Journal of Cardiovascular Development and Disease

15 pages, 2606 KB

Open AccessSystematic Review

Effect of GLP-1 Receptor Agonists in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis

by Benjamin J. Behers, Christian Sanchez, Omar Hozayen, Yousef Hozayen, Rheiner Kammer, William T. Corrigan, Christoph A. Stephenson-Moe, Matthew W. Miller, Mohab Idriss, Luis E. Cekan, Alan D. King, Garrett H. Brown and Karen M. Hamad

J. Cardiovasc. Dev. Dis. 2026, 13(2), 103; https://doi.org/10.3390/jcdd13020103 - 21 Feb 2026

Cited by 2 | Viewed by 2336

Abstract

Heart failure with preserved ejection fraction (HFpEF) affects 32 million people worldwide and is responsible for tens of billions of dollars in healthcare expenditure annually, with costs primarily driven by hospitalizations. HFpEF is notoriously difficult to treat, but emerging studies suggest that glucagon-like [...] Read more.

Heart failure with preserved ejection fraction (HFpEF) affects 32 million people worldwide and is responsible for tens of billions of dollars in healthcare expenditure annually, with costs primarily driven by hospitalizations. HFpEF is notoriously difficult to treat, but emerging studies suggest that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may be effective therapies. We performed a systematic review and meta-analysis of six randomized controlled trials with 5564 total participants investigating GLP-1 RAs in patients with HFpEF. Overall, no significant effect was noted for GLP-1 RAs on our primary outcomes of cardiovascular mortality and worsening heart failure (HF) events, although they were associated with improvement in quality of life measures. Furthermore, safety data favored the GLP-1 RA group, although tolerability did not differ compared with placebo. While the pooled analysis of all GLP-1 RAs showed neutral effects versus hard endpoints, sensitivity analyses excluding older-generation agents (exenatide) revealed a significant 41% reduction in HF events, suggesting that newer, more potent agents (semaglutide, tirzepatide) may offer disease-modifying benefits in HFpEF. Although future studies are needed, GLP-1 RAs appear to be promising for the treatment of HFpEF. Full article

(This article belongs to the Special Issue Heart Failure: Advanced Imaging and New Treatments)

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12 pages, 570 KB

Open AccessArticle

Nurse-Led Secondary Prevention After Acute Coronary Syndrome: Bridging the Gender Gap in Cardiovascular Outcomes—A Sub-Analysis of the BEAT-HF Study

by Oona Meroño Dueñas, Mar Iraculis Sanchez, Marc Llagostera Martin, Marta Ruiz Muñoz, Marta Gomez Cuba, Laia Alcober Morte, Natalia López Fernández, Guillem Cirera Salleras, Adrian Ricarte Marin, Maria Soler Cera, Alberto Garay Melero, Gemma Simo Cubel, Joan Antoni Gomez Hospital, Cristina Capdevila Aguilera and Josep Comin Colet

J. Cardiovasc. Dev. Dis. 2026, 13(2), 102; https://doi.org/10.3390/jcdd13020102 - 21 Feb 2026

Viewed by 767

Abstract

Background: Despite advances in the management of acute coronary syndrome (ACS), women continue to experience higher long-term mortality and lower access to secondary prevention compared with men. Objective: This study aimed to assess whether a universally inclusive, nurse-led secondary prevention program implemented at [...] Read more.

Background: Despite advances in the management of acute coronary syndrome (ACS), women continue to experience higher long-term mortality and lower access to secondary prevention compared with men. Objective: This study aimed to assess whether a universally inclusive, nurse-led secondary prevention program implemented at a University Hospital improved post-ACS outcomes and reduced gender disparities in risk factor control and mortality. Methods: This retrospective, observational study compared two cohorts of ACS survivors discharged from Bellvitge University Hospital: a pre-intervention cohort (2018) and a post-intervention cohort (2022). The nurse-led program included universal enrollment of all ACS patients, early follow-up, pharmacological optimization, therapeutic exercise, lifestyle counseling, and coordination with primary care. Outcomes included lipid and glycemic control and 18-month mortality, stratified by sex. Results: A total of 409 patients were included (2018: n = 200; 2022: n = 209), of whom 130 were women. Women were older and had more comorbidities. Post-program implementation, the proportion of patients without post-discharge blood testing dropped from >50% to <17% in both sexes. Lipid and glycemic control improved significantly at both early (1–4 months) and late (9–18 months) follow-up. Early differences favoring men disappeared by 18 months. Mortality decreased by 27.5% in men and 47.6% in women, representing a significantly greater relative reduction among women (p = 0.0001). Conclusions: A structured, nurse-led secondary prevention program with systematic inclusion improved clinical outcomes and significantly narrowed the gender gap in cardiovascular mortality. These findings demonstrate that equitable, protocolized care led by advanced practice nurses can reduce systemic inequities in cardiovascular health. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

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11 pages, 1001 KB

Open AccessArticle

The Left Axillary Artery as an Alternative Inflow Source in Minimally Invasive Coronary Artery Bypass Grafting: Safety, Feasibility, and Mid-Term Outcomes

by Jian Song, Tong Ding, Rui Li, Yichen Gong, Ruitao Zhang, Yuanhao Fu, Luyu Meng, Song Wu, Zhongqi Cui, Ya Wu, Chen Yang, Ming Cui and Yunpeng Ling

J. Cardiovasc. Dev. Dis. 2026, 13(2), 101; https://doi.org/10.3390/jcdd13020101 - 21 Feb 2026

Viewed by 675

Abstract

Objective: The objective of this study is to evaluate the safety, feasibility, and mid-term outcomes of using the left axillary artery (AXA) as an alternative inflow source for the proximal anastomosis of the saphenous vein graft (SVG) in MICS-CABG, focusing on intraoperative graft [...] Read more.

Objective: The objective of this study is to evaluate the safety, feasibility, and mid-term outcomes of using the left axillary artery (AXA) as an alternative inflow source for the proximal anastomosis of the saphenous vein graft (SVG) in MICS-CABG, focusing on intraoperative graft haemodynamics, early patency, and clinical outcomes. Methods: We retrospectively analyzed consecutive patients who underwent MICS-CABG between April 2020 and August 2025 at a single center. Patients were divided into two groups based on the inflow source: the ascending aorta (n = 292) or the left axillary artery (n = 90). After propensity score matching, 80 matched pairs were analyzed. Intraoperative graft haemodynamics were assessed. Early graft patency was evaluated using coronary angiography or CT angiography. Mid-term outcomes, including overall survival and major adverse cardiac and cerebrovascular events (MACCEs), were compared between groups. Results: Both groups demonstrated comparable intraoperative hemodynamic performance. The AXA group demonstrated an early graft occlusion rate comparable to that of the AOR group (1.32% vs. 3.16%, RR = 0.42, 95% CI = 0.08–2.11, and p = 0.45). Overall survival (93.2% vs. 100%, p = 0.06) and the MACCE-free metric (91.9% vs. 92.1%, p = 0.83) showed no significant difference between groups. Conclusions: The left axillary artery is a safe and feasible alternative inflow source in MICS-CABG. This approach provides acceptable intraoperative flow dynamics, early patency, and mid-term outcomes to conventional ascending aortic inflow. Full article

(This article belongs to the Special Issue Coronary Artery Bypasses: Techniques, Outcomes, and Complications)

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12 pages, 360 KB

Open AccessArticle

Saudi Secondary Prevention Survey Study in Patients with Prior Acute Myocardial Infarction (4S Registry): Study Design and Pilot Phase Results

by Rakan K. Alhabib, Naji Kholaif, Mohammed Mahmoud, Abdulrahman Alnwiji, Fayez Al Zubair, Hassan Almir, Ahmad Saad Alzoman, Abdulmalik Abdullah Alqahtani, Rasha Alsharkawy, Zahra Mohammed Albahar and Khalid F. Alhabib

J. Cardiovasc. Dev. Dis. 2026, 13(2), 100; https://doi.org/10.3390/jcdd13020100 - 20 Feb 2026

Viewed by 1043

Abstract

Patients with prior acute myocardial infarction (AMI) generally show low rates of achieving secondary prevention targets. Here we evaluated adherence to guideline-recommended secondary prevention strategies after AMI in Saudi Arabia. This ambispective multicenter cohort study included consecutive patients seen for follow-up visits 6–24 [...] Read more.

