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The American Journal of Cardiology

Elsevier BV

Preprints posted in the last 30 days, ranked by how well they match The American Journal of Cardiology's content profile, based on 15 papers previously published here. The average preprint has a 0.06% match score for this journal, so anything above that is already an above-average fit.

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Predicting 30-Day Heart Failure Readmissions Using Machine Learning: Insights From the Kansas Health Information Network (KHIN)

Kim, M.; Yan, J.; Wasfy, J. H.; Aseltine, R.

2026-05-21 cardiovascular medicine 10.64898/2026.05.18.26353537 medRxiv
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Background: Heart failure (HF) is a major contributor to inpatient hospital utilization, with persistently high 30-day readmission rates. Existing prediction tools are frequently restricted to primary-diagnosis HF admissions, potentially excluding clinically relevant HF-related hospitalizations. Objectives: To develop and validate risk prediction models using machine learning (ML)-based risk prediction models to predict 30-day readmissions among patients with HF using the Kansas Health Information Network, a statewide health information exchange. Methods: This retrospective cohort study analyzed HF hospitalizations using predictors including demographics, comorbidities, laboratory results, medications, clinical quality metrics for diabetes and kidney disease management, and prior healthcare utilization. Five ML models, including regularized logistic regression, random forest, extreme gradient boosting, categorical boosting, and deep neural network, were trained using stratified 5-fold cross-validation. Model performance was evaluated on an independent test set using the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), misclassification rate (MCR), and Brier score. Results: Among 2,734 HF patients, the 30-day readmission rate was 27%. The XGBoost model achieved the best discrimination (AUROC=0.75; AUPRC=0.58; MCR=0.21). Patients in the highest-risk decile had a positive predictive value of 76%, accounted for approximately one-third of all 30-day readmissions, and had a 3.3-fold enrichment compared with baseline risk. The key predictors included prior hospital utilization, diabetes and kidney disease management indicators, and comorbidity burden. Conclusions: Risk stratification using routinely collected clinical data identified a subgroup at elevated risk for 30-day readmission. These findings support the potential role of data-driven risk prediction to inform targeted transitional care.

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The association of Red Cell Distribution Width and Red Cell Distribution Width related indices with the in-Hospital Mortality of Congestive Heart Failure in a retrospective observational cohort study

wang, d.; yuan, x.; Lv, D.; wang, y.

2026-06-04 cardiovascular medicine 10.64898/2026.05.29.26354291 medRxiv
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Background: Red cell distribution width (RDW), a readily available hematological parameter reflecting erythrocyte size heterogeneity, has been increasingly recognized as a prognostic marker in congestive heart failure (CHF), with elevated levels independently associated with adverse outcomes. However, RDW-derived composite indices-particularly the RDW-to-platelet ratio (RPR) and RDW-to-hemoglobin ratio (RHR), which integrate inflammatory, hemostatic, and oxygen-delivery pathways-remain largely unexplored in CHF populations. Whether these indices provide incremental prognostic value beyond RDW alone in critically ill patients with CHF has not been established. Methods: This retrospective cohort study included 30,409 participants from the MIMIC-IV and eICU-CRD databases. Multivariable logistic regression, restricted cubic spline (RCS) analysis, and subgroup analyses were employed to evaluate the associations between RDW, RDW-derived indices (RPR and RHR), and in-hospital mortality in patients with congestive heart failure. Results: Based on a pooled cohort of 30,409 patients with CHF from the MIMIC-IV and multi-center eICU-CRD databases (15,983 and 14,426, respectively), 16,295 (53.6%) were male and 14,114 were female, with a median age of 71.7 years. The mean RDW was 16.0 {+/-} 2.5, and the overall in-hospital mortality rate was 12.6%. Higher RDW quintiles were associated with progressively increased in-hospital mortality. In the fully adjusted model, RDW, RPR, and RHR were all significantly associated with increased in-hospital mortality, with adjusted odds ratios (ORs) of 2.46 (95% CI: 2.17-2.79) for RDW, 1.55 (95% CI: 1.38-1.73) for RPR, and 2.43 (95% CI: 2.09-2.82) for RHR. Sensitivity analyses using restricted cubic splines demonstrated that the association between RDW and RHR with in-hospital mortality was linear (P for nonlinearity > 0.05), whereas that for RPR exhibited a non-linear pattern (P = 0.02 for non-linearity). Conclusions. Elevated RDW, RPR, and RHR were independently associated with increased in-hospital mortality in patients with congestive heart failure. Notably, RPR exhibited a non-linear threshold association with in-hospital mortality.

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The LV-LA Health Score: A Novel Marker of Integrated Myocardial Structure and Function

Estrella, F.; Chiswell, K.; Sun, J.-L.; Duckworth, M.; Vasan, R. S.; Pattison, B.; Provencher, A.; Judd, S. E.; Velagaleti, R.; Douglas, P. S.; Bloomfield, G. S.; Soliman, E.; Chen, Y.-D. I.

