Front Physiol. 2025 Jun 4;16:1579815. doi: 10.3389/fphys.2025.1579815. eCollection 2025.
ABSTRACT
Numerous reports investigating channelopathies, including Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), have successfully reproduced using cardiomyocytes (CMs) differentiated from human induced pluripotent stem cells (hiPSCs). However, the relationship between action potentials (AP) and calcium transient waveforms-especially after drug treatment-remains unclear. In this study, we simultaneously loaded a membrane potential dye FluoVolt and the new calcium indicator CalbryteTM 590 AM and optimized stimulation and detection of both dyes to successfully obtain a higher signal-to-noise (S/N) ratio than the conventional membrane potential dye-red fluorescence Ca2+ dye combination, thus enabling the simultaneous recording of both AP and calcium transient waveforms in single hiPSC-CMs, which continued even after gradual increases in drug concentration. In drug-loading experiments on CPVT1 (RyR2-I4587V) hiPSC-derived ventricular-like CMs, carvedilol and flecainide demonstrated some effectiveness, while JTV519 at 3 µM exhibited both efficacy and alterations in AP waveforms. The Ca2+/calmodulin-dependent serine-threonine protein kinase II (CaMKII) inhibitor KN-93 at 1 µM was highly effective (93%) at reducing Ca2+ transient abnormalities without altering AP waveforms.
PMID:40534641 | PMC:PMC12175672 | DOI:10.3389/fphys.2025.1579815
J Am Coll Cardiol. 2025 Jun 24;85(24):2386-2398. doi: 10.1016/j.jacc.2025.04.028.
ABSTRACT
BACKGROUND: Survival for hypoplastic left heart syndrome (HLHS) and variants has improved over the past 4 decades; however, survival remains low compared with other forms of congenital heart disease. There is a paucity of data concerning long-term outcomes.
OBJECTIVES: This study aims to: 1) examine long-term survival and the impact of patient factors on survival for newborns with HLHS; and 2) examine functional and health outcomes, including quality-of-life (QOL) in adulthood.
METHODS: The study cohort included patients with HLHS and variants undergoing the Norwood or hybrid procedure between January 1984 and December 2023. Data on patient characteristics and management were abstracted from medical records. Vital status was ascertained by direct subject and family contact, review of the medical record, and publicly available data. Functional outcomes and QOL in adults (≥18 years of age) were assessed by patient reports. The primary outcome was death or cardiac transplantation at last follow-up.
RESULTS: In the study period, 2,012 neonates underwent staged reconstructive surgery for HLHS (Norwood, n = 1,921 and hybrid, n = 91). Transplant-free survival was 31.0% at 35 years. Transplant-free survival improved over time but is not different across recent eras. Most responders reported good to excellent general health.
CONCLUSIONS: In this cohort of newborns undergoing staged reconstructive surgery for HLHS, fewer than one-third are alive without a transplant at 35 years of age. Survival has not improved in recent years. However, there is a group of survivors who report good to excellent outcomes and QOL, consistent with a "high-performing" Fontan phenotype.
PMID:40533128 | DOI:10.1016/j.jacc.2025.04.028
Ecotoxicol Environ Saf. 2025 Jun 17;302:118474. doi: 10.1016/j.ecoenv.2025.118474. Online ahead of print.
ABSTRACT
Air pollution poses a significant global health threat, largely due to its role in triggering chronic inflammation through molecular pathways. Among these, The NF-κB signaling cascade, comprising nuclear factor kappa-light-chain-enhancer elements in B lymphocytes, serves as a pivotal regulator in orchestrating innate defense mechanisms against anthropogenic contaminants through transcriptional activation processes.This review explores how air pollutants such as particulate matter (PM2.5), heavy metals, NF-κB signaling is activated by exposure to diesel exhaust, triggering the expression of inflammatory mediators including cytokines and chemokines with pro-inflammatory properties.The activation of this pathway involves upstream stimuli including Toll-like receptors (TLRs) and reactive oxygen species (ROS), Modified sentence:These processes serve to amplify pro-inflammatory signaling pathways. Prolonged activation of the NF-κB pathway is implicated in the pathogenesis of pulmonary disorders.cardiovascular conditions, and immune dysfunction. Understanding these mechanisms is crucial for identifying therapeutic targets and designing effective interventions. Strategies including the use of NF-κB inhibitors and public health regulations to reduce exposure are discussed as avenues for mitigating pollutant-induced inflammation and associated diseases.
