Journal of Cardiovascular Development and Disease

17 pages, 364 KB

Open AccessReview

Addressing Complications in Cardiac Implantable Electronic Devices: A Guideline to Prevention of CIED Infection

by Benito Baldauf, Roberto Cemin, Mauro Biffi, Antonio Rapacciuolo, Giulio Zucchelli, Maria Grazia Bongiorni, Ernesto Casorelli, Gianfranco Mitacchione, Felix Hohendanner, Emanuele Durante-Mangoni, Veronica Dusi, Paul William Xavier Foley, Angelo Pan, Giuseppe Arena, Archana Rao, Sebastian Spencker, Alexander Steger, Carlo Tascini, Valerio Zacà, Federico Migliore, Ojan Assadian, Marzia Giaccardi, Hendrik Bonnemeier and Kerstin Bode Show full author list Hide full author list

J. Cardiovasc. Dev. Dis. 2025, 12(10), 406; https://doi.org/10.3390/jcdd12100406 (registering DOI) - 13 Oct 2025

Abstract

Background: Cardiac implantable electronic devices (CIEDs) are vital for managing arrhythmias but carry a notable risk of infection, which increases patient morbidity, mortality, and healthcare burden. This review examines current evidence on risk factors and preventive strategies for CIEDI. Methods: A structured search [...] Read more.

Background: Cardiac implantable electronic devices (CIEDs) are vital for managing arrhythmias but carry a notable risk of infection, which increases patient morbidity, mortality, and healthcare burden. This review examines current evidence on risk factors and preventive strategies for CIEDI. Methods: A structured search was performed in PubMed, Embase, and the Cochrane Library using terms such as “CIED,” “infection,” “pacemaker,” “ICD,” “infection prevention,” “biofilm,” “antibiotic prophylaxis,” and “antibiotic-eluting envelope.” Study selection followed PRISMA guidelines. Results: For well-established topics, recommendations are based on high-quality evidence from the literature. In areas with limited CIED-specific data, evidence from related surgical fields was considered, and expert consensus was used to guide recommendations. Conclusions: This review offers practical guidance for clinicians on CIED infection prevention, addressing gaps not previously covered in existing guidelines. Full article

(This article belongs to the Section Electrophysiology and Cardiovascular Physiology)

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13 pages, 644 KB

Open AccessArticle

Pilot Study Assessing the Hemodynamic Impact and Post-Exercise Hypotension Induced by High- Versus Low-Intensity Isometric Handgrip in Patients with Ischemic Heart Disease

by Giuseppe Caminiti, Matteo Vitarelli, Maurizio Volterrani, Giuseppe Marazzi, Vincenzo Manzi, Valentino D’Antoni, Simona Fecondo, Sara Vadalà, Barbara Sposato, Domenico Mario Giamundo, Alberto Grossi, Valentina Morsella, Ferdinando Iellamo and Marco Alfonso Perrone

J. Cardiovasc. Dev. Dis. 2025, 12(10), 405; https://doi.org/10.3390/jcdd12100405 (registering DOI) - 12 Oct 2025

Abstract

Background: Isometric handgrip (IHG) exercise reduces blood pressure (BP) in both normotensive and hypertensive individuals. However, there are few studies specifically addressing its effects in hypertensive patients with ischemic heart disease (IHD). This research aimed to compare acute hemodynamic responses and post-exercise [...] Read more.

Background: Isometric handgrip (IHG) exercise reduces blood pressure (BP) in both normotensive and hypertensive individuals. However, there are few studies specifically addressing its effects in hypertensive patients with ischemic heart disease (IHD). This research aimed to compare acute hemodynamic responses and post-exercise hypotension to single bouts of IHG handgrip performed at two different intensities in patients with IHD. Methods: Fifty-four sedentary patients were enrolled and randomly assigned to one of three groups: (1) high-intensity isometric handgrip performed at 70% of maximal voluntary contraction (MVC) (IHG-70%); (2) low-intensity isometric handgrip performed at 30% of MVC (IHG-30%); (3) control group (no exercise). Heart rate and BP were measured, and transthoracic echocardiography was performed at baseline, during exercise (lasting 3 min), and after 15 min post-exercise. BP was also measured at 30, 45, and 60 min of recovery. Results: No significant changes in systolic BP occurred during the exercise phase between the three study groups. Systolic BP decreased significantly in IHG-70% compared to the control at 30 (−7.7 ± 1.9; p = 0.035) and 45 min (−8.1 ± 2.3; p = 0.021) post-exercise, while there were no significant differences between IHG-70% and IHG-30% at different time-points. There were no significant changes in diastolic BP between the two active groups and between IHG-70 and IHG-30 versus control at different time-points (repeated-measures ANOVA p = 0.257). Global work efficiency was unchanged in IHG-70% (−4%) and IHG-30% (+1%) compared to control (ANOVA p = 0.154). Conclusions: High-intensity and low-intensity isometric handgrip exercises did not cause hemodynamic impairment in IHD. High-intensity exercise was more effective than low-intensity in reducing post-exercise systolic BP. Full article

(This article belongs to the Special Issue Sports Cardiology: From Diagnosis to Clinical Management, 2nd Edition)

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9 pages, 2750 KB

Open AccessBrief Report

Minimally Invasive Repair of Sinus Venosus Atrial Septal Defects and Anomalous Pulmonary Venous Connections via Vertical Right Axillary Thoracotomy

by Sameh M. Said, Ali H. Mashadi, Yasin Essa, Kristin Greathouse, Nicholas Brown, Mahmoud I. Salem and Joseph Giamelli

J. Cardiovasc. Dev. Dis. 2025, 12(10), 404; https://doi.org/10.3390/jcdd12100404 (registering DOI) - 11 Oct 2025

Abstract

(1) Background: There has been an increase in the utilization of the minimally invasive vertical right axillary thoracotomy approach for repairing congenital heart defects in children recently. We aim, in the current study, to evaluate the outcomes of this approach in repairing anomalous [...] Read more.

(1) Background: There has been an increase in the utilization of the minimally invasive vertical right axillary thoracotomy approach for repairing congenital heart defects in children recently. We aim, in the current study, to evaluate the outcomes of this approach in repairing anomalous pulmonary venous connections with or without an associated sinus venosus defect. (2) Methods: A total of 23 consecutive patients underwent surgical repair of anomalous pulmonary venous connections between April 2018 and February 2024. Perioperative and clinical follow-up data were obtained. (3) Results: The median age and weight were 36 months (1–277 months) and 14.4 kg (3.6–79.4 kg), respectively. More than half were females (13; 56.5%). There was no conversion to sternotomy. Partial anomalous pulmonary venous connections were the most frequent primary diagnoses (14; 60.9%), followed by scimitar syndrome (3; 13%), while two patients (8.7%) had total anomalous pulmonary venous connections. Repair techniques included single patch in 10 patients (43.5%), Warden in 6 (26.1%), and two-patch technique in 4 (17.4%). The median cardiopulmonary bypass and aortic cross-clamp times were 91 and 62 min, respectively. All patients were extubated in the operating room. The median length of hospital stay was 2 days. There were no mortalities or reoperations for pulmonary/systemic venous pathway obstruction. (4) Conclusions: Vertical right axillary thoracotomy is a valuable approach for repairing anomalous pulmonary venous connections with or without sinus venosus defects. All repair techniques, including Warden and scimitar, can be performed safely through this approach. The cosmetic superiority and short hospital stay make this approach worth considering. Full article

(This article belongs to the Section Cardiac Surgery)

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17 pages, 883 KB

Open AccessArticle

Trends in Conventional Heart Failure Therapy in a Real-World Multinational ATTR-CA Cohort

by Eva H. van der Geest, Nina Ajmone Marsan, Dorien Laenens, Philippe J. M. R. Debonnaire, Mathias Claeys, Fauto Pinto, Dulce Brito, Erwan Donal, Steven Droogmans, Nico Van de Veire, Philippe Bertrand, Takeru Nabeta, Francesca Graziani and Madelien V. Regeer

J. Cardiovasc. Dev. Dis. 2025, 12(10), 403; https://doi.org/10.3390/jcdd12100403 (registering DOI) - 11 Oct 2025

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Abstract

Background: Conventional HF treatment in transthyretin cardiac amyloidosis (ATTR-CA) resulting in restrictive cardiomyopathy is debated due to absent trial evidence in this specific sub-population of heart failure (HF) patients. Current European Society of Cardiology guidelines recommend the use of diuretics and mineralocorticoid receptor [...] Read more.

