Frontiers in Cardiovascular Medicine最新文献

Background: Cardiac injury is a frequent and severe complication of COVID-19, yet the molecular mechanisms driving myocardial involvement remain incompletely understood. Dysregulated autophagy, telomerase/telomere biology, and endothelial dysfunction have emerged as biologically plausible and potentially interconnected contributors to COVID-19-associated cardiac injury.

Methods: We conducted a narrative, evidence-graded review of literature retrieved from PubMed and EMBASE, with Google Scholar used selectively as a supplementary source to capture emerging or cross-disciplinary studies. Eligible studies included human investigations and relevant animal models reporting genetic, epigenetic, or molecular alterations in autophagy, telomerase, or endothelial pathways with cardiovascular relevance. Non-English publications, studies lacking primary data, and reports unrelated to cardiovascular or systemic disease mechanisms were excluded. Evidence was stratified as Level I (direct evidence in COVID-19-associated cardiac injury), Level II (COVID-19 systemic or vascular evidence with plausible cardiac relevance), and Level III (non-COVID cardiovascular or systemic disease; hypothesis-generating).

Findings: Across viral, cardiovascular, and systemic contexts, key candidate genes, including ATG5, ATG7, Beclin-1, TERT, ICAM1, and eNOS -emerged as potential mediators of COVID-19-related cardiac injury. While endothelial activation is supported by relatively consistent clinical and molecular evidence, direct cardiac-tissue data linking autophagy and telomerase pathways to COVID-19-associated myocardial injury remain limited. These gaps highlight substantial uncertainty regarding causal mechanisms and inter-individual susceptibility.

Conclusion: Autophagy dysregulation, telomere attrition, and endothelial dysfunction represent convergent and biologically plausible mechanisms contributing to COVID-19-associated cardiac injury; however, current evidence remains largely indirect and derived from systemic or vascular compartments rather than cardiac tissue. Cardiac-specific, longitudinal genetic and epigenetic studies are required before these pathways can be considered for biomarker development or therapeutic targeting.

Background: Patients with atrioventricular block (AVB) who require pacemaker implantation frequently present with varying degrees of mitral regurgitation (MR), which may influence left ventricular (LV) remodeling and function. This study aimed to evaluate the impact of left bundle branch pacing (LBBP) versus right ventricular septum pacing (RVSP) on MR severity and LV performance.

Methods: A total of 137 consecutive AVB patients undergoing pacemaker implantation via LBBP or RVSP were retrospectively enrolled, after excluding those with previous mitral valve surgery or structural valvular abnormalities. Baseline and follow-up echocardiography evaluations were used to assess changes in MR severity and LV function. Subgroup analyses were performed among patients with baseline MR.

Results: Out of the total cohort, 88 patients (64.2%) successfully underwent LBBP, while the remaining 49 patients (35.8%) received RVSP when LBBP could not be achieved. The average age and sex distribution were similar between the two groups. Significant changes in MR area and severity at follow-up were observed in patients with LBBP compared to those with RVSP (P < 0.05). LBBP was independently associated with a higher likelihood of MR improvement among patients who received pacemaker implants [hazard rate (HR) = 0.238, CI = 0.105-0.538; P < 0.001]. At follow-up, those in the LBBP subgroup with moderate or severe MR demonstrated significantly shorter lead-TVA distance, increased left atrium diameters, poor LV ejection fraction (LVEF), and higher mitral E/A ratios (P < 0.05) compared with those in the none or mild MR subgroup. Among LBBP patients who showed a reduction in MR severity, there was a significant improvement in LV remodeling (ΔLVEDD) from the baseline (P = 0.009). Furthermore, these patients demonstrated a non-significant trend toward better LV function, reflected by greater changes in LVEF and E/A ratio (ΔLVEF and ΔE/A).

Conclusion: LBBP significantly reduced MR severity and improved LV remodeling and systolic function compared with RVSP. Moreover, LBBP and baseline LVEDD were independently associated with a reduction in MR severity among AVB patients undergoing pacemaker implantation, highlighting the superiority of LBBP as a preferred pacing strategy in this population.