2026-06-09 cardiovascular medicine 10.64898/2026.06.08.26353379 medRxiv
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Background Myocardial remodeling precedes symptomatic heart failure, which is important to detect early. We assessed feasibility and clinical correlates of a novel integrated assessment of myocardial remodeling in a large rural cohort in the Southeastern United States. Methods Echoes were obtained with AI assistance (Caption guidance) in 3100 adults in the NHLBI-funded RURAL cohort study. Of those, 1895 had quantifiable global longitudinal strain (GLS), left ventricular mass (LVM), and left atrial volume (LAV). LV-LA Health was based on a simple count of sex-specific abnormalities (0-3), indexed to body surface area (BSA) or height (Table 1). Relationships with demographics and risk factors were compared with Spearman correlation and Mantel-Haenszel tests, with moderate and severe results combined. Results Median (IQR) age was 49 (40-58). Impaired LV-LA Health is common even in a low PREVENT cardiovascular (CV) risk population (median 10-year risk 3.3%; 25th, 75th 1.2,7.2) with preserved ejection fraction (EF; 60%; 57,62). The prevalence of abnormalities differed greatly by indexing method: 18.2% with BSA (15.1% mild; 3.1% mod/severe) vs 51% with height (38.3% mild; 12.7% mod/severe) (Figure 1). LV-LA impairment increased with age, PREVENT CV risk score and cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity); all p<0.001. Impairment was more common in Black vs White people (p<0.001) and differed by sex only with height indexation. Conclusions A novel LV-LA health composite of routinely acquired echocardiographic measures identifies substantial subclinical cardiac remodeling in a middle-aged rural community cohort, not detected by PREVENT score or ejection fraction. This is the first application of this framework in a large, unselected community sample. Indexation method affects prevalence, with BSA likely underestimating risk in adiposity-enriched populations. Findings suggest a high rural burden and longitudinal evaluation with future CV events is ongoing.

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Transcatheter Bicaval Valve Implantation For Treatment Of Severe Tricuspid Regurgitation: A Single Centre Registry

Ghazi, A. M.; Ow, J. K.; Quah, W. J.; Azmi Yahaya, S.

2026-05-27 cardiovascular medicine 10.64898/2026.05.26.26354174 medRxiv
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Background: Heterotopic caval valve implantation using the TricValve(R) (OrbusNeich P&F) is a unique interventional approach for treatment of severe Tricuspid Regurgitation in patients who are deemed ineligible for surgery. Given the complexity and novelty of TricValve(R) implantation, there is a pressing need for robust clinical data to evaluate its safety, efficacy, and long-term outcomes. Our study assesses the clinical results of patients followed up for 1 year from our center. Methods: Retrospective, single center registry involving patients who have undergone TricValve(R) Transcatheter Bicaval Valves System (OrbusNeich P&F) implantation for the treatment of severe tricuspid regurgitation. Results: Fourteen patients were included. The mean age was 67.5 {+/-} 8.7 years, with high surgical risk (mean EuroSCORE II 6.1 {+/-} 3.7). Procedural success was achieved in thirteen patients, with no reported in-hospital mortality or stroke among all fourteen patients. At 1-year, significant improvements were observed in New York Heart Association (NYHA) functional class (86% Class III at baseline to 0% Class III at 1 year, P=0.002) and Kansas City Cardiomyopathy Questionnaire (KCCQ-12) scores (mean 32.0 {+/-} 7.4 to 42.4 {+/-} 12.0, P=0.015). TR Regurgitant Volume significantly decreased (65.5 {+/-} 16.9 ml to 38.2 {+/-} 13.6 ml, P=0.005). No deaths or strokes occurred during follow-up. Rehospitalization due to heart failure occurred in 14% (2 out of 14) of patients. Conclusion: In this single-center registry of high-risk patients, TricValve(R) implantation was associated with a favorable safety profile, significant reduction in tricuspid regurgitant volume, and meaningful improvements in functional status and quality of life at 1 year follow-up.

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ECG abnormalities are strongly associated with incident heart failure events in low-risk individuals using the PREVENT HF risk equations

Alawad, M. J.; Soliman, E. Z.; Brown, T. M.; Akinyelure, O.; Khodneva, Y.; Quezada Pinedo, H. G.; Mostafa, M. A.; Satish, M.; Goyal, P.; Soroka, O.; Safford, M. M.

2026-05-21 cardiovascular medicine 10.64898/2026.05.18.26353538 medRxiv
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Background: Resting electrocardiogram (ECG) are associated with heart failure (HF) events, even though it is not currently recommended in risk assessment. Objective: To examine the association between ECG abnormalities and incident HF events according to the 2023 PREVENT HF equation. And identify a subgroup of individuals who are misclassified as being at low risk. Design: Secondary data analysis from the REasons for Geographic And Racial Differences in Stroke (REGARDS) prospective cohort, including study participants without baseline HF. Exposure: ECG abnormalities were classified by Minnesota Code (MC) as normal, only minor, or any major abnormality at baseline (2003-2007). Outcome: Participants were followed for expert adjudicated incident HF hospitalizations/ deaths through December 2021. Results: Among 20,923 participants (mean age at baseline 63.6 years, 53.7% female), 26.0% of the sample was classified as low risk (<3%), 17.5% as borderline risk (3-<5%), 27.5% as intermediate risk (5%-<10%), and 29.0% as high risk (10%). Compared to those without ECG abnormality, the adjusted HR for incident HF was 1.56 (95% CI 1.35-1.80) for any minor abnormality and 2.56 (2.18-3.00) for any major abnormality. 43.5% of the population were in the less than 5% risk by PREVENT among whom 45.8% had any ECG abnormalities. The fully adjusted HR for only minor ECG abnormalities in the <3% was 1.47 (95% CI 0.72-3.01), and the fully adjusted HR for any major ECG abnormality was 5.22 (95% CI 2.42-11.30). In the borderline risk group, the fully adjusted HR for only minor ECG abnormalities was 1.37 (95% CI 0.89 - 2.11), and the fully adjusted HR for any major ECG abnormality was stronger than the HR in the intermediate and high-risk groups; 3.05 (95% CI 1.85 - 5.03). Conclusion: ECG abnormalities were common and associated with HF events across all PREVENT risk groups, especially in the low/borderline risk groups with major ECG abnormalities.

