3 ng/L; LoDs of 0.8 ng/L (plasma) and 0.9 ng/L (whole blood); and LoQs of 1.1 ng/L (plasma) and 1.4 ng/L (whole blood). The analytical measuring range was 1.1-9,000 ng/L. Imprecision at the common 99th percentile URL (14 ng/L) was 5.8%; for men (URL=16 ng/L) 5.6% and for women (URL=10 ng/L) 6.3%. Greater than 85.2% (94.0% and 76.1% in men and women, respectively) of healthy individuals showed measurable cTnI above the LoD. CONCLUSIONS The SPINCHIP hs-cTnI assay meets the IFCC high-sensitivity requirements, demonstrating <10% imprecision at the 99th percentile, reliable low-concentration precision and cTnI detection in more than half of healthy individuals.

Background: Sex differences in cerebrovascular disease are established determinants of outcome in acute stroke care and vascular interventions, but evidence in cerebrovascular bypass surgery remains limited. This study examined whether biological sex was associated with outcome after superficial temporal artery to middle cerebral artery (STA-MCA) bypass in patients with atherosclerotic cerebrovascular disease (ACVD). Methods: We retrospectively screened adults undergoing extracranial-to-intracranial (EC-IC) bypass (2012?2025) and included ACVD patients treated by STA-MCA bypass with available follow-up. The primary outcome was modified Rankin Scale (mRS) at latest follow-up, analyzed using proportional odds regression. Multivariable models adjusted for age, preoperative mRS, and vascular comorbidities. Cerebrovascular reserve capacity (CVRC) was analyzed in a subgroup. Results: A total of 140 patients (30.7% female) were included. Disease morphology varied by sex, with more multivessel (65.1% vs. 47.4%) and stenotic disease (39.5% vs. 20.6%) in females and more isolated internal carotid artery occlusion in males (43.3% vs. 16.3%). The 30-day risk of symptomatic ischemic stroke was higher in females than in males (9.3% vs. 1.0%). A similar pattern was observed at follow-up (median 13.5 months), with ischemic events predominating in females (16.3% vs. 7.2%) and hemorrhagic events occurring exclusively in males (5.2%). Female sex was independently associated with worse functional outcome (OR 2.59, 95% CI 1.28?5.30, p=0.008). Preoperative mRS was the strongest determinant of outcome (OR 4.30, 95% CI 3.07?6.18, p<0.001). Adjusted analysis detected no significant association between CVRC and outcome (OR 0.80, 95% CI 0.24?2.70, p=0.721). Conclusions: Female sex was independently associated with worse functional outcome after STA-MCA bypass, independent of preoperative functional status, hemodynamic impairment and cardiovascular comorbidities. These findings identify sex as a clinically relevant determinant of outcome in cerebrovascular bypass surgery and should be considered in future risk stratification and trial design.

Background: Unplanned emergency readmissions remain common following hospitalisation for heart failure (HF). Residual congestion, atrial fibrillation, frailty, and other comorbidities contribute to adverse outcomes after discharge. Identifying patients at high risk of readmission or death may help target post-discharge management. Methods: We conducted a retrospective cohort study of patients hospitalised with HF in selected New South Wales hospitals who were discharged alive and not documented as receiving end-of-life care. Clinical, laboratory, medication, and text-derived variables extracted from electronic health records were used to develop predictive models and corresponding risk scores for emergency readmission and all-cause mortality within 180 days of discharge. Feature importance methods were used to identify key predictors and explain individual risk estimates. To illustrate model predictions while preserving patient privacy, we generated representative synthetic patient profiles by summarising the characteristics of groups of patients with similar predicted risk patterns and visualised the major contributors to their predicted risks using Shapley values. Results: The study included 5,202 hospitalisations among 3,933 patients. Within 180 days of discharge, 45.2% of patients experienced at least one emergency readmission and 12.4% died. The most common causes of emergency readmission were recurrent HF, followed by atrial fibrillation, chest pain, and pneumonia. Predictive performance was moderate for emergency readmission (AUC 0.70; calibration slope 1.30) and good for mortality (AUC 0.84; calibration slope 1.01). Emergency readmission risk was primarily associated with greater prior healthcare utilisation, a higher number of active medical problems, high risk of falls, older age, and impaired kidney function. Mortality risk was most strongly associated with abnormal red blood cell distribution width, elevated blood urea, older age, and lower systolic blood pressure. A lower number of discharge medications, particularly cardiovascular therapies, was associated with a higher risk of emergency readmission and a lower risk of mortality. Representative synthetic patient profiles demonstrated heterogeneity in the factors contributing to predicted risks, illustrating the value of patient-level risk visualisation. Conclusions: Predictive models identified clinically meaningful predictors of emergency readmission and mortality following HF hospitalisation. Patient-level visualisation of individual risk drivers may support more personalised post-discharge management.

