Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13070295

Authors: Yuanzheng Ye He Wang Yongying Lan Wenqi Pan Ning Zhang Tianyou Ling Yun Xie Hongzhen Wang Qiancheng Ma Chengze Lin Baopeng Tang Liqun Wu

Background: Oxidative stress is pivotal in pulmonary hypertension. The uric acid-to-albumin ratio (UAR) is a readily available composite biomarker reflecting oxidative stress, inflammation and nutritional status. However, its clinical value for short-term risk stratification in PH remains unclear. Objective: This study aimed to evaluate the association of UAR with in-hospital mortality, clinically recorded PH severity grades, and selected cardiac structural and functional indicators in hospitalized patients with PH. Methods: This single-center retrospective cohort study included 8763 PH patients. Patients were stratified by UAR quartiles. Ordinal logistic regression, multivariable logistic regression, and linear regression were used to assess associations of UAR with clinically recorded PH severity grades, in-hospital mortality, left ventricular ejection fraction (LVEF), and right ventricular internal diameter (RVID). Restricted cubic spline analyses, subgroup analyses, receiver operating characteristic curve analyses, and incremental prediction analyses using C-statistics, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) were also performed. Results: In-hospital mortality increased stepwise across UAR quartiles (0.5% vs. 1.0% vs. 1.8% vs. 2.8%, p < 0.001). In the fully adjusted model, each 1-unit increase in UAR was associated with higher odds of a more severe clinically recorded PH grade (OR = 1.11, 95% CI: 1.09–1.13, p < 0.001) and higher odds of in-hospital mortality (OR = 1.09, 95% CI: 1.04–1.14, p < 0.001). Higher UAR was also associated with lower LVEF (β = −0.53, 95% CI: −0.58 to −0.47, p < 0.001) and greater RVID (β = 0.18, 95% CI: 0.15–0.22, p < 0.001). Adding UAR to a model containing routinely available clinical, laboratory, and echocardiographic variables improved the C-statistic from 0.6922 to 0.7230, with significant improvements in NRI and IDI. Conclusions: UAR was independently associated with in-hospital mortality, clinically recorded PH severity, LVEF, and RVID, and provided incremental prognostic information. UAR may serve as a low-cost, routinely available, complementary biomarker for short-term in-hospital risk stratification in patients with PH.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13070294

Authors: Mehmet Aslan Mustafa Özgül Umut Serhat Sanrı Oğuz Karahan

Background: Although chronic venous insufficiency is often treated as a localized problem, it is a systemic condition that can negatively affect cardiac hemodynamics. This study investigates the associated effects of eliminating the pathologic venous reservoir on right ventricular (RV) functions, systolic pulmonary artery pressure (sPAP), and inferior vena cava (IVC) diameter in patients undergoing endovenous radiofrequency ablation (RFA) for severe great saphenous vein (GSV) insufficiency. Methods: This retrospective observational study included 154 patients who presented between September 2023 and May 2025 with GSV insufficiency (CEAP C3-C4b) and underwent endovenous RFA. Patients with major cardiopulmonary diseases were strictly excluded. Preoperative and 6-month postoperative transthoracic echocardiography records were analyzed to evaluate RV diastolic diameter, tricuspid annular plane systolic excursion (TAPSE), sPAP, the TAPSE/sPAP ratio, and IVC diameter. Results: At 6 months post-RFA, compared to preoperative values, a significant decrease was detected in the mean sPAP (14.7 ± 2.5 vs. 11.8 ± 1.8 mmHg, p < 0.001) and IVC diameter (2.1 ± 0.2 vs. 1.9 ± 0.2 cm, p < 0.001). Furthermore, significant improvements were observed in TAPSE (20.0 ± 2.0 vs. 21.5 ± 1.8 mm, p < 0.001) and the TAPSE/sPAP ratio (1.36 ± 0.15 vs. 1.82 ± 0.18 mm/mmHg, p < 0.001). Conclusions: Endovenous RFA is associated with favorable changes in right heart parameters. Eliminating pathologic extremity blood pooling may optimize venous return kinetics and subclinically improve right ventricular–pulmonary arterial coupling.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13070293

Authors: Can Zhang Lixia Dai Annemien E. van den Bosch Vehpi Yildirim Mathijs S. van Schie Yannick J. H. J. Taverne Natasja M. S. de Groot

Background: The prognostic value of electrocardiography (ECG)- and continuous rhythm monitoring (CRM)-derived markers for predicting atrial fibrillation (AF) onset and progression remains unclear in patients with congenital heart disease (CHD). Methods: We retrospectively analyzed 573 CHD patients who underwent 24 h Holter monitoring between 2003 and 2015. Baseline ECG and CRM parameters were assessed. Cox regression identified predictors of new-onset AF and AF progression, and interaction analyses explored effect modification by left atrial (LA) dilatation. Results: During 13 ± 5 years of follow-up, AF occurred in 107 patients (18.7%), of whom 32 (29.9%) progressed to persistent/permanent AF (PeAF). Patients with AF more frequently had prolonged PR and QTc intervals and higher atrial ectopy (AE) and ventricular ectopy burdens. Independent predictors of new-onset AF were older age, LA dilatation, higher AE burden, atrial tachycardia, and pacemaker implantation. AF progression was independently associated with older age, LA dilatation, higher AE burden, and prolonged PR interval. AE burden showed a stronger association with AF risk in patients without LA dilatation. Conclusions: In CHD patients, baseline ECG PR-intervals and CRM-derived AE burden independently predict AF onset and/or progression. These noninvasive markers may improve risk stratification and support earlier personalized rhythm management.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13070292

Authors: Ning Wu Hairui Sun Siyao Zhang Jiaqi Fan Tong Yi Ruimin Liu Yihua He

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, accounting for a substantial proportion of global deaths. Increasing evidence indicates that cardiovascular susceptibility is shaped during fetal development, where the intrauterine environment plays a critical role. Maternal–fetal crosstalk, mediated largely through placental function, coordinates the transfer of metabolic, endocrine, and immune signals that are essential for normal cardiac and vascular development. Disruptions in maternal physiology—including metabolic disorders, hypertensive conditions, inflammation, and environmental stress—can perturb this communication network and alter the intrauterine milieu. These changes induce persistent modifications in cardiomyocyte growth, endothelial function, and key regulatory pathways, thereby contributing to long-term cardiovascular risk. Emerging studies highlight that cardiovascular programming is governed by interconnected mechanisms involving epigenetic regulation, mitochondrial function, immune signaling, and intercellular communication. This review synthesizes current evidence on how maternal–fetal crosstalk shapes cardiovascular development beyond genetic determinants and provides an integrated framework linking early-life exposures to lifelong cardiovascular health.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13070291

Authors: Daniel G. Yang Shaleen Thakur Harriet Akunor Richard B. Stacey Bharathi Upadhya

Heart failure (HF) with preserved ejection fraction (HFpEF) is increasingly prevalent and now recognized as a systemic syndrome with diverse clinical phenotypes and multiorgan involvement. The predominant clinical phenotype has evolved from patients with isolated hypertensive heart disease to individuals with cardiometabolic (CM) abnormalities [obesity, insulin resistance, increased waist circumference (a surrogate for visceral adiposity), dyslipidemia, type 2 diabetes, and hypertension] that result in metabolic alterations leading to CM-HFpEF. Indeed, CM-HFpEF and metabolic dysfunction-associated fatty liver disease are recognized as two sides of the same coin. Chronic systemic inflammation is a defining pathophysiologic feature of CM-HFpEF, with visceral adipose tissue serving as a central driver. In this regard, lifestyle changes, including diet and exercise, are crucial for managing HFpEF. Several recent studies have shown that exercise training (aerobic and resistance combined) with or without calorie restriction is an effective therapeutic management strategy for improving exercise capacity, physical function, and quality of life in patients with clinically stable HFpEF. Also, the pharmacologic interventions that have proven beneficial in HFpEF so far (sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists) are effective due to their metabolic protective effects. In this review, we outline the current available evidence on lifestyle interventions in HFpEF management and therapeutics, discussing their modalities and potential mechanisms.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13070290

Authors: Anıl Avcı Emre Kipritçi İbrahim Veyisoğlu Selahattin Akyol Emrah Bayam Serdar Fidan Ramazan Kargın

Background: Low-flow, low-gradient aortic stenosis with reduced left ventricular ejection fraction is a heterogeneous condition with challenging severity assessment. Aortic valve calcification reflects fibro-calcific remodeling, while oxidative stress plays a key role in its pathogenesis. Serum uric acid, a marker of oxidative stress, may be associated with valvular calcification. This study investigated the relationship between serum uric acid levels and aortic valve calcification in this population. Methods: This retrospective study included 85 patients. Aortic valve calcification was quantified using computed tomography with the Agatston method, and patients were categorized as true severe or pseudo-severe according to sex-specific calcium thresholds. Of the patients, 57 were classified as true severe and 28 as pseudo-severe aortic stenosis. Results: Patients with higher calcification burden had significantly elevated serum uric acid levels (6.77 ± 1.57 vs. 5.08 ± 1.10 mg/dL, p < 0.001). Serum uric acid showed a modest correlation with aortic valve calcium score (ρ = 0.339, p = 0.002) and remained independently associated with CT-defined true severe low-flow, low-gradient aortic stenosis in multivariable analysis. ROC analysis yielded an area under the curve of 0.823 and identified a serum uric acid threshold of 5.45 mg/dL associated with a greater likelihood of CT-defined true severe low-flow, low-gradient aortic stenosis. Conclusions: Serum uric acid is associated with CT-derived aortic valve calcification and may provide insight into underlying fibro-calcific remodeling in this population.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13070289

Authors: Mislav Radić Petra Šimac Prižmić Tina Bečić Hana Đogaš Ivana Jukić Jonatan Vuković Damir Fabijanić Josipa Radić

Background: Pericardial involvement is the most common cardiac manifestation of systemic lupus erythematosus (SLE), ranging from mild effusion to recurrent pericarditis and cardiac tamponade. The influence of antiphospholipid syndrome (APS) on lupus-related pericardial disease remains unclear. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO. PubMed, Web of Science, Scopus, and the Cochrane Library were searched from inception to January 2026 for observational studies evaluating pericardial manifestations in adult SLE patients. APS/aPL status was considered a potential modifying factor when reported. Results: Seven observational studies were included. Pericardial involvement ranged from acute and recurrent pericarditis to large effusions and cardiac tamponade. Across studies, it was consistently associated with higher disease activity and markers of immune activation. Recurrent pericarditis emerged as a clinically relevant phenotype linked to more severe disease and worse outcomes. Cardiac tamponade, although rare, was associated with significant morbidity and mortality. APS/aPL-related data were heterogeneous and inconsistently reported across studies. No consistent APS-specific association with pericardial disease could be established, although APS or aPL-related findings were occasionally reported in selected severe or clinically complex presentations. Conclusions: Pericardial involvement in SLE reflects systemic inflammatory burden and spans a broad clinical spectrum. Current evidence regarding APS remains limited and heterogeneous, although APS may contribute to disease complexity in selected severe presentations. Importantly, isolated aPL positivity should not be interpreted as equivalent to formally classified APS. Prospective studies with standardized definitions and systematic assessment of APS are needed.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13070288

Authors: Rohit S. Loomba Diane E. Spicer Robert H. Anderson

Background: It is rare in clinical practice to encounter a common arterial trunk when the ventricular septum is intact. In this setting, other clinical diagnoses, such as hypoplastic left heart syndrome with aortic atresia, may be mistaken for a common arterial trunk. Data for this combination is largely limited to case reports and small case series. We have conducted a systematic review of reported cases, performing cluster analyses to provide an objective grouping of the cases. Methods: A systematic review of the literature was performed to identify cases of a common arterial trunk with an intact ventricular septum. Cases for which individual data were available were included in the final analyses. Cluster analysis using K-means clustering was conducted to provide an objective grouping of the hearts based on morphologic findings. Results: K-means clustering identified three distinct groups among hearts with a common arterial trunk with intact ventricular septum. The commitment of the common ventriculo-arterial junction to the left, right, or both ventricles was the defining feature of each group. Hearts with a common trunk committed to one of the ventricles demonstrated significant hypoplasia or atresia of structures related to the other ventricle. Conclusions: Distinct patterns can be identified when a common arterial trunk is found with an intact ventricular septum. They depend on the ventricle or ventricles, which support the common ventriculo-arterial junction.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060287

Authors: Maxime Tijskens Benjamin De Becker Michael Wolf Bruno Schwagten Yves De Greef

Background: The presence of left atrial fibrosis is a marker of advanced remodeling and is associated with a worse outcome after pulmonary vein isolation (PVI). Conventional fluoroscopy-only cryoballoon ablation (CBA) lacks this prognostic information. The addition of electroanatomical mapping (EAM) using the inner lumen spiral catheter allows accurate voltage assessment of the left atrial posterior wall. However, the value of the finding of posterior wall low-voltage zones (pwLVZs) is unknown. Purpose: To study the value of left atrial voltage maps during CBA by comparing clinical and procedural characteristics and clinical outcome between patients with and without pwLVZs. Methods: A cohort of 250 consecutive patients who underwent index CBA for atrial fibrillation was analyzed. All patients underwent pre- and post-procedural EAM using the AchieveTM catheter and EnSiteTM mapping system. The presence of LVZs was evaluated at the postprocedural voltage map of the posterior wall. Clinical success was defined as freedom from documented AF or atrial tachycardia (AT) >30 s after 1 year. Results: PwLVZs were found in 41/250 (16.4%) of patients. Patients with pwLVZs were older (69.3 ± 8.5 vs. 64.2 ± 10.4; p = 0.003), more frequently female (63.4% vs. 32.5%; p < 0.001) and had higher CHA2DS2-VASc scores (3.0 ± 1.6 vs. 2.0 ± 1.5; p < 0.001). The incidence of obesity (31.7% vs. 25.8%; p = 0.048), structural heart disease (35.5% vs. 17.4%; p = 0.021) and persistent AF (68.3% vs. 43.8%; p = 0.004) was higher in the pwLVZs group. Kaplan–Meier analysis of clinical outcome showed a higher recurrence rate in the pwLVZs group. The finding of pwLVZs was a predictor of atrial arrhythmia recurrence during follow-up (HR 2.583; 95%CI: 1.334–5.002; p = 0.005). Conclusions: In CBA facilitated by integrated EAM, pwLVZ was associated with older age, female sex, higher CHADS-VASc scores, obesity, structural heart disease and persistent AF. The finding of pwLVZs is predictive of a worse clinical outcome.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060286

Authors: Shanquan Gao Xiaodi Tang

The development of atrial fibrillation involves the synergistic effects of electrical remodeling, structural remodeling and neural remodeling, among which remodeling of the autonomic nervous system (ANS) plays a pivotal role in disease initiation and progression. Heart rate variability (HRV), as an important tool for assessing autonomic function, has been widely applied in cardiovascular research. In particular, ultra-short-term heart rate variability (usHRV) analysis has demonstrated significant value in the early prediction of atrial fibrillation.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060285

Authors: Tsubasa Morioka Shingo Kato Kouta Mitsutake Hidenao Yanagisawa Toshiharu Izumi Tomokazu Sakano Eiji Ishikawa Hiroyuki Kamide Daisuke Utsunomiya

Background: Optimal phase selection in coronary computed tomography angiography (CCTA) is crucial. While the mid-diastolic slow-filling (SF) phase is typically predicted using a conventional formula based on heart rate and atrioventricular conduction time, its validity in complete left bundle branch block (CLBBB)—where pronounced QRS prolongation induces severe mechanical dyssynchrony—remains unclear. We evaluated the impact of bundle branch block on cardiac-phase selection and validated a QRS-corrected predictive model. Methods: We retrospectively analyzed 94 patients (sinus rhythm, n = 40; complete right bundle branch block [CRBBB], n = 36; CLBBB, n = 18). Measured SF at the proximal right coronary artery was compared against predictions from the conventional formula (SF = −362 + 0.742 × [RR − PQ]) and a proposed QRS-corrected formula incorporating a “−(QRS − 100)” subtraction. To test the necessity of a novel model, regression analyses were reconstructed exclusively for the CLBBB cohort. Results: In CLBBB patients, the conventional formula critically overestimated SF by an average of 37.9 ms (RMSE 42.5 ms). Reconstructing simple and multivariate regression models exclusively for the CLBBB group yielded coefficients remarkably similar to the conventional formula, indicating that the fundamental physiological dependency on RR and PQ intervals remains intact despite the bundle branch block. Crucially, the simple proposed QRS-corrected formula successfully eliminated the overestimation bias (mean error −6.9 ms; p = 0.176) and demonstrated the highest predictive accuracy (RMSE 21.2 ms). Conclusions: A completely new predictive regression model is unnecessary for CLBBB patients. Simply incorporating a theoretical subtraction of pathological QRS prolongation optimally corrects the diastolic resting phase.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060284

Authors: Hui Zhen Lo Sanjay Patel Jamie Layland

Coronary artery disease (CAD) is the leading cause of mortality and morbidity in the world. While low-density lipoprotein cholesterol has been the main target of secondary prevention, inflammation has gained traction as a potential target for reducing adverse cardiovascular events. Hence, in this review, we aim to outline the current evidence base for the use of colchicine in CAD to provide more clarity from the findings in the recent trials and meta-analyses (LoDoCo2, COLCOT, COPS, CONVINCE, CLEAR-SYNERGY, COLOCT, and EKSTROM). Given colchicine’s low cost and widespread availability, it is a potential adjunct to lipid-lowering therapy. However, it may not be as effective in the secondary prevention of CAD as previously thought. Ongoing research on colchicine remains vital to determine its utility in patient populations beyond those with CAD as well as to better understand the fine balance between its therapeutic benefits and potential side effects.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060283

Authors: İrfan Yaman Hasan Korkmaz Arzu Etem Akağaç Tuğçe Kaymaz Rauf Önder Ebru Etem Önalan

Background: Pulmonary arterial hypertension (PAH) is a rare and progressive disorder characterized by increased pulmonary vascular resistance and vascular remodeling. Genetic polymorphisms, epigenetic modifications, and ion channel dysregulation are increasingly recognized as key contributors to disease pathogenesis. Anoctamin-1 (ANO1/TMEM16A), a calcium-activated chloride channel, plays a critical role in vascular tone regulation. Objective: This study aimed to investigate the association between ANO1 gene polymorphisms (rs7127129 and rs2509153), promoter methylation status, and serum chloride levels in patients with idiopathic pulmonary arterial hypertension (IPAH), congenital heart disease (CHD), and chronic thromboembolic pulmonary hypertension (CTEPH). Methods: A total of 106 IPAH patients, 40 CHD patients, and 30 CTEPH patients, together with 125 healthy controls, were included. The control group had a comparable age distribution, with a balanced sex ratio, whereas females predominated in all three PH groups. Genotyping was performed using TaqMan-based real-time PCR. Promoter methylation was analyzed using bisulfite conversion followed by quantitative real-time PCR. Serum chloride levels were measured using an ion-selective electrode method. Results: No significant association was observed between rs7127129 and rs2509153 polymorphisms and IPAH or CTEPH (p > 0.05). However, rs7127129 showed a significant association with CHD (p < 0.05). After excluding hypertensive patients, both polymorphisms remained significantly associated with CHD. Serum chloride levels differed significantly among groups (p < 0.001), with higher levels observed particularly in the CTEPH and CHD groups compared to controls, while IPAH patients exhibited intermediate but still elevated levels relative to controls. In contrast, promoter methylation levels were significantly lower in all patient groups compared to controls. An inverse relationship between chloride levels and methylation status was observed. Conclusions: ANO1 polymorphisms are not major determinants of IPAH or CTEPH but may contribute to CHD susceptibility. Increased serum chloride levels, together with decreased promoter methylation, suggest a potential mechanistic link between ion channel dysregulation and epigenetic alterations in pulmonary hypertension. Further large-scale and functional studies are warranted.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060282

Authors: Qiheng Wan Song Wen Jiquan Xiao Feihuang Han Zehan Huang Dunliang Ma Feng Wang Yuqing Huang Bin Zhang

Introduction: The uric acid-to-albumin ratio (UAR) is a novel cardiovascular biomarker, but its prognostic value in patients undergoing percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) remains unknown. Materials and Methods: This retrospective study enrolled 1513 consecutive patients who underwent successful CTO-PCI at a single center from February 2011 to December 2023. Patients were stratified by baseline UAR tertiles. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE), and the secondary endpoint was all-cause mortality. Multivariable Cox regression and restricted cubic spline (RCS) analyses were performed. Results: During a median follow-up of 810 days, patients in the highest UAR tertile had significantly higher rates of MACCE (18.5%, 10.1%, and 7.5% across tertiles; p < 0.001) and all-cause mortality (10.7%, 3.8%, and 2.0%; p < 0.001). After multivariable adjustment, each one-unit increase in UAR was associated with a 6% higher risk of MACCE (HR 1.06; 95% CI 1.02–1.10; p = 0.002) and a 9% higher risk of all-cause mortality (HR 1.09; 95% CI 1.04–1.14; p < 0.001). Patients in the highest UAR tertile had significantly increased risks of MACCE (HR 1.90; 95% CI 1.25–2.90; p = 0.003) and all-cause mortality (HR 3.40; 95% CI 1.62–7.12; p = 0.001) compared with those in the lowest UAR tertile. RCS analysis showed significant overall associations between UAR and both MACCE and all-cause mortality, with no significant evidence of nonlinearity. Conclusions: Elevated baseline UAR was independently associated with long-term MACCE and all-cause mortality after successful CTO-PCI. These findings support UAR as a readily available prognostic marker but do not establish causality or support UAR-guided therapeutic decision-making. Prospective studies are needed for validation.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060281

