Journal of Cardiovascular Development and Disease

12 pages, 829 KB

Open AccessArticle

Use of Echocardiography Under Hypoxic Stress Without Exercise to Assess Right to Left Shunting

by Cecilia Villa Etchegoyen, Rachel E. Wraith, Lisa S. Brown, Karen K. Breznak, Rohit Mital, Steven J. Lester, Chadi Ayoub, Said Alsidawi, Justin N. Shipman, Juan M. Farina, Reza Arsanjani and Jan Stepanek

J. Cardiovasc. Dev. Dis. 2025, 12(11), 435; https://doi.org/10.3390/jcdd12110435 - 3 Nov 2025

Abstract

Acute exposure to hypoxia will induce right ventricular (RV) hemodynamic changes and may increase the degree of right-to-left shunting, which can contribute to dyspnea at altitude. In this retrospective study, 125 patients (median age 66 years; 50.4% women) with unexplained dyspnea at altitude [...] Read more.

Acute exposure to hypoxia will induce right ventricular (RV) hemodynamic changes and may increase the degree of right-to-left shunting, which can contribute to dyspnea at altitude. In this retrospective study, 125 patients (median age 66 years; 50.4% women) with unexplained dyspnea at altitude underwent hypoxic simulation testing (HST) with transthoracic echocardiography (TTE). During simulated hypoxia (mode (Min-Max) altitude: 8000 (6000–18,000) ft, were observed a significant decrease in oxygen saturation (97% (95–98) vs. 88% (82–92), p < 0.001) and RV free wall longitudinal strain (−19.6 ± 3.99% vs. −17.3 ± 4.17%, p < 0.01), an increase in RV systolic pressure (RVSP: 26 (23–30.5) vs. 29 (25–36.5) mmHg, p < 0.001). No significant changes were observed in TAPSE (20 (18–23) vs. 20 (19–24) mm) or S wave (0.12 (0.11–0.14) vs. 0.13 (0.12–0.14) m/s). Right-to-left shunting was present in 47.2% of patients and 11.9% exhibited inducible shunting only under hypoxia. However, under hypoxia, there were no significant differences in RV hemodynamic parameters or saturation between those with and without shunting. TTE with HST is useful to characterize both cardiopulmonary response and the dynamic changes in right-to-left shunt behavior under hypoxic stress. Full article

(This article belongs to the Special Issue The Role of Echocardiography in Cardiovascular Diseases)

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27 pages, 1591 KB

Open AccessReview

Human-Induced Pluripotent Stem Cell Models for Amyloid Cardiomyopathy: From Mechanistic Insights to Therapeutic Discovery

by Yufeng Liu and Muhammad Riaz

J. Cardiovasc. Dev. Dis. 2025, 12(11), 434; https://doi.org/10.3390/jcdd12110434 - 2 Nov 2025

Abstract

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering [...] Read more.

Amyloid cardiomyopathy (ACM), driven by transthyretin (TTR) and immunoglobulin light chain (LC) amyloid fibrils, remains a major clinical challenge due to limited mechanistic understanding and insufficient preclinical models. Human-induced pluripotent stem cells (iPSCs) have emerged as a transformative platform to model ACM, offering patient-specific and genetically controlled systems. In this review, we summarize recent advances in the use of iPSC-derived cardiomyocytes (iPSC-CMs) in both two-dimensional (2D) monolayer cultures and three-dimensional (3D) constructs—including spheroids, organoids, cardiac microtissues, and engineered heart tissues (EHTs)—for disease modeling, mechanistic research, and drug discovery. While 2D culture of iPSC-CMs reproduces hallmark proteotoxic phenotypes such as sarcomeric disorganization, oxidative stress, and apoptosis in ACM, 3D models provide enhanced physiological relevance through incorporating multicellularity, extracellular matrix interactions, and mechanical load-related features. Genome editing with Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 further broadens the scope of iPSC-based models, enabling isogenic comparisons and the dissection of mutation-specific effects, particularly in transthyretin-related amyloidosis (ATTR). Despite limitations such as cellular immaturity and challenges in recapitulating aging-associated phenotypes, ongoing refinements in differentiation, maturation, and dynamic training of iPSC-cardiac models hold great promise for overcoming these barriers. Together, these advances position iPSC-based systems as powerful human-relevant platforms for modeling and elucidating disease mechanisms and accelerating therapeutic development to prevent ACM. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

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Graphical abstract

13 pages, 643 KB

Open AccessReview

Antithrombotic Therapy in Transcatheter Aortic Valve Implantation: Focus on Gender Differences

by Mattia De Gregorio, Andrea Denegri, Filippo Luca Gurgoglione, Giorgio Benatti, Iacopo Tadonio, Emilia Solinas, Davide Carino, Andrea Agostinelli, Luigi Vignali and Giampaolo Niccoli

J. Cardiovasc. Dev. Dis. 2025, 12(11), 433; https://doi.org/10.3390/jcdd12110433 - 2 Nov 2025

Abstract

Antithrombotic therapy plays a pivotal role in reducing thromboembolic complications, including stroke and valve thrombosis, following Transcatheter Aortic Valve Implantation (TAVI). However, the benefits of such therapy must be balanced against the increased risk of major bleeding events. The optimal antithrombotic strategy in [...] Read more.

