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J Appl Biomed. 2025 Sep;23(3):97-106. doi: 10.32725/jab.2025.014. Epub 2025 Sep 25.

ABSTRACT

Acute rejection (AR) following heart transplantation (HTx) is a common complication, especially in the early post-HTx period. Mitochondrial DNA (mtDNA), released into circulation from stressed mitochondria, mimics ongoing immune activation and facilitates the release of pro-inflammatory substances. Our study aimed to assess cell-free mtDNA levels to identify early indicators of acute rejection progression. The absolute concentration of cf-mtDNA (cp/μl) was measured in 77 adult patients using quantitative polymerase chain reaction. Blood samples (n = 300) were collected before their corresponding biopsy according to the timeline within the first year post-HTx. The median cf-mtDNA levels in samples with confirmed AR (n = 57) was higher compared to samples without diagnosed rejection (n = 210; Padj < 0.01). When acute cellular (ACR; n = 39) and antibody-mediated rejection (AMR; n = 18) were analyzed separately, only AMR demonstrated higher levels compared to samples without diagnosed rejection (Padj = 0.02). The highest cf-mtDNA levels were detected in samples collected during early post-HTx complications compared to samples without rejection and AR samples (for both Padj < 0.0001). Both ACR and AMR were observed throughout the one-year period, with the majority (3rd quartile) occurring during the first 200 days post-HTx. Post-HTx complications, such as graft dysfunction or acute kidney injury, were observed within the first 11 days, with the majority (71.4%) occurring within 5 days post-HTx. The presence of AR, and specifically AMR, is associated with elevated levels of cf-mtDNA. The increase in plasma cf-mtDNA levels strongly reflects the occurrence of early complications following HTx.

PMID:41026944 | DOI:10.32725/jab.2025.014

Eur J Prev Cardiol. 2025 Sep 30:zwaf593. doi: 10.1093/eurjpc/zwaf593. Online ahead of print.

ABSTRACT

AIMS: Patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT) are at increased risk of cardiovascular complications; however, comprehensive data on these risks in large cohorts remain limited. This study aims to identify predictors of cardiovascular events in a large cohort of alloHSCT patients.

METHODS: We conducted a retrospective monocentric study including all consecutive patients aged 15 years and older with haematological malignancies who underwent alloHSCT between 2011 and 2020. Data were extracted from electronic medical records, including demographic, clinical, and transplant-specific variables. The primary composite outcome was cardiotoxicity including cardiovascular death, heart failure (HF), rhythm/conduction disorders, acute arterial events, venous thromboembolism (VTE), and myopericarditis. Predictors of cardiotoxicity were analysed using Cox proportional hazards regression and Fine-and-Gray models.

RESULTS: Among 1,027 patients recruited (age 45±16 years, 62% male), 30% experienced cardiotoxicity after a median (interquartile range, IQR) follow-up of 4 (1-7) years. The median (IQR) time to the first event was 8 months (3-17). In multivariable analysis, independent predictors for early events (≤100 days) were age, hypertension, history of HF, cancer therapy-related cardiac dysfunction (CTRCD), and high-dose administration of cyclophosphamide (≥100 mg/kg). For late events (>100 days), independent predictors were age, hypertension, history of VTE, atrial fibrillation/flutter, history of HF, CTRCD, previous liposomal anthracycline exposure, and high-risk hematopoietic cell transplantation-comorbidity index(HCT-CI) score category.

CONCLUSION: Our study identifies independent predictors of early and late cardiotoxicity, including demographic data, cardiovascular risk factors, history of cardiovascular disease and oncologic history.

PMID:41026898 | DOI:10.1093/eurjpc/zwaf593

Eur Heart J Qual Care Clin Outcomes. 2025 Sep 30:qcaf117. doi: 10.1093/ehjqcco/qcaf117. Online ahead of print.

ABSTRACT

History of substance use is assessed in potential heart transplantation evaluations. The evidence base for this highly consequential practice, linking substance use disorders with poor post-transplantation outcomes, presents methodological limitations. We conducted a retrospective cohort study to address these limitations using high dimensional propensity score matching to compare heart transplant outcomes of patients with and without substance use disorders. Key outcomes included mortality, hospitalization, and organ rejection rates, controlling for confounders. A national dataset of electronic health records of >120 million patients in the United-States (2015-2023) was used to identify heart transplantation patients with substance use disorders (n=808) and controls (n=7066), matched for medical comorbidities and demographic variables. Only after adjusting for sociodemographic and comorbidities of heart transplant recipients, the results revealed no significant differences between groups with and without substance use disorders at one year in mortality (Odds Ratio (OR)=0.96 (95% CI: 0.54, 1.69, p=0.88), hospitalization (OR=1.02 (95% CI: 0.83, 1.25, p=0.840)), organ rejection rates (OR=0.96 (95% CI: 0.78, 1.18, p=0.670)), nor at 5 years in mortality (Hazards Ratio (HR) =1.15 (95% CI: 0.82, 1.61, p=0.410) and organ rejection (HR=0.98 (95% CI: 0.84, 1.14, p=0.810). Future studies must consider confounding factors when evaluating transplant criteria and outcomes in patients with substance use disorders.

