Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 59 appraisals
The Journal of clinical endocrinology and metabolism
The effects of glucose-dependent insulinotropic polypeptide on net splanchnic blood flow in lean humans.
CONTEXT: Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone with potent vasoactive and metabolic effects in adipose tissue, but its effects on splanchnic blood flow (SBF) in humans remain unclear. Investigating potential regional differences is important for understanding the vascular actions of GIP in humans. OBJECTIVE: The aim of this study was to examine the effects of GIP on SBF, both independently and in combination with hyperglycemia and hyperinsulinemia. METHODS: In a randomized, controlled crossover study, 8 healthy, lean male participants underwent 4 separate experimental conditions. The interventions included intravenous infusions of either GIP at a rate of 1.5 pmol-1 kg-1 minute-1 or saline, administered alone or in combination with a hyperglycemic and hyperinsulinemic clamp, respectively. Splanchnic blood flow was measured by Fick's Principle after catheterization of a hepatic vein, using indocyanine green as indicator. RESULTS: Splanchnic blood flow remained comparable across all experimental conditions, including GIP and saline infusions, both with and without the hyperglycemic and hyperinsulinemic clamp (P = .42). CONCLUSION: Under the applied conditions, GIP does not appear to play a substantial role in the acute regulation of net SBF, either alone or in combination with induced hyperglycemia and hyperinsulinemia.
17 July 2026
Read appraisal →Journal of the American Heart Association
Social Determinants of Health and Cardiovascular Disease-Related Outcome Disparities Among Breast Cancer Survivors: A Systematic Review
BACKGROUND: Breast cancer is the most commonly diagnosed malignancy worldwide. Breast cancer survivors face an increased risk of cardiovascular disease (CVD), a leading cause of death in this group. Social determinants of health (SDoHs), operationalized as economic, environmental, and psychosocial factors, play an important role in CVD disparities. However, few studies have examined how SDoHs are associated with CVD disparities in this population, and no systematic review has addressed their multilevel influences. METHODS: This systematic review summarizes the current evidence on the relationships between SDoHs at different levels and CVD disparities among breast cancer survivors. Using the 2024 American College of Cardiology/American Heart Association framework, SDoHs were categorized at the individual, interpersonal, or community levels. Studies published in peer-reviewed journals between January 1, 2010, and November 30, 2025, were identified through searching electronic databases (PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Web of Science, PsycINFO) and citations. RESULTS: Of 6550 unique records, 37 articles that addressed the impact of SDoHs on CVD outcomes were selected. Most (n=31) were conducted in the United States and used retrospective designs (n=29). Most (n=30) focused on individual-level SDoHs such as race, income, or education; 2 on interpersonal-level SDoHs (ie, psychosocial stress); and 13 on community-level SDoHs, including neighborhood socioeconomic status and residential area. Black race, lower neighborhood socioeconomic status, and rural residence were associated with a higher incidence of CVD and increased cardiovascular death. CONCLUSIONS: This review highlights the urgent need to address SDoHs and emphasizes the importance of multilevel interventions to reduce CVD disparities among breast cancer survivors.
9 July 2026
Read appraisal →Journal of the American Heart Association
Diagnostic and Prognostic Utility of Mitral Annular Plane Systolic Excursion: A Systematic Review and Meta-Analysis
BACKGROUND: Movement of the mitral annulus toward the left ventricular (LV) apex during systole, termed atrioventricular plane displacement or mitral annular plane systolic excursion (MAPSE), was first observed by Leonardo da Vinci in the 15th century. MAPSE, a measure of longitudinal movement, shows good agreement between transthoracic echocardiography and cardiovascular magnetic resonance imaging and can also be measured by transesophageal echocardiography and cardiac computed tomography. Measurement is fast, simple, and easily automated. However, no major imaging guidelines advise routine measurement. METHODS: We present a systematic review of studies appraising the diagnostic and prognostic performance of MAPSE from PubMed, Medline, Google Scholar, and Embase until September 2025 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Studies assessing MAPSE in adult populations were included, and non-English publications, abstracts, and studies of congenital heart disease were excluded. Newcastle-Ottawa Scale assessed study quality. Correlation coefficients between MAPSE and markers of systolic function were pooled using Hunter-Schmidt meta-analysis. Heterogeneous diagnostic and prognostic outcomes were synthesized narratively. RESULTS: The review included 92 studies. MAPSE correlated with LV ejection fraction (r=0.64 [95% CI, 0.54-0.74]) and global longitudinal strain (r=0.53 [95% CI, 0.45-0.63]), showing a modest association with systolic function, particularly useful in patients with poor echocardiographic windows. MAPSE was frequently reduced despite preserved LV ejection fraction across multiple pathologies, enabling earlier detection of systolic impairment. MAPSE also demonstrated strong prognostic value, outperforming LVEF and global longitudinal strain in predicting adverse events in several studies. CONCLUSIONS: Overall, MAPSE has a clinically important role meriting integration into routine cardiac imaging and care.
9 July 2026
Read appraisal →Molecular pharmaceutics
Platelets as Programmable Drug Depots: Toward Predictive and Mechanistic Drug Loading
Efficient drug delivery remains a major challenge in pharmaceutical science, with synthetic nanocarriers often facing limitations in real biological systems. While blood platelets have been explored as biomimetic carriers, their intrinsic capacity for molecular storage and stimulus-triggered release remains largely underutilized. Here, we propose that platelet granules can be viewed as programmable drug depots, whose loading can be rationally controlled using physicochemical principles and endogenous transport mechanisms. In contrast to empirical approaches, we outline a framework based on two complementary pathways: passive accumulation driven by ion trapping of weakly basic compounds in acidic granules, and active uptake mediated by vesicular transporters. Building on recent advances in structural biology and computational modeling, we further argue that drug loading into platelets can be predicted and optimized using molecular descriptors, docking approaches, and machine learning models to estimate transporter compatibility and accumulation efficiency. This perspective introduces a conceptual design loop linking prediction and molecular optimization─i.e., enabling both selection of suitable drug candidates and rational modification of their structures to enhance platelet compatibility. Together, these concepts position platelets not simply as biomimetic carriers but as model-guided and engineerable platforms for drug delivery, bridging biological systems with rational design strategies.
6 July 2026
Read appraisal →Molecular biology reports
Recent advances in the detection and functional analysis of circRNAs with short-read RNA sequencing-based methods
Circular RNAs (circRNAs) were first identified approximately 50 years ago in pathogenic viroids as single-stranded, covalently closed RNA molecules. Initially considered by-products of splicing, circRNAs are now recognised as an important class of regulatory RNAs involved in microRNA sponging, RNA-protein interactions, and cellular pathways. Their closed-loop structure, generated through backsplicing, confers resistance to exonucleolytic degradation and contributes to their stability. Owing to their tissue- and disease-specific expression, circRNAs have emerged as promising biomarkers for cancer, neurodegenerative disorders, and cardiovascular disease. Over the past decade, numerous bioinformatics tools utilising RNA-sequencing (RNA-seq) data have been developed for circRNA detection and analysis. Detection methods have evolved from manual split-read inspection to automated identification of the back spliced junction, while annotation pipelines now resolve the genomic origins and structural characteristics of circRNAs. Because individual circRNA callers vary considerably in sensitivity and specificity, a combined usage of tools in circRNA detection has become the preferred strategy for generating high-confidence datasets. Beyond their non-coding functions, increasing evidence suggests that some circRNAs possess protein-coding potential through open reading frames, cap-independent translation mechanisms, internal ribosome entry sites (IRESs), and N6-methyladenosine modifications. A new generation of bioinformatic tools can now assess the protein-coding potential of circRNAs, integrating the above features, as well as machine learning and deep learning approaches refining these predictions. This review summarises recently developed short-read RNA-seq bioinformatics tools for circRNA detection, consensus calling, annotation, and protein-coding potential prediction, with a particular focus on advances from the past five years that facilitate the identification of translatable circRNAs.
5 July 2026
Read appraisal →Medicine
Molecular profiling of coronary stent restenosis: A systematic review and functional analysis of implicated genes
BACKGROUND: Coronary stent restenosis occurs in approximately 5% of patients treated with drug-eluting stents (DES) and is associated with adverse clinical outcomes. Elucidating the genetic mechanisms underlying restenosis may support precision medicine approaches to improve patient management.This systematic review aimed to synthesize evidence on genes and biological pathways associated with DES-related restenosis and to perform functional analysis of the implicated genes using bioinformatics tools. METHODS: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. A systematic search of PubMed, Scopus, and Web of Science was performed for human studies investigating genetic or genomic factors in coronary restenosis, with the last search conducted in March 2024. Eligibility criteria included original studies reporting genetic associations with DES restenosis. Screening and data extraction were performed by a single reviewer. Identified genes underwent gene set enrichment analysis using Enrichr (Ma'ayan Laboratory, Computational Systems Biology) and ClueGo extension on Cytoscape (National Resource for Network Biology). RESULTS: Seventeen studies met the inclusion criteria. The studies highlighted multiple genes involved in extracellular matrix remodeling, inflammatory signaling, and the renin-angiotensin system. Gene enrichment analysis confirmed the overrepresentation of these biological pathways in DES-associated restenosis. CONCLUSIONS: This systematic review synthesizes the genetic and molecular contributors to DES-associated restenosis and identifies potential targets for future research and personalized therapies. No external funding was received, and the protocol was not registered.
28 June 2026
Read appraisal →Cardiovascular research
Proteins targeting ischaemic-reperfusion injury and repair after myocardial infarction: a systematic literature review.
Following myocardial infarction (MI), reperfusion strategies ensure that blood flow is promptly restored to salvage the ischaemic myocardium. However, the sudden restoration of blood flow can inflict further damage to the ischaemic tissue, known as myocardial ischaemia/reperfusion injury (MIRI). Therapeutic strategies aimed at reducing MIRI and promoting cardiac repair remain an important clinical need. Protein-based therapies might exert benefits that limit damage and promote cardiac repair post-MI. To explore this further, we performed a systematic review of data from preclinical studies and clinical trial registries evaluating the cardioprotective effects of proteins post-MI. Medline and EMBASE were searched for preclinical studies that examined the potential cardioprotective effects of protein-based therapies to limit damage and/or mediate cardiac repair when administered after MI and/or reperfusion. Studies registered with ClinicalTrials.gov and EudraCT were also reviewed. In total, 84 studies were included in the final analysis, which included 46 different proteins. Overall, our findings support the concept that transiently applying recombinant or modified proteins after acute MI has the potential to promote lasting improvements in heart function via multiple pleiotropic mechanisms. Many of these proteins converge on a limited set of well-established signalling pathways involved in cardiac repair and remodelling after MI, with a few proteins demonstrating consistent and robust effects across multiple outcomes and models (small and large animals; reperfused and non-reperfused models). Despite this, the high potential cardioprotective benefit reported in preclinical studies has not translated into approved therapies for use in patients. Although the previous failure of protein therapies in clinical development does not invalidate the potential relevance of their downstream pathways, our research underlines the challenges in translating preclinical findings of protein-based therapies into the clinical setting. Future preclinical and clinical research should examine the optimal treatment effect and fully characterize the therapeutic potential of proteins involved in post-MI remodelling.
28 June 2026
Read appraisal →Reviews on environmental health
Air quality and public health co-benefits of national transport policies
INTRODUCTION: Transport is a major contributor to urban air pollution and premature mortality worldwide. This systematic review evaluates the air-quality and public health co-benefits of national and regional transport policies aimed at reducing population exposure to air pollution. CONTENT: Following PRISMA 2020 guidelines, this review synthesized evidence published between 2011 and 2024 on the health and environmental impacts of national or regional transport policies. Ten eligible studies were reviewed, covering diesel vehicle phase-outs, inspection and maintenance programs, electric vehicle incentives, fuel taxation, and promotion of public or active transport. SUMMARY: Across multiple settings, these policies were associated with reductions in PM2.5 concentrations and with avoided premature mortality, respiratory and cardiovascular hospitalizations, and healthcare costs. The largest and most consistent health benefits were observed for integrated policy packages, particularly those combining regulatory and technological measures such as fuel quality improvements, vehicle electrification and diesel phase-out, complemented by behavioral or fiscal instruments. Most available evidence originates from high-income countries, while studies from low- and middle-income regions remain scarce. The limited number of eligible studies and their concentration in specific regions and modeling approaches constrain generalizability, especially to settings with different transport systems, resource availability, and air-quality profiles. OUTLOOK: Embedding health-impact assessment within transport planning and expanding long-term evaluations in low- and middle-income countries are essential to ensure equitable and sustained air-quality and health improvements. Future policy frameworks should prioritize source-oriented regulatory and technological measures such as vehicle electrification, fuel-quality regulation, and diesel phase-out implemented within integrated policy packages to maximize public-health co-benefits.
25 June 2026
Read appraisal →Biogerontology
RNA-binding proteins in aging and age-related diseases: roles, mechanisms, and a large language model analysis
Aging is a progressive and irreversible biological process that contributes to the pathogenesis of numerous age-related diseases. Elucidating the molecular mechanisms of aging is crucial for promoting healthy aging and extending healthspan. RNA-binding proteins (RBPs) are pivotal regulators of post-transcriptional gene expression and play essential roles in diverse biological processes. RBPs interact with both coding and non-coding RNAs to regulate RNA metabolism, stability, localization, and translation. Dysregulated RBP-RNA interactions have been closely associated with aging and age-related diseases. This review systematically summarizes the structural characteristics of RBPs and the evolution of methods used to study them. We focus on the molecular mechanisms of six key RBPs, namely HuR, AUF1, TTP, IGF2BP2, QKI, and LARP7, in the context of aging and age-related diseases. In addition, we discuss the regulatory functions of post-translational modifications of RBPs. Furthermore, we provide a multidimensional overview of RBP involvement in aging and age-related diseases through large language model (LLM)-based text-mining analysis. Our study provides a foundation for the comprehensive characterization of RBPs in aging and age-related diseases.
