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21 pages, 1832 KB  
Review
A Review of the Therapeutic Efficacy and Safety of Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes in Preclinical Models of Subacute and Chronic Myocardial Infarction
by Kristen Callender and Godfrey Smith
J. Cardiovasc. Dev. Dis. 2026, 13(1), 42; https://doi.org/10.3390/jcdd13010042 (registering DOI) - 12 Jan 2026
Abstract
For the past decade, cell-based therapies have been the focus of research to investigate their potential to treat ischemic heart disease. The translation to human clinical studies depends on the demonstration of therapeutic efficacy and safety, particularly when transplanted in the subacute and [...] Read more.
For the past decade, cell-based therapies have been the focus of research to investigate their potential to treat ischemic heart disease. The translation to human clinical studies depends on the demonstration of therapeutic efficacy and safety, particularly when transplanted in the subacute and chronic post-MI phase. A number of studies were identified that reported the effect of hiPSC-CMs on cardiac outcomes when transplanted at least 7 days post-myocardial infarction. The mean sample size of the published studies was 30 (±17) animals with a mean follow-up duration of 51 (±37) days. hiPSC-CM transplantation enhanced systolic function through augmented myocardial contractility, decreased infarct size, attenuated ventricular remodeling, and enhanced angiogenesis in the infarct and border zones in both small and large animal models. This effect was enhanced by co-transplantation with cells of vascular or adipose origin and is associated with high expression of VEGF in most studies. Despite this effect, transplanted hiPSC-CMs were structurally immature with limited survival at the endpoint. Epicardial delivery was associated with better efficacy outcomes and lower rates of arrhythmia. No study reported teratoma formation or immune rejection. From the current literature, there appears to be no consensus on the extent to which hiPSC-CMs improved systolic function, nor the degree to which this arises directly from integration of the new myocardium or from a paracrine-mediated mechanism. The nature of this paracrine mechanism and ways to improve the maturity and survival of implanted cardiomyocytes are issues that have yet to be resolved. In summary, while therapeutic benefit from cell therapy is clear, further research is required to establish whether the key mechanisms require a cellular component. Full article
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25 pages, 12897 KB  
Review
Echocardiographic Assessment of Left Ventricular Diastolic Function in Adults Between Old and New: Progress and Challenges
by Luca Dell’Angela and Gian Luigi Nicolosi
Diagnostics 2026, 16(2), 235; https://doi.org/10.3390/diagnostics16020235 - 11 Jan 2026
Abstract
Echocardiographic left ventricular (LV) diastolic function assessment represents one of the mainstays for routine, comprehensive transthoracic echocardiography in adults. Estimation of LV filling pressures is an integral part of LV diastolic function evaluation. Additionally, LV diastolic function assessment is crucial for the study [...] Read more.
Echocardiographic left ventricular (LV) diastolic function assessment represents one of the mainstays for routine, comprehensive transthoracic echocardiography in adults. Estimation of LV filling pressures is an integral part of LV diastolic function evaluation. Additionally, LV diastolic function assessment is crucial for the study of subjects with potential heart failure with preserved LV ejection fraction. Beyond the “old” LV diastolic function parameters, to date, mostly strain-based (and generally artificial intelligence-assisted) additional “new” echocardiographic techniques have emerged to optimize the study of LV diastole. The purpose of the present narrative critical review is to report and discuss the optimal echocardiographic assessment of LV diastolic function in light of the recent literature, with the aim of trying to outline the gaps in the current evidence in view of future developments. To date, multiparametric diastolic evaluation and grading seem advisable, using as many “old and new” measurements as possible—associated with their adequate selection related to the patients’ comorbidities—aiming to cumulatively increase the advantages of diastolic parameters and possibly minimize their limitations. Taking into account the considerable number of echocardiographic measurements to perform and describe, at present, the timing of optimal echocardiography performance and reporting should be adequately adapted to the current technical needs and real-life routine clinical practice. Importantly, contextual clinical and (if needed) multimodality assessment should be included in the diagnostic workflow, in order to enable a more individualized approach. Full article
(This article belongs to the Special Issue Recent Advances in Echocardiography, 2nd Edition)
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6 pages, 3587 KB  
Case Report
Autosomal Recessive Atrial Dilated Cardiomyopathy Due to NPPA Mutation in a Young Patient
by Massimiliano Marini, Manuela Iseppi, Silvia Quintarelli, Francesca Tedoldi, Flavia Ravelli, Roberto Bonmassari and Eloisa Arbustini
J. Cardiovasc. Dev. Dis. 2026, 13(1), 37; https://doi.org/10.3390/jcdd13010037 - 9 Jan 2026
Viewed by 70
Abstract
Background: Atrial dilated cardiomyopathy (ADCM) related to homozygous Natriuretic Peptide Precursor A (NPPA) pathogenic variants is an exceptionally rare inherited atrial cardiomyopathy characterized by progressive atrial enlargement, supraventricular arrhythmias, and eventual atrial standstill. Case summary: We report the case of a [...] Read more.
