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The American Journal of Cardiology

Elsevier BV

Preprints posted in the last 7 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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CPAP/BiPAP Compliance Improves Survival in LVAD Recipients with Obstructive Sleep Apnea

Carlquist, J.; Scott, S. S.; Wright, J. C.; Jianing, M.; Peng, J.; Mokadam, N. A.; Whitson, B. A.; Smith, S.

2026-04-22 cardiovascular medicine 10.64898/2026.04.20.26351345 medRxiv
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PurposeObstructive sleep apnea (OSA) is a common comorbidity in heart failure (HF) patients with prevalence increasing as HF severity worsens. While CPAP/BiPAP has been shown to reduce disease burden and mortality in the general HF population, it is unclear whether these benefits extend to patients with left ventricular assist devices (LVADs). We sought to determine whether OSA affects long-term survival in newly implanted LVAD patients and whether CPAP/BiPAP treatment confers mortality benefits. MethodsThis single-center retrospective study included patients who underwent LVAD implantation between January 2007 and February 2022. Recipients were stratified by OSA status (OSA vs No-OSA), and those with OSA were further categorized based on CPAP/BiPAP compliance. Comparative statistics and Kaplan-Meier survival analyses were performed, with log-rank tests used to compare groups and assess survival differences. A Cox proportional hazards model was conducted to evaluate the association between risk factors and survival among patients with OSA and No-OSA. ResultsBefore LVAD implantation, patients with OSA had higher body mass index, hypertension, and a higher rate of implantable cardioverter-defibrillator placement than those without OSA. OSA was not associated with increased postoperative complications. Although survival did not differ significantly between OSA and No-OSA patients (p=0.33), CPAP/BiPAP-compliant OSA patients had significantly better survival than noncompliant patients (p=0.0099). ConclusionsLVAD patients with OSA who consistently use CPAP/BiPAP have better survival than those who do not. CPAP/BiPAP is a simple, low-risk treatment that can reduce mortality in this population. Therefore, increased perioperative screening for OSA should be considered for patients receiving LVADs. Multicenter studies are needed to confirm our findings further.

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Interleukin-1 Receptor Antagonist Levels In Patients With Heart Failure And Reduced Ejection Fraction Treated With Anakinra

Kelly, J.; Mezzaroma, E.; Roscioni, A.; McSkimming, C.; Mauro, A.; Narayan, P.; Golino, M.; Trankle, C.; Canada, J. M.; Toldo, S.; Van Tassell, B. W.; Abbate, A.

2026-04-25 cardiovascular medicine 10.64898/2026.04.17.26351024 medRxiv
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Background. Patients with heart failure and reduced ejection fraction (HFrEF) commonly show signs of systemic inflammation. Interleukin-1 (IL-1) is a pro-inflammatory cytokine, known to modulate cardiac function. We aimed to determine the effects of treatment with anakinra, recombinant IL-1 receptor antagonist (IL-1Ra), on plasma IL-1Ra levels. Methods. We measured IL-1Ra levels at baseline and longest available follow-up to 24 weeks in 63 patients (44 males, 40 self-identified Black-Americans) with recent hospitalization for HFrEF, and systemic inflammation (C reactive protein [CRP] levels >2 mg/L) who were assigned to anakinra (N=42 [66.7%]) or placebo (N=21 [33.3%]) as part of the REDHART2 clinical trial (NCT0014686). Cardiorespiratory fitness was measured as peak oxygen consumption (peak VO2). Results. Baseline plasma IL-1Ra levels were 380 pg/ml (290 to 1046). On-treatment IL-1Ra levels were significantly higher in the patients treated with anakinra vs placebo (3,994 pg/ml [3,372 to 5,000] vs 492 pg/ml [304 to 1370], P<0.001). The longest available follow-up was 6 weeks in 10 patients (15.9%), 12 weeks in 12 patients (19%) and 24 weeks in 41 patients (65.1%). On-treatment IL-1Ra levels and interval change in IL-1Ra showed a modest inverse correlation with on-treatment CRP levels (R=-0.269, P=0.033 and R=-0.355, P=0.004, respectively) and no statistically significant correlations with peak VO2 values (P>0.05). Conclusions. Patients with recently decompensated HFrEF and systemic inflammation treated with recombinant IL-1Ra, anakinra, have a significant several-fold increase in plasma IL-1Ra levels. On-treatment IL-1Ra levels however show only a modest correlation with CRP levels and not with peak VO2.

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Comparison of the Expert Guidelines With Artificial Intelligence-Driven Echocardiographic Assessment of Diastolic Function

Tokodi, M.; Kagiyama, N.; Pandey, A.; Nakamura, Y.; Akama, Y.; Takamatsu, S.; Toki, M.; Kitai, T.; Okada, T.; Lam, C. S.; Yanamala, N.; Sengupta, P.

