J. Cardiovasc. Dev. Dis., Volume 13, Issue 1 (January 2026) – 57 articles

Background: Childhood obesity represents the most common nutritional and metabolic disorder in industrialized countries and constitutes a major public health concern. In Italy, 20–25% of school-aged children are overweight and 10–14% are obese, with marked regional variability. Excess adiposity in childhood is frequently associated with hypertension, dyslipidemia, insulin resistance, and non-alcoholic fatty liver disease (NAFLD), predisposing to future cardiovascular disease (CVD). Objective: To investigate anthropometric indicators of cardiometabolic risk in 810 children and adolescents aged 7–17 years who underwent assessment for competitive sports eligibility at the Sports Medicine Unit of Modena, evaluate baseline knowledge of cardiovascular health aligned with ESC, AAP (2023), and EASO guidelines. Methods: 810 children and adolescents aged 7–17 years undergoing competitive sports eligibility assessment at the Sports Medicine Unit of Modena underwent evaluation of BMI percentile, waist circumference (WC), waist-to-height ratio (WHtR), and blood pressure. Cardiovascular knowledge and lifestyle habits were assessed via a previously used questionnaire. Anthropometric parameters, blood pressure (BP), and lifestyle-related knowledge and behaviors were assessed using standardized procedures. Overweight and obesity were defined according to WHO BMI-for-age percentiles. Elevated BP was classified based on the 2017 American Academy of Pediatrics age-, sex-, and height-specific percentiles. Statistical analyses included descriptive statistics, group comparisons, chi-square tests with effect size estimation, correlation analyses, and multivariable logistic regression models. Results: Overall, 22% of participants were overweight and 14% obese. WHtR > 0.5 was observed in 28% of the sample and was more frequent among overweight/obese children (p < 0.001). Elevated BP was detected in 12% of participants with available measurements (n = 769) and was significantly associated with excess adiposity (χ² = 7.21, p < 0.01; Cramér’s V = 0.27). In multivariable logistic regression analyses adjusted for age and sex, WHtR > 0.5 (OR 2.14, 95% CI 1.32–3.47, p = 0.002) and higher sedentary time (OR 1.41 per additional daily hour, 95% CI 1.10–1.82, p = 0.006) were independently associated with elevated BP, whereas BMI percentile lost significance when WHtR was included in the model. Lifestyle knowledge scores were significantly lower among overweight and obese participants compared with normal-weight peers (p < 0.01). Conclusions: WHtR is a sensitive early marker of cardiometabolic risk, often identifying at-risk children missed by BMI alone. Baseline cardiovascular knowledge was suboptimal. The observed gaps in cardiovascular knowledge underscore the importance of integrating anthropometric screening with structured educational interventions to promote healthy lifestyles and long-term cardiovascular prevention. Full article

Background: Vascular aging (VA) reflects arterial biological aging and is closely linked to cardiovascular risk. Carotid–femoral pulse wave velocity (cfPWV) is the gold standard for assessing arterial stiffness and VA. However, evidence is limited on cfPWV-derived vascular age and its association with subclinical target organ damage (TOD) in the general population. This study evaluated whether Δ-age (vascular age minus chronological age) could identify individuals at higher risk of early vascular injury in a Chinese community cohort. Methods: This cross-sectional study included participants from two Beijing communities. Δ-age was calculated as cfPWV-derived vascular age minus chronological age. Participants were categorized as supernormal vascular aging (SUPERNOVA, <10th percentile), normal VA, and early vascular aging (EVA, 90th percentile). TOD included mean and maximum carotid intima-media thickness (CIMT), and carotid plaque. Associations between Δ-age and TOD were analyzed using multivariable regression models adjusted for conventional cardiovascular risk factors and cfPWV. Results: A total of 6305 participants (mean age 62.5 ± 7.8 years; 34.2% male) were included. Higher Δ-age was associated with increased mean and maximum CIMT and higher carotid plaque prevalence, independent of cfPWV. EVA participants had a higher risk, whereas SUPERNOVA participants had a lower risk of TOD compared with normal VA. After cfPWV adjustment, EVA remained associated with increased mean CIMT and carotid plaque, while SUPERNOVA showed a nonsignificant trend toward a lower risk. Associations were consistent across subgroups. Conclusions: Δ-age, independent of cfPWV, was an independent risk factor for TOD. This simple, practical indicator may help identify individuals at risk of early vascular damage in community settings. Full article

Background: Insulin resistance (IR) has been implicated in cardiovascular diseases, and a correlation between IR and the slow flow phenomenon (CSF)has been identified. The triglyceride–glucose index (TGI), a simple surrogate marker for IR, has recently emerged as a potential predictor of CSF, though data are limited. The aim of this study was to evaluate the association of TGI and other prognostic parameters in patients with CSF. Methods: This retrospective study included 693 patients who underwent diagnostic coronary angiography between January 2022 and December 2024. A total of 132 patients were diagnosed with CSF based on the corrected TIMI frame count (cTFC > 27 in at least one epicardial coronary artery), while 561 patients had normal coronary flow (NCF). Patients with confounding cardiovascular or systemic conditions were excluded. Clinical, demographic, and laboratory data were gathered, and TGI was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2].Results: Statistically significant distinctions were found between the CSF and NCF groups regarding TGI, age, glucose, HbA1c, creatinine, sodium, CRP, platelet count, heart rate, PR interval, and cQT interval (p < 0.05). Age, hypertension, diabetes mellitus, HbA1c, glucose, sodium, and cQT were identified as potential clinical and laboratory factors associated with CSF in univariate logistic regression analysis; however, no independent predictor was found in multivariate analysis. ROC analysis showed that a TGI cut-off value of ≥8.93 predicted CSF with 67.6% sensitivity and 66.7% specificity. Conclusions: Our study demonstrated that TGI was significantly greater in patients with CSF compared to those with NCF. Although TGI showed limited sensitivity and specificity in discriminating CSF, its possible value as a prognostic indicator warrants further validation in prospective, large-scale studies. Full article

