Heart Rhythm

PurposeObstructive sleep apnea (OSA) is a common comorbidity in heart failure (HF) patients with prevalence increasing as HF severity worsens. While CPAP/BiPAP has been shown to reduce disease burden and mortality in the general HF population, it is unclear whether these benefits extend to patients with left ventricular assist devices (LVADs). We sought to determine whether OSA affects long-term survival in newly implanted LVAD patients and whether CPAP/BiPAP treatment confers mortality benefits. MethodsThis single-center retrospective study included patients who underwent LVAD implantation between January 2007 and February 2022. Recipients were stratified by OSA status (OSA vs No-OSA), and those with OSA were further categorized based on CPAP/BiPAP compliance. Comparative statistics and Kaplan-Meier survival analyses were performed, with log-rank tests used to compare groups and assess survival differences. A Cox proportional hazards model was conducted to evaluate the association between risk factors and survival among patients with OSA and No-OSA. ResultsBefore LVAD implantation, patients with OSA had higher body mass index, hypertension, and a higher rate of implantable cardioverter-defibrillator placement than those without OSA. OSA was not associated with increased postoperative complications. Although survival did not differ significantly between OSA and No-OSA patients (p=0.33), CPAP/BiPAP-compliant OSA patients had significantly better survival than noncompliant patients (p=0.0099). ConclusionsLVAD patients with OSA who consistently use CPAP/BiPAP have better survival than those who do not. CPAP/BiPAP is a simple, low-risk treatment that can reduce mortality in this population. Therefore, increased perioperative screening for OSA should be considered for patients receiving LVADs. Multicenter studies are needed to confirm our findings further.

The recently published EHRA/EACVI consensus statement on a standardized bi-atrial regionalization provides new opportunities for consistent regional analyses across patients, imaging modalities and clinical centers. To make this standardized regionalization widely accessible, we developed the open-source software DIVAID, which automatically divides bi-atrial geometries according to the proposed regions, ensuring consistency, reproducibility and operator independence. We evaluated the accuracy of the algorithm by comparing its results to manual expert annotations across 140 geometries from multiple modalities and centers. Veins were automatically clipped correctly in 81% and orifices annotated correctly in 100% of cases. The median (interquartile range; IQR) Dice similarity coefficient (DSC) for left atrial regions was 0.98 (0.96-1.00) for DIVAID-expert and 0.98 (0.94-1.00) for inter-expert comparisons. For right atrial geometries, DSC was higher for DIVAID-expert than for inter-expert comparisons at 0.90 (0.80-0.95) and 0.88 (0.74-0.94), respectively. To assess the accuracy of regional boundaries, we computed the mean average surface distance (MASD) for boundaries derived from automatic or manual annotations. The median (IQR) MASD between DIVAID and experts was 0.17 mm (0.03-0.78) and 1.93 mm (0.65-3.96) in the left and right atrium, respectively. To conclude, DIVAID robustly divides anatomically diverse bi-atrial geometries according to the 15-segment model, while outperforming cardiac experts in both speed and consistency, and demonstrating an accuracy of regional boundaries comparable to the spatial resolution of cardiac imaging modalities. By providing automated, consistent atrial regionalization, DIVAID enables large-scale, standardized regional analyses and data-driven investigation of harmonized, multi-dimensional datasets, which may advance atrial arrhythmia research and personalized treatment strategies.

