Evidence-Based Medicine

Research Appraisals

Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.

Showing 55 appraisals

Systematic ReviewEvidence: Moderate
45CEBM

The American journal of cardiology

Systematic Review of Coronary Computed Tomography Angiography Guidance for Chronic Total Occlusion Percutaneous Coronary Intervention

Coronary computed tomography angiography (CCTA) is emerging as a valuable adjunct for chronic total occlusion (CTO) percutaneous coronary intervention (PCI), particularly for lesions in which angiography incompletely defines procedural anatomy. In this systematic review, the authors evaluated the role of CCTA in CTO diagnosis, lesion characterization, prediction of guidewire crossing and procedural success, and procedural guidance. CCTA provides a detailed assessment of key features that directly influence CTO PCI strategy and outcomes. Randomized and observational data suggest that preprocedural CCTA can improve procedural planning, increase technical success in complex lesions, and support safer and more efficient CTO PCI through fluoroscopic co-registration and other real-time guidance applications. These findings highlight the clinical value of CCTA as a tool that can enhance case selection, optimize crossing strategy, and improve procedural success in contemporary CTO PCI.

18 July 2026

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Systematic ReviewEvidence: Weak
20CEBM

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

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Randomised Controlled TrialEvidence: Weak
35CEBM

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

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Systematic ReviewEvidence: Strong
95CEBM

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

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Systematic ReviewEvidence: Moderate
55CEBM

The American journal of cardiology

Transcatheter Chordal Repair for Degenerative Mitral Regurgitation: Systematic Review and Meta-analysis

Transcatheter chordal repair enables off-pump, echocardiography-guided treatment of degenerative mitral regurgitation, but real-world outcomes remain variably reported. We performed a systematic review and meta-analysis of studies evaluating outcomes after transcatheter chordal repair in adults with primary degenerative mitral regurgitation. Pooled event rates were calculated using random-effects models. Seventeen studies (n = 3,787) were included. Mitral regurgitation ≤ mild was achieved in 93.9% of patients at discharge and 82.5% at 30 days, while moderate mitral regurgitation occurred in 5.0% and 17.5%, respectively. Procedural success was 96.2%, although small-study effects were suggested. Early adverse events were infrequent, with 30-day mortality of 1.2%, stroke of 0.7%, and myocardial infarction of 1.2%. Reintervention occurred in 4.5%. In conclusion, transcatheter chordal repair demonstrates high technical success and favorable early safety; however, early mitral regurgitation recurrence and heterogeneity highlight the need for anatomy-guided patient selection and cautious interpretation given single-arm study limitations.

15 June 2026

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Randomised Controlled TrialEvidence: Moderate
50CEBM

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

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Randomised Controlled TrialEvidence: Strong
60CEBM

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

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Randomised Controlled TrialEvidence: Moderate
85CEBM

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

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Randomised Controlled TrialEvidence: Strong
85CEBM

The New England journal of medicine

Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism

BACKGROUND: Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain. METHODS: We conducted a multinational, adaptive-design trial with blinded outcome adjudication. Patients with intermediate-risk pulmonary embolism (with a ratio of right ventricular end-diastolic diameter to left ventricular end-diastolic diameter of ≥1.0 and an elevated troponin level) were eligible if they had at least two indicators of cardiorespiratory distress (systolic blood pressure of ≤110 mm Hg, a heart rate of ≥100 beats per minute, or a respiratory rate of >20 breaths per minute). Patients were randomly assigned to undergo ultrasound-facilitated, catheter-directed fibrinolysis with alteplase plus anticoagulation (the intervention group) or anticoagulation alone (the control group) according to prespecified treatment protocols. The primary outcome was a composite of pulmonary embolism-related death, cardiorespiratory decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days. RESULTS: The intention-to-treat population comprised 544 patients: 273 in the intervention group and 271 in the control group. The mean (±SD) age was 58.2±13.5 years, and 42.6% of the patients were women. A primary-outcome event occurred in 11 patients (4.0%; 95% confidence interval [CI], 2.3 to 7.1) in the intervention group and 28 (10.3%; 95% CI, 7.2 to 14.5) in the control group (relative risk, 0.39; 95% CI, 0.20 to 0.77; P = 0.005). The effect was driven primarily by a lower risk of cardiorespiratory decompensation or collapse in the intervention group. Major bleeding occurred within 7 days after randomization in 11 patients (4.1%) in the intervention group and 6 (2.2%) in the control group (P = 0.32); major bleeding occurred within 30 days in 11 patients (4.1%) and 8 patients (3.0%), respectively (P = 0.64). No substantial between-group differences in the incidence of other serious adverse events were observed up to 30 days after randomization; no intracranial hemorrhage occurred. CONCLUSIONS: In patients with acute, intermediate-risk pulmonary embolism, ultrasound-facilitated, catheter-directed fibrinolysis plus anticoagulation led to a lower risk of the composite of pulmonary embolism-related death, cardiopulmonary decompensation or collapse, or symptomatic recurrence of pulmonary embolism within 7 days than anticoagulation alone. (Funded by Boston Scientific; HI-PEITHO ClinicalTrials.gov number, NCT04790370.).

29 May 2026

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Systematic ReviewEvidence: Weak
50CEBM

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

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observationalEvidence: Insufficient
50CEBM

Circulation journal : official journal of the Japanese Circulation Society

Association of Lipid Core Burden Index With Early Progression of Cardiac Allograft Vasculopathy in Patients After Heart Transplantation

BACKGROUND: The association of the lipid-core burden index (LCBI), measured using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), with early progression of cardiac allograft vasculopathy remains unclear. METHODS AND RESULTS: We prospectively examined 12 consecutive heart transplant recipients who underwent NIRS-IVUS and IVUS. Patients were stratified according to the median maximum LCBI in a 4-mm segment (maxLCBI4 mm) of 223 at 1 month. The magnitude of maximal intimal thickness (MIT) progression was greater in the higher maxLCBI4 mmgroup. CONCLUSIONS: Patients with a higher maxLCBI4 mmat baseline exhibited greater MIT progression during the first post-transplant year.

26 May 2026

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Randomised Controlled TrialEvidence: Moderate
80CEBM

Journal of ethnopharmacology

Comparative efficacy and safety of Chinese patent medicines in coronary heart disease patients after percutaneous coronary intervention: A systematic review and network meta-analysis

ETHNOPHARMACOLOGICAL RELEVANCE: Patients with coronary heart disease (CHD) remain at high risk of major adverse cardiovascular events (MACEs) after percutaneous coronary intervention (PCI). Chinese Patent Medicines (CPMs) have demonstrated therapeutic potential as adjunctive therapies, however, direct comparative evidence regarding their effectiveness is lacking. AIM OF THE STUDY: This network meta-analysis (NMA) aims to systematically evaluate and compare the clinical efficacy and safety of CPMs combined with conventional therapy (CT) in post-PCI management. MATERIALS AND METHODS: A systematic literature search was performed in PubMed, Web of Science, Embase, Cochrane Library, CNKI, CBM, VIP, and Wanfang databases up to December 24, 2024. Randomized controlled trials investigating CPMs in CHD patients following PCI were included. Methodological quality was assessed using the Cochrane Risk of Bias tool. Outcome measures included major adverse cardiovascular events (MACEs), left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP), and nitric oxide (NO) levels. NMA was implemented using STATA 16.0 and R 4.1.2. Odds ratios and standardized mean differences with 95% confidence intervals were calculated for dichotomous and continuous outcomes, respectively. Model selection was guided by heterogeneity assessed using the I2 statistic. Intervention rankings were estimated using the surface under the cumulative ranking curve (SUCRA), with robustness and publication bias evaluated through sensitivity analyses and funnel plots. RESULTS: A total of 84 RCTs involving 10,524 patients and eight CPMs were included. For the primary outcome (MACEs), the SUCRA ranking indicated that Tongxinluo capsules combined with conventional therapy (TXLJN + CT) was the most effective intervention, followed by Shensong Yangxin capsules plus CT (SSYXJN + CT), Shexiang Baoxin pills plus CT (SXBXW + CT), Qili Qiangxin capsules plus CT (QLQXJN + CT), Qishen Yiqi dripping pills plus CT (QSYQDW + CT), Xinyu capsules plus CT (XYJN + CT), Fufang Danshen Dripping Pills plus CT (FFDSDW + CT), and Guanxin Shutong capsules plus CT (GXSTJN + CT), while CT alone ranked last. Correspondingly, the NMA demonstrated that TXLJN + CT was associated with the greatest reduction in LVEDD (SMD -1.01, 95% CI -1.35 to -0.66) and hs-CRP levels (SMD -2.50, 95% CI -3.33 to -1.68). The most significant improvement in LVEF (SMD 1.25, 95% CI 0.85 to 1.64) and NO levels (SMD 1.02, 95% CI 0.73 to 1.29) was observed with QSYQDW + CT. Meanwhile, SXBXW + CT showed the greatest efficacy in reducing NT-proBNP levels (SMD -3.43, 95% CI -4.68 to -2.18). CONCLUSION: CPMs combined with CT may provide clinical benefits in post-PCI management. According to SUCRA rankings, TXLJN + CT ranked first in reducing MACE and in lowering LVEDD and hs-CRP levels. QSYQDW + CT ranked first in improving LVEF and NO levels, while SXBXW + CT showed the highest ranking for reducing NT-proBNP levels. However, larger-scale, high-quality RCTs are needed to validate these findings.

