Journal of Cardiovascular Development and Disease

17 pages, 13437 KB

Open AccessArticle

Virtual Stenting Based on Fractional Flow Reserve Derived from Computed Tomography in Predicting Post-Percutaneous Coronary Intervention Functional Outcomes: A Retrospective Cohort Study

by Han Zhao, Yanlong Ren, Jiang Li, Mingduo Zhang, Lijun Zhang, Rongliang Chen, Jia Liu, Zhengzheng Yan and Xiantao Song

J. Cardiovasc. Dev. Dis. 2025, 12(9), 373; https://doi.org/10.3390/jcdd12090373 - 22 Sep 2025

Viewed by 128

Abstract

With the advancement of fractional flow reserve (FFR) derived from computed tomography (FFR_CT), virtual stenting technology has gradually developed. This study investigated the performance of virtual stenting based on FFR_CT in predicting post-percutaneous coronary intervention (PCI) FFR. Data from 75 [...] Read more.

With the advancement of fractional flow reserve (FFR) derived from computed tomography (FFR_CT), virtual stenting technology has gradually developed. This study investigated the performance of virtual stenting based on FFR_CT in predicting post-percutaneous coronary intervention (PCI) FFR. Data from 75 patients (78 blood vessels) was collected retrospectively. We randomly allocated the participants to discovery (n = 26) and validation (n = 52) cohorts. The FFR_CT was calculated using pre-PCI coronary computed tomography angiography images. Virtual stent implantation was simulated using blinded and non-blinded virtual stenting methods to obtain post-virtual stenting FFR_CT. The median FFR_CT before PCI and invasive FFR were 0.70 (0.60–0.77) and 0.69 (0.63–0.76), respectively. The median FFR_CT were 0.91 (0.86–0.95) and 0.91 (0.87–0.94) in the blinded and non-blinded groups, respectively; the invasive post-PCI FFR was 0.90 (0.88–0.93). The difference between the FFR_CT after using the blinded/non-blinded method and the invasive post-PCI FFR were 0.010 (95% limits of agreement: −0.064 to 0.084) and 0.009 (−0.050 to 0.068) in the discovery cohort and −0.005 (−0.075 to 0.064) and −0.0002 (−0.064 to 0.064) in the validation cohort, respectively. Virtual stenting technology based on FFR_CT can effectively predict functional outcomes after PCI and could be a reliable tool for PCI procedural planning. Full article

► Show Figures

Figure 1

16 pages, 1481 KB

Open AccessArticle

Extracellular Volume Fraction Analysis on Cardiac Computed Tomography Is Useful for Predicting the Prognosis of Hypertrophic Cardiomyopathy

by Shuhei Aoki, Hiroyuki Takaoka, Tomonori Kanaeda, Kazunari Asada, Joji Ota, Yoshitada Noguchi, Moe Matsumoto, Yusei Nishikawa, Katsuya Suzuki, Satomi Yashima, Makiko Kinoshita, Noriko Suzuki-Eguchi, Haruka Sasaki, Kohei Takahashi, Yoshihito Ozawa, Yosuke Inaba and Yoshio Kobayashi

J. Cardiovasc. Dev. Dis. 2025, 12(9), 372; https://doi.org/10.3390/jcdd12090372 - 19 Sep 2025

Viewed by 237

Abstract

Extracellular volume fraction (ECV) analysis on computed tomography (CT) is now available. The purpose of this study was to assess the usefulness of CT-derived ECV analysis for predicting outcomes in patients with hypertrophic cardiomyopathy (HCM). One hundred and one HCM patients (67 males, [...] Read more.

Extracellular volume fraction (ECV) analysis on computed tomography (CT) is now available. The purpose of this study was to assess the usefulness of CT-derived ECV analysis for predicting outcomes in patients with hypertrophic cardiomyopathy (HCM). One hundred and one HCM patients (67 males, 66 ± 11 years old) who received cardiac CT between January 2009 and December 2021 were included. We measured left ventricular (LV) ECV (LV-ECV) on CT and investigated the relationship between LV-ECV and the major adverse cardiac events (MACE) after CT. Fifteen patients (15%) experienced MACE. The patients with MACE had a significantly higher LV-ECV, left atrial diameter, LV end-systolic diameter, and lower LVEF than those without MACE. The proportion of dilated phase HCM was significantly higher in the patients with MACE than those without MACE. LV-ECV and LVEF were significant predictors of MACE based on the multivariate analysis by Cox proportional hazards model. The optimal threshold of LV-ECV to predict MACE was 37.6% based on the receiver operating characteristic analysis. The patients with LV-ECV ≥ 37.6% (30 patients) experienced significantly higher MACE than those with LV-ECV < 37.6% (p < 0.001). CT-derived ECV analysis suggested potential usefulness for predicting MACE in patients with HCM. Full article

(This article belongs to the Special Issue Clinical Applications of Cardiovascular Computed Tomography (CT))

► Show Figures

Graphical abstract

17 pages, 15283 KB

Open AccessArticle

ADAMTS5 Orchestrates Cell Lineage Specific Patterning and Extracellular Matrix Organization During Semilunar Valve Development

by Loren E. Dupuis, Joshua J. Mifflin, Amy L. Marston, Jeremy P. Laxner and Christine B. Kern

J. Cardiovasc. Dev. Dis. 2025, 12(9), 371; https://doi.org/10.3390/jcdd12090371 - 19 Sep 2025

Viewed by 161

Abstract

Aortic valve (AV) disease affects about 5% of the aging population, with AV replacement as the only treatment option. Histopathology indicates that accumulation of extracellular matrix (ECM) proteoglycans correlates with dysfunctional AVs. Proteoglycan content is controlled by ECM proteolytic cleavage, with the cleaved [...] Read more.

Aortic valve (AV) disease affects about 5% of the aging population, with AV replacement as the only treatment option. Histopathology indicates that accumulation of extracellular matrix (ECM) proteoglycans correlates with dysfunctional AVs. Proteoglycan content is controlled by ECM proteolytic cleavage, with the cleaved and intact forms of the proteoglycan Versican (VCAN) occupying different cell lineage-specific regions throughout AV development. To test the hypothesis that VCAN cleavage is required for lineage specific cell behaviors and ECM stratification, the cardiac neural crest (CNC) lineage was traced in mice with global inactivation of the proteoglycan protease Adamts5. By mid-gestation, Adamts5^−/− mice exhibited disorganized CNC patterning with excess VCAN and enlarged semilunar valve (SLV) morphology. Use of the Adamts5 floxed mice indicated that Adamts5 was required in the endothelial cells and their mesenchymal derivatives (EndoMT lineage) to prevent VCAN accumulation, initiate ECM stratification, and promote normal SLV morphology. These data suggest that the ECM remodeling event of VCAN cleavage may orchestrate cell lineage distinct behaviors and interactions to control proteoglycan levels throughout AV development and to prevent disease. Understanding mechanisms that regulate VCAN content may lead to the discovery of effective pharmacological targets for the treatment of AV disease. Full article

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

► Show Figures

Figure 1

21 pages, 2386 KB

Open AccessArticle

Differences in the Early In Vitro Development of Preimplantation Human IVF Embryos Which Go on to Develop Congenital Heart Disease

by Sophie Markham, Alison Campbell, Sue Montgomery and Iain M. Dykes

J. Cardiovasc. Dev. Dis. 2025, 12(9), 370; https://doi.org/10.3390/jcdd12090370 - 19 Sep 2025

Viewed by 307

Abstract

There is a clinical need for improved antenatal diagnosis of congenital heart disease (CHD). Increasing numbers of children are born to parents undergoing fertility treatment. We asked whether time-lapse imaging of in vitro preimplantation development provides diagnostic information. We performed a retrospective multicentre [...] Read more.

There is a clinical need for improved antenatal diagnosis of congenital heart disease (CHD). Increasing numbers of children are born to parents undergoing fertility treatment. We asked whether time-lapse imaging of in vitro preimplantation development provides diagnostic information. We performed a retrospective multicentre analysis of morphokinetic data from patients undergoing fertility treatment. A total of 96/18,799 CHD cases were identified (rate: 0.51%). Thirty-two were included in the analysis and stratified into three cohorts: complex CHD (n = 7), mild CHD (n = 11) and murmur only (n = 14). Comparison to a large unmatched control group (n = 352) revealed no differences in time of preimplantation developmental events but suggested an increase in cleavage synchronicity during the third cell cycle of mild CHD embryos. Pairwise comparison to matched controls revealed a delay in mild CHD embryos relative to controls in reaching the morphokinetic timepoints fading of pronuclei, 2-cell stage and 4-cell stage together with a possible increase in duration of blastulation in complex CHD. Our data raises the possibility that screening of preimplantation embryos at fertility clinics could reduce the rate of CHD. However, these results are preliminary, and further work is required to confirm the findings in a larger study. Full article

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

► Show Figures

Figure 1

13 pages, 737 KB

Open AccessArticle

Impaired Left Atrial Strain as an Early Marker of Cardiac Involvement in Type 2 Diabetes Mellitus: A Cross-Sectional Study

by Laura-Cătălina Benchea, Larisa Anghel, Nicoleta Dubei, Răzvan-Liviu Zanfirescu, Gavril-Silviu Bîrgoan, Radu Andy Sascău and Cristian Stătescu

J. Cardiovasc. Dev. Dis. 2025, 12(9), 369; https://doi.org/10.3390/jcdd12090369 - 19 Sep 2025

Viewed by 218

Abstract

Background: Diabetic cardiomyopathy is a major contributor to cardiovascular morbidity, often progressing silently before overt heart failure. Left atrial (LA) strain, assessed via speckle-tracking echocardiography, could serve as an early indicator of subclinical myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM). [...] Read more.

