Journal of Cardiovascular Development and Disease

14 pages, 1471 KiB

Open AccessReview

Left Ventricular Ring-like Pattern: The Arrhythmic Tale of a Scarred Heart

by Vanda Parisi, Claudio Bergami, Ferdinando Pasquale, Maria Alessandra Schiavo, Irene Ruotolo, Naomi Fanciullo, Nicolò Sini, Matteo Ziacchi, Mauro Biffi, Raffaello Ditaranto, Maddalena Graziosi and Elena Biagini

J. Cardiovasc. Dev. Dis. 2025, 12(7), 275; https://doi.org/10.3390/jcdd12070275 - 17 Jul 2025

Abstract

Cardiac magnetic resonance (CMR) imaging provides significant advantages in the non-invasive diagnosis of cardiac diseases. An emerging phenotype is increasingly being described in CMR reports, the LGE “ring-like” pattern, which resembles a circumferential/semi-circumferential LV scar. Different conditions exhibit this fibrosis distribution, the majority [...] Read more.

Cardiac magnetic resonance (CMR) imaging provides significant advantages in the non-invasive diagnosis of cardiac diseases. An emerging phenotype is increasingly being described in CMR reports, the LGE “ring-like” pattern, which resembles a circumferential/semi-circumferential LV scar. Different conditions exhibit this fibrosis distribution, the majority of them being genetically determined and mostly involving cardiomyopathy-causative genes (desmosomal but also other non-desmosomal related genes). Furthermore, inflammatory diseases, such as myocarditis or sarcoidosis, could be responsible for LV fibrosis, potentially exhibiting an RL distribution. Given the heterogeneity of such conditions, effective patient management requires a stepwise and multiparametric diagnostic work-up that integrates clinical, instrumental, and genetic data to identify the specific aetiology and guide personalised treatments. Full article

(This article belongs to the Special Issue Arrhythmic Risk Stratification in Cardiomyopathies)

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14 pages, 704 KiB

Open AccessReview

From Rare Genetic Variants to Polygenic Risk: Understanding the Genetic Basis of Cardiomyopathies

by Ana Belen Garcia-Ruano, Elena Sola-Garcia, Maria Martin-Istillarty and Jose Angel Urbano-Moral

J. Cardiovasc. Dev. Dis. 2025, 12(7), 274; https://doi.org/10.3390/jcdd12070274 - 17 Jul 2025

Abstract

Cardiomyopathies represent a heterogeneous group of myocardial disorders, traditionally classified by phenotype into hypertrophic, dilated, and arrhythmogenic. Historically, these conditions have been attributed to high-penetrance rare variants in key structural genes, consistent with a classical Mendelian pattern of inheritance. However, emerging evidence suggests [...] Read more.

Cardiomyopathies represent a heterogeneous group of myocardial disorders, traditionally classified by phenotype into hypertrophic, dilated, and arrhythmogenic. Historically, these conditions have been attributed to high-penetrance rare variants in key structural genes, consistent with a classical Mendelian pattern of inheritance. However, emerging evidence suggests that this model does not fully capture the full spectrum and complexity of disease expression. Many patients do not harbor identifiable pathogenic variants, while others carrying well-known disease-causing variants remain unaffected. This highlights the role of incomplete penetrance, likely modulated by additional genetic modifiers. Recent advances in genomics have revealed a broader view of the genetic basis of cardiomyopathies, introducing new players such as common genetic variants identified as risk alleles, as well as intermediate-effect variants. This continuum of genetic risk, reflecting an overall genetic influence, interacts further with environmental and lifestyle factors, likely contributing together to the observed variability in clinical presentation. This model offers a more realistic framework for understanding genetic inheritance and helps provide a clearer picture of disease expression and penetrance. This review explores the evolving genetic architecture of cardiomyopathies, spanning from a monogenic foundation to intermediate-risk variants and complex polygenic contribution. Recognizing this continuum is essential for enhancing diagnostic accuracy, guiding family screening strategies, and enabling personalized patient management. Full article

(This article belongs to the Section Genetics)

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15 pages, 1907 KiB

Open AccessArticle

Plasma Soluble ST2 as a Prognostic Biomarker for Cardiovascular Events and Mortality in COVID-19 Patients

by Yongcui Yan, Yan Zhuang, Huihui Li and Dao Wen Wang

J. Cardiovasc. Dev. Dis. 2025, 12(7), 273; https://doi.org/10.3390/jcdd12070273 - 17 Jul 2025

Abstract

Background: Coronavirus disease 2019 (COVID-19) is frequently complicated by cardiovascular involvement. Soluble growth stimulation-expressed gene 2 (sST2) is a promising cardiovascular biomarker, but its prognostic value in COVID-19 remains unclear. Methods: This retrospective cohort study included 314 hospitalized COVID-19 patients classified into mild/moderate [...] Read more.