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Echocardiographic Characteristics, Measures of Severity and Natural History of Isolated Calcific Mitral Stenosis.

Haines, J.; Jacobson, T.; Ocran, S.; Kalvin, L.; Redmon, V.; Zhang, L.; Pan, A.; Garster, N.; Lewandowski, D.; Widlansky, M.; Mohananey, D.

2026-05-14 cardiovascular medicine 10.64898/2026.05.11.26352948 medRxiv
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IntroductionWith improved life expectancy, mitral annular calcification and calcific mitral stenosis (CMS) are increasing in prevalence. Echocardiographic evaluation of CMS is challenging due to acoustic shadowing and lack of CMS specific data on assessment of severity and outcomes. MethodsWe retrospectively identified patients with isolated CMS between the years 1/1/2010 and 4/5/2022. Severe CMS was defined as MVAcont [&le;]1.5 cm2. The primary outcome was a composite of all-cause mortality, mitral valve replacement (MVR) and ischemic stroke. Outcomes were collected through electronic health records with follow up through 8/15/2025. ResultsOur cohort included a total of n=717 patients with CMS of which n=140 had severe CMS. The mean age was 74{+/-}13 years and cohort was predominantly female. We found that MVAPHT consistently overestimates the MVA and is a poor predictor of severe CMS. Mean gradient >5 mm Hg had 81% specificity and 57% sensitivity for severe CMS. Over a median follow up of 36 (IQR 10.5-49.7) months, a total of n=331 (46.2%) patients died, and the primary composite outcome occurred in n=370 (51.6%). Although MVAcont [&le;]1.5 cm2 [aHR 1.3 (95% CI 0.9-1.8),p=0.29] was not an independent predictor of the primary outcome we found that mTMG was a significant independent predictor primary outcome [aHR 1.5 (95% CI 1.1-2), p<0.01]. Patients with MVAcont [&le;]1.5 cm2 and mean gradient [&ge;] 5 mmHg had the highest risk for the primary outcome [aHR 2 (95% CI 1.1-3.7),p=.02]. ConclusionPatients with severe CMS are older, female with a high burden of comorbidities and carry an overall poor prognosis. mTMG is an independent prognostic marker in these patients. Patients with MVA [&le;]1.5 cm2 and mTMG [&ge;]5 mmHg have the worst prognosis.

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Early Prediction of Post-TAVR Left Ventricular Remodeling Using CT-Derived Radiomics and Clinical Variables

Rezaeitaleshmahalleh, M.; Masoumi, S.; Razaviamri, F.; Rouhollahi, A.; Zancanaro, E.; Danesi, T. H.; Ayers, B. C.; Jassar, A.; Sabe, A.; Nezami, F. R.

2026-06-02 cardiovascular medicine 10.64898/2026.05.28.26354361 medRxiv
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Background: Adverse left ventricular (LV) remodeling after transcatheter aortic valve replacement (TAVR) is associated with impaired functional recovery and adverse long-term outcomes, yet imaging-based risk stratification remains limited. Objectives: This study sought to determine whether CT-derived radiomic and geometric myocardial features, integrated with procedural and clinical variables, can predict adverse LV remodeling after TAVR. Methods: We retrospectively analyzed 232 consecutive TAVR recipients with paired pre- and post-procedural LV mass index (LVMI) measurements. Adverse remodeling was defined as a [&ge;]10% increase in LVMI at follow-up. Pre-procedural CT was used to derive three-dimensional LV geometric descriptors, ray-tracing wall-thickness metrics, and myocardial texture radiomic features. Random forest classifiers were developed across six models of sequentially increasing complexity. Results: Adverse LV remodeling occurred in 52 patients (22.4%). Geometry-only model showed limited discrimination (AUC 0.62), whereas wall-thickness radiomics substantially improved performance (AUC 0.84). A multimodal pre-procedural model combining CT radiomics with pre-procedural LVMI, residual valve insufficiency, and prior coronary revascularization achieved an AUC of 0.86 (95% CI 0.73 to 0.98). Addition of post-procedural mean transvalvular gradient further improved discrimination (AUC 0.91, 95% CI 0.81 to 0.98). SHAP analysis identified post-procedural mean aortic gradient and radiomic markers of myocardial heterogeneity as the leading predictors. Conclusions: CT-derived radiomic characterization of myocardial heterogeneity provides incremental prognostic information beyond conventional geometric assessment for identifying patients at risk of adverse LV remodeling after TAVR. These findings extend the role of pre-procedural CT beyond anatomical planning toward quantitative myocardial phenotyping and individualized risk stratification, although prospective validation is required to establish clinical utility.

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Sex Differences in Mortality and Treatment Utilization Across Cardiogenic Shock Phenotypes: A National Cohort Study

Alencar, A. P.; li, x.; Sawant, A.; Ibrahim, A.; Bashir, M.; Bandi, V.; Bhatt, K.; Jalil, A.; Chennareddy, V.

