Heart

Background: Bailout cardiac surgery during transcatheter aortic valve replacement (TAVR) is uncommon but remains associated with substantial morbidity and mortality. Although registries have described its incidence and major causes, they often provide limited detail regarding device-related failure mechanisms, attempted transcatheter rescue, and the clinical pathway leading to surgical conversion. We aimed at analyzing post-marketing safety reports from the U.S. Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database to characterize the mechanisms, management strategies, and reported outcomes of bailout surgery during or shortly after TAVR. Methods: We retrospectively analyzed FDA MAUDE reports received from July 1, 2016, through June 30, 2026. Eligible reports described unplanned urgent or emergent open cardiac surgery during or immediately after TAVR. Candidate reports were screened, adjudicated, and deduplicated at the clinical-event level. Events were classified by precipitating complication, transcatheter rescue, operative pathway, and reported outcome. Associations were evaluated using permutation tests, Fisher exact tests with Benjamini?Hochberg correction, adjusted regression models, and sensitivity analyses. Results: After screening 43,239 initial reports, we identified 376 bailout-surgery events, with survival status was documented in 254, including 104 deaths and 150 survivors, corresponding to 40.9% reported mortality. Valve embolization, migration, or malposition was the most frequent complication phenotype (32.4%), whereas ventricular perforation or laceration was associated with the highest mortality (74.1%; OR, 4.86; 95% CI, 1.97?11.99). Mortality differed across complication phenotypes (p<0.001) and operative pathways (p<0.001), but not across transcatheter rescue pathways (p=0.355). Valve explantation with SAVR was associated with lower reported mortality (18.9%; OR, 0.29; 95% CI, 0.12?0.69), whereas unspecified surgery or access/support alone was associated with higher mortality (56.9%; OR, 3.04; 95% CI, 1.80?5.12). Ancillary analyses identified potential platform-specific differences in complication and management patterns, while bailout timing was not independently associated with mortality after adjustment. Conclusions: In this MAUDE analysis, bailout cardiac surgery after TAVR was most commonly precipitated by valve embolization, migration, or malposition, whereas ventricular perforation or laceration was associated with the highest reported mortality. Outcomes differed across complication and operative pathways but not across transcatheter rescue strategies or bailout timing after adjustment. These findings identify clinically relevant post-marketing safety signals but should not be interpreted as incidence estimates, comparative device risks, or causal treatment effects.

Background: Myocardial infarction (MI) and heart failure (HF) impose a physical and emotional toll that has not been measured nationally with a standard instrument. Methods: We pooled the 2019 to 2024 Medical Expenditure Panel Survey into 4 mutually exclusive groups of adults aged 18 and older: MI without HF, HF without MI, both conditions, and neither condition. Quality of life was assessed with the Veterans RAND 12-item component summaries, T scores (mean 50, SD 10) on which higher is better and 3 points is minimally important. Survey-weighted linear regression adjusted for demographics, socioeconomic factors, and comorbidity. Results: Among 79,853 adults representing 253.8 million US adults, 4.2% (3,340) had MI alone, 0.6% (480) HF alone, and 0.3% (236) both. Unadjusted physical scores ranged from 33.2 with HF alone to 39.1 with MI alone, versus 50.5 with neither. Adjusted physical scores were lower by 3.84 points (95% CI, 3.20-4.47) with MI alone, 8.32 (95% CI, 7.04-9.61) with HF alone, and 7.74 (95% CI, 5.73-9.76) with both, each beyond the minimally important threshold. Adjusted mental scores were lower by 1.35 points with MI alone, 1.20 with HF alone, and 1.69 with both, all below that threshold. Adults with both conditions did not differ from those with HF alone (0.58 points; 95% CI, -1.76 to 2.92). Emergency visits, inpatient discharges, and expenditure were higher in every cardiac group and highest with both conditions, where annual expenditure reached $37,198 versus $7,845 with neither. Conclusions: Physical quality of life fell steadily across the cardiac groups, with HF rather than prior MI accounting for most of it. The difference in mental quality of life did not persist after adjustment. Utilization and spending were highest with both conditions.

