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PubMed2026

Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are linked to coronary heart disease (CHD), but underlying mechanisms remain unclear. We aimed to identify EDC-related genes and evaluate their causal roles in CHD. METHODS: We curated EDC-related genes from a compound-gene interaction database and integrated them with CHD genome-wide association study (GWAS) summary statistics and tissue-specific expression quantitative trait loci (eQTL) data. Two-sample Mendelian randomization (MR) and Bayesian colocalization were applied to infer causality. Functional enrichment, single-cell RNA sequencing of human coronary arteries, and EDC-gene networks were further analyzed. RESULTS: After FDR correction, 39 genes were significantly associated with CHD risk via MR. Four genes-ZNF827, FCHO1, IPO9 (protective), and RPL13 (risk-increasing)-showed strong colocalization (PPH4 > 0.9). Pathway and single-cell analyses of coronary artery tissue indicated that vascular and immune pathways mediate these effects. An interaction network highlighted associations between specific EDCs and candidate genes implicated in CHD susceptibility. CONCLUSION: This integrative genomic study provides evidence that EDCs influence CHD susceptibility through distinct gene networks, revealing potential mechanisms and molecular targets for prevention and therapy.

Humans↗
PubMed2026

Stratified medicine with eplerenone for myocardial infarction or injury and no obstructive coronary arteries: A registry-based basket trial.

BACKGROUND: Myocardial Infarction with No Obstructive Coronary Arteries (MINOCA) or Nonischemic Myocardial Injury affects approximately 1 in 9 patients presenting with acute coronary syndrome, yet evidence-based therapies are lacking. Coronary microvascular dysfunction is implicated in the pathogenesis of suspected MINOCA, but its prevalence, prognostic implications and treatment are uncertain. The objectives are, first, to assess the prevalence of coronary microvascular dysfunction in patients with suspected MINOCA and, second, to implement endotype-informed stratified medicine involving patients with coronary microvascular dysfunction to treatment with eplerenone, a cardio- and vasculo-protective mineralocorticoid receptor antagonist. METHODS: This is a prospective, registry-based, multicenter, diagnostic study and nested, randomized, controlled, open-label, blinded-endpoint (PROBE) basket trial. Up to 400 patients with clinically suspected MINOCA and one or more cardiovascular risk factors will be enrolled into a registry-based diagnostic study. Coronary microvascular function will be assessed during invasive angiography using thermodilution. Patients with an index of coronary microvascular resistance (IMR) ≥ 25 will be randomized 1:1 to eplerenone (25-50 mg daily for 6 months) or standard care without eplerenone (control group) (n = 150 randomized). Final endotypes will be centrally adjudicated by a panel of blinded cardiologists. The primary outcome of the diagnostic study is the proportion of patients with IMR ≥ 25 during index coronary angiography. Secondary outcomes include coronary flow reserve, cardiovascular MRI parameters, patient-reported outcome measures, biomarkers of myocardial fibrosis and vascular inflammation, health outcomes and health economic assessments. The primary outcome of the randomized trial is the within-individual change in NT-proBNP at baseline, 1 month, and 6 months, based on intention-to-treat. Secondary outcomes include mechanistic blood biomarkers and patient-reported outcome measures. VALUE: This registry-based randomized trial will provide novel evidence on endotype-informed secondary prevention therapy with eplerenone for suspected MINOCA.

Humans↗
PubMed2026

Combined Effects of Nicorandil and Enhanced External Counterpulsation on Coronary Microcirculation and Exercise Capacity in Patients With Coronary Slow Flow Phenomenon: A Randomized, Controlled, 3-Arm Trial.