Antithrombotic therapy plays a pivotal role in reducing thromboembolic complications, including stroke and valve thrombosis, following Transcatheter Aortic Valve Implantation (TAVI). However, the benefits of such therapy must be balanced against the increased risk of major bleeding events. The optimal antithrombotic strategy in this setting remains a matter of ongoing debate, given the heterogeneity of patient profiles and procedural variables. Among TAVI recipients, women represent a growing proportion and exhibit distinct anatomical, physiological, and clinical characteristics that influence both thrombotic and bleeding risk. Compared to men, women more frequently experience vascular complications and major bleeding events, despite better survival outcomes. These differences are driven by smaller vessel caliber, higher vascular tortuosity, and altered platelet reactivity. Consequently, sex-specific risk stratification is essential when considering antiplatelet or anticoagulant regimens post-TAVI. This review provides a comprehensive synthesis of current evidence regarding antithrombotic strategies in the post-TAVI setting, with a dedicated focus on sex-related differences. Particular emphasis is placed on the female population, assessing ischemic and hemorrhagic outcomes and the implications for long-term management. Improving outcomes in women undergoing TAVI necessitates tailored antithrombotic strategies that balance efficacy and safety. Ongoing research and dedicated trials are essential to refine these strategies and to inform future guideline updates in this expanding patient population. Full article

(This article belongs to the Special Issue Transcatheter and Surgical Approaches to Complications of Transcatheter Procedures: Current Trends and Future Challenges)

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16 pages, 686 KB

Open AccessReview

Safety and Efficacy of Salt Restriction Across the Spectrum of Heart Failure

by Panagiotis Stachteas, Athina Nasoufidou, Markella Koiliari, Vasiliki Arampatzi, Chrysa Alexaki, Christos Kofos, Paschalis Karakasis, Efstratios Karagiannidis, Theocharis Koufakis, Nikolaos Fragakis and Dimitrios Patoulias

J. Cardiovasc. Dev. Dis. 2025, 12(11), 432; https://doi.org/10.3390/jcdd12110432 - 2 Nov 2025

Abstract

Dietary sodium restriction is widely recommended in heart failure (HF) management; however, its benefits and risks remain a subject of ongoing debate. While moderate sodium reduction may improve symptoms and quality of life in selected patients, excessive restriction can trigger maladaptive neurohormonal activation, [...] Read more.

Dietary sodium restriction is widely recommended in heart failure (HF) management; however, its benefits and risks remain a subject of ongoing debate. While moderate sodium reduction may improve symptoms and quality of life in selected patients, excessive restriction can trigger maladaptive neurohormonal activation, worsen renal function, and increase the risk of hyponatremia, malnutrition, and cachexia. Patient response is heterogeneous, influenced by clinical risk profile, salt sensitivity, comorbidities, and age, with some high-risk patients experiencing neutral or adverse outcomes. Additional challenges arise from hidden sodium in processed foods, medications, and meals, which complicate monitoring and adherence. Effective sodium management in HF therefore requires a nuanced, individualized approach that integrates risk stratification, dietary counseling, and public health measures targeting the food industry. Future research should refine patient selection criteria and establish optimal sodium targets to balance therapeutic efficacy with safety in real-world practice. Full article

(This article belongs to the Special Issue Cardiovascular Disease and Nutrition)

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15 pages, 579 KB

Open AccessArticle

Pericardial Closure Preserves Early Right Ventricular Function After Cardiac Surgery: A Retrospective Cohort Study

by Hannah Breuer, Marjolijn C. Sales, Natasja W. M. Ramnath, Yusuf Shieba, Alish Kolashov, Ajay Moza, Lachmandath Tewarie, Rashad Zayat and Nima Hatam

J. Cardiovasc. Dev. Dis. 2025, 12(11), 431; https://doi.org/10.3390/jcdd12110431 - 31 Oct 2025

Abstract

Background: Perioperative right ventricular (RV) dysfunction is a frequent complication of cardiac surgery linked to poor outcomes and may result from the loss of pericardial support. We investigated whether pericardial closure preserves early postoperative RV function. Methods: We compared patients with pericardial closure [...] Read more.

Background: Perioperative right ventricular (RV) dysfunction is a frequent complication of cardiac surgery linked to poor outcomes and may result from the loss of pericardial support. We investigated whether pericardial closure preserves early postoperative RV function. Methods: We compared patients with pericardial closure versus open pericardium. Co-primary endpoints were early postoperative RV longitudinal function by tricuspid annular plane systolic excursion (TAPSE) and tricuspid annular systolic velocity (TASV). Adjusted comparisons used analysis-of-covariance (postoperative value adjusted for baseline) with prespecified covariates (baseline outcome, LV global longitudinal strain, left-ventricular ejection fraction, LVEDVI, sex, procedure; cardiopulmonary bypass and cross-clamp times when available). Holm correction-controlled multiplicity across the co-primary endpoints. Sensitivity linear mixed-effects models (time × group) were performed. Results: Pericardial closure was associated with better early RV longitudinal function after multivariable adjustment. TAPSE: adjusted mean difference (AMD, Closed–Open) 1.531 mm (95% CI 0.130–2.931; p = 0.033). TASV: AMD 1.694 cm/s (95% CI 0.437–2.951; p = 0.009; Holm-adjusted p = 0.018). Sensitivity analyses yielded consistent estimates. Conclusions: Pericardial closure was independently associated with improved early RV longitudinal function. These adjusted findings address baseline LV imbalances and support considering closure to preserve RV performance; confirmation in prospective trials is warranted. Full article

(This article belongs to the Section Cardiac Surgery)

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29 pages, 2257 KB

Open AccessArticle

Ventricular Topology in Congenital Heart Defects Associated with Heterotaxy: Can We Find Patterns Reflecting the Syndrome-Specific Tendency for Visceral Symmetry?

by Takhfif Othman, Abdulsalam Mohammad Adnan Alsaiad, Abdulraouf M. Z. Jijeh, Jörg Männer and Talat Mesud Yelbuz

J. Cardiovasc. Dev. Dis. 2025, 12(11), 430; https://doi.org/10.3390/jcdd12110430 - 31 Oct 2025

Abstract

Heterotaxy syndrome is characterized by a tendency for bilaterally symmetric arrangement (isomerism) of inner organs. It is frequently associated with complex congenital heart defects (CHDs). In “heterotaxic” hearts, the tendency for isomerism is confined to the atria. The ventricular segment always shows asymmetric [...] Read more.