Abstract: Background: Vascular access is essential in treating patients undergoing prolonged endovenous therapy such as chemotherapy, antibiotics, and parenteral nutrition. Since the 1990s, when PICCs (peripherally inserted central catheters) appeared, vascular access options have expanded significantly, revolutionizing the treatment landscape for all types of patients. Objective: To analyze and describe the profile of the use of PICCs in a Brazilian quaternary hospital over 10 years with data collected by the infusion therapy team. Evaluating the number of PICCs implanted over the years, patients epidemiology and clinical characteristics, insertion details, associated complications, and the reason for removal. Methods: A retrospective cohort study that employs a quantitative, non-experimental approach to classify and statistically analyze past events associated with 21,652 PICCs implanted from January 2012 to December 2021 in a quaternary hospital at Sao Paulo - Brazil. All the catheters were implanted, and the data was collected by a team of nurses specializing in infusion therapy. We analyzed the number of catheters implanted over the years, insertion characteristics, patients epidemiology and clinical data, possible associated complications, and the reason for removal. Statistical analyses were conducted using R software (version 4.4.1) and SPSS (version 29) for Windows (IBM Corp, Armonk, NY). Results: During the specified period, 21,652 catheters were analyzed. The patients gender distribution was nearly balanced (48.2% versus 51.8%), and the average age was 66 years. Cardiovascular and metabolic issues were the most common comorbidities, and between 2020 and 2021, 29.3% of the sample tested positive for COVID-19. The most common location of hospitalization and implantation was the medical-surgical clinic (31.6% - 41.4%), and the most used type of catheter was the Power Picc (83.9%). The estimated complication incidence density is 2.94 complications per 1,000 catheter-days. Almost all the PICCs (98,2%) were adequately located at the cavo-atrial junction after the first attempt, 82.2% of catheters were removed after therapy, and the median duration of catheter use was 12 days. Conclusion: PICCs are widely employed for drug infusion, with their use growing progressively due to specialized teams greater availability and training. The high efficiency of these devices with a relatively low risk of complications already observed in previous studies was reinforced by the findings of this study of more than 20,000 catheters.

Sickle cell disease (SCD) is associated with substantial cardiovascular morbidity, but echocardiographic data from Latin American populations remain scarce. We aimed to characterise the structural, functional, and haemodynamic echocardiographic profile of adults with SCD attending a tertiary referral centre in Cali, Colombia. We conducted an observational, cross-sectional study based on systematic review of medical records and transthoracic echocardiography reports of consecutive adult patients ([≥]18 years) with confirmed SCD evaluated between January 2022 and December 2024. Patients with complex congenital heart disease, severe valvular disease of unrelated aetiology, pregnancy, or echocardiograms of insufficient quality were excluded. Of 669 patients screened, 57 met inclusion criteria. Reporting followed STROBE recommendations. The median age was 24 years (interquartile range [IQR] 21-32) and 59.6% were female; the SS genotype was the most frequent (76.4%) and 71.4% were on hydroxyurea. Median haemoglobin was 10.2 g/dL (IQR 9.3-11.4) and median NT-proBNP 491 pg/mL (IQR 98-1290). Most patients had preserved left ventricular dimensions and systolic function (median ejection fraction 63%, IQR 57-66.5; mean global longitudinal strain -18.9% {+/-} 2.9). Right ventricular function was preserved (mean tricuspid annular plane systolic excursion 25.4 {+/-} 4.6 mm). Left ventricular geometry was normal in 42.1%, with concentric remodelling in 24.6%, concentric hypertrophy in 21.1%, and eccentric hypertrophy in 12.3%. Diastolic function was normal in 71.4%. Valvular disease, when present, was predominantly mild. Tricuspid regurgitation velocity exceeded 2.5 m/s in 29.8% of patients and exceeded 3.0 m/s in 10.5%, identifying a substantial subgroup at intermediate-to-high probability of pulmonary hypertension. In this Colombian cohort of relatively young adults with SCD, cardiac structure and biventricular function were largely preserved, but nearly one-third of patients had echocardiographic findings suggestive of pulmonary hypertension. These findings support the routine use of transthoracic echocardiography as an accessible tool for early cardiovascular risk stratification in adults with SCD in low- and middle-income settings.

Objective The decline of the perinatal demise rate is slowing and demises are often unexplained. Significant research has been done regarding diagnostic yield and genetic causes of demise, but little is known about how Geneticist involvement impacts outcomes. The goal of the study was to evaluate post-mortem genetic testing practices and effects of the geneticists involvement. Methods Retrospective data from 111 perinatal demise cases was examined, including rates of prenatal genetic counseling, post-delivery genetics consult, genetic testing, and autopsy investigation. Results In this cohort 54% received genetic testing and 25% received a genetics consult. When compared to those without, cases with genetic specialist involvement were associated with significant increases in testing uptake (p=0.007), diagnostic yield (p<0.001), and patient education (p<0.001). Second trimester stillbirths and those with fewer ultrasound (US) abnormalities were less likely to receive genetic testing (both p values <0.001) and consults (p<0.001, p=0.020). Conclusion Though it was not possible to avoid ascertainment bias, this data demonstrates that geneticist involvement correlates with a higher rate of testing, greater diagnostic yield, and more thorough counseling. These findings underscore the importance of integrating genetics providers into perinatal postmortem healthcare teams.

