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Volume 12
Issue 11
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J. Cardiovasc. Dev. Dis., Volume 12, Issue 11 (November 2025) – 38 articles

Cover Story (view full-size image): Amyloid cardiomyopathy (ACM) is a progressive and often fatal heart disease caused by misfolded transthyretin (TTR) or immunoglobulin light chains that infiltrate and stiffen the myocardium. Human-induced pluripotent stem cells (iPSCs) now turn this challenge into an opportunity by providing a patient-specific window into ACM pathogenesis. In this review, Liu & Riaz illustrate how hepatocytes derived from patient-specific TTR-mutant iPSCs recapitulate amyloid secretion, whereas iPSC-derived cardiomyocytes model amyloid-induced proteotoxic stress in both two- and three-dimensional engineered tissues. The integration of CRISPR-Cas9 genome editing and dynamic 3D conditioning further enhances mechanistic fidelity and enables drug screening. Together, these human-relevant platforms link genotype to phenotype and accelerate precision drug discovery for ACM. View this paper
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15 pages, 12518 KB  
Article
The Conducting Tissues of the Mouse Heart
by Yolanda Macías, Damián Sánchez-Quintana, Eduardo Back Sternick and Robert H. Anderson
J. Cardiovasc. Dev. Dis. 2025, 12(11), 452; https://doi.org/10.3390/jcdd12110452 - 20 Nov 2025
Viewed by 209
Abstract
Background: Since the study of Lev and Thaemert in 1973, little has been published concerning the overall arrangement of the murine conduction tissues, in particular with relation to gross anatomical landmarks. We recently emphasised the potential value of the mouse as an experimental [...] Read more.
Background: Since the study of Lev and Thaemert in 1973, little has been published concerning the overall arrangement of the murine conduction tissues, in particular with relation to gross anatomical landmarks. We recently emphasised the potential value of the mouse as an experimental animal in determining the role, if any, of the superior septal pathways in ventricular activation, comparing the findings to the arrangement in the human heart. Our previous study, however, was confined to the atrioventricular conduction axis. In the light of recent controversies regarding atrial conduction, we have now extended our study to evaluate the overall arrangement of the conduction tissues in the murine heart. Methods: We have re-examined serially sectioned histological datasets previously prepared from adult mouse hearts, incorporating new datasets to permit assessment in the three orthogonal planes, correlating the histological findings with the gross anatomy as revealed in episcopic datasets prepared from late foetal and neonatal mice. Results: The overall arrangement of the conduction tissues is comparable with the human arrangement, but with subtle differences. The sinus node straddles the superior cavoatrial junction, rather than being embedded within the terminal groove. Conduction from the node to the atrial walls is through working atrial myocardium. The atrioventricular conduction axis, as we have recently emphasised, is much more comparable, in particular with presence of well-formed nodo-ventricular and fasciculo-ventricular pathways. In many of the hearts it is also possible to recognise a well-formed retro-aortic node. Conclusions: Despite the differences in the arrangement of the sinus node, mouse is an ideal model for further investigations of cardiac conduction, in particular to clarify the potential roles of the superior septal pathways and the retro-aortic node. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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10 pages, 1803 KB  
Review
Left Ventricular Apical Cannulation in Acute Type A Aortic Dissection
by Benedetto Ferraresi, Antonio Nenna, Mohamad Jawabra, Diletta Corrado, Filippo Barberi, Carmelo Dominici, Giovanni Casali, Massimo Chello and Mario Lusini
J. Cardiovasc. Dev. Dis. 2025, 12(11), 451; https://doi.org/10.3390/jcdd12110451 - 19 Nov 2025
Viewed by 259
Abstract
Background and objectives: In cases of acute type A aortic dissection, including iatrogenic cases following transcatheter procedures, the choice of arterial cannulation site has a critical influence on early haemodynamics, organ protection and the risk of malperfusion. Transapical left ventricular cannulation has been [...] Read more.
Background and objectives: In cases of acute type A aortic dissection, including iatrogenic cases following transcatheter procedures, the choice of arterial cannulation site has a critical influence on early haemodynamics, organ protection and the risk of malperfusion. Transapical left ventricular cannulation has been suggested as a ‘central’ approach for rapidly establishing cardiopulmonary bypass with antegrade true-lumen flow. This review summarises the current evidence on TAC in acute type A dissection, focusing on indications, technical aspects and clinical outcomes. Materials and methods: We conducted a narrative review of observational studies and technical reports describing TAC for the surgical repair of acute type A aortic dissection. Particular attention was paid to patient selection, operative technique, perioperative complications, and early and mid-term results. Results: Across the published series, TAC is primarily employed in haemodynamically unstable patients or when the peripheral arteries are dissected, diseased, or unsuitable. A long arterial cannula is introduced through the left ventricular apex, crosses the aortic valve and is positioned in the true lumen of the ascending aorta under echocardiographic guidance. This configuration enables the rapid initiation of CPB, shortens skin-to-pump times, and provides reliable antegrade inflow. Early mortality and stroke rates are comparable to those associated with other cannulation strategies. Reported complications include malperfusion requiring site conversion, apical bleeding and rare local structural damage. These can be minimised through standardised technique and systematic imaging. Conclusions: TAC is a valuable bail-out option and, in selected patients, a primary cannulation option for acute type A aortic dissection when conventional arterial access is unsafe or ineffective. Although it offers fast and reproducible establishment of antegrade true-lumen flow, it requires specific expertise in apical exposure and intraoperative echocardiography. It should therefore be integrated into a structured perfusion and repair strategy. Full article
(This article belongs to the Special Issue Transcatheter and Surgical Approaches to Complications of Transcatheter Procedures: Current Trends and Future Challenges)
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13 pages, 1861 KB  
Review
Late Complications After Aortic Coarctation Repair
by Annarita Santoro, Fiorenza De Lisio, Alexandra Fedorovna Bezborodova, Roberto Chiesa and Germano Melissano
J. Cardiovasc. Dev. Dis. 2025, 12(11), 450; https://doi.org/10.3390/jcdd12110450 - 19 Nov 2025
Viewed by 335
Abstract
Aortic coarctation (CoA) is a congenital vascular anomaly characterized by luminal narrowing of the aorta, representing approximately 5–8% of all congenital heart defects, and is frequently associated with a bicuspid aortic valve and additional vascular malformations. The clinical spectrum is broad, ranging from [...] Read more.
Aortic coarctation (CoA) is a congenital vascular anomaly characterized by luminal narrowing of the aorta, representing approximately 5–8% of all congenital heart defects, and is frequently associated with a bicuspid aortic valve and additional vascular malformations. The clinical spectrum is broad, ranging from severe neonatal heart failure to asymptomatic systemic hypertension in adulthood, with the severity of presentation directly influencing the timing of diagnosis and therapeutic intervention. Over recent decades, management strategies have transitioned from conventional surgical techniques—such as end-to-end anastomosis, subclavian flap aortoplasty, and patch augmentation—to endovascular modalities including balloon angioplasty and stent implantation, with covered stents now constituting the preferred approach in most cases. Nonetheless, late complications remain clinically significant. Post-coarctation aneurysms (pCoAA), particularly following patch aortoplasty, have been reported in up to 50% of patients and necessitate lifelong imaging surveillance. Re-coarctation persists as a therapeutic challenge, especially in neonates, with recurrence risk influenced by anatomical factors and the initial repair method. Optimal outcomes require an individualized, anatomy-tailored approach that judiciously integrates surgical, endovascular, and hybrid techniques. Lifelong surveillance remains essential to mitigate long-term risks, including systemic hypertension, aneurysm formation, and the need for re-intervention. Full article
(This article belongs to the Special Issue Congenital Heart Disease: Technological Innovations in Cardiac Surgery and Interventional Therapy)
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26 pages, 2754 KB  
Article
Cardiomyocyte Nuclear Pleomorphism in a Mouse Model of Inherited Hypertrophic Cardiomyopathy
by Jamie R. Johnston, Isabella Leite Coscarella, Carson L. Rose, Yun Shi, Hosna Rastegarpouyani, Karissa M. Dieseldorff Jones, Jennifer M. Le Patourel, Feyikemi Ogunfuwa, Adriano S. Martins, Kathryn M. Crotty, Katherine M. Ward Molla, Tyler R. Reinoso, Taylor L. Waldmann, Jerome Irianto, Yue Julia Wang, Lili Wang, Björn C. Knollmann, Jose R. Pinto and Prescott Bryant Chase
J. Cardiovasc. Dev. Dis. 2025, 12(11), 449; https://doi.org/10.3390/jcdd12110449 - 19 Nov 2025
Viewed by 501
Abstract
Mutations in genes encoding sarcomeric proteins are a common cause of cardiomyopathy and sudden cardiac death in humans. We evaluated the hypothesis that myofilament dysfunction is coupled to morphological and functional alterations of cardiomyocyte nuclei in a Tnnc1-targeted knock-in (Tnnc1-p.A8V) [...] Read more.