Cardiogenic pulmonary edema (CPE) is a life-threatening manifestation of acute heart failure characterized by rapid accumulation of fluid in the interstitial and alveolar spaces, leading to severe dyspnea, hypoxemia, and respiratory failure. The condition arises from elevated left-sided filling pressures that increase pulmonary capillary hydrostatic pressure, disrupt alveolo-capillary barrier integrity, and impair gas exchange. Neurohormonal activation further perpetuates congestion and increases myocardial workload, creating a vicious cycle of hemodynamic overload and respiratory compromise. Respiratory support is a cornerstone of management in CPE, aimed at stabilizing oxygenation, reducing the work of breathing, and facilitating ventricular unloading while definitive therapies, such as diuretics, vasodilators, inotropes, or mechanical circulatory support (MCS), address the underlying cause. Among available modalities, non-invasive ventilation (NIV) with continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) has the strongest evidence base in moderate-to-severe CPE, consistently reducing the need for intubation and providing rapid relief of dyspnea. High-flow nasal cannula (HFNC) represents an emerging alternative in patients with moderate hypoxemia or intolerance to mask ventilation, and should be considered an adjunctive option in selected patients with less severe disease or NIV intolerance, although its efficacy in severe presentations remains uncertain. Invasive mechanical ventilation is reserved for refractory cases, while extracorporeal membrane oxygenation (ECMO) and other advanced circulatory support modalities may be necessary in cardiogenic shock. Integration of respiratory strategies with hemodynamic optimization is essential, as positive pressure ventilation favorably modulates preload and afterload, synergizing with pharmacological unloading. Future directions include personalization of ventilatory strategies using advanced monitoring, novel interfaces to improve tolerability, and earlier integration of MCS. In summary, respiratory support in CPE is both a bridge and a decisive therapeutic intervention, interrupting the cycle of hypoxemia and hemodynamic deterioration. A multidisciplinary, individualized approach remains central to improving outcomes in this high-risk population. Full article

Background: Structural and functional adaptation of the heart to chronic exercise is dependent on multiple factors, including the volume and type of training, and has direct implications for pre-participation cardiac screening (PPCS). Sailing is a unique multi-training modality sport with limited prior description of cardiac adaptation to training. The aims of this study are (1) to describe electrocardiogram (ECG) changes in sailors, informing PPCS guidelines; (2) to assess structural and functional cardiac changes in sailors; and (3) to examine sex- or discipline-specific cardiac adaptations in sailors. Methods: Seventy elite sailors (33 females) underwent standard ECG and echocardiography. Echocardiographic data were compared to population norms and analysed by sex and sailing discipline based on training type: isometric (IG), pumping (PG), and movement (MG). Results: One sailor presented with abnormal ECG findings (T wave inversion) which warranted further investigation. Primary training-related ECG changes noted were early repolarisation (24%) and sinus bradycardia (30%). The left ventricular volume index was dilated in 18% of all sailors compared to reference values, with similar findings noted on right ventricular parameters for 22% of the study population, although in males only. The impact of predominant training stimulus (IG, PG, MG) did not mediate differences in the structure of any cardiac chambers (p > 0.05). Ejection fraction was lower in the PG (Δ4%, p ≤ 0.001), whereas global longitudinal strain was higher (Δ2%, p = 0.02) compared to MG and IG. Conclusions: Elite-level sailors present with electrical and structural cardiac phenotypes associated with exercise adaptation, with dilation of both left- and right-sided chambers. These data should be considered when interpreting results of PPCS in male and female sailors from different, specific disciplines. Full article

Understanding thrombosis in acute coronary syndromes (ACSs) has evolved through advances in biomarkers, intracoronary imaging, and emerging analytical tools, improving diagnostic accuracy and risk stratification in high-risk patients. This narrative review provides an integrative overview of contemporary evidence from clinical trials, meta-analyses, and international guidelines addressing circulating biomarkers, intracoronary imaging modalities—including optical coherence tomography (OCT), intravascular ultrasound (IVUS), and near-infrared spectroscopy (NIRS)—artificial intelligence–based analytical approaches, and emerging antithrombotic therapies. High-sensitivity cardiac troponins and natriuretic peptides remain the most robust and guideline-supported biomarkers for diagnosis and prognostic assessment in ACS, whereas inflammatory markers and multimarker strategies offer incremental prognostic information but lack definitive validation for routine therapeutic guidance. Intracoronary imaging with IVUS or OCT is supported by current guidelines to guide percutaneous coronary intervention in selected patients with ACS and complex coronary lesions, leading to improved procedural optimization and clinical outcomes compared with angiography-guided strategies. Beyond procedural guidance, OCT enables detailed plaque characterization and mechanistic insights into ACS, while NIRS provides complementary information on lipid-rich plaque burden, primarily for risk stratification based on observational evidence. Artificial intelligence represents a rapidly evolving tool for integrating clinical, laboratory, and imaging data, with promising results in retrospective and observational studies; however, its clinical application in thrombosis management remains investigational due to the lack of outcome-driven randomized trials. In the therapeutic domain, factor XI inhibitors have demonstrated favorable safety profiles with reduced bleeding and preserved antithrombotic efficacy in phase II and early phase III studies, but their definitive role in ACS management awaits confirmation in large, outcome-driven randomized trials. Overall, the integration of biomarkers, intracoronary imaging, and emerging analytical and pharmacological strategies highlights the potential for more individualized cardiovascular care. Nevertheless, careful interpretation of existing evidence, rigorous validation, and alignment with guideline-directed practice remain essential before widespread clinical adoption. Full article

