Open Heart

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: 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.

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.

Importance: Autistic people have increased risks of cardiometabolic conditions and premature mortality; however, no studies specifically assess risks of major ischaemic events in the autistic population. Objective: To determine whether autistic people are at increased risk of major ischaemic events after accounting for known risk factors. Design: A retrospective matched cohort study from 1/1/1990 to 31/12/2019. Cox regression models accounting for matching factors, sociodemographic characteristics, intellectual disability, and cardiovascular risk factors were employed. Setting: This population-based study leveraged lifetime primary and secondary care electronic health records from the Clinical Practice Research Datalink and Hospital Episode Statistics, as well as sociodemographic, ethnicity, and death registration data from the Office of National Statistics. Participants: 23,612 autistic people were matched 1:5 on birth year (+/-2 years), general practitioner practice ID, and gender to 118,060 non-autistic people. Autistic people were defined as those with a clinical autism diagnosis recorded during the study period. Patients missing Indices of Multiple Deprivation and ethnicity data, and an end date prior to their CPRD start date were excluded along with their matched set. Exposure: Clinical diagnosis of autism. Secondary exposures included health conditions associated with cardiovascular disease with some additional conditions relevant to autism. Main Outcome and Measures: Time to first major ischaemic event (any of myocardial infarction, angina, other ischaemic heart disease, ischaemic stroke, and transient ischaemic attacks). Results: Autistic people had a greater risk of a major ischaemic event in the study period in the minimally adjusted Model 1 (HR 1.19; 95% CI: 1.00, 1.42) as well as for autistic females even after accounting for risk factors (adjusted HR 1.71; 95% CI: 1.10, 2.67). There was also evidence that several cardiometabolic risk factors had a higher prevalence among the autistic group such as severe mental illness, dyslipidaemia, and obesity (all P<0.001). Conclusions and Relevance: Autistic people have an increased risk of major ischaemic events and need improved cardiometabolic risk management. This risk remained in autistic women after adjusting for cardiometabolic and sociodemographic factors. As cardiovascular disease is a primary cause of death globally, research is needed to better understand the mechanism that drives this association.

Introduction: Shared medical appointments (SMAs) are medical visits where multiple individuals are seen together in a group setting. For patients with inherited cardiovascular disease, where multiple family members often require ongoing cardiac care and screening, family SMAs may be particularly valuable as a tool to facilitate family communication and comprehension of their condition. This research aimed to identify patient perspectives on the potential benefits and challenges of family SMAs in comparison to an existing individual clinic model. Methods: Qualitative semi-structured interviews were conducted with adult family representatives. Each family had at least one family member seen at the adult and pediatric inherited cardiovascular disease clinics. Interview recordings were transcribed verbatim and inductively coded using a content analysis approach. Results: Sixteen families were interviewed in this study. The mean age of the family representative interviewed was 43.4 years ({+/-} 9.3 SD), and they were followed at Stanford Health Care for a mean of 7.3 years ({+/-} 4.2 SD). 81.2% (13/16) of families said they would find family SMAs beneficial. For interested families who consented to recorded interviews (n=12), benefits and challenges fell into two major categories: care quality and access and logistics. Interested families thought family SMAs would provide an added care quality benefit by increasing understanding among adults, children, and providers (83.3%, 10/12). Six of twelve participants interested in having family SMA visits felt there would be logistical/access-based benefits to this new model (50%, 6/12). Families also identified possible challenges with this model, such as less individualized care, potential privacy concerns, and concerns regarding the smoothness of the clinic process in coordinating a family SMA. Conclusion: The majority of families believed a family SMA model would provide added benefit to families with inherited cardiovascular disease, but requires thoughtful implementation and should be tailored to families? unique needs.

Background: Thoracic aortopathy is a disorder with genetic influence usually presenting in adulthood for which family screening is potentially desirable. Family screening is recommended, but the predictors of a positive screen and real-world pickup rates are unknown. Methods: This was a retrospective cohort of 1022 probands (first affected family member identified) with thoracic aortopathy and one or more features suggestive of a genetic etiology, and their presenting family members, assessed in a cardiac clinic (2009?2024). Imaging and genetic testing were employed in family screening. The prespecified outcomes were uptake and pickup rate of family screening, and proband and family member specific characteristics that predicted a positive family screen. Results: Among probands, 43.5% had one or more family member screened, with an average of 3 relatives per successful proband. 27.6% of family members screened positive. A pre-existing family history of aortopathy was the only variable predicting a higher incidence rate for positive family screen (p = 0.0003). Age of presentation < 60 was not predictive. For family members, extravascular features (p < 0.0001), closer relation to the proband (p < 0.02), male sex (p < 0.0001) and older age (p< 0.0001) all predicted a positive screen. Family members were eight times more likely to screen positive through imaging as compared to genetic testing. Probands with a genetic diagnosis of Marfan and Loeys Dietz syndromes accounted for only 4% of the total. Conclusions: Proband-initiated family screening for thoracic aortopathy has a high yield of affected individuals, even among older probands.