Patients with prior acute myocardial infarction (AMI) generally show low rates of achieving secondary prevention targets. Here we evaluated adherence to guideline-recommended secondary prevention strategies after AMI in Saudi Arabia. This ambispective multicenter cohort study included consecutive patients seen for follow-up visits 6–24 months after hospitalization for AMI. A standardized questionnaire was used to evaluate control of blood pressure (<130/80 mmHg), HbA1c (<7%), LDL-C (<1.4 mmol/L), lipoprotein(a) (<50 mg/dL), body mass index (18.5–24.9 kg/m²), physical activity targets, smoking habits, guideline-directed medical therapy (GDMT), and referral to cardiac rehabilitation. Among 108 AMI patients (mean age 58.4 ± 10.9 years; 80.6% male; 76.9% Saudi nationals), 53.7% had uncontrolled blood pressure, ~40% uncontrolled glucose, and 67% above-target LDL-C levels. Most participants were overweight (40.7%) or obese (37%), and 28.7% achieved the physical activity targets. One-third of patients were not receiving all GDMT, 15.7% were current smokers, and 25% had been referred to cardiac rehabilitation. No patient met all guideline-recommended secondary prevention targets. This pilot study highlights gaps in secondary prevention among AMI survivors. Upcoming study phases will aim for national representation and help identify key clinical and demographic drivers to improve secondary prevention efforts across Saudi Arabia. Full article

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23 pages, 2270 KB

Open AccessEditor’s ChoiceReview

Short-Term Percutaneous Mechanical Circulatory Support in Acute Coronary Syndrome with Cardiogenic Shock: Which Device to Choose?

by Nardi Tetaj, Annunziata Nusca, Francesco Piccirillo, Geza Halasz, Domenico Gabrielli, Gian Paolo Ussia and Francesco Grigioni

J. Cardiovasc. Dev. Dis. 2026, 13(2), 99; https://doi.org/10.3390/jcdd13020099 - 18 Feb 2026

Cited by 1 | Viewed by 1620

Abstract

Cardiogenic shock (CS) remains a life-threatening syndrome characterized by reduced cardiac output and end-organ hypoperfusion, most commonly resulting from acute myocardial infarction (AMI). Despite advances in early revascularization and increasing use of percutaneous mechanical circulatory support (MCS), short-term mortality in AMI-related CS (AMI-CS) [...] Read more.

Cardiogenic shock (CS) remains a life-threatening syndrome characterized by reduced cardiac output and end-organ hypoperfusion, most commonly resulting from acute myocardial infarction (AMI). Despite advances in early revascularization and increasing use of percutaneous mechanical circulatory support (MCS), short-term mortality in AMI-related CS (AMI-CS) remains high. This review summarizes the contemporary evidence on short-term percutaneous MCS in AMI-CS, with a focus on intra-aortic balloon pump (IABP), Impella microaxial flow pumps, and venoarterial extracorporeal membrane oxygenation (VA-ECMO), and provides insights into device selection and implementation in clinical practice. We performed a comprehensive analysis of the most relevant randomized controlled trials and key guideline recommendations from European and North American societies concerning the use of MCS. Despite its long-standing, IABP has not demonstrated a mortality benefit in contemporary trials and is no longer recommended for routine use in AMI-CS without mechanical complications. Nevertheless, it remains widely used due to its simplicity, safety profile, and broad availability. In contrast, Impella devices provide active left ventricular unloading and have shown promising hemodynamic effects, with the DanGer Shock trial suggesting a potential survival benefit in carefully selected patients, at the expense of higher complication rates. VA-ECMO offers full cardiopulmonary support but is associated with the highest complication rates and increases left ventricular afterload, often requiring adjunctive unloading with devices such as Impella (ECPELLA). However, recent randomized trials have not demonstrated a clear survival advantage for VA-ECMO, and concerns regarding its complications persist. In conclusion, CS continues to pose major therapeutic challenges, and no single MCS device has consistently shown a survival benefit across all AMI-CS patient populations. Individualized, phenotype-driven strategies that incorporate hemodynamic profiling and timely escalation of support are essential. Further randomized studies are urgently needed to define optimal device selection, the timing of placement, and appropriate patient selection criteria. Institutional protocols guided by clinical stage, etiology, and available expertise will be pivotal in improving outcomes. Full article

(This article belongs to the Special Issue Further Understanding of Myocardial Infarction: Risk Factors, Treatment, and Clinical Outcomes)

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16 pages, 4132 KB

Open AccessEditor’s ChoiceArticle

Intraoperative Quantification of Severe Mitral Regurgitation: A Comparative Assessment of Two-Dimensional Flow Convergence, Three-Dimensional Volumetric, and Doppler-Based Methods

by Hany R. Elgamal, Volodymyr Protsyk, Massimiliano Meineri, Joerg Ender and Waseem Zakhary

J. Cardiovasc. Dev. Dis. 2026, 13(2), 98; https://doi.org/10.3390/jcdd13020098 - 18 Feb 2026

Cited by 1 | Viewed by 663

Abstract

Accurate quantification of mitral regurgitation (MR) is central to perioperative decision-making, yet the agreement and interchangeability of commonly used echocardiographic methods remain uncertain. This study evaluated quantitative MR parameters individually and within a multiparametric framework using three-dimensional (3D) vena contracta area (VCA) as [...] Read more.

Accurate quantification of mitral regurgitation (MR) is central to perioperative decision-making, yet the agreement and interchangeability of commonly used echocardiographic methods remain uncertain. This study evaluated quantitative MR parameters individually and within a multiparametric framework using three-dimensional (3D) vena contracta area (VCA) as an intraoperative reference. In this single-center retrospective analysis, intraoperative echocardiographic data from 85 patients undergoing mitral valve intervention between July 2024 and June 2025 were analyzed. Regurgitant volume (RVol) and regurgitant fraction (RF) were quantified using two-dimensional proximal isovelocity surface area (PISA), a 3D volumetric method, and a Doppler-based continuity equation. Agreement was assessed by Bland–Altman analysis, and categorical concordance was assessed by Cohen’s kappa for individual and multiparametric grading strategies. Agreement between individual quantitative methods was limited, with substantial bias and wide limits of agreement for both RVol and RF, resulting in poor-to-fair concordance for MR severity classification. Incorporation of RVol and RF into multiparametric grading strategies improved concordance. Compared with 3D VCA, multiparametric integration incorporating PISA-derived measures showed the best overall performance, with high accuracy and sensitivity and moderate specificity. These findings indicate limited interchangeability of standalone quantitative echocardiographic methods and support reporting the applied technique and using a multiparametric approach anchored to 3D VCA when cardiac magnetic resonance imaging is unavailable. Full article

(This article belongs to the Special Issue Advanced Cardiovascular Imaging in Structural Heart Disease: Diagnostic, Prognostic, and Therapeutic Perspectives)

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17 pages, 648 KB

Open AccessArticle

Sporting Careers After ICD Implantation in Elite Athletes

by Marco Vecchiato, Florian Egger and Stefano Palermi

J. Cardiovasc. Dev. Dis. 2026, 13(2), 97; https://doi.org/10.3390/jcdd13020097 - 17 Feb 2026

Viewed by 976

Abstract

Background: The use of implantable cardioverter defibrillators (ICDs) in elite athletes following sudden cardiac arrest (SCA) or the diagnosis of high-risk cardiac conditions presents a complex interplay of medical, psychological, and legal challenges. Despite evolving guidelines, data on clinical outcomes and return-to-sport (RTS) [...] Read more.

Background: The use of implantable cardioverter defibrillators (ICDs) in elite athletes following sudden cardiac arrest (SCA) or the diagnosis of high-risk cardiac conditions presents a complex interplay of medical, psychological, and legal challenges. Despite evolving guidelines, data on clinical outcomes and return-to-sport (RTS) trajectories in elite athletes remain limited. Objective: To describe the clinical profiles, management strategies, and career outcomes of elite athletes who received ICDs. Methods: A retrospective multilingual media and literature search was performed up to January 2026 to identify elite athletes with ICDs. Inclusion criteria required evidence of professional or Olympic-level competition, confirmed ICD implantation, and sufficient clinical and career data. Cases were analyzed for demographics, underlying diagnosis, prevention type, post-ICD outcomes, and RTS status. Results: Thirty-seven elite athletes were identified (mean age 25.8 ± 4.3 years). The most common sport was football (n = 25). Hypertrophic cardiomyopathy, non-ischemic LV scar, and arrhythmogenic cardiomyopathy were the most frequent diagnoses, although 49% of etiologies remained unspecified. ICDs were implanted for secondary prevention in 70% of cases. Following ICD implantation, 25 athletes (68%) completed RTS, including 24 (65%) at the professional level. Among these, nine experienced shocks, and four ultimately discontinued competition. The sole fatality occurred in an athlete who had voluntarily explanted the ICD. Conclusions: A substantial proportion of elite athletes with ICDs successfully return to high-level sport, but clinical outcomes, risk tolerance, and legal frameworks remain variable. These findings support continued shifts towards personalized shared decision making and highlight the need for standardized, sport-specific RTS protocols, long-term registries, and psychosocial support in this population. Full article

(This article belongs to the Special Issue The Present and Future of Sports Cardiology and Exercise, 2nd Edition)

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23 pages, 1629 KB

Open AccessReview

Transcatheter Paravalvular Leak Closure: A Step-by-Step Guide

by Georgios E. Papadopoulos, Ilias Ninios, Sotirios Evangelou, Andreas Ioannides and Vlasis Ninios

J. Cardiovasc. Dev. Dis. 2026, 13(2), 96; https://doi.org/10.3390/jcdd13020096 - 16 Feb 2026

Viewed by 1330

Abstract

Paravalvular leak (PVL) remains a clinically important complication after surgical or transcatheter valve implantation, presenting predominantly with heart failure (HF) and/or high-shear hemolysis. While redo surgery can be definitive, contemporary candidates frequently carry prohibitive operative risk, positioning transcatheter PVL closure as a key [...] Read more.