22 June 2026
Read appraisal →The American journal of cardiology
Limus- Versus Paclitaxel-Coated Balloons for In-Stent Restenosis Treatment: A Systematic Review and Study-Level Meta-Analysis of Randomized Controlled Trials
Drug-coated balloons are the preferred treatment for in-stent restenosis (ISR), avoiding the need for a second metallic layer. While both paclitaxel-coated balloons (PCB) and limus-coated balloons (LCB, typically sirolimus or biolimus) are used, direct comparative evidence is limited, particularly regarding their long-term angiographic efficacy and clinical safety. We conducted a systematic review and study-level meta-analyzis of studies comparing LCB with PCB for coronary ISR. A comprehensive search was performed across PubMed, Embase, Cochrane, Scopus, Web of science for randomized controlled trials. Outcomes were compared using risk ratios (RR) for categorical data and mean differences for continuous data in a random-effects model. Heterogeneity was assessed using the I2 statistic. Six randomized controlled trials involving 1,038 patients were included (552 in the LCB group and 481 in the PCB group). Compared with PCB, LCB were associated with a significantly higher risk of clinically driven target lesion revascularization (RR: 1.48; 95% CI: 1.02 to 2.14; p = 0.04; I2 = 0%) and target lesion failure (RR: 1.19; 95% CI: 0.87 to 1.62; p = 0.27; I2 = 0%). In contrast, both platforms demonstrated no differences in all-cause mortality (RR: 0.98; p = 0.96), myocardial infarction (RR: 0.73; p = 0.46), stent thrombosis (RR: 0.66; p = 0.57), or MACE (RR: 1.09; p = 0.58). Angiographic outcomes were comparable, including late lumen loss (mean differences: -0.00 mm; p = 0.65; I2 = 74.7%) and minimal lumen diameter (mean differences: -0.12 mm; p = 0.07). In patients with ISR, PCB reduced repeat revascularization compared with LCB. These data suggest a modest advantage for PCB in preventing restenosis following drug-coated balloon angioplasty for ISR.
16 June 2026
Read appraisal →European journal of pediatrics
Ambulatory hypertension and left ventricular hypertrophy in pediatric chronic kidney disease: a systematic review and meta-analysis
UNLABELLED: Cardiovascular disease is the leading cause of mortality in pediatric patients with chronic kidney disease (CKD). In the general pediatric population, hypertension is associated with an increased risk of left ventricular hypertrophy (LVH); however, the strength of this association varies in the pediatric CKD literature. A lack of consensus on optimal blood pressure (BP) targets for this population contributes to variability in clinical practice. This study aims to determine the association between ambulatory hypertension and LVH in pediatric CKD. A systematic literature search was conducted on five databases from 1974 to 2025. The mean left ventricular mass index (LVMI) and odds of LVH was compared between normotensive and hypertensive groups. The association between LVMI and 24-h systolic/diastolic blood pressure, day/night systolic/diastolic blood pressure, and 24-h mean arterial pressure (MAP), was determined. Fifty-one full text studies (n = 6509 children) were eligible for inclusion in the meta-analysis. Pediatric CKD patients with ambulatory hypertension demonstrated increased LVMI (mean difference 5.15 g/m2.7 (95% CI 3.16, 7.15) and increased risk of LVH odds ratio 2.82 (95% CI 2.18, 3.65) to normotensive controls. LVMI was significantly lower among children with a 24-h MAP < 50th percentile (- 8.2 g/m2.7, 95% CI - 16.0, - 0.4) and 24-h SBP between the 50 and 90th percentiles (- 10.8 g/m2.7, 95% CI - 20.8, - 0.8) compared to those with 24-h MAP or 24 h SBP > 90th percentile, respectively. CONCLUSION: In children with CKD, ambulatory hypertension is associated with elevated risk of LVH and increased LVMI. However, there was significant heterogeneity among the included studies with respect to study design and definition of outcomes. Timely detection of hypertensive target organ injury is imperative to mitigate future cardiovascular disease in pediatric CKD patients.Prospero Registration: CRD 42023426891. WHAT IS KNOWN: • Hypertension is a critical predictor of adverse cardiovascular outcomes in children with CKD. Hypertension-induced target organ damage such as LVH may predict future cardiovascular outcomes in high-risk populations. Despite this, there remains considerable variability in clinical blood pressure targets and monitoring practices. Our findings highlight the importance of ambulatory blood pressure monitoring (ABPM) in detecting subclinical cardiovascular injury, supporting its integration into routine CKD care to improve risk stratification and treatment decisions. WHAT IS NEW: • This meta-analysis establishes a robust association between ambulatory hypertension and left ventricular hypertrophy (LVH) in children with CKD, demonstrating that higher blood pressure burden is linked to increased left ventricular mass index (LVMI). Notably, children with 24-h mean arterial pressure (MAP) and systolic blood pressure (SBP) above the 90th percentile exhibited significantly greater LVMI, reinforcing the impact of sustained hypertension on cardiac remodelling in pediatric CKD. • The strong association between ambulatory hypertension and LVH underscores the urgent need for evidence-based BP thresholds that minimize cardiovascular risk in pediatric CKD. Early identification of hypertensive target organ damage may enable timely therapeutic interventions to prevent long-term cardiovascular complications. Future studies should focus on defining optimal BP targets and evaluating the efficacy of antihypertensive strategies tailored to pediatric CKD. Standardizing BP measurement approaches may further refine hypertension management and improve cardiovascular outcomes in this vulnerable population.
14 June 2026
Read appraisal →The New England journal of medicine
Intravascular Ultrasound-Guided or Angiography-Guided Complex High-Risk PCI
BACKGROUND: Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) has been associated with increased stent optimization and reduced adverse events among patients with complex coronary-artery lesions, but adoption of this strategy in Western countries remains low. Although practice guidelines recommend intracoronary imaging for anatomically complex lesions, evidence from current European practice is limited. METHODS: In this investigator-initiated, international, open-label, randomized, controlled trial, we assigned patients undergoing complex PCI to either IVUS-guided PCI, performed with the use of prespecified stent-optimization criteria, or angiography-guided PCI. The primary end point was target-vessel failure, defined as a composite of death from cardiac causes, target-vessel myocardial infarction, or clinically indicated target-vessel revascularization. RESULTS: Of the 2020 patients who underwent randomization, 1010 in the IVUS-guided PCI group and 1009 in the angiography-guided PCI group were included in the primary analysis. The mean age of the patients was 69 years, 79.4% were men, and 27.4% presented with an acute coronary syndrome. The mean procedure duration was 88.8 minutes with IVUS-guided PCI and 66.2 minutes with angiography-guided PCI. Dilation with balloon angioplasty after stent implantation was performed in 91.3% of the IVUS-guided PCI procedures and in 84.5% of the angiography-guided PCI procedures. At a median follow-up of 19.0 months (interquartile range, 15.2 to 23.4), target-vessel failure had occurred in 140 patients (13.9%) in the IVUS-guided PCI group and in 112 patients (11.1%) in the angiography-guided PCI group (hazard ratio, 1.25; 95% confidence interval, 0.97 to 1.60; P = 0.08). Procedural complications occurred in 11.3% of the IVUS-guided PCI procedures and in 10.2% of the angiography-guided PCI procedures. The frequency of adverse events appeared to be similar in the two groups. CONCLUSIONS: Among patients undergoing complex high-risk PCI, a strategy of routine IVUS-guided PCI performed with the use of prespecified stent-optimization criteria was not associated with a lower risk of target-vessel failure than angiography-guided PCI alone. (Funded by Boston Scientific; IVUS-CHIP ClinicalTrials.gov number, NCT04854070.).
13 June 2026
Read appraisal →The New England journal of medicine
IVUS-Guided versus Angiography-Guided PCI in Unprotected Left Main Coronary Disease
BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used for revascularization of unprotected left main coronary artery disease. Whether intravascular ultrasonographic (IVUS) guidance during PCI results in better clinical outcomes than conventional angiographic guidance alone is uncertain. METHODS: In an international, multicenter, open-label trial, we randomly assigned patients with unprotected left main coronary artery disease in a 1:1 ratio to undergo either IVUS-guided PCI or angiography-guided PCI. The primary end point was a patient-oriented composite of any stroke, any myocardial infarction, any revascularization, or death from any cause at the longest follow-up. RESULTS: A total of 806 patients underwent randomization; 401 were assigned to undergo IVUS-guided PCI and 405 to undergo angiography-guided PCI. The mean (±SD) age of the patients was 71.4±10.7 years, 78.4% of the patients were men, and 34.7% had diabetes. At a median follow-up of 2.9 years, a primary end-point event had occurred in 135 patients (33.7%) in the IVUS-guided PCI group and in 125 patients (30.9%) in the angiography-guided PCI group (hazard ratio, 1.11; 95% confidence interval, 0.87 to 1.42; P = 0.40). The incidence of death, myocardial infarction, or revascularization appeared to be similar in the two groups. The percentages of patients with procedure-related and overall safety events also appeared to be similar in the two groups. CONCLUSIONS: Among patients with unprotected left main coronary artery disease, IVUS-guided PCI showed no additional benefit over angiography-guided PCI with respect to the incidence of stroke, myocardial infarction, any revascularization, or death from any cause at a median follow-up of 2.9 years. (Funded by Philips Image Guided Therapy Devices and Boston Scientific; OPTIMAL ClinicalTrials.gov number, NCT04111770.).
12 June 2026
Read appraisal →Circulation
Determining the Physiological Threshold for Angina (ORBITA-FIRE): A Double-Blind, Randomized, Placebo-Controlled Study
BACKGROUND: In stable coronary artery disease, the primary goal of percutaneous coronary intervention (PCI) is symptom relief. Fractional flow reserve (FFR) and nonhyperemic pressure ratios such as resting full-cycle ratio (RFR) are used to guide revascularization. Although these indices correlate with myocardial ischemia, they have never been validated against the onset of angina. The physiological thresholds for angina, FFRangina and RFRangina, angina (FFRangina at rest and during exercise remain undefined. METHODS: ORBITA-FIRE (Finding the Invasive Threshold for Symptom Relief in Exertional Angina) was a multicenter, double-blind, randomized, placebo-controlled study in patients with stable angina and single-vessel coronary artery disease. After imaging-guided PCI, an in-stent balloon was incrementally inflated until angina occurred at rest. This angina threshold was verified against placebo inflation, and corresponding FFRangina and RFRangina values were recorded at symptom onset. The protocol was repeated during low- and high-intensity exercise to assess changes in angina thresholds with increasing cardiac workload. RESULTS: Sixty-five patients were enrolled (mean age, 63.9±8.7 years; 74% male; 69% hypertensive; 23% diabetic; 91% with Canadian Cardiovascular Society class II-III angina). Median pre-PCI FFR was 0.59 (interquartile range [IQR], 0.46-0.70) and RFR was 0.61 (IQR, 0.40-0.82). Median FFRangina at rest was 0.29 (IQR, 0.23-0.35), increasing to 0.38 (IQR, 0.30-0.48) during low-intensity exercise and 0.45 (IQR, 0.36-0.55) during high-intensity exercise. RFRangina similarly increased from 0.22 (IQR, 0.16-0.30) at rest to 0.26 (IQR, 0.18-0.36) and 0.32 (IQR, 0.23-0.46) during low- and high-intensity exercise. All thresholds were significantly lower than clinical diagnostic cut points (P<0.001). Lower FFRangina and RFRangina thresholds were associated with greater symptom reproducibility across rest, low- and high-intensity exercise conditions (FFRangina: P=0.008, P<0.001, P<0.001, respectively; RFRangina: P=0.015, P<0.001, P=0.002, respectively). Lower angina thresholds across all conditions predicted higher baseline angina burden and greater symptom relief with PCI (probability of interaction >0.999). CONCLUSIONS: Physiological thresholds for angina, FFRangina and RFRangina, are highly individualized, vary with cardiac workload, and are consistently lower than the universal ischemia-based thresholds used to guide revascularization. These findings support integrating personalized, symptom-linked physiology to refine patient selection and to improve symptomatic response to PCI.
9 June 2026
Read appraisal →Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation
Association of intensive blood pressure lowering with health-related quality of life after endovascular thrombectomy: a post-hoc analysis of the ENCHANTED2/MT trial
BACKGROUND AND PURPOSE: Intensive blood pressure (BP) targets of less than 120 mm Hg have been shown to worsen functional outcomes after endovascular thrombectomy (EVT) for acute ischemic stroke. However, their effects on self-reported health-related quality of life (HRQoL) remain uncertain. METHODS: This post-hoc exploratory analysis used data from ENCHANTED2/MT, an open-label, blinded-endpoint randomized trial conducted in 44 Chinese hospitals. Adults with elevated BP within 3 h after successful reperfusion were randomized to intensive (< 120 mmHg) or less intensive (140-180 mmHg) systolic BP targets. HRQoL at 90 days was assessed using the EQ-5D-3 L and EQ visual analogue scale (EQ VAS). Functional outcome was measured by the modified Rankin Scale (mRS). Treatment effects were estimated using adjusted regression models, and causal mediation analysis was performed to explore indirect and direct pathways. RESULTS: Of 816 randomized patients, EQ-5D data were available in 685. At 90 days, both EQ-5D index (0.66 vs. 0.72) and EQ VAS (73.01 vs. 76.84) were lower in the more intensive BP group. Adjusted mean differences favored the less intensive treatment group: 0.06 (95% CI, 0.01 ~ 0.11; P = 0.017) for EQ-5D index and 3.49 (95% CI, 0.38 ~ 6.60; P = 0.028) for EQ VAS. Mediation analysis showed that the association of intensive BP lowering with worse HRQoL was mainly indirect via worse mRS outcomes. CONCLUSIONS: Intensive BP lowering after EVT was associated with modestly worse HRQoL at 90 days. The observed differences were small in magnitude, particularly for EQ VAS relative to commonly reported thresholds for clinical importance. These findings are consistent with less intensive BP targets after EVT and highlight the importance of incorporating patient-reported outcomes in acute stroke trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT04140110 the Registration Date, 22/10/2019.
