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Open Heart

BMJ

Preprints posted in the last 7 days, ranked by how well they match Open Heart's content profile, based on 19 papers previously published here. The average preprint has a 0.04% match score for this journal, so anything above that is already an above-average fit.

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Healthcare professionals' perspectives on a multilevel cardiovascular risk management intervention (PROSPERA programme)

Bongaerts, V. A. M. C.; van Gestel, L. C.; van Peet, P. G.; Vuijk, M.-L. S.; Hageman, S. H. J.; Dorresteijn, J. A. N.; Bonten, T. N.; Numans, M. E.; van Os, H. J. A.; Vos, R. C.

2026-06-09 cardiovascular medicine 10.64898/2026.06.08.26355169 medRxiv
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Background: Two-thirds of Dutch cardiovascular risk management (CVRM) for patients at risk of cardiovascular disease is delivered in primary care practices. While individual risk scores are increasingly used during consultation, a population-level structure for risk-based patient outreach is not currently available. We therefore developed the PROSPERA programme, a multilevel intervention comprising population-level risk stratification and individual-level support tools. Aim: To assess anticipated and experienced barriers and facilitators among healthcare professionals (HCPs) to inform implementation in primary care. Methods: We conducted four focus groups and six interviews with nine primary care HCPs to explore anticipated and experienced barriers and facilitators. Inductive codes were thematically analysed and assigned to corresponding domains of the Theoretical Domains Framework (TDF) and the related Capability, Opportunity, Motivation model of Behaviour. Results: Barriers and facilitators were identified in 11 TDF domains. Population-level barriers included altered professional roles and limitations in technological infrastructure. Individual-level barriers were limited skills in interpreting risk calculations and difficulty integrating tools into clinical routine. Facilitators were related to beliefs on the importance of providing proactive care (population level), the use of U-Prevent for risk communication (individual level) and positive patient responses to the Lifestylecheck questionnaire (individual level). Conclusion: Addressing barriers and facilitators identified at both the population and individual levels can support implementation of the PROSPERA programme. Opportunities exist in education and training of HCPs in risk communication, as well as support in restructuring the physical and digital environment.

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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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Recognition and Treatment of Primary Aldosteronism in the Updated Guideline Era

Tsai, C.-H.; Chang, Y.-C.; Chang, C.-C.; Wu, W.-C.; Chang, Y.-Y.; Chen, U.-L.; Lee, B.-C.; Hung, C.-S.; Huang, K.-H.; Chueh, J. S.; Wu, V.-C.; Lin, Y.-H.

2026-06-10 cardiovascular medicine 10.64898/2026.06.08.26355219 medRxiv
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Background: Primary aldosteronism (PA) is increasingly recognized as a common cause of hypertension. The 2025 Endocrine Society guideline introduced a simplified diagnostic framework, but its real-world clinical implications remain unclear. Methods: We conducted a multicenter retrospective cohort study of hypertensive patients undergoing PA testing in Taiwan. PA was defined biochemically according to the 2025 Endocrine Society criteria. Multivariable logistic regression identified factors associated with PA diagnosis and aldosterone-targeted therapy. Among patients with suppressed renin (?1 ng/mL/h), restricted cubic splines evaluated the adjusted association between renin and PA probability. Results: Among 18,766 patients undergoing PA testing, 6,760 (36.0%) met diagnostic criteria for PA. PA was associated with older age, female sex, lower potassium, resistant hypertension, and a higher antihypertensive medication burden. Among patients with suppressed renin, lower renin remained significantly associated with higher adjusted PA probability. However, only 39.0% of patients with PA received aldosterone-targeted therapy, including 28.2% who received mineralocorticoid receptor antagonist therapy within 6 months and 9.4% who underwent adrenalectomy during follow-up. Lower renin, higher aldosterone, lower potassium, and resistant hypertension were associated with aldosterone-targeted therapy, while younger patients with fewer comorbidities were more likely to undergo adrenalectomy. Conclusions: Using the updated diagnostic framework, PA was highly prevalent among hypertensive patients undergoing PA testing. Nevertheless, many patients who met these biochemical criteria did not receive aldosterone-targeted therapy in routine care. These findings highlight the potential treatment implications of broader PA recognition and support the development of practical pathways to guide MRA therapy, adrenalectomy referral, and individualized management.