Chronic kidney disease and heart failure disproportionately burden populations of African ancestry, yet Mendelian randomisation (MR) studies of the causal relationship between kidney function and heart failure subtypes have been conducted exclusively in European ancestry populations. We performed a forward two-sample MR analysis to evaluate the causal effect of genetically predicted estimated glomerular filtration rate (eGFR) on heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) in individuals of African ancestry. Genetic instruments were selected from an African ancestry eGFR genome-wide association study (N = 67,943) at genome-wide significance, with linkage disequilibrium clumping using an African ancestry reference panel. Heart failure subtype summary statistics were obtained from the Million Veteran Program (HFpEF: 5,379 cases / 113,041 controls; HFrEF: 9,104 cases / 109,632 controls). Six independent SNPs (F-statistics 30.5 &#8211 107.3; R&#178 = 0.62%) were retained as instruments. The primary inverse-variance weighted analysis provided no evidence of a causal effect of eGFR on HFpEF (OR 0.92, 95% CI 0.80 &#8211 1.06, p = 0.248) or HFrEF (OR 0.98, 95% CI 0.78 &#8211 1.23, p = 0.878). Sensitivity analyses were directionally consistent. There was no evidence of heterogeneity or directional pleiotropy. Minimum detectable effects at 80% power were OR 1.28 for HFpEF and OR 1.22 for HFrEF. These null findings should be interpreted as inconclusive given current power constraints; larger ancestry-matched studies are needed.

Background: The optimal timing of percutaneous coronary intervention (PCI) in patients undergoing transcatheter aortic valve replacement (TAVR) remains unclear, particularly regarding its impact on renal outcomes. Methods: We conducted systematic review and meta-analysis of studies comparing staged versus concomitant PCI in patients with aortic stenosis and coronary artery disease undergoing TAVR. We searched MEDLINE, Embase, and Cochrane databases comprehensively. Using a random-effects model, we calculated odds ratios (OR) with 95% confidence intervals (CI) to assess the incidence of contrast-induced acute coronary injury (CI-AKI) across different stages. Results: The analysis included 11 studies encompassing 7,119 patients. Overall, staged PCI did not significantly differ from concomitant PCI in reducing CI-AKI (OR 1.02; 95% CI 0.53 to 1.98; p = 0.959; Figure 2A). Subgroup analysis revealed no significant differences in stage 1 (OR 1.99; 95% CI 0.38 to 10.47; p = 0.417; Figure 2B) or stage 2 CI-AKI (OR 1.01; 95% CI 0.39 to 2.64; p = 0.978; Figure 2C). However, a statistically significant difference emerged for stage 3/4 CI-AKI, favoring the staged approach (OR 0.48; 95% CI 0.24 to 0.99; p = 0.046; Figure 2D). Conclusion: While staged PCI does not consistently reduce CI-AKI in patients undergoing TAVR, it may offer potential benefits for more severe kidney injury (stages 3/4). Given the observed heterogeneity, large-scale randomized controlled trials are essential to establish the relationship between procedural timing and renal outcomes.

Minimally invasive endovascular procedures offer reduced surgical trauma, shorter recovery times, and improved outcomes, but rely on 2D fluoroscopic X-ray imaging, which provides limited depth perception and exposes patients and clinicians to ionizing radiation. Here we present an augmented reality (AR) system that fuses intravascular ultrasound (IVUS) and electromagnetic (EM) position tracking with preoperative computed tomography (CT) to produce an anatomically accurate, deformation-corrected navigational reference. A robotic device performs ECG-gated pullback of the IVUS probe, capturing 4D aortic motion across the cardiac cycle. We introduce a deep learning architecture for extracting vascular lumen boundaries and side-branch orifices from artifact-prone IVUS streams, and a semantically driven non-rigid CT-IVUS fusion pipeline robust to false positive landmarks. We evaluate the platform with trained surgeons in benchtop phantom studies and in-vivo ovine models, and demonstrate its application to fenestrated endovascular aneurysm repair (FEVAR). Compared to fluoroscopy alone, AR guidance significantly reduces cannulation time, radiation exposure, and cognitive workload, while improving procedural efficiency and safety. Our IVUS-EM and CT aortic datasets are released open source.