Continuous, non-invasive cardiovascular monitoring is limited by the superficial sensing depth of Photoplethysmography (PPG), which is susceptible to peripheral artifacts. This study evaluates a wearable dual-modality prototype integrating dryelectrode Impedance Plethysmography (IPG) and PPG within a smartwatch form factor. Results from a pilot study (N=2) demonstrate that IPG signals exhibit a temporal lead over PPG across ventral and dorsal sites, supporting its greater penetration depth. During brachial artery modulation, IPG showed superior sensitivity to arterial recovery on the ventral forearm. Furthermore, 60-minute napping sessions revealed that while PPG remained morphologically stable, IPG signals underwent significant evolution, capturing distinct pulsewave archetypes. These findings suggest that wearable IPG provides a high-fidelity window into deep systemic hemodynamics typically reserved for clinical instrumentation.

Aims: Assessment of treatment response in HFrEF has largely relied on left ventricular (LV)-centric parameters, yet the left atrium (LA) plays a central role in modulating LV filling and reflects the cumulative hemodynamic burden. Whether discordant recovery between LV and LA function carries distinct prognostic implications in patients treated with ARNI-based therapy remains unknown. Methods and results: From the multicenter STRATS-HF-ARNI registry, 1,182 patients with HFrEF who underwent serial echocardiography at baseline and one-year follow-up were included. Patients were classified into four strain recovery phenotypes according to the direction of change in LVGLS and LASr at one year: Group A, concordant recovery (57.4%); Group B, discordant atrial non-recovery (11.2%); Group C, discordant ventricular non-recovery (15.6%); and Group D, concordant non-recovery (16.0%). Clinical outcomes included all-cause mortality, cardiovascular mortality, and HF hospitalization. Despite achieving LV functional improvement, Group B exhibited persistent LASr deterioration, accompanied by less favorable hemodynamic trajectories compared with Group A. On multivariable Cox regression, Group B was associated with significantly higher risks of all-cause mortality (adjusted hazard ratio [aHR] 3.53, 95% confidence interval [CI] 1.60-7.79) and cardiovascular mortality (aHR 5.68, 95% CI 1.91-16.92), comparable to Group D. Group C demonstrated higher HF hospitalization risk (aHR 2.25, 95% CI 1.31-3.86). The adverse prognostic impact of discordant atrial non-recovery was consistently observed across subgroups stratified by baseline LVGLS and LASr levels. Conclusion: In HFrEF patients treated with ARNI-based therapy, persistent LA dysfunction despite LV functional improvement identifies a high-risk phenotype comparable to concordant non-recovery. These findings suggest that concurrent assessment of LV and LA strain may provide incremental prognostic value beyond LV-centric metrics alone.

Definitive radiotherapy (RT) for prostate cancer (PC) with dose intensification and/or focal boosting has excellent oncologic outcomes, but many patients experience adverse events. Dose escalation to the whole prostate improves outcomes at the expense of increased late adverse events. Intraprostatic recurrence after definitive RT typically occurs at the site of the primary tumor, suggesting that dose to the site of the dominant lesion is an important predictor of future failure. The efficacy and safety of tumor-focused RT compared to that of standard RT for definitive treatment of localized PC has not been assessed. RadTARGET (RAdiation Dose TAiloRing Guided by Enhanced Targeting) is a phase II randomized trial that aims to demonstrate superior safety of image-guided, tumor-focused RT compared to standard RT for acute genitourinary (GU) or gastrointestinal (GI) in the setting of definitive RT for intermediate- and high-risk PC. The study intervention is image-guided, tumor-focused RT with dose intensification of cancer visible on imaging and dose de-intensification to remaining prostate. Patients will be randomized to two arms: those who receive standard RT dose and those that receive tumor-focused RT. The study population will be patients with intermediate- or high-risk PC planning to undergo definitive RT with or without systemic therapy. The primary endpoint to compare between randomized arms is acute GU or GI grade [&ge;]2 adverse events. Participant and study duration are 5 years and 8 years, respectively. RadTARGET will compare the efficacy and safety of tumor-focused RT to that of standard RT for definitive treatment of localized PC. We hypothesize that the tumor-focused approach will substantially reduce adverse events after prostate RT while retaining high efficacy. If this hypothesis is confirmed, we will conclude that a phase III randomized control trial is warranted to formally establish oncologic non-inferiority compared to the current standard of whole-gland dose escalation.