Paravalvular leak (PVL) remains a clinically important complication after surgical or transcatheter valve implantation, presenting predominantly with heart failure (HF) and/or high-shear hemolysis. While redo surgery can be definitive, contemporary candidates frequently carry prohibitive operative risk, positioning transcatheter PVL closure as a key therapeutic alternative. However, available outcome data are largely derived from observational series and registries with heterogeneity in PVL mechanisms, prosthesis types, imaging protocols, and endpoint definitions. Standardized frameworks—such as those proposed by the PVL Academic Research Consortium—support harmonized PVL grading and clinically meaningful composite endpoints that integrate imaging/hemodynamic results with patient-centered outcomes. Across datasets, the most consistent determinant of benefit is residual PVL severity: procedural efficacy is most commonly defined as achieving ≤ mild residual regurgitation without prosthetic leaflet interference, device embolization, or major complications. This review provides a step-by-step, phenotype-driven approach to transcatheter PVL closure, emphasizing multimodality imaging (TEE and cardiac CT, with adjunct CMR and PET when appropriate), access and support planning tailored to valve position, and morphology-matched device selection—often requiring modular multi-device strategies for elongated crescentic channels, particularly in hemolysis-predominant presentations. We also synthesize evidence on complications and bailout management, with a focus on preventable high-severity events (leaflet impingement, embolization, stroke/air, vascular injury, tamponade) and standardized pre-release safety checks. Collectively, contemporary practice supports high implant success in experienced programs, with clinical improvement tightly coupled to procedural endpoint quality and careful Heart Team selection. Full article

(This article belongs to the Special Issue Emerging Trends and Advances in Interventional Cardiology)

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14 pages, 1616 KB

Open AccessArticle

Echocardiographic Features and Clinical Outcomes of Functional vs. Anatomical Pulmonary Atresia with Intact Ventricular Septum in Neonates

by Yalun Qu, Shuang Yang, Yuefeng Cao, Jiachen Li, Zhongyi Han, Dong Wang, Yao Yang, Yongtao Wu and Qiang Wang

J. Cardiovasc. Dev. Dis. 2026, 13(2), 95; https://doi.org/10.3390/jcdd13020095 - 15 Feb 2026

Viewed by 667

Abstract

(1) Background: Functional pulmonary atresia (FPA) and pulmonary atresia with intact ventricular septum (PA/IVS) are rare neonatal congenital heart diseases with similar early clinical manifestations but distinct pathophysiology and treatment strategies, making early and accurate differentiation clinically important. (2) Methods: This single-center retrospective [...] Read more.

(1) Background: Functional pulmonary atresia (FPA) and pulmonary atresia with intact ventricular septum (PA/IVS) are rare neonatal congenital heart diseases with similar early clinical manifestations but distinct pathophysiology and treatment strategies, making early and accurate differentiation clinically important. (2) Methods: This single-center retrospective study included 43 neonates diagnosed with FPA (n = 12) or PA/IVS (n = 31) between December 2016 and March 2025. Echocardiographic parameters and clinical data were compared between groups, and receiver operating characteristic curve analysis was performed to evaluate the usefulness of selected echocardiographic indices for differentiation in clinical practice. (3) Results: Compared with PA/IVS, neonates with FPA exhibited significantly larger right atrial area, relatively better preserved right ventricular development, larger patent ductus arteriosus diameter, and lower peak tricuspid regurgitation velocity. Several parameters, including right atrial area and the right-to-left ventricular ratio, demonstrated strong between-group discrimination in this cohort. Clinically, most FPA neonates were managed conservatively with favorable outcomes, whereas PA/IVS neonates required surgical intervention and experienced higher perioperative mortality. (4) Conclusions: FPA and PA/IVS differ significantly in right heart morphology, hemodynamic characteristics, and management strategies. A comprehensive multi-parameter echocardiographic evaluation demonstrated discriminatory ability in this cohort, facilitating appropriate treatment decisions and potentially helping to avoid unnecessary high-risk surgical interventions. Full article

(This article belongs to the Special Issue Congenital Heart Disease: Technological Innovations in Cardiac Surgery and Interventional Therapy)

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7 pages, 6120 KB

Open AccessCase Report

A Rare Cause of Life-Threatening Chest Pain: Kounis Syndrome

by Liangliang Jia, Yabin Liu, Xi Chen and Yufei Wang

J. Cardiovasc. Dev. Dis. 2026, 13(2), 94; https://doi.org/10.3390/jcdd13020094 - 14 Feb 2026

Viewed by 611

Abstract

Kounis syndrome, defined as an acute coronary syndrome triggered by allergic or hypersensitivity reactions, is a rare yet potentially life-threatening condition. This report details the case of a 50-year-old female patient presenting with recurrent chest pain, hypereosinophilia, and allergic comorbidities, who was ultimately [...] Read more.

Kounis syndrome, defined as an acute coronary syndrome triggered by allergic or hypersensitivity reactions, is a rare yet potentially life-threatening condition. This report details the case of a 50-year-old female patient presenting with recurrent chest pain, hypereosinophilia, and allergic comorbidities, who was ultimately diagnosed with type I Kounis syndrome. Modifications to her treatment regimen, including the administration of diltiazem and prednisolone, led to a complete resolution of her symptoms. This case highlights the critical importance of early diagnosis and timely intervention in managing Kounis syndrome. Early recognition is essential to prevent potentially fatal outcomes, thereby emphasizing the need for increased awareness among healthcare professionals. Full article

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14 pages, 754 KB

Open AccessEditor’s ChoiceReview

The Present and Future of Zone 0 Endovascular Arch Reconstruction

by Ming Hao Guo, Robert-James Doonan and Mark Rockley

J. Cardiovasc. Dev. Dis. 2026, 13(2), 93; https://doi.org/10.3390/jcdd13020093 - 13 Feb 2026

Viewed by 603

Abstract

Thoracic aortic pathology involving the aortic arch is most commonly treated with open total arch replacement. However, open surgery is still associated with significant risk of mortality and morbidity, particularly in the elderly, patients with high-risk comorbidities, and those with previous cardiac surgery. [...] Read more.

Thoracic aortic pathology involving the aortic arch is most commonly treated with open total arch replacement. However, open surgery is still associated with significant risk of mortality and morbidity, particularly in the elderly, patients with high-risk comorbidities, and those with previous cardiac surgery. Multiple endovascular approaches to enable zone 0 arch reconstruction have been developed, including custom-made, physician-modified, and off-the-shelf fenestrated/branched endografts. The initial experiences of this approach have been plagued by high incidence of stroke; although improvements have been made over the past decade, it remains suboptimal. Several factors contribute to this stagnation, including limited descriptive studies with small sample sizes, heterogeneous patient populations, varied techniques, and lack of data granularity and standardization. These limitations reduce the ability to analyze factors that could improve patient selection, device design, and procedural techniques. In addition, consistent follow-ups have not been reported, and the long-term outcome of these interventions are unknown. To address these issues, a randomized controlled trial of open versus endovascular arch repair or multicenter registry with standardized data reporting, follow-up protocol, and sufficient sample size would be needed. High-quality data will help identify patient clinical or anatomical features as well as procedural factors that can improve outcomes. Full article

(This article belongs to the Special Issue Current Status and Future Challenges of Aortic Arch Surgery)

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6 pages, 413 KB

Open AccessCase Report

Orthotopic Heart Transplantation with Concurrent Coronary Artery Bypass Grafting Using In Situ Internal Thoracic Artery

by Arjun Verma, Andreas Habertheuer, Nikhil Prasad, Sameer Hirji, Michael M. Givertz, Jonathan W. Cunningham, Mandeep R. Mehra and Akinobu Itoh

J. Cardiovasc. Dev. Dis. 2026, 13(2), 92; https://doi.org/10.3390/jcdd13020092 - 13 Feb 2026

Viewed by 584

Abstract

Heart transplantation remains the definitive therapy for end-stage heart failure, but donor coronary artery disease (CAD) is a common reason for allograft refusal, limiting organ availability. We describe a case of orthotopic heart transplantation using a donor heart with isolated coronary artery disease [...] Read more.

