Journal of Cardiovascular Development and Disease

17 pages, 4074 KB

Open AccessEditor’s ChoiceArticle

Time to Reperfusion Dictates Cardiac Function and Myocardial Strain in a 7-Tesla Magnetic Resonance Imaging Rat Model

by Mako Ito, Junpei Ueda, Sei Yasuda, Isamu Yabata, Koji Itagaki, Natsuo Banura and Shigeyoshi Saito

J. Cardiovasc. Dev. Dis. 2026, 13(1), 10; https://doi.org/10.3390/jcdd13010010 - 22 Dec 2025

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Abstract

This study used a rat model of coronary artery reperfusion imaged with preclinical 7-tesla magnetic resonance imaging (7T-MRI) to evaluate cardiac function, myocardial deformation, and the impact of infarction-to-reperfusion time. Wistar rats were assigned to control (n = 6), 20 min infarction [...] Read more.

This study used a rat model of coronary artery reperfusion imaged with preclinical 7-tesla magnetic resonance imaging (7T-MRI) to evaluate cardiac function, myocardial deformation, and the impact of infarction-to-reperfusion time. Wistar rats were assigned to control (n = 6), 20 min infarction (n = 10), 30 min infarction (n = 6), and 40 min infarction (n = 6) groups. Myocardial infarction occurred in all infarction groups but not in controls. Imaging included short- and long-axis slices. Cardiac function was assessed using end-diastolic volume, end-systolic volume, and left-ventricular ejection fraction. Myocardial deformation was analyzed by circumferential strain, radial strain (RS), and longitudinal strain (LS, four-chamber and two-chamber) using feature tracking. The 30 and 40 min infarction groups showed significant reductions in cardiac function and strain compared to the controls. RS decreased significantly between the control and 20 min infarction groups (40.6 ± 4.7% and 34.0 ± 4.1%, p < 0.05). No significant LS difference was observed between 30 and 40 min. Consequently, RS detects early myocardial changes (20 min), whereas LS may reflect compensatory contractility in severe infarction. Preclinical 7T-MRI provides valuable insights into the impact of infarction duration on cardiac function and myocardial deformation. Full article

(This article belongs to the Section Basic and Translational Cardiovascular Research)

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20 pages, 5348 KB

Open AccessEditor’s ChoiceArticle

Early Cytoskeletal Remodeling Drives Hypertrophic Cardiomyopathy Pathogenesis in MYH6/7 Mutant hiPSC-Derived Cardiomyocytes

by Mohammad Shameem, Hassan Salih, Ahmed Sharara, Roshan Nicholas Rochus John, Leo Ogle and Bhairab N. Singh

J. Cardiovasc. Dev. Dis. 2025, 12(12), 500; https://doi.org/10.3390/jcdd12120500 - 17 Dec 2025

Viewed by 482

Abstract

Hypertrophic cardiomyopathy (HCM) is a common and deadly cardiac disease characterized by enlarged myocytes, increased myocardial wall thickening, and fibrosis. A majority of HCM cases are associated with mutations in the β-myosin heavy chain (MYH7) converter domain locus, which leads to [...] Read more.

Hypertrophic cardiomyopathy (HCM) is a common and deadly cardiac disease characterized by enlarged myocytes, increased myocardial wall thickening, and fibrosis. A majority of HCM cases are associated with mutations in the β-myosin heavy chain (MYH7) converter domain locus, which leads to varied pathophysiological and clinical manifestations. Using base-editing technology, we generated mutant human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) harboring HCM-causing myosin converter domain mutations (MYH7 c.2167C>T [R723C]; MYH6 c.2173C>T [R725C]) to define HCM pathogenesis in vitro. In this study, we integrated transcriptomic analysis with phenotypic and molecular analyses to dissect the HCM disease mechanisms using MYH6/7 myosin mutants. Our KEGG analysis of bulk RNA-sequencing data revealed significant upregulation of transcripts associated with HCM in the mutant hiPSC-CMs. Further, in-depth transcriptomic analysis using Gene-Ontology (GO-term) analysis for biological process showed upregulation of several transcripts associated with heart development and disease. Notably, our analysis showed robust upregulation of cytoskeletal transcripts, including actin-cytoskeleton networks, sarcomere components, and other structural proteins in the mutant CMs. Furthermore, cellular and nuclear morphological analysis showed that the MYH6/7 mutation induced cellular hypertrophy and increased aspect ratio compared to the isogenic control. Immunostaining experiments showed marked sarcomere disorganization with lower sarcomeric order and higher dispersion in the mutant hiPSC-CMs, highlighting the remodeling of the myofibril arrangement. Notably, the MYH6/7 mutant showed reduced cortical F-actin expression and increased central F-actin expression compared to the isogenic control, confirming the cytoskeletal remodeling and sarcomeric organization during HCM pathogenesis. These pathological changes accumulated progressively over time, underscoring the chronic and evolving nature of HCM driven by the MYH6/7 mutations. Together, our findings provide critical insights into the cellular and molecular underpinnings of MYH6/7-mutation-associated disease. These findings offer valuable insights into HCM pathogenesis, aiding in future therapies. Full article

(This article belongs to the Section Cardiac Development and Regeneration)

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15 pages, 2151 KB

Open AccessEditor’s ChoiceArticle

Development and Validation of an Acute Large Animal Model for Type A Aortic Dissection

by Ezin Deniz, Sibylle Marsen, Florian Helms, Heike Krüger, Naoki Arima, Jasmin Hanke, Ali Saad Merzah, Sadeq Al-Hasan-Al-Saegh, Sara Knigge, Saman Alhowaizy, Tanja Meyer, Rabea Hinkel, Morsi Arar, Aron F. Popov, Günes Dogan, Bastian Schmack, Alexander Weymann, Arjang Ruhparwar, Salaheldien Ali Mohamed-Glüer and Jan D. Schmitto

J. Cardiovasc. Dev. Dis. 2025, 12(12), 496; https://doi.org/10.3390/jcdd12120496 - 16 Dec 2025

Viewed by 319

Abstract

Background: Animal models are essential for translating diagnostic and therapeutic strategies into clinical practice and offer valuable insights into the pathophysiology of diseases such as aortic dissection. This study presents a novel acute in vivo large animal model of Stanford type A aortic [...] Read more.

Background: Animal models are essential for translating diagnostic and therapeutic strategies into clinical practice and offer valuable insights into the pathophysiology of diseases such as aortic dissection. This study presents a novel acute in vivo large animal model of Stanford type A aortic dissection, combining open surgical access with endovascular techniques to leverage the advantages of both. The model aims to reproducibly simulate acute dissections in swine, providing a standardized platform for evaluating diagnostics, disease mechanisms, and treatment strategies. Methods: Six pigs underwent a standardized protocol to induce aortic dissection. Arterial pressure was monitored via femoral and carotid catheterization. A conventional sternotomy was performed, followed by tangential cross-clamping of the ascending aorta and a controlled incision proximal to the brachiocephalic trunk. The intima and the media were separated using a guidewire and catheter-based technique to create a false lumen. A re-entry tear was also established to allow for controlled intraluminal access. Animals were monitored for 12 h post-intervention, with serial blood sampling. At the end of the experiment, the animals were euthanized and the aortas harvested for macroscopic and histological analysis. Results: In all 6 animals, the placement of arterial catheters in femoral and carotid arteries, as well as the sternotomy, was established without any complications. The dissection model was successfully created in 5 out of 6 animals by clinical signs such as adventitial hematoma, macroscopic wall separation and/or decreased femoral blood pressure. One animal experienced complete aortic perforation. Five animals completed the full observation period of 12 h. Conclusion: A standardized, reproducible, and robust large animal model of acute Stanford type A aortic dissection using a hybrid approach was developed. This model closely simulates the clinical and pathological features of human aortic dissection, making it a valuable tool for preclinical research in diagnostics, pathophysiology, and treatment development. Full article

(This article belongs to the Special Issue Aortic Surgery—Back to the Roots and Looking to the Future)

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10 pages, 1864 KB

Open AccessEditor’s ChoiceArticle

2020 ESC Guidelines on Sports Cardiology: Impact of CMR Criteria on Return-to-Play Clearance After Acute Myocarditis

by Carlo Maria Gallinoro, Alessandra Scatteia, Dario Catapano, Carmine Emanuele Pascale, Giuseppe Russo, Franca Di Meglio and Santo Dellegrottaglie

J. Cardiovasc. Dev. Dis. 2025, 12(12), 469; https://doi.org/10.3390/jcdd12120469 - 29 Nov 2025

Viewed by 1682

Abstract

Cardiovascular magnetic resonance (CMR) imaging is a key component of current diagnostic pathways in subjects with acute myocarditis. The 2020 ESC Guidelines on Sports Cardiology recommend athletes with acute myocarditis to abstain from sports during the recovery phase from inflammation and to undergo [...] Read more.

Cardiovascular magnetic resonance (CMR) imaging is a key component of current diagnostic pathways in subjects with acute myocarditis. The 2020 ESC Guidelines on Sports Cardiology recommend athletes with acute myocarditis to abstain from sports during the recovery phase from inflammation and to undergo comprehensive evaluation—including CMR—before safely returning to play. This retrospective study analyzed 95 non-competitive athletes presenting with acute myocarditis and evaluated by initial and repeated CMRs. CMR exams assessed myocardial inflammation, edema, and scarring as defined based on the updated Lake Louise criteria. As per 2020 ESC Guidelines, eligibility was granted by excluding extensive myocardial damage. Initial CMR showed 84% positive STIR (edema) and 79% with LGE ≥ 3 segments. After 3–6 months, STIR positivity dropped to 12%, LGE extent remained globally stable, but with some reduction in 42%. Few experienced recurrent myocarditis or LVEF decline; 24% met return-to-play criteria by repeated CMR. Our study shows that few non-competitive athletes recovering from acute myocarditis meet ESC CMR criteria to resume competitive sports at prescribed follow-up evaluation. The long-term prognostic value of CMR markers like LGE and edema remains unclear, highlighting the need for further research to refine return-to-play guidelines and ensure athlete safety. Full article

(This article belongs to the Special Issue Advanced Cardiovascular Imaging in Structural Heart Disease: Diagnostic, Prognostic, and Therapeutic Perspectives)

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15 pages, 12518 KB

Open AccessEditor’s ChoiceArticle

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 495

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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26 pages, 2754 KB

Open AccessEditor’s ChoiceArticle

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 921

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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27 pages, 1591 KB

Open AccessEditor’s ChoiceReview

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 1346

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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14 pages, 503 KB

Open AccessEditor’s ChoiceReview

Iron Deficiency in Heart Failure: Cellular Mechanisms and Therapeutic Implications

by Anastasios Tsarouchas, Vassilios P. Vassilikos, Dimitrios Mouselimis, Christodoulos E. Papadopoulos, Dimitrios Tachmatzidis, Aikaterini Vassilikou and Constantinos Bakogiannis

J. Cardiovasc. Dev. Dis. 2025, 12(11), 415; https://doi.org/10.3390/jcdd12110415 - 22 Oct 2025

Viewed by 2763

Abstract

Iron deficiency (ID) is a prevalent comorbidity in heart failure (HF), affecting 37–75% of patients and contributing significantly to symptom burden and adverse outcomes independent of anemia status. Current diagnostic criteria for ID in HF include absolute deficiency (ferritin <100 μg/L) and functional [...] Read more.

Iron deficiency (ID) is a prevalent comorbidity in heart failure (HF), affecting 37–75% of patients and contributing significantly to symptom burden and adverse outcomes independent of anemia status. Current diagnostic criteria for ID in HF include absolute deficiency (ferritin <100 μg/L) and functional deficiency (ferritin 100–299 μg/L with transferrin saturation <20%). Major clinical trials including AFFIRM-AHF, IRONMAN, HEART-FID, and FAIR-HF2 have demonstrated that intravenous iron therapy, particularly ferric carboxymaltose, reduces HF hospitalizations and improves quality of life and exercise capacity. The 2023 European Society of Cardiology guidelines recommend intravenous ferric carboxymaltose for symptomatic iron-deficient patients with heart failure with reduced ejection fraction. Despite these advances, significant knowledge gaps remain regarding optimal diagnostic approaches, the relationship between ID and ferroptosis in cardiac tissue, and the efficacy of newer iron formulations. This review synthesizes current understanding of ID in HF and highlights emerging therapeutic strategies. Full article

(This article belongs to the Special Issue Heart Failure: Clinical Diagnostics and Treatment, 2nd Edition)

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13 pages, 601 KB

Open AccessEditor’s ChoiceArticle

The Association Between Short-Term Blood Pressure Variability and Inflammation in Healthy Young Adults

by Charles J. Weeks, Bayu B. Bekele, Michelle Altvater, Jie Cheng, Haidong Zhu, Ying Huang, Deborah A. Jehu, Abigayle B. Simon, Wenjun Li and Yanbin Dong

J. Cardiovasc. Dev. Dis. 2025, 12(10), 399; https://doi.org/10.3390/jcdd12100399 - 9 Oct 2025

Viewed by 1432

Abstract

Blood pressure variability (BPV) is linked to cardiovascular disease (CVD) and systemic inflammation in adults, but its relevance in young, healthy populations remains unclear. This study examined the association between short-term BPV and inflammatory markers in 447 normotensive participants (mean age, 22.9 years) [...] Read more.