Mutations in genes encoding sarcomeric proteins are a common cause of cardiomyopathy and sudden cardiac death in humans. We evaluated the hypothesis that myofilament dysfunction is coupled to morphological and functional alterations of cardiomyocyte nuclei in a Tnnc1-targeted knock-in (Tnnc1-p.A8V) mouse model of hypertrophic cardiomyopathy (HCM). Tnnc1 is the gene that codes for the isoform of the Ca2+-regulatory protein troponin C (cTnC) that is expressed in cardiomyocytes and slow skeletal muscle fibers and resides on thin filaments of sarcomeres in those muscles. This pathogenic mutation in a sarcomere gene alters many aspects of cardiomyocyte function, including sarcomere contractility, cytoplasmic Ca2+ buffering, and gene expression. Analysis of myocardial histological sections and isolated cardiomyocytes from adult Tnnc1-p.A8V mouse hearts revealed significantly smaller (cross-sectional area and volume) and rounder nuclei compared to those from age-matched, wild-type control mice. Changes in nuclear morphology could not be explained by differences in cardiomyocyte size or ploidy. Isolated wild-type and mutant cardiomyocyte nuclei, which are embedded centrally within myofibrils, undergo compression during contraction of the cardiomyocyte, indicating that during each heartbeat cardiomyocyte nuclei would be mechanically deformed as well as being exposed to elevated cytoplasmic Ca2+. Immunoblotting analysis indicated decreased nuclear localization of cardiac troponin C and decreased histone H4 expression in Tnnc1-p.A8V mouse hearts. Next, we investigated the influence of nucleocytoplasmic transport by immunofluorescence microscopy, and we could not confirm nuclear localization of cardiac troponin C in fixed myocardial tissue from adult mice. However, cardiac troponin C could be detected in healthy human-induced pluripotent stem cell-derived cardiomyocyte nuclei. We conclude that pathological myofilament dysfunction due to a pathogenic, cardiomyopathy-associated mutation can be linked to altered protein composition of cardiomyocyte nuclei and aberrant nuclear morphology. Full article
(This article belongs to the Section Genetics)
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13 pages, 692 KB  
Article
CaReMe-CKD-HF–Epidemiology of Heart Failure in Chronic Kidney Disease: A Retrospective Analysis of Routine Administrative Data from a German Hospital Network
by Lars Stellmacher, Sebastian König, Johannes Leiner, Vincent Pellissier, Sven Hohenstein, Jakob Birnbaum, Stefan Kwast, Carolin Schanner, Ralf Kuhlen and Andreas Bollmann
J. Cardiovasc. Dev. Dis. 2025, 12(11), 448; https://doi.org/10.3390/jcdd12110448 - 19 Nov 2025
Viewed by 295
Abstract
Background: Heart failure (HF) is a frequent and clinically relevant comorbidity in patients with chronic kidney disease (CKD). Both conditions are closely linked through hemodynamic, neurohormonal, and inflammatory mechanisms, resulting in excess morbidity and mortality. However, nationwide epidemiological data for hospitalized patients with [...] Read more.
Background: Heart failure (HF) is a frequent and clinically relevant comorbidity in patients with chronic kidney disease (CKD). Both conditions are closely linked through hemodynamic, neurohormonal, and inflammatory mechanisms, resulting in excess morbidity and mortality. However, nationwide epidemiological data for hospitalized patients with CKD in Germany are scarce. This study aimed to determine the prevalence and outcomes of HF in CKD using a large real-world dataset. Materials and methods: We conducted a retrospective, observational study analyzing administrative data from 87 German hospitals between 2016 and 2022 (n = 48,011 CKD index cases). Patients were stratified into CKD with HF (n = 22,085; 46%) and CKD without HF (n = 25,926; 54%). Additional electronic medical records (EMR) from 23,377 CKD patients of the Heart Center Leipzig were included. All hospital readmissions were considered during the follow-up period. Comparative statistics are presented for each group. Results: CKD patients with HF were older (76.5 ± 10.8 vs. 71.5 ± 14.3 years, p < 0.001), more frequently affected by cardiovascular and metabolic comorbidities, and had worse renal function. In-hospital mortality was higher in CKD-HF than CKD-no-HF patients (16.5% vs. 6.7%; odds ratio [OR] 2.73, 95% CI 2.58–2.89; p < 0.001). During follow-up, readmissions occurred earlier (175 ± 266 vs. 212 ± 309 days, p < 0.001) and more frequently in the CKD-HF group (20.3 vs. 17.7 events per 100 patient–years). Follow-up in-hospital mortality was also increased in CKD-HF patients (13.3% vs. 8.7%; OR 1.62, 95% CI 1.52–1.73; p < 0.001). Discussion: In this large, multicenter, real-world cohort, HF was highly prevalent in CKD and associated with substantially increased morbidity and mortality. These findings highlight the considerable public health burden of HF in CKD and the urgent need for targeted prevention and management strategies. Full article
(This article belongs to the Section Acquired Cardiovascular Disease)
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18 pages, 2422 KB  
Article
Sex-Specific Expression Patterns of MYH6 and MYH7 Gene Transcripts in Large Cohorts of Non-Failing and Failing Human Left Ventricular Tissues
by Zdenko Červenák, Ján Somorčík, Yashar Jalali, Žaneta Zajacová, Marian Baldovič, Andrea Gažová and Ján Kyselovič
J. Cardiovasc. Dev. Dis. 2025, 12(11), 447; https://doi.org/10.3390/jcdd12110447 - 17 Nov 2025
Viewed by 333
Abstract
The transcriptional regulation of MYH6 and MYH7 genes has been extensively investigated in healthy versus failing hearts; however, their expression dynamics in healthy human hearts across age and sex, particularly in the context of cardiovascular risk factors such as hypertension, remain poorly characterised. [...] Read more.
The transcriptional regulation of MYH6 and MYH7 genes has been extensively investigated in healthy versus failing hearts; however, their expression dynamics in healthy human hearts across age and sex, particularly in the context of cardiovascular risk factors such as hypertension, remain poorly characterised. This study aimed to carry out a reanalysis of MYH6 and MYH7 transcript levels in a large cohort of non-failing human left ventricular samples, stratified by sex, age, and hypertensive status. Furthermore, we examined how age and sex influence gene expression differences between non-failing and failing hearts, the latter affected by dilated cardiomyopathy (DCM). Normalised expression values for MYH6 and MYH7 transcripts from both healthy and failing left ventricles were extracted using the GEO2R online analysis tool from the publicly available RNA-sequencing library GSE141910. This library provides transcriptomic profiles of left ventricular (LV) tissue from both healthy individuals and patients with cardiomyopathies. The Mann–Whitney U test was employed for pairwise comparisons between different groups stratified by sex, age, and hypertensive status. Statistical analysis demonstrates sex-specific differences in MYH6 and MYH7 expression in healthy left ventricles, with postmenopausal females (aged > 50 years) with hypertension emerging as a distinct group. Conversely, in end-stage DCM hearts, the expression levels of both myosin genes seemed to be primarily influenced by disease-related pathophysiological mechanisms rather than by sex or age. Comparison between healthy and failing hearts revealed a consistent and significant downregulation of MYH6 in all comparisons, irrespective of sex or age. On the other hand, MYH7 expression exhibited greater variability, particularly among males, with age and hypertensive status influencing its expression. The results underscore the importance of considering age, sex, and comorbidities in interpreting cardiac gene expression patterns and highlight potential regulatory divergence in contractile gene expression during cardiac remodelling. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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1 pages, 153 KB  
Retraction
RETRACTED: Quazi, S.; Malik, J.A. A Systematic Review of Personalized Health Applications through Human–Computer Interactions (HCI) on Cardiovascular Health Optimization. J. Cardiovasc. Dev. Dis. 2022, 9, 273
by Sameer Quazi and Javid Ahmad Malik
J. Cardiovasc. Dev. Dis. 2025, 12(11), 446; https://doi.org/10.3390/jcdd12110446 - 17 Nov 2025
Viewed by 180
Abstract
The Journal of Cardiovascular Development and Disease retracts the article “A Systematic Review of Personalized Health Applications through Human–Computer Interactions (HCI) on Cardiovascular Health Optimization” [...] Full article
21 pages, 611 KB  
Review
Lipid Profile and Management of Dyslipidemias in Pregnancy
by Constantine E. Kosmas, Loukianos S. Rallidis, Ioannis Hoursalas, Eleni-Angeliki Zoumi and Christina E. Kostara
J. Cardiovasc. Dev. Dis. 2025, 12(11), 445; https://doi.org/10.3390/jcdd12110445 - 16 Nov 2025
Viewed by 507
Abstract
Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). Abnormal maternal lipid profiles in pregnancy are associated with pregnancy complications including preeclampsia, gestational diabetes, and pre-term delivery as well as increased ASCVD risk for both mother and child. Dyslipidemia management remains [...] Read more.