Background: Atrial dilated cardiomyopathy (ADCM) related to homozygous Natriuretic Peptide Precursor A (NPPA) pathogenic variants is an exceptionally rare inherited atrial cardiomyopathy characterized by progressive atrial enlargement, supraventricular arrhythmias, and eventual atrial standstill. Case summary: We report the case of a 9-year-old girl identified through population genetic screening as a homozygous carrier of the NPPA c.449G>A (p.Arg150Gln) variant who subsequently developed symptomatic paroxysmal atrial fibrillation (AF) at the age of 18. Although baseline cardiac investigations were normal, her current evaluation shows biatrial enlargement with preserved ventricular function. She underwent radiofrequency pulmonary vein isolation; however, recurrent symptomatic AF persists, requiring ongoing antiarrhythmic therapy and long-term oral anticoagulation (CHA2DS2-VA: 0; HAS-BLED: 0). Notably, patients with NPPA-related ADCM have a markedly increased thromboembolic risk due to progressive atrial mechanical failure, and anticoagulation should therefore be considered irrespective of conventional clinical risk scores. Discussion and conclusions: This case highlights the importance of genetic testing in young patients with atrial fibrillation and no underlying structural heart disease. The early identification of NPPA-related atrial dilated cardiomyopathy may aid in risk stratification and guide rhythm and anticoagulation management. Expanding genetic screening in select individuals with isolated atrial fibrillation may facilitate earlier diagnosis in this exceptionally rare condition. Full article
(This article belongs to the Special Issue Modern Approach to Complex Arrhythmias, 2nd Edition)
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27 pages, 1334 KB  
Review
Insights into Cardiomyocyte Regeneration from Screening and Transcriptomics Approaches
by Daniela T. Fuller, Aaron H. Wasserman and Ruya Liu
Int. J. Mol. Sci. 2026, 27(2), 601; https://doi.org/10.3390/ijms27020601 - 7 Jan 2026
Viewed by 150
Abstract
Human adult cardiomyocytes (CMs) have limited regenerative capacity, posing a significant challenge in restoring cardiac function following substantial CM loss due to an acute ischemic event or chronic hemodynamic overload. Nearly half of patients show no improvement in left ventricular ejection fraction during [...] Read more.
Human adult cardiomyocytes (CMs) have limited regenerative capacity, posing a significant challenge in restoring cardiac function following substantial CM loss due to an acute ischemic event or chronic hemodynamic overload. Nearly half of patients show no improvement in left ventricular ejection fraction during recovery from acute myocardial infarction. At baseline, both humans and mice exhibit low but continuous cell turnover originating from the existing CMs. Moreover, myocardial infarction can induce endogenous CM cell cycling. Consequently, research has focused on identifying drivers of CM rejuvenation and proliferation from pre-existing CMs. High-throughput screening has facilitated the discovery of novel pro-proliferative targets through small molecules, microRNAs, and pathway-specific interventions. More recently, omics-based approaches such as single-nucleus RNA sequencing and spatial transcriptomics have expanded our understanding of cardiac cellular heterogeneity. The big-data strategies provide critical insights into why only a subset of CMs re-enter the cell cycle while most remain quiescent. In this review, we compare several high-throughput screening strategies used to identify novel targets for CM proliferation. We also summarize the benefits and limitations of various screening models—including zebrafish embryos, rodent CMs, human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), and cardiac organoids—underscoring the importance of integrating multiple systems to uncover new regenerative mechanisms. Further work is needed to identify translatable and safe targets capable of inducing functional CM expansion in clinical settings. By integrating high-throughput screening findings with insights into CM heterogeneity, this review provides a comprehensive framework for advancing cardiac regeneration research and guiding future therapeutic development. Full article
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14 pages, 938 KB  
Review
Tricuspid Transcatheter Edge-to-Edge Repair at a Crossroads: Prognosis-Shaping Intervention or High-Tech Palliation?
by Andreas Mitsis, Marios Ioannides, Christis Rotos, Nikolaos P. E. Kadoglou and Christos Eftychiou
J. Clin. Med. 2026, 15(2), 443; https://doi.org/10.3390/jcm15020443 - 6 Jan 2026
Viewed by 145
Abstract
Tricuspid regurgitation (TR) has historically been undertreated despite its strong association with morbidity and mortality. Surgical correction of isolated TR is not routinely performed and has shown limited survival benefit, leaving a substantial unmet need for minimally invasive therapies. Transcatheter edge-to-edge repair (T-TEER) [...] Read more.
