Introduction: Pulmonary Arterial Hypertension (PAH) is characterized by progressive pulmonary vascular remodeling, in which Pulmonary Arterial Endothelial Cell (PAEC) dysfunction and inflammation play important roles. The gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) has been associated with PAH and vascular inflammation, but the relationship between TMAO, PAEC pyroptosis, and post-translational regulation of Caspase-1 in PAH remains incompletely understood. The association between elevated TMAO and PAEC pyroptosis and SUMOylation-related Caspase-1 signaling in monocrotaline (MCT)-induced PAH was investigated. Methods: PAH was induced in rats by a single intraperitoneal injection of MCT (60 mg/kg). Hemodynamic parameters, right ventricular hypertrophy, and pulmonary vascular remodeling were assessed. Plasma TMAO, IL-1β, and IL-18 levels were measured, whereas GSDMD, Caspase-1, and SUMO-1 expression in CD31-positive pulmonary arterial endothelial cells was examined by immunofluorescence. Potential SUMOylation sites on Caspase-1 were predicted using SUMOplot, JASSA, and GPS-SUMO. 3,3-Dimethyl- 1-butanol (DMB), a microbial TMA production inhibitor, was used to reduce circulating TMAO levels. Results: MCT-induced PAH was accompanied by increased plasma TMAO levels, pulmonary vascular remodeling, right ventricular hypertrophy, increased GSDMD expression in CD31-positive PAECs, and elevated circulating IL-1β and IL-18. Bioinformatic analyses identified several putative SUMOylation sites on Caspase-1, with K256 showing a high prediction score. SUMO-1 and Caspase-1 expression were also increased in PAECs from MCT-treated rats. DMB treatment reduced circulating TMAO levels and attenuated hemodynamic abnormalities, right ventricular hypertrophy, and pulmonary vascular remodeling. These changes were accompanied by reduced GSDMD, SUMO-1, and Caspase-1 expression and lower plasma IL-1β and IL-18 levels. Discussion: Elevated circulating TMAO in MCT-induced PAH was accompanied by increased GSDMD, SUMO-1, and Caspase-1 expression in PAECs and elevated plasma IL-1β and IL-18 levels, whereas reduction of TMAO by DMB attenuated these molecular changes together with pulmonary vascular remodeling. These findings extend the previously recognized association between TMAO and PAH by linking elevated TMAO to pyroptosis-associated alterations in the pulmonary arterial endothelium. The coordinated changes in SUMO-1 and Caspase-1, together with the bioinformatic prediction of potential SUMOylation sites on Caspase-1, further suggest the possible involvement of SUMOylation-related Caspase-1 signaling. However, direct SUMO conjugation of Caspase-1 and modification of the predicted K256 site were not experimentally demonstrated; therefore, this regulatory mechanism remains a hypothesis requiring further validation. Conclusion: Elevated TMAO is associated with enhanced PAEC pyroptosis-related signaling and coordinated increases in SUMO-1 and Caspase-1 expression in MCT-induced PAH. Reducing circulating TMAO with DMB attenuates these molecular abnormalities, pulmonary hemodynamic alterations, right ventricular hypertrophy, and pulmonary vascular remodeling. These findings support a potential link between TMAO and SUMOylation-related Caspase-1 signaling in PAH and identify this pathway as a candidate mechanism for future investigation.
Abstract: Coronary Artery Calcium (CAC) scoring has become a central tool for detecting subclinical atherosclerosis and refining cardiovascular risk assessment, particularly in individuals with intermediate or atypical risk profiles. Traditional risk models such as the ASCVD Pooled Cohort Equations remain foundational but have important limitations, especially in younger adults and those with nontraditional risk patterns. CAC scoring provides direct visualization of atherosclerotic burden and can outperform serum biomarkers in predicting cardiovascular events. Recent cohort data suggest that CAC can be detected decades earlier than current guideline thresholds imply, and that early CAC presence and progression carry significant prognostic value, although evidence to support routine screening below current guideline-recommended age thresholds remains investigational rather than established practice. With advances in imaging technology and expanding population-based evidence, CAC scoring is evolving from a decision aid into an increasingly central tool in preventive cardiology, one whose benefits must be weighed against radiation exposure, incidental findings, overdiagnosis, and cost. This review summarizes current evidence on the biology of coronary calcification, available imaging techniques, CAC scoring systems, and the clinical application and limitations of CAC in primary prevention of cardiovascular diseases and situates guideline-endorsed uses of CAC alongside areas that remain hypothesis-generating.