Background. Patients with heart failure and reduced ejection fraction (HFrEF) commonly show signs of systemic inflammation. Interleukin-1 (IL-1) is a pro-inflammatory cytokine, known to modulate cardiac function. We aimed to determine the effects of treatment with anakinra, recombinant IL-1 receptor antagonist (IL-1Ra), on plasma IL-1Ra levels. Methods. We measured IL-1Ra levels at baseline and longest available follow-up to 24 weeks in 63 patients (44 males, 40 self-identified Black-Americans) with recent hospitalization for HFrEF, and systemic inflammation (C reactive protein [CRP] levels >2 mg/L) who were assigned to anakinra (N=42 [66.7%]) or placebo (N=21 [33.3%]) as part of the REDHART2 clinical trial (NCT0014686). Cardiorespiratory fitness was measured as peak oxygen consumption (peak VO2). Results. Baseline plasma IL-1Ra levels were 380 pg/ml (290 to 1046). On-treatment IL-1Ra levels were significantly higher in the patients treated with anakinra vs placebo (3,994 pg/ml [3,372 to 5,000] vs 492 pg/ml [304 to 1370], P<0.001). The longest available follow-up was 6 weeks in 10 patients (15.9%), 12 weeks in 12 patients (19%) and 24 weeks in 41 patients (65.1%). On-treatment IL-1Ra levels and interval change in IL-1Ra showed a modest inverse correlation with on-treatment CRP levels (R=-0.269, P=0.033 and R=-0.355, P=0.004, respectively) and no statistically significant correlations with peak VO2 values (P>0.05). Conclusions. Patients with recently decompensated HFrEF and systemic inflammation treated with recombinant IL-1Ra, anakinra, have a significant several-fold increase in plasma IL-1Ra levels. On-treatment IL-1Ra levels however show only a modest correlation with CRP levels and not with peak VO2.

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.

We completed a video-based, four-night, in-home, level 3 sleep apnea study of healthy, low-risk pregnant participants and their bed partners in order to characterize sleep physiology in the third trimester of pregnancy. Demographic, anthropometric, and baseline sleep health characteristics were recorded, and the NightOwl home sleep apnea test device was used to measure sleep breathing, posture, and architecture parameters. Symptoms of restless legs syndrome were elicited in the exit interview. Forty-one pregnant participants and 36 bed partners completed the study. Bed partners had a significantly higher prevalence of sleep apnea than their pregnant co-sleepers (31% vs. 5.9%). Bed partners also had more severe sleep apnea than their pregnant co-sleepers, and this persisted on an adjusted analysis for baseline differences in factors known to increase risk of sleep apnea. In pregnant participants, increasing gestational age was found to be protective against mild respiratory events but not more severe events. While the correlation between STOP-Bang score and measures of sleep apnea severity was weak, an affirmative response to the witnessed apneas item on the STOP-Bang questionnaire was a strong predictor of more severe sleep apnea for all participants. Smoking history also increased sleep apnea risk. Pregnant participants had lower sleep efficiency and longer self-reported sleep onset latency. Restless legs syndrome was experienced by 39.5% of the pregnant participants but no bed partners. From a sleep breathing perspective, people with healthy, low-risk pregnancies have better sleep than their bed partners despite lower sleep efficiency and higher rates of restless legs syndrome.