Objectives: Non-ST-segment elevation myocardial infarction (NSTEMI) in the elderly is frequently complicated by multiple comorbidities, which influence clinical outcomes. However, the prognostic significance of atrial fibrillation (AF) in this context remains uncertain. This study aimed to evaluate the impact of AF on short- and long-term mortality in elderly patients (≥65 years) with NSTEMI. Methods: This cross-sectional observational study included 474 NSTEMI patients aged 65 years and older. Participants were stratified into four groups based on age (65–74 vs. ≥75 years) and the presence or absence of AF. One-month and one-year all-cause mortality were assessed as the primary and secondary endpoints, respectively. Results: AF was detected in 23 (11.6%) of 199 patients aged 65–74 and in 80 (29.1%) of 275 patients aged ≥75. While one-month mortality did not differ significantly among the four groups (p = 0.514), one-year mortality showed a statistically significant difference (p < 0.001). Univariate analysis revealed that AF was not predictive of one-month mortality. In multivariate Cox regression analysis, AF, reduced creatinine clearance, and left ventricular ejection fraction <50% were identified as independent predictors of one-year mortality. Conclusion: AF is not associated with short-term mortality in elderly NSTEMI patients; however, it serves as an independent predictor of one-year mortality. These findings highlight the importance of long-term rhythm monitoring and management in this high-risk population. Full article

Background: There exists some inconsistent evidence on the relationship between altered cardiac morphology, its function, and frailty. Therefore, this study aimed to assess the associations among frailty, lean body mass, central arterial stiffness, and cardiac structure and geometry in older people with a normal ejection fraction. Methods: A total of 205 patients >65 years were enrolled into this ancillary analysis of the FRAPICA study and were assessed for frailty with the Fried phenotype scale. Left ventricular dimensions and geometry were assessed with two-dimensional echocardiography. Fat-free mass was measured using three-site skinfold method. Parametric and non-parametric statistics and analysis of covariance were used for statistical calculations. Results: Frail patients were older and women comprised the majority of the frail group. Frail men and women had comparable weight, height, fat-free mass, blood pressure, central blood pressure, and carotid–femoral pulse wave velocity to their non-frail counterparts. There was a linear correlation between the sum of frailty criteria and left ventricular end-diastolic diameter (Spearman R = −0.17; p < 0.05) and relative wall thickness (Spearman R = 0.23; p < 0.05). In the analysis of covariance, frailty and gender were independently associated with left ventricular mass (gender: β of −0.37 and 95% CI of −0.50–−0.24 at p < 0.001), the left ventricular mass index (gender: β of −0.23 and 95% CI of −0.37–−0.09 at p < 0.001), and relative wall thickness (frailty: β of −0.15 and 95% CI of −0.29–−0.01 at p < 0.05; gender: β of 0.23 and 95% CI of 0.09–0.36 at p < 0.01). Frailty was associated with a shift in heart remodeling toward concentric remodeling/hypertrophy. Conclusions: Frailty is independently associated with thickening of the left ventricular walls and a diminished left ventricular end-diastolic diameter, which are features of concentric remodeling or hypertrophy. This association appears to be more pronounced in women. Such adverse cardiac remodeling may represent another phenotypic feature linked to frailty according to the phenotype frailty criteria. Full article

The pharmacologic management of patent ductus arteriosus (PDA) presents a challenge to clinicians due to the interindividual variability in drug response to available medications. There is evidence that CYP2C9 is associated with the response to PDA treatment; however, no data from the Middle East is available. This study aimed to investigate the association between CYP2C8 and CYP2C9 genetic polymorphisms and response to ibuprofen or indomethacin in neonates with PDA. We conducted a retrospective cohort study of neonates with a gestational age < 32 weeks and birthweight < 1500 g with PDA between 2019 and 2023. Eligible neonates were those diagnosed with PDA and treated with at least one course of ibuprofen or indomethacin. Genotyping was performed to identify four single-nucleotide polymorphisms (SNPs), namely CYP2C8*3 rs10509681, CYP2C9*2 rs1799853, CYP2C9 rs2153628, and CYP2C9*3 rs1057910. Allele frequencies were compared between responders and non-responders, and non-genetic predictors were assessed using logistic regression. A total of 146 infants were identified. Of these, 86 were enrolled. Genetic analysis showed that the heterozygote genotype (TC) for the CYP2C8 gene was the most common (45%), while wild-type alleles were predominant for CYP2C9 variants. No significant differences in allele frequencies were found between responders and non-responders to the treatment (p > 0.05). In a secondary analysis, the need for multiple surfactant doses independently predicted poor response (aOR 0.244, 95% CI 0.086–0.693, p = 0.008), while extremely low birth weight showed a borderline association (aOR 0.281, 95% CI 0.062–1.268, p = 0.099). Carriers of CYP2C8*3 rs10509681, CYP2C9*2 rs1799853, CYP2C9 rs2153628, and CYP2C9*3 rs1057910 were not associated with variations in response to NSAIDs. Full article