PMID:41026891 | DOI:10.1093/ehjqcco/qcaf117

JACC Case Rep. 2025 Sep 30:105543. doi: 10.1016/j.jaccas.2025.105543. Online ahead of print.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) can trigger life-threatening immune-related adverse events, including myocarditis. Steroid-refractory cases pose significant therapeutic challenges.

CASE SUMMARY: A 57-year-old woman with metastatic non-small cell lung cancer developed fulminant myocarditis with bidirectional ventricular tachycardia and biventricular dysfunction after pembrolizumab therapy. Despite early high-dose corticosteroids, cardiac biomarkers remained elevated and arrhythmias persisted. Second-line agents (mycophenolate mofetil, intravenous immunoglobulin) were discontinued owing to adverse effects. Off-label ruxolitinib was initiated after interdisciplinary discussion. This led to sustained clinical improvement, return to sinus rhythm, and recovery of biventricular function.

DISCUSSION: This case highlights the therapeutic challenges in steroid-refractory ICI-associated myocarditis. Ruxolitinib may offer a promising option in these settings, though prospective data are lacking.

TAKE-HOME MESSAGES: ICI-associated myocarditis can present with ventricular arrhythmia and heart failure. Ruxolitinib may be considered in steroid-refractory cases.

PMID:41026064 | DOI:10.1016/j.jaccas.2025.105543

Sarcoidosis Vasc Diffuse Lung Dis. 2025 Sep 30;42(3):16865. doi: 10.36141/svdld.v42i3.16865.

ABSTRACT

BACKGROUND AND AIM: Recurrence of cardiac sarcoidosis (CS) following heart transplantation (HT) is a rare but clinically significant complication that influences management strategies and prognosis. This review examines existing evidence on the diagnosis and treatment of post-transplant CS recurrence. Additionally, we present a case report of CS recurrence in a patient after HT.

METHODS: We analyzed clinical studies, case reports, and systematic reviews published up to January 2025, focusing on the recurrence of CS after transplantation.

RESULTS: Limited data suggest that immunosuppressive therapies are crucial in managing post-transplant CS recurrence. Diagnosis relies on imaging modalities such as Positron Emission Tomography (PET-CT), Cardiac Magnetic Resonance (CMR), and endomyocardial biopsies. Treatment generally involves intensifying immunosuppressive therapy.

CONCLUSIONS: Standardized guidelines are essential to improve the management of this rare and complex condition and to enhance long-term patient outcomes.

PMID:41026015 | DOI:10.36141/svdld.v42i3.16865

N Engl J Med. 2025 Sep 30. doi: 10.1056/NEJMoa2508170. Online ahead of print.

ABSTRACT

BACKGROUND: Sotatercept, an activin-signaling inhibitor, reduces morbidity and mortality among patients with long-standing pulmonary arterial hypertension. Its effects in patients with pulmonary arterial hypertension within the first year after diagnosis are unclear.

METHODS: In this phase 3 trial, we enrolled adult patients with World Health Organization functional class II or III pulmonary arterial hypertension who had received the diagnosis less than 1 year earlier, had an intermediate or high risk of death, and were receiving double or triple background therapy. Patients were randomly assigned to receive add-on therapy with subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; escalated to target dose, 0.7 mg per kilogram) or placebo every 21 days. The primary end point was clinical worsening, a composite of death from any cause, unplanned hospitalization lasting at least 24 hours for worsening of pulmonary arterial hypertension, atrial septostomy, lung transplantation, or deterioration in performance in exercise testing due to pulmonary arterial hypertension, assessed in a time-to-first-event analysis.