Background: The etiology and nosological status of seasonal affective disorder (SAD) as a specifier of depressive episodes versus a transdiagnostic disorder are the subject of debate. In this study, we investigated the underlying etiology of SAD and dimensional seasonality by examining their association with latitude and genetic risk for a range of traits, and investigated gene-environment interactions. Methods: This study included 12,460 adults aged 18-90 with a history of depression from the Australian Genetics of Depression Study. Regression models included predictors for latitude (distance from equator) and polygenic scores for eight traits; major depressive disorder, bipolar disorder, anxiety disorders, chronotype, sleep duration, body mass index, vitamin D levels, and educational attainment. Outcomes were SAD status and general seasonality score. Results: SAD was positively associated with latitude (OR[95%CI] = 1.05[1.03-1.06], padjusted<0.001), and there was nominal evidence of additive and multiplicative interactions between chronotype genetic risk and latitude (OR = 0.99[0.99-0.99], padjusted=0.381; OR=0.98[0.97-0.99], padjusted=0.489). General seasonality score was associated with latitude (IRR=1.01[1.01-1.01], padjusted 0.001) and genetic risk for major depressive disorder (IRR =1.02[1.01-1.03], padjusted<0.001), bipolar disorder (IRR=1.02[1.01-1.03], padjusted=0.001), anxiety disorders (IRR=1.03[1.01-1.04], padjusted<0.001), vitamin D levels (OR=0.89[0.80-0.95], padjusted=0.048), and educational attainment (IRR=0.97[0.96-0.99], padjusted<0.001). Conclusions: These findings enhance understanding of SAD etiology, highlighting contributions of psychiatric genetic risk and geographic measures on seasonal behavior, and support examining seasonality as a continuous dimension.

ObjectiveOnly preliminary investigations on the use of the 445 nanometer wavelength blue light laser (BLL) for various laryngeal pathologies have been described. Currently, no standard exists for reporting treatment technique and tissue effect with this modality. Here, we aim to establish and validate a classification system to describe laser-induced tissue effects. Study DesignRetrospective video-based study for classification development and reliability validation. MethodsVideo recordings from procedures performed with the BLL by multiple academic laryngologists were retrospectively reviewed. A preliminary 6-point classification (BLL 1-6) was developed based on expert consensus. Thirteen additional procedural clips were independently rated utilizing the classification schema to assess perceived tissue effect, and measure inter- and intra-rate reliability. ResultsThe final 5-point classification system (BLL 1-5) included angiolysis, blanching, tissue vaporization, ablation with mechanical tissue removal, and cutting. The consensus of the combined reviewers in rating all cases was 89% (58 of 65). Complete consensus was not achieved in 11% (7/65) of cases. Of those incorrect, 57% (4/7) were of clips illustrating the BLL-2 classification. Intra-rater reliability amongst the reviewers was 100%. ConclusionTissue effect of the 445 nm blue light laser can reliably be standardized with this proposed classification system. This rating system can be used to facilitate future systematic study of outcomes and effective communication between laryngologists and trainees.

Conflicting evidence on scatter correction (SC) methods plagues quantitative myocardial perfusion SPECT (MPI), hindering standardized clinical protocols. This simulation study, utilizing the SIMIND Monte Carlo program and a highly realistic 4D XCAT phantom, systematically evaluates Dual Energy Window (DEW, with k=0.5) and Triple Energy Window (TEW) SC techniques. We uniquely investigate their performance across various photopeak window widths (2, 4, and 6 keV) and novel overlapped/non overlapped configurations specifically for Tc 99m MPI parameters largely unexplored in realistic cardiac models. Images were reconstructed with OSEM under uncorrected (UC), SC, and combined attenuation and scatter corrected (ACSC) conditions. Quantitative analysis focused on signal to noise ratio (SNR), contrast to noise ratio (CNR), defect contrast, and relative noise to background (RNB). Our findings consistently show ACSC's superior performance in CNR, SNR, and defect contrast, confirming its critical role. Interestingly, SC alone reduced noise but compromised defect contrast relative to UC, highlighting a potential trade-off without attenuation correction. Crucially, this study reveals minimal influence of photopeak window width and overlap configuration on image quality, and no significant difference between DEW and TEW across most metrics. These results provide essential evidence for optimizing quantitative MPI protocols, suggesting that for Tc 99m, the choice between DEW and TEW, and specific window settings, may be less critical than ensuring robust attenuation correction.

