Trasplante cardíaco

Biomolecules. 2025 Sep 9;15(9):1298. doi: 10.3390/biom15091298.

ABSTRACT

INTRODUCTION: In renal transplant recipients (RTRs), kidney graft failure and cardiovascular (CV) disease are prevalent and associated with mortality.

OBJECTIVES: The objective of the study was to evaluate biomarkers, (cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP)), to identify RTRs who are at greater risk of death, CV event, and graft renal survival.

PATIENTS AND METHODS: A total of 342 stable RTRs were enrolled in this study, with a median follow-up time of 54 months. The probability of death, CV event, and renal graft survival were calculated using Kaplan-Meier analysis for the group defined by cTnT and NT-proBNP levels above the cutoff values.

RESULTS: The probability of death for troponin T level above the cut-off was 23% and for NT-proBNP 29%. For CV events the probability for troponin T was 20% and for NT-proBNP it was 21%. Troponin T concentrations above the cutoff point suggested a 25% probability of death-censored graft survival. For NT-proBNP, it was 26%. The probability of overall graft survival was 38% for patients with higher troponin T levels, and 40% for NT proBNP.

CONCLUSIONS: These data suggest that cTnT and NT-proBNP could potentially identify patients at high risk for death, CV event, and graft survival.

PMID:41008605 | PMC:PMC12467138 | DOI:10.3390/biom15091298

Biomedicines. 2025 Sep 3;13(9):2146. doi: 10.3390/biomedicines13092146.

ABSTRACT

Background/Objectives: Fulminant myocarditis (FM) is an uncommon but potentially reversible form of myocardial inflammation that can rapidly progress to cardiogenic shock (CS). In patients who are refractory to conventional treatment, venoarterial extracorporeal membrane oxygenation (VA-ECMO) represents an effective life support strategy. However, the factors that determine functional recovery remain uncertain. The primary objective of this study was to characterize patients who recover ventricular function. Secondary objectives included analyzing VA-ECMO-related complications and overall patient survival. Methods: This was a retrospective, single-center, observational study including all consecutive patients diagnosed with FM between 2008 and 2025 who were supported with VA-ECMO (n = 22). Clinical, biochemical, echocardiographic, and imaging variables were collected. Patients were classified based on their outcomes as either recovery or death/transplantation. Differential factors potentially affecting myocardial recovery, survival, and complications were analyzed. Results: The mean age was 49.7 ± 11 years, with 36% being male. Severe cardiogenic shock was the most common initial presentation (86%), and the average time from symptom onset to hospital admission was 5.7 days. Regarding mechanical support, the non-recovery group required longer ECMO support (328 ± 225 h vs. 188 ± 103 h; p = 0.03). The presence of fibrosis on cardiac magnetic resonance imaging (MRI) was associated with a lower probability of recovery (100% vs. 44.4%; p = 0.03). Renal failure and vascular complications were more frequent in the non-recovery group, with a significantly higher rate of surgical reintervention (50% vs. 10%; p = 0.04). Echocardiography performed before discharge (recovery group) vs. before death/transplant (non-recovery group) showed significant differences in left ventricular ejection fraction (51.1% vs. 29.5%; p = 0.04), along with better levels of creatinine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), leukocytes, and C-reactive protein (CRP) in the recovery group. In-hospital survival for the entire cohort was 63.6%, significantly higher in the recovery group (100% vs. 33.3%; p < 0.01). One-year survival was 59%, which was also greater among those who recovered (90% vs. 33.3%; p = 0.02). Conclusions: FM is associated with an acceptable in-hospital survival rate. The presence of myocardial fibrosis on MRI and longer ECMO support duration were observed to be associated with a lower likelihood of cardiac recovery. Patients who recovered showed better ventricular function at discharge, as well as reduced systemic inflammation and renal dysfunction. These findings highlight the importance of early identification of predictors of myocardial recovery to optimize management and therapeutic decision making in this high-risk population.

PMID:41007709 | PMC:PMC12467035 | DOI:10.3390/biomedicines13092146

Bioengineering (Basel). 2025 Aug 30;12(9):940. doi: 10.3390/bioengineering12090940.