Abstract Background: Heart failure (HF) is a major public health challenge in ageing populations and a leading cause of unplanned hospital readmissions. Biological, social, and economic factors contribute to recurrent hospitalisation, but gaps remain in understanding how these factors interact and patterns of healthcare use following hospitalisation. Methods: We conducted an explanatory sequential mixed-methods study of patients aged ?60 years with an HF hospital admission between 2016 and 2020 who completed the Sax Institute?s 45 and Up Study baseline questionnaire. Data were linked to Admitted Patient Data Collection, Medicare Benefits Schedule, and Pharmaceutical Benefits Scheme data. HF readmission within 30 days of the index admission was the outcome. Cox proportional hazards models estimated crude and adjusted hazard ratios (HRs and adjHRs) with 95% confidence intervals (CIs). Kaplan-Meier curves and log-rank tests compared survival between groups. Time-series plots mapped healthcare interactions over 1 year following the index admission. Results: Among 4,252 patients with HF, 409 were readmitted within 30 days. Significant predictors included age ?80 years (adjHR, 1.30; 95%CI, 1.01?1.67), 1 chronic condition (adjHR, 2.49; 95%CI, 1.41?4.40), ?2 chronic conditions (adjHR, 1.75; 95%CI, 1.04?2.95), and alcohol consumption above national guidelines (adjHR, 1.45; 95%CI, 1.06?1.98). Time-series analysis indicated that participants with readmission had more frequent out-of-hospital health service contact following their initial HF admission than those without readmission. Conclusions: Older age, chronic conditions, and high alcohol intake increased 30-day HF readmission risk. Differences in healthcare use after admission highlight opportunities for targeted and coordinated post-discharge care.

Background: CPR is the primary intervention for cardiac arrest, and the mortality trends before and after the pandemic remain are not fully understood. Methods: This cross-sectional study used the National Inpatient Sample (NIS) database from 2016-2022 and International Classification of Diseases, Tenth Revision (ICD-10) codes to evaluate the mortality trend for adult patients undergoing CPR after in-hospital cardiac arrest (IHCA). Primary exposures were calendar year, demographics, socioeconomic factors, and hospital characteristics. Multivariable weighted logistic regression was performed to identify predictors of mortality after CPR for IHCA. Results: Among 612,930 weighted adult hospitalizations undergoing CPR for IHCA between 2016 and 2022, overall in-hospital mortality was 67.8%. Risk-adjusted mortality declined through 2019 before increasing sharply during the COVID-19 pandemic, peaking in 2021 and remaining above pre-pandemic levels in 2022. Compared with 2016, admission in 2020 (aOR 1.18, 95% CI 1.12-1.25; p<0.001) and 2021 (aOR 1.26, 95% CI 1.19-1.33; p<0.001) was independently associated with higher mortality, whereas admission in 2019 was associated with lower mortality (aOR 0.89, 95% CI 0.84-0.95; p<0.001). Higher mortality was also associated with increasing age (aOR 1.01 per year; p<0.001), female sex (aOR 1.05, 95% CI 1.02-1.08; p<0.001), Black (aOR 1.14, 95% CI 1.10-1.18; p<0.001) and Hispanic race/ethnicity (aOR 1.20, 95% CI 1.15-1.26; p<0.001), and self-pay insurance (aOR 1.62, 95% CI 1.51-1.74; p<0.001). Protective factors included private insurance (aOR 0.91, 95% CI 0.87-0.94; p<0.001), residence in the highest income quartile (aOR 0.91, 95% CI 0.87-0.94; p<0.001), and treatment at private, non-profit hospitals (aOR 0.89, 95% CI 0.85-0.94; p<0.001). Conclusion: This large nationwide patient database analysis demonstrates that mortality following CPR for IHCA declined before the COVID-19 pandemic but increased during 2020, remaining above pre-pandemic levels through 2022. Independent predictors of mortality reveal socioeconomic disparities in mortality outcomes.

Background: Sex-related disparities in acute coronary syndrome (ACS) recognition and management remain a global health concern. We examined sex-based differences in clinical presentation, management, and outcomes among patients with chest pain attended by emergency medical services (EMS) across Brazil. Methods: We conducted a retrospective study using a registry from 14 Brazilian states between January 2020 and June 2024 within a private hospital network. Patients with chest pain were classified by cardiologists as unstable angina (UA), ST-elevation myocardial infarction (STEMI), or non-ST-elevation myocardial infarction (NSTEMI). Multivariable regression evaluated sex differences in diagnosis, treatment, and outcomes. Sensitivity analyses included state-clustered standard errors and E-values for unmeasured confounding. Results: Among 7,171 patients with confirmed ACS (68.2% male), median age was 63.0 years [IQR 20.0]; women were older than men (67.0 [20.0] vs 61.0 [19.0] years). Diagnoses were UA in 46.7%, STEMI in 18.8%, and NSTEMI in 34.6%. Overall, 91.7% received aspirin and 89.6% at least one additional antiplatelet agent. After adjustment, women had higher odds of chest pain classified as probably or possibly ischemic versus definitely ischemic (adjusted OR 1.51 [95% CI 1.33-1.72] and 1.60 [1.37-1.86], respectively) and lower odds of STEMI and NSTEMI relative to UA (adjusted OR 0.59 [0.51-0.68] and 0.74 [0.66-0.83], respectively). Door-to-ECG time was longer in women unadjusted ({beta}=1.53 minutes [0.24-2.82]) but not after adjustment ({beta}=1.04 [-0.27 to 2.36]). In-hospital mortality did not differ between sexes, with no evidence of excess short-term mortality in women. Conclusions: Within a private hospital network in Brazil, women with confirmed ACS were more often classified with less definitely ischemic chest pain and less frequently with STEMI or NSTEMI than men. Door-to-ECG differences did not persist after adjustment, and mortality did not differ by sex. These findings support sex-sensitive triage and diagnostic protocols to reduce inequities in ACS recognition and treatment.

