Journal of Cardiovascular Development and Disease最新文献

For the past decade, cell-based therapies have been the focus of research to investigate their potential to treat ischemic heart disease. The translation to human clinical studies depends on the demonstration of therapeutic efficacy and safety, particularly when transplanted in the subacute and chronic post-MI phase. A number of studies were identified that reported the effect of hiPSC-CMs on cardiac outcomes when transplanted at least 7 days post-myocardial infarction. The mean sample size of the published studies was 30 (±17) animals with a mean follow-up duration of 51 (±37) days. hiPSC-CM transplantation enhanced systolic function through augmented myocardial contractility, decreased infarct size, attenuated ventricular remodeling, and enhanced angiogenesis in the infarct and border zones in both small and large animal models. This effect was enhanced by co-transplantation with cells of vascular or adipose origin and is associated with high expression of VEGF in most studies. Despite this effect, transplanted hiPSC-CMs were structurally immature with limited survival at the endpoint. Epicardial delivery was associated with better efficacy outcomes and lower rates of arrhythmia. No study reported teratoma formation or immune rejection. From the current literature, there appears to be no consensus on the extent to which hiPSC-CMs improved systolic function, nor the degree to which this arises directly from integration of the new myocardium or from a paracrine-mediated mechanism. The nature of this paracrine mechanism and ways to improve the maturity and survival of implanted cardiomyocytes are issues that have yet to be resolved. In summary, while therapeutic benefit from cell therapy is clear, further research is required to establish whether the key mechanisms require a cellular component.

Background: Stage B heart failure (SBHF) increases the risk of symptomatic HF. Current guideline criteria for SBHF lack sex and ethnic thresholding and cardiac magnetic resonance (CMR) imaging cut-offs. We aimed to assess the prevalence of SBHF in a large cohort of people with type 2 diabetes (T2D) and healthy controls and propose a refined CMR definition for SBHF.

Methods: Sex- and ethnic-specific thresholds for imaging criteria were derived from 373 healthy controls, who underwent CMR cine imaging. The current definition for SBHF and refined criteria was applied to our prospectively recruited and intensively phenotyped cohort of asymptomatic people with T2D and no evidence of cardiovascular disease. The prevalence of SBHF by different definitions was calculated and patient characteristics, including exercise capacity, were compared between those classified as Stage A vs. B HF. Finally, the refined criteria were also applied to the following two historical cohorts with symptomatic cardiovascular disease: severe aortic stenosis (AS n = 70) and HF with preserved ejection fraction (HFpEF n = 136).

Results: A total of 423 people with T2D and a subset of 102 healthy controls who underwent echocardiography were prospectively recruited. Current guideline criteria classified 91% of those with T2D and 69% of the healthy controls as SBHF, suggesting a lack of specificity. Applying derived sex- and ethnicity-specific thresholds, combining echo and CMR measures, the prevalence of SBHF was reduced to 30% in those with T2D. Using the refined definition, those with Stage B HF had lower exercise capacity than those with Stage A HF (percentage predicted maximal oxygen consumption 81 ± 16% vs. 91 ± 20%, p < 0.001). Applying the refined definition to symptomatic AS and HFpEF participants classified 89% and 85% with abnormal cardiac remodelling.

Conclusion: Current guideline criteria for SBHF are non-specific and likely of limited value in clinical practice. Refining these criteria with sex- and ethnic-specific thresholds may improve identification of those at risk of developing symptomatic disease. Further research is required to validate these criteria.

Background and objective: Evidence of percutaneous left atrial appendage closure (LAAC) and oral anticoagulants (OACs) in non-valvular atrial fibrillation (NVAF) patients with intermediate-to-borderline high stroke risk is scarce. We aimed to compare the efficacy and safety of these treatments in the latter clinical population.

Methods: This retrospective cohort study included NVAF patients with CHA₂DS₂-VA scores of 1-2 and used 1:1 propensity score matching (184 patients per group) to compare efficacy and safety outcomes. The primary efficacy outcome was a composite of stroke, transient ischemic attacks, systemic embolism, and cardiovascular death during follow-up. Adverse safety events were categorized into peri-procedure (LAAC group) and non-procedural (both groups) events.

