Journal of Cardiovascular Development and Disease最新文献

Objectives: Systemic inflammation, malnutrition, and immune dysregulation have emerged as important determinants of long-term outcomes after transcatheter aortic valve implantation (TAVI). The C-reactive protein-albumin-lymphocyte (CALLY) index is a novel immunonutritional biomarker that integrates these pathophysiological domains; however, its prognostic value in TAVI patients has not yet been investigated. This study aimed to evaluate the association between the CALLY index and 1-year mortality after TAVI.

Methods: This retrospective observational study included 532 consecutive patients who underwent TAVI at a tertiary-care center between 2014 and 2023. Baseline laboratory parameters were obtained before the procedure, and the CALLY index was calculated as (albumin × lymphocyte count)/(C-reactive protein × 10). The primary endpoint was 1-year mortality. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminative ability of the CALLY index and conventional surgical risk scores. Multivariable regression analyses were used to identify independent predictors of mortality.

Results: During the 1-year follow-up period, 85 patients (15.9%) died. Patients who died had significantly lower baseline CALLY index values compared to survivors (p < 0.001). The CALLY index demonstrated good discriminative performance for 1-year mortality (AUC: 0.797), outperforming EuroSCORE II (AUC: 0.705) and the Society of Thoracic Surgeons (STS) score (AUC: 0.619). A CALLY cut-off value of 0.45, derived using Youden's index, was associated with a more than threefold increased risk of mortality. In multivariable analysis, the CALLY index remained independently associated with 1-year mortality, along with EuroSCORE II and more than mild mitral regurgitation.

Conclusions: The CALLY index is a strong and independent predictor of 1-year mortality after TAVI and provides incremental prognostic value beyond conventional surgical risk scores. Given its simplicity and reliance on routinely available laboratory parameters, the CALLY index may serve as a practical tool for long-term risk stratification in patients undergoing TAVI.

Excessive right heart load imposes an acute or chronic injury on the right ventricle (RV), predisposing critically ill neonates and cardiac surgical patients to RV failure, low cardiac output syndrome, and death. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that improves ventilation-perfusion matching and unloads the RV without systemic hypotension; nonetheless, its application beyond established neonatal indications remains contentious. Our review synthesizes current mechanistic, translational, and clinical evidence regarding iNO use in three major settings characterized by excessive RV load: (1) neonatal pulmonary hypertension, particularly PPHN; (2) acute and chronic RV overload in older children and adults, including secondary pulmonary hypertension, acute respiratory distress syndrome (ARDS), and acute pulmonary embolism; and (3) perioperative and post-cardiopulmonary bypass (CPB) management in congenital and adult cardiac surgery. In term and near-term infants with hypoxic respiratory failure, pivotal randomized trials show that iNO consistently improves oxygenation and reduces extracorporeal membrane oxygenation (ECMO) use, but this has little effect on survival and long-term neurodevelopment. In ARDS and other adult critical-care indications, iNO provides transient improvements in gas exchange and RV performance without reducing mortality or ventilator duration, and meta-analyses signal an increased risk of acute kidney injury, particularly with prolonged use. In contrast, perioperative studies around CPB demonstrate that prophylactic postoperative iNO and intra-CPB nitric oxide administration can attenuate pulmonary hypertensive crises, facilitate separation from CPB, shorten ventilation and intensive care stay, and, in selected high-risk cohorts, may reduce cardiac surgery-associated acute kidney injury, although survival benefits remain unproven. Across these scenarios, iNO should be used judiciously and in a pathophysiology-driven manner as a time-limited, targeted adjunct to stabilize patients with documented or anticipated RV strain rather than a disease-modifying therapy. Future work should refine patient selection, timing, dosing, and weaning strategies, and define the long-term safety and cost-effectiveness of iNO within contemporary multimodal RV support pathways.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and both metabolic reprogramming and autophagy have been implicated in its pathogenesis. However, the expression pattern of autophagy-related genes during metabolic reprogramming in AF remains elusive. We aimed to characterize the expression profiles of autophagy- and metabolic reprogramming-related genes in atrial tissue to gain pathophysiological insights into AF. Three datasets obtained from the Gene Expression Omnibus (GSE2240, GSE79768, and GSE14975) that included atrial tissue samples from patients with or without AF were subjected to a bioinformatics analysis, which identified 2812 differentially expressed genes. Eight autophagy- and metabolic reprogramming-related differentially expressed genes (A&MRRDEGs) were identified as key candidates through least absolute shrinkage and selection operator regression combined with the random forest approach. Meanwhile, mice underwent transverse aortic constriction (TAC) for 2 weeks in an AF model, and gene expression in atrial tissue was analyzed. In atrial tissues from TAC mice, only Akt1 and Hspa5 of the eight A&MRRDEGs exhibited expression changes concordant with the human datasets, while Glud1 showed discordant regulation. Collectively, these cross-species findings highlight that the eight A&MRRDEGs, particularly AKT1 and HSPA5, are potentially involved in autophagy and metabolic reprogramming during AF pathogenesis.

