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Open Heart

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Preprints posted in the last 90 days, ranked by how well they match Open Heart's content profile, based on 21 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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Public interest in postural orthostatic tachycardia syndrome in the United Kingdom, 2004-2026: a Google Trends infodemiology study

Bogle, R. G.; Bogle, C. M.

2026-08-24 cardiovascular medicine 10.64898/2026.08.21.26361021 medRxiv
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Background: Public and clinical attention to postural orthostatic tachycardia syndrome (POTS) has increased, particularly since the COVID-19 pandemic. We quantified changes in United Kingdom Google search interest and examined whether searches increasingly used diagnostic and self-assessment language. Methods: We extracted monthly Google Trends relative search volume (RSV; 0-100) for the Health-category search term 'Pots syndrome' in the United Kingdom from January 2004 through July 2026. Five extraction attempts were made; two returned complete, identical monthly series and were retained. Prespecified eras were summarised and an exploratory interrupted time-series model at March 2020 used ordinary least squares with Newey-West heteroskedasticity and autocorrelation consistent standard errors (12 lags). Comparator searches included conventional orthostatic diagnoses, POTS diagnostic terms, associated conditions and YouTube searches. Results: The primary series comprised 271 complete months. Mean RSV increased from 18.6 during 2015-2019 to 64.8 during 2022-2023 (3.49-fold) and remained 50.6 during January 2024-July 2026 (2.73-fold above baseline). Search interest peaked in October 2022 (RSV 100); July 2026 RSV was 57. The interrupted time-series model estimated an immediate March 2020 level increase of 21.8 points (95% CI 2.8-40.7; p=0.024), while the slope change was not statistically supported (0.069 points/month, 95% CI 0.299 to 0.438; p=0.713). Searches for 'POTS symptoms', 'POTS test' and 'POTS heart rate' increased more steeply than the general term, although low baseline volumes made fold changes unstable. Conclusions: UK Google search interest in POTS rose before 2020, increased sharply after the pandemic began, and remained substantially above its prepandemic baseline. The results demonstrate a sustained change in public attention, not disease incidence or social-media causation. The growth of symptom- and testing-oriented searches is compatible with increased diagnostic self-investigation and warrants linkage to referral, diagnosis and social-media exposure data.

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Patient Perspectives on Potential Implementation of Coordinated Family Care Visits for Inherited Cardiovascular Disease

Draisin, E. R.; Badar, H.; Naik, H.; Platt, J.; Kaufman, B.; Salisbury, H.; Ison, H. E.

2026-08-07 cardiovascular medicine 10.64898/2026.08.05.26359830 medRxiv
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Introduction: Shared medical appointments (SMAs) are medical visits where multiple individuals are seen together in a group setting. For patients with inherited cardiovascular disease, where multiple family members often require ongoing cardiac care and screening, family SMAs may be particularly valuable as a tool to facilitate family communication and comprehension of their condition. This research aimed to identify patient perspectives on the potential benefits and challenges of family SMAs in comparison to an existing individual clinic model. Methods: Qualitative semi-structured interviews were conducted with adult family representatives. Each family had at least one family member seen at the adult and pediatric inherited cardiovascular disease clinics. Interview recordings were transcribed verbatim and inductively coded using a content analysis approach. Results: Sixteen families were interviewed in this study. The mean age of the family representative interviewed was 43.4 years ({+/-} 9.3 SD), and they were followed at Stanford Health Care for a mean of 7.3 years ({+/-} 4.2 SD). 81.2% (13/16) of families said they would find family SMAs beneficial. For interested families who consented to recorded interviews (n=12), benefits and challenges fell into two major categories: care quality and access and logistics. Interested families thought family SMAs would provide an added care quality benefit by increasing understanding among adults, children, and providers (83.3%, 10/12). Six of twelve participants interested in having family SMA visits felt there would be logistical/access-based benefits to this new model (50%, 6/12). Families also identified possible challenges with this model, such as less individualized care, potential privacy concerns, and concerns regarding the smoothness of the clinic process in coordinating a family SMA. Conclusion: The majority of families believed a family SMA model would provide added benefit to families with inherited cardiovascular disease, but requires thoughtful implementation and should be tailored to families? unique needs.

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Efficacy and safety of PCSK9 inhibitors for children and adolescents with heterozygous familial hypercholesterolaemia: Systematic review and meta-analysis of randomised controlled trials

Llewellyn, A.; Simmonds, M.; Marshall, D.; Harden, M.; Humphries, S. E.; Woods, B.; Gomes, M.; Priestley-Barnham, L.; Ramaswami, U.; Fisher, M.; Qureshi, N.; Tata, L. J.

2026-08-06 cardiovascular medicine 10.64898/2026.08.04.26359681 medRxiv
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Background Statins and ezetimibe are the preferred lipid-lowering therapies (LLTs) for children with heterozygous familial hypercholesterolaemia (HeFH). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are newer add-on therapies for individuals not achieving low-density lipoprotein-cholesterol (LDL-C) targets. We evaluated the efficacy and safety of PCSK9i in children aged <18 years with HeFH. Methods Systematic review and pairwise meta-analyses of randomised-controlled trials (RCTs) of evolocumab, alirocumab and inclisiran. Comprehensive bibliographic searches were conducted in February 2026. Risk of bias was assessed with Cochrane RoB 2. Results Of 2798 unique records screened, three RCTs were included (n=451, mean age 13 years, follow-up 24 to 47 weeks). Each trial evaluated either evolocumab, alirocumab or inclisiran against placebo as add-on to baseline LLT. Participants had elevated LDL-C (>3.4 mmol/L [130 mg/dL]) despite stable LLT. Overall risk of bias was low. PCSK9i reduced LDL-C by an average of 35.44% (95% CI -41.74 to -29.14, I2=50.8%) and by 1.63 mmol/L [62.93 mg/dL] (95% CI -1.86 to -1.39, I2=18.6%) compared with placebo. There was no evidence of differences between PCSK9i and placebo in tolerability, growth and maturation, and overall incidence of adverse events. Conclusions PCSK9i add-on therapy leads to substantial reductions in LDL-C in paediatric patients with HeFH failing to achieve LDL-C targets with standard LLT. While the findings of this review support the use of PCSK9i in a subset of children and young people with HeFH, limited trial numbers and short follow-up periods underscore the need for future high-quality studies evaluating long-term safety, effectiveness and cost-effectiveness.

