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: 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.

Background: Postoperative atrial fibrillation (POAF) is a frequent complication following coronary artery bypass grafting (CABG) and is associated with increased acute morbidity and resource utilization. However, its independent role in driving post-discharge adverse events in contemporary practice remains debated. Objective: To evaluate the association between POAF and short-term outcomes after CABG, and to utilize empirical Bayesian risk updating to stratify 90-day post-discharge vulnerabilities. Methods: A retrospective cohort analysis of 4,684 adult patients who underwent isolated CABG in Florida between January 1, 2021, and June 30, 2024, was conducted, excluding those with documented preoperative AFib. We employed multivariable negative binomial and logistic regression models to assess length of stay (LOS), discharge disposition, 90-day readmission, and 90-day composite complications. Additionally, a Bayesian Beta-Binomial conjugate model with an objective Jeffreys Prior was utilized to estimate the posterior probabilities of adverse outcomes across key clinical phenotypes. Results: POAF occurred in 355 patients (7.58%). Multivariable analysis demonstrated a 30% relative increase in expected LOS (IRR 1.30, 95% CI [1.23 - 1.36], P < .001) and 33% higher odds of facility discharge (OR 1.33, 95% CI [1.03 - 1.72], P = .030) for patients with POAF. However, POAF was not independently associated with 90-day readmission (OR 1.25, P = .063) or composite complications (OR 1.20, P = .118). Chronic heart failure (CHF) emerged as the dominant predictor. Bayesian risk updating revealed that while the baseline posterior probability for a 90-day complication was 27.2%, the synergistic presence of both POAF and CHF radically shifted this posterior risk to 42.6% (Probability of Direction > 0.999 vs. baseline). Conclusions: POAF prolongs hospitalization and drives non-home discharges, but it does not independently dictate 90-day morbidity. Bayesian stratification demonstrates that post-discharge outcomes are predominantly driven by underlying chronic conditions. Effective reduction of readmissions requires robust transition-of-care frameworks, empowering primary care clinicians to aggressively optimize heart failure and metabolic disease rather than focusing solely on the acute surgical arrhythmic event.

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: Transthyretin amyloidosis cardiomyopathy (ATTR-CM) is an infiltrative cardiomyopathy and an increasingly recognized cause of heart failure. With improved survival from disease-modifying therapies, an increasing number of patients are presenting for surgery and may be at increased risk of adverse postoperative outcomes. This study reports outcomes of ATTR-CM patients undergoing surgery and evaluates the utility of the Revised Cardiac Risk Index (RCRI), a perioperative risk tool. Methods: A total of 145 ATTR-CM patients were included, among which 51 patients underwent at least one eligible surgical procedure. Preoperative risk was assessed using the RCRI, analyzed both as a categorical and as a dichotomized ({greater than or equal to}3 vs <3) variable. Postoperative outcomes included unplanned hospital admission, length of stay (LOS), prolonged hospitalization (>48 hours), and major adverse cardiac events. Models were adjusted for frailty (Clinical Frailty Scale {greater than or equal to}5) and major surgery, using multivariable, ordinal, and Firth penalized logistic regression analyses. Results: Patients were predominantly male (86%) with a mean age of 76 {plus minus} 9 years, and 61% were frail. Higher RCRI scores were associated with unplanned postoperative hospital admission (RCRI {greater than or equal to}3: adjusted OR 48.9, 95% CI 4.8-502.2) and longer LOS (RCRI {greater than or equal to}3: adjusted OR 40.7, 95% CI 4.3-382.8). RCRI {greater than or equal to}3 was also associated with prolonged hospitalization (>48 hours) in Firth penalized logistic regression, whereas frailty was not independently associated. Conclusions: In a real-world ATTR-CM cohort undergoing major non-cardiac surgery, the overall risk of adverse outcomes was low, and higher RCRI scores were associated with increased postoperative hospital admission and longer LOS, including hospitalization exceeding 48 hours. The RCRI retains prognostic utility in this high-risk cohort and may support peri-operative risk stratification.