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Prevalence and factors associated with peripheral artery disease among patients with diabetes mellitus: A cross-sectional study at tertiary hospital in Eastern Uganda

Imalingat, J.; Muyinda, A.; Iraguha, D.; Katuramu, R.; Masaba, P.; Apio, E.; Kebesu, J.; Nankunda, O.; Kirabo, E.; Epuitai, J.; Bwayo, D.

2026-06-05 cardiovascular medicine 10.64898/2026.06.03.26354843 medRxiv
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Abstract Background Peripheral artery disease (PAD) is a major contributor to morbidity and mortality, particularly among individuals with diabetes mellitus (DM), in whom its prevalence is markedly increased. PAD is often asymptomatic and under-diagnosed, especially in low-resource settings. This study aimed to determine the prevalence of PAD and associated factors among adults with DM in Eastern Uganda. Methods We conducted a hospital-based cross-sectional study at Mbale Regional Referral Hospital from 10th/12/ 2024 to 30th/4/2025. A total of 300 adult patients with DM were consecutively enrolled. Data on sociodemographic characteristics, clinical characteristics, comorbidities, and behavioural risk factors were collected using an interviewer-administered data tool. PAD was assessed using the ankle-brachial index (ABI), defined as [&le;] 0.90. Modified Poisson regression was used to identify factors associated with PAD. As a secondary measure for PAD, we administered the Edinburgh Claudication Questionnaire (ECQ) to capture symptomatic PAD. Results The majority of the participants had a low fruit intake (68%), physical inactivity (54%), and elevated low-density lipoprotein (60%). The prevalence of PAD as measured by ABI was 42.3% (127/300; 95% CI 0.38-0.48), while the magnitude of PAD as measured by ECQ, combining participants with possible claudication and definite claudication was 37.3% 95% CI 31.9 - 42.8). Out of participants with PAD, 15.8% (20/127) were classified as having severe PAD (ABI <0.4). Socio-demographic and clinical factors were assessed for association with PAD. We found no evidence of association between the examined factors such as age (aPR 1.24 95% CI 0.73 - 2.09), sex (aPR 1.46 95% CI 0.84 - 2.55), cholesterol level (aPR 1.39 95% CI 0.86 - 2.25), glycemic control (aPR 1.35 95% CI 0.72 - 2.53), and sedentary behaviour (aPR 1.28 95% CI 0.79-2.08) and PAD. Conclusion The prevalence of PAD was high among adults with DM in Eastern Uganda. Routine health education, and ABI screening of PAD should be done for patients living with DM. The absence of significant associations despite high prevalence of PAD may reflect unmeasured factors e.g. chronic inflammation that may be unique to this population, future prospective studies with larger sample size and more detailed objective measures e.g. inflammatory markers are needed to determine locally relevant modifiable risk factors.

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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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Minimally Invasive Aortic Root Surgery Without Sternotomy: Clinical and Quality-of-Life Benefits of a Totally Endoscopic Approach

Hamiko, M.; Salamate, S.; Bayram, A.; Piekarski, F.; Rogaczewski, J.; Eghbalzadeh, K.; Silaschi, M.; Kruse, J.; El-Sayed Ahmad, A.; Bakhtiary, F.