2026-04-24 cardiovascular medicine 10.64898/2026.04.23.26350072 medRxiv
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Backgound: Accurate assessment of diastolic function and left ventricular (LV) filling pressure is central to heart failure diagnosis and risk stratification. Contemporary guideline algorithms rely on complex parameters that are not consistently available in routine clinical practice. Objective: To compare the diagnostic and prognostic performance of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) and 2025 ASE guidelines with a deep learning model based on routinely acquired echocardiographic variables. Methods: This study evaluated the guideline-based algorithms and a deep learning model in participants from the Atherosclerosis Risk in Communities (ARIC) cohort (n=5450) for prognostication and two invasive hemodynamic validation cohorts from the United States (n=83) and Japan (n=130) for detection of elevated left ventricular filling pressure. Results: In the ARIC cohort, the deep learning model demonstrated superior prognostic performance compared with the 2016 and 2025 guidelines (C-index: 0.676 vs. 0.638 and 0.602, respectively; both p<0.001). Similar findings were observed among participants with preserved ejection fraction (C-index: 0.660 vs. 0.628 and 0.590; both p<0.001), with improved performance compared with the H2FPEF score (C-index: 0.660 vs. 0.607; p<0.001). In the US hemodynamic validation cohort, the deep learning model showed higher diagnostic performance than the 2025 guidelines (AUC: 0.879 vs. 0.822; p=0.041) and similar performance compared with the 2016 guidelines (AUC: 0.879 vs. 0.812; p=0.138). In the Japanese hemodynamic validation cohort, the deep learning model outperformed both guidelines (AUC: 0.816 vs. 0.634 and 0.694; both p<0.05). Conclusions: A deep learning model leveraging routinely available echocardiographic parameters demonstrated improved diagnostic and prognostic performance compared with contemporary guideline-based approaches, potentially offering a scalable alternative for assessing diastolic function and left ventricular filling pressures.

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Antecedent autonomic symptoms predict contemporary autonomic symptom burden and reduced health-related quality of life after spontaneous coronary artery dissection

Seeley, M.-C.; Tran, D. X. A.; Marathe, J. A.; Sharma, S.; Wilson, G.; Atkins, S.; Lau, D. H.; Gallagher, C.; Psaltis, P. J.

2026-04-23 cardiovascular medicine 10.64898/2026.04.21.26351434 medRxiv
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Introduction: Spontaneous coronary artery dissection (SCAD) is frequently accompanied by persistent symptoms of unknown pathogenesis after the index event. Autonomic dysfunction is a plausible mechanism for these but has not been systematically characterized. We quantified antecedent and contemporary autonomic symptoms in survivors of SCAD and examined their associations with cardiac and extra-cardiac symptoms and health-related quality of life. Methods: This cross-sectional study recruited 227 volunteers from multiple countries with a self-reported history of SCAD. Participants completed validated patient-reported measures, including the Composite Autonomic Symptom Score-31 (COMPASS-31), Anxiety Sensitivity Index-3 (ASI-3), and EuroQol-5 Dimension-5L (EQ-5D-5L). They also completed an internally derived retrospective autonomic predisposition score assessing symptoms during adolescence and early adulthood. Results: Participants were predominantly female (97.8%), median age 53 (47-58) years, and were surveyed a median of 3 (1-5) years after their index SCAD event. 21.6% reported SCAD recurrence. Moderate autonomic symptom burden (COMPASS-31 20) was present in 56.4% and severe burden (40) in 16.3%. History of antecedent autonomic symptoms was the strongest independent predictor of contemporary autonomic symptom burden after adjustment for demographic and clinical covariates (=0.514; P <0.001). Greater autonomic symptom burden independently predicted lower EQ-5D health utility (=0.150; P=0.029) and was associated with the ASI-3 physical concerns (=0.232; P <0.001), but not social concerns domain. Autonomic symptoms were not associated with SCAD recurrence. Conclusion: Symptoms of autonomic dysregulation are common in survivors of SCAD and are associated with reduced quality of life. Their association with antecedent dysautonomic features during adolescence and early adulthood suggests a longstanding predisposition, the significance of which warrants further evaluation.

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Persistent Atrial Myopathy Despite Ventricular Recovery: Prognostic Significance of Discordant LV-LA Strain Patterns in HFrEF

Park, J.; Hwang, I.-C.; Kim, H.-K.; Bae, N. Y.; Lim, J.; Kwak, S.; Bak, M.; Choi, H.-M.; Park, J.-B.; Yoon, Y. E.; Lee, S. P.; Kim, Y.-J.; Cho, G.-Y.

2026-04-23 cardiovascular medicine 10.64898/2026.04.22.26351480 medRxiv
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Aims: Assessment of treatment response in HFrEF has largely relied on left ventricular (LV)-centric parameters, yet the left atrium (LA) plays a central role in modulating LV filling and reflects the cumulative hemodynamic burden. Whether discordant recovery between LV and LA function carries distinct prognostic implications in patients treated with ARNI-based therapy remains unknown. Methods and results: From the multicenter STRATS-HF-ARNI registry, 1,182 patients with HFrEF who underwent serial echocardiography at baseline and one-year follow-up were included. Patients were classified into four strain recovery phenotypes according to the direction of change in LVGLS and LASr at one year: Group A, concordant recovery (57.4%); Group B, discordant atrial non-recovery (11.2%); Group C, discordant ventricular non-recovery (15.6%); and Group D, concordant non-recovery (16.0%). Clinical outcomes included all-cause mortality, cardiovascular mortality, and HF hospitalization. Despite achieving LV functional improvement, Group B exhibited persistent LASr deterioration, accompanied by less favorable hemodynamic trajectories compared with Group A. On multivariable Cox regression, Group B was associated with significantly higher risks of all-cause mortality (adjusted hazard ratio [aHR] 3.53, 95% confidence interval [CI] 1.60-7.79) and cardiovascular mortality (aHR 5.68, 95% CI 1.91-16.92), comparable to Group D. Group C demonstrated higher HF hospitalization risk (aHR 2.25, 95% CI 1.31-3.86). The adverse prognostic impact of discordant atrial non-recovery was consistently observed across subgroups stratified by baseline LVGLS and LASr levels. Conclusion: In HFrEF patients treated with ARNI-based therapy, persistent LA dysfunction despite LV functional improvement identifies a high-risk phenotype comparable to concordant non-recovery. These findings suggest that concurrent assessment of LV and LA strain may provide incremental prognostic value beyond LV-centric metrics alone.