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Defining cost-effectiveness of mechanical circulatory support escalation among patients with acute myocardial infarction complicated by cardiogenic shock

Kamalakkannan, A.; Yang, Y.; Batchelor, R.; Backhouse, B.; Munro, K.; Groen, F.; Yanase, F.; Anstey, J.; Taylor, A.; Dyett, J.; French, C.; McGain, F.; Lefkovits, J.; Cox, N.; Chan, W.

2026-09-10 cardiovascular medicine 10.64898/2026.09.08.26362578 medRxiv
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Background: Temporary mechanical circulatory support (MCS) for acute myocardial infarction complicated by cardiogenic shock (AMI-CS) includes microaxial-flow pumps (mFP), venoarterial extracorporeal membrane oxygenation (VA-ECMO), and combined mFP-ECMO support. These strategies differ substantially in haemodynamic capability and resource use, but their short-term cost-effectiveness has not been compared within a common decision framework. Methods: We developed a 4-strategy decision-analytic model comparing No MCS (standard care without temporary MCS), mFP, VA-ECMO, and mFP-ECMO from the perspective of a publicly funded Australian health system over 30 days. Costs were estimated from individual resource components in 2025?26 Australian dollars and benchmarked against hospital casemix data. The primary outcome was cost per additional 30-day survivor. Scenario analyses and probabilistic sensitivity analysis assessed parameter uncertainty. Results: Expected per-patient costs were A$34,562 for No MCS, A$125,269 for mFP, A$133,573 for VA-ECMO, and A$177,481 for mFP-ECMO. Assigned 30-day survival probabilities were 56.1%, 74.2%, 54.3%, and 53.9%, respectively. mFP was the only non-dominated MCS strategy, with an incremental cost-effectiveness ratio of A$502,695 per additional survivor compared with No MCS. Under the assigned cross-cohort inputs, VA-ECMO and mFP-ECMO were more costly and less effective, remained strictly dominated across all prespecified scenarios, and required 30-day survival above 74.2% to escape dominance. Intensive care unit (ICU) bed-days were the largest cost component. At a willingness-to-pay threshold of A$500,000 per additional survivor, the probabilities of being optimal were 44.0% for No MCS, 54.1% for mFP, 1.7% for VA-ECMO, and 0.2% for mFP-ECMO. Conclusions: Under the assigned cross-cohort inputs, escalation of MCS beyond mFP in AMI-CS increased costs without improving modelled 30-day survival. Nevertheless, VA-ECMO and mFP-ECMO remain essential for selected patients requiring greater circulatory or respiratory support.

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Hidden in Plain Sight: Clinical Profile, Diagnosis, and Outcomes of Cardiac Amyloidosis in Cali, Colombia

Barbosa-Balaguera, S.; Castano, O.; Echeverry, E. J.; Llano, C. D. M.; Muriel Ruiz, A. J.; Diaz, J. B.; Cordoba, A. M. T.; Ayala-Zapata, S.; Velasquez-Trujillo, L. A.; Escandon, A. H.

2026-10-20 cardiovascular medicine 10.64898/2026.10.15.26365704 medRxiv
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Background Cardiac amyloidosis is an increasingly recognized cause of heart failure in older adults, yet Colombian data, and data from the southwest of the country in particular, remain scarce. We describe the clinical, diagnostic, imaging and outcome profile of patients with cardiac amyloidosis at two high-complexity institutions in Cali. Methods Observational, descriptive, retrospective, two-center study. Patients were identified in the institutional registries of both centers using ICD-10 codes for amyloidosis, and clinical data were abstracted manually from medical records. Continuous variables are reported as median (interquartile range) and categorical variables as counts and percentages over the number of patients with available data. Results Thirty-two patients were analyzed (median age 77 years; 68.8% men). Heart failure (90.6%), atrial fibrillation (46.9%) and carpal tunnel syndrome (31.2%) were frequent. The etiological classification depended on the test considered: bone scintigraphy was positive (Perugini 2-3) in 23 of 26 patients studied (88.5%), but a monoclonal protein was screened for in only 22, and the full non-invasive criteria for ATTR were met in 16 of 32 (50.0%). Genetic testing was positive in 9 of 18 tested, and the variant was Val142Ile in all 8 patients in whom it was characterized. The working diagnosis was ATTR in 26 patients (81.2%) and AL in 6 (18.8%). Tafamidis was used in 37.5%. Eleven of the 31 patients with known vital status died (35.5%), and NT-proBNP was markedly higher among those who died (6640 vs 1186 pg/mL; p=0.003). Conclusions In this southwestern Colombian cohort, cardiac amyloidosis presented as the classic transthyretin phenotype, with the Val142Ile variant in all 8 patients in whom it was characterized. Bone scintigraphy was frequently positive, but screening for a monoclonal protein was often omitted, so only half the cohort met the full non-invasive criteria for ATTR. Mortality was high and closely associated with NT-proBNP.

