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Keywords = cardiac risk stratification

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13 pages, 1424 KiB  
Article
Comparison of Artificial Intelligence–Derived Heart Age with Chronological Age Using Normal Sinus Electrocardiograms in Patients with No Evidence of Cardiac Disease
by Myoung Jung Kim, Sung-Hee Song, Young Jun Park, Young-Hyun Lee, Jongwoo Kim, JaeHu Jeon, KyungChang Woo, Juwon Kim, Ju Youn Kim, Seung-Jung Park, Young Keun On and Kyoung-Min Park
J. Clin. Med. 2025, 14(15), 5548; https://doi.org/10.3390/jcm14155548 - 6 Aug 2025
Abstract
Background/Objectives: Chronological age (CA) is commonly used in clinical decision-making, yet it may not accurately reflect biological aging. Recent advances in artificial intelligence (AI) allow estimation of electrocardiogram (ECG)-derived heart age, which may serve as a non-invasive biomarker for physiological aging. This [...] Read more.
Background/Objectives: Chronological age (CA) is commonly used in clinical decision-making, yet it may not accurately reflect biological aging. Recent advances in artificial intelligence (AI) allow estimation of electrocardiogram (ECG)-derived heart age, which may serve as a non-invasive biomarker for physiological aging. This study aimed to develop and validate a deep learning model to predict ECG-heart age in individuals with no structural heart disease. Methods: We trained a convolutional neural network (DenseNet-121) using 12-lead ECGs from 292,484 individuals (mean age: 51.4 ± 13.8 years; 42.3% male) without significant cardiac disease. Exclusion criteria included missing age data, age <18 or >90 years, and structural abnormalities. CA was used as the target variable. Model performance was evaluated using the coefficient of determination (R2), Pearson correlation coefficient (PCC), mean absolute error (MAE), and root mean square error (RMSE). External validation was conducted using 1191 independent ECGs. Results: The model demonstrated strong predictive performance (R2 = 0.783, PCC = 0.885, MAE = 5.023 years, RMSE = 6.389 years). ECG-heart age tended to be overestimated in younger adults (≤30 years) and underestimated in older adults (≥70 years). External validation showed consistent performance (R2 = 0.703, PCC = 0.846, MAE = 5.582 years, RMSE = 7.316 years). Conclusions: The proposed AI-based model accurately estimates ECG-heart age in individuals with structurally normal hearts. ECG-derived heart age may serve as a reliable biomarker of biological aging and support future risk stratification strategies. Full article
(This article belongs to the Section Cardiology)
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24 pages, 649 KiB  
Review
Desmosomal Versus Non-Desmosomal Arrhythmogenic Cardiomyopathies: A State-of-the-Art Review
by Kristian Galanti, Lorena Iezzi, Maria Luana Rizzuto, Daniele Falco, Giada Negri, Hoang Nhat Pham, Davide Mansour, Roberta Giansante, Liborio Stuppia, Lorenzo Mazzocchetti, Sabina Gallina, Cesare Mantini, Mohammed Y. Khanji, C. Anwar A. Chahal and Fabrizio Ricci
Cardiogenetics 2025, 15(3), 22; https://doi.org/10.3390/cardiogenetics15030022 - 1 Aug 2025
Viewed by 86
Abstract
Arrhythmogenic cardiomyopathies (ACMs) are a phenotypically and etiologically heterogeneous group of myocardial disorders characterized by fibrotic or fibro-fatty replacement of ventricular myocardium, electrical instability, and an elevated risk of sudden cardiac death. Initially identified as a right ventricular disease, ACMs are now recognized [...] Read more.