ABSTRACT

Myocardial infarction-induced cardiovascular diseases remain a leading cause of mortality worldwide. Excessive post-infarct fibrosis contributes to adverse cardiac remodeling and the progression to heart failure. In vivo reprogramming strategies offer a promising avenue for heart regeneration by directly converting resident fibroblasts into cardiomyocytes through enforced expression of cardiogenic genes. This approach circumvents the need for invasive biopsies, cell expansion, induction of pluripotency, or autologous transplantation. Despite these advantages, key challenges persist, including low reprogramming efficiency and limited cellular targeting specificity. A critical factor for effective anti-fibrotic therapy is the precise and efficient delivery of reprogramming effectors specifically to fibrotic fibroblasts, while minimizing off-target effects on non-fibroblast cardiac cells and fibroblasts in non-cardiac tissues. In this review, we discuss the cellular and molecular mechanisms underlying in vivo cardiac reprogramming, with a focus on fibroblast heterogeneity, key transcriptional drivers, and relevant intercellular interactions. We also examine current advances in fibroblast-specific delivery systems employing both viral and non-viral vectors for the administration of lineage-reprogramming factors such as cDNA overexpressions or microRNAs. Finally, we underscore innovative strategies that hold promise for enhancing the precision and efficacy of cellular reprogramming, ultimately fostering translational development and paving the way for rigorous preclinical assessment.

PMID:41007184 | PMC:PMC12466987 | DOI:10.3390/bioengineering12090940

Diabetes Res Clin Pract. 2025 Sep 24:112923. doi: 10.1016/j.diabres.2025.112923. Online ahead of print.

ABSTRACT

BACKGROUND: Bariatric surgery causes changes in the levels of metabolically active hormones that control energy expenditure. This study aims to [1] validate a Roux-en-Y gastric bypass (RYGB) rat model in comparison to RYGB operated humans and [2] investigate the correlation of amino acids with GLP-1 and PYY levels in both species.

METHODS: Fasting plasma samples were derived from the randomized controlled WAS trial (NCT01352403; RYGB = 20, Controls = 17) at baseline and after 12 months and from male Wistar rats with diet-induced obesity seven weeks after surgery (RYGB = 12, sham surgery = 12). 18 peptide hormones and 21 amino acids were measured using magnetic multiplex assays, ELISA and LC-MS/MS.

RESULTS: Levels of GLP-1 and PYY3-36 were found to be significantly lower in humans after RYGB (both p < 0.001), while in rats a trend towards an increase was observed. Fasting insulin was found to be lower in humans (p < 0.001) and rats (p < 0.01) after RYGB. Leptin was significantly lower in humans (p < 0.001) and rats (p < 0.05) after RYGB. The cytokines IL-6 and MCP-1 were significantly lower in humans (p < 0.01, p < 0.05), but unchanged in rats after RYGB. Interestingly, GLP-1 levels in humans before RYGB correlated positively with the weight change after 12 months (Pearson's r = 0.733;p < 0.05). Leucine showed a positive correlation with GLP-1 levels 12 months after RYGB in humans (Pearson's r = 0.588;p < 0.05), but not in rats.

CONCLUSION: Preoperative GLP-1 levels in humans correlate with weight loss after RYGB and could potentially be predictive. The investigated rat model shows largely comparable patterns of incretins and adipokines. Given its physiological similarity, this model is suitable for testing pharmacological agents that mimic anorexigenic hormones, potentially guiding novel treatments for severe obesity.

PMID:41005747 | DOI:10.1016/j.diabres.2025.112923

Thromb Res. 2025 Sep 22;255:109493. doi: 10.1016/j.thromres.2025.109493. Online ahead of print.

ABSTRACT

INTRODUCTION: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, prompting increasing use of antiplatelet agents for primary and secondary prevention. Despite guidelines from multiple professional societies on the perioperative management of antiplatelet agents, we hypothesized that their implementation varies, leading to inconsistencies in perioperative practices across the United States (US).

METHODS: We surveyed eleven members of the Systems-Based Hematology Committee of the Venous ThromboEmbolism Network US (VENUS) to gather their institutions' guidelines on the perioperative management of antiplatelet agents for non-cardiac surgery. Institutional guidelines were compared with five professional society guidelines.

RESULTS: Of the 11 academic medical centers (AMCs), 8 (72.7 %) had institutional guidelines on perioperative management of antiplatelet agents (aspirin and three P2Y12 inhibitors) prior to non-cardiac surgery. Of the remaining three, two had guidelines on the management of antiplatelet agents prior to interventional radiology procedures (n = 1) and for neuraxial anesthesia (n = 1). Five AMCs gave differing recommendations on managing phosphodiesterase inhibitors perioperatively, while none of the five society guidelines addressed them. Five AMCs provided variable recommendations on the timing of postoperative resumption of antiplatelet agents ranging from as soon as possible to 12-24 h postoperatively depending on bleeding risk. Only two AMCs provided recommendations for those on antiplatelet agents who have life-threatening peri-operative bleeding or undergoing urgent high-bleeding risk surgery.

CONCLUSION: AMCs vary in their recommendations on the perioperative management of antiplatelet agents prior to non-cardiac surgery. Further research is needed to determine if this variability impacts patient outcomes and to identify ways to improve guideline implementation.