Background Statins and ezetimibe are the preferred lipid-lowering therapies (LLTs) for children with heterozygous familial hypercholesterolaemia (HeFH). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are newer add-on therapies for individuals not achieving low-density lipoprotein-cholesterol (LDL-C) targets. We evaluated the efficacy and safety of PCSK9i in children aged <18 years with HeFH. Methods Systematic review and pairwise meta-analyses of randomised-controlled trials (RCTs) of evolocumab, alirocumab and inclisiran. Comprehensive bibliographic searches were conducted in February 2026. Risk of bias was assessed with Cochrane RoB 2. Results Of 2798 unique records screened, three RCTs were included (n=451, mean age 13 years, follow-up 24 to 47 weeks). Each trial evaluated either evolocumab, alirocumab or inclisiran against placebo as add-on to baseline LLT. Participants had elevated LDL-C (>3.4 mmol/L [130 mg/dL]) despite stable LLT. Overall risk of bias was low. PCSK9i reduced LDL-C by an average of 35.44% (95% CI -41.74 to -29.14, I2=50.8%) and by 1.63 mmol/L [62.93 mg/dL] (95% CI -1.86 to -1.39, I2=18.6%) compared with placebo. There was no evidence of differences between PCSK9i and placebo in tolerability, growth and maturation, and overall incidence of adverse events. Conclusions PCSK9i add-on therapy leads to substantial reductions in LDL-C in paediatric patients with HeFH failing to achieve LDL-C targets with standard LLT. While the findings of this review support the use of PCSK9i in a subset of children and young people with HeFH, limited trial numbers and short follow-up periods underscore the need for future high-quality studies evaluating long-term safety, effectiveness and cost-effectiveness.

Background: Blood volume (BV) in patients with chronic heart failure (HF) is characterized by heterogeneity in volume profiles; one profile being "normal BV". While overall intravascular volume may be considered normal clinically, the relative contributions of red blood cell (RBC) mass and plasma volume (PV) may not be. Objective: Assess how normal is a "normal BV" based on quantitative measures of RBC mass and PV. Methods: Retrospective analysis was undertaken in 395 patients with Class II-III HF. BV was quantitated using indicator-dilution methodology. Cohort was stratified by normal and hypervolemic BV. Results: Of the cohort, 31% (123/395) demonstrated normal total BV and 62% (244/395) hypervolemic BV. Of patients with "normal BV", 36% (44/123) demonstrated normal RBC mass and 60% normal PV (74/123). Importantly, 60% (74/123) demonstrated a deficit in RBC mass (true anemia), while a low hemoglobin (<12 g/dL) was present in just 29% (36/123). An excess in RBC mass (erythrocytosis) in 4% (5/123). Notably, true normal BV (i.e., normal RBC mass and normal PV) was observed in only 30% (37/123) of patients with an overall "normal" intravascular volume. Conclusions: Findings reveal that "normal BV" can be misleading by concealing substantial variability in RBC mass (including unrecognized anemia and erythrocytosis) as well as different degrees of PV expansion and contraction. An actual normal BV was identified in a minority of "normal BV" patients. This underscores the importance of looking beyond overall "normal BV" to the contributing elements of RBC mass and PV with significant implications for patient management and 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: Heart Failure is a complex clinical syndrome of growing public health concern in sub-Saharan Africa, yet the data from Sierra Leone are absent. The aim of the study is to characterise the clinical profile, etiological and temporal trends of hospitalised HF patients at Choithrams Memorial Hospital (CMH), Freetown, Sierra Leone, to confirm specific management strategies. Methods: This single-center, retrospective observational cohort study analysed data on HF patients (>18years) admitted at the CMH between January 2021 to 31 December 2025. The clinical definition of HF was based on the Framingham criteria and the European Society of Cardiology (ESC) guidelines , including standard echocardiographic parameters. All variables, including patients demographics, HF. phenotype, aetiology, medical history and hospital outcomes were extracted from the digital record. Non-parameteric tests, multivariable logistic regression to identify variables associated with etiology, Wilcoxon rank-sum test to compare groups and Kruskal-Wallis test to analyse trends over time were utilised. Result: A total of 765 patients were included in the study, with a median age of 53 years (IQR 42-61) and male predominance of 55.3%. Patients with recurrent HF (60.9%) were more common than those with de novo HF (39.1%), were older (54 years vs 53 years), had a higher comorbidity burden (34% vs 4%, p < 0.001), and presented with a cold-wet hemodynamic profile (18.4% vs 8.4%, p < 0.001). HFrEF (61.3%) was the most predominant phenotype, though HFpEF increased with age. Dilated Cardiomyopathy (37.0%), Hypertensive Heart Disease (31.2%) and Valvular Heart Failure (17.1%) were the leading etiologies, while ischemic heart disease (6.3%) was relatively uncommon. A majority of the patients were referred (77.9%), and 50.8% presented with NYHA IV. The strongest independent predictor for HF was hypertensive heart disease [AOR = 17.81; C.I 95%: (3.13-48.76), p <0.001]. An analysis of the trends in etiologies and demographics over the five-year period demonstrated no significant changes (all p-values > 0.05 for age, sex, aetiology, and most comorbidities). Conclusion: HF affects the younger adult population in Sierra Leone and is mainly caused by DCM and HHD. The late case presentations, the high prevalence of recurrent HF, and the associated high burden of comorbidities emphasize an urgent need to develop and implement improved strategies for the prevention, early detection, and long-term management of HF within Sierra Leone's healthcare system.