7 June 2026
Read appraisal →Neurology
Associations of Baseline Clinical Phenotypes With White Matter Hyperintensity Volume Change: A Study of 4,329 UK Biobank Participants
BACKGROUND AND OBJECTIVES: White matter hyperintensities (WMHs) relate to cognitive and physical impairment. Although WMHs typically progress over time, regression has also been observed. Our aim was to explore baseline clinical phenotypes associated with subsequent WMH volume change in the UK Biobank (UKB). METHODS: We included participants with total volume of WMHs at first and follow-up brain MRI. We assessed 107 preselected clinical phenotypes measured at baseline and preprocessed using the Phenome Scan Analysis Tool (PHESANT). We derived a measure of WMH change as the residual from a linear regression of follow-up WMH volumes on baseline WMH volumes to account for baseline WMH burden. We ran (1) linear regressions for continuous WMH change as the outcome and (2) multinomial logistic regressions comparing progression, regression, and stable groups after categorizing WMH volume change using an established percentile-based approach. Models were unadjusted, partially adjusted (age, sex, total brain tissue volume, follow-up time), or fully adjusted (further adding blood pressure; BP). We corrected p values using false discovery rate (FDR) correction. RESULTS: We included 4,329 participants (median age 52; interquartile range 12), 54.6% female, with a median follow-up of 2.3 years (range 1-7 years). Across follow-up, total brain volume decreased (mean decrease 16,058 mm3) and WMH volume increased (median increase 293 mm3; both p < 0.001). WMHs progressed in 53.9% of participants, regressed in 26.01%, and remained stable in 20%. In fully adjusted linear models, higher diastolic BP was the only baseline phenotype associated with greater WMH progression (0.10 SD higher WMH change per 1 SD higher inverse-rank normal transformed diastolic BP; 95% CI 0.05-0.15, FDR p < 0.05). In multinomial models, hip pain lasting more than 3 months (odds ratio [OR] 0.25, 95% CI 0.11-0.58) and faster walking pace (OR 0.79, 95% CI 0.66-0.95) were inversely associated with WMH progression, whereas hip pain was also inversely associated with WMH regression vs stability (OR 0.31, 95% CI 0.12-0.79; all FDR p < 0.05). DISCUSSION: We established vascular risk factors associated with subsequent WMH volume change in the studied cohort. Distinct clinical and demographic profiles characterized WMH progression, regression, and stable groups. Results suggest that vascular factors relate to WMH change but are sensitive to covariate control. Further studies should establish factors differentially and causally related to WMH progression, regression, and stability.
1 June 2026
Read appraisal →BMJ open
Role of community pharmacy in the prevention of cardiovascular disease in minority ethnic groups in the UK including barriers and facilitators: a mixed-methods systematic review
OBJECTIVES: To evaluate the role of community pharmacy in the prevention of cardiovascular disease (CVD) among minority ethnic groups and to identify key barriers and facilitators influencing engagement with pharmacy-based CVD prevention services. DESIGN: Systematic review using thematic synthesis to analyse both qualitative data and narratively synthesised quantitative data taking a convergent data synthesis approach. Searches were conducted from inception to 16 October 2024 across CINAHL Ultimate (EBSCOhost), EMBASE (Ovid), PubMed (NLM), Scopus (Elsevier) and Web of Science (Clarivate), supplemented by Google Scholar for grey literature and backward and forward citation tracking to identify additional studies. SETTING: Community pharmacy settings across multiple countries, including the UK and international contexts. PARTICIPANTS: Minority ethnic groups accessing community pharmacy services and community pharmacy professionals involved in delivering CVD prevention interventions. INTERVENTIONS: Community pharmacy-based CVD prevention interventions, specifically services addressing CVD risk factors. OUTCOME MEASURES: Outcomes comprised qualitative insights, including barriers and facilitators to engagement with community pharmacy-led CVD prevention services. RESULTS: Twenty-three studies met the eligibility criteria. Five overarching themes were identified: trust, systemic barriers, culturally tailored language, cultural and religious influences and family and social networks. Community pharmacies undertook varied CVD-related roles, most commonly CVD screening and diabetes management with additional contributions to smoking cessation, weight and lipid management, health promotion and medication adherence. Community pharmacies showed potential to support CVD prevention among minority ethnic groups. However, engagement was limited by language barriers, cultural beliefs, lack of trust in healthcare providers and organisational constraints such as time pressures and limited training. Facilitators included culturally tailored interventions, language concordance and strong pharmacist-patient relationships. CONCLUSIONS: Evidence from the UK remains limited, highlighting a need for further research into the role of community pharmacy in reducing CVD disparities among minority ethnic groups. International evidence suggests significant potential for pharmacy-based interventions, but improved cultural competence, targeted service design and greater awareness of determinants of equitable healthcare are essential. Future research should focus on optimising culturally responsive pharmacy-led CVD prevention strategies. PROSPERO REGISTRATION NUMBER: CRD42024579766.
29 May 2026
Read appraisal →European respiratory review : an official journal of the European Respiratory Society
Muscle sympathetic nerve activity in COPD: a systematic review and meta-analysis
BACKGROUND: Cardiovascular disease is a primary driver of mortality in COPD. Elevated sympathetic nerve activity is a key proposed mechanism, but the magnitude of this autonomic overactivity has not been quantified in a pooled analysis. OBJECTIVE: To determine if adults with COPD exhibit higher resting muscle sympathetic nerve activity (MSNA) than healthy controls, assess associated cardiorespiratory effects, and evaluate the short-term impact of COPD interventions on MSNA. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, eight databases were searched from inception to 15 May 2025 to inform this systematic review and meta-analysis (PROSPERO CRD420251044931). Eligible studies included adults with spirometry-defined COPD in whom MSNA was measured by microneurography at rest. Primary outcomes were MSNA burst frequency (bursts·min-1) and incidence (bursts per 100 heartbeats). Secondary outcomes included resting heart rate and blood pressure. RESULTS: A total of 11 studies (171 COPD participants, 105 controls) met inclusion criteria. Compared with controls, COPD was associated with markedly higher MSNA, burst frequency (+18.5, 95% CI 9.4-27.7 bursts·min-1) and burst incidence (+21.3, 95% CI 9.2-33.4 bursts per 100 heartbeats). Resting heart rate was also elevated (+10.7, 95% CI 6.1-15.3 beats·min-1), while blood pressure did not differ significantly. Three studies on noninvasive ventilation or inhaled β2-agonists found no significant pooled changes in MSNA. CONCLUSIONS: Resting MSNA is significantly elevated in patients with COPD despite normal blood pressure. This chronic sympathetic excitation likely contributes to COPD-related cardiovascular morbidity and exercise intolerance, highlighting the importance of developing therapies that reduce sympathetic nerve activity.
29 May 2026
Read appraisal →Molecular biology reports
The role of non-coding RNAs in the coronary no-reflow phenomenon: a systematic review
Coronary no-reflow poses a challenge in interventional cardiology. Increasing attention has been directed toward the potential role of non-coding RNAs (ncRNAs) in predicting coronary no-reflow (CNR), with no prior systematic review available to date. We aimed to systematically review the available evidence on the potential clinical utility of ncRNAs in CNR and/or microvascular obstruction (MVO). Embase, MEDLINE Ultimate, PubMed, Scopus, and Web of Science were searched, last on February 9, 2026. Studies enrolling adult patients with CNR and/or MVO that evaluated the expression of ncRNAs or investigated genetic variants within ncRNA-related pathways were included. Risk of bias was not assessed. Upregulation of miR-1, miR-7a/b, miR-98-5p, miR-133a, miR-133b, miR-208a, miR-224-3p, miR-660-5p, long non-coding RNA (lncRNA) TUG1, lncRNA MALAT1, and downregulation of miR-30e, miR-126, miR-155, and miR-542-3p were reported in patients with STEMI with CNR and/or MVO compared with those without CNR/MVO. Almost all ncRNAs were reported by a single study, with the exception of miR-30e, which was consistently reported in three independent studies. Several ncRNAs may demonstrate good performance in identifying patients at risk of CNR and/or MVO occurrence. Nevertheless, the available evidence is scarce and limited by the low robustness of the reported findings. Circulating ncRNAs are promising biomarkers for CNR. Nevertheless, several limitations persist, highlighting the need for further studies with standardized methodology to validate the clinical utility of ncRNAs.
28 May 2026
Read appraisal →Medicine
Machine learning identifies a NETs-related four-gene diagnostic signature for abdominal aortic aneurysm
Abdominal aortic aneurysm (AAA) is a chronic degenerative disease characterized by localized aortic dilation and persistent inflammation. While neutrophil extracellular traps (NETs) are increasingly recognized as key drivers of vascular inflammation and aneurysm progression, the transcriptomic landscape of NETs-related genes (NRGs) in AAA remains inadequately characterized. This study aimed to identify reliable diagnostic biomarkers and explore the immune heterogeneity of AAA to facilitate early risk stratification. We integrated transcriptomic datasets from the Gene Expression Omnibus to elucidate the role of dysregulated NRGs. A comprehensive bioinformatics pipeline was employed, combining weighted gene co-expression network analysis with differential expression profiling to screen for AAA-specific NRGs. Rigorous feature selection was conducted through the intersection of 3 machine learning algorithms - least absolute shrinkage and selection operator, support vector machine-recursive feature elimination, and random forest - to derive a diagnostic signature. The model was constructed using the GSE232911 cohort and validated in an independent external cohort. A robust 4-gene diagnostic signature comprising CXCR4, GZMB, ITGA6, and CD47 was identified. This signature demonstrated a favorable diagnostic performance, achieving an area under the curve of 0.920 in the training cohort. The model maintained consistent discriminatory ability in the external validation cohort, primarily driven by the high discriminative ability of CXCR4 and GZMB. Consensus clustering based on these hub genes revealed 2 distinct molecular subtypes, with Cluster 2 characterized by significant enrichment of neutrophils and innate immune pathways, suggesting intense NETosis activity. Furthermore, drug prediction analyses identified candidate therapeutic compounds, including Eugenol and Tretinoin, offering potential avenues for targeting the NETs-associated molecular landscape. Our findings underscore the pivotal role of NETs-mediated inflammation in AAA pathogenesis and validate a robust 4-gene signature for early diagnosis. By delineating immune-related molecular subtypes and identifying potential drug candidates, this study provides a foundational framework for precision risk stratification and the development of targeted nonsurgical therapies for aneurysm management.
25 May 2026
Read appraisal →JMIR research protocols
Protocol for Monitoring Postpartum Hypertension Outcomes via a Smartphone App (MOMitor): Ecological Momentary Assessment
BACKGROUND: Postpartum hypertension defined as elevated blood pressure after childbirth, affects approximately 20% of women after delivery. Digital health interventions that include remote monitoring therefore, present an important opportunity to facilitate regular blood pressure assessment in this high-risk population. OBJECTIVE: The primary objective is to assess within- and between-person changes in hypertension status over the first 6 weeks postpartum using a smartphone-based ecological momentary assessment protocol. The secondary objective is to characterize the trajectory of hypertension indicators across the 6-week period and to compare hypertension screening results from week one and week six within participants. METHODS: This study uses a time-series design using data from prospectively enrolled patients within a large health system. Patients eligible for recruitment were women aged 18 years or older who spoke English, owned a smartphone, had a liveborn neonate, and were willing to download an app and respond to survey questions within the app. Throughout the study period, all participants received hypertension screening items that asked whether their blood pressure was greater than 140/90 mm Hg and whether they felt dizzy or lightheaded, short of breath, or had a severe headache. A subset of participants were additionally asked to report their blood pressure readings. We estimate within- and between-participant effects using a generalized linear mixed model for a positive hypertension screen during weeks one through six. The model includes both fixed and random effects, controlling for age, race, marital status, education, insurance status, mode of delivery, total number of pregnancies, and history of diabetes mellitus. RESULTS: The study was funded July 2021 and data collection was initiated in November 2021. Data collection for this study, per protocol, was completed in June 2025, though other participants continue to be enrolled in the ongoing parent study. Data analysis is expected to be completed by Spring 2026 with publication planned for Summer 2026. CONCLUSIONS: The study findings will provide insight into trajectories of hypertension outcomes in postpartum women and the utility for smartphone app-based remote blood pressure monitoring among postpartum women whose blood pressure was regularly tracked. Findings will provide evidence to support whether widespread implementation of this digital health surveillance approach to improve outcomes in maternal health, especially in the postpartum period, is clinically warranted.
23 May 2026
Read appraisal →Current cardiology reports
Bridging Pediatric to Adult Care: A Scoping Review on Transitional Care for Individuals with Congenital Heart Disease Using Data Mining Techniques to Identify Key Topics
BACKGROUND: Adolescents and young adults with congenital heart disease (CHD) face significant challenges when transitioning from pediatric to adult care. Despite growing recognition of its importance, transitional care remains inconsistently implemented across healthcare systems, and a summary of published literature in this regard is still missing. This scoping review aims to systematically map the literature on CHD transitional care and identify key topics and trends. METHODS: Following Joanna Briggs Institute guidelines, we conducted a comprehensive search across seven electronic databases using the Population, Concept, and Context framework. A total of 73 studies were included. Data were extracted and analyzed using Latent Dirichlet Allocation to identify core topics, and Multiple Correspondence Analysis was applied to explore thematic relationships and validate topic structure. Lexicometric analysis assessed the linguistic complexity and specificity of the literature. RESULTS: Three major themes emerged: (1) Education, Self-Management, and Structured Support, (2) Timing, Knowledge Transfer, and Developmental Needs, and (3) Transition Program Implementation and Coordination. These themes reflect an increasing focus on structured educational strategies, developmentally tailored care, and system-level program delivery. Education-focused interventions were more frequently found in recent, high-quality experimental studies. In contrast, studies addressing timing and developmental needs and those focused on implementation were more common in earlier-phase or heterogeneous research contexts. CONCLUSION: Transitional care for individuals with CHD requires more standardized, evidence-based approaches. Improved documentation when reporting transitional care is essential to enhance fidelity, scalability, and long-term impact. This review provides a foundation for developing outcome-focused research and supports designing individualized, high-quality transition programs.
