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Prospective cohort study of TIMP-1 and myocardial fibrosis in Chagas disease at a reference clinic in Pernambuco, Brazil: PTICH trial protocol

Por: Martins · S. M. · Macedo · C. T. · Meira · C. S. · Paim Santos · L. H. · Larocca · T. F. · Cavalcanti da Silva · F. F. · Leandro Lira · C. N. · da Silva · I. P. M. · De Araujo · L. T. · Soares · M. B. P.
Background

Chagas disease affects millions of individuals across Latin America and imposes a substantial economic burden on healthcare systems, particularly in rural and underserved regions. Chronic Chagasic cardiomyopathy remains one of the leading causes of heart failure-related mortality in endemic countries. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has emerged as a potential biomarker of myocardial fibrosis in cardiomyopathies. This study was designed to investigate the association between TIMP-1 and myocardial fibrosis in chronic Chagas disease and to assess its potential as an early biomarker of fibrotic remodelling.

Methods and analysis

Bottom of form: The PTICH trial is a single-centre, prospective observational cohort study conducted at a government reference clinic in Pernambuco, Brazil. The study aims to enrol 210 adults with Chagas heart disease: 140 without ventricular dysfunction (left ventricular ejection fraction (LVEF) ≥52% in women and ≥54% in men) and 70 with ventricular dysfunction (LVEF

Ethics and dissemination

The Research Ethics Committee (REC) of Chagas disease and heart failure outpatient clinic—PROCAPE approved the PTICH trial (CAAE number: 65746322.8.1001.5192). Written informed consent has been obtained from all participants enrolled to date, and data handling is in compliance with applicable privacy and data protection regulations. Study findings will be disseminated through targeted outreach to civil society, the scientific community, healthcare professionals and Brazilian Unified Health System (SUS) policymakers; school-based science communication activities conducted in collaboration with state education departments (potentially including oral health educational materials); policy briefs and targeted reports for public health managers; technical meetings and institutional presentations; a plain-language summary published on the institutional website; and submissions to peer-reviewed journals and presentations at academic and health policy conferences.

Trial registration number

RBR-3dcrj98.

Retinal vascular phenotyping for early detection of coronary artery disease: quantitative assessment and diagnostic modelling

Por: Wu · Z. · Jiang · X. · Xin · Y. · Liu · J. · Ling · S. · Guo · C.
Objectives

To investigate the association between quantitative retinal vascular parameters and coronary artery disease (CAD) and to evaluate the efficacy of a retinal phenotype-based diagnostic model as a non-invasive tool for early CAD screening.

Design

A retrospective cross-sectional study.

Setting

A single-centre study conducted at the Cardiovascular Center of Beijing Tongren Hospital, Capital Medical University, China, between January and October 2024.

Participants

417 patients with suspected angina undergoing their first coronary angiography (CAG) were enrolled. Inclusion criteria were age >18 years and high-quality fundus photography within 24 hours pre-CAG. Major exclusions were prior coronary interventions, severe systemic/valvular heart diseases and ocular conditions impairing retinal vascular visualisation.

Primary and secondary outcome measures

The primary outcome was the association between quantitative retinal vascular parameters and the presence of CAD (defined as ≥50% stenosis). Secondary outcomes included the diagnostic performance area under the receiver operating characteristic curve (AUROC) of three predictive models: one based on quantitative retinal vascular parameters alone, one based on traditional risk factors and a combined model integrating both retinal and clinical variables.

Results

This study enrolled 417 patients undergoing initial CAG. Compared with non-CAD controls (n=190), patients with CAD (n=227) had higher prevalence of hypertension, dyslipidaemia and diabetes, along with elevated levels of fasting blood glucose, lipoprotein(a) (Lp(a)), triglyceride (TG) and glycated haemoglobin (HbA1c) (all p

Conclusion

Our findings, derived from an artificial intelligence-based fully automated quantitative retinal vascular parameters measurement method, revealed that multiple quantitative fundus parameters—including FD, VD and other morphological parameters were significantly associated with CAD risk. The CAD diagnostic model we developed demonstrates strong performance and high interpretability, making it suitable for early CAD screening and diagnosis.

Psychosocial risk screening in the inpatient care of physically ill patients: study protocol for a feasibility study

Por: Feder · S. C. · Simsek · Z. · Simon · J. J. · Hartmann · M. · Bruns · B. · Bugaj · T. J. · Hoch · J. · Dugas · M. · Friederich · H.-C.
Background

The length of hospital stay for patients with physical illnesses is longer for those with mental health comorbidity, particularly in the presence of severe physical multimorbidity. Integrating psychosocial risk screening at hospital admission, with a subsequent care pathway, could address psychosomatic and social care needs early and reduce length of stay. However, implementation may be hindered by organisational factors such as increased staff workload and timely integration into existing processes. In addition, patient factors such as low acceptance of screening and follow-up may affect uptake. This pilot study aims to assess the feasibility of implementing this integrated approach to screening and follow-up in preparation for a confirmatory trial.

Methods

The present study is a single centre, randomised feasibility study conducted on a pilot ward. Patients will be enrolled and assigned to the intervention or the control group. Only the intervention group will receive tablet-based psychosocial risk screening conducted by ward physicians or medical students in their practical year. If the psychosomatic screening is positive and the patient agrees, he or she is referred to the psychosomatic consultation service. If the social service screening is positive, the patient will be seen by a social worker. The main objective of this study is to assess the feasibility of conducting a full-sized confirmatory trial. An informed consent rate of 30% of eligible patients is set as the feasibility criterion. A study period of 4 months is planned for the feasibility study. The feasibility study will be analysed using descriptive statistics.