PMID:41005027 | DOI:10.1016/j.thromres.2025.109493

Int J Cardiovasc Imaging. 2025 Sep 26. doi: 10.1007/s10554-025-03522-7. Online ahead of print.

ABSTRACT

Myocardial work indices (MW) have been validated with respect to their efficiency for predicting cardiac events in patients with heart failure. However, the measurement of MW requires specific vendor software that may not be ubiquitous accessible. We aimed to explore the feasibility of using a nonproprietary method, peak myocardial work index (PMW) = systolic blood pressure * global longitudinal strain, as a potential substitute to global constructive work (GCW) for the assessment of left ventricular function. A retrospective analysis of 116 patients with dilated cardiomyopathy (DCM) and an equal number of age- and sex-matched healthy controls examined from June 2009 to July 2014 was conducted. Compared to healthy controls, the PMW index and GCW were significantly lower in DCM patients: 1371 ± 541 vs. 2520 ± 361 mm Hg%, 1318 ± 502 vs. 2322 ± 333 mm Hg%, respectively (p < 0.001 for each). Additionally, PMW showed an excellent correlation with GCW (r = 0.99, p < 0.001). During a mean follow-up time of 5.1 years, 34 patients (29.3%) reached the composite endpoints: 5 patients received cardiac transplantation, 17 patients were hospitalized due to heart failure, 9 patients received appropriate ICD therapy and 3 patients died. PMW per 50 mm Hg% increase (HR = 0.92, 95%CI 0.89-0.96, p < 0.001) and GCW per 50 mm Hg% increase (HR = 0.91, 95%CI 0.88-0.95, p < 0.001) performed comparably in predicting adverse outcomes in DCM patients in the univariate Cox regression analyses. PMW and GCW were the independent prognostic factors after adjusting for significant parameters of the univariate analysis. Patients with PMW < 1,286 mm Hg% (HR = 3.71, 95%CI 1.18-11.63, p = 0.025) and GCW < 1,238 mm Hg% (HR = 4.8, 95%CI 1.57-14.68, p = 0.006) had higher risks of MACE. PMW index might serve as an alternative echocardiographic method for evaluating left ventricular systolic function, providing similar diagnostic and prognostic capacity comparable to GCW.

PMID:41003949 | DOI:10.1007/s10554-025-03522-7

JACC Case Rep. 2025 Sep 26:105530. doi: 10.1016/j.jaccas.2025.105530. Online ahead of print.

ABSTRACT

OBJECTIVE: To present the surgical management of a 22-year-old patient with midaortic syndrome, symptomatic for claudication and renovascular hypertension, with infected aortic and renal stent grafts.

KEY STEPS: Procedures were performed as follows: 1) right renal autotransplantation through a transperitoneal approach and midline abdominal incision; 2) thoracotomy with left visceral rotation and visceral vessel exposure; 3) left-heart bypass and "debranch-first" technique, with warm blood perfusion for the splanchnic vessels and cold Custodiol solution for renal perfusion; 4) aortic replacement with a tubular xenopericardium graft; and 5) separate reattachment of visceral vessel to the main tubular graft.

POTENTIAL PITFALLS: Recurrent infections of the xenopericardium graft, kidney parenchyma loss, and major complications such as spinal cord ischemia, represent potential pitfalls to this procedure.

TAKE-HOME MESSAGE: Kidney autotransplantation allows right renal-infected stent graft removal before in situ thoracoabdominal reconstruction through left thoracoabdominal access, preserving renal function against renovascular hypertension.

PMID:41003453 | DOI:10.1016/j.jaccas.2025.105530

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

ABSTRACT

BACKGROUND: Despite its use in patients awaiting heart transplant (HT), the impact of continuous inotropic support on short-term complications and long-term transplant outcomes remains unclear. This study evaluated inotrope use at the time of HT on perioperative complications and post-transplant survival, comparing outcomes at 30 days, 1 year, and 10 years with mechanical circulatory support (MCS) strategies including ECMO, IABP, and VADs.

METHODS: A retrospective analysis of the United Network for Organ sharing (UNOS) registry was performed, stratifying patients based on bridge strategy at the time of transplant: inotropes, ECMO, IABP, or VADs. Baseline characteristics, perioperative complications, and 30-day, 1-year, and 10-year post-transplant survival outcomes were analyzed across groups. Survival was assessed using Kaplan-Meier and Cox proportional hazards models.