Arrhythmogenic cardiomyopathies (ACMs) are a phenotypically and etiologically heterogeneous group of myocardial disorders characterized by fibrotic or fibro-fatty replacement of ventricular myocardium, electrical instability, and an elevated risk of sudden cardiac death. Initially identified as a right ventricular disease, ACMs are now recognized to include biventricular and left-dominant forms. Genetic causes account for a substantial proportion of cases and include desmosomal variants, non-desmosomal variants, and familial gene-elusive forms with no identifiable pathogenic mutation. Nongenetic etiologies, including post-inflammatory, autoimmune, and infiltrative mechanisms, may mimic the phenotype. In many patients, the disease remains idiopathic despite comprehensive evaluation. Cardiac magnetic resonance imaging has emerged as a key tool for identifying non-ischemic scar patterns and for distinguishing arrhythmogenic phenotypes from other cardiomyopathies. Emerging classifications propose the unifying concept of scarring cardiomyopathies based on shared structural substrates, although global consensus is evolving. Risk stratification remains challenging, particularly in patients without overt systolic dysfunction or identifiable genetic markers. Advances in tissue phenotyping, multi-omics, and artificial intelligence hold promise for improved prognostic assessment and individualized therapy. Full article
(This article belongs to the Section Cardiovascular Genetics in Clinical Practice)
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21 pages, 1699 KiB  
Review
Cardiac Hypertrophy: A Comprehensive Review from Prenatal Life to Young Adulthood
by Martina Avesani, Elettra Pomiato, Sara Moscatelli, Jolanda Sabatino, Nunzia Borrelli, Leonie Luedke, Rosalba De Sarro, Sara Pavesi, Giulia Pelaia, Claudio Mastellone, Isabella Leo and Giovanni Di Salvo
Children 2025, 12(8), 989; https://doi.org/10.3390/children12080989 - 28 Jul 2025
Viewed by 349
Abstract
Myocardial hypertrophy (MH) represents a complex and heterogeneous condition in the pediatric and young adult population. While rare in children, MH encompasses a wide spectrum of physiological and pathological entities, ranging from transient hypertrophy in the infants of diabetic mothers to progressive genetic [...] Read more.
Myocardial hypertrophy (MH) represents a complex and heterogeneous condition in the pediatric and young adult population. While rare in children, MH encompasses a wide spectrum of physiological and pathological entities, ranging from transient hypertrophy in the infants of diabetic mothers to progressive genetic hypertrophic cardiomyopathies (HCM) with significant morbidity and mortality. Differential diagnosis is critical, as many phenocopies—including metabolic, mitochondrial, and syndromic diseases—can mimic HCM. Echocardiography remains the first-line imaging modality, with cardiac magnetic resonance (CMR) and molecular diagnostics increasingly used for detailed characterization. Risk stratification tools, such as the HCM Risk-Kids model, support clinical decision-making but must be integrated with individualized assessment. Advances in prenatal screening and genetic testing have significantly improved outcomes, though long-term management requires multidisciplinary care. Understanding age-specific presentations and the underlying etiologies is essential for accurate diagnosis and targeted treatment. This review provides a comprehensive overview of cardiac hypertrophy from fetal life through young adulthood, with a focus on etiologies, diagnostic approaches, imaging modalities, and therapeutic strategies, and aims to guide clinicians through the evolving landscape of MH, emphasizing early recognition, comprehensive evaluation, and personalized care. Full article
(This article belongs to the Special Issue Evaluation and Management of Children with Congenital Heart Disease)
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15 pages, 1406 KiB  
Article
Arterial Stiffness and Early Cardiac Dysfunction in Type 2 Diabetes Mellitus: A Potential Role for 25 OH Vitamin D3 Deficiency
by Laura Maria Craciun, Florina Buleu, Stela Iurciuc, Daian Ionel Popa, Gheorghe Nicusor Pop, Flavia Goanta, Greta-Ionela Goje, Ana Maria Pah, Marius Badalica-Petrescu, Olivia Bodea, Ioana Cotet, Claudiu Avram, Diana-Maria Mateescu and Adina Avram
Medicina 2025, 61(8), 1349; https://doi.org/10.3390/medicina61081349 - 25 Jul 2025
Viewed by 157
Abstract
Background and Objectives: Type 2 diabetes mellitus (T2DM) is associated with subclinical cardiovascular changes, such as increased arterial stiffness and myocardial dysfunction. Vitamin D deficiency has been recognized as a potential contributing factor to vascular disease; however, its impact on early cardiac [...] Read more.