Abstract Background Non-cardiac chest pain (NCCP) is commonly regarded as a low-risk condition. However, long-term mortality, cause-specific death, and high-risk subgroup characteristics remain poorly defined. Methods In this multicentre registry-linked cohort study, we linked the Chest Pain Center Registry from 101 hospitals in Hunan, China, with the Mortality and Cause of Death Registry. Adults diagnosed with NCCP from Jan 1, 2017, to Dec 31, 2021, were included. We assessed 3-year all-cause, cardiovascular, and non-cardiovascular mortality using Cox, restricted cubic spline, and Fine-Gray models. Findings Among 160,245 patients, 4674 deaths occurred within 3 years (2.9%). Mortality increased sharply after 60.5 years. Age [&ge;] 60.5 years (adjusted hazard ratio [aHR] 7.49 [95% CI 6.89-8.14]), rural residence (time-varying aHR 1.46 [1.35-1.57] in year 1 and 1.66 [1.46-1.89] in years 1-3), and male sex (aHR 1.47 [1.38-1.57]) independently predicted death. Three-year mortality ranged from 0.3% in younger urban women to 8.4% in older rural men. Cardiovascular diseases accounted for 56.4% of deaths among older patients, whereas other non-cardiovascular causes (22.8%) and malignancy (20.8%) were the largest categories among younger decedents. Interpretation NCCP is not uniformly benign. Age, rural residence, and sex identify patients who could benefit from risk-stratified follow-up, with cardiovascular prevention prioritised for older rural men and broader non-cardiovascular assessment considered for younger patients.

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: 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.

Background: Left atrial volume index (LAVI) reflects atrial remodeling in heart failure with preserved ejection fraction (HFpEF), but its nonlinear, hemodynamic, and time-varying associations with atrial fibrillation (AF) remain uncertain. Objectives: To assess the association of baseline LAVI with documented incident AF in HFpEF. Methods: We studied 764 patients with HFpEF without documented AF in a Hong Kong registry. LAVI was analyzed continuously, by tertiles, and with restricted cubic splines. Incident AF was the first qualifying AF diagnosis or electrocardiographic record after echocardiography. Cause-specific Cox and Fine-Gray models were used, with death before AF as a competing event. A hemodynamic overlap-adjusted model additionally included E/e' ratio and pulmonary artery systolic pressure. Results: During a median follow-up of 5.81 years, 360 patients developed documented incident AF and 272 died before AF was documented. In the primary clinical model, each 10-mL/m2 increase in LAVI was associated with incident AF in cause-specific Cox regression (HR, 1.08; 95% CI, 1.06-1.11) and Fine-Gray regression (sHR, 1.06; 95% CI, 1.04-1.09). After hemodynamic overlap adjustment, the continuous association was attenuated. However, the highest LAVI tertile remained associated with incident AF (HR, 1.78; 95% CI, 1.28-2.49; sHR, 1.47; 95% CI, 1.05-2.04). Splines showed nonlinear excess risk at higher LAVI, and period-specific analyses showed the strongest association during the first year. Conclusions: Marked left atrial enlargement identified a structural-hemodynamic phenotype associated with early documented incident AF and may support risk-enriched rhythm surveillance.

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: Suspected acute coronary syndrome is a frequent Emergency Department (ED) presentation, requiring safe and efficient assessment. We interrogated long-term trends in whole population care for these patients using a new multi-centre regional registry. Methods: The DataLoch Heart Disease Registry links relevant data from primary and secondary healthcare records, with national administrative data for patients registered within the Lothian Health Board region of Scotland (~1M population). We included all adult patients presenting to secondary- or tertiary-care EDs in the region between 2014 and 2024, in whom high-sensitivity cardiac troponin was measured within 24 hours of presentation. Annual diagnostic rates for myocardial infarction, pharmacological and interventional management, and outcomes up to 1 year after ED presentation were studied. Logistic regression models were used to report change in annual trends for myocardial infarction, cardiac death, cardiovascular death and all-cause mortality, adjusted for age, sex, ethnicity, socioeconomic deprivation and comorbidity. Results: Over 10 years, 117,142 consecutive patients (mean age 58 +/- 18 years, 48% female, 6.6% with confirmed myocardial infarction) were included. Cardiac troponin testing increased year on year, from 61 per 1000 ED attendances in 2014 to 103 per 1000 in 2024 (P<0.001), but the proportion of patients admitted to hospital fell (59% in 2014 to 38% in 2024, P<0.001). Associated with these trends, the tested population had fewer cardiovascular risk factors and myocardial infarction incidence fell from 73 per 1000 tested patients in 2014 to 47 per 1000 in 2024 (adjusted odds ratio 0.62, 95% confidence intervals 0.56 to 0.69, P<0.001). In patients diagnosed with myocardial infarction, prescriptions of preventative therapies and numbers of revascularisation procedures were unchanged. After adjustment, no change over time was observed in one-year cardiac or cardiovascular mortality in those with a diagnosis of myocardial infarction. Conclusions: ED testing using cardiac troponin has extended to a broader population at lower risk of myocardial infarction. Despite this trend, early rule-out pathways have reduced hospital admissions, without observable changes in outcomes for those with myocardial infarction.

