Recent evidence questioned the overall safety and efficacy of colchicine in patients with coronary artery disease (CAD), as novel evidence focusing on acute coronary syndromes (ACSs) gave neutral results, while trials focusing on chronic coronary syndrome supported colchicine administration to improve long-term outcomes. However, no study has ever explored whether there is a true therapeutic difference across the populations or these discrepancies are due to additional confounders. Against this background, we performed a systematic review and meta-analysis of randomized trials of colchicine in patients with CAD. The primary endpoints were trial-defined major adverse cardiovascular events (MACE) and serious adverse events (SAEs). Secondary endpoints included all-cause death, measures of ischemia (cardiovascular death, myocardial infarction [MI], any revascularization, stroke) and measures of safety (serious infections or sepsis and gastrointestinal adverse events). All analyses included an interaction term for the clinical presentation. Sensitivity analyses were performed to explore sources of heterogeneity. After literature search, 20 trials encompassing a total of 21,486 patients (65.4% ACS) were included. Colchicine significantly reduced MACE (incidence rate ratio [IRR]: 0.70; 95% CI 0.55-0.87) without increasing risk for SAEs. Colchicine also reduced MI (IRR 0.81; 95% CI 0.70-0.94) and any revascularization (IRR 0.71; 95% CI 0.51-0.99), while increasing the risk of gastrointestinal adverse events (IRR 1.68; 95% CI 1.23-2.28). No statistically significant interaction was noted for clinical presentation for any endpoint, but a significant interaction for the drug dosage administered and the relationship with the COVID-19 pandemic was noted. In conclusion, the use of colchicine in patients with CAD reduces MACE without significantly increasing SAEs compared to control, although increasing gastrointestinal adverse events, without interaction by clinical presentation.

AIMS:Patients at high bleeding risk (HBR) and acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) are at high risk of adverse outcomes. We investigated the clinical outcomes and their consistency after biodegradable polymer sirolimus-eluting (BP-SES) or durable polymer zotarolimus-eluting stent (DP-ZES) implantation in HBR patients with or without ACS. METHODS AND RESULTS:The per-protocol population of the BIOFLOW-DAPT randomized control trial (RCT) consisted of HBR patients with (n = 541) or without ACS (n = 1245) who were randomized to BP-SES or DP-ZES and underwent 1 month dual antiplatelet therapy (DAPT). The primary efficacy and safety endpoints were target lesion failure (TLF), defined as the composite endpoint of cardiac death, target vessel myocardial infarction (TV-MI), or clinically driven target lesion revascularization (cd-TLR) as well as major bleeding defined as BARC 3 or 5 (according to Bleeding Academic Research Consortium classification) and definite/probable stent thrombosis (ST). At 1 year, patients with ACS suffered from higher cardiac death rates (3.4 vs. 1.3%, log-rank P = 0.004) but similar TLF (6.8 vs. 6.7%, P = 0.992), TV-MI (2.8 vs. 4.5%, P = 0.100), cd-TLR (1.4 vs. 2.1%, P = 0.300), major bleeding (4.2 vs. 3.1%, P = 0.266), and ST (0.2 vs. 0.9%, P = 0.098) compared with no ACS patients. The rate of TLF and of all secondary endpoints was consistent with BP-SES or DP-ZES across ACS strata. CONCLUSION:HBR patients with ACS are at higher risk of cardiac death than those without ACS and experience a consistent outcome with BP-SES or DP-ZES followed by 1 month DAPT at 1 year follow-up. CLINICAL TRIAL REGISTRATION:NCT04137510.

In patients with acute or chronic coronary syndromes undergoing percutaneous coronary intervention, dual antiplatelet therapy - with aspirin and a P2Y12 inhibitor - is the cornerstone of pharmacological treatment to prevent stent thrombosis and atherothrombotic complications. However, the timing of P2Y12 inhibitor initiation has been a matter of considerable debate. Administering a P2Y12 inhibitor added to aspirin before percutaneous coronary intervention without knowing coronary anatomy has the potential to ensure antithrombotic protection at percutaneous coronary intervention and to reduce procedural thrombotic complications, but also exposes patients to an increased bleeding risk, may prevent or retard surgical myocardial revascularization when needed, and may be futile or even dangerous in patients not requiring percutaneous coronary intervention. The latest 2023 European Society of Cardiology guidelines have downgraded previous recommendations to pretreatment also in ST-elevation myocardial infarction. The present Systematic Review and Consensus Document aims at reviewing clinical evidence on pretreatment across various clinical scenarios, proposing a nuanced approach that considers clinical presentation, time to treatment, the clinical setting and the probability of non-thrombotic primary causes.