23 May 2026
Read appraisal →Journal of the American Heart Association
Determinants of Successful Implementation: A Mixed-Methods Evaluation of a Team-Based Telehealth Hypertension Management Program for Underserved Patients
BACKGROUND: Hypertension management using home blood pressure monitoring-guided pharmacotherapy is more effective than clinic-based care, but the benefit is attenuated in underserved patients. We evaluated implementation determinants of a team-based telehealth hypertension management program providing home blood pressure monitoring-guided pharmacotherapy and self-management and social support. METHODS: We used Exploration, Preparation, Implementation and Sustainment, and Health Equity Implementation Frameworks for semistructured interviews and inductive/deductive coding using thematic analysis of qualitative data and quantitative analysis to evaluate team-based telehealth hypertension management program implementation facilitators, barriers, acceptability, appropriateness, and feasibility. We purposefully sampled 20 patients with hypertension and 16 clinic key players from 2 safety-net clinics in North Carolina. Quantitative measures were Acceptability of Intervention Measure, Intervention Appropriateness Measure, Feasibility of Intervention Measure, Patient Assessment of Chronic Illness Care, Organizational Readiness for Implementing Change (all measures' score ranged 1-5; higher score is better). We used concurrent embedded mixed methods (qualitative + quantitative) for convergence and complementarity. RESULTS: Five qualitative themes emerged around (1) staffing barriers, coordinated teamwork, and friendly study tools; (2) the program's patient and provider centeredness; (3) ease of home blood pressure monitoring; (4) personalized, comprehensive self-management calls; and (5) social support. Patients and clinic key players found the program acceptable (mean±SD, 4.42±0.84 and 4.56±0.59), appropriate (4.42±0.86 and 4.61±0.50), and feasible (4.40±0.89 and 4.44±0.53), respectively. Patient Assessment of Chronic Illness Care and Organizational Readiness for Implementing Change scores were 4.22±1.01 and 4.11±0.78, respectively. CONCLUSIONS: Implementing a team-based telehealth hypertension management program depends on its tailoring to patients and providers and having their endorsement; a user-friendly and trust-promoting model; and having a viable financial plan. Future studies should assess clinical and cost effectiveness of the program. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05424744.
20 May 2026
Read appraisal →Journal of the American Heart Association
Residual Angina Following Complete Revascularization in the ISCHEMIA Trial: Frequency, Clinical Characteristics, Health Status, and Cardiovascular Outcomes
BACKGROUND: The frequency of residual angina and its impact on health status and death following anatomic complete revascularization in symptomatic patients with chronic coronary disease are unknown. METHODS: Data were analyzed from ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) trial participants randomized to invasive management with baseline angina (Seattle Angina Questionnaire Angina Frequency score <100), no prior coronary artery bypass graft surgery, and anatomic complete revascularization within 90 days of randomization. The primary outcome was frequency of residual angina after revascularization, defined as a Seattle Angina Questionnaire Angina Frequency score <100 within 6 months of randomization. Secondary outcomes included 6-month health status and medication use and 5-year all-cause and cardiovascular death. RESULTS: Among 2588 participants randomized to invasive management, 1442 (56%) had baseline angina and no prior coronary artery bypass graft surgery; 1034 underwent revascularization within 90 days, and 436 achieved anatomic complete revascularization. Of these, 184 (42.2%) had residual angina within 6 months. Baseline characteristics were similar between those with and without residual angina. Percutaneous coronary intervention was more common than coronary artery bypass graft surgery in those with residual angina (88% versus 80%, P=0.03). At 6 months, residual angina participants reported lower quality of life (Seattle Angina Questionnaire Quality of Life: 70±20 versus 83±20, P<0.001), greater physical limitation (Seattle Angina Questionnaire Physical Limitation: 84±20 versus 95±11, P<0.001), more dyspnea (Rose Dyspnea Scale score: 1±1.3 versus 0.4±0.8, P<0.001), and more antianginal medication use (P=0.006). Five-year all-cause and cardiovascular death did not differ significantly between groups. CONCLUSIONS: Residual angina is common (>40%) following anatomic complete revascularization for chronic coronary disease and is associated with reduced quality of life and greater antianginal medication use but no increase in death. REGISTRATION: Unique Identifier: NCT01471522.
20 May 2026
Read appraisal →Journal of the American Heart Association
Incremental Prognostic Power of Coronary Flow Reserve and Artificial Intelligence-Enabled ECG-Derived Filling Pressure in Angina With Nonobstructive Coronary Arteries
BACKGROUND: Coronary flow reserve reflects microvascular function, whereas filling pressure indicates myocardial hemodynamic burden. In angina with nonobstructive coronary arteries, abnormalities in either could contribute to a supply-demand mismatch; however, their combined prognostic significance remains unclear. METHODS: Patients with angina with nonobstructive coronary arteries who underwent invasive coronary reactivity tests were studied retrospectively. Coronary microvascular dysfunction (CMD) was coronary flow reserve <2.5. An artificial intelligence-enabled ECG marker of elevated filling pressure (AIEFP) was applied as a scalable prognostic marker of myocardial hemodynamic stress. Associations with major adverse cardiovascular events were evaluated using Cox regression and propensity score overlap weighting. RESULTS: Among 1957 patients with angina with nonobstructive coronary arteries (median age, 51.8 years; 67.2% women), CMD+ was identified in 26.4% and AIEFP+ in 6.6%. Over 8 years, 204 patients (10.4%) experienced major adverse cardiovascular events. In nested models, both CMD (hazard ratio [HR]=1.42 [95% CI=1.13-1.78]; P=0.002) and AIEFP (HR=2.28 [95% CI=1.67-3.11]; P<0.001) remained associated with major adverse cardiovascular events after adjustment. Adding AIEFP to the base model improved model fitness (Δχ2=23.65, P<0.001; ΔAkaike Information Criterion=-21.7) and modestly improved discrimination (ΔHarrell concordance index=0.02, P=0.02). In a 4-group model, adjusted risks increased in a graded manner. Overlap-weighted analysis after covariate balance demonstrated distinct temporal risk trajectories: CMD+/AIEFP+ had the highest 1-year risk (12.7%), and AIEFP+ had the highest cumulative 8-year risk (57% in CMD- and 51.8% in CMD+). CONCLUSIONS: CMD and AIEFP provide complementary prognostic information, with AIEFP remaining significantly associated with outcomes after multivariable adjustment. A dual-axis framework integrating myocardial hemodynamic stress (AIEFP) and microvascular function (coronary flow reserve) may enhance risk stratification and enable identification of clinically distinct angina with nonobstructive coronary arteries phenotypes with divergent trajectories.
20 May 2026
Read appraisal →European heart journal
Mitral transcatheter edge-to-edge repair and outcomes according to baseline health status: the RESHAPE-HF2 trial
BACKGROUND AND AIMS: Mitral transcatheter edge-to-edge repair (M-TEER) using the MitraClip device improves clinical outcomes in patients with moderate-to-severe ventricular secondary mitral regurgitation (vSMR) and heart failure (HF). This study evaluated whether the effects of M-TEER on clinical outcomes vary by baseline health status, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ), and assessed the impact of M-TEER on health status post-randomization. METHODS: The RESHAPE-HF2 trial included patients with symptomatic HF and moderate-to-severe vSMR (mean effective regurgitant orifice area .25 cm2; 14% >.40 cm2, 23% <.20 cm2). The impact of baseline KCCQ-clinical summary score (CSS) on the effect of M-TEER on clinical outcomes was assessed using Cox proportional hazards models. Changes post-randomization in health status and responder analyses were performed to assess the odds ratio (OR) of improvement and deterioration in KCCQ scores. RESULTS: Among 505 patients, M-TEER reduced cardiovascular death or HF hospitalization risk [hazard ratio (HR): .71 (.48-1.05), .50 (.29-.85), and .73 (.38-1.41)] across KCCQ-CSS tertiles of <38.9, 38.9-66.1, and >66.1, respectively (P-trend = .53). Similar results were seen for total HF hospitalization (P-trend = .48). M-TEER improved KCCQ-CSS, total symptom score, and overall summary score at 1, 6, 12, and 24 months compared to medical therapy alone (P < .05 at all time points). More patients in the M-TEER arm experienced a ≥5-point [OR 3.38 (2.09-5.45)], ≥10-point [OR 3.12 (1.93-5.02)], and ≥15-point [OR 3.25 (1.94-5.45)] improvement, and less patients had a ≥5-point deterioration [OR .34 (.19-.57)] in KCCQ-CSS at 6 months. Similar results were seen across other KCCQ domains and all time points. CONCLUSIONS: In patients with HF and moderate-to-severe vSMR, M-TEER showed a consistent trend towards a lower risk of HF hospitalization, with or without cardiovascular death, across all KCCQ-CSS tertiles and improved health status over time.
19 May 2026
Read appraisal →European journal of preventive cardiology
Elevated blood pressure levels among 533 167 adults living in Sub-Saharan Africa: a systematic review and meta-analysis
AIMS: Synthesizing contemporary data from sub-Saharan African countries, we did a systematic review and meta-analysis of blood pressure (BP) levels and hypertension among adults living in the region. METHODS AND RESULTS: We searched PubMed and other databases to identify studies published from 1 January 2010 to 31 December 2021. We used a random-effects model to estimate the pooled-prevalence of hypertension and mean systolic/diastolic BP overall and on a sex- and age-specific basis. Heterogeneity (I²) was assessed via the χ² test on Cochran's Q statistic. We identified 170 high-quality studies (195 samples) comprising 533 167 adults living in 26 countries. The pooled prevalence of hypertension was 30.5% (95% CI 28.4-32.6%). Overall mean systolic/diastolic BP was 128 (95% CI 127-129)/80 (95% CI 79-80) mmHg, with males recording higher mean BP levels (3.10 [95% CI 2.30-3.90]/0.69 [95% CI 0.10-1.29] mmHg) compared with females. Reflecting increasingly higher BP levels with age, the pooled estimates of hypertension prevalence initially rose three-fold (from 10.6% [95% CI 8.2-13.0%] to 30.9% [95% CI 27.8-34.0%]) in those aged 21-30 to 41-50 years, and then two-fold to 66.4% (95% CI 64.2-68.7%) among those aged 71-80 years, respectively. Hypertension prevalence was lower in healthy weight [28.4% (95% CI 26.1-30.6%)] compared with overweight [35.8% (95% CI 31.4-40.1%)] adults. Regionally, prevalent hypertension was lowest in those living in Eastern Africa [27.2% (95% CI 24.8-29.7%)]. CONCLUSION: Our findings suggest a steep age-related pattern of increasing BP levels in the region that will adversely affect millions of people within the next 10-20 years without urgent intervention. A detailed review and analysis of 170 studies involving more than half a million adult men and women living in 26 sub-Saharan Africa countries, revealed that one in three have elevated blood pressure/hypertension.Elevated blood pressure levels, and the markedly increased risk of suffering a debilitating or fatal cardiovascular event at an early age, rose steeply from around one in ten affected at age 20–30 years to around one in three by the age of 50 years.Beyond the influence of age, the risk of having elevated blood pressure was different, given it increased markedly for overweight men and women, whilst those living in (mainly poorer) Eastern African countries had the lowest blood pressure levels.
16 May 2026
Read appraisal →Biology of sex differences
Importance of integrating biological sex and age analyses in health research
Research findings in human, animal and cell populations may be influenced by biological sex and age. The traditional statistical approach to sex and/or age differences that are discovered in research data is to consider them as confounders that interfere with the ability to make accurate estimations and thus need to be controlled for. This article provides examples of how combining sexes or controlling for sex and/or age may lead to inaccurate findings and overlook important insights. Rather than treating these variables as confounding factors, they should be viewed as variables of importance to the research question. We contend that data should be analyzed according to sex/age as the primary analysis, while controlling for sex and age should be conducted as a secondary analysis. This topic is increasingly important as data are made publicly available and deep learning models/artificial intelligence are used to analyze large volumes of data. Mechanistic insights will continue to be lost if prompt action is not taken to report data according to sex and age and to analyze data by sex and age in health research.
14 May 2026
Read appraisal →Signal transduction and targeted therapy
Acute hemodynamic effects of TPN171H in pulmonary arterial hypertension: a randomized, controlled, phase 2a trial
Pulmonary arterial hypertension (PAH) has a poor prognosis despite available treatments. TPN171H, structurally modified from traditional Chinese medicine (Epimedium), was reported to have a high affinity for phosphodiesterase type 5 and exhibited anti-inflammatory and vasodilatory effects in preclinical studies. This phase 2a randomized trial (NCT04483115) evaluated the hemodynamic effects and safety of TPN171H in PAH. Sixty patients with PAH were randomly assigned to receive placebo, TPN171H (2.5, 5, or 10 mg) or tadalafil (20 or 40 mg) and evaluated for hemodynamic changes for 24 h. The primary endpoint was the maximum change (%) in pulmonary vascular resistance (PVR) from baseline. The key secondary endpoint was the change (%) in PVR to systemic vascular resistance (SVR) ratio at each observation point from baseline. Compared to the placebo group, the least square mean differences in the maximum change in PVR were -16.8% (95% CI, -29.1 to -4.5, p = 0.008) in TPN171H 5 mg, -15.4% (95% CI, -28.2 to -2.7, p = 0.019) in tadalafil 20 mg, and -13.3% (95% CI, -25.6 to -0.9, p = 0.036) in the tadalafil 40 mg group. Moreover, TPN171H 5 mg, but none of the tadalafil doses, showed a significant reduction in PVR/SVR ratio at 2 h (p = 0.026), 3 h (p = 0.030), and 5 h (p = 0.046) compared to the placebo group. No serious adverse events occurred. TPN171H 5 mg demonstrated favorable acute hemodynamic effects and an acceptable short-term safety profile in this exploratory trial, supporting further evaluation in adequately powered trials.