Background: Given around 50% of people with heart failure have a degree of iron deficiency, guidelines recommend screening. It is uncertain to what extent this is done in primary care and whether testing is equitable. Aim: To report the proportion of people with incident heart failure who undergo a ferritin test within 12 months. Design and setting: Retrospective primary care cohort study using Clinical Practice Research Datalink Aurum data, between 2016 and 2021. Methods: We report the proportion of adults with an incident diagnosis of heart failure who received a ferritin test within 12 months. Multivariable logistic regression was used to examine the odds of testing based on key demographic covariates and co-morbidities. Results: Among 105,749 individuals with an incident diagnosis of heart failure (mean age 71.6 years, SD 14.3), only 35,688 (33.7%) received a ferritin test within the subsequent year. Increasing age (odds ratio 1.25 per 10-year increase, 95% CI: 1.24-1.27), female sex (male sex OR 0.86, 0.84-0.89) and Asian ethnicity (OR 1.70, 1.59-1.80) were all associated with increased odds of testing as were diagnoses of coeliac disease (OR 1.86, 1.58-2.21), type 1 diabetes (OR 1.82, 1.51-2.19) and cirrhosis (OR 1.64, 1.43-1.87). There was geographic variation in testing, even in adjusted analyses. Conclusion: In a large primary care dataset, two thirds of people with incident heart failure did not receive a ferritin test for iron deficiency within a year of diagnosis demonstrating a gap in current practice and an opportunity for improvements in service delivery.

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.

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.

Background: Short and long sleep duration have been linked to atrial fibrillation (AF), but their influence on arrhythmia recurrence after catheter ablation is uncertain. We evaluated the association between nocturnal sleep duration and the risk of recurrent arrhythmias in patients undergoing catheter ablation for AF in the PREDIMAR trial. Methods: The PREDIMAR study is a multicentre, randomized, controlled, single-blind trial evaluating a Mediterranean diet enriched with extra-virgin olive oil for preventing arrhythmia recurrence after catheter ablation for AF. Nocturnal sleep duration was categorized as adequate (6?8 h/day) or inadequate (<6 h/day or >8 h/day). Multivariable Cox regression models estimated the association between sleep duration and the risk of recurrent atrial flutter (AFL) or AF. Results: Among 720 participants, we observed 226 incident cases of AF relapse and 107 cases of AFL. Inadequate nocturnal sleep duration was associated with a significantly higher risk of AFL recurrence compared with adequate sleep (adjusted HR = 1.87; 95% CI 1.18?2.96). No significant association was observed for AF recurrence (HR = 0.99; 95% CI 0.70?1.41). The association with AFL recurrence was particularly evident in patients with persistent AF at baseline before ablation (adjusted HR = 3.42; 95% CI 1.47?7.97), whereas no significant relationship was observed in those with baseline paroxysmal AF. Conclusions: Inadequate nocturnal sleep duration (<6 h/day or >8 h/day) may increase the risk of AFL recurrence following AF ablation. These findings highlight the relevance of sleep habits as a modifiable behavioural factor potentially influencing post-ablation outcomes.