Authors: Macala Maney Carson Richardson Isaac Kistler Samantha Fichtner Hannah Jacobs Julie B. Aldrich Clifford L. Cua

Background: Ventricular septal defects (VSD) are the most common form of congenital heart disease (CHD). Current guidelines recommend surveillance transthoracic echocardiograms (TTE) following surgical closure of perimembranous VSDs (pVSD); however, duration of screening is not explicitly stated. The goal of this study is to determine the utility of follow-up TTEs after uncomplicated pVSD surgical closure. Methods: Single-site retrospective analysis was conducted on patients who underwent pVSD surgical closure. Patients were excluded if diagnosed with other CHD, had complications 1 year post-repair, or lacked data 1 year post-repair. Serial TTEs were reviewed. A Kaplan–Meier curve was used to illustrate the 5-year complication-free survival. Results: A total of 117 patients met inclusion criteria. A 97% 5-year complication-free survival was observed. Four patients had complications >1 year post-repair: one non-obstructive subaortic ridge, one pulmonary vein stenosis, one pinhole residual pVSD, and one ventricular ectopy with ventricular dysfunction. Of the 113 complication-free patients, 197 TTEs were performed with no change in clinical management. Conclusions: Beyond 1 year post-repair, the occurrence of new complications following uncomplicated pVSD surgical closure is rare. Unless clinical concerns arise, the utility of routine TTEs > 1 year post-repair in this uncomplicated post-surgical cohort should be reassessed. Larger multicenter studies are needed to determine the utility of routine TTEs.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060280

Authors: Alexander Gall Rui Li Ciaran Grafton-Clarke Zia Mehmood Kurian Thampi Amanda Noyes David Hewson Victoria Underwood Rebekah Girling David Marlevi Peter P Swoboda Rob J. van der Geest Gareth Matthews Pankaj Garg

Four-dimensional (4D) flow cardiovascular magnetic resonance assesses advanced haemodynamic parameters like kinetic energy (KE), vorticity, and viscous energy loss (vEL). However, gradient-based metrics (vorticity, vEL) are highly sensitive to partial volume effects near the fluid–tissue boundary. This study investigated the impact of systematic contour boundary offsets on these parameters to standardise analysis. Five cases underwent 4D flow imaging. Deep learning-derived automated segmentations of the cardiac chambers were generated. Haemodynamics were analysed using three contouring methods: the baseline mask, a one-voxel inward offset, and a two-voxel inward offset. KE, vorticity, and vEL decreased progressively with larger offsets. KE declined modestly with erosion (by approximately 18% and 35% at one- and two-voxel offsets, respectively), a reduction commensurate with the loss of integration volume rather than the removal of boundary artefacts. By contrast, the gradient-based metrics were disproportionately sensitive to boundary proximity. In the left ventricle, mean full-cycle vorticity decreased from 249.6 ± 79.9 s−1 (baseline) to 157.0 ± 60.4 s−1 (two-voxel offset; Hedges’ g 2.11), whilst vEL decreased from 549.4 ± 303.0 µW to 351.3 ± 230.0 µW (Hedges’ g 2.00). A one-voxel inward offset optimally reduces boundary noise for sensitive gradient-based parameters. While KE analysis remains satisfactory using unmodified baseline contours, we recommend the uniform application of a one-voxel offset across all parameters to ensure methodological simplicity and pipeline standardisation.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060279

Authors: Manuela Montatore Marco Rella Eleonora Indolfi Federica Masino Ruggiero Tupputi Eluisa Muscogiuri Giuseppe Guglielmi

Background: Risk stratification in non-ischemic dilated cardiomyopathy (DCM) remains challenging because left ventricular ejection fraction (LVEF) and late gadolinium enhancement (LGE) do not fully capture the underlying myocardial substrate. Septal native T1 mapping provides a quantitative assessment of diffuse myocardial abnormalities and may contribute to myocardial tissue characterization within a multiparametric CMR framework. Methods: This retrospective single-center study included 45 consecutive patients with non-ischemic DCM referred for clinically indicated CMR at Perrino Hospital, Brindisi, Italy, between November 2023 and November 2025. All examinations were performed using a standardized CMR protocol including cine imaging, LGE, and native T1 mapping on a 1.5-T Siemens Healthineers scanner. Septal native T1 was used as the primary mapping parameter because of its established reproducibility and robustness for myocardial tissue characterization. Patients were followed for a composite endpoint including all-cause mortality, major ventricular arrhythmic events, appropriate ICD therapy, and hospitalization for heart failure. Endpoint coding was verified, and all analyses were performed using the final validated dataset. Results: During a median follow-up of 15 months, 14 patients (31.1%) experienced the composite endpoint. Patients with events had lower LVEF (27.1 ± 7.8% vs. 48.3 ± 10.5%; p < 0.001), higher LVEDVi (142.6 ± 28.5 vs. 110.6 ± 23.4 mL/m2; p = 0.001), and higher septal native T1 values among patients with available T1 measurements (1047.5 ± 25.0 vs. 1031.5 ± 24.3 ms; p = 0.065). ROC analysis identified a septal native T1 threshold of 1042 ms for prediction of the composite endpoint, with an exploratory AUC of 0.70. Event-free survival was lower in patients with septal native T1 ≥ 1042 ms. Given the limited number of events, all regression and hierarchical analyses should be interpreted as exploratory and hypothesis-generating. Conclusions: Higher septal native T1 values were observed in patients experiencing adverse clinical outcomes; however, native T1 was not independently associated with the composite endpoint in exploratory Cox regression analyses.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060278

Authors: Albaraa Al-Holy Nandor Marczin Sunil K. Bhudia Shahzad G. Raja

Objectives: The optimal conduit strategy for coronary artery bypass grafting (CABG) in patients with moderate left ventricular dysfunction (LVEF 30–49%) remains debated. While total arterial grafting (TAG) has shown benefits in broader populations, its role in this higher-risk subgroup is unclear. This study aimed to compare short-term outcomes and long-term survival between single arterial grafting (SAG) and TAG in patients with moderate LV dysfunction undergoing CABG. Methods: A retrospective analysis of 1866 patients was performed, with 640 patients matched using propensity scores (320 SAG vs. 320 TAG). Preoperative, intraoperative, and postoperative variables were assessed. Survival was evaluated using Kaplan–Meier analysis and Cox regression. Results: Matched cohorts were well balanced across baseline characteristics. Long-term survival at 10 and 15 years was numerically higher in the TAG group (85.8% and 79.7%) compared to SAG (81.7% and 74.2%), though not statistically significant (log-rank p = 0.862). Multivariate Cox regression identified age (HR 1.045, p < 0.001), NYHA class (NYHA III HR 0.610, p = 0.003), previous cardiac surgery (HR 0.501, p = 0.006), and off-pump CABG (HR 1.521, p < 0.001) as independent predictors of mortality. Grafting strategy (TAG vs. SAG) was not independently associated with long-term mortality (HR 1.005, p = 0.966). Conclusion: TAG is safe and feasible in patients with moderate LV dysfunction undergoing isolated CABG, with comparable short-term outcomes. Although unadjusted analyses suggested improved long-term survival, this difference was not observed after propensity matching or multivariable adjustment, and grafting strategy was not independently associated with mortality.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060277

Authors: Eray Aksoy Zumrut Tuba Demirozu Sami Gurkahraman Mehmet Sanser Ates

The continuous suture technique is not routinely used in surgical aortic valve replacement (SAVR), and data regarding its clinical outcomes remain limited. This retrospective observational study evaluated early and mid-term outcomes after continuous suture SAVR in a real-world cohort. Eighty-eight consecutive patients who underwent SAVR using a continuous suture technique between November 2015 and July 2024 were included. Both isolated and concomitant procedures were analyzed. The operative technique consisted of three 2-0 polypropylene sutures, one placed along each aortic cusp. Clinical outcomes, postoperative complications, and survival were assessed. The mean age was 62.22 ± 15.22 years, and 71.6% of patients were male. Bioprosthetic valves were implanted in 61.4% of cases, and the mean prosthesis size was 25.02 ± 0.93 mm. Concomitant procedures were performed in 86.4% of patients. There were no in-hospital deaths. New-onset atrial fibrillation occurred in 26.1% of patients, and permanent pacemaker implantation was required in 3.4%. The median cross-clamp time was 41.50 min. During a mean follow-up of 18.38 months, one- and three-year overall survival was 92.9%. No prosthetic valve dysfunction related to thrombus, pannus formation, or clinically significant paravalvular leak was observed. Continuous suture SAVR appears feasible and safe, with acceptable early and mid-term outcomes, although the retrospective, non-comparative design requires cautious interpretation.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060276

Authors: Umit Kahraman Emrah Oguz Vusali Kasumovi Aysen Yaprak Kapkin Ahmet Daylan Serkan Ertugay Sanem Nalbantgil Cagatay Engin Mustafa Ozbaran Tahir Yagdi

Background: Continuous-flow left ventricular assist devices (LVADs) generate non-pulsatile circulation, rendering conventional oscillometric blood pressure measurements unreliable. Accurate monitoring is critical to prevent complications including stroke, pump thrombosis, and aortic regurgitation. Doppler-based measurement is widely used as a non-invasive alternative, yet its accuracy relative to invasive arterial pressure remains insufficiently characterized. Methods: In this prospective single-centre study, 32 adult continuous-flow LVAD patients underwent simultaneous invasive radial artery and Doppler blood pressure measurements twice daily over three consecutive days (192 paired readings; Day 3: n = 27 due to technical recording issues). Pulsatility was assessed by means of peripheral pulse palpation and transthoracic echocardiography. Spearman’s rho, Wilcoxon signed-rank test, and Bland–Altman analysis were applied. Results: Median invasive MAP was 73.0 [IQR 66–80] mmHg and median Doppler pressure was 75.0 [IQR 70–80] mmHg. Doppler measurements demonstrated strong-to-excellent correlation with invasive MAP across all time points (r = 0.78–0.91, p < 0.001), with no significant paired differences (all p > 0.05). Bland–Altman analysis revealed a bias of −0.35 mmHg with limits of agreement of −9.10 to +8.40 mmHg, within the accepted ±10 mmHg threshold. Correlation with systolic pressure was lower (r = 0.66–0.89, p < 0.001), with a positive bias of +13.47 mmHg and wide limits of agreement (+1.28 to +25.67 mmHg), indicating clinically unacceptable agreement. Conclusions: Doppler-derived blood pressure may provide a reliable estimate of invasive MAP in continuous-flow LVAD patients, whereas its utility for systolic pressure estimation appears limited. Doppler measurement represents a practical, non-invasive tool for routine MAP monitoring in both inpatient and outpatient settings.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060275

Authors: Yan Li Puhan Song Mengyi Zheng Yanyao Jia Juan Wang Qian Zhang Xiaorong Xu Zhiyong Zhang Zongsheng Guo Lin Zhao Jing Cheng

Background: The triglyceride–glucose (TyG) index is a simple surrogate marker of insulin resistance (IR) and has been associated with coronary artery disease (CAD). However, the association between the TyG index and coronary chronic total occlusion (CTO) remains limited. Methods: In this retrospective study, 1157 patients who underwent coronary angiography at Beijing Chaoyang Hospital from January 2024 to January 2026 were enrolled and classified into the CTO group (n = 317) and the non-CTO group (n = 840). Multivariable logistic regression analyses were performed to assess the association between the TyG index and CTO. Restricted cubic spline analysis was used to examine the linear dose–response relationship. Subgroup analyses were conducted according to age, sex, smoking status, hypertension, and diabetes mellitus. Results: Patients with CTO had a significantly higher TyG index than those without CTO (8.98 [8.46, 9.45] vs. 8.79 [8.41, 9.26], p = 0.003). In the multivariable logistic regression analysis, the TyG index was independently associated with the presence of CTO (OR = 1.377, 95% CI 1.082–1.752, p = 0.009). In a sensitivity analysis further adjusted for diabetes mellitus, the association remained significant (OR = 1.356, 95% CI 1.052–1.747, p = 0.018). Restricted cubic spline curve analysis showed a nonlinear dose–response relationship (p for nonlinear = 0.005) between the TyG index and CTO risk. In the subgroup analyses, the association was directionally consistent across subgroups. Nominally significant associations were observed in elderly participants (OR 1.68, 95% CI 1.20–2.37, p = 0.003), men (OR 1.40, 95% CI 1.06–1.86, p = 0.018), and patients with hypertension (OR 1.55, 95% CI 1.14–2.11, p = 0.005). Conclusions: An elevated TyG index was independently associated with the presence of CTO. The association was generally consistent across major clinical subgroups, with no significant interactions observed.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060274

Authors: Yunlong Ling Tao Yu Ye Xu Quan Wan Yang Pang Guijian Liu Chaofeng Chen Kuan Cheng Wenqing Zhu Qingxing Chen Junbo Ge

Background: Intracardiac echocardiography (ICE)-guided percutaneous endocardial septal ablation (PESA) is a promising alternative strategy for symptomatic hypertrophic obstructive cardiomyopathy (HOCM). However, the extent of left ventricular outflow tract gradient (LVOTG) reduction after PESA varies considerably among patients, and reliable echocardiographic predictors of procedural efficacy remain unclear. We aimed to identify echocardiographic predictors of procedural efficacy and to describe our ablation strategy. Methods: We retrospectively analyzed 30 consecutive symptomatic HOCM patients who underwent ICE-guided PESA. The primary endpoint was the absolute change in resting LVOTG from baseline to the 1-year follow-up; a key secondary endpoint was significant gradient reduction, defined as a ≥50% decrease in resting LVOTG. Associations between LVOTG reduction and baseline echocardiographic parameters, particularly anterior mitral leaflet length (AMLL) and interventricular septal thickness (IVST), were evaluated. Results: At 1 year, the mean resting LVOTG decreased from 86.03 ± 24.30 mmHg to 41.43 ± 18.49 mmHg (p < 0.001). For the key secondary endpoint (≥50% resting LVOTG reduction), AMLL was the only variable associated with the outcome in the prespecified multivariable logistic model (OR per 1 mm increase: 0.429; p = 0.006), with consistent findings in a Firth penalized logistic regression sensitivity analysis. ROC analysis identified an exploratory AMLL cutoff of approximately 29 mm (AUC 0.920; sensitivity 90%; specificity 80%). In the continuous-outcome analysis, each 1 mm increase in AMLL corresponded to approximately 4.3 mmHg less LVOTG reduction (β = −4.32; p < 0.001). Thinner IVST was not significantly associated with greater procedural efficacy (p = 0.052), suggesting a potential thickness-dependent limit that warrants further investigation. Conclusions: ICE-guided PESA effectively reduces LVOT obstruction in HOCM. Shorter AMLL predicted greater LVOT gradient reduction in this exploratory cohort, and a Youden-derived AMLL cutoff of approximately 29 mm may help identify patients who are more likely to achieve substantial gradient reduction.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060273

Authors: Giulia Elena Mandoli Maria Barilli Maria Concetta Pastore Silvia Foli Nicolò Ghionzoli Federico Landra Marta Focardi Enrico Emilio Diviggiano Flavio D’Ascenzi Luna Cavigli Sonia Bernazzali Massimo Maccherini Serafina Valente Matteo Cameli

(1) Background: Left ventricular assist device (LVAD) implantation is a valuable alternative as a bridge to transplant but also as a destination therapy in ineligible patients. Right ventricular failure (RVF) is a major cause of short- and long-term mortality post-LVAD. We aimed to validate echocardiographic and hemodynamic parameters predictive of RVF and adverse outcomes post-LVAD; (2) Methods: We screened a population of patients with end-stage heart failure selected for LVAD implantation according to SIENA protocol and standard international indications, including right heart catheterization (RHC). Individuals were followed up for 1 year with different time points for the development of RVF (primary endpoint) or mortality and hospitalization (secondary endpoint); (3) Results: The population included 29 patients with a mean age of 63 ± 7 years with a mean ejection fraction of 23 ± 4%, mostly due to ischemic etiology. All the patients had a SIENA protocol score of 0–1 before LVAD, and none met the primary endpoint. Regarding the secondary endpoint, among all the tested clinical, laboratory, echo, and RHC indices, only a central venous pressure/wedge pressure (CVP/PCWP) ratio > 0.63 was significantly associated with adverse outcomes (ß = 2.99, p = 0.026); (4) Conclusions: Excluding a pre-implantation RV dysfunction according to SIENA protocol significantly reduces the risk of post-LVAD RVF. The CVP/PCWP ratio may be an additional prognostic marker for mortality and rehospitalization in LVAD patients.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060272

Authors: Albaraa Al-Holy Nandor Marczin Sunil K. Bhudia Shahzad G. Raja

Background: Multiple arterial grafting (MAG) is associated with superior long-term outcomes in coronary artery bypass grafting (CABG). The influence of prior myocardial infarction (MI) on outcomes following MAG remains uncertain. This study evaluates in-hospital outcomes and long-term survival of MAG in patients with and without previous MI. Methods: A retrospective single-center observational analysis of 2468 patients undergoing MAG was performed. Propensity score matching yielded 911 pairs based on preoperative variables. Kaplan–Meier survival analysis and Cox regression were used to assess long-term survival and predictors of mortality. Results: In the unmatched cohort, patients with prior MI had significantly higher rates of diabetes (30.6% vs. 23.9%, p < 0.001), smoking history (p < 0.001), and impaired left ventricular function (fair/poor LVEF: 32.4% vs. 11.1%, p < 0.001), along with higher logistic EuroSCORE (3.81 vs. 3.11, p < 0.001). After matching, baseline characteristics were balanced. In-hospital outcomes, including 30-day mortality (1.5% vs. 1.9%, p = 0.587), stroke, reoperation, and renal complications, were similar. Long-term survival at 10, 15, and 20 years was comparable (log-rank p = 0.814). Multivariate Cox regression identified age (HR 1.065, p < 0.001), NYHA class, diabetes (HR 0.779, p = 0.008), and off-pump CABG (HR 1.444, p < 0.001) as independent predictors of mortality. Prior MI was not associated with increased long-term mortality (HR 0.872, p = 0.105). Conclusions: Despite worse baseline risk profiles, patients with prior MI undergoing MAG had equivalent in-hospital outcomes and long-term survival. MAG remains a robust revascularization strategy irrespective of MI history, supporting its broader use in CABG. These findings should be interpreted in the context of a single-center experience from a high-volume arterial grafting program.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060271

Authors: Omer Ozkan Duman Ummu Taş Sedat Taş Erkan Alpaslan

Background: Obesity is an independent and major risk factor for cardiovascular diseases. However, the presence of common comorbidities such as diabetes and hypertension makes it difficult to understand the direct impact of obesity on the myocardium. The aim of this study is to evaluate the isolated effects of weight loss achieved after bariatric surgery on left ventricular (LV) geometry and diastolic functions in individuals with the “Metabolically Healthy Obese” (MHO) phenotype. Materials and Methods: The study included 28 patients (Surgical Group) who underwent Laparoscopic Sleeve Gastrectomy (LSG) between January 2022 and December 2025, had a preoperative Body Mass Index (BMI) > 40 kg/m2, and had no known cardiovascular or metabolic diseases. The control group consisted of 25 age- and gender-matched metabolically healthy morbidly obese patients who had not undergone surgery. Demographic and echocardiographic data of all participants were analyzed at baseline and at 6 months. Results: Weight Loss: In the surgical group, BMI decreased from 46.21 kg/m2 to 37.11 kg/m2 at the 6th month, while no significant change was observed in the control group. Cardiac Structure: In the surgical group, Left Ventricular Mass Index was significantly decreased from 51.11 g/m2 to 44.57 g/m2. Cardiac Function: The E/A ratio, an indicator of diastolic function, increased significantly from 1.19 to 1.34 in the surgical group, indicating notable improvement. No clinically meaningful change in systolic function was detected. Metabolic Parameters: The surgical group exhibited marked improvements in glucose and lipid profiles (decrease in Total Cholesterol, increase in HDL). Conclusions: The study demonstrates that bariatric surgery, independent of metabolic comorbidities, directly provides “reverse remodeling” of cardiac structure and improves function through reduction of adipose tissue and alleviation of hemodynamic load. These results support the effectiveness of surgery in reducing cardiovascular risk and preserving cardiac structure even in morbidly obese patients without comorbidities.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060270