Heterotaxy syndrome is characterized by a tendency for bilaterally symmetric arrangement (isomerism) of inner organs. It is frequently associated with complex congenital heart defects (CHDs). In “heterotaxic” hearts, the tendency for isomerism is confined to the atria. The ventricular segment always shows asymmetric arrangements (D-hand or L-hand topology). This study aimed to determine the statistical distribution of ventricular topology among patients with CHDs associated with heterotaxy and to identify possible associations between ventricular topology and cardiovascular disorders and survival. It is a retrospective cross-sectional study on 192 patients treated at a single center between 2000 and 2023. Our cohort had 115 patients of left atrial isomerism (LAI) and 77 of right atrial isomerism (RAI). The whole cohort (n = 192) showed a bias towards ventricular D-hand topology (67%), which was statistically significant in LAI (74%). In contrast, RAI showed an almost equal distribution (57% D-hand, 43% L-hand). No significant associations were found between ventricular topology and major CHDs or mortality. Significant associations were observed between ventricular topology and cardiac apex position, direction of p-wave axis, and aortic arch sidedness. We conclude that, in the setting of heterotaxy, especially RAI, ventricular topology and aortic arch sidedness both behave as binary anatomical variables showing a tendency for randomized occurrence. This tendency for statistically symmetric distribution is interpreted as reflecting the syndrome-specific tendency for bilateral symmetry. Full article

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15 pages, 1287 KB

Open AccessArticle

Abnormal Blood Biomarkers and Cumulative Disability Burden in Middle-Aged and Older Adults: Evidence from Two Nationally Representative Surveys in the United States and China

by Raoping Tu, Jin-Jing Pei, Alexander Wolthon, Yueping Li and Hui-Xin Wang

J. Cardiovasc. Dev. Dis. 2025, 12(11), 429; https://doi.org/10.3390/jcdd12110429 - 31 Oct 2025

Abstract

Background: Few studies have simultaneously examined how blood biomarkers for inflammation, metabolic, and cardiovascular function are associated with disability incidence. This study aimed to comprehensively examine these associations. Methods: We used data from adults aged 50 and older in the Health and Retirement [...] Read more.

Background: Few studies have simultaneously examined how blood biomarkers for inflammation, metabolic, and cardiovascular function are associated with disability incidence. This study aimed to comprehensively examine these associations. Methods: We used data from adults aged 50 and older in the Health and Retirement Study (n = 9250) and the China Health and Retirement Longitudinal Study (n = 6844), with biennial follow-up over a 4-year period. We defined abnormal biomarker values using standard clinical cut-off points for three biological systems. Disability burden was quantified as the cumulative number of impairments in basic and instrumental activities of daily living. Multivariate linear mixed-effects models were used to analyze the associations. Results: At baseline, 42% of participants had abnormal biomarker values in at least one system, 28% in two systems, and 7% in all three. A dose–response relationship was observed between the rate of disability accumulation and the number of systems with abnormal biomarker values. Compared to individuals with normal values across all systems, those with abnormalities in two systems had a significantly faster annual increase in disability burden (β = 0.06, 95% CI: 0.02–0.09), while those with abnormalities in all three systems exhibited an even steeper increase (β = 0.1, 95% CI: 0.05–0.16). Conclusions: The presence of abnormal levels in any two or all three of the systems significantly accelerated the rate of disability accumulation over a 4-year period. These findings highlight the importance of integrated biomarker monitoring for early identification of individuals at risk and inform the development of targeted preventive strategies. Full article

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

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18 pages, 290 KB

Open AccessArticle

The Relationship Between Resting Heart Rate and Cardiovascular Risk Factors Among Adults Aged 18 Years and Above in the Rural Ellisras Population: Ellisras Longitudinal Study

by Mohale Gift Maake, Kotsedi Daniel Monyeki and Machoene Derrick Sekgala

J. Cardiovasc. Dev. Dis. 2025, 12(11), 428; https://doi.org/10.3390/jcdd12110428 - 30 Oct 2025

Abstract

(1) Background: Resting heart rate (RHR) is an easily measurable cardiovascular risk indicator, yet its relationship with cardiometabolic risk factors remains understudied in rural African populations. This study investigated the association between RHR and cardiovascular risk factors among adults in the rural Ellisras [...] Read more.