11 May 2026
Read appraisal →EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
Derivation and external validation of a deep learning model to predict changes in coronary plaque burden
BACKGROUND: Predicting the progression/regression of coronary plaque burden is challenging. AIMS: We aimed to develop a deep learning model to forecast changes in percent atheroma volume (ΔPAV) using intravascular ultrasound (IVUS). METHODS: We analysed data from IBIS-4 and PACMAN-AMI. Core lab measurements of plaque burden were available from IVUS pullbacks. Each model consists of a bidirectional Long Short-Term Memory (biLSTM) layer followed by two fully connected layers with one neuron each, resulting in both a classification for input progression/regression and an estimation of the ΔPAV. RESULTS: For the derivation and validation, a total of 1,960 regions of interest (ROIs) from the IBIS-4 dataset were used. The mean±standard deviation of the model accuracy was 0.85±0.02, the Matthews correlation coefficient was 0.70±0.04, and the F1 score was 0.85±0.02 for both progression and regression classes. In the testing (external validation) process with the PACMAN-AMI dataset, 5,283 ROIs were utilised. The mean ΔPAV was -0.31±5.63, for which 2,665 featured regression with a mean ΔPAV of -4.57±3.73, and 2,618 presented progression with a mean ΔPAV of 4.02±3.55, representing 49.6% of plaque progression prevalence. The predictive performance across the 100 trained models in the testing dataset showed an accuracy of 0.84, a Matthews correlation coefficient of 0.68, and an F1 score for the progression and regression classes of 0.84. CONCLUSIONS: This is the first deep learning model capable of detecting changes in plaque progression by analysing the rate of plaque burden change between adjacent frames.
10 May 2026
Read appraisal →EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
Quantitative flow ratio versus fractional flow reserve: 2-year follow-up of the FAVOR III Europe trial
BACKGROUND: Quantitative flow ratio (QFR) is an angiography-based method for estimating fractional flow reserve (FFR). The FAVOR III Europe trial showed that QFR guidance did not meet non-inferiority to FFR guidance, as measured by a composite endpoint of all-cause death, myocardial infarction, and unplanned revascularisation at 12 months. AIMS: We sought to report the 2-year outcomes of the QFR-guided diagnostic strategy and the FFR-guided strategy as applied in the FAVOR III Europe trial. METHODS: FAVOR III Europe was a multicentre, randomised, open-label, non-inferiority trial. A total of 2,000 patients from 34 European medical centres were randomised to undergo QFR- or FFR-guided revascularisation of intermediate coronary artery stenoses. Endpoints assessed at the 2-year follow-up included the rates of major adverse cardiac events (MACE) and its individual components of all-cause death, myocardial infarction, and unplanned revascularisation. The rates of MACE were compared for superiority by unadjusted Cox regression analysis. The outcomes from 1 to 2 years were explored in a landmark analysis. RESULTS: At 2 years, the rates of MACE were 9.7% in the QFR group and 7.4% in the FFR group (hazard ratio [HR] 1.34, 95% confidence interval [CI]: 0.98-1.81; p=0.064). In the landmark analysis, the rates of MACE between 1 and 2 years were 3.2% in the QFR group and 3.2% in the FFR group (HR 0.97, 95% CI: 0.58-1.62; p=0.92). CONCLUSIONS: The excess risks associated with QFR-guided revascularisation compared with FFR were confined to the first year. From 1 to 2 years, the rates of MACE developed similarly in the QFR and the FFR groups.
10 May 2026
Read appraisal →European journal of heart failure
The efficacy and safety of qiliqiangxin according to baseline ejection fraction in patients with heart failure and reduced ejection fraction in QUEST.
AIMS: Qiliqiangxin (QLQX), a Chinese traditional medicine, improved outcomes in patients with heart failure and reduced ejection fraction (HFrEF) when added to guideline-directed therapy. As treatment effects in heart failure (HF) may vary with left ventricular ejection fraction (LVEF), this post hoc analysis of the QUEST (Qiliqiangxin in Heart Failure: Assessment of Reduction in Mortality) trial examined whether baseline LVEF modified the efficacy and safety of QLQX. METHODS: QUEST randomized 3110 patients with symptomatic HF and LVEF ≤40%. The primary outcome was cardiovascular death or first HF hospitalization. Baseline LVEF was categorized as ≤25% (n = 482), >25-30% (n = 692), >30-35% (n = 829), and >35% (n = 1107). RESULTS: Mean LVEF was 32% (median 33%, interquartile range 28%-37%). Patients with LVEF ≤25% had the highest rate of the primary outcome (25.4 per 100 patient-years), while rates were similar across higher LVEF groups (18.7-19.8). After multivariable adjustment, lower LVEF was independently associated with higher risks of the primary outcome and mortality. The effect of QLQX on the primary outcome was consistent across LVEF categories (hazard ratio [95% CI] from the lowest to highest: 0.91 [0.64-1.30], 0.65 [0.47-0.89], 0.94 [0.71-1.26], and 0.71 [0.55-0.91], respectively; Pinteraction = .28), and as a continuous variable (Pinteraction = .45). Similar results were observed for individual components and total HF hospitalizations (all Pinteraction > .10). The safety of QLQX was also consistent across LVEF categories. CONCLUSION: In patients with HFrEF, lower LVEF was associated with worse cardiovascular outcomes. QLQX reduced cardiovascular events consistently across the range of LVEF examined in QUEST, despite the limited use of sodium-glucose co-transporter 2 inhibitors. CHICTR REGISTRATION: ChiCTR1900021929.
10 May 2026
Read appraisal →Medical image analysis
Robust fine-grained echocardiographic view classification with supervised contrastive learning
Accurate classification of echocardiographic views is fundamental for automated cardiac analysis. However, clinical practice relies on a large, heterogeneous set of fine-grained acquisitions that introduce substantial inter-observer variability. Existing studies have primarily focused on limited view sets, often collapsing specialised views into broad categories, which limits their clinical relevance. We address this limitation by introducing TTE47, the first publicly available benchmark comprising 47 clinically meaningful views annotated independently by three experts. This dataset enables the rigorous quantification of inter-observer agreement and establishes a foundation for reproducible, clinically relevant evaluation. To tackle the dual challenges of subtle inter-class distinctions and structured label variability, we propose a novel supervised contrastive learning framework incorporating a tailored loss function. Our method outperforms cross-entropy and standard supervised contrastive baselines, achieving leading performance among evaluated methods on TTE47 and surpassing prior work on TMED-2 without dataset-specific pretraining, using a model pretrained on TTE47. Beyond accuracy, we introduce clustering-based metrics, Detection Rate and Label Recovery Precision, that measure semantic coherence and the model's ability to resist annotation variability. Results show that the learned feature space aligns more strongly with underlying anatomical structure than with any single annotator's style, enabling resilience to label shifts and maintaining robustness comparable to human-level disagreement. By integrating multi-expert evaluation, robust representation learning, and interpretable feature-space analysis, this work establishes a scalable and clinically relevant framework for fine-grained echo view classification. Our findings highlight the potential of contrastive pretraining to standardise interpretation, mitigate subjectivity, and enhance the reliability of AI-assisted echocardiography in diverse clinical settings.
6 May 2026
Read appraisal →Annual review of biomedical engineering
Digital Twins for Biofluids
Digital twins-virtual representations dynamically linked to physical systems-have the potential to transform biomedical engineering by enabling real-time prediction, optimization, and personalization in health and disease. In biofluids, digital twins offer a framework for integrating physics-based models with data from clinical imaging, sensors, and physiological measurements to support diagnostics, therapeutic planning, and device design. This article reviews modeling approaches used in the construction of digital twins for biofluid applications. We survey high-fidelity numerical methods alongside emerging machine learning techniques, highlighting their respective strengths and limitations. Key requirements for digital twins are discussed, emphasizing the bidirectional interaction between physical and virtual assets and the importance of selecting modeling strategies tailored to specific biomedical contexts. While notable progress has been made over the past decade, significant challenges remain, particularly in integrating multiphysics models with data-driven methods and in establishing standardized protocols for data acquisition, interoperability, and sharing.
5 May 2026
Read appraisal →Environmental science. Processes & impacts
Adverse outcome pathway-informed machine learning for predicting vascular toxicity of emerging organic pollutants
Emerging organic pollutants (EOPs) are increasingly detected in wastewater and pose potential vascular toxicity risks that remain inadequately assessed in current regulatory frameworks. This study developed an adverse outcome pathway (AOP)-informed machine learning approach to evaluate vascular toxicity for 312 EOPs. By integrating ToxCast high-throughput bioassay data with Morgan fingerprints, we trained fourteen multilayer perceptron (MLP) models targeting key events in AOP 509, including Nrf2 inhibition, oxidative stress, mitochondrial dysfunction, apoptosis, endothelial impairment, and angiogenesis disruption. Our optimized models achieved high predictive accuracy (70-95%), enabling activity classification for both tested and untested chemicals. The predicted activation profiles prioritized chemicals such as ketoconazole, sertraline, and miconazole, with literature evidence supporting their vascular toxicity potential. This AOP-guided modelling framework demonstrates how integrating mechanistic pathways with machine learning can inform chemical risk assessment and prioritization, supporting hazard evaluation and environmental decision-making for pollutants with limited toxicological data.
4 May 2026
Read appraisal →Journal of medical Internet research
Application of Digital Health Technologies in Cardiac Rehabilitation for Patients With Coronary Heart Disease: Scoping Review
BACKGROUND: The high mortality and recurrence rates associated with coronary heart disease (CHD) impose substantial health care costs and economic burdens globally. Identifying effective interventions to improve patient outcomes is paramount. Digital health technologies (DHTs) offer novel solutions to overcome the challenge of low participation rates in traditional cardiac rehabilitation (CR). OBJECTIVE: This review aims to systematically map the scope of application, intervention objectives, and evaluation metrics of DHTs in CR for patients with CHD, thereby providing a structured evidence base for future research and practice. METHODS: This scoping review adheres to the Joanna Briggs Institute's methodology and is reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. A systematic search was conducted across 5 major databases, PubMed, Web of Science, Embase, Cochrane Library, and EBSCO, covering the period from inception to February 2026. Inclusion criteria were developed based on the participants, concept, and context framework. Studies focused on the application of various DHTs within CR settings for patients with CHD. Eligible literature comprised randomized controlled trials, quasi-randomized controlled trials, and longitudinal before-and-after studies published in peer-reviewed journals. Two researchers (XZ and ZL) independently conducted literature screening and data extraction. Findings were presented through a comprehensive narrative synthesis and evidence gap maps. RESULTS: A total of 43 studies were included, predominantly randomized controlled trials (n=40). Findings revealed (1) diverse technological formats, categorized into 3 main types: digital health tools, real-time remote support, and asynchronous communication. Multitechnology combined interventions have become the mainstream model (36/43, 83.7%). (2) Intervention objectives were multifaceted, consolidating into 4 dimensions: motivation and guidance, knowledge and skills, monitoring and security, and social and group dynamics. (3) Evaluation metrics were multidimensional, encompassing clinical physiological indicators, health behaviors, patient-reported outcomes, service use rates, and technological feasibility. DHTs demonstrated positive effects in improving short-term physiological function and health behaviors; however, evidence remains insufficient regarding their impact on long-term clinical outcomes such as reducing adverse events. CONCLUSIONS: The innovation of this scoping review lies in integrating highly heterogeneous evidence to reveal the field's evolution from isolated tools toward systematic, integrated solutions. Research confirms that DHTs effectively overcome temporal and spatial constraints, enhancing rehabilitation accessibility and engagement. They serve as crucial strategic tools for bridging geographical disparities in health care resources and advancing equity in cardiovascular health services. However, the evidence base remains limited, including insufficient long-term efficacy data and inadequate exploration of vulnerable populations such as older people and those with low digital literacy. Future research urgently requires large-scale, long-term follow-up clinical trials, alongside enhanced studies on adaptability for specific populations and considerations of health equity. This will propel digital CR toward greater scientific rigor, universal applicability, and precision.
3 May 2026
Read appraisal →Journal of the American College of Cardiology
Intravascular Imaging- vs Angiography-Guided Complex PCI: 5-Year Outcomes From a Randomized Trial
BACKGROUND: Data regarding long-term outcomes of intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary artery lesions, compared with angiography-guided PCI, remain limited. OBJECTIVES: The authors sought to present long-term clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. METHODS: Eligible patients with complex coronary artery lesions were randomly assigned 2:1 to undergo intravascular imaging-guided PCI or angiography-guided PCI in this prospective multicenter open-label superiority trial performed in South Korea. The primary endpoint was a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: A total of 1,639 patients underwent randomization with 1,092 assigned to imaging-guided PCI and 547 assigned to angiography-guided PCI. At a median follow-up of 5.3 years (Q1-Q3: 4.4-6.2 years), the primary endpoint occurred in 109 of 1,092 patients (10.5%) in the intravascular imaging-guided PCI group and 78 of 547 patients (14.9%) in the angiography-guided PCI group (HR: 0.68; 95% CI: 0.51-0.91; P = 0.009). Cardiac death or target vessel-related myocardial infarction occurred in 78 patients (7.6%) in the intravascular imaging-guided PCI group and in 56 patients (10.7%) in the angiography-guided PCI group, clinically driven target vessel revascularization in 45 (4.4%) and 32 (6.2%), and definite stent thrombosis in 1 (0.1%) and 4 (0.7%), respectively. There were no apparent differences in procedure-related safety events between the groups. CONCLUSIONS: In patients with complex coronary artery lesions undergoing PCI, intravascular imaging guidance reduced the risk of a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization at median follow-up of 5.3 years, compared to angiography guidance. (Intravascular Imaging- Versus Angiography-Guided Percutaneous Coronary Intervention for Complex Coronary Artery Disease [RENOVATE-COMPLEX-PCI]; NCT03381872).