Dyslipidemia is a significant risk factor for atherosclerotic cardiovascular disease (ASCVD). Abnormal maternal lipid profiles in pregnancy are associated with pregnancy complications including preeclampsia, gestational diabetes, and pre-term delivery as well as increased ASCVD risk for both mother and child. Dyslipidemia management remains a central tenet for atherosclerotic cardiovascular disease prevention for women who are thinking about becoming pregnant or are already pregnant. Effective individualized guidance and multidisciplinary lifestyle/dietary strategies, along with targeted pharmacological interventions, are required for the successful management of lipid disorders in pregnancy in order to optimize outcomes. This review discusses the physiological changes occurring in lipid metabolism during pregnancy and provides an overview of the current strategies for managing dyslipidemia during pregnancy, with a special focus on consideration of pharmacological therapy. Full article
(This article belongs to the Special Issue Effect of Lipids and Lipoproteins on Atherosclerosis)
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19 pages, 667 KB  
Article
Comparison of Clinical Features and Hemodynamics of Single Ventricle Patients With and Without Interventional Closure of Veno-Venous or Aortopulmonary Collaterals
by Helena Link, Alessia Callegari, Walter Knirsch, Oliver Kretschmar and Daniel Quandt
J. Cardiovasc. Dev. Dis. 2025, 12(11), 444; https://doi.org/10.3390/jcdd12110444 - 13 Nov 2025
Viewed by 317
Abstract
In single ventricle (SV) patients, veno-venous (VVCs) and major aortopulmonary collaterals (APCs) are common. We aim to determine the differences between patients with and without interventional closure of VVCs or APCs in this single-center, retrospective analysis of 135 SV patients (2006–2021). Anatomical, surgical [...] Read more.
In single ventricle (SV) patients, veno-venous (VVCs) and major aortopulmonary collaterals (APCs) are common. We aim to determine the differences between patients with and without interventional closure of VVCs or APCs in this single-center, retrospective analysis of 135 SV patients (2006–2021). Anatomical, surgical and clinical features, hemodynamics and PA dimensions were compared. VVC closure was performed in 34 (25%) patients. VVC closure was associated with comprehensive stage I + II (p = 0.05), left PA patch procedure (p = 0.04), Fontan fenestration (p < 0.001), PA pressure >/= 16 mmHg pre-BCPC (p = 0.04) and >/= 15 mmHg pre-TCPC (p = 0.021), lower saturation pre-TCPC (p = 0.04) and smaller PAs (Nakata p = 0.03, total lower lobe index p = 0.001). Patients with VVC closure had a longer hospitalization post-BCPC (p = 0.008) and post-TCPC (p = 0.04) and longer ICU time post-BCPC (p = 0.04). APC closure was performed in 53 (39%) patients. Male sex (p = 0.001), Norwood I procedure (p = 0.04), younger age at BCPC (p = 0.02), higher end-diastolic pressure pre-TCPC (p = 0.04), lower oxygen levels pre-BCPC (p < 0.001) and smaller PAs (Nakata p = 0.08; McGoon p < 0.001) were related to APC closure. Patients with APC closure had a longer hospital (p < 0.001) and ICU (p = 0.005) stay post-TCPC. Significant VVC and APCs are linked to poorer PA growth, worse hemodynamics, lower sats and prolonged hospital/ICU stays, highlighting the need for targeted attention. Full article
(This article belongs to the Special Issue Congenital Heart Disease: Technological Innovations in Cardiac Surgery and Interventional Therapy)
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11 pages, 502 KB  
Article
Nonlinear Association Between Atherogenic Index of Plasma and Unstable Carotid Plaque: A Single-Center Retrospective Study
by Guijun Huo, Yao Tang and Dayong Zhou
J. Cardiovasc. Dev. Dis. 2025, 12(11), 443; https://doi.org/10.3390/jcdd12110443 - 11 Nov 2025
Viewed by 381
Abstract
Background: The atherogenic index of plasma (AIP) is a marker of lipids and atherosclerosis. However, the association between the AIP and the risk of unstable carotid plaque remains unclear. Methods: A total of 10,732 patients were enrolled. Carotid ultrasound was used to assess [...] Read more.
Background: The atherogenic index of plasma (AIP) is a marker of lipids and atherosclerosis. However, the association between the AIP and the risk of unstable carotid plaque remains unclear. Methods: A total of 10,732 patients were enrolled. Carotid ultrasound was used to assess the stability of carotid plaque. The AIP was calculated using the formula AIP = log (TG/HDL-C). Logistic regression was used to investigate the association between the AIP and unstable carotid plaque. The nonlinear association between the AIP and unstable carotid plaque was analyzed using restricted cubic splines (RCSs), and a two-segment logistic regression risk model was constructed for both sides of the inflection point. Results: Of the total number of patients, 7834 had stable carotid plaque and 2898 had unstable carotid plaque. Our findings demonstrated an inverted U-shaped association between the AIP and the risk of unstable carotid plaque (threshold = 0.10). When the AIP was <0.10, a significant positive association with unstable carotid plaque emerged (OR: 1.24, 95% CI: 1.07, 1.44); when the AIP was ≥0.10, it showed a significant negative association with unstable carotid plaque (OR: 0.78, 95% CI: 0.70, 0.88). Conclusions: Our findings demonstrated an inverted U-shaped association between the AIP and the risk of unstable carotid plaque, with a threshold of 0.10. The AIP could serve as a potential biomarker for unstable carotid plaque risk assessment. Full article
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12 pages, 559 KB  
Review
Role of Coronary Artery Calcium Score CT in Risk Stratification of Asymptomatic Individuals
by Darío Gómez-Díaz, Pablo Díez-Villanueva, Beatriz López-Melgar, Luis Flores, Gianluca De Toffol, Agustín Ramos, Álvaro Montes, Alberto Cecconi, Jesús Jiménez-Borreguero and Fernando Alfonso
J. Cardiovasc. Dev. Dis. 2025, 12(11), 442; https://doi.org/10.3390/jcdd12110442 - 9 Nov 2025
Viewed by 725
Abstract
Background: The evaluation of coronary artery disease has undergone significant transformation in recent years, with increasing emphasis on the detection and characterization of subclinical atherosclerotic plaques in order to improve cardiovascular prevention. In this context, coronary computed tomography (CT) has emerged as a [...] Read more.
Background: The evaluation of coronary artery disease has undergone significant transformation in recent years, with increasing emphasis on the detection and characterization of subclinical atherosclerotic plaques in order to improve cardiovascular prevention. In this context, coronary computed tomography (CT) has emerged as a promising tool. Coronary artery calcium scoring (CACS) is a powerful predictor of cardiovascular events. Methods: A narrative review on the role of CACS in risk stratification of asymptomatic adults is conducted through a structured search in PubMed (2010–2025), including guidelines, consensus documents, observational studies, and clinical trials published in English. Results: CACS reliably identifies subclinical atherosclerosis and stratifies cardiovascular risk in asymptomatic individuals. Large studies, including the Multi-Ethnic Study of Atherosclerosis (MESA), demonstrate that CACS predicts 10-year cardiovascular events, improves risk reclassification beyond traditional scores, and identifies very low-risk individuals (those with a CAC of 0). Moreover, CACS retains prognostic value across age, sex, and ethnic subgroups; supports decision-making for lipid-lowering therapy and aspirin use; and correlates with non-gated CT assessments. Progression of CAC further informs risk, although its interpretation is influenced by preventive therapies and is complemented by more comprehensive plaque imaging. Conclusions: CACS is a validated tool for detecting subclinical atherosclerosis and refining cardiovascular risk in asymptomatic individuals. CACS thus complements traditional risk scores and represents a key component of contemporary and future cardiovascular prevention in clinical practice. Full article
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20 pages, 5420 KB  
Article
Effect of Antihypertensive Losartan on Ca2+ Mobilization in the Aorta of Middle-Aged Spontaneously Hypertensive Female Rats
by Swasti Rastogi, Jessica Liaw, Yingnan Zhai, Tatiana Karpova, Linxia Gu and Kenia Nunes
J. Cardiovasc. Dev. Dis. 2025, 12(11), 441; https://doi.org/10.3390/jcdd12110441 - 7 Nov 2025
Viewed by 413
Abstract
Hypertension, a leading factor for cardiovascular diseases (CVD), is a particularly heavy burden in women during middle age, when cardioprotective hormones begin to decline. The abnormal handling of calcium (Ca2+) in vascular smooth muscle cells (VSMCs) leads to increased vasoconstriction, remodeling, [...] Read more.