Background and Objectives: Type 2 diabetes mellitus (T2DM) is associated with subclinical cardiovascular changes, such as increased arterial stiffness and myocardial dysfunction. Vitamin D deficiency has been recognized as a potential contributing factor to vascular disease; however, its impact on early cardiac changes associated with T2DM remains poorly understood. Our aim was to evaluate the association between serum levels of 25-hydroxyvitamin D3 [25(OH)D3], arterial stiffness, and left ventricular global longitudinal strain (LV GLS) in patients with T2DM who do not have a clinically evident cardiovascular disease. Material and methods: This cross-sectional study evaluated the carotid intima–media thickness (IMT), aortic pulse wave velocity (PWVao), LV GLS, and serum 25(OH)D3 levels in patients diagnosed with T2DM (n = 65) compared to healthy control subjects (n = 55). Independent predictors of arterial stiffness were identified by a multivariate logistic regression analysis. Results: Patients with T2DM showed a significant increase in IMT and PWVao, a reduction in LV GLS, and low levels of 25(OH)D3 compared to subjects in the control group (all p < 0.05). Both vitamin D deficiency and T2DM were found to be independently associated with an increased arterial stiffness, with odds ratios of 2.4 and 4.8, respectively. A significant inverse relationship was identified between 25(OH)D3 levels and markers of arterial stiffness, as well as LV GLS, suggesting a possible association between the vitamin D status and the early onset of cardiovascular dysfunction. Conclusions: Patients with T2DM show early signs of heart and blood vessel problems, even with an ejection fraction that remains within normal limits. There is a significant correlation between vitamin D deficiency and increased arterial stiffness, along with impaired LV GLS, indicating its possible involvement in cardiovascular complications associated with diabetes. These findings support the utility of integrating vascular, myocardial, and vitamin D assessments in early cardiovascular risk stratification for T2DM patients. Full article
(This article belongs to the Special Issue Cardiovascular Diseases and Type 2 Diabetes: 2nd Edition)
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17 pages, 751 KiB  
Review
The Role of Chloride in Cardiorenal Syndrome: A Practical Review
by Georgios Aletras, Maria Bachlitzanaki, Maria Stratinaki, Ioannis Petrakis, Theodora Georgopoulou, Yannis Pantazis, Emmanuel Foukarakis, Michael Hamilos and Kostas Stylianou
J. Clin. Med. 2025, 14(15), 5230; https://doi.org/10.3390/jcm14155230 - 24 Jul 2025
Viewed by 538
Abstract
Chloride, long considered a passive extracellular anion, has emerged as a key determinant in the pathophysiology and management of heart failure (HF) and cardiorenal syndrome. In contrast to sodium, which primarily reflects water balance and vasopressin activity, chloride exerts broader effects on neurohormonal [...] Read more.
Chloride, long considered a passive extracellular anion, has emerged as a key determinant in the pathophysiology and management of heart failure (HF) and cardiorenal syndrome. In contrast to sodium, which primarily reflects water balance and vasopressin activity, chloride exerts broader effects on neurohormonal activation, acid–base regulation, renal tubular function, and diuretic responsiveness. Its interaction with With-no-Lysine (WNK) kinases and chloride-sensitive transporters underscores its pivotal role in electrolyte and volume homeostasis. Hypochloremia, frequently observed in HF patients treated with loop diuretics, is independently associated with adverse outcomes, diuretic resistance, and arrhythmic risk. Conversely, hyperchloremia—often iatrogenic—may contribute to renal vasoconstriction and hyperchloremic metabolic acidosis. Experimental data also implicate chloride dysregulation in myocardial electrical disturbances and an increased risk of sudden cardiac death. Despite mounting evidence of its clinical importance, serum chloride remains underappreciated in contemporary risk assessment models and treatment algorithms. This review synthesizes emerging evidence on chloride’s role in HF, explores its diagnostic and therapeutic implications, and advocates for its integration into individualized care strategies. Future studies should aim to prospectively validate these associations, evaluate chloride-guided therapeutic interventions, and assess whether incorporating chloride into prognostic models can improve risk stratification and outcomes in patients with heart failure and cardiorenal syndrome. Full article
(This article belongs to the Special Issue New Insights into Cardiorenal Metabolic Syndrome)
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23 pages, 1464 KiB  
Article
Immunonutritional Markers and the Protective Role of Sternal Irrigation and Antibiotic-Impregnated Membranes in Sternal Wound Infection: A Retrospective Cohort Study
by Ebubekir Sönmez, İzatullah Jalalzai, Ümit Arslan, Alperen Yıldız, Furkan Çelik and Merve Çetin
Life 2025, 15(8), 1163; https://doi.org/10.3390/life15081163 - 23 Jul 2025
Viewed by 349
Abstract
Background: Sternal wound infections (SWIs) remain a significant complication following cardiac surgery. Inflammatory and nutritional status are increasingly recognized as key contributors to their development. This study aimed to investigate the predictive utility of immunonutritional biomarkers and to evaluate the protective effect of [...] Read more.
