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Biophysics and Clinical Effectiveness of Irreversible Electroporation for Catheter Ablation of Atrial Fibrillation
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Genetic Spectrum of Lithuanian Familial Hypercholesterolemia Patients
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Leaving Nothing Behind: Expanding the Clinical Frontiers of Drug-Coated Balloon Angioplasty in Coronary Artery Disease
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Percutaneous Coronary Intervention for Left Main Disease in High Bleeding Risk: Outcomes from a Subanalysis of the Delta 2 Registry
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Patients with Gastrointestinal Bleeding and Atrial Fibrillation: Potential Ideal Target for Epicardial Appendage Occlusion
Journal Description
Journal of Cardiovascular Development and Disease
Journal of Cardiovascular Development and Disease
is an international, scientific, peer-reviewed, open access journal on cardiovascular medicine published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Cardiac and Cardiovascular Systems) / CiteScore - Q2 (General Pharmacology, Toxicology and Pharmaceutics )
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 28.8 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
Impact Factor:
2.3 (2024);
5-Year Impact Factor:
2.7 (2024)
Latest Articles
Indirect Myocardial Injury in Polytrauma: Mechanistic Pathways and the Clinical Utility of Immunological Markers
J. Cardiovasc. Dev. Dis. 2025, 12(7), 268; https://doi.org/10.3390/jcdd12070268 (registering DOI) - 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,
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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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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
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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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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
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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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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
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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.
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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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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
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(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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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
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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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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
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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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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
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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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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
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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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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
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(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
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(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.
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Open AccessReview
The Diagnostic Value of Copy Number Variants in Genetic Cardiomyopathies and Channelopathies
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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
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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
Open AccessCase Report
A Tale of Two “Unexpected” Asystoles
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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
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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
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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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Open AccessReview
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
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
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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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Open AccessSystematic Review
Discordant High-Gradient Aortic Stenosis: A Systematic Review
by
Nadera N. Bismee, Mohammed Tiseer Abbas, Hesham Sheashaa, Fatmaelzahraa E. Abdelfattah, Juan M. Farina, Kamal Awad, Isabel G. Scalia, Milagros Pereyra Pietri, Nima Baba Ali, Sogol Attaripour Esfahani, Omar H. Ibrahim, Steven J. Lester, Said Alsidawi, Chadi Ayoub and Reza Arsanjani
J. Cardiovasc. Dev. Dis. 2025, 12(7), 255; https://doi.org/10.3390/jcdd12070255 - 3 Jul 2025
Abstract
Aortic stenosis (AS), the most common valvular heart disease, is traditionally graded based on several echocardiographic quantitative parameters, such as aortic valve area (AVA), mean pressure gradient (MPG), and peak jet velocity (Vmax). This systematic review evaluates the clinical significance and prognostic implications
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Aortic stenosis (AS), the most common valvular heart disease, is traditionally graded based on several echocardiographic quantitative parameters, such as aortic valve area (AVA), mean pressure gradient (MPG), and peak jet velocity (Vmax). This systematic review evaluates the clinical significance and prognostic implications of discordant high-gradient AS (DHG-AS), a distinct hemodynamic phenotype characterized by elevated MPG despite a preserved AVA (>1.0 cm2). Although often overlooked, DHG-AS presents unique diagnostic and therapeutic challenges, as high gradients remain a strong predictor of adverse outcomes despite moderately reduced AVA. Sixty-three studies were included following rigorous selection and quality assessment of the key studies. Prognostic outcomes across five key studies were discrepant: some showed better survival in DHG-AS compared to concordant high-gradient AS (CHG-AS), while others reported similar or worse outcomes. For instance, a retrospective observational study including 3209 patients with AS found higher mortality in CHG-AS (unadjusted HR: 1.4; 95% CI: 1.1 to 1.7), whereas another retrospective multicenter study including 2724 patients with AS observed worse outcomes in DHG-AS (adjusted HR: 1.59; 95% CI: 1.04 to 2.56). These discrepancies may stem from delays in intervention or heterogeneity in study populations. Despite the diagnostic ambiguity, the presence of high gradients warrants careful evaluation, aggressive risk stratification, and timely management. Current guidelines recommend a multimodal approach combining echocardiography, computed tomography (CT) calcium scoring, transesophageal echocardiography (TEE) planimetry, and, when needed, catheterization. Anatomic AVA assessment by TEE, CT, and cardiac magnetic resonance imaging (CMR) can improve diagnostic accuracy by directly visualizing valve morphology and planimetry-based AVA, helping to clarify the true severity in discordant cases. However, these modalities are limited by factors such as image quality (especially with TEE), radiation exposure and contrast use (in CT), and availability or contraindications (in CMR). Management remains largely based on CHG-AS protocols, with intervention primarily guided by transvalvular gradient and symptom burden. The variability among the different guidelines in defining severity and therapeutic thresholds highlights the need for tailored approaches in DHG-AS. DHG-AS is clinically relevant and associated with substantial prognostic uncertainty. Timely recognition and individualized treatment could improve outcomes in this complex subgroup.