25 May 2026

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Systematic ReviewEvidence: Moderate
85CEBM

Open heart

Prognostic value of CT-derived fractional flow reserve for major adverse cardiovascular events in patients with suspected or known coronary artery disease: a systematic review and meta-analysis

BACKGROUND: Fractional flow reserve derived from CT (FFR-CT) enables non-invasive functional assessment of coronary stenoses in patients with suspected or known coronary artery disease, but evidence regarding its prognostic value remains fragmented. We conducted a systematic review and meta-analysis to quantify the association between abnormal FFR-CT and major adverse cardiovascular events (MACE), updating the 2022 meta-analysis by Nørgaard et al METHODS: We searched PubMed, Embase and Scopus through December 2025 for studies comparing outcomes in patients with suspected or known coronary artery disease with FFR-CT ≤0.80 versus >0.80 (PROSPERO: CRD420261276897). Random-effects meta-analysis with Hartung-Knapp-Sidik-Jonkman adjustment was performed. Subgroup analyses examined FFR-CT technology, geography and follow-up duration. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool and certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method. RESULTS: Twenty-two studies with 20 067 patients were included, representing a fourfold increase from the prior meta-analysis. Follow-up ranged from 12 to 120 months. Patients with FFR-CT ≤0.80 had significantly higher MACE risk (HR 3.94; 95% CI 2.92 to 5.31; p<0.0001) with substantial heterogeneity (I²=79.9%). However, restricting to hard endpoints (death/myocardial infarction; k=6) yielded HR 3.28 (95% CI 2.25 to 4.79) with zero heterogeneity (I²=0%). No significant differences emerged across FFR-CT technologies (p=0.812), including HeartFlow, machine learning and deep learning algorithms. Trim-and-fill analysis suggested possible publication bias, with adjusted HR 2.35. GRADE certainty was moderate. CONCLUSIONS: Abnormal FFR-CT is associated with nearly fourfold increased risk of MACE in patients with suspected or known coronary artery disease, with consistent prognostic value across technologies. The absence of heterogeneity for hard endpoints supports FFR-CT as a reliable prognostic marker. These findings address the evidence gap identified by current guidelines regarding FFR-CT prognostic utility. PROSPERO REGISTRATION NUMBER: CRD420261276897. CLINICAL TRIAL NUMBER: Not applicable (as this is a Systematic Review and Meta-Analysis and not a Clinical Trial).

22 May 2026

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Randomised Controlled TrialEvidence: Weak
55CEBM

European heart journal. Acute cardiovascular care

Guided de-escalation of antiplatelet treatment in patients at high atherothrombotic risk presenting with acute coronary syndrome: a post hoc analysis of the TROPICAL-ACS trial

AIMS: Platelet function testing (PFT)-guided de-escalation of dual antiplatelet therapy (DAPT) after acute coronary syndrome (ACS) has been shown to reduce bleeding risk without increasing ischaemic events. Patients with high atherothrombotic risk (ATR) remain a challenging subgroup for such strategies. This study evaluated the safety and efficacy of early PFT-guided DAPT de-escalation according to ATR status. METHODS AND RESULTS: In the TROPICAL-ACS trial, 2610 ACS patients were randomized to standard 12-month prasugrel therapy or PFT-guided DAPT de-escalation. For this post hoc analysis, patients were stratified by ATR. High ATR was defined as age ≥ 65 years, polyvascular disease, or ≥2 risk factors (diabetes, smoking, or renal dysfunction). Hazard ratios (HRs) for clinical endpoints were derived using multistate Cox regression. High-ATR patients (n = 990) had a higher incidence of the primary net clinical benefit endpoint-composite of cardiovascular death, myocardial infarction, stroke, or Bleeding Academic Research Consortium 2-5 bleeding-compared with low-ATR patients (n = 1620) (11.0% vs. 6.7%; HR 1.67, 95% confidence interval 1.28-2.18; P < 0.001). Platelet function testing-guided de-escalation showed no significant interaction by ATR status for the primary endpoint [high ATR: 10.5% vs. 11.5%, HR 0.90 (0.61-1.32), P = 0.586; low ATR: 5.6% vs. 7.7%, HR 0.71 (0.48-1.04), P = 0.082; Pinteraction = 0.394] or ischaemic events [high ATR: 3.7% vs. 4.4%, HR 0.83 (0.44-1.56); low ATR: 1.8% vs. 2.6%, HR 0.68 (0.35-1.34); Pinteraction = 0.666]. CONCLUSION: Early PFT-guided de-escalation from prasugrel to clopidogrel was safe across atherothrombotic risk categories, supporting individualized DAPT optimization in ACS patients with both low and high ischaemic risk.

21 May 2026

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Randomised Controlled TrialEvidence: Moderate
70CEBM

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

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observationalEvidence: Moderate
70CEBM

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

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Systematic ReviewEvidence: Moderate
90CEBM

Journal of the American Heart Association

Sex Differences Among Young Patients With ST-Segment-Elevation Myocardial Infarction: A Systematic Review and Meta-Analysis

BACKGROUND: Female sex is associated with lower incidence of myocardial infarction, especially at younger ages. However, sex differences in mortality and coronary artery disease patterns among young patients with ST-segment-elevation myocardial infarction are not well established. This study evaluated sex differences in in-hospital and 1-year all-cause death and in the extent of coronary artery disease in patients aged ≤45 years with ST-segment-elevation myocardial infarction. METHODS: A systematic review (December 9, 2025) was conducted using PubMed, Cochrane, Embase, major cardiology conference proceedings, and ClinicalTrials.gov. Studies comparing sexes for outcomes were included. Non-English publications, abstracts without full text, and studies published before 2010 were excluded. A random-effects meta-analysis was performed, with results presented as relative risks (RR) and 95% CIs. Heterogeneity was assessed using τ and I2, risk of bias using the Risk of Bias in Nonrandomized Studies of Interventions tool. The study was registered on the International Prospective Register of Systematic Reviews. RESULTS: Eleven studies including 738 029 patients with ST-segment-elevation myocardial infarction (22% women) were analyzed. Female sex was associated with higher unadjusted in-hospital (RR, 1.56 [95% CI, 1.40-1.74]; τ=0.04; I2=0%) and 1-year mortality rate (RR, 1.78 [95% CI, 1.50-2.12]; τ=0.00; I2=0%). Women more frequently had single-vessel disease (73% versus 60%; RR, 1.13 [95% CI, 1.03-1.23]; τ=0.07; I2=67%), while men had 2-vessel (23% versus 18%; RR, 0.76 [95% CI, 0.68-0.85]; τ=0.00; I2=0%;) and 3-vessel disease (16% versus 9%; RR, 0.49 [95% CI, 0.27-0.86]; τ=0.41; I2=33%). CONCLUSIONS: In young patients with ST-segment-elevation myocardial infarction, female sex is associated with higher unadjusted in-hospital and 1-year death despite less extensive CAD. Further studies adjusting for comorbidities and standardizing CAD definitions are needed.