PURPOSE: To evaluate the combined efficacy and safety of combined nicorandil and enhanced external counterpulsation (EECP) therapy compared with respective monotherapies in patients with coronary slow flow phenomenon (CSFP). METHODS: In this prospective, randomized, 3-arm clinical trial, 309 patients with angiographically defined CSFP based on corrected TIMI frame count were assigned (1:1:1) to the Nicorandil group (N group, n = 103), the EECP group (E group, n = 103), or the Combined therapy group (N+E group, n = 103). The trial was prospectively registered at ClinicalTrials.gov (NCT07534410). IMR and CFR were measured to characterize coronary microvascular physiological status and treatment response. The primary endpoint was corrected TFC at 6 months. Key secondary endpoints included invasive physiological indices (IMR and CFR), Seattle Angina Questionnaire scores, 6-minute walk test (6MWT) distance, peak oxygen uptake via cardiopulmonary exercise testing, and the 12-month rate of re-hospitalization due to recurrent angina. FINDINGS: At 6 months, the N+E group demonstrated superior improvement in coronary hemodynamics compared to the N and E monotherapy groups, with significantly lower TFC (30.4 &#xb1; 3.5 vs 38.2 &#xb1; 3.8 and 37.5 &#xb1; 4.0, respectively; P < 0.001) and IMR (21.2 &#xb1; 2.8 vs 28.4 &#xb1; 3.2 and 27.6 &#xb1; 3.5, respectively; P < 0.001). Clinical symptoms and functional capacity showed the most substantial gains in the N+E group, with significantly higher Seattle Angina Questionnaire angina frequency scores (87.5 &#xb1; 8.8) and 6MWT distances (506.8 &#xb1; 41.8 m) compared to monotherapy groups (all P < 0.001). Furthermore, peak oxygen uptake in the N+E group increased to 23.5 &#xb1; 2.6 mL/kg/min, significantly outperforming the N and E groups (P < 0.001). During the 12-month follow-up, the observed rate of re-hospitalization due to recurrent angina was lower in the N+E group (5.8%) than in the N group (17.5%, P = 0.017), although this clinical outcome should be interpreted cautiously because the trial was powered primarily for physiological endpoints. No significant differences were observed in the incidence of adverse reactions among the 3 groups (P = 0.954). IMPLICATIONS: For patients with CSFP, the combination of Nicorandil and EECP improved coronary microvascular function, anginal symptoms, and objective exercise tolerance more effectively than either active monotherapy. The lower observed rate of angina-related re-hospitalization suggests a potential clinical benefit, but this finding should be considered exploratory and requires confirmation in trials adequately powered for clinical outcomes.

Humans↗
PubMed2026

Ultrashort vs Standard-Duration Dual Antiplatelet Therapy in Acute Coronary Syndrome Patients Undergoing PCI: A Meta-Analysis.

BACKGROUND: The efficacy and safety of ultrashort (&#x2264;1-month) dual antiplatelet therapy (DAPT) followed by antiplatelet monotherapy remain uncertain in acute coronary syndrome (ACS) patients. OBJECTIVES: This study sought to compare ultrashort vs standard-duration DAPT in patients with ACS undergoing percutaneous coronary intervention (PCI). METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials until February 15, 2026. Primary outcomes were major adverse cardiac and cerebrovascular events (MACCE), major bleeding, and net adverse clinical event (NACE). Prespecified subgroup analyses examined by ethnicity (East Asian vs non-East Asian) and abbreviation strategy (intensive: &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy vs moderate: &#x2265;2-week DAPT, followed by ticagrelor/prasugrel monotherapy). RESULTS: Across 10 trials (n = 29,232), ultrashort DAPT did not increase MACCE risk (HR: 1.06; 95% CI: 0.93-1.20; P = 0.38; I2 = 24%), with higher MACCE risk observed in ST-segment elevation myocardial infarction (STEMI) but not non-ST-segment elevation ACS (NSTE-ACS), and significantly reduced major bleeding (HR: 0.47; 95% CI: 0.35-0.64; P < 0.00001; I2 = 44%), resulting in a net clinical benefit (HR: 0.83; 95% CI: 0.72-0.97; P = 0.02; I2 = 61%). Bleeding reduction was more pronounced in East Asians (HR: 0.35; 95% CI: 0.25-0.49; P < 0.00001; I2 = 0%) than non-East Asians (HR: 0.63; 95% CI: 0.43-0.93; P = 0.02; I2 = 44%), with a significant interaction (P = 0.02). The abbreviation strategy significantly modified outcomes (P for interaction = 0.003): intensive abbreviation raised MACCE risk (HR: 1.37; 95% CI: 1.11-1.69; P = 0.003; I2 = 0%), while moderate abbreviation had no statistically significant difference (HR: 0.96; 95% CI: 0.85-1.08; P = 0.47; I2 = 0%). CONCLUSIONS: In patients with ACS undergoing PCI, ultrashort DAPT reduced bleeding without increasing ischemic events overall, although a signal of increased MACCE was observed in STEMI but not in NSTE-ACS. Bleeding reduction was greater in East Asians, while &#x2264;1-week DAPT or clopidogrel/aspirin monotherapy may increase ischemic risk.