Heart transplantation remains the definitive therapy for end-stage heart failure, but donor coronary artery disease (CAD) is a common reason for allograft refusal, limiting organ availability. We describe a case of orthotopic heart transplantation using a donor heart with isolated coronary artery disease managed with concurrent surgical revascularization. A 66-year-old male with end-stage non-ischemic cardiomyopathy requiring temporary mechanical circulatory support underwent heart transplantation using a donor allograft with a focal lesion in a large first diagonal artery. Following standard implantation, a left internal mammary artery–to–first diagonal artery bypass was performed prior to reperfusion. The patient was successfully weaned from cardiopulmonary bypass with improving left ventricular function and had an uncomplicated postoperative course aside from transient delirium and dysphagia. Echocardiography demonstrated recovery of normal left ventricular function, and the patient remained clinically well with preserved biventricular function at 7-month follow-up. This case demonstrates the feasibility of orthotopic heart transplantation with concurrent coronary artery bypass grafting using an arterial conduit and supports surgical optimization of select donor hearts, with focal coronary disease as a potential strategy to expand the donor pool without compromising short-term outcomes. Full article

(This article belongs to the Section Cardiac Surgery)

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14 pages, 2472 KB

Open AccessArticle

Cardiac Catheterization for Coronary Artery Fistulas in Children: Evaluation, Management, and Outcomes—A Single-Center Experience

by Hayrettin Hakan Aykan, Nilay Korgal, Alpay Çeliker and Tevfik Karagöz

J. Cardiovasc. Dev. Dis. 2026, 13(2), 91; https://doi.org/10.3390/jcdd13020091 - 12 Feb 2026

Viewed by 711

Abstract

Coronary artery fistulas (CAFs) are rare congenital coronary anomalies in children and are frequently detected incidentally; however, the optimal management of asymptomatic cases and long-term outcomes remain debated. We retrospectively evaluated patients <18 years who underwent cardiac catheterization and coronary angiography for CAF [...] Read more.

Coronary artery fistulas (CAFs) are rare congenital coronary anomalies in children and are frequently detected incidentally; however, the optimal management of asymptomatic cases and long-term outcomes remain debated. We retrospectively evaluated patients <18 years who underwent cardiac catheterization and coronary angiography for CAF at a single tertiary center between 2003 and 2022, analyzing demographic, clinical, angiographic, procedural, and follow-up data; fistulas were classified using a modified Sakakibara system, and temporal changes in institutional clinical approach and device selection were also assessed. Forty-two patients (mean age 7.4 ± 5.9 years) were included, most of whom were asymptomatic (80.9%); the left coronary artery was the most frequent origin and 85% drained to right-sided chambers. Transcatheter closure was attempted in 25 patients and was technically successful in 23 (92%); complete occlusion was achieved angiographically in 61% immediately and exceeded 90% during follow-up due to spontaneous resolution of residual shunts. One patient required surgery for persistent moderate residual flow, and no major procedural complications, thrombotic events, or ischemic outcomes were observed. In selected children, transcatheter CAF closure is safe and effective, while conservative follow-up appears appropriate for small, hemodynamically insignificant fistulas, supporting individualized, anatomy-guided management. Full article

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

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11 pages, 721 KB

Open AccessArticle

Left Atrioventricular Coupling Index Predicts Poor Prognosis in Acute Myocardial Infarction: A Single-Center Cohort Study

by Chuyun Chen, Haolei Huang, Jia Jia, Fangfang Fan, Jie Jiang, Ying Yang and Yan Zhang

J. Cardiovasc. Dev. Dis. 2026, 13(2), 90; https://doi.org/10.3390/jcdd13020090 - 11 Feb 2026

Viewed by 560

Abstract

(1) Background: The left atrioventricular coupling index (LACI) is a novel parameter for evaluating cardiac function. This study focused on its association with major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) patients. (2) Methods: A retrospective cohort of AMI patients from [...] Read more.

(1) Background: The left atrioventricular coupling index (LACI) is a novel parameter for evaluating cardiac function. This study focused on its association with major adverse cardiovascular events (MACEs) in acute myocardial infarction (AMI) patients. (2) Methods: A retrospective cohort of AMI patients from Peking University First Hospital was enrolled. All underwent transthoracic echocardiography on admission for LACI measurement. The primary endpoint was MACE (a composite of nonfatal stroke, nonfatal myocardial infarction, and cardiovascular death). (3) Results: Among 843 AMI patients (62.07 ± 12.24 years, 77.94% male), the median LACI was 0.24 (IQR 0.18–0.33). During a median follow-up of 4.31 years, 151 patients (17.91%) developed MACE. The optimal LACI cutoff for risk stratification was 0.257. After multivariable adjustment, each standard deviation increase in LACI was associated with significantly elevated risks of MACE (HR 1.17, 95% CI 1.02–1.34), all-cause death (HR 1.19, 95% CI 1.05–1.35), cardiovascular death (HR 1.33, 95% CI 1.10–1.61), and stroke (HR 1.23, 95% CI 1.05–1.43). (4) Conclusions: LACI is an independent predictor of poor prognosis in AMI patients and may serve as a valuable tool for risk stratification in secondary prevention. Full article

(This article belongs to the Section Cardiovascular Clinical Research)

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25 pages, 1324 KB

Open AccessReview

Atherogenic Dyslipidemia in Children and Adolescents: Current Evidence, Clinical Challenges, and Future Perspectives

by Marco Giussani, Manuela Casula, Antonina Orlando, Gianfranco Parati and Simonetta Genovesi

J. Cardiovasc. Dev. Dis. 2026, 13(2), 89; https://doi.org/10.3390/jcdd13020089 - 11 Feb 2026

Viewed by 1473

Abstract

Atherogenic dyslipidemia is a condition characterized by high lipid levels that promote the development of atherosclerosis. While the clinical manifestations of atherosclerosis typically manifest in adulthood, early vascular damage can be identified in children and adolescents. Dyslipidemia is not uncommon in childhood and [...] Read more.

Atherogenic dyslipidemia is a condition characterized by high lipid levels that promote the development of atherosclerosis. While the clinical manifestations of atherosclerosis typically manifest in adulthood, early vascular damage can be identified in children and adolescents. Dyslipidemia is not uncommon in childhood and adolescence, and its development depends on the interaction between genetic and environmental factors. Forms caused by genetic defects tend to manifest earlier and usually require drug treatment. Forms caused by unhealthy lifestyles and eating habits tend to manifest later and often only require dietary and behavioural treatment. The review describes the most common primary forms, diagnostic criteria and treatment options, both pharmacological and non-pharmacological, emphasizing the differences and specificities of dyslipidemia in children compared to adults. The review’s objective is also to provide a clinically focused summary of the current evidence on atherogenic dyslipidemia in children and adolescents. Full article

(This article belongs to the Section Pediatric Cardiology and Congenital Heart Disease)

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13 pages, 4019 KB

Open AccessArticle

High-Risk Coronary Plaques and Carotid Duplex Findings in Asymptomatic Patients Undergoing Primary Prevention Assessment

by Lucio Addeo, Pasquale Guarini, Carlo Tedeschi, Antonio Rapacciuolo, Salvatore Severino, Mario De Michele, Milena Sidiropulos, Mattia Silvestre, Carlo Liguori, Luigi Cocchiara, Stefano Nardi, Luigi Argenziano, Vittoria Marino, Pasquale Campana, Roberto Franco Enrico Pedretti, Maurizio Bussotti and Laura Adelaide Dalla Vecchia

J. Cardiovasc. Dev. Dis. 2026, 13(2), 88; https://doi.org/10.3390/jcdd13020088 - 11 Feb 2026

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Abstract

Subclinical coronary atherosclerosis is common but its biological aggressiveness and interplay with extracoronary disease in asymptomatic individuals remain unclear. We evaluated the prevalence of high-risk coronary plaques (HRPs) and their relationship with mild carotid atherosclerosis and coronary calcium in a cardiovascular (CV) high-risk [...] Read more.

Subclinical coronary atherosclerosis is common but its biological aggressiveness and interplay with extracoronary disease in asymptomatic individuals remain unclear. We evaluated the prevalence of high-risk coronary plaques (HRPs) and their relationship with mild carotid atherosclerosis and coronary calcium in a cardiovascular (CV) high-risk cohort in primary prevention. This retrospective multicenter study enrolled 269 asymptomatic adults with multiple CV risk factors who underwent Coronary Computed Tomography Angiography (CCTA) after prior carotid duplex ultrasound (CDUS). Coronary artery disease (CAD) was graded as absent, non-obstructive (<50% stenosis) or obstructive (≥50%), and HRPs were identified by ≥1 adverse morphological feature (low attenuation, positive remodeling, napkin-ring sign, spotty calcification). Carotid disease was classified as CDUS 0 (no plaque), CDUS 1–49% (mild), or CDUS ≥ 50% (significant). Pre-specified analyses explored prevalence of HRPs across CDUS–calcium-score strata (cut-off 100 Agatston) and independent predictors within the CDUS 1–49% subgroup. CAD was absent in 31%, non-obstructive in 41%, and obstructive in 28%. HRPs were present in 30.9% of all cases, in 26.6% of non-obstructive and in 64.6% of obstructive CAD. HRPs prevalence rose step-wise from 10.0% (CDUS 0 + Ca < 100) to 27.7% (CDUS 1–49% + Ca < 100), 41.2% (CDUS 0 + Ca ≥ 100) and 59.4% (CDUS 1–49% + Ca ≥ 100). In patients with CDUS 1–49%, current smoking independently predicted HRPs (OR 2.1, 95% CI 1.0–4.5; p = 0.049). Nearly one-third of asymptomatic adults with high CV risk already showed HRPs. Mild carotid atherosclerosis synergized with a calcium score ≥ 100 to identify a subgroup in which six of ten individuals exhibited HRPs. Smoking was the only independent clinical correlate identified of plaque vulnerability. Combined carotid ultrasound, calcium scoring and CCTA may substantially refine primary prevention risk stratification beyond traditional factors. Full article

(This article belongs to the Special Issue Advances in the Prevention and Treatment of Cardiovascular Diseases: What We Addressed and What We Still Need to Address)

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16 pages, 955 KB

Open AccessArticle

Structural and Non-Structural Deterioration After Biological Aortic Valve Replacement: Long-Term Outcomes of 918 High-Risk Patients

by Jan Hlavička, Julian Landgraf, Andreas Winter, Mascha von Zeppelin, Yasemin Ilgin, Razan Salem, Florian Hecker, Thomas Walther and Tomas Holubec

J. Cardiovasc. Dev. Dis. 2026, 13(2), 87; https://doi.org/10.3390/jcdd13020087 - 11 Feb 2026

Viewed by 894

Abstract

Introduction: The global disease burden of aortic valve disease is already substantial and is projected to rise significantly in the coming decades. Aortic valve replacement (AVR) with a biological prosthesis has become highly popular and commonly used. This study aims to assess long-term [...] Read more.