Background: Conventional HF treatment in transthyretin cardiac amyloidosis (ATTR-CA) resulting in restrictive cardiomyopathy is debated due to absent trial evidence in this specific sub-population of heart failure (HF) patients. Current European Society of Cardiology guidelines recommend the use of diuretics and mineralocorticoid receptor antagonists (MRAs). However, beta-blockers (BBs) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) are often discontinued due to hypotension or bradycardia. This study assesses real-world HF treatment patterns and their impact on survival in a multinational ATTR-CA cohort. Methods: A retrospective analysis of 794 ATTR-CA patients examined baseline BB, ACEi/ARB, and MRA prescriptions. The cohort was divided based on guideline publication dates. Results: Patients were predominantly male (73.2%) with a median age of 78 years. Prescription of diuretics (52.8%) and disease-modifying therapy (44.9%), mostly tafamidis, was common. BBs (43.7%) and ACEi/ARBs (41.2%) were prescribed more often in patients with higher NYHA class, elevated NT-proBNP, and more comorbidities. Blood pressure and heart rate were similar regardless of BB or ACEi/ARB use. BB prescription and combination therapy with BB and ACEi/ARB increased over time. Neither BB nor ACEi/ARB use significantly impacted mortality when analyzed in a multivariate Cox proportional hazard regression. Conclusions: Use of BBs and ACEi/ARBs has increased over time, particularly in advanced-stage ATTR-CA patients, and although these therapies appear to be reasonably tolerated, survival was not significantly altered. Full article

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3 pages, 173 KB

Open AccessEditorial

Shaping the Future of Cardiac Surgery: The Rise of Minimal-Access Techniques

by Heen Shamaz and Jason Ali

J. Cardiovasc. Dev. Dis. 2025, 12(10), 402; https://doi.org/10.3390/jcdd12100402 - 10 Oct 2025

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Abstract

Minimal access techniques are increasingly shaping the landscape of cardiac surgery [...] Full article

(This article belongs to the Special Issue Minimal Access Cardiac Surgery: State of the Art and Future Perspectives)

5 pages, 198 KB

Open AccessEditorial

Extensive Approach to Atrial Fibrillation: Background and Future Perspectives

by Henri Xhakupi and Matteo Anselmino

J. Cardiovasc. Dev. Dis. 2025, 12(10), 401; https://doi.org/10.3390/jcdd12100401 - 10 Oct 2025

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Abstract

For decades, atrial fibrillation (AF) has been managed through a narrow lens—prevent strokes, rate or rhythm control, and accept recurrences as inevitable [...] Full article

(This article belongs to the Special Issue Extensive Approach to Atrial Fibrillation: Background and Future Perspectives)

16 pages, 6728 KB

Open AccessArticle

Beyond the Obvious: Evaluating Incidence and Causes of False Positive Patent Foramen Ovale Diagnoses in Cryptogenic Ischemic Stroke—A Retrospective Analysis

by Raphael Phinicarides, Kira Berning, Houtan Heidari, Dominika Kanschik, Amin Polzin, Nikos Werner, Malte Kelm, Christian Jung, Kathrin Klein, Tobias Zeus and Shazia Afzal

J. Cardiovasc. Dev. Dis. 2025, 12(10), 400; https://doi.org/10.3390/jcdd12100400 - 10 Oct 2025

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Abstract

(1) Background: Transesophageal echocardiography (TEE) is the gold standard for diagnosing patent foramen ovale (PFO) in cryptogenic ischemic stroke. However, false-positive diagnoses remain clinically relevant, exposing patients to unnecessary invasive procedures. (2) Methods: We retrospectively analyzed 346 patients with cryptogenic ischemic stroke who [...] Read more.

(1) Background: Transesophageal echocardiography (TEE) is the gold standard for diagnosing patent foramen ovale (PFO) in cryptogenic ischemic stroke. However, false-positive diagnoses remain clinically relevant, exposing patients to unnecessary invasive procedures. (2) Methods: We retrospectively analyzed 346 patients with cryptogenic ischemic stroke who underwent TEE for PFO from 2012–2021. PFO was confirmed in 326 patients (94.2%), whereas 20 patients (5.8%, 95% CI 3.6–8.9%) were adjudicated as false positives during subsequent cardiac catheterization (intracardiac echocardiography, angiography, and inability to cross the interatrial septum). Univariable and multivariable logistic regression identified predictors of diagnostic accuracy. (3) Results: False-positive cases were associated with less frequent use of the mid-esophageal bicaval view (50% vs. 87%, p < 0.001) and absence of early bubble transit. Multivariable analysis confirmed the mid-esophageal bicaval view as an independent predictor of accurate diagnosis (OR 5.23, 95% CI 2.11–12.9, p < 0.001). (4) Conclusion: False-positive PFO diagnoses occur in ~6% of patients referred for closure. Three quality criteria—mid-esophageal aortic valve short axis, bicaval view, and bubble test with x-plane analysis—may improve diagnostic reliability. These hypothesis-generating findings require prospective validation and alignment with ASE/ESC guidelines to reduce unnecessary invasive procedures. Full article

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

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13 pages, 601 KB

Open AccessArticle

The Association Between Short-Term Blood Pressure Variability and Inflammation in Healthy Young Adults

by Charles J. Weeks, Bayu B. Bekele, Michelle Altvater, Jie Cheng, Haidong Zhu, Ying Huang, Deborah A. Jehu, Abigayle B. Simon, Wenjun Li and Yanbin Dong

J. Cardiovasc. Dev. Dis. 2025, 12(10), 399; https://doi.org/10.3390/jcdd12100399 - 9 Oct 2025

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Abstract

Blood pressure variability (BPV) is linked to cardiovascular disease (CVD) and systemic inflammation in adults, but its relevance in young, healthy populations remains unclear. This study examined the association between short-term BPV and inflammatory markers in 447 normotensive participants (mean age, 22.9 years) [...] Read more.

Blood pressure variability (BPV) is linked to cardiovascular disease (CVD) and systemic inflammation in adults, but its relevance in young, healthy populations remains unclear. This study examined the association between short-term BPV and inflammatory markers in 447 normotensive participants (mean age, 22.9 years) from the Georgia Stress and Heart (GSH) study, a cohort of Non-Hispanic Black and White individuals. Participants underwent 24 h ambulatory blood pressure monitoring and assessment of serum inflammatory markers, including hs-CRP, IFN-γ, IL-6, and TNF-α. BPV was quantified using average real variability (ARV), and generalized estimating equations (GEEs) were used to evaluate associations, adjusting for age, sex, race, and mean blood pressure. Diastolic BPV was significantly, positively associated with hs-CRP and TNF-α, whereas systolic BPV was not associated with any inflammatory marker. Specifically, 24 h diastolic BPV was positively associated with hs-CRP (p = 0.001) and TNF-α (p = 0.015), while daytime diastolic BPV was positively associated with hs-CRP (p = 0.002). Nighttime diastolic BPV was positively associated with both hs-CRP (p = 0.020) and TNF-α (p = 0.007). No significant associations were found between BPV and IL-6 or IFN-γ. These findings suggest diastolic BPV may be a marker of low-grade inflammation in healthy young adults and could represent an early cardiovascular risk factor that warrants longitudinal study. Full article

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

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12 pages, 386 KB

Open AccessArticle

Predictors and Prognostic Impact of Perioperative Hypotension During Transcatheter Aortic Valve Implantation: The Role of Diabetes Mellitus and Left Ventricular Dysfunction

by Zeynep Ece Demirbaş, Şahin Yılmaz, Fatma Can, Gönül Zeren and Can Yücel Karabay

J. Cardiovasc. Dev. Dis. 2025, 12(10), 398; https://doi.org/10.3390/jcdd12100398 - 9 Oct 2025

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Abstract

Background: Perioperative hypotension is a frequent but underrecognized complication during transcatheter aortic valve implantation (TAVI). Although reduced left ventricular ejection fraction (EF) and low baseline blood pressure have been linked to hemodynamic instability, the role of metabolic comorbidities and procedural factors remains less [...] Read more.

