Salvatore Giordano

Background: Coronary microcatheters are essential in chronic total occlusion (CTO) percutaneous coronary intervention (PCI), but their structural failure has mainly been described through passive surveillance. Aims: We aimed to determine the incidence, predictors, and procedural impact of microcatheter structural damage during contemporary CTO PCI. Methods: The prospective multicentre CROSS registry included 2137 CTO PCI procedures performed at high‐volume centers between 2024 and 2025. Suspected damaged microcatheters underwent centralized assessment and were classified as grade 1 (superficial deformation), grade 2 (significant deformation without complete fracture), or grade 3 (complete fracture). Results: Structural damage occurred in 109 procedures (5.1%); 58.7%, 5.5%, and 35.8% were grade 1, 2, and 3, respectively. Independent predictors of structural microcatheter damage were moderate‐to‐severe calcification (adjusted OR, 1.93; 95% CI, 1.27–2.94), retrograde approach (adjusted OR, 1.71; 95% CI, 1.10–2.67), moderate‐to‐severe tortuosity (adjusted OR, 1.61; 95% CI, 1.04–2.50), and longer procedure duration (adjusted OR per 30‐min increase, 1.17; 95% CI, 1.06–1.30). Structural damage was associated with increased periprocedural complications (25.7% vs. 7.7%; OR: 4.12, 95% CI: 2.60–6.52; p < 0.0001) and failed CTO PCI (11.0% vs. 3.1%; OR: 3.86, 95% CI: 2.01–7.39; p < 0.0001). Conclusions: Structural microcatheter damage occurred in approximately 1 in 20 CTO PCIs and was associated with anatomical complexity, demanding procedural circumstances, and substantially worse procedural outcomes.

Micropeptides are small proteins that generally comprise fewer than 100 amino acids and are translated from short or noncanonical open reading frames. They were long overlooked, but their role is being actively explored as biologically active regulators with potential pharmacological relevance. Advances in ribosome profiling, proteogenomics, peptidomics, and computational modelling have enabled the identification and characterization of a substantially larger repertoire of micropeptides. Yet, it is important to focus on rigorous validation of endogenous translation, molecular targets, concentration-dependent activity, and peptide-specific effects. In particular, cardiovascular micropeptides can regulate myocardial calcium handling and contractility, exemplified by DWORF, which activates sarcoplasmic reticulum Ca ²⁺ -ATPase 2a and has shown therapeutic potential in multiple preclinical models of cardiomyopathy and heart failure. Other candidates, including mitoregulin, mitolamban, BRAWNIN, IAMP, SPAAR, and MFRLP, have been linked to distinct aspects of mitochondrial bioenergetics, inflammatory signalling, ischemia-reperfusion injury, angiogenesis, vascular smooth-muscle phenotypic switching, and arterial remodeling. Collectively, these findings suggest that micropeptides may provide novel therapeutic targets or pharmacological tools across several cardiovascular conditions, including heart failure, ischemia–reperfusion injury, and vascular remodeling. However, clinical translation will require advances in tissue-specific delivery, control of expression and stoichiometry, pharmacokinetic characterization, safety assessment, biomarker development, and demonstration of reproducible effectiveness in human-relevant and large-animal models before evaluation in clinical trials.