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Central Adiposity And Infective Endocarditis: A Cohort Study of UK Biobank Participants

Song, W.; Zhang, J.; Zhipeng, W.; Sun, P.; Ke, Z.; Chenzhen, X.; chuanjie, Y.; Zhang, Y.; Li, L.; He, L.; Yu, J.; Lai, Y.; Cui, H.; Ren, C.

2026-04-24 cardiovascular medicine 10.64898/2026.04.22.26351534 medRxiv
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Abstract Aims: While traditional anthropometric indices are established cardiovascular predictors, their prognostic value for incident infective endocarditis (IE) remains undefined. Methods: We included 386,859 participants (mean age 57.0 years; 52.9% female) from the UK Biobank between 2006 and 2010 with standardized baseline data on BMI, waist circumference (WC), waist-to-height ratio (WhtR), and the triglyceride-glucose (TyG) index.Multivariable Cox proportional hazard models with restricted cubic splines were used to estimate the hazard ratio (HR) of these indices, adjusting for demographic and clinical risk factors. Results: Over 16.87 median years (25th, 16.02; 75th, 17.60 percentile) of follow-up, there were a total of 1,124 incident IE events. During the follow-up period, 38,342 total deaths were recorded, of which 8,524 were cardiovascular disease (CVD)-related.Overall, compared to individuals with normal weight and baseline metabolic indices, those in the fourth quartile of WC, WHtR, and TyG index exhibited the highest risk of incident IE. Compared to other metabolic indices, WC (HR = 1.53, 95% CI 1.23?1.90,P < 0.001) and WHtR (HR = 1.46, 95% CI 1.20?1.78,P < 0.001) demonstrated higher relative increases in risk associated with IE. Furthermore, the risk of IE was significantly elevated among the younger population with abdominal obesity and concomitant diabetes. However, no significant increase in IE risk was observed among participants with pre-existing valvular heart disease (P = 0.796). Conclusion: Compared with BMI, higher WC and WHtR were robustly associated with increased risk of IE, even after adjusting for traditional risk factors. Furthermore, the risk of IE was markedly elevated among younger individuals with abdominal obesity and diabetes.

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Addition of Bupropion or Varenicline to Nicotine Replacement Therapy After Acute Coronary Syndrome: A Propensity-Matched Real-World Analysis

Qadeer, A.; Gohar, N.; Maniyar, P.; Shafi, N.; Juarez, L. M.; Mortada, I.; Pack, Q. R.; Jneid, H.; Gaalema, D. E.

2026-04-23 cardiovascular medicine 10.64898/2026.04.21.26351432 medRxiv
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Introduction: Smoking cessation after acute coronary syndrome (ACS) is a Class I recommendation, yet prescription pharmacotherapy use remains low and its real-world cardiovascular effectiveness when added to nicotine replacement therapy (NRT) is poorly characterized. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Network (67 healthcare organizations). Adults hospitalized with ACS who received NRT within one month, serving as a proxy for active smoking status, were identified. Two co-primary propensity-matched (1:1, 50 covariates, caliper 0.10 SD) comparisons evaluated bupropion + NRT and varenicline + NRT individually versus NRT alone; a supportive analysis evaluated combined pharmacotherapy versus NRT alone. All-cause mortality was the primary endpoint. Secondary outcomes included MACE, heart failure exacerbations, major bleeding, TIA/stroke, emergency rehospitalizations, and cardiac rehabilitation utilization, assessed at 6 months and 1 year via Kaplan-Meier analysis. Hazard ratios (HRs) greater than 1.0 indicate higher hazard in the NRT-only group. Results: After matching, the combined analysis comprised 8,574 pairs, the bupropion analysis 4,654 pairs, and the varenicline analysis 2,126 pairs. At 1 year, the combined pharmacotherapy group had significantly lower all-cause mortality (HR 1.26, 95% CI 1.16-1.37), MACE (HR 1.16, 95% CI 1.12-1.21), heart failure exacerbations (HR 1.16, 95% CI 1.08-1.25), major bleeding (HR 1.18, 95% CI 1.08-1.28), and greater cardiac rehabilitation utilization (HR 0.82, 95% CI 0.74-0.92; all p < 0.001). TIA/stroke did not differ significantly. Six-month results were consistent. Both varenicline and bupropion individually showed lower mortality and MACE. A urinary tract infection falsification endpoint showed no between-group differences, supporting matching validity. The pharmacotherapy group had higher rates of new-onset depression, driven predominantly by bupropion recipients. Conclusions: In this propensity-matched real-world analysis, adding prescription smoking cessation pharmacotherapy to NRT after ACS was associated with lower mortality and fewer adverse cardiovascular events, supporting broader integration into post-ACS care pathways.

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Beyond Doppler: Scalable AI Detection of LVOT Obstruction in HCM

Crystal, O.; Farina, J. M. M.; Scalia, I. G.; Ayoub, C.; Park, H.-B.; Kim, K. A.; Arsanjani, R.; Lester, S. J.; Banerjee, I.