Humans↗
PubMed2026

Systematic review of machine learning approaches for predicting sickle cell crisis and mortality risk at the climate-health nexus.

BACKGROUND: Sickle cell anemia (SCA) is a severe genetic blood disorder characterized by recurrent vaso-occlusive crises and increased mortality, with the greatest burden occurring in low- and middle-income countries. Climatic and environmental conditions, including temperature variability, humidity, rainfall, air pollution, and seasonal changes, have been associated with disease exacerbation. However, the extent to which these factors have been incorporated into predictive models remains unclear. This study systematically reviews the application of machine learning (ML) models for predicting SCA crises and mortality in relation to climate and environmental factors. METHODOLOGY: The PRISMA guidelines were used, and 34 peer-reviewed studies published between 2005 and 2026 were analyzed to identify the climate variables, ML approaches employed, and predictive performance. The reviewed studies applied a range of ML techniques, including artificial neural networks, random forests, support vector machines, decision trees, logistic regression, and deep learning models. Temperature, humidity, rainfall, wind speed, air quality indicators, and seasonal patterns were the most frequently examined environmental variables. RESULTS: The findings indicate that most existing models rely predominantly on clinical and demographic data, with limited integration of climate information and inadequate representation of high-burden regions, especially Sub-Saharan Africa. Studies incorporating environmental variables reported improved predictive performance and highlighted the potential of climate-informed early warning systems for SCA management. CONCLUSION: The review recommends development of interdisciplinary, climate-aware ML frameworks, expansion of longitudinal environmental datasets, and increased research in underrepresented regions to support climate-resilient and patient-centered SCA care.

Humans↗
PubMed2026

Mechanistic Insights Into the Association Between Gut Microbiota Diversity and Atherosclerosis, Acute Coronary Syndrome, and Peripheral Arterial Disease Progression.

BACKGROUND: The gut microbiome has emerged as a potential contributor to cardiovascular diseases (CVDs), including atherosclerosis, acute coronary syndrome (ACS), and peripheral arterial disease (PAD). While observational studies link dysbiosis to CVD, causal relationships remain uncertain. METHODS: This narrative review synthesizes evidence from human observational studies, clinical interventions, and experimental models to distinguish association from mechanistic plausibility and clinical causality. Literature was searched through July 2026 in PubMed/MEDLINE, Web of Science, and Scopus. RESULTS: Microbial metabolites-including trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, and lipopolysaccharide (LPS)-modulate endothelial function, immune cell programming, platelet activity, and plaque stability through receptor-mediated signaling and epigenetic regulation. SCFAs demonstrate potentially protective effects via GPCR and HDAC pathways, while TMAO is associated with atherothrombotic risk. However, much mechanistic evidence derives from preclinical studies. Heterogeneity from diet, geography, host characteristics, renal function, and medications substantially influences microbiota-CVD associations. CONCLUSION: The gut-vascular connection is biologically plausible, but definitive clinical causality remains unproven. Microbiome-directed therapies (dietary modulation, pre/pro/synbiotics, targeted metabolite inhibition) are investigational. Prospective, standardized, adequately powered human studies with clinically meaningful outcomes are essential before routine cardiovascular application.

Gastrointestinal Microbiome↗
PubMed2026

Impact of Diabetes on Outcomes of Contemporary PCI Guided by OCT vs Angiography: The ILUMIEN IV Trial.

BACKGROUND: Patients with diabetes are at higher risk for adverse events after percutaneous coronary intervention (PCI) compared with patients without diabetes. OBJECTIVES: This study sought to assess the influence of diabetes and complex lesions on the outcomes of patients undergoing PCI with and without optical coherence tomography (OCT) guidance during a follow-up period of 2 years. METHODS: Patients in ILUMIEN IV randomized to OCT-guided vs angiography-guided PCI were grouped into those with (n = 1,044) and without diabetes (n = 1,443). Study endpoints were target vessel failure (TVF) and serious major adverse cardiovascular events (MACE). RESULTS: After adjustment for differences in clinical and angiographic characteristics, the 2-year rates of both TVF (9.9% vs 6.3%; adjusted HR: 1.48; 95% CI: 1.09-2.02; P = 0.01) and serious MACE (5.3% vs 2.7%; adjusted HR: 1.77; 95% CI: 1.14-2.76; P = 0.01) were increased in diabetic compared with nondiabetic patients, consistently in patients with and without complex lesions (Pinteraction = 0.22 and 0.14, respectively), although the highest 2-year rates were in patients with diabetes and complex lesions. In all randomized patients, OCT guidance compared with angiography guidance did not reduce TVF or serious MACE. These effects were consistent in patients with and without diabetes (Pinteraction = 0.41 and 0.20, respectively), and were not modified by treatment of complex lesions. CONCLUSIONS: In the large-scale ILUMIEN IV trial, patients with diabetes remained at increased risk for adverse events after PCI compared with nondiabetic patients despite the use of OCT procedural guidance. Patients with diabetes and complex lesions were at particularly high risk for adverse outcomes after PCI.