Background: Coronavirus disease 2019 (COVID-19) is frequently complicated by cardiovascular involvement. Soluble growth stimulation-expressed gene 2 (sST2) is a promising cardiovascular biomarker, but its prognostic value in COVID-19 remains unclear. Methods: This retrospective cohort study included 314 hospitalized COVID-19 patients classified into mild/moderate (n = 168) and severe/critical (n = 146). Plasma sST2 were measured using an enzyme-linked immunosorbent assay. Correlation analyses evaluated associations between sST2 and clinical parameters. Cox regression assessed the independent predictive value for cardiovascular events and all-cause mortality. Results: sST2 levels were significantly higher in severe/critical patients (16.877 ng/mL) than in mild/moderate cases (6.189 ng/mL) and healthy controls (4.003 ng/mL). sST2 positively correlated with cardiac injury markers (cTnI, CK-Mb, NT-proBNP), inflammatory indices (IL-1β, hsCRP), D-dimer, and inversely correlated with a left ventricular ejection fraction (r = −0.86). Elevated sST2 independently predicted cardiovascular events (HR = 2.972) and mortality (HR = 4.681). The Kaplan–Meier survival analysis demonstrated higher cardiovascular event rates and lower survival probabilities in patients with elevated sST2. The ROC curve indicated sST2 outperformed cTnI and NT-proBNP in predicting cardiovascular events (AUC = 0.898) and mortality (AUC = 0.871). Conclusion: Elevated sST2 is associated with myocardial injury, inflammation, and poor prognosis in COVID-19, supporting its value for risk stratification. Full article

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11 pages, 589 KiB

Open AccessArticle

Long-Term Prognosis in Patients with ST-Elevation Myocardial Infarction Complicated by Heart Failure with Preserved Left Ventricular Ejection Fraction

by Lidija Savic, Damjan Simic, Ratko Lasica, Gordana Krljanac, Dragan Matic, Milika Asanin, Sanja Stankovic, Nebojsa Antonijevic and Igor Mrdovic

J. Cardiovasc. Dev. Dis. 2025, 12(7), 272; https://doi.org/10.3390/jcdd12070272 - 16 Jul 2025

Abstract

Background/aim: We aimed to analyze eight-year mortality in patients with ST-elevation myocardial infarction (STEMI) complicated by the development of in-hospital heart failure with preserved ejection fraction (HFpEF). Method: We analyzed 3260 STEMI patients treated with primary PCI (pPCI). Reduced EF was defined as [...] Read more.

Background/aim: We aimed to analyze eight-year mortality in patients with ST-elevation myocardial infarction (STEMI) complicated by the development of in-hospital heart failure with preserved ejection fraction (HFpEF). Method: We analyzed 3260 STEMI patients treated with primary PCI (pPCI). Reduced EF was defined as value <50% and preserved EF as value ≥50%. Patients were divided in three groups: without HF, with HFpEF, and with HF with reduced EF (HFrEF). Patients with cardiogenic shock at admission were excluded. Results: In-hospital HF was registered in 759 (23.2%) patients. Among the patients with in-hospital HF, 80 (10.5%) patients had HFpEF. Patients with HFpEF had significantly higher 8-year mortality compared with patients without HF (11.2% vs. 3.5%, respectively, p < 0.001), but significantly lower mortality compared with patients with HFrEF: 11.2% vs. 25.1%, respectively, p < 0.001. In the Cox regression model, HFpEF and HFrEF were independent predictors for 8-year mortality-HFpEF: HR1.85 (95%CI 1.26–4.25); HFrEF: 4.89 (95%CI 3.19–6.42). Conclusion: Development of in-hospital HFpEF in STEMI patients was an independent predictor for long-term mortality. The negative prognostic impact of HFpEF was weaker when compared to the impact of in-hospital HFrEF. Full article

(This article belongs to the Section Cardiovascular Clinical Research)

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7 pages, 618 KiB

Open AccessCommunication

Oral Anticoagulants in Chronic Thromboembolic Pulmonary Hypertension: Tradition or Innovation?

by Domenico Laviola, Giovanna Manzi, Tommaso Recchioni, Maria Cristina Luise, Valentina Mercurio, Alexandra Mihai, Roberto Badagliacca, Silvia Papa and Carmine Dario Vizza

J. Cardiovasc. Dev. Dis. 2025, 12(7), 271; https://doi.org/10.3390/jcdd12070271 - 16 Jul 2025

Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) can complicate the clinical course of patients with acute pulmonary embolism, with a variable prevalence of 0.5–4%. Beyond specific therapeutic strategies, including pulmonary endarterectomy, balloon pulmonary angioplasty and pulmonary vasodilators, lifelong anticoagulation still represents the mainstay of treatment [...] Read more.

Chronic thromboembolic pulmonary hypertension (CTEPH) can complicate the clinical course of patients with acute pulmonary embolism, with a variable prevalence of 0.5–4%. Beyond specific therapeutic strategies, including pulmonary endarterectomy, balloon pulmonary angioplasty and pulmonary vasodilators, lifelong anticoagulation still represents the mainstay of treatment for this condition. The main historical experience supports the use of vitamin K antagonists (VKAs) in CTEPH patients; conversely, the efficacy and safety of direct oral anticoagulants (DOACs) in this setting are unclear. Growing experience, mainly from small studies and registries, is improving our knowledge, showing that DOACs may represent a valid and promising alternative to warfarin in CTEPH patients. Therefore, in the management of cases with a newly diagnosed CTEPH, clinicians are very often in the difficult position of (a) having to choose which anticoagulant to initiate in anticoagulant-naïve patients or (b) having to evaluate whether it is necessary to switch to a VKA in patients already on DOACs. This article aims to critically summarize the current evidence comparing DOACs and VKAs in CTEPH, discussing their efficacy and safety profiles and exploring their clinical applicability. Full article