2026-04-20 cardiovascular medicine 10.64898/2026.04.17.26351151 medRxiv
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BackgroundAccurate assessment of left ventricular outflow tract (LVOT) gradients is critical for hypertrophic cardiomyopathy (HCM) management, yet Doppler-based measurements are technically demanding and require expertise. ObjectiveTo develop a multi-view deep learning model capable of classifying LVOT obstruction (> 20mmHg) using routine 2D echocardiographic windows without reliance on Doppler imaging. MethodsWe trained and externally validated a cross-attention-based video-to-video fusion framework that integrated EchoPrime-derived video representations from three standard transthoracic echocardiographic views to classify LVOT gradients. ResultsTraining was performed on a derivation cohort (N = 1833) from a tertiary care system in the United States, with model performance evaluated on an internal held-out test set (N = 275) and a Korean external validation cohort (N = 46). Single-view baselines showed limited discrimination (external AUROCs 0.47-0.70). Conversely, domain-specific foundational model (EchoPrime) achieved superior single-view performance (AUROCs 0.75-0.80 internal; 0.79-0.83 external), highlighting the importance of echo-specific pretraining and temporal modeling. The proposed multi-view fusion further enhanced predictive performance, with the late fusion model reaching an AUROC of 0.84 on the external cohort with significant population-shift. ConclusionsThese results suggest LVOT physiology is encoded in routine 2D imaging and can be leveraged for clinically relevant gradient classification without Doppler input- proposed AI-guided strategy demonstrates substantial cost savings compared with the screen-all approach. By integrating complementary spatial-temporal information across multiple views, our approach generalizes robustly across populations and may enable real-time decision support, extend LVOT assessment to portable or resource-limited settings, and complement Doppler-based evaluation for longitudinal HCM management.

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Echocardiographic characterization and markers of cardiovascular risk in adults with sickle cell disease in a Colombian tertiary referral centre: a cross-sectional study

Arrieta-Mendoza, M. E.; Barbosa-Balaguera, S.; Betancourt, J. R.; Ayala-Zapata, S.; Messu-Llanos, C. D.; Rosales-Melo, J. P.; Andrade-Hoyos, D. F.; Herrera-Escandon, A.; Aguilar-Molina, O. E.

2026-04-20 cardiovascular medicine 10.64898/2026.04.16.26351071 medRxiv
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Sickle cell disease (SCD) is associated with substantial cardiovascular morbidity, but echocardiographic data from Latin American populations remain scarce. We aimed to characterise the structural, functional, and haemodynamic echocardiographic profile of adults with SCD attending a tertiary referral centre in Cali, Colombia. We conducted an observational, cross-sectional study based on systematic review of medical records and transthoracic echocardiography reports of consecutive adult patients ([&ge;]18 years) with confirmed SCD evaluated between January 2022 and December 2024. Patients with complex congenital heart disease, severe valvular disease of unrelated aetiology, pregnancy, or echocardiograms of insufficient quality were excluded. Of 669 patients screened, 57 met inclusion criteria. Reporting followed STROBE recommendations. The median age was 24 years (interquartile range [IQR] 21-32) and 59.6% were female; the SS genotype was the most frequent (76.4%) and 71.4% were on hydroxyurea. Median haemoglobin was 10.2 g/dL (IQR 9.3-11.4) and median NT-proBNP 491 pg/mL (IQR 98-1290). Most patients had preserved left ventricular dimensions and systolic function (median ejection fraction 63%, IQR 57-66.5; mean global longitudinal strain -18.9% {+/-} 2.9). Right ventricular function was preserved (mean tricuspid annular plane systolic excursion 25.4 {+/-} 4.6 mm). Left ventricular geometry was normal in 42.1%, with concentric remodelling in 24.6%, concentric hypertrophy in 21.1%, and eccentric hypertrophy in 12.3%. Diastolic function was normal in 71.4%. Valvular disease, when present, was predominantly mild. Tricuspid regurgitation velocity exceeded 2.5 m/s in 29.8% of patients and exceeded 3.0 m/s in 10.5%, identifying a substantial subgroup at intermediate-to-high probability of pulmonary hypertension. In this Colombian cohort of relatively young adults with SCD, cardiac structure and biventricular function were largely preserved, but nearly one-third of patients had echocardiographic findings suggestive of pulmonary hypertension. These findings support the routine use of transthoracic echocardiography as an accessible tool for early cardiovascular risk stratification in adults with SCD in low- and middle-income settings.

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Improving Care by FAster risk-STratification through use of high sensitivity point-of-care troponin in patients presenting with possible acute coronary syndrome in the EmeRgency department (ICare-FASTER): a stepped-wedge cluster randomized trial

Than, M.; Pickering, J. W.; Joyce, L. R.; Buchan, V. A.; Florkowski, C. M.; Mills, N. L.; Hamill, L.; Prystowsky, J.; Harger, S.; Reed, M.; Bayless, J.; Feberwee, A.; Attenburrow, T.; Norman, T.; Welfare, O.; Heiden, T.; Kavsak, P.; Jaffe, A. S.; apple, f.; Peacock, W. F.; Cullen, L.; Aldous, S.; Richards, A. M.; Lacey, C.; Troughton, R.; Frampton, C.; Body, R.; Mueller, C.; Lord, S. J.; George, P. M.; Devlin, G.

2026-04-23 cardiovascular medicine 10.64898/2026.04.21.26351433 medRxiv
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BACKGROUND Point-of-care (POC) high-sensitivity cardiac troponin (hs-cTn) testing has the potential to expedite decision-making and reduce emergency department (ED) length of stay for patients presenting with possible myocardial infarction (MI) by ensuring that results are consistently available when looked for by clinicians. We assessed the real-life effectiveness and safety of implementing POC hs-cTn testing in the ED. METHODS We conducted a pragmatic, stepped-wedge cluster randomized trial. The control arm was usual care with an accelerated diagnostic pathway utilizing a single-sample rule-out step with a central laboratory hs-cTn assay. The intervention arm used the same pathway with a POC hs-cTnI. The primary effectiveness outcome was ED length of stay assessed using a generalized linear mixed model, and the safety outcome was 30-day MI or cardiac death. RESULTS Six sites participated with 59,980 ED presentations (44,747 individuals, 61{+/-}19 years, 49.5% female) from February 2023 to January 2025, in which 31,392 presentations were during the intervention arm. After adjustment for co-variates associated with length of stay, the intervention reduced length of stay by 13% (95% confidence intervals [CI], 9 to 16%. P<0.001), corresponding to a reduction of 47 minutes (95%CI, 33 to 61 minutes) from a mean length of stay in the control arm of 376 minutes. The 30-day MI or cardiac death rate was similar in the control and intervention arms (0.39% and 0.39% respectively, P=0.54). CONCLUSIONS Implementation of whole-blood hs-cTnI testing at the POC into an accelerated diagnostic pathway was safe and reduced length of stay in the ED compared with laboratory testing.