Background: Perioperative hypotension is a frequent but underrecognized complication during transcatheter aortic valve implantation (TAVI). Although reduced left ventricular ejection fraction (EF) and low baseline blood pressure have been linked to hemodynamic instability, the role of metabolic comorbidities and procedural factors remains less well established. Methods: We retrospectively analyzed 123 patients who underwent transfemoral TAVI between June 2016 and June 2022. Perioperative hypotension was defined as a sustained systolic blood pressure < 90 mmHg or ≥30% reduction from baseline for at least 5 min. Clinical, laboratory, and procedural predictors were assessed using multivariate logistic regression, and model performance was evaluated by ROC curve analysis. Results: Perioperative hypotension occurred in 57% of patients. Independent predictors were diabetes mellitus (OR 2.79, 95% CI 1.03–7.56, p = 0.044), reduced EF (<50%) (OR 2.87, 95% CI 1.13–7.31, p = 0.027), lower baseline diastolic blood pressure (OR 0.935 per mmHg, 95% CI 0.893–0.978, p = 0.004), and longer procedural duration (OR 1.038 per minute, 95% CI 1.001–1.076, p = 0.044). The predictive model demonstrated good calibration and discrimination (AUC 0.844). Patients with hypotension had significantly higher in-hospital mortality (12.9% vs. 1.9%, p = 0.027) and longer ICU stay. An exploratory finding suggested less frequent use of sugammadex among hypotensive patients (11.4% vs. 32.1%, p = 0.005). Conclusions: Perioperative hypotension is common during TAVI and strongly associated with early mortality. Our study uniquely identifies diabetes mellitus as an independent predictor, alongside ventricular dysfunction, baseline blood pressure, and procedural duration. These findings suggest that careful preprocedural risk stratification, hemodynamic vigilance, and optimization of anesthetic management may improve outcomes in vulnerable patients. Full article

(This article belongs to the Special Issue Transcatheter Aortic Valve Implantation (TAVI): 3rd Edition)

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12 pages, 1101 KB

Open AccessArticle

Accuracy of a Bedside Heparin Anticoagulation Monitoring Test in Critically Ill Patients

by María Teresa Cruces Moreno, Raimundo García del Moral and Manuel Colmenero

J. Cardiovasc. Dev. Dis. 2025, 12(10), 397; https://doi.org/10.3390/jcdd12100397 - 7 Oct 2025

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Abstract

Anticoagulation therapy with unfractionated heparin (UHF) is a mandatory treatment for many critically ill patients. While the gold standard for monitoring this therapy remains the laboratory-based aPTT (aPTT-lab), the need for immediate results has led to an increase in the development of point-of-care [...] Read more.

Anticoagulation therapy with unfractionated heparin (UHF) is a mandatory treatment for many critically ill patients. While the gold standard for monitoring this therapy remains the laboratory-based aPTT (aPTT-lab), the need for immediate results has led to an increase in the development of point-of-care (POC) measurement systems. This study assessed the correlation and agreement between activated clotting time-low range (ACT-LR) and aPTT-POC measurements using aPTT-lab in a cohort of critically ill patients requiring anticoagulation. This prospective cohort study involved patients admitted to the intensive care unit (ICU) who were treated with UFH between January 2022 and January 2024. We performed simultaneous measurements of aPTT-lab, aPTT-POC, and ACT-LR and analyzed 14 samples from healthy volunteers (the control group) to determine the range of normality and mean aPTT-POC. The aPTT-lab value was considered the gold standard measure of coagulation. A poor correlation was observed between ACT-LR and aPTT-lab in the global sample (r = 0.51), which improved slightly when excluding patients with invasive devices (r = 0.61). aPTT-POC showed moderate agreement (bias of 10.4%) but underestimated the aPTT ratio (bias = −0.23), which was similar in patients with and without devices. Agreement was very high in the control group (bias = −0.003). The accuracy of POC anticoagulation monitoring systems is limited in critically ill patients. The aPTT-POC measurements showed better agreement than the ACT-LR measurements. A clinical validation study is needed to adjust for systematic bias in patients with aPTT-POC. Full article

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7 pages, 3652 KB

Open AccessCase Report

Transfemoral TAVI in a High-Risk Patient with Porcelain Aorta and Severe Subrenal Abdominal Aortic Stenosis: A Case Report

by Anees Al Jabri, Marcello Ravani, Giuseppe Trianni, Tommaso Gasbarri, Marta Casula and Sergio Berti

J. Cardiovasc. Dev. Dis. 2025, 12(10), 396; https://doi.org/10.3390/jcdd12100396 - 7 Oct 2025

Viewed by 194

Abstract

Aortic stenosis (AS) is a common degenerative valvular disease in elderly patients, causing obstruction of left ventricular outflow and presenting with symptoms such as angina, syncope, and heart failure. Although surgical aortic valve replacement (SAVR) remains the gold standard, its high perioperative risk [...] Read more.

Aortic stenosis (AS) is a common degenerative valvular disease in elderly patients, causing obstruction of left ventricular outflow and presenting with symptoms such as angina, syncope, and heart failure. Although surgical aortic valve replacement (SAVR) remains the gold standard, its high perioperative risk in frail patients has led to the adoption of transcatheter aortic valve implantation (TAVI) as a less invasive and effective alternative. The transfemoral (TF) access route is generally preferred, but severe peripheral arterial disease may limit its feasibility. We report the case of a 71-year-old woman with critical AS complicated by multiple comorbidities, including extensive vascular calcifications, a porcelain aorta, and significant subrenal abdominal aortic stenosis. Multimodal imaging, including computed tomography, was essential for procedural planning, revealing complex iliofemoral anatomy unsuitable for conventional device passage without intervention. Intravascular lithotripsy (IVL) was used to disrupt calcific plaques and facilitate safe vascular access. The TAVI procedure was successfully performed under local anesthesia via TF access using a 65 cm GORE® DRYSEAL Flex Introducer Sheath (W. L. Gore & Associates, Flagstaff, AZ, USA) (18-Fr). After balloon valvuloplasty performed over a SAFARI2™ Pre-Shaped TAVI Guidewire, Extra Small (Boston Scientific, Marlborough, MA, USA) Curve in the left ventricle, a self-expanding Medtronic Evolut™ FX 26 (Medtronic, Minneapolis, MN, USA)mm transcatheter valve was implanted. Postoperative imaging confirmed optimal valve function and vascular integrity without complications. This case highlights the role of IVL as an innovative adjunctive technique enabling TF-TAVI in patients with challenging vascular anatomy, thereby expanding treatment options for high-risk individuals with severe AS. Full article

(This article belongs to the Special Issue Transcatheter Aortic Valve Implantation (TAVI): 3rd Edition)

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14 pages, 2225 KB

Open AccessArticle

Diagnostic Accuracy of Coronary CT Angiography in Ruling Out Significant Coronary Artery Disease in Candidates for Transcatheter Aortic Valve Replacement

by Chiara Gallo, Alfonso Campanile, Carmine Izzo, Sonia Paoletta, Valentina Russo, Pierpaolo Chivasso, Francesco Vigorito, Marco Di Maio, Michele Ciccarelli, Amelia Ravera, Tiziana Attisano, Giuliano Maraziti, Davide Di Gennaro, Enrico Coscioni, Carmine Vecchione and Oliviero Caleo

J. Cardiovasc. Dev. Dis. 2025, 12(10), 395; https://doi.org/10.3390/jcdd12100395 - 6 Oct 2025

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Abstract

Obstructive coronary artery disease (CAD) is common in patients undergoing transcatheter aortic valve implantation (TAVI). While invasive coronary angiography (ICA) is the gold standard for coronary evaluation, coronary computed tomography angiography (cCTA) is gaining interest for its potential to exclude obstructive CAD during [...] Read more.