RESULTS: Among the 11,801 heart transplant patients included, 9330 were on inotropes, 372 were on ECMO, 1072 received an IABP, and 1027 had VADs. Inotrope-bridged patients had significantly lower 30-day and 1-year mortality rates compared to the ECMO, IABP, and VAD groups. They also experienced reduced incidences of post-transplant dialysis and stroke. At 10 years, the inotrope group demonstrated superior long-term survival, with significantly lower mortality risk compared to ECMO (HR: 1.81; CI: 1.49-2.20, p < 0.001), IABP (HR: 1.19; CI: 1.06-1.32, p = 0.005), and VAD (HR: 1.18; CI: 1.10-1.27, p < 0.001).

CONCLUSIONS: Continuous use of inotropes after waitlisting is associated with lower short, intermediate, and long-term mortality and does not lead to worse outcomes compared to ECMO, IABP, and VAD support. When mechanical support is not an option, inotropic therapy remains a viable and effective strategy.

PMID:41002643 | PMC:PMC12471187 | DOI:10.3390/jcdd12090364

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

ABSTRACT

BACKGROUND: Beyond its established inotropic effects, levosimendan has been reported to enhance renal function in patients with chronic heart failure. In this study, we investigated whether changes in renal function following levosimendan administration in patients listed for heart transplantation were associated with early post-transplant renal outcomes.

METHODS: We retrospectively analyzed data from 99 patients with advanced heart failure and renal insufficiency (eGFR < 90 mL/min/1.73 m2) who were listed for heart transplantation and received levosimendan therapy within 1 to 6 months prior to transplantation. Renal function was assessed immediately before and 24 h after levosimendan administration. A favorable renal response was defined as any increase in eGFR at 24 h. Post-transplant renal function was evaluated on postoperative days 1 and 7 using standard renal function parameters.

RESULTS: Favorable renal response to levosimendan prior to heart transplantation was present in 73 of 99 patients (74%, Group A), and 26 patients (26%) displayed no increase in eGFR (Group B). In the first week after heart transplantation, we found a significant improvement in renal function in Group A (ΔeGFR: +14 ± 3 mL/min/1.73 m2, p < 0.001), and worsening of renal function in Group B (ΔeGFR: -4 ± 3 mL/min/1.73 m2, p < 0.01). Favorable response to levosimendan prior to heart transplantation was an independent correlate of improved renal function after heart transplantation (p = 0.01).

CONCLUSION: In patients awaiting heart transplantation, improvement in renal function after levosimendan therapy was associated with better early post-transplant renal outcomes. Levosimendan response may thus help identify reversible renal dysfunction and serve as a simple tool for transplant evaluation.

PMID:41002636 | PMC:PMC12470588 | DOI:10.3390/jcdd12090357

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

ABSTRACT

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

PMID:41002630 | PMC:PMC12471063 | DOI:10.3390/jcdd12090351

Eur J Prev Cardiol. 2025 Sep 26:zwaf617. doi: 10.1093/eurjpc/zwaf617. Online ahead of print.

ABSTRACT

AIMS: Exercise training (ET) provides numerous benefits for heart transplant (HTx) recipients. However, direct comparisons between ET modalities remain limited. This study aims to compare the efficacy and safety of multiple ET modalities on peak oxygen consumption (peak VO2) and key secondary outcomes in HTx recipients.

METHODS AND RESULTS: We systematically searched eight electronic databases from inception to September 2024. Traditional random-effects models and Bayesian network meta-analysis were employed. Confidence in the results was evaluated using the Confidence in Network Meta-Analysis (CINeMA) tool. Thirteen randomized controlled trials involving 473 HTx recipients were analyzed. The network meta-analysis identified high-intensity interval training (HIIT) (mean difference [MD]: 4.34 ml.kg⁻¹.min⁻¹; 95% credible interval [CrI], 1.41 to 5.6) and combined training (CT) (MD: 3.49 ml.kg⁻¹.min⁻¹; 95%CrI, 1.15 to 7.44) as the most effective interventions for improving peak VO2 compared to usual care. HIIT was also more effective than moderate-intensity continuous training (MICT) (MD: 2.09 ml.kg⁻¹.min⁻¹; 95%CrI, 0.05 to 4.03). No significant differences were observed between MICT, home-based MICT, home-based CT, and usual care. The certainty of evidence ranged from moderate to very low across comparisons. No significant differences were observed between ET modalities regarding heart rate response or ventilatory efficiency. ET was associated with improvements in specific quality of life subdomains. No exercise-related adverse events were reported.

CONCLUSION: This review demonstrates that ET significantly improves peak VO₂ in HTx recipients, with HIIT and CT outperforming usual care. HIIT also surpasses MICT in improving peak VO2. Overall, ET modalities are safe and effective for this population.

PMID:41002251 | DOI:10.1093/eurjpc/zwaf617

medRxiv [Preprint]. 2025 Sep 18:2025.09.15.25335831. doi: 10.1101/2025.09.15.25335831.