Background: Diabetic cardiomyopathy is a major contributor to cardiovascular morbidity, often progressing silently before overt heart failure. Left atrial (LA) strain, assessed via speckle-tracking echocardiography, could serve as an early indicator of subclinical myocardial dysfunction in patients with type 2 diabetes mellitus (T2DM). Objectives: The objectives of this study were to evaluate LA strain parameters in patients with T2DM versus non-diabetic controls and investigate their association with glycemic control and diabetes duration. Methods: This cross-sectional study, designed according to STROBE reporting guidelines, included 47 participants (25 with T2DM and 22 controls) undergoing comprehensive echocardiographic and biochemical evaluation. LA reservoir (LASr), conduit (LAScd), and booster-pump (LASbp) strain values were measured. Associations with glycosylated hemoglobin (HbA1c) and diabetes duration were assessed via multivariate analysis. ROC curves were used to evaluate predictive performance. Results: Diabetic patients had significantly lower LASr (20.4 ± 7.25% vs. 26.7 ± 8.0%, p = 0.007), LAScd (−10.9 ± 5.4% vs. −15.6 ± 6.5%, p = 0.010), and LASbp (−9.9 ± 4.2% vs. −12.9 ± 5.0%, p = 0.034). LASr and LAScd remained independent predictors in multivariate models. ROC analysis showed good discrimination (AUC: LAScd = 0.78; LASr = 0.73). Conclusions: This study demonstrates that LASr and LAScd are independently associated with type 2 diabetes mellitus and can reliably identify subclinical atrial dysfunction before the onset of structural or symptomatic heart disease. Full article

(This article belongs to the Special Issue Clinical Burden of Comorbidities on Cardiovascular System and Beyond: 2nd Edition)

► Show Figures

Graphical abstract

19 pages, 264 KB

Open AccessArticle

Early and 3-Year Outcomes of Frozen Elephant Trunk Procedure with Evolving E-vita Hybrid Grafts: A Retrospective Single-Centre Cohort Study over 11 Years

by Isabelle Doll, Christoph Salewski, Luise Vöhringer, Michael Baumgaertner, Attila Nemeth, Christian Schlensak and Medhat Radwan

J. Cardiovasc. Dev. Dis. 2025, 12(9), 368; https://doi.org/10.3390/jcdd12090368 - 18 Sep 2025

Viewed by 231

Abstract

Background/Objectives: The frozen elephant trunk (FET) technique is a cornerstone procedure for complex thoracic aortic pathologies. This single-center retrospective study evaluates early and midterm outcomes of total arch replacement (TAR) using three generations of the E-vita Open hybrid prosthesis over 11 years. Methods: [...] Read more.

Background/Objectives: The frozen elephant trunk (FET) technique is a cornerstone procedure for complex thoracic aortic pathologies. This single-center retrospective study evaluates early and midterm outcomes of total arch replacement (TAR) using three generations of the E-vita Open hybrid prosthesis over 11 years. Methods: From January 2013 to June 2024, 51 patients underwent TAR with the FET technique using the E-vita Open prostheses. Exclusion criteria were isolated ascending or descending aortic replacement, partial arch replacement, TAR without FET, and use of other stent grafts. We analyzed outcomes including in-hospital mortality, survival, stroke, spinal cord injury, and renal complications across three prosthesis generations. Results: The cohort included 52.9% males, with a mean age of 61.5 ± 10.51 years. FET as reoperation was performed in 52.9% patients. In-hospital mortality was 7.8% and, unexpectedly, only occurred with the newest E-vita Open Neo (23.5%), despite this being the latest generation. Overall survival was 72.5% at one year, 60.8% at two years, and 54.9% at three years. Stroke occurred in 17.6% with marked variation by pathology: 0% in dissection, 31.6% in aneurysm, and 13.6% in combined disease. Spinal cord injury occurred in 7.8%. Re-operation was a significant risk factor for complications and was strongly associated with renal complications (85.7% of dialysis patients) but not mortality. Secondary endovascular procedures were required in 49% of patients. Conclusions: The FET technique with E-vita Open prostheses demonstrates acceptable outcomes in high-risk patients with complex aortic pathologies. While perioperative morbidity is significant, particularly in reoperative cases, it varies significantly by underlying pathology and prosthesis generation, with unexpected trends suggesting that technological advancement does not automatically translate into improved outcomes. Despite this, the procedure enables comprehensive management of extensive aortic disease through a staged approach. Full article

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

► Show Figures

Graphical abstract

26 pages, 854 KB

Open AccessReview

Sjogren’s Disease and Elevated Cardiovascular Risk: Mechanisms and Treatment

by Jennifer Behbodikhah, Billy Ding, Belin Jacob, Nuzhat Batool, Elise Belilos, Joshua De Leon, Steven E. Carsons and Allison B. Reiss

J. Cardiovasc. Dev. Dis. 2025, 12(9), 367; https://doi.org/10.3390/jcdd12090367 - 18 Sep 2025

Viewed by 332

Abstract

Autoimmune disorders are known to accelerate atherosclerosis, increasing the rate of cardiovascular disease. As the number one cause of morbidity and mortality in the general population, this risk is only enhanced in inflammatory conditions. Substantial evidence links increased cardiovascular disease to systemic lupus [...] Read more.

Autoimmune disorders are known to accelerate atherosclerosis, increasing the rate of cardiovascular disease. As the number one cause of morbidity and mortality in the general population, this risk is only enhanced in inflammatory conditions. Substantial evidence links increased cardiovascular disease to systemic lupus erythematosus and rheumatoid arthritis. However, Sjogren’s Disease (SjD) tends to follow a more indolent disease course, and its chronic inflammatory burden is often underrecognized. Pharmacologic agents are also limited and symptom management is often the mainstay of treatment. The majority of studies investigating cardiovascular disease in SjD show conflicting results. In this review, we shed some light on the association of SjD and cardiovascular disease. Furthermore, we also explore potential risk factors and mechanisms through which SjD may accelerate cardiovascular disease. We address the impact of standard CVD and SjD treatments on heart health and highlight clinically relevant tools for monitoring subclinical atherosclerosis in the SjD patient population. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

► Show Figures

Figure 1

8 pages, 591 KB

Open AccessBrief Report

Right Ventricular Phenotyping Can Lead to Pulmonary Vascular Therapy Response in Those with Pulmonary Hypertension with COPD: A Single-Center Cohort Study

by Oluwafeyijimi Salako and Abhishek Singh

J. Cardiovasc. Dev. Dis. 2025, 12(9), 366; https://doi.org/10.3390/jcdd12090366 - 18 Sep 2025

Viewed by 193

Abstract

Pulmonary hypertension (PH) with chronic obstructive pulmonary disease (COPD) is associated with poor survival with no approved therapies. We report on the response to inhaled treprostinil (iTRE) of a small retrospective cohort of PH-COPD patients with a baseline “PH-right ventricular (RV) phenotype”, defined [...] Read more.

Pulmonary hypertension (PH) with chronic obstructive pulmonary disease (COPD) is associated with poor survival with no approved therapies. We report on the response to inhaled treprostinil (iTRE) of a small retrospective cohort of PH-COPD patients with a baseline “PH-right ventricular (RV) phenotype”, defined by a RV-dependent circulatory limitation derived from a combination of echocardiographic and hemodynamic criteria. Patients were started on inhaled treprostinil with significant improvement in six-minute walk distance, NT-proBNP, and improved RV metrics by echocardiography. The preliminary findings of this cohort provide evidence for the importance of precision phenotyping of PH-COPD. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

► Show Figures

Graphical abstract

33 pages, 2564 KB

Open AccessReview

Between Air and Artery: A History of Cardiopulmonary Bypass and the Rise of Modern Cardiac Surgery

by Vasileios Leivaditis, Andreas Maniatopoulos, Francesk Mulita, Paraskevi Katsakiori, Nikolaos G. Baikoussis, Sofoklis Mitsos, Elias Liolis, Vasiliki Garantzioti, Konstantinos Tasios, Panagiotis Leventis, Nikolaos Kornaros, Andreas Antzoulas, Dimitrios Litsas, Levan Tchabashvili, Konstantinos Nikolakopoulos and Manfred Dahm

J. Cardiovasc. Dev. Dis. 2025, 12(9), 365; https://doi.org/10.3390/jcdd12090365 - 18 Sep 2025

Viewed by 368

Abstract

Cardiopulmonary bypass (CPB) is one of the most groundbreaking medical innovations in history, enabling safe and effective heart surgery by temporarily replacing the function of the heart and lungs. This review starts with ancient concepts of cardiopulmonary function and then traces the evolution [...] Read more.