Tricuspid regurgitation (TR) has historically been undertreated despite its strong association with morbidity and mortality. Surgical correction of isolated TR is not routinely performed and has shown limited survival benefit, leaving a substantial unmet need for minimally invasive therapies. Transcatheter edge-to-edge repair (T-TEER) has emerged as a promising therapeutic option for patients with symptomatic severe or greater (≥severe) TR who are unsuitable for surgery. Recent randomized trials, including the TRILUMINATE Pivotal and the Tri-FR study, and real-world registries consistently demonstrate significant improvements in TR severity, functional status, and quality of life following T-TEER. Although benefits in hard clinical endpoints such as mortality or heart failure hospitalizations remain less conclusive, growing evidence suggests potential prognostic advantage in selected patients, particularly those with preserved or mid-range right ventricular function. Anatomical suitability, RV performance, and optimized patient selection are crucial determinants of success. As ongoing large-scale trials continue to evaluate long-term outcomes, T-TEER currently occupies a therapeutic space between palliative intervention and disease-modifying therapy, providing substantial symptom relief with the potential for broader clinical benefit. This review summarizes current evidence, patient selection strategies, and perspectives on the evolving role of T-TEER in the management of severe TR. Full article
(This article belongs to the Special Issue Advances in Structural Heart Diseases)
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13 pages, 1597 KB  
Article
Right Ventricular Functional Improvement After Lung Transplantation and Adjunctive Pulmonary Rehabilitation: An Echocardiographic Analysis
by Meltem Altınsoy, Deniz Çelik, Fadime Bozduman Habip, Pınar Ergün, Hasret Gizem Kurt, Sertan Bulut, Hüsnü Baykal and Yusuf Taha Güllü
J. Clin. Med. 2026, 15(2), 437; https://doi.org/10.3390/jcm15020437 - 6 Jan 2026
Viewed by 95
Abstract
Background: Right ventricular (RV) dysfunction is common in advanced lung disease due to chronic pressure overload and altered pulmonary vascular mechanics. Lung transplantation (LTx) reduces RV afterload, and pulmonary rehabilitation (PR) may further enhance functional recovery. However, the combined effects of LTx and [...] Read more.
Background: Right ventricular (RV) dysfunction is common in advanced lung disease due to chronic pressure overload and altered pulmonary vascular mechanics. Lung transplantation (LTx) reduces RV afterload, and pulmonary rehabilitation (PR) may further enhance functional recovery. However, the combined effects of LTx and structured PR on RV myocardial deformation—particularly using speckle-tracking echocardiography (STE)—remain insufficiently characterized. Methods: This single-arm pre–post study included 20 bilateral lung transplant recipients who completed an 8-week, twice-weekly supervised outpatient PR program. Echocardiographic evaluation—including 2D measurements, M-mode, tissue Doppler imaging (TDI), and STE-derived strain parameters—was performed immediately post-discharge (baseline) and after PR. RV global longitudinal strain (RVGLS) and RV free-wall longitudinal strain (RVFWS) served as primary functional outcomes. Results: Improvements were observed in RV myocardial deformation after PR. RVGLS improved from a median of 15.52% to 16.64% (p = 0.004), and RVFWS increased from 15.82% to 17.10% (p = 0.001). RV mid-cavity diameter decreased significantly (p = 0.042), reflecting favorably altered RV geometry. Conventional parameters—including TAPSE, S′ velocity, RVEDA, and FAC—showed no statistically significant changes. These findings indicate that STE parameters are more sensitive than traditional indices for detecting early RV remodeling in the post-transplant period. Conclusions: Lung transplantation combined with a structured PR program was associated with early improvements in RV deformation indices measurable by STE, even when traditional echocardiographic indices remained within normal limits. STE may therefore serve as a sensitive tool for monitoring subclinical RV recovery after LTx and for assessing the additive benefits of PR. Full article
(This article belongs to the Section Respiratory Medicine)
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13 pages, 805 KB  
Article
Short- and Middle-Term Nephroprotective and Cardioprotective Effects of Pentoxifylline in Patients with Diabetic Nephropathy: A Randomized Controlled Trial
by Oliva Mejía-Rodríguez, Marcela Ávila-Díaz, Carmen Prado-Uribe, María Eugenia Galván-Plata, Helios Vega Gómez, Cleto Álvarez-Aguilar, Miguel Angel Cuevas-Budhart and Ramón Paniagua
Med. Sci. 2026, 14(1), 26; https://doi.org/10.3390/medsci14010026 - 6 Jan 2026
Viewed by 122
Abstract
Background/Objectives. Pentoxifylline (PTF) is an effective treatment to delay the progress of Diabetic Nephropathy; it also has beneficial effects on heart failure, two closely related clinical conditions. However, the simultaneous Nephroprotective and Cardioprotective effects of PTF have not been appropriately analyzed. The [...] Read more.