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In-Hospital Mortality Trends Among Hospitalized Adults With Cardiac Arrest, 2016-2022

Nedunuri, R.; Hashemzadeh, M.; Movahed, M. R.

2026-09-28 cardiovascular medicine 10.64898/2026.09.25.26364059 medRxiv
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Background: CPR is the primary intervention for cardiac arrest, and the mortality trends before and after the pandemic remain are not fully understood. Methods: This cross-sectional study used the National Inpatient Sample (NIS) database from 2016-2022 and International Classification of Diseases, Tenth Revision (ICD-10) codes to evaluate the mortality trend for adult patients undergoing CPR after in-hospital cardiac arrest (IHCA). Primary exposures were calendar year, demographics, socioeconomic factors, and hospital characteristics. Multivariable weighted logistic regression was performed to identify predictors of mortality after CPR for IHCA. Results: Among 612,930 weighted adult hospitalizations undergoing CPR for IHCA between 2016 and 2022, overall in-hospital mortality was 67.8%. Risk-adjusted mortality declined through 2019 before increasing sharply during the COVID-19 pandemic, peaking in 2021 and remaining above pre-pandemic levels in 2022. Compared with 2016, admission in 2020 (aOR 1.18, 95% CI 1.12-1.25; p<0.001) and 2021 (aOR 1.26, 95% CI 1.19-1.33; p<0.001) was independently associated with higher mortality, whereas admission in 2019 was associated with lower mortality (aOR 0.89, 95% CI 0.84-0.95; p<0.001). Higher mortality was also associated with increasing age (aOR 1.01 per year; p<0.001), female sex (aOR 1.05, 95% CI 1.02-1.08; p<0.001), Black (aOR 1.14, 95% CI 1.10-1.18; p<0.001) and Hispanic race/ethnicity (aOR 1.20, 95% CI 1.15-1.26; p<0.001), and self-pay insurance (aOR 1.62, 95% CI 1.51-1.74; p<0.001). Protective factors included private insurance (aOR 0.91, 95% CI 0.87-0.94; p<0.001), residence in the highest income quartile (aOR 0.91, 95% CI 0.87-0.94; p<0.001), and treatment at private, non-profit hospitals (aOR 0.89, 95% CI 0.85-0.94; p<0.001). Conclusion: This large nationwide patient database analysis demonstrates that mortality following CPR for IHCA declined before the COVID-19 pandemic but increased during 2020, remaining above pre-pandemic levels through 2022. Independent predictors of mortality reveal socioeconomic disparities in mortality outcomes.

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Why A "Normal Blood Volume" Is Not Always Normal - An Overlooked Issue In Heart Failure Management

Miller, W. L.

2026-08-23 cardiovascular medicine 10.64898/2026.08.18.26360762 medRxiv
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Background: Blood volume (BV) in patients with chronic heart failure (HF) is characterized by heterogeneity in volume profiles; one profile being "normal BV". While overall intravascular volume may be considered normal clinically, the relative contributions of red blood cell (RBC) mass and plasma volume (PV) may not be. Objective: Assess how normal is a "normal BV" based on quantitative measures of RBC mass and PV. Methods: Retrospective analysis was undertaken in 395 patients with Class II-III HF. BV was quantitated using indicator-dilution methodology. Cohort was stratified by normal and hypervolemic BV. Results: Of the cohort, 31% (123/395) demonstrated normal total BV and 62% (244/395) hypervolemic BV. Of patients with "normal BV", 36% (44/123) demonstrated normal RBC mass and 60% normal PV (74/123). Importantly, 60% (74/123) demonstrated a deficit in RBC mass (true anemia), while a low hemoglobin (<12 g/dL) was present in just 29% (36/123). An excess in RBC mass (erythrocytosis) in 4% (5/123). Notably, true normal BV (i.e., normal RBC mass and normal PV) was observed in only 30% (37/123) of patients with an overall "normal" intravascular volume. Conclusions: Findings reveal that "normal BV" can be misleading by concealing substantial variability in RBC mass (including unrecognized anemia and erythrocytosis) as well as different degrees of PV expansion and contraction. An actual normal BV was identified in a minority of "normal BV" patients. This underscores the importance of looking beyond overall "normal BV" to the contributing elements of RBC mass and PV with significant implications for patient management and outcomes.

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Sex-Based Differences in Clinical Presentation, Management, and Outcomes of Acute Coronary Syndrome in Brazilian Emergency Medical Services

Fagundes, A.; Stephanus, A. D.; Moll-Bernardes, R. J.; Albuquerque, D. C.; Silva Camiletti, A.; Horacio Medei, E.; Feldman, A.; Noya, M.; Mary Frajtag, R.; Ferreira de Souza, O.