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Missed Opportunities for Stroke Prevention in Hypertensive Patients: A Retrospective Case-Control Study

Yang, H.; Liu, Y.; Kim, C.; Huang, C.; Sawano, M.; Young, P.; McPadden, J.; Anderson, M.; Burrows, J. S.; Krumholz, H. M.; Brush, J. E.; Lu, Y.

2026-04-22 cardiovascular medicine 10.64898/2026.04.21.26351407 medRxiv
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BackgroundHypertension is the leading modifiable risk factor for ischemic stroke, yet the adequacy of preventative hypertension care in routine clinical practice remains suboptimal. Whether gaps in hypertension management represent missed opportunities for stroke prevention remains unclear. ObjectiveTo evaluate the association between hypertension care delivery and the risk of incident ischemic stroke. MethodsWe conducted a retrospective, matched, nested case-control study among adults with hypertension using electronic health record data from a large regional health system (2010-2024). Patients with a first-ever ischemic stroke were matched 1:2 to controls on age, sex, race and ethnicity, and calendar time. Three care metrics were assessed during follow-up: (1) outpatient visits with blood pressure (BP) measurement per year; (2) number of antihypertensive medication ingredients; and (3) medication intensification score. Conditional logistic regression estimated adjusted odds ratios (aORs). ResultsThe study included 13,476 cases and 26,952 matched controls (N = 40,428). Mean (SD) age was 64.8 (12.2) years, 54.1% were female, and mean follow-up was 2,497 (1,308) days. Cases had fewer BP visits per year (median, 2.50 vs. 3.01; p < 0.001), similar number of medication ingredients (2.00 vs 2.00), and lower treatment intensification scores (-0.211 vs - 0.125). In adjusted models, >5 BP visits per year was associated with lower stroke odds (aOR, 0.55; 95% CI, 0.51-0.59) compared with [&le;]1 visit. Use of 2-3 medication ingredients (vs 0) was also associated with reduced stroke odds (aOR, 0.80; 95% CI, 0.75-0.86), whereas >3 ingredients was not significant. The highest quartile of treatment intensification showed the strongest association (aOR, 0.47; 95% CI, 0.44-0.51). Findings were consistent across subgroup and sensitivity analyses, including strata defined by baseline SBP and follow-up SBP. ConclusionsGreater engagement in hypertension care was associated with lower odds of ischemic stroke, suggesting that gaps in routine management may represent missed opportunities for prevention.

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Drug-Target Mendelian Randomization and Imaging Mediation Analyses Reveal Therapeutic Targets and Causal Mechanisms for Cardiomyopathies

Wang, P.; Song, Y.; Zhang, B.; Yang, J.

2026-04-22 cardiovascular medicine 10.64898/2026.04.20.26351344 medRxiv
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Abstract Background: Hypertrophic (HCM) and dilated (DCM) cardiomyopathy constitute the principal phenotypes of primary cardiomyopathy, yet both lack sufficient therapeutic options. Integrating genetic insights with detailed cardiac phenotyping offers a promising strategy to prioritize targets and elucidate their mechanisms of action. Methods: We conducted an three-stage analysis. First, drug-target Mendelian randomization (MR) was performed using cis-acting protein (pQTL) and expression (eQTL) quantitative trait loci as genetic instruments for potential drug targets. Second, we examined causal associations between 82 cardiac magnetic resonance (CMR)-derived imaging traits and HCM/DCM risk in a CMR-based MR analysis. Third, mediation MR was employed to quantify the proportion of the genetic effect of prioritized drug targets on cardiomyopathy risk that was mediated through specific CMR phenotypes. Results: Our analyses identified 19 and 13 potential therapeutic targets for HCM and DCM, respectively. CMR-based MR revealed that HCM risk was causally associated with increased right ventricular ejection fraction (RVEF) and greater left ventricular wall thickness, whereas DCM risk was linked to ventricular dilation, impaired myocardial strain, and altered aortic dimensions. Critically, mediation analysis established that these CMR traits served as significant intermediate pathways. The protective effect of ALPK3 on HCM risk was mediated through a reduction in myocardial wall thickness. Conversely, the effects of PDLIM5, HSPA4, and FBXO32 on DCM risk were exerted in part via alterations in aortic dimensions. Conclusion: This integrative genetic and imaging study systematically identify candidate therapeutic targets for HCM and DCM and delineates the specific CMR phenotypes through which they likely exert their causal effects. Our findings advance the understanding of disease pathogenesis and highlight new possibilities for improving the diagnosis and management of cardiomyopathy.

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Liver Biomarker Improves AHA/ACC 10-year ASCVD Risk Prediction in US and China Cohorts with ML

Peng, T.; Liu, C. l.