Ethics and dissemination

The study protocol was approved by the Ethics Committee of the Medical Faculty of Heidelberg University (S-301/2024) on 24 May 2024. The results of this feasibility study will be published in a peer-reviewed journal.

Trial registration number

NCT06651164.

Gender differences in clinical profiles, management and outcomes of valvular heart disease in China: insights from a nationwide cohort

Por: Ma · H. · Lu · Q. · Li · Z. · Ye · Y. · Zhang · B. · Wang · W. · Liu · Q. · Lv · J. · Zhao · Z. · Duan · Z. · Wang · B. · Yu · Z. · Guo · S. · Zhao · Y. · Gao · R. · Wu · Y. · Xu · H.
Objective

To compare the distribution, aetiology, treatment patterns and 2-year outcomes of moderate to severe valvular heart disease (VHD) between men and women in China.

Design

Nationwide, prospective, multicentre cohort study.

Setting

46 tertiary hospitals across China, representing a mix of primary and secondary care settings.

Participants

A total of 13 917 adult patients with moderate-to-severe VHD were enrolled between April and June 2018. Of these, 6296 (45.24%) were women. Inclusion criteria included moderate or severe native valve disease, infective endocarditis or prior valve intervention.

Interventions

Patients received either conservative therapy or valve interventions, including surgical repair/replacement or transcatheter procedures. Intervention decisions were based on clinical assessment.

Main outcome measures

2-year all-cause mortality, cardiovascular mortality, heart failure hospitalisation and major adverse cardiovascular events. Multivariable Cox and logistic regression analyses were conducted to identify outcome predictors.

Results

The overall intervention rate was 31.72%, with no gender difference (men: 31.26% vs women: 32.27%). Among the 5427 patients with severe symptomatic VHD, 49.11% received interventional therapy. The sex-specific pattern was particularly significant in severe symptomatic multiple valvular heart disease, where women had a higher propensity for intervention (p

The 2-year survival rate was 90.85% with no gender difference (men: 90.41% vs women: 91.38%, p=0.086). Valve intervention improved survival to 97.0%, with no gender disparity (men: 96.92% vs women: 97.01%, p=0.87). Multivariate Cox regression confirmed no significant gender effect (p>0.05).

Conclusions

Significant gender differences exist in VHD aetiology and subtypes in China. Women had more rheumatic VHD, while men had more degenerative and functional VHD. Intervention improved survival, with no gender disparity. Age and VHD subtype influenced intervention rates and prognosis, supporting individualised, sex- and age-stratified management strategies.

Trial registration number

NCT03484806.

Association of systolic blood pressure time in target range and all-cause mortality in patients with atherosclerotic cardiovascular disease: an analysis of a prospective cohort study

Por: Zhao · J. · Zhang · X. · Zhang · L. · Wu · S. · Chen · S. · Zhao · L. · Chen · B. · Li · W.
Objectives

To investigate the association between systolic blood pressure time in target range (SBP-TTR) and the risk of all-cause mortality in patients with atherosclerotic cardiovascular disease (ASCVD).

Design

Analysis of data from a prospective cohort.

Setting

This study used data from the Kailuan Study. Participants diagnosed with ASCVD from 11 hospitals affiliated with the Kailuan Group in Tangshan, China were included in the analysis.

Participants

We included 6732 participants who developed ASCVD between 1 July 2006 and 31 December 2013, and who had two or more blood pressure measurements recorded between the ASCVD diagnosis date and 31 December 2017. All participants were followed up until 31 December 2022.

Outcome measures

SBP-TTR was defined as the proportion of time during which SBP remained within the target range, calculated using the linear interpolation method. Participants were stratified into five SBP-TTR categories: 0%, >0% to

Results

When the target SBP range was defined as 120–140 mm Hg, compared with the SBP-TTR=0% group, the multivariable-adjusted HRs (95% CIs) for all-cause mortality were 0.92 (0.78 to 1.07), 0.82 (0.72 to 0.94), 0.79 (0.68 to 0.92) and 0.76 (0.65 to 0.89) for the SBP-TTR groups of

Conclusions

This study demonstrated a significant inverse association between SBP-TTR and all-cause mortality among patients with ASCVD. The association between maintaining SBP within the 120–140 mm Hg target range and reduced mortality was more evident in younger individuals. These findings suggest that sustained and stable blood pressure control may improve long-term survival in patients with ASCVD.

Trial registration number

ChiCTR-TNC-11001489.

PCSK9 inhibitoRs for Early Passivation of coRonary athEroSclerotic plaqueS in acute coronary syndromes (REPRESS): study protocol for a multicentre randomised controlled trial

Por: Chen · Z. · Ma · S. · Zhang · J. · Zhang · R. · Zhou · M. · Li · C. · Chen · Y. · Wang · H. · He · Y. · for the REPRESS trial investigator
Introduction

The ‘strike early and strike strong’ lipid-lowering strategy emphasises rapid reduction of low-density lipoprotein cholesterol (LDL-C) in patients with acute coronary syndrome (ACS). Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are increasingly used alongside statins to achieve guideline-recommended LDL-C targets after ACS. However, despite substantial LDL-C reductions with early PCSK9i initiation, their effects on non-culprit coronary atherosclerotic plaques remain unclear. This study aims to assess the impact of early intensive LDL-C lowering with PCSK9i added to moderate-intensity statin therapy on optical coherence tomography (OCT)-derived plaque characteristics in non-culprit coronary lesions in patients with ACS.