Objectives: To assess how patients with non-valvular atrial fibrillation (NVAF) receiving oral anticoagulants are managed in routine primary care practice in Spain. Methods: This observational, descriptive study included patients with NVAF treated with oral anticoagulants for at least 6 months before enrolment and managed in primary care settings in Spain. The Barthel and ACTS questionnaires were administered to evaluate functional autonomy and treatment satisfaction, respectively. Results: A total of 1,901 patients were included: 428 received vitamin K antagonists (VKAs) and 1,473 direct oral anticoagulants (DOACs). Compared with patients receiving DOACs, those treated with VKAs were significantly older and had a higher prevalence of more hypertension. Mean treatment duration was 7.6 years for VKAs and 3.8 years for DOACs. Among patients receiving VKAs, 56.2% and 59.0% achieved good anticoagulation control according to the direct and Rosendaal methods, respectively. Patients in the DOAC group reported greater satisfaction across several domains, including perceived treatment benefits, lower impact on daily life, and overall positive treatment effect. Event incidence rates (per 1,000 person-years) were higher with DOACs than with VKAs for stroke (1.75; 95% CI 1.05-2.92), ischemic stroke (1.78; 95% CI 1.06-3.00), acute myocardial infarction (1.64; 95% CI 0.97-2.79), and major bleeding (3.68; 95% CI 1.81-7.46). Conclusions: In routine primary care practice in Spain, patient profiles and treatment duration varied by oral anticoagulant type. These differences may partly explain the higher rates of stroke and major bleeding observed with DOACs versus VKAs, despite greater treatment satisfaction among patients receiving DOACs.

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: 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: Patients with Fontan are prone to sequelae related to chronic elevations in central venous pressures. Interventions that improve venous pressures without compromising ventricular filling may therefore be of benefit. Methods We conducted a multi-center, open label, single arm pilot study of 4 weeks of dapagliflozin 10mg in adult patients with Fontan. The primary outcome was change in resting peripheral venous pressure (PVP). Secondary outcomes included changes in post-exercise PVP, peak VO2, Ve/VCO2, oxygen pulse, oxygen uptake efficiency slope (OUES), total body water, and patient reported health status according to the ACHD PRO. Results The total of 29 patients were enrolled between 11/1/2023 and 2/3/2026 across 2 centers, of whom 26 completed all study procedures. Average age was 31.2 years and 19 had a morphologic left ventricle. Dapagliflozin decreased PVP by 1.3mmHg (IQR -2.6, 0.4, p=0.012) with a greater effect in those with higher baseline PVP. Dapagliflozin improved patient reported health status and resulted in a trend towards an improvement in peak VO2 (0.2ml/kg/min, IQR -0.9, 2.2, p=0.064) and oxygen pulse (0.3ml/beat, IQR -0.6-1.1, p=0.074) without any impact on other cardiopulmonary exercise test parameters or total body water. Dapagliflozin was well tolerated in participants with no significant adverse events. Conclusions Dapagliflozin decreased PVP and improved patient reported health status in adult patients with Fontan over 4 weeks of therapy and was generally well tolerated.

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.