Blood pressure variability (BPV) is linked to cardiovascular disease (CVD) and systemic inflammation in adults, but its relevance in young, healthy populations remains unclear. This study examined the association between short-term BPV and inflammatory markers in 447 normotensive participants (mean age, 22.9 years) from the Georgia Stress and Heart (GSH) study, a cohort of Non-Hispanic Black and White individuals. Participants underwent 24 h ambulatory blood pressure monitoring and assessment of serum inflammatory markers, including hs-CRP, IFN-γ, IL-6, and TNF-α. BPV was quantified using average real variability (ARV), and generalized estimating equations (GEEs) were used to evaluate associations, adjusting for age, sex, race, and mean blood pressure. Diastolic BPV was significantly, positively associated with hs-CRP and TNF-α, whereas systolic BPV was not associated with any inflammatory marker. Specifically, 24 h diastolic BPV was positively associated with hs-CRP (p = 0.001) and TNF-α (p = 0.015), while daytime diastolic BPV was positively associated with hs-CRP (p = 0.002). Nighttime diastolic BPV was positively associated with both hs-CRP (p = 0.020) and TNF-α (p = 0.007). No significant associations were found between BPV and IL-6 or IFN-γ. These findings suggest diastolic BPV may be a marker of low-grade inflammation in healthy young adults and could represent an early cardiovascular risk factor that warrants longitudinal study. Full article

(This article belongs to the Special Issue Risk Factors and Prevention of Cardiovascular Diseases—Second Edition)

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13 pages, 1410 KB

Open AccessEditor’s ChoiceArticle

Clinical, Imaging, and Serum Biomarker Predictors of Malignant Cerebral Infarction

by Alejandro Rodríguez-Vázquez, Salvatore Rudilosso, Antonio Doncel-Moriano, Andrea Cabero-Arnold, Carlos Laredo, Darío Ramis, David Moraleja, Mònica Serrano, Yolanda González-Romero, Arturo Renú, Inés Bartolomé-Arenas, Irene Rosa-Batlle, Guillem Dolz, Ramón Torné, Martha Vargas, Xabier Urra and Ángel Chamorro

J. Cardiovasc. Dev. Dis. 2025, 12(10), 392; https://doi.org/10.3390/jcdd12100392 - 4 Oct 2025

Cited by 1 | Viewed by 1740

Abstract

Malignant cerebral infarction (MCI) is rare but often fatal. Early identification helps guide monitoring and decompressive surgery. This study evaluated whether serum biomarkers add predictive value beyond clinical and imaging data in severe stroke patients with anterior circulation large vessel occlusion (LVO). In [...] Read more.

Malignant cerebral infarction (MCI) is rare but often fatal. Early identification helps guide monitoring and decompressive surgery. This study evaluated whether serum biomarkers add predictive value beyond clinical and imaging data in severe stroke patients with anterior circulation large vessel occlusion (LVO). In this prospective study, 73 acute severe LVO stroke patients underwent whole-brain CT perfusion (CTP) with rCBV-based core measurement at admission and follow-up MRI at 24 ± 12 h for infarct and edema volume assessment. Serum biomarkers (s100b, NSE, VEGF, ICAM1) were sampled a median of 20.5 h after baseline imaging. Logistic regression models predicted MCI using baseline variables (NIHSS, ASPECTS, rCBV < 30%), adding treatment data (rtPA, mTICI, NIHSS posttreatment), and adding serum biomarkers. Performance was assessed by AUC, accuracy, F1, and cross-validated R². MCI occurred in 18/73 (24%) patients. Baseline models showed an AUC of 0.72; adding treatment improved the AUC to 0.88. Biomarkers slightly increased the AUC (0.90) but did not improve F1. Higher s100b was associated with more severe injury but did not enhance the prediction of MCI. Models with baseline imaging and treatment best explained infarct (R² ≈ 0.27) and edema (R² ≈ 0.58). In conclusion, admission severity, CTP, and early treatment response are the main predictors of MCI and aid early risk stratification of patients. Despite their pathophysiologic relevance, serum biomarkers do not add substantial predictive value. Full article

(This article belongs to the Section Stroke and Cerebrovascular Disease)

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19 pages, 428 KB

Open AccessEditor’s ChoiceReview

Homocysteine in the Cardiovascular Setting: What to Know, What to Do, and What Not to Do

by Saverio D’Elia, Mariarosaria Morello, Gisella Titolo, Valentina Maria Caso, Achille Solimene, Ettore Luisi, Chiara Serpico, Andrea Morello, Lucia La Mura, Francesco S. Loffredo, Francesco Natale, Paolo Golino and Giovanni Cimmino

J. Cardiovasc. Dev. Dis. 2025, 12(10), 383; https://doi.org/10.3390/jcdd12100383 - 27 Sep 2025

Viewed by 5892

Abstract

Homocysteine has long been studied as a potential cardiovascular risk factor due to its biochemical role in endothelial dysfunction, oxidative stress, inflammation, and thrombogenesis. Despite strong epidemiological and mechanistic support, the translation of homocysteine-lowering interventions into clinical benefit remains controversial. This non-systematic review [...] Read more.

Homocysteine has long been studied as a potential cardiovascular risk factor due to its biochemical role in endothelial dysfunction, oxidative stress, inflammation, and thrombogenesis. Despite strong epidemiological and mechanistic support, the translation of homocysteine-lowering interventions into clinical benefit remains controversial. This non-systematic review aims to clarify the current understanding of homocysteine in the cardiovascular setting by distinguishing between well-established facts, clinically relevant interventions, and persistent misconceptions. We first revisit the historical emergence of homocysteine as a cardiovascular biomarker and explore its pathophysiological mechanisms, including endothelial damage, atherosclerosis progression, and prothrombotic effects—supported by in vitro and animal model studies. Subsequently, we evaluate evidence-based interventions such as B-vitamin supplementation (folate, B6, B12), lifestyle modifications, and the clinical relevance of homocysteine monitoring in specific populations (e.g., MTHFR mutations, chronic kidney disease). We then discuss common pitfalls, including the overinterpretation of genetic variants, the inappropriate use of supplementation, and the overreliance on surrogate biomarkers in clinical trials. Although elevated homocysteine remains a reproducible biomarker of cardiovascular risk, current evidence does not support routine intervention in unselected populations. A precision medicine approach—targeting high-risk subgroups and integrating homocysteine into broader cardiometabolic management—may help unlock its therapeutic relevance. Future pharmacological strategies should prioritize mechanistic insight, patient stratification, and clinically meaningful endpoints. Full article

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19 pages, 1503 KB

Open AccessEditor’s ChoiceReview

Rethinking Childhood-Onset Hypertrophic Cardiomyopathy: A Review of Molecular Mechanisms and Unique Therapy Considerations

by Caitlin Menzies and Vernon W. Dolinsky

J. Cardiovasc. Dev. Dis. 2025, 12(10), 374; https://doi.org/10.3390/jcdd12100374 - 23 Sep 2025

Viewed by 1738

Abstract

Childhood-onset hypertrophic cardiomyopathy (HCM) is a cardiac disorder presenting unique diagnostic and therapeutic challenges in children that require tailored clinical attention compared to HCM arising at other life stages. Despite this, current treatment strategies specific to childhood-onset HCM are lacking and are predominantly [...] Read more.

Childhood-onset hypertrophic cardiomyopathy (HCM) is a cardiac disorder presenting unique diagnostic and therapeutic challenges in children that require tailored clinical attention compared to HCM arising at other life stages. Despite this, current treatment strategies specific to childhood-onset HCM are lacking and are predominantly extrapolated from adult-specific treatment guidelines. This review explores the molecular basis, clinical implications, and management strategies specific to childhood-onset HCM. Advances in molecular genetics have elucidated diverse pathogenic pathways and genotype-phenotype correlations, revealing age-specific disease modifiers distinct from adult-onset forms. Current management includes pharmacologic, surgical, and device-based interventions, tailored to individualized needs. However, there is a lack of evidence for the efficacy and safety profiles of these treatments in children, meaning children may be receiving sub-optimal care. Emerging approaches, such as gene-targeted therapies and precision medicine frameworks, show promise, but require further investigation. Enhancing early diagnosis and personalized care is crucial for improving outcomes and reducing long-term disease burden in affected children. This review underscores the necessity for specific research to refine risk stratification and treatment paradigms for childhood-onset HCM. Full article

(This article belongs to the Special Issue 10th Anniversary of JCDD—'Pediatric Cardiology and Congenital Heart Disease' Section)

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15 pages, 1482 KB

Open AccessEditor’s ChoiceReview

Targeting Telomere Shortening in Vascular Aging and Atherosclerosis: Therapeutic Promise of Astragalus membranaceus

by Paola Canale and Maria Grazia Andreassi

J. Cardiovasc. Dev. Dis. 2025, 12(9), 341; https://doi.org/10.3390/jcdd12090341 - 4 Sep 2025

Viewed by 5221

Abstract

Telomere dysfunction has emerged as a pivotal contributor to vascular senescence, a fundamental process in the pathogenesis of age-related cardiovascular diseases such as atherosclerosis. This connection underscores the therapeutic potential of targeting telomere biology to prevent or mitigate the progression of vascular aging. [...] Read more.

Telomere dysfunction has emerged as a pivotal contributor to vascular senescence, a fundamental process in the pathogenesis of age-related cardiovascular diseases such as atherosclerosis. This connection underscores the therapeutic potential of targeting telomere biology to prevent or mitigate the progression of vascular aging. In this context, Astragalus membranaceus and its bioactive constituents, including astragaloside IV, cycloastragenol, and the commercial telomerase activator TA-65, demonstrate significant promise in attenuating vascular aging and atherosclerotic disease. These compounds exert a range of pleiotropic effects, including anti-inflammatory, antioxidant, endothelial-protective, and lipid-modulating actions, while also modulating telomerase activity and supporting telomere maintenance. This review provides an overview of the mechanistic basis underlying the anti-atherosclerotic effects of Astragalus-derived compounds and underscores critical key knowledge gaps. It also outlines future research directions necessary to validate their efficacy and therapeutic potential in the prevention and treatment of atherosclerosis and other age-related vascular disorders. Full article

(This article belongs to the Section Basic and Translational Cardiovascular Research)

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33 pages, 6066 KB

Open AccessEditor’s ChoiceReview

When Functional Assessment Meets Intravascular Imaging in Patients with Coronary Artery Disease

by Grigorios Tsigkas, Kassiani-Maria Nastouli, Anastasios Apostolos, Panagiota Spyropoulou, Maria Bozika, Michail I. Papafaklis, Stella Rouzi, Effrosyni Tsimara, Antonios Karanasos, Virginia Mplani and Periklis Davlouros

J. Cardiovasc. Dev. Dis. 2025, 12(8), 319; https://doi.org/10.3390/jcdd12080319 - 20 Aug 2025

Cited by 2 | Viewed by 2925

Abstract

Percutaneous Coronary Intervention (PCI) has advanced significantly with the incorporation of imaging and physiology assessment techniques. Fractional Flow Reserve (FFR) and Non-Hyperemic Pressure indices (NHPIs) provide information regarding the functional significance of coronary lesions, while Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) [...] Read more.

Percutaneous Coronary Intervention (PCI) has advanced significantly with the incorporation of imaging and physiology assessment techniques. Fractional Flow Reserve (FFR) and Non-Hyperemic Pressure indices (NHPIs) provide information regarding the functional significance of coronary lesions, while Intravascular Ultrasound (IVUS) and Optical Coherence Tomography (OCT) enhance anatomical characterization and guide stent implantation. This review explores the implementation of physiology- and imaging-guided strategies in clinical practice, comparing their efficacy and limitations. Novel technologies now allow for physiology estimation without hyperemic agents, and hybrid techniques, such as OCT-derived FFR, are increasingly integrated into clinical practice. These approaches offer the combined advantages of functional assessment and detailed anatomical imaging. Full article

(This article belongs to the Special Issue Advanced Cardiovascular Imaging in Structural Heart Disease: Diagnostic, Prognostic, and Therapeutic Perspectives)

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19 pages, 3343 KB

Open AccessEditor’s ChoiceArticle

Echocardiographic Assessment of Pulmonary Hemodynamics and Right Ventricular Performance in Neonatal Murine Hypoxia

by Kel Vin Woo, Philip T. Levy, Carla J. Weinheimer, Amanda L. Hauck, Aaron Hamvas, David M. Ornitz, Attila Kovacs and Gautam K. Singh

J. Cardiovasc. Dev. Dis. 2025, 12(8), 316; https://doi.org/10.3390/jcdd12080316 - 19 Aug 2025

Viewed by 985

Abstract

Background: Right heart catheterization (RHC) is the gold-standard for diagnosis of pulmonary hypertension (PH) but is a terminal procedure in neonatal mice. The objective was to validate echocardiographic measures of PH to establish the diagnostic capability against pulmonary vascular histology in neonatal mice. [...] Read more.