BACKGROUND:Neurologic events (NEs) remain a feared complication after transcatheter aortic valve implantation (TAVI). The relationship between NE timing and prognosis remains uncertain. In this study we aimed to assess the impact of NE on mortality according to NE timing. METHODS:Patients undergoing TAVI at 18 European centers between 2007 and 2022, included in the Transfusion Requirements in Transcatheter Aortic Valve Implantation (NCT03740425) registry, were stratified according to the timing of NEs. NEs were defined as periprocedural (≤ 30 days) or non-periprocedural (> 30 days) according to the Valvular Academic Research Consortium-3 criteria. The primary endpoint was 2-year all-cause mortality as assessed using restricted mean survival time. RESULTS:Among 10,079 patients undergoing TAVI, 263 (2.6%) experienced an NE over a median follow-up of 20.6 (interquartile range 9.8-38.3) months after TAVI. A total of 171 NEs (65.0%) were periprocedural and 92 (35.0%) non-periprocedural. Fatal stroke accounted for 6.4% of periprocedural NEs and 40.2% of non-periprocedural NEs. Median time from NE to death was 20.4 (9.4-38.1) months. Both types of NEs were associated with significantly reduced 2-year survival time: -164.7 days for periprocedural NEs and -360.5 for non-periprocedural NEs (P for trend = 0.029). The adverse prognostic impact of NE increased progressively over time. CONCLUSIONS:In this large multicenter registry, all types of NEs after TAVI were associated with reduced midterm survival. NEs that occurred later had the greatest detrimental effect on life expectancy, showing a significant temporal gradient across NE categories. Further studies are warranted to evaluate preventive strategies and long-term monitoring approaches.

Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and a P2Y12 receptor inhibitor (P2Y12i) for 12 months represents the standard of care after acute coronary syndrome (ACS). However, balancing ischaemic protection against bleeding risk remains challenging, providing the rationale for the development of de-escalation strategies. European and U.S. guidelines allow shortening the duration of DAPT in patients at high bleeding risk, whilst still maintaining 12 months as the reference recommendation. Interest in abbreviated DAPT regimens has been driven by improvements in percutaneous coronary intervention devices and techniques, as well as by a better understanding of the temporal evolution of ischaemic and bleeding risks. Several trials have shown that short-duration DAPT followed by monotherapy-particularly with a P2Y12i-is not inferior in terms of ischaemic outcomes and significantly reduces bleeding events. In this context, the NEO-MINDSET trial failed to demonstrate the non-inferiority of immediate P2Y12i monotherapy compared with standard DAPT. In contrast, the TARGET-FIRST study confirmed the safety of ASA discontinuation after 30 days in selected patients, with a clear bleeding benefit. Overall, the available evidence indicates that immediate discontinuation of ASA in patients with acute coronary syndrome is not universally safe, whereas strategies based on at least 1 month of DAPT followed by monotherapy with a potent P2Y12i currently represent the most balanced approach for selected patients. More refined personalization of antiplatelet therapy, guided by an integrated assessment of ischaemic and bleeding risks, represents the future perspective in this field.