Background: Sternal wound infections (SWIs) remain a significant complication following cardiac surgery. Inflammatory and nutritional status are increasingly recognized as key contributors to their development. This study aimed to investigate the predictive utility of immunonutritional biomarkers and to evaluate the protective effect of combining sternal irrigation with an antibiotic-impregnated membrane. Methods: This retrospective cohort study included 480 patients undergoing off-pump coronary artery bypass grafting. Patients were categorized based on sternal management strategy (standard closure or local prophylaxis using gentamicin-enriched irrigation combined with an antibiotic-impregnated fascia lata membrane) and according to the severity of SWIs, classified as superficial or deep. Inflammatory and nutritional markers—including C-reactive protein (CRP), neutrophils, lymphocytes, albumin, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein-to-albumin ratio (CAR), and prognostic nutritional index (PNI)—were assessed at three time points: preoperatively, on postoperative day 3, and after week 1. Results: SWIs were observed in 93 patients, including 75 superficial and 18 deep infections. The combined prophylactic approach was associated with a nearly 1.8-fold reduction in deep SWIs (OR: 0.55; 95% CI: 0.15–0.87) and a modest reduction in superficial infections (OR: 0.89; 95% CI: 0.5–1.3; p = 0.061). Threshold values of 3.75 for preoperative NLR, 9.8 for ΔNLR, and 16.7 for ΔCAR demonstrated strong predictive capacity for identifying patients at increased risk of developing deep SWIs. Patients receiving local prophylaxis exhibited significantly lower CRP, NLR, and CAR values and higher PNI levels at all time points. Conclusions: The combination of sternal irrigation and local antibiotic prophylaxis appears to confer protection against SWIs, potentially by mitigating postoperative inflammation. Immunonutritional biomarkers offer a promising means for early risk stratification. To confirm their clinical utility and broader applicability, these results should be validated in prospective, multicenter studies encompassing a wider range of cardiac surgical procedures. Full article
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16 pages, 249 KiB  
Article
The Role of Echocardiographic Right Atrial Strain Parameters in Evaluating Atrial Fibrillation Recurrence in Patients Undergoing Atrial Fibrillation Ablation
by Hasan Can Konte, Emir Dervis, Idris Yakut and Dursun Aras
J. Clin. Med. 2025, 14(14), 5155; https://doi.org/10.3390/jcm14145155 - 21 Jul 2025
Viewed by 313
Abstract
Background: Atrial fibrillation (AF) recurrence following catheter ablation remains a significant clinical challenge despite technological advancements, with recurrence rates in the range of 20–40%. While left atrial parameters have been extensively studied as predictors of recurrence, the contribution of right atrial mechanical function [...] Read more.