Background: Right heart catheterization (RHC) is the gold-standard for diagnosis of pulmonary hypertension (PH) but is a terminal procedure in neonatal mice. The objective was to validate echocardiographic measures of PH to establish the diagnostic capability against pulmonary vascular histology in neonatal mice. Methods: Adult mice, exposed to hypoxia or normoxia, were assessed by echocardiography and RHC to evaluate right ventricle (RV) morphometry and function. Echocardiographic measures identified in adult mice were then used to evaluate PH characteristics in hypoxia-exposed neonatal mice. Physiological parameters were compared to histopathology in all mice. Results: Hypoxia-challenged adult mice developed PH with RHC, demonstrating confirmed elevated RV systolic pressure (RVSP), RV hypertrophy, and increased cross-sectional area and neomuscularization of pulmonary vessels. Echocardiography-derived RV free wall (RVFW) thickness correlated with RV mass. Tricuspid valve annulus tissue Doppler imaging (TV TDI), tricuspid annular plane systolic excursion (TAPSE), pulmonary artery acceleration measures (PAAT), and TAPSE × PAAT (a measure of RV work) all correlated with RVSP determined by RHC. In neonatal mice exposed to hypoxia, PAAT, TV TDI, TAPSE, and TAPSE × PAAT were decreased and RVFW thickness was increased, correlating with the histologic phenotype of PH. Conclusions: Echocardiographic indices of RV morphology and function provide reliable estimates of invasive RV hemodynamics in hypoxia-induced PH. Full article

(This article belongs to the Section Basic and Translational Cardiovascular Research)

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14 pages, 1157 KB

Open AccessEditor’s ChoiceReview

Mitral Annular Disjunction: Epidemiology, Diagnostic Methods, Prognosis, and Novel Implications

by Vasileios Tsimpiris, Georgia Kousourna, Aristi Boulmpou, Magdalini Petridou, Chalil Tsavousoglou, Dimitrios Kotzadamis, Christodoulos Papadopoulos, Dimitrios Ntelios, Theodoros Moysiadis, Vassilios Vassilikos and Efstathios Pagourelias

J. Cardiovasc. Dev. Dis. 2025, 12(8), 311; https://doi.org/10.3390/jcdd12080311 - 18 Aug 2025

Cited by 2 | Viewed by 2349

Abstract

Mitral annular disjunction (MAD) is an increasingly recognized structural abnormality of the mitral valve apparatus, often associated with mitral valve prolapse and a heightened risk of ventricular arrhythmias and sudden cardiac death. It is defined by a separation between the mitral annulus and [...] Read more.

Mitral annular disjunction (MAD) is an increasingly recognized structural abnormality of the mitral valve apparatus, often associated with mitral valve prolapse and a heightened risk of ventricular arrhythmias and sudden cardiac death. It is defined by a separation between the mitral annulus and the left ventricular myocardium, best visualized during systole. In this review, we present an updated and comprehensive overview of MAD, drawing from recent large-scale imaging studies, expert consensus documents, and newly proposed classifications such as true versus pseudo-MAD. We discuss its prevalence, anatomical features, and diagnostic challenges across multiple imaging modalities, including transthoracic and transesophageal echocardiography, cardiovascular magnetic resonance, and computed tomography. We also explore its pathophysiological role in arrhythmogenesis, its prognostic implications, and current management strategies. Special attention is given to risk stratification based on imaging and cardiac rhythm findings, and we propose a practical clinical framework to guide decision-making. This review aims to support clinicians in recognizing MAD as a potentially arrhythmogenic condition that requires systematic evaluation and follow-up. Full article

(This article belongs to the Special Issue State of the Art in Mitral Valve Disease)

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11 pages, 647 KB

Open AccessEditor’s ChoiceReview

Atrioventricular Node Dysfunction in Heart Failure: New Horizons from Pathophysiology to Therapeutic Perspectives

by Isabella Fumarulo, Elia Nunzio Maria Salerno, Andrea De Prisco, Salvatore Emanuele Ravenna, Maria Chiara Grimaldi, Francesco Burzotta and Nadia Aspromonte

J. Cardiovasc. Dev. Dis. 2025, 12(8), 310; https://doi.org/10.3390/jcdd12080310 - 15 Aug 2025

Cited by 1 | Viewed by 1903

Abstract

Heart failure (HF) is characterized by adverse myocardial remodeling involving both the contractile cardiomyocytes and the conduction tissue. HF is often associated with atrioventricular (AV) node dysfunction, which frequently leads to conduction delays and subsequent dyssynchrony ultimately related to adverse clinical outcomes. Despite [...] Read more.

Heart failure (HF) is characterized by adverse myocardial remodeling involving both the contractile cardiomyocytes and the conduction tissue. HF is often associated with atrioventricular (AV) node dysfunction, which frequently leads to conduction delays and subsequent dyssynchrony ultimately related to adverse clinical outcomes. Despite its clinical relevance, AV node pathology in HF remains poorly explored. This review aims to investigate the pathophysiology underlying AV node dysfunction and the clinical implications for patients with HF, and to provide an overview of current therapeutic approaches, including an analysis of potential future treatments. Full article

(This article belongs to the Special Issue Updates on Atrio-Ventricular Node Anatomy and Physiology and on AVNRTs Circuit)

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20 pages, 1630 KB

Open AccessEditor’s ChoiceReview

Fractional Flow Reserve from Coronary CT: Evidence, Applications, and Future Directions

by Arta Kasaeian, Mohadese Ahmadzade, Taylor Hoffman, Mohammad Ghasemi-Rad and Anoop Padoor Ayyappan

J. Cardiovasc. Dev. Dis. 2025, 12(8), 279; https://doi.org/10.3390/jcdd12080279 - 22 Jul 2025

Cited by 1 | Viewed by 4940

Abstract

Coronary computed tomography angiography (CCTA) has emerged as the leading noninvasive imaging modality for the assessment of coronary artery disease (CAD), offering high-resolution visualization of the coronary anatomy and plaque characterization. The development of fractional flow reserve derived from CCTA (FFR-CT) has further [...] Read more.

Coronary computed tomography angiography (CCTA) has emerged as the leading noninvasive imaging modality for the assessment of coronary artery disease (CAD), offering high-resolution visualization of the coronary anatomy and plaque characterization. The development of fractional flow reserve derived from CCTA (FFR-CT) has further transformed the diagnostic landscape by enabling the simultaneous evaluation of both anatomical stenosis and lesion-specific ischemia. FFR-CT has demonstrated diagnostic accuracy comparable to invasive FFR. The combined use of CCTA and FFR-CT is now pivotal in a broad range of clinical scenarios, including the evaluation of stable and acute chest pain, assessment of high-risk and complex plaque features, and preoperative planning. As evidence continues to mount, CCTA and FFR-CT are positioned to become the primary gatekeepers to the cardiac catheterization laboratory, potentially reducing the number of unnecessary invasive procedures. This review highlights the growing clinical utility of FFR-CT, its integration with advanced plaque imaging, and the future potential of these technologies in redefining the management of CAD, while also acknowledging current limitations, including image quality requirements, cost, and access. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Imaging: An Exciting Future to Revolutionize the Diagnosis and Management of Cardiovascular Disease)

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15 pages, 584 KB

Open AccessEditor’s ChoiceReview

The Role of Non-HDL Cholesterol and Apolipoprotein B in Cardiovascular Disease: A Comprehensive Review

by Vasiliki Katsi, Nikolaos Argyriou, Christos Fragoulis and Konstantinos Tsioufis

J. Cardiovasc. Dev. Dis. 2025, 12(7), 256; https://doi.org/10.3390/jcdd12070256 - 4 Jul 2025

Cited by 7 | Viewed by 8703

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains the leading global cause of morbidity and mortality, even in the era of aggressive low-density lipoprotein cholesterol (LDL-C) lowering. This persistent residual risk has prompted a reevaluation of atherogenic lipid markers, with non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein [...] Read more.

Atherosclerotic cardiovascular disease (ASCVD) remains the leading global cause of morbidity and mortality, even in the era of aggressive low-density lipoprotein cholesterol (LDL-C) lowering. This persistent residual risk has prompted a reevaluation of atherogenic lipid markers, with non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B (Apo B) emerging as superior indicators of the total atherogenic particle burden. Unlike LDL-C, non-HDL-C includes cholesterol from all atherogenic lipoproteins, while Apo B reflects the total number of atherogenic particles regardless of cholesterol content. Their clinical relevance is underscored in populations with diabetes, obesity, and hypertriglyceridemia, where LDL-C may not adequately reflect cardiovascular risk. This review explores the biological, clinical, and genetic foundations of non-HDL-C and Apo B as critical tools for risk stratification and therapeutic targeting. It highlights discordance analysis, inflammatory mechanisms in atherogenesis, the influence of metabolic syndromes, and their utility in specific populations, including those with chronic kidney disease and children with familial hypercholesterolemia. Additionally, the role of lipoprotein (a), glycation in diabetes, and hypertriglyceridemia are examined as contributors to residual risk. Clinical trials and genetic studies support Apo B and non-HDL-C as more robust predictors of cardiovascular events than LDL-C. Current guidelines increasingly endorse these markers as secondary or even preferred targets in complex lipid disorders. The incorporation of Apo B and non-HDL-C into routine clinical practice, especially for patients with residual risk, represents a paradigm shift toward personalized cardiovascular prevention. The review concludes with recommendations for guideline integration, emerging therapies, and future directions in biomarker-driven cardiovascular risk management. Full article

(This article belongs to the Special Issue Effect of Lipids and Lipoproteins on Atherosclerosis)

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11 pages, 1065 KB

Open AccessEditor’s ChoiceArticle

Short-Term Outcomes of Partial Upper Ministernotomy for Aortic Valve Replacement Within the Learning Curve Context

by Tomáš Toporcer, Marián Homola, Anton Bereš, Michal Trebišovský, Tomáš Lopuchovský, Štefánia Mižáková, Lukáš Vajda, Štefan Lukačín and Adrián Kolesár

J. Cardiovasc. Dev. Dis. 2025, 12(7), 254; https://doi.org/10.3390/jcdd12070254 - 1 Jul 2025

Viewed by 1074

Abstract

Background: In recent decades, aortic valve surgery has transitioned from conventional median sternotomy (MS) to minimally invasive techniques, including partial upper mini-sternotomy (PUMS) and right anterolateral mini-thoracotomy (RAMT). This study retrospectively compares the outcomes of aortic valve replacement (AVR) using PUMS during the [...] Read more.

Background: In recent decades, aortic valve surgery has transitioned from conventional median sternotomy (MS) to minimally invasive techniques, including partial upper mini-sternotomy (PUMS) and right anterolateral mini-thoracotomy (RAMT). This study retrospectively compares the outcomes of aortic valve replacement (AVR) using PUMS during the learning phase with those of standard MS. Methods: A retrospective analysis was conducted on patients (n = 211) who underwent AVR for aortic stenosis. They were divided into MS (n = 119) and PUMS (n = 92) groups. Various preoperative, surgical and postoperative parameters, including survival, were examined. Results: Preoperatively, the main difference was age, with PUMS patients being older (67.5 ± 7 vs. 66.5 ± 9.6; p = 0.010). PUMS patients also had longer cardiopulmonary bypass (CPB) and cross-clamping times (99 ± 25 vs. 80 ± 16 min; p < 0.002; 79 ± 18 vs. 65 ± 13 min; p < 0.024). There were no significant differences in body mass index, prosthesis size, indexed effective orifice area, hospitalisation duration or any other monitored parameter. Echocardiographic follow-up found no differences in prosthetic pressure gradients, flow velocity or paravalvular leak between the PUMS and MS groups. Survival rates were similar over 1000 days. Conclusions: The data suggest that PUMS offers comparable surgical outcomes to MS for AVR with additional cosmetic benefits, undeterred by a learning curve. Full article

(This article belongs to the Section Cardiac Surgery)

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21 pages, 26629 KB

Open AccessEditor’s ChoiceReview

The Anatomy of the Atrioventricular Node

by Robert H. Anderson, Damián Sánchez-Quintana, Jorge Nevado-Medina, Diane E. Spicer, Justin T. Tretter, Wouter H. Lamers, Zihan Hu, Andrew C. Cook, Eduardo Back Sternick and Demosthenes G. Katritsis

J. Cardiovasc. Dev. Dis. 2025, 12(7), 245; https://doi.org/10.3390/jcdd12070245 - 26 Jun 2025

Cited by 3 | Viewed by 3222

Abstract

The anatomical arrangement of the atrioventricular node has been likened to a riddle wrapped up in an enigma. There are several reasons for this alleged mystery, not least the marked variability in structure between different species. Lack of detailed knowledge of the location [...] Read more.