RESULTS: The trial was stopped early owing to loss of clinical equipoise after the reporting of positive results from previous sotatercept trials. A total of 320 patients were included (160 each in the sotatercept and placebo groups). The median duration of follow-up was 13.2 months. At least one primary end-point event occurred in 17 patients (10.6%) in the sotatercept group and in 59 patients (36.9%) in the placebo group (hazard ratio, 0.24; 95% confidence interval, 0.14 to 0.41; P<0.001). Deterioration in performance in exercise testing due to pulmonary arterial hypertension occurred in 8 patients (5.0%) in the sotatercept group and in 46 patients (28.8%) in the placebo group; unplanned hospitalization for worsening of pulmonary arterial hypertension occurred in 3 patients (1.9%) and 14 patients (8.8%), respectively; and death from any cause occurred in 7 patients (4.4%) and 6 patients (3.8%). No cases of atrial septostomy or lung transplantation occurred. The most common adverse events with sotatercept were epistaxis (31.9%) and telangiectasia (26.2%).

CONCLUSIONS: Among adults with pulmonary arterial hypertension who had received the diagnosis less than 1 year earlier, the addition of sotatercept to background therapy resulted in a lower risk of clinical worsening than placebo. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; HYPERION ClinicalTrials.gov number, NCT04811092.).

PMID:41025556 | DOI:10.1056/NEJMoa2508170

Circ Heart Fail. 2025 Sep 30:e012787. doi: 10.1161/CIRCHEARTFAILURE.125.012787. Online ahead of print.

ABSTRACT

BACKGROUND: The purpose of the current study was to investigate the clinical implications of elevated donor-derived cell-free DNA (dd-cfDNA) levels in heart transplantation recipients without evidence of rejection observed on endomyocardial biopsy.

METHODS: We retrospectively analyzed dd-cfDNA samples from all consecutive heart transplantation recipients between 2019 and 2023, excluding those with multiorgan transplants. Each sample was paired with an endomyocardial biopsy (<30 days). A positive biopsy was defined based on International Society for Heart and Lung Transplantation criteria of ≥1R/1B or pAMR >0. Elevated dd-cfDNA was defined as ≥0.12%, with a subanalysis using a threshold of 0.20%. Graft dysfunction was defined as an ejection fraction<50%. We excluded dd-cfDNA samples with concurrent histologically positive biopsy results, focusing on those with positive dd-cfDNA and negative biopsy findings. A mixed model Cox regression approach was applied to assess for mortality and graft dysfunction.

RESULTS: Of 643 dd-cfDNA samples from 227 patients, 238 samples (37%) from 110 patients showed positive dd-cfDNA results with negative endomyocardial biopsy. The median age was 56 years, with 27% females and 53% White patients. The median time from heart transplantation to sample collection was 5 months (interquartile range, 3-12). Among the positive samples, the median dd-cfDNA level was 0.24% (interquartile range, 0.16%-0.53%) with 63% exceeding 0.20%. A higher prevalence of prior treated antibody-mediated rejection was observed in the dd-cfDNA positive group (15% versus 5%; P=0.002). Patients with elevated dd-cfDNA results ≥ 0.20% demonstrated a near 5-fold increased risk of mortality (hazard ratio, 4.6 [95% CI, 1.6-13.4]; P=0.005) and a 3-fold risk of graft dysfunction (hazard ratio, 3.4 [95% CI, 1.0-11.9]; P=0.054) compared with those with negative dd-cfDNA.

CONCLUSIONS: In our cohort, patients with positive dd-cfDNA levels and negative biopsy results had higher rates of adverse outcomes, including graft dysfunction and mortality.

PMID:41025234 | DOI:10.1161/CIRCHEARTFAILURE.125.012787

World J Gastroenterol. 2025 Oct 7;31(37):110164. doi: 10.3748/wjg.v31.i37.110164.

ABSTRACT

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a silent epidemic having substantial clinical implications, with liver transplantation being one of the areas most impacted. The increasing prevalence of metabolic fatty liver disease has reduced the quality of available donor organs. While noninvasive methods are increasingly applied to evaluate liver steatosis in deceased donors, liver biopsy remains the gold standard. Many aspects of liver biopsies are not yet fully standardized. Macrovesicular hepatic steatosis is associated with decreased allograft quality and poorer short- and long-term transplant outcomes, especially in moderate and severe steatotic cases. Donation after cardiac arrest further exacerbates these poor outcomes. Matching marginal allografts with suitable recipients based on recipient characteristics is crucial for improving transplant outcomes. Living donor liver transplant is a feasible option for addressing organ shortages. Noninvasive evaluation is preferred for assessing liver health; however, when the results are inconclusive, a liver biopsy is recommended. Lifestyle modifications can improve graft, living donor and recipient outcomes. Analysis of the impact of MASLD on the donor pool and the implementation of new optimization strategies are essential to ensure the sustainability of transplantation as a curative treatment for advanced liver cirrhosis. The aim of this review was to summarize the effect of MASLD on the liver donor population, highlighting how to evaluate steatosis in donors, and to discuss its clinical implications as well as strategies to optimize organ allocation in the MASLD era.