2026-06-08 cardiovascular medicine 10.64898/2026.06.06.26354391 medRxiv
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Background Totally endoscopic aortic root (AR) surgery via right anterior minithoracotomy (RAMT) may reduce surgical trauma and accelerate recovery compared with full sternotomy (FS). However, the approach is technically demanding due to limited access and anatomical complexity. This study compares early clinical outcomes and quality of life (QoL) after RAMT versus FS to evaluate the feasibility and safety of the totally endoscopic approach. Methods This single-center, retrospective study included 149 patients underwent AR surgery via RAMT (n=74) or FS (n=75) between January 2021 and March 2026. Patients with aortic dissection, infective endocarditis, redo surgery, concomitant procedures, or arch replacement were excluded. Operative outcomes, postoperative recovery, 30-day and 1-year mortality were analyzed. QoL was assessed using the Short Form-8 (SF-8) questionnaire. Results The median age was 60.0 years, and 79.9% of patients were male. Bentall procedure was performed in 84.6% of patients, 15.4% underwent a David procedure. Compared with FS-AR, RAMT-AR was associated with shorter median operative time (147.0 vs. 178.0 min; p<0.001), lower median chest drainage volume (650.0 vs. 850.0 mL; p<0.001), and shorter median ICU stay (24.0 vs. 25.0 h; p=0.008) and hospital stay (6.0 vs. 8.0 days; p=0.028). Overall, 30-day and 1-year mortality was 0.7%. SF-8 analysis demonstrated significantly higher physical and mental component scores in RAMT-AR patients. Conclusion In specialized centers, totally endoscopic AR surgery via RAMT is a safe and feasible minimally invasive approach associated with favorable early outcomes and a potential benefit in postoperative physical and mental QoL by reducing surgical trauma.

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Virtually Delivered Psychosocial Intervention for Mothers Expecting a Baby with Congenital Heart Disease: A Proof-of-Concept Study of HEARTPrep

Sood, E.; Canter, K.; Arasteh, K.; Kazak, A. E.

2026-06-05 cardiovascular medicine 10.64898/2026.06.03.26354861 medRxiv
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Background: Maternal mental health problems are common after prenatal diagnosis of congenital heart disease (CHD), with long-term implications for child and family wellbeing. HEARTPrep is a prenatal psychosocial intervention with three self-paced modules and corresponding telehealth sessions, delivered during pregnancy via mobile app to improve mental health and wellbeing for mothers expecting a baby with CHD. This proof-of-concept study evaluated the feasibility of HEARTPrep and examined maternal mental health and psychosocial functioning throughout participation. Methods: Participants were mothers receiving care for a fetal CHD diagnosis within one health system. Feasibility was assessed via rates of enrollment and completion. Mothers completed 4-item PROMIS questionnaires assessing anxiety, depression, and social isolation and reported self-efficacy and hope on a weekly basis throughout HEARTPrep. Results: Of 34 recruited mothers, 29 (85%) enrolled and two were subsequently not eligible (delivery prior to participation, change in fetal diagnosis), resulting in a final sample of 27 mothers. The majority (n = 22, 81%) completed all three telehealth sessions and Modules 1 (n = 22, 81%) and 2 (n = 19, 70%), with just over half (n = 14, 52%) completing Module 3 prior to delivery. Mean PROMIS depression T-scores decreased from 57.5 to 52.9, and 48% of mothers had a decrease in depression scores exceeding the meaningful change threshold (half standard deviation). The percentage of mothers reporting high self-efficacy increased from 19% to 48%. Conclusions: HEARTPrep is feasible and corresponds with reduced maternal depression and increased self-efficacy, supporting proof-of-concept. A randomized controlled trial is needed to determine whether HEARTPrep improves outcomes compared to a control group.

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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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Structural Cardiac Abnormalities, Ventricular Dysfunction Phenotypes, and Heart Failure Risk among Antiretroviral Therapy-treated People Living with HIV in South Africa

Omar, Z.; PHIZA Study Team, ; Ahmed, A. A.; Wolfson, J.; Huang, Z.; Mgidlana, M.; Black, A.; Abd El Hadi, M.; Aremu, O. O.; Peterson, T. E.; Ntusi, N. A. B.; Meintjes, G.; Ntsekhe, M.; Baker, J. V.