Cardiopulmonary bypass (CPB) is one of the most groundbreaking medical innovations in history, enabling safe and effective heart surgery by temporarily replacing the function of the heart and lungs. This review starts with ancient concepts of cardiopulmonary function and then traces the evolution of CPB through important physiological and anatomical discoveries, culminating in the development of the modern heart–lung machine. In addition to examining the contributions of significant figures like Galen, Ibn al-Nafis, William Harvey, and John Gibbon, we also examine the ethical and technical challenges faced in the early days of open heart surgery. Modern developments are also discussed, such as miniature extracorporeal systems, off-pump surgical techniques, and the increasing importance of extracorporeal membrane oxygenation (ECMO) and extracorporeal life support (ECLS), while the evolving role of perfusionists in diverse cardiac teams and the variations in global access to CPB technology are also given special attention. We look at recent advancements in CPB, including customized methods, nanotechnology, artificial intelligence-guided perfusion, and organ-on-chip testing, emphasizing CPB’s enduring significance as a technological milestone and a living example of the cooperation of science, medicine, and human inventiveness because it bridges the gap between the past and the future. Full article

► Show Figures

Figure 1

12 pages, 783 KB

Open AccessArticle

Outcomes of Use of Inotropes at Waitlisting Through Heart Transplantation: The UNOS Experience

by Marco Gemelli, Ilias P. Doulamis, Thanakorn Rojanathagoon, Aspasia Tzani, Athanasios Rempakos, Polydoros Kampaktsis, Alvise Guariento, Ernesto Ruiz Dunque, Rabea Asleh, Paulino Alvarez, Vincenzo Tarzia, Gino Gerosa and Alexandros Briasoulis

J. Cardiovasc. Dev. Dis. 2025, 12(9), 364; https://doi.org/10.3390/jcdd12090364 - 17 Sep 2025

Viewed by 260

Abstract

Background: Despite its use in patients awaiting heart transplant (HT), the impact of continuous inotropic support on short-term complications and long-term transplant outcomes remains unclear. This study evaluated inotrope use at the time of HT on perioperative complications and post-transplant survival, comparing outcomes [...] Read more.

Background: Despite its use in patients awaiting heart transplant (HT), the impact of continuous inotropic support on short-term complications and long-term transplant outcomes remains unclear. This study evaluated inotrope use at the time of HT on perioperative complications and post-transplant survival, comparing outcomes at 30 days, 1 year, and 10 years with mechanical circulatory support (MCS) strategies including ECMO, IABP, and VADs. Methods: A retrospective analysis of the United Network for Organ sharing (UNOS) registry was performed, stratifying patients based on bridge strategy at the time of transplant: inotropes, ECMO, IABP, or VADs. Baseline characteristics, perioperative complications, and 30-day, 1-year, and 10-year post-transplant survival outcomes were analyzed across groups. Survival was assessed using Kaplan–Meier and Cox proportional hazards models. Results: Among the 11,801 heart transplant patients included, 9330 were on inotropes, 372 were on ECMO, 1072 received an IABP, and 1027 had VADs. Inotrope-bridged patients had significantly lower 30-day and 1-year mortality rates compared to the ECMO, IABP, and VAD groups. They also experienced reduced incidences of post-transplant dialysis and stroke. At 10 years, the inotrope group demonstrated superior long-term survival, with significantly lower mortality risk compared to ECMO (HR: 1.81; CI: 1.49–2.20, p < 0.001), IABP (HR: 1.19; CI: 1.06–1.32, p = 0.005), and VAD (HR: 1.18; CI: 1.10–1.27, p < 0.001). Conclusions: Continuous use of inotropes after waitlisting is associated with lower short, intermediate, and long-term mortality and does not lead to worse outcomes compared to ECMO, IABP, and VAD support. When mechanical support is not an option, inotropic therapy remains a viable and effective strategy. Full article

(This article belongs to the Section Acquired Cardiovascular Disease)

► Show Figures

Graphical abstract

17 pages, 3469 KB

Open AccessArticle

Association of Pan-Immune-Inflammation Value with All-Cause and Cardiovascular Mortality in Survivors of Myocardial Infarction: NHANES 2001–2018 Analysis

by Qingyi Liu, Wenling Yang, Ruiyu Zhang, Xiaopeng Guo and Yumiao Wei

J. Cardiovasc. Dev. Dis. 2025, 12(9), 363; https://doi.org/10.3390/jcdd12090363 - 17 Sep 2025

Viewed by 421

Abstract

Background: Inflammatory responses critically impact long-term outcomes in myocardial infarction (MI) survivors, yet few biomarkers comprehensively evaluate systemic immune-inflammatory status. This study assessed the prognostic utility of a novel marker—the pan-immune-inflammation value (PIV)—for predicting all-cause and cardiovascular mortality post-MI. Methods: Using the National [...] Read more.

Background: Inflammatory responses critically impact long-term outcomes in myocardial infarction (MI) survivors, yet few biomarkers comprehensively evaluate systemic immune-inflammatory status. This study assessed the prognostic utility of a novel marker—the pan-immune-inflammation value (PIV)—for predicting all-cause and cardiovascular mortality post-MI. Methods: Using the National Health and Nutrition Examination Survey data (2001–2018), 1559 MI survivors were included. PIV was calculated as (neutrophils × platelets × monocytes)/lymphocytes. Weighted Cox models assessed the association between log-transformed PIV (LnPIV) and mortality. Restricted cubic spline (RCS) models explored non-linear dose–response relationships, and predictive performance was evaluated via time-dependent ROC analysis. Results: Over a median 75-month follow-up, 675 deaths occurred. LnPIV showed significant non-linear associations with all-cause (p < 0.0001) and cardiovascular mortality (p = 0.0471). When LnPIV ≥ 5.59, each unit increase was associated with an 85% (HR = 1.85, 95% CI: 1.49–2.28) higher all-cause mortality risk; for cardiovascular mortality, the risk increased by 77% (HR = 1.77, 95% CI: 1.20–2.63) when LnPIV ≥ 5.68. Time-dependent ROC analysis confirmed strong prediction above these thresholds. Conclusion: PIV demonstrates threshold-dependent mortality risk stratification in MI patients, particularly effective in high-inflammatory subgroups, offering a potential tool for personalized risk stratification. Full article

► Show Figures

Figure 1

12 pages, 575 KB

Open AccessArticle

Clinical Outcomes After Immediate Coronary Angiography in Elderly Versus Younger Patients Suffering from Acute Coronary Syndrome

by Anja Radunovic, Ivan Ilic, Milica Matic, Miljana Ostojic, Dejan Kojic, Ana Golocevac, Nikola Lazarevic, Aleksandar Mandic, Milosav Tomovic and Petar Otasevic

J. Cardiovasc. Dev. Dis. 2025, 12(9), 362; https://doi.org/10.3390/jcdd12090362 - 17 Sep 2025

Viewed by 276

Abstract

(1) Aims: This study aimed to compare cardiovascular outcomes in patients older than 75 years with those of younger patients who underwent interventional treatment for acute coronary syndrome (ACS) at a tertiary university hospital. (2) Methods and Results: This was a retrospective, observational [...] Read more.

(1) Aims: This study aimed to compare cardiovascular outcomes in patients older than 75 years with those of younger patients who underwent interventional treatment for acute coronary syndrome (ACS) at a tertiary university hospital. (2) Methods and Results: This was a retrospective, observational study conducted between January 2016 and December 2021, including 1846 consecutive patients with ACS (older than 75 years n = 203, 11%; younger than 75 years n = 1643, 89%). After admission, patients underwent coronary angiography and subsequently received percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or medical therapy. The mean age in the older group (O75) was 80 ± 4 years versus 59 ± 9 years in the younger group (Y75) (p < 0.001). Older patients more frequently presented with multivessel coronary disease (O75: 114 [56%] vs. Y75: 727 [44%], p = 0.004), and the left anterior descending artery (LAD) was more often the culprit vessel (O75: 105 [52%] vs. Y75: 684 [41%]). Major adverse cardio-cerebral events (MACCEs) occurred more frequently in patients older than 75 years, mainly due to higher mortality (O75: 14 [6.9%] vs. Y75: 27 [1.6%], p < 0.001) and stroke (O75: 3 [1.5%] vs. Y75: 2 [0.1%], p < 0.001). Multivessel disease was the only factor independently associated with MACCEs (HR 1.417, 95% CI 1.058–1.898, p = 0.02). The incidence of significant bleeding (Bleeding Association Research Consortium (BARC) class ≥ 3) was similar between groups (Y75: 123/1643 [7.5%] vs. O75: 13/203 [6.5%], p = 0.587). (3) Conclusions: Patients older than 75 years have worse short- and long-term prognoses following ACS compared with younger patients. Special attention and a multidisciplinary, personalized approach are required to optimize outcomes in this population. Full article

► Show Figures

Graphical abstract

18 pages, 1192 KB

Open AccessReview

Active Endothelial Inactivation of Hyperpermeability: The Role of Nitric Oxide-Driven cAMP/Epac1 Signaling

by Mauricio A. Lillo, Pía C. Burboa and Walter N. Durán

J. Cardiovasc. Dev. Dis. 2025, 12(9), 361; https://doi.org/10.3390/jcdd12090361 - 17 Sep 2025

Viewed by 359

Abstract

Endothelial hyperpermeability is a hallmark of diverse inflammatory and vascular pathologies, including sepsis, acute respiratory distress syndrome (ARDS), ischemia–reperfusion injury, and atherosclerosis. Traditionally considered a passive return to baseline following stimulus withdrawal, barrier recovery is now recognized as an active, endothelial-driven process. Earlier [...] Read more.