Epicardial adipose tissue (EAT), a metabolically active visceral fat depot anatomically contiguous with the myocardium, has emerged as a critical mediator and promising metabolic therapeutic target in atrial fibrillation (AF), particularly in the context of obesity and diabetes mellitus. Pathological expansion and dysfunction of EAT promote AF through paracrine and vasocrine secretion of pro-inflammatory and pro-fibrotic cytokines, release of extracellular vesicles carrying arrhythmogenic cargo, direct infiltration, and modulation of local electrophysiology and autonomic signaling, thereby creating a substrate for atrial cardiomyopathy, fibrosis, electrical remodeling, and AF initiation/persistence. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), beyond their glucoregulatory and weight-loss benefits, exhibit potential cardioprotective effects that may be relevant to AF. Notably, GLP-1 receptors are expressed in both human EAT and atrial tissue. Preclinical and clinical studies suggest that GLP-1RAs may reduce EAT volume/thickness, potentially exceeding overall weight loss, attenuate EAT inflammation and fibrosis, improve cardiomyocyte calcium handling, mitigate oxidative stress, and suppress pulmonary vein ectopy, thereby potentially reducing AF susceptibility and recurrence post-ablation. While evidence from genetic studies, meta-analyses, and specific cardiovascular outcome trials (CVOTs) supports an association between certain GLP-1RAs and reduced AF risk, conflicting data exist regarding drug-specific effects, underscoring the need for further mechanistic and outcome research. Targeting EAT modulation via GLP-1RAs represents a compelling strategy to disrupt the obesity-diabetes-AF axis, although challenges remain in elucidating precise molecular mechanisms, standardizing EAT assessment, understanding response heterogeneity, and defining the clinical role of specific GLP-1RAs within AF management algorithms.

Objective: We conducted a scoping review of the literature focusing on combining biomarker detection and psychological evaluation according to the biopsychosocial approach to expound the multifactorial aspects of cardiological care.

Method: The search strategy was restricted to the 2014-2024 period. The core of this evidence-based analysis was the investigation of emotional and behavioural signs in cardiovascular (CV) risk/disease, the characteristics of adherence, and the efficacy of psychological treatments, especially highlighting the evidence of studies based on pre-post study design models for the investigation of psychological treatment efficacy in CV risk/disease.

Results: The literature includes systematic reviews and meta-analyses on patient education for the effectiveness of psychological interventions on psychosocial aspects and, consequently, on adherence to therapeutic prescriptions. From this perspective, it is important to adopt the biopsychosocial approach in the prevention, evaluation, and management of CV disease to understand all determinants of disease and multidisciplinary treatments. Topics are arranged into six themes: (1) epidemiological aspects of the included studies, (2) medical and psychological insights into CV research protocols from an integrated biopsychological perspective, (3) evidence of emotional and behavioural symptoms in CV risk, (4) evidence of emotional and behavioural symptoms in CV disease, (5) characteristics of adherence and psychological treatment, and (6) evidence of pre- and post-psychological treatment in CV risk/disease.

Conclusions: This review demonstrates that interventions are required to address patient factors, such as emotional, behavioural, and cognitive dimensions, that can improve the quality of life and adherence to medication. The link between physical and mental care is crucial and should be supported by extensive evidence-based outcomes in terms of tailored actions in health monitoring and management of CV risk/disease clinical targets.

Objective: Isolated nocturnal hypertension (INH) is an underrecognized blood pressure (BP) phenotype that is associated with a greater burden of cardiovascular risk despite normal daytime BP values. Metabolic disturbances together with sustained low-level inflammatory activity have been implicated in circadian BP abnormalities; however, data regarding simple and widely available biomarkers for identifying INH remain limited. The aim of the present study was to explore the relationships between metabolic indices and inflammatory markers in the context of INH and to further evaluate their potential value in predicting this condition.

Methods: We conducted a retrospective observational analysis at a single institution, including individuals who were evaluated using 24-hour ambulatory blood pressure monitoring (ABPM) between March 2024 and March 2025. INH was defined by a mean daytime BP below 135/85 mmHg in the presence of a mean nighttime BP of at least 120/70 mmHg. Demographic characteristics, laboratory parameters, C-reactive protein (CRP) levels and several metabolic indices-namely the triglyceride-glucose (TyG) index, its body mass index-adjusted form (TyG-BMI), and the atherogenic index of plasma (AIP)-were included in the analysis. Independent determinants of INH were examined using logistic regression models, while diagnostic accuracy was evaluated through receiver operating characteristic (ROC) curve analysis.

Results: The study population consisted of 241 participants, including 137 individuals with INH and 104 normotensive controls. Compared with the control group, those with INH exhibited significantly elevated TyG index, TyG-BMI, AIP and CRP levels (all p < 0.001). In multivariate logistic regression analysis, TyG-BMI [odds ratio [OR] 1.030, 95% confidence interval [CI] 1.002-1.059; p = 0.034] and CRP (OR 3.878, 95% CI 2.609-5.763; p < 0.001) remained independently associated with INH. ROC analysis demonstrated moderate discriminatory ability for TyG-BMI [area under the curve (AUC) 0.696, p < 0.001] and high discriminatory performance for CRP (AUC 0.861, p < 0.001).

