Search Results (151)

Background: Chronic coronary syndrome (CCS) has evolved from a stenosis-centered concept to a dynamic clinical entity in which obstructive and non-obstructive coronary disease, microvascular dysfunction, and vasomotor abnormalities coexist with complex neurohormonal and endocrine activation. However, CCS has rarely been examined through an integrated endocrine lens, and no unified hormonal-phenotype framework currently links neurohormonal, sex-hormone, thyroid, and cardiometabolic pathways across CCS presentations. Objective: To synthesize contemporary evidence on how neurohormonal and endocrine pathways shape CCS phenotypes and to outline potential endocrine targets for phenotype-guided therapy. Methods for Synthesis of Data: We performed a structured literature appraisal in PubMed, Embase, the Cochrane Library, and ScienceDirect from inception to May 2026, using CCS/stable coronary artery disease and hormone-related search terms, and included comparative clinical studies in adults that evaluated neurohormonal or endocrine interventions with clinically relevant cardiovascular outcomes. Results: From 851 records, 34 studies were retained for qualitative synthesis, encompassing randomized trials, observational cohort studies, systematic reviews, and consensus documents. These data support a central role for renin–angiotensin–aldosterone and sympathetic activation, counterregulatory natriuretic peptides, endothelin-1, sex and thyroid hormones, and adipose-derived mediators in modulating CCS phenotypes, symptoms, and residual risk. Hormone-targeting therapies—including RAAS blockade, beta-blockers, mineralocorticoid receptor antagonists, sex- and thyroid-hormone modulation, and cardiometabolic agents such as GLP-1 receptor agonists and SGLT2 inhibitors—show variable yet often significant impact on outcomes across specific CCS subsets. Conclusions: CCS is best conceptualized as a state of coordinated neurohormonal and endocrine disturbance rather than a purely anatomical disease. A hormonal phenotype framework may support more biologically rational, individualized management and define a research agenda for phenotype-stratified trials in CCS. This review proposes a hormonal-phenotype framework that is conceptually novel compared with anatomy- or comorbidity-based CCS classifications and is intended to be hypothesis-generating rather than prescriptive, by highlighting specific knowledge gaps and potential endocrine targets for future phenotype-guided trials. Full article

Background: Inflammation plays a key role in atherosclerosis and thromboinflammatory processes involved in ischemic stroke. Colchicine, an anti-inflammatory agent that inhibits microtubule polymerization and inflammasome activation, has demonstrated cardiovascular benefits in coronary artery disease. However, its effectiveness in secondary prevention after ischemic stroke remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating colchicine in two pre-specified populations: (i) patients with non-cardioembolic ischemic stroke or high-risk transient ischemic attack (TIA), and (ii) atherosclerotic cardiovascular disease (ASCVD) cohorts reporting cerebrovascular outcomes, with pre-planned subgroup and sensitivity analyses restricted to stroke/TIA-only trials to address indirectness. Methods: We searched PubMed, Scopus, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to 20 October 2025, with no language restrictions, using a fully reported strategy combining controlled vocabulary (MeSH/Emtree) and free-text terms for colchicine and cerebrovascular/atherosclerotic outcomes. The primary outcome was recurrent stroke. Secondary outcomes included composite major vascular events, serious adverse events, any adverse events, and treatment discontinuation due to adverse events. A pre-specified subgroup analysis compared stroke/TIA-dedicated trials versus ASCVD trials reporting cerebrovascular outcomes, and a sensitivity analysis was restricted to stroke/TIA-only trials. Random-effects meta-analysis was performed using risk ratios (RR) with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic, and the certainty of evidence was evaluated using the GRADE framework. Results: Five randomized controlled trials, including 18,336 participants, were included. Colchicine did not significantly reduce the risk of recurrent stroke compared with control therapy (RR 0.86, 95% CI 0.65–1.12). Similarly, no significant reduction in vascular events was observed (RR 0.70, 95% CI 0.40–1.23), with substantial heterogeneity across studies. Colchicine was not associated with a significant increase in serious adverse events (RR 1.14, 95% CI 0.43–2.97). When restricted to stroke/TIA-dedicated trials (CHANCE-3, CONVINCE, COPS), the point estimate for recurrent stroke remained close to the null. Across trials reporting tolerability, colchicine was associated with higher rates of gastrointestinal adverse events and study-drug discontinuation, although the magnitude varied across studies. According to GRADE, the certainty of evidence ranged from moderate for recurrent stroke to low for vascular events and serious adverse events. Conclusions: Colchicine did not significantly reduce recurrent stroke or vascular events in patients with ischemic stroke or transient ischemic attack. Current evidence does not support routine use of colchicine for secondary stroke prevention, and further randomized trials are needed to identify potential subgroups that may benefit from anti-inflammatory therapy. Full article