Humans↗
PubMed2026

Angiography-Based Index of Microcirculatory Resistance in Assessing the MVO and Infarct Size in STEMI Patients.

OBJECTIVES: To evaluate angiography-based index of microcirculatory resistance (angio-IMR) in assessing microvascular obstruction (MVO) and infarct size (IS) in ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The effect of thrombolysis on post-percutaneous coronary intervention (PCI) angio-IMR, and its associations with MVO and IS remains unclear. METHODS: One hundred twenty-three STEMI patients randomized to receive 5&#x2009;mg intravenous bolus of recombinant staphylokinase (r-SAK) or normal saline (NS) before PCI were recruited. Angio-IMR was computed in infarct-related arteries. MVO and IS were detected by cardiac magnetic resonance imaging. RESULTS: Compared with NS group, r-SAK group exhibited numerically lower post-PCI angio-IMR (39.12 U vs. 42.57 U; p&#x2009;=&#x2009;0.567), MVO (54.0% vs. 70.9%; p&#x2009;=&#x2009;0.059), MVO extent (0.70% vs. 1.90%; p&#x2009;=&#x2009;0.101) and IS (21.30% vs. 24.50%; p&#x2009;=&#x2009;0.079). Post-PCI angio-IMR was positively correlated with MVO extent (&#x3c1;&#x2009;=&#x2009;0.347; p&#x2009;<&#x2009;0.001) and IS (&#x3c1;&#x2009;=&#x2009;0.324; p&#x2009;<&#x2009;0.001). Receiver operating characteristic analyses showed moderate diagnostic performance of angio-IMR for MVO (area under the curve [AUC] = 0.750; p&#x2009;<&#x2009;0.001), MVO&#x2009;>&#x2009;2.6% (AUC&#x2009;=&#x2009;0.735; p&#x2009;<&#x2009;0.001) and IS&#x2009;>&#x2009;25% (AUC&#x2009;=&#x2009;0.712; p&#x2009;<&#x2009;0.001). The exploratory optimal cut-off values for these endpoints were approximately 40&#x2009;U. CONCLUSIONS: In STEMI patients, a single bolus of r-SAK before PCI was associated with numeric reductions in post-PCI angio-IMR, MVO, MVO extent and IS. Additionally, angio-IMR exhibited a significantly positive correlation with both MVO extent and IS, demonstrating the diagnostic value of this wire-free method for assessing microvascular injury.

Humans↗
PubMed2026

The role of adjunctive aqueous suppressants for anti-vascular endothelial growth factor therapy: A systematic review.

Our goal is to determine whether adjunctive aqueous suppressants (topical &#x3b2;-blockers, carbonic anhydrase inhibitors, or oral acetazolamide) enhance outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for diabetic macular edema (DME), retinal vein occlusion (RVO), and neovascular age-related macular degeneration (nAMD), focusing on retinal thickness, visual acuity, injection burden, intraocular pressure (IOP), and safety. DME, RVO, and nAMD are leading causes of vision loss treated with repeated intravitreal injections, yet many eyes show persistent fluid. Aqueous suppressants are inexpensive and widely available, with potential to prolong intravitreal drug residence and improve outcomes, but their clinical value remains uncertain. Following a registered protocol, we searched 4 databases (January, 2000 toMay, 2025) for randomized and comparative studies evaluating adjunct aqueous suppressants with anti-VEGF therapy. Primary outcome was change in retinal thickness; secondary outcomes included visual acuity, injection burden, IOP, and adverse events. Risk of bias was assessed and findings synthesized narratively. Twelve studies (7 randomized trials; 495 eyes) met inclusion criteria. In DME, 3 of 4 trials showed greater thickness reduction with adjunctive dorzolamide (&#xb1;timolol), although visual gains were inconsistent. In RVO, 1 trial suggested transient anatomical benefit, whereas oral acetazolamide showed no added effect. In nAMD, adjunctive dorzolamide-timolol reduced residual fluid in refractory cases without visual or treatment-sparing benefit. Topical therapy produced modest IOP reductions without serious adverse events. Adjunct aqueous suppressants may provide limited short-term anatomical benefit, particularly in DME and refractory nAMD, but consistent functional or durability effects are not found in this study. Larger, longer-term randomized studies are needed.