Background/Objectives. Pentoxifylline (PTF) is an effective treatment to delay the progress of Diabetic Nephropathy; it also has beneficial effects on heart failure, two closely related clinical conditions. However, the simultaneous Nephroprotective and Cardioprotective effects of PTF have not been appropriately analyzed. The objective of this study was to analyze if both effects occur together in Diabetic patients. Material and Methods. A Randomized Controlled Trial was performed to compare Placebo (P-G) vs. PTF (400 mg/8 h) (PTF-G) in patients with CKD stages III–IV (KDIGO) due to Diabetic Nephropathy. Creatinine-Cystatin C-based Estimated Glomerular Filtration Rate (eGFRCysCCr) and Microalbuminuria were evaluated at baseline, six, and twelve months. Echocardiographic assessment of heart morphology and function was performed. Results. Ninety-three patients were available for the final analysis, 52 in the PTF group and 41 in the P group. There were no differences in clinical and biochemical parameters between groups at baseline. At 6 months, microalbuminuria changed 27.96 ± 43.06 in P-G and −30.27 ± 41.48 mg/24 h in PTF-G (p < 0.001), eGFRCysCCr changed −1.55 ± 7.10 in P-G and 1.40 ± 7.28 mL/min/1.73 m2 in PTF-G (p = 0.083), and left ventricular mass index (LVMI) changed 10.86 ± 16.40 in P-G and −2.71 ± 19.52 g/m2 in PTF-G (p = 0.001). At 12 months, microalbuminuria changed 24.10 ± 43.28 in P-G and −43.18 ± 52.13 mg/24 h in PTF-G (p < 0.001), eGFRCysCCr changed −6.55 ± 10.18 in P-G and 0.98 ± 8.17 mL/min/1.73 m2 in PTF-G (p = 0.008), and LVMI changed 20.79 ± 20.06 in P-G and −0.82 ± 25.95 g/m2 in PTF-G (p = 0.028). No significant adverse events occurred in any group. Conclusions. Pentoxifylline is a safe and effective treatment with combined Nephroprotective and Cardioprotective effects in advanced diabetic nephropathy. Full article
(This article belongs to the Section Nephrology and Urology)
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17 pages, 297 KB  
Article
Ejection Fraction-Related Differences in Left Ventricular and Atrial Strain Indices Among Pediatric Fontan Circulation with Systemic Left Ventricle Morphology
by Carmen Corina Șuteu, Amalia Fagarasan, Nicola Suteu, Andreea Cerghit-Paler, Liliana Gozar, Cristina Oana Mărginean, Maria Oana Săsăran and Mihaela Iancu
Diagnostics 2026, 16(1), 171; https://doi.org/10.3390/diagnostics16010171 - 5 Jan 2026
Viewed by 154
Abstract
Background: Ventricular function assessments in Fontan patients remain challenging. Ejection fraction (EF) lacks sensitivity for early dysfunction, and the roles of strain and advanced imaging in systemic left ventricle (LV) physiology are not fully defined. We aimed to compare (i) LV and [...] Read more.
Background: Ventricular function assessments in Fontan patients remain challenging. Ejection fraction (EF) lacks sensitivity for early dysfunction, and the roles of strain and advanced imaging in systemic left ventricle (LV) physiology are not fully defined. We aimed to compare (i) LV and atrial strain indices between pediatric Fontan patients with preserved EF (P-LVEF) versus reduced EF (R-LVEF) and (ii) echocardiographic global longitudinal strain, segmental longitudinal strain indices, and conventional 2D and 3D echocardiographic parameters through cardiac morphology. Methods: Pediatric patients with Fontan circulation and systemic LV morphology underwent clinical, hemodynamic, and multimodality echocardiographic evaluation, including 2D/3D parameters, global and segmental LV strain, and left atrial strain. Outcomes were analyzed according to EF status and congenital morphology. Significant results from multiple comparisons were followed by post hoc analysis, where appropriate. Results: Patients with a reduced EF exhibited a worse clinical status, a higher pulmonary vascular resistance index, and greater systemic congestion compared with those with a preserved EF. Conventional 2D indices showed no significant differences between the two studied groups except for LV end-systolic volume (ESV) (p = 0.0315) and LV end-systolic longitudinal diameter (ESL) (p = 0.0024), which showed higher values in the R-LVEF group. Although the relative frequency of impaired deformation was higher in Fontan patients with an unbalanced atrioventricular canal compared with the Fontan patients with a tricuspid atresia + pulmonary stenosis + ventricular septal defect, the difference did not reach statistical significance (p = 0.1365). Most segmental longitudinal strain values were not significantly different across patients with different cardiac morphology, except for the basal anterior segment and apical inferoseptal segment (p < 0.05). Conclusions: In pediatric Fontan patients with systemic LV morphology, a reduced EF was associated with a worse clinical and hemodynamic status. Conventional echocardiographic indices showed a limited ability to differentiate between the compared groups. Although no statistically significant differences were detected between pediatric Fontan patients with preserved EF and reduced EF, LV and atrial strain indices provided complementary information on ventricular–atrial interactions and myocardial deformation. These findings are exploratory and warrant confirmation in larger, prospective studies. Full article
(This article belongs to the Special Issue Advances in Pediatric Cardiology: Diagnosis and Management)
10 pages, 1778 KB  
Case Report
NF1 with Multiple Cardiac Structural Abnormalities Leading to Cerebral Infarction
by Jingwei Ye, Yiyi Jiang, Hanmin Wang and Dan Wang
Diagnostics 2026, 16(1), 163; https://doi.org/10.3390/diagnostics16010163 - 4 Jan 2026
Viewed by 209
Abstract
Background/Objectives: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder driven by mutations in the NF1 gene, whose pathogenesis centers on the loss of neurofibromin function and subsequent hyperactivation of the RAS/MAPK pathway. Notably, to the best of our knowledge and following [...] Read more.