The anatomical arrangement of the atrioventricular node has been likened to a riddle wrapped up in an enigma. There are several reasons for this alleged mystery, not least the marked variability in structure between different species. Lack of detailed knowledge of the location of the node relative to the atrial and ventricular septal structures has also contributed to previous misunderstandings. Recent studies comparing the findings of gross dissection with virtual dissection of living datasets, combined with access to a large number of serially sectioned human and animal hearts, have served to provide the evidence to solve the riddle. We summarise these findings in this review. We explain how the node is located within the atrial walls of the inferior pyramidal space. It becomes the non-branching component of the atrioventricular conduction axis as the axis extends through the plane of atrioventricular insulation to enter the infero-septal recess of the left ventricular outflow tract. The node itself is formed by contributions from the tricuspid and mitral vestibules, with extensive additional inputs from the base of the atrial septum. We show how knowledge of development enhances the appreciation of the arrangements and offers an explanation as to why, on occasion, there can be persisting nodoventricular connections. We discuss the findings relative to the circuits producing atrioventricular re-entry tachycardia. We conclude by emphasising the significance of the variation of the anatomical arrangements within different mammalian species. Full article

(This article belongs to the Special Issue Updates on Atrio-Ventricular Node Anatomy and Physiology and on AVNRTs Circuit)

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4 pages, 186 KB

Open AccessEditor’s ChoiceEditorial

Stroke: Risk Factors, Mechanisms, Outcomes and Ethnicity

by Narayanaswamy Venketasubramanian

J. Cardiovasc. Dev. Dis. 2025, 12(6), 199; https://doi.org/10.3390/jcdd12060199 - 23 May 2025

Cited by 1 | Viewed by 2339

Abstract

Stroke remains a leading cause of death and disability globally [...] Full article

(This article belongs to the Special Issue Stroke: Risk Factors, Mechanisms, Outcomes and Ethnicity)

22 pages, 1675 KB

Open AccessEditor’s ChoiceReview

Cardiac Magnetic Resonance in Heart Failure: Diagnostic and Prognostic Assessments

by Sara Pezzini, Francesca Daus, Giorgia Galli, Andrea Farina, Gabriele Fragasso and Roberto Spoladore

J. Cardiovasc. Dev. Dis. 2025, 12(6), 200; https://doi.org/10.3390/jcdd12060200 - 23 May 2025

Cited by 2 | Viewed by 2983

Abstract

With its high spatial resolution and tissue contrast, cardiac magnetic resonance (CMR) is an extremely flexible imaging technique that enables a thorough morphological and functional evaluation of the heart and vascular system. From diagnosis to treatment planning and risk assessment, CMR is being [...] Read more.

With its high spatial resolution and tissue contrast, cardiac magnetic resonance (CMR) is an extremely flexible imaging technique that enables a thorough morphological and functional evaluation of the heart and vascular system. From diagnosis to treatment planning and risk assessment, CMR is being utilized more and more in the evaluation of patients with heart failure (HF). CMR offers a variety of techniques for characterizing myocardial tissue, aiding in identifying the cause of HF, as well as whole-heart cine imaging for precise measurement of biventricular dimensions and function. The aim of this review is to the describe the role of CMR in chronic heart failure, in particular for diagnostic workups, differential diagnosis, and information on how CMR influences treatment planning choices. Full article

(This article belongs to the Special Issue Role of Cardiovascular Imaging in Heart Failure)

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10 pages, 1458 KB

Open AccessEditor’s ChoiceReview

The Ross Procedure in Children with Congenital Heart Disease

by Nabil Dib, Nancy Poirier, Ismail Bouhout and Paul Khairy

J. Cardiovasc. Dev. Dis. 2025, 12(5), 186; https://doi.org/10.3390/jcdd12050186 - 15 May 2025

Viewed by 1214

Abstract

Aortic valve disease accounts for approximately 5% of all congenital heart defects in children. Choosing the optimal valve replacement in this population is challenging, as it must ensure durability, accommodate growth, and minimize the need for long-term anticoagulation. Biological valves do not require [...] Read more.

Aortic valve disease accounts for approximately 5% of all congenital heart defects in children. Choosing the optimal valve replacement in this population is challenging, as it must ensure durability, accommodate growth, and minimize the need for long-term anticoagulation. Biological valves do not require anticoagulation but lack durability and growth potential, leading to frequent reoperations. Mechanical valves offer longevity but necessitate lifelong anticoagulation and do not grow with the child. Among the available surgical options, the Ross procedure has emerged as a preferred approach due to its favorable hemodynamic performance, growth potential, and freedom from anticoagulation. First described in 1967, this technique involves replacing the diseased aortic valve with a pulmonary autograft and reconstructing the right ventricular outflow tract using a human or non-human valve substitute. Despite its advantages, the procedure is technically demanding, has a considerable learning curve, and transforms a single-valve pathology into a bivalvular condition. This narrative review provides an updated perspective on the Ross procedure in children, focusing on long-term survival, reoperation rates, and the role of percutaneous valve replacement in delaying surgical reintervention. By synthesizing the latest evidence, we aim to clarify the current standing of the Ross procedure as a durable and effective solution for pediatric aortic valve disease. Full article

(This article belongs to the Special Issue 10th Anniversary of JCDD—'Pediatric Cardiology and Congenital Heart Disease' Section)

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20 pages, 6091 KB

Open AccessEditor’s ChoiceReview

The Role of Cardiac Magnetic Resonance Imaging in the Management of Hypertrophic Cardiomyopathy

by Luca Pugliese, Alessandra Luciano and Marcello Chiocchi

J. Cardiovasc. Dev. Dis. 2025, 12(5), 189; https://doi.org/10.3390/jcdd12050189 - 15 May 2025

Viewed by 1692

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy, caused by either sarcomere protein or other gene mutations. It is a complex and highly heterogeneous disorder, with phenotypes ranging from asymptomatic to severe disease, characterized by asymmetric left ventricular (LV) hypertrophy unexplained by [...] Read more.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy, caused by either sarcomere protein or other gene mutations. It is a complex and highly heterogeneous disorder, with phenotypes ranging from asymptomatic to severe disease, characterized by asymmetric left ventricular (LV) hypertrophy unexplained by loading conditions, which is also associated with myocardial fiber disarray, and preserved or increased ejection fraction without LV dilation. Comprehensive personal and family history, physical examination, and ECG testing raise suspicion of HCM, and echocardiogram represents the first-line imaging modality for confirming a diagnosis. Moreover, contrast-enhanced cardiac magnetic resonance (CMR) imaging has increasingly emerged as a fundamental diagnostic and prognostic tool in HCM management. This article reviews the role of CMR in HCM identification and differentiation from phenotypic mimics, characterization of HCM phenotypes, monitoring of disease progression, evaluation of pre- and post-septal reduction treatments, and selection of candidates for implantable cardioverter-defibrillator. By providing information on cardiac morphology and function and tissue characterization, CMR is particularly helpful in the quantification of myocardial wall thickness, the detection of hypertrophy in areas blind to echocardiogram, subtle morphologic features in the absence of LV hypertrophy, myocardial fibrosis, and apical aneurysm, the evaluation of LV outflow tract obstruction, and the assessment of LV function in end-stage dilated HCM. Full article

(This article belongs to the Special Issue Diagnosis, Treatment, and Genetics of Cardiomyopathy)

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13 pages, 1708 KB

Open AccessEditor’s ChoiceArticle

Patients with Gastrointestinal Bleeding and Atrial Fibrillation: Potential Ideal Target for Epicardial Appendage Occlusion

by Stefano Branzoli, Massimiliano Marini, Domenico Catanzariti, Cecilia Pravadelli, Luigi Pannone, Giovanni D’Onghia, Mauro Fantinel, Fabrizio Guarracini, Gaia Franceschini, Mirco Zadro, Giulia Baroni, Silvia Casagrande, Donatella Ottaviani, Renato Turco, Serena Nicolussi Paolaz, Luciano Annicchiarico, Francesco Corsini, Roberto Rordorf, Kausilia Krishnadath, Flavia Ravelli, Carlo de Asmundis and Mark La Meir Show full author list Hide full author list

J. Cardiovasc. Dev. Dis. 2025, 12(5), 173; https://doi.org/10.3390/jcdd12050173 - 1 May 2025

Viewed by 1457

Abstract

Background: Gastrointestinal bleeding in patients with atrial fibrillation is an indication for left appendage occlusion. All endovascular devices mandate antithrombotic therapies: rebleeding risk remains an issue. To date, there are no reports on gastrointestinal rebleeding and stroke prevention by left appendage occlusion without [...] Read more.

Background: Gastrointestinal bleeding in patients with atrial fibrillation is an indication for left appendage occlusion. All endovascular devices mandate antithrombotic therapies: rebleeding risk remains an issue. To date, there are no reports on gastrointestinal rebleeding and stroke prevention by left appendage occlusion without any antithrombotic therapy in this category of patients. Methods: A total of 129 patients (male 85, mean age 76.6 ± 7.1, CHA₂DS₂Vasc 3.8 ± 1.5, HASBLED 3.3 ± 1.0; upper GI bleeding 10%, lower GI bleeding 86%, obscure occult 4.6%, on NOACS full dose 77.5%, NOACs reduced dose 13.1%, on anti-vitamin K 9.3%) with atrial fibrillation and history of repetitive gastrointestinal bleeding from ten centers underwent standalone thoracoscopic epicardial appendage closure without antithrombotic therapy for the entire follow up. Results: The observed bleeding rate was 0.91 events per year, equivalent to a relative risk of RR = 0.17 (p = 0.02) and a relative risk reduction (RRR) of 83%. The observed relative risk of stroke was 0.91 events per year, with a relative risk of RR = 0.19 (p = 0.03) and a relative risk reduction (RRR) of 81%. Conclusion: Standalone epicardial appendage occlusion without antithrombotic therapy in patients with repetitive gastrointestinal bleeding is safe and promising when rebleeding and stroke risk reduction need to be optimized. Full article

(This article belongs to the Special Issue Hybrid Ablation of the Atrial Fibrillation)

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9 pages, 516 KB

Open AccessEditor’s ChoiceArticle

Beyond the Echo: Is Comprehensive Vascular Exploration Valuable in Cases of Non-Syndromic Thoracic Aortic Aneurysms or Bicuspid Aortic Valve?

by Austin Saugstad, Srekar Ravi, George Bcharah, Christine E. Firth, Hend Bcharah, Hussein Abdul Nabi, Hoang Nhat Pham, Ramzi Ibrahim, Sant J. Kumar, Mahmoud Abdelnabi, Linnea M. Baudhuin, Yuxiang Wang, Mayowa A. Osundiji and Fadi Shamoun

J. Cardiovasc. Dev. Dis. 2025, 12(5), 167; https://doi.org/10.3390/jcdd12050167 - 24 Apr 2025

Viewed by 1091

Abstract

Bicuspid aortic valve (BAV) and thoracic aortic aneurysms and dissections (TAAD) are recognized in syndromic connective tissue diseases (CTD), but most cases occur sporadically. The extent to which non-syndromic BAV or TAAD predisposes to additional arteriopathies, particularly in younger individuals, remains unclear. We [...] Read more.

Bicuspid aortic valve (BAV) and thoracic aortic aneurysms and dissections (TAAD) are recognized in syndromic connective tissue diseases (CTD), but most cases occur sporadically. The extent to which non-syndromic BAV or TAAD predisposes to additional arteriopathies, particularly in younger individuals, remains unclear. We retrospectively analyzed 1438 patients (mean age = 48.0, 67.7% female), excluding those with CTDs. Participants were ≤60 years old and categorized by the presence of BAV and/or TAAD. We examined co-existing arterial pathologies, including fibromuscular dysplasia, spontaneous coronary artery dissection, abdominal aortic aneurysms (AAA), mesenteric, peripheral extremity, and carotid/cerebral arteriopathies. Overall, 44.6% had either BAV or TAAD, and 27.2% had multiple arteriopathies. While vascular diseases were frequently noted, odds ratios demonstrated no significantly increased risk of extra-aortic arteriopathies in the BAV or TAAD cohorts. AAA exhibited a non-significant trend toward higher prevalence in TAAD patients. These findings support current guidelines recommending targeted imaging (transthoracic echocardiography of the aortic root and ascending aorta) over comprehensive “head-to-pelvis” screening for non-syndromic BAV or TAAD patients without additional risk factors. Ongoing genetic analyses may elucidate whether particular variants predispose to multi-site aneurysms or dissections. Consequently, targeted surveillance remains appropriate, with broader imaging reserved for patients with genetic or clinical indicators of higher risk. Full article

(This article belongs to the Special Issue Models and Methods for Computational Cardiology: 2nd Edition)

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11 pages, 1507 KB

Open AccessEditor’s ChoiceArticle

Right Ventricular and Left Atrial Strain Predict Volumetric Response to Cardiac Resynchronization Therapy

by Shing Ching, Jeffrey Ji-Peng Li, Stefanie Maria Werhahn, Rebecca Elisabeth Beyer, Misael Estepa, Christian Stehning, Djawid Hashemi, Natalia Solowjowa, Christoph Klein, Henryk Dreger, Sebastian Kelle and Patrick Doeblin

J. Cardiovasc. Dev. Dis. 2025, 12(4), 152; https://doi.org/10.3390/jcdd12040152 - 11 Apr 2025

Viewed by 1222

Abstract

Background: While left-bundle-branch-block-related contraction patterns as well as echocardiography-derived strain are variably associated with the volumetric response to cardiac resynchronization therapy (CRT), the role of CMR-derived strain parameters is unexplored. Methods: A total of 50 patients receiving CRT implantation were retrospectively analyzed, all [...] Read more.