Methods and analysis

In this prospective, multicentre, open-label trial, 212 patients with ACS will be randomised 1:1 to an early intensified lipid-lowering strategy (PCSK9i added to moderate-intensity statin) or guideline-directed medical therapy for 6 months. Serial OCT imaging of non-culprit coronary arteries with 20–70% stenosis will be performed at baseline and 6 months. The primary endpoint is the absolute change in minimum fibrous cap thickness within a matched target arterial segment from baseline to 6 months. Secondary endpoints include changes in minimum lumen area, maximum lipid arc, presence of macrophage infiltration, LDL-C reduction and achievement of LDL-C targets. The primary endpoint will be analysed using analysis of covariance, adjusting for treatment group, baseline LDL-C stratification (≥1.8 vs

Ethics and dissemination

Ethics approval was granted by the Biomedical Research Ethics Committee of West China Hospital of Sichuan University (2024 Review No 1943). Results will be disseminated via peer-reviewed publications and presentations at academic conferences.

Trial registration number

NCT06791031.

Burden of atherosclerosis, cardiovascular risk factors and atrial fibrillation in individuals with covert brain infarcts in late midlife: the Akershus Cardiac Examination 1950 Study

Por: Ihle-Hansen · H. · Walle-Hansen · M. M. · Berge · T. · Ihle-Hansen · H. · Ronningen · P. S. · Omland · T. · Rosjo · H. · Tveit · A. · Beyer · M. · Steine · K. · Lyngbakken · M. N. · Ronning · O. M. · Vigen · T. · Quinn · T. · Cameron · A. · Hagberg · G.
Background

Current expert consensus statements generally suggest cardiovascular risk assessment, including atrial fibrillation (AF) screening, on detection of covert brain infarctions (CBIs). However, evidence to guide management of CBI remains limited. In the absence of randomised clinical trials specifically targeting CBI populations, observational studies comparing individuals with and without CBI can provide insights into the prevalence and burden of cardiovascular risk factors.

Objectives

We aimed to compare the burden of atherosclerosis and cardiovascular risk factors in participants with CBI to those without, and to explore the yield of AF screening in individuals with CBI.

Design

A prospective population-based birth cohort study including men and women born in 1950 and resident in Akershus County, Norway.

Setting

The two hospitals serving the population of Akershus county, Norway.

Participants

Participants included in the Akershus Cardiac Examination (ACE) 1950 study who also underwent a subsequent MRI examination were eligible for this study.

Outcome measures

Cardiovascular risk assessment was performed at study inclusion (2012–2015). Carotid ultrasound was used to quantify atherosclerosis through a carotid plaque score, and CHA2DS2-VA and Systematic COronary Risk Evaluation 2 (SCORE2) scores were calculated to estimate cardiovascular risk. Brain MRI was performed in a randomly selected, blood pressure-stratified subset of participants (2016–2024). CBI was defined as focal lesions consistent with ischaemia in the absence of clinical stroke. Participants with CBI were offered 72-hour ambulatory ECG monitoring for AF detection.

Results

MRI was performed in 414 of 3706 (11%) participants in the ACE 1950 Study. The mean age at the time of the MRI examination was 70.2±2.3 years, and 165 (41%) were women. CBI was identified in 54 participants (13%), of whom 45 (83%) completed 72-hour ambulatory ECG monitoring. There were no differences in mean carotid plaque score, SCORE2 or CHA2DS2-VA score between participants with CBI compared with those with normal MRI findings. AF was detected in one (2%) participant with CBI.

Conclusions

In this community-based cohort of individuals in late midlife, individuals with CBI did not have an increased cardiovascular risk compared with those without, as indicated by SCORE2, CHA2DS2-VA score, age-appropriate carotid plaque burden and a low prevalence of AF.

Trial registration number

URL: https://www.clinicaltrials.gov. Unique identifier: NCT01555411.

Research on latent class of multisymptom characteristics and transition mechanism of patients with coronary heart disease after PCI: protocol for a multicentre cross-sectional and prospective longitudinal study

Por: You · J.-C. · Li · Q. · Chen · R. · Zhang · W.-K. · Liu · Y.-Q. · Zeng · W. · Huang · Y.
Background

Post-percutaneous coronary intervention (PCI) patients frequently experience multidimensional symptoms (somatic, psychological, social), yet research remains fragmented. Current evidence lacks integration of dynamic symptom interactions and longitudinal evolution patterns. This study addresses critical gaps by characterising latent symptom classes and transition mechanisms during recovery, accounting for sociodemographic environmental influences across three Chinese provinces.

Methods and analysis

A multicentre study combines cross-sectional baseline assessment (T0) with prospective longitudinal follow-ups at 1 month (T1) and 6 months (T2) post-PCI. We will recruit 600 patients presenting with acute coronary syndrome and undergoing their first PCI from six Class A Tertiary Hospitals across Hunan, Jiangsu and Hainan provinces (July 2025–January 2026). Symptom phenotyping will use validated instruments: Patient-Reported Outcomes Measurement Information System-29, Tampa Scale for Kinesiophobia and Gastrointestinal Symptom Rating Scale. Latent profile analysis will identify baseline symptom profiles; latent transition analysis will model probabilities of transitioning between classes over time. Model selection will optimise fit indices (Akaike information criterion/Bayesian information criterion/bootstrap likelihood ratio test bootstrap) and clinical interpretability. Covariate-adjusted analyses will explore sociodemographic and environmental effects on symptom trajectories.

Ethics and dissemination

Approved by the University of South China Ethics Committee (2024NHHL037). Written informed consent precedes participation, with data deidentified and securely stored. Findings will be published in peer-reviewed journals following Strengthening the Reporting of Observational Studies in Epidemiology guidelines and presented at international cardiovascular conferences.

Trial registration number

ChiCTR2500097028.