Abstract Background Premature, or early-onset, coronary artery disease (CAD) carries lifelong consequences. Ethnic inequalities in CAD are established in the UK, but risk estimates mostly derive from events after middle age, while ethnicity is aggregated for South Asian and Black populations. Disaggregated, sex-specific risk estimates would permit better recognition and more targeted prevention. Methods We used Clinical Practice Research Datalink (CPRD) Aurum, an English primary care database linked to hospital, mortality, and deprivation data. We included adults aged 18-45 of White European, South Asian (Indian, Pakistani, Bangladeshi), or Black (African, Caribbean) ethnicity, followed for up to 20 years. Incident premature CAD (onset [&le;]45) was a first myocardial infarction or coronary revascularisation. We estimated age-adjusted and fully adjusted incidence rate ratios (IRRs) versus White Europeans by Poisson regression, testing an ethnicity-sex interaction. Findings Among 14.8 million adults contributing 80.9 million person-years, 16,001 premature CAD events occurred (77.6% in men). In men, the combined South Asian age-adjusted IRR was 1.87 [95% CI 1.77, 1.99], ranging from 1.39 [1.28, 1.50] in Indian to 2.79 [2.52, 3.07] in Bangladeshi men, persisting after full adjustment and already evident at ages 18-26. The combined Black IRR was 0.64 [0.57, 0.71], lowest in African (0.57[0.50, 0.65]) and highest in Caribbean men (0.82 [0.68, 0.98]). In women, the combined South Asian IRR showed no overall excess (1.10 [0.95, 1.26]), concealing a clear excess in Pakistani women (1.56 [1.29, 1.89]). The ethnicity-sex interaction was significant (p<0.001); the male-to-female ratio was highest in Bangladeshi individuals (8.4:1 versus 3.3:1 in White Europeans). Interpretation Aggregated ethnic categories conceal sex-specific subgroups at high risk of premature CAD, a risk already present in early adulthood. Current screening and health check programmes beginning at age 40, start too late to reach these higher-risk, underserved groups. Funding: Kusuma Trust and NIHR UCLH BRC.

Background: Pulsed field ablation (PFA) has been rapidly adopted for atrial fibrillation (AF) on the premise of greater safety than thermal ablation. Real-world signals of hemolysis, coronary spasm, and neurologic events have since emerged, and prior Manufacturer and User Facility Device Experience (MAUDE) analyses relied on term matching without prospective signal detection. Methods: We queried MAUDE for AF ablation catheter reports received January 2016 through June 2026 and assigned each to PFA, radiofrequency ablation (RFA), or cryoballoon ablation. We adjudicated injury and death narratives into predefined complication families and severity tiers with a large language model, checked against a larger model and by physician review. We calculated reporting odds ratios (ROR) and Bayesian shrinkage estimators compared against an empirical null, applied interrupted time series and prospective sequential detection, and repeated estimates on a 2026 hold-out. Results: Among 44,623 reports, 30.1% were PFA, 50.9% RFA, and 19.0% cryoballoon, with 91.8% model agreement on event occurrence (? = 0.83). PFA carried an ROR of 527 (95% CI, 33, 8,509) for hemolysis, 2.83 (2.55, 3.16) for arrhythmia, 2.83 (2.30, 3.48) for coronary, and 2.39 (2.10, 2.73) for cerebrovascular events, against 0.024 (0.008, 0.075) for esophageal and 0.34 (0.32, 0.37) for pericardial events. The cerebrovascular excess was largest for VARIPULSE, but without it the class proportional reporting ratio was 1.36 (1.13, 1.65), concordant with the 1.56 measured in EMBOL-AF. In the hold-out, the cerebrovascular, arrhythmia and hemolysis signals replicated, and coronary events kept their direction without meeting the signal rule. Prospective detection flagged cerebrovascular events 13 months before AVANT GUARD published its neurologic events. Conclusions: PFA showed disproportionate reporting of hemolysis, cerebrovascular, coronary, and arrhythmic events across sequential testing. Machine learning methods allowed for flagging these signals months before confirmatory trials, demonstrating a scalable tool for early detection of procedural risk.