2026-06-08 cardiovascular medicine 10.64898/2026.06.04.26354960 medRxiv
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Background: The manifestations of cardiovascular disease (CVD) among people with HIV (PWH) differ by region globally. While HIV disease is associated with increased atherosclerotic CVD risk in the global North, non-ischemic heart failure (HF) is more common in sub-Saharan Africa, the global HIV epicenter. We estimated the effect of treated HIV on the frequency and phenotype of HF and its cardiac precursors in South Africa (SA). Methods: In an observational study, we recruited PWH on antiretroviral therapy (ART), age [&ge;]40 years and people without HIV (PWoH) with similar distributions of age, sex, ethnicity, and hypertension, from a community clinic in Khayelitsha (Cape Town, SA). Procedures included a clinical assessment, echocardiography (Echo), and b-type natriuretic peptide (BNP) measure. Echo parameters defined structural abnormalities, left ventricle (LV) filling pressure, and LV systolic and diastolic dysfunction (DD). HF was defined by symptoms and/or BNP [&ge;]35pg/mL and LV dysfunction, subcategorized as reduced, mildly reduced, or preserved ejection fraction (HFrEF, HFmrEF, and HFpEF). Comparisons by HIV status were adjusted for age, sex, hypertension, smoking, obesity, diabetes, elevated LDL-cholesterol, and hazardous alcohol use. Results: Between September 2022 and August 2025, we enrolled 1008 PWH and 500 controls [median (Q1-Q3) age 48 years (43-53), 77% female]. Among PWH and controls respectively, 37% and 39% had hypertension, 21% and 25% were current smokers, 40% and 45% were obese, and 9% and 17% had diabetes. LV systolic dysfunction (1%) and HFrEF (1%) were rare, and undiagnosed HFpEF (8%) was the predominant HF phenotype. Compared to controls, PWH had higher odds of elevated LV mass index (LVMI) (OR 2.1; 95%CI 1.5-3.0) and DD (OR 1.4; 95%CI 1.0-2.0). Risk for elevated LVMI and DD was greatest among women with HIV, who also had an increased risk for undiagnosed HFpEF (OR 1.9; 95%CI 1.2-3.2), compared to women without HIV; effects which were not seen among men (p=0.051 for HIV*Sex interaction). Conclusions: In a peri-urban SA community with a high burden of cardiometabolic risk factors, the frequency of abnormal structural and functional cardiac precursors of HFpEF was greater amongst ART-treated PWH. This was most pronounced amongst women with HIV, who also had increased risk of undiagnosed HFpEF.

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Perceived Social Support and Self-Efficacy as Mediators Between Health Literacy and Quality of Life Among Middle-Aged and Older Adults with Hypertension: A Cross-Sectional Study in Six Central Provinces of China

Zhao, Y.; Yun, Y.; Bai, T.; Xiong, L.; Ruan, Y.; Zhao, H.; Wang, W.; Wang, F.

2026-06-08 public and global health 10.64898/2026.06.06.26355051 medRxiv
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Abstract Objective: The onset of hypertension occurs at a younger age in China, and the relationship between health literacy and quality of life among middle-aged and older hypertensive patients remains unclear. This study explored whether perceived social support and self-efficacy mediate the association between health literacy and quality of life in middle-aged and older hypertensive patients. Methods: A questionnaire was administered to 1,015 middle-aged and older hypertensive adults from communities in six central provinces of China. The EQ-5D scale, Perceived Social Support (PSS) scale, Self-Efficacy Scale (SES), and Health Literacy Scale (HLS) were used to assess quality of life, social support, self-efficacy, and health literacy, respectively. Mplus 8.3 software was used to construct a structural equation model for path analysis. Results: The mean PSS, SES, HLS, EQ-5D, and EQ-VAS scores were 15.57{+/-}3.45, 10.61{+/-}2.41, 9.49{+/-}2.86, 0.88{+/-}0.18, and 71.06{+/-}17.49, respectively. Health literacy and quality of life scores significantly differed among middle-aged and older hypertensive patients, and both showed positive correlations with perceived social support and self-efficacy (both P<0.001). Perceived social support and self-efficacy exhibited a chain mediated effect on the relationship between health literacy and quality of life (EQ-5D utility index and EQ-VAS), accounting for 28.57% of the total effect of the EQ-5D utility index and 27.26% of that of the EQ-VAS. This study is the first to elucidate the mechanism by which health literacy influences quality of life in middle-aged and older hypertensive patients through the chain-mediated effect of perceived social support and self-efficacy. Conclusion : Health literacy is significantly correlated with quality of life in middle-aged and older hypertensive patients. This correlation can directly or indirectly explain the impact on quality of life through mediating pathways involving perceived social support and self-efficacy. Keywords: hypertensive patients, perceived social support, self-efficacy, health literacy, quality of life, mediating effect