Treatment gaps in guideline-directed medical therapy for HFrEF in Singapore: findings from a multicentre retrospective cohort study

Por: Senanayake · S. · Lee · A. S. Y. · Graves · N. · Win · P. P. S. · Lee · A. · Lau · Y. H. · Hausenloy · D. J. · Yeo · K.-K. · Chan · M. Y.-Y. · Wong · R. C. C. · Loh · S. Y. · Sim · K. L. D. · Chow · W. · Tan · K. B. · Kularatna · S.
Objectives

To describe prescription patterns, dosing and persistence of guideline-directed medical therapy (GDMT) among patients with heart failure with reduced ejection fraction in Singapore, and to identify factors associated with the use of quadruple therapy (ACE inhibitor (ACEi)/angiotensin II receptor blocker (ARB)/angiotensin receptor-neprilysin inhibitor (ARNI), β-blocker, mineralocorticoid receptor antagonist (MRA) and sodium-glucose cotransporter-2 (SGLT2) inhibitor).

Design

Retrospective, observational cohort study.

Setting

Secondary and tertiary care settings across seven public hospitals in Singapore.

Participants

3999 adults hospitalised from 2020 to 2022 with a first heart failure-related admission and left ventricular ejection fraction ≤40%. Patients with absolute contraindications to specific GDMT classes were excluded from eligibility calculations.

Primary and secondary outcome measures

Primary outcomes were the proportions of eligible patients prescribed each GDMT class and quadruple therapy at discharge. Secondary outcomes were 6-month prescription patterns, dose attainment and predictors of quadruple therapy use.

Results

Among eligible patients, 80%–99% met criteria for each GDMT drug class, yet only 29% received quadruple therapy at discharge in 2022. Prescription rates for ACEi/ARB/ARNI (67%), beta-blockers (89%), MRAs (40%), and SGLT2 inhibitors (46%) remained suboptimal despite high eligibility. At discharge, over 90% of patients on ACEi/ARB/ARNI and beta-blockers received ≤50% of target doses. By 6 months, prescription rates declined by 16% for ACEi/ARB/ARNI, 26% for beta-blockers and 7% for MRAs, while SGLT2 inhibitor use increased. Older age (OR 0.97, 95% CI 0.96 to 0.98) and chronic kidney disease stage 3a–4 (OR 0.65 to 0.04) were associated with lower odds of receiving quadruple therapy, while significant institutional variation was observed.

Conclusions

Despite high eligibility, uptake and optimisation of GDMT remain poor in Singapore, with substantial treatment gaps driven by underprescription, inadequate dosing and discontinuation. Interventions targeting clinician awareness, postdischarge support and institutional practice variation may improve adherence to guideline-recommended therapy.

Protocol for an open-label, randomised, controlled trial to evaluate the efficacy and safety of sotatercept add-on therapy compared with pulmonary vasodilator-based standard of care for pulmonary vasodilator-resistant pulmonary arterial hypertension assoc

Por: Yoshida · K. · Hosokawa · K. · Hiraide · T. · Akagi · S. · Ejiri · K. · Taniguchi · Y. · Adachi · S. · Inami · T. · Nakanishi · N. · Kataoka · M. · Satoh · T. · Tatebe · S. · Shinke · T. · Tomita · H. · Akazawa · Y. · Higaki · T. · Tagawa · K. · Ishikita · A. · Asakawa · S. · Abe · K.
Introduction

Eisenmenger syndrome and pulmonary arterial hypertension (PAH) due to unrepaired congenital shunts, including atrial septal defect (ASD), ventricular septal defect (VSD) and patent ductus arteriosus (PDA), remain life-threatening conditions despite advances in congenital heart disease (CHD) care. In this population, vasodilator-based therapies effective in other forms of PAH have shown limited benefit, and no disease-modifying treatment has been established. Sotatercept, an activin-signalling inhibitor, improved exercise capacity and haemodynamics in phase 2/3 PAH trials; however, patients with unrepaired CHD, including Eisenmenger syndrome, were excluded. The efficacy and safety of sotatercept in this population remain unknown.

Methods and analysis

The SuMILE trial is a prospective, exploratory, multicentre, open-label, randomised, controlled trial conducted at 11 Japanese tertiary centres. 36 adults with vasodilator-resistant PAH due to unrepaired ASD, VSD or PDA, including Eisenmenger syndrome, will be randomised 2:1 to sotatercept add-on therapy plus vasodilator-based PAH therapy versus vasodilator-based PAH therapy alone. Sotatercept will be administered subcutaneously every 3 weeks in accordance with label-approved dose-modification rules for haemoglobin and platelet changes. The primary endpoint is the change in 6-min walk distance from baseline to week 24. Key clinical events will be independently adjudicated. Secondary endpoints include all-cause mortality or lung transplantation; pulmonary hypertension-related hospitalisation or initiation of parenteral prostacyclin and changes in WHO functional class, N-terminal pro-brain natriuretic peptide and emPHasis-10. Exploratory endpoints include genotype, right heart catheterisation and cardiac MRI parameters. The primary analysis will use ANCOVA, adjusting for baseline 6-min walk distance and randomisation stratum in the intention-to-treat population.

Ethics and dissemination

The protocol has been reviewed and approved by the certified central review board (Kyushu University Hospital Clinical Ethics Review Board) and participating institutions. Written informed consent will be obtained from all participants. Findings will be disseminated through peer-reviewed journals, scientific conferences and trial registries.