Background/Objectives: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder driven by mutations in the NF1 gene, whose pathogenesis centers on the loss of neurofibromin function and subsequent hyperactivation of the RAS/MAPK pathway. Notably, to the best of our knowledge and following a systematic literature search conducted by our research team, no cases of NF1 complicated by severe cardiac structural abnormalities that ultimately lead to cerebral infarction have been reported to date. Thus, it is of paramount importance to avoid missed diagnosis by performing comprehensive cardiac-related examinations in patients with NF1. Case Presentation: A 20-year-old male patient diagnosed with NF1 presented with right-sided limb weakness and was initially identified with cerebral infarction. To clarify the underlying etiology, a comprehensive clinical evaluation was performed, including cardiac imaging assessments (to characterize cardiac structural changes) and whole-exome sequencing (to identify the presence of procoagulant gene mutations). Comprehensive evaluation revealed a spectrum of cardiac structural abnormalities in the patient: aortic valve prolapse with severe regurgitation, non-infective vegetations on the aortic valve leaflets, mild-to-moderate mitral regurgitation, left ventricular hypertrophy and dilation, and left atrial dilation. Whole-exome sequencing detected exclusively a pathogenic variant in the NF1 gene, with no other pathogenic/likely pathogenic variants or thrombophilia-associated polymorphisms being found. Laboratory investigations ruled out infectious etiologies, supporting the notion that NF1-mediated cardiac structural and developmental anomalies are the primary driver of cardiac vegetation formation, given the absence of other identified contributing factors; embolization of one such vegetation ultimately led to both splenic and cerebral infarction. Conclusions: This case emphasizes the necessity of implementing early and proactive cardiac evaluations in patients with NF1. Additionally, for NF1 individuals—particularly those presenting with suggestive vascular or cardiac symptoms—a comprehensive multifactorial assessment of thrombotic risk is critical. Collectively, maintaining clinical vigilance for cardiac abnormalities in NF1 patients and avoiding diagnostic oversight is essential to reduce life-threatening risks. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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13 pages, 788 KB  
Review
The Incremental Role of Stress Echocardiography in Valvular Heart Disease: A Narrative Review
by Adriana Correra, Alfredo Mauriello, Carmen Del Giudice, Celeste Fonderico, Matilde Di Peppo, Vincenzo Russo, Antonello D’Andrea, Giovanni Esposito and Natale Daniele Brunetti
Diagnostics 2026, 16(1), 148; https://doi.org/10.3390/diagnostics16010148 - 2 Jan 2026
Viewed by 282
Abstract
Background/Objectives: The diagnosis and risk stratification of valvular heart disease have traditionally relied on resting echocardiography. However, in a significant portion of patients, resting findings do not fully reflect the hemodynamic severity of the condition, particularly in asymptomatic individuals with severe valvular disease [...] Read more.