Hypertension, a leading factor for cardiovascular diseases (CVD), is a particularly heavy burden in women during middle age, when cardioprotective hormones begin to decline. The abnormal handling of calcium (Ca2+) in vascular smooth muscle cells (VSMCs) leads to increased vasoconstriction, remodeling, and altered arterial compliance during hypertension. The Spontaneously Hypertensive Rats (SHR) is a model of essential hypertension, and middle-aged females with hypertension represent a stage of disease where vascular dysfunction is prominent but understudied. Losartan, a widely prescribed angiotensin II (AngII) receptor (AT1R) blocker, exerts antihypertensive effects by affecting Ang II/Ca2+ signaling. However, whether it corrects the Ca2+ mishandling in the aorta of middle-aged female SHR has not been established. In this study, the thoracic aorta from 36-week-old female SHRs treated with losartan was assessed for Ca2+ mishandling using myography and biochemical assays. Meanwhile, biomechanical properties and stiffness were evaluated using Pulse Wave Velocity (PWV), Atomic Force Microscopy (AFM), and assessments of collagen and elastin contents. Compared with normotensive controls, SHR demonstrated disrupted Ca2+ handling, increased stiffness, and Extracellular Matrix (ECM) remodeling in middle-aged females. Treatment with losartan abrogated Ca2+ mishandling influx and efflux in the VSMC, decreased stiffness, and restored the aortic structural changes. These findings demonstrate that losartan abolishes Ca2+ mishandling and highlight a mechanistic role of AT1R blockade in restoring vascular function in the aorta of middle-aged females during hypertension. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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24 pages, 1709 KB  
Review
Pharmacological and Interventional Prevention and Treatment of Microvascular Obstruction Following Primary PCI in STEMI
by Giovanni Occhipinti, Michele Strosio, Riccardo Rinaldi, Andrea Ruberti and Salvatore Brugaletta
J. Cardiovasc. Dev. Dis. 2025, 12(11), 440; https://doi.org/10.3390/jcdd12110440 - 7 Nov 2025
Viewed by 696
Abstract
Microvascular obstruction (MVO) accounts for up to 50% of patients diagnosed with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The pathogenesis is multifactorial and includes myocardial ischemia, distal embolization, and ischemia–reperfusion injury, in a context of individual susceptibility. Its occurrence [...] Read more.
Microvascular obstruction (MVO) accounts for up to 50% of patients diagnosed with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). The pathogenesis is multifactorial and includes myocardial ischemia, distal embolization, and ischemia–reperfusion injury, in a context of individual susceptibility. Its occurrence has been related to adverse outcomes. Despite an extensive body of research, no single pharmacological or interventional strategy has proven effectiveness. The inconclusive nature of the evidence can be attributed to lack of standardization among studies in terms of drugs used and their dosage, the variability in study designs, and the fact that available studies performed a decade ago feature reperfusion strategies and drugs used that differ significantly from the current standard of care. In this context, our review aims to discuss the pharmacological and interventional approaches to MVO. Full article
(This article belongs to the Special Issue Acute Myocardial Infarction: Pharmacological and Interventional Treatment)
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23 pages, 5643 KB  
Review
Coronary Bifurcation PCI—Part II: Advanced Considerations
by Rongras Damrongwatanasuk, Sara Pollanen, Ju Young Bae, Jason Wen, Michael G. Nanna, Abdulla A. Damluji, Mamas A Mamas, Elias B. Hanna and Jiun-Ruey Hu
J. Cardiovasc. Dev. Dis. 2025, 12(11), 439; https://doi.org/10.3390/jcdd12110439 - 6 Nov 2025
Viewed by 796
Abstract
Performance of percutaneous coronary intervention (PCI) for bifurcation lesions involves complex decision-making informed by anatomic, hemodynamic, technical, and clinical factors. Building on the procedural foundations discussed in the companion paper in this two-part series, this second paper focuses on advanced considerations in bifurcation [...] Read more.
Performance of percutaneous coronary intervention (PCI) for bifurcation lesions involves complex decision-making informed by anatomic, hemodynamic, technical, and clinical factors. Building on the procedural foundations discussed in the companion paper in this two-part series, this second paper focuses on advanced considerations in bifurcation PCI. Factors associated with side branch (SB) compromise are discussed, including bifurcation angle and distribution of plaque location, along with strategies for SB protection and SB rewiring. Outcomes of landmark randomized controlled trials of provisional versus two-stent approaches, as well as specific two-stent techniques, are summarized. Based on these factors, an algorithmic approach for bifurcation PCI is outlined. Lastly, the use of drug-coated balloons, dedicated bifurcation stents, bioresorbable vascular scaffolds, bioadaptor stents, physiologic testing, intravascular imaging, and other emerging innovations are explored to provide a perspective on the future of bifurcation PCI. Full article
(This article belongs to the Special Issue Advances in Diagnosis and Interventional Therapy of Coronary Artery Disease)
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14 pages, 1815 KB  
Article
Role of P2X7 Receptor on Hypoxia-Induced Vascular Endothelial Growth Factor Gene Expression in H9c2 Rat Cardiomyocytes
by Anfal F. Bin Dayel, Reem M. Alhejji, Asma S. Alonazi and Nouf M. Alrasheed
J. Cardiovasc. Dev. Dis. 2025, 12(11), 438; https://doi.org/10.3390/jcdd12110438 - 6 Nov 2025
Viewed by 304
Abstract
Purinergic P2X7 receptors (P2X7Rs) may provide cardioprotection against ischemic heart disease. Cardiac angiogenesis is an endogenous adaptive response of hypoxic cardiomyocytes, mediated by vascular endothelial growth factor (VEGF) via hypoxia-inducible factor-1α (HIF-1α). The study aimed to determine whether P2X7Rs can regulate cardiac pro-angiogenic [...] Read more.
Purinergic P2X7 receptors (P2X7Rs) may provide cardioprotection against ischemic heart disease. Cardiac angiogenesis is an endogenous adaptive response of hypoxic cardiomyocytes, mediated by vascular endothelial growth factor (VEGF) via hypoxia-inducible factor-1α (HIF-1α). The study aimed to determine whether P2X7Rs can regulate cardiac pro-angiogenic signaling in hypoxic H9c2 cardiomyocytes by modulating the angiogenic factor VEGF through HIF-1α genes. H9c2 rat cardiomyocytes were exposed to hypoxia alone or in combination with the P2X7R antagonist A740003. Subsequently, ATP levels and LDH activity were measured. The expression of P2X7R, HIF-1α, and VEGF was detected. Intracellular ATP level was significantly lower in hypoxia cardiomyocytes, whereas extracellular ATP, HIF-1α, and LDH levels were significantly higher in hypoxic cardiomyocytes. These effects were associated with increased P2X7R and VEGF gene expressions. Pretreatment with A740003 reversed HIF-1α and VEGF expressions in hypoxic cardiomyocytes. The findings suggest that P2X7Rs regulate pro-angiogenic signaling in hypoxic cardiomyocytes through the HIF-1α/VEGF pathway. Thus, the P2X7R-mediated HIF-1α/VEGF pathway may represent a novel approach to stimulating angiogenesis and preventing heart failure in ischemic heart disease. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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9 pages, 652 KB  
Article
Early Ventricular Arrhythmias Correlate with Adverse Outcome in Takotsubo Syndrome: Analysis of a Large Single-Center Database
by Sati Güler-Eren, Fatih Güner, Charleen-Therese Wanjek, Hilke Könemann, Nawar Alhourani, Fabienne Kreimer, Julian Wolfes, Benjamin Rath, Christian Ellermann, Julia Köbe, Florian Reinke, Gerrit Frommeyer, Felix Wegner and Lars Eckardt
J. Cardiovasc. Dev. Dis. 2025, 12(11), 437; https://doi.org/10.3390/jcdd12110437 - 6 Nov 2025
Viewed by 384
Abstract
Background: Takotsubo syndrome (TTS) is an acute cardiac condition characterized by transient left ventricular dysfunction. Although generally considered reversible, early arrhythmias are a dreaded complication and their prognostic significance remains incompletely understood. Methods: In this study, 104 consecutive patients diagnosed with TTS (January [...] Read more.