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(This article belongs to the Special Issue Cardiovascular Imaging in Heart Failure and in Valvular Heart Disease)
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Open AccessArticle
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
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
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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.
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(This article belongs to the Section Cardiac Surgery)
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Open AccessArticle
The Prognostic Potential of Insulin-like Growth Factor-Binding Protein 1 for Cardiovascular Complications in Peripheral Artery Disease
by
Ben Li, Farah Shaikh, Houssam Younes, Batool Abuhalimeh, Abdelrahman Zamzam, Rawand Abdin and Mohammad Qadura
J. Cardiovasc. Dev. Dis. 2025, 12(7), 253; https://doi.org/10.3390/jcdd12070253 - 1 Jul 2025
Abstract
Background/Objectives: Patients with peripheral artery disease (PAD) have a heightened risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and death. Despite this, limited progress has been made in identifying reliable biomarkers to prognosticate such outcomes. Circulating growth factors, known to
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Background/Objectives: Patients with peripheral artery disease (PAD) have a heightened risk of major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and death. Despite this, limited progress has been made in identifying reliable biomarkers to prognosticate such outcomes. Circulating growth factors, known to influence endothelial function and the progression of atherosclerosis, may hold prognostic value in this context. The objective of this research was to evaluate a broad range of blood-based growth factors to investigate their potential as predictors of MACE in patients diagnosed with PAD. Methods: A total of 465 patients with PAD were enrolled in a prospective cohort study. Baseline plasma levels of five different growth factors were measured, and participants were monitored over a two-year period. The primary outcome was the occurrence of MACE within those two years. Comparative analysis of protein levels between patients who did and did not experience MACE was performed using the Mann–Whitney U test. To assess the individual prognostic significance of each protein for predicting MACE within two years, Cox proportional hazards regression was performed, adjusting for clinical and demographic factors including a history of coronary and cerebrovascular disease. Subgroup analysis was performed to assess the prognostic value of these proteins in females, who may be at higher risk of PAD-related adverse events. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), and area under the receiver operating characteristic curve (AUROC) were calculated to assess the added value of significant biomarkers to model performance for predicting 2-year MACE when compared to using demographic/clinical features alone. Kaplan–Meier curves stratified by IGFBP-1 tertiles compared using log-rank tests and Cox proportional hazards analysis were used to assess 2-year MACE risk trajectory based on plasma protein levels. Results: The average participant age was 71 years (SD 10); 31.1% were female and 47.2% had diabetes. By the end of the two-year follow-up, 18.1% (n = 84) had experienced MACE. Of all proteins studied, only insulin-like growth factor-binding protein 1 (IGFBP-1) showed a significant elevation among patients who suffered MACE versus those who remained event-free (20.66 [SD 3.91] vs. 13.94 [SD 3.80] pg/mL; p = 0.012). IGFBP-1 remained a significant independent predictor of 2-year MACE occurrence in the multivariable Cox analysis (adjusted hazard ratio [HR] 1.57, 95% CI 1.21–1.97; p = 0.012). Subgroup analyses revealed that IGFBP-1 was significantly associated with 2-year MACE occurrence in both females (adjusted HR 1.52, 95% CI 1.16–1.97; p = 0.015) and males (adjusted HR 1.04, 95% CI 1.02–1.22; p = 0.045). Incorporating IGFBP-1 into the clinical risk prediction model significantly enhanced its predictive performance, with an increase in the AUROC from 0.73 (95% CI 0.71–0.75) to 0.79 (95% CI 0.77–0.81; p = 0.01), an NRI of 0.21 (95% CI 0.07–0.36; p = 0.014), and an IDI of 0.041 (95% CI 0.015–0.066; p = 0.008), highlighting the prognostic value of IGFBP-1. Kaplan–Meier analysis showed an increase in the cumulative incidence of 2-year MACE across IGFBP-1 tertiles. Patients in the highest IGFBP-1 tertile experienced a significantly higher event rate compared to those in the lowest tertile (log-rank p = 0.008). In the Cox proportional hazards analysis, the highest tertile of IGFBP-1 was associated with increased 2-year MACE risk compared to the lowest tertile (adjusted HR 1.81; 95% CI: 1.31–2.65; p = 0.001). Conclusions: Among the growth factors analyzed, IGFBP-1 emerged as the sole biomarker independently linked to the development of MACE over a two-year span in both female and male PAD patients. The addition of IGFBP-1 to clinical features significantly improved model predictive performance for 2-year MACE. Measuring IGFBP-1 levels may enhance risk stratification and guide the intensity of therapeutic interventions and referrals to cardiovascular specialists, ultimately supporting more personalized and effective management strategies for patients with PAD to reduce systemic vascular risk.