Authors: Göksel Güz Rasim Onur Karaoğlu Sezen Kumaş Solak Serdar Demirgan

Objective: Restless leg syndrome (RLS) has been associated with an increased risk of vascular disorders, which suggests that endothelial dysfunction plays an important role in the pathogenesis of RLS. In this study, we aimed to evaluate coronary endothelial dysfunction in RLS patients using coronary flow velocity reserve (CFVR) and compared it with healthy controls. Methodology: In this study, the participants were divided into two groups as group RLS (n = 42) and group HC (n = 41). The primary outcome was the CFVR compared between groups. The number of participants with a CFVR value below 2.0 was also evaluated. In addition, a correlation between the international restless legs scale (IRLS) and CFVR, white-blood-cell-count (WBC), and C-reactive protein (CRP) was analyzed. Secondary outcomes were the WBC, hemoglobin, CRP, blood glucose, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and creatinine compared between the two groups. Results: In the group RLS, CFVR was measured lower than healthy controls (p < 0.001). When the groups were compared in terms of the number of participants with a CFVR less than 2.0, the difference between the groups was significant (p < 0.001, 0/41 in group HC and 14/42 in group RLS). Patients with RLS had higher WBC and CRP values. There was a negative correlation between CFVR and IRLS (p < 0.001). The relationship between WBC, CRP, and IRLS was not statistically significant (p = 0.691). Conclusions: In this exploratory study, RLS patients had lower CFVR compared with healthy controls and a negative correlation was observed between RLS severity and CFVR. These findings warrant confirmation in larger, prospectively designed studies with multivariable adjustment. Therefore, we think that it may be beneficial to follow-up patients with RLS in terms of coronary heart disease. Clinical trial number: not applicable.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060269

Authors: Aristi Boulmpou Efstathios Pagourelias Georgios Zormpas Dimitrios Ntelios Vassilios Vassilikos Christodoulos Papadopoulos

Background: Predicting atrial fibrillation (AF) recurrence remains a major clinical challenge, as conventional echocardiographic parameters often fail to capture the complex electro-mechanical substrate of the arrhythmia. The prognostic significance of right ventricular (RV) function and atrial mechanical–structural coupling in paroxysmal AF (PAF) remains underexplored. Methods: We prospectively enrolled patients with PAF in sinus rhythm undergoing comprehensive echocardiography. A wide range of conventional left-sided, right-sided, and novel coupling indices was assessed. Univariable analysis was performed to screen for potential AF recurrence predictors. Based on the initial findings, receiver operating characteristic (ROC) analysis was used to determine the optimal cutoff for RV fractional area change (RV FAC). Finally, multivariable logistic regression identified independent predictors of AF recurrence over a 12-month follow-up. Results: A total of 73 patients were included, of whom 31 (42.5%) experienced AF recurrence during 12-month follow-up. Conventional left atrial (LA) indices, including LA volume index (LAVI) and reservoir strain, showed no significant association with recurrence. In univariable analysis, RV FAC, LA contraction strain, and the novel LA contraction strain/LAVI ratio were all significant predictors. ROC analysis identified an RV FAC cutoff of 42.5%, with lower values associated with significantly higher recurrence rates. In multivariable analysis, lower RV systolic performance determined by RV FAC ≤ 42.5% emerged as a primary independent predictor of recurrence (p = 0.003), while the LA contraction strain/LAVI ratio demonstrated a strong trend towards significance (p = 0.076). Conclusions: In this exploratory study of patients with PAF, atrial mechanical–structural mismatch emerged as a primary marker of the arrhythmic substrate. Additionally, an exploratory signal suggested that a subclinical reduction in RV performance may also correlate with recurrence, though this warrants further investigation in larger cohorts.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060268

Authors: Can Zhao Wei Yao Jianping Xu Guangyu Pan Shen Liu

Background: Postoperative hyperbilirubinemia is a serious complication after cardiac surgery and has been associated with increased perioperative morbidity and mortality. However, data specifically addressing patients undergoing redo valve surgery remain limited. This study aimed to determine the incidence and risk factors of postoperative hyperbilirubinemia after redo valve surgery, and evaluate its association with early postoperative outcomes. Methods: We retrospectively reviewed 259 adult patients who underwent elective redo valve surgery under cardiopulmonary bypass (CPB) between March 2018 and July 2024. Postoperative hyperbilirubinemia was defined as a serum total bilirubin level > 3 mg/dL at any time after surgery. Patients were divided into a hyperbilirubinemia group and a non-hyperbilirubinemia group. Perioperative variables were compared between groups. Univariable and multivariable logistic regression analyses were performed to identify risk factors for postoperative hyperbilirubinemia. Postoperative complications and in-hospital mortality were also compared. Results: Postoperative hyperbilirubinemia occurred in 101 of 259 patients (39.0%). Compared with patients without hyperbilirubinemia, those with hyperbilirubinemia had longer mechanical ventilation and intensive care unit stay, and higher rates of pneumonia, reintubation, tracheostomy, continuous renal replacement therapy, and in-hospital mortality. Univariable logistic regression showed that higher EuroSCORE II, higher preoperative total bilirubin and direct bilirubin levels, lower hemoglobin and platelet count, pulmonary hypertension, anemia, longer operative time, CPB duration, and aortic cross-clamp time, lower nasopharyngeal temperature, greater intraoperative blood loss, larger red blood cell and plasma transfusion volumes, and concomitant surgery on all three valves were associated with postoperative hyperbilirubinemia. Multivariable analysis identified elevated preoperative direct bilirubin, prolonged CPB duration, and more plasma transfusion as independent risk factors. Receiver operating characteristic analysis showed that peak postoperative total bilirubin had moderate prognostic discrimination for in-hospital mortality, with an optimal cut-off value of 3.95 mg/dL (AUC 0.756, sensitivity 66.7%, specificity 80.2%, p = 0.003). Conclusions: Postoperative hyperbilirubinemia is common after redo valve surgery and is associated with worse early postoperative outcomes and higher in-hospital mortality. In this setting, postoperative bilirubin elevation should be interpreted primarily as a prognostic marker of perioperative stress and hepatic vulnerability rather than a direct causal driver of adverse outcomes. Elevated preoperative direct bilirubin, prolonged CPB duration, and greater plasma transfusion were independently associated with the development of postoperative hyperbilirubinemia in this high-risk population.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060267

Authors: Mohamed Salem Martin Leroy Thomas Zajons Mohammed Al-Tawil Assad Haneya Susanne Skrzypek Joseph Thul Matthias Müller Christian Jux Hakan Akintürk

Background: Heart transplantation (HTx) is a well-established therapy for pediatric patients with end-stage heart failure. Over the past decades, the field has considerably evolved, with noticeable changes in surgical techniques and post-transplant outcomes. This study presents our center’s experience over the past three decades. Methods: Between 1988 and 2024, we performed 256 heart transplants in pediatric patients (<18 years) with congenital heart defects (CHD) or myopathy. We divided our cohort into three periode, eras: Era1 (1988–1999), Era2 (2000–2011), and Era3 (2012–2024). We analyzed and reported baseline patient data, postoperative outcomes, and survival analysis. Results: In the first era, most HTx recipients were infants (75%), with CHD accounting for 75% of cases. In the latest era, older children and adolescents were transplanted more frequently with infants representing only 22%, and myopathies became a more predominant indication, representing 57% of patients. The use of mechanical circulatory support increased significantly (<0.001), and a complete shift towards the bi-caval surgical technique was achieved in the recent era. In terms of post-HTx outcomes, 30-day mortality and allograft vasculopathy significantly decreased in the recent era compared with previous periods (<0.001). Conversely, operative time and post-HTx hemodialysis were more frequently observed in the recent era (<0.001). Long-term survival numerically improved in the middle and recent eras compared with the early era; however, no statistically significant difference in Kaplan–Meier survival across eras was observed (log-rank p = 0.19). Conclusions: Over the past three decades, HTx in pediatric patients has evolved, with improvements in early survival and reduced allograft vasculopathy. Changes in patient demographics, surgical technique, and use of MCS in the recent era highlight the ongoing progress as well as the remaining challenges in this complex population.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060266

Authors: Zehao Feng Xing Li Ai Zhou Han Zhang Kaixuan Tang Yumo Yang Ying Chen Li Zhang Lingmei Qian

Myocardial ischemia–reperfusion (I/R) injury is a frequent complication of acute myocardial infarction (AMI), yet clinical biomarkers and targets remain limited. Although tRNA-derived small RNAs (tsRNAs) are emerging cardiovascular regulators, their roles in I/R injury are not fully elucidated. We identified tsRNA-3025a via sequencing in mouse I/R models and validated its clinical significance. Circulating tsRNA-3025a was significantly upregulated in AMI and unstable angina patients, independently predicting adverse events within 30 days. Functionally, tsRNA-3025a exacerbated apoptosis and mitochondrial dysfunction in vitro, while its in vivo silencing reduced infarct size, improved cardiac function and increased the proportion of Ki67- and pH3-positive cardiomyocytes. Mechanistically, tsRNA-3025a aggravated injury by targeting PIK3C2A, thereby suppressing autophagosome formation and impairing protective autophagic flux during reperfusion. In conclusion, circulating tsRNA-3025a serves as a prognostic biomarker for post-PCI patients. Targeting tsRNA-3025a attenuates myocardial I/R injury and restores myocardial regeneration and repair by regulating PIK3C2A-mediated protective autophagy flux.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060265

Authors: Zihong Qi Chenggang Zhang Huilin Shi Wen Li Yuqing Xia Xiaofeng Yan Xiyan Zhou Jiaqi Ling Guochun Liu

Acute cardiovascular events driven by atherosclerosis primarily originate from thrombosis triggered by vulnerable plaque rupture or endothelial erosion. Endothelial barrier destabilization—characterized by glycocalyx impairment, intercellular junction disassembly, and abnormal cytoskeletal tension—is a core upstream pathological stage that promotes atherogenic lipoprotein leakage, inflammatory cell infiltration, and matrix degradation. Hemodynamics, primarily through wall shear stress (WSS), shape the spatial distribution and plaque phenotypes of atherosclerosis; notably, low or oscillatory shear stress is associated with, and in experimental systems can promote, pro-inflammatory, pro-oxidant and pro-permeability endothelial phenotypes that contribute to plaque initiation and vulnerability. Conversely, regular exercise training, as an intervention that modulates hemodynamics, is widely suggested to promote anti-inflammatory, antioxidant, and antithrombotic endothelial phenotypes by significantly increasing antegrade shear stress and reducing detrimental retrograde/oscillatory shear stress. With a central focus on the axis of “exercise-shear stress-glycocalyx-cytoskeleton/junction-permeability-plaque stability,” this review integrates evidence from in vitro flow chambers, animal models and human studies to critically discuss: (1) the spatiotemporal heterogeneity of WSS and its relationship with plaque vulnerability; (2) the composition, barrier function, and plasticity of the glycocalyx as the primary interface for shear stress; (3) the mechanosensory complexes at the glycocalyx and junctions that transduce shear stimuli to protective pathways such as Phosphoinositide 3-kinase (PI3K)-Akt-endothelial nitric oxide synthase (eNOS) and Krüppel-like factor 2 (KLF2), thereby stabilizing adherens/tight junctions; (4) how improved barrier homeostasis promotes the maintenance of the fibrous cap collagen scaffold by reducing lipoprotein leakage and dampening the inflammation–matrix metalloproteinase (MMP) axis. Finally, this review highlights the boundary conditions of the biological effects of shear stress: low/oscillatory shear stress is primarily associated with plaque initiation and susceptible sites, whereas focal, extremely high WSS in established stenotic lesions may contribute to late-stage high-risk remodeling. Therefore, the protective hemodynamic adaptations induced by exercise should not be simply equated with the pathologically high WSS found at stenotic sites.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060264

Authors: Makiko Kinoshita Hiroyuki Takaoka Yusei Nishikawa Yoshitada Noguchi Katsuya Suzuki Shuhei Aoki Satomi Yashima Kazuki Yoshida Haruka Sasaki Noriko Suzuki-Eguchi Tomonori Kanaeda Yusuke Kondo Yoshio Kobayashi

Left ventricular (LV) extracellular volume fraction (ECV) quantified by cardiac computed tomography (CT) reflects diffuse myocardial fibrosis. In patients with atrial fibrillation (AF) and reduced LV ejection fraction (LVEF), distinguishing tachycardia-induced cardiomyopathy from underlying myocardial disease remains challenging. The prognostic value of ECV for predicting reverse remodeling (RR) after catheter ablation for AF remains uncertain. We retrospectively analyzed 102 patients with LVEF ≤ 50% on echocardiography who underwent cardiac CT before AF ablation between May 2015 and April 2025. RR was defined as a ≥15% reduction in LV end-systolic volume with recovery of LVEF > 50%, or an absolute increase in LVEF of ≥15%. RR occurred in 49 patients (48%). ECV was significantly lower in patients with RR than in those without (31.2 ± 3.5% vs. 37.6 ± 7.8%, p < 0.001). Receiver operating characteristic analysis identified an optimal cutoff of 34.8% (area under the curve 0.77; sensitivity 88%; specificity 62%, p < 0.001). In multivariable logistic regression analysis, lower ECV remained independently associated with RR (odds ratio 0.84; 95% confidence interval 0.75–0.95; p = 0.006). CT-derived ECV was associated with RR after AF ablation in patients with reduced LVEF and may provide additional information for clinical decision-making.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060263

Authors: Peter Jakub Tomáš Toporcer Matúš Marcin Michal Trebišovský Anton Bereš Marián Homola Štefan Lukačín Adrián Kolesár

The aim of this study was to retrospectively compare modified Del Nido and blood-based St. Thomas cardioplegia in adult patients undergoing isolated aortic valve replacement (AVR). This retrospective study included adult patients undergoing isolated AVR because of aortic valve stenosis between 2024 and 2025. Patients were stratified into blood-based St. Thomas and modified Del Nido groups. The main modification of the Del Nido solution was the adjustment of the crystalloid-to-blood ratio to 1:4. Preoperative and perioperative variables, as well as postoperative biomarkers, including high-sensitivity troponin I, creatine kinase (CK), CK-MB, and lactate, were analyzed. A total of 93 patients were included in the study (blood-based St. Thomas: n = 22; modified Del Nido: n = 71). No significant differences were observed in cardiopulmonary bypass time [98 min (IQR 84–110) vs. 90 min (IQR 74–110); p = 0.184] or aortic cross-clamp time [75 min (IQR 67–86) vs. 73 min (IQR 62–87); p = 0.345]. High-sensitivity troponin I levels at 24 h were numerically, but not statistically significantly, lower in the blood-based St. Thomas group [1961 ng/L (IQR 1367–4423) vs. 2819 ng/L (IQR 1698–5054); p = 0.240]. CK levels at 6 h were comparable between the groups [8.4 μkat/L (IQR 6.5–10.1) vs. 8.5 μkat/L (IQR 6.0–12.7); p = 0.632], as were CK-MB and lactate levels at all evaluated time points. In exploratory multivariable analyses adjusted for age, sex, preoperative LVEF, cardiopulmonary bypass time, and aortic cross-clamp time, cardioplegia type was not independently associated with postoperative biomarker levels. The less frequent dosing and membrane-stabilizing properties of modified Del Nido cardioplegia did not translate into statistically significant clinical or biochemical advantages in the setting of relatively short, isolated AVR procedures.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060262

Authors: Georgios Mitsiou Savvas P. Tokmakidis Irini Patsaki Katherina Psarra Christos Kourek Eleftherios Karatzanos George Papathanasiou Stavros Dimopoulos

Endothelial progenitor cells (EPCs) constitute a cell population that enters the circulation during aerobic exercise and facilitates vascular function. In a similar action, hematopoietic progenitor cells (HPCs) are also released into circulation in response to exercise. Peripheral vascular dysfunction is frequently present in patients with heart failure. Whether acute interval exercise performed with high intensity induces EPC and HPC mobilization and affects microcirculation remains under investigation. The study population consisted of nineteen male patients with chronic heart failure (CHF) and eleven age-matched healthy individuals who underwent a high-intensity interval exercise session. Blood was drawn before, immediately after exercise, and 40 min after exercise to identify the numbers of circulating EPCs and HPCs by flow cytometry. Microcirculatory assessment was performed using near-infrared spectroscopy before and after exercise. Vascular endothelial growth factor (VEGF) change was also assessed before and after exercise in patients with CHF using flow cytometry. The interval exercise protocol revealed significant effects (p < 0.05) on EPC and HPC mobilization and systemic microcirculation (p < 0.05) in patients with CHF and healthy individuals. No significant differences were observed between patients with CHF and healthy individuals during interval exercise. VEGF did not reveal any changes immediately after interval exercise in CHF patients. Acute high-intensity interval training was associated with increased EPC and HPC mobilization and changes in microcirculation in patients with CHF and healthy individuals.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060261

Authors: Bushra Shahida Rana Brian Clapp Iqbal Saeed Malik

Transcatheter secundum atrial septal defect (ASD) closure is the preferred approach in the majority of cases. Building skill sets through understanding complex ASD anatomies is essential. Such anatomies include ASD associated with aneurysmal septum, multiple defects, absence of anterosuperior or posteroinferior rim and malaligned septum This expert-based review will focus on the key role of advanced TOE imaging during transcatheter ASD closure in challenging anatomies. We describe our institutional experience and provide a practical approach of how to plan and navigate device choice and its delivery to ensure optimal outcomes.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060260

Authors: Silvia Prosperi Sara Monosilio Andrea D’Amato Danilo Angotti Domenico Filomena Lucrezia Netti Giovanni Tonti Gianni Pedrizzetti Sara Cimino Roberto Badagliacca Paolo Severino Carmine Dario Vizza Viviana Maestrini

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) promote beneficial effects on cardiac reverse remodeling (RR) in heart failure (HF). However, most imaging evidence focuses on single chambers, mainly the left ventricle (LV) or left atrium (LA), whereas integrated biventricular and atrial remodeling remains less explored. Moreover, real-world data are limited, and myocardial–flow coupling markers, such as hemodynamic forces (HDFs), are scarcely investigated, with uncertain sex-related differences. Purpose: To evaluate multi-chamber cardiac RR after SGLT2i initiation in a real-world HF population. Secondary aims are to assess whether changes in HDFs provide additional functional insight into myocardial–flow coupling beyond conventional echocardiographic indices, and to descriptively explore sex-related differences in echocardiographic remodeling. Methods: Patients with HF and ejection fraction (EF) ≤ 45%, naive to SGLT2i and on stable guideline-directed medical therapy for ≥3 months, were enrolled. Standard and advanced echocardiography were performed at baseline and follow-up, including speckle-tracking and HDFs assessment. NYHA class and NT-proBNP were collected. Analyses were performed overall and stratified by sex. Results: Sixty-eight patients were included. After 6 months, RR was observed across all chambers: LV-RR in 33 patients (49%), right ventricular (RV) RR in 35 (52%), biventricular RR in 18 (27%), and LA-RR in 14 (21%). HDFs showed significant realignment, suggesting association with improved myocardial–flow coupling. RR effects were comparable between sexes (p > 0.05). NT-proBNP significantly decreased. Conclusions: In this real-world cohort, SGLT2i therapy was associated with significant multi-chamber RR and HDFs realignment, supporting improved myocardial–flow coupling beyond conventional indices. Exploratory sex-related analyses showed no significant differences. Larger and longer-term randomized studies are warranted.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060259

Authors: Hussein Abdul Nabi Luke Dreher Michael Liu Soad Al Osta Suganya A. Karikalan Eiad Habib Hicham Z. El Masry

Background: AF in the setting of cardiac amyloidosis is associated with a high risk of TEs, irrespective of CHA2DS2-VASc score. While warfarin has been the traditional anticoagulant, DOACs offer a promising alternative, but their safety in this population remains underexplored. This study aimed to evaluate the prevalence of thromboembolic events (TEs), including stroke and transient ischemic attack (TIA), and major bleeding events in patients with cardiac amyloidosis (CA) and atrial fibrillation (AF) treated with either warfarin or direct oral anticoagulants (DOACs). Additionally, we aimed to explore whether DOACs are at least as effective as warfarin in protecting against TEs in this population. Methods: This retrospective cohort study analyzed 422 patients with confirmed CA and AF from Mayo Clinic, with a median follow-up of 4.3 years. Data on anticoagulation therapy, baseline characteristics, and outcomes (TEs and bleeding) were collected. Statistical analyses included chi-square tests, t-tests, and Cox regression to assess the relationship between anticoagulation and TE. Results: Among 422 patients, 21 experienced a TE. The annual event rate was 0.83% for warfarin and 0.67% for DOACs, with no significant difference (HR 0.66, CI 0.22–2.01, p = 0.5). Patients with anticoagulation interruptions > 5 days had increased TE risk (HR 3.19, CI 0.97–10.5, p = 0.056). The bleeding rate was 9.9% over 4.3 years (2.33% per year), with no significant differences between anticoagulants. Conclusions: Both warfarin and DOACs have similar, low risks of TEs in CA and AF patients. However, anticoagulation interruptions were associated with increased TE risk, emphasizing the challenges in managing anticoagulation in this population.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060258

