Background: Lipoprotein(a) (Lp(a)) is a genetically determined lipid particle associated with atherosclerotic cardiovascular disease. Despite growing evidence supporting the clinical relevance of Lp(a) in cardiovascular risk stratification and the emergence of potential therapies targeting elevated Lp(a) levels, Lp(a) testing remains underutilized, with reported rates below 20-30%. This study aims to explore Lp(a) levels in the Lebanese population and their association with the vascular and metabolic burden of diseases. Methods: We conducted a retrospective observational study of patients who underwent Lp(a) level testing at the American University of Beirut Medical Center between 2010 and 2023. Data were extracted using the EPIC electronic medical record system, and statistical analyses were performed using IBM SPSS Statistics Version 28. Results: This study included 456 patients; the mean age was 50 ± 13, and the mean Lp(a) level was 25 ± 28 mg/dL. Mean Lp(a) was higher in females than in males (28 ± 32 mg/dL versus 23 ± 25 mg/dL), and 25.9%, 12.9%, and 7.6% of the population had Lp(a) levels ≥ 30, ≥50, and ≥70 mg/dL respectively. Logistic regression analysis showed no significant association between Lp(a) levels and cardiovascular factors including dyslipidemia, hypertension, coronary artery disease, previous coronary artery bypass graft, and previous myocardial infarction. Similarly, no significant correlation was found between Lp(a) and LDL, HDL, total cholesterol, triglyceride, and HbA1c. Subgroup analysis showed a significant relationship between Lp(a) levels > 50 mg/dL and atrial fibrillation. Conclusions: This study explores the distribution of Lp(a) levels in a Middle Eastern tertiary-care population and provides population-specific descriptive data, addressing an important gap in the existing literature.

Progression in understanding the relationships among cardiovascular, kidney, and metabolic diseases necessitates reappraising these concepts. Here, this narrative review explains the evolution of the ideas behind cardiovascular-kidney-metabolic syndrome (CKMS), focusing both on the impact of kidney disease on the cardiovascular system and metabolic syndrome and, conversely, on the effects of metabolic syndrome on cardiovascular and kidney diseases. Merging these concepts has resulted in a holistic approach more pertinent to managing the increased pressure from civilization diseases. In light of recent guidelines, early laboratory assessment is critical for risk stratification by improved patient classification, enabling individualized therapeutic strategies. Moreover, understanding the molecular mechanisms common to these systemic disorders not only enhances diagnostic accuracy but also facilitates the implementation of preventive measures that target multiple organ pathologies simultaneously. This review summarizes selected laboratory parameters that may support the diagnosis and management of cardiovascular-kidney-metabolic syndrome, aligning current knowledge with emerging clinical recommendations.

We are pleased to introduce the Special Issue of the Journal of Clinical Medicine, dedicated to "Recent Clinical Advances in Cardiac Rehabilitation", which addresses one of the most critical topics in secondary prevention of cardiovascular diseases [...].

Background/Objectives: Synthetic artificial intelligence (AI) is increasingly used in cardiovascular medicine to generate realistic clinical data from limited samples while preserving patient privacy. Despite its promise, concerns remain regarding the clinical reliability of synthetic datasets, which hampers their integration into routine practice. This article introduces the TIMA method (Team-Implementation Multidisciplinary Approach), designed to involve clinicians directly in every phase of synthetic data development. The objective of this work is to describe the TIMA framework and to illustrate how structured clinician-data scientist collaboration can enhance the clinical robustness and plausibility of synthetic AI outputs. Methods: The TIMA approach structures the synthetic data generation workflow around continuous interaction between clinicians and data scientists. Cardiologists define clinical constraints, verify inter-variable relationships, and assess the coherence and plausibility of generated records. The framework is illustrated through multiple cardiology use cases, including atrial fibrillation risk prediction and surgical mortality estimation in infective endocarditis, to demonstrate its adaptability across different clinical contexts. Each phase includes iterative validation steps aimed at ensuring alignment with established clinical knowledge rather than reporting quantitative performance outcomes. Results: Application of the TIMA framework supported the development of synthetic datasets that adhered more closely to clinical logic and domain-specific constraints. Clinician-data scientist collaboration enabled early detection of implausible variable interactions, improved interpretability of synthetic data patterns, and enhanced internal consistency across different cardiology-oriented scenarios. Conclusions: TIMA represents a scalable and replicable methodological model for integrating synthetic AI into cardiology by embedding clinical expertise throughout the data generation process. Its structured, multidisciplinary workflow supports the production of synthetic data that is not only statistically coherent but also clinically meaningful, thereby strengthening trust and reliability in AI-assisted cardiovascular research.