(This article belongs to the Special Issue Pulmonary Hypertension: Far from a Rare Disease—a Journey from Diagnosis to Treatment)

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20 pages, 2693 KiB

Open AccessReview

Navigating Cardiotoxicity in Immune Checkpoint Inhibitors: From Diagnosis to Long-Term Management

by Simone Nardin, Beatrice Ruffilli, Pietro Costantini, Rocco Mollace, Ida Taglialatela, Matteo Pagnesi, Mauro Chiarito, Davide Soldato, Davide Cao, Benedetta Conte, Monica Verdoia, Alessandra Gennari and Matteo Nardin

J. Cardiovasc. Dev. Dis. 2025, 12(7), 270; https://doi.org/10.3390/jcdd12070270 - 16 Jul 2025

Abstract

The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, significantly improving patient outcomes across multiple malignancies. Nonetheless, these therapies are associated with immune-related adverse effects, including cardiotoxicity, which remains a critical concern. This review provides a comprehensive analysis of ICI-related cardiotoxicity, [...] Read more.

The advent of immune checkpoint inhibitors (ICIs) has revolutionized cancer treatment, significantly improving patient outcomes across multiple malignancies. Nonetheless, these therapies are associated with immune-related adverse effects, including cardiotoxicity, which remains a critical concern. This review provides a comprehensive analysis of ICI-related cardiotoxicity, encompassing its pathophysiological mechanisms, risk factors, diagnostic modalities, and management strategies. The onset of cardiotoxicity varies widely, ranging from acute myocarditis to long-term cardiovascular complications. Early identification through clinical assessment, biomarkers, and advanced imaging techniques is crucial for timely intervention. Management strategies include high-dose corticosteroids, other immunosuppressive agents, and supportive therapies, with a focus on balancing oncologic efficacy and cardiovascular safety. Additionally, rechallenging patients with ICIs following cardiotoxic events remains a complex clinical decision requiring multidisciplinary evaluation. As immunotherapy indications expand to include high-risk populations in a curative setting too, optimizing screening, prevention, and treatment strategies is essential to mitigate cardiovascular risks. A deep understanding of the molecular and clinical aspects of ICI-related cardiotoxicity will enhance patient safety and therapeutic decision-making, underscoring the need for ongoing research in this rapidly evolving field. Full article

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14 pages, 4004 KiB

Open AccessArticle

Viability and Longevity of Human Miniaturized Living Myocardial Slices

by Ziyu Zhou, Yvar P. van Steenis, Surya Henry, Elisa C. H. van Doorn, Jorik H. Amesz, Pieter C. van de Woestijne, Natasja M. S. de Groot, Olivier C. Manintveld, Beatrijs Bartelds and Yannick J. H. J. Taverne

J. Cardiovasc. Dev. Dis. 2025, 12(7), 269; https://doi.org/10.3390/jcdd12070269 - 15 Jul 2025

Abstract

Living myocardial slices (LMSs) have shown great promise in cardiac research, allowing multicellular and complex interplay analyses with disease and patient specificity, yet their wider clinical use is limited by the large tissue sizes usually required. We therefore produced mini-LMSs (<10 mm² [...] Read more.

Living myocardial slices (LMSs) have shown great promise in cardiac research, allowing multicellular and complex interplay analyses with disease and patient specificity, yet their wider clinical use is limited by the large tissue sizes usually required. We therefore produced mini-LMSs (<10 mm²) from routine human cardiac surgery specimens and compared them with medium (10–30 mm²) and large (>30 mm²) slices. Size effects on biomechanical properties were examined with mathematical modeling, and viability, contraction profiles, and histological integrity were followed for 14 days. In total, 34 mini-, 25 medium, and 30 large LMS were maintained viable, the smallest measuring only 2 mm². Peak twitch force proved to be size-independent, whereas time-to-peak shortened as slice area decreased. Downsized LMSs displayed excellent contractile behavior for five to six days, after which a gradual functional decline and micro-architectural changes emerged. These findings confirm, for the first time, that mini-LMSs are feasible and viable, enabling short-term, patient-specific functional studies and pharmacological testing when tissue is scarce. Full article

(This article belongs to the Special Issue In Vitro Models for Cardiac Development, Regeneration, and Disease: Advances and Challenges)

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19 pages, 3514 KiB

Open AccessReview

Indirect Myocardial Injury in Polytrauma: Mechanistic Pathways and the Clinical Utility of Immunological Markers

by Makhabbat Bekbossynova, Timur Saliev, Murat Mukarov, Madina Sugralimova, Arman Batpen, Anar Kozhakhmetova and Aknur Zhanbolat

J. Cardiovasc. Dev. Dis. 2025, 12(7), 268; https://doi.org/10.3390/jcdd12070268 - 14 Jul 2025

Abstract

Myocardial injury following polytrauma is a significant yet often underdiagnosed condition that contributes to acute cardiac dysfunction and long-term cardiovascular complications. This review examines the role of systemic inflammation, oxidative stress, neuro-hormonal activation, and immune dysregulation in trauma-induced myocardial damage. Key immunological markers, [...] Read more.