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Healthy Heart Actions Right Time (HHART): Co-design priorities to connect Aboriginal and Torres Strait Islander community and clinic activities for healthy hearts

Wyber, R.; Zagler, J.; Liu, C.; Yadav, U. N.; O'Dwyer, Z.; Hart, K.; Chapman, K.; McGrady, L.; Kohn, A.; Winterfield, N.; Williams, D.; Watson, N.; Morey, K.; Pearson, O.

2026-06-10 primary care research 10.64898/2026.06.05.26354870 medRxiv
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Aim: Healthy Heart Actions Right Time (HHART) is a multi-phased research project that seeks to identify, implement and evaluate strategies to connect community and clinical activities to reduce the burden of heart disease for Aboriginal and Torres Strait Islander people. The aim in Phase One was to identify priority activities for two participating services. Background: The ongoing effects of colonisation drive a disproportionate burden of heart disease for Aboriginal and Torres Strait Islander people. Clinical and community groups both have established strengths in reducing the risk of heart disease, but these are not always well connected. Methods: Using a case study methodology in two locations we partnered in a 12-month co-design process to identify priority activities to connect clinical and community activities. Findings: Three priorities emerged from the Phase One co-design process: (i) community-led gardening as a strategy to promote heart health through connection and healthy lifestyles; (ii) community days to increase engagement in heart checks and strengthen community-clinic relationship; and (iii) clinic-led development of culturally relevant education resources to promote clinician confidence and community heart health knowledge.

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Integrating a Non-Communicable Disease Care Cascade within Ghana's Community-Based Health Planning and Services (CHPS) Program: the COMBINE Pilot Implementation Trial

Heller, D. J.; Elkersh, Y.; Nonterah, E. A.; Kuwolamo, I.; Horowitz, C. R.; Alvarez, E. E.; Awine, T.; Govindarajulu, U.; Squires, A. P.; Aborigo, R. A.

2026-06-05 primary care research 10.64898/2026.06.03.26354834 medRxiv
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Introduction: Hypertension is the world's leading cause of death, and depression its leading cause of disability. Control rates for these noncommunicable diseases (NCDs) are low in low and middle-income countries (LMICs). Many LMICs have programs to screen and treat underserved communities for infectious diseases, but evidence to adapt them to treat NCDs is limited. We developed and tested a non-communicable disease program through Ghana's Community-Based Health Planning and Services (CHPS) primary care initiative. Methods: We trained 8 CHPS nurses to diagnose and treat hypertension and depression through door-to-door screening and pharmacotherapy. Physician assistants provided telehealth supervision. We combined this treatment with volunteer counseling to boost medication adherence, improve mood, and change health behaviors. We called the 90-day intervention the CHPS Opportunity for Mentally and Behaviorally Integrated NCD Engagement (COMBINE). Results: We recruited 60 adults from 580 screened: 37 with hypertension (mean blood pressure (BP) of 149/91 mm Hg) and 23 with depression (mean physician health questionnaire (PHQ-9) score of 13.3). After 90 days, 57/60 (95%) completed the intervention: 32/37 (86%) achieved blood pressure control (mean BP 122/75 mm Hg), and 19 of 20 (95%) achieved depression control (mean PHQ-9 score 2.0). After 12 months, 51/60 were retained: 33/37 with hypertension (89%) and 18/23 with depression (78%), with a mean BP of 121/75 and PHQ-9 score of 1.4 respectively. All 51 (100%) achieved disease control at 12 months. 5 persons left by migration and 4 by escalation to higher-level care. Conclusions: The COMBINE model achieved high levels of diagnosis, care retention, and disease control, with minimal adverse events, in a remote setting with limited usual NCD care. This model suggests a novel means to improve the care cascade for these and other noncommunicable diseases through existing non-physician care models in LMICs, warranting further controlled testing at scale.