PMID:41025004 | PMC:PMC12476651 | DOI:10.3748/wjg.v31.i37.110164

Respir Res. 2025 Sep 29;26(1):276. doi: 10.1186/s12931-025-03361-z.

ABSTRACT

BACKGROUND: The mechanism of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) remains poorly understood. Fibulin 5, a multifunctional extracellular matrix protein, was reinduced in balloon-injured vessels and may contribute to vascular remodelling. This study aimed to investigate the role and molecular mechanism of action of fibulin 5 in the pathogenesis of CHD-PAH.

METHODS & RESULTS: We found elevated fibulin 5 expression in pulmonary artery smooth muscle cells (PASMCs) from CHD-PAH patients and shunt-induced PAH rats. In vivo, downregulation of fibulin-5 expression by intratracheally delivered adeno-associated viral vectors prevents shunt-associated PAH and associated pulmonary artery remodeling. In vitro, fibulin 5 expression in human PASMCs (hPASMCs) was changed through transduction with lentiviruses. We found fibulin 5 overexpression enhanced TGF-β1-induced proliferation and migration, as assessed by EdU, cell count, and transwell assays. Western blotting showed altered expression of contractile and synthetic phenotype markers. These effects were reversed by the PI3K/AKT inhibitor LY294002, suggesting fibulin 5 acts through the TGF-β1/PI3K/AKT pathway.

CONCLUSIONS: Overall, our data provide new insights into the influence of fibulin 5 on the modification of hPASMC dysfunction and pulmonary artery remodelling in shunt-associated PAH.

PMID:41024156 | PMC:PMC12482218 | DOI:10.1186/s12931-025-03361-z

BMC Infect Dis. 2025 Sep 29;25(1):1205. doi: 10.1186/s12879-025-11648-1.

ABSTRACT

BACKGROUND: Solid organ transplant (SOT) recipients receive immunosuppressive drugs that predispose them to opportunistic infections, including cytomegalovirus (CMV) infection. In these patients, CMV infection can lead to life-threatening consequences, such as transplant rejection. This systematic review and meta-analysis investigated the role of CMV infection in the development of acute rejection in SOT recipients.

METHODS: PubMed, Embase, Scopus, and Web of Science databases were systematically searched for eligible publications until Jan 31, 2025. English-language studies reporting the association between CMV infection and acute rejection in adult SOT recipients were included. Baseline characteristics, transplanted organs, and CMV infection and acute rejection status in SOT recipients were independently extracted by two reviewers. The pooled odds ratio (ORs) with a 95% confidence interval (CI) was calculated using the random effect model.

RESULTS: Overall, 27 studies with 6308 SOT recipients entered the meta-analysis. Acute rejection was significantly higher in SOT recipients with CMV infection than those without CMV infection (OR = 2.02, 95%CI 1.64-2.49, I2 = 40.44%). Acute rejection was significantly higher in recipients of liver (OR = 4.43, 95%CI 2.20-8.92, I2 = 0.00%), kidney (OR = 2.22, 95%CI 1.70-2.89, I2 = 48.72%), and lung (OR = 1.38, 95%CI 1.01-1.90, I2 = 0.00%), if they were infected with CMV. While acute rejection was not significantly associated with CMV infection in heart transplant recipients (OR = 1.49, 95%CI 0.54-4.12, I2 = 18.83%). Furthermore, Egger's test did not indicate any evidence of publication bias (P = 0.7440).

CONCLUSIONS: CMV infection approximately doubles the risk of acute rejection in SOT recipients. This association differs between various organs, with liver transplants indicating the highest risk, followed by kidney and lung transplants.

PMID:41023683 | PMC:PMC12482134 | DOI:10.1186/s12879-025-11648-1

Sci Rep. 2025 Sep 30;15(1):33811. doi: 10.1038/s41598-025-02542-6.