2026-04-23 cardiovascular medicine 10.64898/2026.04.22.26351466 medRxiv
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Introduction: Accurate stratification of hard atherosclerotic cardiovascular disease (ASCVD) risk remains challenging despite advances in prevention. Liver function biomarkers (LFBs), particularly gamma - glutamyl transferase (GGT), have been linked to cardiovascular outcomes, yet their contribution to hard ASCVD risk prediction is not well defined. Methods: This study analyzed data from the National Health and Nutrition Examination Survey (NHANES, 2005 - 2018) to assess cross - sectional associations between LFBs and 10 - year hard ASCVD risk estimated by the ACC/AHA Pooled Cohort Equations. Multivariable regression, restricted cubic splines, and mediation analyses were applied to examine independent and dose - response relationships. External validation was performed in the China Health and Retirement Longitudinal Study (CHARLS) and NHANES using machine learning models (CoxBoost, Naive Bayes and Random Forest). Results: Among 5,731 NHANES participants, GGT showed an independent linear association with hard ASCVD risk (P - trend = 0.003), partly mediated by systolic blood pressure (44.8%), HbA1c (19.0%), and high density lipoprotein cholesterol (13.4%). Machine learning (ML) models incorporating GGT, alkaline phosphatase (ALP), and globulin alongside traditional risk factors improved predictive accuracy, with Naive Bayes achieving an AUC of 0.751 in NHANES validation. Conclusions: GGT is an independent and biologically plausible biomarker of hard ASCVD risk, acting through cardiometabolic pathways. Incorporating LFBs into risk prediction models, particularly with machine learning, enhances risk stratification and may facilitate early identification of high - risk individuals.

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Postnatal signals for later cardiovascular morbidity after preterm pre-eclampsia

Leslie, A.; Maadh, S.; Lee, M.; Jones, O.; Priestner, L.; Duhig, K.; Farrant, J. P.; Hutchings, D. C.; Naish, J. H.; Miller, C. A.; Myers, J.; Ormesher, L.

2026-04-22 cardiovascular medicine 10.64898/2026.04.20.26351347 medRxiv
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IntroductionPreterm pre-eclampsia is associated with increased risk of later cardiovascular disease. This study examines cardiometabolic health 3-6 years post-preterm pre-eclampsia and explores whether early postnatal cardiovascular phenotypes relate to later cardiovascular morbidity. MethodsPICk-UP trial participants who experienced preterm pre-eclampsia underwent assessments including anthropometry, blood pressure (BP), arteriography, echocardiography, biomarkers and cardiac magnetic resonance (CMR) imaging 3-6 years postpartum. The primary outcome was hypertension prevalence, with secondary outcomes including cardiac fibrosis, remodelling, and function, obesity, and lipid abnormalities. Associations between baseline, pregnancy and postnatal characteristics with the primary and secondary outcomes were explored. ResultsForty-five women were included; 37 underwent echocardiography and 20 had CMR. At 3-6 years, 53% had hypertension, 32% developed de novo hypertension, 30% had adverse left ventricular (LV) remodelling, 49% had diastolic dysfunction, and 27% were obese. Myocardial fibrosis was detected in 35% of CMR participants. No cardiovascular measures changed from 6 months postpartum to 3-6 years. Women who developed hypertension demonstrated higher BP and LV mass index, from 6 weeks postpartum, with distinct postnatal BP trajectories. Women with myocardial fibrosis exhibited higher sFlt and CRP concentrations from 6 weeks postpartum, with sFlt correlating with native T1 at 3-6 years. DiscussionWomen with prior preterm pre-eclampsia show significant cardiometabolic morbidity 3-6 years postpartum. Early postnatal phenotypes indicate long-term cardiovascular risk. Persistent anti-angiogenic imbalance and inflammation may contribute to myocardial fibrosis. Early BP, weight, and biomarker measurement may help identify at-risk women, warranting further studies on optimising postnatal care to mitigate cardiovascular risk after preterm pre-eclampsia.

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Vision Language Model for Coronary Angiogram Analysis and Report Generation: Development and Evaluation Study

Jiang, Q.; Ke, Y.; Sinisterra, L. G.; Elangovan, K.; Li, Z.; Yeo, K. K.; Jonathan, Y.; Ting, D. S. W.

2026-04-21 cardiovascular medicine 10.64898/2026.04.19.26351241 medRxiv
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Coronary artery disease is a leading cause of morbidity and mortality. Invasive coronary angiography is currently the gold standard in disease diagnosis. Several studies have attempted to use artificial intelligence (AI) to automate their interpretations with varying levels of success. However, most existing studies cannot generate detailed angiographic reports beyond simple classification or segmentation. This study aims to fine-tune and evaluate the performance of a Vision-Language Model (VLM) in coronary angiogram interpretation and report generation. Using twenty-thousand angiogram keyframes of 1987 patients collated across four unique datasets, we finetuned InternVL2-4B model with Low-Rank Adaptor weights that can perform stenosis detection, anatomy labelling, and report generation. The fine-tuned VLM achieved a precision of 0.56, recall of 0.64, and F1-score of 0.60 for stenosis detection. In anatomy segmentation, it attained a weighted precision of 0.50, recall of 0.43, and F1-score of 0.46, with higher scores in major vessel segments. Report generation integrating multiple angiographic projection views yielded an accuracy of 0.42, negative predictive value of 0.58 and specificity of 0.52. This study demonstrates the potential of using VLM to streamline angiogram interpretation to rapidly provide actionable information to guide management, support care in resource-limited settings, and audit the appropriateness of coronary interventions. AUTHOR SUMMARYCoronary artery disease has heavy disease burden worldwide and coronary angiogram is the gold standard imaging for its diagnosis. Interpreting these complex images and producing clinical reports require significant expertise and time. In this study, we fine-tuned and investigated an open-source VLM, InternVL2-4B, to interpret and report coronary angiogram images in key tasks including stenosis detection, anatomy identification, as well as full report generation. We also referenced the fine-tuned InternVL2-4B against state-of-the-art segmentation model, YOLOv8x, which was evaluated on the same test sets. We examined how machine learning metrics like the intersection over union score may not fully capture the clinical accuracy of model predictions and discussed the limitations of relying solely on these metrics for evaluating clinical AI systems. Although the model has not yet achieved expert-level interpretation, our results demonstrate the potential and feasibility of automating the reporting of coronary angiograms. Such systems could potentially assist cardiologists by improving reporting efficiency, highlightning lesions that may require review, and enabling automated calculations of clinical scores such as the SYNTAX score.