Myocardial injury following polytrauma is a significant yet often underdiagnosed condition that contributes to acute cardiac dysfunction and long-term cardiovascular complications. This review examines the role of systemic inflammation, oxidative stress, neuro-hormonal activation, and immune dysregulation in trauma-induced myocardial damage. Key immunological markers, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1), and adhesion molecules (ICAM-1, VCAM-1), are implicated in endothelial dysfunction, myocardial apoptosis, and ventricular remodeling. The interplay between these factors potentially exacerbates cardiac injury, increasing the risk of heart failure. Biomarker-guided approaches for early detection, combined with advanced imaging techniques such as speckle-tracking echocardiography and cardiac MRI, offer promising avenues for risk stratification and targeted interventions. Anti-inflammatory and oxidative stress-modulating therapies may mitigate myocardial damage and improve outcomes. This article highlights the clinical relevance of integrating immunological markers into diagnostic and therapeutic strategies to enhance the management of trauma-related cardiac dysfunction and reduce long-term morbidity. Full article

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

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Graphical abstract

13 pages, 450 KiB

Open AccessSystematic Review

Activated Clotting Time and Haemostatic Complications in Patients Receiving ECMO Support: A Systematic Review

by Daniel Schwaiger, Lukas Schausberger, Benedikt Treml, Dragana Jadzic, Nicole Innerhofer, Christoph Oberleitner, Zoran Bukumirić, Igor Spurnić and Sasa Rajsic

J. Cardiovasc. Dev. Dis. 2025, 12(7), 267; https://doi.org/10.3390/jcdd12070267 - 13 Jul 2025

Abstract

Background: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to prevent clotting, typically using unfractionated heparin (UFH). However, anticoagulation carries a bleeding risk, necessitating monitoring. Activated clotting time (ACT) is a commonly used monitoring tool for UFH anticoagulation. However, systematized evidence linking ACT [...] Read more.

Background: Extracorporeal membrane oxygenation (ECMO) requires systemic anticoagulation to prevent clotting, typically using unfractionated heparin (UFH). However, anticoagulation carries a bleeding risk, necessitating monitoring. Activated clotting time (ACT) is a commonly used monitoring tool for UFH anticoagulation. However, systematized evidence linking ACT monitoring with haemostatic complications (bleeding and thrombosis) is missing. Methods: A systematic review (Scopus and PubMed, up to 13 July 2024) including studies reporting on the patients receiving ECMO support with UFH anticoagulation monitored using ACT was performed. Results: A total of 3536 publications were identified, of which 30 (2379 patients) were included in the final review. Thirteen studies found no significant association between ACT values and haemorrhage, while four studies suggested a relationship between elevated ACT levels and bleeding events. Eight studies demonstrated no association between ACT values and the occurrence of thrombosis. Major bleeding was most common (49%, 13 studies with 501 events), while the pooled rate of thrombosis was 25% (16 studies with 309 events) and in-hospital mortality was 51% (17 studies, 693/1390 patients). Conclusions: Despite advancements in ECMO, the optimal approach for anticoagulation monitoring remains undefined. Most studies in this review did not establish a significant relationship between ACT levels and haemostatic complications. Based on the current evidence, ACT does not appear to be a reliable tool for monitoring anticoagulation in patients receiving ECMO, and alternative methods should be considered. Full article

(This article belongs to the Special Issue Critical Care Update: Cardiology)

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20 pages, 2891 KiB

Open AccessReview

MAPK, PI3K/Akt Pathways, and GSK-3β Activity in Severe Acute Heart Failure in Intensive Care Patients: An Updated Review

by Massimo Meco, Enrico Giustiniano, Fulvio Nisi, Pierluigi Zulli and Emiliano Agosteo

J. Cardiovasc. Dev. Dis. 2025, 12(7), 266; https://doi.org/10.3390/jcdd12070266 - 10 Jul 2025

Abstract

Acute heart failure (AHF) is a clinical syndrome characterized by the sudden onset or rapid worsening of heart failure signs and symptoms, frequently triggered by myocardial ischemia, pressure overload, or cardiotoxic injury. A central component of its pathophysiology is the activation of intracellular [...] Read more.

Acute heart failure (AHF) is a clinical syndrome characterized by the sudden onset or rapid worsening of heart failure signs and symptoms, frequently triggered by myocardial ischemia, pressure overload, or cardiotoxic injury. A central component of its pathophysiology is the activation of intracellular signal transduction cascades that translate extracellular stress into cellular responses. Among these, the mitogen-activated protein kinase (MAPK) pathways have received considerable attention due to their roles in mediating inflammation, apoptosis, hypertrophy, and adverse cardiac remodeling. The canonical MAPK cascades—including extracellular signal-regulated kinases (ERK1/2), p38 MAPK, and c-Jun N-terminal kinases (JNK)—are activated by upstream stimuli such as angiotensin II (Ang II), aldosterone, endothelin-1 (ET-1), and sustained catecholamine release. Additionally, emerging evidence highlights the role of receptor-mediated signaling, cellular stress, and myeloid cell-driven coagulation events in linking MAPK activation to fibrotic remodeling following myocardial infarction. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling cascade plays a central role in regulating cardiomyocyte survival, hypertrophy, energy metabolism, and inflammation. Activation of the PI3K/Akt pathway has been shown to confer cardioprotective effects by enhancing anti-apoptotic and pro-survival signaling; however, aberrant or sustained activation may contribute to maladaptive remodeling and progressive cardiac dysfunction. In the context of AHF, understanding the dual role of this pathway is crucial, as it functions both as a marker of compensatory adaptation and as a potential therapeutic target. Recent reviews and preclinical studies have linked PI3K/Akt activation with reduced myocardial apoptosis and attenuation of pro-inflammatory cascades that exacerbate heart failure. Among the multiple signaling pathways involved, glycogen synthase kinase-3β (GSK-3β) has emerged as a key regulator of apoptosis, inflammation, metabolic homeostasis, and cardiac remodeling. Recent studies underscore its dual function as both a negative regulator of pathological hypertrophy and a modulator of cell survival, making it a compelling therapeutic candidate in acute cardiac settings. While earlier investigations focused primarily on chronic heart failure and long-term remodeling, growing evidence now supports a critical role for GSK-3β dysregulation in acute myocardial stress and injury. This comprehensive review discusses recent advances in our understanding of the MAPK signaling pathway, the PI3K/Akt cascade, and GSK-3β activity in AHF, with a particular emphasis on mechanistic insights, preclinical models, and emerging therapeutic targets. Full article