Background: Artificial intelligence (AI) is increasingly being integrated into cardiovascular medicine, with potential applications across image analysis, procedural planning, risk stratification, decision support, and workflow optimization. However, its adoption in interventional cardiology remains heterogeneous and may be influenced by several factors. We aimed to conduct a nationwide survey to assess attitudes towards AI among Italian interventional cardiologists. Methods: We conducted a nationwide, cross-sectional, web-based survey of Italian interventional cardiologists. A structured questionnaire collected information on professional characteristics, familiarity with and current use of AI, perceived clinical applications, expected benefits, trust, implementation barriers, and training needs. Conditional branching was used to obtain additional details from respondents who reported current use of AI-based tools, while all responses were collected voluntarily and analyzed in anonymized, aggregate form. Categorical variables and Likert-scale responses were summarized using descriptive statistics, with exploratory comparisons performed across prespecified professional and institutional subgroups. Results: Among 129 respondents, 70.5% reported at least moderate familiarity with AI and 77.5% reported some current use, although only 60.5% reported regular or occasional professional use, and applications were concentrated mainly in research, education, and information synthesis rather than direct procedural support. Nearly half (48.1%) expected AI to become standard in many procedures within 5 years, while 69.0% anticipated either routine use or particular value in complex cases. Attitudes were broadly favorable, with 85.3% agreeing that AI could improve diagnostic and procedural precision, 86.8% expressing strong interest in future use, and 76.7% stating that AI should support rather than replace physician judgment. The leading barriers were medico-legal uncertainty (45.0%), poor integration with existing clinical systems (34.9%), and cultural resistance or operator distrust (29.5%), whereas preservation of physician control was the most frequently cited requirement for adoption (58.9%). Greater AI familiarity was independently associated with current AI use (p < 0.001) and good or high trust (p < 0.001). Compared with no prior training, one and multiple AI training experiences were independently associated with good or high familiarity (both p < 0.05). Conclusions: Italian interventional cardiologists showed substantial exposure to AI, strong interest in future adoption, and generally favorable expectations regarding its contribution to diagnostic precision, workflow, and procedural support. Acceptance remained conditional on physician oversight, stronger clinical validation, reliable interoperability, and clear medico-legal governance, and previous AI-focused education appeared independently associated with greater familiarity.

Background: Bailout cardiac surgery during transcatheter aortic valve replacement (TAVR) is uncommon but remains associated with substantial morbidity and mortality. Although registries have described its incidence and major causes, they often provide limited detail regarding device-related failure mechanisms, attempted transcatheter rescue, and the clinical pathway leading to surgical conversion. We aimed at analyzing post-marketing safety reports from the U.S. Food and Drug Administration (FDA) Manufacturer and User Facility Device Experience (MAUDE) database to characterize the mechanisms, management strategies, and reported outcomes of bailout surgery during or shortly after TAVR. Methods: We retrospectively analyzed FDA MAUDE reports received from July 1, 2016, through June 30, 2026. Eligible reports described unplanned urgent or emergent open cardiac surgery during or immediately after TAVR. Candidate reports were screened, adjudicated, and deduplicated at the clinical-event level. Events were classified by precipitating complication, transcatheter rescue, operative pathway, and reported outcome. Associations were evaluated using permutation tests, Fisher exact tests with Benjamini–Hochberg correction, adjusted regression models, and sensitivity analyses. Results: After screening 43,239 initial reports, we identified 376 bailout-surgery events, with survival status was documented in 254, including 104 deaths and 150 survivors, corresponding to 40.9% reported mortality. Valve embolization, migration, or malposition was the most frequent complication phenotype (32.4%), whereas ventricular perforation or laceration was associated with the highest mortality (74.1%; OR, 4.86; 95% CI, 1.97–11.99). Mortality differed across complication phenotypes ( p p p =0.355). Valve explantation with SAVR was associated with lower reported mortality (18.9%; OR, 0.29; 95% CI, 0.12–0.69), whereas unspecified surgery or access/support alone was associated with higher mortality (56.9%; OR, 3.04; 95% CI, 1.80–5.12). Ancillary analyses identified potential platform-specific differences in complication and management patterns, while bailout timing was not independently associated with mortality after adjustment. Conclusions: In this MAUDE analysis, bailout cardiac surgery after TAVR was most commonly precipitated by valve embolization, migration, or malposition, whereas ventricular perforation or laceration was associated with the highest reported mortality. Outcomes differed across complication and operative pathways but not across transcatheter rescue strategies or bailout timing after adjustment. These findings identify clinically relevant post-marketing safety signals but should not be interpreted as incidence estimates, comparative device risks, or causal treatment effects.