Authors: Marwan Hamiko Lamis Keswani Ali Bayram Teresa Rondorf Andre Spaeth Miriam Silaschi Sebastian Zimmer Chris Probst Georg Nickenig Ali El-Sayed Ahmad Farhad Bakhtiary Nadjib Schahab

(1) Background: Coronary artery disease (CAD) frequently coexists with thoracic aortic disease and may increase the risk of adverse outcomes after thoracic endovascular aortic repair (TEVAR). Whether routine preoperative coronary angiography (CAG) improves outcomes remains unclear. (2) Methods: We retrospectively analyzed 177 patients undergoing elective TEVAR between 2015 and 2025 with a median follow-up of 4.9 years. Two analyses were performed: patients who underwent preoperative CAG versus those who did not, and patients with versus without CAD. Survival was assessed using Kaplan–Meier analysis and overlap-weighted Cox regression. (3) Results: Preoperative CAG was performed in 94 patients (53.1%) and identified newly diagnosed or progressive CAD in 42 (44.7%). Overall, 24 patients (13.6%) underwent coronary revascularization before TEVAR. Patients with CAD were older and had a greater comorbidity burden. Despite these differences, preoperative CAG was not associated with differences in in-hospital mortality (2.1% vs. 6.0%, p = 0.159), major adverse cardiovascular events (11.3% vs. 9.0%, p = 0.754), or long-term survival (log-rank p = 0.10). Patients with CAD showed higher unadjusted long-term mortality than those without CAD (31.7% vs. 17.5%; log-rank p = 0.003). However, after overlap weighting, CAD was no longer significantly associated with mortality (adjusted HR 1.4, 95% CI 0.71–2.8). Among patients with angiographically verified coronary disease, preoperative revascularization before TEVAR was not associated with improved long-term survival (HR 2.20, 95% CI 0.69–6.98). (4) Conclusions: Preoperative CAG detects clinically relevant, often unrecognized CAD in a substantial proportion of TEVAR candidates and enables revascularization before surgery. Despite a higher coronary burden, patients who underwent CAG had outcomes comparable to those who did not, and the crude long-term survival disadvantage of CAD was largely explained by the accompanying systemic atherosclerotic burden. Routine preoperative coronary assessment appears justified in elective TEVAR.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060257

Authors: Georgiana Pintea Bentea Marielle Morissens Pierre-Emmanuel Massart Jose Castro Rodriguez

A 40-year-old man with complex congenital heart disease (double-inlet left ventricle with transposition of the great arteries), previously treated with a Blalock–Taussig shunt in infancy and a modified Fontan procedure (including superior vena cava-to-pulmonary artery anastomosis, atriopulmonary connection, and tricuspid valve closure with a Dacron patch), presented to the emergency department with worsening dyspnea and hypoxemia (SpO2 < 80%). Echocardiography suggested a shunt through the tricuspid patch, possibly related to prior atrial flutter ablation. Cardiac catheterization confirmed an approximately 10 mm fenestration in the calcified patch causing a significant bidirectional shunt, along with two fistulae between the innominate vein and the left atrium. The fenestration was successfully closed using a septal occluder via right femoral venous access under transesophageal echocardiographic guidance. The venous collaterals were occluded with vascular plugs via right femoral and left brachial approaches. Technical success of the closure of the intracardiac and the venous shunts was confirmed angiographically at the end of the procedure. Oxygen saturation improved immediately from 72% to 91% and remained stable at the 2-year follow-up. Similarly, NYHA functional class improved from IV to II and episodes of tachycardia became less frequent and better tolerated, with sustained benefit throughout follow-up.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060256

Authors: Rita B. Gagyi Ioan A. Minciuna Mate Vamos Attila Nemes Peter Ruppersberg Wim Bories Tamas Szili-Torok

Aims: To assess the spatiotemporal stability of extra-pulmonary vein (PV) sources in patients with persistent atrial fibrillation (AF). Methods and results: Nine patients (mean age 63 ± 9 years, 55% male) with persistent AF were included who underwent an initial and at least one redo catheter ablation procedure utilizing panoramic atrial mapping (PAM) systems (CardioInsight, electrographic flow (EGF), and/or charge density (CDM) mapping). Procedures were performed in the following combinations: CDM-CDM (1 patient), CDM-EGF (1 patient), EGF-CDM (3 patients), CardioInsight-CDM (1 patient), EGF-EGF (3 patients). We reviewed maps and analyzed the location of AF sources. Spatiotemporal stability was defined as the presence of an AF source of identical location on available maps during the initial and the redo procedure. In 4 patients (44.4%), localization of AF sources mapped at the repeat procedure corresponded with the localization of sources mapped during the index procedure. In two patients, no sources were identified during the second procedure. In the remaining 3 patients, the localization of sources was detected at different locations. Conclusions: Our findings suggest the presence of spatiotemporal stability of AF sources; however, novel sources can also be found during the repeated procedure, consistent with disease progression.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060255

Authors: Emmanouil Chourdakis Kambis Mashayekhi Ulrich Schäfer Christos Katsouras

Hypertrophic cardiomyopathy (HCM), with or without obstructive phenomena, remains underdiagnosed and undertreated. This condition often involves pathological changes in the mitral valve leaflets and apparatus, which can lead to relevant mitral regurgitation (MR). The mechanism of MR is mostly related to the systolic anterior motion (SAM) of the anterior mitral leaflet. The treatment of patients with hypertrophic obstructive cardiomyopathy (HOCM) with persistent symptoms despite optimal pharmacological therapy includes septal myectomy or transcoronary ablation of septal hypertrophy (TASH). Percutaneous edge-to-edge repair of the mitral valve represents an innovative alternative therapy with promising results regarding clinical symptoms and echocardiographic findings. In this article, we provide a concise, critical overview of the current evidence on this technique in HOCM and delineate future perspectives and unresolved issues.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060254

Authors: Hani Ali-Ghosh Jason Kho Fotios Leventis Sanjay Asopa Geoffrey Tsang Sunil K. Ohri

Carcinoid heart disease is a progressive right-sided valvulopathy caused by serotonin and other vasoactive mediators released by metastatic neuroendocrine tumours. As oncological therapies have extended survival, cardiac disease has become a leading determinant of mortality. Operative mortality has decreased to 5–6% in contemporary high-volume centres, and long-term survival appears increasingly determined by tumour biology rather than cardiac disease when surgery is appropriately timed. The principal determinant of operative outcome is preoperative right ventricular function; symptom-based referral alone is insufficient because many patients remain compensated until ventricular dysfunction is advanced. This review synthesises the evidence on surgical timing, operative strategy, prosthesis selection, perioperative endocrine management, and emerging transcatheter options. Tricuspid valve replacement is required in the majority of patients, with concomitant pulmonary valve replacement advocated where concurrent disease is present. Bioprosthetic valves are preferred. Continuous perioperative octreotide infusion has substantially reduced the incidence of carcinoid crisis. Structured multidisciplinary decision-making integrating echocardiographic surveillance, biomarker monitoring, and oncological status assessment is essential.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060252

Authors: Rauf Önder Salih Özçobanoğlu

Objective: The present study aimed to determine clinical and surgical variables associated with postoperative morbidity and 10-year mortality in isolated mitral valve replacement (MVR) and to assess the association between sex and postoperative outcomes. Materials and Methods: A total of 1629 patients undergoing isolated MVR in one center during the period between January 2000 and December 2015 were retrospectively analyzed. Hospital records provided demographic, clinical, echocardiographic, and operative data. Cox regression analyses were used to determine factors associated with postoperative morbidity and long-term mortality. The Kaplan–Meier method was used to analyze long-term survival, and the log-rank test was used to compare the groups. Results: A total of 866 (53.1%) patients were male and 763 (46.9%) were female, and the average age was 63.8 ± 10.9 years. There were no significant differences in female and male patients regarding basic demographic and clinical characteristics. The first 30-day in-hospital morbidity rate was also significantly greater in women than in men (25.7% vs. 20.6%; p = 0.015). The in-hospital mortality was more prevalent among women (5.0% vs. 3.0%; p = 0.043). Age, sex (female), diabetes mellitus, pulmonary hypertension, chronic obstructive pulmonary disease, critical preoperative condition, high body mass index, longer cardiopulmonary bypass time, and low left ventricular functioning were significantly associated with postoperative morbidity in multivariable analysis. The total mortality rate during a 10-year follow-up was 33.2%, which was considerably higher among women compared to men (36.3 vs. 30.5; p = 0.013). Kaplan–Meier analysis demonstrated significantly lower long-term survival in female patients (log-rank p = 0.011). Conclusions: Morbidity and mortality following isolated MVR are closely related to patient-related factors. Female sex showed a significant adjusted association with higher 10-year mortality in multivariable analysis, warranting careful long-term risk assessment in female patients.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060253

Authors: Hayrettin Hakan Aykan Musa Öztürk Yasemin Nuran Dönmez İlker Ertuğrul Alpay Çeliker Tevfik Karagöz

The increasing use of cardiac implantable electronic devices (CIEDs) in pediatric and adolescent populations has led to a growing need for transvenous lead extraction (TLE). However, data on long-term outcomes remain limited. This study aimed to evaluate the efficacy and safety of TLE using mechanical rotational dilator sheaths in a pediatric cohort. This retrospective single-center study included 35 patients who underwent TLE between 2007 and 2025. Outcomes were compared between Evolution® (Cook Medical, Bloomington, IN, USA) and TightRail™ (Spectranetics/Philips, Colorado Springs, CO, USA) sheath systems. A total of 40 leads were extracted (mean age at extraction: 15.1 ± 4.2 years; 57% male). The most common indication for extraction was lead fracture/dysfunction (22/35–63%). Complete success with the procedure was achieved in 23 (66%) patients, and clinical success in 30 (86%). Major complications requiring surgery occurred in 5 (14%) patients, and minor complications in 2 (6%). Notably, all major complications occurred in patients with implantable cardioverter-defibrillator (ICD) leads (p = 0.013), including innominate vein injury, pericardial effusion, tricuspid entrapment, and cardiac perforation. A comparison of the Evolution® (n:20) and TightRail™ (n:15) sheath groups showed no statistically significant differences in complete procedural success (p = 0.603), clinical success (p = 0.604), or the incidence of major complications (p = 0.640). No procedure-related mortality was observed. TLE using mechanical rotational dilator sheaths in pediatric patients is feasible and provides acceptable clinical success rates. However, the risk of major complications remains considerable, particularly in patients with ICD leads. These findings highlight the importance of careful procedural planning and performing TLE in experienced centers with immediate surgical backup.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060251

Authors: Lisa Simioni Wesley Bennar Giulia S. Beretta Thais Pittet Giacomo Maria Cioffi Julius Jelisejevas Peter Wenaweser Pascal Meier Serban Puricel Mario Togni Stéphane Cook Ioannis Skalidis

Background: Obesity is increasing worldwide and remains a major contributor to cardiovascular morbidity and mortality. It is strongly associated with hypertension, dyslipidemia, diabetes mellitus, endothelial dysfunction, and chronic inflammation, all of which promote coronary artery disease and acute coronary syndrome (ACS). Despite this well-established risk profile, multiple studies have described an “obesity paradox,” suggesting that obese patients may experience better outcomes after percutaneous coronary intervention (PCI) for ACS than normal-weight individuals. Objective: This narrative review aims to discuss the pathophysiological basis of the obesity paradox and to synthesize contemporary evidence regarding the relationship between body mass index (BMI), major adverse cardiovascular events (MACE), and mortality after PCI in patients presenting with ACS. Results: Contemporary observational cohorts consistently suggest a non-linear relationship between BMI and MACE outcomes after PCI. Overweight and mildly obese patients often demonstrate lower crude mortality and fewer MACE, whereas underweight patients consistently show the poorest prognosis. However, after adjustment for age, left ventricular ejection fraction (LVEF), renal function, frailty, and nutritional status, obesity is less consistently associated with improved outcomes. Overweight status appears to be more reproducibly associated with better prognosis than obesity itself. Conclusions: The obesity paradox is likely driven less by a true protective effect of excess adiposity and more by younger age at presentation, preserved physiological reserve, lower frailty burden, and the limitations of BMI as a marker of cardiovascular risk. Underweight status emerges as the strongest predictor of adverse outcomes. Nutritional assessment and body composition should complement BMI in risk stratification after ACS.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060249

Authors: Graziella Pompei Manfredi Arioti Carolina Moretti Francesco Bendandi Riccardo Panevino Sebastiano Sanna Gavino Casu Andrea Rubboli

Over the past two decades, the combined use of long-term anticoagulation and antiplatelet therapy following percutaneous coronary intervention has been extensively investigated. Efforts to define an optimal antithrombotic strategy—balancing protection against thrombotic and thromboembolic events with minimization of bleeding risk—have led to the design and conduct of randomized clinical trials. This narrative review synthesizes the main evidence comparing different antithrombotic approaches in this setting, with particular focus on regimens stratified by oral anticoagulant type and on the direct comparison between aspirin- and clopidogrel-based double antithrombotic therapy, as evaluated in a limited number of recent studies. Further large-scale randomized data comparing these two regimens are needed to strengthen the current evidence and clarify this issue, as well as to evaluate the role of platelet function and/or genetic testing in guiding the selection of the optimal antiplatelet agent.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060250

Authors: Mhd Nawar Alachkar Johannes Schlegl Marwin Bannehr Tanja Kücken Michael Lichtenauer Vera Paar Michael Neuß Anja Haase-Fielitz Christoph Edlinger Christian Butter

Background: The TRI-SCORE was developed to predict mortality after tricuspid valve surgery and has demonstrated prognostic value in patients undergoing transcatheter tricuspid valve interventions (TTVI). Right ventricular–pulmonary arterial (RV–PA) uncoupling assessed by the TAPSE/sPAP ratio has emerged as a prognostic marker in selected populations; however, its incremental value within established risk scores remains unclear. Methods: In this prospective single-centre cohort, 109 patients undergoing TTVI were included. The original TRI-SCORE was calculated for all patients. A modified TRI-SCORE was proposed by substituting the definition of right ventricular dysfunction based on TAPSE with RV–PA uncoupling, defined as TAPSE/sPAP <0.406 using invasively measured systolic pulmonary artery pressure. The endpoints were 12-month all-cause mortality and a combined endpoint of death or cardiovascular rehospitalization. Results: At 12 months, all-cause mortality occurred in 19.3% of patients, and the combined endpoint in 40.4%. Both original and modified TRI-SCOREs were significantly associated with 12-month mortality (OR 1.80 per point increase, 95% CI 1.30–2.48; p < 0.001 and OR 1.81 per point increase, 95% CI 1.31–2.49; p < 0.001, respectively) and demonstrated comparable discrimination (AUC 0.78 for both; DeLong p = 0.90). Furthermore, both scores were significantly associated with the combined endpoint (TRI-SCORE: OR 1.36 per point increase, 95% CI 1.08–1.71; p = 0.008; modified TRI-SCORE; OR of 1.33 per one-point increase, 95% CI 1.07–1.66; p = 0.009) with modest and comparable AUCs (~0.65). Conclusion: In patients undergoing TTVI, replacing TAPSE with RV–PA uncoupling did not improve the prognostic performance of the TRI-SCORE for mortality or combined clinical outcomes.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060248

Authors: Chun Shing Kwok Pippa Hamnett Matt Palmer Dennis Chong

Background: The care of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) is often fragmented and routine datasets rarely capture real-world clinical trajectories and reasons for diagnosis. We introduce a novel approach, called forensic data acquisition and pathway analysis, to examine the real-world experiences of patients with ATTR-CM in our district general hospital. Methods: We retrospectively evaluated inpatient and outpatient healthcare records for our hospital between 2019 to 2025 as a part of a quality improvement project. Results: We identified 26 cases of confirmed or likely wild-type ATTR-CM and four hereditary cases from two families carrying the S77Y variant and estimate the prevalence of transthyretin cardiac amyloidosis to be 1 per 10,000 patients. Many red flags were present in patients, including carpal tunnel syndrome (63.3%) and lumbar spinal stenosis (26.7%), as well as echocardiographic features of left ventricular hypertrophy (86.7%), left atrial dilatation (76.7%), right ventricular hypertrophy (43.3%), and a dense or speckled myocardial appearance (43.3%). Among patients with wild-type disease, the most frequent trigger for further investigation was the presence of suspicious features on transthoracic echocardiography, accounting for 13 cases. Incidental abnormalities detected on cardiac MRI contributed to another six diagnoses. In two patients, non-invasive imaging did not provide sufficient diagnostic certainty, and myocardial biopsy was required to confirm ATTR-CM. Conclusions: Forensic data acquisition and pathway analysis provides a powerful approach for revealing real-world clinical activity in ATTR-CM, exposing diagnostic patterns and missed opportunities that remain hidden in routine datasets.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060247

Authors: Fausto Biancari Angelo M. Dell’Aquila Timo Mäkikallio Giuseppe Gatti Francesco Onorati Andrea Perrotti Stefano Rosato Paola D’Errigo Matteo Pettinari Sven Peterss Joscha Buech Tatu Juvonen Caius Mustonen Till J. Demal Marek Pol Petr Kacer Konrad Wisniewski Igor Vendramin Daniela Piani Mauro Rinaldi Luisa Ferrante Eduard Quintana Robert Pruna-Guillen Antonio Fiore Giovanni Mariscalco Metesh Acharya Mark Field Manoj Kuduvalli Francesco Nappi Sebastien Gerelli Dario Di Perna Javier Rodriguez-Lega Lenard Conradi

Background: The nature and prognosis of type A intramural hematoma (TAIMH) are not well established. In this study, we evaluated the early and late outcome after surgery for this emergency condition. Methods: The ERTAAD registry included consecutive patients who underwent surgery for acute type A aortic dissection (TAAD) or TAIMH at 18 European centers for cardiac surgery. In this study, we compared the early and late outcomes of TAIMH and typical TAAD. Results: In total, 3902 consecutive patients were included in the ERTAAD registry, and 386 (9.9%) patients had TAIMH. Penn class a was present in 43.1% TAAD patients and in 34.5% TAIMH patients (p < 0.001). Among 3-month survivors, 10-year relative survival was 0.80 (95%CI 0.77–0.84) in TAAD patients and 0.76 (95%CI 0.63–0.88) in TAIMH patients. Propensity-score matching yielded 386 pairs of patients, and no significant difference was observed between the study groups in terms of early and late outcomes. In-hospital mortality rates were comparable (TAIMH 13.5% vs. TAAD 16.3%, p = 0.266). Ten-year mortality was 51.3% among TAIMH patients and 51.6% among TAAD patients (p = 0.274). TAIMH and TAAD had similar 10-year cumulative incidence rates of proximal (4.2% vs. 3.3%, p = 0.738) and distal aortic reoperations (12.6% vs. 7.6%, p = 0.779). Conclusions: This cohort study showed that the prevalence of patients with TAIMH requiring surgery is low and their risk profile is significantly different as shown by the Penn classification. The early and late outcomes of the study groups were not statistically different compared to typical TAAD when adjusted for baseline and operative variables. The relative survivals of 90-day TAIMH and TAAD survivors were low compared to the matched general population, indicating that surgically treated TAIMH demonstrated postoperative outcomes are poor and comparable to surgically treated TAAD after adjustment. Post-hoc power analysis suggested that much larger studies are needed to confirm these findings. These results are limited to TAIMH patients who underwent surgery, and this study did not address the outcome of patients who were conservatively treated.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060246

Authors: Qinchao Wu Xu Liu Zhuo Liang Yanguang Li Qiaoyuan Li Sixian Weng Lili Wang Yijie Liu Zhipeng Hu Jiawei Zhang Ran Xiong Yunlong Wang

Background: Ethanol infusion into the vein of Marshall (EI-VOM) is widely used to facilitate atrial fibrillation ablation and block of the mitral isthmus. However, it cannot be completed in some anatomically challenging cases. This study aimed to introduce and evaluate a novel reversed U curve method of EI-VOM. Methods: This case-series study enrolled consecutive patients with atrial fibrillation or atrial flutter who were scheduled for EI-VOM. When VOM venography was successfully performed, the conventional EI-VOM method was attempted first. If this approach failed or took ≥20 min, the novel method was applied. The success rate, complications, and applicable anatomical conditions of the new method were summarized. Results: Of the 205 patients enrolled in this study, the novel method was applied to 45 patients, and technical success was achieved in 42 patients (93.3%). Among the patients who underwent the novel method, twenty-four (53.3%) had a long cavotricuspid isthmus, nineteen (42.2%) had a VOM ostium close to the coronary sinus ostium, and sixteen (35.6%) had a prominent Eustachian ridge. The total mean procedure time of EI-VOM using the novel method was 30.00 ± 4.5 min. Acute bidirectional mitral isthmus block was achieved in 40 cases (88.9%), and the mean ethanol volume injected was 8.21 ± 1.5 mL. No serious in-hospital complications were documented in patients treated with the novel method. Conclusions: In this single-center case series, the reversed U curve method appeared feasible as a femoral bailout strategy for EI-VOM in selected anatomically challenging cases. Further prospective, multicenter studies involving multiple operators are required to confirm its reproducibility, efficacy, and safety over conventional approaches.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060245

