Journal of Cardiovascular Development and Disease最新文献

Coronary bifurcation lesions are considered among the most challenging lesions to treat with percutaneous coronary intervention (PCI), particularly in cases of extensively diseased branches. In the event of failure of a provisional (one-stent) approach, many two-stent bifurcation techniques can be performed for the treatment of coronary bifurcation lesions. Two techniques (culotte and T/TAP) are suggested by the European Bifurcation Club, but a reverse crush is performed by some operators. This study aims to retrospectively compare these two different approaches (EBC-recommended techniques vs. reverse crush).

Proteins exist as multiple chemical and sequence-specific proteoforms, each of which may serve as a critical mediator of physiological or pathological signalling. This diversity arises from processes such as alternative splicing of gene transcripts, translation into amino acid sequences, and various post-translational modifications (PTMs), leading to an exponential increase in biological complexity. This manuscript provides an overview of the mechanisms underlying proteoform generation in biological systems and highlights strategies for their analysis using mass spectrometry (MS)-based proteomics and bioinformatics. Additionally, it focuses on recent findings linking PTMs to cardiovascular disease (CVD), highlighting the MS-based methods and workflows that have been used to study uncommon PTMs and their role in CVD. This review provides a comprehensive collection of tools and knowledge to explore the breadth of proteoforms, particularly PTMs, within their specific areas of interest in cardiovascular physiology.

Background: Thoracic aortic aneurysm (TAA) is driven by complex molecular mechanisms beyond size thresholds, yet the role of cyclic nucleotide metabolism remains unclear. Phosphodiesterases (PDEs), which hydrolyze cAMP and cGMP in compartmentalized microdomains, act as key regulators of vascular integrity and remodeling.

Methods: We performed a hypothesis-driven, transcriptomic analysis of 20 PDE isoforms using the GSE26155 dataset (43 TAA vs. 43 controls). Raw microarray data underwent background correction, log2 transformation, and false-discovery adjustment. Differential expression, logistic regression, receiver-operating characteristic (ROC) curves, calibration testing, correlation analysis, and interactome/enrichment mapping were conducted.

Results: Thirteen PDE isoforms were significantly dysregulated in TAA. Upregulated transcripts included PDE10A, PDE2A, PDE4B, PDE7A, and PDE8A, whereas PDE1A/B/C, PDE3B, PDE5A, PDE6C, and PDE8B were downregulated. PDE10A achieved excellent discrimination for TAA (AUC = 0.838), while other isoforms demonstrated fair discriminatory ability. Correlation architecture revealed coordinated regulation between PDE subfamilies, including inverse relationships between PDE2A and PDE8B (r = -0.68). Interactome analysis highlighted dense connections with cyclic nucleotide and purinergic signaling hubs, enriched in vascular tone, NO-cGMP-PKG, and junctional assembly pathways. Integrating these findings with epigenetic and junctional frameworks suggests that PDE dysregulation promotes endothelial barrier fragility and maladaptive smooth-muscle remodeling.

Conclusions: Family-wide PDE dysregulation characterizes human TAA, with PDE10A emerging as a central transcriptomic signature. Altered cAMP/cGMP microdomain signaling aligns with junctional failure and epigenetic control, supporting the potential of PDE isoforms as biomarkers and therapeutic targets. These results provide experimental evidence that cyclic nucleotide hydrolysis is re-wired in TAA, supporting PDE10A as a novel biomarker and therapeutic target that bridges molecular dysregulation with clinical risk stratification in thoracic aortic disease.

Recent advances in oncology have contributed to a steady rise in cancer survivorship. However, many cancer therapies are associated with cardiovascular adverse events, leading to increased rates of cardiovascular morbidity and mortality. As a result, cardio-oncology has emerged as a rapidly advancing discipline that relies on multidisciplinary collaboration. Cardiovascular multimodality imaging (CVMI) is an essential diagnostic and surveillance tool for cardiovascular toxicity, along with clinical evaluation and biomarkers. CVMI plays a central role in diagnosing cancer therapy-related cardiac dysfunction (CTRCD) and myocarditis, while also supporting the assessment of vascular toxicity and arrhythmias. It is essential for baseline cardiac evaluation and continuous monitoring throughout and following cancer therapy. CVMI enables early detection of cardiovascular toxicity, facilitating prompt initiation of cardioprotective therapy and allowing cancer therapy to proceed without compromising safety. Echocardiography is the primary imaging modality for screening, diagnosing, and monitoring CTRCD. Moreover, it is the first-line imaging test for cardiac structural and functional assessment in patients who develop immune checkpoint inhibitor (ICI)-related myocarditis. Advanced imaging techniques, such as cardiac magnetic resonance (CMR), nuclear imaging, and cardiac computed tomography, may help determine the cause and severity of left ventricular dysfunction, as well as assess cardiac masses and vascular toxicity. Not least, CMR is the gold standard imaging modality to diagnose myocarditis. This article is a narrative review that focuses on the various modalities of CVMI and their applications in cardio-oncology. Since the issue addressed is very extensive, this review was designed to be concise.