PMID:40532606 | DOI:10.1016/j.ecoenv.2025.118474
Chem Biodivers. 2025 Jun 18:e03431. doi: 10.1002/cbdv.202403431. Online ahead of print.
ABSTRACT
Self-healing zwitterionic hydrogels (ZIHs) have sparked widespread attention because of their intriguing properties and potential applications. One of the key features of ZIHs is their inherent antifouling properties, making them appealing for various biomedical applications. A notable characteristic of ZIHs is their self-healing capability, enabling them to mend damage and restore their mechanical properties, hence prolonging their lifespans and enhancing their functionality. Self-healing ZIHs exhibit excellent properties as wound-dressing materials by creating a moist environment that promotes the healing process. In addition to their antifouling, self-healing, wound-healing, and wound-dressing applications, zwitterionic self-healing hydrogels have shown promise in cardiac tissue engineering and cell encapsulation. In cell encapsulation, ZIHs provide promising platforms for the encapsulation and delivery of numerous cell types, including stem cells and therapeutic cells, as well as enable controlled release and protection during transplantation. The self-healing feature of ZIHs provides long-term stability and durability of these materials. This review focuses on state-of-the-art advancements in the synthesis strategies, self-healing mechanisms, and applications of ZIHs, offering an integrated perspective not previously addressed in the literature.
PMID:40531749 | DOI:10.1002/cbdv.202403431
ASAIO J. 2025 Jun 18. doi: 10.1097/MAT.0000000000002488. Online ahead of print.
NO ABSTRACT
PMID:40530717 | DOI:10.1097/MAT.0000000000002488
J Thorac Dis. 2025 May 30;17(5):3297-3306. doi: 10.21037/jtd-2025-259. Epub 2025 May 28.
ABSTRACT
BACKGROUND: Organ shortage remains a considerable challenge in the field of lung transplantation. There is an urgent need now for a new standard that can include more donor lungs and expand the donor pool to benefit more patients. To increase lung utilization rates and facilitate the standardization of the lung donor evaluation process, Heiden et al. formulated a novel lung donor (LUNDON) acceptability score. Our study applied data from a Chinese hospital to this model to demonstrate the practicability of the new model and reveal its potential to expand the donor lung pool and improve the efficiency and success rate of lung transplantation.
METHODS: This study was conducted in one of the largest lung transplant centers in China. Our study retrospectively analyzed a cohort of patients who underwent lung transplantation in Wuxi People's Hospital, Jiangsu Province, China, between January 1, 2018 and December 31, 2022, and applied the same exclusion criteria as those described in Heiden et al.'s study. The LUNDON score is an integer score established based on the model. Higher scores correspond to an increased likelihood of lung acceptance.
RESULTS: A total of 553 donor lungs were used for transplantation. According to the LUNDON score, the donors' integer-based score ranged from 9 to 30 points, and the predicted probability of donor lung acceptance was about 6.0% to 95.3%. Utilization of low-LUNDON-score donors increased progressively over the study period. The LUNDON score demonstrated concordance with the lung acceptance rate as designated by the International Society for Heart and Lung Transplantation (ISHLT) standard score. There was a statistically significant difference in the survival rate between donors and recipients with high or low LUNDON scores (P=0.03). The survival rate at 1 year after transplantation was 66.1% for the high-score group and 55.7% for the low-score group. The LUNDON score, as a newly developed practical model, can promote a further understanding of donor lung assessment and has the potential to effectively expand the donor pool.