Background: Takotsubo syndrome (TTS) is an acute cardiac condition characterized by transient left ventricular dysfunction. Although generally considered reversible, early arrhythmias are a dreaded complication and their prognostic significance remains incompletely understood. Methods: In this study, 104 consecutive patients diagnosed with TTS (January 2007 to September 2024) were examined for the prognostic relevance of in-hospital arrhythmias during monitoring at the time of diagnosis. The median follow-up was 2.1 years. The primary combined endpoint included cardiac death, TTS recurrence, occurrence of arrhythmias, and rehospitalization for cardiac causes. Results: In-hospital arrhythmias occurred in 35.6% of the patients. Ventricular arrhythmias were significantly associated with an increased risk of adverse cardiac events (odds ratio 3.94, 95% confidence interval 1.22–12.69; p = 0.021). Reduced left ventricular ejection fraction and QTc prolongation, while frequently observed, were not independently associated with adverse outcomes when analyzed separately from arrhythmic events. Supraventricular arrhythmias exhibited a non-significant trend (p = 0.145). Conclusions: In a large registry of consecutive TTS patients, in-hospital ventricular arrhythmias at diagnosis were significantly associated with adverse outcomes, underscoring the importance of early rhythm monitoring. Full article
(This article belongs to the Special Issue Ventricular Arrhythmias: Epidemiology, Diagnosis and Treatment)
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14 pages, 480 KB  
Systematic Review
Mitral Valve Surgery with and Without Mitral Annular Disjunction: A Meta-Analysis
by Massimo Baudo, Francesco Cabrucci, Francesca Maria Di Muro, Dimitrios E. Magouliotis, Beatrice Bacchi, Arian Arjomandi Rad, Andrew Xanthopoulos, Tulio Caldonazo and Michele D’Alonzo
J. Cardiovasc. Dev. Dis. 2025, 12(11), 436; https://doi.org/10.3390/jcdd12110436 - 4 Nov 2025
Viewed by 644
Abstract
Background/Objectives: Despite growing awareness of mitral annular disjunction’s (MAD) clinical significance, robust data regarding the outcomes of surgical interventions on MAD remain sparse. This meta-analysis aims to systematically evaluate the current evidence on the efficacy and safety of mitral valve (MV) surgery in [...] Read more.
Background/Objectives: Despite growing awareness of mitral annular disjunction’s (MAD) clinical significance, robust data regarding the outcomes of surgical interventions on MAD remain sparse. This meta-analysis aims to systematically evaluate the current evidence on the efficacy and safety of mitral valve (MV) surgery in patients with MAD. Methods: A systematic review was conducted from inception until May 2025 for studies comparing patients undergoing MV surgery with and without MAD and was registered in PROSPERO: CRD42025649821. Results: Patients with MAD were generally younger (59.3 ± 5.0 vs. 63.4 ± 2.2 years, standardized mean difference: −0.3073), had fewer comorbidities but more complex valve lesions (41.0% vs. 13.7%, risk difference: 0.2627) compared to those without MAD. MV replacement was performed less frequently in the MAD group than in the No-MAD group (risk ratio, RR: 0.690 [95% confidence interval, CI: 0.508; 0.937], p = 0.017), probably related to the significant difference in age between the two groups. The MAD cohort demonstrated a higher incidence of ventricular arrhythmia both after surgery (RR: 7.255 [95%CI: 1.231; 42.763], p = 0.029) and during follow-up (incidence rate ratio, IRR: 2.750 [95%CI: 1.372; 5.512], p = 0.004). Although the MAD group experienced more arrhythmic events over time, this did not translate into a significant difference in overall mortality compared to patients without MAD (IRR: 0.573 [95%CI: 0.072; 4.555], p = 0.599). Conclusions: This meta-analysis revealed significant baseline differences between the populations. Our findings suggest that patients with MAD remained at significantly higher risk for both postoperative and long-term arrhythmias. These results highlight the need for close arrhythmic surveillance in this population. Full article
(This article belongs to the Special Issue State of the Art in Mitral Valve Disease)
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12 pages, 829 KB  
Article
Use of Echocardiography Under Hypoxic Stress Without Exercise to Assess Right to Left Shunting
by Cecilia Villa Etchegoyen, Rachel E. Wraith, Lisa S. Brown, Karen K. Breznak, Rohit Mital, Steven J. Lester, Chadi Ayoub, Said Alsidawi, Justin N. Shipman, Juan M. Farina, Reza Arsanjani and Jan Stepanek
J. Cardiovasc. Dev. Dis. 2025, 12(11), 435; https://doi.org/10.3390/jcdd12110435 - 3 Nov 2025
Viewed by 353
Abstract
Acute exposure to hypoxia will induce right ventricular (RV) hemodynamic changes and may increase the degree of right-to-left shunting, which can contribute to dyspnea at altitude. In this retrospective study, 125 patients (median age 66 years; 50.4% women) with unexplained dyspnea at altitude [...] Read more.
Acute exposure to hypoxia will induce right ventricular (RV) hemodynamic changes and may increase the degree of right-to-left shunting, which can contribute to dyspnea at altitude. In this retrospective study, 125 patients (median age 66 years; 50.4% women) with unexplained dyspnea at altitude underwent hypoxic simulation testing (HST) with transthoracic echocardiography (TTE). During simulated hypoxia (mode (Min-Max) altitude: 8000 (6000–18,000) ft, were observed a significant decrease in oxygen saturation (97% (95–98) vs. 88% (82–92), p < 0.001) and RV free wall longitudinal strain (−19.6 ± 3.99% vs. −17.3 ± 4.17%, p < 0.01), an increase in RV systolic pressure (RVSP: 26 (23–30.5) vs. 29 (25–36.5) mmHg, p < 0.001). No significant changes were observed in TAPSE (20 (18–23) vs. 20 (19–24) mm) or S wave (0.12 (0.11–0.14) vs. 0.13 (0.12–0.14) m/s). Right-to-left shunting was present in 47.2% of patients and 11.9% exhibited inducible shunting only under hypoxia. However, under hypoxia, there were no significant differences in RV hemodynamic parameters or saturation between those with and without shunting. TTE with HST is useful to characterize both cardiopulmonary response and the dynamic changes in right-to-left shunt behavior under hypoxic stress. Full article
(This article belongs to the Special Issue The Role of Echocardiography in Cardiovascular Diseases)
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27 pages, 1591 KB  
Review
Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery
by Yufeng Liu and Muhammad Riaz
J. Cardiovasc. Dev. Dis. 2025, 12(11), 434; https://doi.org/10.3390/jcdd12110434 - 2 Nov 2025
Viewed by 861
Abstract
Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering [...] Read more.
Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs—including spheroids, organoids, cardiac microtissues, and engineered heart tissues (EHTs)—for disease modeling, mechanistic research, and drug discovery. While 2D culture of iPSC-CMs reproduces hallmark proteotoxic phenotypes such as sarcomeric disorganization, oxidative stress, and apoptosis in ACM, 3D models provide enhanced physiological relevance through incorporating multicellularity, extracellular matrix interactions, and mechanical load-related features. Genome editing with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 further broadens the scope of iPSC-based models, enabling isogenic comparisons and the dissection of mutation-specific effects, particularly in transthyretin-related amyloidosis (ATTR). Despite limitations such as cellular immaturity and challenges in recapitulating aging-associated phenotypes, ongoing refinements in differentiation, maturation, and dynamic training of iPSC-cardiac models hold great promise for overcoming these barriers. Together, these advances position iPSC-based systems as powerful human-relevant platforms for modeling and elucidating disease mechanisms and accelerating therapeutic development to prevent ACM. Full article
(This article belongs to the Section Acquired Cardiovascular Disease)
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13 pages, 643 KB  
Review
Antithrombotic Therapy in Transcatheter Aortic Valve Implantation: Focus on Gender Differences
by Mattia De Gregorio, Andrea Denegri, Filippo Luca Gurgoglione, Giorgio Benatti, Iacopo Tadonio, Emilia Solinas, Davide Carino, Andrea Agostinelli, Luigi Vignali and Giampaolo Niccoli
J. Cardiovasc. Dev. Dis. 2025, 12(11), 433; https://doi.org/10.3390/jcdd12110433 - 2 Nov 2025
Viewed by 704
Abstract
Antithrombotic therapy plays a pivotal role in reducing thromboembolic complications, including stroke and valve thrombosis, following Transcatheter Aortic Valve Implantation (TAVI). However, the benefits of such therapy must be balanced against the increased risk of major bleeding events. The optimal antithrombotic strategy in [...] Read more.