2026-08-19 cardiovascular medicine 10.64898/2026.08.17.26360642 medRxiv
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Background: Sex-related disparities in acute coronary syndrome (ACS) recognition and management remain a global health concern. We examined sex-based differences in clinical presentation, management, and outcomes among patients with chest pain attended by emergency medical services (EMS) across Brazil. Methods: We conducted a retrospective study using a registry from 14 Brazilian states between January 2020 and June 2024 within a private hospital network. Patients with chest pain were classified by cardiologists as unstable angina (UA), ST-elevation myocardial infarction (STEMI), or non-ST-elevation myocardial infarction (NSTEMI). Multivariable regression evaluated sex differences in diagnosis, treatment, and outcomes. Sensitivity analyses included state-clustered standard errors and E-values for unmeasured confounding. Results: Among 7,171 patients with confirmed ACS (68.2% male), median age was 63.0 years [IQR 20.0]; women were older than men (67.0 [20.0] vs 61.0 [19.0] years). Diagnoses were UA in 46.7%, STEMI in 18.8%, and NSTEMI in 34.6%. Overall, 91.7% received aspirin and 89.6% at least one additional antiplatelet agent. After adjustment, women had higher odds of chest pain classified as probably or possibly ischemic versus definitely ischemic (adjusted OR 1.51 [95% CI 1.33-1.72] and 1.60 [1.37-1.86], respectively) and lower odds of STEMI and NSTEMI relative to UA (adjusted OR 0.59 [0.51-0.68] and 0.74 [0.66-0.83], respectively). Door-to-ECG time was longer in women unadjusted ({beta}=1.53 minutes [0.24-2.82]) but not after adjustment ({beta}=1.04 [-0.27 to 2.36]). In-hospital mortality did not differ between sexes, with no evidence of excess short-term mortality in women. Conclusions: Within a private hospital network in Brazil, women with confirmed ACS were more often classified with less definitely ischemic chest pain and less frequently with STEMI or NSTEMI than men. Door-to-ECG differences did not persist after adjustment, and mortality did not differ by sex. These findings support sex-sensitive triage and diagnostic protocols to reduce inequities in ACS recognition and treatment.

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30-Day Heart Failure Readmission and Post-Discharge Healthcare Use Among Older Australians: A Linked-Data Mixed-Methods Study

Leong, C. S.; Kabir, A.; Barr, M. L.

2026-10-12 cardiovascular medicine 10.64898/2026.10.09.26365178 medRxiv
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Abstract Background: Heart failure (HF) is a major public health challenge in ageing populations and a leading cause of unplanned hospital readmissions. Biological, social, and economic factors contribute to recurrent hospitalisation, but gaps remain in understanding how these factors interact and patterns of healthcare use following hospitalisation. Methods: We conducted an explanatory sequential mixed-methods study of patients aged ?60 years with an HF hospital admission between 2016 and 2020 who completed the Sax Institute?s 45 and Up Study baseline questionnaire. Data were linked to Admitted Patient Data Collection, Medicare Benefits Schedule, and Pharmaceutical Benefits Scheme data. HF readmission within 30 days of the index admission was the outcome. Cox proportional hazards models estimated crude and adjusted hazard ratios (HRs and adjHRs) with 95% confidence intervals (CIs). Kaplan-Meier curves and log-rank tests compared survival between groups. Time-series plots mapped healthcare interactions over 1 year following the index admission. Results: Among 4,252 patients with HF, 409 were readmitted within 30 days. Significant predictors included age ?80 years (adjHR, 1.30; 95%CI, 1.01?1.67), 1 chronic condition (adjHR, 2.49; 95%CI, 1.41?4.40), ?2 chronic conditions (adjHR, 1.75; 95%CI, 1.04?2.95), and alcohol consumption above national guidelines (adjHR, 1.45; 95%CI, 1.06?1.98). Time-series analysis indicated that participants with readmission had more frequent out-of-hospital health service contact following their initial HF admission than those without readmission. Conclusions: Older age, chronic conditions, and high alcohol intake increased 30-day HF readmission risk. Differences in healthcare use after admission highlight opportunities for targeted and coordinated post-discharge care.

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Coronary revascularisation in people with multiple long-term conditions: a systematic review and meta-analysis

Cheng, A.; Alhashimi, A.; Lim, C. J.; Cheong, S. C.; Shahbaz, H.; Abbasciano, R.; Pufulete, M.; Murphy, G. J.

2026-09-08 cardiovascular medicine 10.64898/2026.09.04.26362027 medRxiv
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Introduction People presenting for multivessel coronary revascularisation commonly have multiple long-term conditions that influence prognosis. The aim of this study was to review the evidence for revascularisation choices in these groups. Methods Randomised trials of Coronary Artery Bypass Grafting (CABG) versus Percutaneous Coronary Intervention (PCI) reporting outcomes by pre-specified comorbidities were included. Treatment effects were estimated using inverse variance random effects models and presented as Risk Ratios (95% Confidence Intervals). The certainty of evidence for outcomes was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results 19 studies from nine RCTs with 10,594 participants were included. Reported baseline comorbidities included diabetes (49%), CKD (25%), LVSD (9%), female sex (14%), and older age (40%). Trials were unblinded, resulting in some bias concerns. For people with diabetes and CKD, CABG reduced the risks of all-cause death and repeat revascularisation, with no treatment effect on MI or stroke, versus PCI. There was no difference in mortality or stroke for female sex, or older age. No data was reported for people with peripheral vascular disease or frailty. Patient reported outcomes favoured CABG in people with diabetes. GRADE showed that the certainty of the evidence was generally Low to Very Low with the exception of people with diabetes (Moderate Certainty). Conclusion There is a knowledge gap with respect to the risks and benefits of CABG versus PCI in people with common comorbidities. Registration PROSPERO CRD420251032665

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Feasibility of continuous finger arterial pressure recording with synchronised facial video in a hypertension clinic cohort: the BP-WAVE pilot study

Singh, J.; Feeney, A.; Teh, J. W.; Mannion, E.; Murphy, R.; Coen, E.; Sharif, F.; Judge, C.