Background: Cardiovascular (CV) screening is critical for personnel deploying to Antarctica, where geographic isolation and limited medical care make the management of acute cardiovascular events challenging. The utility of contemporary risk prediction tools such as the AHA PREVENT equations in this unique population remains uncertain. Methods: We retrospectively analyzed 154 individuals referred for enhanced CV evaluation before deployment to the U.S. Antarctic Program (USAP). Participants were evaluated across three temporal cohorts (2018-2020, 2021-2023, and 2024-2026). Demographics, CV risk factors, cardiac testing, and deployment clearance outcomes were collected. Risk was estimated using the Framingham Risk Score (FRS), AHA/ACC Pooled Cohort Equations (PCE), and AHA PREVENT risk models. Results: The cohort was predominantly male (79.9%; mean age 44.6 {+/-} 14.6 years), and abnormal ECG was the most common referral trigger (70.8%). Median 10-year risk was low by PREVENT and FRS and borderline elevated by PCE (PREVENT 2.7% [IQR 1.1-6.6], FRS 2.3% [IQR 0.5-7.1], and PCE 6.1% [IQR 2.4-9.2]). Among 72 participants with all scores, 51% were classified discordantly; PREVENT ASCVD agreed closely with FRS (=0.77) but poorly with PCE (=0.24-0.35), which consistently estimated higher risk. PCE was calculable in 52.6% versus 70.8% for PREVENT. Overall, 132 participants (85.7%) were cleared for deployment, while 8 (5.2%) were not physically qualified (NPQ); 6 of these NPQs were due to cardiovascular causes. Of 22 cardiac medical evacuations during the study period, 21 involved individuals without prior advanced cardiovascular screening. One screened individual was evacuated for symptoms subsequently found to have no cardiac cause. Conclusions: Risk calculators disagree substantially in the fitness-selected population. We recommend PREVENT as the primary risk-stratification tool as it is the most contemporary derivation, incorporates renal function, is race-agnostic, extends to heart failure, applies from age 30, and agrees closely with FRS, easing transition. Targeted imaging, including coronary artery calcium scoring, may supplement intermediate-risk candidates.

Background: In obstructive hypertrophic cardiomyopathy, surgical myectomy is highly effective but carries a recognized risk of postoperative conduction disturbances. Percutaneous intramyocardial septal radiofrequency ablation (Liwen procedure) is a less invasive alternative, but head-to-head comparisons of longitudinal hemodynamic trajectories and conduction system safety remain scarce, limiting evidence-based treatment selection. Methods: This single-center retrospective cohort included 211 patients treated 2018?2023 (124 Liwen, 87 modified Morrow myectomy). The primary longitudinal analysis included 133 patients with 1-year follow-up and serial data (75 Liwen, 58 modified Morrow myectomy). Repeated outcomes were analyzed using linear mixed-effects models and generalized estimating equations, adjusted for baseline covariates. Results: Both procedures reduced LVOT gradient, but trajectories differed (interaction P=0.002). At 1 year, the covariate-adjusted mean LVOT gradient remained higher after Liwen than after myectomy (16.1 vs 1.3 mmHg, P<0.001). However, the adjusted 1-year predicted probability of new conduction abnormalities was markedly lower after Liwen (5% vs 62%, P<0.001), with no permanent pacemaker implantations in the Liwen group. Most patients achieved gradient <30 mmHg in both groups (82% vs 96%; nominal P=0.308). Liwen had shorter procedure duration (80 vs 185 min) and hospital stay (11 vs 16 days). Serious adverse event rates were similar (8.1% vs 9.2%) but profiles differed. Conclusions: Modified Morrow myectomy achieved more complete LVOT gradient reduction at 1 year, whereas Liwen ablation had fewer conduction abnormalities, shorter procedure duration, and shorter hospital stay. These findings highlight a clinically relevant trade-off between more complete hemodynamic relief and lower conduction-system injury and require prospective confirmation.