Obstructive coronary artery disease (CAD) is common in patients undergoing transcatheter aortic valve implantation (TAVI). While invasive coronary angiography (ICA) is the gold standard for coronary evaluation, coronary computed tomography angiography (cCTA) is gaining interest for its potential to exclude obstructive CAD during pre-procedural imaging. This study aimed to assess the diagnostic accuracy of cCTA in ruling out significant CAD in TAVI candidates. We retrospectively analyzed 95 TAVI candidates (mean age 77.7 ± 8.5 years) who underwent both cCTA and ICA. Diagnostic performance of cCTA—sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy—was assessed using ICA as the reference, in both patient- and vessel-based models. Obstructive CAD was defined as ≥50% luminal stenosis or occlusion of a stent/bypass graft. ICA detected obstructive CAD in 27 patients (28.4%). Excluding non-evaluable cases, cCTA showed a negative predictive value (NPV) of 97% (patient-level) and 95% (vessel-level), with a diagnostic accuracy of 85% and 87%, respectively. Including all patients, regardless of scan quality, the NPV remained high (97%), although overall accuracy dropped to 67% (patient-level) and 66% (vessel-level). cCTA demonstrated high accuracy in excluding significant CAD, with a stable NPV of 95–97%. The relatively high rate of non-diagnostic scans and the single-center, retrospective design suggest that its role should be considered complementary to ICA, potentially reducing—but not replacing—the need for ICA in selected TAVI candidates. 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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19 pages, 1699 KB

Open AccessArticle

Real-World Patterns and Outcomes of Anticoagulation Therapy in Pulmonary Embolism: An Observational Dual-Centre Registry Analysis

by Ivana Jurin, Josip Pejić, Karlo Gjuras, Fran Šaler, Tea-Terezija Cvetko, Nevenka Piskač Živković, Zdravko Mitrović, Šime Manola, Marin Pavlov, Aleksandar Blivajs, Kristina Marić Bešić, Dalibor Divković and Irzal Hadžibegović

J. Cardiovasc. Dev. Dis. 2025, 12(10), 394; https://doi.org/10.3390/jcdd12100394 - 6 Oct 2025

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Abstract

Background: Pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality. Guidelines favor direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs), but real-world Croatian data are scarce. Methods: A prospective dual-center registry included 773 patients discharged with acute PE between [...] Read more.

Background: Pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality. Guidelines favor direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs), but real-world Croatian data are scarce. Methods: A prospective dual-center registry included 773 patients discharged with acute PE between 2013 and 2024. Clinical, laboratory, and socioeconomic data were collected. The primary outcome was all-cause mortality; secondary outcomes were recurrent venous thromboembolism (VTE) and major bleeding. Results: DOAC users were younger, with higher education and income, than VKA or heparin patients. Median follow-up was 1106 days. Mortality reached 60.3% with VKA, 26.0% with DOAC, and 84.1% with heparin (p < 0.001). VTE recurrence did not differ significantly. Major bleeding occurred in 9.3% of VKA versus 2.9% of DOAC patients (p = 0.003). Adjusted analysis showed a lower mortality risk with DOAC versus VKA (HR 0.62, 95% CI 0.48–0.80, p < 0.001), while heparin predicted higher mortality (HR 3.63, 95% CI 2.54–5.21, p < 0.001). Higher PESI class independently increased mortality and recurrence. Conclusion: In the first Croatian PE cohort, DOACs were linked to reduced mortality and bleeding risk compared with VKAs, with similar recurrence. Clinical, socioeconomic, and policy factors strongly influenced prescribing patterns and outcomes. Full article

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14 pages, 275 KB

Open AccessArticle

Impact of Hypertension on Physical and Cognitive Performance Under Single- and Dual-Task Conditions in Older Adults

by Daniel Estévez-Caro, María Melo-Alonso, Miguel A. Hernández-Mocholí, Santos Villafaina and Francisco Javier Domínguez-Muñoz

J. Cardiovasc. Dev. Dis. 2025, 12(10), 393; https://doi.org/10.3390/jcdd12100393 - 4 Oct 2025

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Abstract

Background: Up to 40% of people with hypertension (HTN) develop mild cognitive impairment and Alzheimer’s disease during their lifetime. This study aimed to compare physical and cognitive performance in older adults, classified as non-HTN or with HTN, under single-task (ST) and dual-task (DT) [...] Read more.

Background: Up to 40% of people with hypertension (HTN) develop mild cognitive impairment and Alzheimer’s disease during their lifetime. This study aimed to compare physical and cognitive performance in older adults, classified as non-HTN or with HTN, under single-task (ST) and dual-task (DT) conditions. Methods: In total, 46 individuals (71 ± 5.96 years), divided equally into non-HTN and HTN groups, participated. Normality of the data was tested using the Shapiro–Wilk test. In this cross-sectional study, groups were compared using the Mann–Whitney U test applied to non-parametric variables and the independent samples t-test applied to parametric ones. Physical and cognitive functions were evaluated using the Short Physical Performance Battery (SPPB), HandGrip Strength (HGS), Timed Up and Go (TUG), and the L-Test, both in ST and DT conditions (with arithmetic tasks). Results: Significant differences were observed between groups in MoCA and the physical performance of SPPB, TUG, and L-Test under ST. In the DT condition, differences were found in the physical performance of TUG, L-test, and SPPB total score as well as in different components such as the 3 m walk and the Sit to Stand (STS). Regarding physical–cognitive interference, there was a statistically significant difference in the SPPB dual task cost between the HTN and non-HTN groups. Conclusions: Individuals with HTN exhibit impairments compared to non-HTN individuals in physical performance under DT conditions as well as in physical–cognitive interference. Static balance and HGS appear unaffected; however, differences are evident in gait (TUG and L-Test) and lower-limb strength (STS). Full article

(This article belongs to the Special Issue Sports Cardiology: From Diagnosis to Clinical Management, 2nd Edition)

13 pages, 1410 KB

Open AccessArticle

Clinical, Imaging, and Serum Biomarker Predictors of Malignant Cerebral Infarction

by Alejandro Rodríguez-Vázquez, Salvatore Rudilosso, Antonio Doncel-Moriano, Andrea Cabero-Arnold, Carlos Laredo, Darío Ramis, David Moraleja, Mònica Serrano, Yolanda González-Romero, Arturo Renú, Inés Bartolomé-Arenas, Irene Rosa-Batlle, Guillem Dolz, Ramón Torné, Martha Vargas, Xabier Urra and Ángel Chamorro

J. Cardiovasc. Dev. Dis. 2025, 12(10), 392; https://doi.org/10.3390/jcdd12100392 - 4 Oct 2025

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Abstract

Malignant cerebral infarction (MCI) is rare but often fatal. Early identification helps guide monitoring and decompressive surgery. This study evaluated whether serum biomarkers add predictive value beyond clinical and imaging data in severe stroke patients with anterior circulation large vessel occlusion (LVO). In [...] Read more.

