Atherosclerosis, a condition characterized by the accumulation of lipids and a culprit behind cardiovascular events, has long been studied. However, in recent years, there has been an increase in interest in its initiation, with researchers shifting focus from traditional pathways involving the vascular infiltration of oxidized lipids and towards the novel presence of chronic inflammatory pathways. The accumulation of pro-inflammatory cytokines, in combination with the activation of transcription factors, creates a positive feedback loop that drives the creation and progression of atherosclerosis. From the upregulation of the nod-like receptor protein 3 (NLRP3) inflammasome and the Notch and Wnt pathways to the increased expression of VEGF-A and the downregulation of connexins Cx32, Cx37, and Cx40, these processes contribute further to endothelial dysfunction and plaque formation. Herein, we aim to provide insight into the molecular pathways and mechanisms implicated in the initiation and progression of atherosclerotic plaques, and to review the risk factors associated with their development.

The L-type calcium channels (LTCCs) function as the main entry points that convert myocyte membrane depolarization into calcium transients, which drive every heartbeat. There is increasing evidence to show that maladaptive remodeling of these channels is the cause of heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Recent experimental, translational, and clinical studies have improved our understanding of the roles LTCC expression, micro-domain trafficking, and post-translational control have in disrupting excitation–contraction coupling, provoking arrhythmias, and shaping phenotype specific hemodynamic compromise. We performed a systematic search of the PubMed and Google Scholar databases (2015–2025, English) and critically evaluated 17 eligible publications in an effort to organize the expanding body of work. This review combines existing data about LTCC density and T-tubule architecture with β-adrenergic and Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) signaling and downstream sarcoplasmic reticulum crosstalk to explain how HFrEF presents with contractile insufficiency and how HFpEF shows diastolic calcium overload and stiffening. Additionally, we highlight the emerging therapeutic strategies aimed at restoring calcium homeostasis such as CaMKII inhibitors, ryanodine receptor type 2 (RyR2) stabilizers, and selective LTCC modulators without compromising systolic reserve. The review establishes LTCC dysregulation as a single mechanism that causes myocardial dysfunction while remaining specific to each phenotype, thus offering clinicians and researchers a complete reference for current concepts and future precision therapy approaches in heart failure.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by structural abnormalities, arrhythmias, and a spectrum of genetic and clinical manifestations. Clinically, ARVC is structurally distinguished by right ventricular dilation due to increased adiposity and fibrosis in the ventricular walls, and it manifests as cardiac arrhythmias ranging from non-sustained ventricular tachycardia to sudden cardiac death. Its prevalence has been estimated to range from 1 in every 1000 to 5000 people, with its large range being attributed to the variability in genetic penetrance from asymptomatic to significant burden. It is even suggested that the prevalence is underestimated, as the presence of genotypic mutations does not always lead to clinical manifestations that would facilitate diagnosis. Additionally, while set criteria have been in place since the 1990s, newer understanding of this condition and advancements in cardiac technology have prompted multiple revisions in the diagnostic criteria for ARVC. Novel discoveries of gene variants predisposing patients to ARVC have led to established screening techniques while providing insight into genetic counseling and management. This review aims to provide an overview of the genetics, pathophysiology, and clinical approach to ARVC. It will also focus on clinical presentation, ARVC diagnostic criteria, electrophysiological findings, including electrocardiogram characteristics, and imaging findings from cardiac MRI, 2D, and 3D echocardiogram. Current management options—including anti-arrhythmic medications, device indications, and ablation techniques—and the effectiveness of treatment will also be reviewed.

Background/Objectives: Chronic aortic regurgitation (AR) can remain asymptomatic despite progressive myocardial damage. While current surgical guidelines rely heavily on left ventricular ejection fraction (LVEF) and symptoms, these measures may fail to detect subclinical myocardial dysfunction. Global longitudinal strain (GLS), a sensitive echocardiographic marker, has emerged as a potential early biomarker in valvular disease. Therefore, this systematic review aims to assess whether impaired GLS is significantly associated with adverse clinical outcomes including symptom onset, reduced LVEF, and the need for aortic valve intervention among patients with asymptomatic moderate to severe AR and preserved LVEF. Methods: This systematic review and meta-analysis followed PRISMA guidelines and was registered with PROSPERO (CRD42024579540). Comprehensive searches of PubMed, Embase, and the Cochrane Library were completed on November 28, 2024. Screening, deduplication, and blinding were conducted using Rayyan. Eligible studies included adults with chronic, asymptomatic moderate to severe AR and preserved LVEF who underwent GLS measurement. Risk of bias was assessed using the National Heart, Lung, and Blood Institute (NHLBI) tool. A random-effects meta-analysis was performed on studies reporting multivariate hazard ratios (HRs) and 95% confidence intervals. Results: Twelve studies (N = 3278) were included in the systematic review, and four studies (n = 1125) were eligible for meta-analysis. Impaired GLS was significantly associated with adverse outcomes, yielding a pooled HR of 1.359 (95% CI: 1.106–1.668; p = 0.003). Heterogeneity was substantial (I² = 77%), and the 95% prediction interval ranged from 0.553 to 3.340, indicating potential variability in future settings. Conclusions: GLS is a promising prognostic biomarker for identifying subclinical cardiac dysfunction in asymptomatic moderate to severe AR with preserved LVEF. Its use may enhance early risk stratification and optimize timing for surgical intervention. Larger prospective studies are needed to validate specific GLS thresholds for clinical decision-making.

Although arrhythmogenic right ventricular cardiomyopathy (ARVC) has been a well-described entity, the condition still remains a growing topic in research. Clinically, ARVC is structurally distinguished by right ventricular dilation due to increased adiposity and fibrosis in the ventricular walls, and it manifests as cardiac arrhythmias ranging from nonsustained ventricular tachycardia to sudden cardiac death. Its prevalence has been estimated to range between 1 in every 1000-5000 people, with its large range being attributed to the variability in genetic penetrance from asymptomatic to significant burden. It is even suggested that the prevalence is underestimated, as the presence of genotypic mutations does not always lead to clinical manifestations that would facilitate diagnosis. Additionally, while set criteria have been in place since the 1990s, newer understanding of this condition and advancements in cardiac technology have prompted multiple revisions in the diagnostic criteria for ARVC. Known and newer discoveries of gene variants predisposing patients to ARVC have led to established screening techniques while providing insight into genetic counseling and management. This review will cover important information regarding the genetics and pathophysiology of ARVC. It will also focus on clinical presentation, ARVC diagnostic criteria, electrophysiological findings, including electrocardiogram characteristics, and imaging findings from cardiac MRI, 2D, and 3D echocardiogram. Current management options—including anti-arrhythmic medications, device indications, and ablation techniques—and the effectiveness of treatment will also be reviewed.