20 May 2026

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Randomised Controlled TrialEvidence: Moderate
80CEBM

Circulation

Prehospital Heparin Administration in Patients With STEMI Undergoing Primary PCI: HEPARIN-STEMI Randomized Controlled Trial

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for patients with ST-segment-elevation myocardial infarction (STEMI). We investigated the benefits and safety of pretreatment with unfractionated heparin (UFH) in patients with STEMI referred to primary PCI. METHODS: In HEPARIN-STEMI (Pretreatment With Unfractionated Heparin for ST Elevation Myocardial Infarction)-a single-center, open-label, randomized controlled trial-patients with STEMI with ≤6 hours symptom duration were assigned to receive either a 70- to 100-IE/kg bolus of UFH at first prehospital medical contact plus a supplemental dose before PCI, adjusted to activated clothing time ≥250 seconds, or to a control group receiving standard UFH at the time of PCI. The primary efficacy end point was TIMI (Thrombolysis in Myocardial Infarction) flow grade 2-3 in the infarct-related artery at initial coronary angiography. The primary safety end point was BARC (Bleeding Academic Research Consortium) type 3-5 bleeding during the index hospital stay. RESULTS: From March 2022 to February 2025, 298 patients were randomized to UFH pretreatment and 295 to the control group. The groups were comparable in age, sex, risk factors, previous cardiovascular events, and median delay from symptoms to coronary angiography (145 versus 150 minutes; P=0.814). The median time from UFH pretreatment to coronary angiography was 60 minutes (25th-75th interquartile range, 47-55 minutes). TIMI flow grade 2-3 in the infarct-related artery was documented in 43% of patients with UFH pretreatment and 27% of patients in the control group (relative risk, 1.59 [95% CI, 1.27-1.98]; P<0.001), with no significant difference in BARC type 3-5 bleeding (2.4% versus 2.0%; relative risk, 1.16 [95% CI, 0.39-3.45]; P=0.789). CONCLUSIONS: In patients with STEMI undergoing primary PCI, in a mature STEMI network, pretreatment with UFH at first prehospital medical contact was associated with an absolute 16% increase in infarct-related artery patency without an increased risk of bleeding. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05247424.

19 May 2026

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Randomised Controlled TrialEvidence: Moderate
70CEBM

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

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otherEvidence: Moderate
70CEBM

Physics in medicine and biology

Nonperiodic dynamic CT reconstruction using backward-warping implicit neural representation with diffeomorphism regularization

Objective.Motion artifacts remain a major obstacle in dynamic computed tomography (CT) reconstruction, particularly for nonperiodic rapid motion such as cardiac imaging in patients with fast or irregular heart rates, where ECG-gated approaches are unreliable. The extreme limited-angle problem arising from insufficient angular coverage within a single cardiac phase makes accurate reconstruction of fine cardiac structures especially challenging. This work aims to develop a self-supervised framework that recovers high-resolution dynamic CT images from nonperiodic motion scenarios without external training datasets.Approach.We propose BIRD, an implicit neural representation (INR) framework for nonperiodic dynamic CT reconstruction, with three components: (1) a dual-feature representation decomposing the dynamic scene into topology-preserving and free-form features, enabling modeling of both deformable motion and residual variations such as contrast kinetics; (2) a backward-warping deformation model enabling direct ray-based training, overcoming the resolution limitations of prior forward-warping INR approaches at clinically relevant sub-millimeter resolution; and (3) a diffeomorphism-based regularization enforcing anatomically plausible deformation vector fields through bidirectional inverse consistency, without restricting representational capacity.Main results.BIRD was validated on digital and physical cardiac phantoms and retrospective patient data. In the XCAT phantom study under severe limited-angle conditions (0.5 s rot-1, 120 bpm), BIRD improved peak signal-to-noise ratio over the next-best method by 1.43 dB on the right coronary artery and 1.21 dB on the right ventricle. Curved planar reformation confirmed improved vessel continuity and boundary sharpness. On real projection data from a physical cardiac phantom and a retrospective patient scan, BIRD reduced motion artifacts and improved depiction of cardiac and vascular structures compared with conventional reconstructions.Significance.The proposed framework performs self-supervised reconstruction of nonperiodic dynamic CT images solely from projection data. It offers potential clinical applications including non-ECG-gated cardiac imaging for patients with arrhythmia, cinematic image sequences, and retrospective motion artifact correction in conventional CT scans.

19 May 2026

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diagnosticEvidence: Moderate
70CEBM

European heart journal

Deep learning electrocardiogram model for risk stratification of coronary revascularization need in the emergency department

BACKGROUND AND AIMS: Identification of patients with acute coronary syndrome requiring coronary revascularization can be challenging due to inconclusive electrocardiogram (ECG) findings or biomarker results. A deep learning model to detect ECG patterns associated with revascularization likelihood was developed, aiming to guide further assessment and reduce diagnostic uncertainty. METHODS: A convolutional neural network model was trained on 144 691 ED visits from a US cohort (60 ± 19 years; 53% female; 0.6% revascularization), tested on a separate test cohort (n = 35 995), and benchmarked against clinician ECG interpretation and cardiac troponin T (TnT). External validation was performed for the outcomes revascularization and Type 1 myocardial infarction (MI) on 18 673 ED visits from Europe (55 ± 21 years; 49% female; 1.5% revascularization; 1% Type 1 MI). Primary performance metric was area under the receiver operating characteristic curve (AUROC). RESULTS: In the test cohort, the model achieved an AUROC of 0.91 (95% confidence interval [CI] 0.91-0.91), outperforming clinician ECG interpretation (AUROC 0.65, 95% CI 0.54-0.76) and conventional cardiac TnT (AUROC 0.71). In the external validation cohort, ECG model AUROC was 0.81 (95% CI 0.81-0.82) for revascularization, and 0.85 (95% CI 0.84-0.85) for Type 1 MI, compared with 0.70 (95% CI 0.57-0.83) and 0.74 (95% CI 0.56-0.92) for clinician interpretation, and 0.85 and 0.87 for high-sensitivity (hs)-TnT, respectively. The ECG model had higher specificity but lower sensitivity compared with high-sensitivity-troponin T. CONCLUSIONS: The model was able to detect revascularization and Type 1 MI with competitive performance, suggesting a potential role to complement current clinical assessment.

16 May 2026

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otherEvidence: Strong
100CEBM

Journal of radiological protection : official journal of the Society for Radiological Protection

Fast occupational upper-limb radiation dose prediction using machine learning and Monte Carlo simulation

Interventional procedures expose physicians to scattered radiation, particularly to their upper extremities, posing occupational health risks. Existing extremity dosimeters such as thermoluminescents, optically stimulated luminescence rings and active personal dosimeters provide limited spatial information, exhibit angular and energy dependence and offer little or no real-time feedback. This study develops machine learning (ML) models to estimate radiation dose values at discrete upper-limb locations using Monte Carlo (MC)-derived data and procedure-specific parameters. A dataset of 10 000 MC dose maps was generated under varied clinical and geometric conditions. After log-transformation and normalisation, several ML models, including deep neural networks and tree-based regressor, were trained and assessed using five-fold cross-validation. Mean absolute error and relative error (RE) were evaluated on the original dose scale, and an ensemble of the three best-performing models was constructed to improve robustness. The ensemble consistently outperformed individual models, achieving an average RE of 3.69% and demonstrating stable performance across anatomical regions and dose levels. Highest accuracy was obtained for standard beam geometries, whereas larger discrepancies occurred in extreme configurations with steep dose gradients. Predicted dose patterns were consistent with the expected distributions across the upper-limb regions. The findings demonstrate the feasibility of ML-based extremity dose estimation in interventional environments. The proposed ensemble provides a rapid (around 10 ms), scalable alternative to full MC simulations, enabling near real-time predictions of upper-limb occupational dose and supporting optimisation of radiation protection practices in image-guided procedures.