Background As transcatheter aortic valve replacement (TAVR) expands to younger patients with longer life expectancy, understanding long-term reintervention and clinically significant valve failure has become increasingly important. Objectives To evaluate temporal trends in TAVR outcomes, characterize the incidence and timing of aortic valve reintervention, compare outcomes after redo-TAVR (TAVR-in-TAVR) versus surgical explantation, and assess freedom from clinically significant valve failure requiring repeat intervention after TAVR versus surgical bioprosthetic aortic valve replacement (SAVR). Methods We performed a retrospective cohort study using the Epic Cosmos. Adults undergoing index TAVR between February 2010 and May 2026 were identified. Primary outcomes included aortic valve reintervention and 30-day major adverse cardiovascular events (MACE). Reintervention incidence was estimated using competing-risk methods with death as the competing event. Propensity-score matching compared redo-TAVR with surgical explantation and TAVR with SAVR. A prespecified 1-year landmark analysis evaluated clinically significant valve failure requiring repeat intervention. Results Among 300,927 patients undergoing TAVR, annual procedural volume increased more than tenfold between 2016 and 2025. Thirty-day MACE decreased from 31.8% before 2017 to 18.6% after 2022 (P<0.001), while mortality declined from 3.0% to 1.4% (P<0.001). During follow-up, 3,315 patients underwent redo-TAVR and 347 underwent surgical explantation. The cumulative incidence of reintervention was 1.1%, 1.2%, 1.5%, and 2.7% at 3, 5, 7, and 10 years, respectively, with significantly lower rates in contemporary procedural eras (Gray test, P<0.001). Compared with surgical explantation, redo-TAVR was associated with lower 30-day mortality, stroke, acute kidney injury, and major bleeding. However, among propensity-matched hospital survivors, surgical explantation was associated with superior long-term survival (hazard ratio: 0.64; 95% CI: 0.44 - 0.93; P=0.018). In the landmark analysis, clinically significant valve failure requiring repeat intervention occurred earlier after TAVR than after SAVR despite a lower overall cumulative incidence of repeat intervention following TAVR. Conclusions Contemporary TAVR is associated with progressively improving procedural outcomes and a low incidence of repeat aortic valve intervention. Redo-TAVR offers lower perioperative risk than surgical explantation, whereas surgical explantation is associated with superior long-term survival among selected patients. Earlier clinically significant valve failure requiring repeat intervention after TAVR underscores the importance of lifetime management strategies as TAVR expands to younger populations.

Background: Percutaneous mechanical circulatory support (pMCS) is increasingly used in critically ill patients, yet its value in relation to cost and outcomes remains unclear. We evaluated national variation in utilization, outcomes, and cost, and introduced a value of care framework integrating risk-adjusted outcomes and expenditures. Methods: We performed a retrospective cohort study using the National Inpatient Sample to identify non-elective hospitalizations of critically ill patients undergoing intra-aortic balloon pump (IABP) or percutaneous left ventricular assist device (pLVAD) placement using ICD-10 codes. Multivariable logistic regression and generalized linear models were used to estimate expected outcomes and costs. Observed-to-expected (O/E) ratios were calculated, and a value index was derived to compare procedural strategies. Results: A total of 57,910 weighted hospitalizations were included (IABP 78%, pLVAD 22%). In-hospital mortality exceeded 30% across regions. Significant regional variation was observed, with the West demonstrating the highest costs and the Midwest the lowest (p<0.001). Mean hospital charges were higher for pLVAD compared with IABP ($403,731 vs $320,769). Both strategies achieved outcomes better than expected after risk adjustment (O/E 0.92); however, costs were higher than expected for both, with greater relative cost inflation observed for IABP (O/E 1.41) and higher absolute costs for pLVAD. In value-of-care analysis, IABP was associated with lower cost and comparable outcomes, while pLVAD demonstrated higher cost without proportional outcome improvement. Conclusion: Substantial variation exists in the cost, outcomes, and value of pMCS strategies. While both IABP and pLVAD achieve favorable risk-adjusted outcomes, pLVAD is associated with higher costs without commensurate clinical benefit.

Aims: Iron deficiency is common among people with heart failure and associated with morbidity and mortality. While intravenous iron improves clinical outcomes, oral iron continues to be prescribed in routine practice despite limited evidence of benefit. Methods: We completed a retrospective primary care cohort study (2016 to 2021) to investigate the proportion of people with an incident diagnosis of heart failure who had iron deficiency identified (defined as ferritin <100 micrograms/L) and subsequently received a first prescription for oral iron within 12 months. Multivariable logistic regression was used to report the odds ratio (OR) of receiving oral iron in relation to key demographic covariates and co-morbidities. Results: Among 105,749 people with an incident diagnosis of heart failure, 35,688 underwent a ferritin test within the first year of whom 11,237 had iron deficiency and no prior prescription for oral iron. Of these, 2,734 (24.3%) were subsequently prescribed oral iron. Increasing age (OR per 10-year increase 1.14, 95%CI: 1.10-1.19), Asian ethnicity (1.33, 1.08-1.64), cirrhosis (2.01, 1.29-3.14) and diabetes (1.36, 1.24-1.49) were associated with increased odds of receiving oral iron. Among 1,357 (49.6%) people who had their ferritin level re-tested, the median change was 26 micrograms/L (interquartile range 7 to 61) among people who were prescribed oral iron compared to 4 micrograms/L (IQR -9 to 34) among people not prescribed oral iron. Conclusions: One in four individuals with heart failure and low ferritin received oral iron replacement, despite this not being recommended in international guidelines. Treatment could be improved and standardised in primary care.