Prolonged dual antiplatelet therapy (DAPT) with ticagrelor 60 mg is recommended in post-myocardial infarction (MI) patients at moderate to high ischemic risk. Beyond physician-led discontinuation, persistence with therapy in real-world settings may be limited due to adverse effects and patient choices. The aim of this study is to assess the real-world incidence of non-compliance with prolonged DAPT and to elucidate reasons for discontinuation. A retrospective observational study was conducted in three high-volume Italian PCI centers, involving patients with prior MI (1-3 years before) prescribed with ticagrelor 60 mg twice daily. Demographic, clinical, and procedural data were collected, with follow-up to determine therapy discontinuation and reasons for it. Among 244 enrolled patients, mean age was 66 years, and 83.6% were male. During follow-up (mean duration: 27.6 months), 10.2% (95% CI: 6.7% to 14.8%) discontinued ticagrelor. Key reasons included voluntary decision (40.0% [21.1% to 61.3%]) and bleeding events (40.0% [21.1% to 61.3%]), with some switching to high-dose regimens post-revascularization. In univariate analysis, ticagrelor discontinuation was significantly associated with female sex, higher BMI, prior PCI or CABG, high bleeding risk, and the absence of multivessel disease or primary PCI. However, in multivariable analysis, only multivessel disease remained independently associated with a lower likelihood of discontinuation (P<0.001). Real-world persistence with prolonged DAPT remains a challenge, often hindered by patient-driven discontinuation and adverse events. Enhanced patient education on therapy benefits and adherence may improve long-term outcomes.

Bleeding risk assessment is a critical component of the management of patients with ST-segment elevation myocardial infarction (STEMI), yet the optimal approach to risk stratification remains controversial. Although several bleeding risk scores have been developed, their predictive performance in STEMI populations is still evolving. Importantly, bleeding risk in STEMI is dynamic and influenced by clinical status, procedural factors, and antithrombotic strategies, underscoring the need for continuous reassessment throughout hospitalization. Bleeding avoidance measures—including radial access, judicious use of anticoagulation, and individualized antiplatelet therapy—play a pivotal role in reducing complications. Balancing ischemic and hemorrhagic risks is particularly challenging in patients with concomitantly high thrombotic and bleeding risks, requiring tailored management strategies. As bleeding remains a major determinant of prognosis, refining risk stratification tools and integrating evidence-based bleeding prevention strategies into clinical practice are essential. This narrative review summarizes the current evidence regarding the identification of high bleeding risk in hospitalized patients with STEMI and discusses its clinical implications. Also, this review proposes a dynamic, phase-specific framework for in-hospital bleeding risk assessment and management in patients with STEMI.

Background: Transcatheter aortic valve implantation (TAVI) has transitioned from a therapy for inoperable or extreme-risk patients to a standard option across broader risk categories. How this evolution has reshaped patient selection, procedural practice, and early outcomes within a mature program over extended time remains incompletely described. Methods: We conducted a single-center retrospective observational cohort study including all consecutive patients undergoing TAVI for severe symptomatic aortic stenosis between 2012 and 2024. Patients were stratified into three temporal eras (2012–2015, 2016–2020, 2021–2024). Baseline clinical, imaging, and procedural variables were prospectively recorded. The primary endpoint was 1-month major adverse events (MAE), defined as a composite of all-cause death, stroke, myocardial infarction, major vascular complications, or major bleeding. Comparisons across eras used ANOVA and chi-square or Fisher exact tests, as appropriate; multivariable logistic regression was applied to identify independent predictors of MAE. Results: A total of 1,946 patients were included (n=230, 396, and 1,320 across the three eras). Mean age (~81 years) and sex distribution (~60% women) remained stable, whereas cardiovascular risk factors became more prevalent over time (dyslipidemia 46.4% to 89.9%, hypertension 90.9% to 97.7%, smoking 1.1% to 11.2%; all p<0.001). Functional status improved (NYHA III–IV 78.2% to 18.0%; p<0.001), and EuroSCORE II decreased (5.7±5.1 to 3.2±3.6; p<0.001). Angiographically significant coronary artery disease and bicuspid valves were more frequently treated in the most recent era. Transfemoral access under local anesthesia remained predominant, while fluoroscopy time, contrast volume, and procedural duration significantly decreased (all p≤0.003). Residual aortic regurgitation ≥moderate became rare, with none/trace regurgitation increasing from 57.8% to 91.3% (p<0.001). Hospital stay shortened (7.3±2.8 to 6.1±3.1 days; p<0.001). MAE declined from 17.4% to 7.2% (p<0.001), driven by marked reductions in major bleeding (10.0% to 0.7%; p<0.001) and stroke (2.6% to 0.3%; p=0.002), while 1-month mortality remained low (2.6% to 1.0%; p=0.087). The need for new permanent pacemaker implantation was frequent but stable (~17–19%; p=0.645). Conclusions: Over 12 years, this high-volume TAVI program has progressively shifted towards patients with more conventional cardiovascular risk profiles, lower surgical risk, and more complex coronary and valvular anatomy, while achieving shorter, more efficient procedures and improved early safety. These findings support the robustness of a structured Heart Team approach and underscore the importance of continuous optimization of TAVI pathways in an evolving and increasingly heterogeneous patient population.