2026-05-27 cardiovascular medicine 10.64898/2026.05.26.26354172 medRxiv
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Abstract Background Cardiogenic shock (CS) is a heterogeneous syndrome with diverse etiologies, treatment pathways, and outcomes. Prior studies of sex differences in CS have largely focused on acute myocardial infarction-related CS or evaluated CS as a single entity. Whether sex-based differences in outcomes and treatment utilization vary across distinct CS phenotypes remains incompletely defined. Methods We performed a retrospective cohort study using the National Inpatient Sample, a nationally representative all-payer database of United States hospitalizations. Adult hospitalizations with CS were identified using ICD-10-CM code R57.0 and categorized into clinically relevant phenotypes, including acute myocardial infarction (AMI), heart failure (HF), arrhythmia-related shock, myocarditis/Takotsubo, valvular disease, and other etiologies. Survey-weighted analyses accounting for the complex sampling design were used for primary analyses. The primary outcome was in-hospital mortality. Secondary outcomes included use of mechanical circulatory support (MCS) and mechanical ventilation. Propensity score-matched analyses were performed as sensitivity analyses. Results Among 254,691 weighted CS hospitalizations, 158,747 (62.3%) occurred in men and 95,896 (37.7%) in women. In survey-weighted analyses, women had higher in-hospital mortality in AMI-related CS (36.1% versus 31.3%; OR, 1.24; 95% CI, 1.19-1.28), HF-related CS (30.5% versus 25.8%; OR, 1.27; 95% CI, 1.23-1.30), and arrhythmia-related CS (37.3% versus 31.6%; OR, 1.28; 95% CI, 1.20-1.38). Women were less likely to receive ECMO (2.4% versus 2.9%), IABP/Impella (13.1% versus 18.9%), or any MCS (14.6% versus 20.4%), but were more likely to receive mechanical ventilation (44.9% versus 42.9%). In propensity-matched analyses, mortality differences were attenuated but persisted in AMI-related, HF-related, and valvular CS. Conclusions Sex differences in CS outcomes and treatment utilization are strongly phenotype dependent. Women experienced higher mortality in major CS phenotypes while receiving less advanced mechanical circulatory support. These findings support early recognition, rapid phenotype classification, and sex-conscious but non-delayed escalation strategies for women with CS.

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Early Hemodynamic Instability and Major Adverse Cardiovascular Events Among Acute Coronary Syndrome Patients Presenting to the Emergency Department: A Retrospective Cohort Analysis

Qi, Q.; Ong, M. E. H.; Radjamin, F. E. T.; Chan, M.; Han, L. S.

2026-05-30 cardiovascular medicine 10.64898/2026.05.27.26354184 medRxiv
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Acute coronary syndrome (ACS) remains a major contributor to cardiovascular mortality despite advances in emergency cardiovascular intervention and coronary revascularization strategies. This retrospective cohort study evaluated the association between early hemodynamic instability and major adverse cardiovascular events (MACE) among 1,248 ACS patients admitted between January 2023 and December 2025. Patients were categorized into stable and unstable groups based on early emergency department hemodynamic assessment including blood pressure, lactate level, Killip classification, vasopressor requirement, and cardiac output estimation. The primary outcome consisted of 30-day MACE including cardiovascular mortality, recurrent myocardial infarction, cardiogenic shock, ventricular arrhythmia, and urgent revascularization. A total of 372 patients (29.8%) demonstrated early hemodynamic instability and experienced significantly higher rates of cardiogenic shock, ventricular arrhythmia, mechanical ventilation, ICU admission, and 30-day mortality compared with stable patients. Multivariable regression analysis identified serum lactate >4 mmol/L (adjusted OR 3.42; 95% CI 2.10-5.11), systolic blood pressure <90 mmHg (adjusted OR 2.96; 95% CI 1.88-4.47), and left ventricular ejection fraction <35% (adjusted OR 2.71; 95% CI 1.77-4.09) as independent predictors of MACE. Early hemodynamic instability was strongly associated with poor short-term cardiovascular outcomes, suggesting that integrated emergency hemodynamic profiling may improve early risk stratification and facilitate timely cardiovascular intervention.

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Language-Related Disparities in History Documentation in Patients Admitted for Heart Failure

Gottlieb, E. R.; Mullan, I. D.; Celi, L. A. A.

2026-05-22 cardiovascular medicine 10.64898/2026.05.19.26353593 medRxiv
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Introduction Patients hospitalized with heart failure who do not speak English as their primary language face communication barriers, however the impact on documented History of Present Illness (HPI) and Review of Systems (ROS) has not been reported. Methods This retrospective cohort study was based on MIMIC-IV, an anonymized clinical database. Adult patients admitted to general medicine or cardiology services with heart failure (by DRG) were identified. Multivariable linear regression was used to assess for an association between language (English vs. non-English) and word counts for HPI+ROS and HPI word counts. Qualitative differences in texts were also analyzed using Claude Opus 4.6. Results In a cohort of 552 patients, non-English language (N = 81) was associated with a shorter HPI+ROS (coef. -33.387, 95% CI [-62.076, -4.697], p = 0.023) controlling for age (coef. -1.023, 95% CI [-1.817, -0.230], p = 0.012) and Elixhauser score (coef. 10.391, 95% CI [7.078, 13.705], p<0.001). Similar associations were found for HPI alone. Qualitative differences included less discussion of symptoms and timing of onset. Discussion HPI+ROS and HPI were more abbreviated when the primary documented language was not English. This has important implications for equitable care and the development of emerging translation and documentation technologies.