(1) Background: Resting heart rate (RHR) is an easily measurable cardiovascular risk indicator, yet its relationship with cardiometabolic risk factors remains understudied in rural African populations. This study investigated the association between RHR and cardiovascular risk factors among adults in the rural Ellisras community, South Africa. (2) Methods: A cross-sectional analysis was conducted among 629 participants (306 males, 323 females) aged 18 years and above from the Ellisras Longitudinal Study. Anthropometric measurements, blood pressure, biochemical parameters, and lifestyle factors were assessed. RHR was categorized as normal (60–100 bpm), bradycardia (<60 bpm), or tachycardia (>100 bpm). Statistical analysis included descriptive statistics, chi-square tests, Pearson correlations, and logistic regression to identify predictors of abnormal RHR. (3) Results: The mean age was 25.55 ± 1.97 years, with significant gender differences in cardiovascular parameters. Females had higher RHR (81.78 ± 11.73 vs. 70.36 ± 12.89 bpm, p < 0.001), body mass index (BMI) (24.62 vs. 20.67 kg/m², p < 0.001), and waist circumference (WC) (81.00 vs. 73.50 cm, p < 0.001). Resting heart rate (RHR) distribution varied significantly by gender (p < 0.001), with bradycardia more prevalent in males (91.3% vs. 8.7%) and tachycardia in females (75.0% vs. 25.0%). Significant positive correlations were observed between RHR and age (r = 0.105, p = 0.009), diastolic blood pressure (DBP) (r = 0.135, p < 0.001), fasting blood glucose (FBG) (r = 0.098, p = 0.016), total cholesterol (TCHOL) (r = 0.168, p < 0.001), LDL-C (r = 0.201, p < 0.001), WC (r = 0.169, p < 0.001), and sum of 4 skinfolds (bicep, tricep, subscapular and supraspinale) and (r = 0.184, p < 0.001). A negative correlation was found with systolic blood pressure (SBP) (r = −0.105, p < 0.001). In the logistic regression analysis, participants aged >25 years had significantly lower odds of abnormal RHR (OR = 0.50, 95% CI: 0.26–0.97, p = 0.039), after adjusting for confounders. In the fully adjusted model, RHR remained significantly associated with DBP (β = 0.59, p < 0.001), LDL-C (β = 2.76, p = 0.008), WC (β = 0.10, p = 0.012), and triglycerides (TG) (β = 2.78, p = 0.002). (4) Conclusions: RHR demonstrates significant associations with multiple cardiovascular risk factors in this rural South African population, with distinct gender-specific patterns. Age emerged as the primary independent predictor of abnormal RHR. These findings suggest that RHR could serve as a valuable, cost-effective screening tool for cardiovascular risk assessment in resource-limited rural settings. Full article

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

14 pages, 1861 KB

Open AccessArticle

The Synergistic Risk of Insulin Resistance and Renal Dysfunction in Acute Coronary Syndrome Patients After Percutaneous Coronary Intervention

by Guoshu Yang, Maoling Jiang, Lin Liu, Dongyue Jia, Jie Feng, Yan Luo, Tao Ye, Long Xia, Hanxiong Liu, Zhen Zhang, Jinjuan Fu, Lin Cai, Qiang Chen and Shiqiang Xiong

J. Cardiovasc. Dev. Dis. 2025, 12(11), 427; https://doi.org/10.3390/jcdd12110427 - 28 Oct 2025

Abstract

Background: Despite percutaneous coronary intervention (PCI) for revascularization, patients with acute coronary syndrome (ACS) still face residual risks of adverse outcomes. Insulin resistance (IR) and renal impairment are independent predictors of poor prognosis in these patients, yet their interaction and underlying mechanisms linked [...] Read more.

Background: Despite percutaneous coronary intervention (PCI) for revascularization, patients with acute coronary syndrome (ACS) still face residual risks of adverse outcomes. Insulin resistance (IR) and renal impairment are independent predictors of poor prognosis in these patients, yet their interaction and underlying mechanisms linked to post-PCI outcomes remain incompletely elucidated. Methods: A retrospective cohort study was conducted involving patients with ACS who underwent PCI at the Third People’s Hospital of Chengdu from July 2018 to December 2020. Insulin resistance (IR) was quantified using the triglyceride–glucose (TyG) index, and renal function was evaluated via the estimated glomerular filtration rate (eGFR). The primary endpoint was major adverse cardiovascular events (MACEs), a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Multivariable Cox proportional hazards regression and mediation analyses were applied to explore the associations of TyG index and eGFR with patient prognosis, and to quantify the mediating effect of eGFR on the relationship between TyG index and prognosis. Results: A total of 1340 patients with ACS were included in the final analysis. Over a median follow-up duration of 31.02 (interquartile range [IQR]: 27.34–35.03) months, 124 patients (9.25%) experienced MACEs. After adjusting for potential confounders, both the TyG index and eGFR were identified as significant independent predictors of MACEs in the overall population and across predefined subgroups. Specifically, each one-unit increase in the TyG index was associated with a 73.8% higher risk of MACEs (HR 1.738; 95% CI 1.273–2.372), whereas each ten-unit decrease in eGFR was linked to a 12.7% increased MACEs risk (HR 1.127; 95% CI 1.032–1.232). Importantly, after further adjustment for confounders, eGFR significantly mediated 9.63% of the total effect of the TyG index on MACEs risk. Conclusions: Renal impairment partially mediates the association between IR and adverse cardiovascular outcomes in ACS patients undergoing PCI. This finding underscores the clinical importance of the metabolic–cardiorenal axis in this population, suggesting that a comprehensive assessment targeting both IR and renal function-related pathways may enhance risk-stratification accuracy and optimize therapeutic strategies for ACS patients. Full article

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12 pages, 1264 KB

Open AccessSystematic Review

Progression of Untreated Mild Aortic Valve Disease in Patients Undergoing Rheumatic Mitral Valve Surgery: A Meta-Analysis of Reconstructed Time-to-Event Data

by Chong Luo, Xiaoli Qin, Honghua Yue, Weitao Liang and Zhong Wu

J. Cardiovasc. Dev. Dis. 2025, 12(11), 426; https://doi.org/10.3390/jcdd12110426 - 28 Oct 2025

Abstract

(1) Background: Concomitant mild aortic valve disease is frequently found in patients undergoing rheumatic mitral valve surgery. To date, only a limited number of single-center studies have specifically addressed the untreated baseline aortic valve disease long-term progression and reoperation rate. Thus, we conducted [...] Read more.