Cigarette smoking is an established cardiovascular risk factor, but the association between electronic cigarette (e-cigarette) use and hypertension remains unclear. We examined this association in a nationally representative adult population in Scotland using pooled cross-sectional data from 22,187 adults aged ≥16 years in the Scottish Health Survey (2017-2022). Participants were classified into five mutually exclusive groups: never users (n = 11,760), former smokers (n = 6,201), current cigarette smoking only (n = 2,747), current e-cigarette use only (n = 907), and current dual use (n = 572). Hypertension was defined as self-reported doctor-diagnosed high blood pressure, excluding pregnancy-related hypertension. Multivariable logistic regression estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Secondary analyses disaggregated current e-cigarette use only by smoking history, and propensity score matching was performed as a sensitivity analysis. Overall hypertension prevalence was 26.5%, ranging from 19.0% among current exclusive e-cigarette users to 33.5% among former smokers. Compared with never users, current e-cigarette use only was associated with lower odds of hypertension (OR 0.77, 95% CI 0.63-0.93), whereas former smokers had higher odds (OR 1.10, 95% CI 1.02-1.20). No significant associations were observed for current cigarette smoking only (OR 0.94, 95% CI 0.84-1.06) or current dual use (OR 0.95, 95% CI 0.75-1.20). The inverse association for exclusive e-cigarette use was confined to former smokers who had switched to vaping (OR 0.77, 95% CI 0.63-0.94). In propensity score-matched analyses, the inverse association for current exclusive e-cigarette use was attenuated and no longer statistically significant, suggesting that this finding may partly reflect healthy switcher bias and residual confounding rather than a protective effect.

BACKGROUND:Dual pathway inhibition (DPI) with low-dose rivaroxaban and aspirin offers superior ischemic protection compared with single-agent therapy in patients with peripheral artery disease (PAD). However, its real-world adoption remains limited. We aimed to determine the proportion of revascularized PAD patients eligible for DPI, and to explore reasons for ineligibility and associated clinical outcomes. METHODS:Consecutive patients undergoing lower limb revascularization for PAD between May 2021 and May 2023 were prospectively enrolled in the RAPID (RivAroxaban for PerIpheral artery Disease) registry and followed up for a median time of 283 (interquartile range 142-445) days. VOYAGER PAD eligibility criteria were applied. The primary outcome was eligibility for DPI. Exploratory clinical outcomes included major adverse limb events (MALE) - defined as the composite of cardiovascular death, acute limb ischemia, or repeat limb revascularization - and major bleeding. RESULTS:A total of 196 patients were enrolled during the study period. Among them, 98 (50.0%) met DPI eligibility criteria; however, DPI was administered only to 4.1% of eligible patients. The most frequent exclusion factors were high bleeding risk (99.0%), low hemoglobin (48.8%), and age at least 75 years (36.7%). MALE occurred in 35 patients (28%), driven by recurrent revascularization (20%), while major bleeding occurred in nine patients (5%). DPI eligibility was associated with a lower risk of MALE (hazard ratio 0.42; 95% confidence interval 0.20-0.85), but this association faded out after statistical adjustment. Major bleeding did not differ between eligible and noneligible patients. CONCLUSION:In a contemporary population of PAD patients undergoing revascularization, only half met the VOYAGER PAD eligibility criteria. Bleeding-related exclusions prevailed, highlighting the need for systematic anemia correction and bleeding avoidance strategies to broaden eligibility for DPI and improve clinical outcomes.