Authors: Rauf Avcı Fatih Han Kumtaş

Background: Atrial septal defect (ASD) is common in adults and may cause chronic right ventricular (RV) volume overload and remodeling. Electrocardiography (ECG) may serve as a screening adjunct to echocardiography. Objectives: To evaluate the association of the terminal D1S + D3R ECG pattern, defined as a terminal S wave in lead I plus a terminal R wave in lead III, with structural and hemodynamic right heart involvement in adult secundum ASD. Methods: A total of 161 adult patients with secundum ASD were retrospectively analyzed. Right heart involvement was assessed using pulmonary-to-systemic flow ratio (Qp/Qs) ≥ 1.5 and a right ventricular/left ventricular (RV/LV) ratio > 1. ECG parameters, including right bundle branch block (RBBB), right axis deviation, V1–V2 R-wave positivity, and terminal D1S + D3R, were evaluated by two blinded cardiologists, with final classifications determined by consensus. Multivariable Firth penalized logistic regression, correlation analyses, and receiver operating characteristic (ROC) analyses were performed. Results: In the multivariable Firth penalized logistic regression model, pulmonary artery pressure (PAP) and ASD diameter were independently associated with Qp/Qs ≥ 1.5, whereas the terminal D1S + D3R pattern was not. The terminal D1S + D3R pattern was independently associated with RV dilatation after adjustment for age, sex, PAP, and ASD diameter (odds ratio [OR]: 9.90, 95% confidence interval [CI]: 2.82–38.20, p < 0.001) and showed good discriminatory performance for RV dilatation (area under the curve [AUC]: 0.881, 95% CI: 0.831–0.932). Conclusions: In adults with secundum ASD, a positive terminal D1S + D3R ECG pattern is independently associated with RV dilatation and may serve as a practical adjunctive screening marker. However, it should not replace echocardiographic assessment.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060244

Authors: Vedat Aslan Sefa Sural Özerdem Özçalışkan Gökhan Gökaslan

Total coronary revascularization via anterior thoracotomy (TCRAT) enables complete anatomical revascularization without sternotomy; however, data on its impact on left ventricular function remain limited. This study compared left ventricular functional outcomes between TCRAT and median sternotomy coronary artery bypass grafting (MS-CABG) in 554 patients undergoing elective isolated CABG at four centers (January 2020–January 2025) with preoperative and ≥3-month follow-up echocardiography. Patients were grouped as TCRAT (n = 241) or MS-CABG (n = 313). Stabilized inverse probability of treatment weighting was applied to reduce selection bias, achieving adequate covariate balance (all standardized mean differences < 0.10). The primary endpoint was follow-up left ventricular ejection fraction, assessed using IPTW-weighted analysis of covariance adjusted for preoperative values. No significant difference was observed between groups (β = 0.13; 95% CI, −0.63 to 0.90; p = 0.734). Adjusted left ventricular end-diastolic diameter was modestly higher in the MS-CABG group (β = 0.57 mm; 95% CI, 0.17–0.98; p = 0.006), while end-systolic diameter was similar. TCRAT was associated with longer operative times but shorter intensive care unit and hospital stays, along with lower transfusion requirements. These findings suggest that there was no statistically significant difference in follow-up systolic function between the surgical approaches. Although a modest difference in LVEDD was identified, its clinical significance remains uncertain.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060243

Authors: Benjamin J. Behers Christoph A. Stephenson-Moe Sammy Shihadeh Tonya S. King Omar Hozayen Joseph Hozayen Maria Moreno Karen M. Hamad Antonio Moretta

Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with significant morbidity and mortality. Catheter ablation of AF has been shown to result in a significant reduction in AF burden and recurrence. Pulsed field ablation (PFA) is a new modality of catheter ablation that is noninferior to its thermal ablation counterparts, coupled with a more favorable safety profile. This study seeks to compare clinical outcomes between two PFA systems: PulseSelect™ (Medtronic, Minneapolis, MN, USA) (circular catheter) and FARAPULSE™ (Boston Scientific, Marlborough, MA, USA) (pentaspline catheter). Secondary aims are to evaluate the impacts of post-ablation mapping with a high-density mapping catheter (PAHDMC) and both procedure and fluoroscopy times on recurrence. Overall, across 895 patients with a median follow-up of 12.5 months, there was a recurrence rate of 39%. PFA system, PAHDMC, and procedure time all had no effect on recurrence. To our knowledge, this is the first study to compare recurrence rates between different PFA systems. Fluoroscopy time, however, was a significant predictor of recurrence. In the pentaspline catheter group, the odds of recurrence were 60% greater for every 15 min increase in fluoroscopy time. Future studies are needed to continue comparing outcomes amongst PFA systems and assess whether PAHDMC improves outcomes in PFAs.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060242

Authors: Débora Andrea Castiglioni Alves Pamela Carvalho da Rosa Andréa Castiglioni Alves Teixeira e Silva Joceli Fernandes Alencastro Bettini de Albuquerque Lins Gisela Arsa Lucieli Teresa Cambri

Background: Heart rate variability (HRV), the physiological variation between consecutive heartbeats and a non-invasive marker of autonomic regulation, is associated with cardiovascular health. This retrospective cross-sectional study investigated the associations of severe obesity, hypertension, and physical activity with 24 h HRV in patients undergoing evaluation for bariatric surgery. Methods: A total of 1048 individuals were classified according to obesity class, hypertension diagnosis, and physical activity level. Results: Severe obesity was associated with lower 24 h HRV indices (p < 0.001) and higher odds ratio of hypertension (OR 2.04 [1.60–2.63]) and antihypertensive medication use (OR 1.98 [1.53–2.58]) compared to class II obesity. Hypertension was associated with lower HRV indices (p < 0.001), higher odds of diabetes (OR 4.20 [2.88–6.12]) and dyslipidemia (OR 2.85 [2.17–3.74]), greater use of related medications (OR 3.53 [2.18–5.70)] and 2.96 [1.99–4.40]), respectively), and lower physical activity (OR 0.64 [0.47–0.87]). Physical activity was associated with higher 24 h HRV indices (p < 0.001) and lower odds of hypertension (OR 0.64 [0.47–0.87]) and antihypertensive medication use (OR 0.70 [0.50–0.97]). Conclusions: Severe obesity and hypertension were associated with reduced 24 h HRV, whereas physical activity was associated with more favorable HRV parameters in adults undergoing evaluation for bariatric surgery, supporting its relevance for cardiovascular health in this population.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060241

Authors: Masatsugu Okamura Sandra Palus Wolfram Döehner Stephan von Haehling Stefan D. Anker Michael Brines Jochen Springer

Background: Cancer cachexia is a serious condition during the last stages of the disease, which is characterized by the loss of muscle and fat mass in patients with cancer. There are no effective treatments for cancer cachexia, and new treatment interventions are urgently needed. We have previously demonstrated that 5 mg/kg/day bisoprolol and 1.7 µg/kg/day ARA 284, a small non-erythropoietic tissue protective peptide, separately have positive effects in a rat model of cancer cachexia. Methods: We investigated the compound effects of both bisoprolol and ARA 284 by targeting multiple pathways in the Yoshida hepatoma rat model of cancer cachexia. Rats were randomly allocated to one of the following treatment groups: bisoprolol (5 mg/kg/day), ARA 284 (1.7 µg/kg/day), a 25% combination (1.25 mg/kg/day bisoprolol + 0.425 µg/kg/day ARA 284), a 75% combination (3.75 mg/kg/day bisoprolol + 1.275 µg/kg/day ARA 284), or placebo. Results: The combination of 3.75 mg/kg/day bisoprolol and 1.275 µg/kg/day ARA 284 showed the strongest overall effects compared with the respective effective monotherapies, respectively, or placebo across multiple endpoints, including body weight, lean mass, food intake, spontaneous activity, and cardiac function in a rat model of cancer cachexia (p < 0.01, respectively). Furthermore, this combination therapy had the strongest effects on survival against the placebo (hazard ratio 0.08, 95% confidence interval 0.04 to 0.17, p < 0.001). Conclusions: Our findings show that the combination of bisoprolol and ARA 284 is beneficial in a hepatoma cachexia model and may provide greater overall effects than either monotherapy alone.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060239

Authors: Ahmed Mahmoud Elsoudy Luciano Candilio

Background: Interventional cardiology is increasingly being reshaped by rapid progress in non-invasive cardiovascular imaging. Coronary computed tomography angiography (CTCA), once used mainly to exclude obstructive coronary artery disease (CAD), is now being adopted as a broader planning instrument before percutaneous coronary intervention (PCI). Its ability to generate high-resolution three-dimensional visualization of the coronary tree, together with functional assessment through CT-derived fractional flow reserve (FFR-CT) and more advanced plaque analysis supported by artificial intelligence (AI), has expanded its relevance from diagnosis alone to strategic procedural preparation. In this setting, CTCA can help refine lesion assessment, anticipate technical complexity, and support better procedural and clinical outcomes. Technological Advancements: The value of CTCA for both diagnosis and risk stratification has increased substantially with recent technical innovation. Among the most important developments is the maturation of FFR-CT, which enables non-invasive physiological interrogation of coronary stenoses using computational modeling. At the same time, artificial intelligence and deep learning tools are reshaping the CTCA workflow by improving automation, facilitating plaque analysis, and highlighting adverse plaque characteristics such as positive remodeling, spotty calcification, and the napkin-ring sign. Clinical Applications: In modern catheterization practice, CTCA is increasingly used to address anatomically demanding scenarios. Its role is particularly valuable in chronic total occlusion (CTO) intervention, where it can delineate occlusion length, stump characteristics, vessel course, and collateral anatomy before the procedure. Its usefulness also extends beyond CTO PCI by supporting vessel sizing, stent planning, and anticipation of lesion preparation requirements in complex coronary disease. Challenges: Despite these advantages, several barriers continue to limit wider implementation, including blooming from heavy calcification, radiation burden, contrast-related renal concerns, and the practical difficulty of embedding CTCA-based planning into routine workflows. Conclusions: CTCA is becoming an increasingly important adjunct in PCI planning because it can combine anatomical definition, physiological interpretation, and plaque-level information before invasive treatment is undertaken. Overall, this review emphasizes CTCA not only as a diagnostic modality, but also as a practical pre-procedural roadmap that can guide lesion selection, stent planning, calcium modification strategies, and overall PCI strategy.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060240

Authors: Osama Alkouri Walid Al-Qerem Mohamad Jarrah Ghaleb Alharbi Nour Ali Alrida Rahma Musaed Alabkal Ayman Jaber Hammoudeh Mohamed Ezzelregal Abdelgawad Abdulkareem Alshehri Abdullah Yaqoub Hasan Mohannad AbuRuz Fatma Refaat Ahmed Mohammed Aldalaykeh

Background: Metabolic syndrome (MS), characterized by a constellation of interrelated cardiometabolic abnormalities, markedly amplifies cardiovascular risk. Despite the high prevalence of atherosclerotic cardiovascular disease (ASCVD) in the Middle East, evidence regarding the burden and determinants of MS in this high-risk population remains limited. This study aimed to estimate the prevalence of MS and identify its independent predictors among Middle Eastern patients with established ASCVD. Methods: This comprehensive analysis integrated data from two complementary sources: a prospective cohort derived from the Jordan SMuRF-less Study, which enrolled adults (≥18 years) with confirmed ASCVD across nine centers in Jordan, and a pooled retrospective dataset from six regional cardiovascular registries. Standardized case report forms were used to collect demographic, clinical, and laboratory data. Participants were stratified according to the number of standard modifiable risk factors (SMuRFs) into three categories (0, 1–2, and 3–4 SMuRFs). Multivariable logistic regression analysis was conducted to determine independent predictors of MS. Results: Among 1016 patients with ASCVD, MS was present in 42.7% of the cohort. The prevalence of MS demonstrated a significant graded increase with higher SMuRF burden, rising from 2.2% in patients without SMuRFs to 28.3% in those with one to two SMuRFs and 62.2% in those with three to four SMuRFs (p < 0.001). Patients with MS were significantly older and exhibited higher body mass index and triglyceride levels, lower high-density lipoprotein cholesterol, and a greater prevalence of hypertension, diabetes mellitus, dyslipidemia, chronic kidney disease, and heart failure (all p < 0.001). Independent predictors of MS included advanced age, diabetes mellitus, hypertension, chronic kidney disease, heart failure, elevated body mass index, and increased triglyceride levels. In contrast, higher HDL cholesterol and smoking were inversely associated with MS. Conclusions: MS is highly prevalent among Middle Eastern patients with ASCVD and is strongly associated with cumulative SMuRF burden in a graded manner. These findings highlight the urgent need for targeted, region-specific strategies focusing on early identification and comprehensive management of cardiometabolic risk in this vulnerable population.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060237

Authors: Juan Manuel Castillo-Casas Carlos García-Padilla Rita Carmona Estefanía Lozano-Velasco Diego Franco

The epicardium is an embryonic tissue layer essential for heart morphogenesis, providing progenitor cells and regulatory signals that support myocardial growth and coronary vessel formation. Epicardial cells arise from the proepicardium (PE) and spread over the myocardium to form the embryonic epicardium (EE), a transition that requires tight coordination between proliferation, migration, and lineage priming. However, the molecular mechanisms controlling this developmental timing remain incompletely understood. Here, we identify Trim71 as a key regulator of epicardial cell behaviour during the PE-to-EE transition. Trim71 is enriched in the PE and subsequently downregulated as cells acquire migratory competence. Functional analyses show that loss of Trim71 function decreases proliferation while promoting migration, as well as inducing the expression of epicardial commitment markers, suggesting that Trim71 is a controller of a progenitor-like state. We further demonstrate that Trim71 is necessary for these processes through a reciprocal feedback loop with the microRNAs let-7c and miR-30c. Our findings establish Trim71 as a temporal gatekeeper that coordinates the balance between progenitor maintenance and migration during early epicardial development. This Trim71-miRNAs axis constitutes a novel post-transcriptional layer of regulation that ensures the correct timing of epicardium development during cardiogenesis.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060238

Authors: Andrea Falcetta Francesca Giordana Paolo Desalvo Giorgio Baralis Domenico Vitale Giuseppe Lauria Roberta Rossini

Coronary–bronchial artery fistulas (CBAFs) represent a rare subset of coronary artery fistulas characterised by an abnormal communication between an epicardial coronary artery and the bronchial arterial circulation. Although historically considered incidental findings, the widespread use of multimodality cardiovascular imaging—particularly coronary computed tomography angiography—has led to increasing recognition of these anomalies in contemporary clinical practice. The clinical significance of CBAFs varies widely and depends primarily on fistula size, shunt magnitude, and associated cardiopulmonary conditions. While many small fistulas remain asymptomatic, larger or haemodynamically significant lesions may result in myocardial ischaemia due to coronary steal, ventricular remodelling, pulmonary manifestations such as haemoptysis, and aneurysmal degeneration of the fistulous tract. A comprehensive evaluation typically requires an integrated multimodality approach combining anatomical imaging, functional ischaemia testing, and, in selected cases, invasive haemodynamic assessment. Management strategies range from conservative surveillance in small asymptomatic fistulas to percutaneous or surgical closure in symptomatic or haemodynamically significant lesions. This review provides an updated overview of the epidemiology, pathophysiology, diagnostic evaluation, and management of CBAFs. Particular emphasis is placed on size-based clinical stratification, multimodality imaging strategies, and contemporary therapeutic approaches, with the aim of offering a practical framework for the diagnosis and longitudinal management of patients with this uncommon but clinically relevant coronary anomaly.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060236

Authors: Marin Jacobwitz Kushal J. Kapse Julius Ngwa Josepheen De Asis-Cruz Yao Wu Rathinaswamy Govindan Caitlin McDermott Mary T. Donofrio Adre du Plessis Catherine Limperopoulos Nickie Andescavage

Background: The primary objective of this study was to compare the in vivo placenta volume across gestation in fetuses with congenital heart disease (CHD) and healthy controls. The second objective was to determine the relationship between placental volume and both CHD characteristics and neonatal birth anthropometrics. Methods: Pregnant women with a fetal diagnosis of CHD and healthy pregnancies were enrolled in a longitudinal observational study at Children’s National Hospital. A total of 451 fetal MRIs were analyzed from 284 pregnant women (112 mothers/182 scans with CHD; 172 controls/261 scans). In vivo placentas were manually segmented to derive volumes and z-scores. Z-scores were computed from placental volume data derived from control participants for weekly GA bins using means and standard deviations. Z-scores were then assigned to the CHD cohort. A linear mixed effects model with random intercepts clustered by subject was applied to examine the associations between placental volumes and CHD characteristics, including comparing placental volumes between groups according to gestational windows. Results: Overall, placental volumes in CHD were not significantly different than placental volumes from controls. However, in infants delivered at term age, CHD placental volume plateaued in the final four weeks of gestation. Smaller in vivo CHD placental volume z-scores were associated with decreased weight at delivery (p ≤ 0.0001). Conclusions: This study identifies that in vivo CHD placentas are abnormal in the final four weeks of gestation. Smaller CHD placentas were associated with decreased birth weight, underscoring the importance of placental development in neonatal anthropometrics.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060235

Authors: Hiba Abuelhija Asaf Mandel Salmas Watad Hai Zemmour Eitan Keizman David Mishaly Esther Arfi Levy Alain E. Serraf Uri Pollak

Circulating cell-free DNA (cfDNA) is released during tissue injury and systemic inflammation, but its association with postoperative organ injury following pediatric cardiac surgery remains incompletely defined. We evaluated the relationship between early postoperative cfDNA levels and acute kidney injury (AKI) and biochemical hepatic injury in children undergoing open-heart surgery with cardiopulmonary bypass (CPB). This retrospective observational cohort study included 50 pediatric patients (<18 years) who underwent CPB at a tertiary congenital heart center between 2017 and 2018. Plasma cfDNA concentrations were measured perioperatively, with the 6 h postoperative value analyzed as an early biomarker window. AKI was classified using Kidney Disease: Improving Global Outcomes criteria, and hepatic injury was assessed using serial liver enzyme measurements. cfDNA levels increased significantly within 6 h after CPB and were higher in patients with more severe AKI. Six-hour cfDNA concentrations correlated with postoperative creatinine, urea, alanine aminotransferase, and aspartate aminotransferase. In multivariable regression analyses adjusting for cardiopulmonary bypass duration, aortic cross-clamp time, and preoperative oxygen saturation, cfDNA at 6 h remained independently associated with AKI severity and peak liver enzyme levels. These exploratory findings suggest that early postoperative cfDNA elevation is associated with AKI severity and biochemical hepatic injury after pediatric cardiac surgery with CPB. Larger prospective studies are needed to determine its independent predictive value and clinical utility.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060234

Authors: Federica Marzano Ermanno Nardi Ciro Cotticelli Mariafrancesca Di Santo Simone Agizza Giuseppe Maria Abbellito Fabrizio Perrone Filardi Laura Liccardi Salvatrice Di Sarno Isabel Martone Stefania Paolillo Paola Gargiulo Sara Maria Pizzileo Francesco Pizzolorusso Andrea Igoren Guaricci Giuseppe Guglielmi Pasquale Perrone Filardi

A substantial proportion of cardiovascular (CV) events occurs in individuals without previously diagnosed CV disease, underscoring the need for improved primary prevention strategies. Traditional risk scores provide probabilistic estimates but fail to directly identify the presence and heterogeneity of subclinical atherosclerosis. This review summarizes current evidence on advanced multimodality imaging approaches for identifying high-risk individuals without prior CV events. Evidence from cohort studies, randomized trials, and meta-analyses was examined to evaluate the role of coronary artery calcium (CAC) scoring, coronary computed tomography angiography (CCTA), perivascular fat attenuation index (FAI), and vascular ultrasound in risk stratification. CAC scoring remains the most validated and widely recommended tool, offering robust prognostic value and significant risk reclassification, particularly in intermediate-risk individuals. CCTA provides additional insights into plaque burden and high-risk phenotypes, while FAI enables noninvasive assessment of coronary inflammation, improving risk prediction beyond anatomical measures. Vascular ultrasound offers a radiation-free, accessible method for detecting systemic plaque burden and refining risk estimation. Overall, multimodality imaging enhances the identification of subclinical disease and supports more individualized, disease-based risk assessment. Future research should clarify cost effectiveness, optimize patient selection, and determine whether imaging-guided strategies improve long-term clinical outcomes.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060233

Authors: Amin Thwairan Ismail Dalyanoglu Luis Jaime Vallejo Castano Esma Yilmaz Mohammed Morjan Johanna Wedy Jamal Azouagh Mohamed Chiboub Artur Lichtenberg Hannan Dalyanoglu