ABSTRACT

The pathogenesis of NEC in term infants with critical congenital heart defects (CHD) is mainly associated with hypoxic-ischemic events that initiate an exaggerated systemic inflammatory response. Herein, we investigated the cumulative impact of the cytokine landscape and gut microbiota on the pathobiology leading to NEC onset in term newborns with CHD. This study involved 36 newborns who underwent surgical correction of CHD during the first two weeks of life; eight of them developed NEC within one week after cardiac surgery. Blood and fecal samples were collected at two time points: before and after surgery. Newborns without NEC exhibited significant changes in the levels of 22 cytokines, whereas newborns with NEC had changes in only 4 cytokines during the perioperative period. A panel including IL-1RA, IL-5, IL-18, and MCP-1 showed impressive test performance characteristics for diagnosing NEC at the preclinical stage with an AUC of 0.938, a sensitivity of 100.0%, and a specificity of 85.7%. Fifteen bacterial taxa were differentially abundant between feces samples of newborn groups. The pathobionts Collinsella and Mediterraneibacter gnavus group, known to be associated with increased intestinal permeability, were enriched in NEC newborns' feces before cardiac surgery. Our study demonstrated that the gut microbiota mediates the equilibrium of cytokine network dynamics under a broad spectrum of "friend or foe" conditions, effectively suppressing excessive inflammatory responses during early postnatal adaptation. In contrast, under conditions of low microbial diversity, a strong imbalanced cytokine feedback loop formed, resulting in deviations from normal immune response maturation. These findings offer new insights into understanding the fine-tuning of gut microbiota-immune system interactions in the first days of life.

PMID:41028028 | PMC:PMC12484952 | DOI:10.1038/s41598-025-02542-6

J Pediatr Psychol. 2025 Sep 30:jsaf089. doi: 10.1093/jpepsy/jsaf089. Online ahead of print.

ABSTRACT

OBJECTIVE: To gather parents' perspectives on the experiences of siblings of young children with congenital heart disease (CHD), the impact of CHD on siblings, and the types of resources and supports they need to adjust to CHD within their family.

METHODS: A community advisory council guided the study. Parents of children with CHD, currently 1-7 years old, who had surgery in their first year of life, were eligible for participation if they were fluent in written English and had internet access. Recruitment through several CHD-specific nonprofit organizations produced a national sample of parents (N = 108). Of the 73 who had non-bereaved heart-healthy children, 59 (81%) provided sibling-relevant data for this study. Most parents were non-Hispanic White (n = 54; 91.5%) mothers (n = 41; 69.5%; Mage = 36.10; SDage = 5.0) reporting on siblings older than the child with CHD (n = 44; 74.6%). Data were qualitative, collected through crowdsourcing, and coded to distill themes.

RESULTS: Three themes emerged: (1) CHD directly affects siblings' psychosocial functioning and daily activities, (2) CHD alters roles and relationships within the family, with impacts to siblings, and (3) families seek and appreciate support for heart-healthy siblings from extended family and friends, the healthcare team, and the community, but resources are variable.

CONCLUSION: Parents described specific ways that CHD impacts their heart-healthy children, including their psychosocial functioning, role in the family, and support from the community. Findings highlight the need for family-centered care in CHD, including screening to identify siblings at risk for psychosocial difficulties and provision of appropriate supports to meet sibling and family needs.

PMID:41027595 | DOI:10.1093/jpepsy/jsaf089

Clin Imaging. 2025 Sep 26;127:110627. doi: 10.1016/j.clinimag.2025.110627. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe the lymphatic imaging findings in patients with both Trisomy 21 and congenital heart disease and to depict the most common central lymphatic abnormalities in these patients.

MATERIALS AND METHODS: We conducted a single-center retrospective review of patients with a confirmed history of Trisomy 21 and congenital heart disease who presented for lymphatic imaging over a 7-year period. Clinical history and outcomes were extracted from the medical records. Lymphatic distribution and flow were evaluated by two pediatric radiologists from dynamic contrast-enhanced MR lymphangiography studies, which included T2-weighted and dynamic contrast-enhanced T1-weighted images, conventional lymphangiography studies were also evaluated.

RESULTS: We identified 16 patients (12 male): 8 infants, 6 children, and 2 adults. 12 patients had cardiac surgery including Fontan (n = 5), hemi-Fontan (n = 1), Glenn (n = 1), and other cardiac surgeries (n = 5). Presenting symptoms included chylothorax, plastic bronchitis, chylous ascites, protein losing enteropathy, pericardial effusion, lymphedema, and anasarca. Two patients died (12 %) by the time of data collection. T2-weighted MR imaging demonstrated lymphatic edema in all patients. T1-weighted dynamic imaging revealed abnormal pulmonary and/or mesenteric lymphatic perfusion in 15 patients (88 %) across intranodal, intrahepatic, and intramesenteric access types. The thoracic duct was tortuous and/or dilated in most cases. Conventional lymphangiography confirmed thoracic duct obstruction.