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Nonlinear Dynamics of Left Ventricular Mass Remodeling in Chagas Cardiomyopathy

Benchimol-Barbosa, P. R.; Loayza-Benchimol-Barbosa, A. C.; Carvalhaes, C. G.; Kantharia, B. K.

2026-04-20 biophysics 10.64898/2026.04.16.719099 medRxiv
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AbstractO_ST_ABSBackgroundC_ST_ABSLeft ventricular (LV) remodeling in chronic Chagas cardiomyopathy (CCC) is progressive, but whether population-level LV mass dynamics follow nonlinear patterns and whether the loss of dynamic complexity tracks mortality is unknown. MethodsFifty outpatients from SEARCH-Rio cohort were followed-up for 10 years. Serial echocardiography provided paired LV mass measurements fitted to the logistic equation x = {middle dot}x{middle dot}(1-{gamma}{middle dot}x). Lyapunov exponents (LE) were computed from consecutive inter-patient derivatives. A clinical risk score was developed using Firth penalized logistic regression with bootstrap validation (B = 1,000) and Cox-Firth sensitivity analysis. ResultsLV mass remodeling adjusted the logistic equation with = 3.91 {+/-} 0.18 and {gamma} = 1.27 {+/-} 0.06, which was compatible with dynamics near the complexity threshold ( {approx} 3.57). Survivors showed positive LE (+0.339 {+/-} 0.543), and nonsurvivors showed negative LE (-0.825 {+/-} 0.972; p = 0.015). The fixed-point equilibrium of {approx} 280 g was approached by 63 % of patients at follow-up (p = 0.0003), a pattern indistinguishable from regression to the mean in the present design. Firth regression identified EF < 51.7 % and maximum heart rate < 109 bpm as independent predictors (optimism-corrected AUC = 0.959); the derived score showed a monotonic mortality gradient accompanied by lower LE across strata (Spearman {rho} = -0.369, p = 0.004). ConclusionsThese exploratory findings are compatible with nonlinear LV mass remodeling in Chagas disease and the association between loss of dynamic complexity and mortality. Replication in larger cohorts, formal model comparisons, and prospective validation of the score are warranted. Nonstandard Abbreviations and AcronymsASE, American Society of Echocardiography; AUC, area under the receiver operating characteristic curve; CCC, chronic Chagas cardiomyopathy; CHF, congestive heart failure; CI, confidence interval; EF, ejection fraction; HRV, heart rate variability; IQR, interquartile range; IVS, interventricular septum; LA, left atrial; LAHB, left anterior hemiblock; LBBB, left bundle branch block; LE, Lyapunov exponent; LV, left ventricular; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; NSVT, nonsustained ventricular tachycardia; NYHA, New York Heart Association; OR, odds ratio; PSVT, paroxysmal supraventricular tachycardia; PVC, premature ventricular complex; PW, posterior wall; RBBB, right bundle branch block; ROC, receiver operating characteristic; SAECG, signal-averaged electrocardiogram; SD, standard deviation; SDNN, standard deviation of normal-to-normal intervals; SEM, standard error of the mean; SVE, supraventricular ectopy

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Patient perspectives on living with hypertension: Social media listening analysis across predominantly high-income countries

Di Somma, S.; Gervais, R.; Bains, M.; Carter-Williams, S.; Messner, S.; Onsongo, N.

2026-04-23 cardiovascular medicine 10.64898/2026.04.22.26351483 medRxiv
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Background: Chronic conditions such as hypertension can significantly disrupt daily life and emotional wellbeing. The interaction between patients' perceptions, adherence to antihypertensive medication and quality of life (QoL) remains underexplored outside structured clinical settings. Objectives: To capture unprompted patient perspectives and assess whether hypertension affects QoL and to investigate if patient reported experiences are associated with self-reported antihypertensive medication adherence. Methods: Social media listening (SML) study analyzing 86,368 anonymized posts from individuals with hypertension in 12 countries, collected between January 2022 and May 2024. Posts from 11 countries (n=81,368) were analyzed using artificial intelligence-enabled natural language processing. Posts from China (n=5,000) were analyzed separately using a harmonized framework. Quantitative and qualitative methods assessed variations by country, age, and gender, and associations between emotional expression and antihypertensive medication adherence. Results: Across the 11-country core sample, 45% of posts mentioned at least one QoL impact, most commonly worry/anxiety (11%). Impacts varied across countries. Among 8,096 posts with age identified, individuals <40 years reported emotional balance impacts in 28% of posts versus 22% among those aged 40+. Work/Education impacts were mentioned in 17% of posts by those <40 years vs 12% in 40+. Among 7968 posts explicitly referencing adherence, expressed worry was associated with stricter adherence (62% association score), as were structured routines (79% score), home monitoring (77%), dietary changes (77%), and exercise (71%). In contrast, sadness/depression was associated with inconsistent adherence (71%), as were forgetfulness (79%), side effects (73%), and cost/insurance concerns (65%). Conclusions: These results emphasize the importance of the psychological and emotional impact of hypertension, including on adherence to medication regimens, reinforcing the value of a holistic approach to patient care.

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Cardiac Rehabilitation and Functional Capacity Improvement: Montana Outcomes Project Cardiac Rehabilitation Registry Findings

Claus, L.; McNamara, M.; Oser, C.; Fogle, C.; Canine, B.