Humans↗
PubMed2026

International study of coronary microvascular angina (iCorMicA): A registry-based diagnostic study and nested randomized trial.

BACKGROUND: Angina is a debilitating condition caused by coronary artery disease and microvascular dysfunction. Following coronary angiography angina and no obstructive coronary arteries is a common outcome, and women are disproportionately affected. The objectives are first, to assess causes of angina in patients undergoing invasive management; and second, to assess effects of coronary function test-guided management on clinical outcomes. METHODS: This is an international, multicenter, prospective, registry-based study and nested, randomized, controlled, triple-blind, and endpoint trial. Participants, community care providers, and outcomes assessors are masked. Consented participants enter the registry. Participants without obstructive coronary artery disease (luminal stenosis <50%, or fractional flow reserve >0.80) are eligible for randomization. Index of microcirculatory resistance (IMR; abnormal &#x2265;25) and coronary flow reserve (CFR; abnormal <2.0; gray zone 2.0-2.5) are measured by bolus thermodilution, and results are disclosed (intervention) or not (control group) to the attending cardiologist. RESULTS: The primary outcome of the registry is the Seattle Angina Questionnaire summary score at baseline described by coronary artery disease status. Secondary outcomes include the prevalence of obstructive coronary artery disease, patient reported outcome measures and clinical outcomes. The primary outcome of the randomized trial is the within-individual change in Seattle Angina Questionnaire summary score at 12-months from baseline. Secondary outcomes include safety, diagnostic accuracy, patient reported outcome measures for quality of life, physical and psychological function, cardiovascular risk, clinical outcomes, health economics and mechanistic biomarkers. The first patient was screened on December 18, 2020 and the last patient was enrolled on June 30, 2026. Forty sites were included in the United Kingdom (n = 35), Republic of Ireland (n = 2), Holland (n = 2), and Poland (n = 1). In total, 1,483 participants were enrolled into the registry of whom 1,047 were randomized and 386 were not randomized (registry-only). CONCLUSION: This international, registry-based clinical trial will provide novel evidence on the natural history of angina and stratified therapy for angina with no obstructive coronary arteries. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT04674449. UNIQUE IDENTIFIER: NCT04674449.

Humans↗
PubMed2026

Endovascular intervention for acute stroke in the very late window: A meta-analysis of 90-day mRS and procedural outcomes.

OBJECTIVE: This study investigates the effectiveness of Endovascular Therapy (EVT) in very late windows (beyond 24&#xa0;h) for patients with ischemic stroke, focusing on 90-day mortality, functional outcomes, and procedural success. METHODS: This systematic review and meta-analysis followed Cochrane and PRISMA guidelines to evaluate the effectiveness of endovascular therapy (EVT) in acute ischemic stroke patients. Literature from PubMed, Embase, Web of Science, and Scopus was reviewed using specific keywords. Studies included those after 2000 with outcomes such as functional independence (mRS 0-2), mortality, TICI scores, and neurological improvements. RESULTS: The data findings reveal mixed outcomes across studies on EVT beyond 24&#xa0;h. Sarraj et al. (2023) found a significant improvement in functional independence with EVT (38% vs. 10%, p&#xa0;<&#xa0;0.05), despite an increased risk of sICH. The forest plots for mRS and procedural outcomes show some significant results, such as Sarraj (2023) for mortality (p&#xa0;<&#xa0;0.05), but most other studies indicated no statistically significant differences (p&#xa0;>&#xa0;0.05). CONCLUSION: The study has concluded that Endovascular Therapy (EVT) beyond 24&#xa0;h can improve functional outcomes and reduce mortality in selected ischemic stroke patients, though patient selection remains crucial.

Humans↗
PubMed2026

Effects of CPAP on endothelial activation and fibrinolytic balance in coronary artery disease with obstructive sleep apnea: The RICCADSA randomized controlled trial.