CONCLUSION: This is a descriptive study of central lymphatic diseases in patients with Trisomy 21, congenital heart disease and clinical evidence of lymphatic dysfunction. Common findings in these patients include retrograde dermal lymphatic flow, pulmonary and mesenteric lymphatic perfusion as well as the presence of a dilated and tortuous duct.

PMID:41027150 | DOI:10.1016/j.clinimag.2025.110627

Dimens Crit Care Nurs. 2025 Nov-Dec 01;44(6):313-319. doi: 10.1097/DCC.0000000000000723.

ABSTRACT

BACKGROUND: The Complexity Assessment and Monitoring to Ensure Optimal Outcomes (CAMEO) acuity tool was developed to inform nurse staffing decisions and projections. We propose a novel use of the CAMEO data, ie, CAMEO Acuity Curves, to identify high-acuity periods after congenital heart surgery.

OBJECTIVES: The aims of this study were to describe CAMEO acuity scores for selected congenital heart surgeries and examine acuity trends during the cardiac intensive care unit (CICU) admissions.

METHODS: We performed a retrospective review of 3 common congenital heart procedures between January 2017 and January 2020: stage I palliation for single ventricle (stage I), Arterial Switch Operation (ASO) for dextro transposition of great arteries with or without ventricular septal defect repair (ASO), and tetralogy of Fallot repair. Postoperative acuity was assessed using CAMEO Acuity Curves stratified by severity of residual lesions in anatomic area of repair as assessed by the Residual Lesion Score (RLS).

RESULTS: Among 205 cases (stage I, n = 45; ASO, n = 60; tetralogy of Fallot repair, n = 100), the overall mean CAMEO scores varied in acuity by procedure, with the highest acuity during cardiac intensive care unit stay noted for stage I (76%), followed by ASO (69%) and tetralogy of Fallot repair (62%). When stratified by RLS, acuity increased for each procedure, with RLS 3 having a higher acuity than RLS 1 and 2.

DISCUSSION: The CAMEO Acuity Curves enabled construction of postoperative acuity timeline in cardiac intensive care unit, allowing description and comparison of acuity across various case complexities, which may guide clinical decision-making and optimize staffing to meet patient care resource needs.

PMID:41026053 | DOI:10.1097/DCC.0000000000000723

Turk Kardiyol Dern Ars. 2025 Sep 30. doi: 10.5543/tkda.2025.67916. Online ahead of print.

ABSTRACT

Double-inlet left ventricle (DILV) are rarely encountered congenital heart defects which are also known as single-ventricle defects and have a complex structure in which the blood exiting both atriums flows into a single ventricle, and they constitute approximately 1.5% of all congenital heart diseases. The 37-year-old female patient who did not have a history of cardiac disease visited our outpatient clinic for routine cardiological assessments. Transthoracic echocardiography (TTE) was performed upon hearing a 3/6 pansystolic murmur at the mesocardiac focus and a 3/6 systolic ejection murmur at the pulmonary focus on cardiac auscultation. The TTE of the patient revealed that the atrioventricular valves opened into one ventricular chamber in four-chamber apical imaging. There was no noticeable interventricular septum, while a rudimentary right ventricle and a ventricular septal defect (VSD) were observed. There was a gradient of 38 mmHg in the pulmonary valve. Mild-to-moderate pulmonary stenosis was present. In the transesophageal echocardiography (TEE), a rudimentary interventricular septum and the right ventricle were observed. Because the patient did not have any symptoms or cyanosis, the patient was given information about a potential need for occasional infective endocarditis prophylaxis and phlebotomy, and close medical follow-up was decided. A double-inlet left ventricle is known as a severe congenital heart anomaly that is typically symptomatically diagnosed in childhood and requires surgical intervention. However, in the literature, cases with an asymptomatic course reaching adulthood without surgical intervention, albeit very rare, have been reported.

PMID:41025493 | DOI:10.5543/tkda.2025.67916

Trials. 2025 Sep 29;26(1):374. doi: 10.1186/s13063-025-09067-3.

ABSTRACT

BACKGROUND: Opioids were considered the main analgesics for pain management during and after cardiac surgery. There are many complications associated with the use of opioids. Paravertebral block (PVB) is injecting Anaesthetics into the paravertebral space. We designed a randomised controlled trial to investigate whether PVB-based opioid-free general Anaesthesia, as compared to traditional low-dose opioid-based fast-track anaesthesia, can reduce opioid consumption within 24 h after thoracotomy incision cardiac surgery with cardiopulmonary bypass (CPB) in paediatric patients.