16 May 2026

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diagnosticEvidence: Moderate
55CEBM

BMC medical imaging

Development and validation of a novel deep learning coronary artery plaque quantification model

BACKGROUND: Coronary Computed Tomography Angiography (CCTA) is an established tool for assessing coronary artery disease. CCTA determined total coronary artery plaque volume predicts cardiovascular events, but manual quantification is impractical for routine use. Deep learning-based methods offer a promising solution for automated plaque volume assessment. METHODS: We developed and validated a novel software, QuantiPlaque, powered by deep learning models, for automated segmentation of total and calcified coronary plaque volume. Expert manual annotation served as the reference standard. Correlations between deep learning and expert segmentation were evaluated using intraclass correlation coefficient (ICC), Pearson's r, and Spearman's rho, and agreements were evaluated with Bland-Altman analyses. RESULTS: A total of 115 CCTA scans were included. Mean (range) age was 58 (51-64) and 51% were females. The mean coronary artery calcium score was 56 Agatston units, ranging from 0 to 601. The model demonstrated strong correlation and agreement with expert annotation for per-patient total plaque volume (ICC 0.95, mean difference - 8.35 mm3, 95% limit of agreement - 102 to 85 mm3, Spearman's rho 0.87, Pearson's r 0.95) and calcified plaque volume (ICC 0.90, mean difference - 0.28 mm3, 95% limits of agreement - 21.97 to 21.42 mm3, Spearman's rho 0.93, Pearson's r 0.90). Per-vessel analysis showed strong correlation in the left anterior descending artery and right coronary artery but was weaker in the left circumflex artery territory. CONCLUSION: The evaluated deep learning model provides accurate quantification of total and calcified plaque burden, with strong correlation and agreement to expert annotation.

16 May 2026

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Randomised Controlled TrialEvidence: Strong
95CEBM

BMJ (Clinical research ed.)

Efficacy of dual antiplatelet therapy for three months versus 12 months after coronary artery bypass grafting: multicentre, double blinded, randomised controlled trial

OBJECTIVES: To evaluate the efficacy of dual antiplatelet therapy (DAPT) for three months versus 12 months in saphenous vein graft occlusion while reducing bleeding risk. DESIGN: Multicentre, non-inferiority, double blind, randomised controlled trial. SETTING: 13 cardiac surgery centres in China, with enrolment between February 2023 and July 2024. PARTICIPANTS: 2300 participants aged 18 to 80 years who underwent elective primary coronary artery bypass grafting with ≥1 saphenous vein graft. INTERVENTIONS: Participants were randomly assigned (1:1) to receive DAPT (ticagrelor 90 mg twice daily plus aspirin 100 mg once daily) for 12 months or the same dual antiplatelet regimen for the first three months, followed by placebo plus aspirin for nine months. MAIN OUTCOME MEASURES: The primary outcomes were saphenous vein graft occlusion at one year (non-inferiority) and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding (superiority). Secondary outcomes were major adverse cardiovascular events (MACCE), saphenous vein graft failure, venous or arterial graft stenosis, and venous or arterial graft occlusion. RESULTS: 2290 patients (mean age 61.5 (standard deviation (SD) 8.4) years, 20.6% (n=472) women) were included in the modified intention-to-treat set. The mean number of saphenous vein graft segments was 2.5 (SD 0.8). 2070 patients (90.4%) with a total of 5125 saphenous vein graft segments were assessed at one year. Saphenous vein graft occlusion occurred in 280 of 2596 (10.8%) in the three month DAPT group and 283 of 2529 (11.2%) in the 12 month DAPT group (absolute difference -0.31%, 95% confidence interval (CI) -3.13% to 2.52%; P=0.008 for non-inferiority). During a median follow-up of 368 (interquartile range 358-382) days, BARC type 2, 3, or 5 bleeding occurred in 95 patients (8.3%) in the three month DAPT group and 149 patients (13.2%) in the 12 month DAPT group (absolute difference -4.67%, 95% CI -7.18% to -2.16%; P<0.001). The number needed to treat to prevent one bleeding event was 21 (95% CI 13 to 46). MACCE occurred in 26 (2.3%) patients in the three month DAPT group and 27 (2.7%) in the 12 month DAPT group (absolute difference -0.11%, 95% CI -1.48% to 1.26%). The findings for other secondary outcomes were also similar between the two groups. CONCLUSIONS: A three month DAPT strategy was non-inferior to the 12 month DAPT strategy in saphenous vein graft occlusion and was superior in reducing bleeding risk. TRIAL REGISTRATION: ClinicalTrials.gov NCT05380063.

15 May 2026

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diagnosticEvidence: Moderate
65CEBM

Nature communications

A deep learning ECG model for identification and localization of occlusion myocardial infarction.

Rapid identification and localization of an acute coronary occlusion are vital to prevent myocardial damage, yet reliance on ST-segment ECG criteria misses many acute occlusion myocardial infarctions (OMI) and triggers unnecessary acute angiographies. Here, we present a trained and validated deep learning model using 540,372 emergency ECGs paired with definitive catheterization outcomes. The model has a C-statistic of ≥0.95 for OMI and ≥0.87 for non-OMI infarctions and can localize culprit lesions in the three main coronary branches, which can guide the angiographer. Performance is similar across age, sex, and ECG hardware subgroups. Obviating dependence on ST-elevations and troponins, this model for the identification and localization of OMI has the potential to shorten the time to reperfusion of an acute coronary occlusion and save resources. Because human oversight of OMI detection on the ECG is limited, randomized clinical trials with patient-relevant outcomes are warranted.

15 May 2026

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Systematic ReviewEvidence: Moderate
75CEBM

JACC. Cardiovascular interventions

Durability of Mitral Valve Transcatheter Edge-to-Edge Repair: An Expert Overview

BACKGROUND: Mitral regurgitation (MR) is a globally endemic heart disease burden with significant morbidity and mortality. Mitral transcatheter edge-to-edge repair (M-TEER) has emerged as a minimally invasive treatment with established safety and intermediate-term efficacy. OBJECTIVES: The aim of this study was to determine M-TEER durability and the incidence, risk factors, and treatment strategies of M-TEER failure. METHODS: A comprehensive literature review was performed, identifying 457 records, from which 33 full-text papers were included. Definitions of MR recurrence, reintervention, and M-TEER durability and failure were provided. On the basis of these definitions, weighted means with 95% CIs were calculated for the rates of MR recurrence, reintervention, and their composite for both the overall population and the primary and secondary MR subgroups. RESULTS: The pooled weighted means of MR recurrence and reintervention ranged between 5% and 10% in the first months after the index procedure, remained relatively stable for the first 3 years, and increased at 5 years to 17% and 9%, respectively. MR recurrence and reintervention weighted means were numerically higher in primary than secondary MR, and 41% of primary MR patients experienced MR recurrence or reintervention at 5 years. Redo transcatheter edge-to-edge repair for M-TEER failure seemed safer than surgery but was associated with 1-year MR recurrence rates between 20% and 40%. Mitral valve replacement was the most common surgical technique for M-TEER failure. CONCLUSIONS: The incidence of M-TEER failure after a successful index procedure increases after 3 years and is more pronounced with primary than secondary MR. More systematic, longer term follow-up data after M-TEER are required to better define M-TEER durability.

14 May 2026

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Randomised Controlled TrialEvidence: Strong
50CEBM

The New England journal of medicine

Left Ventricular Unloading in High-Risk Percutaneous Coronary Intervention

BACKGROUND: Complex percutaneous coronary intervention (PCI) in patients with severely impaired left ventricular function carries a high risk of death and complications. Whether percutaneous left ventricular unloading improves outcomes remains unclear. METHODS: We randomly assigned 300 patients with severe left ventricular dysfunction and extensive coronary artery disease in a 1:1 ratio to a strategy of elective unloading with a microaxial flow pump or to standard care during planned complex PCI. The primary outcome was a hierarchical composite that included death from any cause, disabling stroke, spontaneous myocardial infarction, hospitalization for cardiovascular causes, or periprocedural myocardial injury at a minimum of 12 months, as analyzed according to a win ratio. RESULTS: A total of 148 patients were assigned to receive a microaxial flow pump and 152 to receive standard care. At a median of 22 months (interquartile range, 16 to 30), 36.6% of pairwise comparisons favored the microaxial flow pump, and 43.0% favored standard care (win ratio, 0.85; 95% confidence interval [CI], 0.63 to 1.15; difference, -6.4 percentage points; P = 0.30). Death from any cause occurred in 47 patients in the microaxial-flow-pump group and 33 in the standard-care group (hazard ratio, 1.54; 95% CI, 0.99 to 2.41). There was no material between-group difference in the risk of bleeding or vascular complications. CONCLUSIONS: Among patients with severely impaired left ventricular function undergoing complex PCI, elective left ventricular unloading with a microaxial flow pump did not reduce the risk of major adverse clinical outcomes at a minimum of 12 months. (Funded by the U.K. National Institute for Health and Care Research; CHIP-BCIS3 ClinicalTrials.gov number, NCT05003817.).

