Background: The cardiovascular effects of nicotine-containing e-cigarettes are well-established; however, far less is known about nicotine-free formulations, which are often perceived as safer alternatives. Yet, these products generate complex aerosols that may still pose toxicological risks. Methods: Following the PRISMA 2020 guidelines, we systematically searched PubMed, Scopus, Web of Science, and the Cochrane Library up to 27 August 2025. Eligible studies included human and animal research on nicotine-free e-cigarettes evaluating vascular, hemodynamic, arrhythmic, oxidative, or inflammatory outcomes. Owing to the heterogeneity of the studies, the findings were synthesized qualitatively. Results: Nine studies met the inclusion criteria. Human trials consistently demonstrated acute vascular impairments, including endothelial dysfunction, oxidative stress, increased arterial stiffness, and transient blood pressure elevations. Experimental models corroborated these findings and further revealed systemic inflammation, mitochondrial injury, and developmental cardiotoxicity. Conclusions: Nicotine-free e-cigarettes produce reproducible acute cardiovascular effects. Although the long-term outcomes remain uncertain, preclinical evidence highlights biologically plausible mechanisms, including mitochondrial dysfunction and proarrhythmogenic potential. Until large-scale longitudinal studies have been conducted to clarify their risk profile, nicotine-free products should not be regarded as risk-free.

Background and Objectives: Cardiometabolic disease, a term encompassing metabolic syndrome (MS) and cardiovascular disease (CVD), represents a major and growing global health burden driven by interconnected metabolic and cardiovascular dysfunction. Emerging evidence suggests that the gut microbiota plays a central role in modulating metabolic, inflammatory, and cardiovascular (CV) pathways, giving rise to the concept of the heart–gut axis. However, human evidence integrating microbiome-mediated mechanisms across the cardiometabolic spectrum remains incompletely synthesized. This focused systematic review aimed to synthesize the current human evidence on microbiome-mediated mechanisms linking metabolic syndrome (MS) and related metabolic phenotypes with cardiovascular risk (CVR) and subclinical cardiovascular (CV) outcomes within the conceptual framework of the heart–gut axis. Materials and Methods: A systematic literature search was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library in accordance with PRISMA 2020 guidelines. Human observational and interventional studies evaluating gut microbiota composition, function, or microbiota-derived metabolites in relation to cardiometabolic, and CV outcomes were included. Risk of bias was assessed using the Cochrane RoB 2 and ROBINS-I tools, and findings were synthesized narratively. Results: Ten human studies published between 2016 and 2025 met the inclusion criteria. Across these studies, gut dysbiosis was consistently associated with adverse cardiometabolic risk profiles and subclinical CV outcomes, including insulin resistance, systemic inflammation, subclinical atherosclerosis, and CV prognosis in high-risk populations. Microbiota-derived metabolites, particularly trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), as well as emerging metabolites such as phenylacetylglutamine (PAGln) and imidazole propionate (ImP), were identified as key mediators linking metabolic syndrome and related metabolic disturbances with CVR and subclinical cardiovascular disease (CVD). Markers of intestinal barrier dysfunction and endotoxemia further supported the role of chronic low-grade inflammation within the heart–gut axis. Conclusions: Current human evidence supports the heart–gut axis as a biologically plausible and clinically relevant contributor to cardiometabolic disease. Gut microbiota-derived metabolites, intestinal barrier dysfunction, and systemic inflammation represent interconnected pathways linking MS with CVR. Advancing our understanding of these mechanisms may inform the development of microbiome-targeted strategies to complement established approaches for cardiometabolic and CV prevention.

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by microvascular dysfunction, immune activation, and progressive fibrosis affecting multiple organs, including the heart. Myocardial involvement represents an important but frequently underrecognized manifestation of SSc and may develop even in the absence of overt clinical symptoms. Cardiac manifestations include ventricular dysfunction, arrhythmias, conduction abnormalities, and heart failure, contributing substantially to morbidity and mortality. The underlying pathophysiology involves coronary microvascular dysfunction, immune-mediated myocardial inflammation, and progressive myocardial fibrosis, which often precede clinically apparent cardiac disease. This review aims to summarize the current understanding of myocardial involvement in SSc and to provide a comprehensive overview of contemporary multimodality cardiovascular imaging techniques for its detection, characterization, and risk stratification. A comprehensive overview of the current literature was conducted focusing on established and emerging cardiovascular imaging modalities for the evaluation of myocardial involvement in SSc. Particular attention was given to echocardiography, cardiac magnetic resonance (CMR), nuclear imaging techniques including positron emission tomography (PET) and single-photon emission computed tomography (SPECT), and cardiac computed tomography (CT). Recent advances in imaging biomarkers, parametric mapping, myocardial strain analysis, and emerging technologies such as artificial intelligence (AI), radiomics, and molecular imaging were also considered. Multimodality cardiovascular imaging plays a central role in the early detection and comprehensive assessment of myocardial involvement in SSc. Advanced imaging techniques enable improved identification of subclinical myocardial dysfunction, microvascular impairment, inflammation, and fibrosis. An integrated imaging approach combining echocardiography, CMR, nuclear imaging, and CT may facilitate earlier diagnosis, enhance risk stratification, and ultimately improve cardiovascular outcomes in patients with SSc.