(This article belongs to the Topic Molecular and Cellular Mechanisms of Heart Disease)

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19 pages, 2429 KiB

Open AccessReview

Cardiac Rehabilitation After Mitral Valve Intervention: Tailored Assessment, Management, and Exercise Training

by Francesco Perone, Monica Loguercio, Federica Sabato, Annalisa Pasquini, Marina Ostojic, Ashot Avagimyan, Vaida Sileikiene, Joanna Popiolek-Kalisz, Aneta Aleksova and Marco Ambrosetti

J. Cardiovasc. Dev. Dis. 2025, 12(7), 265; https://doi.org/10.3390/jcdd12070265 - 9 Jul 2025

Abstract

Cardiac rehabilitation should be suggested after mitral valve intervention. Physical exercise is associated with improved cardiorespiratory fitness and clinical outcome and reduced rehospitalization and mortality in patients after heart valve surgery. Tailored assessment is the first step before starting a cardiac rehabilitation program. [...] Read more.

Cardiac rehabilitation should be suggested after mitral valve intervention. Physical exercise is associated with improved cardiorespiratory fitness and clinical outcome and reduced rehospitalization and mortality in patients after heart valve surgery. Tailored assessment is the first step before starting a cardiac rehabilitation program. Physical examination, electrocardiogram, echocardiography, and peak exercise capacity stratify the risk of these patients when prescribing appropriate supervised aerobic and resistance exercise training. Cardiac rehabilitation participation impacts physical capacity, psychosocial function, and prognosis in patients after mitral valve surgery and transcatheter edge-to-edge repair. However, further evidence is needed on the efficacy and safety of cardiac rehabilitation programs, as well as standardization. In this review, we provide a contemporary and comprehensive update on the role of cardiac rehabilitation in patients after mitral valve intervention, after both mitral valve surgery and transcatheter mitral valve implantation. Specifically, we focus our review on the tailored assessment and management of these patients from post-operative to cardiac rehabilitation. Full article

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15 pages, 3765 KiB

Open AccessArticle

Diagnostic Performance of Dynamic Myocardial Perfusion Imaging Using Third-Generation Dual-Source Computed Tomography in Patients with Intermediate Pretest Probability of Coronary Artery Disease

by Sung Min Ko, Sung-Jin Cha, Hyunjung Kim, Pil-Hyun Jeon, Sang-Hyun Jeon, Sung Gyun Ahn and Jung-Woo Son

J. Cardiovasc. Dev. Dis. 2025, 12(7), 264; https://doi.org/10.3390/jcdd12070264 - 9 Jul 2025

Abstract

(1) Background: Our aim was to evaluate the diagnostic performance of combined coronary computed tomography angiography (CCTA) and dynamic CT myocardial perfusion imaging (CT-MPI) for detecting hemodynamically significant coronary artery disease (CAD) in patients with intermediate pretest probability. (2) Methods: Patients with an [...] Read more.

(1) Background: Our aim was to evaluate the diagnostic performance of combined coronary computed tomography angiography (CCTA) and dynamic CT myocardial perfusion imaging (CT-MPI) for detecting hemodynamically significant coronary artery disease (CAD) in patients with intermediate pretest probability. (2) Methods: Patients with an intermediate pretest probability of CAD were retrospectively enrolled. All patients underwent CCTA and dynamic CT-MPI using a third-generation dual-source CT scanner prior to invasive coronary angiography (ICA). Anatomically significant stenosis was defined as ≥50% luminal narrowing on both CCTA and ICA. Fractional flow reserve (FFR) was performed during ICA in selected cases. Hemodynamically significant CAD was defined per vessel as FFR ≤ 0.80, angiographic stenosis ≥70%, or having undergone revascularization. The diagnostic performance of CCTA alone and CCTA combined with CT-MPI was compared against this reference standard. (3) Results: Seventy-four patients (mean age, 66.8 ± 11.1 years; 59 men) were included. The median coronary calcium score was 508.5 Agatston units (interquartile range: 147–1173). ICA and CCTA detected anatomically significant stenoses in 137 (61.7%) and 146 (65.8%) coronary vessels, respectively, and in 62 (83.8%) and 71 (95.9%) patients, respectively. Hemodynamically significant stenosis was present in 56 patients (76%) and 99 vessels (45%). On a per-vessel basis, CCTA alone yielded a sensitivity of 96.7%, specificity of 60.3%, positive predictive value (PPV) of 64.4%, and negative predictive value (NPV) of 96.1%. Combined CCTA and CT-MPI demonstrated a sensitivity of 90.1%, specificity of 84.3%, PPV of 82.7%, and NPV of 91.1%. The area under the receiver operating characteristic curve improved from 0.787 (95% confidence interval: 0.73–0.84) for CCTA to 0.872 (95% confidence interval: 0.82–0.91) for the combined approach (p < 0.05). The median total radiation dose for both CCTA and CT-MPI was 8.05 mSv (interquartile range: 6.71–11.0). (4) Conclusions: In patients with intermediate pretest probability of CAD, combining CCTA with dynamic CT-MPI significantly enhances the diagnostic performance for identifying hemodynamically significant coronary stenosis compared to CCTA alone. 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, 4136 KiB