Atrial fibrillation (AF) is closely linked to atrial remodeling, while its underlying immune mechanisms remain elusive. This study sought to investigate the role of SPP1⁺ macrophages in the development and progression of AF and further elucidate the underlying mechanisms. Single-nucleus RNA sequencing was performed on right atrial tissues from 3 patients with persistent AF and 3 with sinus rhythm (all with rheumatic valvular heart disease). The results revealed significant immune cell infiltration in AF atrial tissues, with a marked increase in the proportion of SPP1⁺ macrophages, which exhibited the strongest intercellular communication with cardiomyocytes. Phenotypic scoring indicated that apoptosis was the dominant mode of cardiomyocyte death in AF. Immunohistochemical and Western blot analyses confirmed elevated levels of pro-apoptotic proteins (Bax, Cleaved-Caspase3) and reduced levels of the anti-apoptotic protein Bcl2 in AF tissues. In a mouse model with macrophage-specific SPP1 overexpression, increased AF inducibility and duration were observed, accompanied by enhanced cardiomyocyte apoptosis. In vitro co-culture experiments using SPP1-overexpressing RAW264.7 macrophages and HL-1 cardiomyocytes confirmed that SPP1⁺ macrophages could induce cardiomyocyte apoptosis. Mechanistically, KEGG and GSEA analyses identified downregulation of the PI3K/AKT pathway in AF. Treatment with the PI3K/AKT activator Recilisib reversed apoptosis and restored p-PI3K/p-AKT levels in HL-1 cells co-cultured with SPP1-overexpressing RAW264.7 macrophages. These findings demonstrate that SPP1⁺ macrophages accumulate in atrial tissues of AF patients and induce cardiomyocyte apoptosis by downregulating the PI3K/AKT pathway, thereby increasing AF susceptibility.

Introduction: The serum apelin level in patients with heart failure with reduced ejection fraction (HFrEF) and its relationship with ventricular tachycardia (VT) are not clearly known. This study aimed to investigate changes in serum apelin levels in patients with HFrEF and their relationship with VT.

Method: This retrospective pilot study included 90 patients with 30 patients in each group: Group I: HFrEF with documented VT; Group II: HFrEF without VT; Group III: control group without HFrEF. In addition to routine parameters, apelin levels were measured. All parameters were compared between Group I-II-III. Parameters associated with VT were identified.

Result: Apelin levels were found to be significantly lower in Group I-II than in Group III. Serum glucose, creatinine, and left atrial diameter were shown to be significantly higher in Group I-II than in Group III. HDL cholesterol and left ventricular ejection fraction (LVEF) levels were significantly lower in Group I-II compared with Group III. A positive and negative correlation was found between plasma apelin levels and LVEF and age, respectively. In logistic regression analysis, apelin levels and LVEF were found to independently determine VT (OR = 0.313, 95%CI: 0.124-0.788, p = 0.014 and OR = 0.912, 95%CI: 0.877-0.968, p < 0.001). In the ROC analysis, the cut-off value for apelin was determined to be 0.80 ng/mL, and it distinguished VT status in this sample with acceptable sensitivity and specificity.