BACKGROUND: Obstructive sleep apnea (OSA) promotes endothelial activation and a prothrombotic milieu through intermittent hypoxia, oxidative stress, and systemic inflammation, mechanisms closely linked to atherosclerosis progression. The vascular effects of continuous positive airway pressure (CPAP) therapy in patients with established coronary artery disease (CAD) remain incompletely understood. OBJECTIVE: To evaluate the longitudinal effects of CPAP treatment on endothelial adhesion molecules and fibrinolytic balance in patients with CAD and OSA. METHODS: In this randomized controlled analysis from the RICCADSA trial, 210 revascularized CAD patients with moderate-to-severe OSA were assigned to CPAP (n&#xa0;=&#xa0;104) or no-CPAP (n&#xa0;=&#xa0;106) and had available biomarker measurements at baseline and 12&#xa0;months. Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1) were assessed. Linear mixed-effects models were used to examine longitudinal changes and time-by-treatment interactions adjusted for cardiometabolic covariates. RESULTS: For ICAM-1, no significant time-by-treatment interaction was observed. For PAI-1, a borderline time-by-treatment interaction suggested a numerically smaller increase in the CPAP group compared with no-CPAP (p&#xa0;=&#xa0;0.09). CPAP treatment was associated with a significantly greater reduction in VCAM-1 over time compared with no-CPAP (time-by-treatment interaction p&#xa0;=&#xa0;0.045 in adjusted models). CONCLUSIONS: CPAP treatment was associated with selective modulation of vascular biomarkers in patients with CAD and OSA, characterized by attenuation of endothelial activation reflected by reduced VCAM-1 levels, while fibrinolytic imbalance appeared largely resistant to intervention. These findings support pathway-specific vascular responses to CPAP and provide mechanistic insight into residual atherosclerotic risk in this high-risk population.

Aged↗
PubMed2026

Colchicine to prevent cardiovascular events in thoracic surgery patients with or without coronary artery disease: a secondary analysis.

OBJECTIVES: This exploratory post hoc secondary analysis of the Colchicine for the Prevention of Perioperative Atrial Fibrillation (COP-AF) randomised controlled trial evaluated the association between coronary artery disease (CAD) and postoperative ischaemic outcomes after non-cardiac thoracic surgery and assessed whether colchicine had differential effects by CAD status. METHODS: Patients were randomised to colchicine 0.5&#x2009;mg or placebo two times per day for 10 days. Follow-up was 14 days. The primary outcome was myocardial injury after non-cardiac surgery (MINS). A key secondary outcome was the composite of death, MINS and stroke. Cox proportional hazards models assessed the association between CAD and outcomes, with interaction terms to explore whether colchicine had differential effects by CAD status. RESULTS: Of 3209 patients enrolled, 331 (10.3%) had CAD. MINS occurred in 29.3% (n=97) and 18.2% (n=523) of patients with and without CAD, adjusted HR (aHR) 1.53 (95% CI 1.22 to 1.92; p<0.001). For colchicine versus placebo, the HR for MINS was 0.82 (95% CI 0.55 to 1.22) in CAD versus 0.91 (95% CI 0.77 to 1.08) in non-CAD patients (p for interaction=0.61). Death, stroke or MINS occurred in 30.2% (n=100) vs 18.6% (n=535), respectively (aHR 1.53, 95% CI 1.22 to 1.91; p<0.001). Colchicine HRs were 0.77 (95% CI 0.52 to 1.14)&#x2009;vs 0.91 (95% CI 0.76 to 1.07; p for interaction=0.45). CONCLUSIONS: Patients with CAD undergoing thoracic surgery had a higher risk of MINS and other ischaemic outcomes than non-CAD patients. There was no evidence that the effect of colchicine differed between patients with and without CAD; however, these analyses were limited by sample size and do not exclude modest differences between subgroups.

Humans↗
PubMed2026

Clopidogrel vs Aspirin According to Diabetes Mellitus: A Prespecified Analysis of the SMART-CHOICE 3 Trial.