2026-04-21 public and global health 10.64898/2026.04.20.26351126 medRxiv
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Cardiovascular disease (CVD) remains the leading cause of mortality in the United States, despite being largely preventable through effective management of risk factors. This study evaluates the impact of Phase II cardiac rehabilitation (CR) on functional capacity and quality of life, using data from the Montana Outcomes Project Cardiac Rehabilitation Registry. Functional capacity improvements were assessed via the six-minute walk test (6MWT) and Dartmouth COOP questionnaire, with statistical analyses exploring the influence of CR session attendance, demographic factors, and referring diagnoses. Results demonstrated significant gains in 6MWT, with a mean improvement of 330.73 feet (p < .0001), and quality of life scores across all subgroups. A dose-response relationship was observed, indicating greater improvements with increased CR sessions (p < .0001), though diminishing returns were observed beyond 24-35 visits. Demographic factors and complex conditions influenced outcomes, underscoring the need for tailored strategies to enhance CR access and effectiveness. These findings highlight the critical role of CR in improving patient outcomes and emphasize the importance of addressing barriers to participation in underserved populations.

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Noncoaxial Transcatheter Aortic Valve Deployment Creates Cusp-Specific Thrombogenic Microenvironments Through Altered Sinus Hemodynamics

Natarajan, T.; Kim, J. H.; Salgado, C. D.; Jha, A.; Baker, C.; Sellers, S. L.; Aslan, J. E.; Hinds, M. T.; Yoganathan, A. P.; Dasi, L. P.

2026-04-21 bioengineering 10.64898/2026.04.17.719323 medRxiv
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BackgroundTranscatheter aortic valve replacement has transformed the management of aortic stenosis; however, adverse outcomes such as leaflet thrombosis and hypoattenuating leaflet thickening remain clinically significant concerns. Flow disturbances resulting from valve canting may alter local hemodynamics and promote thrombogenic conditions. We investigated how modest transcatheter heart valve canting alters cusp-specific sinus flow and washout and promotes localized thrombogenic microenvironments associated with leaflet surface thrombus formation using particle image velocimetry, a physiologic blood loop, and tissue analysis. MethodsA patient-derived aortic root model was used to evaluate the hemodynamic and thrombogenic effects of THV canting at -10{degrees} (anti-curvature), 0{degrees} (neutral), and +10{degrees} (along-curvature). High-resolution particle image velocimetry quantified sinus flow fields and washout characteristics, and complementary whole-blood loop experiments enabled histologic assessment of leaflet-associated thrombus formation. ResultsCanting redistributed systolic jet orientation and sinus recirculation in a direction-dependent manner while preserving global hemodynamic measurements. The most spatially constrained cusp showed the largest increase in stasis and the slowest washout. In the right coronary cusp, anti-curvature canting increased the fraction of sinus area with velocity magnitude <0.05 m/s to 92% versus 43% in neutral and 10% in along-curvature deployments, and prolonged neo-sinus (T90) washout to 4.7 cycles versus 2.9 and 1.8 cycles, respectively. Histology localized surface-adherent platelet/fibrin thrombus to these poorly washed regions, most prominently on the right coronary cusp leaflet in anti-curvature deployments. Left and noncoronary cusp responses shifted with tilt direction, indicating redistribution rather than uniform worsening of thrombogenic conditions. ConclusionsEven modest noncoaxial deployment is sufficient to create sinus-resolved throm-bogenic microenvironments that are not captured by global gradient or effective orifice area. Deployment configuration is therefore a modifiable determinant of post-TAVR leaflet throm-bosis risk and may contribute to HALT.

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DIVAID: Consistent division of atrial geometries from multimodal imaging according to the EHRA/EACVI 15-segment bi-atrial model

Goetz, C.; Eichenlaub, M.; Schmidt, K.; Wiedmann, F.; Invers Rubio, E.; Martinez Diaz, P.; Luik, A.; Althoff, T.; Schmidt, C.; Loewe, A.

2026-04-23 cardiovascular medicine 10.64898/2026.04.22.26351448 medRxiv
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The recently published EHRA/EACVI consensus statement on a standardized bi-atrial regionalization provides new opportunities for consistent regional analyses across patients, imaging modalities and clinical centers. To make this standardized regionalization widely accessible, we developed the open-source software DIVAID, which automatically divides bi-atrial geometries according to the proposed regions, ensuring consistency, reproducibility and operator independence. We evaluated the accuracy of the algorithm by comparing its results to manual expert annotations across 140 geometries from multiple modalities and centers. Veins were automatically clipped correctly in 81% and orifices annotated correctly in 100% of cases. The median (interquartile range; IQR) Dice similarity coefficient (DSC) for left atrial regions was 0.98 (0.96-1.00) for DIVAID-expert and 0.98 (0.94-1.00) for inter-expert comparisons. For right atrial geometries, DSC was higher for DIVAID-expert than for inter-expert comparisons at 0.90 (0.80-0.95) and 0.88 (0.74-0.94), respectively. To assess the accuracy of regional boundaries, we computed the mean average surface distance (MASD) for boundaries derived from automatic or manual annotations. The median (IQR) MASD between DIVAID and experts was 0.17 mm (0.03-0.78) and 1.93 mm (0.65-3.96) in the left and right atrium, respectively. To conclude, DIVAID robustly divides anatomically diverse bi-atrial geometries according to the 15-segment model, while outperforming cardiac experts in both speed and consistency, and demonstrating an accuracy of regional boundaries comparable to the spatial resolution of cardiac imaging modalities. By providing automated, consistent atrial regionalization, DIVAID enables large-scale, standardized regional analyses and data-driven investigation of harmonized, multi-dimensional datasets, which may advance atrial arrhythmia research and personalized treatment strategies.