Introduction: The global disease burden of aortic valve disease is already substantial and is projected to rise significantly in the coming decades. Aortic valve replacement (AVR) with a biological prosthesis has become highly popular and commonly used. This study aims to assess long-term outcomes after biological AVR with regard to structural and non-structural deterioration. Methods: In this single-centre retrospective study, 918 patients undergoing surgical AVR with a biological prosthesis at the University Hospital Frankfurt from January 2006 to July 2009 were included. The primary endpoints were freedom from reoperation and from structural and non-structural deterioration, and the secondary was long-term survival. Follow-up was completed in 95.6% with a median of 7.6 years, accounting 6610 patient-years. The mean age was 74.9 years and a median EuroSCORE II (range) was 3.34 (0.77–62.4). Twenty-two percent of surgeries were either emergent or urgent. Many patients had concomitant surgery, while coronary artery bypass grafting in 45.3% of patients was the most common. Three prosthetic valve models were used in our patient population: Carpentier Edwards Perimount (CEP) Model 2900, Model 3000 and Medtronic Mosaic (MM). Results: Reoperation occurred in 36 patients (3.9%) due to endocarditis (2.0%), aortic root aneurysm (0.1%), isolated or combined aortic stenosis or aortic regurgitation (1.9%). Freedom from reoperation at 5, 10 and 15 years was 97 ± 0.6%, 95.6 ± 0.8% and 90.3 ± 2.3%, respectively. Freedom from major stroke at 5, 10 and 15 years was 97.9 ± 0.0%, 96.4 ± 0.8%, and 96.1 ± 0.08%, and freedom from major bleeding event at 5, 10 and 15 years was 98.5 ± 0.4%, 95.7 ± 0.9% and 92.7 ± 2.2%, respectively. A subgroup analysis of the Carpentier Edwards (CEP) valves and the Medtronic Mosaic (MM) valves showed no significant differences regarding the primary endpoints. The overall survival at 5, 10 and 15 years was 67 ± 1.7%, 39.8 ± 1.8%, and 15.1 ± 2.2% respectively. The Kaplan–Meier survival estimator was 96 ± 2.2 months. Conclusion: This study showed a good long-term survival of surgical AVR with biological prostheses in relatively high-risk and elderly patient population. All biological prosthetic valves showed good long-term durability with low levels of complications and reoperations. The different models did not show any significant differences. Surgical AVR remains a valuable therapeutic option even though transcatheter aortic valve implantation has been greatly expanded since its introduction. Full article

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15 pages, 1469 KB

Open AccessReview

Aging-Induced QT Prolongation as a Potential Contributor to Longevity

by Simon W. Rabkin

J. Cardiovasc. Dev. Dis. 2026, 13(2), 86; https://doi.org/10.3390/jcdd13020086 - 9 Feb 2026

Viewed by 969

Abstract

The objective of this paper was to review the possibility that the QT interval may be a marker of adult human longevity or life expectancy. Following a literature review, data supporting this possibility was assembled and consists of the following. First, in adults, [...] Read more.

The objective of this paper was to review the possibility that the QT interval may be a marker of adult human longevity or life expectancy. Following a literature review, data supporting this possibility was assembled and consists of the following. First, in adults, QT interval increases with increasing age. This is analogous to aging-induced hypertension and diabetes mellitus, both of which are associated with shorter longevity. Second, older persons frequently die suddenly regardless of whether or not they have chronic illnesses for which death is expected. Third, longer QTintervals are associated with increased probability of sudden death. Fourth, patients with two conditions associated with accelerated brain aging, namely dementia and Parkinson’s disease, show longer QTcs than age-matched controls. Both of these conditions are associated with sudden cardiac death. Fifth, aging processes may affect the molecular determinants of the QT interval, alter heart composition with increased myocardial fibrosis, or alter the amount of sympathetic and parasympathetic tone, any or all of which can alter myocardial repolarization and the duration of the QTc. Sixth, considering the molecular determinants of the QT interval in the aging heart, which has longer transmembrane action potentials, several factors can account for this change, including changes in late inward Na⁺ current (I_NaL), I_Kr, I_ca, I_to, and K_ATP channels. Transgenic mice overexpressing the Kir6.1 subunit of a K_ATP channel show a prolonged QT interval and reduced longevity, with animals appearing to die suddenly. Seventh, chronic kidney disease, which is associated with a reduced lifespan, is associated with reduced expression of the anti-aging factor Klotho and Klotho-deficient mice have a prolonged QTc and a reduced lifespan. Taken together, there is a cogent case for factors that increase action potential duration in the aging heart, as recognized by increased QTc, to act in concert with other factors to produce fatal arrhythmias leading to sudden cardiac death and shortened longevity. Full article

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22 pages, 1461 KB

Open AccessReview

Atherosclerosis: A Pathologist’s Perspective

by Ludmila Verboova, Adam Nedoroscik, Terezia Kiskova-Simkova, Adriana Smirjakova, Peter Bohus, Marek Kollar, Michal Virag, Kristína Mazarova and Martina Zavacka

J. Cardiovasc. Dev. Dis. 2026, 13(2), 85; https://doi.org/10.3390/jcdd13020085 - 9 Feb 2026

Cited by 1 | Viewed by 2218

Abstract

Atherosclerosis is a chronic, progressive disease of the arterial wall and the principal pathological substrate underlying most cardiovascular diseases, including ischemic heart disease, stroke, and peripheral arterial disease. Despite advances in prevention, imaging, and therapy, atherosclerosis remains the leading cause of cardiovascular morbidity [...] Read more.

Atherosclerosis is a chronic, progressive disease of the arterial wall and the principal pathological substrate underlying most cardiovascular diseases, including ischemic heart disease, stroke, and peripheral arterial disease. Despite advances in prevention, imaging, and therapy, atherosclerosis remains the leading cause of cardiovascular morbidity and mortality worldwide. From a pathological perspective, the disease represents a dynamic and heterogeneous process characterized by endothelial dysfunction, lipid retention and modification, chronic inflammation, immune activation, smooth muscle cell phenotypic modulation, extracellular matrix remodeling, and thrombogenic surface alterations. This review provides a comprehensive overview of atherosclerosis from a pathologist’s perspective, integrating classical morphological concepts with contemporary insights into immunopathology, plaque classification, and mechanisms of plaque instability. We summarize the structure and function of the arterial wall, the stepwise pathogenesis of lesion initiation and progression, and the histopathological classification systems established by the American Heart Association and subsequently refined through Virmani’s framework. Particular emphasis is placed on plaque instability, highlighting the qualitative features—such as fibrous cap thinning, necrotic core expansion, macrophage-driven inflammation, plaque erosion, and calcification patterns—that determine clinical outcomes rather than luminal stenosis alone. Furthermore, the review discusses the expanding role of immunohistochemical markers in defining plaque biology, including lineage markers and functional indicators of inflammation, matrix integrity, osteogenic signaling, and local anticoagulant balance. These pathological insights are integrated with contemporary risk assessment tools, imaging modalities, preventive strategies, and therapeutic interventions, including emerging lipid-lowering and RNA-based therapies. In conclusion, pathology remains central to understanding atherosclerosis as a biologically active disease and to refining concepts of plaque instability. Integrating histopathology with molecular profiling, imaging, and clinical data is essential for advancing precision prevention and targeted treatment strategies in atherosclerotic cardiovascular disease. Full article

(This article belongs to the Special Issue Risk Factors and Prevention of Cardiovascular Diseases—Second Edition)

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20 pages, 2612 KB

Open AccessCase Report

Multimodality Imaging in Cardiac Metastasis of Cutaneous Melanoma: Case Report and Systematic Review

by Karina L. Lara-Sampayo, Juan Carlos Ibarrola-Peña, Miranda de la Pena-Tamez, Jose A. Salinas-Casanova, Rafael Garcia, Carlos Jerjes-Sanchez, Jose Gildardo Paredes-Vazquez and Erasmo de la Pena-Almaguer

J. Cardiovasc. Dev. Dis. 2026, 13(2), 84; https://doi.org/10.3390/jcdd13020084 - 9 Feb 2026

Viewed by 752

Abstract

Background: Cardiac metastases from cutaneous melanoma are uncommon and often underdiagnosed due to their variable and frequently asymptomatic presentation. To better describe their clinical features, diagnostic strategies, and outcomes, we performed a systematic review of published case reports and present an illustrative clinical [...] Read more.