(1) Background: Concomitant mild aortic valve disease is frequently found in patients undergoing rheumatic mitral valve surgery. To date, only a limited number of single-center studies have specifically addressed the untreated baseline aortic valve disease long-term progression and reoperation rate. Thus, we conducted a meta and landmark analysis to systematically review the issue. (2) Methods: This study investigated the long-term prognostic of baseline mild aortic valve disease in patients undergoing rheumatic mitral valve surgery, based on evidence from PubMed, Embase, Cochrane Library, and Web of Science databases. (3) Results: Meta analysis revealed that patients with mild aortic valve disease had a higher risk of disease progression, with a 3.3-fold risk in the 0–5-year follow-up, which jumped to a hazard ratio of 6.42 in longer-term follow-up (5–25 years). Patients with aortic stenosis had an 8.37-fold risk of progression compared with aortic regurgitation and appeared to be poorly related to the time cut-off. Similarly, higher reoperation rates at long-term follow-up were seen in aortic stenosis patients. (4) Conclusions: This study suggests that patients with mild aortic valve disease at baseline have poorer long-term aortic valve-related progression and reoperation rates, especially aortic stenosis. For those with concomitant aortic stenosis, further investigation of the impact of lesion progression is warranted. Full article

(This article belongs to the Special Issue Heart Valve Surgery: Repair and Replacement)

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9 pages, 1278 KB

Open AccessArticle

Coronary Calcium Scoring as Prediction of Coronary Artery Diseases with Low-Dose Dual-Source CT

by Enrico Schwarz, Valentina Tambè, Silvia De Simoni, Roberto Moltrasi, Matteo Magazzeni, Elena Ciortan, Stefano Bentivegna, Anastasia Esseridou and Francesco Secchi

J. Cardiovasc. Dev. Dis. 2025, 12(11), 425; https://doi.org/10.3390/jcdd12110425 - 27 Oct 2025

Abstract

The aim of this paper is to evaluate the correlation between the coronary calcium score (CCS) and coronary artery disease (CAD), patients underwent coronary CT angiography (CTA). Four hundred and five patients who underwent a coronary CT with CCS analysis were considered for [...] Read more.

The aim of this paper is to evaluate the correlation between the coronary calcium score (CCS) and coronary artery disease (CAD), patients underwent coronary CT angiography (CTA). Four hundred and five patients who underwent a coronary CT with CCS analysis were considered for this retrospective study. Coronary CTA was performed using a dual-source (256-slice) CT scanner (SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany). Before injecting the contrast medium, non-contrasted cardiac CT was performed in a longitudinal scan field from the tracheal carina down to the diaphragm. The corresponding images for calcium scoring were reconstructed with a slice width of 1.5 mm and a slice interval of 1 mm, and the tube voltage was 120 kVp. The total calcium score was calculated using dedicated software. The calcium score based on the Agatston method was defined as the presence of a lesion with an area greater than 1 mm² and peak intensity greater than 130 Hounsfield Units, which was automatically identified and marked with color by the software. From the radiological report, the degree of coronary stenosis was retrieved. A score of 1 corresponds to the absence of stenosis, a score of 2 to mild stenosis (<50%), and a score of 3 to moderate/severe stenosis (>50%). The total coronary gravity score (CGS) for each patient was calculated by summing the score of each coronary artery. The Spearman test was used for correlation. Out of the 405 patients, 217 were male. The mean and standard deviation age was 72 ± 11 years. The overall amount of calcium was an Agatston score of 393 ± 709. A positive correlation between CCS and CGS was found (r = 0.835 and p < 0.001). A ROC curve with AUC 0.917 (p ≤ 0.001) was obtained. The optimal cutoff point of the calcium score for discriminating CGS < 2 was 112, yielding sensitivity of 90% and specificity of 81%. This study confirms the important relationship between the coronary artery calcium score and the presence and extension of coronary artery disease. Full article

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17 pages, 1074 KB

Open AccessArticle

Impact of T-AMYLO Risk Score and Red Flag Findings on Cardiovascular Outcomes in Patients with Cardiac Conduction Defects Treated with Intracardiac Device Implantation

by Hidayet Ozan Arabaci, Sukru Arslan, Cem Kurt, Pelinsu Hunkar, Fatih Ozkan, Muhammet Heja Gecit, Seyma Arslan and Mustafa Yildiz

J. Cardiovasc. Dev. Dis. 2025, 12(11), 424; https://doi.org/10.3390/jcdd12110424 - 26 Oct 2025

Abstract

Background: Cardiac amyloidosis is more common than previously thought with an incidence of up to 15% in aortic stenosis and heart failure with preserved ejection fraction. Pacemaker need in these patients ranges from 9.5% to 20%; however, its prevalence and clinical relevance in [...] Read more.