Malignant cerebral infarction (MCI) is rare but often fatal. Early identification helps guide monitoring and decompressive surgery. This study evaluated whether serum biomarkers add predictive value beyond clinical and imaging data in severe stroke patients with anterior circulation large vessel occlusion (LVO). In this prospective study, 73 acute severe LVO stroke patients underwent whole-brain CT perfusion (CTP) with rCBV-based core measurement at admission and follow-up MRI at 24 ± 12 h for infarct and edema volume assessment. Serum biomarkers (s100b, NSE, VEGF, ICAM1) were sampled a median of 20.5 h after baseline imaging. Logistic regression models predicted MCI using baseline variables (NIHSS, ASPECTS, rCBV < 30%), adding treatment data (rtPA, mTICI, NIHSS posttreatment), and adding serum biomarkers. Performance was assessed by AUC, accuracy, F1, and cross-validated R². MCI occurred in 18/73 (24%) patients. Baseline models showed an AUC of 0.72; adding treatment improved the AUC to 0.88. Biomarkers slightly increased the AUC (0.90) but did not improve F1. Higher s100b was associated with more severe injury but did not enhance the prediction of MCI. Models with baseline imaging and treatment best explained infarct (R² ≈ 0.27) and edema (R² ≈ 0.58). In conclusion, admission severity, CTP, and early treatment response are the main predictors of MCI and aid early risk stratification of patients. Despite their pathophysiologic relevance, serum biomarkers do not add substantial predictive value. Full article

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

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13 pages, 4743 KB

Open AccessSystematic Review

Impact of Atrial Fibrillation on the Outcome of Patients with Brugada Syndrome: A Meta-Analysis

by Max Aboutorabi, Mahmood Ahmad, Jonathan J. H. Bray, Daniel A. Gomes and Rui Providencia

J. Cardiovasc. Dev. Dis. 2025, 12(10), 391; https://doi.org/10.3390/jcdd12100391 - 3 Oct 2025

Viewed by 302

Abstract

Introduction: Atrial fibrillation (AF) is common in patients with Brugada syndrome (BrS). The impact and significance of AF in this patient population needs to be further clarified. Method: We performed a systematic review and meta-analysis of studies comparing the risks of developing major [...] Read more.

Introduction: Atrial fibrillation (AF) is common in patients with Brugada syndrome (BrS). The impact and significance of AF in this patient population needs to be further clarified. Method: We performed a systematic review and meta-analysis of studies comparing the risks of developing major arrhythmic events (MAEs) in patients with BrS with and without AF. Databases including MEDLINE, Embase, and Cochrane CENTRAL were searched from inception to July 2024, using appropriate search and MeSH terms. Data were sought on the comparison of patients with BrS with and without AF. The protocol was specified prior to the searches being performed, and standard meta-analytic techniques were used. Results: Thirteen observational studies were included (a total of 5413 patients). A significant increase in MAEs was observed in patients with both BrS and AF (20.6% vs. 7.8%; OR 2.81, 95% CI 1.82–4.34; p < 0.0001; I² = 46%). Significantly higher rates of syncope (33.3% vs. 23.4%; OR 1.97, 95% CI 1.04–3.76; p = 0.04, I² = 59%) and a significant increase in all-cause mortality (11.3% vs. 3.7%; OR 4.21, 95% CI 1.69–10.45; p = 0.002, I² = 0%) and sodium channel mutations (43.1% vs. 29.9%; OR 1.87, 95% CI 1.07–3.29; p = 0.028, I² = 0%) were observed for patients with BrS and AF. Conclusions: Patients with both BrS and AF seem to have a more severe disease phenotype. More research into the added role of AF in risk stratification of asymptomatic BrS patients is needed, but the prognostic implications of AF may need to be considered when developing future personalised medicine approaches in the BrS population. Full article

(This article belongs to the Special Issue Atrial Fibrillation: Risk Stratification, Epidemiology, Treatment Advances and Prognostic Interventions)

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21 pages, 1199 KB

Open AccessReview

The Glymphatic System and Diaphragmatic Dysfunction in Patients with Chronic Obstructive Pulmonary Disease and Chronic Heart Failure: The Importance of Inspiratory Rehabilitation Training

by Bruno Bordoni, Bruno Morabito, Vincenzo Myftari, Andrea D’Amato and Paolo Severino

J. Cardiovasc. Dev. Dis. 2025, 12(10), 390; https://doi.org/10.3390/jcdd12100390 - 2 Oct 2025

Viewed by 1096

Abstract

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) are pathologies that impact mortality and morbidity worldwide. These chronic diseases have multiple causes, and they share some common clinical symptoms, such as diaphragm dysfunction (DD) and cognitive decline (CD), which, in turn, [...] Read more.

Chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) are pathologies that impact mortality and morbidity worldwide. These chronic diseases have multiple causes, and they share some common clinical symptoms, such as diaphragm dysfunction (DD) and cognitive decline (CD), which, in turn, increase the mortality and morbidity rates in patients with COPD and CHF. One of the causes of CD is impaired glymphatic system function, with an accumulation of proteins and metabolites in the central nervous system. The glymphatic system is a structure that has not yet been widely considered by researchers and clinicians. Three key factors stimulate the ongoing physiological function of the glymphatic system: autonomic balance, heart rate, and, most importantly, the diaphragm. All these factors are altered in patients with COPD and CHF. This article reviews the relationship between the importance of the diaphragm, the glymphatic system, and CD, focusing on inspiratory rehabilitation training (IMT). Based on the data reported in this narrative review, we can strongly speculate that a consistent regimen of IMT in patients can improve cognitive status, reducing the cascade of symptoms that follow the diagnosis of CD. Further research is needed to understand whether targeting the glymphatic system with IMT is an effective option for helping patients delay the onset of CD. Full article

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

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20 pages, 1335 KB

Open AccessReview

Advances in Epicardial Biology: Insights from Development, Regeneration, and Human Cardiac Organoids

by Shasha Lyu, Alvin Gea Chen Yao, Yu Xia and Jingli Cao

J. Cardiovasc. Dev. Dis. 2025, 12(10), 389; https://doi.org/10.3390/jcdd12100389 - 2 Oct 2025

Viewed by 377

Abstract

The epicardium plays a pivotal role in heart development, regeneration, and disease response through its contributions to multiple cardiac lineages and its dynamic paracrine signaling. Recent advances in lineage tracing, single-cell technologies, and, particularly, human pluripotent stem cell (hPSC)-derived cardiac organoid models have [...] Read more.

The epicardium plays a pivotal role in heart development, regeneration, and disease response through its contributions to multiple cardiac lineages and its dynamic paracrine signaling. Recent advances in lineage tracing, single-cell technologies, and, particularly, human pluripotent stem cell (hPSC)-derived cardiac organoid models have illuminated the cellular heterogeneity, developmental plasticity, and intercellular crosstalk of epicardial cells with other cardiac cell types. These models have revealed conserved and divergent mechanisms of epicardial function across species, offering new insights into epicardial–myocardial–endothelial–immune interactions and the regulation of cardiac repair. This review highlights recent key findings from developmental and regenerative studies, integrating them with emerging data from human cardiac organoids to provide an updated framework for understanding epicardial biology and its therapeutic potential. Full article

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

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9 pages, 1207 KB

Open AccessArticle

Hypertrabeculation in Olympic Athletes: Advanced LV Function Analysis by CMR

by Alessandro Spinelli, Sara Monosilio, Giuseppe Di Gioia, Gianni Pedrizzetti, Giovanni Tonti, Cosimo Damiano Daniello, Maria Rosaria Squeo, Antonio Pelliccia and Viviana Maestrini

J. Cardiovasc. Dev. Dis. 2025, 12(10), 388; https://doi.org/10.3390/jcdd12100388 - 2 Oct 2025

Viewed by 170

Abstract

Left ventricular (LV) hypertrabeculation is increasingly recognized as a phenotype that may reflect physiological adaptation, particularly in athletes exposed to chronic overload, although its functional relevance remains uncertain. This study evaluated the prevalence of excessive trabeculation and its physiological correlation with LV remodeling. [...] Read more.