Importance In patients with atrial fibrillation (AF), oral anticoagulation (OAC) is the gold standard for preventing ischemic stroke, at the expense of a higher risk of bleeding. Catheter-based left atrial appendage closure (LAAC) has been proposed as an alternative strategy to prevent stroke, but the efficacy and safety compared to OAC are uncertain. Objective To evaluate the efficacy and safety of catheter-based LAAC compared to OAC in patients with AF at high risk of stroke. Data Sources PubMed, Cochrane Central, and Web of Science were screened up to March 2026. The websites of leading cardiology societies, news outlets, and reference lists of each eligible study were also inspected. Study Selection Studies enrolling patients with AF randomly assigned to catheter-based LAAC or OAC and reporting at least 1 outcome of interest were included. Data Extraction and Synthesis Two investigators independently extracted data of interest and assessed data quality. Catheter-based LAAC vs OAC comparisons were pooled as incidence rate ratios (IRRs) using a frequentist random-effect model. Main Outcomes and Measures Primary and coprimary outcomes were long-term stroke and major bleeding. Secondary outcomes included the composite of cardiovascular death, stroke, or systemic embolism, all-cause death, the single components of the composite end point, ischemic stroke, hemorrhagic stroke, and nonprocedural major bleeding. Periprocedural events (ie, stroke, major bleeding, death, device embolization, and pericardial effusion) were also combined. Results Eight trials (7434 patients) were included in the meta-analysis. After a weighted mean follow-up of 37.9 months, no significant differences were detected for stroke (IRR, 1.08; 95% CI, 0.82-1.41) and major bleeding (IRR, 0.96; 95% CI, 0.81-1.14). However, catheter-based LAAC was associated with a higher risk of ischemic stroke (IRR, 1.34; 95% CI, 1.01-1.77) and a lower risk of nonprocedural major bleeding (IRR, 0.73; 95% CI, 0.58-0.92) compared with OAC. Periprocedural events per 1000 patients were 5 strokes, 9 episodes of bleeding, 1 death, 5 episodes of device embolization, and 9 pericardial effusions. Conclusions and Relevance In patients with AF, at long-term follow-up, transcatheter LAAC was associated with similar rates of any type of stroke and major bleeding compared with OAC, while increasing the risk of ischemic stroke and lowering the risk of nonprocedure-related major bleeding. These findings do not support the routine use of LAAC as a first-line strategy for stroke prevention in patients with AF at moderate to high risk of stroke.

Myocardial bridging is a dynamic coronary anomaly in which systolic compression may extend into early diastole, particularly under conditions of increased heart rate and contractility. In patients with cardiogenic shock, this creates a potential physiological conflict, as catecholaminergic support may worsen coronary flow impairment rather than improve haemodynamics. A 66-year-old man presented with inferolateral ST-segment elevation myocardial infarction due to thrombotic occlusion of the proximal left circumflex artery, successfully treated with primary percutaneous coronary intervention. Coronary angiography also showed a long myocardial bridge involving the mid left anterior descending artery. After revascularization, the patient devoped cardiogenic shock requiring norepinephrine and dobutamine, but remained haemodinamically unstable, with persistent tachycardia, low cardiac index, reduced stroke volume index, and progressive respiratory failure. Given the presence of myocardial bridging, a tachicardia-mediated limitation of dyastolic coronary perfusion was hypothesized. Low-dose landiolol, an ultra-short-acting and highly β1-selective blocker, was introduced under continuous haemodynamic monitoring. Heart rate decreased from 127 to 83 bpm and was accompained by a marked improvement in stroke volume index, cardiac index, and lactate levels, while vasopressor requirements remained stable. This case illustrates an "inotrope paradox" in which adrenergic stimulation may aggravate haemodynamic compromise in the presence of myocardial bridging by increasing heart rate and contractility, thereby intensifying systolic compression and shortening diastolic perfusion time. In this setting, physiology-guided heart rate reduction may restore coronary flow dynamics and improve systemic output. In selected patients with cardiogenic shock and myocardial bridging, ultra-short-acting β1-blockade may represent a targeted strategy to reverse tachycardia-mediated haemodynamic deterioration and support a diastole-centered approach to resuscitation.

BACKGROUND:Whether strut thickness influences clinical outcomes after percutaneous coronary intervention (PCI) for bifurcation lesions remains debated. AIMS:To compare the safety and efficacy of ultrathin (< 70 µm) drug-eluting stents (DES) with thicker DES in coronary bifurcations. METHODS:We pooled patient-level data from the ULTRA and BIFURCAT registries. Stents were classified as thick (≥ 100 µm), thin (70-100 µm), or ultrathin (< 70 µm). The primary endpoint was target-lesion revascularization (TLR). Inverse probability of treatment weighting (IPTW) balanced baseline characteristics overall and within procedural subgroups (provisional vs. planned two-stent strategy). RESULTS:Among 6753 patients (median follow-up 800 days, IQR 400-900), 514 (8%) received thick, 5139 (76%) thin, and 1100 (16%) ultrathin stents. Crude TLR rates were 3.3%, 2.8%, and 1.1%, respectively (p = 0.001). After IPTW adjustment, ultrathin DES significantly reduced TLR compared with thick DES (HR 0.38, 95% CI = 0.16-0.89, p = 0.03) and with thin DES (HR 0.41, 95% CI 0.21-0.81, p = 0.01). In provisional-stenting cases, TLR risk did not differ across groups (HR: 0.53 vs. thick, p = 0.27; HR: 0.49 vs. thin, p = 0.07). Conversely, in planned two-stent procedures ultrathin DES resulted associated with TLR reduction versus thick DES (HR: 0.21, 95% CI 0.04-0.93, p = 0.04), with a nonsignificant trend for thin DES (HR: 0.31, p = 0.07). CONCLUSIONS:In contemporary bifurcation PCI, ultrathin DES are associated with a clinically and statistically significant reduction in repeat revascularization compared with thicker-strut platforms, a benefit driven predominantly by lesions treated with an upfront two-stent approach.