METHODS: This is a single-centre, single-blinded, randomised controlled trial with a 1:1 allocation ratio. Patients will be randomised into two groups (control group and PVB group); 20 children will be enrolled in this trial, with 10 subjects in each group. Block randomisation will be performed. Patients aged 1-6 years, with the diagnosis of atrial and/or ventricular septal deficient And scheduled for cardiac surgery via a right thoracotomic incision, will be eligible for enrolment. The primary outcome is opioid consumption during the first 24 h after surgery. The main secondary outcomes include the perioperative stress response, inflammatory level, and intraoperative haemodynamics.

DISCUSSION: This is the first randomised clinical study investigating opioid-free anaesthesia based on PVB for paediatric congenital thoracotomy surgery with CPB. If the OPTION trial proves that opioid-free anaesthesia based on PVB is safe for children undergoing thoracotomic cardiac surgery, we would be glad to provide an OPTION for the perioperative management of these children, especially in the era of ERAS.

TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200066517 ( www.chictr.org.cn ), Registered on December 7, 2022.

PMID:41024258 | PMC:PMC12482201 | DOI:10.1186/s13063-025-09067-3

Respir Res. 2025 Sep 29;26(1):276. doi: 10.1186/s12931-025-03361-z.

ABSTRACT

BACKGROUND: The mechanism of pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) remains poorly understood. Fibulin 5, a multifunctional extracellular matrix protein, was reinduced in balloon-injured vessels and may contribute to vascular remodelling. This study aimed to investigate the role and molecular mechanism of action of fibulin 5 in the pathogenesis of CHD-PAH.

METHODS & RESULTS: We found elevated fibulin 5 expression in pulmonary artery smooth muscle cells (PASMCs) from CHD-PAH patients and shunt-induced PAH rats. In vivo, downregulation of fibulin-5 expression by intratracheally delivered adeno-associated viral vectors prevents shunt-associated PAH and associated pulmonary artery remodeling. In vitro, fibulin 5 expression in human PASMCs (hPASMCs) was changed through transduction with lentiviruses. We found fibulin 5 overexpression enhanced TGF-β1-induced proliferation and migration, as assessed by EdU, cell count, and transwell assays. Western blotting showed altered expression of contractile and synthetic phenotype markers. These effects were reversed by the PI3K/AKT inhibitor LY294002, suggesting fibulin 5 acts through the TGF-β1/PI3K/AKT pathway.

CONCLUSIONS: Overall, our data provide new insights into the influence of fibulin 5 on the modification of hPASMC dysfunction and pulmonary artery remodelling in shunt-associated PAH.

PMID:41024156 | PMC:PMC12482218 | DOI:10.1186/s12931-025-03361-z

J Am Heart Assoc. 2025 Oct 7;14(19):e043819. doi: 10.1161/JAHA.125.043819. Epub 2025 Sep 30.

ABSTRACT

BACKGROUND: Given the relatively high morbidity and death associated with transcatheter edge-to-edge repair for secondary mitral regurgitation, the development of optimal risk stratification models is imperative. The J-MACS (Japanese Registry for Mechanically Assisted Circulatory Support) score is a recently developed tool designed to stratify risk in patients with advanced heart failure undergoing durable left ventricular assist device implantation.

METHODS: Data were obtained from the OCEAN-Mitral (Optimized Catheter Valvular Intervention-Mitral) registry on patients with secondary mitral regurgitation and left ventricular ejection fraction <50% who underwent transcatheter edge-to-edge repair. A newly innovated modified J-MACS score, incorporating age, history of cardiac surgery, serum creatinine levels, and postprocedural moderate or greater tricuspid regurgitation, was calculated. Its prognostic significance regarding the primary outcome, comprising all-cause death and heart failure-related hospitalizations, was assessed.

RESULTS: A total of 2006 patients (median age, 77 years; 63% men) were included in the study. The median modified J-MACS score was 13.7 (interquartile range, 12.0-16.2). Based on statistically calculated optimal cutoff values of 11.4 and 14.0, patients were stratified into 3 risk categories: low, moderate, and high. The 2-year cumulative incidence of the primary outcome differed significantly among these groups (26%, 37%, and 51%, respectively; P<0.001). Risk group classification remained independently associated with the primary outcome, with an adjusted hazard ratio of 1.42 (95% CI, 1.13-1.71; P<0.001) for the intermediate risk versus low risk and 2.27 (95% CI, 1.67-2.96; P<0.001) for the high risk versus low risk.