2026-10-13 cardiovascular medicine 10.64898/2026.10.12.26365325 medRxiv
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Introduction. Whether the arterial pressure waveform carries structural vascular information that brachial pressure does not, and whether its shape can be read from facial video, are both uncertain, and recording a continuous pressure reference with synchronised video in a hypertension clinic has not been reported. We sought to determine whether continuous finger arterial pressure recording with synchronised facial video, linked to existing coronary calcium imaging, is feasible in adults attending a hypertension clinic, whether a consumer camera recovers heart rate and pulse shape in that setting, and to generate exploratory estimates of association between waveform morphology and coronary calcium. Methods. BP-WAVE is a single-site prospective observational pilot study. The primary outcome was feasibility, pre-specified as recruitment, consent, completeness of waveform recording, imaging availability and data completeness. Secondary outcomes were waveform quality, device agreement, feature extraction, and recovery of heart rate and pulse shape from video. The exploratory outcome was the Spearman correlation of 14 waveform features with the Agatston calcium score, with exact permutation p values adjusted within each family of tests. Results. Nine of ten planned participants were recorded over 12 days (median age 55 years, range 40 to 74; five women); all nine completed the recording with video and had a calcium score (median 351, range 33 to 1816). Of 4,178 detected beats, 2,965 (71%) passed quality control. Video recovered heart rate within 0.4 to 4.1 beats per minute in eight of nine participants and pulse shape above a phase-randomised noise bound in six of nine (held-out r 0.48 to 0.76). Form factor had the strongest correlation with calcium (rho -0.68, exact p 0.050, q 0.68); no feature was associated with calcium after Benjamini-Hochberg adjustment within any of the nine families of 14 tests (126 tests in all; smallest q 0.17). Conclusion. In this single-site pilot of nine adults from a hypertension clinic, continuous finger arterial pressure recording with synchronised facial video and linkage to coronary calcium was feasible, a consumer camera recovered heart rate in eight and pulse shape in six participants, and no waveform feature was associated with coronary calcium after correction for multiple testing.

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Factors Associated with Adherence to Anti-Hypertensive Medication Among Patients Attending a Primary Health Centre in Ndola, Zambia: A Cross-Sectional Study

Sikantongwe, N.; Musonda, E.; Mabaso, F.; Chibwaya, E.; Sikantongwe, E.; Mapiki, C.

2026-09-17 cardiovascular medicine 10.64898/2026.09.11.26362862 medRxiv
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Background: Hypertension is a leading modifiable risk factor for cardiovascular disease and premature death worldwide. Despite effective pharmacological therapy, poor adherence to anti-hypertensive medication remains the primary barrier to achieving blood pressure control, with non-adherence rates reaching 45-65% in sub-Saharan African settings. In Zambia, uncontrolled hypertension contributes substantially to hospital morbidity and mortality, yet context-specific data on adherence barriers remain limited. This study assessed factors associated with adherence to anti-hypertensive medication among patients attending Railway Surgery Urban Health Centre in Ndola, Zambia. Methods: A cross-sectional study was conducted among 237 hypertensive patients attending Railway Surgery Urban Health Centre in Ndola. A structured, interviewer-administered questionnaire assessed socio-demographic characteristics, clinical factors, and medication adherence using the modified Hill-Bone Compliance Scale. Data were analysed using descriptive statistics, chi-square tests, and multivariable logistic regression (p<0.05). Results: The overall adherence rate was 41.4%, with 58.6% of participants classified as non-adherent. The mean adherence score was 19.8 (SD=4.6) out of a possible 32. The most common reasons for non-adherence were running out of pills (mean=2.6), being away from home (mean=2.5), and forgetting to take medication (mean=2.4). Age (p=0.006), education level (p=0.001), and monthly income (p=0.001) were significantly associated with adherence. Clinical factors significantly associated with poorer adherence included presence of comorbidities (p=0.027), experience of side effects (p<0.001), and medication regimen complexity (p=0.007). Multivariable analysis identified age [&ge;]51 years (AOR=2.89-3.24), secondary/tertiary education (AOR=2.84-3.56), monthly income [&ge;]K1,000 (AOR=2.21-5.89), absence of comorbidities (AOR=0.51), absence of side effects (AOR=0.36), and simpler regimens (AOR=0.34) as factors independently associated with adherence. Health system barriers included long distances, reliance on public transport, missed appointments due to transport problems (35.4%), medication stock-outs (38.4%), and inadequate counselling time (49.8% received <5 minutes). Conclusion: Adherence to anti-hypertensive medication at Railway Surgery Urban Health Centre is suboptimal, with multiple socio-demographic, clinical, and health system factors associated with non-adherence. Interventions should focus on regimen simplification, proactive side effect management, enhanced patient education, and addressing systemic barriers including medication supply and transport access.

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Reliability and accuracy of medication-based performance measures for assessment of outpatient cardiology clinicians

Chow, C.; Gunzburger, E.; Wilson, C.; Salahuddin, T.; Hess, P. L.; Essien, U.; Rodriguez, F.; Yang, K.-C.; Ziaeian, B.; Doll, J. A.