Background: Cardiac amyloidosis is more common than previously thought with an incidence of up to 15% in aortic stenosis and heart failure with preserved ejection fraction. Pacemaker need in these patients ranges from 9.5% to 20%; however, its prevalence and clinical relevance in patients with unexplained cardiac conduction defects remain unclear. Methods: This retrospective, single-center cohort study evaluated 1107 patients who underwent intracardiac device implantation for unexplained cardiac conduction defects between 2015 and 2024. Patients with secondary conduction defects or known cardiomyopathy were excluded. The prognostic value of the T-AMYLO score and associated red flag findings were assessed in relation to the composite primary endpoint: all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke. Results: Over a median of 58 months for follow-up, 460 patients experienced a primary event, including 346 deaths. Higher event rates were observed in older males, those with atrioventricular block, and patients receiving single-lead ventricular devices. T-AMYLO score and the presence of red flag findings, particularly aortic valve disease, AV block, peripheral neuropathy, low voltages and increased septal thickness were significantly associated with adverse outcomes. Multivariate Cox regression identified elevated T-AMYLO score (HR: 1.06, p = 0.012), aortic valve disease (HR: 1.29, p = 0.016), and AV block (HR: 1.43, p = 0.009) as independent predictors of mortality. Survival analyses confirmed a stepwise decline in prognosis with an increasing T-AMYLO risk group and red flag burden (p < 0.001). Conclusion: These findings highlight the importance of incorporating T-AMYLO scoring and red flags assessment in patients with conduction defects to improve early detection of cardiac amyloidosis and guide risk stratification for outcomes. Full article

(This article belongs to the Section Cardiovascular Clinical Research)

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13 pages, 1504 KB

Open AccessReview

Unusual, Uncommon, Intriguing, and Significant Causes of Kounis Syndrome: Important Medications and Chemicals Used to Treat Kounis Syndrome and Myocardial Infarction Can Cause Kounis Syndrome

by Nicholas G. Kounis, Cesare de Gregorio, Ming-Yow Hung, Grigorios Giamouzis, Marina A. Michalaki, Uğur Özkan, Alexandr Ceasovschih, Virginia Mplani, Periklis Dousdampanis, Sophia N. Kouni, Alexandros Stefanidis, Kassiani-Maria Nastouli, Maria Bozika, Nicholas Patsouras and Ioanna Koniari

J. Cardiovasc. Dev. Dis. 2025, 12(11), 423; https://doi.org/10.3390/jcdd12110423 - 24 Oct 2025

Abstract

Mast cell degranulation and other interacting and linked cells, including T-lymphocytes, macrophages, eosinophils, and platelets, as well as a range of inflammatory mediators produced during an anaphylactic or allergic reaction, constitute the main causes of Kounis syndrome. Acute ischemia episodes, coronary spasm, atheromatous [...] Read more.

Mast cell degranulation and other interacting and linked cells, including T-lymphocytes, macrophages, eosinophils, and platelets, as well as a range of inflammatory mediators produced during an anaphylactic or allergic reaction, constitute the main causes of Kounis syndrome. Acute ischemia episodes, coronary spasm, atheromatous plaque erosion/rupture, and platelet activation can all be caused by histamine, tryptase, arachidonic acid derivatives, and chymase in the Kounis syndrome cascade. Kounis syndrome can be triggered by a variety of factors, including medications, hymenopteran stings, metals, foods, environmental exposures, illnesses, and immunizations. In addition, some unusual, rare, intriguing, and significant causes of Kounis syndrome have been discovered recently, namely the “kiss of death”, where human kissing and pet kissing can induce fatal Kounis syndrome. Moreover, the clinical conundrum is that several of the main drugs and substances used to treat myocardial infarction and Kounis syndrome, such as adrenaline (epinephrine), aspirin, atropine, clopidogrel, corticosteroids, heparins, protamine sulfate, and hirudotherapy can also initiate it. Therefore, physicians should be aware of this clinical discrepancy to prevent catastrophic consequences. Full article

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

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11 pages, 379 KB

Open AccessSystematic Review

ChatGPT Applications in Heart Failure: Patient Education, Readability Enhancement, and Clinical Utility

by Robert S. Doyle, Jack Hartnett, Hugo C. Temperley, Cian P. Murray, Ross Walsh, Jamie Walsh, John McCormick, Catherine McGorrian, Katie Murphy and Kenneth McDonald

J. Cardiovasc. Dev. Dis. 2025, 12(11), 422; https://doi.org/10.3390/jcdd12110422 - 24 Oct 2025

Abstract

Background: Heart failure (HF) affects over 64 million people globally, imposing substantial morbidity, mortality, and economic burdens. Despite advances in guideline-directed therapies, adherence remains suboptimal due to low health literacy and complex regimens. ChatGPT, an advanced large language model by OpenAI, offers conversational [...] Read more.

Background: Heart failure (HF) affects over 64 million people globally, imposing substantial morbidity, mortality, and economic burdens. Despite advances in guideline-directed therapies, adherence remains suboptimal due to low health literacy and complex regimens. ChatGPT, an advanced large language model by OpenAI, offers conversational capabilities that could enhance HF education, management, and research. This systematic review synthesizes evidence on ChatGPT’s applications in HF, evaluating its accuracy in patient education and question-answering, enhancing readability, and clinical documentation/symptom extraction. Methods: Following PRISMA guidelines, we searched PubMed, Embase, and Cochrane up to July 2025 using the terms “ChatGPT” and “heart failure”. Inclusion: Studies on ChatGPT (3.5 or 4) in HF contexts, such as in education, readability and symptom extraction. Exclusion: Non-HF or non-ChatGPT AI. Data extraction covered design, objectives, methods, and outcomes. Thematic synthesis was applied. Results: From 59 records, 7 observational studies were included. Themes included patient education/question-answering (n = 5), readability enhancement (n = 2), and clinical documentation/symptom extraction (n = 1). Accuracy ranged 78–98%, with high reproducibility; readability improved to 6th–7th grade levels; and symptom extraction achieved up to 95% F1 score, outperforming traditional machine learning baselines. Conclusions: ChatGPT shows promise in HF care but requires further randomized validation for outcomes and bias mitigation. Full article

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14 pages, 491 KB

Open AccessArticle

Metabolic Syndrome and Outcome Predictions: Friends or Foes?

by Alessandro Menotti and Paolo Emilio Puddu

J. Cardiovasc. Dev. Dis. 2025, 12(11), 421; https://doi.org/10.3390/jcdd12110421 - 23 Oct 2025

Abstract

Objectives: An analysis based on epidemiological material to show whether the term Metabolic Syndrome (MS) should be adopted when aiming at predicting coronary heart disease (CHD) and major cardiovascular disease (CVD) fatal events. Material and Methods: MS was defined according to the International [...] Read more.