Introduction: Spontaneous coronary artery dissection (SCAD) is frequently accompanied by persistent symptoms of unknown pathogenesis after the index event. Autonomic dysfunction is a plausible mechanism for these but has not been systematically characterized. We quantified antecedent and contemporary autonomic symptoms in survivors of SCAD and examined their associations with cardiac and extra-cardiac symptoms and health-related quality of life. Methods: This cross-sectional study recruited 227 volunteers from multiple countries with a self-reported history of SCAD. Participants completed validated patient-reported measures, including the Composite Autonomic Symptom Score-31 (COMPASS-31), Anxiety Sensitivity Index-3 (ASI-3), and EuroQol-5 Dimension-5L (EQ-5D-5L). They also completed an internally derived retrospective autonomic predisposition score assessing symptoms during adolescence and early adulthood. Results: Participants were predominantly female (97.8%), median age 53 (47-58) years, and were surveyed a median of 3 (1-5) years after their index SCAD event. 21.6% reported SCAD recurrence. Moderate autonomic symptom burden (COMPASS-31 20) was present in 56.4% and severe burden (40) in 16.3%. History of antecedent autonomic symptoms was the strongest independent predictor of contemporary autonomic symptom burden after adjustment for demographic and clinical covariates (=0.514; P <0.001). Greater autonomic symptom burden independently predicted lower EQ-5D health utility (=0.150; P=0.029) and was associated with the ASI-3 physical concerns (=0.232; P <0.001), but not social concerns domain. Autonomic symptoms were not associated with SCAD recurrence. Conclusion: Symptoms of autonomic dysregulation are common in survivors of SCAD and are associated with reduced quality of life. Their association with antecedent dysautonomic features during adolescence and early adulthood suggests a longstanding predisposition, the significance of which warrants further evaluation.

BackgroundAccurate assessment of left ventricular outflow tract (LVOT) gradients is critical for hypertrophic cardiomyopathy (HCM) management, yet Doppler-based measurements are technically demanding and require expertise. ObjectiveTo develop a multi-view deep learning model capable of classifying LVOT obstruction (> 20mmHg) using routine 2D echocardiographic windows without reliance on Doppler imaging. MethodsWe trained and externally validated a cross-attention-based video-to-video fusion framework that integrated EchoPrime-derived video representations from three standard transthoracic echocardiographic views to classify LVOT gradients. ResultsTraining was performed on a derivation cohort (N = 1833) from a tertiary care system in the United States, with model performance evaluated on an internal held-out test set (N = 275) and a Korean external validation cohort (N = 46). Single-view baselines showed limited discrimination (external AUROCs 0.47-0.70). Conversely, domain-specific foundational model (EchoPrime) achieved superior single-view performance (AUROCs 0.75-0.80 internal; 0.79-0.83 external), highlighting the importance of echo-specific pretraining and temporal modeling. The proposed multi-view fusion further enhanced predictive performance, with the late fusion model reaching an AUROC of 0.84 on the external cohort with significant population-shift. ConclusionsThese results suggest LVOT physiology is encoded in routine 2D imaging and can be leveraged for clinically relevant gradient classification without Doppler input- proposed AI-guided strategy demonstrates substantial cost savings compared with the screen-all approach. By integrating complementary spatial-temporal information across multiple views, our approach generalizes robustly across populations and may enable real-time decision support, extend LVOT assessment to portable or resource-limited settings, and complement Doppler-based evaluation for longitudinal HCM management.

