Journal of Cardiovascular Development and Disease

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 (registering DOI) - 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 (registering DOI) - 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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15 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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11 pages, 365 KB

Open AccessReview

The Importance of Early Diagnosis and Treatment to Limit the Impact of Dystrophic Cardiomyopathy—We’ve Seen This Film Before, and We Didn’t Like the Ending

by DeWayne Townsend

J. Cardiovasc. Dev. Dis. 2025, 12(11), 416; https://doi.org/10.3390/jcdd12110416 - 22 Oct 2025

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Abstract

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder that is characterized by skeletal muscle wasting, loss of ambulation, and respiratory failure. In addition to these obvious external signs of disease, heart disease, the leading cause of death in DMD patients, is also [...] Read more.

Duchenne muscular dystrophy (DMD) is a rare neuromuscular disorder that is characterized by skeletal muscle wasting, loss of ambulation, and respiratory failure. In addition to these obvious external signs of disease, heart disease, the leading cause of death in DMD patients, is also progressing. Dystrophic cardiomyopathy is largely clinically silent with cardiac dysfunction masked by concurrent loss of skeletal muscle function. In older DMD patients the prevalence of heart disease is very high, offering the unique potential to predict impending heart disease from a much earlier genetic diagnosis. Randomized clinical trial data and subsequent retrospective studies in DMD demonstrate that early initiation of cardiac directed therapy results in a significant delay in the onset of cardiac dysfunction and prolonged survival. Clinical guidelines reflect this, recommending the initiation of cardiac therapy at an age of 10 years old, even in the absence of documented contractile dysfunction. Despite this data, a recent examination of registry data reveals that most DMD patients are not receiving the treatments recommended by these guidelines. While there is great excitement regarding newly developed therapies for DMD, there are so many signs that deploying the safe and effective therapies we already have can improve clinical outcomes. This review will highlight the basic science behind and clinical importance of using early cardiac directed therapy to extend the duration and quality of life of DMD patients and will offer some suggestions that may aid in achieving this goal. Full article

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

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14 pages, 503 KB

Open AccessReview

Iron Deficiency in Heart Failure: Cellular Mechanisms and Therapeutic Implications

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

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

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Abstract

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

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

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

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J. Cardiovasc. Dev. Dis., Volume 12, Issue 11 (November 2025) – 9 articles

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