Background: Intentional occlusion of the internal iliac artery (IIA) during endovascular repair of aorto-iliac aneurysms may predispose patients to pelvic ischemic complications such as gluteal claudication, erectile dysfunction, and bowel ischemia. Iliac branch devices (IBDs) have been developed to preserve hypogastric perfusion. E-Liac (Artivion/Jotec) is one of the latest modular IBDs yet reports on mid-term performance are limited to small single-center cohorts with short follow-up. The CAMpania PugliA bRanch IliaC (CAMPARI) study is a multicenter investigation of E-Liac outcomes. Methods: A retrospective observational cohort study was conducted across five Italian vascular centers. All consecutive patients undergoing E-Liac implantation for aorto-iliac or isolated iliac aneurysms between January 2015 and December 2024 were identified from prospectively maintained registries. Inclusion criteria comprised elective or urgent endovascular repair of aorto-iliac aneurysms in which an adequate distal sealing zone was not available without covering the IIA and suitability for the E-Liac device according to its instructions for use (IFU). Patients with a life expectancy < 1 year or hostile anatomy incompatible with the IFU were excluded. The primary end point was freedom from branch instability (occlusion/stenosis, kinking, or detachment of the bridging stent). Secondary end points included freedom from any endoleak, freedom from device-related reintervention, freedom from gluteal claudication, aneurysm-related and all-cause mortality, acute renal failure, and sac regression > 5 mm. Results: A total of 69 consecutive patients (68 male, 1 female, median age 72.0 years) received 74 E-Liac devices, including 5 bilateral implantations. The mean infrarenal aortic diameter was 45 mm and the mean CIA diameter 34 mm; 14 patients (20.0%) had a concomitant IIA aneurysm (>20 mm). Concomitant fenestrated or branched aortic repair was performed in 23% of procedures. Two patients received a standalone IBD without implantation of a proximal aortic endograft. Technical success was achieved in 71/74 cases (96.0%); three failures occurred due to inability to catheterize the IIA. Distal landing was in the main IIA trunk in 58 cases and in the posterior branch in 13 cases. Over a median follow-up of 18 (6; 36) months, there were four branch instability events (5.4%): three occlusions and one bridging stent detachment. Seven patients (9.5%) developed endoleaks (one type Ib, two type II, two type IIIa, and two type IIIc). Five patients (6.8%) required reintervention, and five (6.8%) reported gluteal claudication. There were seven all-cause deaths (10%), none within 30 days or related to aneurysm rupture; causes included COVID-19 pneumonia, acute coronary syndrome, melanoma, gastric cancer, and stroke. No acute renal or respiratory failure occurred. Kaplan–Meier analysis showed 92% (95% CI 77–100) freedom from branch instability in the main-trunk group and 89% (60–100) in the posterior-branch group (log-rank p = 0.69). Freedom from any endoleak at 48 months was 87% (95% CI 75–95), and freedom from reintervention was 93% (95% CI 83–98). Conclusions: In this multicenter cohort, the E-Liac branched endograft demonstrated high technical success and favorable early–mid-term outcomes. Preservation of hypogastric perfusion using E-Liac was associated with low rates of branch instability, endoleak, and reintervention, with no 30-day mortality or aneurysm-related deaths. These findings support the safety and efficacy of E-Liac for aorto-iliac aneurysm management, although larger prospective studies with longer follow-up are needed. Full article

Machine learning is increasingly applied to cardiovascular disease prediction yet reported performance metrics often appear implausibly high due to methodological errors. Recent work has reported nearly perfect predictive accuracy (≈99%) using a k-Nearest Neighbors (kNN) model on CDC heart-disease data. Such performance greatly exceeds typical BRFSS-based benchmarks and strongly indicates data leakage. In this commentary, we replicate and re-analyze the original workflow, showing that the authors applied the SMOTE-ENN resampling method prior to the train/test split, thereby allowing synthetic data generated from the full dataset to contaminate the test set. Combined with an excessively small neighborhood parameter (k = 2), this produced misleadingly high accuracy. It is noted that (1) with SMOTE-ENN performed globally, synthetic samples appear nearly identical to test points, leading to near-perfect classification, and (2) this kNN choice is unusually small for a dataset of this scale and further amplifies leakage bias. Correcting the workflow by restricting oversampling to the training data or using undersampling restores realistic results, reducing predictive accuracy to approximately 80%, confirming the inflation caused by pre-split resampling and aligning with literature norms. This case underscores the critical importance of rigorous validation, transparent reporting, and leakage-free pipelines in medical AI. We outline practical guidelines for avoiding such pitfalls and ensuring reproducible, realistic, and clinically reliable machine-learning studies. Full article

Fontan patients experience anatomical remodeling over time, yet the mechanisms driving these changes remain unclear. This study aimed to characterize full-route Fontan remodeling and evaluate whether observed morphological changes arise from somatic growth alone or from the combined influence of conduit properties, surgical design, thoracic anatomy, and mechanical forces. Five Fontan patients (four extracardiac, one lateral tunnel) underwent analysis using two MRI-derived 3D models obtained between 1 and 4 years apart. Directional displacement was assessed using 3D shape overlays, surface geometry was quantified using the Koenderink Shape Index (KSI), and patient-specific growth mapping estimated localized tissue dynamics. Statistical analyses included a one-sample t-test for mean anterior displacement, the Grubbs’ test for outlier detection, and the Wilcoxon signed-rank test for KSI comparisons across time points. All patients exhibited anterior displacement of the Fontan route, with a mean shift of 0.29″ ± 0.33″ and one significant outlier (lateral tunnel, 0.87″). Four of five patients showed increased convexity over time. Growth mapping revealed minimal, heterogeneous native-tissue expansion, with localized growth up to 0.2 mm/year. Individual remodeling trajectories varied and did not consistently align with localized anterior growth, indicating that Fontan route remodeling is highly individualized and cannot be explained by somatic growth alone. This retrospective longitudinal case series study highlights the value of quantitative 3D geometric tools for assessing subtle Fontan route remodeling and supports the feasibility of growth-aware, patient-specific modeling frameworks in single-ventricle physiology. Full article

Low QRS voltage relative to left ventricle (LV) thickness is one of the red flag characteristics in the diagnosis of cardiac amyloidosis, and it can be measured by specific indexes. Few studies have clearly defined the diagnostic threshold of voltage indexes for light chain amyloidosis cardiomyopathy (AL-CA) patients and other patients with LV hypertrophy. This case–control study analyzed electrocardiograms and echocardiograms of patients with AL-CA, hypertrophic cardiomyopathy (HCM), and hypertension left ventricular hypertrophy (HTN-LVH) seen at a single university center from 2008 to 2022. Low QRS voltage and three different precordial voltage indexes were evaluated. Diagnostic thresholds for rule-in and rule-out were calculated for AL-CA against each control group. A single voltage–mass ratio based on cross-sectional area (CSA) exhibited most accurate diagnostic accuracy, and the value of ≤1.72 aids the rule-in of AL-CA against other causes of left ventricular hypertrophy, providing a positive predictive value (PPV) of 86% versus HCM and 75% versus HTN-LVH. Full article