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(This article belongs to the Section Cardiovascular Clinical Research)
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Open AccessArticle
Trends, Prevalence of Bradyarrhythmia and Pacemaker Implantation in Patients with Parkinson’s Disease
by
Tochukwu Nzeako, Olayemi Adeniran, Shoshanah Kahn and Neil Wimmer
J. Cardiovasc. Dev. Dis. 2025, 12(7), 252; https://doi.org/10.3390/jcdd12070252 - 30 Jun 2025
Abstract
Bradyarrhythmia is associated with an increased risk of falls, syncope, and sudden cardiac arrest in Parkinson’s disease (PD). However, studies investigating bradyarrhythmia in PA have been scarce. Therefore, we aimed to assess trends, prevalence, and risk factors of bradyarrhythmia and pacemaker implantation in
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Bradyarrhythmia is associated with an increased risk of falls, syncope, and sudden cardiac arrest in Parkinson’s disease (PD). However, studies investigating bradyarrhythmia in PA have been scarce. Therefore, we aimed to assess trends, prevalence, and risk factors of bradyarrhythmia and pacemaker implantation in PD patients. The National Inpatient Sample was utilized to identify patients’ data with primary and secondary diagnoses of Parkinson’s disease (PD) from 2016 to 2020. A total of 333,242 patients had a PD diagnosis; of these, 5092 (1.5%) had comorbid diagnoses of bradyarrhythmia. The prevalence of bradyarrhythmia in patients with PD was 351.9 per 10,000 hospitalizations (3.5%), with an increase from 291.9 to 463.8 per 10,000. However, the trends remained relatively stable. The overall prevalence of pacemaker implantation in patients with PD was 79.9 per 10,000 hospitalizations (0.8%). The overall trend of pacemaker implantation was stable in patients with PD. Age ≥ 65, male sex, and comorbidities (atrial fibrillation, coronary artery disease, heart failure, hypertension, liver failure, obesity, peripheral vascular disease, renal failure) were associated with a higher likelihood of bradyarrhythmia in patients with PD. This study’s findings revealed an increase in the prevalence of bradyarrhythmia. However, the prevalence of pacemaker implantation remained relatively stable over the study period.
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Open AccessCase Report
A Clinical Case of Aneurysmal Dilatation of the Aortic Arch Distal to the Origin of an Aberrant Right Subclavian Artery Treated with Castor Single-Branch Stent Graft Implantation and Right Carotid-Subclavian Bypass
by
Antonio Rizza, Silvia Di Sibio, Angela Buonpane, Giancarlo Trimarchi, Marta Casula, Michele Murzi, Pierandrea Farneti, Cataldo Palmieri, Marco Solinas and Sergio Berti
J. Cardiovasc. Dev. Dis. 2025, 12(7), 251; https://doi.org/10.3390/jcdd12070251 - 29 Jun 2025
Abstract
Advancements in endovascular stent graft design have enabled the treatment of distal aortic arch pathologies. However, the length of the proximal landing zone remains a limitation, especially with vascular anomalies like an aberrant right subclavian artery (ARSA) posing additional challenges. A 78-year-old patient
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Advancements in endovascular stent graft design have enabled the treatment of distal aortic arch pathologies. However, the length of the proximal landing zone remains a limitation, especially with vascular anomalies like an aberrant right subclavian artery (ARSA) posing additional challenges. A 78-year-old patient underwent computed tomography angiography (CTA), which revealed progressive enlargement of a distal aortic arch aneurysm located beyond an ARSA that coursed between the esophagus and trachea. Following evaluation by the multidisciplinary Aortic Team, a hybrid procedure was planned. A right carotid-to-ARSA bypass was performed and a Castor single-branched stent graft (CSBSG) was deployed in the aortic arch with its side branch directed into the left subclavian artery (LSA), thereby covering the origin of the ARSA. To prevent a type II endoleak, plug embolization of the ARSA origin was subsequently performed. CSBSG is a feasible treatment for distal aortic arch aneurysms, even in the presence of vascular anomalies such as ARSA.