Background: Atrial fibrillation (AF) recurrence following catheter ablation remains a significant clinical challenge despite technological advancements, with recurrence rates in the range of 20–40%. While left atrial parameters have been extensively studied as predictors of recurrence, the contribution of right atrial mechanical function has received limited attention. The hypothesis that the combined assessment of right and left atrial strain parameters may provide superior predictive value represents an important clinical question with potential implications for post-ablation risk stratification and follow-up strategies. Methods: This single-center, retrospective cohort study included 100 consecutive adult patients who underwent AF ablation between May 2022 and June 2024 with at least one-year follow-up. Patients were divided into two groups: those with recurrence (n = 13) and those without recurrence (n = 87). A comprehensive echocardiographic assessment, including the speckle-tracking strain analysis of both atria, was performed. Results: The median follow-up was 365 days [range: 150–912 days] in patients with recurrence. In the multivariable analysis, right ventricular diameter (OR: 0.74; 95% CI: 0.61–0.90; p = 0.001), left ventricular end-diastolic volume (OR: 1.04; 95% CI: 1.00–1.08; p = 0.022), and left ventricular global longitudinal strain rate (OR: 1.22; 95% CI: 1.05–1.40; p = 0.007) emerged as independent predictors of recurrence. Conclusions: The significant association of right atrial longitudinal reservoir strain with recurrence in univariable analysis, although not retained as an independent predictor in the multivariable model, suggests the importance of comprehensive cardiac assessment including right heart parameters in predicting AF recurrence. Full article
(This article belongs to the Section Cardiology)
23 pages, 2304 KiB  
Review
Machine Learning for Coronary Plaque Characterization: A Multimodal Review of OCT, IVUS, and CCTA
by Alessandro Pinna, Alberto Boi, Lorenzo Mannelli, Antonella Balestrieri, Roberto Sanfilippo, Jasjit Suri and Luca Saba
Diagnostics 2025, 15(14), 1822; https://doi.org/10.3390/diagnostics15141822 - 19 Jul 2025
Viewed by 499
Abstract
Coronary plaque vulnerability, more than luminal stenosis, drives acute coronary syndromes. Optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography (CCTA) visualize plaque morphology in vivo, but manual interpretation is time-consuming and operator-dependent. We performed a narrative literature survey of [...] Read more.
Coronary plaque vulnerability, more than luminal stenosis, drives acute coronary syndromes. Optical coherence tomography (OCT), intravascular ultrasound (IVUS), and coronary computed tomography angiography (CCTA) visualize plaque morphology in vivo, but manual interpretation is time-consuming and operator-dependent. We performed a narrative literature survey of artificial intelligence (AI) applications—focusing on machine learning (ML) architectures—for automated coronary plaque segmentation and risk characterization across OCT, IVUS, and CCTA. Recent ML models achieve expert-level lumen and plaque segmentation, reliably detecting features linked to vulnerability such as a lipid-rich necrotic core, calcification, positive remodelling, and a napkin-ring sign. Integrative radiomic and multimodal frameworks further improve prognostic stratification for major adverse cardiac events. Nonetheless, progress is constrained by small, single-centre datasets, heterogeneous validation metrics, and limited model interpretability. AI-enhanced plaque assessment offers rapid, reproducible, and comprehensive coronary imaging analysis. Future work should prioritize large multicentre repositories, explainable architectures, and prospective outcome-oriented validation to enable routine clinical adoption. Full article
(This article belongs to the Special Issue Machine Learning in Precise and Personalized Diagnosis)
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16 pages, 544 KiB  
Article
Cardiovascular Events and Preoperative Beta-Blocker Use in Non-Cardiac Surgery: A Prospective Holter-Based Analysis
by Alexandru Cosmin Palcău, Liviu Ionuț Șerbanoiu, Livia Florentina Păduraru, Alexandra Bolocan, Florentina Mușat, Daniel Ion, Dan Nicolae Păduraru, Bogdan Socea and Adriana Mihaela Ilieșiu
Medicina 2025, 61(7), 1300; https://doi.org/10.3390/medicina61071300 - 18 Jul 2025
Viewed by 308
Abstract
Background and Objectives: The perioperative use of beta-blockers remains controversial due to conflicting evidence of their risks and benefits. The aim of this study was to evaluate the association between chronic beta-blocker (bb) therapy and perioperative cardiac events in non-cardiac surgeries using [...] Read more.