Background: Stage B heart failure (SBHF) increases the risk of symptomatic HF. Current guideline criteria for SBHF lack sex and ethnic thresholding and cardiac magnetic resonance (CMR) imaging cut-offs. We aimed to assess the prevalence of SBHF in a large cohort of people with type 2 diabetes (T2D) and healthy controls and propose a refined CMR definition for SBHF. Methods: Sex- and ethnic-specific thresholds for imaging criteria were derived from 373 healthy controls, who underwent CMR cine imaging. The current definition for SBHF and refined criteria was applied to our prospectively recruited and intensively phenotyped cohort of asymptomatic people with T2D and no evidence of cardiovascular disease. The prevalence of SBHF by different definitions was calculated and patient characteristics, including exercise capacity, were compared between those classified as Stage A vs. B HF. Finally, the refined criteria were also applied to the following two historical cohorts with symptomatic cardiovascular disease: severe aortic stenosis (AS n = 70) and HF with preserved ejection fraction (HFpEF n = 136). Results: A total of 423 people with T2D and a subset of 102 healthy controls who underwent echocardiography were prospectively recruited. Current guideline criteria classified 91% of those with T2D and 69% of the healthy controls as SBHF, suggesting a lack of specificity. Applying derived sex- and ethnicity-specific thresholds, combining echo and CMR measures, the prevalence of SBHF was reduced to 30% in those with T2D. Using the refined definition, those with Stage B HF had lower exercise capacity than those with Stage A HF (percentage predicted maximal oxygen consumption 81 ± 16% vs. 91 ± 20%, p < 0.001). Applying the refined definition to symptomatic AS and HFpEF participants classified 89% and 85% with abnormal cardiac remodelling. Conclusion: Current guideline criteria for SBHF are non-specific and likely of limited value in clinical practice. Refining these criteria with sex- and ethnic-specific thresholds may improve identification of those at risk of developing symptomatic disease. Further research is required to validate these criteria. Full article

For the past decade, cell-based therapies have been the focus of research to investigate their potential to treat ischemic heart disease. The translation to human clinical studies depends on the demonstration of therapeutic efficacy and safety, particularly when transplanted in the subacute and chronic post-MI phase. A number of studies were identified that reported the effect of hiPSC-CMs on cardiac outcomes when transplanted at least 7 days post-myocardial infarction. The mean sample size of the published studies was 30 (±17) animals with a mean follow-up duration of 51 (±37) days. hiPSC-CM transplantation enhanced systolic function through augmented myocardial contractility, decreased infarct size, attenuated ventricular remodeling, and enhanced angiogenesis in the infarct and border zones in both small and large animal models. This effect was enhanced by co-transplantation with cells of vascular or adipose origin and is associated with high expression of VEGF in most studies. Despite this effect, transplanted hiPSC-CMs were structurally immature with limited survival at the endpoint. Epicardial delivery was associated with better efficacy outcomes and lower rates of arrhythmia. No study reported teratoma formation or immune rejection. From the current literature, there appears to be no consensus on the extent to which hiPSC-CMs improved systolic function, nor the degree to which this arises directly from integration of the new myocardium or from a paracrine-mediated mechanism. The nature of this paracrine mechanism and ways to improve the maturity and survival of implanted cardiomyocytes are issues that have yet to be resolved. In summary, while therapeutic benefit from cell therapy is clear, further research is required to establish whether the key mechanisms require a cellular component. Full article

Background and objective: Evidence of percutaneous left atrial appendage closure (LAAC) and oral anticoagulants (OACs) in non-valvular atrial fibrillation (NVAF) patients with intermediate-to-borderline high stroke risk is scarce. We aimed to compare the efficacy and safety of these treatments in the latter clinical population. Methods: This retrospective cohort study included NVAF patients with CHA₂DS₂-VA scores of 1–2 and used 1:1 propensity score matching (184 patients per group) to compare efficacy and safety outcomes. The primary efficacy outcome was a composite of stroke, transient ischemic attacks, systemic embolism, and cardiovascular death during follow-up. Adverse safety events were categorized into peri-procedure (LAAC group) and non-procedural (both groups) events. Results: Over a mean follow-up of 48.93 ± 28.50 months, a total of 26 patients (7.07%) reached the primary composite efficacy endpoint. The LAAC group showed a significantly higher incidence of the efficacy endpoint compared to the OAC group (HR = 3.09; 95% CI 1.22–7.85; log-rank p = 0.01). Procedure-related events occurred in five LAAC patients (one contributing to primary endpoint), while non-procedural bleeding rates were similar (0.54% vs. 1.09%; p = 0.56). Subgroup analyses suggested concomitant ablation of NVAF in LAAC group did not significantly improve efficacy composite endpoints (HR = 0.47). Conclusions: In NVAF patients with intermediate-to-high stroke risk, OACs were more effective than LAAC in preventing thromboembolic events, with comparable rates of clinically relevant bleeding. Full article

Severe mitral regurgitation (MR) is one of the most common valvular heart diseases and is frequently associated with advanced left ventricular (LV) systolic dysfunction. Transcatheter edge-to-edge repair (TEER) offers effective symptom relief but may induce abrupt hemodynamic changes leading to afterload mismatch and acute LV failure. Levosimendan may help mitigate this complication by improving contractility, yet evidence supporting its use in this setting is scarce. Therefore, the aim of this study was to systematically evaluate the evidence on the effects of Levosimendan in patients with severe MR and LV dysfunction undergoing TEER. We performed a comprehensive search of PubMed, Embase, Scopus, and Google Scholar. Primary outcomes were postprocedural LV ejection fraction (LVEF) and systolic pulmonary artery pressure (sPAP). Secondary outcomes included procedural success, procedure duration, and in-hospital complications. Five studies comprising 315 patients (n = 141 Levosimendan, n = 174 controls) met the inclusion criteria. Pooled analysis showed no significant difference in postprocedural LVEF between Levosimendan-treated patients and controls (mean difference 0.45%, 95% CI [−1.46–2.35] p = 0.65) and no significant change from baseline. Similarly, postprocedural sPAP did not differ significantly. Procedural success was higher with Levosimendan, and procedure duration was shorter. These hypothesis-generating findings highlight the need for larger, prospective randomized trials to clarify the role of Levosimendan in this setting. Full article