Background: Heart failure (HF) is a major and growing public health problem, and prior studies support a meaningful genetic contribution to HF susceptibility. Clinically, HF is commonly categorized into the major clinical sub-types of HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF), which differ in pathophysiology and clinical profiles. However, previous genome-wide association studies have focused on autosomal variation and have routinely excluded the X chromosome, leaving X-linked genetic contributions to HF and its subtypes under-characterized. Methods: We performed X-chromosome wide association study (XWAS) utilizing directly genotyped data from 590,568 Million Veteran Program participants, including 90,694 HF cases across European, African, Hispanic, and Asian Americans. Sex- and ancestry-stratified logistic regression was used with XWAS quality control measures, adjusting for age and population structure, followed by fixed-effects multi-ancestry meta-analysis. Functional annotation, gene-based testing, fine-mapping, and colocalization were performed. We replicated genetic associations with all-cause HF in the UK Biobank. Results: In the multi-ancestry meta-analysis, we identified five X-chromosome-wide significant loci for all-cause HF, five for HFrEF, and one locus for HFpEF in males. No loci reached significance in female-specific analyses. In sex-combined analyses, we identified six loci for all-cause HF and four for HFrEF. The strongest and most emphasized signals mapped to genes were BRWD3, FHL1, and CHRDL1. Ancestry-specific analyses revealed additional loci, including NDP and WDR44 in African ancestry and PHF8 in Hispanic ancestry. One locus, BRWD3, was replicated in UK Biobank HF cohort. Integrated post-GWAS analyses (fine-mapping, colocalization and pleiotropy trait association studies) reinforced the biological plausibility of the X-linked signals. Conclusions: This multi-ancestry, sex-stratified XWAS identifies X-linked genetic contributions to HF and its subtypes and highlights the role of X-chromosome in heart failure pathogenesis.

BackgroundHypertension is the leading modifiable risk factor for ischemic stroke, yet the adequacy of preventative hypertension care in routine clinical practice remains suboptimal. Whether gaps in hypertension management represent missed opportunities for stroke prevention remains unclear. ObjectiveTo evaluate the association between hypertension care delivery and the risk of incident ischemic stroke. MethodsWe conducted a retrospective, matched, nested case-control study among adults with hypertension using electronic health record data from a large regional health system (2010-2024). Patients with a first-ever ischemic stroke were matched 1:2 to controls on age, sex, race and ethnicity, and calendar time. Three care metrics were assessed during follow-up: (1) outpatient visits with blood pressure (BP) measurement per year; (2) number of antihypertensive medication ingredients; and (3) medication intensification score. Conditional logistic regression estimated adjusted odds ratios (aORs). ResultsThe study included 13,476 cases and 26,952 matched controls (N = 40,428). Mean (SD) age was 64.8 (12.2) years, 54.1% were female, and mean follow-up was 2,497 (1,308) days. Cases had fewer BP visits per year (median, 2.50 vs. 3.01; p < 0.001), similar number of medication ingredients (2.00 vs 2.00), and lower treatment intensification scores (-0.211 vs - 0.125). In adjusted models, >5 BP visits per year was associated with lower stroke odds (aOR, 0.55; 95% CI, 0.51-0.59) compared with [&le;]1 visit. Use of 2-3 medication ingredients (vs 0) was also associated with reduced stroke odds (aOR, 0.80; 95% CI, 0.75-0.86), whereas >3 ingredients was not significant. The highest quartile of treatment intensification showed the strongest association (aOR, 0.47; 95% CI, 0.44-0.51). Findings were consistent across subgroup and sensitivity analyses, including strata defined by baseline SBP and follow-up SBP. ConclusionsGreater engagement in hypertension care was associated with lower odds of ischemic stroke, suggesting that gaps in routine management may represent missed opportunities for prevention.