Postoperative atrial fibrillation (POAF) is a frequent complication following cardiac surgery and has been associated with an increased risk of thromboembolic events. However, cardiac surgical populations are heterogeneous, and the long-term thromboembolic implications of POAF may differ according to the index surgical procedure. This systematic review and meta-analysis evaluated the procedure-specific association between POAF and long-term thromboembolic outcomes after adult cardiac surgery, with particular emphasis on coronary artery bypass grafting (CABG) and isolated valve surgery. PubMed and Scopus were searched from database inception through August 3, 2026. Studies reporting long-term thromboembolic outcomes in patients with new-onset POAF compared with patients without POAF were evaluated, with eligible evidence classified according to the index surgical procedure. Four observational studies were included in the primary quantitative synthesis, with two studies contributing to the CABG analysis and two to the isolated valve-surgery analysis. Adjusted hazard ratios (HRs) were pooled separately by procedure using inverse-variance methods, and a formal between-subgroup interaction test was performed. Following CABG, POAF was associated with an increased long-term thromboembolic hazard (pooled HR 1.147, 95% CI 1.053-1.249; I^2=0%). A stronger association was observed following isolated valve surgery (pooled HR 1.362, 95% CI 1.181-1.573; I^2=0%). The between-subgroup interaction was statistically significant ({chi}^2=4.10, P=0.043), providing exploratory evidence that the magnitude of the association may differ according to surgical procedure. These findings suggest that the long-term thromboembolic implications of POAF may not be uniform across cardiac surgical populations. However, because only two studies contributed to each procedure subgroup and the available evidence was observational, the interaction should be considered hypothesis-generating. Further adequately powered studies with standardized outcome definitions and procedure-specific reporting are required to confirm these findings and determine their implications for long-term risk stratification and anticoagulation strategies.

Background Postoperative atrial fibrillation (POAF) is a common complication of cardiac surgery with POAF susceptibility thought to be primarily the result of pre-existing structural atrial disease, specifically fibrosis. We tested this hypothesis directly by combining preoperative imaging of atrial fibrosis with continuous physiological monitoring before POAF onset. Methods This prospective single center study (2023?2025) comprised 6,697 adults without prior atrial fibrillation (AF) undergoing elective cardiac surgery. Subjects were enrolled into three prespecified, non-overlapping cohorts: a mechanistic imaging cohort (n=52) to test whether preoperative atrial fibroblast activation predicts POAF; a physiological monitoring cohort (n=3,183) to characterize peri-event autonomic dynamics via time-resolved HRV analysis; and an independent prospective observability cohort (n=3,451) for validation. The prespecified primary analyses assessed time-domain and frequency-domain HRV across six consecutive 10-minute intervals during the 60 minutes preceding POAF onset. Generalized estimating equations models were applied. Results Preoperative atrial fibroblast activation did not differ significantly between patients with (n=22) or without POAF (n=52). By contrast, in a physiological monitoring cohort (n=3,183), time-resolved heart rate variability analysis revealed progressive autonomic destabilization beginning approximately 20 minutes before POAF onset, with significant divergence in heart-rate-corrected SDNN in the final 10-minute pre-event interval (marginal mean difference 0.0139, 95% CI 0.0113?0.0164; P<0.001; Cohen's d=0.728). This signal was independently validated in a prospective observability cohort (n=3,451), achieving fragment-level sensitivity of 69.6% and specificity of 97.5% at the 10-minute horizon. Conclusions POAF is more closely associated with immediately preceding detectable autonomic destabilization than with preoperative structural substrate. These findings challenge the hypothesis that POAF susceptibility is structurally determined(structural-determinism) and reframe this frequent complication as a dynamic, state-dependent process that may be a target for active prevention.

Background. Information is lacking about everyday psychological states of individuals with a recent myocardial infarction (MI) and whether they influence outcomes. We investigated real world psychological experiences and their association with subsequent cardiovascular events in survivors of an MI. Methods. We studied 287 individuals [&le;] 60 years of age within 8 months from an MI. At the baseline visit, we assessed sociodemographic and clinical factors, and administered a battery of psychological scales of depression, anxiety, anger, perceived stress and social support. Participants underwent a 7-day home monitoring of mood and stress using ecological momentary assessments, and a momentary negative affect (MNA) score, integrating daily mean ratings of sadness, anxiety, anger, distress and loneliness, was calculated. Participants were followed for a median time of 28 months. The study endpoint was a composite index of major adverse cardiovascular events (MACE), including cardiovascular death, nonfatal MI, stroke or hospitalizations for heart failure. Cox proportional hazards models adjusted for sociodemographic and clinical factors. Results. The mean age of the sample was 51 years, and 43% of participants were women. Each standard deviation increase in MNA was significantly associated with a 60% increased risk of MACE (95% confidence interval (CI), 20% to 100%), irrespective of adjustment for sociodemographic factors and clinical characteristics. The association was similar in women and men. Momentary positive mood and momentary perceived stress were not associated with MACE. The MNA score showed a larger independent contribution to MACE compared to the combined battery of baseline psychological assessments and the association was independent of baseline history of depression. Conclusion. Among individuals after MI, moment-to-moment negative affect during one week of monitoring in daily life is a powerful predictor of subsequent cardiovascular events. A prospective evaluation of negative mood during everyday living could represent a novel strategy to uncover residual risk after MI.