Background: Arrhythmia recurrence after cryoballoon ablation remains a clinically relevant problem in atrial fibrillation (AF). However, factors associated with documented recurrence in low-risk patients without major comorbidities are not well defined. This study aimed to evaluate factors associated with documented arrhythmia recurrence after cryoballoon ablation in a highly selected low-risk AF population. Methods: This retrospective, single-center study included 153 eligible patients selected from an institutional cryoablation database after application of predefined exclusion criteria. Only patients with a CHA₂DS₂-VA (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, stroke/transient ischemic attack/thromboembolism, vascular disease, and age 65–74 years) score ≤ 1 and without major comorbidities, including diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, cerebrovascular disease, and heart failure, were included. Recurrence was defined as electrocardiographically documented AF or atrial tachyarrhythmia after the 3-month blanking period over 1 year of follow-up; Holter-detected episodes were required to last ≥30 s. The primary multivariable model included sex, age, AF type, and absolute left atrial diameter; a sensitivity model replaced absolute left atrial diameter with left atrial diameter indexed to body surface area (BSA). Results: The study population included 70 women (45.8%) and 83 men (54.2%). Paroxysmal AF was present in 125 patients (81.7%), whereas 28 patients (18.3%) had persistent AF. Documented arrhythmia recurrence occurred in 40 patients (26.1%). Female sex was more frequent in the recurrence group than in the no-recurrence group (62.5% vs. 39.8%, p = 0.013). The complete-case primary multivariable model included 126 patients with 36 recurrence events. Female sex was associated with documented arrhythmia recurrence (odds ratio [OR] 2.69, 95% confidence interval [CI] 1.14–6.37; p = 0.024). The estimate for left atrial diameter was directionally positive but statistically uncertain (OR 1.086 per mm, 95% CI 0.989–1.192; p = 0.085). In the BSA-indexed sensitivity model (n = 123), the female-sex estimate was attenuated and statistically uncertain (OR 2.16, 95% CI 0.90–5.18; p = 0.084), while left atrial diameter/BSA was also statistically uncertain (OR 1.145 per mm/m², 95% CI 0.977–1.343; p = 0.095). Conclusions: In this selected low-risk cohort undergoing second-generation cryoballoon ablation, female sex was associated with clinically detected, electrocardiographically documented arrhythmia recurrence in the primary model under an intermittent rhythm-surveillance strategy based on scheduled 12-lead electrocardiograms (ECGs) and symptom-driven evaluations. However, the estimate was attenuated and statistically uncertain after indexing left atrial diameter to BSA. Given the retrospective, single-center design, non-systematic rhythm monitoring, and sensitivity of the sex estimate to body-size adjustment, these findings should be interpreted as hypothesis-generating. Full article