Antithrombotic therapy plays a pivotal role in reducing thromboembolic complications, including stroke and valve thrombosis, following Transcatheter Aortic Valve Implantation (TAVI). However, the benefits of such therapy must be balanced against the increased risk of major bleeding events. The optimal antithrombotic strategy in this setting remains a matter of ongoing debate, given the heterogeneity of patient profiles and procedural variables. Among TAVI recipients, women represent a growing proportion and exhibit distinct anatomical, physiological, and clinical characteristics that influence both thrombotic and bleeding risk. Compared to men, women more frequently experience vascular complications and major bleeding events, despite better survival outcomes. These differences are driven by smaller vessel caliber, higher vascular tortuosity, and altered platelet reactivity. Consequently, sex-specific risk stratification is essential when considering antiplatelet or anticoagulant regimens post-TAVI. This review provides a comprehensive synthesis of current evidence regarding antithrombotic strategies in the post-TAVI setting, with a dedicated focus on sex-related differences. Particular emphasis is placed on the female population, assessing ischemic and hemorrhagic outcomes and the implications for long-term management. Improving outcomes in women undergoing TAVI necessitates tailored antithrombotic strategies that balance efficacy and safety. Ongoing research and dedicated trials are essential to refine these strategies and to inform future guideline updates in this expanding patient population. Full article
(This article belongs to the Special Issue Transcatheter and Surgical Approaches to Complications of Transcatheter Procedures: Current Trends and Future Challenges)
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16 pages, 686 KB  
Review
Safety and Efficacy of Salt Restriction Across the Spectrum of Heart Failure
by Panagiotis Stachteas, Athina Nasoufidou, Markella Koiliari, Vasiliki Arampatzi, Chrysa Alexaki, Christos Kofos, Paschalis Karakasis, Efstratios Karagiannidis, Theocharis Koufakis, Nikolaos Fragakis and Dimitrios Patoulias
J. Cardiovasc. Dev. Dis. 2025, 12(11), 432; https://doi.org/10.3390/jcdd12110432 - 2 Nov 2025
Viewed by 1291
Abstract
Dietary sodium restriction is widely recommended in heart failure (HF) management; however, its benefits and risks remain a subject of ongoing debate. While moderate sodium reduction may improve symptoms and quality of life in selected patients, excessive restriction can trigger maladaptive neurohormonal activation, [...] Read more.
Dietary sodium restriction is widely recommended in heart failure (HF) management; however, its benefits and risks remain a subject of ongoing debate. While moderate sodium reduction may improve symptoms and quality of life in selected patients, excessive restriction can trigger maladaptive neurohormonal activation, worsen renal function, and increase the risk of hyponatremia, malnutrition, and cachexia. Patient response is heterogeneous, influenced by clinical risk profile, salt sensitivity, comorbidities, and age, with some high-risk patients experiencing neutral or adverse outcomes. Additional challenges arise from hidden sodium in processed foods, medications, and meals, which complicate monitoring and adherence. Effective sodium management in HF therefore requires a nuanced, individualized approach that integrates risk stratification, dietary counseling, and public health measures targeting the food industry. Future research should refine patient selection criteria and establish optimal sodium targets to balance therapeutic efficacy with safety in real-world practice. Full article
(This article belongs to the Special Issue Cardiovascular Disease and Nutrition)
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15 pages, 579 KB  
Article
Pericardial Closure Preserves Early Right Ventricular Function After Cardiac Surgery: A Retrospective Cohort Study
by Hannah Breuer, Marjolijn C. Sales, Natasja W. M. Ramnath, Yusuf Shieba, Alish Kolashov, Ajay Moza, Lachmandath Tewarie, Rashad Zayat and Nima Hatam
J. Cardiovasc. Dev. Dis. 2025, 12(11), 431; https://doi.org/10.3390/jcdd12110431 - 31 Oct 2025
Viewed by 325
Abstract
Background: Perioperative right ventricular (RV) dysfunction is a frequent complication of cardiac surgery linked to poor outcomes and may result from the loss of pericardial support. We investigated whether pericardial closure preserves early postoperative RV function. Methods: We compared patients with pericardial closure [...] Read more.
Background: Perioperative right ventricular (RV) dysfunction is a frequent complication of cardiac surgery linked to poor outcomes and may result from the loss of pericardial support. We investigated whether pericardial closure preserves early postoperative RV function. Methods: We compared patients with pericardial closure versus open pericardium. Co-primary endpoints were early postoperative RV longitudinal function by tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (TASV). Adjusted comparisons used analysis-of-covariance (postoperative value adjusted for baseline) with prespecified covariates (baseline outcome, LV global longitudinal strain, left-ventricular ejection fraction, LVEDVI, sex, procedure; cardiopulmonary bypass and cross-clamp times when available). Holm correction-controlled multiplicity across the co-primary endpoints. Sensitivity linear mixed-effects models (time × group) were performed. Results: Pericardial closure was associated with better early RV longitudinal function after multivariable adjustment. TAPSE: adjusted mean difference (AMD, Closed–Open) 1.531 mm (95% CI 0.130–2.931; p = 0.033). TASV: AMD 1.694 cm/s (95% CI 0.437–2.951; p = 0.009; Holm-adjusted p = 0.018). Sensitivity analyses yielded consistent estimates. Conclusions: Pericardial closure was independently associated with improved early RV longitudinal function. These adjusted findings address baseline LV imbalances and support considering closure to preserve RV performance; confirmation in prospective trials is warranted. Full article
(This article belongs to the Section Cardiac Surgery)
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29 pages, 2503 KB  
Article
Ventricular Topology in Congenital Heart Defects Associated with Heterotaxy: Can We Find Patterns Reflecting the Syndrome-Specific Tendency for Visceral Symmetry?
by Takhfif Othman, Abdulsalam Mohammad Adnan Alsaiad, Abdulraouf M. Z. Jijeh, Jörg Männer and Talat Mesud Yelbuz
J. Cardiovasc. Dev. Dis. 2025, 12(11), 430; https://doi.org/10.3390/jcdd12110430 - 31 Oct 2025
Viewed by 441
Abstract
Heterotaxy syndrome is characterized by a tendency for bilaterally symmetric arrangement (isomerism) of inner organs. It is frequently associated with complex congenital heart defects (CHDs). In “heterotaxic” hearts, the tendency for isomerism is confined to the atria. The ventricular segment always shows asymmetric [...] Read more.
Heterotaxy syndrome is characterized by a tendency for bilaterally symmetric arrangement (isomerism) of inner organs. It is frequently associated with complex congenital heart defects (CHDs). In “heterotaxic” hearts, the tendency for isomerism is confined to the atria. The ventricular segment always shows asymmetric arrangements (D-hand or L-hand topology). This study aimed to determine the statistical distribution of ventricular topology among patients with CHDs associated with heterotaxy and to identify possible associations between ventricular topology and cardiovascular disorders and survival. It is a retrospective cross-sectional study on 192 patients treated at a single center between 2000 and 2023. Our cohort had 115 patients of left atrial isomerism (LAI) and 77 of right atrial isomerism (RAI). The whole cohort (n = 192) showed a bias towards ventricular D-hand topology (67%), which was statistically significant in LAI (74%). In contrast, RAI showed an almost equal distribution (57% D-hand, 43% L-hand). No significant associations were found between ventricular topology and major CHDs or mortality. Significant associations were observed between ventricular topology and cardiac apex position, direction of p-wave axis, and aortic arch sidedness. We conclude that, in the setting of heterotaxy, especially RAI, ventricular topology and aortic arch sidedness both behave as binary anatomical variables showing a tendency for randomized occurrence. This tendency for statistically symmetric distribution is interpreted as reflecting the syndrome-specific tendency for bilateral symmetry. Full article
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15 pages, 1287 KB  
Article
Abnormal Blood Biomarkers and Cumulative Disability Burden in Middle-Aged and Older Adults: Evidence from Two Nationally Representative Surveys in the United States and China
by Raoping Tu, Jin-Jing Pei, Alexander Wolthon, Yueping Li and Hui-Xin Wang
J. Cardiovasc. Dev. Dis. 2025, 12(11), 429; https://doi.org/10.3390/jcdd12110429 - 31 Oct 2025
Viewed by 417
Abstract
Background: Few studies have simultaneously examined how blood biomarkers for inflammation, metabolic, and cardiovascular function are associated with disability incidence. This study aimed to comprehensively examine these associations. Methods: We used data from adults aged 50 and older in the Health and Retirement [...] Read more.