Aims: Sex differences in cardiac electrophysiology and cardiovascular (CV) risk are well established, but the extent to which circulating hormonal markers contribute to electrocardiogram (ECG) morphology remains unclear. We investigated whether hormone-related ECG components are associated with incident CV events and whether these associations differ by sex and menopausal status. Methods: In a prospective cohort (N=8,056 UK Biobank participants; median follow-up: 12.8 years), we first evaluated direct associations between sex hormones and incident CV disease. Based on initial risk signals, two-stage analyses focused on premenopausal females and males. Linear regressions evaluated associations between standardized hormonal markers and residualized lead-I ECG parameters after confounders adjustment. Cox proportional hazards models then tested whether the hormone-predicted ECG components were associated with incident CVD events. Results: In premenopausal females (N=980), higher free androgen index (FAI) was positively associated with QRS amplitude ({beta}=19.17V, p-value=0.038) and the FAI-predicted QRS amplitude component was associated with incident CVD (Hazard Ratio [HR]=1.41, p-value=0.02). In males (N=3,997), FAI was inversely associated with QTc duration ({beta}=-0.95ms, p-value=0.005), and its predicted component with increased CVD risk (HR=1.32, p-value<0.001). Conversely, higher sex hormone-binding globulin (SHBG) prolonged QTc, with its predicted component also conferring risk (HR=1.15, p-value=0.004). Additionally, FAI directly associated with ST segment deviation ({beta}=19.17V), whose predicted component was protective (HR=0.76, p-value<0.001). Conclusions: This study shows that SHBG and FAI subtly modulate specific depolarization and repolarization ECG parameters. Relative androgen excess in premenopausal females and lower androgenic status in males appear to be associated with subclinical electrophysiological variations linked to long-term CV risk.

Background: Public and clinical attention to postural orthostatic tachycardia syndrome (POTS) has increased, particularly since the COVID-19 pandemic. We quantified changes in United Kingdom Google search interest and examined whether searches increasingly used diagnostic and self-assessment language. Methods: We extracted monthly Google Trends relative search volume (RSV; 0-100) for the Health-category search term 'Pots syndrome' in the United Kingdom from January 2004 through July 2026. Five extraction attempts were made; two returned complete, identical monthly series and were retained. Prespecified eras were summarised and an exploratory interrupted time-series model at March 2020 used ordinary least squares with Newey-West heteroskedasticity and autocorrelation consistent standard errors (12 lags). Comparator searches included conventional orthostatic diagnoses, POTS diagnostic terms, associated conditions and YouTube searches. Results: The primary series comprised 271 complete months. Mean RSV increased from 18.6 during 2015-2019 to 64.8 during 2022-2023 (3.49-fold) and remained 50.6 during January 2024-July 2026 (2.73-fold above baseline). Search interest peaked in October 2022 (RSV 100); July 2026 RSV was 57. The interrupted time-series model estimated an immediate March 2020 level increase of 21.8 points (95% CI 2.8-40.7; p=0.024), while the slope change was not statistically supported (0.069 points/month, 95% CI 0.299 to 0.438; p=0.713). Searches for 'POTS symptoms', 'POTS test' and 'POTS heart rate' increased more steeply than the general term, although low baseline volumes made fold changes unstable. Conclusions: UK Google search interest in POTS rose before 2020, increased sharply after the pandemic began, and remained substantially above its prepandemic baseline. The results demonstrate a sustained change in public attention, not disease incidence or social-media causation. The growth of symptom- and testing-oriented searches is compatible with increased diagnostic self-investigation and warrants linkage to referral, diagnosis and social-media exposure data.