Background/Objectives: The diagnosis and risk stratification of valvular heart disease have traditionally relied on resting echocardiography. However, in a significant portion of patients, resting findings do not fully reflect the hemodynamic severity of the condition, particularly in asymptomatic individuals with severe valvular disease or those with nonspecific symptoms. In this context, stress echocardiography emerges as a vital imaging modality, providing a dynamic assessment of valvular, ventricular, and pulmonary function under hemodynamic load (from physical exercise or pharmacological agents). Methods: We conducted a comprehensive synthesis and critical evaluation of the current landscape, recent advancements, and future directions regarding the application of stress echocardiography in valvular heart disease. Results: This comprehensive review explores the incremental role of stress echocardiography in valvular heart disease, analyzing the evolution of its clinical applications, from low-flow, low-gradient aortic stenosis to the evaluation of contractile reserve and exercise-induced pulmonary hypertension in mitral stenosis and regurgitation. We discuss standardized protocols, key parameters to monitor, and the diagnostic and prognostic outcomes from major clinical trials and current guidelines. Attention is given to stress echocardiography’s ability to unmask the true severity of the disease and to identify patients at high risk for adverse events, thereby guiding crucial clinical decisions, such as the optimal timing for surgical or transcatheter intervention. Conclusions: The review evaluates the limitations of modality and outlines future research directions, including its integration with new technologies like 3D echocardiography and speckle tracking techniques, to further optimize the role of stress echocardiography as a decision-making tool in the multidisciplinary management of valvular heart disease. Full article
(This article belongs to the Special Issue Recent Advances in Echocardiography, 2nd Edition)
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29 pages, 14826 KB  
Review
How to Use Multimodality Imaging in Cardio-Oncology
by Anca Doina Mateescu, Raluca Ileana Mincu and Ruxandra Oana Jurcut
J. Cardiovasc. Dev. Dis. 2026, 13(1), 27; https://doi.org/10.3390/jcdd13010027 - 1 Jan 2026
Viewed by 202
Abstract
Recent advances in oncology have contributed to a steady rise in cancer survivorship. However, many cancer therapies are associated with cardiovascular adverse events, leading to increased rates of cardiovascular morbidity and mortality. As a result, cardio-oncology has emerged as a rapidly advancing discipline [...] Read more.
Recent advances in oncology have contributed to a steady rise in cancer survivorship. However, many cancer therapies are associated with cardiovascular adverse events, leading to increased rates of cardiovascular morbidity and mortality. As a result, cardio-oncology has emerged as a rapidly advancing discipline that relies on multidisciplinary collaboration. Cardiovascular multimodality imaging (CVMI) is an essential diagnostic and surveillance tool for cardiovascular toxicity, along with clinical evaluation and biomarkers. CVMI plays a central role in diagnosing cancer therapy-related cardiac dysfunction (CTRCD) and myocarditis, while also supporting the assessment of vascular toxicity and arrhythmias. It is essential for baseline cardiac evaluation and continuous monitoring throughout and following cancer therapy. CVMI enables early detection of cardiovascular toxicity, facilitating prompt initiation of cardioprotective therapy and allowing cancer therapy to proceed without compromising safety. Echocardiography is the primary imaging modality for screening, diagnosing, and monitoring CTRCD. Moreover, it is the first-line imaging test for cardiac structural and functional assessment in patients who develop immune checkpoint inhibitor (ICI)-related myocarditis. Advanced imaging techniques, such as cardiac magnetic resonance (CMR), nuclear imaging, and cardiac computed tomography, may help determine the cause and severity of left ventricular dysfunction, as well as assess cardiac masses and vascular toxicity. Not least, CMR is the gold standard imaging modality to diagnose myocarditis. This article is a narrative review that focuses on the various modalities of CVMI and their applications in cardio-oncology. Since the issue addressed is very extensive, this review was designed to be concise. Full article
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14 pages, 2395 KB  
Article
Systemic Metabolomic Remodeling in Pressure Overload-Induced Heart Failure Indicates Modulation of a Gut–Liver–Heart Axis by the Adiponectin Receptor Agonist ALY688
by Yubin Lei, Benjie Li, Tori Gosse, Sungji Cho, Hye Kyoung Sung, Jiarui Chen and Gary Sweeney
Metabolites 2026, 16(1), 38; https://doi.org/10.3390/metabo16010038 - 1 Jan 2026
Viewed by 229
Abstract
Background/Objectives: Numerous studies have documented cardioprotective effects of adiponectin in animal models of cardiometabolic disease (CMD). Adiponectin receptor agonist ALY688 has demonstrated functional significance against pressure overload-induced cardiac remodeling events in a mouse model of heart failure with reduced ejection fraction (HFrEF), potentially [...] Read more.