Background: Refractory cardiac arrest, cardiogenic shock, and severe acute respiratory failure remain associated with substantial mortality despite advances in advanced life support and extracorporeal membrane oxygenation (ECMO). Transportable ECMO platforms may enable rapid deployment, uninterrupted extracorporeal support, and safer in-hospital transport, but early real-world experience with newer systems remains limited. Methods: We conducted a retrospective single-center observational cohort study including all VitalFlow veno-arterial ECMO (VA-ECMO) and veno-venous ECMO (VV-ECMO) deployments performed between November 2025 and March 2026 at a high-volume tertiary cardiac surgery center. Fifteen cases were analyzed, comprising 12 VA-ECMO and 3 VV-ECMO deployments. Data were extracted from electronic health records, perfusion protocols, and ICU documentation. Outcomes included survival to hospital discharge, 30-day survival, neurological outcomes, and complications. Analyses were descriptive. Results: The cohort was exclusively male and clinically unstable at implantation, with high lactate and low pH levels consistent with severe hypoperfusion. Median time-to-flow was 33 min, and median ECMO duration was 8 days. Survival to discharge was 60% overall (66.7% VA-ECMO, 33.3% VV-ECMO), with ECMO weaning success in 86.7% and the primary death cause being multiorgan failure (83.3% of non-survivors). All survivors achieving a favorable neurologic outcome (CPC 1). Thirty-day survival was 73.3%. No major bleeding or stroke occurred. Limb ischemia was observed in 4 patients, with 2 patients requiring fasciotomy, all in the VA-ECMO group. Bronchial infection occurred in 3 patients. Lactate levels improved within the first 24 h, and survivors showed a more pronounced metabolic response. Conclusions: In this early single-center experience, VitalFlow ECMO was feasible and associated with rapid flow establishment, survival to discharge of 60% of patients, and good neurologic outcome among survivors. The complication profile was acceptable, with limb ischemia as the main adverse event. These findings support further evaluation of this transportable ECMO platform in larger multicenter cohorts.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060232

Authors: Xiaotong Pan Xinfang Zhang Yonglin Wang Xiaoxia Chen Xi Cao

Aim: To investigate self-care behaviors and their associated factors in adult patients with congenital heart disease. Design: A cross-sectional study. Methods: This study was conducted among 225 adult patients with congenital heart disease. Data on demographic characteristics, self-care behaviors, knowledge of congenital heart disease, social support, and self-efficacy were collected. Multiple linear regression was used to explore factors associated with self-care behaviors. Result: The mean scores for self-care maintenance, self-care monitoring, and self-care management were 63.87 ± 9.19, 55.30 ± 13.64, and 83.99 ± 11.67, respectively. Using a cutoff score of 70 for adequate self-care, 27.1%, 15.1%, and 83.6% of participants achieved adequate levels in maintenance, monitoring, and management, respectively. Multivariable linear regression analysis revealed that classification of congenital heart disease complexity (B = 1.867, 95% CI [0.427–3.307], p = 0.011), self-efficacy (B = 0.187, 95% CI [0.105–0.270], p < 0.001), and social support utilization (B = 1.513, 95% CI [0.772–2.253], p < 0.001) were independently associated with self-care maintenance. Furthermore, knowledge questionnaire score (B = 0.158, 95% CI [0.034–0.281], p = 0.013) was independently associated with self-care monitoring. Objective support (B = 0.743, 95% CI [0.115–1.370], p = 0.021) and social support utilization (B = 0.178, 95% CI [0.035–2.121], p = 0.043) were independently associated with self-care management. Conclusions: Chinese adult congenital heart disease patients showed poor self-care maintenance and monitoring behaviors despite their adequate self-care management behaviors. Disease knowledge, social support, and self-efficacy may affect self-care behaviors in patients with congenital heart disease.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060231

Authors: Paweł Gać Przemysław Cheładze Rafał Poręba

Background/Objectives: Epicardial adipose tissue (EAT), a visceral fat depot located between the myocardium and the visceral pericardium, has emerged as a potential imaging biomarker of cardiometabolic dysfunction and cardiovascular health. This study aimed to evaluate whether computed tomography (CT)-derived epicardial adipose tissue volume (EATV) and epicardial adipose tissue density (EATD) may serve as markers of the effects of major cardiovascular disease risk factors. Methods: This cross-sectional study included 105 participants (mean age: 62.12 ± 11.20 years; 58.1% women) examined with coronary computed tomography angiography. Clinical evaluation included anthropometric assessment, blood pressure measurement, laboratory testing, and questionnaire-based smoking status. EAT was assessed using semi-automatic segmentation on a dedicated post-processing workstation, with visual verification and manual correction, when necessary, within an attenuation range of −190 to −30 HU. Two parameters were analyzed: EATV and EATD. Results: EATV was significantly higher in men, participants with overweight/obesity, participants with dyslipidemia, and participants with type 2 diabetes. EATD was significantly lower in participants with overweight/obesity, dyslipidemia, and type 2 diabetes. Both EATV and EATD were associated with the total number of CVRFs. Correlation analysis showed that EATV was positively associated with age (r = 0.20, p = 0.04), BMI (r = 0.54, p = 0.01), fasting glycemia (r = 0.46, p = 0.01), and total CVRF number (r = 0.51, p = 0.01), whereas EATD was negatively associated with age (r = −0.26, p = 0.01), BMI (r = −0.40, p = 0.01), triglycerides (r = −0.44, p = 0.02), fasting glycemia (r = −0.49, p = 0.01), and total CVRF number (r = −0.40, p = 0.01). In regression analysis, older age, higher BMI, male gender, and dyslipidemia were independent risk factors for higher EATV, while dyslipidemia and type 2 diabetes were independent risk factors for lower EATD. Conclusions: Greater exposure to major cardiovascular disease risk factors was associated with higher EAT volume and lower EAT density, supporting the role of EAT as a structural and metabolic marker of the effects of cardiovascular disease risk factors on cardiovascular health.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060230

Authors: Ziyad Gunga Augustin Rigollot Elsa Hoti Zied Ltaief Gabriel Saiydoun Anna Nowacka Valentina Rancati Florine Valliet Matthias Kirsch

Background: An aorto-right ventricular fistula (ARVF) secondary to membranous septum rupture is an exceptionally rare complication after surgical aortic valve replacement (SAVR). While sutureless prostheses such as the Perceval valve have gained wide acceptance due to reduced cross-clamp times and procedural simplification, the reported adverse events predominantly include conduction disturbances and paravalvular leaks. Structural septal disruption remains sparsely described. We report a case of an early ARVF after Perceval implantation and review the pathophysiological and procedural mechanisms implicated in septal injury following sutureless and transcatheter aortic valve interventions. Case Description: A 66-year-old woman with severe bicuspid aortic valve stenosis underwent SAVR via a median sternotomy using a Perceval XL prosthesis after meticulous annular decalcification and sizing. Immediate intraoperative transesophageal echocardiography (TEE) confirmed optimal seating without any paravalvular regurgitation. Within 24 h, the patient developed a complete atrioventricular block followed by cardiogenic shock. A repeat TEE revealed a large ARVF with significant left-to-right shunt. Emergent re-exploration identified a membranous septum tear. The Perceval prosthesis was explanted, the defect was closed with a reinforced patch repair, and a 27 mm Inspiris Resilia bioprosthesis was implanted. Peripheral veno-arterial ECMO support was required temporarily. The patient recovered and remained free of prosthetic dysfunction at the two-year follow-up. Discussion: Membranous septum rupture after AVR has an estimated incidence of 0.4–1.5% in TAVR cohorts but is virtually unreported with Perceval valves. The mechanisms are thought to be chronic radial stress from oversized or malpositioned prostheses. Case reports with TAVR devices emphasize oversizing as a risk factor. Predictive factors for septal injury in sutureless AVR mirror those for conduction disturbances: valve oversizing, shallow infra-annular septal length, heavy calcification, and prior valve surgery. Preventive measures, such as strict sizing protocols, the avoidance of balloon dilation, and optimized implantation depth, have reduced conduction complications and may mitigate septal trauma. The treatment choice, whether percutaneous or surgical closure, depends on hemodynamic stability, defect size and anatomy, and operative risk. Conclusions: Early ARVF after Perceval implantation is exceedingly rare but potentially catastrophic. Strict adherence to sizing principles, awareness of septal anatomy, and prompt management, percutaneous in selected stable cases or surgical in acute large defects, are essential to optimize outcomes in sutureless AVR.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060229

Authors: Zihan Li Chunjuan Wang

Stroke is one of the leading causes of disability and mortality worldwide, and approximately 87% of cases are acute ischemic stroke (AIS). For patients with AIS, rapid administration of reperfusion therapy within the therapeutic time window remains the most effective treatment strategy. Over the past decade, numerous high-quality clinical trials have driven rapid advances in treatment strategies. Meanwhile, increasing attention has been directed toward cytoprotective therapies aimed at mitigating ischemic and reperfusion-related brain injury, which may act synergistically with reperfusion strategies. Although many related clinical trials have failed to demonstrate clear clinical benefit, they have provided valuable insights for the development of future cytoprotective agents. This review focuses on recent advances and remaining challenges in reperfusion therapy and cytoprotection for AIS.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060228

Authors: Qirun Wang Wenjuan Li Jiaojiao Wan Li Wei Yuting Xia Yimin Hua Kaiyu Zhou Di Qie Weikai Li Yifei Li

Objective: Kawasaki disease (KD) is characterized as an acute systemic vasculitis predominantly affecting young children, with coronary artery lesions (CALs) representing the most serious complication. Therapeutic resistance to intravenous immunoglobulin (IVIG) remains a significant clinical challenge. Consequently, numerous investigations have sought to identify predictive risk factors for IVIG resistance (IVIGR) and CAL development. Limited research has systematically evaluated the prognostic utility of electrocardiographic (ECG) parameters in KD outcome prediction. This study was therefore undertaken to assess the contributory value of ECG analysis in determining KD prognosis and therapeutic responses. Methods: This prospective cohort study enrolled 255 hospitalized children diagnosed with KD at West China Second University Hospital between July 2022 and December 2024. Initially, univariate analysis was performed to identify risk factors differentiating IVIGR from non-IVIGR patients and CAL from non-CAL patients. Statistically significant parameters were subsequently incorporated into machine learning analyses. Random forest algorithms were employed to construct predictive models based on the following: (1) complete blood count parameters, (2) biochemical and metabolic profiles, (3) electrocardiographic features, and (4) a comprehensive multimodal model integrating all parameters. These models generated feature importance scores, providing hierarchical rankings that quantified the relative contribution of each predictor to outcome prediction. Results: Univariate analysis demonstrated that alterations in hematological parameters, biochemical and metabolic profiles, and electrocardiographic features were significantly associated with therapeutic responses to IVIG and CAL development. Machine learning analysis revealed that ECG parameters individually contributed modest predictive weight for KD prognosis. However, the integration of ECG features into the comprehensive model substantially enhanced the discriminatory capacity, elevating the area under the curve (AUC) to 0.92 for CAL prediction. For IVIGR prediction, ECG-exclusive models demonstrated suboptimal performance in early disease management. Nevertheless, the multimodal integration of ECG with inflammatory and metabolic biomarkers achieved a comparable AUC of 0.92 for IVIGR prediction. Conclusions: This study establishes that ECG parameter alterations are significantly associated with CAL development and IVIGR in KD patients. Although ECG features demonstrate a limited independent predictive capacity compared to inflammatory and metabolic biomarkers, their integration into comprehensive predictive models substantially enhances discriminatory performance. These findings underscore the complementary value of electrocardiographic assessment in multimodal risk stratification strategies for KD management, supporting the clinical utility of ECG analysis as an adjunctive prognostic tool when combined with conventional laboratory parameters.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060227

Authors: Mattia Corianò Nicola Pradegan Francesco Putortì Arianna Calonaci Andrea Golfetto Vincenzo Tarzia Annalisa Angelini Chiara Tessari Marny Fedrigo Giuseppe Toscano Gino Gerosa Francesco Tona

Pulmonary hypertension (PH) is associated with adverse outcomes after heart transplantation (HT). In 2022, the European Society of Cardiology introduced lower thresholds for pulmonary vascular resistance (PVR) to distinguish isolated post-capillary PH (IpcPH) and combined post-capillary PH (CpcPH). We conducted a single-center retrospective study on 357 patients who underwent HT between 1985 and 2020 and had right heart catheterization prior to transplant, investigating the ability of the new PVR threshold to predict one-year mortality. Overall, 65 patients had no PH, 84 had IpcPH, and 208 had CpcPH. One-year survival was higher in patients without PH and similar between IpcPH and CpcPH (p = 0.04). Reclassification under the 2022 guidelines did not improve risk prediction. Only mean pulmonary artery pressure (mPAP) >20 mmHg independently predicted 1-year mortality. In conclusion, elevated mPAP, rather than PVR, was associated with post-transplant outcomes. This finding opens up the possibility of rethinking indication for reversibility tests and mechanical circulatory support in HT recipients.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060226

Authors: Gianni Dall’Ara Miriam Compagnone Simone Grotti Andrea Santarelli Marco Balducelli Caterina Cavazza Carlo Savini Carolina Moretti Filippo Ottani Andrea Rubboli Marcello Galvani Carmine Pizzi Fabio Felice Tarantino

In many countries, patients’ access to transcatheter aortic valve implantation (TAVI) is limited by reimbursement issues or delayed admission to heart valve centers, thus increasing the risk of adverse events in wait-listed patients. The TAVI AT HOME (TAH) is a single-arm, multicenter study aiming to evaluate the safety and efficacy of transfemoral TAVI performed at centers without on-site cardiac surgery by expert operators. The primary endpoint is 30-day all-cause mortality. This study focuses on the run-in phase of the registry, which was required by the ethics committee to perform an interim safety analysis. The outcome of 20 TAH patients enrolled at three Italian centers from May 2023 to May 2024 was compared to 41 TAVI cases included in the permanent local registry, matching the TAH inclusion/exclusion criteria. The two groups had similar baseline characteristics. Significantly more patients in the TAH group were deemed at prohibitive risk (85.0% vs. 56.1%; p = 0.026) but had similar surgical risk scores. A self-expanding device was used in most cases (60.7%). Technical success did not differ between groups (95.0% in the TAH vs. 85.4%, p = 0.409). No deaths at 30 days (primary endpoint) were observed. The 1-year survival rate did not differ between groups. After interim data analysis, the ethics committee authorized the completion of the TAH enrollment and extension to other centers. The TAH approach might represent an alternative model to allow timely access to TAVI without compromising safety and effectiveness.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060225

Authors: Shuofang Ren Lanlin Zhang Yuanhang Zhai Sheng Yang Jianzhou Liu Xingrong Liu Shangdong Xu Guotao Ma Jun Zheng Chaoji Zhang

Background: Adults with congenital heart disease (CHD) are at markedly increased risk of infective endocarditis (IE); however, data comparing clinical characteristics and outcomes in surgically treated IE patients with and without CHD remain limited. This study aimed to evaluate differences in clinical profile, microbiology, complications, and outcomes between these groups. Methods: We conducted a retrospective cohort study of 773 adult patients who underwent surgery for IE at a tertiary center in China between October 2013 and August 2025. Patients were categorized into CHD (n = 188) and non-CHD (n = 585) groups. Baseline characteristics, microbiological findings, operative data, and postoperative outcomes were compared. Inverse probability of treatment weighting (IPTW) was applied to adjust for baseline differences. Long-term survival was assessed using Kaplan–Meier analysis. Results: Patients with CHD were significantly younger and had fewer cardiovascular comorbidities than non-CHD patients. CHD was associated with a higher prevalence of right-sided and multivalvular infection, whereas non-CHD patients predominantly had left-sided disease. Streptococcus species were the most common pathogens in both groups, with no significant intergroup differences in microbiological profiles. After IPTW adjustment, no significant differences were observed in major postoperative complications, length of stay, or early mortality. Overall and in left-sided IE, long-term survival was comparable between groups, whereas in right-sided IE, patients with CHD appeared to have more favorable long-term survival (HR = 0.17, 95% CI: 0.04–0.66, p = 0.01). Conclusions: Despite distinct clinical characteristics, adults with and without CHD undergoing surgery for IE had similar overall outcomes, although CHD was associated with better long-term survival in right-sided IE.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060224

Authors: Yashraj Srivastava Korri Hershenhouse Isaac Faith Tanner Nelson Brandon E. Ferrell Ahren J. Alberto Tadahisa Sugiura

Background: Immune dysregulation and clinical immunosuppression are biologically plausible contributors to thoracic aortic wall vulnerability through endothelial injury, protease-mediated extracellular matrix remodeling, vascular smooth muscle cell dysfunction, and impaired vascular repair. Yet, the clinical relevance of immunomodulated states to thoracic aortic aneurysm (TAA) incidence or growth and acute aortic syndromes remains undefined. Methods: This comprehensive review synthesizes clinical and translation evidence linking immunomodulated states in solid organ transplantation, autoimmune disease (predominantly systemic lupus erythematosus), HIV, and oncologic therapies to thoracic aortic dilation, aneurysmal progression, and acute aortic events. Principal Findings: Across transplant, autoimmune, and HIV cohorts, recurring themes include chronic immune dysregulation, endothelial dysfunction, proteolytic matrix remodeling, and impaired vascular repair capacity, although thoracic segment-specific longitudinal growth data remain limited and are often embedded within analyses of multiple vascular beds. In oncologic cohorts, aggregate analyses generally do not demonstrate uniform acceleration of aneurysm growth with malignancy or chemotherapy exposure, although agent-level models suggest that regimen-specific effects may be obscured in pooled estimates. Two studies most directly addressed our question in thoracic-relevant contexts reported (1) very low mean annual ascending aortic aneurysm growth (0.18 ± 0.64 mm/year) with no detectable association with chemotherapy or radiotherapy and (2) prior immunosuppressive/cytostatic chemotherapy exposure to be common in a proximal TAA surgical cohort (39.3%) without a clear difference in thoracic phenotype at presentation or postoperative outcomes. In HIV cohorts, available evidence supports modest but reproducible proximal aortic remodeling and a clinically meaningful aneurysm burden across vascular beds, yet definitive thoracic segment-specific natural history data remain limited. Conclusions: The available literature supports clinical vigilance and exposure-aware surveillance, while suggesting that thoracic aortic risk is unlikely to be uniform across immunosuppressive and cytotoxic therapies. Standardized, segment-specific longitudinal imaging with granular agent-level exposure characterization (dose, duration, sequencing, and combination regimens), consistent definitions of baseline diameter and growth, careful adjustment for key confounders, and prospective ascertainment of dissection/rupture and operative endpoints are needed to translate immunobiology into actionable risk stratification and long-term management strategies.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060223

Authors: Daniela Di Lisi Cristina Madaudo Francesca Macaione Francesca Castro Francesco Bongiorno Francesco Stabile Andrea Micarelli Alfredo Ruggero Galassi Giuseppina Novo

Background: Myocarditis is an inflammatory disease of the myocardium with multiple causes and evolutions. The aim of our study was to design a prognostic multiparametric score in patients with myocarditis, to identify those at higher risk of cardiovascular outcomes. Methods: A prospective study was performed enrolling 98 patients with myocarditis: 72 M, 26 F; median age 27 [IQR 20–40]. Patients were divided into two groups: complicated (CM) and uncomplicated myocarditis (UM). Six months after hospital admission, cardiac magnetic resonance (CMR) and cardiological consultation were repeated. Cardiovascular outcomes (death, hospitalization for heart failure, heart transplant, ICD implantation, and heart failure development) were evaluated at 6 months and after 3 years. Results: We found 67 UM and 31 CM. Cardiovascular outcomes were significantly higher in patients with CM. We found a significant correlation between cardiovascular outcomes and reduced LVEF at hospital admission, reduced global longitudinal strain in absolute values, septal late gadolinium enhancement (LGE) at CMR, longer persistence time of increased troponin, LGE extension progression or persistence at 6 months of CMR. A myocarditis prognostic score was developed. A score ≥ 5 showed higher sensitivity (100%) and specificity (87%)—AUC 1, to identify cardiovascular outcomes in patients with myocarditis. A score between 3 and 4 showed high sensitivity but low specificity. A score ≤ 2 was associated with low probability of cardiovascular outcomes. Conclusion: Our study confirms the high probability of cardiovascular outcomes in patients with CM and it suggests a myocarditis prognostic score to identify patients at higher risk of cardiovascular outcomes.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060222

Authors: Faizan Ahmed Saifullah Khan Madeeha Shafqat Najam Gohar Muhammad Hassan Muhammad Hussain Haris Bin Tahir Tehmasp Rehman Mirza Muhammad Abdullah Syed Muhammad Murtaza Ishaq Haider Hussain Shah Mohammad Hamza Mohammad Omar Butt Fenilkumar Kotadiya Amro Taha Swapnil Patel Fawaz Alenezi