3 May 2026
Read appraisal →Circulation
Prognostic Factors for Long-Term Risk of Stroke After Transient Ischemic Attack or Minor Stroke: A Systematic Review and Meta-Analysis
BACKGROUND: Patients with a transient ischemic attack (TIA) or minor stroke have an increased risk of subsequent stroke that persists for at least 10 years. We aimed to identify prognostic factors associated with long-term risk of stroke in this patient group and estimate their population attributable fraction (PAF). METHODS: A systematic review was performed of MEDLINE, Embase, and Web of Science for cohort studies including patients with TIA or minor stroke that evaluated factors for subsequent stroke over a follow-up period of ≥1 year. We pooled hazard ratios adjusted for relevant confounders using random-effect meta-analysis and determined the PAF of factors based on their pooled prevalence and adjusted hazard ratio. We assessed certainty of evidence using the grading of recommendations, assessment, development, and evaluation approach. The study is registered in PROSPERO (CRD42023476551). RESULTS: From 14 732 identified citations, we included 28 cohort studies comprising 86 810 patients with TIA or minor stroke (median age, 69 years [interquartile range, 65-71]; 52%-60% male patients). Factors that had high certainty evidence of association with increased long-term risk of stroke included older age (adjusted hazard ratio, 1.04 per year increase [95% CI, 1.02-1.05]); male sex (1.25, 1.15-1.36; PAF 13.0% [95% CI, 7.8-18.7]); atrial fibrillation (1.34, 1.18-1.52; 3.8% [95% CI, 0.3-9.9]); diabetes (1.52, 1.32-1.75; 7.7%, 3.1-14.1); hypertension (1.60, 1.31-1.94; 19.3%, 8.4-31.6); ischemic heart disease (1.67, 1.28-2.18; 10.7%, 2.8-22.9); history of stroke or TIA before the index event (1.70, 1.43-2.02; 12.0%, 5.2-21.4); smoking (1.29, 1.05-1.60; 11.2%, 1.0-30.7); ABCD2 (age, blood pressure, clinical features, duration of TIA, and presence of diabetes) score of ≥4 (1.59, 1.31-1.94; 18.0%, 2.9-39.9); presence of acute infarct on neuroimaging (1.97, 1.41-2.74; 19.0%, 5.2-38.9), including diffusion-weighted imaging-positive lesions (1.86, 1.02-3.37; 14.0%, 7.0-25.0); minor stroke as index event (1.75, 1.35-2.27 versus TIA; 28.0%, 10.2-47.6); presentation with aphasia or dysarthria (1.45, 1.24-1.69; 19.2%, 0.2-53.1); presentation with paresis (1.45, 1.15-1.84; 22.0%, 3.8-43.4); and etiologic stroke subtypes, including cardioembolism (2.16, 1.53-3.05; 14.6%, 3.1-33.5), large-artery atherosclerosis (2.19, 1.68-2.86; 13.2%, 5.1-25.5), and small-vessel disease (1.69, 1.14-2.49; 16.8%, 5.0-34.3). CONCLUSIONS: These findings can help identify patients with a particularly enduring risk of stroke who are most likely to benefit from ongoing monitoring and treatment and facilitate the development and implementation of targeted stroke prevention strategies.
3 May 2026
Read appraisal →Journal of the American College of Cardiology
Using Artificial Intelligence to Adjudicate Major Adverse Cardiovascular Events in Clinical Trials
BACKGROUND: Major adverse cardiovascular events (MACE)-cardiovascular (CV) death, nonfatal myocardial infarction (MI), and nonfatal stroke-are highly relevant clinical outcomes. In global randomized trials, medical records review by a physician clinical events committee (CEC) is the conventional standard for adjudicating MACE but is labor intensive. Automated adjudication with the use of artificial intelligence (AI) could reduce cost and improve reproducibility. OBJECTIVES: In this study, the authors sought to develop and validate an AI-based adjudication system for MACE and compare its performance with CEC adjudication in a large global randomized trial. METHODS: We developed an AI-based system ("Auto-MACE") that uses an iteratively refined prompt of the OpenAI o1-mini language model to adjudicate MACE events, and a Clinical Longformer model trained on adjudicated events to assign a confidence level. We validated Auto-MACE against CEC adjudication in the PARADISE-MI global clinical trial comparing sacubitril/valsartan and ramipril in 5,661 patients with MI complicated by systolic dysfunction or pulmonary congestion. RESULTS: Auto-MACE provided a confident adjudication in 315/455 deaths (69%), 301/659 potential MIs (46%), and 136/167 potential strokes (81%). Auto-MACE agreed with the CEC adjudication in 97%, 89%, and 88% of confident events, respectively. Among all events, Auto-MACE agreed with CEC adjudications in 86% of deaths, 76% of potential MIs, and 84% of potential strokes. The estimated effect of sacubitril/valsartan vs ramipril on composite MACE was similar with Auto-MACE adjudication (HR: 0.91; 95% CI: 0.78-1.07) and CEC adjudication (HR: 0.90; 95% CI: 0.77-1.05). CONCLUSIONS: AI-based adjudication of MACE showed high agreement with human CEC adjudication, especially for CV death and stroke, and where the model was confident. Initial AI-based adjudication with CEC review of uncertain events may reduce workload while maintaining accuracy.
24 Apr 2026
Read appraisal →Scientific reports
Food preferences and mortality risk in the prospective cohort of UK Biobank participants.
Food preferences may serve as less biased proxies for self-reported food intake in predicting health outcomes but have not yet been linked to mortality risk. We included 177,148 UK Biobank participants who completed a food preference questionnaire (FPQ), with a mean follow-up of 3.4 years (607,779 person-years; 3355 deaths). High versus low preference for 140 food items was tested using Cox regression with Holm adjustment. Sensitivity analyses excluded participants with key health conditions, additional supplement use, or short follow-up, added BMI and physical activity as covariates, and redefined preference groups. Higher preference for asparagus (hazard ratio (95% confidence interval)): 0.69 (0.62, 0.77)), aubergine (0.79 (0.72, 0.87)), black pepper (0.72 (0.64, 0.81)), broccoli (0.69 (0.61, 0.79)), butternut squash (0.75 (0.68, 0.83)), and extra virgin olive oil (0.67 (0.58, 0.78)) was linked to lower all-cause mortality, whereas higher preference for regular fizzy drinks (1.38 (1.24, 1.54)) was linked to higher mortality across all analyses. Specific food preferences are associated with all-cause mortality risk. FPQs may, therefore, complement conventional dietary assessments. Further studies should examine their associations with metabolic and cardiovascular outcomes.
19 Apr 2026
Read appraisal →International journal of cardiology
Predicting functional results of percutaneous coronary intervention using machine learning modelling
BACKGROUND: Post-percutaneous coronary intervention (PCI) Murray's law-based quantitative flow ratio (μFR) is associated with long-term clinical outcomes. A tool capable of accurately predicting post-PCI μFR before intervention could support procedural planning, reduce the risk of suboptimal physiological results, and improve prognosis. OBJECTIVES: To develop and validate machine-learning models that predict continuous post-PCI μFR using only pre-procedural angiographic, physiological and clinical data, and to assess their ability to classify PCI outcomes as optimal (μFR ≥ 0.91) or sub-optimal (μFR < 0.91). METHODS: Four machine learning models were trained using pre-PCI variables. Internal bootstrap validation (1000 iterations) identified the best-performing model based on lowest root mean square error (RMSE) for continuous prediction. Predicted μFR values were subsequently used to classify PCI outcomes. RESULTS: In 343 vessels (291 patients), machine learning achieved high accuracy for continuous post-PCI μFR prediction (RMSE 0.036; 95% CI: 0.033-0.040; mean absolute error 0.030; 95% CI: 0.027-0.032; mean absolute percentage error 3.2%; 95% CI: 2.9-3.5), indicating reliable estimation of post-PCI μFR using only pre-procedural data. When the predicted μFR was used to classify PCI outcomes, performance remained clinically meaningful, with accuracy 0.72 (95% CI: 0.70-0.75), area under the curve 0.72 (95% CI: 0.69-0.74), sensitivity 0.90 (95% CI: 0.88-0.93), and specificity 0.29 (95% CI: 0.23-0.34). The high sensitivity ensures reliable upfront identification of vessels likely to achieve optimal physiology. CONCLUSIONS: Machine-learning models accurately predict post-PCI μFR and reliably distinguish optimal from sub-optimal outcomes before intervention. This approach supports personalized PCI planning and improves strategy selection.
17 Apr 2026
Read appraisal →The American journal of cardiology
Mavacamten and Aficamten in Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis of Randomized Trials
Myosin inhibitors represent a novel therapeutic class for hypertrophic cardiomyopathy (HCM). While both mavacamten and aficamten have been evaluated in randomized trials, comparative evidence across the 2 agents remains limited. We performed a systematic review and meta-analysis of 8 randomized controlled trials of myosin inhibitors in HCM. Outcomes included improvement in the New York Heart Association (NYHA) functional class, Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), postexercise and resting left ventricular outflow tract (LVOT) gradients, mean rest LVOT peak gradient, mean Valsalva LVOT peak gradient, change in left ventricular ejection fraction (LVEF), peak oxygen uptake, N-terminal pro-B-type natriuretic peptide (NT-proBNP), treatment-emergent adverse events, and serious adverse events. Pooled effects were estimated twice using random-effects models, once stratified by drug and once pooled altogether. Results showed that myosin inhibitors improved clinical and hemodynamic outcomes versus placebo. Both mavacamten and aficamten yielded improvements in New York Heart Association functional class and KCCQ-CSS, while reducing LVOT gradients and proBNP levels. Effect magnitudes were generally larger with mavacamten; aficamten demonstrated concordant but smaller effects and was the only agent to increase peak oxygen uptake. Safety was favorable for both agents, with pooled estimates indicating a marginally more favorable safety profile for aficamten. In conclusion, myosin inhibitors improve functional status, quality of life, and hemodynamics in HCM with an acceptable safety profile. Mavacamten generally demonstrates more robust benefits, while aficamten appears to have a more favorable safety profile. Additional trials directly comparing these agents are warranted to better clarify relative efficacy and safety.
17 Apr 2026
Read appraisal →BMJ open
Association between ambient air pollution exposure levels and the risk of developing pulmonary embolism in the Chinese population: findings from the Chinese Cardiovascular Association (CCA) Database-Chest Pain Centre
OBJECTIVE: To analyse the associations between exposure to different air pollutants and the morbidity of pulmonary embolism (PE). DESIGN: Time series study with a distribution lag non-linear model. SETTING: 275 cities in China, 1 January 2015 to 31 March 2022. PARTICIPANTS: 27 369 cases of PE. MAIN OUTCOME MEASURES: The associations between exposure to different air pollutants and the morbidity of PE. RESULTS: During the study period, 27 369 cases of PE were recorded. PM2.5(Particulate Matter 2.5), PM10(Particulate Matter 10) and NO2(Nitrogen Dioxide) exposure levels were associated with an increased risk of developing PE in the single-pollutant model. PM2.5 exposure caused the greatest risk of developing PE at lag 1 in the single-day lag model, with a relative risk (RR) value of 1.033 (95% CI 1.007 to 1.058). PM10 and NO2 exposure had the greatest effects at lag 0, with RR values of 1.038 (95% CI 1.016 to 1.059) and 1.039 (95% CI 1.009 to 1.068), respectively. No associations were found between CO(Carbon Monoxide), O3(Ozone) or SO2(Sulfur Dioxide) exposure levels and the risk of developing PE. PM2.5, PM10 and NO2 exposure levels were most strongly associated with the development of PE at lag 01 in the cumulative lag model, with RR values of 1.052 (95% CI 1.009 to 1.095), 1.053 (95% CI 1.020 to 1.086) and 1.058 (95% CI 1.005 to 1.111), respectively. CONCLUSIONS: Short-term exposure to PM2.5, PM10 and NO2 can increase the risk of developing PE, especially in females. The effects of PM2.5 and PM10 exposure were more significant in cold seasons and in North China.
17 Apr 2026
Read appraisal →Neurology
Systolic Blood Pressure Trajectory and Outcomes in Acute Intracerebral Hemorrhage: Pooled Analysis of the 4 INTERACT and ATACH-II Clinical Trials
BACKGROUND AND OBJECTIVES: While moderate and rapid systolic blood pressure (SBP) lowering was associated with better functional outcomes after intracerebral hemorrhage (ICH), large reductions in SBP within 1 hour, for example, reductions from >200 to <140 mm Hg, diminished or even reversed these beneficial effects. We aimed to define the optimal trajectory of SBP control in relation to favorable functional outcomes after acute ICH. METHODS: We conducted a pooled analysis of individual patient-level data from all 4 Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT) and second Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH-II) trials, which were international, randomized, open-label, blinded, end point-assessed, controlled trials that determined the effectiveness of early intensive SBP control in acute ICH. Latent class analysis grouped SBP trajectories over the first 24 hours (9 measurements) into defined clusters. The primary outcome was functional recovery at 90 days after randomization, defined as modified Rankin Scale (mRS) scores of 3-6. Logistic regression models with adjustment for baseline covariates and trial were used to determine associations between SBP cluster trajectories and outcomes in INTERACT, with validation in ATACH-II. RESULTS: A total of 11,269 patients (INTERACT n = 10,269; ATACH-II n = 1,000; mean age 62.4 years; female 36.4%) with at least 1 postrandomization SBP reading were included. Six SBP trajectories were identified: low, moderate-to-low, moderate, high, high-to-moderate, and high-to-low. Compared with the low SBP group, associations with poor functional outcome (mRS scores 3-6) increased progressively across other groups in INTERACT (p = 0.04 for trend). Adjusted odds ratios (95% CI) for groups 2 to 6 were 1.16 (0.98-1.37), 1.44 (1.18-1.75), 1.46 (1.15-1.87), 1.90 (1.32-2.73), and 1.28 (1.02-1.60), respectively. A similar albeit nonsignificant trend was observed in ATACH-II due to limited power. DISCUSSION: Distinct SBP trajectories over 24 hours defined prognosis after ICH, with a severe hypertensive group having the highest odds of death or disability, regardless of the BP-lowering strategy used. These findings highlight the importance of well-controlled but tailored SBP management strategies after ICH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that distinct SBP trajectories over 24 hours are associated with prognosis after acute ICH, with a severe hypertensive group having the highest odds of poor functional outcome, regardless of the BP-lowering strategy used. TRIAL REGISTRATION INFORMATION: (INTERACT1 NCT00226096; INTERACT2 NCT00716079; INTERACT3 NCT03209258; INTERACT4 NCT03790800; ATACH-2 NCT01176565).