Background and Objectives: The perioperative use of beta-blockers remains controversial due to conflicting evidence of their risks and benefits. The aim of this study was to evaluate the association between chronic beta-blocker (bb) therapy and perioperative cardiac events in non-cardiac surgeries using 24 h continuous Holter monitoring. Materials and Methods: A prospective observational study was conducted on patients undergoing elective or emergency non-cardiac surgery at a Romanian tertiary care hospital. The patients were divided into two groups: G1 (not receiving Bb) and G2 (on chronic Bb). The incidences of perioperative cardiac events, such as severe bradycardia (<40 b/min), new-onset atrial fibrillation (AF), extrasystolic arrhythmia (Ex), and sustained ventricular tachycardia (sVT) and arterial hypotension, were compared between the two groups using clinical, electrocardiography (ECG), and Holter ECG data. Beta-blocker indications, complications, and outcomes were analyzed using chi-squared tests and logistic regression. Results: A total of 100 consecutive patients (63% men, mean age of 53.7 years) were enrolled in the study. G2 included 30% (n = 30) of patients on chronic beta-blocker therapy. The indications included atrial fibrillation (46.7%, n = 14), arterial hypertension (36.7%, n = 11), extrasystolic arrhythmias (10%, n = 3), and chronic coronary syndrome (6.6%, n = 2). Beta-blocker use was significantly associated with severe bradycardia (n = 6; p < 0.001) in G2, whereas one patient in G1 had bradycardia, and 15 and 1 patients had hypotension (p < 0.001) in G1 and G2, respectively. The bradycardia and arterial hypotension cases were promptly treated and did not influence the patients’ prognoses. The 14 patients with AF in G2 had a 15-fold higher odds of requiring beta-blockers (p < 0.001, odds ratio (OR) = 15.145). No significant associations were found between beta-blocker use and the surgery duration (p = 0.155) or sustained ventricular tachycardia (p = 0.857). Ten patients developed paroxysmal postoperative atrial fibrillation (AF), which was related to longer surgery durations (165 (150–180) vs. 120 (90–150) minutes; p = 0.002) and postoperative anemia [hemoglobin (Hg): 10.4 (9.37–12.6) vs. 12.1 (11–13.2) g/dL; p = 0.041]. Conclusions: Patients under chronic beta-blocker therapy undergoing non-cardiac surgery have a higher risk of perioperative bradycardia and hypotension. Continuous Holter monitoring proved effective in detecting transient arrhythmic events, emphasizing the need for careful perioperative surveillance of these patients, especially the elderly, in order to prevent cardiovascular complications These findings emphasize the necessity of tailored perioperative beta-blocker strategies and support further large-scale investigations to optimize risk stratification and management protocols. Full article
(This article belongs to the Special Issue Early Diagnosis and Treatment of Cardiovascular Disease)
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13 pages, 1000 KiB  
Article
The Emerging Role of Left Atrial Strain in Cardiovascular Risk Stratification for Multiple Myeloma Patients Undergoing Carfilzomib Therapy
by Anna Colomba, Lorenzo Airale, Alice Lasagno, Giulia Mingrone, Anna Astarita, Fabrizio Vallelonga, Dario Leone, Martina Sanapo, Arianna Paladino, Francesca Novello, Sara Bringhen, Francesca Gay, Franco Veglio and Alberto Milan
Cancers 2025, 17(14), 2375; https://doi.org/10.3390/cancers17142375 - 17 Jul 2025
Viewed by 270
Abstract
Background: Carfilzomib (CFZ) is a proteasome inhibitor with known cardiotoxic effects used in multiple myeloma (MM) treatment. Cardio-oncology guidelines recommend cardiovascular risk assessment via echocardiography. Left atrial strain (LAS) is not yet included as a marker of cardiotoxicity, but it is emerging as [...] Read more.