Discussion: According to the results of our study, apelin levels are significantly reduced in patients with HFrEF, and reduced apelin levels are associated with the presence of VT in these patients.

Background: Previous studies identified epicardial adipose tissue (EAT) as a metabolic risk factor for atrial remodeling. However, given the distinct physiological changes associated with aging, findings from the general population may not translate directly to older adults. This study aims to clarify the relationship between EAT and left atrial (LA) diameter in older adults specifically.

Methods: This retrospective cross-sectional study was conducted among in an older adult cohort (aged ≥ 65 years) at Peking Union Medical College Hospital. The association between EAT and LA diameter was evaluated using multivariable linear regression, a generalized additive model, and restricted cubic spline (RCS) modeling.

Results: Among 353 participants (median age 75 years), EAT was independently associated with LA diameter (β = 0.286, p < 0.001) after adjusting for confounders including age, BMI, and LDL-C. Notably, RCS analysis revealed a J-shaped relationship between EAT volume and LA dimensions. Specifically, when EAT exceeded 110.7 cm³, the LA diameter increased significantly by 0.22 mm per 10 cm³ increase in EAT (p = 0.004).

Conclusions: EAT accumulation shows a non-linear association with left atrial remodeling in older adults, with an identifiable threshold at 110.7 cm³. EAT may be a valuable biomarker for cardiovascular risk stratification, suggesting that EAT burden monitoring could be beneficial in older populations.

Human iPSC-derived cardiomyocytes (iPSC-CMs) exhibit fetal-like mitochondrial networks and limited oxidative metabolism, constraining their translational utility. The key bottleneck is mitochondrial immaturity, resulting from blunted PGC-1α-NRF1/2-TFAM axis activation and insufficient nuclear-mitochondrial coordination, rather than sarcomeric or electrophysiological immaturity alone. This review synthesizes genome-guided interventions (CRISPRa and mtDNA editing) and complementary environmental strategies-including metabolic substrate switching, electromechanical stimulation, and extracellular vesicle (EV)-mediated mitochondrial transfer-to drive mitochondrial biogenesis and maturation in iPSC-CMs. We systematically reviewed studies (2005-2025) targeting (1) key regulators of mitochondrial biogenesis (PGC-1α, NRF1/2, TFAM), (2) CRISPR-based transcriptional activators/repressors and mtDNA editors (DdCBE, mitoTALENs), and (3) maturation approaches such as metabolic conditioning, electromechanical stimulation, 3D tissue culture, and EV-mediated mitochondrial transfer. CRISPRa-mediated activation of PGC-1α, NRF1, and GATA4, combined with mtDNA base editors, enhances mitochondrial mass and OXPHOS function, while integration with environmental maturation strategies further promotes adult-like phenotypes. Integrative approaches that combine genome-guided interventions (CRISPRa, mtDNA editing) with environmental maturation cues yield the most adult-like iPSC-CM phenotypes reported to date. CRISPR-guided mitochondrial biogenesis thus represents a frontier for producing metabolically competent, structurally mature iPSC-CMs for disease modeling and therapy. Remaining translational challenges include efficient mitochondrial delivery, metabolic homeostasis, and multi-omics validation. We propose standardized workflows to couple nuclear and mitochondrial editing with maturation strategies.

Background: Cor triatriatum dexter (CTD) is a rare congenital heart defect where a membrane divides the right atrium into two chambers, resulting from the incomplete regression of the right valve of the sinus venosus. Due to its rarity, only individual case reports and a limited number of case series have been published to date. This study constitutes the most extensive comprehensive review conducted in this area. Eight factors were evaluated: age at diagnosis, sex, clinical presentation, electrocardiographic findings, imaging (ultrasound, CT, or MRI), associated cardiac anomalies, and patient outcomes.

Methods: The electronic databases PubMed and Scopus were searched from their inception until 30 October 2025. Only case reports and case series were considered for inclusion. Studies involving foetuses, autopsies, and animals were excluded. The collected data were primarily presented as percentages.