Trial registration number

Japan Registry of Clinical Trials no. 1071250069; ClinicalTrials.gov NCT07356778. Protocol version and date: V.1.3; 23 October 2025

Hybrid drug-coated balloon strategy for coronary bifurcation lesions: a systematic review and meta-analysis

Por: Dillen · D. M. M. · van Beek · K. A. J. · Vermeer · A. J. E. · Vlaar · P.-J. · El Farissi · M. · Demandt · J. P. A. · Eerdekens · R. · van het Veer · M. · Tonino · P. A. L. · Teeuwen · K.
Objectives

Recently, drug-coated balloons (DCB) have emerged as a promising alternative for side branch treatment in coronary bifurcation lesions, in combination with drug-eluting stent (DES) implantation in the main vessel, the hybrid DCB approach. We aimed to evaluate clinical outcomes in patients treated with the hybrid DCB approach and to compare this strategy with other bifurcation techniques.

Design

A systematic review and meta-analysis.

Data sources

MEDLINE and EMBASE were searched up until January 2025.

Eligibility criteria

We included randomised controlled trials and observational studies investigating clinical outcomes in patients treated with the hybrid DCB approach for coronary bifurcation lesions.

Data extraction and synthesis

Two independent reviewers extracted data and assessed the risk of bias. The outcome of interest was the combined endpoint of cardiac death, myocardial infarction (MI) or target lesion revascularisation (TLR) at the longest available follow-up. Crude event rates, stratified by treatment strategy, were provided for the overall incidence of the primary endpoint. Furthermore, we conducted meta-analyses on the combined endpoint, comparing different bifurcation percutaneous coronary intervention (PCI) strategies. The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation tool.

Results

13 studies, consisting of 2393 patients, were included in our systematic review. Investigated techniques were the hybrid DCB approach in all studies, and a two-stent strategy or the combination of DES in main vessel and balloon angioplasty (BA) in the side branch as potential comparators. Median follow-up duration was 12 months (IQR 7.5–12). The combined endpoint of cardiac death, MI or TLR was found in 5.6% in the hybrid DCB group, 15.4% in the two-stent group and in 10.0% in the BA group. The pooled analyses, including three and two studies, respectively, showed that the hybrid DCB approach was associated with a lower risk of the composite endpoint of cardiac death, MI or TLR when compared with a two-stent strategy (7.9% vs 15.4%; risk ratio (RR): 0.53; 95% CI 0.33 to 0.85) and compared with BA in the side branch (5.6% vs 10.0%; RR: 0.57; 95% CI 0.37 to 0.88). The certainty of the evidence was graded as very low.

Conclusion

The results of this systematic review and meta-analysis suggest that the hybrid DCB approach is a feasible and promising treatment approach for bifurcation lesions, when compared with other bifurcation PCI strategies. However, the results should be interpreted cautiously as the certainty of evidence was graded as very low, underlining the importance of larger trials to confirm these findings.

Trial registration number

CRD420250651469.

Targeting Vascular Inflammation In Patients with Community-Acquired Pneumonia (TIN-CAP): protocol for a multicentre, randomised, double-blind, placebo-controlled trial

Por: Stotts · C. · Corrales-Medina · V. F. · deKemp · R. A. · Wells · G. A. · Beanlands · R. · Raggi · P. · Ferrara · G. · Sligl · W. · A Connelly · K. · Paul · N. · Brouwers · M. · Contreras-Dominguez · V. · Yadav · K. · Torres · C. · Tavoosi · A. · Wiefels · C. · Kirpalani · A. · Romsa · J.
Introduction

Inflammation plays a central role in atherosclerosis development and subsequent cardiovascular complications, including heart attack and stroke. Patients with inflammatory conditions such as community-acquired pneumonia (CAP) present with an elevated risk of cardiovascular events, which is likely driven by unresolved systemic inflammation. Targeting this heightened inflammatory burden may present a novel therapeutic strategy to attenuate heart attack risk in CAP survivors. Icosapent ethyl (IPE), an omega-3 fatty acid, demonstrates both pro-resolving and cardioprotective properties. The Targeting Vascular Inflammation In Patients with CAP (TIN-CAP) trial aims to evaluate the efficacy of IPE in mitigating vascular inflammation in CAP survivors.

Methods and analysis

TIN-CAP is a multicentre, randomised, double-blind, placebo-controlled trial. Eligible adults diagnosed with CAP in hospital or the emergency department will complete baseline assessments within 14 days of diagnosis including 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT angiography, bloodwork and quality of life evaluation (EuroQol – 5 Dimensions (EQ-5D)). Participants will then be randomised 1:1 to receive IPE (4 g/day) or placebo for 6 months. Follow-up visits will occur at 30 days (bloodwork and EQ-5D only) and 6 months. The primary endpoint is the change in FDG uptake in the ascending aorta from baseline to 6 months between IPE and placebo groups. Secondary endpoints include FDG uptake in the bone marrow, spleen, lungs and other vasculature, in addition to major adverse cardiac events and quality of life assessments. An initial lead-in cohort of 18 patients will be enrolled to assess recruitment, imaging feasibility and IPE tolerability prior to full trial enrolment. These patients will remain blinded and will be included in the final analysis (Vanguard design).

Ethics and dissemination

The TIN-CAP trial has been approved provincially by the Clinical Trials Ontario Research Ethics Board (approval number: 5045). Participants will provide written informed consent prior to enrolment. Study findings will be disseminated through peer-reviewed publications and conference presentations.

Trial registration number

NCT06710080.

Relationship between the urinary albumin-to-creatinine ratio and cardiovascular adverse outcomes in the Beijing community population: a prospective cohort study

Por: Liu · S. · Jia · J. · Huo · Y. · Fan · F. · Zhang · Y.
Objectives

To investigate the correlation between the urinary albumin-to-creatinine ratio (UACR) and adverse cardiovascular outcomes in the Beijing community population.

Design

Prospective cohort study.

Setting

Beijing, China, from May 2014 to December 2021.