Left ventricular (LV) hypertrabeculation is increasingly recognized as a phenotype that may reflect physiological adaptation, particularly in athletes exposed to chronic overload, although its functional relevance remains uncertain. This study evaluated the prevalence of excessive trabeculation and its physiological correlation with LV remodeling. We conducted a single-center, cross-sectional study involving 320 Olympic-level athletes without cardiovascular disease. All underwent cardiac magnetic resonance (CMR). Hypertrabeculation was defined by the Petersen criteria. Athletes meeting these criteria were classified as hypertrabeculated and compared with non-hypertrabeculated matched for age, sex, and sport category. LV morphology, function, strain parameters, and hemodynamic forces (HDFs) were analyzed. Hypertrabeculation was identified in 9% of the cohort. No significant differences were observed between groups for training exposure (p = 0.262), body surface area (p = 0.762), LV volumes (end-diastolic volume indexed p = 0.397 end-systolic volume indexed p = 0.118), ejection fraction (p = 0.101), mass (p = 0.919), sphericity index (p = 0.419), myocardial wall thickness (p = 0.394), tissue characterization (T1 mapping p = 0.366, T2 mapping p = 0.833), global longitudinal strain (GLS p = 0.898), global circumferential strain (GCS p = 0.219), or HDFs. All values were within the normal range. In our cohort, LV hypertrabeculation, evaluated by CMR, was relatively common but not associated with structural or functional abnormalities, supporting its interpretation as a benign variant in asymptomatic athletes with normal cardiac function. Full article

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

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12 pages, 830 KB

Open AccessArticle

Effect of Acute Grape Seed Extract Supplementation on Heart Rate Recovery in Young Individuals

by Dae Sik Song, William Boyer, Trevor Gillum, Sean Sullivan, Iltark Yoon, Junbei Bai, Seung-Jae Kim and Jong-Kyung Kim

J. Cardiovasc. Dev. Dis. 2025, 12(10), 387; https://doi.org/10.3390/jcdd12100387 - 1 Oct 2025

Viewed by 280

Abstract

Evidence has suggested that post-exercise heart rate recovery (PHRR) is a useful tool in evaluating cardiac autonomic function. Altered cardiac autonomic function is characterized by heightened sympathetic activation and the abnormal reactivation of the parasympathetic nervous system and is associated with delayed HRR. [...] Read more.

Evidence has suggested that post-exercise heart rate recovery (PHRR) is a useful tool in evaluating cardiac autonomic function. Altered cardiac autonomic function is characterized by heightened sympathetic activation and the abnormal reactivation of the parasympathetic nervous system and is associated with delayed HRR. Although grape seed extract (GSE) supplementation has been shown to increase nitric oxide production and modify sympathetic output, there is limited evidence on its potential beneficial effects on PHRR. We investigated the effect of GSE supplementation on PHRR during sympathetic overactivation induced by muscle metaboreflex activation (MMA) in young individuals. Participants were randomly assigned, via a double-blind, cross-over design, to either receive GSE (300 mg, two capsules) or PL (300 mg, two capsules), with a washout period of at least 72 h. between trials. A submaximal exercise test was performed using a cycle ergometer combined with an isometric handgrip exercise using a handgrip dynamometer and blood flow occlusion by placing a cuff over the brachial artery of the dominant arm. PHRR was measured at 5 s. intervals throughout the experiment. The PHRR was evaluated between GSE and PL at every min. for 300 s. PHRR kinetics significantly improved following GSE supplementation (74.3 ± 7.5 s) compared with the PL condition (86.2 ± 10.4 s). Our results suggest that GSE is effective in improving HRR kinetics during heightened sympathetic activity induced by MMA in young individuals (p = 0.034; ES = 0.4). Thus, regular treatment with GSE may provide a nonpharmacological intervention to reduce sympathetic hyperactivity in conditions where excessive sympathetic activity is consistently present. Full article

(This article belongs to the Special Issue Exercise Testing and Interventions in Cardiovascular Disease)

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16 pages, 1412 KB

Open AccessReview

Early Currents: Developmental Electrophysiology and Arrhythmia in Pediatric Congenital Heart Disease

by Lixia Dai, Weilin Liu, Vehpi Yildirim, Mathijs S. van Schie, Yannick J. H. J. Taverne and Natasja M. S. de Groot

J. Cardiovasc. Dev. Dis. 2025, 12(10), 386; https://doi.org/10.3390/jcdd12100386 - 1 Oct 2025

Viewed by 395

Abstract

Arrhythmias significantly contribute to morbidity and mortality in patients with congenital heart disease (CHD). While postoperative factors predisposing to arrhythmias are well-established, early electrophysiological alterations in pediatric CHD remain poorly understood. This review summarizes current knowledge on postnatal cardiac maturation, conduction-system development, and [...] Read more.

Arrhythmias significantly contribute to morbidity and mortality in patients with congenital heart disease (CHD). While postoperative factors predisposing to arrhythmias are well-established, early electrophysiological alterations in pediatric CHD remain poorly understood. This review summarizes current knowledge on postnatal cardiac maturation, conduction-system development, and electrophysiological abnormalities in pediatric patients with and without CHD. Importantly, arrhythmia prevalence, mechanisms, and clinical relevance are systematically discussed across three pediatric groups, including healthy children and patients with unrepaired and repaired CHD. Understanding developmental arrhythmogenic mechanisms may facilitate early risk stratification, guide clinical management decisions, and improve long-term outcomes for pediatric patients with CHD. This review discusses the complex interplay between cardiac maturation, congenital defects, and arrhythmogenesis. It also outlines future directions that include noninvasive monitoring, selective intraoperative mapping, animal model studies, and standardized data collection to improve early risk stratification and long-term outcomes in children with CHD. Full article

(This article belongs to the Special Issue 10th Anniversary of JCDD—'Pediatric Cardiology and Congenital Heart Disease' Section)

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12 pages, 1639 KB

Open AccessArticle

Effects of Physical Activity, Metabolic Syndrome, and Social Status on ECG Parameters in Children: A Prospective Cohort Study

by Árpád Kézdi, Viktor József Horváth, Regina Hangács, Ádám Gyula Tabák, Dominic Joseph Fogarasi, Dániel Vadon, György Grósz, Ferenc Fekete and Anikó Nagy

J. Cardiovasc. Dev. Dis. 2025, 12(10), 385; https://doi.org/10.3390/jcdd12100385 - 29 Sep 2025

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Abstract

(1) Background: Physical activity, altered metabolic parameters, and socio-economic status may affect electrocardiographic (ECG) parameters in children. However, a direct comparison of their effects on resting ECG has not yet been performed. (2) Methods: A total of 139 participants (60 male), aged 10–17 [...] Read more.

(1) Background: Physical activity, altered metabolic parameters, and socio-economic status may affect electrocardiographic (ECG) parameters in children. However, a direct comparison of their effects on resting ECG has not yet been performed. (2) Methods: A total of 139 participants (60 male), aged 10–17 years, were recruited. Resting 1-minute ECG recordings and clinical and laboratory investigations were obtained, while socio-economic status and physical activity were assessed using a questionnaire. Associations between these factors and ECG parameters were analyzed using analysis of covariance (ANCOVA). (3) Results: Age, sex, metabolic syndrome, and physical activity significantly influenced the average RR interval (η² = 0.292, 0.070, 0.078, and 0.070, respectively). Similar effects were observed on the T_end–P interval. The PR, QRS, QTc, and T_peak–T_end intervals were moderately influenced by age (η² = 0.084, 0.056, 0.072, and 0.049, respectively). QTc was additionally affected by sex (η² = 0.060). None of the modifiable factors had any effect on depolarization or repolarization parameters. Socio-economic status had no significant effect on resting ECG. (4) Conclusions: Physical activity exerts similar effects on resting ECG in both sexes, while metabolic syndrome is an independent determinant of several ECG parameters. Further studies are warranted to clarify the clinical relevance of these findings. Full article

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

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22 pages, 1235 KB

Open AccessReview

Metabolic Reprogramming and Cell Interaction in Atherosclerosis: From Molecular Mechanisms to Therapeutic Strategies

by Yu-Xin Liu, Feng-Ming Guo, Wen-Jun Qiu, Yi-Peng Gao, Xue-Yu Han and Bo Shen

J. Cardiovasc. Dev. Dis. 2025, 12(10), 384; https://doi.org/10.3390/jcdd12100384 - 28 Sep 2025

Viewed by 442

Abstract

Atherosclerosis is a complex systemic inflammatory metabolic disease, which originates from endothelial dysfunction and progresses through plaque formation involving vascular smooth muscle cells (VSMCs) and macrophage uptake of modified low-density lipoprotein (LDL). These processes lead to vascular stenosis, plaque rupture, and potentially sudden [...] Read more.