Heart transplantation is still the definitive therapy for end-stage heart failure, yet the persistent shortage of suitable donor organs limits its application. Traditionally, static cold storage (SCS) has served as an effective standard preservation method, providing safe and adequate protection for preservation times under four hours. Yet, the need to extend this window and the specific metabolic requirements of donation after circulatory death (DCD) hearts have prompted interest in machine perfusion (MP) technologies. This literature review investigates the influence of temperature in ex situ heart perfusion, comparing normothermic (NMP), hypothermic (HMP), and subnormothermic (SNMP) strategies. Evidence from experimental models and emerging clinical studies suggests that MP can prolong preservation times, mitigate ischemic injury, and enable real-time metabolic and viability assessment of donor hearts prior to transplantation. These strategies represent a central trade-off: NMP enables real-time functional assessment of the beating heart, while HMP and SNMP approaches prioritize profound metabolic suppression to mitigate ischemic injury. Nonetheless, current data are limited by high costs, significant resource requirements, variability in perfusion protocols, and the scarcity of randomized controlled trials, particularly for HMP and SNMP. Standardization of methodologies, direct comparative studies, and the adoption of a risk-stratified preservation ecosystem are needed to clarify optimal temperature strategies. However, recent clinical successes with hypothermic strategies in traditionally normothermia-dependent donor types, such as DCD hearts, signal a potential paradigm shift, challenging established value propositions and prompting a critical re-evaluation of optimal preservation strategies.

Rapid and effective clearance of apoptotic cells, known as efferocytosis, is essential for maintaining tissue homeostasis. Efferocytosis removes apoptotic cells before the occurrence of membrane rupture from which the cell contents, often inflammatory and toxic, are released into surrounding tissues. Through this way, efferocytosis protects the surrounding tissues from toxic enzymes and oxides inside the apoptotic cells as well as from cellular contents such as anti-proteinase and cystatins. Driven by the ongoing advancements in bioinformatics and molecular biology, many researchers have explored the mechanism of efferocytosis and its association with systemic diseases. Multiple studies have demonstrated that impaired efferocytosis mechanisms significantly contribute to the onset and progression of chronic inflammation. The presence of chronic inflammation significantly exacerbates the advancement of cardiovascular diseases, including atherosclerosis, myocardial infarction, heart failure subsequent to myocardial infarction, and even myocarditis. This review aims to provide a brief introduction to the mechanisms involved in cellular efferocytosis, followed by an examination of the molecular and pathway aspects of efferocytosis with the risk of cardiovascular diseases, contributing to the identification of potential therapeutic targets for related diseases.

(1) Background: Coronary artery bypass grafting (CABG) reduces the risk of target vessel revascularization compared to percutaneous coronary intervention (PCI), yet coronary reintervention may still occur. This study aims to evaluate the incidence and underlying etiology of reintervention after CABG. (2) Methods: A single-center retrospective cohort study of all patients undergoing isolated CABG (January 2016-December 2021) was performed. Surgical or percutaneous reinterventions were analyzed until December 2022 using institutional data linked to the Netherlands Heart Registration (NHR) and chart review. (3) Results: Amongst 4814 patients, 8.7% (n = 418) underwent coronary reintervention during a median 4.5 [3.8-4.8] year follow-up. Causes of reintervention included graft failure (64.6%), progression of coronary artery disease (20.3%), incomplete revascularization (10.5%), or combined factors (4.1%). Mortality did not differ significantly between reintervention and non-reintervention groups (10.8% vs. 7.9%, p = 0.095). Multivariable analysis identified diabetes (HR 1.02, 95% CI 1.00-1.04, p = 0.011), single arterial graft (HR 2.26, 95% CI 1.31-3.91, p = 0.003), and ventilation > 24 h (HR 4.61, 95% CI 1.85-11.51, p = 0.001) as independent risk factors for coronary reintervention. (4) Conclusions: After CABG, 8.7% of patients underwent coronary reintervention at mid-term follow-up. Graft failure was the predominant etiology, followed by coronary artery disease progression. Overall survival did not differ between patients with or without reintervention.