ABSTRACT

BACKGROUND: Cardiac acute rejection (AR) is a risk factor for poor outcomes, however there are limited risk prediction models to stratify patients for death or sustained LV dysfunction. This study assesses the prognostic utility of percentage donor-derived cell-free DNA (%dd-cfDNA) at the diagnosis of AR for poor outcomes.

METHODS: The prospective multicenter GRAfT study enrolled heart transplant recipients and collected serial plasma samples to quantitate %dd-cfDNA. AR was defined as acute cellular rejection (ACR), antibody-mediated rejection (AMR), as well as biopsy-negative AMR (donor-specific antibody positivity with LV dysfunction). AR was classified as mild-to-moderate (ACR grade 2 or AMR grade 1) or severe (ACR grade ≥3, AMR grade ≥2, or DSA+/LV dysfunction) and further stratified by a %dd-cfDNA threshold of 0.25%. Regression models assessed the association between AR and %dd-cfDNA levels at the AR diagnosis with the primary composite outcome of sustained LVEF decline <50% and/or death.

RESULTS: The study included 275 patients and 3,190 %dd-cfDNA assessments. Over the median of 4.6 (IQR 1.8 - 5.0) years follow-up, 51 patients experienced the composite outcome of death or prolonged EF reduction, and 75 patients developed AR, including 16.2% patients with ACR, 9.4% with pathologic AMR, and 6.6% with DSA+/LV dysfunction. Thirty-two (42.7%) patients had severe AR and 43 (57.3%) had mild-to-moderate AR. Severe-but not mild-to-moderate- AR was associated with an increased risk of the primary composite endpoint (HR = 5.17, 95% CI 2.38 - 11.3, p < 0.001). Among those with severe AR, a %dd-cfDNA level greater than 0.25% at diagnosis was associated with a higher risk of the primary outcome (HR, 6.06, 95% CI, 1.78- 20.6; p = 0.004). Percent dd-cfDNA remained elevated in severe AR patients with adverse outcomes.

CONCLUSION: Severe AR with high %dd-cfDNA levels is associated with an increased risk of poor outcomes, offering novel prognostic utility.

CLINICAL PERSPECTIVE: What is New?: Percent donor-derived cell-free DNA (%dd-cfDNA) can risk stratify cardiac transplant patients with severe acute rejection for death and/or prolonged EF reductionPercent dd-cfDNA remain persistently elevated in patients with severe acute rejection who develop poor outcomes, which could reflect ineffective treatment.In the contemporary era of cardiac transplantation, acute rejection defined by biopsy or by donor specific antibodies plus LV dysfunction is associated with poor outcomesWhat are the Clinical Implications?: Percent dd-cfDNA could serve as a bedside tool to risk stratify patients with severe acute rejection for poor outcomes.Trends of %dd-cfDNA could serve to monitor response to treatment for severe acute rejection.Percent dd-cfDNA levels at diagnosis of rejection could be leveraged for patient selection in clinical trials to test novel therapies or treatment strategies.

PMID:41001507 | PMC:PMC12458610 | DOI:10.1101/2025.09.15.25335831

medRxiv [Preprint]. 2025 Sep 15:2025.09.12.25335606. doi: 10.1101/2025.09.12.25335606.

ABSTRACT

BACKGROUND: In the United States heart allocation system, when transplant centers submit applications for status exceptions to increase waitlist priority, patients obtain the requested status upgrades immediately while their applications are sent to the regional review boards (RRBs) and reviewed retrospectively. How much time elapses between obtaining a status upgrade through exception and application receipt by the RRBs and how often transplants occur during this period is unknown.

METHODS: Using the Scientific Registry of Transplant Recipients (SRTR), we identified all adult heart transplant candidates listed between October 18, 2018 and December 31, 2023 with submitted applications for status exceptions. We assessed 1) the amount of time elapsed between submission of exception applications and their receipt by the RRBs and 2) the rate of heart transplantation during this "travel" time, stratified by whether the applications were eventually approved or denied. Additionally, using complete match run data, we estimated how many listed patients were skipped by candidates who received transplants with exceptions that were ultimately denied.

RESULTS: 135 transplant centers submitted status exception requests on behalf of 8,269 adult candidates during the study period, of whom 608 (7.4%) received a denial at least once. The median time from obtaining higher priority statuses immediately via exceptions to application receipt by the RRBs was 3 days. 2,087 out of 8,269 (25.2%) patients received transplants before the RRBs even received their applications, with 115 (18.9%) among 608 with eventual denials and 1,972 (25.7%) among 7,661 with approvals. The cumulative incidence of heart transplantation before application receipt for eventual denials was 19.1% (95% CI [16.0%, 22.3%]) and that for approvals was 26.2% (95% CI [25.2%, 27.1%]) (p < 0.001) at 2 weeks. Based on match run data, the 115 patients who received transplants with denied exceptions bypassed more than seven thousand potential transplant recipients.