12 May 2026

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Randomised Controlled TrialEvidence: Strong
75CEBM

European heart journal

Tricuspid valve replacement outcomes by baseline tricuspid regurgitation severity: the TRISCEND II trial

BACKGROUND AND AIMS: The TRISCEND II trial demonstrated superior clinical benefits for patients with ≥severe tricuspid regurgitation (TR) treated with the EVOQUE transcatheter tricuspid valve replacement (TTVR) system plus medical therapy vs medical therapy alone. This work reports 1-year and 18-month outcomes in patients stratified by baseline TR severity. METHODS: The multicentre, prospective TRISCEND II trial enrolled 400 patients with symptomatic, ≥severe TR, and randomized 2:1 to TTVR (n = 267) or control (n = 133). In a post hoc analysis, patients were stratified into severe TR (n = 172) and massive/torrential TR (n = 220) cohorts. Clinical and quality-of-life outcomes were reported at 1 year, with Kaplan-Meier estimates for all-cause mortality and heart failure (HF) hospitalization assessed at 18 months. Study oversight included an independent echocardiographic core laboratory, clinical events committee, and data safety monitoring board. RESULTS: One year after TTVR, TR was ≤mild in 95.2% of severe TR and 95.3% of massive/torrential TR patients. The primary safety and effectiveness endpoint (win ratio) favoured TTVR over control regardless of baseline TR severity: severe {1.64 [95% confidence interval (CI): 1.11, 2.43]} and massive/torrential [2.20 (1.55, 3.14)]. At 18 months, TTVR patients had similar mortality to controls [rate difference: severe 0.2% (-11.6, 11.9), massive/torrential -5.8% (-17.6, 6.0)], whereas HF hospitalization rates favoured TTVR in the massive/torrential cohort [vs control, severe 9.8% (-3.0, 22.7), massive/torrential -15.2% (-28.9, -1.5)]. CONCLUSIONS: Patients with ≥severe TR benefit from TTVR, experiencing improvements in TR severity, functional capacity, and quality of life regardless of baseline TR severity, with a signal for greater benefit in patients with more advanced disease.

11 May 2026

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Randomised Controlled TrialEvidence: Moderate
60CEBM

European heart journal

Temporal modulation of antiplatelet therapy in high-risk patients undergoing complex percutaneous coronary intervention: the TAILORED-CHIP randomized clinical trial

BACKGROUND AND AIMS: Limited data exist on optimal antiplatelet strategies for high-risk patients undergoing complex percutaneous coronary intervention (PCI). This study aimed to investigate the efficacy and safety of tailored antiplatelet treatment with temporal modulation of the intensity of platelet inhibition in patients undergoing complex high-risk PCI. METHODS: We randomly assigned 2018 patients with high-risk anatomical or clinical characteristics undergoing complex PCI to a tailored antiplatelet strategy with early escalation (low-dose ticagrelor at 60 mg twice daily plus aspirin <6 months) and late de-escalation (clopidogrel monotherapy >6 months) or dual antiplatelet therapy (clopidogrel plus aspirin for 12 months). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, stent thrombosis, unplanned urgent revascularization, and clinically relevant bleeding (Bleeding Academic Research Consortium Type 2, 3, or 5) at 12 months. RESULTS: The mean age was 64.0 years, 22.6% had left main PCI, 19.5% had complex bifurcation PCI, 84.1% had diffuse long lesions, 93.7% had multivessel PCI, and 36.7% had medically treated diabetes. At 12 months, a primary outcome event occurred in 105 patients (10.5%) assigned to tailored antiplatelet therapy and in 89 patients (8.8%) assigned to dual antiplatelet therapy [hazard ratio, 1.19; 95% confidence interval (CI), 0.90-1.58; P = .21]. The incidence of major ischaemic events appeared to be similar in both groups. The incidence of clinically relevant bleeding at 12 months was 7.2% in the tailored-therapy group and 4.8% in the dual-therapy group (difference, 2.45% points; 95% CI, 0.37-4.53). CONCLUSIONS: Among high-risk patients undergoing complex PCI, tailored antiplatelet strategy with early escalation and late de-escalation, as compared with dual antiplatelet therapy, did not decrease the incidence of primary net adverse events at 12 months. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number, NCT03465644.

11 May 2026

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observationalEvidence: Moderate
60CEBM

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

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Randomised Controlled TrialEvidence: Moderate
60CEBM

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

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Systematic ReviewEvidence: Moderate
75CEBM

Polish archives of internal medicine

Systematic review and meta-analysis of the safety and efficacy of transvenous lead extraction in octogenarian patients

INTRODUCTION: As the global population ages and the use of cardiac implantable electronic devices (CIEDs) increases, transvenous lead extraction (TLE) is being performed more frequently in elderly patients. Concerns remain regarding its safety and efficacy in octogenarians, and age‑specific recommendations are limited. OBJECTIVES: We aimed to assess procedural success, complication rates, and mortality associated with TLE in patients aged 80 years or older in comparison with younger individuals. PATIENTS AND METHODS: A systematic search of PubMed, Cochrane CENTRAL, SciELO, and ScienceDirect was conducted up to December 2024. Studies reporting TLE outcomes in octogenarians and younger patients were included according to predefined criteria. A meta‑analysis was performed to compare procedural success, complications, and mortality between the age groups. RESULTS: Seventeen studies including 15 984 patients were analyzed. Complete lead extraction success was 96.7% in octogenarians and 96.2% in the patients aged below 80 years. No significant differences were observed in major or minor procedural complications. In‑hospital mortality was low and comparable between the groups. Although long‑term mortality was higher in the octogenarians, this reflected greater baseline comorbidity and frailty rather than increased procedural risk. None of the included studies demonstrated higher periprocedural danger of TLE in elderly patients. CONCLUSIONS: TLE is safe and effective in patients aged 80 years and older, with outcomes comparable to younger individuals. Advanced age alone should not preclude referral for lead extraction.

3 May 2026

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Randomised Controlled TrialEvidence: Moderate
75CEBM

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

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Randomised Controlled TrialEvidence: Moderate
85CEBM

Heart (British Cardiac Society)

Revascularisation strategies for non-acute myocardial ischaemic syndromes

BACKGROUND: Contemporary guidelines by the European Society for Cardiology and American College of Cardiology/American Heart Association for the treatment of non-acute myocardial ischaemic syndromes dispute the value of revascularisation and differ in their recommendation to perform revascularisation. A Bayesian network meta-analysis was performed, evaluating the strength of evidence for the comparative incremental effectiveness of coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) over medical therapy on long-term outcomes. METHODS: A hierarchical Bayesian network meta-analysis was designed (PROSPERO CRD42024541215, date 20 May 2024), including randomised controlled trials (RCTs) published between 2005 and 10 June 2025, which consisted of three initial treatment modalities: optimal medical therapy (OMT), PCI+OMT and CABG+OMT. The primary outcome was all-cause mortality at maximum follow-up; secondary outcomes were trates of the rates of myocardial infarction, stroke and re-revascularisation at maximum follow-up, expressed in HRs and 95% credible intervals (CrIs), accompanied by surface under the cumulative ranking curve (SUCRA) scores. RESULTS: 10 RCTs, comprising 10 742 patients, were included. For all-cause mortality, the estimated median HR of CABG+OMT versus OMT was 0.84 (95% CrI 0.68-1.07); the HR of PCI+OMT versus OMT was 0.93 (0.79-1.16); and the HR of CABG+OMT versus PCI+OMT was 0.91 (0.71-1.13). The SUCRAs of a CABG+OMT strategy ranking as the optimal revascularisation treatment regarding mortality, myocardial infarction, stroke and re-revascularisation were 88.1%, 99.7%, 17.5% and 99.5%, respectively. Results were consistent across sensitivity analyses, including in the node-splitting models. CONCLUSIONS: This Bayesian network meta-analysis found that an initial CABG (+OMT) revascularisation strategy was associated with higher probabilities of optimal outcomes, with the exception of stroke, compared with an initial PCI (+OMT) revascularisation strategy, although CrIs overlapped, suggesting that some uncertainty remains. PROSPERO REGISTRATION NUMBER: CRD42024541215.