Background: While left-bundle-branch-block-related contraction patterns as well as echocardiography-derived strain are variably associated with the volumetric response to cardiac resynchronization therapy (CRT), the role of CMR-derived strain parameters is unexplored. Methods: A total of 50 patients receiving CRT implantation were retrospectively analyzed, all of whom had undergone CMR imaging within one year before, and echocardiography within 6 months before and 6–12 months after CRT implantation. We assessed CMR-derived morphological and functional parameters with regard to the echocardiographic response, defined as a reduction in the left ventricular end-systolic volume of ≥15%. Results: Among the standard CMR parameters, the indexed right ventricular volumes in end-diastole (RVEDVi) (74.5 ± 19.5 vs. 94.8 ± 30.2 mL/m², p = 0.006) and end-systole (RVESVi) (43.2 ± 13.3 vs. 61.6 ± 28.8 mL/m², p = 0.003), as well as the left atrial (LA) area (24.8 ± 3.5 vs. 30.4 ± 9.5 cm², p = 0.020), differed significantly between CRT responders and non-responders. In strain analysis, CRT responders showed a significantly better LA global longitudinal strain (GLS) (25.1 ± 10.4 vs. 15.3 ± 10.5, p = 0.002), LA global circumferential strain (GCS) (27.9 ± 14.7 vs. 17.1 ± 13.1%, p = 0.012), RV GLS (−25.0 ± 6.5 vs. −18.9 ± 7.6%, p = 0.004) and RV free wall strain (−31.1 ± 7.9 vs. −24.9 ± 9.5, p = 0.017). Conclusions: CMR-derived peak septal circumferential strain and RVEDVi correlated with the echocardiographic volumetric response to CRT at 6–12 months. Full article

(This article belongs to the Section Imaging)

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13 pages, 753 KB

Open AccessEditor’s ChoiceArticle

The Dilemma of Surgical Timing in Acute Aortic Valve Endocarditis: Does Early Surgery Improve Risks or Prognosis?

by Michele D’Alonzo, Lorenzo Di Bacco, Antonio Fiore, Massimo Baudo, Francesca Zanin, Chiara Baldelli, Cyrus Moini, Thierry Folliguet and Claudio Muneretto

J. Cardiovasc. Dev. Dis. 2025, 12(4), 153; https://doi.org/10.3390/jcdd12040153 - 11 Apr 2025

Viewed by 1560

Abstract

Background: Acute aortic valve infective endocarditis (IE) presents a critical surgical timing dilemma. This study investigates whether early surgical intervention (within seven days of targeted antibiotic therapy initiation) affects mortality and clinical outcomes compared to delayed/conventional surgery. Methods: A retrospective, multicenter analysis of [...] Read more.

Background: Acute aortic valve infective endocarditis (IE) presents a critical surgical timing dilemma. This study investigates whether early surgical intervention (within seven days of targeted antibiotic therapy initiation) affects mortality and clinical outcomes compared to delayed/conventional surgery. Methods: A retrospective, multicenter analysis of 204 patients with aortic IE was conducted, excluding emergency cases requiring immediate intervention. Patients were stratified into EARLY (≤7 days) and LATE (>7 days) surgical groups. Primary endpoints included in-hospital mortality and major adverse events, while secondary endpoints assessed long-term survival, recurrence, and reintervention rates. Results: No significant differences in in-hospital mortality were observed between groups (16% in both). The LATE group exhibited a trend toward increased permanent pacemaker implantation (16% vs. 8.2%; p = 0.100) and a higher incidence of postoperative atrial fibrillation (36% vs. 24%, p = 0.048). Infective endocarditis recurrence and long-term survival did not significantly differ between groups. Predictors of one-year mortality included chronic kidney disease, annular abscess, extracorporeal membrane oxygenation (ECMO) use, and prolonged mechanical ventilation. Conclusions: These findings suggest that early surgery, following a short course of antibiotics, does not compromise outcomes nor increase recurrence risk, challenging the conventional preference for delayed intervention in non-emergency IE cases. Full article

(This article belongs to the Section Cardiac Surgery)

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12 pages, 663 KB

Open AccessEditor’s ChoiceReview

Neuroprotective Strategies in Coronary Artery Disease Interventions

by Maurish Fatima, Akbar Bazarbaev, Asama Rana, Ruman Khurshid, Victory Effiom, Nyle Khalid Bajwa, Afsheen Nasir, Katherine Candelario, Sair Ahmad Tabraiz, Samantha Colon, Chanseo Lee, Sedem Dankwa and Irbaz Hameed

J. Cardiovasc. Dev. Dis. 2025, 12(4), 143; https://doi.org/10.3390/jcdd12040143 - 8 Apr 2025

Cited by 1 | Viewed by 2133

Abstract

Neuroprotective strategies in coronary artery interventions are essential due to the rising number of high-risk patients undergoing procedures like coronary artery bypass grafting (CABG), totally endoscopic coronary artery bypass (TECAB), and hybrid revascularization. In this review article, we summarize the neurological complications associated [...] Read more.

Neuroprotective strategies in coronary artery interventions are essential due to the rising number of high-risk patients undergoing procedures like coronary artery bypass grafting (CABG), totally endoscopic coronary artery bypass (TECAB), and hybrid revascularization. In this review article, we summarize the neurological complications associated with coronary artery disease intervention and the risk mitigation strategies. CABG carries significant risks, including ischemic stroke, encephalopathy, seizures, and peripheral nerve injuries. Risk factors include advanced age, hypertension, diabetes, and atherosclerosis. Off-pump CABG minimizes stroke risk by avoiding aortic manipulation and CPB. TECAB and hybrid revascularization have fewer reported neurological complications but still pose risks of stroke and cranial nerve injuries. Pharmacological neuroprotection includes agents such as barbiturates, volatile anesthetics, lidocaine, NMDA receptor antagonists, magnesium, nimodipine, corticosteroids, and aprotinin. Deep hypothermic circulatory arrest (DHCA) is reserved for complex aortic cases requiring a bloodless surgical field. Intraoperative strategies involve cerebral perfusion monitoring, embolic protection devices, and therapeutic hypothermia. Preoperative optimization targets risk factors, arrhythmia prevention, and antiplatelet therapy management. Postoperatively, timely antiplatelet administration, glucose control, hemodynamic stabilization, and cognitive monitoring are critical. Comprehensive neuroprotective approaches, spanning pre- to postoperative phases, aim to reduce neurological complications and enhance outcomes in coronary interventions. Full article

(This article belongs to the Special Issue 2nd Edition: Interventional Therapies and Management in Coronary Artery Disease)

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9 pages, 838 KB

Open AccessEditor’s ChoiceArticle

Gender Differences for His Bundle Pacing Long-Term Performance in the Elderly Population

by Catalin Pestrea, Ecaterina Cicala, Dragos Lovin, Adrian Gheorghe, Florin Ortan and Rosana Manea

J. Cardiovasc. Dev. Dis. 2025, 12(3), 88; https://doi.org/10.3390/jcdd12030088 - 26 Feb 2025

Cited by 1 | Viewed by 931

Abstract

Background and aims: His bundle pacing (HBP) is considered the most physiological form of cardiac pacing. Although feasibility studies have included older patients, specific data for HBP in this population are scarce. This study aimed to evaluate gender differences in HBP long-term performance [...] Read more.

Background and aims: His bundle pacing (HBP) is considered the most physiological form of cardiac pacing. Although feasibility studies have included older patients, specific data for HBP in this population are scarce. This study aimed to evaluate gender differences in HBP long-term performance in elderly patients with atrioventricular (AV) block. Methods: This retrospective study included 73 patients aged over 65 years with successful HBP and at least 2 years of follow-up. The patients’ baseline and follow-up clinical and procedural characteristics were recorded. Results: The mean age of the cohort was 72.8 ± 6.3 years, with 43 males and 30 females. The paced QRS complex was significantly narrower than the baseline value for both genders. Females had a narrower-paced QRS complex without differences in detection, type of His bundle capture, impedance, or fluoroscopy time. The pacing threshold increased progressively, reaching statistical significance compared to the baseline values at the two-year follow-up. The pacing threshold increased by more than 1 V over the follow-up period in twenty-four patients (32.9%) and by more than 2 V in six patients (8.2%), with no significant difference between genders. The pacing threshold increase occurred within the first year for most patients, without gender differences. Multivariate Cox regression analysis demonstrated that the paced QRS duration, left ventricular ejection fraction, and ischemic cardiomyopathy were significantly associated with the pacing threshold increase over time. Conclusion: In elderly patients with AV block, HBP remains a feasible pacing method, without significant gender differences, over a long-term follow-up period. Pacing threshold increases are expected in up to one-third of the patients, requiring regular follow-ups to adjust the programmed parameters and optimize battery longevity. Full article

(This article belongs to the Special Issue Cardiac Device Therapy: 2nd Edition)

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13 pages, 6590 KB

Open AccessEditor’s ChoiceReview

Not All SAVR Are Created Equal: All the Approaches Available for Surgical Aortic Valve Replacement

by Francesco Cabrucci, Serge Sicouri, Massimo Baudo, Dimitrios E. Magouliotis, Yoshiyuki Yamashita, Beatrice Bacchi, Dario Petrone, Beman Wasef, Aleksander Dokollari, Massimo Bonacchi and Basel Ramlawi

J. Cardiovasc. Dev. Dis. 2025, 12(3), 84; https://doi.org/10.3390/jcdd12030084 - 24 Feb 2025

Cited by 2 | Viewed by 4050

Abstract

Surgical Aortic Valve Replacement (SAVR) is still one of the pillars of cardiac surgery practice, and its role is evolving into a more complex operation. The competition with structural valve therapies and the urgent demand for less invasive solutions have unleashed surgeons’ creativity [...] Read more.

Surgical Aortic Valve Replacement (SAVR) is still one of the pillars of cardiac surgery practice, and its role is evolving into a more complex operation. The competition with structural valve therapies and the urgent demand for less invasive solutions have unleashed surgeons’ creativity in adapting to these new challenges. All the possible ways to surgically replace the aortic valve are analyzed in this review. Surgical techniques, advantages and disadvantages, and key differences are listed, helping surgeons navigate the available options. Sternotomy SAVR is the benchmark, but that is becoming obsolete and, in some cases, no longer performed for teaching purposes. Mini sternotomy is the easiest way to achieve minimal invasiveness in all anatomic situations, while right anterior thoracotomy is an elegant solution mastered by fewer surgeons. Endoscopic and robotic-assisted techniques are shaping the future of SAVR, yet they still lack wide adoption. The choice of approach is mainly dictated by the anatomic features of the patient and the surgeon’s skills. A flow diagram to overcome the learning curve and advance toward more complex surgery is provided here. Mastering as many techniques as possible is paramount when offering a patient-tailored approach and performing a safe and less invasive operation. Full article

(This article belongs to the Special Issue Feature Review Papers in Cardiovascular Clinical Research)

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11 pages, 473 KB

Open AccessEditor’s ChoiceArticle

Determinants of Longitudinal Changes in Exercise Blood Pressure in a Population of Young Athletes: The Role of BMI

by Francesca Battista, Marco Vecchiato, Kiril Chernis, Sara Faggian, Federica Duregon, Nicola Borasio, Sara Ortolan, Giacomo Pucci, Andrea Ermolao and Daniel Neunhaeuserer

J. Cardiovasc. Dev. Dis. 2025, 12(2), 74; https://doi.org/10.3390/jcdd12020074 - 15 Feb 2025

Cited by 1 | Viewed by 2295

Abstract

AIM: Higher exercise blood pressure in adults correlates with many cardiometabolic markers. The aim of this study was to investigate the main determinants of longitudinal variations in exercise blood pressure in young athletes. METHODS: A longitudinal retrospective study was conducted on adolescent athletes [...] Read more.