CONCLUSIONS: More than 25% of patients with status exception requests receive heart transplants before their applications are even received by their respective RRBs, let alone reviewed. This raises significant concerns about the efficacy and fairness of retrospective review of exception requests for the allocation of valuable donor hearts.

PMID:41001456 | PMC:PMC12458605 | DOI:10.1101/2025.09.12.25335606

United European Gastroenterol J. 2025 Sep 26. doi: 10.1002/ueg2.70119. Online ahead of print.

ABSTRACT

INTRODUCTION: Since the publication of the first European Society for the Study of Coeliac Disease (ESsCD) guidelines in 2019, significant advancements have emerged in the diagnosis of coeliac disease (CeD) in adults. These 2025 guidelines incorporate new evidence to refine diagnostic strategies, aiming for improved accuracy of testing, and enhance overall quality of clinical care.

METHODS: A multidisciplinary panel of experts revised the ESsCD guidelines using the AGREE II instrument (Appraisal of Guidelines for Research and Evaluation II) and the GRADE methodology (The Grading of Recommendations Assessment, Development, and Evaluation). Clinical questions were structured using the PICO format, and statements and recommendations were finalised through a Delphi consensus process. Literature quality was assessed using AMSTAR-2 and QUADAS-2 tools.

RESULTS: The updated guidelines are presented in two parts. Part 1 focuses on adult CeD diagnosis, introducing major changes such as a conditional no-biopsy approach for selected adults with high-titre IgA anti-TG2 serology (≥ 10 × ULN). Regarding serology, the use of validated high-performance ELISAs displaying a high diagnostic accuracy is emphasised, while routine use of IgA anti-Endomysium serology is no longer recommended for confirmation. Revised duodenal biopsy protocols now mandate at least four samples from the second part of the duodenum, with bulb biopsies conditionally included. The guidelines provide structured approaches for diagnosing potential CeD, seronegative villous atrophy, and CeD in individuals already on a gluten-free diet. HLA-DQ2/DQ8 typing is recommended for diagnostic clarification in select cases.

CONCLUSIONS: The updated 2025 ESsCD guidelines provide a comprehensive framework for the diagnosis of CeD in adults. By integrating evolving diagnostic strategies, minimising over-testing, and patient-centred care approaches, they aim to optimise patient outcomes, quality of life and use of diagnostic resources at the same time.

PMID:40999951 | DOI:10.1002/ueg2.70119

Kidney Blood Press Res. 2025 Sep 18:1-25. doi: 10.1159/000548172. Online ahead of print.

ABSTRACT

Introduction Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease and mortality. However, data on the prediction of long-term adverse outcomes in advanced predialysis CKD patients is lacking. Methods We studied the factors associated with mortality and major adverse cardiovascular and cerebrovascular events (MACCE, including cardiovascular death, myocardial infarction, stroke and coronary revascularization) in a cohort of 210 patients with non-dialysis CKD stage 4-5 during a five-year follow-up. The participants underwent stress ergometry testing to study maximal exercise capacity (Wmax%), a plain lateral abdominal radiograph to study abdominal aortic calcification score (AAC) and laboratory tests including cardiac troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (ProBNP). Furthermore, a dichotomous composite covariate was created and explored by combining ProBNP and Wmax% using the cut-offs determined with the Youden index. The associations between covariates of interest and study outcomes were explored using multivariable Cox proportional hazards models adjusted with age, sex, coronary artery disease (CAD) and incident kidney transplantation (KTx). Results Median age at baseline was 65 (52-73) years and eGFR 12 (10-15) ml/min/1.73 m2, 34.8 % were female and 44.8 % had diabetes. Altogether 67 (31.9 %) patients died during follow-up and 65 (31.0%) were observed with a MACCE. In separate multivariable Cox proportional hazards models adjusted for age, gender, CAD and KTx, Wmax% (HR 0.983 [95 % CI: 0.968-0.999], p=0.019), TnT (HR 1.004 [95 % CI: 1.002-1.005], p<0.001 and) and ProBNP (HR 1.036 per 1000 ng/l [95 % CI: 1.014-1.059], p=0.002 were independently associated with mortality. In similarly adjusted multivariable Cox models Wmax% (HR 0.977 [95 % CI: 0.962-0.992], p=0.003), TnT (HR 1.004 [95 % CI: 1.002-1.005], p<0.001) and ProBNP (HR 1.034 per 1000 ng/l [95 % CI: 1.010-1.058], p=0.006) were independently associated with the occurrence of MACCE during follow-up. AAC was associated with the risk of an incident MACCE (HR 1.080 [95% CI 1.028-1.135], p=0.002) but, surprisingly, not with mortality (HR 1.046 [95% CI 0.994-1.101], p=0.083). Finally, in participants with Wmax ≤50 % and ProBNP ≥1270 ng/l the risk of mortality (HR 8.760 [95 % CI: 4.730-16.222], p<0.001) and MACCE (HR 3.293 [95 % CI: 1.850-5.862], p<0.001) was significantly greater than those with Wmax>50% and/or ProBNP <1270 ng/L. Conclusion Wmax% and ProBNP separately and together as a composite risk factor may serve as important predictors of long-term all-cause mortality and MACCE in patients with CKD stage 4-5 not undergoing dialysis at baseline.