Background: Cardiac involvement is a major cause of morbidity and mortality in systemic sclerosis (SSc). Autoantibodies may help identify patients at increased cardiovascular (CV) risk. This systematic review aimed to assess the predictive value of classical and emerging SSc-related autoantibodies for cardiac involvement and their integration with imaging and cardiac biomarkers. Methods: A comprehensive literature search was conducted in PubMed, Web of Science, Scopus, and the Cochrane Library up to 16 July 2025. Studies were included if they reported associations between specific autoantibodies and cardiac outcomes (e.g., myocardial fibrosis, conduction abnormalities, arrhythmias, ventricular dysfunction) in adult patients with SSc. Data extraction and quality assessment followed PRISMA 2020 guidelines. The review protocol was registered in PROSPERO (registration ID: CRD420251107782). Results: Anti-topoisomerase I antibodies were associated with myocardial fibrosis, subclinical systolic and diastolic dysfunction, elevated cardiac biomarkers, and pathological findings on cardiac magnetic resonance imaging. Anti-centromere antibodies were linked to conduction system abnormalities, particularly among older individuals. Anti-RNA polymerase III and anti-U3 ribonucleoprotein antibodies correlated strongly with arrhythmias and pericardial involvement. Novel autoantibodies, such as anti-heart antibodies and anti-intercalated disk antibodies, were linked to early myocardial injury, although their clinical utility requires further validation. Across studies, serological markers alone were insufficient to predict cardiac outcomes without concurrent imaging or biomarker evaluation. Conclusions: Autoantibody profiling plays an important role in CV risk stratification in SSc. Combining serological testing with cardiac biomarkers and advanced imaging enhances early detection and supports individualized monitoring. Further longitudinal studies are needed to validate predictive models and optimize patient outcomes.

Background/Objectives: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by chronic inflammation, microvascular injury, and fibrosis of the skin and internal organs. Although there are therapies, there is a need for treatments targeting early pathogenic mechanisms. Type I interferons (IFN-I) are key mediators linking immune dysregulation to vascular and fibrotic damage in SSc. This review summarizes the current evidence supporting IFN-I blockade with anifrolumab as a novel therapeutic strategy. Methods: A narrative review of preclinical, translational, and emerging clinical studies was conducted to evaluate the role of IFN-I signaling in SSc and the therapeutic potential of anifrolumab. Particular focus was placed on the IFN signature, upregulation of interferon-stimulated genes (ISGs), and the association with disease activity and organ involvement. Results: Anifrolumab, a fully human monoclonal antibody targeting the IFN-I receptor subunit 1 (IFNAR1), inhibits the signaling of all IFN-I isoforms, suppressing downstream JAK–STAT activation and ISG expression. Mechanistic data suggest that IFNAR blockade modulates vascular injury, immune activation, and fibrosis. Early findings and ongoing trials indicate potential benefits, particularly in patients with a high IFN signature or rapidly progressive cutaneous and cardiac disease. Conclusions: The current evidence supports IFN-I pathway inhibition as a promising approach in SSc. Ongoing trials will help to determine the clinical efficacy, safety, and optimal patient selection for anifrolumab in this rare but severe disease.

Background: Echocardiographic imaging has become central to planning and guiding percutaneous left atrial appendage occlusion (LAAO), particularly in patient populations in whom long-term anticoagulation is unsuitable. This systematic review synthesizes current evidence on transesophageal (TEE) and intracardiac echocardiography (ICE) guidance during LAAO, with special emphasis on outcomes in high-risk cohorts, including chronic liver disease (CLD) and prior gastrointestinal (GI) bleeding. Methods: Following PRISMA 2020 guidelines, four databases (PubMed, Scopus, Web of Science, and Cochrane CENTRAL) were searched up to 5 December 2025. Eligible studies included adult patients with atrial fibrillation (AF) undergoing percutaneous LAAO with intraprocedural echocardiographic guidance. Eight studies (n = 1739 patients) met the inclusion criteria. Data were synthesized qualitatively due to heterogeneity across devices, imaging protocols, and outcomes. Results: TEE was the predominant imaging modality (62.5%), providing high spatial resolution for transseptal puncture, device positioning, and peri-device leak (PDL) assessment. ICE-guided LAAO (25.0%) was associated with high procedural success and favorable safety profiles in selected observational cohorts, while reducing anesthesia requirements and fluoroscopy time. Across all studies, procedural success ranged from 93 to 100%, with low rates of major complications. Reported follow-up durations varied substantially across studies and were predominantly short- to mid-term, limiting assessment of long-term device-related outcomes. Evidence specific to patients with chronic liver disease and prior gastrointestinal bleeding was limited, with only two included studies directly evaluating these populations, while remaining insights were extrapolated from broader LAAO cohorts. In high-risk groups, LAAO remained feasible: cirrhotic patients demonstrated high implantation success with acceptable bleeding profiles, while patients with prior GI bleeding showed low recurrence after closure. Conclusions: Both TEE and ICE provide reliable intraprocedural imaging for LAAO, with ICE offering workflow and safety advantages in patients unsuitable for general anesthesia. The available evidence suggests that LAAO is a feasible and potentially safe therapeutic option in selected patients with CLD and prior GI bleeding, although direct data remain limited. Future studies should compare imaging modalities prospectively in high-risk cohorts and evaluate emerging 3D/4D ICE technologies.