15 Apr 2026
Read appraisal →Lancet (London, England)
Deferral of percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation (PRO-TAVI): an investigator-initiated, multicentre, open-label, non-inferiority, randomised controlled trial
BACKGROUND: Coronary artery disease is common in patients undergoing transcatheter aortic valve implantation (TAVI). We aimed to assess whether deferral of percutaneous coronary intervention (PCI) is non-inferior to routine PCI before TAVI in patients with coronary artery disease. METHODS: In this investigator-initiated, open-label, randomised controlled trial, done at 12 hospitals in the Netherlands, TAVI patients with coronary artery disease were randomly assigned in a 1:1 ratio to deferral of PCI or PCI before TAVI. Randomisation was done by use of a web-based system with random block sizes of 2 and 4, and stratification by presence of coronary artery disease involving proximal left anterior descending artery. The primary endpoint was a composite of all-cause mortality, myocardial infarction, stroke, and major bleeding at 1 year. Non-inferiority testing was done in the intention-to-treat population against the prespecified margin of 11 percentage points. The study is registered with ClinicalTrials.gov (NCT05078619) and long-term follow-up is ongoing. FINDINGS: Between Oct 7, 2021, and Nov 19, 2024, 466 patients were enrolled: 233 were assigned to deferral of PCI and 233 to PCI before TAVI. Median age was 81 years (IQR 78-84), and 166 (36%) of 466 patients were female. The primary endpoint occurred in 56 (24%) of 233 patients in the deferral group as compared with 60 (26%) of 233 patients in the PCI group (rate difference -1·7% [95% CI -9·5 to 6·2]; hazard ratio 0·89 [95% CI 0·62-1·28]; p=0·0008 for non-inferiority; p=0·68 for superiority). INTERPRETATION: In patients with coronary artery disease undergoing TAVI, deferral of PCI was non-inferior to PCI before TAVI for the 1-year composite of all-cause mortality, myocardial infarction, stroke, and major bleeding. These findings suggest that an initial conservative strategy can be appropriate in selected patients, although patient-tailored treatment decisions remain essential. FUNDING: ZonMw.
14 Apr 2026
Read appraisal →International journal of pharmaceutics
Optimization of drug diffusion in drug-eluting stents for coronary artery based on deep reinforcement learning
Drug-eluting stents (DES) are extensively used to treat coronary artery disease, and improving their therapeutic efficacy remains a long-standing research objective. Existing optimization strategies for DES drug delivery lack adaptive, learning-based frameworks capable of simultaneously enhancing drug concentration and uniformity in the therapeutic domain while regulating levels in the non-treatment domain, and show limited capacity to address complex, nonlinear optimization problems. This study applies a deep reinforcement learning (DRL)-based framework to optimize drug diffusion in DES. By integrating neural networks with the proximal policy optimization (PPO) algorithm, the framework enables closed-loop, feedback-driven regulation of drug diffusion in real time and demonstrates robustness to stochastic disturbances and parametric variations. The method was systematically evaluated across three stent embedding configurations: half-embedded, fully embedded, and non-embedded. Results show the DRL agent successfully balances the three therapeutic objectives and adopts distinct control strategies for different configurations. All configurations exhibited improved overall performance. For the half-embedded configuration, the DRL policy increased therapeutic domain concentration by 6.99%, accompanied by a slight rise in the non-treatment domain and a minor decrease in uniformity within the therapeutic domain. Under the fully embedded configuration, concentrations in both domains remained essentially unchanged, whereas uniformity in the therapeutic domain improved by 8.14%. For the non-embedded configuration, both therapeutic domain concentration and uniformity increased (by 2.04% and 6.30%, respectively), with negligible change in the non-treatment domain. These results demonstrate the feasibility of DRL for adaptive DES optimization and highlight its potential for patient-specific applications and guidance in clinical selection of drug-embedding configurations.
12 Apr 2026
Read appraisal →Journal of the American Heart Association
Comparison of Intravascular Imaging-, Physiology-, or Angiography-Guided Approaches for Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis
BACKGROUND: Despite current guidelines recommending physiology- and intravascular imaging-guided percutaneous coronary intervention (PCI) in specific lesion subsets, angiography-guided PCI remains common in practice. The comparative effectiveness of these strategies remains uncertain. We aimed to compare clinical outcomes of PCI guided by intravascular imaging or physiological assessment versus conventional angiography. METHODS: We conducted a systematic review and network meta-analysis of randomized controlled trials, searching PubMed and EMBASE up to May 31, 2025. Eligible studies compared at least 2 of the following 6 guidance modalities in PCI: angiography, intravascular ultrasound (IVUS), optical coherence tomography/optical frequency domain imaging, fractional flow reserve, angiography-derived fractional flow reserve, and instantaneous wave-free ratio. The primary outcome was trial-defined major adverse cardiovascular events (MACEs). Hazard ratios (HRs) with 95% CIs were pooled using a frequentist random-effects network meta-analysis. Subgroup analyses assessed clinical presentation and guidance objectives such as decision making and procedural optimization. RESULTS: We identified 43 randomized controlled trials involving 39 291 patients. IVUS-guided PCI (HR, 0.69 [95% CI, 0.60-0.79]), optical coherence tomography/optical frequency domain imaging-guided PCI (HR, 0.75 [95% CI, 0.63-0.90]), and fractional flow reserve-guided PCI (HR, 0.81 [95% CI, 0.70-0.95]) were associated with a lower risk of MACEs compared with angiography-guided PCI. Furthermore, IVUS-guided PCI was associated with a lower risk of MACEs compared with instantaneous wave-free ratio-guided PCI (HR, 0.74 [95% CI, 0.55-1.00]). IVUS-guided PCI reduced the risk of MACE in both acute coronary syndrome and non-acute coronary syndrome patients. CONCLUSIONS: IVUS- and optical coherence tomography/optical frequency domain imaging-guided PCI were superior to angiography-guided PCI in reducing MACEs. Among the physiology-based approaches, only fractional flow reserve showed a clear benefit.
9 Apr 2026
Read appraisal →BMJ open
Evaluation of equity in quality improvement for multiarterial grafting in females and patients with low socioeconomic status: retrospective analysis of a statewide collaborative database
OBJECTIVES: Quality collaboratives improve quality of care at the hospital and collaborative levels, but less is understood about how such efforts affect patient-level disparities. This study evaluated how a quality improvement (QI) effort (increasing multiarterial grafting during coronary artery bypass grafting (CABG)) translated into populations which historically receive lower-quality care (females and patients of low socioeconomic status). DESIGN: Retrospective cohort study. SETTING: All non-federal hospitals in the state of Michigan that perform cardiac surgery and participate in a statewide collaborative database (n=33). PARTICIPANTS: Patients undergoing first-time, isolated CABG receiving at least two bypass grafts from 2011 to 2022 were identified. PRIMARY ENDPOINTS: Association of sex and socioeconomic status with multiarterial grafting was evaluated across the study period. The distressed community index (DCI), a socioeconomic ranking (0-not distressed, 100-severely distressed), was matched to the patient's zip code. Hierarchical regression modelling was performed to associate DCI and sex with multiarterial grafting, incorporating patient factors and hospital and surgeon effects. A sex-surgery year and DCI-surgery year interaction term was performed to assess the change in the rate of multiarterial grafting. RESULTS: A total of 40 322 patients underwent CABG at 33 centres with a median age of 66 years and 24% were female. The rate of multiarterial grafting was 15%, although lower among females (10% vs 17%) and the highest (vs lowest) DCI quartile (14% vs 18%). After risk adjustment, females were less likely to receive multiarterial grafting (ORadj 0.51 (95% CI 0.45 to 0.58), p<0.001). Patients living in zip codes with a higher DCI had lower adjusted odds of receiving multiarterial grafting (ORadj 0.35 per 10-point increase (95% CI 0.24 to 0.51), p<0.001), a finding that was independent of study time (sex-year and DCI-year interaction terms p>0.05). CONCLUSIONS: Despite a large overall increase in multiarterial grafting due to QI efforts, females and patients with low socioeconomic status had lower rates of multiarterial grafting. QI efforts should be evaluated both overall and among patients who historically receive lower quality care to improve quality and equity.
9 Apr 2026
Read appraisal →Journal of the American Heart Association
Ex Vivo Effect of Apixaban on Hemostatic Biomarkers in Children With Heart Disease: A SAXOPHONE Trial Substudy
BACKGROUND: The SAXOPHONE (Safety of Apixaban on Pediatric Heart Disease on the Prevention of Embolism) trial demonstrated the safety of apixaban for thromboprophylaxis in children with heart disease. Included a priori in the trial design was an exploratory biomarker substudy to evaluate the effects of apixaban on surrogate biomarkers of efficacy, thrombin generation capacity, and hemostatic proteins. The study assessed changes in d-dimer, thrombin generation assay parameters, factor VIII, fibrinogen, protein C, and protein S in children receiving apixaban compared with standard-of-care vitamin K antagonists (VKAs) or low-molecular-weight heparin. METHODS: SAXOPHONE participants aged >1 year (n=182) had blood samples for biomarkers collected at baseline, week 2, or month 6. Participants were randomized to apixaban (n=123) or standard of care (VKA or low-molecular-weight heparin; n=59). Subgroup analyses accounted for prior VKA exposure. RESULTS: d-dimer levels decreased at month 6 in all treatment groups and remained stable during VKA-to-apixaban bridging. Apixaban significantly prolonged thrombin generation assay lag time and time to peak compared with VKAs and decreased peak thrombin similarly to VKAs in anticoagulant-naïve participants. Apixaban was associated with decreased fibrinogen and factor VIII at month 6, with no effect on protein C or S. Prior VKA exposure produced carryover effects, suppressing baseline d-dimer, thrombin generation assay parameters, and proteins C and S. CONCLUSIONS: Apixaban reduced hypercoagulability, as shown by decreased d-dimer levels and prolonged lag time, and preserved endogenous thrombin potential in thrombin generation assay, changes consistent with adult data. These findings align with SAXOPHONE's primary outcomes, supporting apixaban's favorable risk-benefit profile as a thromboprophylaxis option in children with heart disease.
8 Apr 2026
Read appraisal →EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
Ischaemic and bleeding events after complex versus non-complex PCI: a systematic review and meta-analysis
BACKGROUND: Complex percutaneous coronary intervention (PCI) is increasingly performed among patients undergoing myocardial revascularisation. AIMS: We conducted a systematic review and meta-analysis to evaluate the association between complex PCI and the risk of ischaemic and bleeding outcomes. METHODS: Hazard ratios (HRs) were pooled using a random-effects model within a Bayesian framework. The primary analysis was restricted to studies providing adjusted risk estimates, whereas the secondary analysis included unadjusted risk estimates. The primary outcomes were myocardial infarction and major bleeding. The secondary outcomes were all-cause death, stent thrombosis, cardiovascular death, target lesion or vessel revascularisation, and stroke. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for prognostic studies was used to determine the level of certainty in the association between complex PCI and the risk of events. RESULTS: We included 290,039 patients, of whom 94,633 (33%) underwent complex PCI. Compared with non-complex PCI, patients undergoing complex PCI had a higher risk of myocardial infarction (adjusted HR 1.71, 95% credible interval [CrI]: 1.49-1.96), major bleeding (adjusted HR 1.24, 95% CrI: 1.14-1.35), all-cause death (adjusted HR 1.21, 95% CrI: 1.12-1.32), cardiovascular death (adjusted HR 1.29, 95% CrI: 1.15-1.46), stent thrombosis (adjusted HR 1.76, 95% CrI: 1.49-2.14), target lesion or vessel revascularisation (adjusted HR 1.99, 95% CrI: 1.58-2.50), and stroke (adjusted HR 1.21, 95% CrI: 1.03-1.42). The posterior probability of a higher risk associated with complex versus non-complex PCI was >99% for all study outcomes. Except for stroke (which was low certainty), the certainty of evidence was moderate to high for all other outcomes. Secondary analysis, including unadjusted risk estimates, provided consistent results. CONCLUSIONS: Patients undergoing complex PCI have an increased risk of both ischaemic and bleeding events compared with patients undergoing non-complex PCI (PROSPERO: CRD420250656254).
8 Apr 2026
Read appraisal →Lancet (London, England)
Percutaneous coronary intervention versus coronary artery bypass grafting for unprotected left main stenosis: 10-year final results from the randomised, open-label, non-inferiority NOBLE trial
BACKGROUND: Coronary artery bypass grafting (CABG) is recommended over percutaneous coronary intervention (PCI) for patients with significant unprotected left main coronary artery disease. We aim to provide long-term outcome data comparing PCI with newer generation drug-eluting stents and CABG, which are scarce. METHODS: This previously published, prospective, randomised, open-label, non-inferiority trial enrolled patients with unprotected left main coronary artery stenosis at 36 hospitals in Denmark, Estonia, Finland, Germany, Latvia, Lithuania, Norway, Sweden, and the UK. Eligibility was determined by a multidisciplinary heart team and defined by clinical criteria (chronic or acute coronary syndrome and a life expectancy of >1 year) and angiographic criteria (left main coronary artery diameter stenosis ≥50% or fractional flow reserve ≤0·80 in the left main ostium, mid-shaft, or bifurcation). Patients with ST elevation myocardial infarction within 24 h or considered at too high risk for CABG or PCI were excluded. Patients with angiographically confirmed significant left main coronary artery disease were randomly assigned (1:1) to PCI or CABG using an online system and stratified by site, sex, distal left main coronary artery bifurcation lesions, and diabetes. The primary outcome was the difference in 10-year all-cause mortality in the intention-to-treat (ITT) population, which was analysed using Kaplan-Meier estimates and unadjusted Cox regression. Patients were censored at the date of death, emigration, withdrawal, or loss to follow-up. Variation in all-cause mortality was assessed in prespecified subgroups. The trial is registered with ClinicalTrials.gov, NCT01496651 (active, not recruiting). FINDINGS: From Dec 9, 2008, to Jan 21, 2015, 1201 patients were randomly assigned to PCI (n=598) or CABG (n=603). 17 patients were lost to follow-up before 1 year. 592 patients in each group were included in the ITT population. Mean age was 66·2 years (SD 9·9) in the PCI group and 66·2 years (9·4) in the CABG group. 256 (22%) of 1184 participants were female and 928 (78%) were male. There was no difference in all-cause mortality at 10 years (136 [23%] of 592 in the PCI group and 145 [25%] of 592 in the CABG group; hazard ratio 0·93 [95% CI 0·74-1·18]; p=0·56). No significant difference in all-cause mortality with SYNTAX score was identified. INTERPRETATION: There was no significant difference in all-cause mortality at 10 years between PCI and CABG for patients with unprotected left main coronary artery disease and no additional complex lesions, indicating that PCI is equally as safe as CABG in patients eligible for both treatments. These results will aid heart teams in developing an individualised patient-centred strategy. FUNDING: Biosensors and Aarhus University Hospital.