Background Hospitalizations and mortality due to heart failure (HF) are rising in rural areas. However, inpatient outcomes for young adults with HF are not well understood. We aimed to compare in-hospital mortality, advanced procedure utilization, length of stay, and total charges among rural and urban HF patients ages 18-45. Methods We analyzed hospitalizations from the National Inpatient Sample (2016-2022), categorizing discharges as rural (National Center for Health Statistics [NCHS] 5-6), small and medium metropolitan (NCHS 3-4), and urban (NCHS 1-2). Generalized estimating equations were used to model outcomes and adjust for demographics, comorbidities, and hospital characteristics. Outcomes are reported as adjusted rate (aIRRs) or risk ratios (aRRs) with 95% confidence intervals. Results Among 79,258 HF hospitalizations among young adults, 45,075 and 10,722 were for patients from urban and rural areas, respectively. Rural patients had higher rates of in-hospital mortality (1.6% vs. 1.2%; aIRR = 1.28, 95% CI = 1.05, 1.56, p = 0.043), advanced cardiac procedure utilization (15.0% vs. 14.8%; aIRR = 1.19, 95% CI = 1.11, 1.28, p < 0.001), and longer hospital stays (aIRR = 1.10, 95% CI = 1.05, 1.14, p = 0.003). Small and medium metropolitan residents had similar outcomes to urban residents. In interaction analyses, the association between rural-urban residence and mortality differed by race (pint = 0.003) and payer type (pint < 0.001). Conclusions Young adults in rural areas may be prone to poor outcomes following hospitalization for HF. Strategies to identify rural adults at risk for HF and provide affordable and timely care may improve disparities.

Condensed Abstract: Using the 2016?2022 National Inpatient Sample, this study evaluated temporal trends and demographic adoption patterns of percutaneous left atrial appendage occlusion (LAAO). Among 190,020 weighted procedures, annual volume increased from 4,875 to 60,445. In-hospital mortality was exceptionally low (0.1%). Age-adjusted procedural rates rose from 34.19 to 379.87 per 100,000 population. However, significant disparities persisted, characterized by heavy centralization in urban teaching hospitals (87.0%) and disproportionately lower absolute age-adjusted utilization among female, Black, Hispanic, and Asian/Pacific Islander patients compared to male and White cohorts. Targeted initiatives are needed to ensure equitable access to structural heart interventions.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a pan-ethnic disease, at least as common in Black as in White Americans, yet Black patients reach specialist care later, undergo septal reduction less often, and die sooner. Whether the defining trials enrolled representatively is unknown. We sought to measure Black participation in the landmark HCM trials against three expectations of increasing stringency, and to test whether trial site geography or quantitative eligibility thresholds account for the shortfall. METHODS: Of 197 registered interventional HCM trials, 32 met prespecified landmark tiers; demographics were extracted for 16 and 13 reported race. The Black share of Black plus White participants was pooled by random-effects meta-analysis and compared with the US adult population, with each trial?s own site counties, and with a disease-referenced echocardiographic expectation. Site geography and eligibility thresholds were tested using site addresses, census data, and NHANES. RESULTS: Across 13 trials, 70 of 1,780 Black or White participants were Black. The pooled Black share was 3.98% (95% CI 2.68-5.86), against a population expectation of 16.5%, giving a participation-to-prevalence ratio (PPR) of 0.24 (95% CI 0.16-0.36), the lowest of any racial and/or ethnic minority group. The clinical trial site network reached 63.7% of Black and 47.5% of White US adults, with geospatial analysis predicting 26.4% Black enrollment; however, every trial fell below this expectation. Quantitative eligibility thresholds closed only 2.0% of the enrollment gap. CONCLUSIONS: Black participation was about one quarter of the population expectation. Neither site geography nor eligibility thresholds explain it.

Background. Real-world 12-lead electrocardiograms (ECGs) often have missing or corrupted leads. A deep-learning classifier can be prepared for this by random lead masking during training, or by injecting clinical knowledge, for example by pulling its attention towards the leads that guidelines use for each diagnosis. Whether this knowledge adds robustness beyond masking is unknown. Methods. Pre-registered comparison of three arms sharing one network (per-lead 1D-ResNet encoder and per-diagnosis attention over the 12 leads): standard training (M0); random whole-lead masking (M1); masking plus a Kullback-Leibler penalty pulling attention towards a fixed guideline-derived key-lead map (M2, guideline-based attention guidance). Six diagnoses; five seeds per arm. Development on PTB-XL (21,799 ECGs); single sealed evaluation on PTB-XL fold 10 (2,198 ECGs) and on CODE-15% (233,204 exams, external validation). Primary endpoint: AUROC difference M2 - M1, averaged over first-degree AV block, right and left bundle branch block and atrial fibrillation and over 1 to 6 lost (zeroed) leads, with a patient-level paired BCa bootstrap 95% confidence interval. Results. The guidance did not change robustness: {Delta}AUROC -0.0010 (95% CI -0.0033 to +0.0006), an interval entirely within the pre-specified +-0.02 margin; the result was unchanged with another bootstrap seed, other interval methods and leave-one-diagnosis-out analyses. Masking improved AUROC: M1 - M0 = +0.0134 (95% CI +0.0102 to +0.0172) when one key lead was lost, and the number of lost leads tolerated before AUROC fell by more than 0.02 rose from 7 (M0) to 10 (M1). M2 attention matched the map and M2 was non-inferior on intact ECGs, but its calibration slope was lower for all six diagnoses in both datasets. M2 lost slightly more when all key leads were lost together (-0.0067) and gained only when one to three leads remained (exploratory; AUROC 0.9408 vs 0.9210 with 11 leads lost). CODE-15% reproduced every pattern (primary -0.0007, 95% CI -0.0011 to -0.0003). Conclusions. Random lead masking suffices to make an ECG classifier robust to missing leads; adding guideline knowledge aligns attention with clinical criteria but adds no robustness and worsens calibration. Guideline-aligned attention should not be taken as evidence of robustness.