Frailty is a multidimensional state of reduced physiological reserve that is increasingly recognized as a major determinant of outcomes in cardiovascular diseases (CVDs). As populations age and cardiometabolic multimorbidity becomes more prevalent, understanding how frailty interacts with CVD pathology has important implications for risk stratification, clinical decision-making, and patient-centered care. Across diverse cardiovascular conditions and interventions, frailty independently predicts higher risks of mortality, major adverse cardiovascular events (MACE), rehospitalization, procedural complications, functional decline, and reduced quality of life. Shared biological mechanisms-including chronic inflammation, sarcopenia, endothelial dysfunction, and the effects of multimorbidity and polypharmacy-help explain the strong and often bidirectional relationship between frailty and CVD, one that is reported by recent data to be multiplicative as well as additive. Importantly, frailty demonstrates prognostic value beyond traditional risk factors and varies in predictive performance depending on the assessment tool used. Finally, frailty should not be viewed as immutable; evidence shows that appropriate conditioning may slow the decline or even reverse frail or prefrail states. This narrative review aims to synthesize contemporary evidence on frailty definitions and assessment, epidemiology, mechanistic pathways linking frailty with CVD, associated outcomes, prognostic value, and emerging interventions relevant to CVD prevention and management.

Background/Objectives: Coronary artery disease (CAD) remains one of the leading cardiovascular diseases worldwide. While obstructive CAD is well characterized and managed, identification of patients with non-obstructive CAD (NOCAD) remains challenging. Unlike the coronary vasculature, the eye's microcirculation can be easily and non-invasively assessed. Therefore, this systematic review summarized the ophthalmological diagnostic methods used to assess microvascular alterations associated with coronary microvascular dysfunction (CMD), angina with non-obstructive coronary arteries (ANOCA), or ischemia with non-obstructive coronary arteries (INOCA). Methods: According to PRISMA guidelines, PubMed/MEDLINE and Embase databases were screened by two independent reviewers from inception to 25 November 2025. Original articles that examined ophthalmological microvascular changes by any method in adults with CMD or its subtypes were included. The quality of the studies was assessed using the JBI Critical Appraisal Checklist. Results: Of 101 identified articles, nine studies met the inclusion criteria, comprising 1894 patients. Optical coherence tomography angiography was the most frequently used imaging modality, followed by optical coherence tomography, slit-lamp smartphone imaging, and fundus photography. Five investigations employed blinded image analysis, three did not, and one study used it partially. Four studies used semi-automated measurements, four employed fully automated methods, and one study applied manual and automated measurements for different parameters. Conclusions: Despite a limited number of studies, retinal and conjunctival microvascular alterations helped differentiate CAD subtypes and may reflect systemic microcirculatory impairment among patients with ANOCA/INOCA. Ophthalmological imaging techniques have the potential to serve as non-invasive tools for detecting microvascular alterations associated with CMD in ANOCA and INOCA patients. PROSPERO Registration Number: CRD420251239875.

Acute kidney injury (AKI) is a frequent and prognostically relevant complication of COVID-19. However, reliance on static creatinine values or binary AKI definitions may overlook clinically meaningful early renal dynamics. We evaluated whether early renal function trajectories within the first 24-48 h of hospitalization provide incremental prognostic information.

We conducted a retrospective, single-center cohort study of adults hospitalized with laboratory-confirmed COVID-19 between December 2020 and December 2021. Early renal function patterns were defined using KDIGO-based changes in serum creatinine between admission and 24-48 h, classifying patients as stable, early improvement, or early deterioration. The primary outcome was in-hospital mortality. Multivariable logistic regression adjusted for age, sex, chronic kidney disease, comorbidities, inflammatory burden (C-reactive protein), nutritional status (albumin), pulmonary involvement, and treatment variables.

Among 721 patients, 65.2% had stable renal function, 22.5% had early improvement, and 12.3% had early deterioration. In-hospital mortality differed significantly across dynamic patterns (p = 0.007). Mortality was lowest in the stable group (35.1%) and higher in both early improvement (48.1%) and early deterioration (44.9%). After multivariable adjustment, early improvement remained independently associated with higher in-hospital mortality compared with stable renal function (adjusted OR 1.53, 95% CI 1.03-2.28), while early deterioration showed a directionally similar but non-significant association. Early improvement was also associated with higher AKI burden and increased need for acute de novo hemodialysis.

Early renal function change patterns within the first 24-48 h of hospitalization carry prognostic value beyond static creatinine measures. Apparent early creatinine improvement may reflect recovery from prior injury or systemic instability rather than true renal recovery, identifying a subgroup at heightened risk. Classification based on early renal function assessment may enhance early risk stratification in hospitalized patients with COVID-19.