27 Apr 2026

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observationalEvidence: Moderate
95CEBM

Heart (British Cardiac Society)

Variation in mechanical circulatory support use for acute myocardial infarction cardiogenic shock

BACKGROUND: Cardiogenic shock (CS) is a leading cause of mortality following acute myocardial infarction (AMI). Some patients may require intra-aortic balloon pump (IABP) or percutaneous ventricular assist device (PVAD) placement; however, there is a paucity of standardised algorithms to guide the deployment of each device. The present study evaluated interhospital variation in the use of IABP and PVAD for AMI CS and identified institutional factors associated with hospital-level device preference. METHODS: All non-elective adult hospitalisations entailing AMI and CS were identified within the 2019 Nationwide Readmissions Database. Patients were grouped into IABP, PVAD and non-mechanical circulatory support cohorts. The primary aim was to quantify the degree of interhospital variation in the use of IABP and PVAD. Escalation to extracorporeal membrane oxygenation (ECMO), left ventricular assist device (LVAD) implantation, length of stay and hospitalisation costs were secondarily assessed. Hospital factors, such as percutaneous coronary intervention (PCI) volume and safety net status, were also analysed. RESULTS: Among 53 903 patients, 23.4% received IABP, and 12.5% received PVAD. After adjustment for patient factors, approximately 13% (11-14%) of variation in IABP use and 18% (15-20%) of PVAD use were attributable to centre-level differences. High-PVAD hospitals had higher annual PCI volume (257 (185-369) vs 204 (148-276) cases/year, p=0.032) and were more commonly safety net institutions (27.4% vs 11.3%, p=0.023), compared to high-IABP hospitals. Patients treated at high-IABP and high-PVAD hospitals faced similar length of stay (β -0.16, 95% CI -1.82 to 1.49) and costs (β -$3500, 95% CI -16 600 to 9600). Those at high-PVAD hospitals had lower adjusted risk of escalation to ECMO (0.52, 95% CI 0.29 to 0.95) and LVAD implantation (0.28, 95% CI 0.08 to 0.94). CONCLUSIONS: The present study identified wide interhospital variation in the use of IABP and PVAD for AMI CS. Although the likelihood of escalation to ECMO or LVAD differed between hospital types, resource utilisation was similar.

27 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
65CEBM

Journal of medical Internet research

Personalized Smartphone Messaging for Secondary Prevention After Percutaneous Coronary Intervention: Randomized Controlled Trial

BACKGROUND: Cardiac rehabilitation improves outcomes after percutaneous coronary intervention (PCI), but participation remains suboptimal due to barriers such as distance, cost, and lack of referral. Mobile health interventions may enhance accessibility and engagement. OBJECTIVE: This study evaluated the effectiveness and user acceptability of a smartphone messaging app (AnSim) in improving cardiovascular risk factors among patients who recently underwent PCI. METHODS: A 2-arm randomized controlled trial was conducted at 2 Korean hospitals; 120 patients who had undergone PCI within the prior month were randomized (1:1) to receive AnSim plus usual care (intervention) or usual care alone (control). The intervention comprised personalized messages tailored by behavioral stage and risk profile, delivered 6 times/week for 6 months. Outcomes were assessed at baseline, 6 months, and 9 months. The primary outcome was change in blood pressure (BP) at 6 and 9 months. Secondary outcomes were lipid profiles, hemoglobin A1c, BMI, smoking status, physical activity, and achievement of guideline-recommended risk-factor targets. User acceptability was assessed by questionnaire. RESULTS: Overall, 115 (95.8%; intervention: n=58, control: n=57) participants completed follow-up at 6 months and 110 (91.7%; intervention: n=54, control: n=56) at 9 months. At 6 months, systolic BP was 124.9 (SD 16.7) mmHg in the intervention group and 124.8 (SD 13.1) mmHg in the control group (between-group difference 0.1 mmHg, 95% CI -5.4 to 5.6), and diastolic BP was 80.2 (SD 11.4) mmHg vs 78.4 (SD 10.6) mmHg (difference 1.8 mmHg, 95% CI -2.3 to 5.9). At 9 months, systolic BP was 126 (SD 14.2) mmHg vs 128 (SD 15.4) mmHg (difference -2 mmHg, 95% CI -7.6 to 3.6), and diastolic BP was 80.8 (SD 13.2) mmHg vs 81.3 (SD 12.0) mmHg (difference -0.5 mmHg, 95% CI -5.3 to 4.3). No significant between-group differences were observed in secondary outcomes. In post hoc analyses, participants with above-median message reading were more likely to achieve ≥4 of 5 guideline-recommended risk-factor targets at 9 months (69% vs 19.2%; relative risk 3.59, 95% CI 1.57-8.18; P<.001) and logged more diary entries (mean difference 203.4 entries, 95% CI 79.3-327.5; P=.001). BP responders at 9 months read messages on more days than nonresponders (110.3 vs 83.3 d; mean difference 27 d, 95% CI 4.6-49.3; P=.02). Among survey respondents (54/60, 90%), 87% (47/54) found the messages helpful and 81.4% (44/54) wished to continue. Two events occurred in the control group (P=.50). CONCLUSIONS: This trial found no between-group improvement in BP with low-intensity personalized messaging compared to an attention-matched diary app, but exploratory analyses suggest engagement may be a key determinant of potential benefit. Unlike comprehensive app-based cardiac rehabilitation programs, AnSim provides scalable behavioral reinforcement that can be integrated into post-PCI follow-up with minimal burden. These findings support future pragmatic trials optimizing engagement strategies and evaluating longer-term clinical and implementation outcomes.

25 Apr 2026

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otherEvidence: Moderate
50CEBM

Journal of the American College of Cardiology

Cardiovascular Science, Medicine, and Society: The Brave New World: The ACC Braunwald Lecture 2025

Recent scientific and technological advances have dramatically expanded the possibilities in cardiovascular medicine. Landmark clinical trials have introduced transformative therapies for lipid disorders, heart failure, and obesity, offering clinicians powerful new tools to manage increasingly complex patient populations. Discoveries in molecular medicine, including gene therapies and RNA therapeutics, have ushered in new biopharmaceutical platforms and promise the potential for curative or infrequent dosing regimens. Minimally invasive, percutaneous, and robotic surgical techniques, along with next-generation devices and interventional procedures, are enhancing patient outcomes and broadening access to advanced care. The rapid rise of artificial intelligence and digital health technologies is reshaping how we gather, interpret, and act on data across the care continuum. Together, these developments mark the arrival of a brave new world in cardiovascular medicine. Yet the promise of this new era is tempered by unequal access, ethical dilemmas, and potential unintended consequences at both the patient and societal levels. This review is written in honor of Dr Eugene Braunwald, who has been a pioneer in cardiovascular science and technological innovation. The paper summarizes recent milestones in cardiovascular medicine and offers a forward-looking perspective on how to realize the full potential of innovation by translating scientific progress into equitable, responsible care and improved health outcomes.

25 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
75CEBM

EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology

Impact of renal function on edoxaban antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease: a prespecified analysis of the EPIC-CAD trial

BACKGROUND: Renal function is a critical factor of ischaemic and bleeding risks in patients with atrial fibrillation (AF) receiving antithrombotic therapy. AIMS: This study aimed to evaluate the impact of renal dysfunction in patients with AF and stable coronary artery disease (CAD) undergoing antithrombotic therapy. METHODS: The Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease (EPIC-CAD) trial randomised patients to edoxaban monotherapy or dual antithrombotic therapy (edoxaban plus a single antiplatelet agent). In this prespecified analysis, patients were stratified by creatinine clearance into low (<50 mL/min) or high (≥50 mL/min) groups according to edoxaban dose-reduction criteria. The primary endpoint was net adverse clinical events (NACE: death from any cause, myocardial infarction, stroke, systemic embolism, urgent revascularisation, or major/clinically relevant non-major bleeding) at 12 months. RESULTS: Of 1,040 randomised patients, 252 (24.2%) had low creatinine clearance; these patients were older and had more comorbidities compared with the 788 patients (75.8%) with high creatinine clearance. Patients with low creatinine clearance experienced higher risks of NACE (hazard ratio [HR] 1.72, 95% confidence interval [CI]: 1.19-2.49; p=0.004), ischaemic events (HR 2.70, 95% CI: 1.09-6.70; p=0.032), and bleeding (HR 1.54, 95% CI: 1.01-2.34; p=0.046). At 12 months, edoxaban monotherapy reduced NACE compared with dual therapy in both the low (12.1% vs 21.7%, HR 0.52, 95% CI: 0.28-0.98; p=0.042) and high creatinine clearance groups (5.2% vs 14.5%, HR 0.40, 95% CI: 0.25-0.65; p<0.001), with no interaction (p for interaction=0.53). CONCLUSIONS: In patients with AF and stable CAD, edoxaban monotherapy led to a lower risk of primary NACE than dual antithrombotic therapy, regardless of renal function. (ClinicalTrials.gov: NCT03718559).