Participants

Recruited from a survey conducted as part of an ongoing atherosclerosis cohort study in the communities of Gucheng and Pingguoyuan, Shijingshan District in Beijing, China. Excluded participants who already had a history of stroke or myocardial infarction at baseline. Finally, 3627 eligible participants were included in this analysis.

Exposure

The participants were divided into three groups on the basis of baseline UACR: the normal group (UACR

Primary and secondary outcome measures

The primary endpoint was a composite endpoint (major adverse cardiovascular event, MACE) of cardiovascular death, first acute myocardial infarction or first stroke, whereas secondary endpoints included cardiovascular death, first acute myocardial infarction, first stroke or all-cause death.

Results

The study included 3627 participants. According to the multivariable Cox model, compared with those in the normal group, the risks of MACE (HR=1.47; 95% CI 1.06 to 2.06; p=0.023), cardiovascular death (HR=3.03; 95% CI 1.56 to 5.88; p=0.001) and all-cause mortality (HR=1.91; 95% CI 1.23 to 2.97; p=0.004) were significantly greater in the microalbuminuria group. The risk of MACE (HR=3.65; 95% CI 2.14 to 6.23; p

Conclusions

This study indicates that an elevated UACR is a significant risk factor for adverse cardiovascular outcomes within the community population. This association remains consistent in individuals with low-grade albuminuria.

Protocol of the RADIO-STAR trial: a phase 1 safety and dose finding study of hypofractionated radiotherapy to the stellate ganglia for the treatment of ventricular arrhythmia

Por: Bussmann · B. M. · George · B. · Robinson · M. · Grist · J. · Sukumar · P. · Chinherende · E. · Sheerin · F. · Enzhil · V. · Rider · O. · Jones · B. · Sabharwal · A. · Herring · N.
Introduction

Sympathetic activation is the hallmark of cardiac disease, driving disease progression and triggering ventricular arrhythmia (VA). Despite optimal medical therapy, many patients experience recurrent VAs refractory to medical therapy, leading to repetitive implantable cardioverter defibrillator (ICD) therapy, worse quality of life and adverse outcomes. Cardiac sympathetic denervation (CSD) through surgical removal of the stellate ganglia is an effective treatment for refractory VAs but carries a high complication rate. We hypothesise that high precision image guided radiotherapy can be used to target the stellate ganglia to achieve CSD non-invasively.

Methods and analysis

RADIO-STAR (hypofractionated radiotherapy to the stellate ganglia for ventricular arrhythmia) is a first-in-human, phase 1 safety and dose finding study of radiotherapy to the stellate ganglia in patients with recurrent VAs. Patients with structural heart disease requiring recurrent ICD therapy for VAs are invited to undergo radiotherapy bilaterally to their stellate ganglia with a predetermined sample size of n=13. Radiotherapy dose will be determined by a prespecified dose escalation protocol. The primary outcome is safety defined as any treatment-related grade 3–5 toxicity occurring within 6 months of radiotherapy treatment, as defined by the Common Terminology Criteria for Adverse Events or any treatment-related side effects detected on patient symptom questionnaires and clinical examination during study visits. Secondary outcome measures to evaluate feasibility and efficacy include ability to safely deliver radiotherapy and consequent changes in circulating catecholamines and neuropeptide-Y, heart rate variability, structural changes in the stellate ganglia on MRI imaging and ICD therapy burden.

Ethics and dissemination

This study has received ethical approval by the South Central—Oxford B Research Ethics Committee (REC/SC/0005). Study findings will be submitted for publication in peer-reviewed scientific journals and presented at national and/or international scientific conferences.

Trial registration number

ISRCTN49861434.

Association between angiotensin receptor-neprilysin inhibitor use and clinical outcomes in patients with heart failure: a 1-year prospective cohort study from Jordan

Por: Odeh · R. S. · Abdel Jalil · M. · Qudah · M. A. · Al-Makhamreh · H. K. · Saleh · A. · Awwad · O.
Objectives

Heart failure (HF) is associated with complex symptoms and frequent hospitalisation that reduce patients’ quality of life (QoL). This study aims to assess the association between angiotensin receptor-neprilysin inhibitor (ARNI) use and changes in QoL and disease-related outcomes among patients with HF in Jordan.

Design

Prospective observational cohort study.

Setting and participants

The study was conducted among patients with HF attending the outpatient cardiology clinics at Jordan University Hospital, a tertiary care centre in Amman, Jordan. Patients either initiated on ARNI or receiving angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) were included in the study at a 1:2 ratio. All participants were followed up for up to 1 year after recruitment. The study period was from 4 February 2024 to 29 May 2025.

Primary and secondary outcome measures

Data on QoL, New York Heart Association (NYHA) functional class and left ventricular ejection fraction (LVEF) were collected at baseline and after 3 months of treatment. Hospitalisation data were collected for the preceding year and the year following participants’ recruitment. Medication adherence and ARNI side effects were assessed after 3-month of follow-up period.

Results

A total of 227 patients with HF were included; 74 were initiated on ARNI, and 153 were receiving ACEIs/ARBs. At baseline, significantly lower QoL scores and LVEF were observed in the ARNI group compared with the ACEIs/ARBs group. After 3-month, the ARNI group showed improvements in all QoL scores, NYHA functional class and LVEF (p

Conclusions

ARNI use was associated with favourable QoL, NYHA class, and LVEF as well as lower hospitalisation rates among patients with HF in Jordan. The safety profile was consistent with previous studies.