Background: Carfilzomib (CFZ) is a proteasome inhibitor with known cardiotoxic effects used in multiple myeloma (MM) treatment. Cardio-oncology guidelines recommend cardiovascular risk assessment via echocardiography. Left atrial strain (LAS) is not yet included as a marker of cardiotoxicity, but it is emerging as a potential indicator of cardiac dysfunction. Objective: This study evaluates LAS as a predictor of CFZ-related hypertensive cardiovascular adverse events (CVAEs) in MM patients, with or without prior hypertension. Methods: A total of 125 MM patients treated with CFZ at the Hypertension Center, “Città della Salute e della Scienza” in Turin, were enrolled. Baseline assessments included transthoracic echocardiography for LAS analysis via Philips QLAB software. Results: During CFZ therapy, 52% of patients experienced hypertensive events. LAS conduit was significantly impaired in those who experienced CVAEs (−16.20 [−20.75; −12.65] vs. −20.80 [−26.30; −15.40], p = 0.006) and LAS conduit > −22 acted as a predictor of hypertensive adverse events in the normotensive population (OR 2.37 [1.02; 5.50]). Conclusion: These findings indicate that alterations in LAS conduit are linked to an increased risk of hypertensive adverse events during CFZ treatment. Incorporating LAS measurement into cardiovascular risk assessments may improve personalized risk stratification for MM patients, especially those without pre-existing hypertension. Full article
(This article belongs to the Special Issue Cardio-Oncology: An Emerging Paradigm in Modern Medicine: 2nd Edition)
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17 pages, 919 KiB  
Article
Necroptotic and Apoptotic Pathways in Sepsis: A Comparative Analysis of Pediatric and Adult ICU Patients
by George Briassoulis, Konstantina Tzermia, Kalliopi Bastaki, Marianna Miliaraki, Panagiotis Briassoulis, Athina Damianaki, Eumorfia Kondili and Stavroula Ilia
Biomedicines 2025, 13(7), 1747; https://doi.org/10.3390/biomedicines13071747 - 17 Jul 2025
Viewed by 363
Abstract
Background: Necroptosis, a regulated form of inflammatory cell death, is increasingly recognized as a key driver of sepsis and critical illness. The balance between necroptosis and apoptosis may influence immune responses and outcomes in ICU patients. Objective: To evaluate necroptosis- and apoptosis-related protein [...] Read more.
Background: Necroptosis, a regulated form of inflammatory cell death, is increasingly recognized as a key driver of sepsis and critical illness. The balance between necroptosis and apoptosis may influence immune responses and outcomes in ICU patients. Objective: To evaluate necroptosis- and apoptosis-related protein expression in critically ill pediatric and adult patients with sepsis/septic shock, trauma/SIRS, or cardiac conditions, and assess their association with clinical outcomes. Methods: In this prospective, observational study, 88 patients admitted to a tertiary ICU were categorized into four groups: sepsis/septic shock, trauma/SIRS, cardiac disease, and healthy controls. Serum levels of RIPK1, RIPK3, MLKL, A20, caspase-8, IL-1β, and IL-18 were measured within 24 h of admission using ELISA. Biomarkers were analyzed by disease group, age, and severity indices. Results: Patients with sepsis—both adults and children—exhibited significantly elevated levels of RIPK1, IL-1β, and IL-18 (p < 0.001) and reduced levels of caspase-8 (p = 0.015), indicating activation of the necroptosis pathway. A20 was significantly upregulated (p < 0.001) and independently associated with lactate levels. RIPK1, IL-1β, and IL-18 were positively correlated with ICU length of stay and illness severity, whereas caspase-8 showed an inverse correlation. ROC analysis demonstrated strong predictive performance for sepsis/septic shock using RIPK1 (AUC = 0.81), IL-18 (AUC = 0.71), and A20 (AUC = 0.71); conversely, caspase-8 was inversely associated with sepsis (AUC = 0.32). Conclusions: Necroptosis appears to play a central role in the pathophysiology of sepsis across age groups. Elevated levels of RIPK1, IL-1β, IL-18, and A20 may serve as biomarkers of disease severity, while reduced caspase-8 supports a shift away from apoptosis toward necroptotic cell death. These findings highlight the potential of necroptosis-related pathways as targets for risk stratification and therapeutic intervention in critically ill patients of all ages. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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15 pages, 1907 KiB  
Article
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
Viewed by 329
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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13 pages, 236 KiB  
Review
Anesthetic Management for Delivery in Parturients with Heart Disease: A Narrative Review
by Shahab Ahmadzadeh, Drake P. Duplechin, Paris D. Bailey, Dillon T. Duplechan, Alexia J. Enache, Peyton Moore and Sahar Shekoohi
Biomedicines 2025, 13(7), 1736; https://doi.org/10.3390/biomedicines13071736 - 16 Jul 2025
Viewed by 365
Abstract
Cardiac disease remains a leading cause of maternal morbidity and mortality, particularly in developed countries where improved survival has increased the number of pregnant patients with congenital heart disease. The physiological changes of pregnancy, such as increased blood volume, cardiac output, and hypercoagulability, [...] Read more.