21 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
70CEBM

Open heart

Non-invasive endotyping improves treatment satisfaction and prescribing appropriateness in patients with angina and no obstructive coronary artery disease.

BACKGROUND: Patients with angina and no obstructive coronary artery disease (ANOCA) frequently receive empirical antianginal therapy that fails to target underlying pathophysiological mechanisms. Whether stress perfusion cardiac magnetic resonance (CMR)-guided endotyping and stratified medical therapy improves treatment satisfaction and appropriate medication prescribing in this population is uncertain. METHODS: In the Coronary Microvascular Angina CMR Imaging Trial, 250 patients with suspected ANOCA, who had undergone invasive coronary angiography demonstrating no obstructive disease, were enrolled and underwent stress perfusion CMR with quantification of myocardial blood flow. Participants were randomised 1:1 to CMR-guided management (intervention) or angiography-guided management (control). Treatment satisfaction was assessed using the validated Treatment Satisfaction Questionnaire for Medication (TSQM-9) at baseline, 6 months and 12 months. Medication prescriptions were documented at these time points. RESULTS: Stress CMR imaging led to diagnostic reclassification in 53.0% of patients, with microvascular angina diagnosed in 51.0%. At 12 months, global treatment satisfaction was significantly higher in the intervention group compared with controls (adjusted difference, 19.30 units (95% CI 13.89 to 24.71); p<0.001), with consistent improvements across the effectiveness and convenience domains. CMR-guided management was associated with more appropriate prescribing, including higher use of preventive therapies (85.5% vs 67.5%; p=0.001), and more targeted antianginal prescribing, including calcium channel blockers (43.5% vs 27.0%; p=0.008) and long-acting nitrates (56.5% vs 32.5%; p<0.001). CONCLUSIONS: In patients with ANOCA, non-invasive CMR-guided endotyping substantially improves treatment satisfaction and enables more appropriate, mechanism-targeted pharmacotherapy compared with angiography-guided care. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov ID NCT04805814.

19 Apr 2026

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Systematic ReviewEvidence: Weak
55CEBM

Journal of neurointerventional surgery

Intravascular lithotripsy in calcified carotid stenosis: technical and clinical outcomes

INTRODUCTION: Carotid artery stenosis (CAS) is a major cause of stroke, disability, and mortality worldwide. While medical therapy and revascularization remain the cornerstones of management, both surgical and endovascular approaches can be limited by complex anatomy and heavily calcified plaques, which increase procedural risk. Intravascular lithotripsy (IVL), originally developed for coronary and peripheral interventions, has recently emerged as a potential strategy for plaque modification in CAS. By delivering localized shockwave pulses, IVL fractures vascular calcium, facilitating safer angioplasty and stent deployment. However, its use in CAS remains off-label and poorly described. METHODS: A systematic search of PubMed, Google Scholar, and Embase was conducted in September 2025 in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included patients with CAS undergoing IVL with reported procedural success and/or clinical outcomes. Risk of bias was assessed using the Joanna Briggs Institute (JBI) appraisal tools. RESULTS: Fifteen studies comprising 120 patients were included. The mean age ranged from 50 to 82 years, and the degree of stenosis from 70%-95%. Technical success was reported in 100% of cases. Across the pooled cohort, 101 of 120 patients (84.2%) achieved residual stenosis ≤30%. Seven patients (5.8%) experienced ipsilateral stroke or transient ischemic attack within 30 days. CONCLUSION: IVL for CAS is an emerging therapy demonstrating consistent technical feasibility and favorable short-term safety across published studies. These findings suggest that IVL may benefit patients with complex calcified plaques at high risk for standard revascularization; however, randomized controlled trials are needed to confirm its role in clinical practice.

17 Apr 2026

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diagnosticEvidence: Moderate
70CEBM

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

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Randomised Controlled TrialEvidence: Moderate
60CEBM

Journal of the American College of Cardiology

Pulsed Field Ablation vs Standard Radiofrequency Ablation for Typical Atrial Flutter: ADVANTAGE AF Trial Substudy

BACKGROUND: ADVANTAGE AF examined the safety and efficacy of pulsed field ablation (PFA) to treat persistent atrial fibrillation (AF). During AF ablation, typical atrial flutter (AFL) is commonly treated with cavotricuspid isthmus (CTI) ablation. OBJECTIVES: Adjunctive CTI ablation in ADVANTAGE AF was performed with radiofrequency ablation (RFA; phase 1) or bipolar linear PFA (phase 2). Here, we compared lesion characteristics, CTI ablation efficacy, and safety between the ablation modalities. METHODS: A preclinical study assessed lesion dimensions with a novel 2.0 kV bipolar linear PFA catheter. In ADVANTAGE AF, after AF ablation with a pentaspline PFA catheter, CTI ablation was performed: in phase 1 with irrigated RFA, and in phase 2 with the linear PFA catheter (Farapoint). Before PFA CTI ablation ,patients were treated with a vasopressor bolus followed by high-dose intravenous nitroglycerin. RESULTS: Preclinical assessment showed lesion depth increasing at higher field strength and plateauing after 2 applications. In ADVANTAGE AF, 50 and 141 patients received CTI ablation with RFA and PFA, respectively. Patient characteristics across the 2 cohorts were similar (RFA vs PFA). Acute CTI conduction block was similar between techniques (50 of 50 RFA [100%] vs 139 of 141 PFA [98.6%]; P = 1.00). PFA was associated with a shorter CTI ablation time (median: RFA 5 min [Q1-Q3: 4-8 min] vs 14 min [Q1-Q3: 9-19 min]; P = 0.001). RFA and PFA had similar safety event rates (RFA 2.0% vs PFA 2.1%; P = 0.96). With the use of nitroglycerin pretreatment, there was no clinical manifestation of coronary artery spasm with PFA. CONCLUSIONS: This subanalysis of ADVANTAGE AF extends the primary results by allowing comparison of bipolar linear PFA and RF ablation for CTI, integrating preclinical lesion modeling with clinical dosing, and establishing a standardized reliable coronary safety protocol. Although not randomized comparisons, these findings suggest that CTI ablation with a linear PFA catheter is associated with safety and efficacy similar to RF ablation and greater efficiency. (A Prospective Single Arm Open Label Study of the FARAPULSE Pulsed Field Ablation System in Subjects With Persistent Atrial Fibrillation [ADVANTAGE AF; NCT05443594]).

16 Apr 2026

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Systematic ReviewEvidence: Weak
60CEBM

The American journal of cardiology

FFR-Guided Complete versus Culprit-Only Revascularization in Patients With Myocardial Infarction: A Systematic Review and Meta-Analysis

In patients with myocardial infarctions (MI) and multivessel coronary artery disease (CAD), the effect of fractional flow-reserve (FFR)-guided complete revascularization during index hospitalization versus culprit-only revascularization remains unclear. Our objective is to determine whether FFR-guided complete revascularization during index hospitalization reduces major adverse cardiac events (MACE) among patients with MI and multivessel CAD. We systematically searched MEDLINE, EMBASE, and the Cochrane Library for randomized controlled trials (RCTs) comparing FFR-guided complete versus culprit-only revascularization in patients with MI and multivessel CAD. The primary outcome was MACE, as defined by a composite endpoint of all-cause death, MI or unplanned revascularization, at a minimum 1-year follow-up. Count data were pooled across trials using random-effects models to estimate risk ratios (RRs) and 95% confidence intervals (CIs). A total of 3 RCTs (n = 3,054) were included. The majority (77.5%) of participants were male. The pooled RR of MACE for FFR-guide complete versus culprit-only revascularization was 0.63 (95% CI: 0.37-1.05; I2 = 90%). FFR-guided complete revascularization was associated with reduced unplanned revascularization events, with a pooled RR 0.43 (95% CI: 0.21-0.87; I2 = 88%). There was no significant difference in the risk of recurrent MI (RR: 0.9; 95% CI: 0.61-1.33; I2 =30%). The risk of major bleeding was low in both FFR-guided complete (23/1373) and culprit-only (29/1681) revascularization groups across the 3 trials. In conclusion, in patients with MI and multivessel CAD, FFR-guided complete revascularization during the index hospitalization reduces the risk of unplanned revascularizations and may reduce the risk of MACE compared to culprit-only revascularization.