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CarotidMamba: Foundation Model-Enabled CTA Phenotyping of Symptomatic Carotid Plaques in a Multi-Center Retrospective Study

Liu, Y.-S.; Dou, X.-W.; Zheng, P.-Y.; Feng, W.; Ma, L.-J.; You, Y.-N.; Shao, G.-W.; Shen, J.-G.; Yu, X.; Qiao, C.; Cheng, Z.-W.; Li, Z.-W.; Su, F.; Zhang, B.-W.; Qu, X.-H.; Jiang, g.

2026-06-05 cardiovascular medicine 10.64898/2026.06.02.26354776 medRxiv
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Background: Treatment decisions for carotid atherosclerotic disease rely primarily on luminal stenosis, although plaque vulnerability and symptomatic status better reflect short-term cerebrovascular risk. A scalable CTA tool for automated phenotyping of symptomatic carotid disease is lacking. Materials & Methods: In this multi-institutional retrospective study, 689 patients (mean age, 67.9 {+/-} 7.7 years; 366 men) from four hospitals were analyzed after screening 705 CTA examinations. 423 patients from one center were used for five-fold development and internal validation, and 266 patients from three centers for independent external validation. CarotidMamba, a deep learning framework combining dual foundation-model encoders with Mamba-based sequence modeling, was developed and benchmarked against clinical, radiomics, clinic-radiomics, CNN, and transformer comparators. Results: In the development cohort, CarotidMamba achieved an AUC of 0.839 (95% CI, 0.799-0.879) and accuracy of 0.825 (95% CI, 0.793-0.857), outperforming the strongest comparator by 0.066 and 0.050, respectively. External validation yielded AUCs of 0.897 (95% CI, 0.835-0.959) in YCH, 0.809 (95% CI, 0.720-0.898) in DCH, and 0.762 (95% CI, 0.649-0.875) in GH-NTC. CarotidMamba showed the lowest Brier score and expected calibration error across cohorts, with calibration slopes near 1.0. Conclusion: CarotidMamba provides an interpretable, clinically oriented, and externally validated CTA framework for phenotyping symptomatic carotid plaques, supporting vulnerability-aware imaging assessment beyond stenosis alone.

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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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Development of Longitudinal, Linked Maternal-Infant Cohorts using the Epic Cosmos Electronic Health Record Dataset

Leonard, S. A.; Dysart, K.; Callahan, A.; Siadat, S.; Zhang, J.; Handley, S. C.; Huybrechts, K. F.; Igbinosa, I.; Bateman, B. T.

2026-06-04 epidemiology 10.64898/2026.06.02.26354757 medRxiv
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Background: Epic Cosmos is a relatively new centralized electronic health record dataset with high potential utility in perinatal epidemiologic research. Objectives: The study objectives were to develop replicable steps to create longitudinal, linked maternal-infant cohorts in Cosmos, assess completeness of key variables, evaluate potential selection bias with restrictions for longitudinal healthcare encounters, and provide an example epidemiologic analysis. Methods: We created maternal-infant cohorts by starting with live births during 2023-2024 recorded in the BirthFact data table and joining with additional data tables as needed. We selected and created variables for perinatal characteristics, common comorbidities, and routinely measured vital signs and laboratory values, and assessed variable completeness. We sequentially restricted the birth cohort for maternal-infant linkage and longitudinal healthcare from first-trimester prenatal care encounter through infant follow-up care within 12 weeks post-discharge from birth hospitalization. Finally, we conducted an example analysis of the association between high systolic blood pressure in the first trimester ([&ge;]140 mm Hg) and later onset of preeclampsia among those with chronic hypertension. Results: The total linked birth cohort included 2,624,186 pregnancies. Completeness was >90% for most variables assessed but was 77% for racial and ethnic group and 76% for body mass index at delivery. Characteristics of the cohort were similar to those reported for the entire United States birth population based on birth certificate data, including similar regional and racial-ethnic composition. Longitudinal cohort restriction requiring linked records from first trimester prenatal care through infant follow-up care reduced the cohort size to 509,148 pregnancies. However, restriction had minimal effects on cohort characteristics. In the example analysis, high systolic blood pressure was associated with increased risk of preeclampsia among those with chronic hypertension (aRR: 1.26; 95% CI: 1.22, 1.30). Conclusions: This study provides a rigorous and reproducible approach to creating longitudinal, linked maternal-infant cohorts in Epic Cosmos and the analytical findings suggest high data quality and representativeness.