Antiplatelet therapy is the cornerstone of treatment in patients with established atherosclerotic disease. The use of a single antiplatelet agent is commonly recommended for the long-term management of these patients. Although aspirin has represented the mainstay of antiplatelet therapy for decades, emerging evidence suggests that P2Y₁₂ inhibitors may be more than just a viable alternative to aspirin and may be preferred over aspirin. This review examines the current evidence comparing the efficacy and safety of aspirin vs P2Y12 inhibitors in reducing cardiovascular events in patients with atherosclerotic disease. Special attention is given to the practical challenges and considerations surrounding the use of aspirin vs P2Y12 inhibitor monotherapy, including interindividual variability in drug response, side effects, costs, and real-world implementation. By evaluating the strengths and limitations of these treatment options, this article aims to guide clinicians in optimizing the selection of single antiplatelet strategies for long-term secondary prevention in patients with atherosclerotic disease.

BACKGROUND:Management of valvular heart disease (VHD) has shifted from predominantly surgical approaches to widespread use of transcatheter interventions, including transcatheter aortic valve replacement (TAVR), mitral transcatheter edge-to-edge repair (M-TEER), transcatheter mitral valve replacement (TMVR), and emerging tricuspid transcatheter valve intervention (TTVI). Although ESC/EACTS and ACC/AHA guidelines recognize frailty as a major determinant of mortality, complications, and recovery, they offer limited guidance on how to modify frailty before intervention. CONTENT:Frailty is highly prevalent in VHD, particularly among transcatheter candidates, and represents a dynamic, potentially reversible syndrome driven by sarcopenia, deconditioning, malnutrition, inflammation, and psychological vulnerability. It influences symptoms, procedural selection, and recovery, exerting prognostic effects beyond valve anatomy. Prehabilitation offers a strategy to convert the preprocedural interval from passive waiting into a therapeutic opportunity. Evidence from cardiac surgery and hemodynamic interventions shows that multimodal prehabilitation (including aerobic and resistance exercise, respiratory training, nutritional optimization and psychological support) can improve functional capacity, reduce pulmonary complications, and shorten hospitalization. In TAVR candidates, early data suggest that even short programs may enhance functional performance, mitigate frailty and reduce major adverse cardiovascular events. In contrast, dedicated trials for M-TEER, TMVR and TTVI remain limited, and current practice depends on evidence from other procedural settings. Ongoing studies are testing exercise-based, nutritional, and psychological interventions, including telemedicine-supported and home-based models, while incorporating objective measures of frailty reversal. SUMMARY:As procedural risk declines, patients' physiological reserve becomes the principal barrier to long-term benefit. Prehabilitation may provide a scalable strategy to bridge anatomical correction with meaningful functional recovery.

Cardiac wall perforation is a recognized complication of pacemaker lead fixation. It is typically associated with deterioration of electrical parameters; however, this case demonstrates that perforation may occur despite normal parameters and apparently normal device function. In patients with recent cardiac electronic device implantation, persistent or pleuritic chest pain should raise suspicion of myocardial perforation. Transthoracic echocardiography may be diagnostic, and cardiac computed tomography provides definitive confirmation when uncertainty remains.