CONCLUSIONS: This study confirmed the practicability of the newly developed lung donor (LUNDON) scoring model. The LUNDON score was found to be a valuable tool and may revolutionize and optimize the allocation of scarce organ resources. It is possible that the novel model can be applied to various populations, expand the pool of potential available lungs, and enhance the efficiency and success of lung transplantation.
PMID:40529731 | PMC:PMC12170127 | DOI:10.21037/jtd-2025-259
JACC Heart Fail. 2025 Jun 16;13(8):102495. doi: 10.1016/j.jchf.2025.03.039. Online ahead of print.
ABSTRACT
BACKGROUND: Recent advances in heart procurement techniques have facilitated the utilization of hearts obtained after circulatory death. However, discerning the population that stands to benefit most requires an understanding of waitlist outcomes.
OBJECTIVES: The objective of this study was to evaluate waitlist and post-transplant outcomes among patients listed for donation after circulatory death (DCD) hearts in the United States, stratified by listing status.
METHODS: The UNOS (United Network for Organ Sharing) database was queried for all adult patients waitlisted for isolated heart transplantation between October 2018 and June 2024. Patients were stratified by approval for donation after brain death vs DCD hearts. DCD patients were subdivided into those who were DCD candidates at time of listing or later during their waitlist period. Waitlist and post-transplant outcomes were compared using Fine & Gray and Kaplan-Meier analyses.
RESULTS: A total of 24,970 patients were identified; of these, 8,191 (33%) were listed as DCD candidates. DCD status 2, 3, 4, and 6 patients were more likely to be transplanted and less likely to die on the waitlist. There were no differences in post-transplant survival in any group. Receipt of a DCD heart was not predictive of mortality. Patients initially listed as DCD candidates were significantly more likely to be transplanted than those who became DCD candidates later during their waitlist course.
CONCLUSIONS: With exception of status 1, patients waitlisted for DCD hearts experience shorter waitlist duration, improved rates of transplantation, and comparable long-term survival with donation after brain death recipients.
PMID:40527153 | DOI:10.1016/j.jchf.2025.03.039
Metab Syndr Relat Disord. 2025 Jun 17. doi: 10.1089/met.2025.0028. Online ahead of print.
ABSTRACT
Background: Metabolic syndrome (MetS) is increasingly prevalent globally and is linked to inflammation in cardiac tissues. Cardiac allograft vasculopathy (CAV) is a significant inflammatory condition and a leading cause of graft failure after orthotopic heart transplantation (OHT). The relationship between MetS and CAV remains poorly understood. Methods: A literature search was conducted from inception to September 2024, including studies that reported associations between MetS or its components (obesity, hypertension, dyslipidemia, and diabetes mellitus) and CAV. The primary endpoint was the development of CAV after OHT. Results were presented as odds ratios (OR) or hazard ratios (HR) with 95% confidence intervals (CI), employing both random and fixed-effect models based on heterogeneity. Results: A total of 16 studies involving 3,366 patients were included. The prevalence of MetS was high before OHT (32%, 95% CI: 24-41%, I2 = 75%) and increased after OHT (37%, 95% CI: 18-61%, I2 = 83%). MetS was significantly associated with CAV (OR = 1.99, 95% CI: 1.28-3.09, I2 = 36%). Key components of MetS linked to CAV included obesity (OR = 1.54, 95% CI: 1.11-2.13, I2 = 0%) and dyslipidemia (OR = 1.87, 95% CI: 1.49-2.36, I2 = 0%). New-onset diabetes mellitus after transplantation increases the risk of CAV with an HR of 1.71 (95% CI: 1.56-1.88, I2 = 0%). Conclusion: The high prevalence of MetS both before and after OHT is associated with an increased risk of CAV, highlighting the need for targeted interventions to manage MetS in heart transplant recipients.
