Journal of Cardiovascular Development and Disease最新文献

Severe mitral regurgitation (MR) is one of the most common valvular heart diseases and is frequently associated with advanced left ventricular (LV) systolic dysfunction. Transcatheter edge-to-edge repair (TEER) offers effective symptom relief but may induce abrupt hemodynamic changes leading to afterload mismatch and acute LV failure. Levosimendan may help mitigate this complication by improving contractility, yet evidence supporting its use in this setting is scarce. Therefore, the aim of this study was to systematically evaluate the evidence on the effects of Levosimendan in patients with severe MR and LV dysfunction undergoing TEER. We performed a comprehensive search of PubMed, Embase, Scopus, and Google Scholar. Primary outcomes were postprocedural LV ejection fraction (LVEF) and systolic pulmonary artery pressure (sPAP). Secondary outcomes included procedural success, procedure duration, and in-hospital complications. Five studies comprising 315 patients (n = 141 Levosimendan, n = 174 controls) met the inclusion criteria. Pooled analysis showed no significant difference in postprocedural LVEF between Levosimendan-treated patients and controls (mean difference 0.45%, 95% CI [-1.46-2.35] p = 0.65) and no significant change from baseline. Similarly, postprocedural sPAP did not differ significantly. Procedural success was higher with Levosimendan, and procedure duration was shorter. These hypothesis-generating findings highlight the need for larger, prospective randomized trials to clarify the role of Levosimendan in this setting.

Background: Coronary artery bypass grafting (CABG) is a well-established revascularization strategy for patients with multivessel coronary artery disease. The effectiveness of CABG is significantly influenced by antiplatelet therapy aimed at maintaining graft patency and reducing thrombotic complications. However, substantial inter-individual variability exists in platelet function responses to standard therapies such as aspirin and clopidogrel, leading to antiplatelet resistance. This variability has been linked to increased risks of myocardial infarction, stroke, and early graft failure. Platelet function testing (PFT) offers a potential strategy to identify resistance and guide more personalized antiplatelet therapy. This study aims to evaluate the association between perioperative platelet function test results and clinical outcomes following CABG. By assessing platelet responsiveness at multiple timepoints and correlating findings with postoperative events, the study seeks to determine whether PFT can stratify risk and improve patient management.

Methods: This is a prospective, single-centre, observational cohort study conducted at a tertiary NHS cardiac surgery centre. Patients having elective or urgent isolated CABG will be enrolled and undergo perioperative PFT using the TEG6s system. Clinical outcomes will be monitored for 12 months postoperatively, with primary endpoints assessing the correlation between platelet function results and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints will include the prevalence of antiplatelet resistance, demographic predictors, and the feasibility of integrating PFT into clinical workflows.

Results: This study will report the prevalence of aspirin and clopidogrel resistance in CABG patients based on TEG6s PFT, as well as the correlation between platelet function results and MACCE, postoperative bleeding, and the need for surgical re-exploration. Additionally, it will examine the associations between demographic and clinical factors-such as diabetes status, renal function, BMI, and surgical technique-and variability in platelet responsiveness. The feasibility of incorporating PFT into perioperative workflows will also be evaluated, assessing whether results could support personalized antiplatelet management in future clinical trials.

Conclusions: Findings from this study will provide real-world evidence regarding platelet function variability in CABG patients and suggest that PFT may identify those at increased risk of thrombotic complications. This exploratory analysis supports the need for larger interventional trials aimed at optimizing individualized postoperative antiplatelet therapy to improve surgical outcomes.

Apolipoprotein B (APOB) is a key structural component of atherogenic lipoproteins and one of the principal genes implicated in familial hypercholesterolemia (FH). However, APOB genetic variation remains poorly characterized in Latin American and admixed populations. In this study, we performed a descriptive analysis of APOB variants in 60 Ecuadorian mestizo patients with inherited cardiac conditions using next-generation sequencing (NGS) and genetic ancestry inference. A total of 227 APOB variants were identified, the majority of which were classified as benign (n = 220) or likely benign (n = 3) according to ACMG criteria, while three variants were classified as variants of uncertain significance (VUS). The most frequently observed variants included rs1042034, rs679899, rs676210, and rs1367117. Comparative allele-frequency analyses using ALFA and PAGE Latin American reference datasets demonstrated that the APOB variant frequencies observed in the cohort were comparable to those reported in other Latin American populations, reflecting the admixed genetic background of Ecuadorian mestizos, predominantly of Native American and European ancestry. No pathogenic APOB variants were detected. Although lipid measurements were not available and genotype-phenotype associations could not be assessed, this study provides the first comprehensive overview of APOB variation in Ecuadorian mestizo individuals. These findings expand population-specific genomic data for an underrepresented group and underscore the importance of regional reference datasets for accurate variant interpretation in admixed populations.