Conclusion: Metabolic dysregulation and systemic inflammation are strongly associated with INH. TyG-BMI and CRP, derived from routinely available clinical data, may act as practical markers to identify individuals at increased risk for this clinically important BP phenotype.

The association between metabolic syndrome (MetS) and its components with cardiovascular disease (CVD) incidence represents a key global public health focus. However, given the unique dietary patterns of the population in southern Xinjiang, China, the differential effects of various Mets components on CVD onset and the interactions among these components remain poorly elucidated. This retrospective cohort study was conducted from 2018 to 2023, enrolling 144,966 participants from a county in southern Xinjiang with a median follow-up duration of 5.0 years. Cox proportional hazards regression and interaction analysis were applied to systematically explore the dose-response relationship between the number of abnormal values of the five core Mets indicators and CVD incidence. Among the 144,966 participants with no baseline CVD, the prevalence of Mets was 14.8%; Mets patients had a significantly higher mean age [(50.96 $\pm$ 13.28) vs. (40.30 $\pm$ 15.94) years, $P<0.001$ ]. During a median follow-up of 5.0 years, the incidence of CVD was 5.13% (51.3 cases/1,000 person-years) in the Mets group and 2.18% in the non-Mets group. After adjusting for confounders, elevated waist circumference (adjusted hazard ratio(aHR) = 1.12, 95%CI:1.08-1.15, $P<0.001$ ), elevated blood pressure (aHR = 1.24, 95%CI:1.20-1.29, $P<0.001$ ), and high blood glucose (aHR = 1.14, 95%CI:1.10-1.18, $P<0.001$ ) were independently associated with increased incident CVD events, while elevated triglycerides (aHR = 1.03, 95%CI:1.00-1.07, $P=0.065$ ) and low high-density lipoprotein cholesterol (aHR = 1.00, 95%CI:0.97-1.03, $P=0.8788$ ) showed no significant effect. Incident CVD events increased progressively with the number of abnormal Mets components (aHR = 1.22-2.72, $P$ for trend <0.001). Significant positive additive interaction was observed between waist circumference and blood pressure, but not between other component pairs. These findings underscore the value of integrated waist circumference and blood pressure management for CVD prevention in similar populations, though recall bias and limited causal inference exist due to the retrospective design.

Aims: Patients with acute coronary syndrome (ACS) who require coronary artery bypass grafting (CABG) remain at very high ischemic risk due to diffuse native disease and vein graft vulnerability. This study aimed to assess whether very early in-hospital initiation of evolocumab, a Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitor, on top of statins improves cholesterol control and mid-term cardiovascular outcomes in this high-risk population.

Methods: We performed a single-center, retrospective cohort study of 74 ACS patients undergoing isolated CABG (January 2022-July 2023) at Anthea Hospital GVM Care & Research, Bari, Italy. All received high-intensity statin therapy ± ezetimibe (STANDARD, n = 43), while 31 also received evolocumab 140 mg every two weeks (EVOLOCUMAB), initiated pre-angiography, preoperatively, or within 72 h post-CABG. The primary endpoints were LDL cholesterol (LDL-C) trajectory and attainment of <55 mg/dL at 24 months, and major adverse cardiovascular events (MACE: cardiovascular death, spontaneous myocardial infarction, or any revascularization).

Results: Seventy-one patients completed 24-month follow-up (EVOLOCUMAB n = 30; STANDARD n = 41). Baseline LDL-C was similar between groups (∼156 mg/dL). Evolocumab produced rapid and durable LDL-C reduction: at 24 months, mean LDL-C was 52 ± 11 mg/dL (EVOLOCUMAB) vs. 82 ± 18 mg/dL (STANDARD, p < 0.001). LDL-C < 55 mg/dL was achieved by 73.3% of EVOLOCUMAB vs. 29.3% of STANDARD patients (p < 0.001). MACE occurred in 10.0% (EVOLOCUMAB) vs. 24.4% (STANDARD), with lower risk in EVOLOCUMAB (HR 0.48, 95% CI 0.22-0.94; p = 0.035), mainly due to fewer repeat revascularizations. Evolocumab was well tolerated; no discontinuations due to adverse events were observed.

Conclusion: In ACS patients undergoing CABG, very-early in-hospital evolocumab plus statins achieved sustained LDL-C lowering and fewer adverse cardiovascular events over two years. Given the retrospective observational design, causal inference is limited and residual confounding cannot be excluded. These findings are hypothesis-generating and require confirmation in randomized trials.