Background: Perioperative cardiovascular complications remain a major concern in patients undergoing noncardiac surgery. Coronary computed tomography (CT)-based imaging, including coronary artery calcium (CAC) scoring, coronary CT angiography (CCTA), and CT-derived fractional flow reserve (CT-FFR), enables noninvasive assessment of coronary plaque burden, anatomic stenosis, and functional ischemia. However, the comparative prognostic value of these CT-based imaging markers for predicting perioperative major adverse cardiac events (MACE) has not been systematically evaluated. Methods: We performed a systematic review and meta-analysis of studies evaluating CT-based coronary imaging before noncardiac surgery. PubMed, Embase, and Cochrane CENTRAL were searched from inception through December 2025. Studies were included if they assessed CAC, CCTA, or CT-FFR and reported perioperative MACE. Risk of bias was independently assessed by two reviewers using the Quality In Prognosis Studies (QUIPS) tool. Pooled effect estimates were calculated using a random-effects model. The CT-FFR analysis was pre-specified as exploratory given the limited number of eligible studies. Results: A total of 13 studies including 10,100 patients undergoing noncardiac surgery were included in the systematic review, and 9 studies were eligible for quantitative meta-analysis. Obstructive coronary artery disease detected by CCTA was strongly associated with perioperative MACE (pooled odds ratio [OR] 7.18, 95% confidence interval [CI] 3.89–13.25). CAC burden was also significantly associated with perioperative cardiac risk (pooled OR 2.48, 95% CI 1.76–3.50). One study evaluating CT-FFR demonstrated a strong association between CT-FFR-defined ischemia and perioperative events (OR 10.77, 95% CI 4.64–25.02). These findings suggest that different CT-based imaging markers provide complementary prognostic information, with anatomic and functional assessment offering higher point estimates than plaque burden scoring. Conclusions: CT-based coronary imaging markers are significantly associated with perioperative MACE in patients undergoing noncardiac surgery. CAC burden and obstructive CAD detected on CCTA demonstrated consistent prognostic associations with perioperative cardiovascular events across multiple studies. CT-FFR showed a strong exploratory signal in a single eligible study, suggesting a potential additional role for functional ischemia assessment, although further validation in larger prospective cohorts is required. CT-based coronary imaging may therefore provide valuable complementary information for perioperative cardiovascular risk stratification. Full article

Coronary artery disease (CAD) is the leading cause of death worldwide, highlighting the need for more reliable and efficient diagnostic tools beyond conventional methods. Artificial intelligence (AI), particularly machine learning (ML) and deep learning (DL), has shown strong potential for detecting obstructive CAD by learning complex patterns from electrocardiogram (ECG) and coronary computed tomography angiography (CCTA) data. This rapid systematic review assesses and compares the diagnostic performance and methodological quality of AI models built for CAD prediction using ECG and CCTA data. A systematic search following PRISMA-ScR guidelines was conducted for primary studies published between 2021 and 2025. Eleven studies were included, six using ECG data and five using CCTA data. Methodological quality was evaluated using the PROBAST+AI tool. ECG-based models achieved AUCs of 0.72–0.961 and CCTA-based models showed slightly stronger top-end performance, with AUCs of 0.77–0.97. External validation was uncommon in both groups, applied in only 40% of CCTA studies and 33% of ECG studies, so neither modality demonstrated clearly greater validation maturity. Despite these strong results, PROBAST+AI assessment revealed a high risk of bias in 90.9% of the included studies, largely due to weaknesses in the analysis domain, including poor handling of missing data and the absence of model calibration reporting. AI models show strong diagnostic accuracy for CAD across both modalities, although external validation was limited and applied in a minority of studies. However, the widespread methodological bias means these tools should currently support clinical decision-making rather than replace standard diagnostic methods. Future studies should focus on prospective multicentre validation and the use of multimodal data. Full article

Background: Despite recent advances in reperfusion strategies, acute coronary syndrome (ACS) patients remain at high risk for recurrent major adverse cardiovascular events (MACE). This study aims to investigate the association between lipoprotein(a) (Lp(a)) and MACE in ACS patients, and to systematically evaluate its predictive performance, incremental prognostic value and clinical utility. Methods: This retrospective cohort study included 300 ACS patients with a 1-year follow-up. Serum Lp(a) levels were measured by immunoturbidimetry using fasting venous blood samples collected on the day of admission. Kaplan–Meier and Cox regression analyses were used to assess the association between Lp(a) and MACE. Subgroup and interaction analyses were performed to test the robustness of the findings. Incremental predictive value and net clinical benefit were evaluated using receiver operating characteristic (ROC) curves, the DeLong test, decision curve analysis (DCA) and the integrated discrimination improvement (IDI) index. Results: Baseline Lp(a) levels were significantly higher in the event group (p = 0.006). A significantly lower cumulative survival probability was found in patients with elevated Lp(a) (log-rank p = 0.0014). As a standalone predictor of MACE, Lp(a) yielded an AUC of 0.606 (p = 0.006). The AUC of the baseline model was 0.753 (95% CI: 0.694–0.812), which increased to 0.771 (95% CI: 0.712–0.831) after adding Lp(a). DCA showed that the Lp(a)-guided strategy provided higher net benefit than both the “treat-all” and “treat-none” strategies within a threshold probability range of 0–0.35. Conclusions: Although Lp(a) offers limited incremental value over traditional risk factors and the Gensini score in the low-to-moderate risk range (<0.35), it provides net clinical benefit as a complementary biomarker in ACS. Full article