T1 mapping and extracellular volume (ECV) calculations in cardiac magnetic resonance (CMR) have the potential to identify early fibrosis that is not yet visible using late gadolinium enhancement; however, the need for same-day blood draws due to the temporal variations in hematocrit (Hct) limits the use of ECV. We aimed to determine the reproducibility of synthetic Hct and ECV using different published models among groups of subjects. Healthy subjects and those with diagnosed cardiac amyloidosis, sarcoidosis, and hypertrophic cardiomyopathy (HCM) scanned using a 1.5T scanner with native and post-contrast T1 maps and same-day Hct were included. Among 148 subjects, there was excellent reproducibility (all ICCs ~0.98) between synthetic and measured ECV across the six formulas, despite only modest reproducibility of synthetic/measured Hct (ICCs 0.52-0.66). The levels of accuracy predicting abnormal measured ECV were consistently excellent among the different synthetic ECV models. The difference in the CMR vendor used to generate models did not seem to affect the results of the comparisons. We conclude that synthetic ECV yielded excellent reproducibility compared with ECV calculated using measured hematocrit, possibly obviating the need for blood extraction in cardiac MRI settings without point-of-care Hct.

Background: Early identification of irreversible pulmonary vascular remodeling in congenital heart disease-associated pulmonary arterial hypertension (C-PAH) is critical for optimizing surgical timing. Current noninvasive diagnostic methods are inadequate, and the lung microbiome and metabolome may provide novel insights into disease progression. Methods: We analyzed bronchoalveolar lavage fluid (BALF) from 47 children, including those with C-PAH (n = 15), CHD without PAH (C-NPAH, n = 16), and healthy controls (n = 16), using 16S rRNA gene sequencing and untargeted metabolomics. Differential microbial taxa and metabolites were identified, and their interactions with clinical indicators were assessed via Random Forest (RF) and Mediation Analysis. Results: C-PAH patients exhibited airway microbial dysbiosis, characterized by an elevated Firmicutes/Bacteroidetes (F/B) ratio and increased abundance of g_Lactobacillus. Metabolomic profiling revealed 88 differential metabolites between C-PAH and controls, and 3 between C-PAH and C-NPAH. N1-methylnicotinamide (MNAM) and 2-piperidone emerged as potential biomarkers. Mediation analysis showed that g_Eikenella influenced PAH indirectly through 2-piperidone (β = -0.376, p = 0.026), indicating a microbe-metabolite-host interaction. Conclusions: Integrative microbiome-metabolome profiling of BALF reveals potential biomarkers for C-PAH. These findings provide exploratory evidence that microbial and metabolic biomarkers, particularly 2-piperidone and MNAM, hold potential for the early, noninvasive identification of irreversible pulmonary vascular remodeling, but require further validation in independent cohorts.

Metformin, the most widely prescribed oral antihyperglycemic agent, is established as the first-line therapy for type 2 diabetes mellitus (T2DM) owing to its efficacy, affordability, and safety. Increasing evidence indicates that its benefits extend beyond glycemic control, encompassing cardiovascular protection and diabetes prevention in individuals at elevated cardiometabolic risk. Mechanistic studies demonstrate that metformin exerts pleiotropic effects through activation of AMP-activated protein kinase, modulation of the gut microbiota, inhibition of pro-inflammatory and oxidative stress pathways, and improvements in endothelial function, lipid metabolism, and insulin sensitivity. These actions address core drivers of atherosclerosis and metabolic dysfunction, many of which occur independently of glucose lowering. In patients with T2DM, the cardiovascular benefits of metformin are well recognized, including reductions in all-cause mortality and cardiovascular events. In individuals without diabetes but at high cardiovascular risk-such as those with prediabetes, obesity, or metabolic syndrome-evidence is more limited, as most data are derived from subgroup analyses or trials with surrogate endpoints. Nonetheless, consistent signals suggest that metformin may delay the progression from prediabetes to overt diabetes and potentially confer vascular protection, particularly in carefully selected high-risk populations. Clinical trials and meta-analyses have demonstrated that metformin reduces incident diabetes by approximately one quarter in high-risk adults, with stronger effects observed in younger, overweight individuals, women with prior gestational diabetes, and those treated for longer durations. However, uncertainties remain regarding its long-term cost-effectiveness, optimal dosing strategies, and cardiovascular benefits in non-diabetic populations. The ongoing VA-IMPACT trial (NCT02915198) is expected to clarify whether metformin reduces major cardiovascular events in prediabetic patients with atherosclerotic disease. Taken together, metformin represents more than an antidiabetic drug. Its pleiotropic mechanisms, favorable safety profile, and low cost support its potential integration into broader cardiometabolic prevention strategies, including primary prevention. Expanding its role beyond diabetes management may offer a cost-effective, widely accessible intervention with significant public health impact.