Results: Over a mean follow-up of 48.93 ± 28.50 months, a total of 26 patients (7.07%) reached the primary composite efficacy endpoint. The LAAC group showed a significantly higher incidence of the efficacy endpoint compared to the OAC group (HR = 3.09; 95% CI 1.22-7.85; log-rank p = 0.01). Procedure-related events occurred in five LAAC patients (one contributing to primary endpoint), while non-procedural bleeding rates were similar (0.54% vs. 1.09%; p = 0.56). Subgroup analyses suggested concomitant ablation of NVAF in LAAC group did not significantly improve efficacy composite endpoints (HR = 0.47).

Conclusions: In NVAF patients with intermediate-to-high stroke risk, OACs were more effective than LAAC in preventing thromboembolic events, with comparable rates of clinically relevant bleeding.

Background: Atrial dilated cardiomyopathy (ADCM) related to homozygous Natriuretic Peptide Precursor A (NPPA) pathogenic variants is an exceptionally rare inherited atrial cardiomyopathy characterized by progressive atrial enlargement, supraventricular arrhythmias, and eventual atrial standstill. Case summary: We report the case of a 9-year-old girl identified through population genetic screening as a homozygous carrier of the NPPA c.449G>A (p.Arg150Gln) variant who subsequently developed symptomatic paroxysmal atrial fibrillation (AF) at the age of 18. Although baseline cardiac investigations were normal, her current evaluation shows biatrial enlargement with preserved ventricular function. She underwent radiofrequency pulmonary vein isolation; however, recurrent symptomatic AF persists, requiring ongoing antiarrhythmic therapy and long-term oral anticoagulation (CHA₂DS₂-VA: 0; HAS-BLED: 0). Notably, patients with NPPA-related ADCM have a markedly increased thromboembolic risk due to progressive atrial mechanical failure, and anticoagulation should therefore be considered irrespective of conventional clinical risk scores. Discussion and conclusions: This case highlights the importance of genetic testing in young patients with atrial fibrillation and no underlying structural heart disease. The early identification of NPPA-related atrial dilated cardiomyopathy may aid in risk stratification and guide rhythm and anticoagulation management. Expanding genetic screening in select individuals with isolated atrial fibrillation may facilitate earlier diagnosis in this exceptionally rare condition.

Despite the efficacy of catheter ablation in preventing recurrences of atrial fibrillation (AF), the reasons for its lack of success in some patients remain unknown. The aim of this study was to try to identify a new predictor of AF recurrence following catheter-based treatment. This prospective study enrolled a cohort of patients with AF. Based on the results of a one-year follow-up, patients were divided into two groups: Group 1 ("vein-dependent" AF)-patients who achieved a successful outcome after 1-2 catheter ablation procedures-and Group 2 ("non-vein-dependent" AF)-patients with confirmed complete pulmonary vein isolation (PVI) or with an identified "non-vein-dependent" AF substrate. Blood samples were collected prior to the procedure and biobanked. Initial proteomic profiling of the serum using protein microarrays identified several candidate proteins, whose elevated levels were subsequently confirmed by an enzyme-linked immunosorbent assay (ELISA). This article presents data on one such protein-TAG72. A comparison of TAG72 levels (%OD normalized units) between Group 1 ("vein-dependent" AF) and Group 2 ("non-vein-dependent" AF) revealed a statistically significant increase in the latter group (128.9 [98.2; 284.4] vs. 84.3 [73.8; 92.1], p < 0.001). These data provide the first evidence implicating TAG72 in the pathogenesis of AF.

Intravascular imaging (IVI) was introduced 35 years ago to assess coronary artery pathology and plaque vulnerability. However, from its first applications it became apparent that it can also be useful in percutaneous coronary intervention (PCI) planning and optimizing PCI results. In the early days of PCI, IVI was used to examine the efficacy of emerging endovascular devices and the vessel wall response to therapy, while in the drug-eluting stent (DES) era, IVI was used to guide DES implantation and assess final results post-intervention. The first studies assessing the role of IVI in guiding PCI with DES have failed to demonstrate a prognostic benefit for the use of IVI; however, more recent large-scale randomized trials have underscored its value in this setting. IVI, with its high resolution, allows optimal stent sizing, prompt identification and correction of common causes of stent failure, and it has been shown that it improves outcomes in complex procedures. This review summarizes the evidence supporting the role of IVI in PCI planning in DES era, synopsizes the studies that have highlighted the value of IVI in predicting stent failure, discusses the limitations of the first randomized trials that failed to demonstrate a prognostic benefit from its use, and presents the results of the more recent large-scale outcome studies that underscored its role in complex PCI planning.

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.