Background: Coronary artery disease (CAD) and heart failure with preserved ejection fraction (HFpEF) are major causes of morbidity and mortality. Systemic inflammation contributes to both, suggesting potential benefit from colchicine, though data in CAD-HFpEF are limited. Methods: We conducted a real-world study using the TriNetX Research Network, identifying 480,434 adults with CAD and HFpEF. Patients were categorized as colchicine users (n = 30,254) or non-users (n = 450,180). One-to-one propensity score matching yielded 28,941 patients per group. The primary outcome was a composite of acute myocardial infarction, stroke, all-cause mortality, and acute heart failure. Secondary outcomes included individual components, hospitalizations, atrial fibrillation, and gastrointestinal events, assessed at 1- and 3-year follow-up. Results: At 1 year, the primary outcome occurred in 16.9% of the colchicine group versus 19.8% of non-users (HR: 0.86, 95% CI: 0.81–0.91; p < 0.001). All-cause mortality was 11.4% versus 14.5% (HR: 0.77, 95% CI: 0.73–0.80; p < 0.001). At 3 years, the primary outcome occurred in 34.2% versus 39.7% (HR: 0.88, 95% CI: 0.85–0.92; p < 0.001), with acute heart failure slightly higher in the colchicine group (27.5% vs. 26.5%; HR: 1.04, 95% CI: 1.01–1.08; p = 0.009). Stroke was modestly reduced (HR: 0.93, 95% CI: 0.88–0.99; p = 0.014). No significant differences were seen in all-cause hospitalization, atrial fibrillation, or gastrointestinal events. Conclusions: In patients with CAD and HFpEF, colchicine was associated with lower short- and medium-term risk of composite cardiovascular events and mortality, with modest attenuation over time, suggesting early time-dependent association rather than sustained structural effects. Prospective randomized trials are warranted.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13060221

Authors: Manuela Montatore Ruggiero Tupputi Federica Masino Michela Montatore Eluisa Muscogiuri Giuseppe Guglielmi

Arterial wall fragility represents a unifying pathophysiological substrate underlying a broad spectrum of aortic diseases, including aneurysms, dissections, intramural hematoma, penetrating atherosclerotic ulcers, and aortitis. Rather than distinct entities, these conditions increasingly appear as interconnected manifestations of impaired wall integrity and maladaptive vascular remodeling. This narrative review provides a structured overview of the imaging correlates of arterial wall fragility from a CT-centered, multimodality perspective. Computed Tomography Angiography (CTA) remains the first-line imaging modality in acute settings, enabling rapid and comprehensive assessment of vascular anatomy, luminal integrity, and the presence of life-threatening complications. Complementary modalities, including magnetic resonance imaging and ultrasound, contribute additional information on tissue characterization and hemodynamic evaluation in selected stable patients, follow-up settings, or specific clinical scenarios. Across imaging modalities, specific features—such as false lumen patency, intramural hematoma characteristics, ulcer-like projections, aneurysm morphology, and periaortic inflammatory changes—have been reported as markers of wall instability. These imaging-derived findings may provide clinically relevant information beyond traditional diameter-based assessment and support more refined risk stratification. Emerging approaches, including artificial intelligence, radiomics, computational modeling, and advanced MRI techniques, are expanding the role of imaging toward quantitative evaluation. However, their routine clinical implementation still requires standardization and prospective validation. Overall, a CT-centered multimodality imaging strategy may support a more comprehensive assessment of arterial wall fragility and contribute to individualized clinical decision-making in patients with aortic disease.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050220

Authors: Cyrine Sghaier Marielle Morissens Pierre-Emmanuel Massart Jose Castro Rodriguez Georgiana Pintea Bentea

Background: Although less frequently encountered, aortic valve stenosis is associated with complications separate from its hemodynamic burdens, such as infective endocarditis. Case Summary: We report the case of a 77-year-old female patient with regular cardiac follow-up in the setting of an asymptomatic severe aortic stenosis, who presented to the emergency department with signs and symptoms of sepsis and acute decompensated heart failure. Echocardiography revealed two vegetations attached to the tricuspid valve, an abscess of the anterior aortic ring, and a high-velocity ventricular septal defect. The patient was started on adequate antibiotic therapy. Surgical treatment in an urgent manner (within a few days) was decided by the Heart Team, in accordance with the ESC guidelines on the management of infective endocarditis. Whilst awaiting surgery, the patient presented with a sudden hemodynamic deterioration a few days after diagnosis, with cardiopulmonary arrest and subsequent death. Discussion: We hypothesize that the patient developed an infective endocarditis of the degenerated stenotic aortic valve with extension from left to right via a ventricular septal defect, the development of which was facilitated by the high trans-aortic valve gradient. Some reported cases describe a ventricular septal defect as a complication of native aortic valve endocarditis, though not all involve concomitant aortic stenosis. In conclusion, our case illustrates a very rare scenario of infective endocarditis complicating aortic stenosis with fulminant development. This case highlights a rare, albeit severe complication associated with aortic stenosis and therapeutic challenges in managing the dismal evolution of endocarditis in this setting.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050219

Authors: XinYi Wu Dina Muharib Christine Boesch Julia S. Gauer Robert A. S. Ariëns

Cardiovascular diseases (CVDs) are a significant health burden worldwide. One of the key pathological processes underlying CVD is thrombosis–the formation of a blood clot (thrombus) within the blood vessel. Thrombus composition typically includes fibrin, platelets, red blood cells, leukocytes, and neutrophil extracellular traps (NETs). Polyphenols, a diverse group of naturally occurring compounds abundant in plant-based foods, have shown potential cardiovascular protective properties. This review discusses and summarizes the effects of polyphenols on the endothelium, platelet function and activity, and blood coagulation, and how this may potentially contribute to attenuated thrombus formation. The available evidence discussed in this review suggests that polyphenols may confer cardiovascular benefits not only through antioxidant and anti-inflammatory actions, but also by directly modulating thrombosis-related mechanisms. Nevertheless, in vivo studies remain limited, and the lack of standardized procedures contributes to discrepancies among reported results. Moreover, differences in compound structure, absorption and bioavailability should be considered when interpreting findings and their potential application as part of preventative strategies. The evidence presented in this review suggests that polyphenols may offer benefits towards lowering thrombosis risk and reducing recurrence among patients with thrombosis, although additional studies are required to further explore their mechanistic effects.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050218

Authors: Xiaohang Liu Tongxin Xiao Lihua Zhang Zhongjie Fan Xinglin Yang Zhuang Tian

Recurrent pericarditis (RP) remains challenging, especially in tuberculosis (TB)-endemic regions where empirical anti-TB therapy is often unnecessarily prolonged. We report a 35-year-old woman with three RP episodes over six months, presenting with pleuritic chest pain, elevated inflammatory markers, and moderate-to-large pericardial effusion. Extensive infectious (including TB), autoimmune, and malignancy workups were negative. Cardiac magnetic resonance revealed persistent pericardial late gadolinium enhancement despite clinical remission. Whole-exome sequencing identified a heterozygous MEFV c.442G>C (p.Glu148Gln) variant, suggesting an autoinflammatory predisposition. Although the patient finally achieved sustained symptom-free status for six months on a standardized low-dose colchicine regimen, still over 10% of patients have recurrent symptoms receiving colchicine in addition to conventional anti-inflammatory therapy with aspirin or ibuprofen. This case highlights the shifting paradigm from an infection-centered to an autoinflammatory framework for RP in TB-endemic countries, underscores the role of MEFV variants in idiopathic recurrent pericarditis, and illustrates the real-world gap between genetic insights and therapeutic accessibility to IL-1 inhibitors in resource-limited settings.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050217

Authors: Yao Deng Minzhang Zhao Xiaoyu Zhang Chunjie Mu Runwei Ma

Background: Interventional occlusion procedures for congenital heart disease (CHD) carry the risk of complications requiring reintervention, yet predictive factors remain unclear. Methods: This retrospective case–control study included patients (n = 4190) with simple CHD who underwent transcatheter/interventional procedure (2017–2022). Perioperative and postoperative complications were monitored at 1, 3, and 6 months after occlusion. Among them, 44 patients required reintervention for complications. Statistical analysis was performed on clinical data, ultrasound findings from various locations, and laboratory examination results. Results: For atrial septal defects (ASD), independent predictors were defect size and age grading, while those for ventricular septal defects (VSD) were occluder device size, aortic annulus inner diameter, body surface area class, and whether the defect was isolated. The areas under the curve (AUC) of the receiver operating characteristic (ROC) curve for patients who experienced severe complications requiring surgical repair according to ASD were 0.723, whereas for VSD, the AUCs for occluder device size and aortic valve annulus diameter among patients who experienced severe complications requiring surgical repair were 0.649 and 0.539, respectively. Conclusions: This study provides an inaugural comprehensive analysis of occurrence rates and predictive factors for severe post-interventional occlusion procedure complications requiring reintervention. These findings offer new insights as a reference for the treatment of CHD.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050216

Authors: Predrag Jancic Stefan Milutinovic Dragana Stanojevic

Background: Atrial fibrillation (AF) contributes significantly to global mortality. Its burden is rising, but regional differences remain. We assessed AF prevalence, incidence, mortality, disability-adjusted life years (DALYs), and risk factors in the USA and EU from 1991 to 2021. Methods: AF data from GBD 2021 were extracted, stratified by sex and age. Absolute numbers, age-standardized rates (ASR), and estimated annual percentage change (EAPC) were calculated. DALYs and deaths attributable to common risk factors were also analyzed. Results: From 1991 to 2021, AF incidence increased by 111.6% in the USA (EAPC 2.48) and 47.0% in the EU (EAPC 1.14), with faster growth in males. ASR prevalence and incidence increased in the USA (EAPC 0.57 and 0.55) but were stable in the EU (EAPC −0.05 and −0.21). Mortality rose 161% in the USA (EAPC 3.19) and 124% in the EU (EAPC 3.04), with the sharpest increases in older EU adults and midlife USA adults. Systolic blood pressure (SBP) was the largest contributor to DALYs and deaths, while high body-mass index (BMI) and alcohol grew fastest. Conclusions: AF burden rose markedly in both regions, with steeper increases in the USA and greater impact on males and midlife adults. Hypertension remains the dominant contributor, but obesity and alcohol consumption are emerging challenges.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050215

Authors: Hae Jin Kim Sung Goo Park Sung-A Chang Jinyoung Song Ji Hyuk Yang Sung Mok Kim Yeon Hyeon Choe

Purpose: To evaluate the prevalence and cardiac CT features of inferior left atrial diverticula (ILAD) communicating with the right atrium (RA) or inferior vena cava (IVC), a novel type of interatrial communication. Materials and Methods: This retrospective study included 11,512 consecutive patients who underwent cardiac CT. CT features and prevalence of ILAD communicating with the RA or IVC were analyzed. Shunts were defined as anatomical defects between the two structures with or without visible contrast flow. In a subset of the patients we compared interatrial septal aneurysm (n = 20) and ILAD without shunt (n = 66), assessing the involvement of a wedge-like fatty space bordered by both atria, IVC and coronary sinus. Results: There were 33 patients (19 males and 14 females; aged 59.8 ± 11.2 years; age range, 18–87 years) with ILAD with shunts (ILADSs). The prevalence of ILADSs was 4.2% (33/783) among ILAD and 0.3% (33/11,512) among all patients. Maximal dimensions of ILAD were 17.6 ± 9.9 mm (range, 5.3–41.0 mm). Mean ostial diameters of ILAD and mean sizes of shunts were 6.2 ± 5.6 mm and 3.2 ± 2.9 mm, respectively. Shunts were larger than 5 mm in 6 patients (15.2%) and larger than 3 mm in 10 patients (30.3%). In 30 patients who underwent transthoracic echocardiography, ILADSs were not identified at echocardiography. CT showed involvement of the wedge-like fatty space for all ILAD and for no cases with interatrial septal aneurysm. Conclusions: Cardiac CT enables detection of incidental ILADSs unrecognized at echocardiography.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050214

Authors: Le An Yanhui Ren Jin Yang Zuowei Pei

Objective: The prevalence of coronary heart disease (CHD) continues to rise, and there is a lack of methods for early detection. To identify biomarkers for CHD, we analyzed the CACNA2D1 protein concentration in patients with different degrees of coronary artery stenosis to explore the correlation between plasma CACNA2D1 protein concentration and the severity of coronary artery stenosis. Methods: A total of 267 inpatients from the Department of Cardiology at Dalian Central Hospital who underwent coronary angiography were consecutively enrolled. According to the degree of stenosis, they were divided into four groups: minimal stenosis (70 cases), mild stenosis (68 cases), moderate stenosis (66 cases), and severe stenosis (63 cases). The baseline characteristics, clinical laboratory indicators, and CACNA2D1 protein concentration in blood samples of patients in each group were compared, and the correlations were analyzed. Results: As the degree of coronary artery stenosis worsened, plasma CACNA2D1 protein concentration in patients showed a gradual upward trend. The protein concentration was lowest in the mild stenosis group, at 37.68 ng/mL; it was 45.46 ng/mL in the mild-to-moderate stenosis group; it reached 55.22 ng/mL in the moderate stenosis group; and it was highest in the severe stenosis group, at 79.95 ng/mL. Conclusion: There is a correlation between plasma CACNA2D1 protein concentration and the degree of coronary artery stenosis, demonstrating that it has the potential to serve as a biomarker.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050213

Authors: Yi Shi Ya-Nan Tan Li-Da Wu Li-Guo Wang Yue Gu Wen-Ying Zhou Meng-Qian Shao Jun-Xia Zhang

Background: Atherosclerosis preferentially develops at arterial regions exposed to low shear stress (LSS), highlighting the critical role of local hemodynamic forces in disease initiation and progression. Emerging evidence indicates that endothelial lipid metabolism is a key determinant of vascular homeostasis; however, whether LSS directly regulates endothelial lipid droplets’ (LDs) dynamics remains unclear. In particular, the mechano-transduction pathways linking shear stress to lysosome-mediated lipid processing within the endothelium have yet to be defined. Methods: Complementary in vitro flow systems and in vivo atheroprone models were employed to examine the effects of LSS on endothelial lipid metabolism. Endothelial LDs accumulation, lysosome-dependent lipophagy, and atherosclerotic lesion development were systematically assessed under LSS conditions. Mechanistically, molecular profiling and rapamycin-mediated functional rescue were conducted to delineate the role of the KLF4/TFEB/ATP1A1 signaling axis in LSS-induced impairment of lysosome-dependent lipophagy. Results: We found that LSS induced pathological accumulation of LDs in vascular endothelial cells, accompanied by a marked suppression of lysosome-dependent lipophagy. Elucidation of the mechanism showed that LSS downregulated the shear-responsive transcription factor KLF4, resulting in aberrant phosphorylation of transcription factor EB (TFEB) and impaired TFEB nuclear translocation. Consequently, the TFEB transcriptional program governing lysosomal function was disrupted, including reduced expression of the TFEB target ATP1A1, leading to defective lysosomal acidification and blockade of lipid autophagic flux. Restoration of the KLF4/TFEB/ATP1A1 axis reactivated lipophagy, alleviated endothelial lipid burden, and significantly attenuated atherosclerotic lesion development. Conclusions: Our findings demonstrate that disruption of the KLF4/TFEB/ATP1A1 signaling pathway mediates LSS-induced impairment of endothelial lipophagy, thereby driving pathological LDs accumulation. This highlights the potential of restoring this axis as a therapeutic strategy to attenuate atherosclerotic progression.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050212

Authors: Abdulkader Jamal Eddin Stefan-Iulian Stanciugelu Arnaldo Dario Damian Diana Nitusca Oana Elena Tunea Ioana Monica Mozos

The influence of COVID-19 infection on the association between ABO blood groups and early outcomes in patients with acute pulmonary embolism (PE) remains uncertain. We conducted a retrospective, single-center cohort study including adult patients admitted with a first episode of acute pulmonary embolism (PE). The interaction between ABO blood group (non-O vs. O) and COVID-19 status was evaluated using multivariable logistic regression models adjusted for PE severity assessed by the Pulmonary Embolism Severity Index (PESI). A total of 211 patients were included, of whom 95 (45.0%) were COVID-19-positive. Among COVID-19-positive patients, non-O blood groups were associated with significantly higher odds of invasive mechanical ventilation (IMV) compared with group O (adjusted odds ratio [aOR] 12.87, 95% CI 4.17–39.75), whereas no association was observed among COVID-19–negative patients (aOR 1.20, 95% CI 0.45–3.23). No interaction was identified for 24 h mortality (p = 0.721) or systemic thrombolysis (p = 0.306). Higher PESI class was independently associated with an increased risk of adverse outcomes. ABO blood group modified the association between COVID-19 infection and early respiratory outcomes in acute PE. These findings suggest a potential role of ABO-related differences in coagulation and endothelial biology in the clinical expression of COVID-associated PE and should be interpreted as hypothesis-generating.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050211

Authors: Natalia Kusyn Natalia Zdebik Wojciech Hajdusianek Rafał Poręba Paweł Gać

Heart failure (HF) is a clinical syndrome characterized by structural or functional cardiac abnormalities that impair ventricular filling or ejection, leading to inadequate systemic perfusion and elevated intracardiac pressures. Current epidemiological estimations declare approximately 26 million patients affected worldwide are living with HF. While ischemic heart disease remains the primary etiology, there is a wide range of behavioural factors that significantly influence disease onset and progression. This review focuses on the evidence for established risk factors, including smoking, excessive alcohol consumption, obesity, physical inactivity, poor diet, sleep disorders, and psychological stress. Furthermore, we discuss other novel determinants such as electronic nicotine delivery systems (ENDS), cannabis, high-dose caffeine, and psychostimulants. The basic mechanistic pathways, including endothelial dysfunction, oxidative stress, neurohormonal activation, and direct myocardial toxicity, are also pointed out and reviewed in this paper. The aim of this study is to integrate epidemiological data with pathophysiological insights to identify priority targets for primary prevention and highlight areas for future research.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050210

Authors: Vojislav Parezanovic Dusan Andric Vladimir Chadikovski Vedran Stojanovikj Jordanka Madzoska Vesna Trpkovska Igor Stefanovic

The association of a major aortopulmonary collateral artery (MAPCA) with simple transposition of the great arteries (TGA) is uncommon. Such high-flow lesions in the postoperative period following arterial switch operation (ASO) may lead to pulmonary hypertension, pulmonary hemorrhage, heart failure (HF), failure to thrive and prolonged mechanical ventilation. We report a neonate who developed pulmonary overcirculation and HF in the early postoperative period due to a hemodynamically significant MAPCA. Although the association of MAPCA with simple TGA is infrequent, such lesions should be considered in cases of unexplained cardiovascular compromise following ASO. Following transcatheter occlusion of the MAPCA with a vascular coil, rapid hemodynamic stabilization and subsequent extubation of the patient were achieved.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050209

Authors: Jakub Kuciński Krzysztof Krawczyk Konrad Kieca Aleksander Siniarski Michał Ząbczyk Ewa Konduracka

Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant linked in epidemiological studies to increased coronary artery disease (CAD) risk, higher LDL-cholesterol, hypertension, and other adverse outcomes. However, the mechanisms by which PFOS affects cardiovascular physiology, particularly coagulation, remain insufficiently understood. We evaluated the ex vivo effects of PFOS on fibrin clot structure and thrombin generation in platelet-poor plasma (PPP) and citrated whole blood from ten healthy volunteers (five women, aged 27–32 years; mean serum PFOS: 2.63 ± 0.85 μg/L). PPP samples were incubated with PFOS at 50, 200, and 400 μg/L. Assays included calibrated automated thrombogram, clot permeability (Ks), clot lysis time (CLT), thromboelastography (400 μg/L), and scanning electron microscopy (SEM). PFOS did not significantly modify endogenous thrombin potential or peak thrombin. In contrast, it reduced Ks and prolonged CLT at 200 and 400 μg/L, indicating impaired fibrinolysis. SEM images confirmed the formation of thinner, tightly packed fibrin fibers with reduced pore size at higher PFOS concentrations. These findings were consistent across dilution models, with only minimal changes observed in low-dilution protocols. Overall, PFOS appears to disrupt fibrin polymerization, generating denser and more fibrinolysis-resistant clots without major effects on thrombin generation. Such alterations may promote a prothrombotic state and predispose exposed individuals to clinically relevant thrombotic events, including myocardial infarction and stroke. Further studies are required to define the clinical consequences of PFOS-related coagulation abnormalities in exposed populations.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050208

Authors: Chuli Shi Yuehang Yang Xinyi Liu Hanshen Luo Yongfeng Sun Zhiwen Wang Jiawei Shi