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(This article belongs to the Section Cardiac Development and Regeneration)
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CMR Left Ventricular Filling Pressure Exhibits Strong Haemodynamic Relevance and Outperforms Echocardiography in Multimodal Heart Failure Assessment
by
Aradhai Bana, Rui Li, Zia Mehmood, Craig Rogers, Ciaran Grafton-Clarke, Tiya Bali, David Hall, Mustapha Jamil, Liandra Ramachenderam, Uwais Dudhiya, Hilmar Spohr, Victoria Underwood, Rebekah Girling, Bahman Kasmai, Sunil Nair, David P. Ripley, Gareth Matthews and Pankaj Garg
J. Cardiovasc. Dev. Dis. 2025, 12(7), 250; https://doi.org/10.3390/jcdd12070250 - 27 Jun 2025
Abstract
Background: Left ventricular filling pressure (LVFP) is pivotal in heart failure management, yet non-invasive assessment remains challenging. While echocardiography is the first line, cardiovascular magnetic resonance (CMR) offers enhanced accuracy. This study evaluates the interplay between CMR-derived LVFP and echocardiography, focusing on sex
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Background: Left ventricular filling pressure (LVFP) is pivotal in heart failure management, yet non-invasive assessment remains challenging. While echocardiography is the first line, cardiovascular magnetic resonance (CMR) offers enhanced accuracy. This study evaluates the interplay between CMR-derived LVFP and echocardiography, focusing on sex differences and correlations with N-terminal pro-brain natriuretic peptide (NT-proBNP). Methods: In this prospective study, 222 patients with CMR-derived LVFP > 14 mmHg underwent transthoracic echocardiography (TTE) and CMR. Sex-specific CMR equations (incorporating left atrial volume and ventricular mass) were used to estimate pulmonary capillary wedge pressure (PCWP). Correlations between imaging parameters and NT-proBNP were assessed. Results: CMR-derived LVFP showed no sex-based differences (p = 0.3143), unlike echocardiographic indices: women had higher E/e′ (p < 0.0001) and lower lateral mitral annular velocities (p = 0.0159). CMR-derived LVFP correlated strongly with NT-proBNP (r = 0.47, p < 0.0001), outperforming E/e′ (r = 0.41). Stratification by CMR PCWP tertiles revealed higher NT-proBNP (p = 0.0003), left atrial volumes (p < 0.0001), and septal thickness (p < 0.0001) in the highest tertiles. CMR-derived LVFP demonstrated superior diagnostic accuracy (AUC = 0.754 vs. 0.740 for E/e′) in identifying elevated NT-proBNP (>400 pg/mL). Sex-independent CMR measures contrasted with echocardiography, where parameters like left atrial volume varied by sex (p = 0.012). Conclusions: CMR-derived LVFP is a robust, sex-independent biomarker strongly linked to NT-proBNP, offering superior diagnostic performance over echocardiography. Its integration with echocardiographic indices enhances the non-invasive assessment of cardiac filling pressures, advocating a synergistic imaging approach to refine heart failure management.
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(This article belongs to the Section Cardiovascular Clinical Research)
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Open AccessReview
Role of Computed Tomography and Other Non-Invasive and Invasive Imaging Modalities in Cardiac Allograft Vasculopathy
by
Siddhant Passey, Jagriti Jha, Nirav Patel, Vincent Lipari, Saurabh Joshi, Raymond McKay, Joseph Radojevic and Joseph Ingrassia
J. Cardiovasc. Dev. Dis. 2025, 12(7), 249; https://doi.org/10.3390/jcdd12070249 - 27 Jun 2025
Abstract
Cardiac allograft vasculopathy (CAV) is a leading cause of allograft dysfunction and failure. CAV prevention, early detection, and management are essential to increasing allograft survival. In this comprehensive review, we discuss various invasive and non-invasive modalities that are being utilized for CAV detection.
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Cardiac allograft vasculopathy (CAV) is a leading cause of allograft dysfunction and failure. CAV prevention, early detection, and management are essential to increasing allograft survival. In this comprehensive review, we discuss various invasive and non-invasive modalities that are being utilized for CAV detection. Invasive coronary angiography provides a visualization of vascular anatomy but is limited in detecting the microvasculature and diffuse and early structural changes. The addition of intracoronary assessment techniques, including intravascular ultrasound, optical coherence tomography, and coronary flow reserve assessment, offer(s) superior sensitivity in identifying CAV. Non-invasive imaging modalities, such as cardiac magnetic resonance imaging, computed tomography angiography, and positron emission tomography, provide complementary insights into CAV with myocardial perfusion and allograft function while reducing procedural risks. Our aim is to guide clinicians in selecting appropriate imaging strategies tailored to individual recipients, to improve detection, monitoring, and outcomes in CAV.
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(This article belongs to the Special Issue Advances in Cardiovascular Imaging—Computed Tomography (CT) Focus Issue)
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