BACKGROUND: Recent trials support the superior efficacy of clopidogrel compared to aspirin monotherapy after completion of dual antiplatelet therapy (DAPT) in patients who have undergone percutaneous coronary intervention (PCI). However, limited evidence is available in patients with diabetes mellitus (DM). OBJECTIVES: This study sought to evaluate the comparative efficacy and safety of clopidogrel vs aspirin monotherapy according to the presence of DM. METHODS: This was a prespecified analysis of the SMART-CHOICE 3 trial, which was a multicenter, open-label, randomized controlled trial comparing clopidogrel vs aspirin monotherapy in patients with complex coronary lesions or high-risk clinical characteristics. From August 2020 to July 2023, a total of 5,506 patients who underwent PCI and standard DAPT duration and had complex coronary lesions, DM, or previous myocardial infarction, were randomized to clopidogrel or aspirin monotherapy groups. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), which was defined as a composite of death from any cause, myocardial infarction, or stroke. RESULTS: Of 5,506 patients, 2,089 had DM (1,039 in the clopidogrel group and 1,050 in the aspirin group). At a median follow-up of 2.3 years (IQR: 1.6-3.0 years), DM patients had a higher risk of MACCE compared to non-DM patients (6.8% vs 4.7%; HR: 1.44, 95% CI: 1.10-1.87; P = 0.008). Clopidogrel showed a significantly lower risk of MACCE than aspirin in DM patients (4.5% vs 9.1%; HR: 0.57, 95% CI: 0.38-0.86; P = 0.008). There was no significant interaction between DM and antiplatelet monotherapy regarding MACCE (P for interaction = 0.124). The risk of bleeding was comparable between the 2 groups in DM patients (2.9% vs 2.9%; HR: 1.06, 95% CI: 0.57-1.95; P = 0.855). CONCLUSIONS: Among DM patients who completed the standard duration of DAPT after PCI, clopidogrel monotherapy was associated with a lower risk of a composite of death from any cause, myocardial infarction, and stroke compared with aspirin monotherapy, without increased rates of bleeding. There was no significant interaction between DM and antiplatelet monotherapy with respect to MACCE. (SMART-CHOICE 3 [SMart Angioplasty Research Team: CHoice of Optimal Anti-Thrombotic Strategy in Patients Undergoing Implantation of Coronary Drug-Eluting Stents 3]; NCT04418479).

Humans↗
PubMed2026

Comparison between measured and synthesized posterior lead electrocardiograms during percutaneous coronary intervention-induced myocardial ischemia.

BACKGROUND: Posterior/inferolateral myocardial ischemia is frequently underrecognized on standard 12&#x2011;lead electrocardiography (ECG). Synthesized posterior leads derived from the standard 12&#x2011;lead ECG have been proposed as an alternative to directly measured posterior leads; however, their accuracy under controlled ischemic conditions has not been fully validated. METHODS: We prospectively enrolled 26 consecutive patients undergoing percutaneous coronary intervention (PCI) in whom simultaneously recorded measured and synthesized posterior lead ECGs (V7-V9) were obtained during balloon-induced myocardial ischemia. ST-segment deviation was measured at the ST junction (STJ), 40&#xa0;ms (ST1), and 80&#xa0;ms (ST2) thereafter. Agreement between measured and synthesized posterior leads was assessed using Pearson correlation and Bland-Altman analyses. As an exploratory patient-level analysis, diagnostic performance was compared with reciprocal anterior ST-segment depression (V1-V4). RESULTS: Strong correlations were observed between measured and synthesized posterior lead ST-segment deviations (V7: r&#xa0;=&#xa0;0.89; V8: r&#xa0;=&#xa0;0.86; V9: r&#xa0;=&#xa0;0.83; all P&#xa0;<&#xa0;0.001). Bland-Altman analysis demonstrated minimal systematic bias (within &#xb1;0.004&#xa0;mV) and narrow limits of agreement. Synthesized posterior leads showed higher diagnostic performance than reciprocal anterior ST-segment depression (AUC 0.917 vs. 0.708), although the difference was not statistically significant (DeLong test, P&#xa0;=&#xa0;0.197). Using a 0.05&#xa0;mV threshold, synthesized posterior leads demonstrated 83.3% sensitivity, 100% specificity, and 96.2% overall accuracy. CONCLUSIONS: Synthesized posterior leads closely reproduced measured posterior lead ST-segment deviations during percutaneous coronary intervention (PCI)-induced myocardial ischemia, supporting the technical validity of posterior lead reconstruction. Larger prospective studies are warranted to determine whether synthesized posterior leads provide incremental diagnostic value beyond careful interpretation of the standard 12&#x2011;lead ECG.

Humans↗
PubMed2026

Contrast Heat-Cold Versus Thermoneutral Showering in Trained Combat Sport Athletes: A Randomized Field Trial of Recovery Outcomes.