Background: The prognostic significance of myocardial infarction with non-obstructive coronary arteries (MINOCA) in older adults remains uncertain, particularly in comparison with revascularized acute coronary syndromes (ACS) and other acute myocardial injury phenotypes. Methods: In the prospective population-based cohort of the Malmö Diet and Cancer Study (n = 30,466), 925 participants who experienced an incident coronary event between 2009 and 2018 were classified as revascularized ACS, MINOCA, or other acute myocardial injury phenotypes. All-cause mortality was assessed using Kaplan–Meier estimates and Cox proportional-hazards models. Results: Of 925 patients (mean age, 81 ± 7 years; female sex, 57%), 136 (14.7%) had a non-revascularized event, including 49 (36%) classified as MINOCA and 87 (64%) as other acute myocardial injuries. All non-revascularized cases underwent detailed review of angiographic and clinical records. During a median follow-up of 2.5 years, mortality was substantial across all groups (81%, overall). In unadjusted analyses, survival did not differ significantly among event categories (p = 0.302). In multivariable analysis, MINOCA was associated with increased mortality compared with revascularized ACS (aHR 1.48; 95% CI 1.07–2.05; p = 0.018) and with other acute myocardial injury phenotypes (aHR 1.44; 95% CI 1.01–2.04; p = 0.041). Other acute myocardial injury phenotypes did not differ significantly from revascularized ACS (aHR 1.03; 95% CI 0.78–1.35). Conclusions: MINOCA is associated with higher mortality than both revascularized ACS and other acute myocardial injury phenotypes. Despite the absence of obstructive coronary disease, MINOCA in later life carries an adverse prognosis and commands systematic diagnostic evaluation, careful phenotypic characterization, and appropriate risk-directed management. Full article

Background: Micro- and nanoplastics (MNPs) are emerging contaminants increasingly detected in human tissues and biological fluids. Their presence in blood, vascular tissues, thrombi, and atherosclerotic plaques raises concern about their possible association with cardiovascular disease. This systematic review synthesized evidence on associations between MNPs and cardiovascular pathology. Methods: A systematic search was conducted in October 2025 in PubMed, Scopus, Web of Science, and Embase according to PRISMA guidelines and a PICOS-based strategy. Original human studies from the last 10 years were eligible. Fourteen studies were included. Due to methodological heterogeneity, a narrative synthesis was performed. Risk of bias was assessed using ROBINS-E, and certainty of evidence was evaluated using a GRADE-informed approach. Results: MNPs were detected in multiple cardiovascular-related matrices. Included studies suggested possible associations with major adverse cardiovascular events, acute coronary syndrome, myocardial infarction, arterial stenosis, vascular calcification, thromboembolic disease, hypertension, inflammatory markers, coagulation-related parameters, and lipid profiles. However, the certainty of evidence was very low, and most studies had a high or very high risk of bias. Conclusions: Current evidence suggests a possible association between MNPs and cardiovascular pathology, but causality remains unproven. Larger prospective studies using standardized detection protocols, rigorous contamination control, and adjustment for confounders are needed. Full article