Patients with benign prostatic hyperplasia (BPH) have an increased risk of developing cardiovascular disease. Taking alpha-1 blockers is associated with an increased risk of major adverse cardiovascular events. Patients suffering from ischemic stroke (IS) may develop baroreflex and parasympathetic dysfunction-induced cerebral autoregulation impairment. The relationship between pharmacotherapy for BPH and the risk of recurrent IS remains unclear. The purpose of this study was to determine whether medications for BPH increase the risk of recurrent IS.

This is a retrospective cohort study. Data from patients diagnosed with IS between 2000 and 2015 was collected from Taiwan National Health Insurance Database. Newly diagnosed IS patients were identified (International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9-CM): 433-437). BPH patients with an ICD-9-CM of 600 were identified. The event observed was recurrent IS after the firstever IS. The factors associated with recurrent IS were assessed via Cox proportional hazards regression.

Recurrent IS was associated with BPH with an adjusted hazard ratio (HR) of 1.505 and a 95% confidence interval (CI) of 1.112-1.829, p < 0.001), and a competing risk model showed an adjusted HR of 1.544 (95% CI: 1.128-1.896, p < 0.001). The adjusted HR for treatment with alpha-1 blockers was 1.581 (95% CI: 1.16-1.915, p < 0.001), and increased risk with adjusted HR for treatment with high doses of 5-alpha reductase inhibitors over a long period of time are also at risk of recurrent IS.

These findings highlight the association between BPH incidence and the risk of recurrent IS. The pharmacotherapy for BPH in IS patients should take great care.

Myocardial and vascular injury secondary to SARS-CoV-2 infection and vaccination has emerged as a clinically relevant phenomenon, with distinct but overlapping mechanisms. Myocardial injury in COVID-19 results from a complex interplay between direct viral effects and immune-mediated inflammation, supported by histopathological studies revealing macrophage-rich infiltrates, microthrombosis, and supporting fibrosis in isolated areas. In contrast, vaccine-associated myocarditis-reported predominantly following mRNA vaccines-has a self-limiting clinical course, with mechanisms likely involving molecular mimicry, aberrant immune activation, or hypersensitivity reactions, although these pathways require further validation. Although mRNA vaccines have been associated with a small increase in myocarditis, particularly in young men, the risk is significantly lower than that associated with COVID-19 infection, and the cardiovascular benefits of vaccination far outweigh these rare adverse events in most populations. After the end of the pandemic, the number of patients with severe forms of COVID-19 has decreased significantly, but we consider that cardiac involvement remains an important issue for the acute and long-term prognosis of patients with SARS-CoV-2 infection. Our paper synthesizes the latest epidemiological and mechanistic evidence on the link between COVID-19, vaccination, and myocardial and/or vascular injuries, highlighting the clinical implications and providing practical recommendations for management, as well as future perspectives on risk assessment, targeted immunotherapy, advanced diagnostic tools, and long-term monitoring.

Background/Objectives. Ebstein's anomaly (EA), which accounts for fewer than 1% of congenital heart diseases, and atrioventricular canal defect (AVCD), present in approximately 4-5% of cases, exceptionally coexist, with this combination observed in fewer than 0.5% of patients with AVCD. We aim to report the oldest documented case of a 45-year-old female with the exceptionally rare combination of complete AVCD, EA, and right ventricular hypoplasia and to provide a concise review of these anomalies. Case presentation. Diagnosed in early childhood with a complete AVCD, pulmonary stenosis, and right ventricular (RV) hypoplasia, the patient underwent palliative surgical intervention with a modified Blalock-Taussig shunt at the age of 10 but did not receive subsequent regular follow-up. Over the ensuing 35 years, she remained largely untreated until presentation at 45 years of age with progressive exertional dyspnea, central cyanosis, and palpitations, corresponding to NYHA class III. Comprehensive multimodal imaging, including transthoracic echocardiography and cardiac magnetic resonance, revealed a complete AVCD with moderate-to-severe mitral regurgitation secondary to an anterior mitral leaflet cleft, severe tricuspid regurgitation, RV hypoplasia, and hallmark features of EA. Given the complex cardiac anatomy and the elevated surgical risk, the patient was considered inoperable, and a strategy of conservative management with multidisciplinary follow-up was implemented. Conclusions. This case highlights the exceptional longevity of a patient with the rare coexistence of complete AVCD, EA, and RV hypoplasia, surviving 45 years from diagnosis despite limited early intervention. It underscores the importance of lifelong follow-up in complex congenital heart disease and illustrates the role of multimodal imaging in assessing anatomy and guiding management when surgical options are high-risk or not feasible.