Endothelial hyperpermeability is a hallmark of diverse inflammatory and vascular pathologies, including sepsis, acute respiratory distress syndrome (ARDS), ischemia–reperfusion injury, and atherosclerosis. Traditionally considered a passive return to baseline following stimulus withdrawal, barrier recovery is now recognized as an active, endothelial-driven process. Earlier work identified individual components of this restorative phase, such as cyclic adenosine monophosphate (cAMP)/exchange protein directly activated by cAMP 1 (Epac1) signaling, Rap1/Rac1 activation, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, and targeted cytoskeletal remodeling, as well as kinase pathways involving PKA, PKG, and Src. However, these were often regarded as discrete events lacking a unifying framework. Recent integrative analyses, combining mechanistic insights from multiple groups, reveal that nitric oxide (NO) generated early during hyperpermeability can initiate a delayed cAMP/Epac1 cascade. This axis coordinates Rap1/Rac1-mediated cortical actin polymerization, VASP-driven junctional anchoring, retro-translocation of endothelial nitric oxide synthase (eNOS) to caveolar domains, PP2A-dependent suppression of actomyosin tension, and Krüppel-like factor 2 (KLF2)-driven transcriptional programs that sustain endothelial quiescence. Together, these pathways form a temporally orchestrated, multi-tiered “inactivation” program capable of restoring barrier integrity even in the continued presence of inflammatory stimuli. This conceptual shift reframes NO from solely a barrier-disruptive mediator to the initiating trigger of a coordinated, pro-resolution mechanism. The unified framework integrates cytoskeletal dynamics, junctional reassembly, focal adhesion turnover, and redox/transcriptional control, providing multiple potential intervention points. Therapeutically, Epac1 activation, Rap1/Rac1 enhancement, RhoA/ROCK inhibition, PP2A activation, and KLF2 induction represent strategies to accelerate endothelial sealing in acute microvascular syndromes. Moreover, applying these mechanisms to arterial endothelium could limit low-density lipoprotein (LDL) entry and foam cell formation, offering a novel adjunctive approach for atherosclerosis prevention. In this review, we will discuss both the current understanding of endothelial hyperpermeability mechanisms and the emerging pathways of its active inactivation, integrating molecular, structural, and translational perspectives. Full article

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

► Show Figures

Figure 1

10 pages, 221 KB

Open AccessReview

Cannulation Strategies for Aortic Arch Surgery

by Ishtiaq Rahman, Jason Ali and Ravi De Silva

J. Cardiovasc. Dev. Dis. 2025, 12(9), 360; https://doi.org/10.3390/jcdd12090360 - 17 Sep 2025

Viewed by 255

Abstract

Aortic arch surgery remains associated with significant mortality and morbidity especially in the setting of acute type A aortic dissection. Adequate cerebral protection is essential, and several methods have been proposed to avoid neurological injury during aortic arch surgery. The most common techniques [...] Read more.

Aortic arch surgery remains associated with significant mortality and morbidity especially in the setting of acute type A aortic dissection. Adequate cerebral protection is essential, and several methods have been proposed to avoid neurological injury during aortic arch surgery. The most common techniques include selective antegrade perfusion of brachiocephalic arteries or an interval of deep hypothermic circulatory arrest. A range of cannulation strategies have been employed safely to provide adequate cerebral protection. Optimal cannulation selection is based on the consideration of air or particulate embolism risk; limitation in operative field visibility; end organ perfusion; and interactions with surgical maneuvers. Overall, no technique has been shown to fully mitigate the risk of neurological injury, rather each has utility in different scenarios. Innominate artery cannulation offers high flows on CPB and avoids additional incisions. Right axillary artery is rarely involved in aortic dissections, versatile for use in redo surgery, and altered blood flow patterns reduce embolic stroke rates. Left axillary artery can be utilized when both right axillary and femoral arteries are involved in a dissection process. Novel bi-axillary approach has additionally shown good results. Future multicenter, randomized trials should focus on establishing the relative benefits and risks of each cannulation approach with the aim of delineating the optimal cannulation strategy for different clinical situations to guide aortic surgeons, particularly in the emergency setting of aortic dissection. Full article

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

17 pages, 1386 KB

Open AccessReview

Drug-Coated Balloons Versus Drug-Eluting Stents for Large Vessel Coronary Artery Disease: A Meta-Analysis

by Jinghan Zeng, Yilu Liu, Tianlang Zhao, Jiansong Yuan, Weixian Yang and Man Wang

J. Cardiovasc. Dev. Dis. 2025, 12(9), 359; https://doi.org/10.3390/jcdd12090359 - 17 Sep 2025

Viewed by 334

Abstract

Objective: We aimed to conduct a meta-analysis of treatments for large vessel coronary artery disease between drug-coated balloons and drug-eluting stents. Method: We searched databases including PubMed, Web of Science, Cochrane, CNKI, and Wanfang, and selected randomized controlled trials (RCTs) or cohort studies [...] Read more.

Objective: We aimed to conduct a meta-analysis of treatments for large vessel coronary artery disease between drug-coated balloons and drug-eluting stents. Method: We searched databases including PubMed, Web of Science, Cochrane, CNKI, and Wanfang, and selected randomized controlled trials (RCTs) or cohort studies which compared drug-coated balloons (DCBs) with drug-eluting stents (DESs). The reference vessel diameter (RVD) should be greater than 2.75 mm. The results of 12 studies with a total of 2634 patients were included in this meta-analysis. Results: The results showed that the DCB group was not inferior to the DES group in terms of the incidence of target lesion revascularization (TLR). (RR = 1.25, 95% CI: [0.84, 1.85], p = 0.27, I² = 0%), and the incidence of bleeding events in the DCB group was lower than that in the DES group (RR = 0.30, 95% CI: [0.15, 0.59], p = 0.0004). The results also showed that the post-intervention minimal lumen diameter (MLD) in the DCB group was smaller than that in the DES group. (RR = −0.37, 95% CI: [−0.59, −0.16], p = 0.0007), but the follow-up MLD in the DCB group was not less than that in the DES group (RR = −0.03, 95% CI: [−0.14,−0.08], p = 0.61). Additionally the DCB group had less late lumen loss (LLL) compared with the DES group. (RR = −0.31, 95% CI: [−0.60, −0.02], p < 0.0001). Conclusion: This meta-analysis confirms that in the early and late stages after percutaneous coronary intervention (PCI), DCB is not inferior in efficacy and safety to DES for de novo large coronary lesions with RVD > 2.75 mm. Full article

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

► Show Figures

Figure 1

23 pages, 866 KB

Open AccessReview

Circulating Biomarkers in Failing Fontan Circulation: Current Evidence and Future Directions

by Cecilia Vecoli, Lamia Ait-Alì, Simona Storti and Ilenia Foffa

J. Cardiovasc. Dev. Dis. 2025, 12(9), 358; https://doi.org/10.3390/jcdd12090358 - 16 Sep 2025

Viewed by 223

Abstract

Patients with Fontan circulation are at lifelong risk for a range of complications involving multiple organ systems. As survival into adulthood increases, there is an urgent need to refine strategies for long-term follow-up and the early detection of Fontan-related sequelae. This narrative review [...] Read more.