Aims:Inflammation and hyperlipidaemia play a pivotal role in atherosclerotic cardiovascular disease (ASCVD), and inflammatory risk may outweigh cholesterol risk among statin-treated patients. However, it is unclear how these risks relate to ASCVD outcomes in a real-world population. Methods and results:Observational study of 39 638 ASCVD adults in Stockholm's healthcare (2007-21) who underwent routine testing for high-sensitivity C-reactive protein (hsCRP) and low-density lipoprotein cholesterol (LDL-C). Groups were defined by LDL-C (≥1.8 vs. < 1.8 mmol/L) and hsCRP (≥2 vs. < 2 mg/L): as low risk, high cholesterol risk (CR) alone, high inflammatory risk (IR) alone, and combined high cholesterol and inflammatory risk (CIR). Primary outcome was major adverse cardiovascular (CV) events (MACE); secondary outcomes included all-cause death, CV death, and heart failure (HF) hospitalization. Mean age at baseline was 69 years, 61% were men, 19.4% had chronic kidney disease (CKD), and 61% were receiving lipid-lowering therapy (LLT). Over follow-up (median 4.5 years), 5349 MACE, 7955 deaths (2088 CV deaths) and 4286 HF hospitalizations occurred. Compared with patients with low risk, those with IR or CIR experienced the highest MACE risk (HR 1.39; 95% CI 1.26-1.54 for CIR, HR 1.18; 1.05-1.33 for IR), followed by CR (HR 1.12; 1.01-1.24). Elevated hsCRP, with or without elevated LDL-C, was strongly associated with secondary outcomes, while CR alone was not. Patterns were generally consistent across CKD and LLT subgroups. Conclusion:In routine care high inflammatory risk, alone or with high cholesterol risk, is a stronger predictor of adverse outcomes than high cholesterol alone.

The evolution of percutaneous coronary intervention has improved the outcomes of patients with coronary artery disease, but conventional drug‐eluting stents remain limited by late adverse events, reduced vessel compliance, and the inability to restore physiological function. The DynamX coronary bioadaptor aims to address these issues by combining the mechanical performance of drug‐eluting stents with a bioadaptive mechanism that restores natural vessel motion. The device features a cobalt–chromium scaffold connected by bioresorbable polymer elements that degrade 6 months after implantation. This process unlocks helical strands, enabling vessel pulsatility, compliance, and adaptive remodeling while maintaining lumen integrity. Preclinical studies demonstrated reduced vessel stress and restored physiological rotational motion. In the DYNAMIX (12‐Month Clinical and Imaging Outcomes of the Uncaging Coronary DynamX Bioadaptor System) study, patients exhibited increased vessel area without lumen loss, optimal strut apposition, and complete neointimal coverage at 12 months. The small BIOADAPTOR‐RCT (Randomized Controlled Trial of Sirolimus‐Eluting Bioadaptor Versus Zotarolimus‐Eluting Drug‐Eluting Stent) showed noninferiority to drug‐eluting stents with superior late lumen preservation and reduced neointimal hyperplasia. The larger INFINITY‐SWEDEHEART (Percutaneous Coronary Intervention With a Bioadaptor Compared to a Contemporary Drug‐Eluting Stent) trial confirmed low target‐lesion failure rates and a plateauing of adverse events after 6 months, highlighting the benefits of vessel motion restoration. The DynamX coronary bioadaptor may represent a significant advancement in percutaneous coronary intervention by providing early mechanical support and restoring vessel function. Further studies on complex anatomy and long‐term outcomes are needed to further define its role in interventional cardiology.

Abstract:Prasugrel and ticagrelor are potent oral P2Y12 inhibitors that carry a Class I recommendation for patients with acute coronary syndromes undergoing percutaneous coronary intervention, providing faster and more consistent platelet inhibition than clopidogrel. Despite identical guideline positioning, the optimal choice between the two agents has long remained unsettled, largely because head-to-head randomized data were scarce and the agents were assumed to be clinically interchangeable. That assumption is now substantially challenged by two large randomized trials (ISAR-REACT 5 and TUXEDO-2) whose convergent findings consistently point in the same direction. Here, we argue that the accumulated pharmacological and clinical evidence builds a coherent, mechanistically grounded case for the preferential use of prasugrel in appropriately selected patients, and that persisting therapeutic inertia against this drug is no longer scientifically defensible.