Background: Heart transplantation (HT) remains the definitive therapy for end-stage heart failure, yet rejection and cardiac allograft vasculopathy (CAV) continue to limit long-term outcomes. Beyond donor-specific HLA antibodies, non-HLA antibodies, particularly anti-angiotensin II type 1 receptor antibodies (AT1R-Abs), have been implicated in allograft injury, but published findings are heterogeneous. Aim: The aim of this study is to systematically evaluate the evidence linking AT1R gene expression and anti-AT1R antibodies with key post-heart transplant outcomes. Methods: We conducted a systematic review in accordance with PRISMA guidelines. Scopus, PubMed, Web of Science, and the Cochrane Library were searched (December 2025) for cohort and case–control studies evaluating AT1R gene expression and/or AT1R-Ab status in HT recipients and their association with post-transplant outcomes. Two reviewers independently screened studies, extracted data, and assessed risk of bias using the NIH Quality Assessment Tool. Results: Twelve studies encompassing 951 recipients met the inclusion criteria. Five studies evaluated AT1R mRNA expression, reporting variable patterns: several observed reduced AT1R/AT2R transcription after transplantation without clear clinical correlation, whereas others associated higher donor or recipient AT1R expression with transplant coronary artery disease and recurrent rejection. AT1R-Ab prevalence varied widely and appeared to increase after mechanical circulatory support, with substantial seroconversion reported during LVAD support in initially antibody-negative patients. Associations between AT1R-Ab and acute cellular rejection and antibody-mediated rejection were inconsistent across studies, and survival findings were inconclusive; however, some reports linked elevated AT1R-Abs to poorer long-term freedom from adverse events. Evidence regarding CAV was mixed, with signals of increased vasculopathy risk in some cohorts but not others. Conclusions: Current evidence suggests a potential role for AT1R expression and AT1R-Abs in cardiac allograft dysfunction, including rejection phenotypes and vasculopathy. Larger prospective studies with harmonized testing strategies are needed to define clinically meaningful AT1R-Ab cutoffs and clarify their utility in risk stratification and targeted therapeutic trials. Full article

Background: Patients with spontaneous coronary artery dissection (SCAD) are at increased risk of cardiovascular events, including dissection in other arterial territories such as cervical arteries. Those with combined coronary and cervical arterial dissection (CACAD) may have more widespread arterial abnormalities and worse outcomes, underscoring the need for better risk stratification and personalized care. Objective: This study examined the prevalence of cervical artery dissection (CvAD) in patients diagnosed with SCAD, evaluated potential risk factors for developing CvAD, and assessed their impact on clinical outcomes, including all-cause mortality, SCAD recurrence, and stroke. The goal was to enhance risk stratification by identifying SCAD patients at increased risk for CvAD. Design: In this retrospective cohort study, patients diagnosed with SCAD between 2018 and 2024 across Mayo Clinic sites were identified using ICD-10 codes. Manual chart review confirmed CvAD diagnoses. Patients were stratified based on the presence or absence of CvAD. Chi-square and independent t-tests were used to compare risk factors and comorbidities. Univariate screening and multivariable logistic regression were used to identify predictors of CvAD. Results: Among 1380 patients with SCAD, 131 (9.5%) had CvAD. The median follow-up was 2.02 years (IQR: 1.1–5.2 years). All CvAD diagnoses were identified after the index SCAD event through systematic post-SCAD vascular imaging. The mean age was similar between groups (51.5 ± 11.3 years in CACAD vs. 50.9 ± 10.7 years in SCAD-only, p = 0.540), and the majority were female (93.9% vs. 91.9%, p = 0.529). Multivariable regression identified extremity arterial dissection (OR: 8.13, 95% CI: 3.41–19.36, p < 0.001), fibromuscular dysplasia (FMD) (OR: 7.52, 95% CI: 4.67–12.10, p < 0.001), connective tissue disorders (CTDs) (OR: 6.85, 95% CI: 2.35–19.98, p < 0.001), and anxiety (OR: 1.69, 95% CI: 1.01–2.81, p = 0.044) as significant predictors of CvAD. CvAD was a strong independent predictor of stroke (OR: 6.37, 95% CI: 2.93–13.87, p < 0.001). Mortality and SCAD recurrence did not differ significantly between groups. Conclusions: Patients with CACAD demonstrate a systemic vascular phenotype with significantly higher rates of FMD, connective tissue disease, extremity arterial dissection, and stroke. These findings highlight the importance of comprehensive vascular screening and individualized monitoring in at-risk SCAD patients. Full article