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Clinical, Aetiology and Temporal Trends of Hospitalised Heart Failure Patients in a Private Tertiary Hospital in Sierra Leone (2021-2025)

Russell, J. B. W.; Smith, M.; Alhassan, Y.; Coker, J. M.; Tejan, E. A.; Bharat, K.; Meena Kumari, M. K.; Mahdi, O. Z.; Lisk, D. R.

2026-06-08 cardiovascular medicine 10.64898/2026.06.06.26355075 medRxiv
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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.

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Prevalence, Genetics, and Imaging Characteristics of Patients with Mitral Valve Prolapse and Arrhythmogenic Right Ventricular Cardiomyopathy

Rich, A. H.; Tastet, L.; Cristin, L.; Jhawar, R.; Tang, J. J.; Scheinman, M.; Delling, F.

2026-05-19 cardiovascular medicine 10.64898/2026.05.14.26353246 medRxiv
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Background: Concomitant arrhythmogenic right ventricular cardiomyopathy (ARVC) and mitral valve prolapse (MVP) has only been described in case reports. Little is known about genetic and phenotypic characteristics of these patients. Objective: To describe the prevalence, genetics, and imaging characteristics of MVP in ARVC patients. Methods: We identified 111 definite ARVC cases through medical record review, arrhythmia/cardiomyopathy targeted gene panels, and contrast cardiac magnetic resonance data. MVP was diagnosed on echocardiography as mitral leaflet displacement greater than 2 mm above the annular plane in systole, with borderline MVP defined as less than or equal to 2 mm. Results: We found MVP/borderline MVP in 14% of ARVC patients. Cardiac arrest occurred in 20% of those with MVP/borderline MVP compared to 16% without valve abnormalities. Among 69 ARVC patients with identified genetic variants, PKP2 mutations were highly prevalent (64%), particularly in those with MVP (83%). Most MVPs had posterior prolapse (73%) and trace/mild mitral regurgitation (87%). None had mitral annular disjunction. ARVCs with MVP had higher LV mass (93 vs. 75 g/m2, p = 0.02) and a higher prevalence of LV wall motion abnormalities (27% vs. 5%, p = 0.02) compared to ARVCs without valve abnormalities. Conclusions: MVP is prevalent in ARVC and characterized by PKP2 variants in most cases. Typical features of arrhythmic MVP like bileaflet involvement and annular disjunction are rare in ARVC with MVP; features of arrhythmogenic left-sided cardiomyopathy (increased LV mass index and wall motion abnormalities) are more common. Further studies are needed to understand the role of MVP in arrhythmic risk stratification of ARVC.

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Outcomes of Atrial Fibrillation Catheter Ablation in Patients with Peripheral Artery Disease: A Nationwide Inpatient Sample Study

Nriagu, V. C.; Shakeri, S.; Nduka, T. C.; Ifeagwazi, P.-A.; Etuk, A.; Sorci, S.; Cunn, G.; Patel, R.; Raj, S.; Shani, J.; Odigie-Okon, E.

2026-05-25 cardiovascular medicine 10.64898/2026.05.22.26353913 medRxiv
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Background. Peripheral artery disease (PAD) may amplify procedural risk during atrial fibrillation (AF) catheter ablation, but dedicated evidence is lacking. We aimed to evaluate the association between PAD and in-hospital outcomes among adults undergoing AF ablation in the National Inpatient Sample (NIS). Methods. We identified inpatient AF ablation hospitalizations in the 2016 through 2020 National Inpatient Sample using ICD-10-PCS procedure codes and a concurrent AF diagnosis. PAD was identified from ICD-10-CM diagnosis codes used in prior claims-based PAD studies. Stabilized inverse probability of treatment weighting based on the propensity score was used to balance baseline differences. The primary outcome was in-hospital mortality. Fourteen secondary outcomes and 2 composite end points were prespecified. Results. Among 22,166 AF ablation hospitalizations, 899 (4.06%) involved patients with PAD. Compared with patients without PAD, those with PAD were older and had a substantially greater cardiovascular, renal, and smoking/tobacco comorbidity burden. In-hospital mortality did not differ significantly (1.39% vs 1.06%; aOR, 1.32; 95% CI, 0.66 - 2.64; P= 0.44). PAD was associated with higher odds of major bleeding (aOR, 1.62; 95% CI, 1.17 - 2.24; P = 0.004), vascular or access-site complications (aOR, 1.80; 95% CI, 1.04 - 3.12; P = 0.04), acute kidney injury (aOR, 1.31; 95% CI, 1.05 - 1.64; P = 0.02), and composite major adverse hospital events (aOR, 1.29; 95% CI, 1.05 - 1.59; P = 0.02). Total hospital charges were 13% higher (charge ratio, 1.13; 95% CI, 1.04 - 1.22; P = 0.003). Major bleeding, vascular/access-site complications, cardiac arrest, and composite major adverse in-hospital events remained elevated in sensitivity analysis. Conclusion. PAD was independently associated with higher bleeding risk, vascular or access-site complications, acute kidney injury, and composite major adverse hospital event during AF ablation, identifying a clinically relevant subgroup with elevated periprocedural risk.

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A prospective study of the METS-IR index to predict arrhythmia risk in middle-aged adults

Lu, Q.; Bi, W.; Cheng, Y.; Li, Y.; Tang, H.; Liu, L.-J.