Background: Obstructive hypertrophic cardiomyopathy (oHCM) causes substantial symptom burden and impaired functional capacity. Mavacamten has emerged as a targeted pharmacologic treatment, whereas alcohol septal ablation (ASA) is an established septal reduction therapy (SRT). Direct comparative real-world data remain limited. Methods: In this propensity-controlled observational study, longitudinal registry data from Heidelberg University Hospital were analyzed. Consecutive adults with oHCM, NYHA class ?II symptoms, and a maximum LVOT gradient ?50 mmHg treated with mavacamten or ASA were included. The cohort comprised 107 ASA- and 113 mavacamten-treated patients. Follow-up was performed at 6 and 12 months. The primary endpoint was a composite adverse clinical outcome including cardiovascular death, heart failure hospitalization, SRT, heart transplantation, ventricular assist device implantation, permanent pacemaker implantation for third-degree atrioventricular block, or decline in left ventricular ejection fraction to <40%. Results: Both treatments showed significant improvement in NYHA class and LVOT gradient reduction over 12 months. Mean LVOT gradient decreased from 100.3 to 44.2 mmHg after ASA and from 85.7 to 18.4 mmHg with mavacamten at 12 months (both p<0.001). Between-group differences were not significant at 6 months, whereas residual LVOT gradient was lower with mavacamten at 12 months (p=0.004). NT-proBNP declined in both groups and was lower with mavacamten at both follow-up visits (both p<0.001). Third-degree atrioventricular block occurred more frequently after ASA (6.5% vs 0%, p=0.002). The composite endpoint occurred in 13 ASA- (12.1%) and 4 mavacamten-treated patients (3.5%) (p=0.003), with higher 1-year event-free survival in the mavacamten group (HR 0.19; 95%-CI 0.06-0.60; p=0.001). Conclusions: In this real-world comparative study, both ASA and mavacamten improved symptoms and LVOT obstruction in oHCM. Mavacamten was associated with a more favorable short-term hemodynamic and safety profile at 12 months.

Background: A dose finding trial evaluated safety and adherence for pre-cardiac surgery administration of sodium valproate. Integrated multi-omics analyses of myocardium were used to characterise mechanisms underlying the treatment effects. Methods: Adults undergoing cardiac surgery were randomised 1:1:1:1 with concealed allocation to no treatment (Controls), sodium valproate 15mg/kg/day for 1-2 weeks, 15mg/kg/day for 4-6 weeks, or 25mg/kg/day for 4-6 weeks pre-surgery. The primary analysis evaluated adherence and toxicity. Myocardial injury was defined by high sensitivity serum troponin at 24 hours post-surgery. Single-nucleus Assay for Transposase-Accessible Chromatin with sequencing (snATACseq) and single nuclei RNA sequencing (snRNAseq) of myocardial biopsies collected at surgery assessed treatment effects on chromatin accessibility and gene expression. Candidate mechanisms were validated in in vitro. Results: The analysis cohort included 42 participants enrolled between January 2020 and August 2024. Non-compliance (38%) was highest with longer and higher dosing. Sodium valproate 15mg/kg/day for 1-2 weeks had the highest levels of complete treatment adherence (70%), with 20% experiencing moderate/severe drug related adverse effects. An as-treated analyses demonstrated reductions in troponin release in participants receiving Valproate[&le;]14 days. Myocardial biopsies from trial participants demonstrated activation of hormetic p53 and Akt-GSK-3{beta} ferroptosis protection pathways. Treatment effects were not attributable to chromatin accessibility. Treatment >14 days resulted in a heart failure phenotype with suppression of ferroptosis protection pathways, endothelial mesenchymal transition, and increased myocardial injury. Conclusions: Sodium valproate 15mg/kg/day for [&le;]14 days pre-surgery is well tolerated in adults awaiting cardiac surgery. This treatment was associated with upregulation of ferroptosis protection pathways and reductions in myocardial injury.