Atherosclerosis is a complex systemic inflammatory metabolic disease, which originates from endothelial dysfunction and progresses through plaque formation involving vascular smooth muscle cells (VSMCs) and macrophage uptake of modified low-density lipoprotein (LDL). These processes lead to vascular stenosis, plaque rupture, and potentially sudden death. Metabolic dysregulation and cellular remodeling are fundamental to the pathogenesis of atherosclerosis. In this review, we summarize recent advances in the metabolic reprogramming of major cell types (including endothelial cells, VSMCs, and macrophages) during atherosclerosis progression. Furthermore, we discuss the crosstalk among these cells mediated by such metabolic alterations. Finally, we highlight the implications of metabolic reprogramming for targeted therapeutic strategies, offering insights for precision intervention in aortic atherosclerosis. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

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19 pages, 428 KB

Open AccessReview

Homocysteine in the Cardiovascular Setting: What to Know, What to Do, and What Not to Do

by Saverio D’Elia, Mariarosaria Morello, Gisella Titolo, Valentina Maria Caso, Achille Solimene, Ettore Luisi, Chiara Serpico, Andrea Morello, Lucia La Mura, Francesco S. Loffredo, Francesco Natale, Paolo Golino and Giovanni Cimmino

J. Cardiovasc. Dev. Dis. 2025, 12(10), 383; https://doi.org/10.3390/jcdd12100383 - 27 Sep 2025

Viewed by 775

Abstract

Homocysteine has long been studied as a potential cardiovascular risk factor due to its biochemical role in endothelial dysfunction, oxidative stress, inflammation, and thrombogenesis. Despite strong epidemiological and mechanistic support, the translation of homocysteine-lowering interventions into clinical benefit remains controversial. This non-systematic review [...] Read more.

Homocysteine has long been studied as a potential cardiovascular risk factor due to its biochemical role in endothelial dysfunction, oxidative stress, inflammation, and thrombogenesis. Despite strong epidemiological and mechanistic support, the translation of homocysteine-lowering interventions into clinical benefit remains controversial. This non-systematic review aims to clarify the current understanding of homocysteine in the cardiovascular setting by distinguishing between well-established facts, clinically relevant interventions, and persistent misconceptions. We first revisit the historical emergence of homocysteine as a cardiovascular biomarker and explore its pathophysiological mechanisms, including endothelial damage, atherosclerosis progression, and prothrombotic effects—supported by in vitro and animal model studies. Subsequently, we evaluate evidence-based interventions such as B-vitamin supplementation (folate, B6, B12), lifestyle modifications, and the clinical relevance of homocysteine monitoring in specific populations (e.g., MTHFR mutations, chronic kidney disease). We then discuss common pitfalls, including the overinterpretation of genetic variants, the inappropriate use of supplementation, and the overreliance on surrogate biomarkers in clinical trials. Although elevated homocysteine remains a reproducible biomarker of cardiovascular risk, current evidence does not support routine intervention in unselected populations. A precision medicine approach—targeting high-risk subgroups and integrating homocysteine into broader cardiometabolic management—may help unlock its therapeutic relevance. Future pharmacological strategies should prioritize mechanistic insight, patient stratification, and clinically meaningful endpoints. Full article

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9 pages, 6463 KB

Open AccessEditorial

Advances in Cardiovascular Imaging: A Platform to Share Recent Research Findings Through Utilization of Advanced Imaging Technologies

by Zhonghua Sun

J. Cardiovasc. Dev. Dis. 2025, 12(10), 382; https://doi.org/10.3390/jcdd12100382 - 26 Sep 2025

Viewed by 352

Abstract

Clinical diagnosis of cardiovascular disease has undergone revolutionary changes over the last decades thanks to rapid developments in medical imaging modalities significantly enhancing the diagnostic performance of cardiac imaging in cardiovascular disease [...] Full article

(This article belongs to the Special Issue Advances in Cardiovascular Imaging: An Exciting Future to Revolutionize the Diagnosis and Management of Cardiovascular Disease)

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14 pages, 317 KB

Open AccessArticle

Cardiopulmonary Test in Fontan Patients: Is the Type of Ergometer Critical?

by Federica Gentili, Giulia Cafiero, Eliana Tranchita, Jacopo Kowalczyk, Fausto Badolato, Paola Pagliari, Benedetta Leonardi, Giulio Calcagni, Gabriele Rinelli, Claudia Montanaro, Fabrizio Drago and Ugo Giordano

J. Cardiovasc. Dev. Dis. 2025, 12(10), 381; https://doi.org/10.3390/jcdd12100381 - 25 Sep 2025

Viewed by 285

Abstract

Cardiopulmonary exercise testing (CPET) is recommended as part of routine care in people with congenital heart disease. A significant difference has been observed in many CPET parameters, depending on the ergometer and exercise protocol used. The aim of this study is to investigate [...] Read more.

Cardiopulmonary exercise testing (CPET) is recommended as part of routine care in people with congenital heart disease. A significant difference has been observed in many CPET parameters, depending on the ergometer and exercise protocol used. The aim of this study is to investigate such differences in Fontan patients. All Fontan patients (<40 years old, NYHA class I/I–II) underwent two consecutive CPETs on different ergometers (treadmill with ramped Bruce protocol versus cycle ergometer with ramp protocol) within less than 12 months. The exclusion criterion was the presence of significant clinical/anthropometric changes between the two tests. Anthropometric, surgical, clinical, electrocardiogram (ECG) and CPET data were collected. 47 subjects were enrolled (25 males, mean age 16.4 at first test). Peak heart rate (HR) tended to be higher on the treadmill (p = 0.05 as % of predicted, p = 0.062 in absolute value). Peak oxygen consumption (VO₂) (mL/min, mL/kg/min, and % of predicted) was significantly higher on the treadmill (p < 0.01), as well the VO₂ at the ventilatory anaerobic threshold (VAT) and the peak oxygen pulse. A different kinetics of the oxygen pulse wave was observed in the same patient comparing the two testing modalities. Maximal respiratory-exchange-ratio values (>1.1) were reached more frequently on the cycle ergometer (p < 0.001). The minute ventilation–carbon dioxide output slope (VE/VCO₂ slope) was not different between the two tests (p = 0.400). Many parameters of CPET may differ depending on the ergometer used. These should be considered in clinical evaluation of Fontan patients and when exercise is to be prescribed. Full article

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

14 pages, 2221 KB

Open AccessArticle

Efficacy of Contractility Modulation Therapy in Patients with Transthyretin Amyloid Cardiomyopathy, Mildly Reduced to Reduced EF and NYHA III and IV: A Multicentric, Prospective Pilot Study for AMY-CCM Registry

by Procolo Marchese, Francesca Gennaro, Giovanni Mazzotta, Pierfrancesco Grossi, Luigi Cocchiara, Stefano Guarracini, Lorenzo Mazzocchetti, Matteo Ziacchi, Mauro Biffi, Roberta Magnano, Massimo Di Marco, Matteo Ruzzolini, Antonio Bisignani, Matteo Bianco, Paolo Garrone, Walter Grosso Marra, Margherita Cannillo, Carlo Lavalle, Daniele Masarone and Cristina Chimenti

J. Cardiovasc. Dev. Dis. 2025, 12(10), 380; https://doi.org/10.3390/jcdd12100380 - 25 Sep 2025

Viewed by 645

Abstract

Background: Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy that frequently progresses to symptomatic heart failure (HF), often with mildly reduced or reduced ejection fraction (EF). Standard therapies are limited in NYHA III–IV, and Tafamidis is approved only for the early stages. Cardiac [...] Read more.