Despite the efficacy of catheter ablation in preventing recurrences of atrial fibrillation (AF), the reasons for its lack of success in some patients remain unknown. The aim of this study was to try to identify a new predictor of AF recurrence following catheter-based treatment. This prospective study enrolled a cohort of patients with AF. Based on the results of a one-year follow-up, patients were divided into two groups: Group 1 (“vein-dependent” AF)—patients who achieved a successful outcome after 1–2 catheter ablation procedures—and Group 2 (“non-vein-dependent” AF)—patients with confirmed complete pulmonary vein isolation (PVI) or with an identified “non-vein-dependent” AF substrate. Blood samples were collected prior to the procedure and biobanked. Initial proteomic profiling of the serum using protein microarrays identified several candidate proteins, whose elevated levels were subsequently confirmed by an enzyme-linked immunosorbent assay (ELISA). This article presents data on one such protein—TAG72. A comparison of TAG72 levels (%OD normalized units) between Group 1 (“vein-dependent” AF) and Group 2 (“non-vein-dependent” AF) revealed a statistically significant increase in the latter group (128.9 [98.2; 284.4] vs. 84.3 [73.8; 92.1], p < 0.001). These data provide the first evidence implicating TAG72 in the pathogenesis of AF. Full article

Intravascular imaging (IVI) was introduced 35 years ago to assess coronary artery pathology and plaque vulnerability. However, from its first applications it became apparent that it can also be useful in percutaneous coronary intervention (PCI) planning and optimizing PCI results. In the early days of PCI, IVI was used to examine the efficacy of emerging endovascular devices and the vessel wall response to therapy, while in the drug-eluting stent (DES) era, IVI was used to guide DES implantation and assess final results post-intervention. The first studies assessing the role of IVI in guiding PCI with DES have failed to demonstrate a prognostic benefit for the use of IVI; however, more recent large-scale randomized trials have underscored its value in this setting. IVI, with its high resolution, allows optimal stent sizing, prompt identification and correction of common causes of stent failure, and it has been shown that it improves outcomes in complex procedures. This review summarizes the evidence supporting the role of IVI in PCI planning in DES era, synopsizes the studies that have highlighted the value of IVI in predicting stent failure, discusses the limitations of the first randomized trials that failed to demonstrate a prognostic benefit from its use, and presents the results of the more recent large-scale outcome studies that underscored its role in complex PCI planning. Full article

Background: Atrial dilated cardiomyopathy (ADCM) related to homozygous Natriuretic Peptide Precursor A (NPPA) pathogenic variants is an exceptionally rare inherited atrial cardiomyopathy characterized by progressive atrial enlargement, supraventricular arrhythmias, and eventual atrial standstill. Case summary: We report the case of a 9-year-old girl identified through population genetic screening as a homozygous carrier of the NPPA c.449G>A (p.Arg150Gln) variant who subsequently developed symptomatic paroxysmal atrial fibrillation (AF) at the age of 18. Although baseline cardiac investigations were normal, her current evaluation shows biatrial enlargement with preserved ventricular function. She underwent radiofrequency pulmonary vein isolation; however, recurrent symptomatic AF persists, requiring ongoing antiarrhythmic therapy and long-term oral anticoagulation (CHA₂DS₂-VA: 0; HAS-BLED: 0). Notably, patients with NPPA-related ADCM have a markedly increased thromboembolic risk due to progressive atrial mechanical failure, and anticoagulation should therefore be considered irrespective of conventional clinical risk scores. Discussion and conclusions: This case highlights the importance of genetic testing in young patients with atrial fibrillation and no underlying structural heart disease. The early identification of NPPA-related atrial dilated cardiomyopathy may aid in risk stratification and guide rhythm and anticoagulation management. Expanding genetic screening in select individuals with isolated atrial fibrillation may facilitate earlier diagnosis in this exceptionally rare condition. Full article

Apolipoprotein B (APOB) is a key structural component of atherogenic lipoproteins and one of the principal genes implicated in familial hypercholesterolemia (FH). However, APOB genetic variation remains poorly characterized in Latin American and admixed populations. In this study, we performed a descriptive analysis of APOB variants in 60 Ecuadorian mestizo patients with inherited cardiac conditions using next-generation sequencing (NGS) and genetic ancestry inference. A total of 227 APOB variants were identified, the majority of which were classified as benign (n = 220) or likely benign (n = 3) according to ACMG criteria, while three variants were classified as variants of uncertain significance (VUS). The most frequently observed variants included rs1042034, rs679899, rs676210, and rs1367117. Comparative allele-frequency analyses using ALFA and PAGE Latin American reference datasets demonstrated that the APOB variant frequencies observed in the cohort were comparable to those reported in other Latin American populations, reflecting the admixed genetic background of Ecuadorian mestizos, predominantly of Native American and European ancestry. No pathogenic APOB variants were detected. Although lipid measurements were not available and genotype–phenotype associations could not be assessed, this study provides the first comprehensive overview of APOB variation in Ecuadorian mestizo individuals. These findings expand population-specific genomic data for an underrepresented group and underscore the importance of regional reference datasets for accurate variant interpretation in admixed populations. Full article