Open AccessSystematic Review

Surgical vs. Medical Management of Infective Endocarditis Following TAVR: A Systematic Review and Meta-Analysis

by Dimitrios E. Magouliotis, Serge Sicouri, Massimo Baudo, Francesco Cabrucci, Yoshiyuki Yamashita and Basel Ramlawi

J. Cardiovasc. Dev. Dis. 2025, 12(7), 263; https://doi.org/10.3390/jcdd12070263 - 9 Jul 2025

Abstract

Background: Infective endocarditis after transcatheter aortic valve replacement (TAVR-IE) is a rare but severe complication associated with high morbidity and mortality. The optimal treatment strategy—surgical explantation versus medical therapy—remains uncertain, particularly given the technical demands of TAVR removal and the advanced age of [...] Read more.

Background: Infective endocarditis after transcatheter aortic valve replacement (TAVR-IE) is a rare but severe complication associated with high morbidity and mortality. The optimal treatment strategy—surgical explantation versus medical therapy—remains uncertain, particularly given the technical demands of TAVR removal and the advanced age of many affected patients. Methods: We conducted a systematic review and meta-analysis of studies comparing the surgical and medical management of TAVR-IE. Primary outcomes included 30-day mortality and 1-year survival. Secondary analyses explored microbiological profiles, patient demographics, prosthesis type, postoperative complications, and surgical indications. A qualitative synthesis of surgical explantation techniques and reconstructive strategies was also performed based on recent consensus recommendations. Results: Three studies comprising 1557 patients with TAVR-IE were included; 155 (10.0%) underwent surgical treatment. Thirty-day mortality was comparable between groups (surgical: 9.7%; medical: 8.4%), while the pooled odds ratio for one-year survival did not reach statistical significance (OR: 1.91, 95% CI: 0.36–10.22; I² = 88%). However, single-center outcomes demonstrated markedly improved survival with surgery (96% vs. 51%). The most common surgical indications included severe valvular dysfunction (50.3%), aortic root abscess (26.5%), and large vegetations (21.3%), in line with current guideline recommendations. Postoperative complications included acute renal failure (10%) and longer hospitalizations (19.8 vs. 18 days), although these were not statistically different. Contemporary explant strategies—such as the Double Kocher, Tourniquet, and Y-incision aortic enlargement techniques—were highlighted as critical tools for surgical success. Conclusions: While underutilized, surgical intervention for TAVR-IE may offer significant survival benefits in select patients, particularly when guided by established indications and performed at high-volume centers. Outcomes depend heavily on timing, surgical expertise, and appropriate patient selection. As TAVR expands to younger populations, TAVR-IE will become increasingly relevant, necessitating early multidisciplinary involvement and broader familiarity with advanced explant techniques among cardiac surgeons. Full article

(This article belongs to the Special Issue Contemporary Controversies and Evolving Paradigms in Cardiovascular Surgery)

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6 pages, 1215 KiB

Open AccessCase Report

Aorto-Esophageal Fistula Caused by Vascular Malformation: A Case Description and an Analysis of the Literature

by Wenzhao Zhang, Xu Hu and Jianqun Yu

J. Cardiovasc. Dev. Dis. 2025, 12(7), 262; https://doi.org/10.3390/jcdd12070262 - 8 Jul 2025

Abstract

Aorto-esophageal fistula (AEF) is a condition with an extremely high mortality rate that often causes massive gastrointestinal bleeding, commonly resulting from esophageal perforation due to foreign bodies or aortic aneurysmal malformations. This case report introduces an elderly male patient who experienced hematemesis for [...] Read more.