PMID:40999822 | DOI:10.1159/000548172

Crit Care. 2025 Sep 25;29(1):404. doi: 10.1186/s13054-025-05636-9.

ABSTRACT

BACKGROUND: ECMO outcomes in COVID-19-related respiratory failure among solid organ transplant (SOT) and hematopoietic stem-cell transplant recipients (HSCT) are poorly described. We investigated: (1) whether transplant patients (SOT/HSCT) with COVID-19 have worse outcomes than non-immunocompromised (IC) COVID-19 patients, and (2) whether among transplant recipients (SOT/HSCT), those with COVID-19 have worse outcomes than those with non-COVID-19-related respiratory failure. Additionally, we aimed to identify factors independently associated with mortality among COVID-19 transplants.

METHODS: Retrospective analyses of the Extracorporeal Life Support Organization Registry from 1/1/2017 to 31/07/2023. Two comparisons were made: (1) transplant COVID-19 versus non-IC COVID-19, and (2) transplant COVID-19 versus transplant non-COVID-19 patients. Outcomes were analyzed using propensity score (PS)-adjusted, multivariable, and PS-matched analyses, adjusting for a priori identified confounders. Primary outcome was in-hospital mortality.

RESULTS: Among 38,270 runs, 146 transplant COVID-19, 12,552 non-IC-COVID-19 and 886 transplant non-COVID-19 runs were identified. In-hospital mortality in transplant COVID-19 patients was 75.3% and the risk was invariably increased compared to non-IC-COVID-19 (PS-adjusted OR: 2.36 [95%CI:1.61-3.46], p < 0.001, multivariable OR:2.35 [95%CI:1.59-3.49], p < 0.001, and PS-matched analysis OR: 1.89 [95%CI:1.21-2.95], p < 0.005) and transplant non-COVID-19 patients (PS-adjusted OR: 4.20 [95%CI:2.74-6.44], p < 0.001, multivariable OR: 3.79 [95%CI:2.51-5.74], p < 0.001, and PS-matched analyses OR: 3.17 [95%CI:1.90-5.28], p < 0.001). Mortality difference remained stable over time. Older age independently associated with higher mortality. This was accompanied by higher need for renal replacement therapy compared to non-IC-COVID-19 patients. Compared to transplant non-COVID-19 patients, ECMO runs and time-to-live discharge were invariably prolonged. Hemorrhagic, metabolic, pulmonary and infectious complications consistently occurred more frequently.

CONCLUSIONS: Mortality was high in COVID-19 transplant ECMO patients, warranting cautious use of ECMO in this population.

PMID:40999467 | PMC:PMC12465718 | DOI:10.1186/s13054-025-05636-9

BMC Pulm Med. 2025 Sep 25;25(1):428. doi: 10.1186/s12890-025-03897-2.

ABSTRACT

PURPOSE: Antifibrotics (AF) attenuate the progression of fibrotic interstitial lung disease (ILD), but it is unknown if these drugs affect the progression of pulmonary hypertension (PH) in patients with ILD. We explored whether use of AF therapy was associated with a lower rate of change of mean pulmonary artery pressure (mPAP) in patients with ILD listed for lung transplantation (LTx).

METHODS: All LTx recipients at Inova Fairfax Hospital from 2012 to 2023 with a pre-LTx diagnosis of ILD qualified for the analysis. Demographic data, mPAP at the time of LTx listing, intra-operative mPAP during lung transplantation, use of AF and PH therapy, spirometry, and 6-minute walk test data were collated. 153 patients were included the analysis. The mPAP rate of change (mmHg/month) was compared between patients based on the administration of AF in the pre-LTx period.