Patients with Fontan circulation are at lifelong risk for a range of complications involving multiple organ systems. As survival into adulthood increases, there is an urgent need to refine strategies for long-term follow-up and the early detection of Fontan-related sequelae. This narrative review aims to provide a comprehensive summary of the current evidence regarding the use of circulating blood biomarkers as non-invasive tools for assessing and monitoring Fontan physiology. We critically analyzed available studies investigating serum biomarkers related to key pathological mechanisms associated with Fontan failure, encompassing not only cardiac dysfunction but also systemic inflammation, endothelial dysfunction, hepatic and renal impairment, and altered bone metabolism. Several biomarkers have shown promise in reflecting global systemic impairments as well as end-organ involvement in Fontan patients. However, current data are insufficient to support evidence-based clinical recommendations for standardized specific biomarkers, mainly due to the small sample sizes, heterogeneous patient populations, and limited longitudinal data in the available studies. Only a large-scale, prospective, multi-center, and multidisciplinary research will permit us to identify a panel of specific biomarkers of clinical utility in this population. Artificial intelligence (AI) and machine learning (ML) approaches could be applied to integrate all these heterogeneous datasets. Furthermore, “omics”-based studies, including proteomics, metabolomics, lipidomics, and microRNA profiling, hold great potential for uncovering novel biomarkers and pathophysiological pathways, ultimately paving the way for precision medicine in the management of Fontan patients. Full article

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

► Show Figures

Figure 1

9 pages, 1014 KB

Open AccessArticle

Renal Response to Levosimendan in Advanced Chronic Heart Failure Patients Listed for Heart Transplantation Predicts Early Postoperative Renal Function Course

by Gregor Zemljic, Gregor Poglajen, Sabina Frljak, Andraz Cerar, Renata Okrajsek, Miran Sebestjen, Ivan Knezevic and Bojan Vrtovec

J. Cardiovasc. Dev. Dis. 2025, 12(9), 357; https://doi.org/10.3390/jcdd12090357 - 16 Sep 2025

Viewed by 197

Abstract

Background: Beyond its established inotropic effects, levosimendan has been reported to enhance renal function in patients with chronic heart failure. In this study, we investigated whether changes in renal function following levosimendan administration in patients listed for heart transplantation were associated with early [...] Read more.

Background: Beyond its established inotropic effects, levosimendan has been reported to enhance renal function in patients with chronic heart failure. In this study, we investigated whether changes in renal function following levosimendan administration in patients listed for heart transplantation were associated with early post-transplant renal outcomes. Methods: We retrospectively analyzed data from 99 patients with advanced heart failure and renal insufficiency (eGFR < 90 mL/min/1.73 m²) who were listed for heart transplantation and received levosimendan therapy within 1 to 6 months prior to transplantation. Renal function was assessed immediately before and 24 h after levosimendan administration. A favorable renal response was defined as any increase in eGFR at 24 h. Post-transplant renal function was evaluated on postoperative days 1 and 7 using standard renal function parameters. Results: Favorable renal response to levosimendan prior to heart transplantation was present in 73 of 99 patients (74%, Group A), and 26 patients (26%) displayed no increase in eGFR (Group B). In the first week after heart transplantation, we found a significant improvement in renal function in Group A (ΔeGFR: +14 ± 3 mL/min/1.73 m², p < 0.001), and worsening of renal function in Group B (ΔeGFR: −4 ± 3 mL/min/1.73 m², p < 0.01). Favorable response to levosimendan prior to heart transplantation was an independent correlate of improved renal function after heart transplantation (p = 0.01). Conclusion: In patients awaiting heart transplantation, improvement in renal function after levosimendan therapy was associated with better early post-transplant renal outcomes. Levosimendan response may thus help identify reversible renal dysfunction and serve as a simple tool for transplant evaluation. Full article

(This article belongs to the Special Issue 10th Anniversary of JCDD—Modern Diagnostic and Therapeutic Strategies in Advanced Heart Failure and Heart Transplantation)

► Show Figures

Graphical abstract

18 pages, 1272 KB

Open AccessArticle

Challenging the Paradigm: Long-Term Outcomes in Dialysis-Dependent Patients Undergoing CABG

by Ezin Deniz, Tonita Brunkhorst, Florian Helms, Jasmin Hanke, Ali Merzah, Sadeq Ali-Hasan Al-Saegh, Alina Zubarevich, Felix Fleissner, Issam Ismail, Gregor Warnecke, Günes Dogan, Jan Dieter Schmitto, Bastian Schmack, Alexander Weymann, Arjang Ruhparwar and Aron-Frederik Popov

J. Cardiovasc. Dev. Dis. 2025, 12(9), 356; https://doi.org/10.3390/jcdd12090356 - 16 Sep 2025

Viewed by 190

Abstract

Dialysis-dependent (DD) patients undergoing coronary artery bypass grafting (CABG) remain a particularly high-risk population with impaired outcomes despite advances in surgical techniques. In this single-center, retrospective cohort study, 97 DD patients (2010–2015) were compared with 488 non-dialysis-dependent (NDD) controls. The primary endpoint was [...] Read more.

Dialysis-dependent (DD) patients undergoing coronary artery bypass grafting (CABG) remain a particularly high-risk population with impaired outcomes despite advances in surgical techniques. In this single-center, retrospective cohort study, 97 DD patients (2010–2015) were compared with 488 non-dialysis-dependent (NDD) controls. The primary endpoint was all-cause mortality; the secondary endpoint was major adverse cardiac and cerebrovascular events (MACCE). Median follow-up was 5.4 ± 2.1 years. DD patients had significantly higher perioperative mortality (10.3% vs. 3.1%, p = 0.002) and markedly reduced overall survival (OS) (40.8% vs. 82.1% at 5 years). Dialysis dependence conferred an 8.4-fold increase in mortality risk and a 2.6-fold increase in MACCE risk. Increasing age, diabetes, and critical preoperative state were independent predictors of an adverse long-term outcome. While arterial grafting improved survival in NDD patients, no comparable benefit was observed in DD patients, possibly due to vascular calcification, limited conduit availability, and reduced graft patency. EuroSCORE II adequately predicted perioperative mortality (AUC = 0.78 in DD patients) but demonstrated poor discriminatory power for long-term survival (AUC = 0.67 at 5 years). These findings highlight the urgent need for dialysis-specific risk models. Despite poor long-term prognosis, DD patients with low-risk EuroSCORE II profiles experienced the most relative benefit from CABG. Full article

(This article belongs to the Special Issue Contemporary Controversies and Evolving Paradigms in Cardiovascular Surgery)

► Show Figures

Graphical abstract

15 pages, 1035 KB

Open AccessArticle

The Effects of Inclisiran on the Subclinical Prothrombotic and Platelet Activation Markers in Patients at High Cardiovascular Risk

by Mateusz Maligłówka, Adrianna Dec, Łukasz Bułdak and Bogusław Okopień

J. Cardiovasc. Dev. Dis. 2025, 12(9), 355; https://doi.org/10.3390/jcdd12090355 - 16 Sep 2025

Viewed by 216

Abstract

Atherosclerosis as a multifactorial disease remains the first cause of death worldwide. Current oral lipid-lowering drugs (especially statins) reduce low-density lipoprotein cholesterol (LDLC) levels in the blood, but their clinical efficacy seems to be partially attributed to pleiotropic effects on different pathophysiologic factors [...] Read more.

Atherosclerosis as a multifactorial disease remains the first cause of death worldwide. Current oral lipid-lowering drugs (especially statins) reduce low-density lipoprotein cholesterol (LDLC) levels in the blood, but their clinical efficacy seems to be partially attributed to pleiotropic effects on different pathophysiologic factors of atherosclerosis extending beyond lipid-lowering properties such as anti-inflammatory, antithrombotic and antioxidative features. Novel drugs that interfere with proprotein convertase subtilisin/kexin type 9 (PCSK9) axis of LDL-C receptors (LDLRs) degradation, from the group of monoclonal antibodies (e.g., alirocumab, evolocumab) or small interfering RNA (siRNA), e.g., inclisiran, are effective in reducing LDLC as well. However, data depicting their antithrombotic and antiplatelet activity are scarce, whereas prothrombotic properties of PCSK9 are widely described. Thus, we performed a study to assess the effects of inclisiran on subclinical prothrombotic [fibrinogen, coagulation factor VIII (FVIII), plasminogen activator inhibitor-1 (PAI-1)] and platelet activation markers (platelet factor-4 (PF-4), soluble p-selectin (sCD62P)). Ten patients at high cardiovascular risk with concomitant heterozygous familial hypercholesterolemia (HeFH)—study group 1, and fourteen patients at very high cardiovascular risk without concomitant HeFH—study group 2, were recruited for the study. Lipid profile, subclinical prothrombotic and platelet activation markers were assessed at the beginning and after 3 months of therapy with inclisiran. During therapy, statistically significant reductions in both study groups were seen in total cholesterol levels (study group 1: from 287.6 ± 94.2 to 215.2 ± 89.1 (mg/dL), p = 0.022; study group 2: from 211.7 ± 52.7 to 147.6 ± 55.4 (mg/dL), p < 0.001) and LDL-c (study group 1: from 180.8 ± 73.3 to 114.7 ± 71.5 (mg/dL), p = 0.031; study group 2: from 129.6 ± 46.8 to 63.4 ± 43.6 (mg/dL), p < 0.001). Lipid profile changes were associated with significant decrease in the concentration of FVIII in both groups (study group 1: from 33.3 ± 22 to 22 ± 14.5 (ng/mL), p = 0.006; study group 2: from 37 ±16.9 to 29.3 ±16.4 (ng/mL), p = 0.002) and fibrinogen, but only in study group 2 (from 51.4 (33.2–72.7) to 42.6 (31.3–57.2) (µg/mL), p = 0.035). Among platelet activation markers, a significant decrease in PF-4 in study group 2 was noted (from 286 (272–295.5) to 272 (268–281.5) (ng/mL), p = 0.047). However, there were no statistically significant changes in PAI-1 and sCD62P throughout the study. In our study, inclisiran appeared to be an effective lipid-lowering drug in patients at high cardiovascular risk. Moreover, it was shown that beyond lipid-lowering properties, the drug may also partially affect thrombogenesis and platelet activation. Full article