2026-10-02 cardiovascular medicine 10.64898/2026.09.29.26364366 medRxiv
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Background: Multiple performance measures are used to assess the management of common cardiovascular conditions, such as coronary artery disease (CAD), heart failure with reduced ejection fraction (HFrEF), and atrial fibrillation (AF). These measures are sometimes used to assess individual clinicians, despite lack of evidence of reliability and accuracy. We used national Veteran Affairs (VA) data to test medication-based performance measures for assessment of clinician performance in outpatient cardiology care. Methods: This retrospective study examined VA cardiology clinician/Veteran dyads from 2017-2023 to evaluate 10 medication-based performance measures for CAD, HFrEF, or AF with elevated stroke risk. Achievement of each performance measure was defined as an active prescription of an indicated medication for each eligible patient encounter, summarized at the clinician level. Reliability was calculated using the beta-binomial method. A Bayesian causal model was used to assess the impact of case complexity on performance measure achievement. Finally, we performed peer review of a subset of cases (n=952) to assess the accuracy of three representative performance measures. Results: Of 456,071 unique cardiology encounters, 312,331 included CAD, 224,599 included HFrEF, and 178,678 included AF. These patients were treated by 1,043 cardiology clinicians. Median performance measure achievement ranged from 0.23 (SGLT2i for HFrEF) to 0.99 (beta blocker for HFrEF). Measure reliability varied from 0.63 to 0.90. Case complexity did not significantly affect performance measure achievement. Using peer review as the gold standard, accuracy was poor to moderate (balanced accuracy 0.51-0.73), and measures underestimated performance relative to peer review. Conclusions: Ten medication-based performance measures for CAD, HFrEF, and AF can be efficiently measured using electronic health record data, and most have sufficient reliability to support clinician benchmarking and the identification of potential care gaps. However, suboptimal accuracy compared with a peer review indicates that these measures may be insufficient as a standalone assessment of clinician quality.

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Oral anticoagulation registry in patients with atrial fibrillation treated in Primary Care in clinical practice. The RACOVIR Study.

Polo Garcia, J.; Mico Perez, R. M.; Garcia Gabriel, E.; Romero Vigara, J. C.; Segura Fragoso, A.; Garcia Lerin, A.; Kopytina, V.; Santos Altozano, C.

2026-08-02 primary care research 10.64898/2026.07.30.26358911 medRxiv
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Objectives: To assess how patients with non-valvular atrial fibrillation (NVAF) receiving oral anticoagulants are managed in routine primary care practice in Spain. Methods: This observational, descriptive study included patients with NVAF treated with oral anticoagulants for at least 6 months before enrolment and managed in primary care settings in Spain. The Barthel and ACTS questionnaires were administered to evaluate functional autonomy and treatment satisfaction, respectively. Results: A total of 1,901 patients were included: 428 received vitamin K antagonists (VKAs) and 1,473 direct oral anticoagulants (DOACs). Compared with patients receiving DOACs, those treated with VKAs were significantly older and had a higher prevalence of more hypertension. Mean treatment duration was 7.6 years for VKAs and 3.8 years for DOACs. Among patients receiving VKAs, 56.2% and 59.0% achieved good anticoagulation control according to the direct and Rosendaal methods, respectively. Patients in the DOAC group reported greater satisfaction across several domains, including perceived treatment benefits, lower impact on daily life, and overall positive treatment effect. Event incidence rates (per 1,000 person-years) were higher with DOACs than with VKAs for stroke (1.75; 95% CI 1.05-2.92), ischemic stroke (1.78; 95% CI 1.06-3.00), acute myocardial infarction (1.64; 95% CI 0.97-2.79), and major bleeding (3.68; 95% CI 1.81-7.46). Conclusions: In routine primary care practice in Spain, patient profiles and treatment duration varied by oral anticoagulant type. These differences may partly explain the higher rates of stroke and major bleeding observed with DOACs versus VKAs, despite greater treatment satisfaction among patients receiving DOACs.

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Effectiveness and safety of a New Standardised TrEatment Protocol based on initial/early therapy with single-pill combinations of blood pressure-lowering drugs for improving blood pressure control (NewSTeP): Rationale, design of a randomized clinical trial and baseline characteristics of the trial participants

Dhurjati, R.; Pant, R.; Kumar, A.; Mittal, A.; Chappidi, K.; Satheesh, G.; Puri, P.; Tiruttani, S. K.; Rajaram, S.; Basheer, A.; kaur, P.; Moran, A.; Rosende, A.; Subramani, P.; Mahajan, S.; Lalvani, N.; Bansal, S.; Prabhakaran, D.; Balagopalan, J. P.; Jan, S.; Huffman, M. D.; Jha, V.; Salam, A.

2026-09-11 cardiovascular medicine 10.64898/2026.09.10.26362712 medRxiv
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Background Hypertension is the leading modifiable risk factor for cardiovascular disease (CVD). Despite availability of blood pressure (BP)-lowering therapies, BP control rates remain suboptimal. Reluctance to initiate treatment with combination therapy and delayed treatment intensification contribute to poor control. Early use of single-pill combinations (SPCs) within standardised treatment protocols (STPs) may improve outcomes, but evidence from India is limited. Objective To evaluate the effectiveness and safety of a new STP incorporating initial or early use of SPCs compared with usual care among adults with hypertension. Methods The New Standardised TrEatment Protocol (NewSTeP) trial is a pragmatic, multicentre, randomized, parallel-group, open-label trial conducted in tertiary healthcare centres in India. Adults with hypertension who are untreated or receiving one BP-lowering drug and require treatment initiation or intensification (n = 300) will be randomized 1:1 to either a new STP incorporating early SPC therapy or usual care. Participants will be followed for 6 months. The primary effectiveness outcome is change in home-measured mean systolic BP from randomization to month 6. The primary safety outcome is discontinuation of trial drug due to adverse events. Secondary outcomes include proportion of participants achieving BP control, change in diastolic BP, incidence of adverse events of special interest, treatment adherence, treatment modification, and time to BP control. A process evaluation will assess reach, implementation, acceptability, and sustainability, while an economic evaluation will assess cost-effectiveness of the intervention. Results Between October 2025 and March 2026, 300 participants were randomized across nine sites (150 to New STP; 150 usual care) from 360 screened individuals. Final follow-up is expected in September 2026, with results anticipated in October 2026. Conclusions The NewSTeP trial will provide evidence on the effectiveness, safety, implementation, and cost-effectiveness of an SPC-based STP for hypertension management in India and inform future hypertension control strategies and policies.