INTRODUCTION:Traditional volumetric assessment methods have limitations in the management of HF. The clinical value of impedance-guided monitoring (including bioelectrical impedance analysis [BIA], lung/thoracic impedance [LI], or intrathoracic impedance monitoring [IIM]) for quantifying extracellular fluid status remains controversial. This study aims to systematically evaluate the effect of impedance-guided fluid management on rehospitalization rates, mortality, and other outcomes in patients with HF. METHODS:PubMed, Embase, and Web of Science were searched from inception to May 31, 2025, for randomized controlled trials (RCTs) comparing impedance-guided fluid therapy with standard care in patients with HF. This review was conducted in accordance with the PRISMA guidelines. RESULTS:A total of 4 RCTs or secondary analyses of RCTs involving 650 patients with HF (impedance- guided group: 326 cases) were included. The risk of rehospitalization for HF was reduced without statistical significance in the impedance-guided group (OR: 0.73, 95% CI: 0.22- 2.48), while the risk of mortality for HF demonstrated a statistically significant reduction (OR: 0.33, 95% CI: 0.20-0.56), though these findings should be interpreted with caution given the limited number of included studies. The impedance-guided group demonstrated positive trends in reducing the incidence of acute kidney injury (AKI), lowering N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and improving quality of life. These outcomes were not subjected to analysis due to data heterogeneity. DISCUSSION:This meta-analysis suggests that impedance-guided fluid management did not demonstrate a statistically significant reduction in HF rehospitalization in the pooled analysis, though a consistent directional trend was observed. However, the statistics about HF-related mortality among patients with HF showed that impedance-guided fluid therapy potentially provided a tool for more precise volume management. Also, these findings are based on a limited number of studies with methodological heterogeneity. CONCLUSION:Impedance-guided fluid management may represent a potential adjunct for reducing rehospitalization in patients with HF. Given the methodological heterogeneity and small number of included studies in this research, future large-scale, high-quality RCTs are needed to confirm these results in clinical practice.
INTRODUCTION:Conduction System Pacing (CSP) is a physiologic alternative to right ventricular pacing and may be advantageous in Cardiac Amyloidosis (CA), where conduction disease and septal infiltration are common. METHODS:A systematic review of 9 published studies, including 7 case reports or small series and 2 retrospective cohorts, identified 59 patients with CA who underwent CSP. RESULTS:Left bundle branch area pacing was the predominant technique. Implant success was high overall, ranging between 80 and 95%, with acute capture thresholds between 0.5 and 1.0 V at 0.5 ms and stable performance during follow-up. Paced QRS duration was typically 120-140 ms, representing QRS narrowing in most patients. In individual cases, improvement in New York Heart Association class, natriuretic peptide levels, and left ventricular ejection fraction was observed; however, cohort data demonstrated stable systolic function (45.5% to 41.9%) and unchanged NT-proBNP concentrations. Heart failure hospitalization occurred in 17-35% of patients, and mortality was limited to disease progression in AL amyloidosis. No device-related complications were reported. DISCUSSION:CSP in cardiac amyloidosis appears technically feasible and electrically stable in CA and may mitigate the deleterious effects of chronic right ventricular pacing. However, reproducible and longitudinal clinical benefit has not been demonstrated. CONCLUSION:Conduction system pacing in cardiac amyloidosis is feasible with favourable electrical parameters, but its clinical utility remains uncertain. Larger prospective registries are required to define its role relative to conventional biventricular pacing.
INTRODUCTION:The use of cardiovascular magnetic resonance (CMR) T1 mapping is becoming the dominant method for quantitatively characterizing diffuse tissue abnormalities in the myocardium that cannot be detected by traditional late gadolinium enhancement (LGE). This review provides a comprehensive overview of recent technical advances in T1 mapping, including a critical evaluation of the different acquisition techniques and their clinical applications. It also examines the role of artificial intelligence (AI) in the interpretation of T1 mapping data. It discusses its potential impact on clinical implementation and the translation of T1 mapping into routine practice. METHODS:A narrative review of the current literature related to T1 mapping was conducted using PubMed and Scopus. The search focused on T1 mapping techniques, including their development, normal ranges, clinical applications, and AI approaches to T1 mapping image analysis. RESULTS:Differentiation among T1 mapping techniques (MOLLI, SHMOLLI, SASHA, SMART1Map) based on accuracy, robustness, and acquisition limitations can influence their use in clinical practice. The literature indicates considerable variability in the T1 normal range, which is attributed to sequence type, magnetic field strength, manufacturer, and patient characteristics, making it challenging to create a universal reference range. From a clinical perspective, T1 mapping helps evaluate cardiomyopathy, infiltrative and ischemic disease (including myocarditis), as it shows improved ability to detect diffuse myocardial involvement compared to LGE alone. AI algorithms may be useful for automating segmentation, reducing motion artefacts, and improving measurement consistency. DISCUSSION:Despite its considerable clinical value, the broader implementation of T1 mapping remains challenged by variations in acquisition protocols and the lack of universally standardized reference values. Artificial intelligence may help mitigate some of these limitations by enhancing measurement consistency and facilitating automated image analysis. Nevertheless, further validation studies and greater harmonization across imaging platforms are still necessary before AI-driven approaches can be fully integrated into routine clinical practice. CONCLUSION:T1 mapping represents a valuable non-invasive technique for myocardial tissue characterization. Although AI has the potential to enhance reproducibility, improve image quality, and streamline workflow, broader clinical adoption remains contingent upon further efforts. These include the standardization of acquisition and analysis methods, validation in large multicenter cohorts, and the attainment of regulatory approval.