Aorto-esophageal fistula (AEF) is a condition with an extremely high mortality rate that often causes massive gastrointestinal bleeding, commonly resulting from esophageal perforation due to foreign bodies or aortic aneurysmal malformations. This case report introduces an elderly male patient who experienced hematemesis for longer than 16 h without obvious cause. The patient did not receive relief from endoscopic compression hemostasis. Through computed tomography angiography (CTA), a tortuous and thickened vessel was found in the descending aorta of the patient, which entered the esophagus. The diagnosis was AEF caused by vascular malformation. which has not been previously documented in the literature. Full article

(This article belongs to the Special Issue Clinical Applications of Cardiovascular Computed Tomography (CT))

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16 pages, 2023 KiB

Open AccessArticle

The Prognostic Implication of Left Atrial Strain Parameters with Conventional Left Atrial Parameters for the Prediction of Adverse Outcomes in Asian Patients with Hypertrophic Cardiomyopathy—An Echocardiographic Study

by Andre Seah, Tony Y. W. Li, Novi Yanti Sari, Chi-Hang Lee, Tiong-Cheng Yeo, James W. L. Yip, Yoke Ching Lim, Kian-Keong Poh, William K. F. Kong, Weiqin Lin, Ching-Hui Sia and Raymond C. C. Wong

J. Cardiovasc. Dev. Dis. 2025, 12(7), 261; https://doi.org/10.3390/jcdd12070261 - 8 Jul 2025

Abstract

Background/Objectives: Left atrial function can be a tool for risk stratification for hypertrophic cardiomyopathy (HCM). Over the past decade, there has been growing interest in the application of strain analysis for earlier and more accurate prediction of cardiovascular disease prognosis. This study aimed [...] Read more.

Background/Objectives: Left atrial function can be a tool for risk stratification for hypertrophic cardiomyopathy (HCM). Over the past decade, there has been growing interest in the application of strain analysis for earlier and more accurate prediction of cardiovascular disease prognosis. This study aimed to investigate the performance of left atrial strain analysis compared to conventional left atrial measures in predicting clinical outcomes in Asian patients with HCM. Methods and Results: This was a retrospective study involving 291 patients diagnosed with HCM between 2010 and 2017. Left atrial volumes were assessed using the method of discs in orthogonal plans at both end diastole and end systole. Left atrial (LA) strain was obtained using a post-hoc analysis with TOMTEC software. We tested the various left atrial parameters against outcomes of (1) heart failure hospitalization and (2) event-free survival from a composite of adverse events, including all-cause mortality, ventricular tachycardia (VT)/ventricular fibrillation (VF) events, appropriate device therapy if an implantable cardioverter defibrillator (ICD) was implanted, stroke, and heart failure hospitalization. The patients had a mean age of 59.0 ± 16.7 years with a male preponderance (71.2%). The cumulative event-free survival over a follow-up of 3.9 ± 2.7 years was 55.2% for patients with an abnormal LA strain versus 82.4% for patients without one (p < 0.001). Multivariable Cox regression analyses were performed separately for each LA parameter, adjusting for age, sex, LV mass index, LV ejection fraction (EF), E/e’, the presence of LV outflow tract (LVOT) obstruction at rest, and atrial fibrillation. An analysis showed that all parameters except for LAEF demonstrated an independent association with heart failure hospitalization. Left atrial strain outperformed the rest of the parameters by demonstrating an association with a composite of adverse events. Conclusions: In Asian patients with HCM, measures of left atrial strain were independently associated with heart failure hospitalization and a composite of adverse outcomes. Left atrial strain may be used as a tool to predict adverse outcomes in patients with HCM. Full article

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

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14 pages, 859 KiB

Open AccessReview

Divergent Cardiac Adaptations in Endurance Sport: Atrial Fibrillation Markers in Marathon Versus Ultramarathon Athletes

by Zbigniew Waśkiewicz, Eduard Bezuglov, Oleg Talibov, Robert Gajda, Zhassyn Mukhambetov, Daulet Azerbaev and Sergei Bondarev

J. Cardiovasc. Dev. Dis. 2025, 12(7), 260; https://doi.org/10.3390/jcdd12070260 - 7 Jul 2025

Abstract

Endurance training induces significant cardiac remodeling, with evidence suggesting that prolonged high-intensity exercise may increase the risk of atrial fibrillation (AF). However, physiological responses differ by event type. This review compares AF-related markers in marathon and ultramarathon runners, focusing on structural adaptations, inflammatory [...] Read more.

Endurance training induces significant cardiac remodeling, with evidence suggesting that prolonged high-intensity exercise may increase the risk of atrial fibrillation (AF). However, physiological responses differ by event type. This review compares AF-related markers in marathon and ultramarathon runners, focusing on structural adaptations, inflammatory and endothelial biomarkers, and the incidence of arrhythmias. A systematic analysis of 29 studies revealed consistent left atrial (LA) enlargement in marathon runners linked to elevated AF risk and fibrosis markers such as Galectin-3 and PIIINP. In contrast, ultramarathon runners exhibited right atrial (RA) dilation and increased systemic inflammation, as indicated by elevated high-sensitivity C-reactive protein (hs-CRP) and soluble E-selectin levels. AF incidence in marathoners ranged from 0.43 per 100 person-years to 4.4%, while direct AF incidence data remain unavailable for ultramarathon populations, highlighting a critical evidence gap. These findings suggest distinct remodeling patterns and pathophysiological profiles between endurance disciplines, with implications for athlete screening and cardiovascular risk stratification. Full article

(This article belongs to the Special Issue Extensive Approach to Atrial Fibrillation: Background and Future Perspectives)

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14 pages, 1250 KiB

Open AccessArticle

Stroke Risk Stratification in Incident Atrial Fibrillation: A Sex-Specific Evaluation of CHA2DS2-VA and CHA2DS2-VASc

by Jose L. Clua-Espuny, Anna Panisello-Tafalla, Jorgina Lucas-Noll, Eulàlia Muria-Subirats, Teresa Forcadell-Arenas, Juan M. Carrera-Ortiz, Pedro Molto-Balado, Josep Clua-Queralt, Immaculada Fusté-Anguera and Silvia Reverte-Vilarroya

J. Cardiovasc. Dev. Dis. 2025, 12(7), 259; https://doi.org/10.3390/jcdd12070259 - 5 Jul 2025

Abstract

(1) Background: In the absence of locally validated tools, the CHA2DS2-VA score has been suggested as a substitute for the CHA2DS2-VASc score. This study compared the potential discrepancies between these scores. (2) Methods: The observational, retrospective, and community-based study included a cohort of [...] Read more.