Background: Cardiac metastases from cutaneous melanoma are uncommon and often underdiagnosed due to their variable and frequently asymptomatic presentation. To better describe their clinical features, diagnostic strategies, and outcomes, we performed a systematic review of published case reports and present an illustrative clinical case. Case presentation: We report the case of a 67-year-old man with a history of stage IIA cutaneous melanoma who presented with progressive fatigue and dyspnea. Disease recurrence was confirmed by skin biopsy. Multimodal imaging, including echocardiography, FDG PET-CT, and cardiac magnetic resonance (CMR), demonstrated extensive myocardial infiltration consistent with cardiac metastases. Despite treatment with immunotherapy, the patient experienced progressive clinical deterioration and died six months after diagnosis. Discussion: The systematic review encompassed 23 published articles reporting 27 individual cases, with a mean age at diagnosis of 55.9 years and a clear male predominance. Cardiac involvement exhibited marked heterogeneity in both clinical presentation and anatomical distribution, most frequently affecting the left ventricular free wall and the interventricular septum. Echocardiography consistently served as the initial diagnostic modality, while cardiac magnetic resonance and CT/FDG PET-CT were used to refine lesion characterization and assess extracardiac disease. Notably, a complete multimodal imaging strategy was reported in fewer than one-third of cases, reflecting variability in diagnostic approaches. Survival outcomes were highly heterogeneous, with substantial mortality, underscoring the need for earlier detection and more accurate diagnostic strategies for cardiac involvement in melanoma. Conclusions: Cardiac metastases from melanoma represent advanced disease and remain associated with poor and heterogeneous outcomes. An integrated multimodal imaging approach supports detailed diagnostic characterization and may aid clinical evaluation and management in selected cases. Full article

(This article belongs to the Special Issue Multimodal Cardiac Imaging: New and Controversial Insights)

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15 pages, 1127 KB

Open AccessArticle

Prognostic Value of the C-Reactive Protein–Albumin–Lymphocyte (CALLY) Index for 1-Year Mortality After Transcatheter Aortic Valve Implantation

by Hakan Süygün, Zeynep Seyma Turinay Ertop, Melike Polat, Murat Can Güney, Hüseyin Ayhan, Telat Keleş and Engin Bozkurt

J. Cardiovasc. Dev. Dis. 2026, 13(2), 83; https://doi.org/10.3390/jcdd13020083 - 9 Feb 2026

Viewed by 862

Abstract

Objectives: Systemic inflammation, malnutrition, and immune dysregulation have emerged as important determinants of long-term outcomes after transcatheter aortic valve implantation (TAVI). The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel immunonutritional biomarker that integrates these pathophysiological domains; however, its prognostic value in TAVI patients [...] Read more.

Objectives: Systemic inflammation, malnutrition, and immune dysregulation have emerged as important determinants of long-term outcomes after transcatheter aortic valve implantation (TAVI). The C-reactive protein–albumin–lymphocyte (CALLY) index is a novel immunonutritional biomarker that integrates these pathophysiological domains; however, its prognostic value in TAVI patients has not yet been investigated. This study aimed to evaluate the association between the CALLY index and 1-year mortality after TAVI. Methods: This retrospective observational study included 532 consecutive patients who underwent TAVI at a tertiary-care center between 2014 and 2023. Baseline laboratory parameters were obtained before the procedure, and the CALLY index was calculated as (albumin × lymphocyte count)/(C-reactive protein × 10). The primary endpoint was 1-year mortality. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminative ability of the CALLY index and conventional surgical risk scores. Multivariable regression analyses were used to identify independent predictors of mortality. Results: During the 1-year follow-up period, 85 patients (15.9%) died. Patients who died had significantly lower baseline CALLY index values compared to survivors (p < 0.001). The CALLY index demonstrated good discriminative performance for 1-year mortality (AUC: 0.797), outperforming EuroSCORE II (AUC: 0.705) and the Society of Thoracic Surgeons (STS) score (AUC: 0.619). A CALLY cut-off value of 0.45, derived using Youden’s index, was associated with a more than threefold increased risk of mortality. In multivariable analysis, the CALLY index remained independently associated with 1-year mortality, along with EuroSCORE II and more than mild mitral regurgitation. Conclusions: The CALLY index is a strong and independent predictor of 1-year mortality after TAVI and provides incremental prognostic value beyond conventional surgical risk scores. Given its simplicity and reliance on routinely available laboratory parameters, the CALLY index may serve as a practical tool for long-term risk stratification in patients undergoing TAVI. Full article

(This article belongs to the Section Cardiovascular Clinical Research)

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22 pages, 4200 KB

Open AccessArticle

Bioinformatics Analysis of Genes Associated with Autophagy and Metabolic Reprogramming in Atrial Fibrillation

by Yaqianqian Niu, Kensuke Ihara, Satoshi Iwamiya and Tetsuo Sasano

J. Cardiovasc. Dev. Dis. 2026, 13(2), 82; https://doi.org/10.3390/jcdd13020082 - 8 Feb 2026

Viewed by 714

Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and both metabolic reprogramming and autophagy have been implicated in its pathogenesis. However, the expression pattern of autophagy-related genes during metabolic reprogramming in AF remains elusive. We aimed to characterize the expression profiles of [...] Read more.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and both metabolic reprogramming and autophagy have been implicated in its pathogenesis. However, the expression pattern of autophagy-related genes during metabolic reprogramming in AF remains elusive. We aimed to characterize the expression profiles of autophagy- and metabolic reprogramming-related genes in atrial tissue to gain pathophysiological insights into AF. Three datasets obtained from the Gene Expression Omnibus (GSE2240, GSE79768, and GSE14975) that included atrial tissue samples from patients with or without AF were subjected to a bioinformatics analysis, which identified 2812 differentially expressed genes. Eight autophagy- and metabolic reprogramming-related differentially expressed genes (A&MRRDEGs) were identified as key candidates through least absolute shrinkage and selection operator regression combined with the random forest approach. Meanwhile, mice underwent transverse aortic constriction (TAC) for 2 weeks in an AF model, and gene expression in atrial tissue was analyzed. In atrial tissues from TAC mice, only Akt1 and Hspa5 of the eight A&MRRDEGs exhibited expression changes concordant with the human datasets, while Glud1 showed discordant regulation. Collectively, these cross-species findings highlight that the eight A&MRRDEGs, particularly AKT1 and HSPA5, are potentially involved in autophagy and metabolic reprogramming during AF pathogenesis. Full article

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

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22 pages, 543 KB

Open AccessReview

Clinical Application of Inhaled Nitric Oxide in Conditions of Excessive Right Heart Load: A Review from Neonatal Pulmonary Hypertension to Perioperative Cardiac Surgery Management

by Chengming Hu, Zhe Chen, Lizhi Lv, Yan Zhu, Yan Chen and Qiang Wang

J. Cardiovasc. Dev. Dis. 2026, 13(2), 81; https://doi.org/10.3390/jcdd13020081 - 8 Feb 2026

Cited by 1 | Viewed by 1277

Abstract

Excessive right heart load imposes an acute or chronic injury on the right ventricle (RV), predisposing critically ill neonates and cardiac surgical patients to RV failure, low cardiac output syndrome, and death. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that improves [...] Read more.