2026-06-03 cardiovascular medicine 10.64898/2026.06.01.26354663 medRxiv
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Background: Higher METS-IR has been shown to be associated with a higher risk of major adverse cardiovascular events, but data are lacking regarding cardiac arrhythmias. Objectives: The aim of this study was to assess the association between METS-IR and atrial fibrillation/flutter, ventricular arrhythmia and bradyarrhythmia. Methods: Data from the Atherosclerosis Risk in Communities study spanning 1987 to 2013 was utilized for this analysis. METS-IR scores were assessed at baseline (1987-1989) and arrhythmia episodes were identified using ICD-9 codes. Multivariate-adjusted Cox proportional hazard models were constructed to evaluate the relationship between METS-IR and arrhythmia risk, with dose-response analyses conducted. In addition, we analyzed the predictive value of METS-IR for arrhythmias. Results: Over a mean follow-up of 21.9 years, 2493 cases of AF, 688 cases of bradyarrhythmia, and 1315 cases of ventricular arrhythmia were recorded. Each interquartile range increase in METS-IR was associated with a 49% higher risk of atrial fibrillation(P<0.001), 29% higher risk of bradyarrhythmia(P<0.001), and 42% higher risk of ventricular arrhythmia(P<0.001). After correction for relevant confounders, the METS-IR index was significantly and positively associated with the risk of new-onset atrial fibrillation, bradyarrhythmia, and ventricular arrhythmia (P overall<0.05, P for non-linearity>0.05). Most of the results of the subgroup analyses were not significantly different. The inclusion of METS-IR in the base model improves the predictive value of the risk of arrhythmogenesis. Conclusions: There is a significant association between METS-IR and increased risk of arrhythmias.

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Frozen elephant trunk repair in heritable thoracic aortic disease: Impact of genetic aortopathy on long-term outcomes - A multicenter analysis

Berger, T.; Peterss, S.; Pitts, L.; Kempfert, J.; Nucera, M.; Yildiz, M.; Holubec, T.; Haas, I.; Czerny, M.; Kreibich, M.; Kletzer, J.; Discher, P.; Bialczak, J.; Demal, T. J.; Detter, C.; Gasser, S.; Luehr, M.; Alokhina, A.; Tsagakis, K.; Dohle, D.-S.; Pfeiffer, P.; Radner, C.; Pichlmaier, M.; Goebel, N.; Rylski, B.; Arnold, Z.; Grabenwoeger, M.; Stelzmueller, M.-E.; Dumfarth, J.; Schoenhoff, F. S.; Brickwedel, J.

2026-06-10 cardiovascular medicine 10.64898/2026.06.09.26355316 medRxiv
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Aims This multicenter study aims to compare outcomes of total aortic arch replacement (TAR) using the frozen elephant trunk (FET) technique in patients with and without heritable thoracic aortic disease (HTAD) and to assess whether HTAD influences postprocedural adverse aortic events (AAEs). Methods From 06/2007 to 05/2024, aortic databases from 13 European centers were screened for HTAD patients undergoing TAR with FET. All consecutive dissection and aneurysm non-HTAD patients from the four core centers served as comparator. The primary outcome was AAE, a composite of diameter progression, distal stent graft induced new entry (dSINE), malperfusion, rupture and pseudoaneurysm at 5 years after FET implantation. Results Of 2739 FET patients, 196 (7.2%) were diagnosed with HTAD. The control group consisted of 867 non-HTAD FET patients. Marfan syndrome was the most common condition (72%), followed by Loeys-Dietz syndrome (11%), vascular Ehlers-Danlos syndrome (5.6%) and Turner syndrome (2.0%). Seventeen (8.8%) patients were diagnosed with ns-HTAD. At 5 years 46 (24%) AAEs occurred in the HTAD group, 169 (20%) in the non-HTAD group (p=0.2). Diameter progression was the most common event (10% vs. 12%; p=0.6), followed by dSINE (5.8% vs. 4.5%; p=0.5), malperfusion (4.2% vs. 3.3%; p=0.5), rupture (2.1% vs. 0.7%; p=0.09) and pseudoaneurysm (0.5% vs. 0.2%; p=0.5). Conclusions The FET technique appears safe and effective for acute and chronic aortic disease in HTAD patients, with outcomes comparable to non-HTAD cases and no increase in graft-related complications, challenging traditional concerns about stent graft use in genetically mediated aortic disease.

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Total Beating-Heart Aortic Arch Repair Without Cardiac Arrest: A Proof-of-Concept Study

Wisniewski, K.; Dell'Aquila, A. M.; Carranza Porras, V.; Dinkel, F.; Martens, S.; Rukosujew, A.