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

► Show Figures

Figure 1

10 pages, 220 KB

Open AccessArticle

Safety and Effectiveness of Sodium-Glucose Co-Transporter 2 Inhibitors in Active Cancer Patients with Heart Failure: Results of the Observational TOSCA Trial

by Maria Laura Canale, Iacopo Fabiani, Maria Grazia Delle Donne, Michela Chianca, Valentina Barletta, Eugenia Capati, Monica Solinas, Lara Frediani, Elio Venturini, Giuseppe Arena, Giulio Zucchelli, Emilio Maria Pasanisi, Domenico Amoroso, Giacomo Allegrini, Raffaele De Caterina, Michele Emdin and Andrea Camerini

J. Cardiovasc. Dev. Dis. 2025, 12(9), 354; https://doi.org/10.3390/jcdd12090354 - 13 Sep 2025

Viewed by 240

Abstract

Cancer patients have not been included in landmark trials of SGLT2is in heart failure, so data on safety and effectiveness are lacking. TOSCA is a multi-center observational trial including patients with active cancer receiving SGLT2is for HF treatment. The primary endpoint was safety, [...] Read more.

Cancer patients have not been included in landmark trials of SGLT2is in heart failure, so data on safety and effectiveness are lacking. TOSCA is a multi-center observational trial including patients with active cancer receiving SGLT2is for HF treatment. The primary endpoint was safety, and the secondary endpoint was effectiveness. Exploratory endpoints included drug–drug interactions, treatment of cancer therapy-related cardiac dysfunction (CTRCD), and changes in NT-proBNP. One-hundred and twenty-nine patients (median age 72 [range 44–92] yrs) were enrolled who had been receiving SGLT2i for a median of 3 (range 3–25) months. Prevalent etiology was drug-induced HF with HFrEF as the most frequent clinical presentation. The incidence of urinary tract infections was 1.8%, with no cases of genital infections, hypoglycemia, diabetic ketoacidosis, acute renal injury, thrombosis, or bone fractures. The mean overall EF increased (40.3% vs. 47.4%), and NYHA class improved in 19% of cases. Rates of unplanned cardiology visits (0.9%), use of i.v. diuretics (0.9%), coronary angiography (4.5%), emergency access for HF (1.8%), and new HF episodes (3.6%) were extremely low. In 11 cases (8.5%), the initiation of SGLT2i enabled continuation of anticancer therapy that would have otherwise been delayed or suspended due to HF decompensation. SGLT2is appeared effective in 34 cases of CTRCD. No drug–drug interactions were reported. SGLT2is confirmed their safety and effectiveness in active cancer patients with HF, with a potential cardioprotective effect. No new safety warnings were recorded. Full article

9 pages, 692 KB

Open AccessArticle

Cine MRI-Derived Radiomics for the Detection of Functional Tricuspid Regurgitation in Pulmonary Hypertension: A Proof-of-Concept Study

by Kai Lin, Roberto Sarnari, Daniel Z. Gordon, Michael Markl and James C. Carr

J. Cardiovasc. Dev. Dis. 2025, 12(9), 353; https://doi.org/10.3390/jcdd12090353 - 13 Sep 2025

Viewed by 281

Abstract

(1) Objective: The objective was to test the hypothesis that cine MRI-derived radiomic features can detect functional tricuspid regurgitation (FTR) in the context of pulmonary hypertension (PH). (2) Materials and methods: In total, 53 PH patients were retrospectively enrolled. Thirty-three patients had echocardiography-defined [...] Read more.

(1) Objective: The objective was to test the hypothesis that cine MRI-derived radiomic features can detect functional tricuspid regurgitation (FTR) in the context of pulmonary hypertension (PH). (2) Materials and methods: In total, 53 PH patients were retrospectively enrolled. Thirty-three patients had echocardiography-defined mild-to-severe FTR, while the other twenty patients had no or trivial regurgitation. For all participants, 93 radiomic features were extracted from four-chamber cine MRI using a fixed-size region of interest (ROI) located in the right atrium (RA), 0.5–1 cm above the tricuspid valve. The levels of radiomic features were averaged over the ventricular systole and compared between patients with and without FTR using t tests. In patients with FTR, radiomic features were related to hemodynamic parameters in the right heart using the Pearson correlation coefficient (r). (3) Results: There were no significant differences in demographic information, right heart catheterization (RHC) results, and most cine MRI-derived cardiac function indices between the two subject groups. Eight of ninety-three radiomic features were significantly different between PH patients with and without FTR. Radiomic features can be used to discriminate two subject groups (AUC = 0.77). In patients with FTR, multiple radiomic features are related to the pressure in the RA, right ventricle (RV), and pressure difference between RA and RV (r: 0.4 to 0.55), p values < 0.05. (4) Conclusion: Cine MRI-derived radiomic features of the cardiac blood pool differ between PH patients with and without FTR. Cine MRI shows promise as a method for assessing FTR in the context of complex cardiovascular diseases (CVDs). Full article

(This article belongs to the Section Imaging)

► Show Figures

Figure 1

18 pages, 1618 KB

Open AccessArticle

Cardiovascular Effects of Long-Term Treatment with Enhanced External Counterpulsation in Patients with Ischemic Heart Failure: Randomized, Placebo-Controlled, Open-Label Clinical Trial

by Alexey S. Lishuta, Olga A. Slepova, Nadezhda A. Nikolaeva and Yuri N. Belenkov

J. Cardiovasc. Dev. Dis. 2025, 12(9), 352; https://doi.org/10.3390/jcdd12090352 - 13 Sep 2025

Viewed by 442

Abstract

(1) Background. Although treatment with enhanced external counterpulsation (EECP) in patients with ischemic chronic heart failure (CHF) is pathophysiologically justified, its long-term vascular effects remain insufficiently defined. We aimed to study the vascular effects of long-term complex treatment (36 months) including EECP in [...] Read more.

(1) Background. Although treatment with enhanced external counterpulsation (EECP) in patients with ischemic chronic heart failure (CHF) is pathophysiologically justified, its long-term vascular effects remain insufficiently defined. We aimed to study the vascular effects of long-term complex treatment (36 months) including EECP in patients with ischemic CHF, and to examine the relationship between these effects and clinical outcomes. (2) Methods. A total amount of 120 patients with ischemic CHF were randomized to receive one course of EECP per year (35 h; Group 1), two courses of EECP per year (70 h; Group 2), or one course of placebo-counterpulsation per year (35 h; Group 0;). For a period of 36 months, all patients underwent annual assessments including transthoracic echocardiography, nailfold videocapillaroscopy, finger photoplethysmography, applanation tonometry, exercise tolerance testing, and clinical outcome monitoring. (3) Results. Compared to the placebo group, long-term EECP treatment in patients with ischemic CHF, was accompanied by a significantly greater increase in exercise tolerance (∆23.5–45.0% vs. 7.0%; p < 0.001) and improvements in left ventricular ejection fraction (∆9.9–19.6% vs. 5.6%; p < 0.001) and myocardial stress (decrease in NT-proBNP level ∆−80.4–−82.4% vs. −75.8%; p < 0.001), as well as both functional and structural vascular parameters (p < 0.001). The effect size depended on the annual number of EECP courses. The highest event-free survival was found in Group 2. At 36 months, improvement of vascular parameters emerged as stronger predictors of reduced cardiovascular event risk compared to the 12-month. (4) Conclusions. Long-term EECP treatment of patients with ischemic CHF improves both functional and structural vascular parameters, with an increasing role of their improvement in reducing the risk of cardiovascular events after 36 months. Full article

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

► Show Figures

Graphical abstract

21 pages, 1391 KB

Open AccessArticle

Global Longitudinal Strain as a Sensitive Marker of Left Ventricular Dysfunction in Pediatric Dilated Cardiomyopathy: A Case–Control Study

by Iolanda Muntean, Beatrix-Jullia Hack and Asmaa Carla Hagau

J. Cardiovasc. Dev. Dis. 2025, 12(9), 351; https://doi.org/10.3390/jcdd12090351 - 12 Sep 2025

Viewed by 341

Abstract

Pediatric dilated cardiomyopathy (DCM) is a rare but important cause of heart failure (HF) and a major indication for cardiac transplantation. Early detection of subclinical myocardial dysfunction is essential for risk stratification and management. This study aimed to evaluate left ventricular (LV) systolic [...] Read more.