Aim: The aim of this observational cross-sectional study was to evaluate whether blood renalase concentration, total antioxidant status (TAS), main cardiovascular risk factors, and obstructive sleep apnea severity are associated with the anatomical severity of coronary artery disease assessed by CCTA in patients with suspected OSA. Materials and methods: The study included 93 patients with suspected OSA. All patients were assessed for main risk factors for cardiovascular disease. Polysomnography was performed to verify the suspicion of OSA, as well as coronary computed tomography angiography (CCTA) with a systematic assessment of the severity of coronary artery disease using the CAD-RADS classification. Blood renalase concentration and total antioxidant status (TAS) were determined. Results: The apnea–hypopnea index (AHI) in the study group was 16.57 ± 17.17 /h. OSA was diagnosed in 73.1% of the study group. In CCTA examinations, significant coronary artery disease (CAD-RADS ≥ 3) was suspected in 22.6% of the subjects, including 16.1% classified as CAD-RADS 3, 4.3% as CAD-RADS 4, and 2.1% as CAD-RADS 5. Patients with AHI ≥ median were significantly more often classified as CAD-RADS ≥ 3 than patients with AHI < median. Patients with blood renalase concentration ≥ median were significantly less often classified as CAD-RADS ≥ 3 than patients with blood renalase concentration < median. Similarly, patients with TAS ≥ median were significantly less often classified as CAD-RADS ≥ 3 than those with TAS < median. Older age, higher systolic blood pressure, higher blood cholesterol levels, and lower TAS were independently associated with CAD-RADS ≥ 3 in logistic regression analysis. In multivariable regression analysis, higher pack-years of smoking, higher AHI, and lower blood renalase concentration were independently associated with lower TAS. Conclusions: Higher pack-years of smoking, higher AHI values, and lower blood renalase concentration were associated with lower total antioxidant status, which, along with older age, higher systolic blood pressure, and higher total cholesterol concentration, was independently associated with suspected anatomically significant coronary artery disease on CCTA. Full article

Background/Objectives: The management of dyslipidaemia in Slovakia has undergone significant changes in recent years, particularly through the relaxation of prescription restrictions for existing medications and the introduction of new innovative molecules. Achieving target levels of LDL cholesterol (LDL-C) plays a key role in preventing the onset and progression of atherosclerosis-related cardiovascular (CV) diseases. The aim of this study was to analyse how these changes have affected the effectiveness of reaching target LDL-C levels in patients at very high CV risk. Methods: This project was conducted as a retrospective analysis of anonymised LDL-C values from 2020 to 2023 using data from a collaborating nationwide laboratory. Patients included were those diagnosed with acute coronary syndrome (ACS), stroke, and, more generally, those with high and very high CV risk. Target LDL-C values were assessed based on the 2019 ESC/EAS guidelines. Results: A total of 363,020 LDL-C test records from 115,950 patients were evaluated over the four-year study period. Among patients diagnosed with ACS, 2.2–5% achieved target LDL-C levels in the respective years of observation 2020–2023. As many as 6.5–7.4% had LDL-C levels ≥ 4.9 mmol/L. For patients with stroke, only 4–6.6% reached target LDL-C levels, while 5.6–6.7% had levels ≥ 4.9 mmol/L. In the group with very high CV risk, only 1.7–3% achieved target levels, and 7.5–8.7% had extremely high LDL-C levels ≥ 4.9 mmol/L. Despite these modest improvements, over 93.4% of patients in the highest-performing subgroup failed to reach the absolute guideline target threshold in 2023. Conclusions: While the lifting of prescription constraints and the introduction of innovative treatments correlates with a doubling of absolute target attainment and a contraction of extreme hypercholesterolemia, overall control remains critically low in Slovakia. Systematic, protocol-driven combination regimens and intensive follow-up are urgently needed. Full article