Effectiveness of a co-adapted virtual discharge education app on disease knowledge and health behaviours in patients following heart attack: a multicentre, randomised controlled trial protocol in Sydney, Australia

Por: Zhang · L. · Shi · W. · Zhao · E. · Hyun · K. K. · Zecchin · R. · Gao · Y. · Brunorio · L. · Stanaway · F. · Ellis · T. · Redfern · J. · Clark · R. · Du · H. · Gallagher · R.
Introduction

Active self-management by patients following acute coronary syndrome (ACS) can reduce recurrent events. Patient education for transitioning from hospital to home promotes effective self-management but can be limited in the acute setting due to time and resource pressures. Patients from ethnic minority and immigrant backgrounds face additional language, cultural and health literacy barriers to receiving patient education. Self-administered virtual patient education presents an innovative solution to these challenges. This study aims to evaluate a co-adapted, virtual avatar nurse-guided, discharge education application (app) for Chinese-speaking patients following ACS.

Methods and analysis

This multicentre, assessor-blinded, randomised controlled trial will recruit 98 Chinese-speaking inpatients following ACS with evaluation at 1 and 3 months postdischarge. Control participants in the control group will receive the usual ward-based patient discharge education. Intervention participants will additionally receive the education app installed on their devices before hospital discharge with unlimited access during the study period. Cultural relevance and linguistic accuracy for this Chinese version of an existing app were ensured through co-adaptation with Chinese-speaking consumers; the primary outcome will be coronary heart disease (CHD) knowledge, and secondary outcomes will include knowledge, attitudes and beliefs regarding heart attack symptoms and responses, CHD self-management behaviours, utilisation of healthcare services and quality of life. A process evaluation will be conducted alongside the trial to assess the acceptability and feasibility of the app. Between-group comparisons will be made using 95% CIs, accounting for baseline differences using linear mixed effects or mixed effects logistic regression models.

Ethics and dissemination

The Western Sydney Local Health District Human Research Ethics Committee has approved this study protocol (26 February 2024, amendment number 2) (2024/STE00147), with site-specific authorisations obtained from each participating hospital. The results will be disseminated through peer-reviewed journal articles and presentations at scientific conferences.

Trial registration number

ACTRN12624000408583.

Left atrial appendage closure versus direct oral anticoagulants after pulmonary vein isolation for atrial fibrillation: protocol for a multicentre, prospective, randomised, non-inferiority trial (PROMOTE study)

Por: Shen · L. · Jiang · L. · Hao · Z. · Chu · H. · Wang · X. · Ning · Z. · Zhang · J. · Yang · B. · Xu · Y. · Fang · R. · Kong · L. · Zhang · X. · He · Q. · Zhang · Z. · Zhang · T. · Du · C. · Wu · Y. · Zhao · D. · Huang · H. · Ma · W. · Liang · Z. · Pan · X. · Wang · C. · Miao · Y. · Shen · L. · He · B.
Introduction

Atrial fibrillation (AF), with a prevalence of 1–2%, is the most common cardiac arrhythmia. AF is associated with a fivefold increased risk of cardioembolic events; approximately 20% of all strokes are caused by AF. Pulmonary vein isolation (PVI) has become the first-line treatment for AF. However, PVI cannot eliminate the residual stroke risk. Current guidelines recommend that anticoagulation be continued in this specific group of patients, regardless of the presence or absence of AF. In this large AF population post-PVI, who are considered to be in an earlier stage of AF, it is unknown whether left atrial appendage closure (LAAC) offers an alternative to direct oral anticoagulant (DOAC) therapy.

Methods and analysis

The trial will be a prospective, randomised, multicentre non-inferiority study comparing two treatment strategies in AF patients after atrial ablation. Patients will be randomly assigned to either percutaneous LAAC (group A) or DOAC treatment (group B) in a 1:1 ratio; both sequential and concomitant planned ablation with or without LAAC are accepted. Randomisation will be conducted using web-based randomisation software. A total of 1012 participants (506 patients per group) will be enrolled. The primary effectiveness measure will be the occurrence of any of the specified events within 24 months after randomisation: stroke/transient ischaemic attack/systemic thromboembolism, cerebral haemorrhage, other major haemorrhages (Bleeding Academic Research Consortium ≥2), cardiovascular mortality and all-cause mortality.

Ethics and dissemination

The study was approved by the Ethical Review Board of Shanghai Chest Hospital, China (KS(Y)20287). Written informed consent will be obtained from all participants. The trial will follow the Declaration of Helsinki and Good Clinical Practice. Confidentiality will be maintained with anonymised, securely stored data. Findings will be disseminated through peer-reviewed publications and conferences.

Trial registration number

ChiCTR2000036538.

Development and validation of a machine learning model for prediction of 1-year mortality following ST-elevation myocardial infarction: a retrospective cohort study

Por: Sritharan · H. P. · Nguyen · H. · Ciofani · J. L. · Bhindi · R. · Allahwala · U. K.
Objectives

To develop a machine learning (ML)-based risk prediction model for 1-year mortality in ST-elevation myocardial infarction (STEMI) patients undergoing primary or rescue percutaneous coronary intervention.

Design

Patient data, including demographic, clinical, biochemical, imaging and procedural details, were extracted from electronic medical records. Data were split into training (80%) and test (20%) sets. Eight supervised learning algorithms were evaluated: least absolute shrinkage and selection operator, ridge, Elastic Net (EN, decision tree, support vector machine, random forest, AdaBoost and gradient boosting. Feature selection was performed sequentially with subsets of the top 5/10/15/20/25/30 features. Model hyperparameters were optimised using fivefold cross-validation with area under the curve (AUC) as the scoring metric.

Setting

Single, tertiary Australian centre.

Participants

We analysed data from 1863 consecutive STEMI patients treated at a tertiary Australian centre from July 2010 to December 2019.

Outcome measures

The primary outcome was 1-year all-cause mortality.