Pediatric dilated cardiomyopathy (DCM) is a rare but important cause of heart failure (HF) and a major indication for cardiac transplantation. Early detection of subclinical myocardial dysfunction is essential for risk stratification and management. This study aimed to evaluate left ventricular (LV) systolic function in children with DCM using conventional echocardiographic parameters and speckle-tracking echocardiography (STE) and to explore the relationship between deformation indices, clinical severity and biomarkers. Methods: We conducted a case–control study including 29 children diagnosed with DCM and 27 healthy controls matched by age and sex. All participants underwent clinical evaluation, NT-proBNP measurement, and transthoracic echocardiography. LV systolic function was assessed using conventional echocardiographic parameters, while STE was used to measure LV global longitudinal strain (GLS) and strain rate (SR) from all apical views. Results: GLS and SR were significantly reduced in the DCM group across all apical views (Global GLS: −11.13 ± 6.79% vs. −19.98 ± 3.25%, Global SR: −0.74 ± 0.39 s⁻¹ vs. −1.12 ± 0.16 s⁻¹; p < 0.01). GLS strongly correlated with functional indices (LV ejection fraction, shortening fraction, S′ lateral wave), LV end-diastolic diameter Z-score and NT-proBNP (p < 0.05), but not with MAPSE. In the primary model, GLS was associated with NYHA/Ross III–IV (OR 1.54 per 1% increase; 95% CI 1.14–2.07; p = 0.005); adding systolic blood pressure (p = 0.798) or heart rate (p = 0.973) did not materially change the GLS estimate (Δ ≤ 2%). In separate collinearity-avoiding models, LVEF (OR 1.12 per 1% decrease; 95% CI 1.03–1.22; p = 0.009), LVSF (OR 1.19 per 1% decrease; 95% CI 1.04–1.36; p = 0.011), and NT-proBNP (≈OR 1.11 per 100 units; p = 0.013) were also associated with advanced class. ROC analysis showed excellent discrimination for NT-proBNP (AUC 0.948) and GLS (AUC 0.906), and good–excellent performance for LVEF (AUC 0.869) and LVSF (AUC 0.875). Conclusions: Speckle-tracking derived parameters such as GLS and SR are sensitive and clinically relevant markers of LV dysfunction in pediatric DCM. Global longitudinal strain demonstrated a strong association with both clinical and biochemical markers of disease severity, after accounting for heart rate and blood pressure, supporting its integration into routine evaluation and risk stratification in pediatric DCM. Full article

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

► Show Figures

Figure 1

18 pages, 902 KB

Open AccessReview

Cardiac Computed Tomography for the Assessment of Myocardial Bridging: A Scoping Review of the Emerging Role of Artificial Intelligence and Machine Learning

by Amro Abu Suleiman, Federico Russo, Luigi Della Valle, Davide Ausiello, Ewelina Bukowska-Olech, Vincenzo Iannibelli, M. Omar Al Droubi, Gabriella Sannino, Marco Bernardi and Luigi Spadafora

J. Cardiovasc. Dev. Dis. 2025, 12(9), 350; https://doi.org/10.3390/jcdd12090350 - 12 Sep 2025

Viewed by 304

Abstract

(1) Background: Myocardial bridging (MB) is a congenital coronary anomaly with potential clinical significance. Artificial intelligence (AI) applied to cardiac computed tomography angiography (CCTA), particularly through CT-derived fractional flow reserve (CT-FFR), offers a novel, non-invasive approach for assessing MB. (2) Methods: We conducted [...] Read more.

(1) Background: Myocardial bridging (MB) is a congenital coronary anomaly with potential clinical significance. Artificial intelligence (AI) applied to cardiac computed tomography angiography (CCTA), particularly through CT-derived fractional flow reserve (CT-FFR), offers a novel, non-invasive approach for assessing MB. (2) Methods: We conducted a systematic review of the literature focusing on studies investigating AI-enhanced CCTA in the evaluation of MB. (3) Results: Ten studies were included. AI-based models, including radiomics, demonstrated moderate to high accuracy in predicting proximal plaque formation, and motion correction algorithms improved image quality and diagnostic confidence. Other findings were limited by the types of studies included and conflicting findings across studies. (4) Conclusions: AI-enhanced CCTA shows promise for the non-invasive functional assessment of MB and its risk stratification. Further prospective studies and validation are required to establish standardized protocols and confirm clinical utility. Full article

(This article belongs to the Special Issue Advances in Cardiovascular Imaging—Computed Tomography (CT) Focus Issue)

► Show Figures

Figure 1

22 pages, 3367 KB

Open AccessReview

Multimodal Imaging from Fetal to Adult Life: A Comprehensive Approach to Hypoplastic Left Heart Syndrome (HLHS)

by Sara Moscatelli, Jolanda Sabatino, Isabella Leo, Nunzia Borrelli, Martina Avesani, Giovanni Di Salvo, Claudia Montanaro, Valeria Pergola, Raffaella Motta, Jessica Ielapi, Assunta Di Costanzo, Rosalba De Sarro, Giulia Guglielmi, Irene Cattapan, Gabriella Gaudieri, Leonie Luedke and Marco Alfonso Perrone

J. Cardiovasc. Dev. Dis. 2025, 12(9), 349; https://doi.org/10.3390/jcdd12090349 - 11 Sep 2025

Viewed by 325

Abstract

Hypoplastic Left Heart Syndrome (HLHS) accounts for 2–3% of congenital heart diseases (CHDs). HLHS is characterized by reduced systemic blood flow due to hypoplastic left ventricle (LV) and underdeveloped left-sided cardiac structures. Without a series of staged interventional treatments, HLHS is often fatal, [...] Read more.

Hypoplastic Left Heart Syndrome (HLHS) accounts for 2–3% of congenital heart diseases (CHDs). HLHS is characterized by reduced systemic blood flow due to hypoplastic left ventricle (LV) and underdeveloped left-sided cardiac structures. Without a series of staged interventional treatments, HLHS is often fatal, typically within the first hours or days of life. This manuscript aims to provide a comprehensive overview of the role of echocardiography, cardiovascular magnetic resonance (CMR), and cardiac computed tomography angiography (CCTA) in the optimal management of patients with HLHS. Specifically, it explores the contributions of various non-invasive imaging modalities to the diagnosis, planning of staged palliative interventions, interstage monitoring, and long-term follow-up of HLHS. Furthermore, the advantages and limitations of each imaging technique will be highlighted to aid in clinical decision-making; however, it is important to note that, at present, no universal guidelines exist, and imaging strategies remain largely dependent on individual centre expertise and protocols. Full article

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

► Show Figures

Figure 1

13 pages, 3619 KB

Open AccessArticle

Topography of the Papillary Muscles in the Mitral Valve Complex and Their Relevance for Mitral Valve Function

by Alina-Jutta Van Laethem, Jens Figiel, Andreas H. Mahnken, Rabia Ramzan, Marc Irqsusi, Sebastian Vogt and Ardawan J. Rastan

J. Cardiovasc. Dev. Dis. 2025, 12(9), 348; https://doi.org/10.3390/jcdd12090348 - 11 Sep 2025

Viewed by 271

Abstract

Background: The mitral valve apparatus is a complex system that requires sufficient function of all involved structures. Previous studies have demonstrated that ventricular remodeling can cause displacement of subannular structures, including the papillary muscles, which in turn promotes the development of mitral regurgitation. [...] Read more.

Background: The mitral valve apparatus is a complex system that requires sufficient function of all involved structures. Previous studies have demonstrated that ventricular remodeling can cause displacement of subannular structures, including the papillary muscles, which in turn promotes the development of mitral regurgitation. Furthermore, in such cases, annuloplasty alone is often insufficient to restore optimal valve function. Instead, additional reconstruction of the subannular apparatus is associated with improved clinical outcomes. Our study aimed to analyze the topography of the papillary muscles in the mitral valve complex and their relevance for mitral valve function. Methods: In 148 patients who underwent both cardiac computed tomography (CT) and echocardiography, the position of the papillary muscles within the left ventricle was assessed. CT scans were evaluated in end-diastolic four-chamber view, two-chamber view, and short-axis view. CT analysis involved determining the position of the papillary muscles based on a modified left ventricular segmentation scheme, which subdivided the original segments into “a” and “b” subsegments in a counterclockwise manner. Furthermore, the midventricular diameter, ventricular length, as well as the angle between the papillary muscle (PM) and the left ventricular wall, were measured. Comorbidities were assessed. The presence of mitral regurgitation (MR) and ejection fraction was determined based on echocardiographic data. Echocardiography was conducted either as part of initial cardiological assessments or during follow-up examinations. For detailed statistical analysis, the patients were divided into the following groups: control group, MR-only group, coronary heart disease (CHD)-only group, and combined CHD and MR subgroup. Results: Mitral regurgitation was significantly correlated with age (p < 0.001) and hypertension (r = 0.1900, p = 0.0208), and in the MR-only subgroup, additionally with atrial fibrillation (r = 0.2426, p = 0.0462). The length (p < 0.001) and internal diameter (p < 0.001) of the left ventricle were significantly larger in men than in women. Different positions of the papillary muscles were identified. Segment 7a was significantly correlated with MR in the combined CHD and MR subgroup. In normal-sized ventricles, patients with MR and papillary muscle in 12a (p = 0.0095) or 10a (p = 0.0460) showed a significantly larger angle than patients without MR (overall dataset). Conclusions: Assessment of papillary muscle position is essential in diagnosing mitral regurgitation and should guide the consideration of subannular repair during surgical treatment. Full article