Background: This study aimed to develop and validate a machine learning model to predict postoperative complications in pediatric simple congenital heart disease (CHD) patients undergoing right vertical infra-axillary incision (RVIAI). Methods: A retrospective dataset of 638 patients who underwent treatment for ventricular septal defect and/or atrial septal defect via RVIAI at our hospital between August 2020 and August 2023 was collected. A total of 35 preoperative and intraoperative variables were used to construct 190 machine learning models. The optimal model was selected based on the highest mean C-index. Independent risk factors identified by the optimal model were ranked according to their importance. Kaplan–Meier analysis was used to compare the incidence of postoperative complications between different risk groups. Model performance was evaluated using the area under the receiver operating characteristic curve (ROC). Results: The optimal model, which combined Elastic Net (alpha = 0) and Gradient Boosting Machine, identified 18 baseline variables associated with postoperative complications. The top five predictors were defect size, globulin, activated partial thromboplastin time, red blood cell count, and blood urea nitrogen. Kaplan–Meier curves showed that postoperative complication rates were significantly higher in the high-risk group than in the low-risk group (p < 0.0001). The model demonstrated good discrimination, with area under the curve (AUC) values on postoperative days 5, 10, 15, and 20 remaining above 0.78 in both the training and test sets. Conclusions: This machine learning model provides a potential predictive tool for assessing postoperative risk in simple CHD patients undergoing RVIAI and may support more targeted perioperative management.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050207

Authors: Francesco Martino Angela Sciacqua Tarcisio Niglio Francesco Barillà Eliana Martino Marco Alfonso Perrone Pier Paolo Bassareo

Background. Atherosclerosis is a long-standing process that starts in childhood and leads to a number of major adverse cardiovascular events in adulthood. It is therefore crucial that children at potential risk of atherosclerosis-related harmful consequences are identified. Nevertheless, relatively few studies have focused on primary prevention in paediatric patients. Methods. Fifty-four children (mean age 9.0 ± 2.8 years) and 72 parents (mean age 44.0 ± 8.2 years) were recruited. Blood pressure (BP) was measured and lipid panel was checked, together with carotid intima–media thickness (IMT) and several indexes of carotid stiffness. Results. No statistically significant differences in IMT and indexes of carotid stiffness were detected between children and parents, with the exception of the alpha index (p < 0.05). In children, IMT was correlated with the alpha index (p = 0.01). Seventeen children (31%) had a pathological IMT. The diastolic BP difference between children with normal and pathological IMT was statistically significant (p < 0.05). Parents’ total, LDL and HDL cholesterol, as well as triglyceride levels, differed statistically from those of children with both physiological and pathological IMT: p < 0.05 for all differences. Children with hypercholesterolemia had a three-fold higher likelihood of having a pathological IMT than children with normal cholesterol (p < 0.01). Among children with pathological IMT, 59 percent had one and 41 percent had two parents who were affected by pathological IMT. Conclusions. Carotid stiffness was similar in children and their parents, suggesting early familial influences on vascular properties. Many children had a pathological carotid IMT, highlighting how subclinical atherosclerosis is diffuse even at a young age. IMT in children was associated with cholesterol levels, underscoring the importance of early lipid screening and management. The strong association between pathological IMT in both children and their parents supports the hypothesis of a shared genetic or environmental predisposition to early vascular alterations.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050206

Authors: Ziga Mrak Franjo Husam Naji Dejan Dinevski

(1) Background and Objectives: Current risk stratification strategies for primary prevention of sudden cardiac death (SCD) have limited sensitivity and specificity. Artificial intelligence (AI) applied to electrocardiograms (ECGs) has emerged as a promising tool to predict the risk of future cardiac arrhythmias. This scoping review synthesizes evidence from original studies evaluating AI models trained on ECGs for risk stratification of SCD/malignant ventricular arrhythmias. (2) Materials and Methods: A comprehensive search of MEDLINE, Embase, Web of Science, Scopus and IEEE Xplore was conducted to identify peer-reviewed studies from inception to February 2026. Eligible studies included original investigations in which the model input was an ECG, recorded at baseline or during monitoring, and the outcome was either short-term or long-term SCD/malignant ventricular arrhythmia risk prediction. Extracted variables included study characteristics, ECG data, AI model data, model performance metrics, and the validation strategy. Risk of bias was assessed using PROBAST. (3) Results: Twenty studies met the inclusion criteria. High-risk cardiovascular subgroups (e.g., heart failure cohort, ICD cohort, etc.) or datasets from admitted patients, and conventional machine learning models or deep learning models were used in most studies. AI-ECG algorithms achieved moderate-to-high discriminative performance for identifying patients at an increased risk for imminent SCD/malignant ventricular arrhythmias (nine studies, AUROC ≈ 0.77–0.96) or future SCD/malignant ventricular arrhythmias (eleven studies, AUROC ≈ 0.66–0.94). However, multiple methodological limitations were identified, including limited sample sizes, susceptibility to overfitting, data imbalance-related bias, heterogeneity in dataset and endpoint definitions, inadequate external validation, and incomplete assessment and reporting of model calibration. (4) Conclusions: AI-ECG models demonstrate potential for risk stratification of SCD and malignant ventricular arrhythmias. However, the current evidence base is constrained by several methodological limitations, and further research is required to determine the clinical utility of AI-ECG for predicting SCD.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050205

Authors: Donclair Brown Vishakha Modak Aladin Altic Ali Al Zuwayny James Tauras

Transthyretin (TTR) amyloidosis is a systemic, progressive, and fatal disease. TTR is integral in vitamin A (retinol) transport via its binding to retinol binding protein 4 (RBP4). Current and emerging therapies for TTR amyloid cardiomyopathy (ATTR-CM), including RNAi therapies and potentially CRISPR-based therapies, reduce hepatic transthyretin production and hence decrease serum RBP4, which decreases circulating vitamin A levels. However, despite these reductions in circulating vitamin A, hepatic reserves and alternative delivery mechanisms may prevent clinical manifestations of vitamin A deficiency. Vitamin A functions as a key regulator of immunity, antioxidant function, cell growth and differentiation and vision. This paper aims to serve as a comprehensive review of vitamin A and its metabolites, their transport, and their function in human health and disease. Additionally, we seek to synthesize the relevant outcomes and safety data of TTR silencing therapies and how they relate to circulating vitamin A levels and vitamin A-related clinical outcomes in a manner that is relevant to the cardiac amyloidosis specialist.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050204

Authors: Ziyad Gunga Augustin Rigollot Agnès Godat Lars Niclauss Matthias Kirsch

Background: Post-sternotomy mediastinitis remains a devastating complication of cardiac surgery. Although most cases are bacterial, fungal mediastinitis due to Candida albicans is rare, aggressive, and particularly difficult to treat because of biofilm formation, prosthetic involvement, and limited penetration of systemic antifungal agents into infected tissues. Taurolidine is a taurine-derived antimicrobial compound with broad antibacterial, antifungal, and anti-biofilm properties that has shown promising results in catheter-related infection prevention and cardiac implantable electronic device surgery. Case summary: We report, to our knowledge, the first intramediastinal use of taurolidine for Candida albicans mediastinitis after biological Bentall surgery. Following urgent resternotomy and extensive debridement, 200 mL of taurolidine solution was instilled into the mediastinum for 60 min, then aspirated. Postoperatively, taurolidine irrigation via mediastinal drainage was combined with negative-pressure wound therapy and systemic antifungal treatment. Results: Rapid microbiological sterilization was achieved, inflammatory markers normalized, and follow-up computed tomography demonstrated complete resolution of mediastinal infection. Delayed sternal closure was then performed successfully without recurrence at 6-month follow up. Conclusion: To our knowledge, this represents the first reported use of intramediastinal taurolidine irrigation for fungal mediastinitis following cardiac surgery. Intramediastinal taurolidine irrigation may represent a promising adjunctive strategy for mediastinitis after cardiac surgery in high-risk patients. Further clinical evaluation is warranted.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050203

Authors: Dejan M. Lazovic Milica Karadzic Kocica Stefan Juricic Dragan Ivanisevic Vojkan Aleksic Mladen J. Kocica Danko Grujic Jovana Klac Jovana M. Mihajlovic Vladimir Jovicic Dragan Cvetkovic

The coarctation of the aorta is a congenital anomaly characterized by a local narrowing of the aortic lumen localized near the ductus arteriosus. Typically diagnosed in childhood, but it can remain until symptoms become evident. This aortic anomaly can also coexist with aortic valve stenosis. In our case report, we present a 46-year-old male with chest pain, dyspnea, and a significant blood pressure gradient between upper and lower extremities. Diagnostic examination included transthoracic echocardiography and computerized tomography. This diagnostic imaging showed narrowing of the aortic lumen with a residual lumen dimension of 3 mm and severe aortic stenosis. The patient underwent a complex surgical procedure, replacement of the aortic valve and reconstruction of the aorta. An extra-anatomic ascending-to-descending aortic bypass was constructed using a 20 mm Dacron graft, combined with mechanical aortic valve replacement. The operation was performed through median sternotomy with two arterial canula in the femoral artery and in the aorta, and one venous canula in the right atrium. Two canulae are placed for the safe performance of cardiopulmonary bypass. The patient was discharged at home without complication. This case highlights that a single surgical procedure may represent a definitive treatment of a complex problem with good short-term results.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050202

Authors: Yuehao Song Jili Long Hao Wang

Background: Carotid contrast-enhanced ultrasound (CEUS) provides a noninvasive means of assessing plaque vulnerability and may reflect the systemic burden of atherosclerosis. This study aimed to evaluate the diagnostic performance of carotid CEUS characteristics for identifying functionally significant coronary artery stenosis (CAS) defined by quantitative flow ratio (QFR). Methods: In this preliminary prospective study, 46 patients with suspected stable coronary artery disease who underwent carotid CEUS and coronary angiography with QFR assessment between September 2022 and November 2023 were enrolled. Patients were categorized into a QFR ≥ 0.80 group (n = 18) and a QFR < 0.80 group (n = 28). Carotid plaque burden, morphology, and CEUS-derived quantitative parameters were compared between groups. Univariate and multivariable logistic regression analyses were performed to identify independent factors associated with QFR < 0.80, and receiver operating characteristic (ROC) analysis was used to assess discriminatory performance. Results: Compared with patients with QFR ≥ 0.80, those with QFR < 0.80 had significantly higher mean intima-media thickness (IMT), larger plaque area, higher plaque-to-lumen enhancement ratios (Pmax/Cmax and Pmean/Cmean), and more vulnerable plaque features, including irregular margins and thin fibrous caps. In multivariable analysis, Pmax/Cmax (adjusted OR: 14.394, 95% CI: 2.718–76.220; p = 0.002) and mean IMT (adjusted OR: 7.740, 95% CI: 2.040–29.363; p = 0.003) remained independently associated with QFR < 0.80. ROC analysis showed that the combined model incorporating Pmax/Cmax and mean IMT achieved the best discrimination for QFR < 0.80 (AUC: 0.931, 95% CI: 0.845–0.989), with 78.6% sensitivity and 94.4% specificity. Conclusions: Carotid CEUS-derived plaque enhancement characteristics, particularly Pmax/Cmax, together with mean IMT, were independently associated with functionally significant CAS. These findings suggest that carotid CEUS may provide complementary, noninvasive information for vascular risk stratification, but it should not be considered a substitute for coronary angiography-based physiological assessment.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050201

Authors: Kartik Yadav Sama Ehab Salah Ahmed Mohamed Abdelgader Roann Khalid Murugapathy Veerasamy Arka Das Heerajnarain Bulluck

Aspirin has been the default backbone of antiplatelet therapy after percutaneous coronary intervention (PCI) for over two decades, anchored by landmark trials that established 12-month dual antiplatelet therapy (DAPT) as the standard of care. Three developments have prompted reassessment of this paradigm: the markedly lower thrombotic risk of contemporary drug-eluting stents, the greater potency and consistency of potent P2Y12 inhibitors (ticagrelor, prasugrel), and increasing recognition that major bleeding independently worsens outcomes after PCI. Recent randomised trials have systematically tested aspirin withdrawal at varying time points. Immediate aspirin-free strategies (NEO-MINDSET, STOPDAPT-3) demonstrated an early signal of excess ischaemic events in the ACS component of enrolled populations, suggesting that aspirin remains important during the earliest post-PCI period in ACS. One-month strategies (T-PASS, ULTIMATE-DAPT, TARGET-FIRST) and three-month strategies (TWILIGHT, TICO, DUAL-ACS) showed that transition to P2Y12 monotherapy after an initial DAPT period significantly reduces bleeding without increasing ischaemic events in selected populations. Beyond one year, long-term randomised trials including the HOST-EXAM 10-year follow-up (Lancet 2026) and the STOPDAPT-2 5-year landmark analysis (Circ Cardiovasc Interv 2026), together with study-level meta-analyses (PANTHER) and recent individual patient data meta-analyses, provide converging evidence that clopidogrel monotherapy outperforms aspirin for chronic secondary prevention without excess bleeding. The choice of P2Y12 agent is critical: clopidogrel monotherapy in ACS during the first post-procedural year carries excess thrombotic risk owing to CYP2C19 pharmacogenomic variability, whereas ticagrelor and prasugrel provide more reliable protection. This review synthesises the mechanistic rationale, trial evidence across all time points, special clinical contexts (oral anticoagulation, coronary artery bypass grafting, high bleeding risk), guideline evolution, and methodological considerations, providing a practical framework for individualising post-PCI antiplatelet therapy.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050200

Authors: Şükriye Uslu Gülsüm Meral Yılmaz Öztekin Ahmet Genç Ekin Can Çelik Şakir Arslan

Background: This study investigated the role of lymphocyte-based inflammatory indices (LBIIs) in predicting severe coronary artery disease (CAD) in patients undergoing coronary angiography (CAG) for unstable angina pectoris (USAP). Methods: Records of patients who underwent CAG between January 2023 and December 2024 were retrospectively reviewed. The patients were divided into two groups based on coronary artery stenosis severity: non-severe CAD (<70% stenosis) and severe CAD (≥70% stenosis). Demographic data, risk factors, and complete blood count parameters were recorded. Six LBIIs were calculated: the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), Systemic Immune–Inflammation Index (SII), Systemic Inflammatory Response Index (SIRI), and Systemic Immune–Inflammatory Response Index (SIIRI). Diagnostic performance was evaluated using logistic regression and ROC curve analyses. Results: Out of 505 patients, 234 (46.3%) had severe CAD. Among the six LBIIs, only the SII differed significantly between groups in univariate analysis and showed moderate discrimination in the ROC analysis (AUC 0.71; 95% CI 0.661–0.762; p < 0.001; sensitivity 76.2%; specificity 56.1%). However, the SII was not an independent predictor in the multivariate analysis. Conclusions: LBIIs (NLR, MLR, PLR, SII, SIRI, and SIIRI) do not provide a clinically significant and independent contribution to predicting severe CAD in USAP patients undergoing CAG. Although the SII performed moderately well in the univariate analysis, it lost independence in the multivariate analysis and is thus not suitable for use as a standalone marker in clinical decision-making.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050199

Authors: Charlotte Schöneburg Isabel Uphoff Anna Thußbas Laura Willinger Renate Oberhoffer Peter Ewert Jan Müller

Background: A physically active lifestyle is crucial for long-term cardiovascular health; however, access to supervised exercise programs for children and adolescents with congenital heart disease (CHD) remains limited. Although prior digital exercise interventions for this population have demonstrated safety and feasibility, adherence has often been low. Mobile health approaches integrating gamification may enhance motivation and engagement, particularly among young “digital natives.” FOOTLOOSE is an app-based home exercise program developed specifically for children and adolescents with CHD. This study aimed to evaluate user experience, usability, and perceived impact using a multimethod approach. Methods: Children and adolescents aged 10–18 years with simple, moderate, or complex CHD were recruited between July and December 2025 mainly during routine outpatient visits at the TUM Klinikum Deutsches Herzzentrum. Participants used the FOOTLOOSE app in their daily lives over a two-week period. Evaluation included semi-structured qualitative interviews and standardized questionnaires assessing physical activity self-efficacy, enjoyment of physical activity (PACES-S), user experience (UEQ), and health-related quality of life (KINDL®). Interviews were conducted digitally, transcribed verbatim, and analyzed using qualitative content analysis according to Kuckartz until thematic saturation was reached. Results: A total of 22 participants (mean age 13.4 ± 2.3 years; 54.5% female) were included. Overall, the FOOTLOOSE app was perceived positively, with participants highlighting enjoyment, intuitive usability, and personalized workout creation. Participants contributed diverse and creative suggestions for further app development, particularly regarding more advanced gamification features (e.g., games or rankings). Most participants reported self-perceived increase in physical activity during the intervention period (n = 15). UEQ scores (mean ± SD) were as follows: attractiveness (1.3 ± 0.8), perspicuity (1.7 ± 1.1), efficiency (1.2 ± 0.9), dependability (1.4 ± 0.7), stimulation (1.0 ± 1.1), and novelty (0.6 ± 1.0). Conclusions: This study demonstrates the feasibility and user acceptance of a gamified, app-based home exercise program for children and adolescents with CHD. User-centered feedback highlights important directions for iterative refinement, particularly regarding age-appropriate and engaging gamification elements. These findings provide a foundation for future studies evaluating long-term engagement and effectiveness in larger samples.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050198

Authors: David C. Rotzinger Chiara Pozzessere Guillaume Fahrni

In its three decades of existence, cardiovascular computed tomography (CT) has profoundly transformed patient assessment and established itself as one of the most recommended non-invasive imaging modalities in contemporary cardiology and radiology practice [...]

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050197

Authors: Alexandra Manuela Buzle Priscilla Matache Mădălina Ioana Moisi Corina Cinezan Marc Cristian Ghitea Evelin Claudia Ghitea Timea Claudia Ghitea Ioana Adriana Ardelean Marius Rus Roxana Daniela Brata Mircea Ioachim Popescu

Background: Post-infarction heart failure (HF) remains a major contributor to morbidity and mortality despite advances in reperfusion and pharmacological management. However, the combined influence of clinical background, myocardial injury, neuro-hormonal activation, and angiographic disease on HF severity is not fully defined. Methods: We retrospectively analyzed 181 patients with confirmed myocardial infarction treated in a tertiary cardiology center. Demographics, cardiovascular risk factors, prior chronic HF, inflammatory markers (CRP, fibrinogen, ESR, leukocyte indices), and high-sensitivity troponin (hs-Tn) were measured at admission (pre-intervention), immediately after percutaneous coronary intervention (PCI), and at 48 h, angiographic lesion distributions were collected. HF severity was graded on a five-level scale and further dichotomized as no/mild HF (grade 0–1) versus moderate–severe HF (grade ≥ 2). Group comparisons and multivariable logistic regression were used to identify independent determinants of severe HF. Results: Moderate–severe HF occurred in 42.5% of patients (77/181). Compared to HF 0–1, the HF ≥ 2 group was older (64.0 vs. 60.5 years, p = 0.042) and exhibited substantially higher systemic inflammation (CRP 41.5 vs. 9.75 mg/L, p < 0.001; fibrinogen 435 vs. 346 mg/dL, p = 0.0002; ESR 28 vs. 18 mm/h, p = 0.0004). hs-Tn levels and NT-proBNP were significantly elevated in HF ≥ 2 (NT-proBNP 3449 vs. 1243 pg/mL, p = 0.0003), while left ventricular ejection fraction was reduced. Prior HF increased the likelihood of HF ≥ 2 (54.5% vs. 33.7%, p = 0.0078), and conservative therapy was associated with adverse outcomes (87.5% vs. 40.5%, p = 0.0235). In multivariable analysis, NT-proBNP remained the only independent predictor of moderate–severe HF, while CRP showed a positive but non-significant trend after adjustment. Conclusions: Post-MI HF severity reflects the combined influence of myocardial injury, neurohormonal stress, and systemic inflammatory activation. However, in multivariable analysis, NT-proBNP emerged as the dominant independent predictor of moderate–severe HF, while CRP reflected an associated but non-independent inflammatory signal.

Journal of Cardiovascular Development and Disease doi: 10.3390/jcdd13050196

Authors: Hicran Gül Emral Thao V. N. Nguyen Ilaria Bo Thomas Semple Julene S. Carvalho Piers E. F. Daubeney Michael L. Rigby Sylvia Krupickova

Scimitar syndrome is a rare congenital cardiopulmonary anomaly with marked anatomical and clinical heterogeneity, and long-term outcome data remain limited. We reviewed our single-center experience over a 33-year period. Patients evaluated between 1992 and 2025 were retrospectively analyzed. A total of 104 patients were included, with female predominance (63, 60.6%). The median age at first presentation was 0.4 years (IQR 0.0–16.7; range 1 day–68 years) with 59 patients (56.7%) presenting during infancy. At last follow-up, the median age was 18.5 years (IQR 8.7–30.6; range 60 days–70 years), with a median follow-up duration of 9.5 years (IQR 3.7–16.1). Dextrocardia was observed in 76 patients (73.1%). The most common associated defect was atrial septal defect (37 patients, 35.6%), while 23 patients (22.1%) had no additional cardiac defects. Respiratory manifestations predominated at presentation and follow-up. However, 18 patients (17.3%) were asymptomatic at diagnosis and 44 (42.3%) at follow-up. Partial anomalous pulmonary venous drainage was present in 87 patients (83.6%), and aorto-pulmonary collaterals in 70 (67.3%). Cardiac catheterization was performed in 78 patients (75.0%), and 47 (45.2%) underwent surgery. At last documented follow-up, 101 of 104 patients (97.1%) were alive, with three deaths occurring during follow-up.