Cardiac disease remains a leading cause of maternal morbidity and mortality, particularly in developed countries where improved survival has increased the number of pregnant patients with congenital heart disease. The physiological changes of pregnancy, such as increased blood volume, cardiac output, and hypercoagulability, can exacerbate preexisting cardiac conditions, posing significant anesthetic challenges during cesarean delivery. This review outlines anesthetic strategies for parturients with structural or functional cardiac disease, emphasizing individualized, multidisciplinary care. We examine general and regional anesthesia approaches, intraoperative monitoring, and hemodynamic goals, including fluid balance, venous return optimization, and myocardial oxygen demand reduction. Preoperative risk stratification and coordination with cardiology and obstetric teams are essential. Future efforts should aim to standardize protocols and improve maternal–fetal outcomes through evidence-based anesthetic planning. Full article
(This article belongs to the Section Molecular and Translational Medicine)
33 pages, 4016 KiB  
Article
Integrated Deep Learning Framework for Cardiac Risk Stratification and Complication Analysis in Leigh’s Disease
by Md Aminul Islam, Jayasree Varadarajan, Md Abu Sufian, Bhupesh Kumar Mishra and Md Ruhul Amin Rasel
Cardiogenetics 2025, 15(3), 19; https://doi.org/10.3390/cardiogenetics15030019 - 15 Jul 2025
Viewed by 277
Abstract
Background: Leigh’s Disease is a rare mitochondrial disorder primarily affecting the central nervous system, with frequent secondary cardiac manifestations such as hypertrophic and dilated cardiomyopathies. Early detection of cardiac complications is crucial for patient management, but manual interpretation of cardiac MRI is labour-intensive [...] Read more.
Background: Leigh’s Disease is a rare mitochondrial disorder primarily affecting the central nervous system, with frequent secondary cardiac manifestations such as hypertrophic and dilated cardiomyopathies. Early detection of cardiac complications is crucial for patient management, but manual interpretation of cardiac MRI is labour-intensive and subject to inter-observer variability. Methodology: We propose an integrated deep learning framework using cardiac MRI to automate the detection of cardiac abnormalities associated with Leigh’s Disease. Four CNN architectures—Inceptionv3, a custom 3-layer CNN, DenseNet169, and EfficientNetB2—were trained on preprocessed MRI data (224 × 224 pixels), including left ventricular segmentation, contrast enhancement, and gamma correction. Morphological features (area, aspect ratio, and extent) were also extracted to aid interpretability. Results: EfficientNetB2 achieved the highest test accuracy (99.2%) and generalization performance, followed by DenseNet169 (98.4%), 3-layer CNN (95.6%), and InceptionV3 (94.2%). Statistical morphological analysis revealed significant differences in cardiac structure between Leigh’s and non-Leigh’s cases, particularly in area (212,097 vs. 2247 pixels) and extent (0.995 vs. 0.183). The framework was validated using ROC (AUC = 1.00), Brier Score (0.000), and cross-validation (mean sensitivity = 1.000, std = 0.000). Feature embedding visualisation using PCA, t-SNE, and UMAP confirmed class separability. Grad-CAM heatmaps localised relevant myocardial regions, supporting model interpretability. Conclusions: Our deep learning-based framework demonstrated high diagnostic accuracy and interpretability in detecting Leigh’s disease-related cardiac complications. Integrating morphological analysis and explainable AI provides a robust and scalable tool for early-stage detection and clinical decision support in rare diseases. Full article
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19 pages, 3514 KiB  
Review
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
Viewed by 398
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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