Objectives: An analysis based on epidemiological material to show whether the term Metabolic Syndrome (MS) should be adopted when aiming at predicting coronary heart disease (CHD) and major cardiovascular disease (CVD) fatal events. Material and Methods: MS was defined according to the International Diabetes Federation (IDF) and risk factors were identified in the Italian Risk Factors and Life Expectancy (RIFLE) population study covering over 25,000 adult men from a pool of 19 Italian population samples. The original MS definition and the plain original units of measured risk factors were challenged in Cox proportional hazard models predicting 196 CHD and 412 major CVD fatal events in a seven-year follow-up. Parallel models were run including also total serum cholesterol as a covariate, an unfortunately excluded covariate in the MS definition. The performance of the various models was tested by the log-likelihood statistics treated with the Akaike Information Criterium (AIC). Results: Models using the plain measurements of the risk factors involved were systematically and significantly outperforming any other categorized score based on the IDF-MS classification. An intermediate role was played by a model where the predictive variable was a factor score (derived from a Factor Analysis) where the MS risk factors were linearly combined. The same models also including serum cholesterol provided a significantly better prediction when compared with those without serum cholesterol, based on AIC. Conclusions: The use of a subset of classical CVD risk factors classified according to the IDF-MS criteria adds nothing better than the exclusive use of the risk factors treated by traditional procedures. The addition of serum cholesterol definitely helps in the prediction of the CHD component of major CVD events. Its omission is erroneous. Full article

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

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15 pages, 659 KB

Open AccessArticle

Prediction of Postoperative Mortality After Fontan Procedure: A Clinical Prediction Model Study Using Deep Learning Artificial Intelligence Techniques

by Jacek Kolcz, Anna Budzynska, Justyna Stefaniak, Renata Szydlak and Andrzej A. Kononowicz

J. Cardiovasc. Dev. Dis. 2025, 12(11), 420; https://doi.org/10.3390/jcdd12110420 - 23 Oct 2025

Abstract

Background: The Fontan procedure is a palliative surgery for patients with single-ventricle congenital heart disease (CHD), but it is associated with postoperative and long-term mortality and morbidity. Accurate, individualized risk stratification remains a challenge with traditional models. This study aimed to develop and [...] Read more.

Background: The Fontan procedure is a palliative surgery for patients with single-ventricle congenital heart disease (CHD), but it is associated with postoperative and long-term mortality and morbidity. Accurate, individualized risk stratification remains a challenge with traditional models. This study aimed to develop and validate a deep learning (DL) model to predict postoperative mortality after the Fontan procedure and to identify key predictive factors. Methods: We retrospectively analysed data from 230 patients who underwent the Fontan procedure between 2010 and 2024. A Deep Neural Network (DNN) model was developed using comprehensive preoperative, intraoperative, and postoperative clinical, biochemical, and hemodynamic variables. The dataset was split using five-fold cross-validation, with 80% for training and 20% for testing in each fold. The Synthetic Minority Over-sampling Technique (SMOTE) was used to fix class imbalance. Model performance was evaluated using five-fold stratified cross-validation. We assessed accuracy, precision, recall, F1-score, and Area Under the Receiver Operating Characteristic Curve (AUC-ROC). SHapley Additive exPlanations (SHAP) analysis was employed to enhance model interpretability and identify the importance of features. A user-friendly clinical application interface was developed using Streamlit. This study was reported in accordance with the TRIPOD + AI reporting guidelines. Results: The DNN model demonstrated superior performance in predicting postoperative mortality, achieving an overall accuracy of 91.5% (95% CI: 87.2–94.8%), precision of 83.3% (95% CI: 76.5–89.1%), recall (sensitivity) of 90.9% (95% CI: 85.2–95.1%), specificity of 92.5% (95% CI: 88.3–95.7%), F1-score of 87.0% (95% CI: 82.1–91.3%), and an AUC-ROC of 0.94 (95% CI: 0.88–0.99). SHAP analysis identified key predictors of mortality, such as pulmonary artery pressure, ventricular end-diastolic pressure, preoperative BNP levels, and severity of AV valve regurgitation. The Streamlit application offered a user-friendly interface for personalized risk evaluation. Conclusions: A deep learning model that incorporates detailed clinical data can precisely forecast postoperative mortality in patients undergoing Fontan surgeries. This AI-based method, combined with interpretability techniques, provides a valuable tool for personalized risk assessment. It has the potential to improve preoperative counseling, optimize perioperative care, and enhance patient outcomes. However, additional external validation is needed to verify its broader applicability and clinical usefulness. Full article

(This article belongs to the Special Issue Congenital Heart Disease: Imaging Diagnosis, Treatment, and Future Challenges)

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14 pages, 2028 KB

Open AccessReview

Therapeutic Challenges in Total Situs Inversus Associated with Sick Sinus Syndrome, Ventricular Arrhythmias, and Heart Failure with Preserved Ejection Fraction: Narrative Review and Case Report

by Cristina Tudoran, Mariana Tudoran, Dragos Cozma, Cristina Văcărescu, Ahmed Abu-Awwad, Simona-Alina Abu-Awwad, Dragos Cătălin Jianu and Florica Voitță-Mekereș

J. Cardiovasc. Dev. Dis. 2025, 12(11), 419; https://doi.org/10.3390/jcdd12110419 - 22 Oct 2025

Abstract

Background: Total situs inversus (TSI) is a rare genetic anomaly, and approximately half of the affected individuals also have other associated cardiovascular anomalies. Thus, the concomitance of conduction and rhythm disturbances is seldom described in the medical literature. Methods: We searched the medical [...] Read more.