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Comparative Thermal Effects of Single Shot Pulsed Field Ablation Systems using a Thermochromic Hydrogel

Gill, J.; Saija, C.; Sagar, V.; Zuberi, Z.; Bajpai, A.; Rhode, K.; Leung, L. W.; Gallagher, M. M.

2026-06-04 cardiovascular medicine 10.64898/2026.06.02.26354772 medRxiv
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Background Pulse-field ablation (PFA) is regarded as a non-thermal ablation modality, but there is an increasing range of complications that could be due to thermal effects. Methods The hydrogel undergoes permanent colour change when a target temperature is reached allowing direct visualisation of the surface thermal footprint and depth. Comparative lesion sets using a variable loop circular catheter (VP), circular over-the-wire catheter (PS) and pentaspline catheter (FP) were performed. Protocols included single and stacked applications with variation of force, irrigation, and voltage. The hydrogel lesions were analysed en-face and by section using digital image analysis. Results All 3 PFA catheters tested had significant thermal footprints. The VP catheter had the largest mean surface footprint (156.1mm2) and thermal depth (1.31mm) compared to the other two catheters (PS 55.4mm2 & 1.1mm, FP 29.8mm2 & 1.05mm, p<0.005). Increasing irrigation showed a trend to reduce thermal footprint but did not achieve statistical significance. Increasing voltage increased thermal footprint, but increasing force had negligible effect. Stacked lesions incrementally increased thermal lesion footprint and depth in all catheters. Thermal depths of up to 2.4mm were observed. Areas of darkening and degradation of the hydrogel were observed with the VP and FP catheters, consisting of up to 47% of lesion area. No darkening was observed with the PS catheter. Conclusions There are significant thermal footprints in all the systems tested. Temperatures exceeding 60oC have been demonstrated, comparable to radiofrequency ablation, and this may explain the mechanism of injury in some reports of collateral damage during PFA.

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Prescription intervals of medications for chronic use: a cohort study

Muddiman, R.; Donoghue, P.; Gomez Lemus, J.; Doherty, A. S.; Boland, F.; McCarthy, C.; Moriarty, F.

2026-06-09 primary care research 10.64898/2026.06.08.26355164 medRxiv
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Purpose In deprescribing studies, a prescription-free gap is typically used to determine if patients discontinued their treatment. An appropriate gap depends on the typical time between prescriptions during continued use. This work aims to characterise the interval between prescriptions of chronic drugs using different methods for a cohort of older people in primary care in Ireland. Methods The empirical prescription interval was analysed for 38,154 patients for the twenty most common drug classes and the association between covariates and the interval was analysed using a multi-level model. Estimates were also compared to those obtained from the parametric waiting time distribution (pWTD) approach. Results Available covariates had consistent relationships with prescription intervals across drug classes. For example, each additional prescription issue was associated with an increase in the interval by 5.0 (NSAIDs) to 19.7 days ("Other antidepressants"). Full public health cover was associated with a -29.0 day (inhaled adrenergics) to -11.0 day (opioids) change relative to partial cover, while other/private cover had a -17.9 day (benzodiazepines and associated drugs) to -7.1 day (SSRI and SNRIs) change relative to partial cover. The pWTD also produced consistent estimates of the population interval for most drugs. Conclusions The interval varied substantially within drug classes, due to a mixture of patient, practice and unmodelled factors. Variation between practices was effectively explained, with residual variation between patients and within patients. The pWTD approach is useful for describing complex distributions of intervals, and may be more appropriate for inferring a gap than summarising truncated data.

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AutoClip: AI-Guided TEE Semantic Segmentation for TEER A Proof-of-Concept Study

Chen, M.; Li, X.; Yang, K.; Taramasso, M.