Background/Objectives: Numerous studies have documented cardioprotective effects of adiponectin in animal models of cardiometabolic disease (CMD). Adiponectin receptor agonist ALY688 has demonstrated functional significance against pressure overload-induced cardiac remodeling events in a mouse model of heart failure with reduced ejection fraction (HFrEF), potentially through modulation of the systemic metabolome. However, the specific metabolites and their pathophysiological contribution to cardioprotection in cardiac hypertrophy or heart failure remain unclear. This study aimed to characterize systemic metabolic alterations across five tissues in HFrEF and determine how ALY688 modifies these pathways to mediate cardioprotection in the transverse aortic constriction (TAC) model. Methods: Targeted metabolic profiling was performed on heart, liver, muscle, epididymal white adipose tissue (eWAT), and serum collected five weeks post-surgery from wild-type male C57BL/6 mice. Mice underwent either Sham or TAC-induced left ventricular pressure overload, with or without daily subcutaneous ALY688 administration. Metabolites were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and statistically analyzed at the tissue level. Results: Consistent with pathological cardiac remodeling, the comprehensive metabolomic analysis revealed that TAC induced widespread disruption of systemic metabolic homeostasis. ALY688 treatment significantly modified several key metabolite classes, including triglycerides (TGs) and glycosylceramides (HexCer). Notably, ALY688 also altered multiple gut-derived metabolites, including trimethylamine N-oxide (TMAO), 5-aminovaleric acid (5-AVA), and glycodeoxycholic acid (GDCA), highlighting a potential gut–liver–heart axis mediating its cardioprotective effects. Conclusions: These findings demonstrate that ALY688 mitigates TAC-induced metabolic dysregulation across multiple tissues. The identified metabolic signatures suggest that ALY688 exerts cardioprotective effects, at least in part, through restoration of systemic metabolic homeostasis and engagement of a gut–liver–heart metabolic axis. These results provide mechanistic insight into adiponectin receptor agonism and support further exploration of ALY688 as a potential therapeutic strategy for HFrEF. Full article
(This article belongs to the Special Issue Metabolomics in Respiratory, Cardiovascular and Metabolic Disorders)
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14 pages, 3443 KB  
Case Report
Telovelar Approach for Fourth-Ventricular Epidermoid Cyst: Anatomical Respect, Functional Recovery, and Long-Term Stability
by Cosmin Pantu, Alexandru Breazu, Stefan Oprea, Mugurel Petrinel Rădoi, Octavian Munteanu, Nicolaie Dobrin, Catalina-Ioana Tataru, Alexandru Vladimir Ciurea and Adrian Vasile Dumitru
Diagnostics 2026, 16(1), 129; https://doi.org/10.3390/diagnostics16010129 - 1 Jan 2026
Viewed by 216
Abstract
Background and Clinical Significance: Fourth-ventricular epidermoid cysts are rare intracranial lesions. They account for fewer than 1% of all primary brain tumors. Fourth-ventricular epidermoid cysts grow slowly because they are closely related to brainstem, cerebellum, and major blood vessels, so their treatment [...] Read more.
Background and Clinical Significance: Fourth-ventricular epidermoid cysts are rare intracranial lesions. They account for fewer than 1% of all primary brain tumors. Fourth-ventricular epidermoid cysts grow slowly because they are closely related to brainstem, cerebellum, and major blood vessels, so their treatment requires special caution. Because the cyst capsule attaches to functionally sensitive locations, complete removal is usually not possible without compromising some aspect of brain or spinal cord function. Surgical decision-making always involves weighing the need to remove the entire cyst against the potential loss of function of the affected area. The following case study describes how a patient was treated with a focus on the relationship between the cyst and surrounding anatomy, allowing for successful decompression with minimal risk to the patient’s neurologic status. Case Presentation: A young adult female patient was hospitalized with progressive truncal ataxia, disequilibrium and occipital headache accompanied by papilledema. Her physical examination disclosed significant dysfunction of the midline cerebellar region (SARA score = 18/40, ICARS score = 42/100), gaze-evoked nystagmus and bilaterally elevated grade II papilledema. MRI and MRA demonstrated a large, lobulated, nonenhancing, avascular mass located within the fourth ventricle, encroaching upon the dorsal medulla and obstructing both the foramen of Magendie and foramina of Luschka—findings typical of an epidermoid cyst. Microsurgical resection was accomplished via a median suboccipital craniectomy using a telovelar approach along the embryonic cerebellomedullary fissure to protect the integrity of the vermis and brainstem. The cyst contained layers of keratin embedded in a thin, translucent capsule. The capsule was carefully dissected away from the floor of the fourth ventricle. A very narrow band of capsule attached to the rhomboid fossa was intentionally spared to avoid damaging the cranial nerves. The patient had normal cerebrospinal fluid circulation restored and normal ventricular pulsation observed during surgery. Histopathology confirmed a benign epidermoid cyst consisting of keratinizing stratified squamous epithelium containing cholesterol clefts and laminated keratin debris. After surgery, the patient exhibited continuous neurological improvement including restoration of balance, disappearance of her headaches, and normalization of ocular pursuit. Sequential imaging studies were conducted post-operatively at one week, one month, three months, five months, and seven months to document stable decompression of the fourth ventricle, re-expansion of the fourth ventricle, and no evidence of cyst recurrence. Post-operative course was uncomplicated and the patient has remained free of symptoms and fully independent functionally at most recent follow-up. Conclusions: This case illustrates that when anatomically oriented, “maximal safe resection” can result in long-lasting decompression and clinically meaningful improvement in neurological function in patients with fourth-ventricular epidermoid cysts. Restoration of the patient’s natural cerebrospinal fluid pathway and preservation of neural interface relationships is more beneficial than pursuing aggressive removal of the cyst capsule. Although the risk of late recurrence is present even after nearly total removal, continuous radiologic monitoring is necessary to identify any recurrence. These experiences illustrate that with the principles of surgical restraint and anatomical guidance, there can be a balance between long-term stability and low operative risk. Full article
(This article belongs to the Special Issue Advancing Diagnostics in Neuroimaging)
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10 pages, 1658 KB  
Review
Left Bundle Branch Area Pacing in Transthyretin Cardiac Amyloidosis: A Narrative Review
by Maria Herrera Bethencourt, Arnt V. Kristen, Vincent Algalarrondo, Guram Imnadze and Andreas Müssigbrodt
J. Clin. Med. 2026, 15(1), 305; https://doi.org/10.3390/jcm15010305 - 31 Dec 2025
Viewed by 266
Abstract
Background/Objectives: Transthyretin cardiomyopathy (ATTR-CM) is frequently associated with conduction disease requiring pacing. Conventional right ventricular pacing may worsen cardiac function, whereas left bundle branch area pacing (LBBAP) aims to preserve physiological activation. Evidence for LBBAP in ATTR-CM remains limited. Methods: A [...] Read more.