PMID:40526466 | DOI:10.1089/met.2025.0028
Eur J Heart Fail. 2025 Jun 17. doi: 10.1002/ejhf.3691. Online ahead of print.
ABSTRACT
AIMS: The European Heart Failure (HF) Survey was developed by the Heart Failure Association (HFA) of the European Society of Cardiology (ESC) to map HF management resources, reimbursement of drugs/devices for HF treatment, and structure and activities of HF professional and patient organizations.
METHODS AND RESULTS: The survey encompassed 43 ESC member countries. The median number of hospitals with dedicated HF centres was 2.6 (interquartile range [IQR] 0.9-4.7) per million people. Natriuretic peptide assessment was available at a median of 6.1 (IQR 1.8-10.6) emergency departments and 8.2 (IQR 1.3-14.7) hospitals per million people, respectively, whilst cardiac magnetic resonance was available at a median of 2.0 (IQR 0.9-3.8) hospitals per million people. Short-term and long-term mechanical circulatory support and heart transplantation were available at a median of 1.1 (IQR 0.5-2.4), 0.4 (IQR 0.0-0.5) and 0.3 (0.2-0.5) hospitals per million people, respectively. Whilst essential HF medications were mostly available and reimbursed, gaps were observed in availability and funding of newer and advanced therapies. Density of all diagnostic and therapeutic capabilities was greater in countries with more favourable socioeconomic status. National HF societies were reported in 98% of countries, whilst HF patient organizations in 45% of countries.anaemia.
CONCLUSIONS: The European HF Survey is the result of long-standing HFA/ESC efforts to monitor HF epidemiology, management resources, educational and awareness activities. It offers a valuable assessment of current management capabilities, highlighting challenges in providing contemporary standards of care. It also provides insights into future directions needed to address these gaps.
PMID:40526007 | DOI:10.1002/ejhf.3691
World J Pediatr Congenit Heart Surg. 2025 Jun 17:21501351251340669. doi: 10.1177/21501351251340669. Online ahead of print.
ABSTRACT
Background: The Fontan operation is typically performed between two and five years-of-age in the United States. In this study, we analyzed the immediate outcomes of the Fontan operation performed beyond the first decade of life in the United States using a large administrative database. Methods: Kids' Inpatient Database (2003-2019) and Nationwide Inpatient Sample (2016-2021) datasets were used; 10,245 pediatric patients undergoing the Fontan operation were identified. The cohort was divided into: Traditional Fontan (TF, 2-5 years-of-age, n = 9,900) and Late Fontan (LF, ≥10 years-of-age, n = 345); Survivor and non-survivor status were based on discharge mortality. Demographic and clinical characteristics were assessed using standard statistical tests. Results: Only 3% of the Fontan procedures (n = 345/10,245) belonged to the LF group. LF was comprised predominantly of non-Caucasian ethnicity, higher socioeconomic class, and had a greater comorbidity burden. Heterotaxy syndrome and total anomalous pulmonary venous return were more common in the LF group as compared with hypoplastic left heart syndrome in the TF group. Patients in the LF group experienced higher postoperative morbidity but similar mortality and often required specialized healthcare post-discharge. Multivariate regression analysis revealed inferior survival among Fontan patients with ECMO use, atrioventricular septal defect, coagulopathy, acute kidney injury, infection, prolonged mechanical ventilation, but not age at Fontan. Conclusion: The proportion of patients undergoing LF compared with TF has decreased over time signalling a move toward earlier timing of the Fontan procedure. However, within the LF group, the number of LF patients has increased over time signifying an extended application of the Fontan operation. The patients in the LF group experienced greater postoperative morbidity with an associated higher baseline comorbidity but not short-term mortality after the Fontan procedure.
PMID:40525532 | DOI:10.1177/21501351251340669
Artif Organs. 2025 Jun 17. doi: 10.1111/aor.15044. Online ahead of print.
NO ABSTRACT
PMID:40525466 | DOI:10.1111/aor.15044