CONCLUSIONS: The modified J-MACS score demonstrated an independent association with all-cause death and heart failure-related hospitalization following transcatheter edge-to-edge repair in patients with significant mitral regurgitation and systolic heart failure.

REGISTRATION: URL: https://upload.umin.ac.jp; Unique Identifier: UMIN000023653.

PMID:41025485 | DOI:10.1161/JAHA.125.043819

Intensive Care Med Exp. 2025 Sep 30;13(1):99. doi: 10.1186/s40635-025-00812-1.

ABSTRACT

BACKGROUND: The reach of dialysis in toxicology is limited by two factors, high toxicant volume of distribution and low dialytic extraction of protein bound toxicants in blood. Therapeutic actions for lipid emulsion as antidote are thought involve a "lipid shuttle", whereby lipid droplets in the circulation "shuttle" lipophilic toxicants with "boarding" in well perfused heart and brain tissue with high toxicant concentrations and "exit" to biologically inert slower equilibrating sites such as muscle or adipose where toxicant concentrations are lower. Such a mechanism raises the conceptual possibility of an extracorporeal "exit" potentially mitigating toxicity through increased drug clearance. In experimental models drug binding nanoparticles in dialysate have been shown to mitigate the problem of blood proteins binding toxicant. We investigated whether the addition of intravenous lipid emulsion would increase extraction of amitriptyline into nanoparticle augmented peritoneal dialysate in rats orally dosed with amitriptyline for 1 week.

METHODS: Rats were dosed with amitriptyline in drinking water for a week. On the day of the experiment, anaesthetised rats received either an initial bolus then infusion of lipid emulsion for one hour, or a bolus of saline at the initiation of the experiment equal to the total volume of lipid emulsion given. After a 50 min equilibration period, a 10 min pH gradient nanoparticle augmented peritoneal dialysis dwell was undertaken. Animals were humanely euthanised at the end of the experiment. Blood was sampled 0, 10, 45 and 60 min and peritoneal dialysate was analysed for amitriptyline concentration.

RESULTS: There were no significant differences in baseline physiology, initial amitriptyline blood concentration, nor pulse and blood pressure at any time between groups. Time weighted individual subject mean blood amitriptyline concentrations (median (IQR)); control 104 (87-125) nmol/l, lipid 219 (148-357) nmol/L, p = 0.03 and dialysate amitriptyline concentration; control 31(14-52) nmol/L, lipid 105 (62-185) nmol/L, p = 0.03 were greater in animals given intravenous lipid emulsion.

CONCLUSION: These are the first data to our knowledge showing experimental support for the approach of simultaneously decreasing volume of distribution with an intravascular nanoparticle in conjunction with a drug binding particle in dialysate. Further work in this area is warranted.

PMID:41026446 | PMC:PMC12484478 | DOI:10.1186/s40635-025-00812-1

Trials. 2025 Sep 29;26(1):374. doi: 10.1186/s13063-025-09067-3.

ABSTRACT

BACKGROUND: Opioids were considered the main analgesics for pain management during and after cardiac surgery. There are many complications associated with the use of opioids. Paravertebral block (PVB) is injecting Anaesthetics into the paravertebral space. We designed a randomised controlled trial to investigate whether PVB-based opioid-free general Anaesthesia, as compared to traditional low-dose opioid-based fast-track anaesthesia, can reduce opioid consumption within 24 h after thoracotomy incision cardiac surgery with cardiopulmonary bypass (CPB) in paediatric patients.

METHODS: This is a single-centre, single-blinded, randomised controlled trial with a 1:1 allocation ratio. Patients will be randomised into two groups (control group and PVB group); 20 children will be enrolled in this trial, with 10 subjects in each group. Block randomisation will be performed. Patients aged 1-6 years, with the diagnosis of atrial and/or ventricular septal deficient And scheduled for cardiac surgery via a right thoracotomic incision, will be eligible for enrolment. The primary outcome is opioid consumption during the first 24 h after surgery. The main secondary outcomes include the perioperative stress response, inflammatory level, and intraoperative haemodynamics.

DISCUSSION: This is the first randomised clinical study investigating opioid-free anaesthesia based on PVB for paediatric congenital thoracotomy surgery with CPB. If the OPTION trial proves that opioid-free anaesthesia based on PVB is safe for children undergoing thoracotomic cardiac surgery, we would be glad to provide an OPTION for the perioperative management of these children, especially in the era of ERAS.

TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200066517 ( www.chictr.org.cn ), Registered on December 7, 2022.

PMID:41024258 | PMC:PMC12482201 | DOI:10.1186/s13063-025-09067-3