2026-06-01 cardiovascular medicine 10.64898/2026.05.28.26354390 medRxiv
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Background Cardioplegic arrest during complex aortic arch repair imposes prolonged global myocardial ischaemia, which may contribute to postoperative low cardiac output syndrome (LCOS) and mortality. Whether cardioplegic arrest can be entirely avoided -- performing the complete procedure on a continuously perfused, beating heart -- has not previously been evaluated in a clinical series. Methods and Results Between November 2017 and January 2026, 29 consecutive patients underwent total beating-heart aortic arch repair without any cardioplegic arrest at a single centre. Continuous antegrade myocardial perfusion (warm blood, 34{degrees}C, 300-400 mL/min, perfusion pressure 60-80 mmHg) was delivered via an aortic root needle vent throughout each procedure. Two variants were employed: axillary cannulation with selective antegrade cerebral perfusion (n = 24, 82.8%), and direct aortic cannulation with extra-anatomical left carotid bypass for distal Zone 2 pathology (n = 5, 17.2%). Mean age was 55.4 {+/-} 13.6 years; 41.4% presented with aortic dissection (B/non-A-non-B). No patient required conversion to cardioplegic arrest. Perioperative myocardial infarction and LCOS occurred in none of the patients. Median peak CK-MB was 44.0 U/L. Thirty-day mortality was 10.3% (n = 3); all deaths were due to respiratory failure or visceral ischaemia complicating acute type B dissection. Conclusions Total beating-heart aortic arch repair without cardioplegic arrest is technically feasible and clinically safe in appropriately selected patients and is associated with the complete absence of perioperative myocardial infarction and LCOS across a heterogeneous, high-risk cohort. These findings support prospective, multicentre evaluation of no-arrest myocardial protection as a strategy to reduce the cardiac morbidity of complex arch surgery.

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Acute hemodynamic effects after Impella 5.5 in cardiogenic shock and association with clinical outcomes

Daso, G.; Gupta, P.; Locascio, J. L.; Ton, V.-K.; Coglianese, E.; Drezek, K.; Wald, J. E.; Michel, E.; D'Alessandro, D. A.; Yang, B. Q.

2026-05-21 cardiovascular medicine 10.64898/2026.05.19.26353572 medRxiv
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Cardiogenic shock (CS) is associated with high short-term mortality and the use of temporary mechanical circulatory support (tMCS) devices, especially left-sided microaxial flow pumps (Impella, Abiomed), has increased in recent years. However, few studies have investigated tMCS's effect on right ventricular-pulmonary artery (RV-PA) hemodynamics and its impact on clinical outcomes. We retrospectively analyzed all adult patients implanted with Impella 5.5 at our institution with acute myocardial infarction or acute decompensated heart failure-induced CS between 2019 to 2023. We found that Impella 5.5 led to an early improvement in RV-PA hemodynamics, even in patients with poor baseline RV function. In addition, we found that RV function itself did not predict death, post-heart transplant right ventricular-primary graft dysfunction, or post-left ventricular assist device severe RV failure. However, an increase in right atrial:pulmonary capillary wedge pressure ratio (RA/PCWP) despite tMCS support was a powerful prognosticator. Our study sheds important insight into anticipated hemodynamic changes after Impella 5.5 placement, supports the use of early tMCS even in patients with marginal RV function in the setting of left heart disease, and highlights the importance of serial assessment of RA/PCWP as a key determinant of CS outcomes.

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Should Coronary Revascularization Precede Transcatheter Aortic Valve Replacement? A Meta-Analysis of Randomized Controlled Trials

Soliman, D.; abdelmalek, J.; Puchongmart, C.; Sodsri, T.; Sivakumar, N.; Sly, Z.

2026-05-20 cardiovascular medicine 10.64898/2026.05.15.26353318 medRxiv
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Background: In severe aortic stenosis patients undergoing TAVR, whether coexisting coronary disease prompts revascularization and its optimal timing remain unclear. Aim: To evaluate the efficacy and safety of PCI before TAVR compared to deferred PCI in patients with severe aortic stenosis and concomitant coronary artery disease. Methods: We performed a meta-analysis of RCTs. PubMed, Embase, Scopus, CENTRAL, and Web of Science were searched for RCTs comparing PCI before TAVR versus no PCI. HRs with 95% CIs were pooled using random-effects models. Results: Three RCTs (ACTIVATION, NOTION 3, PRO-TAVI) enrolling 1,156 patients (579 PCI, 577 no PCI) were included. Routine PCI before TAVR did not reduce all-cause mortality (HR 0.88, 95% CI 0.67 to 1.17; p=0.38) or cardiovascular death (HR 0.77, 95% CI 0.49 to 1.19; p=0.23). PCI significantly reduced any revascularization (HR 0.24, 95% CI 0.06 to 0.86; p=0.029), and urgent revascularization (HR 0.33, 95% CI 0.12 to 0.87; p=0.025). MI was not significantly reduced with PCI (HR 0.84, 95% CI 0.44 to 1.59; p = 0.59). Stroke showed a borderline trend favoring PCI (HR 0.69, 95% CI 0.46 to 1.04; p=0.073). PCI significantly increased any bleeding (HR 1.96, 95% CI 1.28 to 3.0; p=0.002) and major bleeding (HR 1.88, 95% CI 1.07 to 3.31, p=0.027). Neither AKI nor rehospitalization differed significantly between groups. Leave-one-out sensitivity analyses confirmed the stability of mortality, stroke, and bleeding estimates. Conclusions: Routine PCI before TAVR does not reduce mortality. It lowers urgent revascularization and trends toward less stroke but nearly doubles bleeding. Findings support selective, individualized PCI rather than routine revascularization before TAVR.

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Resolving Diagnostic Discordance in Group 2 Pulmonary Hypertension Through Staged Physiologic Testing: Insights From PVDOMICS

Rischard, F.; PVCOMICS Study Group, ; Mendoza, M.; Insel, M.; Beck, G.; Erzurum, S.; Frantz, R. P.; Finet, J. E.; Hassoun, P.; Hemnes, A. R.; Hill, N. S.; Horn, E. M.; Leopold, J. A.; Mathai, S. C.; Mehra, R.; Reddy, Y. N. V.; Rosenzweig, E. B.; Systrom, D. M.; Tang, W. H. W.; Waxman, A.; Borlaug, B. A.