6 Apr 2026
Read appraisal →Cardiovascular toxicology
Association Between Environmental Chemicals Phthalates and Stroke Among the US Adults: A Cross-Sectional Study
Stroke has a multifactorial etiology, and phthalates, as widely used environmental chemicals, may play an underexplored role in cerebrovascular health. This study aimed to evaluate the association between urinary phthalate metabolites and stroke risk using data from the National Health and Nutrition Examination Survey (NHANES), complemented by network toxicology, molecular docking, and machine learning approaches. We analyzed data from 10,771 adult participants in NHANES (2003-2018) who had complete records of stroke status, urinary phthalates, and clinical covariates. Multivariable logistic regression and restricted cubic spline (RCS) models were used to assess associations. We constructed protein-protein interaction networks and performed molecular docking to identify potential toxicological targets. Five machine learning algorithms were employed to develop predictive models for phthalate-related stroke risk. Higher levels of MECPP, MCPP, MNBP, and MEOHP were significantly associated with increased stroke prevalence. Network toxicology identified SRC as a key target, and molecular docking confirmed strong binding affinity between MBZP and SRC. Among the machine learning methods, Random Forest achieved the highest predictive performance (AUC = 0.833). Notably, moderate coffee consumption (≤ 170 g/day) was significantly associated with a reduced risk of stroke (OR = 0.63, 95%CI: 0.51-0.77), suggesting potential dietary mitigation against phthalate-related stroke risk. Our findings demonstrate that certain phthalates may increase stroke risk via molecular pathways involving SRC. Furthermore, moderate coffee consumption may mitigate the adverse cerebrovascular effects of these environmental pollutants.
5 Apr 2026
Read appraisal →Medicine
Development of a prediction model for the risk of prolonged ICU length of stay in patients undergoing coronary artery bypass surgery: A retrospective analysis based on the MIMIC-IV database
The duration of hospitalization, particularly in the intensive care unit (ICU), for patients undergoing coronary artery bypass grafting (CABG), is influenced by both patient prognosis and treatment-related costs. Reducing the ICU length of stay (LOS) in CABG patients is critical for improving healthcare resource utilization. This study aimed to develop a model for identifying risk factors associated with prolonged ICU LOS in CABG patients, thus providing a foundation for clinical treatment, healthcare safety, and quality management research. In this single-center, retrospective cohort study, data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were analyzed. Clinical data from 6152 CABG patients who required treatment in ICU were included. The dataset was split into a training set and an internal validation set. Predictor variables were identified using least absolute shrinkage and selection operator regression. A nomogram prediction model was developed based on the identified predictors. The predictors incorporated into the model included the Charlson comorbidity index, acute physiology score III, atrial fibrillation, heart failure (HF), body mass index, acute kidney injury stage, type 1 diabetes mellitus and glucose levels. The prediction model demonstrated robust performance, achieving an area under the curve of 0.789 in the training cohort and 0.790 in the validation cohort. The Hosmer-Lemeshow (H-L) test and calibration plots validated the model's accuracy in both cohorts. The nomogram prediction model proposed in this study provides significant clinical utility for predicting prolonged ICU LOS in patients undergoing CABG. This model can assist clinicians in identifying CABG patients at risk for prolonged ICU LOS, thus enabling timely interventions and improving prognostic outcomes.
5 Apr 2026
Read appraisal →Open heart
Periprocedural evaluation of patients with BAV stenosis undergoing TAVR: a machine learning-based study
BACKGROUND: Transcatheter aortic valve replacement (TAVR) has increasingly emerged as one of the primary treatments for patients with severe bicuspid aortic valve (BAV) stenosis. Nevertheless, these patients encounter multiple procedural challenges. OBJECTIVE: To develop a machine learning (ML) model for assessing the risk of periprocedural adverse events (PAEs) in TAVR population with BAV. METHODS: This multicentre study retrospectively enrolled 1266 patients with BAV stenosis. Clinical characteristics and imaging data of the patients were collected, and an ML prediction model was developed. PAE was collectively defined as all-cause death, disabling stroke, life-threatening haemorrhage, acute kidney injury (≥stage 3), major vascular complications, valve-related dysfunction necessitating reoperation and other major complications that occurred prior to discharge. RESULTS: The average age was 72.6±6.3 years, and 58.3% (n=738) of male. In the derivation dataset, five predictive factors were identified: Type 0 BAV, aortic root calcification volume, horizontal aorta, annular ellipticity and previous atrial fibrillation. A robust risk scoring model was thereby established (area under the curve=0.801 95% CI 0.768 to 0.832). A graded relationship was observed between the quartiles of the score and PAE (0.6%, 1.7%, 3.2% and 9.6%; overall p<0.001). A nomogram was constructed to enable calculation of individual scores and the corresponding PAE probabilities. Additionally, similar results were observed in the validation dataset. CONCLUSIONS: The ML model developed in this study could predict the PAEs occurrence of TAVR in patients with BAV stenosis. This is conducive to individualised procedural planning and in-hospital management.
5 Apr 2026
Read appraisal →Yonsei medical journal
Predicting Post-Induction Hypotension in Diverse Surgical Populations: A Multiclass Classification Universal Model Using Machine Learning Techniques
PURPOSE: Our study aims to develop a machine learning model that not only predicts the occurrence of post-induction hypotension (PIH) but also assesses its severity, addressing a broader patient population than previous studies which mostly focused on a single population. MATERIALS AND METHODS: In our study, we extracted data from 71473 patients aged 18 years and older who underwent general anesthesia for non-cardiac surgery at a tertiary care hospital, using the electronic medical record system for modeling. We used patient demographics, baseline and pre-induction blood pressure, preoperative laboratory tests, surgical details, and anesthetics data, focusing on predicting PIH. The severity of hypotension was assessed by integrating and calculating the integral value of hypotensive periods. We employed several machine learning techniques and evaluated their performance using accuracy, precision, F1-scores, and macro-averaged area under the curve. Additionally, SHapley Additive exPlanation values were used to determine the key factors influencing the predictions. RESULTS: A multiclass classification model, which assesses hypotension severity through the area of hypotension, surpassed the binary model with an F1-score of 0.664. Among various machine learning techniques, the eXtreme Gradient Boosting (XGBoost) model exhibited superior prediction performance, achieving an accuracy of 0.755 and an F1-score of 0.664. Models using preoperative blood pressure and demographic data outperformed those using other datasets. CONCLUSION: We found that using the XGBoost ensemble machine learning technique aids in predicting PIH before surgery, and introducing a multiclass classification model that indicates the severity of hypotension to clinicians leads to an overall enhancement in prediction performance, thereby increasing its clinical utility for real-world applications.
4 Apr 2026
Read appraisal →European radiology
Deep learning-based segmentation of T1 and T2 cardiac MRI maps for automated disease detection.
OBJECTIVES: Parametric tissue mapping enables quantitative cardiac tissue characterization but is limited by inter-observer variability during manual delineation. Traditional approaches relying on average relaxation values and single cutoffs may oversimplify myocardial complexity. This study evaluates whether deep learning (DL) can achieve segmentation accuracy comparable to inter-observer agreement, explores the utility of statistical features beyond mean T1/T2 values, and assesses whether machine learning (ML) combining multiple intensity-based statistical features enhances disease detection. MATERIALS AND METHODS: T1 and T2 maps were manually segmented. The test subset was independently annotated by two observers, and inter-observer variability was assessed. A DL model was trained to segment the left-ventricular blood pool and myocardium. Average (A), lower quartile (LQ), median (M), and upper quartile (UQ) were computed for the myocardial pixels and employed in classification by applying cutoffs or in ML. Dice similarity coefficient (DICE) and mean absolute percentage error evaluated segmentation performance. Bland-Altman plots assessed inter-user and model-observer agreement. Receiver operating characteristic analysis determined optimal cutoffs. Pearson correlation compared features from model and manual segmentations. F1-score, precision, and recall evaluated classification performance. Wilcoxon test assessed differences between classification methods, with p < 0.05 considered statistically significant. RESULTS: 144 subjects (mean age 42.2 years ± 16.1, 76 men) were split into training (100), validation (15) and evaluation (29) subsets. Segmentation model achieved a DICE of 85.4%, surpassing inter-observer agreement. Random forest applied to all features increased F1-score (92.7%, p < 0.001). CONCLUSION: DL facilitates segmentation of T1/ T2 maps. Combining multiple features with ML improves disease detection. KEY POINTS: Question Manual segmentation of myocardial T1/T2 maps is time-consuming and affected by inter-observer variability; relying on single cutoff values for diagnosis may oversimplify myocardial complexity. Findings Deep learning achieves segmentation accuracy within inter-observer agreement, while machine learning improves disease detection compared to singular cutoffs. Clinical relevance Automated segmentation and feature extraction from T1/T2 maps can enhance workflow efficiency, reduce inter-observer variability, and improve diagnostic consistency. The high recall of the machine learning model minimizes missed diagnoses, ensuring more reliable disease detection.
4 Apr 2026
Read appraisal →Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology
Fetal cardiac remodeling in second trimester in pregnancies with pre-eclampsia and/or fetal growth restriction: deep-learning-based approach using population-wide data
OBJECTIVE: Pre-eclampsia (PE) and fetal growth restriction (FGR) have been shown to impact fetal cardiac remodeling in the third trimester and postnatally, with evidence to suggest that this leads to increased long-term cardiovascular risk. This study aimed to examine fetal cardiac remodeling in pregnancies with PE and/or FGR during the second trimester. METHODS: This was a retrospective nationwide cohort study of ultrasound images from routine screening at 18-22 weeks of gestation in Denmark. We included 139 430 singleton pregnancies that were conceived spontaneously for which at least one relevant standardized cardiac plane (four-chamber view and/or three-vessel view) was available from the second-trimester scan. An artificial intelligence model performed automated segmentation and extraction of fetal cardiac biometric measurements. Data were collected for four groups: the reference group, defined as appropriate-for-gestational-age (AGA) fetuses from a normotensive pregnancy (n = 131 150); AGA fetuses from a PE pregnancy (AGA + PE group; n = 3095); FGR fetuses from a normotensive pregnancy (normotensive + FGR group; n = 4572); and FGR fetuses from a PE pregnancy (PE + FGR group; n = 613). Differences between groups in cardiac biometric measurements were presented as Z-scores adjusted for abdominal circumference at the second-trimester scan. RESULTS: Compared with the reference group, fetuses in the PE + AGA group had significantly larger right-sided heart structures, and the main pulmonary artery (MPA) and ventricular septum were wider. Fetuses in the normotensive + FGR group displayed significantly smaller cardiac structures, including smaller MPA and ascending aorta diameters, and increased left ventricular sphericity compared with the reference group. Fetuses in the PE + FGR group differed significantly from the reference group only in terms of smaller left atrial area, narrower ascending aorta and increased left ventricular sphericity. However, PE + FGR fetuses had significantly wider MPA and ventricular septum and larger right-sided structures compared with normotensive + FGR fetuses, mimicking the features of the PE + AGA group, suggesting a distinct effect of PE on fetal cardiac remodeling. CONCLUSIONS: Cardiac remodeling is evident as early as the second trimester, with distinct patterns of modulation in fetuses from pregnancies affected by PE vs FGR. In particular, PE is associated with an enlarged right heart and greater MPA diameter. Understanding these early differences in fetal cardiac morphology may improve risk prediction models and guide early intervention to improve long-term cardiovascular outcome. © 2025 The Author(s). Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
4 Apr 2026
Read appraisal →Eur Heart J
Coronary revascularization: a long-term perspective.
This paper will forecast advancements in coronary revascularization by 2040, drawing on historical trends and recent breakthroughs. Having forecasted in 2000 the impact of innovations like drug-eluting stents, coronary computed tomography angiography, and bioresorbable scaffolds, the authors examine the evolving landscape of coronary artery disease treatment emphasizing artificial intelligence and omics sciences. Imagenomics-the integration of imaging and omics-will be a transformative tool with artificial intelligence enabling more personalized decisions between pharmacological and mechanical revascularization. The shift towards minimally invasive, image-guided procedures is discussed along with the potential obsolescence of current antiplatelet and anticoagulant therapies with novel biomimetic peptides like CD31-covalently bound to metallic or polymeric devices. Advances in photon-counting computed tomography and Fibre Optic Real Shape promise high-resolution imaging with lower radiation, enhancing procedural safety and diagnostic accuracy. It is anticipated that robotics and 3D holograms in percutaneous and surgical revascularization will improve precision and the resulting outcomes. Additionally, the need for mechanical revascularization for younger patients may decline due to effective plaque regression therapies and novel potent anti-atherogenic biologics. However, the aging population will drive demand for mechanical interventions, with advancements in atherectomy and lithotripsy techniques improving outcomes in complex, calcified lesions. This comprehensive analysis outlines a future where myocardial revascularization becomes increasingly personalized, with technology-driven interventions redefining cardiovascular medicine.
1 Feb 2026
Read appraisal →Interv Cardiol Clin
Proximal Cap Ambiguity
This article reviews how to approach the proximal cap of a chronically occluded coronary artery. Safely crossing this region of the lesion is a crucial step in the procedure. While many proximal caps are understood angiographically, a significant proportion are not. This article describes steps that can be taken to resolve anatomic ambiguity, either by the use of supplementary intravascular ultrasound or by more advanced maneuvers, which should enhance the safety and efficiency of the percutaneous coronary intervention.
1 Jan 2026
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