Contrast heat-cold showering is popular for recovery, but multisystem evidence and persistence after cessation remain unclear. To evaluate whether a 4-week post-training contrast heat-cold shower intervention produces an integrated recovery profile across four domains (autonomic, endocrine, perceptual, and microvascular) rather than testing a single isolated physiological pathway, across baseline (T0), post-intervention (T1), and 2-week wash-out (T2). Sixty combat-sport athletes were randomized to contrast showers (10 min alternating warm 38-40&#xb0;C and cold 13-15&#xb0;C) or an active thermoneutral-shower comparator (10 min, 32-34&#xb0;C) after training for 4 weeks. Primary analyses were per-protocol (&#x2265; 75% compliance; n = 57), with intention-to-treat sensitivity analyses. Outcomes were Total Quality Recovery (TQR), morning salivary cortisol (two mornings averaged), resting HRV, and post-occlusive reactive hyperemia (PORH). From T0 to T1, favorable between-group changes were observed for resting HR (&#x394;&#x394; -2.10 bpm, 95% CI -2.24 to -1.96; g -0.65; p < 0.001), lnRMSSD (&#x394;&#x394; 0.123 log units, 95% CI 0.108 to 0.137; g 0.74; p < 0.001), with similar T1 effects for RMSSD and SDNN, and TQR (&#x394;&#x394; 0.61 points, 95% CI 0.27 to 0.95; g 0.80; p < 0.001). These T1 autonomic and perceptual changes were not maintained at T2 (all T2-T0 &#x394;&#x394; p > 0.05). Cortisol and PORH-derived outcomes showed no statistically clear between-group differences at T1 or T2 (all p > 0.05). Compared with thermoneutral showering, 4 weeks of post-training contrast heat-cold showering produced short-term favorable between-group changes in autonomic regulation and perceived recovery, but not in morning cortisol or PORH-derived microvascular reactivity. These effects were not maintained after wash-out; therefore, causal attribution to the shower intervention alone and claims of persistent physiological adaptation should be made cautiously. Trial registration: ISRCTN15418049.

Humans↗
PubMed2026

Impact of renal dysfunction on immediate versus staged revascularization of non-culprit lesions in patients with ST segment elevation myocardial infarction: a pre-specified subgroup analysis of the randomized MULTISTARS AMI trial.

BACKGROUND: Renal dysfunction might affect outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (MVD) undergoing percutaneous coronary intervention (PCI). METHODS: In MULTISTARS AMI, patients with STEMI and MVD were randomized to immediate or staged PCI of non-culprit lesions. In this pre-specified analysis, patients were stratified according to the presence of renal dysfunction at baseline, defined at an estimated glomerular filtration rate (eGFR) of 60&#xa0;ml/min/1.73 m2. Patients with an eGFR&#x2009;<&#x2009;30&#xa0;ml/min/1.73 m2 were excluded from the trial. The primary endpoint was a composite of death, non-fatal myocardial infarction, stroke, unplanned revascularization, or hospitalization for heart failure at 1&#xa0;year. RESULTS: In MULTISTARS AMI, 108 (13%) of 832 patients had renal dysfunction. The primary endpoint occurred more frequently in patients with renal dysfunction (19.4% vs. 11.2%, unadjusted HR 1.82, 95% CI 1.13-2.94), primarily driven by higher rates of death. Among patients with renal dysfunction, the rates of the primary end point were 14.5% and 24.5% in the immediate and staged PCI groups (unadjusted HR 0.55, 95% CI 0.23-1.33). There was no interaction between renal dysfunction and the randomized treatment assignment with respect to the primary end point (adjusted HR 1.30, 95% CI 0.8-2.20, pint 0.82). The occurrence of acute renal insufficiency was statistically similar in patients with renal dysfunction who underwent immediate and staged PCI (10.9% vs. 18.9%, unadjusted HR 0.61, 95% CI 0.22-1.72, pint 0.09). Renal dysfunction at baseline emerged as a strong risk factor for the development of acute renal insufficiency (adjusted HR 5.0, 95% CI 2.30-10.70, p&#x2009;<&#x2009;0.01). CONCLUSIONS: Outcomes with immediate compared to staged multivessel PCI did not appear significantly altered by the presence of renal dysfunction&#xa0;at baseline. (Supported by Boston Scientific; MULTISTARS AMI ClinicalTrials.gov number, NCT03135275).

Humans↗