Results: One hundred fourteen studies were found encompassing 124 patients. The mean age at diagnosis was 33.3 ± 9.4 years The most common clinical presentations were dyspnoea (44.3%) and cyanosis (29.5%). The most commonly encountered ECG changes were supraventricular tachycardia/atrial flutter/atrial fibrillation (33.3%) and right bundle branch block (22.6%). On chest X-ray, cardiomegaly was noted in 46.5%. CTD was suspected or diagnosed by echocardiography in 95.2% of cases. The diagnosis was confirmed by CT and/or MRI in 34.1% of cases. A concomitant congenital heart defect was found in 67.7%, especially in the form of all kinds of atrial septal defect (38.1%) and of right valvular and right ventricular involvement (20.1%). An outcome was reported in 97/124. Surgical correction was the treatment of choice in 51.6%. Since 1991, a percutaneous approach has been employed in selected cases (5.1%). Conservative management was the treatment of choice in 43.3%. The mortality rate was 8.2%.

Discussion: The principal limitation of this systematic review lies in its reliance solely on case reports and small case series, reflecting the absence of large-scale studies on CTD. Nonetheless, it constitutes the most comprehensive analysis available to date.

Background: Cardiac computed tomographic angiography (CTA) detects patent foramen ovale (PFO) with variable accuracy. This study investigated factors affecting CTA detectability for PFO in patients with suspected PFO-associated stroke.

Methods: Consecutive patients with cryptogenic stroke and positive findings on contrast transcranial Doppler (cTCD) examinations were enrolled between November 2020 and April 2023 in this retrospective study. Each participant underwent transesophageal echocardiography (TEE) and cardiac CTA. Patients with confirmed PFO on TEE were categorized into two groups based on CTA detectability: the CTA-positive group (PFO identified by CTA) and the CTA-negative group (PFO missed by CTA). Univariate and multivariate logistic regression analyses were performed to identify predictors of CTA false-negative results.

Results: Among 108 patients (mean age 46.7 ± 14.9 years, 47.2% male), the prevalence of PFO by TEE was 94.4% (102/108). Compared to TEE, cardiac CTA had a sensitivity of 70% (95% CI 61-79%), a specificity of 100% (95% CI 54-100%), a positive predictive value of 100% (95% CI 95-100%), and a negative predictive value of 16% (95% CI 6-32%). Among patients with PFO confirmed by TEE (n = 102), the incidence of moderate to large right-to-left shunts (RLS) was significantly higher in the CTA-positive group than in the CTA-negative (77.5% vs. 22.5%, p < 0.001). After adjusting for confounders, patients with moderate to large shunts showed a significantly lower likelihood of a CTA false-negative result compared to those with small shunts (OR 0.113, 95% CI 0.035-0.365, p < 0.001). In patients with moderate to large RLS, the sensitivity of cardiac CTA for diagnosing PFO increased to 90.16% (95% CI 82.69-97.64%).

Conclusions: Cardiac CTA could be an effective complementary modality for selected patients with suspected PFO-associated stroke. Its diagnostic performance appears more reliable for identifying PFO in patients with moderate-to-large RLS than in those with small RLS.

Endovascular techniques are commonly employed for type B aortic dissections and are rarely reported for type A dissections. We present the case of a 78-year-old female diagnosed with a type A aortic dissection, with coronary arteries and supra-aortic vessels perfused from the true lumen and no significant aortic valve dysfunction. Given her recent cardiovascular surgery, the anticipated prolonged recovery, and multiple comorbidities, a percutaneous approach was preferred, with classical surgery available as stand by. The patient underwent endovascular treatment using two self-expandable, double-disc atrial septal defect occlusion devices. Intracardiac echocardiography facilitated device deployment, offering superior visualization compared with transesophageal echocardiography, which can be partially obscured by the left pulmonary artery. To our knowledge, the false lumen-to-true lumen approach in percutaneous management of type A aortic dissection has not been previously described.