BackgroundPolygenic embryo screening (PES) has recently become available to in-vitro fertilization (IVF) patients, allowing them to evaluate the genetic risk of each of their embryos for polygenic conditions such as heart attack or diabetes. Initial modeling predicted that transferring the embryo with the lowest genetic risk for one or more diseases would substantially reduce prevalence in the next generation, with relative risk reductions up to 50%. However, these models assumed the availability of a prespecified number of embryos and that the embryo with the most favorable polygenic risk is born once transferred to the uterus. In reality, a large percentage of embryo transfers do not lead to live births, and IVF frequently results in no or only a single live birth. MethodsTo quantify the expected risk reduction in the context of IVF, we used two datasets: 6944 ovarian stimulation cycles from 4452 Italian infertility patients and 2138 stimulation cycles of egg donors. In both datasets, we simulated the hypothetical application of PES in these cycles by assigning patients and their embryos randomly drawn polygenic risk scores for a given disease, assuming that embryos have been transferred in increasing order of their risk, and tracing their birth outcomes. We then compared the risk of the embryo born after hypothetical PES to the risk of an embryo born without PES. We either considered only completed cycles or integrated over possible birth outcomes of non-transferred embryos in incomplete cycles. ResultsIn stimulation cycles in infertility patients in which all embryos have been transferred and at least one child was born, we estimate that PES will result in relative risk reductions of just {approx}1-3%. In an intention-to-screen analysis of all completed cycles (regardless of birth outcomes), relative risk reductions are under 0.5%. The risk reductions increase, as expected, with more euploid blastocysts and with younger maternal age. Including incomplete cycles (in which not all embryos have been transferred) increases risk reductions to {approx}2-5%, due to the availability of more euploid blastocysts and a higher live birth rate per transfer in these cycles. Pooling all embryos from all cycles of the same patient increases risk reductions to {approx}5-10%. Relative risk reductions in egg donor cycles reach {approx}20% even with a single stimulation cycle per donor. ConclusionsWith the exception of particularly good-prognosis patients or cycles, typical infertility patients would benefit little from PES. In fertile patients, as represented by egg donors, PES is predicted to achieve greater relative risk reductions. However, even though these reductions are still substantially lower than prior estimates that did not account for realistic live birth rates. Ethical, social, and clinical issues associated with offering PES in the general population should be prioritized in future research.

AimsCaveolae are plasmalemmal microdomains regulating stretch-dependent, nitric oxide (NO), and other signalling pathways governing myocardial structure, function and resilience. We have reported that global deletion of the scaffold protein cavin-1 disrupts caveolar biogenesis and impairs ventricular compliance and tolerance to ischaemic injury. However, cardiomyocyte-specific and sex-dependent roles of cavin-1 and caveolar complexes remain unresolved. Methods and ResultsWe generated a floxed Cavin-1 transgenic mouse, enabling cardiomyocyte-specific knockdown via adeno-associated virus (AAV) mediated expression of iCre recombinase driven by a cardiac-specific troponin T promoter. Knockdown was confirmed by RNA, protein, and immunofluorescence analyses, and cardiac function was assessed via echocardiography, left ventricular pressure-volume (PV) catheterisation, and ex vivo PV analysis of perfused hearts. Conditionally deleted hearts and myocytes exhibited up to 50% knockdown of Cavin-1 mRNA together with 15% deficiency in muscle-specific Caveolin-3, 70% depletion of caveolae, and mislocalisation of NO synthase (NOS) within cardiomyocytes. This was associated with elevated heart rate and shortened PR interval; reduced intraventricular and systolic blood pressures and peripheral resistance; and sex-dependent impairment of ventricular filling (females only). Diastolic dysfunction was detectable ex vivo, to a greater extent in male vs. female hearts. Mechanisms were sex-dependent, linked to interstitial fibrosis in females and NOS overactivity (inhibited by 100 {micro}M L-NAME) in males. Female hearts also exhibited increased susceptibility to ischaemia-reperfusion injury. Coronary function appeared preserved in both sexes, with intact reactive hyperaemic responses. ConclusionThis model identifies cardiomyocyte caveolae and cavin-1 as key determinants of myocardial function and compliance, involving sex-dependent remodelling and NOS signalling. By linking cardiomyocyte disruption to whole-organ and -body dysfunction, this model provides mechanistic insight into impaired function in heart failure and ageing. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=117 SRC="FIGDIR/small/717104v1_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@1aabf7forg.highwire.dtl.DTLVardef@1026839org.highwire.dtl.DTLVardef@108ad11org.highwire.dtl.DTLVardef@9a6dfd_HPS_FORMAT_FIGEXP M_FIG C_FIG