Background: Restenosis after coronary stent implantation remains a major clinical challenge, especially in patients with diabetes, long lesions, or multiple stents. Standard therapy with aspirin and P2Y12 inhibitors does not reliably prevent this complication. Objectives: We reviewed experimental and clinical evidence on cilostazol, a selective phosphodiesterase-3 inhibitor, as a strategy to reduce restenosis after percutaneous coronary intervention (PCI). Methods: Preclinical and clinical studies were critically appraised, focusing on the effects of cilostazol on vascular smooth muscle and endothelial cells, platelet aggregation, lipid metabolism, and restenosis rates. Results: Experimental models show that cilostazol inhibits smooth muscle proliferation and intimal hyperplasia after arterial injury. Clinical trials demonstrate reduced restenosis after balloon angioplasty and stent implantation compared with aspirin, ticlopidine, or clopidogrel. Although approved by the FDA for intermittent claudication, cilostazol remains underused in the prevention of coronary restenosis. Conclusions: Current evidence supports cilostazol as an effective adjunctive therapy to reduce restenosis following PCI. Wider adoption and further large-scale trials are warranted to better define its role in contemporary interventional practice.

(1) Background: Endovascular therapy is widely used for lower limb peripheral artery disease (PAD), yet device performance varies across vascular territories due to anatomical and biomechanical differences. This study evaluated territory- and lesion-specific outcomes following contemporary endovascular strategies in a real-world cohort. (2) Methods: This retrospective single-center study included consecutive patients undergoing endovascular revascularization of the iliac, superficial femoral (SFA), or popliteal arteries between 2010 and 2023. The primary endpoint was 12-month binary restenosis (≥50% diameter loss) assessed by duplex ultrasonography, CT angiography, or invasive angiography. Secondary outcomes included target lesion revascularization and procedural complications. Kaplan-Meier analysis was used to evaluate restenosis-free survival. Multivariable Cox models were constructed separately for each vascular territory, adjusting for relevant clinical and anatomical covariates. (3) Results: A total of 283 lesions were included (iliac n = 135; SFA n = 145; popliteal n = 102). At 12 months, restenosis rates differed substantially by treatment modality and arterial territory. In the iliac segment, covered stents demonstrated the lowest restenosis (12.8%), whereas in the SFA, interwoven nitinol stents yielded the most favorable profile (15.4%). In the popliteal artery, drug-coated balloons were associated with the lowest restenosis rate (16.7%). In multivariable analysis, covered stents (iliac), interwoven nitinol stents (SFA), and drug-coated balloons (popliteal) were independently associated with lower restenosis risk. Procedural success was high and complication rates were low. (4) Conclusions: Endovascular device performance is strongly influenced by arterial territory and lesion characteristics. Tailoring the treatment strategy to vessel biomechanics and lesion morphology may optimize mid-term patency in lower limb PAD. Larger prospective studies are warranted to validate these findings.

Ceramides are bioactive sphingolipids increasingly recognized as mediators of cardiometabolic disease and residual cardiovascular risk. Accumulating evidence from experimental and clinical studies indicates that specific ceramide species contribute to insulin resistance, endothelial dysfunction, myocardial injury, and adverse cardiovascular outcomes. In particular, long-chain ceramides (C16:0, C18:0, C20:0 Cer) are consistently associated with myocardial infarction, heart failure, and cardiovascular mortality, whereas very-long-chain ceramides (C22:0, C24:0 Cer) exhibit neutral or potentially protective associations. This narrative review integrates biochemical, experimental, and clinical evidence to examine ceramide metabolism, molecular diversity, and their emerging role as biomarkers for cardiovascular risk stratification. We also discuss ceramide-based risk scores and their potential clinical utility beyond traditional lipid parameters. Understanding the structure-function relationships of ceramides may support the development of novel diagnostic and therapeutic strategies in cardiovascular prevention.

Total Coronary Revascularization via left Anterior Thoracotomy (TCRAT) represents a modern evolution of sternum-sparing, on-pump multivessel coronary artery bypass grafting. In this review, we will summarize the historical development, detail the surgical principles, and provide a comprehensive overview of the clinical outcomes of TCRAT. The technique combines cardiopulmonary bypass using peripheral arterial as well as venous cannulation and cardioplegic cardiac arrest using transthoracic aortic cross-clamping with surgical access through a left anterior minithoracotomy. By applying special slinging and rotational maneuvers, both a stable exposition of all coronary territories-in particular those of the right and the circumflex coronary artery-and a quiet, bloodless operating field enable complete anatomical revascularization and complex coronary surgery procedures, including all variations in multiarterial grafting in unselected patients. Data from all published clinical series were integrated, and a weighted analysis of a total of 2282 patients was performed. TCRAT proved to be very effective with regard to complete anatomical revascularization and modern grafting strategies, and it showed excellent perioperative safety in an all-comers population. Both the 30-day mortality and perioperative stroke incidence were distinctly below 1.0%. Data from mid-term follow-up, although rare so far, are promising and compare well to those of the important RCTs. The TCRAT approach eliminates sternal complications completely and accelerates recovery. As an on-pump arrested-heart surgery, TCRAT inherently permits the combination of minimally invasive multivessel CABG with a variety of other cardiac operations, mainly the combination with valve procedures. The integration of robotic and endoscopic assistance represents the next evolutionary step. With its reproducibility and broad applicability, TCRAT holds strong potential to become a standard routine technique in the field of minimally invasive cardiac surgery.