Background. Accurate anatomical assessment is essential for pre-procedural planning in structural heart disease. Advanced 3D imaging could offer improved visualization for more accurate reconstruction. We assessed the performance of a novel immersive 3D virtual reality (VEA) for the pre-procedural planning of transcatheter aortic valve implantation (TAVI) candidates. Methods. Measurement of cardiac-gated contrast-enhanced computed tomography (CT) scans was performed with the novel VEA and established tools: 3Mensio and Horos. Results. 50 consecutive patients were included. Annular and LVOT measurements obtained with VEA were strongly correlated with those derived from standard CT analysis. The intraclass correlation coefficient (ICC) confirmed excellent consistency for annular measurements (ICC = 0.93), while the concordance correlation coefficient indicated very good overall agreement (CCC = 0.83, 95% CI 0.73–0.90). Similarly, LVOT measurements obtained with VEA showed strong correlation with CT values, with good consistency (ICC = 0.90) and good overall agreement (CCC = 0.77, 95% CI 0.64–0.86). VEA-based planning improved prosthesis size selection accuracy, achieving higher concordance with implanted valves and a significant net reclassification gain over conventional CT. Conclusions. Given the increasing use of advanced 3D cardiac imaging technologies, understanding their diagnostic accuracy to guide pre-procedural planning of TAVI is paramount. In our study, VEA provided reliable assessment of aortic root anatomy for TAVI planning. This novel 3D software provides accurate, patient-specific reconstructions of the aortic root and surrounding structures that may optimize valve sizing, improve procedural safety and enhance procedural outcomes. This provides a rationale for future studies to assess the procedural benefit derived from a three-dimensional assessment of the aortic valve geometry.

Black individuals undergoing percutaneous coronary intervention (PCI) experience higher rates of major adverse cardiovascular events (MACE) than non‐Black individuals. This study assessed the racial differences in platelet reactivity and clinical outcomes among clopidogrel‐treated participants. Two cohorts were analyzed. The pharmacodynamic (PD) cohort involved patients with atherosclerotic cardiovascular disease on maintenance clopidogrel therapy undergoing platelet function testing. The primary outcome was high platelet reactivity (HPR, i.e., P2Y ₁₂ reaction unit [PRU] > 208). The PCI cohort included participants undergoing PCI on clopidogrel‐based dual antiplatelet therapy. The primary outcome was 1‐year MACE, defined as the composite of cardiovascular death, myocardial infarction (MI), ischemic stroke, or stent thrombosis. Data on clinically significant bleeding and CYP2C19 genotyping alleles were collected. The PD and PCI cohorts included 728 (32.1% Black) and 2,770 (20.5% Black) participants, respectively. Black participants had higher PRU levels (184 [IQR 128–234] vs. 144 [IQR 88–195]; P < 0.001) and higher prevalence of HPR (39.3% vs. 20.6%; P < 0.001). Independent predictors of HPR included Black race, hemoglobin levels, and presence of CYP2C19 loss‐of‐function allele. In the PCI cohort, Black participants had a higher risk of MACE (HR 1.47; 95% CI 1.02–2.11; P = 0.037), primarily driven by MI (HR 1.71; 95% CI 1.09–2.67; P = 0.019), with no significant difference in clinically significant bleeding (HR 1.08; 95% CI 0.65–1.80; P = 0.768). Black participants on clopidogrel exhibit higher platelet reactivity, increased rates of HPR, and an elevated risk of MACE within 1 year after PCI, without significant differences in bleeding compared to non‐Black participants.