Background: Few studies have simultaneously examined how blood biomarkers for inflammation, metabolic, and cardiovascular function are associated with disability incidence. This study aimed to comprehensively examine these associations. Methods: We used data from adults aged 50 and older in the Health and Retirement Study (n = 9250) and the China Health and Retirement Longitudinal Study (n = 6844), with biennial follow-up over a 4-year period. We defined abnormal biomarker values using standard clinical cut-off points for three biological systems. Disability burden was quantified as the cumulative number of impairments in basic and instrumental activities of daily living. Multivariate linear mixed-effects models were used to analyze the associations. Results: At baseline, 42% of participants had abnormal biomarker values in at least one system, 28% in two systems, and 7% in all three. A dose–response relationship was observed between the rate of disability accumulation and the number of systems with abnormal biomarker values. Compared to individuals with normal values across all systems, those with abnormalities in two systems had a significantly faster annual increase in disability burden (β = 0.06, 95% CI: 0.02–0.09), while those with abnormalities in all three systems exhibited an even steeper increase (β = 0.1, 95% CI: 0.05–0.16). Conclusions: The presence of abnormal levels in any two or all three of the systems significantly accelerated the rate of disability accumulation over a 4-year period. These findings highlight the importance of integrated biomarker monitoring for early identification of individuals at risk and inform the development of targeted preventive strategies. Full article
(This article belongs to the Section Epidemiology, Lifestyle, and Cardiovascular Health)
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18 pages, 290 KB  
Article
The Relationship Between Resting Heart Rate and Cardiovascular Risk Factors Among Adults Aged 18 Years and Above in the Rural Ellisras Population: Ellisras Longitudinal Study
by Mohale Gift Maake, Kotsedi Daniel Monyeki and Machoene Derrick Sekgala
J. Cardiovasc. Dev. Dis. 2025, 12(11), 428; https://doi.org/10.3390/jcdd12110428 - 30 Oct 2025
Viewed by 1024
Abstract
(1) Background: Resting heart rate (RHR) is an easily measurable cardiovascular risk indicator, yet its relationship with cardiometabolic risk factors remains understudied in rural African populations. This study investigated the association between RHR and cardiovascular risk factors among adults in the rural Ellisras [...] Read more.
(1) Background: Resting heart rate (RHR) is an easily measurable cardiovascular risk indicator, yet its relationship with cardiometabolic risk factors remains understudied in rural African populations. This study investigated the association between RHR and cardiovascular risk factors among adults in the rural Ellisras community, South Africa. (2) Methods: A cross-sectional analysis was conducted among 629 participants (306 males, 323 females) aged 18 years and above from the Ellisras Longitudinal Study. Anthropometric measurements, blood pressure, biochemical parameters, and lifestyle factors were assessed. RHR was categorized as normal (60–100 bpm), bradycardia (<60 bpm), or tachycardia (>100 bpm). Statistical analysis included descriptive statistics, chi-square tests, Pearson correlations, and logistic regression to identify predictors of abnormal RHR. (3) Results: The mean age was 25.55 ± 1.97 years, with significant gender differences in cardiovascular parameters. Females had higher RHR (81.78 ± 11.73 vs. 70.36 ± 12.89 bpm, p < 0.001), body mass index (BMI) (24.62 vs. 20.67 kg/m2, p < 0.001), and waist circumference (WC) (81.00 vs. 73.50 cm, p < 0.001). Resting heart rate (RHR) distribution varied significantly by gender (p < 0.001), with bradycardia more prevalent in males (91.3% vs. 8.7%) and tachycardia in females (75.0% vs. 25.0%). Significant positive correlations were observed between RHR and age (r = 0.105, p = 0.009), diastolic blood pressure (DBP) (r = 0.135, p < 0.001), fasting blood glucose (FBG) (r = 0.098, p = 0.016), total cholesterol (TCHOL) (r = 0.168, p < 0.001), LDL-C (r = 0.201, p < 0.001), WC (r = 0.169, p < 0.001), and sum of 4 skinfolds (bicep, tricep, subscapular and supraspinale) and (r = 0.184, p < 0.001). A negative correlation was found with systolic blood pressure (SBP) (r = −0.105, p < 0.001). In the logistic regression analysis, participants aged >25 years had significantly lower odds of abnormal RHR (OR = 0.50, 95% CI: 0.26–0.97, p = 0.039), after adjusting for confounders. In the fully adjusted model, RHR remained significantly associated with DBP (β = 0.59, p < 0.001), LDL-C (β = 2.76, p = 0.008), WC (β = 0.10, p = 0.012), and triglycerides (TG) (β = 2.78, p = 0.002). (4) Conclusions: RHR demonstrates significant associations with multiple cardiovascular risk factors in this rural South African population, with distinct gender-specific patterns. Age emerged as the primary independent predictor of abnormal RHR. These findings suggest that RHR could serve as a valuable, cost-effective screening tool for cardiovascular risk assessment in resource-limited rural settings. Full article
(This article belongs to the Section Epidemiology, Lifestyle, and Cardiovascular Health)
14 pages, 1861 KB  
Article
The Synergistic Risk of Insulin Resistance and Renal Dysfunction in Acute Coronary Syndrome Patients After Percutaneous Coronary Intervention
by Guoshu Yang, Maoling Jiang, Lin Liu, Dongyue Jia, Jie Feng, Yan Luo, Tao Ye, Long Xia, Hanxiong Liu, Zhen Zhang, Jinjuan Fu, Lin Cai, Qiang Chen and Shiqiang Xiong
J. Cardiovasc. Dev. Dis. 2025, 12(11), 427; https://doi.org/10.3390/jcdd12110427 - 28 Oct 2025
Viewed by 444
Abstract
Background: Despite percutaneous coronary intervention (PCI) for revascularization, patients with acute coronary syndrome (ACS) still face residual risks of adverse outcomes. Insulin resistance (IR) and renal impairment are independent predictors of poor prognosis in these patients, yet their interaction and underlying mechanisms linked [...] Read more.
Background: Despite percutaneous coronary intervention (PCI) for revascularization, patients with acute coronary syndrome (ACS) still face residual risks of adverse outcomes. Insulin resistance (IR) and renal impairment are independent predictors of poor prognosis in these patients, yet their interaction and underlying mechanisms linked to post-PCI outcomes remain incompletely elucidated. Methods: A retrospective cohort study was conducted involving patients with ACS who underwent PCI at the Third People’s Hospital of Chengdu from July 2018 to December 2020. Insulin resistance (IR) was quantified using the triglyceride–glucose (TyG) index, and renal function was evaluated via the estimated glomerular filtration rate (eGFR). The primary endpoint was major adverse cardiovascular events (MACEs), a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Multivariable Cox proportional hazards regression and mediation analyses were applied to explore the associations of TyG index and eGFR with patient prognosis, and to quantify the mediating effect of eGFR on the relationship between TyG index and prognosis. Results: A total of 1340 patients with ACS were included in the final analysis. Over a median follow-up duration of 31.02 (interquartile range [IQR]: 27.34–35.03) months, 124 patients (9.25%) experienced MACEs. After adjusting for potential confounders, both the TyG index and eGFR were identified as significant independent predictors of MACEs in the overall population and across predefined subgroups. Specifically, each one-unit increase in the TyG index was associated with a 73.8% higher risk of MACEs (HR 1.738; 95% CI 1.273–2.372), whereas each ten-unit decrease in eGFR was linked to a 12.7% increased MACEs risk (HR 1.127; 95% CI 1.032–1.232). Importantly, after further adjustment for confounders, eGFR significantly mediated 9.63% of the total effect of the TyG index on MACEs risk. Conclusions: Renal impairment partially mediates the association between IR and adverse cardiovascular outcomes in ACS patients undergoing PCI. This finding underscores the clinical importance of the metabolic–cardiorenal axis in this population, suggesting that a comprehensive assessment targeting both IR and renal function-related pathways may enhance risk-stratification accuracy and optimize therapeutic strategies for ACS patients. Full article
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12 pages, 1265 KB  
Systematic Review
Progression of Untreated Mild Aortic Valve Disease in Patients Undergoing Rheumatic Mitral Valve Surgery: A Meta-Analysis of Reconstructed Time-to-Event Data
by Chong Luo, Xiaoli Qin, Honghua Yue, Weitao Liang and Zhong Wu
J. Cardiovasc. Dev. Dis. 2025, 12(11), 426; https://doi.org/10.3390/jcdd12110426 - 28 Oct 2025
Viewed by 444
Abstract
(1) Background: Concomitant mild aortic valve disease is frequently found in patients undergoing rheumatic mitral valve surgery. To date, only a limited number of single-center studies have specifically addressed the untreated baseline aortic valve disease long-term progression and reoperation rate. Thus, we conducted [...] Read more.