AIM: Higher exercise blood pressure in adults correlates with many cardiometabolic markers. The aim of this study was to investigate the main determinants of longitudinal variations in exercise blood pressure in young athletes. METHODS: A longitudinal retrospective study was conducted on adolescent athletes who underwent at least two sport-related pre-participation screening visits, including exercise testing with a standardized incremental ramp protocol on treadmill. Blood pressure was assessed at rest (SBP_rest), at the 3rd minute of exercise (SBP_3min), and at peak exercise (SBP_peak). Predictors of blood pressure response (i.e., respective changes vs. baseline (Δ)) were determined by multivariate regression models after adjustment for age, sex, follow-up duration, related baseline SBP values, characteristics of sport, and ΔBMI. RESULTS: A total of 351 young athletes (mean age at baseline 13 ± 2 years, 54% boys, average follow-up duration 3.4 ± 2.2 years) were enrolled. BMI increased by 1.5 ± 1.8 kg/m² (p < 0.001) during follow-up. At baseline, mean SBP_rest was 103 ± 14 mmHg, mean SBP_3min 124 ± 18 mmHg, and mean SBPpeak 154 ± 23 mmHg. A significant between-visit increase in SBP_rest (ΔSBP_rest 7.0 ± 17.4 mmHg; p < 0.001), ΔSBP_3min (4.8 ± 11 mmHg, p < 0.001), and ΔSBP_peak (11.7 ± 24 mmHg, p < 0.001) was observed. ΔSBP_3min was significantly predicted by male sex (p < 0.01), baseline BMI (p < 0.01), ΔBMI (p < 0.01), and number of practiced sports (p < 0.05), whereas ΔSBP_peak was positively predicted by male gender (p < 0.01), baseline BMI (p < 0.05), and ΔBMI (p < 0.01) and negatively by baseline resting heart rate (p < 0.01). In a logistic regression model, ΔBMI was the only independent determinant of passing from a lower to an upper quartile of SBP_3min (p < 0.001), while ΔBMI and male sex were independent determinants of moving to a higher quartile of SBP_peak (p < 0.001). CONCLUSIONS: Increase in BMI during development and male sex are independent determinants of the increase in exercise blood pressure, both at light and maximal intensity, in a population of adolescent athletes. Full article

(This article belongs to the Special Issue Exercise Testing and Interventions in Cardiovascular Disease)

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11 pages, 1677 KB

Open AccessEditor’s ChoiceArticle

Prothrombotic States in Transcatheter Heart Valve Leaflet Thrombosis (PROSTHESIS): Rationale and Early Results of the Observational Cohort Study

by Kajetan Grodecki, Katarzyna Pawlak, Matylda Grodecka, Bartosz Rymuza, Piotr Scislo, Olga Ciepiela, Janusz Kochman and Zenon Huczek

J. Cardiovasc. Dev. Dis. 2025, 12(2), 62; https://doi.org/10.3390/jcdd12020062 - 6 Feb 2025

Viewed by 1448

Abstract

Subclinical leaflet thrombosis is an imaging phenomenon observed after transcatheter aortic valve implantation (TAVI) and characterized by hypoattenuating leaflet thickening (HALT) on computed tomography angiography. The clinical implications and underlying causes remain uncertain. Hypercoagulability, a component of Virchow’s triad, may contribute to thrombus [...] Read more.

Subclinical leaflet thrombosis is an imaging phenomenon observed after transcatheter aortic valve implantation (TAVI) and characterized by hypoattenuating leaflet thickening (HALT) on computed tomography angiography. The clinical implications and underlying causes remain uncertain. Hypercoagulability, a component of Virchow’s triad, may contribute to thrombus formation on bioprosthetic leaflets, but data on hypercoagulable disorders in TAVI patients and their impact on HALT are limited. The PROSTHESIS study (Prothrombotic States in Transcatheter Heart Valve Subclinical Leaflet Thrombosis) is a single-center observational cohort study aiming to include 130 TAVI patients. This pilot study aimed to (i) assess the effect of hypercoagulable disorders on HALT prevalence and (ii) evaluate their impact on the natural history of HALT. Patients were screened for common hypercoagulable disorders using genetic and functional assays and underwent multimodal imaging one year after TAVI to detect HALT. In patients with HALT, post-implant imaging was repeated after three months to assess its progression. Early results comparing 52 TAVI patients with 52 matched controls undergoing coronary angiography showed similar thrombophilia prevalence between the groups (16% vs. 12%, p = 0.565). HALT occurred in 15% of TAVI patients, more extensively in those with thrombophilia (712 mm³ vs. 135 mm³, p = 0.036). However, thrombophilia was not an independent predictor of HALT. One-year follow-up CTA revealed spontaneous HALT resolution in 63%, stability in 25%, and progression in 12%. This study aims to provide insights into HALT and its mechanisms, which may help prevent complications and improve bioprosthesis durability. Full article

(This article belongs to the Section Cardiovascular Clinical Research)

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13 pages, 2282 KB

Open AccessEditor’s ChoiceArticle

Clinical Decision Support for Patient Cases with Asymptomatic Carotid Artery Stenosis Using AI Models and Electronic Medical Records

by Mackenzie Madison, Xiao Luo, Jackson Silvey, Robert Brenner, Kartik Gannamaneni and Alan P. Sawchuk

J. Cardiovasc. Dev. Dis. 2025, 12(2), 61; https://doi.org/10.3390/jcdd12020061 - 6 Feb 2025

Viewed by 2894

Abstract

An artificial intelligence (AI) analysis of electronic medical records (EMRs) was performed to analyze the differences between patients with carotid stenosis who developed symptomatic disease and those who remained asymptomatic. The EMRs of 872 patients who underwent a carotid endarterectomy between 2009 and [...] Read more.

An artificial intelligence (AI) analysis of electronic medical records (EMRs) was performed to analyze the differences between patients with carotid stenosis who developed symptomatic disease and those who remained asymptomatic. The EMRs of 872 patients who underwent a carotid endarterectomy between 2009 and 2022 were analyzed with AI. This included 408 patients who had carotid intervention for symptomatic carotid disease and 464 patients for asymptomatic, >70% stenosis. By analyzing the EMRs, the Support Vector Machine achieved the highest sensitivity at 0.626 for predicting which of these patients would go on to develop a stroke or TIA. Random Forest had the highest specificity at 0.906. The risk for stroke in patients with carotid stenosis was a balance between optimum medical treatment and the underlying disease processes. Risk factors for developing symptomatic carotid disease included elevated glucose, chronic kidney disease, hyperlipidemia, and current or recent smoking, while protective factors included cardiovascular agents, antihypertensives, and beta blockers. An AI review of EMRs can help determine which patients with carotid stenosis are more likely to develop a stroke to assist with decision making as to whether to proceed with intervention or to demonstrate and encourage reduced stroke risk with risk factor modification. Full article

(This article belongs to the Section Stroke and Cerebrovascular Disease)

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18 pages, 3350 KB

Open AccessEditor’s ChoiceReview

Beyond the Lumen: Molecular Imaging to Unmask Vulnerable Coronary Plaques

by Geoffrey Currie and Hosen Kiat

J. Cardiovasc. Dev. Dis. 2025, 12(2), 51; https://doi.org/10.3390/jcdd12020051 - 30 Jan 2025

Cited by 2 | Viewed by 3804

Abstract

Vulnerable coronary atherosclerotic plaque involves a dynamic pathophysiologic process within and surrounding an atheromatous plaque in coronary artery intima. The process drastically increases the risk of plaque rupture and is clinically responsible for most cases of acute coronary syndromes, myocardial infarctions, and sudden [...] Read more.

Vulnerable coronary atherosclerotic plaque involves a dynamic pathophysiologic process within and surrounding an atheromatous plaque in coronary artery intima. The process drastically increases the risk of plaque rupture and is clinically responsible for most cases of acute coronary syndromes, myocardial infarctions, and sudden cardiac deaths. Early detection of vulnerable plaque is crucial for clinicians to implement appropriate risk-mitigation treatment strategies, offer timely interventions, and prevent potentially life-threatening events. There is an imperative clinical need to develop practical diagnostic pathways that utilize non-invasive means to risk-stratify symptomatic patients. Since the early 1990s, the identification of vulnerable plaque in clinical practice has primarily relied on invasive imaging techniques. In the last two decades, CT coronary angiogram (CTCA) has rapidly evolved into the prevalent non-invasive diagnostic modality for assessing coronary anatomy. There are now validated plaque appearances on CTCA correlating with plaque vulnerability. It is worth noting that in clinical practice, most CTCA reports omit mention of vulnerable plaque details because spatial resolution (0.3–0.5 mm) is often insufficient to reliably detect some crucial features of vulnerable plaques, such as thin fibrous caps. Additionally, accurately identifying vulnerable plaque features requires substantial expertise and time, which many cardiologists or radiologists may lack in routine reporting. Cardiac magnetic resonance imaging (cMRI) is also non-invasive and allows simultaneous anatomic and functional assessment of coronary plaques. Despite several decades of research and development, routine clinical application of cMRI in coronary plaque imaging remains hampered by complex imaging protocols, inconsistent image quality, and cost. Molecular imaging with radiotracers, specifically positron emission tomography (PET) with sodium fluoride (Na¹⁸F PET), have demonstrated significant potential as a sensitive and specific imaging procedure for diagnosing vulnerable coronary artery plaque. The study protocol is robust and brief, requiring minimal patient preparation. Compared to CTCA and cMRI, the diagnostic accuracy of this test is less dependent on the experience and expertise of the readers. Furthermore, validated automated quantitative algorithms complement the visual interpretation of the study, enhancing confidence in the diagnosis. This combination of factors makes Na¹⁸F PET a promising tool in cardiology for identifying high-risk coronary plaques. Full article

(This article belongs to the Special Issue Current Practice in Cardiac Imaging)

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14 pages, 1506 KB

Open AccessEditor’s ChoiceReview

Mitochondrial Dysfunction in Congenital Heart Disease

by Julie Pires Da Silva, Mariana Casa de Vito, Carissa Miyano and Carmen C. Sucharov

J. Cardiovasc. Dev. Dis. 2025, 12(2), 42; https://doi.org/10.3390/jcdd12020042 - 25 Jan 2025

Cited by 4 | Viewed by 2639

Abstract

Mitochondria play a crucial role in multiple cellular processes such as energy metabolism, generation of reactive oxygen species, excitation–contraction coupling, cell survival and death. Dysfunction of mitochondria contributes to the development of cancer; neuromuscular, cardiovascular/congenital heart disease; and metabolic diseases, including diabetes. Mitochondrial [...] Read more.

Mitochondria play a crucial role in multiple cellular processes such as energy metabolism, generation of reactive oxygen species, excitation–contraction coupling, cell survival and death. Dysfunction of mitochondria contributes to the development of cancer; neuromuscular, cardiovascular/congenital heart disease; and metabolic diseases, including diabetes. Mitochondrial dysfunction can result in excessive reactive oxygen species, a decrease in energy production, mitophagy and apoptosis. All these processes are known to be dysregulated in cardiovascular diseases. The focus of this review is to summarize our current knowledge of mitochondrial dysfunction, including mitophagy and apoptosis, in pediatric congenital heart disease due to maternal diabetes or due to structural cardiac defects, with a focus on single-ventricle congenital heart disease. We also discuss recent mitochondria-targeted therapies for cardiovascular diseases. Full article

(This article belongs to the Section Pediatric Cardiology and Congenital Heart Disease)

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13 pages, 1177 KB

Open AccessEditor’s ChoiceArticle

High-Risk Plaque Characteristics in Patients with Suspected Stable Coronary Artery Disease and Impaired Glucose Tolerance: A Coronary Computed Tomography Angiography Study

by Thomas Rueskov Andersen, Katrine Schultz Overgaard, Laurits Juhl Heinsen, Roda Abdulkadir Mohamed, Freja Sønder Madsen, Helle Precht, Jess Lambrechtsen, Søren Auscher and Kenneth Egstrup

J. Cardiovasc. Dev. Dis. 2025, 12(2), 37; https://doi.org/10.3390/jcdd12020037 - 22 Jan 2025

Viewed by 1601

Abstract

Impaired glucose tolerance (IGT), a prediabetic state, is a known risk factor for coronary artery disease (CAD). Low-attenuation plaque (LAP) lesions are associated with a high risk of coronary events. We aimed to evaluate high-risk plaque characteristics in LAP lesions between patients with [...] Read more.

Impaired glucose tolerance (IGT), a prediabetic state, is a known risk factor for coronary artery disease (CAD). Low-attenuation plaque (LAP) lesions are associated with a high risk of coronary events. We aimed to evaluate high-risk plaque characteristics in LAP lesions between patients with IGT and normal glucose tolerance (NGT) in patients suspected for stable CAD. Coronary computed tomography angiography (CCTA) identified LAP lesions and assessed plaque volumes, burdens, and high-risk plaque features. Glycemic tolerance was stratified using oral glucose tolerance tests. Among 148 patients, 202 LAP lesions were identified, with 93 patients classified as NGT and 55 as IGT. Patients with IGT had a significantly higher prevalence of LAP lesions compared with NGT (p = 0.007). LAP volume was higher in IGT (16.46 ± 12.52 mm³) compared with NGT (12.66 ± 9.72 mm³, p = 0.01), but this association did not persist in multivariate analysis. The LAP burden was greater in IGT (10.79 ± 6.84%) than NGT (8.62 ± 5.93%, p = 0.02), and the napkin-ring sign was more frequent in IGT (12%) versus NGT (5%, p = 0.02); these associations remained significant in multivariate analysis. Patients with IGT had a higher LAP burden and higher frequency of napkin-ring signs. These findings may help explain the common occurrence of prediabetes in patients with acute myocardial infarction. Full article

(This article belongs to the Special Issue Coronary Artery Disease: Risk Stratification and Optimization of Intervention Strategies)

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13 pages, 822 KB

Open AccessEditor’s ChoiceArticle

Coronary Artery Disease in Very Young Women: Risk Factors and Prognostic Insights from Extended Follow-Up

by Samuel Pintos-Rodríguez, Víctor Alfonso Jiménez Díaz, César Veiga, Carlos Martínez García, Francisco Caamaño Isorna, Andrés Íñiguez Romo and Pablo Juan-Salvadores

J. Cardiovasc. Dev. Dis. 2025, 12(2), 34; https://doi.org/10.3390/jcdd12020034 - 21 Jan 2025

Cited by 3 | Viewed by 2599

Abstract

Coronary artery disease (CAD) is usually associated with the elderly, but an increase in its incidence has been recently reported among young people, including very young women. The aim of this study is to assess the associations between different clinical variables and the [...] Read more.