Background: Coronary artery bypass grafting (CABG) is a well-established revascularization strategy for patients with multivessel coronary artery disease. The effectiveness of CABG is significantly influenced by antiplatelet therapy aimed at maintaining graft patency and reducing thrombotic complications. However, substantial inter-individual variability exists in platelet function responses to standard therapies such as aspirin and clopidogrel, leading to antiplatelet resistance. This variability has been linked to increased risks of myocardial infarction, stroke, and early graft failure. Platelet function testing (PFT) offers a potential strategy to identify resistance and guide more personalized antiplatelet therapy. This study aims to evaluate the association between perioperative platelet function test results and clinical outcomes following CABG. By assessing platelet responsiveness at multiple timepoints and correlating findings with postoperative events, the study seeks to determine whether PFT can stratify risk and improve patient management. Methods: This is a prospective, single-centre, observational cohort study conducted at a tertiary NHS cardiac surgery centre. Patients having elective or urgent isolated CABG will be enrolled and undergo perioperative PFT using the TEG6s system. Clinical outcomes will be monitored for 12 months postoperatively, with primary endpoints assessing the correlation between platelet function results and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints will include the prevalence of antiplatelet resistance, demographic predictors, and the feasibility of integrating PFT into clinical workflows. Results: This study will report the prevalence of aspirin and clopidogrel resistance in CABG patients based on TEG6s PFT, as well as the correlation between platelet function results and MACCE, postoperative bleeding, and the need for surgical re-exploration. Additionally, it will examine the associations between demographic and clinical factors—such as diabetes status, renal function, BMI, and surgical technique—and variability in platelet responsiveness. The feasibility of incorporating PFT into perioperative workflows will also be evaluated, assessing whether results could support personalized antiplatelet management in future clinical trials. Conclusions: Findings from this study will provide real-world evidence regarding platelet function variability in CABG patients and suggest that PFT may identify those at increased risk of thrombotic complications. This exploratory analysis supports the need for larger interventional trials aimed at optimizing individualized postoperative antiplatelet therapy to improve surgical outcomes. Full article

T1 mapping and extracellular volume (ECV) calculations in cardiac magnetic resonance (CMR) have the potential to identify early fibrosis that is not yet visible using late gadolinium enhancement; however, the need for same-day blood draws due to the temporal variations in hematocrit (Hct) limits the use of ECV. We aimed to determine the reproducibility of synthetic Hct and ECV using different published models among groups of subjects. Healthy subjects and those with diagnosed cardiac amyloidosis, sarcoidosis, and hypertrophic cardiomyopathy (HCM) scanned using a 1.5T scanner with native and post-contrast T1 maps and same-day Hct were included. Among 148 subjects, there was excellent reproducibility (all ICCs ~0.98) between synthetic and measured ECV across the six formulas, despite only modest reproducibility of synthetic/measured Hct (ICCs 0.52–0.66). The levels of accuracy predicting abnormal measured ECV were consistently excellent among the different synthetic ECV models. The difference in the CMR vendor used to generate models did not seem to affect the results of the comparisons. We conclude that synthetic ECV yielded excellent reproducibility compared with ECV calculated using measured hematocrit, possibly obviating the need for blood extraction in cardiac MRI settings without point-of-care Hct. Full article

Metformin, the most widely prescribed oral antihyperglycemic agent, is established as the first-line therapy for type 2 diabetes mellitus (T2DM) owing to its efficacy, affordability, and safety. Increasing evidence indicates that its benefits extend beyond glycemic control, encompassing cardiovascular protection and diabetes prevention in individuals at elevated cardiometabolic risk. Mechanistic studies demonstrate that metformin exerts pleiotropic effects through activation of AMP-activated protein kinase, modulation of the gut microbiota, inhibition of pro-inflammatory and oxidative stress pathways, and improvements in endothelial function, lipid metabolism, and insulin sensitivity. These actions address core drivers of atherosclerosis and metabolic dysfunction, many of which occur independently of glucose lowering. In patients with T2DM, the cardiovascular benefits of metformin are well recognized, including reductions in all-cause mortality and cardiovascular events. In individuals without diabetes but at high cardiovascular risk—such as those with prediabetes, obesity, or metabolic syndrome—evidence is more limited, as most data are derived from subgroup analyses or trials with surrogate endpoints. Nonetheless, consistent signals suggest that metformin may delay the progression from prediabetes to overt diabetes and potentially confer vascular protection, particularly in carefully selected high-risk populations. Clinical trials and meta-analyses have demonstrated that metformin reduces incident diabetes by approximately one quarter in high-risk adults, with stronger effects observed in younger, overweight individuals, women with prior gestational diabetes, and those treated for longer durations. However, uncertainties remain regarding its long-term cost-effectiveness, optimal dosing strategies, and cardiovascular benefits in non-diabetic populations. The ongoing VA-IMPACT trial (NCT02915198) is expected to clarify whether metformin reduces major cardiovascular events in prediabetic patients with atherosclerotic disease. Taken together, metformin represents more than an antidiabetic drug. Its pleiotropic mechanisms, favorable safety profile, and low cost support its potential integration into broader cardiometabolic prevention strategies, including primary prevention. Expanding its role beyond diabetes management may offer a cost-effective, widely accessible intervention with significant public health impact. Full article

Background: Early identification of irreversible pulmonary vascular remodeling in congenital heart disease-associated pulmonary arterial hypertension (C-PAH) is critical for optimizing surgical timing. Current noninvasive diagnostic methods are inadequate, and the lung microbiome and metabolome may provide novel insights into disease progression. Methods: We analyzed bronchoalveolar lavage fluid (BALF) from 47 children, including those with C-PAH (n = 15), CHD without PAH (C-NPAH, n = 16), and healthy controls (n = 16), using 16S rRNA gene sequencing and untargeted metabolomics. Differential microbial taxa and metabolites were identified, and their interactions with clinical indicators were assessed via Random Forest (RF) and Mediation Analysis. Results: C-PAH patients exhibited airway microbial dysbiosis, characterized by an elevated Firmicutes/Bacteroidetes (F/B) ratio and increased abundance of g_Lactobacillus. Metabolomic profiling revealed 88 differential metabolites between C-PAH and controls, and 3 between C-PAH and C-NPAH. N1-methylnicotinamide (MNAM) and 2-piperidone emerged as potential biomarkers. Mediation analysis showed that g_Eikenella influenced PAH indirectly through 2-piperidone (β = −0.376, p = 0.026), indicating a microbe–metabolite–host interaction. Conclusions: Integrative microbiome–metabolome profiling of BALF reveals potential biomarkers for C-PAH. These findings provide exploratory evidence that microbial and metabolic biomarkers, particularly 2-piperidone and MNAM, hold potential for the early, noninvasive identification of irreversible pulmonary vascular remodeling, but require further validation in independent cohorts. Full article