(1) Background: In the absence of locally validated tools, the CHA2DS2-VA score has been suggested as a substitute for the CHA2DS2-VASc score. This study compared the potential discrepancies between these scores. (2) Methods: The observational, retrospective, and community-based study included a cohort of 3370 patients with a new diagnosis of atrial fibrillation (AF) between 1 January 2015 and 31 December 2024. (3) Results: AF prevalence was 8.4%, which was significantly higher in men. The mean age was 80.1 (SD ± 6.24) years. Women (42.8%) were older (80.9 SD ± 6.1 vs. 79.5 SD ± 6.23; p < 0.001). Men had more instances of diabetes mellitus, peripheral vascular disease, coronary artery disease, and chronic obstructive pulmonary disease, as well as a higher Charlson Comorbidity Index. Conversely, women exhibited a higher proportion ≥75 years, including cognitive impairment, dyslipidemia, and higher stroke risk, as assessed by the CHA2DS2-VASc score (p < 0.001) but not by the CHA2DS2-VA score (p = 0.071). The CHA2DS2-VA score reduced the sex-based risk stratification differences, and only 3.2% of women were reclassified as being at very low risk (CHA2DS2-VA < 2). (4) Conclusions: The CHA2DS2-VA score notably redefined sex-based thromboembolic risk stratification profiles, with no sex-based disparities in the selection of OAC treatment modality. The clinical utility of CHA2DS2-VA remains a subject of ongoing debate. Full article

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14 pages, 286 KiB

Open AccessReview

The Diagnostic Value of Copy Number Variants in Genetic Cardiomyopathies and Channelopathies

by Valerio Caputo, Virginia Veronica Visconti, Enrica Marchionni, Valentina Ferradini, Clara Balsano, Pasquale De Vico, Leonardo Calò, Ruggiero Mango, Giuseppe Novelli and Federica Sangiuolo

J. Cardiovasc. Dev. Dis. 2025, 12(7), 258; https://doi.org/10.3390/jcdd12070258 - 4 Jul 2025

Abstract

Sudden cardiac death represents an unexpected death for which a strong underlying genetic background has been described. The primary causes are identified in cardiomyopathies and channelopathies, which are heart diseases of the muscle and electrical system, respectively, without coronary artery disease, hypertension, valvular [...] Read more.

Sudden cardiac death represents an unexpected death for which a strong underlying genetic background has been described. The primary causes are identified in cardiomyopathies and channelopathies, which are heart diseases of the muscle and electrical system, respectively, without coronary artery disease, hypertension, valvular disease, and congenital heart malformations. Genetic variants, especially single nucleotide variants and short insertions/deletions impacting essential myocardial functions, have shown that cardiomyopathies display high heritability. However, genetic heterogeneity, incomplete penetrance, and variable expression may complicate the interpretation of genetic findings, thus delaying the management of seriously at-risk patients. Moreover, recent studies show that the diagnostic yield related to genetic cardiomyopathies ranges from 28 to 40%, raising the need for further research. In this regard, investigating the occurrence of structural variants, especially copy number variants, may be crucial. Based on these considerations, this review aims to provide an overview of copy number variants identified in cardiomyopathies and discuss them, considering diagnostic yield. This review will ultimately address the necessity of incorporating copy number variants into routine genetic testing for cardiomyopathies and channelopathies, a process increasingly enabled by advances in next-generation sequencing technologies. Full article

(This article belongs to the Section Genetics)

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Graphical abstract

4 pages, 1337 KiB

Open AccessCase Report

A Tale of Two “Unexpected” Asystoles

by Giacomo Mugnai, Bruna Bolzan, Elena Franchi and Luca Tomasi

J. Cardiovasc. Dev. Dis. 2025, 12(7), 257; https://doi.org/10.3390/jcdd12070257 - 4 Jul 2025

Abstract

We report two cases of prolonged “unexpected” asystoles in patients with a wearable cardioverter-defibrillator (WCD) and a subcutaneous implantable cardioverter-defibrillator (ICD), respectively, which were promptly recognized and successfully managed. As these devices are designed to recognize and treat malignant tachyarrhythmias but do not [...] Read more.

We report two cases of prolonged “unexpected” asystoles in patients with a wearable cardioverter-defibrillator (WCD) and a subcutaneous implantable cardioverter-defibrillator (ICD), respectively, which were promptly recognized and successfully managed. As these devices are designed to recognize and treat malignant tachyarrhythmias but do not provide pacing capabilities, it is crucial to identify patients with paroxysmal conduction disorders who might require backup pacing. For this reason, it is also important to leverage the monitoring features of both devices and their ability to detect the occurrence of bradyarrhythmias. Full article

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Journal of Cardiovascular Development and Disease

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