Background: Transthyretin cardiac amyloidosis (ATTR-CM) is an infiltrative cardiomyopathy that frequently progresses to symptomatic heart failure (HF), often with mildly reduced or reduced ejection fraction (EF). Standard therapies are limited in NYHA III–IV, and Tafamidis is approved only for the early stages. Cardiac contractility modulation (CCM) therapy has shown promise in HF with reduced EF, but its role in ATTR-CM remains unexplored. Methods: This multicentric, prospective pilot study evaluated the safety and efficacy of CCM therapy in ten patients (n = 10) with ATTR-CM, EF between 25 and 45%, and NYHA class III–IV symptoms refractory to optimal medical therapy. All patients underwent implantation of the Optimizer CCM system and were followed for at least 12 months. The primary endpoint was the incidence of worsening heart failure (WHF); secondary endpoints included changes in EF, NYHA class, 6-minute walk test (6MWT), and quality of life metrics. Results: In this cohort (n = 10), CCM therapy significantly reduced WHF episodes (from 0.18 ± 0.09 to 0.025 ± 0.08 hospitalizations/patient-year, p < 0.001) and improved NYHA class and 6MWT (p < 0.001). EF increased by an average of 4.8 ± 6.1%, and 6MWT improved by 31.3 ± 53.3%. Importantly, all patients became eligible for Tafamidis after CCM therapy due to improved functional status. Conclusion: This pilot study suggests that CCM therapy is a feasible and potentially effective option for ATTR-CM patients with advanced HF who are not candidates for existing disease-modifying treatments. These findings support the rationale for larger studies, including the ongoing AMY-CCM registry (NCT05167799), to validate CCM’s therapeutic role in this population. Full article

(This article belongs to the Section Cardiovascular Clinical Research)

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18 pages, 5902 KB

Open AccessReview

Heart at Hand: The Role of Point-of-Care Cardiac Ultrasound in Internal Medicine

by Piero Tarantini, Francesco Cei, Fabiola Longhi, Aldo Fici, Salvatore Tupputi, Gino Solitro, Lucia Colavolpe, Stefania Marengo and Nicola Mumoli

J. Cardiovasc. Dev. Dis. 2025, 12(10), 379; https://doi.org/10.3390/jcdd12100379 - 24 Sep 2025

Viewed by 810

Abstract

Bedside echocardiography stands as a cornerstone diagnostic tool in internal medicine, offering rapid, real-time evaluation of cardiac structure and function across a wide spectrum of acute and chronic conditions. Its application, particularly when combined with lung and inferior vena cava (IVC) ultrasound, significantly [...] Read more.

Bedside echocardiography stands as a cornerstone diagnostic tool in internal medicine, offering rapid, real-time evaluation of cardiac structure and function across a wide spectrum of acute and chronic conditions. Its application, particularly when combined with lung and inferior vena cava (IVC) ultrasound, significantly enhances diagnostic accuracy for fluid balance assessment, dyspnea, and hypotensive states, guiding timely therapeutic decisions. Focused cardiac ultrasound (FoCUS) enables internists to assess left ventricular function, right atrial pressure, valvular abnormalities, and pericardial effusion, facilitating differentiation between cardiac and non-cardiac causes of symptoms such as dyspnea, chest pain, and hemodynamic instability. While operator-dependent, echocardiography can be effectively integrated into internal medicine practice through structured training programs that combine theoretical knowledge with supervised hands-on experience. This integration enhances clinical decision-making, optimizes patient management, and reduces the need for immediate specialist consultation. Widespread adoption of focused ultrasound techniques in internal medicine wards promises not only improved patient outcomes but also more efficient utilization of healthcare resources. Continued education and institutional support are fundamental to embedding echocardiography into routine care, ensuring internists are equipped to leverage this powerful bedside modality. This narrative review aims to underscore the transformative impact of bedside echocardiography in internal medicine, demonstrating its capacity, when combined with lung and IVC ultrasound, to optimize diagnostic pathways and treatment decisions across diverse acute and chronic settings. Full article

(This article belongs to the Section Imaging)

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19 pages, 2466 KB

Open AccessReview

Opening the Sacred Chamber: The Cultural and Ethical Odyssey of Cardiac Surgery

by Vasileios Leivaditis, Georgios Mavroudes, Francesk Mulita, Nikolaos G. Baikoussis, Athanasios Papatriantafyllou, Vasiliki Garantzioti, Konstantinos Tasios, Levan Tchabashvili, Dimitrios Litsas, Paraskevi Katsakiori, Stelios F. Assimakopoulos, Konstantinos Nikolakopoulos, Andreas Antzoulas, Elias Liolis, Spyros Papadoulas, Efstratios Koletsis and Manfred Dahm

J. Cardiovasc. Dev. Dis. 2025, 12(10), 378; https://doi.org/10.3390/jcdd12100378 - 24 Sep 2025

Viewed by 492

Abstract

Cardiac surgery, now a routine medical intervention, was once deemed unthinkable—not merely due to technical limitations, but because of deep-seated cultural, religious, and philosophical prohibitions. This article traces the historical and ethical trajectory of the human heart from a sacred, inviolable symbol of [...] Read more.

Cardiac surgery, now a routine medical intervention, was once deemed unthinkable—not merely due to technical limitations, but because of deep-seated cultural, religious, and philosophical prohibitions. This article traces the historical and ethical trajectory of the human heart from a sacred, inviolable symbol of the soul to a surgically accessible organ. Through an interdisciplinary lens that integrates medical history, anthropology, theology, and contemporary bioethics, we examine how shifts in metaphysical belief, technological progress, and moral reasoning gradually legitimized cardiac intervention. From ancient Egyptian funerary rites and classical cardiocentric models to medieval religious taboos and Enlightenment redefinitions of the body, the heart’s transformation reflects broader changes in how humanity conceives life, death, and identity. The emergence of modern cardiac surgery, especially heart transplantation and extracorporeal technologies, raised new ethical dilemmas, challenging the boundaries between tissue and meaning, biology and personhood. This study argues that despite its clinical secularization, the heart retains a unique symbolic gravity that continues to shape public perception and professional responsibility. In the age of precision medicine, cardiac surgery remains not only a technical act but an existential gesture—a transgression that demands both scientific mastery and moral reverence. Full article

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11 pages, 4777 KB

Open AccessArticle

Subacute Hypoxia Induces Cardiac Remodeling and Mitochondrial Dysfunction via Apoptotic Pathways in a Rabbit Model of Tracheal Stenosis

by Taeyun Kim, Kyoung-Im Cho, Hyoung Kyu Kim, Chulho Oak, Jin Han, Hyoung Shin Lee and Yohan Jeon

J. Cardiovasc. Dev. Dis. 2025, 12(10), 377; https://doi.org/10.3390/jcdd12100377 - 24 Sep 2025

Viewed by 237

Abstract

Myocardial hypoxia is a major cause of cardiac dysfunction, triggering cellular injury and apoptosis. This study aims to investigate the effects of subacute hypoxia on cardiac remodeling and mitochondrial oxygen consumption. This study is based on a rabbit experimental model. Hypoxia was induced [...] Read more.

Myocardial hypoxia is a major cause of cardiac dysfunction, triggering cellular injury and apoptosis. This study aims to investigate the effects of subacute hypoxia on cardiac remodeling and mitochondrial oxygen consumption. This study is based on a rabbit experimental model. Hypoxia was induced using a rabbit tracheal stenosis model. Endotracheal intubation with a 1.5 cm segmented tube wrapped with an absorbable hemostat was used to generate tracheal stenosis in six rabbits. Sham controls (n = 3) underwent tracheotomy, with the tracheal exposure site being sutured immediately. After 1 week, the tube was removed. Echocardiography and mitochondrial function from both groups were morphologically and functionally analyzed at 2 weeks after endoscopic confirmation of tracheal stenosis. Compared to sham group, tracheal stenosis group showed significantly reduced interventricular septal wall thickness (2.3 ± 0.1 mm vs. 2.7 ± 0.2 mm, p = 0.08) and enlarged left ventricular end-diastolic volume (5.86 ± 0.58 mL vs. 5.39 ± 0.18 mL, p = 0.46) with reduced left ventricular ejection fraction (54.5 ± 5.3% vs. 66.9 ± 4.0%, p = 0.005). The tracheal stenosis group showed significantly reduced mitochondrial oxygen consumption at state 3 with reduced respiratory control ratio. Caspase activities (caspase-9 and caspase-3) were increased in the tracheal stenosis group than in the sham group. Subacute hypoxia induced by the tracheal stenosis model causes cardiac remodeling and mitochondrial dysfunction through apoptotic pathways. This study suggests that management of hypoxia could prevent cellular apoptosis and cardiac dysfunction. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

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J. Cardiovasc. Dev. Dis., Volume 12, Issue 10 (October 2025) – 33 articles

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