16 Apr 2026

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diagnosticEvidence: Insufficient
45CEBM

Scientific reports

Region guided mask R-CNN with Haralick ResNet fusion for accurate coronary artery disease detection in computed tomography angiography images

Coronary Computed Tomography Angiography (CCTA) is a non-invasive imaging technique used to visualize the coronary arteries and diagnose coronary artery disease. It provides detailed 3D images which helps in identifying blockages, stenosis and plaques. However, CCTA images often suffer from noise, low contrast, and motion artifacts, which complicate accurate segmentation and analysis. The proposed work addresses the challenges in detecting and classifying coronary artery disease (CAD) from CCTA images. For accurate coronary artery segmentation, Region-Guided Mask R-CNN (RG-Mask R-CNN) combines region growing for initial region identification with Mask R-CNN for precise instance segmentation. This hybrid approach reduces the complexity of the structures in CCTA images and provides better segmentation accuracy. For feature extraction, Haralick-ResNet Fusion (HRF) captures the texture information using Haralick features and ResNet for high-level feature extraction to handle the difficulty of subtle variation differentiation in CCTA images. Finally, a Deep Convolutional Network (DeepConvNet) combines deep learning and convolutional layers to classify CAD efficiently based on the features extracted. This integrated framework offers an accurate solution (98.3%) for CAD detection from CCTA images by overcoming common issues such as noise and complex arterial structures, while improving diagnostic performance.

15 Apr 2026

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Randomised Controlled TrialEvidence: Moderate
80CEBM

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

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Randomised Controlled TrialEvidence: Strong
85CEBM

Lancet (London, England)

Aspirin versus clopidogrel for chronic maintenance monotherapy after percutaneous coronary intervention: 10-year follow-up of the HOST-EXAM trial

BACKGROUND: The long-term clinical outcomes of clopidogrel monotherapy versus aspirin monotherapy after percutaneous coronary intervention (PCI) remain uncertain. We conducted a 10-year follow-up of the HOST-EXAM trial to assess the very long-term effects of clopidogrel versus aspirin monotherapy in this setting. METHODS: In HOST-EXAM, patients who had completed dual antiplatelet therapy without clinical events for 6-18 months after PCI were randomly assigned to receive clopidogrel 75 mg once daily or aspirin 100 mg once daily. This study is an investigator-initiated 10-year extended follow-up of the HOST-EXAM trial. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium type ≥3 bleeding. The primary analysis was done in the intention-to-treat population. The study is registered with ClinicalTrials.gov (NCT02044250) and is complete. FINDINGS: From March 26, 2014, to May 29, 2018, 5530 patients were enrolled and 5438 were randomly assigned to the aspirin group (n=2728) or the clopidogrel group (n=2710). Clinical follow-up status was ascertained on May 1, 2025, resulting in a median follow-up duration of 10·5 years (IQR 9·4-11·4) after PCI and a completion rate of 92·8%. Clopidogrel was associated with a lower rate of the primary composite endpoint than aspirin (Kaplan-Meier estimate 25·4% for the clopidogrel group vs 28·5% for the aspirin group; hazard ratio 0·86 [95% CI 0·77-0·96]; log-rank p=0·0050). Clopidogrel was also associated with a lower rate of the thrombotic endpoint (17·3% vs 20·0%; log-rank p=0·0024) and bleeding endpoint (9·1% vs 10·8%; log-rank p=0·020). All-cause mortality was similar between groups. INTERPRETATION: During 10 years of follow-up, clopidogrel monotherapy, compared with aspirin monotherapy, was associated with lower rates of the primary composite, ischaemic, and bleeding outcomes, but not all-cause mortality after PCI. These findings support consideration of clopidogrel as an alternative to aspirin for long-term antiplatelet monotherapy during the chronic maintenance phase after PCI. FUNDING: Ministry of Health & Welfare, South Korea.

14 Apr 2026

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otherEvidence: Weak
55CEBM

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

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Randomised Controlled TrialEvidence: Strong
80CEBM

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

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Systematic ReviewEvidence: Strong
85CEBM

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

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Randomised Controlled TrialEvidence: Strong
75CEBM

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

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observationalEvidence: Moderate
85CEBM

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

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Randomised Controlled TrialEvidence: Strong
70CEBM

The New England journal of medicine

Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation

BACKGROUND: Catheter-based closure of the left atrial appendage is an alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation. The effectiveness of this strategy, as compared with physician-directed best medical care, in patients at high risk for stroke and bleeding is unknown. METHODS: In this multicenter randomized trial conducted in Germany, we assigned patients with atrial fibrillation and a high risk of stroke and bleeding to undergo left atrial appendage closure or to receive physician-directed best medical care (including direct oral anticoagulants, if eligible). The primary end point, tested for noninferiority, was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding, or cardiovascular or unexplained death, assessed in a time-to-event analysis. The noninferiority margin was a hazard ratio of 1.3. RESULTS: A total of 912 adult patients underwent randomization. The primary end-point analysis included 446 patients who were assigned to undergo left atrial appendage closure (device group) and 442 who were assigned to physician-directed best medical care (medical-therapy group). The mean (±SD) age was 77.9±7.1 years; 38.6% of the patients were women, the mean CHA2DS2-VASc score was 5.2±1.5 (range, 0 to 9, with higher scores indicating a greater risk of stroke), and the mean HAS-BLED score was 3.0±0.9 (range, 0 to 9, with higher scores indicating higher risk of bleeding). After a median follow-up of 3 years (interquartile range, 1.7 to 4.7), a first primary end-point event had occurred in 155 patients (incidence per 100 patient-years, 16.8) in the device group and in 127 patients (incidence per 100 patient-years, 13.3) in the medical-therapy group (difference in restricted mean survival time, -0.36 years; 95% confidence interval, -0.70 to -0.01; P = 0.44 for noninferiority). Serious adverse events occurred in 368 patients (82.5%) in the device group and 342 (77.4%) in the medical-therapy group. CONCLUSIONS: Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to physician-directed best medical care with regard to a composite end point of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death. (Funded by the German Center for Cardiovascular Research; CLOSURE-AF ClinicalTrials.gov number, NCT03463317.).

4 Apr 2026

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otherEvidence: Weak
40CEBM

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

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otherEvidence: Moderate
80CEBM

J Am Coll Cardiol

Contemporary Diagnosis and Treatment of Aortic Regurgitation: A State-of-the-Art Review

Aortic regurgitation (AR) is progressive and frequently under-recognized; without timely intervention it drives adverse left-ventricular remodeling and heart failure. Despite Class I guideline indications, many patients-especially older, frail individuals with multimorbidity-remain untreated. Advancements in high-fidelity multimodality imaging-including cardiac magnetic resonance, 4-dimensional flow, and speckle-tracking echocardiography-have enabled earlier detection of remodeling and more accurate quantification of regurgitant burden. These techniques are redefining thresholds for treatment and may enable biomarker-imaging composite staging of disease. Surgery remains the gold standard of therapy for native AR. Contemporary surgical management is tailored to age, anatomy, and root pathology. Although surgical aortic valve replacement remains the predominant therapy for most candidates, valve-sparing root procedures, the Ross operation, and aortic valve neocuspidization are increasingly offered at experienced centers for carefully selected lower-risk patients. Transcatheter aortic valve replacement is expanding rapidly as a viable option that helps bridge the treatment gap for those at prohibitive or high risk for surgery. Yet, devices optimized for calcific aortic stenosis encounter technical obstacles in native AR-including large, noncalcified annuli, elliptical root geometry, and high stroke volumes-leading to suboptimal anchoring, residual paravalvular regurgitation, and device embolization. Purpose-built AR systems with leaflet-engaging anchoring and enhanced sealing have shown encouraging outcomes in feasibility and pivotal studies and have obtained commercial approval in Europe, and U.S. authorization is anticipated. This state-of-the-art review synthesizes current insights into AR pathophysiology, diagnostic advances, and therapeutic innovations in surgical and transcatheter techniques, highlighting knowledge gaps and proposing research priorities to accelerate access to care for this historically undertreated population.

1 Feb 2026

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otherEvidence: Weak
50CEBM

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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