Excessive right heart load imposes an acute or chronic injury on the right ventricle (RV), predisposing critically ill neonates and cardiac surgical patients to RV failure, low cardiac output syndrome, and death. Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator that improves ventilation–perfusion matching and unloads the RV without systemic hypotension; nonetheless, its application beyond established neonatal indications remains contentious. Our review synthesizes current mechanistic, translational, and clinical evidence regarding iNO use in three major settings characterized by excessive RV load: (1) neonatal pulmonary hypertension, particularly PPHN; (2) acute and chronic RV overload in older children and adults, including secondary pulmonary hypertension, acute respiratory distress syndrome (ARDS), and acute pulmonary embolism; and (3) perioperative and post-cardiopulmonary bypass (CPB) management in congenital and adult cardiac surgery. In term and near-term infants with hypoxic respiratory failure, pivotal randomized trials show that iNO consistently improves oxygenation and reduces extracorporeal membrane oxygenation (ECMO) use, but this has little effect on survival and long-term neurodevelopment. In ARDS and other adult critical-care indications, iNO provides transient improvements in gas exchange and RV performance without reducing mortality or ventilator duration, and meta-analyses signal an increased risk of acute kidney injury, particularly with prolonged use. In contrast, perioperative studies around CPB demonstrate that prophylactic postoperative iNO and intra-CPB nitric oxide administration can attenuate pulmonary hypertensive crises, facilitate separation from CPB, shorten ventilation and intensive care stay, and, in selected high-risk cohorts, may reduce cardiac surgery-associated acute kidney injury, although survival benefits remain unproven. Across these scenarios, iNO should be used judiciously and in a pathophysiology-driven manner as a time-limited, targeted adjunct to stabilize patients with documented or anticipated RV strain rather than a disease-modifying therapy. Future work should refine patient selection, timing, dosing, and weaning strategies, and define the long-term safety and cost-effectiveness of iNO within contemporary multimodal RV support pathways. Full article

(This article belongs to the Section Pediatric Cardiology and Congenital Heart Disease)

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20 pages, 16534 KB

Open AccessArticle

Single-Nucleus RNA Sequencing Reveals SPP1⁺ Macrophages Induce Cardiomyocyte Apoptosis to Promote Atrial Fibrillation Susceptibility

by Weixue Wang, Youzheng Dong, Hong Yi, Lei He, Yuwen Jiang, Lu Long, Zhen Xia and Juxiang Li

J. Cardiovasc. Dev. Dis. 2026, 13(2), 80; https://doi.org/10.3390/jcdd13020080 - 5 Feb 2026

Viewed by 827

Abstract

Atrial fibrillation (AF) is closely linked to atrial remodeling, while its underlying immune mechanisms remain elusive. This study sought to investigate the role of SPP1⁺ macrophages in the development and progression of AF and further elucidate the underlying mechanisms. Single-nucleus RNA sequencing [...] Read more.

Atrial fibrillation (AF) is closely linked to atrial remodeling, while its underlying immune mechanisms remain elusive. This study sought to investigate the role of SPP1⁺ macrophages in the development and progression of AF and further elucidate the underlying mechanisms. Single-nucleus RNA sequencing was performed on right atrial tissues from 3 patients with persistent AF and 3 with sinus rhythm (all with rheumatic valvular heart disease). The results revealed significant immune cell infiltration in AF atrial tissues, with a marked increase in the proportion of SPP1⁺ macrophages, which exhibited the strongest intercellular communication with cardiomyocytes. Phenotypic scoring indicated that apoptosis was the dominant mode of cardiomyocyte death in AF. Immunohistochemical and Western blot analyses confirmed elevated levels of pro-apoptotic proteins (Bax, Cleaved-Caspase3) and reduced levels of the anti-apoptotic protein Bcl2 in AF tissues. In a mouse model with macrophage-specific SPP1 overexpression, increased AF inducibility and duration were observed, accompanied by enhanced cardiomyocyte apoptosis. In vitro co-culture experiments using SPP1-overexpressing RAW264.7 macrophages and HL-1 cardiomyocytes confirmed that SPP1⁺ macrophages could induce cardiomyocyte apoptosis. Mechanistically, KEGG and GSEA analyses identified downregulation of the PI3K/AKT pathway in AF. Treatment with the PI3K/AKT activator Recilisib reversed apoptosis and restored p-PI3K/p-AKT levels in HL-1 cells co-cultured with SPP1-overexpressing RAW264.7 macrophages. These findings demonstrate that SPP1⁺ macrophages accumulate in atrial tissues of AF patients and induce cardiomyocyte apoptosis by downregulating the PI3K/AKT pathway, thereby increasing AF susceptibility. Full article

(This article belongs to the Topic New Research on Atrial Fibrillation)

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12 pages, 983 KB

Open AccessArticle

Apelin Levels in HFrEF and Association with Sustained VT Detected by ICD Interrogation: A Retrospective Pilot Study

by Abdullah Eren Cetin, Mustafa Lutfullah Ardic, Fadime Koca, Hilmi Erdem Sumbul and Mevlut Koc

J. Cardiovasc. Dev. Dis. 2026, 13(2), 79; https://doi.org/10.3390/jcdd13020079 - 4 Feb 2026

Viewed by 578

Abstract

Introduction: The serum apelin level in patients with heart failure with reduced ejection fraction (HFrEF) and its relationship with ventricular tachycardia (VT) are not clearly known. This study aimed to investigate changes in serum apelin levels in patients with HFrEF and their relationship [...] Read more.

Introduction: The serum apelin level in patients with heart failure with reduced ejection fraction (HFrEF) and its relationship with ventricular tachycardia (VT) are not clearly known. This study aimed to investigate changes in serum apelin levels in patients with HFrEF and their relationship with VT. Method: This retrospective pilot study included 90 patients with 30 patients in each group: Group I: HFrEF with documented VT; Group II: HFrEF without VT; Group III: control group without HFrEF. In addition to routine parameters, apelin levels were measured. All parameters were compared between Group I–II–III. Parameters associated with VT were identified. Result: Apelin levels were found to be significantly lower in Group I–II than in Group III. Serum glucose, creatinine, and left atrial diameter were shown to be significantly higher in Group I–II than in Group III. HDL cholesterol and left ventricular ejection fraction (LVEF) levels were significantly lower in Group I–II compared with Group III. A positive and negative correlation was found between plasma apelin levels and LVEF and age, respectively. In logistic regression analysis, apelin levels and LVEF were found to independently determine VT (OR = 0.313, 95%CI: 0.124–0.788, p = 0.014 and OR = 0.912, 95%CI: 0.877–0.968, p < 0.001). In the ROC analysis, the cut-off value for apelin was determined to be 0.80 ng/mL, and it distinguished VT status in this sample with acceptable sensitivity and specificity. Discussion: According to the results of our study, apelin levels are significantly reduced in patients with HFrEF, and reduced apelin levels are associated with the presence of VT in these patients. Full article

(This article belongs to the Special Issue Ventricular Arrhythmias: Epidemiology, Diagnosis and Treatment)

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13 pages, 2074 KB

Open AccessArticle

Epicardial Adipose Tissue Volume and Left Atrial Remodeling: A J-Shaped Association in Older Adults

by Xinyue Zhao, Guangjian Wang, Xuefeng Ni and Hui Lian

J. Cardiovasc. Dev. Dis. 2026, 13(2), 78; https://doi.org/10.3390/jcdd13020078 - 4 Feb 2026

Viewed by 620

Abstract

Background: Previous studies identified epicardial adipose tissue (EAT) as a metabolic risk factor for atrial remodeling. However, given the distinct physiological changes associated with aging, findings from the general population may not translate directly to older adults. This study aims to clarify the [...] Read more.

Background: Previous studies identified epicardial adipose tissue (EAT) as a metabolic risk factor for atrial remodeling. However, given the distinct physiological changes associated with aging, findings from the general population may not translate directly to older adults. This study aims to clarify the relationship between EAT and left atrial (LA) diameter in older adults specifically. Methods: This retrospective cross-sectional study was conducted among in an older adult cohort (aged ≥ 65 years) at Peking Union Medical College Hospital. The association between EAT and LA diameter was evaluated using multivariable linear regression, a generalized additive model, and restricted cubic spline (RCS) modeling. Results: Among 353 participants (median age 75 years), EAT was independently associated with LA diameter (β = 0.286, p < 0.001) after adjusting for confounders including age, BMI, and LDL-C. Notably, RCS analysis revealed a J-shaped relationship between EAT volume and LA dimensions. Specifically, when EAT exceeded 110.7 cm³, the LA diameter increased significantly by 0.22 mm per 10 cm³ increase in EAT (p = 0.004). Conclusions: EAT accumulation shows a non-linear association with left atrial remodeling in older adults, with an identifiable threshold at 110.7 cm³. EAT may be a valuable biomarker for cardiovascular risk stratification, suggesting that EAT burden monitoring could be beneficial in older populations. Full article

(This article belongs to the Special Issue Risk Factors and Prevention of Cardiovascular Diseases—Second Edition)

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36 pages, 1598 KB

Open AccessReview

Engineering Mitochondrial Biogenesis in iPSC-CMs: CRISPR-Guided Approaches for Advanced Cardiomyocyte Development

by Dhienda C. Shahannaz, Tadahisa Sugiura, Brandon E. Ferrell and Taizo Yoshida

J. Cardiovasc. Dev. Dis. 2026, 13(2), 77; https://doi.org/10.3390/jcdd13020077 - 3 Feb 2026

Cited by 4 | Viewed by 1206

Abstract

Human iPSC-derived cardiomyocytes (iPSC-CMs) exhibit fetal-like mitochondrial networks and limited oxidative metabolism, constraining their translational utility. The key bottleneck is mitochondrial immaturity, resulting from blunted PGC-1α–NRF1/2–TFAM axis activation and insufficient nuclear–mitochondrial coordination, rather than sarcomeric or electrophysiological immaturity alone. This review synthesizes [...] Read more.