Coronary artery disease (CAD) is usually associated with the elderly, but an increase in its incidence has been recently reported among young people, including very young women. The aim of this study is to assess the associations between different clinical variables and the risk of early CAD and occurrence of major adverse cardiovascular events (MACEs) during follow-up. Our cohort consists of women ≤40 years referred for coronary angiography due to suspicion of CAD; a nested case–control study was conducted among these patients. In total, 19,321 coronary angiographies were performed between 2006 and 2015, of which 2.6% were in patients ≤40 years old; 52 women were finally included. Family history of CAD was strongly associated with the early onset of the disease [OR 5.94, 95%CI (1.13–31.15); p = 0.035] in young women. The incidence of MACE was also associated with depression [HR 8.20 95%CI (1.03–65.17); p = 0.047] and Castelli Index [HR 11.49, 95%CI (1.40–94.51); p = 0.023]. Primary prevention focused on genetic analysis for high-risk women with a family history of CAD and secondary prevention, targeting a better cholesterol management and mental health assistance must be considered. Full article

(This article belongs to the Section Epidemiology, Lifestyle, and Cardiovascular Health)

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21 pages, 4995 KB

Open AccessEditor’s ChoiceArticle

Ontogeny of Fetal Cardiometabolic Pathways: The Potential Role of Cortisol and Thyroid Hormones in Driving the Transition from Preterm to Near-Term Heart Development in Sheep

by Reza Amanollahi, Stacey L. Holman, Melanie R. Bertossa, Ashley S. Meakin, Kent L. Thornburg, I. Caroline McMillen, Michael D. Wiese, Mitchell C. Lock and Janna L. Morrison

J. Cardiovasc. Dev. Dis. 2025, 12(2), 36; https://doi.org/10.3390/jcdd12020036 - 21 Jan 2025

Cited by 8 | Viewed by 2642

Abstract

Understanding hormonal and molecular changes during the transition from preterm to near-term gestation is essential for investigating how pregnancy complications impact fetal heart development and contribute to long-term cardiovascular risks for offspring. This study examines these cardiac changes in fetal sheep, focusing on [...] Read more.

Understanding hormonal and molecular changes during the transition from preterm to near-term gestation is essential for investigating how pregnancy complications impact fetal heart development and contribute to long-term cardiovascular risks for offspring. This study examines these cardiac changes in fetal sheep, focusing on the changes between 116 days (preterm) and 140 days (near term) of gestation (dG, term = 150) using Western blotting, LC-MS/MS, and histological techniques. We observed a strong correlation between cortisol and T₃ (Triiodothyronine) in heart tissue in near-term fetuses, highlighting the role of glucocorticoid signalling in fetal heart maturation. Protein expression patterns in the heart revealed a decrease in multiple glucocorticoid receptor isoforms (GRα-A, GR-P, GR-A, GRα-D2, and GRα-D3), alongside a decrease in IGF-1R (a marker of cardiac proliferative capacity) and p-FOXO1(Thr24) but an increase in PCNA (a marker of DNA replication), indicating a shift towards cardiomyocyte maturation from preterm to near term. The increased expression of proteins regulating mitochondrial biogenesis and OXPHOS complex 4 reflects the known transition from glycolysis to oxidative phosphorylation, essential for meeting the energy demands of the postnatal heart. We also found altered glucose transporter expression, with increased pIRS-1(ser789) and GLUT-4 but decreased GLUT-1 expression, suggesting improved insulin responsiveness as the heart approaches term. Notably, the reduced protein abundance of SIRT-1 and SERCA2, along with increased phosphorylation of cardiac Troponin I(Ser23/24), indicates adaptations for more energy-efficient contraction in the near-term heart. In conclusion, these findings show the complex interplay of hormonal, metabolic, and growth changes that regulate fetal heart development, providing new insights into heart development that are crucial for understanding pathological conditions at birth and throughout life. Full article

(This article belongs to the Special Issue 10th Anniversary of JCDD—'Cardiac Development and Regeneration' Section — from Development to Regeneration)

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24 pages, 2004 KB

Open AccessEditor’s ChoiceSystematic Review

The Effect of Xanthine Oxidase Inhibitors in the Prevention and Treatment of Stroke: A Systematic Review and Meta-Analysis

by Lin Bai, Gerhard Litscher and Xiaoning Li

J. Cardiovasc. Dev. Dis. 2024, 11(12), 409; https://doi.org/10.3390/jcdd11120409 - 21 Dec 2024

Cited by 2 | Viewed by 2304

Abstract

Background: Xanthine oxidase inhibitors (XOIs) may help prevent stroke. However, heterogeneity can be found in the conclusions of different studies. The relevant evidence was summarized in this systematic review and meta-analysis to further clarify the role of XOIs in the prevention and treatment [...] Read more.

Background: Xanthine oxidase inhibitors (XOIs) may help prevent stroke. However, heterogeneity can be found in the conclusions of different studies. The relevant evidence was summarized in this systematic review and meta-analysis to further clarify the role of XOIs in the prevention and treatment of stroke, with a focus on evaluating the effects of XOIs in primary and secondary prevention of stroke, acute stroke treatment, and reduction of post-stroke complications. Methods: Randomized controlled trials (RCTs) or cohort studies on the effect of XOIs in the prevention and treatment of stroke were searched in PubMed, EMBASE, and Cochrane Library from inception to 3 March 2024, along with hand searching. The analyses were carried out using Review Manager 5.4. Results: The analysis included 14 studies (115,579 patients). While XOIs did not significantly reduce the risk of stroke (RR: 0.89; 95% CI: 0.59–1.34), they improved post-stroke functional outcomes, with a reduction in the modified Rankin scale scores (mean difference: −0.6; 95% CI: −0.8 to −0.4), decreased intercellular adhesion molecule-1 levels (mean difference: −15.2 ng/mL; 95% CI: −22.3 to −8.1), improved augmentation index (AIx) by 4.2% (95% CI: 2.5–5.9%), reduced central blood pressure (mean reduction: 4.8 mmHg; 95% CI: 2.6–6.9), and delayed carotid intima-media thickness progression (mean difference: −0.05 mm/year; 95% CI: −0.08 to −0.02). Full article

(This article belongs to the Special Issue Feature Review Papers in Stroke and Cerebrovascular Disease)

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19 pages, 658 KB

Open AccessEditor’s ChoiceReview

Drug-Induced Myocardial Infarction: A Review of Pharmacological Triggers and Pathophysiological Mechanisms

by Ioana Boarescu and Paul-Mihai Boarescu

J. Cardiovasc. Dev. Dis. 2024, 11(12), 406; https://doi.org/10.3390/jcdd11120406 - 18 Dec 2024

Cited by 5 | Viewed by 20622

Abstract

Myocardial infarction (MI) is a significant cardiovascular event caused by the decrease in or complete cessation of blood flow to a portion of the myocardium. It can arise from a variety of etiological factors, including pharmacological triggers. This review aims to explore the [...] Read more.

Myocardial infarction (MI) is a significant cardiovascular event caused by the decrease in or complete cessation of blood flow to a portion of the myocardium. It can arise from a variety of etiological factors, including pharmacological triggers. This review aims to explore the diverse drugs and substances that might lead to drug-induced myocardial infarction, focusing on their mechanisms of action and the pathophysiological processes involved. Various established and emerging pharmacological agents that could elevate the risk of myocardial infarction, such as nonsteroidal anti-inflammatory drugs, hormonal therapies, anticoagulants, and antipsychotic medications, are discussed. The role of drug-induced endothelial dysfunction, coronary artery spasm, and thrombosis are presented in order to highlight the underlying mechanisms. This review emphasizes the need for increased awareness among healthcare professionals to mitigate the risks associated with different pharmacological therapies to improve patient outcomes. Full article

(This article belongs to the Special Issue Food, Drugs and Environmental Exposures as Triggers of Myocardial Injury and Myocardial Infarction)

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9 pages, 280 KB

Open AccessEditor’s ChoiceReview

Contemporary Review of Minimally Invasive Mitral Valve Surgery: Current Considerations and Innovations

by Sharifa Alsheebani, Daniel Goubran, Benoit de Varennes and Vincent Chan

J. Cardiovasc. Dev. Dis. 2024, 11(12), 404; https://doi.org/10.3390/jcdd11120404 - 14 Dec 2024

Cited by 3 | Viewed by 1958

Abstract

Minimally invasive mitral valve surgery (MIMVS) has become a well-established alternative to traditional median sternotomy at high-volume surgical centers. Advancements in surgical instruments have led to further refinement of MIMVS. However, MIMVS remains limited to select patients in select settings. In this review, [...] Read more.

Minimally invasive mitral valve surgery (MIMVS) has become a well-established alternative to traditional median sternotomy at high-volume surgical centers. Advancements in surgical instruments have led to further refinement of MIMVS. However, MIMVS remains limited to select patients in select settings. In this review, we provide a brief overview of the evolution of MIMVS, as well as a technical description of the most relevant aspects of minimally invasive mitral valve surgery. Full article

12 pages, 1522 KB

Open AccessEditor’s ChoiceArticle

Unifocalization of Major Aortopulmonary Collateral Arteries (MAPCAs) and Native Pulmonary Arteries in Infancy—Application of 3D Printing and Virtual Reality

by Jacek Kolcz, Anna Rudek-Budzynska and Krzysztof Grandys

J. Cardiovasc. Dev. Dis. 2024, 11(12), 403; https://doi.org/10.3390/jcdd11120403 - 13 Dec 2024

Cited by 1 | Viewed by 3155

Abstract

Background. Major aortopulmonary collateral arteries (MAPCAs) are rare remnants of pulmonary circulation embryological development usually associated with complex congenital anomalies of the right ventricular outflow tract and pulmonary arteries. Effective management requires surgical unifocalization of MAPCAs and native pulmonary arteries (NPAs). Traditional imaging [...] Read more.

Background. Major aortopulmonary collateral arteries (MAPCAs) are rare remnants of pulmonary circulation embryological development usually associated with complex congenital anomalies of the right ventricular outflow tract and pulmonary arteries. Effective management requires surgical unifocalization of MAPCAs and native pulmonary arteries (NPAs). Traditional imaging may lack the spatial clarity needed for precise surgical planning. Aim. This study evaluated the feasibility of integrating three-dimensional (3D) printing and virtual reality (VR) into preoperative planning to improve surgical precision, team communication, and parental understanding. In a prospective cohort study, nine infants undergoing MAPCA unifocalization were included. Four patients underwent conventional imaging-based planning (control), while five were additionally assessed using VR and 3D-printed models (intervention). The outcomes measured included operative times, team confidence, collaboration, and parental satisfaction. Statistical analysis was performed using standard tests. Results. The intervention group had shorter operative and cardiopulmonary bypass times compared to the control group. Intraoperative complications were absent in the VR/3D group but occurred in the control group. Medical staff in the VR/3D group reported significantly improved understanding of anatomy, surgical preparedness, and team collaboration (p < 0.05). Parents also expressed higher satisfaction, with better comprehension of their child’s anatomy and surgical plan. Conclusions. VR and 3D printing enhanced preoperative planning, surgical precision, and communication, proving valuable for complex congenital heart surgery. These technologies offer promising potential to improve clinical outcomes and patient–family experiences, meriting further investigation in larger studies. Full article

(This article belongs to the Special Issue Congenital Heart Disease: Technological Innovations in Cardiac Surgery and Interventional Therapy)

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12 pages, 3229 KB

Open AccessEditor’s ChoiceArticle

Extracellular Volume by Computed Tomography Is Useful for Prediction of Prognosis in Dilated Cardiomyopathy Cases with Heart Failure with Reduced Ejection Fraction

by Satomi Yashima, Hiroyuki Takaoka, Joji Ota, Moe Matsumoto, Yusei Nishikawa, Yoshitada Noguchi, Shuhei Aoki, Kazuki Yoshida, Katsuya Suzuki, Makiko Kinoshita, Haruka Sasaki, Noriko Suzuki-Eguchi, Tomonori Kanaeda and Yoshio Kobayashi

J. Cardiovasc. Dev. Dis. 2024, 11(12), 399; https://doi.org/10.3390/jcdd11120399 - 11 Dec 2024

Cited by 2 | Viewed by 1910

Abstract

Objective: Cardiac computed tomography (CT) helps screen coronary artery stenosis in cases with dilated cardiomyopathy (DCM). Extracellular volume fraction (ECV) analysis has recently been eligible for CT. Method: We evaluated the impact of ECV on the CT to predict the prognosis in DCM [...] Read more.