Introduction: Implantable cardioverter-defibrillators (ICDs) reduce the risk of sudden cardiac death caused by ventricular tachycardia or ventricular fibrillation in patients with ischemic and non-ischemic cardiomyopathy. However, the cost-effectiveness of ICD implantation in Japanese patients with heart failure and reduced left ventricular ejection fraction remains unclear. This study aimed to evaluate the cost-effectiveness of ICD implantation in a Japanese setting.

Methods: A Markov model with 1-month cycles was developed to assess the cost-effectiveness of ICD implantation compared with conventional medical therapy. The analysis was conducted from the perspective of a public healthcare payer over a 30-year time horizon. Scenario analyses accounting for waning treatment effects were performed, as along with deterministic and probabilistic sensitivity analyses (PSA).

Results: In the base-case analysis, the incremental cost-effectiveness ratio (ICER) was US $29,838 per quality-adjusted life year (QALY). In the scenario analyses, the ICER increased to US $40,205 and $36,199 per QALY when the treatment effect began to wane after 5 and 10 years, respectively. ICD efficacy and battery longevity had the greatest influence on the ICER. PSA showed that the ICER per QALY ranged from US $19,472 at the 2.5th percentile to US $83,365 at the 97.5th percentile.

Conclusions: In the Japanese healthcare context, ICD implantation for primary prevention was found to be more cost-effective than the reference value. However, depending on several assumptions, the ICER may exceed the reference value. Sensitivity analyses highlighted the significant impact of the hazard ratio and battery longevity on cost-effectiveness. Further research is needed to identify subpopulations with significantly different cost-effectiveness outcomes.

Background: Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is critical for patients with severe cardiac or respiratory failure. Circuit damage, particularly at the proximal hard tube connector, can lead to complications such as blood leakage and hemodynamic instability. This case report examines the repair of a crack in the proximal hard tube connector during V-A ECMO treatment.

Case presentation: A 70-year-old female receiving peripheral V-A ECMO support via femoral cannulation for acute heart failure suffered a crack in the proximal hard tube connector, causing arterial blood leakage. The team performed an emergency repair using bone wax while maintaining low-flow ECMO operation. The repair was successful, and V-A ECMO support was continued without interruption, with stable hemodynamics.

Conclusion: Bone wax proved effective for repairing the V-A ECMO circuit crack in this case. The low-flow operation ensured uninterrupted V-A ECMO support and maintained hemodynamic stability, offering an alternative to full circuit replacement in similar cases.

Background: After coronary artery disease (CAD)-related myocardial injury, reactivation of the epicardium results in cardiac remodeling via paracrine secretion. However, the senescence-related genomic signature that reflects epicardial adipose tissue (EAT) and immune infiltration is not well understood.

Methods: Adipocyte-related differentially expressed genes (DEGs) were identified in EAT and subcutaneous adipose tissue (SAT) from patients with and without CAD. Immune cells and senescence-related DEGs in EATs were identified. A protein-protein interaction network was used to determine the hub genes. To validate these genes, a Gene Expression Omnibus (GEO) dataset investigation, single cell sequencing analysis and the validation of human sub-epicardial adipose and blood samples were performed. To investigate the mechanism, 3T3-L1 cells were used and differentiated to adipocytes and the hub genes were knocked-down and SASPs were determined.

Results: A Venn diagram was used to obtain 82 senescence-related DEGs, and the top 15-degree hub genes were explored. After validating using the GEO datasets and human sub-epicardial adipose samples, STAT3, SERPINE1, CDKN2A, DLG4, PTGS2, MDM2, LRP1, IRS2, PRKCD, CCND2, and CISH were found to be significantly expressed in the group with severe CAD. The hub genes, including STAT3, MDM2, LRP1, IRS2, PRKCD, CCND2, and CISH, were validated to be highly expressed in adipocytes in ischemic cardiomyopathy patients with end-stage heart failure. STAT3, LRP1, PRKCD, CCND2, and CISH were highly expressed in adipocytes under hypoxia. STAT3, LRP1, PRKCD, CCND2, and CISH were knocked-down in 3T3-L1 cell lines. SASPs, including IL1α, IL1β, and TNFα, decreased in hypoxic adipocytes after 5 hub genes knockdown. IL6 decreased in hypoxic adipocytes after STAT3, LRP1, and CISH knockdown, while IL6 increased in hypoxic adipocytes after CCND2 knockdown. The joint ROC of all 5 genes expression was 1.

Conclusion: These screened SASP hub genes, including STAT3, LRP1, PRKCD, CCND2, and CISH, may affect cell senescence after hypoxia, thus inducing CAD progression.