RESULTS: The mPAP average rate of change was 0.9 mmHg/month for the AF group and 0.7 mmHg/month for the no AF group (p = 0.504). On multivariate analysis, age and the use of PH therapy were associated with mPAP rate of change. After accounting for these factors, AF usage was not associated with mPAP rate of change (p = 0.194). Additionally, AF usage was not found to augment the effects of PH therapy on mPAP change. Age was associated with a faster rate of change of mPAP, and PH therapy was associated with slower rate of change in mPAP.

CONCLUSION: AF therapy was not associated with a lower rate of change in mPAP in patients with ILD listed for LTx.

PMID:40999443 | PMC:PMC12465658 | DOI:10.1186/s12890-025-03897-2

BMC Microbiol. 2025 Sep 25;25(1):588. doi: 10.1186/s12866-025-04302-y.

ABSTRACT

Coronary heart disease (CHD) and depression often coexist and complicate patient care. The gut microbiota plays a crucial role in overall health and is involved in both conditions. Dysbiosis, particularly, increased levels of lipopolysaccharides (LPSs), can activate the Toll-like receptor 4 (TLR4), triggering inflammatory pathways associated with CHD and depression. Although some associations have been observed, the direct mechanistic association among gut dysbiosis, LPSs, TLR4 activation, and comorbidity of CHD and depression remains unclear. Thus, in the present study, we aimed to explore this association and the potential of modulating gut microbiota as a therapeutic strategy. METHODS: A rat model of CHD and depression was established using a high-fat diet and chronic unpredictable mild stress and verified by electrocardiogram, behavioral assessments, and cardiac marker analysis. Fecal microbiota transplantation (FMT) was performed by transferring microbiota from diseased rats to healthy rats (FMT-Disease group); the fecal microbiota of the rats from the FMT-Disease and FMT-Normal groups were compared. The TLR4 inhibitor TAK-242 was administered, creating the Disease + TAK-242 and FMT-Disease-TAK-242 groups. Gut microbiota composition was analyzed using 16 S rRNA high-throughput sequencing; LPS levels were measured using enzyme-linked immunosorbent assay. Polymerase chain reaction and western blotting were used to detect the expression of genes and proteins related to the TLR4/MYD88/NF-κB pathway in the heart and hippocampus, respectively. RESULTS: We confirmed that in the FMT-Disease group, the gut microbiota of diseased rats altered the gut microbial composition of healthy rats in terms of β-diversity, α-diversity, and community structure. Notably, LPS levels in the serum of FMT-Disease rats were elevated, thereby activating the TLR4/MYD88/NF-κB inflammatory pathway and increasing susceptibility to CHD comorbid with depression. Additionally, after receiving fecal microbiota from healthy rats, the Disease group showed a restoration of gut microbiota balance, improvement in general condition, and normalization of pathological, biochemical, and inflammatory indicators, indicating a suppressive effect on the progression of CHD with depression. CONCLUSION: Our findings further clarify the interrelationship between gut microbiota and CHD comorbid with depression, enhancing our understanding of its pathogenesis. Moreover, we propose a potential novel therapeutic strategy that focuses on modulating gut microbiota composition to block the TLR4/MYD88/NF-κB inflammatory pathway.

PMID:40999363 | PMC:PMC12465150 | DOI:10.1186/s12866-025-04302-y

BMC Cardiovasc Disord. 2025 Sep 25;25(1):660. doi: 10.1186/s12872-025-05101-z.

ABSTRACT

BACKGROUND: Bariatric surgery is recognized as a viable strategy for treatment of severe obesity in organ transplant recipients. There are limited reports regarding the surgical experience of bariatric surgery in patients who have undergone heart transplantation.

CASE PRESENTATION: A 42-year-old male heart transplant recipient with Class II obesity underwent laparoscopic sleeve gastrectomy (LSG) at Namazi Tertiary Hospital in Shiraz, Iran, to manage post-transplant weight gain and mitigate cardiac transplant rejection risks. Post-operatively, the patient showed notable improvements in cardiac structure and function, including decreased left ventricular dimensions and enhanced tricuspid annular plane systolic excursion. Metabolic parameters stabilized, exemplified by normalized fasting blood sugars and reduced HbA1c levels. Improvements in liver and kidney function also allowed for lowered immunosuppressant dosages. These results demonstrate the potential of LSG to not only enhance cardiac function and metabolic stability but also reduce the need for immunosuppression, underscoring its viability as a strategy to improve transplant outcomes and quality of life.

CONCLUSION: The case highlights the importance of collaborative care and further research to assess long-term benefits in similar patient populations.

PMID:40999349 | PMC:PMC12465320 | DOI:10.1186/s12872-025-05101-z

Ann Intensive Care. 2025 Sep 25;15(1):139. doi: 10.1186/s13613-025-01560-x.

NO ABSTRACT

PMID:40999100 | PMC:PMC12463790 | DOI:10.1186/s13613-025-01560-x