Background: Total situs inversus (TSI) is a rare genetic anomaly, and approximately half of the affected individuals also have other associated cardiovascular anomalies. Thus, the concomitance of conduction and rhythm disturbances is seldom described in the medical literature. Methods: We searched the medical literature for similar cases published as full text, in English, on Clarivate, PubMed, and Google Scholar between 2016 and 2025. Results: We found 9 reports on TSI patients also having sick sinus syndrome (SSS) associated with rhythm disturbances, mainly atrial fibrillation, raising diagnostic and procedural challenges due to the anatomical anomalies requiring a peculiar approach. We describe the case of a 43-year-old woman diagnosed with TSI associated with ventricular arrhythmias in 2015 who experienced SSS requiring the implantation of a pacemaker during 10 years of follow-up but continued to have frequent episodes of nonsustained ventricular tachycardia (NSVT), raising multiple diagnoses and therapeutic challenges. After developing heart failure with preserved ejection fraction, she received guideline-adjusted treatment and, surprisingly, her clinical status improved, and NSVT diminished in frequency and then disappeared. Conclusions: Highlighting TSI′s clinical implications, often associated with other cardiovascular abnormalities, is important for an accurate diagnosis and adapted therapeutic management, considering the procedural challenges and potential complications. Full article

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14 pages, 1036 KB

Open AccessReview

Ocean Acidification, Iodine Bioavailability, and Cardiovascular Health: A Review of Possible Emerging Risks

by Charalampos Milionis, Costas Thomopoulos, Emilia Papakonstantinou and Ioannis Ilias

J. Cardiovasc. Dev. Dis. 2025, 12(11), 418; https://doi.org/10.3390/jcdd12110418 - 22 Oct 2025

Abstract

Anthropogenic climate change drives ocean acidification, which alters marine iodine cycling and increases bioaccumulation in marine ecosystems. This environmental shift may alter marine iodine cycling and, under certain conditions, lead to increased dietary and atmospheric iodine exposure, particularly in coastal populations, with potential [...] Read more.

Anthropogenic climate change drives ocean acidification, which alters marine iodine cycling and increases bioaccumulation in marine ecosystems. This environmental shift may alter marine iodine cycling and, under certain conditions, lead to increased dietary and atmospheric iodine exposure, particularly in coastal populations, with potential risks for thyroid dysfunction and downstream cardiovascular complications. Experimental data suggest that acidification may enhance iodine uptake in marine organisms such as kelp and seafood, with possible implications for consumption by humans. Because chronic iodine excess has already been associated with thyroid disease and its related cardiovascular disorders, these connections are worthy of further examination. In this narrative review we provide a synthesis of the possible mechanistic pathways by which ocean acidification, iodine bioavailability, thyroid function, and cardiovascular health may be connected. We also highlight the need for ongoing investigation, environmental monitoring, and interdisciplinary collaboration to further explain and address these tentative associations. Full article

(This article belongs to the Special Issue Cardiovascular Disease and Nutrition)

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16 pages, 1589 KB

Open AccessArticle

Diagnostic Predictive Scores of Amyloid Cardiomyopathy in Patients with Heart Failure with Preserved Ejection Fraction and Left Ventricular Hypertrophy

by Denise Cristiana Faro, Fabrizia Romeo, Valentina Losi, Dario Simonetti, Davide Capodanno and Ines Paola Monte

J. Cardiovasc. Dev. Dis. 2025, 12(11), 417; https://doi.org/10.3390/jcdd12110417 - 22 Oct 2025

Abstract

Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is a frequent but underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH). Early identification is essential given the availability of disease-modifying therapies. The T-Amylo and Davies scores are non-invasive tools [...] Read more.

Background: Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is a frequent but underdiagnosed cause of heart failure with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH). Early identification is essential given the availability of disease-modifying therapies. The T-Amylo and Davies scores are non-invasive tools for estimating ATTR CM probability, but their comparative performance in the same real-world population is not well defined. Objectives: To compare the diagnostic accuracy of T-Amylo and Davies scores in consecutive patients referred for suspected cardiac amyloidosis. Methods: We retrospectively analyzed 81 patients (mean age 76.8 ± 8.3 years, 74% male) who underwent a standardized work-up: ECG, echocardiography with strain, NT-proBNP and troponin, bone scintigraphy, and immunofixation. ATTR CM was diagnosed according to established non-biopsy criteria. Both scores were calculated retrospectively, and sensitivity, specificity, predictive values, accuracy, and agreement were assessed. Results: ATTR CM was confirmed in 28 patients (34.5%). T-Amylo showed higher sensitivity (91.2% vs. 73.5%) and NPV (89.7% vs. 79.1%), while Davies had greater specificity (85.0% vs. 65.0%) and PPV (80.5% vs. 70.8%). Overall accuracy was comparable (T-Amylo 77.0% vs. Davies 79.7%). Agreement between scores was moderate (κ = 0.59). Conclusions: T-Amylo is best suited as a screening tool for suspected ATTR CM, while Davies offers confirmatory value in high-probability cases. Combining these tools in a sequential strategy may optimize diagnostic efficiency, reduce unnecessary testing, and expedite initiation of disease-modifying therapy. Full article

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