Background: Restenosis after coronary stent implantation remains a major clinical challenge, especially in patients with diabetes, long lesions, or multiple stents. Standard therapy with aspirin and P2Y12 inhibitors does not reliably prevent this complication. Objectives: We reviewed experimental and clinical evidence on cilostazol, a selective phosphodiesterase-3 inhibitor, as a strategy to reduce restenosis after percutaneous coronary intervention (PCI). Methods: Preclinical and clinical studies were critically appraised, focusing on the effects of cilostazol on vascular smooth muscle and endothelial cells, platelet aggregation, lipid metabolism, and restenosis rates. Results: Experimental models show that cilostazol inhibits smooth muscle proliferation and intimal hyperplasia after arterial injury. Clinical trials demonstrate reduced restenosis after balloon angioplasty and stent implantation compared with aspirin, ticlopidine, or clopidogrel. Although approved by the FDA for intermittent claudication, cilostazol remains underused in the prevention of coronary restenosis. Conclusions: Current evidence supports cilostazol as an effective adjunctive therapy to reduce restenosis following PCI. Wider adoption and further large-scale trials are warranted to better define its role in contemporary interventional practice. Full article

Ceramides are bioactive sphingolipids increasingly recognized as mediators of cardiometabolic disease and residual cardiovascular risk. Accumulating evidence from experimental and clinical studies indicates that specific ceramide species contribute to insulin resistance, endothelial dysfunction, myocardial injury, and adverse cardiovascular outcomes. In particular, long-chain ceramides (C16:0, C18:0, C20:0 Cer) are consistently associated with myocardial infarction, heart failure, and cardiovascular mortality, whereas very-long-chain ceramides (C22:0, C24:0 Cer) exhibit neutral or potentially protective associations. This narrative review integrates biochemical, experimental, and clinical evidence to examine ceramide metabolism, molecular diversity, and their emerging role as biomarkers for cardiovascular risk stratification. We also discuss ceramide-based risk scores and their potential clinical utility beyond traditional lipid parameters. Understanding the structure–function relationships of ceramides may support the development of novel diagnostic and therapeutic strategies in cardiovascular prevention. Full article

(1) Background: Endovascular therapy is widely used for lower limb peripheral artery disease (PAD), yet device performance varies across vascular territories due to anatomical and biomechanical differences. This study evaluated territory- and lesion-specific outcomes following contemporary endovascular strategies in a real-world cohort. (2) Methods: This retrospective single-center study included consecutive patients undergoing endovascular revascularization of the iliac, superficial femoral (SFA), or popliteal arteries between 2010 and 2023. The primary endpoint was 12-month binary restenosis (≥50% diameter loss) assessed by duplex ultrasonography, CT angiography, or invasive angiography. Secondary outcomes included target lesion revascularization and procedural complications. Kaplan–Meier analysis was used to evaluate restenosis-free survival. Multivariable Cox models were constructed separately for each vascular territory, adjusting for relevant clinical and anatomical covariates. (3) Results: A total of 283 lesions were included (iliac n = 135; SFA n = 145; popliteal n = 102). At 12 months, restenosis rates differed substantially by treatment modality and arterial territory. In the iliac segment, covered stents demonstrated the lowest restenosis (12.8%), whereas in the SFA, interwoven nitinol stents yielded the most favorable profile (15.4%). In the popliteal artery, drug-coated balloons were associated with the lowest restenosis rate (16.7%). In multivariable analysis, covered stents (iliac), interwoven nitinol stents (SFA), and drug-coated balloons (popliteal) were independently associated with lower restenosis risk. Procedural success was high and complication rates were low. (4) Conclusions: Endovascular device performance is strongly influenced by arterial territory and lesion characteristics. Tailoring the treatment strategy to vessel biomechanics and lesion morphology may optimize mid-term patency in lower limb PAD. Larger prospective studies are warranted to validate these findings. Full article

Total Coronary Revascularization via left Anterior Thoracotomy (TCRAT) represents a modern evolution of sternum-sparing, on-pump multivessel coronary artery bypass grafting. In this review, we will summarize the historical development, detail the surgical principles, and provide a comprehensive overview of the clinical outcomes of TCRAT. The technique combines cardiopulmonary bypass using peripheral arterial as well as venous cannulation and cardioplegic cardiac arrest using transthoracic aortic cross-clamping with surgical access through a left anterior minithoracotomy. By applying special slinging and rotational maneuvers, both a stable exposition of all coronary territories—in particular those of the right and the circumflex coronary artery—and a quiet, bloodless operating field enable complete anatomical revascularization and complex coronary surgery procedures, including all variations in multiarterial grafting in unselected patients. Data from all published clinical series were integrated, and a weighted analysis of a total of 2282 patients was performed. TCRAT proved to be very effective with regard to complete anatomical revascularization and modern grafting strategies, and it showed excellent perioperative safety in an all-comers population. Both the 30-day mortality and perioperative stroke incidence were distinctly below 1.0%. Data from mid-term follow-up, although rare so far, are promising and compare well to those of the important RCTs. The TCRAT approach eliminates sternal complications completely and accelerates recovery. As an on-pump arrested-heart surgery, TCRAT inherently permits the combination of minimally invasive multivessel CABG with a variety of other cardiac operations, mainly the combination with valve procedures. The integration of robotic and endoscopic assistance represents the next evolutionary step. With its reproducibility and broad applicability, TCRAT holds strong potential to become a standard routine technique in the field of minimally invasive cardiac surgery. Full article