2026-06-10 cardiovascular medicine 10.64898/2026.06.04.26354961 medRxiv
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Background World Symposium on Pulmonary Hypertension (WSPH) Group 2 pulmonary hypertension (PH) is a clinically integrated phenotype attributed to left heart disease, whereas pre- versus post-capillary classification is operationalized primarily by pulmonary capillary wedge pressure (PCWP). Although current recommendations emphasize contextual interpretation and provocative testing for intermediate PCWP values, the relationship between PCWP-based classification and underlying phenotype has not been systematically evaluated. We aim to quantify phenotype-hemodynamic discordance across the PCWP spectrum and evaluate a staged physiology-guided framework incorporating inhaled nitric oxide (iNO), ventricular geometry, and provocative testing. Methods We studied 1,032 participants from the NHLBI-sponsored PVDOMICS cohort with multidisciplinary adjudicated phenotypes integrating clinical, imaging, physiologic, and hemodynamic data. Stage-specific PCWP thresholds classified pre- versus post-capillary physiology at rest, during iNO, and during provocation (fluid challenge or invasive cardiopulmonary exercise testing [iCPET]). Echocardiographic right ventricular-to-left ventricular (RV/LV) ratio was evaluated as a marker of ventricular interdependence. Restricted cubic spline and staged concordance analyses defined certainty-based PCWP ranges and incremental diagnostic yield. Results Adjudicated Group 2 phenotype was present in 37.0% of participants. Resting PCWP demonstrated good discrimination (AUC 0.86), but substantial bidirectional phenotype-hemodynamic discordance persisted across intermediate PCWP ranges. At a resting PCWP of 12 mmHg, 25% of participants classified as pre-capillary had adjudicated Group 2 PH, whereas at 18 mmHg, 35% classified as post-capillary remained discordant non-Group 2. Concordance did not approach 90% until PCWP values were <9 mmHg or >24 mmHg. Dynamic testing incrementally improved concordance within these overlap zones. Nearly half of adjudicated Group 2 PH participants (46.5%) were not identified by resting PCWP alone; incorporation of iNO and provocative testing increased cumulative Group 2 identification by 63.4% and improved sensitivity from 79.9% to 83.7%. Model discrimination improved from an AUC of 0.863 to 0.908 (likelihood-ratio P<0.001). iNO increased PCWP in discordant Pre/G2 participants, unmasking latent left-sided limitation, while lowering PCWP in discordant Post/NonG2 participants, consistent with ventricular interdependence. RV/LV ratio [&ge;]0.94 reduced discordant Post/NonG2 classification by 70.5%, and incorporation of PCWP/cardiac output slope improved physiologic specificity during exercise. Conclusions Group 2 PH is a dynamic, load-dependent phenotype inadequately characterized by resting PCWP alone. Intermediate PCWP values represent continuous probabilities of bidirectional discordance rather than discrete diagnostic states. A staged physiology-guided approach integrating iNO, ventricular geometry, and provocative testing improves concordance between hemodynamic classification and clinically integrated phenotype assignment.

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Baseline substrate and response after cardiac resynchronization therapy in non-left bundle branch block heart failure

Liang, Y.; Zhu, Y.; Wang, R.; Gu, R.; Sang, C.; Bao, Z.; Sun, L.; Xia, T.; Xiang, G.

2026-05-19 cardiovascular medicine 10.64898/2026.05.14.26353260 medRxiv
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Background: Response to cardiac resynchronization therapy (CRT) is heterogeneous in patients with non-left bundle branch block (non-LBBB) heart failure. Whether pre-implant substrate or procedural characteristics provide the more stable framework for predicting 1-year echocardiographic response remains uncertain. Methods: We retrospectively analyzed 120 non-LBBB patients undergoing CRT. The primary logistic model included left ventricular end-diastolic diameter (LVEDD), left ventricular ejection fraction (LVEF), left atrial diameter, log-transformed NT-proBNP, baseline QRS duration, fragmented QRS burden across V1?V6 leads, and pulmonary artery pressure. Missing predictor data were handled using multiple imputation with 20 datasets. Model performance was assessed using bootstrap internal validation and recalibration. A prespecified procedural extension added pacing strategy, posterolateral biventricular left ventricular lead location, left ventricular pacing threshold, and right ventricular lead position. Exploratory phenotyping and sensitivity analyses were performed. Results: Echocardiographic response occurred in 51 patients (42.5%). LVEDD (OR, 0.899 [95% CI, 0.826?0.978]; P=0.013) and LVEF (OR, 1.068 [95% CI, 1.000?1.140]; P=0.050) were the most informative predictors. The primary model showed apparent AUC 0.811 and Brier score 0.173, with optimism-corrected AUC 0.766 and calibration slope 0.765. Procedural extension showed no retained incremental value after validation. Exploratory phenotyping identified three response patterns with moderate stability. Conclusions: In non-LBBB CRT, baseline structural, biomarker, and electrocardiographic substrate provided the most stable framework for predicting 1-year echocardiographic response. Procedural variables added limited retained value, suggesting that pacing strategy should be interpreted alongside baseline substrate.