Background/Objectives: Transthyretin cardiomyopathy (ATTR-CM) is frequently associated with conduction disease requiring pacing. Conventional right ventricular pacing may worsen cardiac function, whereas left bundle branch area pacing (LBBAP) aims to preserve physiological activation. Evidence for LBBAP in ATTR-CM remains limited. Methods: A structured narrative review of PubMed and Google Scholar was performed through November 2025 using predefined terms related to LBBAP and ATTR-CM. Peer-reviewed articles, case reports, case series, and relevant abstracts were included. Studies exclusively on light-chain cardiac amyloidosis were excluded. Results: Ten publications met inclusion criteria, comprising three case reports, five case series, one retrospective cohort without a comparator, and one cohort comparing LBBAP with cardiac resynchronization therapy (CRT). In total, 56 patients with ATTR-CM underwent LBBAP. Implantation success was high, with stable acute and mid-term electrical parameters. Follow-up (typically 3–12 months) showed stable electrical parameters with narrow paced QRS complexes and preserved or improved left ventricular ejection fraction in most reports. Symptomatic improvement and reductions in natriuretic peptides were variably described. No major lead-related complications were reported. Comparative data remain sparse and inconclusive. Conclusions: This review suggests that LBBAP is a feasible and safe pacing approach in patients with ATTR-CM and may help to stabilize or improve heart failure symptoms. Further prospective studies are needed to confirm its clinical effectiveness. Full article
(This article belongs to the Special Issue Cardiac Electrophysiology: Focus on Clinical Practice)
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18 pages, 4261 KB  
Article
Design of a Motor-Torsion Driven 3D-Printed Left Ventricular Mock Circulation System and Hemocompatibility Assessment
by Qingyang Cheng, Junlong Meng, Ming Yang, Yuan Liu, Junwen Yu, Yuanfei Zhu and Huaiyuan Guo
Appl. Sci. 2026, 16(1), 438; https://doi.org/10.3390/app16010438 - 31 Dec 2025
Viewed by 158
Abstract
In vitro testing of ventricular assist devices, constructing a mock circulation system that reproduces physiological cardiac function, is critical. However, current ventricular simulators often lack biomimetic fidelity and may introduce hemolysis and coagulation risks during prolonged operation, affecting hemocompatibility assessment. This study proposes [...] Read more.
In vitro testing of ventricular assist devices, constructing a mock circulation system that reproduces physiological cardiac function, is critical. However, current ventricular simulators often lack biomimetic fidelity and may introduce hemolysis and coagulation risks during prolonged operation, affecting hemocompatibility assessment. This study proposes a motor-driven torsional 3D-printed left ventricular simulator to reconstruct the hemodynamics of severe heart failure and related pathological conditions. The system integrates a 3D-printed elastic ventricular model with programmable torsional actuation, allowing the simulation of various cardiac conditions by adjusting the motor torsion angle and rotational speed, peripheral resistance and compliance. Fresh porcine blood was circulated for 4 h in a closed-loop system, with periodic measurements of plasma-free hemoglobin (PfHb), thrombin–antithrombin complex (TAT), and P-selectin. The results show that the system successfully reproduces typical hemodynamic features of severe heart failure, while hemolysis and coagulation markers remain low. After 4 h, PfHb was below 20 mg/dL, with no significant platelet activation or thrombosis. This study demonstrates that the proposed system enhances biomimicry while maintaining excellent hemocompatibility, offering a reliable platform for in vitro performance and safety evaluation of ventricular assist devices. Full article
(This article belongs to the Section Additive Manufacturing Technologies)
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