Introduction: Severe hypercholesterolemia has four primary causes: monogenic familial hypercholesterolemia (FH), polygenic hypercholesterolemia (PRS), severely elevated Lp(a) concentration, and hypercholesterolemia due to environmental/lifestyle/behavioral factors (i.e., no known genetic etiology). Here, we explore patient and clinician perspectives about the identification and management of each of these causes. Methods: Patients with severe hypercholesterolemia with a primary language of English or Spanish and clinicians (primary care, genetic counseling, cardiology) across two health systems (Geisinger, Mount Sinai) participated in semi-structured interviews. Analysis was completed using an a priori codebook informed by Proctor?s implementation outcomes to identify themes influencing the identification and management of the underlying causes of severe hypercholesterolemia. Results: A total of 28 patients and 25 clinicians participated. Patients emphasized the importance of receiving results directly from their clinician, requested take-home resources that mirrored the information from their clinician, were motivated to seek multidisciplinary care, and anticipated all results would be actionable, but that high-risk PRS and elevated Lp(a) may require more support (e.g., specialists, education) to act on. Clinicians stressed the importance of integrating workflows (e.g., test ordering) with the electronic health record, highlighted LDL-C levels and multidisciplinary care coordination as key to management, explained how they would tailor care to individual patients, and expressed a more limited understanding of Lp(a) and PRS result types based on their clinical experiences and, therefore, hesitation about the recommended clinical actions. Conclusions: Patients and clinicians identified complementary determinants influencing the identification and management of the underlying cause of severe hypercholesterolemia. Participants welcomed risk information and requested a higher level of informational support and specialty expertise to appropriately manage high Lp(a) and PRS results. Integrating genomic information into risk assessments will require a partnership between general practitioners and specialists to provide a multidisciplinary approach to the identification and management of the underlying causes of severe hypercholesterolemia.

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 Adults with a systemic right ventricle (sRV) due to congenitally corrected transposition of the great arteries (ccTGA) or atrial switch repair for d-transposition of the great arteries (d-TGA) experience substantial physiologic and psychosocial morbidity. Relationships among exercise capacity, sRV function, and mental health remain incompletely characterized. Objectives To characterize relationships among anatomic subtype, exercise capacity, sRV function, and mental health in adults with sRV physiology. Methods We performed a retrospective cohort study of adults with ccTGA or d-TGA (Mustard/Senning) followed at a tertiary Adult Congenital Heart Disease program from 2000 to 2025. Clinical, imaging, cardiopulmonary exercise testing, and patient-reported data were obtained from electronic health records. Mental health diagnoses were identified from clinical documentation. Functional status was assessed using NYHA class and the Kansas City Cardiomyopathy Questionnaire (KCCQ-12). Results Among 137 adults (ccTGA, n = 51; d-TGA, n = 86), percent-predicted peak VO2 was lower in d-TGA than ccTGA (60% vs 74%, p < 0.001), as was sRV systolic function (41 +/- 11% vs 47 +/- 10%, p < 0.01). Anxiety or depression was more common in d-TGA (46% vs 25%, p < 0.05). Across the cohort, anxiety or depression was associated with lower exercise capacity, worse NYHA functional class, and lower KCCQ scores. Conclusions Adults with d-TGA following atrial switch have lower exercise capacity, reduced sRV systolic function, and greater mental health burden than adults with ccTGA. These findings support integrated assessment of physiologic performance, functional status, and mental health in adults with sRV physiology.

Background: Gaps in care (GIC) among patients with congenital heart disease (CHD) are associated with adverse outcomes, yet the specific social and healthcare-related factors contributing to GIC and the clinical consequences of delayed re-engagement in care remain poorly characterized. Large electronic medical record datasets often cannot distinguish true GIC from clinically appropriate care patterns or capture the patient-level factors contributing to GIC. Methods: We conducted a retrospective cohort study, combining large data with manual chart review, of 1,746 patients of all ages with surgically repaired CHD between 2003 and 2020 at a tertiary care center serving four states. GIC was defined as more than 3 years and 3 months between cardiology visits and exceeding the physician recommended follow-up interval. Results: Of the cohort, 916 patients (52%) met criteria for potential GIC. Following a structured manual chart review, a substantial subset was reclassified as having appropriate care, leaving 275 patients (15.7%) with true GIC. After multivariable adjustment, older age and simple anatomic CHD complexity were independently associated with GIC. Among patients with GIC, 17.8% had a documented contributor, most commonly insurance instability or social factors. Of those 41.5% returned to care (RTC), and many were asymptomatic but had significant disease progression. Thirteen percent of patients who RTC required cardiac intervention, including semi-urgent or urgent procedures, and 26.7% of those requiring intervention experienced significant morbidity or mortality, including stroke, infective endocarditis, urgent transplant referral, or death. These outcomes occurred across all levels of CHD complexity, including patients with simple CHD. Conclusions: GIC remain prevalent in patients with surgically repaired CHD and are associated with significant morbidity and mortality across the full spectrum of anatomic complexity. They are most often driven by insurance instability and social vulnerability rather than clinical factors, and many adverse outcomes may be preventable with consistent longitudinal care. These findings support a shift toward proactive care models that integrate standardized follow-up pathways, systematic assessment of patient-level needs, and emerging analytic tools to identify at-risk patients before GIC occur.

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.