Results

The 1-year mortality rate was 13.6% (n=254) in our cohort. The EN model with five key features (parsimonious model) demonstrated superior performance, achieving an AUC of 0.821, which was comparable to the full 30-variable model (AUC 0.821). Advanced age, pre-hospital cardiac arrest and management with balloon angioplasty alone were identified as predictors of increased mortality risk, while family history of premature coronary disease and higher left ventricular ejection fraction were associated with improved survival. To facilitate clinical implementation, we developed a user-friendly web application for individualised risk assessment.

Conclusion

Our ML model accurately predicts 1-year mortality in STEMI patients using only five clinical variables. This tool offers improved accuracy and ease of use compared with existing risk stratification methods, potentially enhancing patient stratification and guiding treatment decisions in STEMI management.

Assessment of health-related quality of life and treatment satisfaction and their associated factors among older adults with heart failure: a prospective observational study in selected hospitals in Northwest Ethiopia

Por: Tarekegn · G. Y. · Dagnew · F. N. · Wondm · S. A. · Anberbr · S. S. · Tamene · F. B. · Tsega · S. S. · Asmare · Z. A. · Zeleke · T. K. · Dagnew · S. B. · Zerihun · T. E. · Kassaw · A. T. · Mussie · D. A. · Melese · T. B. · Moges · T. A.
Objectives

To assess health-related quality of life (HRQoL), treatment satisfaction and associated factors among older adults with acute heart failure in Northwest Ethiopia.

Design

Prospective, multicentre observational study.

Setting

Three tertiary hospitals in Northwest Ethiopia provide secondary and tertiary care services.

Participants

A total of 422 patients aged ≥60 years with a confirmed diagnosis of acute heart failure were consecutively enrolled between December 2024 and April 2025. Patients with unstable psychiatric conditions or advanced kidney disease were excluded.

Outcome measures

HRQoL was assessed using the WHO Quality of Life – Brief Version questionnaire, and treatment satisfaction was measured using the Treatment Satisfaction Questionnaire for Medication (TSQM). Multiple linear regression identified factors associated with HRQoL and treatment satisfaction.

Results

95% of participants reported moderate HRQoL, and 3% reported poor HRQoL. Weight loss was positively associated with HRQoL (β=1.52; 95% CI 0.04 to 3.07; p=0.021), whereas asthma was negatively associated with HRQoL (β = –3.28; 95% CI 6.94 to 0.37; p=0.001). Regarding treatment satisfaction, 65% of patients were moderately satisfied, with notable concerns regarding medication safety and overall experience. Rural residents reported lower satisfaction than urban residents (β = –0.20; 95% CI 0.34 to 0.05; p=0.007). Patients with New York Heart Association (NYHA) class III had higher satisfaction (β=0.25; 95% CI 0.05 to 0.45; p=0.016). Effective hypertension management was linked to increased satisfaction (β=0.20; 95% CI 0.02 to 0.37; p=0.026), whereas coronary heart disease was associated with lower satisfaction (β = –0.40; 95% CI 0.64 to 0.88; p=0.012).

Conclusions

Among older adults with heart failure in Northwest Ethiopia, 98% reported moderate to low HRQoL. Asthma and polypharmacy negatively affected HRQoL, whereas weight loss was positively associated with HRQoL. An NYHA class III status and well-managed hypertension improved treatment satisfaction, whereas rural residency and coronary heart disease were associated with lower satisfaction. These findings underscore the need for targeted interventions to enhance outcomes and QoL in this vulnerable population.

Social determinants of health and risk of lower extremity amputation in patients with peripheral artery disease in Canada: protocol for a systematic review and meta-analysis

Por: Chowdhury · A. · Sheikh · F. · Azab · S. M. · de Souza · R. J. · Banfield · L. · Balakrishnan · N. · Anand · S. S.
Introduction

Peripheral artery disease (PAD) affected approximately 800 000 Canadians aged 25 years or older in 2015 and it poses a substantial risk of lower extremity amputation (LEA). While clinical risk factors for amputation are well-established, the impact of social determinants of health (SDoH) on amputation risk remains unclear, particularly in a Canadian context.

Objectives

This systematic review aims to: (1) synthesise evidence on the associations between multilevel SDoH domains and LEA (both major and/or minor) risk in Canadian PAD patients including intersectional effects of race and ethnicity with another SDoH domain, and (2) evaluate the statistical methodologies used in the researched literature to inform future study design and analysis approaches.

Methods and analysis

We will systematically search MEDLINE, Embase, EmCare, Global Health, Cumulative Index to Nursing and Allied Health Literature and Web of Science for studies examining SDoH and LEA in Canadian patients with PAD (including chronic limb-threatening ischaemia which is a severe form of PAD). Date limits for each database will be from inception through December 2025. SDoH will be categorised using a modified Healthy People 2030 SDoH framework under six domains: economic stability, education, food, neighbourhood and physical environment, healthcare system and community and social context. Two reviewers will independently screen titles, abstracts and full texts, with discrepancies resolved by a third reviewer. Data will be extracted on study characteristics, SDoH measures, outcomes and statistical methods. Risk of bias will be assessed using RoB 2 for randomised trials, ROBINS-I for non-randomised studies of interventions and ROBINS-E for studies investigating exposures. A narrative synthesis, and where data permit, a Bayesian hierarchical meta-analysis using both effect size and contingency table approaches will be conducted. Statistical heterogeneity will be explored through subgroup analyses and meta-regression, examining study design, SDoH measurement approaches and population characteristics.

Ethics and dissemination

As a systematic review and meta-analysis, ethics approval is not required. For institutional oversight, we provide the contact of Dr Sonia Anand (Associate Vice-President, Global Health, McMaster University; anands@mcmaster.ca). Results will be reported following PRISMA guidelines and disseminated through a peer-reviewed publication.

PROSPERO registration number

CRD420251115759.

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