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Underutilization of Lipoprotein(a) Testing and Its Association with Coronary Interventions: PITT-LIPID Real-world Registry Insights

Awan, R.; Wang, H.; Thoma, F. F.; Zhu, J.; Levene, J.; Mulukutla, S. R.; Koczo, A.; Saeed, A.

2026-09-07 cardiovascular medicine 10.64898/2026.09.03.26361336 medRxiv
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Background: Lipoprotein(a) [Lp(a)], is leading risk factor for premature atherosclerotic cardiovascular disease. Multi-societal guidelines recommend to test Lp(a) amongst adults at least once, however, real-world testing data in primary prevention populations remains scarce. Objectives: To investigate the utilization of Lp(a) testing in a primary prevention cohort and associated outcomes. Methods: We conducted a retrospective cohort study using data from the PITT-LIPID registry, an electronic health record (EHR) based database of primary prevention patients (ages 20-79 years) across a tristate healthcare network. Lp(a) testing status was assessed, and those with Lp(a) measurements were stratified by Lp(a) levels [&le;]125 versus >125 nmol/L. Multivariable Cox proportional hazards models were used to assess associations between Lp(a) levels and coronary artery interventions [percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG)], and mortality. Results: Among 687,780 patients without known coronary artery disease, only 6,340 (0.9%) patients underwent Lp(a) testing. Compared with untested patients, those tested for Lp(a) had higher low density lipoprotein cholesterol, greater percentages of statin and aspirin use, and lower prevalence of diabetes and smoking. Patients with Lp(a) testing had higher rates of PCI (4.5% vs 1.4%; p-value <0.001) and CABG (1.4% vs 0.4%; p-value <0.001) but lower all-cause mortality (2.0% vs 5.0%; p-value < 0.001) incidence. Lp(a) >125 nmol/L was independently associated with risk of PCI (HR 1.67, 95% CI [1.16-2.41]), p=0.006. Conclusion: Lp(a) testing was underutilized and associated with higher burden of PCI events in a primary prevention population across a contemporary healthcare network with diverse practice types.

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Pre-Deployment Cardiovascular Risk Assessment and Outcomes among United States Antarctic Program Participants: Insights from Contemporary Risk Models

LeBlanc, D. P.; Qadeer, A.; Krishna, S. R. G.; Forrester, A.; Patel, A.; Shi, D.; Nagueh, E.; Hsu, J.; Bhobe, N.; Gaalema, D. E.; McKeith, J.; Jneid, H.; Allencherril, J.

2026-10-16 cardiovascular medicine 10.64898/2026.10.14.26365580 medRxiv
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Background: Cardiovascular (CV) screening is critical for personnel deploying to Antarctica, where geographic isolation and limited medical care make the management of acute cardiovascular events challenging. The utility of contemporary risk prediction tools such as the AHA PREVENT equations in this unique population remains uncertain. Methods: We retrospectively analyzed 154 individuals referred for enhanced CV evaluation before deployment to the U.S. Antarctic Program (USAP). Participants were evaluated across three temporal cohorts (2018-2020, 2021-2023, and 2024-2026). Demographics, CV risk factors, cardiac testing, and deployment clearance outcomes were collected. Risk was estimated using the Framingham Risk Score (FRS), AHA/ACC Pooled Cohort Equations (PCE), and AHA PREVENT risk models. Results: The cohort was predominantly male (79.9%; mean age 44.6 {+/-} 14.6 years), and abnormal ECG was the most common referral trigger (70.8%). Median 10-year risk was low by PREVENT and FRS and borderline elevated by PCE (PREVENT 2.7% [IQR 1.1-6.6], FRS 2.3% [IQR 0.5-7.1], and PCE 6.1% [IQR 2.4-9.2]). Among 72 participants with all scores, 51% were classified discordantly; PREVENT ASCVD agreed closely with FRS (=0.77) but poorly with PCE (=0.24-0.35), which consistently estimated higher risk. PCE was calculable in 52.6% versus 70.8% for PREVENT. Overall, 132 participants (85.7%) were cleared for deployment, while 8 (5.2%) were not physically qualified (NPQ); 6 of these NPQs were due to cardiovascular causes. Of 22 cardiac medical evacuations during the study period, 21 involved individuals without prior advanced cardiovascular screening. One screened individual was evacuated for symptoms subsequently found to have no cardiac cause. Conclusions: Risk calculators disagree substantially in the fitness-selected population. We recommend PREVENT as the primary risk-stratification tool as it is the most contemporary derivation, incorporates renal function, is race-agnostic, extends to heart failure, applies from age 30, and agrees closely with FRS, easing transition. Targeted imaging, including coronary artery calcium scoring, may supplement intermediate-risk candidates.

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Persistent Hypertension After Asymptomatic Elevated In-Hospital Blood Pressure: The INDEBP Study

Hausknecht, K.; Mayr, M.; Breidthardt, T.; Burkard, T.; Vischer, A. S.