Human iPSC-derived cardiomyocytes (iPSC-CMs) exhibit fetal-like mitochondrial networks and limited oxidative metabolism, constraining their translational utility. The key bottleneck is mitochondrial immaturity, resulting from blunted PGC-1α–NRF1/2–TFAM axis activation and insufficient nuclear–mitochondrial coordination, rather than sarcomeric or electrophysiological immaturity alone. This review synthesizes genome-guided interventions (CRISPRa and mtDNA editing) and complementary environmental strategies—including metabolic substrate switching, electromechanical stimulation, and extracellular vesicle (EV)-mediated mitochondrial transfer—to drive mitochondrial biogenesis and maturation in iPSC-CMs. We systematically reviewed studies (2005–2025) targeting (1) key regulators of mitochondrial biogenesis (PGC-1α, NRF1/2, TFAM), (2) CRISPR-based transcriptional activators/repressors and mtDNA editors (DdCBE, mitoTALENs), and (3) maturation approaches such as metabolic conditioning, electromechanical stimulation, 3D tissue culture, and EV-mediated mitochondrial transfer. CRISPRa-mediated activation of PGC-1α, NRF1, and GATA4, combined with mtDNA base editors, enhances mitochondrial mass and OXPHOS function, while integration with environmental maturation strategies further promotes adult-like phenotypes. Integrative approaches that combine genome-guided interventions (CRISPRa, mtDNA editing) with environmental maturation cues yield the most adult-like iPSC-CM phenotypes reported to date. CRISPR-guided mitochondrial biogenesis thus represents a frontier for producing metabolically competent, structurally mature iPSC-CMs for disease modeling and therapy. Remaining translational challenges include efficient mitochondrial delivery, metabolic homeostasis, and multi-omics validation. We propose standardized workflows to couple nuclear and mitochondrial editing with maturation strategies. Full article

(This article belongs to the Special Issue Cutting-Edge Advances in Cardiac Development, Anatomy, and Regeneration)

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15 pages, 1918 KB

Open AccessSystematic Review

Cor Triatriatum Dexter: The Largest Comprehensive Review in the Field on 124 Worldwide Cases (1968–Now)

by Pier Paolo Bassareo, Erica Franco, Sophie Duignan, Massimo Chessa, Mariateresa Cascio, Colin Joseph McMahon, Kevin Patrick Walsh and Marco Alfonso Perrone

J. Cardiovasc. Dev. Dis. 2026, 13(2), 76; https://doi.org/10.3390/jcdd13020076 - 3 Feb 2026

Viewed by 1112

Abstract

Background. Cor triatriatum dexter (CTD) is a rare congenital heart defect where a membrane divides the right atrium into two chambers, resulting from the incomplete regression of the right valve of the sinus venosus. Due to its rarity, only individual case reports and [...] Read more.

Background. Cor triatriatum dexter (CTD) is a rare congenital heart defect where a membrane divides the right atrium into two chambers, resulting from the incomplete regression of the right valve of the sinus venosus. Due to its rarity, only individual case reports and a limited number of case series have been published to date. This study constitutes the most extensive comprehensive review conducted in this area. Eight factors were evaluated: age at diagnosis, sex, clinical presentation, electrocardiographic findings, imaging (ultrasound, CT, or MRI), associated cardiac anomalies, and patient outcomes. Methods. The electronic databases PubMed and Scopus were searched from their inception until 30 October 2025. Only case reports and case series were considered for inclusion. Studies involving foetuses, autopsies, and animals were excluded. The collected data were primarily presented as percentages. Results. One hundred fourteen studies were found encompassing 124 patients. The mean age at diagnosis was 33.3 ± 9.4 years The most common clinical presentations were dyspnoea (44.3%) and cyanosis (29.5%). The most commonly encountered ECG changes were supraventricular tachycardia/atrial flutter/atrial fibrillation (33.3%) and right bundle branch block (22.6%). On chest X-ray, cardiomegaly was noted in 46.5%. CTD was suspected or diagnosed by echocardiography in 95.2% of cases. The diagnosis was confirmed by CT and/or MRI in 34.1% of cases. A concomitant congenital heart defect was found in 67.7%, especially in the form of all kinds of atrial septal defect (38.1%) and of right valvular and right ventricular involvement (20.1%). An outcome was reported in 97/124. Surgical correction was the treatment of choice in 51.6%. Since 1991, a percutaneous approach has been employed in selected cases (5.1%). Conservative management was the treatment of choice in 43.3%. The mortality rate was 8.2%. Discussion. The principal limitation of this systematic review lies in its reliance solely on case reports and small case series, reflecting the absence of large-scale studies on CTD. Nonetheless, it constitutes the most comprehensive analysis available to date. Full article

(This article belongs to the Section Pediatric Cardiology and Congenital Heart Disease)

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13 pages, 5351 KB

Open AccessEditor’s ChoiceArticle

Cardiac CT Angiography in Diagnosing Patent Foramen Ovale: A Study on Patients with Suspected Patent Foramen Ovale-Associated Stroke

by Lijie Sun, Chong Zheng, Zhenxing Fan, Jing Gao, Zhi Liu, Jin Si, Keling Xiao, Ming Yi, Haoyu Zhang, Jinghao Sun, Yijin Liu, Yang Hua, Yingqi Xing, Jie Lu and Jing Li

J. Cardiovasc. Dev. Dis. 2026, 13(2), 75; https://doi.org/10.3390/jcdd13020075 - 2 Feb 2026

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Abstract

Background: Cardiac computed tomographic angiography (CTA) detects patent foramen ovale (PFO) with variable accuracy. This study investigated factors affecting CTA detectability for PFO in patients with suspected PFO-associated stroke. Methods: Consecutive patients with cryptogenic stroke and positive findings on contrast transcranial Doppler (cTCD) [...] Read more.

Background: Cardiac computed tomographic angiography (CTA) detects patent foramen ovale (PFO) with variable accuracy. This study investigated factors affecting CTA detectability for PFO in patients with suspected PFO-associated stroke. Methods: Consecutive patients with cryptogenic stroke and positive findings on contrast transcranial Doppler (cTCD) examinations were enrolled between November 2020 and April 2023 in this retrospective study. Each participant underwent transesophageal echocardiography (TEE) and cardiac CTA. Patients with confirmed PFO on TEE were categorized into two groups based on CTA detectability: the CTA-positive group (PFO identified by CTA) and the CTA-negative group (PFO missed by CTA). Univariate and multivariate logistic regression analyses were performed to identify predictors of CTA false-negative results. Results: Among 108 patients (mean age 46.7 ± 14.9 years, 47.2% male), the prevalence of PFO by TEE was 94.4% (102/108). Compared to TEE, cardiac CTA had a sensitivity of 70% (95% CI 61–79%), a specificity of 100% (95% CI 54–100%), a positive predictive value of 100% (95% CI 95–100%), and a negative predictive value of 16% (95% CI 6–32%). Among patients with PFO confirmed by TEE (n = 102), the incidence of moderate to large right-to-left shunts (RLS) was significantly higher in the CTA-positive group than in the CTA-negative (77.5% vs. 22.5%, p < 0.001). After adjusting for confounders, patients with moderate to large shunts showed a significantly lower likelihood of a CTA false-negative result compared to those with small shunts (OR 0.113, 95% CI 0.035–0.365, p < 0.001). In patients with moderate to large RLS, the sensitivity of cardiac CTA for diagnosing PFO increased to 90.16% (95% CI 82.69–97.64%). Conclusions: Cardiac CTA could be an effective complementary modality for selected patients with suspected PFO-associated stroke. Its diagnostic performance appears more reliable for identifying PFO in patients with moderate-to-large RLS than in those with small RLS. Full article

(This article belongs to the Section Stroke and Cerebrovascular Disease)

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24 pages, 1538 KB

Open AccessReview

Mechanisms and Therapeutic Potential of Human Cardiomyocyte Proliferation

by Richard D. McLane, Abhay Cheruku, Ashley B. Williams and Ravi Karra

J. Cardiovasc. Dev. Dis. 2026, 13(2), 74; https://doi.org/10.3390/jcdd13020074 - 2 Feb 2026

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Abstract

The limited capacity for cardiomyocyte proliferation in the adult human heart restricts its ability to recover from injury. Building on discoveries in regenerative model systems, such as zebrafish and neonatal mice, reactivation of a latent potential for cardiomyocyte proliferation is a strategy to [...] Read more.

The limited capacity for cardiomyocyte proliferation in the adult human heart restricts its ability to recover from injury. Building on discoveries in regenerative model systems, such as zebrafish and neonatal mice, reactivation of a latent potential for cardiomyocyte proliferation is a strategy to promote therapeutic heart regeneration. Although cardiomyocyte proliferation remains modest even with the most effective mitogenic stimuli identified to date, evidence for a potential functional benefit in pre-clinical model systems has led to the initiation of several early-phase clinical programs. Here, we review insights from model organisms that inform the potential efficacy and limitations of therapeutic cardiomyocyte proliferation, systems to study human cardiomyocyte proliferation, and the natural history of cardiomyocyte proliferation in the human heart. We also examine the translational trajectory of selected discoveries, including therapeutic delivery modalities, and attendant safety concerns. Finally, we discuss critical challenges that will need to be addressed to enable successful clinical translation. Full article

(This article belongs to the Section Cardiac Development and Regeneration)

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J. Cardiovasc. Dev. Dis., Volume 13, Issue 2 (February 2026) – 46 articles

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