Introduction: Patent ductus arteriosus (PDA) is the most common cardiac anomaly in preterm newborns and may aggravate respiratory disease. Invasive closure options after failure of medical treatment include surgical ligation (SL) and transcatheter closure (TCC). Reports on side effects of intravenous contrast media are scarce.

Methods: In this retrospective single-center study, we compared 35 preterm infants below 1500 g birth weight undergoing SL with 35 matched infants undergoing TCC. Outcomes were procedural success, complications and postprocedural ventilation.

Results: Closure success was high in both groups (97% SL vs. 86% TCC, p = 0.106). One SL patient underwent re-operation after accidental clipping of the left pulmonary artery, and eight patients (24%) had endoscopy-diagnosed vocal cord palsy after SL. Six TCC patients had complications that required further action, including device embolization, device failure and one case of late device migration that resulted in aortic arch obstruction requiring intervention, and 4 TCC patients developed necrotizing enterocolitis (NEC)-like disease within 24 h, requiring surgery in one patient. SL was associated with longer duration of mechanical ventilation (24 h vs. 144 h, p < 0.001), as opposed to TCC, and higher rates of bronchopulmonary dysplasia (86% vs. 53%, p = 0.004).

Discussion: Both techniques achieve high success but differ in complication profiles. TCC may reduce respiratory morbidity. NEC-like disease (probably linked to intravenous administration of contrast agents) warrants further investigation.

Background: Subclinical atrial fibrillation (SCAF), a key risk factor for cryptogenic stroke, is difficult to predict with current tools. This study aimed to develop a novel deep learning framework, ResKAN-Attention, using only routine clinical data to predict SCAF in patients with cardiac implantable electronic device (CIED).

Methods: In this retrospective study, the ResKAN-Attention model was developed using 27 routine parameters from 124 CIED patients without prior AF. This framework features a dual-path architecture combining a Kolmogorov-Arnold Network (KAN) with a traditional multilayer perceptron, fused via a cross-attention mechanism. The model's performance was evaluated against common baselines using five-fold cross-validation, while its decision-making process was assessed through interpretability analysis. A clinically applicable risk scoring system was subsequently derived via knowledge distillation.

Results: Over a 12-month follow-up period, SCAF occurred in 31.5% of patients (39/124). The ResKAN-Attention model significantly outperformed all baseline models, achieving a mean AUC of 0.837 in cross-validation and 0.788 in external validation. Interpretability analysis identified left atrial diameter (LAD), gender, lactate dehydrogenase, BMI, and hypertension as top predictors. The simplified risk score exhibited excellent predictive power (AUC 0.882), retaining 99.1% of the complex model's performance on the fifth fold validation set.

Conclusions: The ResKAN-Attention model demonstrated promising preliminary results for SCAF prediction with enhanced interpretability. The distilled risk score provided a potential method for early risk stratification in clinical settings, demonstrating that advanced artificial intelligence (AI) can effectively predict complex cardiovascular events using readily available data.

Understanding the molecular mechanisms that maintain protein homeostasis in cardiomyocytes is fundamental for the development of causal therapies for heart failure. Chaperones, the ubiquitin-proteasome system and autophagy are major regulators of cardiac homeostasis and are crucial for cardiomyocyte function and survival. In this context, myeloid leukaemia factor 2 (MLF2) emerged as a candidate of interest, as we found it overrepresented in protein aggregates in the hearts of mouse models of desmin-related cardiomyopathies (DRM), and it has also been suggested to be associated with dilated cardiomyopathy (DCM). Here, we identified αB-crystallin (CryAB), among other proteins, as a potential interaction partner of MLF2. Functionally, MLF2 was significantly upregulated in mouse models of heart failure and in two in vitro models of cardiomyocyte hypertrophy, and its overexpression resulted in attenuation of pro-hypertrophic gene expression. Taken together, these findings provide initial evidence supporting a role for MLF2 in regulating protein homeostasis and in modulating hypertrophic signalling in cardiomyocytes.