2026-10-11 cardiovascular medicine 10.64898/2026.10.08.26365097 medRxiv
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Background: Elevated blood pressure (BP) is common during hospitalization. Despite recommendations to avoid routine changes in antihypertensive therapy, clinical practice remains variable. Prospective data on whether elevated in-hospital BP identifies patients with hypertension after discharge are limited. Methods: Adults hospitalized for non-cardiac conditions with asymptomatic routine in-hospital BP ?140 and/or ?90 mmHg on at least two occasions separated by ?24 hours were prospectively enrolled. Antihypertensive therapy was managed at the discretion of treating physicians. Routine in-hospital BP, standardized research BP, and changes in antihypertensive therapy were recorded. Four weeks after discharge, participants underwent 24-hour ambulatory BP monitoring (ABPM). Results: Among 50 participants, 42 (84%; 95% CI, 70.9 ? 92.8) had hypertension on follow-up ABPM. Among 21 participants without known hypertension, 18 (86%) had previously unrecognized hypertension on follow-up ABPM; among 29 participants with known hypertension, 24 (83%) had uncontrolled hypertension. Antihypertensive therapy was changed during hospitalization in 26 participants (52%), with de-escalation more frequent than intensification. Hypertension on follow-up ABPM was present in 88.5% of participants with and 79.2% without in-hospital therapy changes. Standardized research BP, but not routine in-hospital BP, correlated with follow-up ABPM. Conclusion: Asymptomatic elevated routine in-hospital BP identified a population with a high prevalence of hypertension four weeks after discharge, including patients with and without previously diagnosed hypertension. These findings support structured post-discharge BP reassessment rather than assuming that elevated in-hospital BP is transient. URL: www.ClinicalTrials.gov; Unique identifier: NCT06132451

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Rural-Urban Differences in Hospitalization Outcomes Among Young Adults (18-45) With Heart Failure, 2016-2022

Sherr, H.; Benyoucef, W.; Waken, R.; Joynt Maddox, K. E.; Solomon, E. R.; Hoang, V.-A.; Hammond, G.

2026-08-25 cardiovascular medicine 10.64898/2026.08.21.26361079 medRxiv
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Background Hospitalizations and mortality due to heart failure (HF) are rising in rural areas. However, inpatient outcomes for young adults with HF are not well understood. We aimed to compare in-hospital mortality, advanced procedure utilization, length of stay, and total charges among rural and urban HF patients ages 18-45. Methods We analyzed hospitalizations from the National Inpatient Sample (2016-2022), categorizing discharges as rural (National Center for Health Statistics [NCHS] 5-6), small and medium metropolitan (NCHS 3-4), and urban (NCHS 1-2). Generalized estimating equations were used to model outcomes and adjust for demographics, comorbidities, and hospital characteristics. Outcomes are reported as adjusted rate (aIRRs) or risk ratios (aRRs) with 95% confidence intervals. Results Among 79,258 HF hospitalizations among young adults, 45,075 and 10,722 were for patients from urban and rural areas, respectively. Rural patients had higher rates of in-hospital mortality (1.6% vs. 1.2%; aIRR = 1.28, 95% CI = 1.05, 1.56, p = 0.043), advanced cardiac procedure utilization (15.0% vs. 14.8%; aIRR = 1.19, 95% CI = 1.11, 1.28, p < 0.001), and longer hospital stays (aIRR = 1.10, 95% CI = 1.05, 1.14, p = 0.003). Small and medium metropolitan residents had similar outcomes to urban residents. In interaction analyses, the association between rural-urban residence and mortality differed by race (pint = 0.003) and payer type (pint < 0.001). Conclusions Young adults in rural areas may be prone to poor outcomes following hospitalization for HF. Strategies to identify rural adults at risk for HF and provide affordable and timely care may improve disparities.

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Health-Related Quality of Life, Healthcare Utilization, and Expenditure in US Adults With Myocardial Infarction and Heart Failure: The Medical Expenditure Panel Survey 2019 to 2024

Hasan, I.; Jafary, Z. I.; Rana, S.; Thyagaturu, H.

2026-10-02 cardiovascular medicine 10.64898/2026.09.27.26363737 medRxiv
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Background: Myocardial infarction (MI) and heart failure (HF) impose a physical and emotional toll that has not been measured nationally with a standard instrument. Methods: We pooled the 2019 to 2024 Medical Expenditure Panel Survey into 4 mutually exclusive groups of adults aged 18 and older: MI without HF, HF without MI, both conditions, and neither condition. Quality of life was assessed with the Veterans RAND 12-item component summaries, T scores (mean 50, SD 10) on which higher is better and 3 points is minimally important. Survey-weighted linear regression adjusted for demographics, socioeconomic factors, and comorbidity. Results: Among 79,853 adults representing 253.8 million US adults, 4.2% (3,340) had MI alone, 0.6% (480) HF alone, and 0.3% (236) both. Unadjusted physical scores ranged from 33.2 with HF alone to 39.1 with MI alone, versus 50.5 with neither. Adjusted physical scores were lower by 3.84 points (95% CI, 3.20-4.47) with MI alone, 8.32 (95% CI, 7.04-9.61) with HF alone, and 7.74 (95% CI, 5.73-9.76) with both, each beyond the minimally important threshold. Adjusted mental scores were lower by 1.35 points with MI alone, 1.20 with HF alone, and 1.69 with both, all below that threshold. Adults with both conditions did not differ from those with HF alone (0.58 points; 95% CI, -1.76 to 2.92). Emergency visits, inpatient discharges, and expenditure were higher in every cardiac group and highest with both conditions, where annual expenditure reached $37,198 versus $7,845 with neither. Conclusions: Physical quality of life fell steadily across the cardiac groups, with HF rather than prior MI accounting for most of it. The difference in mental quality of life did not persist after adjustment. Utilization and spending were highest with both conditions.