Objective: Cardiac computed tomography (CT) helps screen coronary artery stenosis in cases with dilated cardiomyopathy (DCM). Extracellular volume fraction (ECV) analysis has recently been eligible for CT. Method: We evaluated the impact of ECV on the CT to predict the prognosis in DCM patients with heart failure with reduced ejection fraction (HFrEF). Patients or Materials: We analyzed 101 consecutive DCM cases with HFrEF who underwent cardiac CT. All the patients had a lower left ventricular (LV) ejection fraction (LVEF) of less than 40%. We evaluated the effect of ECV to predict the patients’ prognosis. Cardiovascular death, hospitalization due to heart failure, and fatal arrhythmic events were included in the major adverse cardiac events (MACE). Results: MACE occurred in 27 cases (27%). The patients with MACE (27 cases) had an increased ECV on the LVM on the CT (37.2 ± 6.7 vs. 32.2 ± 3.6%, p = 0.0008) compared to the others (74 cases). Based on the receiver operating characteristics curve analysis, the best cutoff value of the ECV on the LVM to predict the MACE was 32.3%. The patients with ECV ≥ 32.3% had significantly higher MACE based on the Kaplan–Meier analysis. The ECV on the LVM was a significant marker to predict MACE based on the univariate Cox proportional hazard model (hazard ratio of 8.00, 95% confidence interval 1.88–33.97, p = 0.0048). Conclusions: ECV by CT is helpful to predict MACE in cases with DCM and HFrEF. Full article

(This article belongs to the Topic Cardiovascular Disease in Special Populations: From Basic Science to Clinical Practice)

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24 pages, 1158 KB

Open AccessEditor’s ChoiceReview

Tailored Therapies for Cardiogenic Shock in Hypertrophic Cardiomyopathy: Navigating Emerging Strategies

by George E. Zakynthinos, Ioannis Gialamas, Vasiliki Tsolaki, Panteleimon Pantelidis, Athina Goliopoulou, Maria Ioanna Gounaridi, Ioanna Tzima, Andrew Xanthopoulos, Konstantinos Kalogeras, Gerasimos Siasos and Evangelos Oikonomou

J. Cardiovasc. Dev. Dis. 2024, 11(12), 401; https://doi.org/10.3390/jcdd11120401 - 11 Dec 2024

Viewed by 6132

Abstract

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous cardiac disorder, often complicated by cardiogenic shock, a life-threatening condition marked by severe cardiac output failure. Managing cardiogenic shock in HCM patients presents unique challenges due to the distinct pathophysiology of the disease, which includes [...] Read more.

Hypertrophic cardiomyopathy (HCM) is a complex and heterogeneous cardiac disorder, often complicated by cardiogenic shock, a life-threatening condition marked by severe cardiac output failure. Managing cardiogenic shock in HCM patients presents unique challenges due to the distinct pathophysiology of the disease, which includes dynamic left ventricular outflow tract obstruction, diastolic dysfunction, and myocardial ischemia. This review discusses current and emerging therapeutic strategies tailored to address the complexities of HCM-associated cardiogenic shock and other diseases with similar pathophysiology that provoke left ventricular outflow tract obstruction. We explore the role of pharmacological interventions, including the use of vasopressors and inotropes, which are crucial in stabilizing hemodynamics but require careful selection to avoid exacerbating the outflow obstruction. Additionally, the review highlights advancements in mechanical circulatory support devices such as extracorporeal membrane oxygenation (ECMO) and left ventricular assist devices (LVADs), which have become vital in the acute management of cardiogenic shock. These devices provide temporary support and bridge patients to recovery, definitive therapy, or heart transplantation, which remains a critical option for those with end-stage disease. Furthermore, the review delves into the latest research and clinical trials that are refining these therapeutic approaches, ensuring they are optimized for HCM patients. The impact of these treatments on patient outcomes, including survival rates and quality of life, is also critically assessed. In conclusion, this review underscores the importance of a tailored therapeutic approach in managing cardiogenic shock in HCM patients, integrating pharmacological and mechanical support strategies to improve outcomes in this high-risk population. Full article

(This article belongs to the Special Issue Advancements in the Epidemiology, Diagnosis and Treatment of Hypertrophic Cardiomyopathy)

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22 pages, 8866 KB

Open AccessEditor’s ChoiceArticle

Evaluation of the Efficacy and Accuracy of Super-Flexible Three-Dimensional Heart Models of Congenital Heart Disease Made via Stereolithography Printing and Vacuum Casting: A Multicenter Clinical Trial

by Isao Shiraishi, Masaaki Yamagishi, Takaya Hoashi, Yoshiaki Kato, Shigemitsu Iwai, Hajime Ichikawa, Tatsuya Nishii, Hiroyuki Yamagishi, Satoshi Yasukochi, Masaaki Kawada, Takaaki Suzuki, Takeshi Shinkawa, Naoki Yoshimura, Ryo Inuzuka, Yasutaka Hirata, Keiichi Hirose, Akio Ikai, Kisaburo Sakamoto, Yasuhiro Kotani, Shingo Kasahara, Toshiaki Hisada and Kenichi Kurosaki Show full author list Hide full author list

J. Cardiovasc. Dev. Dis. 2024, 11(12), 387; https://doi.org/10.3390/jcdd11120387 - 3 Dec 2024

Cited by 3 | Viewed by 3341

Abstract

Three-dimensional (3D) printing is an advanced technology for accurately understanding anatomy and supporting the successful surgical management of complex congenital heart disease (CHD). We aimed to evaluate whether our super-flexible 3D heart models could facilitate preoperative decision-making and surgical simulation for complex CHD. [...] Read more.

Three-dimensional (3D) printing is an advanced technology for accurately understanding anatomy and supporting the successful surgical management of complex congenital heart disease (CHD). We aimed to evaluate whether our super-flexible 3D heart models could facilitate preoperative decision-making and surgical simulation for complex CHD. The super-flexible heart models were fabricated by stereolithography 3D printing of the internal and external contours of the heart from cardiac computed tomography (CT) data, followed by vacuum casting with a polyurethane material similar in elasticity to a child’s heart. Nineteen pediatric patients with complex CHD were enrolled (median age, 10 months). The primary endpoint was defined as the percentage of patients rated as “essential” on the surgeons’ postoperative 5-point Likert scale. The accuracy of the models was validated by a non-destructive method using industrial CT. The super-flexible heart models allowed detailed anatomical diagnosis and simulated surgery with incisions and sutures. Thirteen patients (68.4%) were classified as “essential” by the primary surgeons after surgery, with a 95% confidence interval of 43.4–87.4%, meeting the primary endpoint. The product error within 90% of the total external and internal surfaces was 0.54 ± 0.21 mm. The super-flexible 3D heart models are accurate, reliable, and useful tools to assist surgeons in decision-making and allow for preoperative simulation in CHD. Full article

(This article belongs to the Section Pediatric Cardiology and Congenital Heart Disease)

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10 pages, 611 KB

Open AccessEditor’s ChoiceReview

Bridging the Gender Gap in Cardiovascular Medicine: Addressing Drug Intolerances and Personalized Care for Women with Angina/Ischemia with Non-Obstructive Coronary Artery Disease

by Johanna McChord and Peter Ong

J. Cardiovasc. Dev. Dis. 2024, 11(12), 381; https://doi.org/10.3390/jcdd11120381 - 28 Nov 2024

Cited by 2 | Viewed by 2136

Abstract

Gender medicine has increasingly underscored the necessity of addressing sex-based differences in disease prevalence and management, particularly within cardiovascular conditions and drug intolerance. Women often present cardiovascular diseases distinctively from men, with a higher prevalence of non-obstructive coronary artery disease and varied ischemic [...] Read more.

Gender medicine has increasingly underscored the necessity of addressing sex-based differences in disease prevalence and management, particularly within cardiovascular conditions and drug intolerance. Women often present cardiovascular diseases distinctively from men, with a higher prevalence of non-obstructive coronary artery disease and varied ischemic manifestations, such as coronary microvascular dysfunction and epicardial or microvascular coronary spasm. This disparity is further exacerbated by elevated drug intolerance rates among women, influenced by hormonal, genetic, and psychosocial factors. The 2024 ESC guidelines for managing chronic coronary syndromes stress the need for personalized approaches to treat angina and ischemia with non-obstructive coronary artery disease (ANOCA/INOCA), recommending a combination of antianginal medications. Despite standard treatments, up to 40% of ANOCA/INOCA patients experience refractory angina, necessitating a multifaceted approach that often involves multiple antianginal drugs, which can increase the likelihood of drug intolerances. Future research should focus on including women in drug studies and addressing sex-specific differences, while healthcare providers must be equipped to manage gender-specific drug intolerances. Enhanced awareness, individualized treatment strategies, and gender-sensitive healthcare policies are crucial for improving outcomes and bridging the gender gap in cardiovascular medicine. Full article

(This article belongs to the Special Issue Women and Cardiovascular Disease: The Gender Gap)

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15 pages, 3197 KB

Open AccessEditor’s ChoiceSystematic Review

Effect of Coenzyme Q10 Supplementation on Lipid and Glycaemic Profiles: An Umbrella Review

by Silvana Patiño-Cardona, Miriam Garrido-Miguel, Carlos Pascual-Morena, Carlos Berlanga-Macías, Maribel Lucerón-Lucas-Torres, Sofía Alfaro-González and Irene Martínez-García

J. Cardiovasc. Dev. Dis. 2024, 11(12), 377; https://doi.org/10.3390/jcdd11120377 - 25 Nov 2024

Cited by 7 | Viewed by 10298

Abstract

Coenzyme Q10 (CoQ10) has been suggested as an adjunct therapy for endocrine and metabolic disorders. The aim of this study was to synthesise the evidence for the effect of CoQ10 supplementation on lipid and/or glycaemic alterations, including total cholesterol (TC), LDL- and HDL-cholesterol [...] Read more.

Coenzyme Q10 (CoQ10) has been suggested as an adjunct therapy for endocrine and metabolic disorders. The aim of this study was to synthesise the evidence for the effect of CoQ10 supplementation on lipid and/or glycaemic alterations, including total cholesterol (TC), LDL- and HDL-cholesterol (LDL-C and HDL-C), lipoprotein a, fasting blood glucose (FBG), haemoglobin A1c (HbA1c), fasting insulin and Homeostatic Model Assessment of Insulin Resistance. A systematic search was conducted in Medline, Scopus, Web of Science and the Cochrane Library from their inception to July 2024. Meta-analyses that evaluated the effect of CoQ10 on the lipid or glycaemic profiles were included. Results were expressed as mean difference (MD) or standardised mean difference (SMD). CoQ10 showed an effect on the glycaemic profile, especially on FBG (MD from −11.21 to −5.2 mg/dL, SMD from −2.04 to −0.17) and on HbA1c (MD from −1.83 to −0.12%, SMD of −0.30). CoQ10 may also have an effect on the lipid profile, such as TC, triglycerides, HDL-C and even LDL-C, although the inconsistency of the results was somewhat higher. Supplementation with CoQ10 may be beneficial, especially in populations with diabetes mellitus or other endocrine and metabolic disorders. It could also have some effect on lipid parameters, which, together with the above, may reduce cardiovascular morbidity and mortality, although this is something that needs further research. Full article

(This article belongs to the Special Issue Food, Drugs and Environmental Exposures as Triggers of Myocardial Injury and Myocardial Infarction)

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16 pages, 563 KB

Open AccessEditor’s ChoiceSystematic Review

Cardiac Rehabilitation After Open Heart Surgery: A Narrative Systematic Review

by Eleni Delimanoli, Olav Muurlink, Pavlos Myrianthefs and Anna Korompeli

J. Cardiovasc. Dev. Dis. 2024, 11(11), 376; https://doi.org/10.3390/jcdd11110376 - 20 Nov 2024

Cited by 5 | Viewed by 5914

Abstract

Background: Postoperative cardiac rehabilitation (CR) programs are increasingly recommended by clinicians, but only a minority of patients who have undergone open heart surgery participate in such programs. Participation rates in postoperative CR, if anything, appear to be declining. This systematic review examines the [...] Read more.

Background: Postoperative cardiac rehabilitation (CR) programs are increasingly recommended by clinicians, but only a minority of patients who have undergone open heart surgery participate in such programs. Participation rates in postoperative CR, if anything, appear to be declining. This systematic review examines the effectiveness of post-operative CR and reveals possible participation barriers. Methods: A search of two scholarly databases for primary research papers published in the last decade examining the impact of post-operative CR was conducted and the resultant papers reviewed. Results: The 21 resulting studies revealed physiological functioning improvement and a reduction in mortality and readmission rates, while highlighting an enhancement in mental status. Some of the studies recognized the need for nutritional support and suggested that age, gender, access to CR centers, and socioeconomic variables impact participation in CR. Conclusions: Post-operative CR participation rates continue to decline despite increasing evidence of the value of the approach. Full article

(This article belongs to the Section Cardiac Surgery)

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