(1) Background: Concomitant mild aortic valve disease is frequently found in patients undergoing rheumatic mitral valve surgery. To date, only a limited number of single-center studies have specifically addressed the untreated baseline aortic valve disease long-term progression and reoperation rate. Thus, we conducted a meta and landmark analysis to systematically review the issue. (2) Methods: This study investigated the long-term prognostic of baseline mild aortic valve disease in patients undergoing rheumatic mitral valve surgery, based on evidence from PubMed, Embase, Cochrane Library, and Web of Science databases. (3) Results: Meta analysis revealed that patients with mild aortic valve disease had a higher risk of disease progression, with a 3.3-fold risk in the 0–5-year follow-up, which jumped to a hazard ratio of 6.42 in longer-term follow-up (5–25 years). Patients with aortic stenosis had an 8.37-fold risk of progression compared with aortic regurgitation and appeared to be poorly related to the time cut-off. Similarly, higher reoperation rates at long-term follow-up were seen in aortic stenosis patients. (4) Conclusions: This study suggests that patients with mild aortic valve disease at baseline have poorer long-term aortic valve-related progression and reoperation rates, especially aortic stenosis. For those with concomitant aortic stenosis, further investigation of the impact of lesion progression is warranted. Full article
(This article belongs to the Special Issue Heart Valve Surgery: Repair and Replacement)
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9 pages, 1278 KB  
Article
Coronary Calcium Scoring as Prediction of Coronary Artery Diseases with Low-Dose Dual-Source CT
by Enrico Schwarz, Valentina Tambè, Silvia De Simoni, Roberto Moltrasi, Matteo Magazzeni, Elena Ciortan, Stefano Bentivegna, Anastasia Esseridou and Francesco Secchi
J. Cardiovasc. Dev. Dis. 2025, 12(11), 425; https://doi.org/10.3390/jcdd12110425 - 27 Oct 2025
Viewed by 768
Abstract
The aim of this paper is to evaluate the correlation between the coronary calcium score (CCS) and coronary artery disease (CAD), patients underwent coronary CT angiography (CTA). Four hundred and five patients who underwent a coronary CT with CCS analysis were considered for [...] Read more.
The aim of this paper is to evaluate the correlation between the coronary calcium score (CCS) and coronary artery disease (CAD), patients underwent coronary CT angiography (CTA). Four hundred and five patients who underwent a coronary CT with CCS analysis were considered for this retrospective study. Coronary CTA was performed using a dual-source (256-slice) CT scanner (SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany). Before injecting the contrast medium, non-contrasted cardiac CT was performed in a longitudinal scan field from the tracheal carina down to the diaphragm. The corresponding images for calcium scoring were reconstructed with a slice width of 1.5 mm and a slice interval of 1 mm, and the tube voltage was 120 kVp. The total calcium score was calculated using dedicated software. The calcium score based on the Agatston method was defined as the presence of a lesion with an area greater than 1 mm2 and peak intensity greater than 130 Hounsfield Units, which was automatically identified and marked with color by the software. From the radiological report, the degree of coronary stenosis was retrieved. A score of 1 corresponds to the absence of stenosis, a score of 2 to mild stenosis (<50%), and a score of 3 to moderate/severe stenosis (>50%). The total coronary gravity score (CGS) for each patient was calculated by summing the score of each coronary artery. The Spearman test was used for correlation. Out of the 405 patients, 217 were male. The mean and standard deviation age was 72 ± 11 years. The overall amount of calcium was an Agatston score of 393 ± 709. A positive correlation between CCS and CGS was found (r = 0.835 and p < 0.001). A ROC curve with AUC 0.917 (p ≤ 0.001) was obtained. The optimal cutoff point of the calcium score for discriminating CGS < 2 was 112, yielding sensitivity of 90% and specificity of 81%. This study confirms the important relationship between the coronary artery calcium score and the presence and extension of coronary artery disease. Full article
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17 pages, 1074 KB  
Article
Impact of T-AMYLO Risk Score and Red Flag Findings on Cardiovascular Outcomes in Patients with Cardiac Conduction Defects Treated with Intracardiac Device Implantation
by Hidayet Ozan Arabaci, Sukru Arslan, Cem Kurt, Pelinsu Hunkar, Fatih Ozkan, Muhammet Heja Gecit, Seyma Arslan and Mustafa Yildiz
J. Cardiovasc. Dev. Dis. 2025, 12(11), 424; https://doi.org/10.3390/jcdd12110424 - 26 Oct 2025
Viewed by 388
Abstract
Background: Cardiac amyloidosis is more common than previously thought with an incidence of up to 15% in aortic stenosis and heart failure with preserved ejection fraction. Pacemaker need in these patients ranges from 9.5% to 20%; however, its prevalence and clinical relevance in [...] Read more.
Background: Cardiac amyloidosis is more common than previously thought with an incidence of up to 15% in aortic stenosis and heart failure with preserved ejection fraction. Pacemaker need in these patients ranges from 9.5% to 20%; however, its prevalence and clinical relevance in patients with unexplained cardiac conduction defects remain unclear. Methods: This retrospective, single-center cohort study evaluated 1107 patients who underwent intracardiac device implantation for unexplained cardiac conduction defects between 2015 and 2024. Patients with secondary conduction defects or known cardiomyopathy were excluded. The prognostic value of the T-AMYLO score and associated red flag findings were assessed in relation to the composite primary endpoint: all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Results: Over a median of 58 months for follow-up, 460 patients experienced a primary event, including 346 deaths. Higher event rates were observed in older males, those with atrioventricular block, and patients receiving single-lead ventricular devices. T-AMYLO score and the presence of red flag findings, particularly aortic valve disease, AV block, peripheral neuropathy, low voltages and increased septal thickness were significantly associated with adverse outcomes. Multivariate Cox regression identified elevated T-AMYLO score (HR: 1.06, p = 0.012), aortic valve disease (HR: 1.29, p = 0.016), and AV block (HR: 1.43, p = 0.009) as independent predictors of mortality. Survival analyses confirmed a stepwise decline in prognosis with an increasing T-AMYLO risk group and red flag burden (p < 0.001). Conclusion: These findings highlight the importance of incorporating T-AMYLO scoring and red flags assessment in patients with conduction defects to improve early detection of cardiac amyloidosis and guide risk stratification for outcomes. Full article
(This article belongs to the Section Cardiovascular Clinical Research)
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13 pages, 1504 KB  
Review
Unusual, Uncommon, Intriguing, and Significant Causes of Kounis Syndrome: Important Medications and Chemicals Used to Treat Kounis Syndrome and Myocardial Infarction Can Cause Kounis Syndrome
by Nicholas G. Kounis, Cesare de Gregorio, Ming-Yow Hung, Grigorios Giamouzis, Marina A. Michalaki, Uğur Özkan, Alexandr Ceasovschih, Virginia Mplani, Periklis Dousdampanis, Sophia N. Kouni, Alexandros Stefanidis, Kassiani-Maria Nastouli, Maria Bozika, Nicholas Patsouras and Ioanna Koniari
J. Cardiovasc. Dev. Dis. 2025, 12(11), 423; https://doi.org/10.3390/jcdd12110423 - 24 Oct 2025
Viewed by 647
Abstract
Mast cell degranulation and other interacting and linked cells, including T-lymphocytes, macrophages, eosinophils, and platelets, as well as a range of inflammatory mediators produced during an anaphylactic or allergic reaction, constitute the main causes of Kounis syndrome. Acute ischemia episodes, coronary spasm, atheromatous [...] Read more.
Mast cell degranulation and other interacting and linked cells, including T-lymphocytes, macrophages, eosinophils, and platelets, as well as a range of inflammatory mediators produced during an anaphylactic or allergic reaction, constitute the main causes of Kounis syndrome. Acute ischemia episodes, coronary spasm, atheromatous plaque erosion/rupture, and platelet activation can all be caused by histamine, tryptase, arachidonic acid derivatives, and chymase in the Kounis syndrome cascade. Kounis syndrome can be triggered by a variety of factors, including medications, hymenopteran stings, metals, foods, environmental exposures, illnesses, and immunizations. In addition, some unusual, rare, intriguing, and significant causes of Kounis syndrome have been discovered recently, namely the “kiss of death”, where human kissing and pet kissing can induce fatal Kounis syndrome. Moreover, the clinical conundrum is that several of the main drugs and substances used to treat myocardial infarction and Kounis syndrome, such as adrenaline (epinephrine), aspirin, atropine, clopidogrel, corticosteroids, heparins, protamine sulfate, and hirudotherapy can also initiate it. Therefore, physicians should be aware of this clinical discrepancy to prevent catastrophic consequences. Full article
(This article belongs to the Section Basic and Translational Cardiovascular Research)
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