2026-06-06 cardiovascular medicine 10.64898/2026.05.29.26354195 medRxiv
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**Abstract** **Background:** Transcatheter edge-to-edge repair (TEER) is an established treatment for mitral regurgitation but remains highly dependent on operator experience and complex transesophageal echocardiography (TEE)-guided intraprocedural imaging. Artificial intelligence (AI)-based semantic segmentation may improve procedural reproducibility and intraprocedural guidance; however, no TEER-specific segmentation framework has been reported. **Objectives:** To develop and evaluate AutoClip, a clinician-driven AI-guided TEE semantic segmentation model designed for simultaneous delineation of mitral valve anatomy and in-vivo TEER device components. **Methods:** A retrospective proof-of-concept study was conducted using 987 intraprocedural TEE frames derived from 10 video clips in 3 patients undergoing MitraClip G4 implantation. Seven semantic labels, including mitral leaflets and device components, were manually annotated using ITK-SNAP. Following standardized preprocessing and region-of-interest extraction, an Attention U-Net architecture was trained frame-wise on bicommissural and corresponding X-plane TEE views. Model performance was assessed using mean intersection-over-union (IoU) and Dice coefficient on an independent test set. **Results:** The Attention U-Net demonstrated improved sensitivity to small device structures compared with conventional U-Net architectures. Preliminary training performance achieved a mean IoU of approximately 0.93, while independent test performance reached a mean IoU of 0.46 across foreground classes. Qualitative assessment demonstrated feasible simultaneous segmentation of mitral leaflets, clip arms, grippers, and delivery shaft during TEER procedures. **Conclusions:** AutoClip represents a proof-of-concept TEER-specific TEE semantic segmentation framework initiated through a clinician-oriented workflow without formal computer science expertise. Although preliminary accuracy remains modest due to limited sample size, this study establishes a reproducible pathway for future AI-assisted intraprocedural guidance systems and larger multicenter development efforts in structural heart interventions.

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Does ECG-Based AI Detect Aortic Stenosis Beyond Conventional LVH Criteria? An Analysis of the CLIDAS Database

Shimada, T.; Kodera, S.; Sawano, S.; Guan, J.; Saitoh, W.; Wakasa, S.; Ito, S.; Yanagishita, T.; Hayashi, Y.; Shibata, A.; Ito, A.; Otsuka, K.; Higashikuni, Y.; Okamura, H.; Tsujita, K.; Node, K.; Yamaguchi, O.; Makimoto, H.; Kabutoya, T.; Imai, Y.; Nakayama, M.; Sato, H.; Fujita, H.; Kohro, T.; Matoba, T.; Takeda, N.; Fukuda, D.; Nagai, R.

2026-06-08 cardiovascular medicine 10.64898/2026.06.07.26355087 medRxiv
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Background: Aortic stenosis (AS) is a progressive valvular disease associated with poor prognosis once symptoms develop, yet routine echocardiographic screening is impractical. While artificial intelligence (AI)-based electrocardiogram (ECG) models have shown promise for AS detection, it remains unclear whether they primarily reflect conventional left ventricular hypertrophy (LVH) voltage criteria or capture additional ECG features. Methods and Results: We developed a deep learning model using 244,816 ECGs from 51,713 patients across six academic institutions in Japan (CLIDAS database). AS labels were derived from inpatient Diagnosis Procedure Combination (DPC) codes. The model achieved an area under the receiver operating characteristic curve (AUC) of 0.849 (95% confidence interval 0.832-0.865) in the independent test cohort, with consistent performance across institutions, sex, and age. At a threshold of 0.1, sensitivity was 79.1%, specificity was 73.9%, and negative predictive value (NPV) was 98.0%. Conventional LVH voltage criteria (Sokolow-Lyon AUC 0.706; Cornell AUC 0.692) showed lower performance, and adding them to the AI model conferred no incremental benefit (AUC 0.849 vs. 0.847). Gradient-weighted class activation mapping (Grad-CAM) revealed predominant attention around QRS complexes in limb leads, beyond regions typically assessed in LVH evaluation. Conclusions: This multicenter AI-ECG model demonstrated strong discrimination for AS and captured ECG features beyond conventional LVH voltage criteria. The high NPV supports its use as a rule-out pre-screening tool.

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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.