Objective: Kawasaki disease (KD) is characterized as an acute systemic vasculitis predominantly affecting young children, with coronary artery lesions (CALs) representing the most serious complication. Therapeutic resistance to intravenous immunoglobulin (IVIG) remains a significant clinical challenge. Consequently, numerous investigations have sought to identify predictive risk factors for IVIG resistance (IVIGR) and CAL development. Limited research has systematically evaluated the prognostic utility of electrocardiographic (ECG) parameters in KD outcome prediction. This study was therefore undertaken to assess the contributory value of ECG analysis in determining KD prognosis and therapeutic responses. Methods: This prospective cohort study enrolled 255 hospitalized children diagnosed with KD at West China Second University Hospital between July 2022 and December 2024. Initially, univariate analysis was performed to identify risk factors differentiating IVIGR from non-IVIGR patients and CAL from non-CAL patients. Statistically significant parameters were subsequently incorporated into machine learning analyses. Random forest algorithms were employed to construct predictive models based on the following: (1) complete blood count parameters, (2) biochemical and metabolic profiles, (3) electrocardiographic features, and (4) a comprehensive multimodal model integrating all parameters. These models generated feature importance scores, providing hierarchical rankings that quantified the relative contribution of each predictor to outcome prediction. Results: Univariate analysis demonstrated that alterations in hematological parameters, biochemical and metabolic profiles, and electrocardiographic features were significantly associated with therapeutic responses to IVIG and CAL development. Machine learning analysis revealed that ECG parameters individually contributed modest predictive weight for KD prognosis. However, the integration of ECG features into the comprehensive model substantially enhanced the discriminatory capacity, elevating the area under the curve (AUC) to 0.92 for CAL prediction. For IVIGR prediction, ECG-exclusive models demonstrated suboptimal performance in early disease management. Nevertheless, the multimodal integration of ECG with inflammatory and metabolic biomarkers achieved a comparable AUC of 0.92 for IVIGR prediction. Conclusions: This study establishes that ECG parameter alterations are significantly associated with CAL development and IVIGR in KD patients. Although ECG features demonstrate a limited independent predictive capacity compared to inflammatory and metabolic biomarkers, their integration into comprehensive predictive models substantially enhances discriminatory performance. These findings underscore the complementary value of electrocardiographic assessment in multimodal risk stratification strategies for KD management, supporting the clinical utility of ECG analysis as an adjunctive prognostic tool when combined with conventional laboratory parameters. Full article

Background/Objectives: Drug-induced hypersensitivity and cardiotoxicity are important yet often underrecognized clinical concerns, and fluoroquinolones are widely used antibiotics with well-documented safety issues. Given the limited systematic evidence and underreporting in pharmacovigilance databases, this study explored a potential association between fluoroquinolones and Kounis syndrome (KS) and the possibility of a class-related effect. Methods: This retrospective descriptive study analyzed individual case safety reports from VigiBase, complemented by published case reports to capture additional cases not recorded in the database. All fluoroquinolones reported as suspected drugs in KS cases were included, and a systematic search of major literature databases was undertaken to identify further case-level evidence. Quantitative data were explored using VigiLyze, while qualitative clinical data were extracted for case characterization. Literature cases underwent Naranjo assessment, and the overall body of evidence was evaluated using a qualitative Bradford Hill framework. Results: A descriptive disproportionality signal for fluoroquinolones was identified in VigiBase (IC₀₂₅ = 1.3). Seventeen cases of fluoroquinolone-associated KS were identified across VigiBase and the published literature, all originating from unsolicited sources. Most cases involved ciprofloxacin and levofloxacin, whereas other fluoroquinolones were only rarely reported. Across cases, a consistent clinical pattern was observed, including a clear temporal relationship between drug exposure, allergic manifestations, and acute coronary events, compatible with hypersensitivity-mediated coronary involvement. Conclusions: KS cases associated with several fluoroquinolones were identified in pharmacovigilance data and the published literature, with the most consistent evidence observed for ciprofloxacin and levofloxacin. Although a class effect was not confirmed, a potential association cannot be excluded. These findings should be interpreted as hypothesis-generating, and further research is required to clarify underlying mechanisms, drug-specific risks, and clinical relevance. Full article

Background: Lipoprotein(a) [Lp(a)] is an inherited cardiovascular risk factor, but its relationship with coronary anatomical complexity, plaque phenotype, and outcomes after percutaneous coronary intervention (PCI) remains incompletely defined. Methods: We conducted a systematic review and meta-analysis of studies evaluating the association between circulating Lp(a) levels and coronary disease characteristics, post-PCI clinical outcomes, stent-related adverse outcomes, and aortic valve disease. Results: Twenty-six studies were included. Elevated Lp(a) levels were associated with greater coronary anatomical complexity and a higher risk of major adverse cardiovascular events after PCI (HR 1.4, 95% CI 1.2–1.7). The strongest associations were observed for stent-related adverse outcomes, including restenosis (OR 3.23, 95% CI 2.2–4.8) and target vessel revascularization (OR 2.6, 95% CI 1.6–4.4). Higher Lp(a) levels were also associated with vulnerable plaque features and aortic valve calcification. Conclusions: Elevated Lp(a) is associated with greater coronary disease complexity and adverse outcomes after PCI. Elevated Lp(a) may represent a biological marker identifying high-risk patients and providing additional insight for personalized risk stratification and procedural decision-making in patients undergoing PCI. Full article