(This article belongs to the Special Issue State of the Art in Mitral Valve Disease)

► Show Figures

Graphical abstract

14 pages, 660 KB

Open AccessArticle

Prognostic Utility of HEFESTOS Score and Complementary Lung Ultrasound for Heart Failure Decompensation in Primary Care Outpatients: A Prospective Cohort Study

by Marcos Haro-Montoya, Rosa Caballol-Angelats, José Fernández-Sáez, Maylin Montelongo-Sol, Laura Conangla-Ferrin, Victoria Cendrós-Cámara, Jose María Verdú-Rotellar and Josep Lluís Clua-Espuny

J. Cardiovasc. Dev. Dis. 2025, 12(9), 347; https://doi.org/10.3390/jcdd12090347 - 11 Sep 2025

Viewed by 227

Abstract

Heart failure (HF) is a major contributor to morbidity, mortality, and healthcare costs, particularly among older adults. Effective outpatient risk stratification remains a clinical challenge, especially following hospital discharge or episodes of acute decompensation. Although both lung ultrasound (LUS) and the HEFESTOS score [...] Read more.

Heart failure (HF) is a major contributor to morbidity, mortality, and healthcare costs, particularly among older adults. Effective outpatient risk stratification remains a clinical challenge, especially following hospital discharge or episodes of acute decompensation. Although both lung ultrasound (LUS) and the HEFESTOS score have shown individual prognostic value, their combined use in primary care settings has not been extensively explored. This prospective cohort study included 107 patients with confirmed HF followed at a primary care center in southern Catalonia. At baseline, all patients underwent LUS and HEFESTOS assessment. The primary outcome was HF decompensation, defined as worsening symptoms requiring medical attention, emergency care, hospitalization, or death. Over a mean follow-up of 72 days, 25 patients (23.3%) experienced decompensation. In multivariate analysis, only the HEFESTOS score was independently associated with decompensation. LUS and HEFESTOS showed moderate agreement (Kappa = 0.456), and LUS demonstrated moderate discriminative capacity (AUC = 0.677) with high sensitivity (81.7%) and positive predictive value (81.7%). These findings support the routine use of the HEFESTOS score in primary care and suggest that LUS may serve as a complementary tool, particularly for identifying subclinical pulmonary congestion. Their combined use could enhance outpatient risk stratification and guide individualized follow-up strategies in HF management. Full article

(This article belongs to the Section Imaging)

► Show Figures

Figure 1

16 pages, 1867 KB

Open AccessSystematic Review

Flow Diverting Stents for the Treatment of Complex Visceral and Renal Aneurysms—A Systematic Review

by Marcello Andrea Tipaldi, Elisa Zaccaria, Nicolò Ubaldi, Edoardo Massaro, Gianluigi Orgera, Tommaso Rossi, Aleksejs Zolovkins, Miltiadis Krokidis, Pasqualino Sirignano and Michele Rossi

J. Cardiovasc. Dev. Dis. 2025, 12(9), 346; https://doi.org/10.3390/jcdd12090346 - 11 Sep 2025

Viewed by 335

Abstract

Flow-diverting stents (FDS) are sophisticated endovascular devices that aim to modulate blood flow and promote aneurysm thrombosis while maintaining branch vessel patency. Initially designed and developed for the treatment of intracranial aneurysms, these devices have since been applied to the peripheral circulation. However, [...] Read more.

Flow-diverting stents (FDS) are sophisticated endovascular devices that aim to modulate blood flow and promote aneurysm thrombosis while maintaining branch vessel patency. Initially designed and developed for the treatment of intracranial aneurysms, these devices have since been applied to the peripheral circulation. However, they are still used sporadically, largely due to a lack of the scientific evidence supporting its use in visceral aneurysms. This review article aims to provide an overview of the current data on the clinical outcomes from the use of FDS in the treatment of complex visceral and renal aneurysms or pseudoaneurysms and to assess the added value of these devices. Full article

(This article belongs to the Special Issue Diagnosis and Treatment of Splanchnic and Peripheral Atherosclerotic Disease)

► Show Figures

Figure 1

30 pages, 1759 KB

Open AccessSystematic Review

AI Applied to Cardiac Magnetic Resonance for Precision Medicine in Coronary Artery Disease: A Systematic Review

by Cristina Jiménez-Jara, Rodrigo Salas, Rienzi Díaz-Navarro, Steren Chabert, Marcelo E. Andia, Julián Vega, Jesús Urbina, Sergio Uribe, Tetsuro Sekine, Francesca Raimondi and Julio Sotelo

J. Cardiovasc. Dev. Dis. 2025, 12(9), 345; https://doi.org/10.3390/jcdd12090345 - 9 Sep 2025

Cited by 1 | Viewed by 670

Abstract

Cardiac magnetic resonance (CMR) imaging has become a key tool in evaluating myocardial injury secondary to coronary artery disease (CAD), providing detailed assessments of cardiac morphology, function, and tissue composition. The integration of artificial intelligence (AI), including machine learning and deep learning techniques, [...] Read more.

Cardiac magnetic resonance (CMR) imaging has become a key tool in evaluating myocardial injury secondary to coronary artery disease (CAD), providing detailed assessments of cardiac morphology, function, and tissue composition. The integration of artificial intelligence (AI), including machine learning and deep learning techniques, has enhanced the diagnostic capabilities of CMR by automating segmentation, improving image interpretation, and accelerating clinical workflows. Radiomics, through the extraction of quantitative imaging features, complements AI by revealing sub-visual patterns relevant to disease characterization. This systematic review analyzed AI applications in CMR for CAD. A structured search was conducted in MEDLINE, Web of Science, and Scopus up to 17 March 2025, following PRISMA guidelines and quality-assessed with the CLAIM checklist. A total of 106 studies were included: 46 on classification, 19 using radiomics, and 41 on segmentation. AI models were used to classify CAD vs. controls, predict major adverse cardiovascular events (MACE), arrhythmias, and post-infarction remodeling. Radiomics enabled differentiation of acute vs. chronic infarction and prediction of microvascular obstruction, sometimes from non-contrast CMR. Segmentation achieved high performance for myocardium (DSC up to 0.95), but scar and edema delineation were more challenging. Reported performance was moderate-to-high across tasks (classification AUC = 0.66–1.00; segmentation DSC = 0.43–0.97; radiomics AUC = 0.57–0.99). Despite promising results, limitations included small or overlapping datasets. In conclusion, AI and radiomics offer substantial potential to support diagnosis and prognosis of CAD through advanced CMR image analysis. 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)

► Show Figures

Graphical abstract

26 pages, 1566 KB

Open AccessReview

Personalized Treatment of Patients with Coronary Artery Disease: The Value and Limitations of Predictive Models

by Antonio Greco and Davide Capodanno

J. Cardiovasc. Dev. Dis. 2025, 12(9), 344; https://doi.org/10.3390/jcdd12090344 - 8 Sep 2025

Viewed by 585

Abstract

Risk prediction models are increasingly used in the management of coronary artery disease (CAD), with applications ranging from diagnostic stratification to prognostic assessment and therapeutic guidance. In the context of CAD and percutaneous coronary intervention, clinical decision-making often relies on risk scores to [...] Read more.

Risk prediction models are increasingly used in the management of coronary artery disease (CAD), with applications ranging from diagnostic stratification to prognostic assessment and therapeutic guidance. In the context of CAD and percutaneous coronary intervention, clinical decision-making often relies on risk scores to estimate the likelihood of ischemic and bleeding events and to tailor antithrombotic strategies accordingly. Traditional scores are derived from clinical, anatomical, procedural, and laboratory variables, and their performance is evaluated based on discrimination and calibration metrics. While many established models are simple, interpretable, and externally validated, their predictive ability is often moderate and may be limited by outdated derivation cohorts, overfitting, or lack of generalizability. Recent advances have introduced artificial intelligence and machine learning models that can process large, high-dimensional datasets and identify patterns not apparent through conventional methods, with the aim to incorporate complex data; however, they are not exempt from limitations and struggle with integration into clinical practice. Notably, ethical issues, such as equity in model application, over-stratification, and real-world implementation, are of critical importance. The ideal predictive model should be accurate, generalizable, and clinically actionable. This review aims at providing an overview of the main predictive models used in the field of CAD and to discuss methodological challenges, with a focus on strengths, limitations and areas of applicability of predictive models. Full article

(This article belongs to the Special Issue Leaders in Cardiovascular Research: A Special Issue Dedicated to Professor Patrick Serruys)

► Show Figures

Figure 1

Journal Menu

Journal Browser

J. Cardiovasc. Dev. Dis., Volume 12, Issue 9 (September 2025) – 53 articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI