Res Sq [Preprint]. 2025 Sep 17:rs.3.rs-7556256. doi: 10.21203/rs.3.rs-7556256/v1.
ABSTRACT
Background: Disrupted cardiomyocyte energy metabolism is a hallmark of heart failure with preserved ejection fraction (HFpEF). Succinate, a key intermediate of the tricarboxylic acid cycle, is markedly decreased in HFpEF myocardium. Beyond its metabolic role, succinate functions as a signaling molecule that activates GPR91 to regulate metabolic and immune pathways. However, the precise contributions and mechanisms of cardiomyocyte succinate-GPR91 signaling in HFpEF pathogenesis remain largely unknown. Methods: HFpEF models were established in wild-type, global GPR91 knockout, and cardiomyocyte-specific GPR91 knockout mice with or without succinate supplementation. Cardiac structure, function, and metabolic phenotypes were assessed using echocardiography, histology, and molecular assays. Transcriptome sequencing of myocardial tissues was performed to identify succinate-GPR91-dependent signaling pathways. Mechanistic studies in isolated cardiomyocytes were conducted to validate pathway regulation and clarify downstream molecular mechanisms. Rescue experiments were further carried out to confirm the functional relevance of succinate-GPR91 signaling in cardiomyocyte metabolism and HFpEF progression. Results: Cardiac succinate levels and GPR91 expression were markedly decreased in HFpEF mice. Succinate supplementation restored systemic metabolism, improved diastolic function, and attenuated myocardial hypertrophy and fibrosis in wild-type (WT) HFpEF mice, but these protective effects were lost in both global Gpr91⁻/⁻ and cardiomyocyte-specific Gpr91 ΔCM knockouts. Transcriptomic analysis demonstrated that succinate activated AMPK signaling and enriched pathways related to glucose-lipid metabolism and NAD⁺ biosynthesis in Gpr91 fl/fl but not in Gpr91 ΔCM hearts. Mechanistically, succinate enhanced AMPK phosphorylation and NAD⁺ production via Gq-mediated signaling, thereby promoting metabolic reprogramming. Conclusion: These findings identify the succinate-GPR91 axis as a critical regulator of cardiometabolic homeostasis and a potential therapeutic target in HFpEF.
PMID:41001528 | PMC:PMC12458547 | DOI:10.21203/rs.3.rs-7556256/v1
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
Pediatr Cardiol. 2025 Sep 26. doi: 10.1007/s00246-025-04020-2. Online ahead of print.
ABSTRACT
Postoperative patients with complex congenital heart disease (CHD), such as those who have undergone Fontan procedures or Tetralogy of Fallot (TOF) repairs, often experience complications, including arrhythmias and heart failure. Heart rate variability (HRV) analysis assesses autonomic function and predicts cardiac outcomes; however, conventional linear methods have limitations, particularly in pediatric populations with variable heart rates. Nonlinear HRV analysis offers a robust alternative. This study evaluated the utility of nonlinear HRV indices to identify early autonomic dysfunction in postoperative patients with CHD. A total of 41 postoperative patients with CHD (22 Fontan, 19 TOF) and 34 age-matched healthy controls underwent 24-h electrocardiogram recordings during sleep. Frequency- and time-domain HRV indices were calculated, alongside nonlinear measures such as Poincaré plot analysis and Higuchi fractal dimension (HFD). Statistical analyses compared the groups and assessed correlations between HRV indices and clinical parameters. Patients who underwent TOF repairs exhibited significantly lower low frequency, high frequency, standard deviation of all normal R-R intervals, and the root mean square of successive differences between R-R intervals values than those in the control group. Nonlinear indices, particularly HFD, were unaffected by heart rate, enhancing reliability in pediatric populations. Age-related declines in fractal indices in postoperative patients with TOF repairs suggest progressive autonomic dysfunction. Nonlinear HRV analysis offers valuable insights into autonomic dysregulation in postoperative patients with CHD, surpassing conventional methods in reliability. These approaches may enable early detection of autonomic deterioration, improving risk stratification and guiding management. Further validation in larger cohorts is warranted.
PMID:41003713 | DOI:10.1007/s00246-025-04020-2
J Pers Med. 2025 Aug 25;15(9):397. doi: 10.3390/jpm15090397.
ABSTRACT
Background/Objectives: The application of additive manufacturing in medicine, and specifically in personalised medicine, has achieved notable development. This article aims to present the results and benefits of applying a comprehensive methodology to simulate, plan, and manufacture customised three-dimensional medical prosthetic devices for use in surgery to restore bone structures with congenital and acquired malformations. Methods: To digitally reconstruct a bone structure in three dimensions from a medical image, a segmentation process is developed to correlate the anatomical model. Then, this model is filtered using a post-processing step to generate stereolithography (STL) files, which are rendered using specialised software. The segmentation of tomographic images is achieved by the specific intensity selection, facilitating the analysis of compact and soft tissues within the anatomical region of interest. With the help of a thresholding algorithm, a three-dimensional digital model of the anatomical structure is obtained, ready for printing the required structure. Results: The described cases demonstrate that the use of anatomical test models, cutting guides, and customised prostheses reduces surgical time and hospital stay, and achieves better aesthetic and functional results. Using materials such as polylactic acid (PLA) for presurgical models, appropriate resins for cutting guides, and biocompatible materials such as polyether ether ketone (PEEK) or polymethylmethacrylate (PMMA) for prostheses, the described improvements are achieved. Conclusions: The achievements attained demonstrate the feasibility of applying these techniques, their advantages and their accessibility in Ecuador. They also reinforce the ideas of personalised medicine in the search for medical treatments and procedures tailored to the needs of each patient.
PMID:41003100 | PMC:PMC12471141 | DOI:10.3390/jpm15090397
J Cardiovasc Dev Dis. 2025 Sep 12;12(9):350. doi: 10.3390/jcdd12090350.
ABSTRACT
(1) Background: Myocardial bridging (MB) is a congenital coronary anomaly with potential clinical significance. Artificial intelligence (AI) applied to cardiac computed tomography angiography (CCTA), particularly through CT-derived fractional flow reserve (CT-FFR), offers a novel, non-invasive approach for assessing MB. (2) Methods: We conducted a systematic review of the literature focusing on studies investigating AI-enhanced CCTA in the evaluation of MB. (3) Results: Ten studies were included. AI-based models, including radiomics, demonstrated moderate to high accuracy in predicting proximal plaque formation, and motion correction algorithms improved image quality and diagnostic confidence. Other findings were limited by the types of studies included and conflicting findings across studies. (4) Conclusions: AI-enhanced CCTA shows promise for the non-invasive functional assessment of MB and its risk stratification. Further prospective studies and validation are required to establish standardized protocols and confirm clinical utility.
PMID:41002629 | PMC:PMC12470274 | DOI:10.3390/jcdd12090350
J Cardiovasc Dev Dis. 2025 Aug 28;12(9):330. doi: 10.3390/jcdd12090330.
ABSTRACT
Pentacuspid aortic valve is an exceptionally rare congenital anomaly that is often associated with functional deterioration and aortopathy. We report a case of a 39-year-old male presenting with severe aortic regurgitation and an ascending aortic aneurysm in the setting of a pentacuspid aortic valve. The patient underwent a successful Bentall and hemiarch replacement using a composite mechanical valved conduit. This case emphasizes the potential association between rare aortic valve morphologies and ascending aortic pathology and includes a brief review of the existing literature on the pentacuspid aortic valve.
PMID:41002609 | PMC:PMC12471185 | DOI:10.3390/jcdd12090330
J Surg Case Rep. 2025 Sep 24;2025(9):rjaf750. doi: 10.1093/jscr/rjaf750. eCollection 2025 Sep.
ABSTRACT
Congenital diaphragmatic hernia (CDH), a rare but potentially life-threatening anomaly resulting from incomplete diaphragm closure during fetal development, typically presents neonatally but can rarely manifest later in infancy as tension gastrothorax-a critical condition of intrathoracic gastric herniation and distension causing severe respiratory distress and mediastinal shift; we describe a 2-month-old male infant who developed sudden dyspnea and mediastinal shift due to a left-sided Bochdalek hernia with a distended stomach occupying the thoracic cavity, requiring emergent laparotomy with gastric decompression and defect repair using non-absorbable sutures, leading to full lung re-expansion and recovery; this case highlights the diagnostic and therapeutic challenges of late-presenting CDH complicated by tension gastrothorax, the importance of distinguishing it from other causes of respiratory distress, and emphasizes that prompt recognition, timely decompression, and surgical repair are vital for favorable outcomes, urging clinicians to maintain high suspicion when imaging reveals an air-filled hemithorax in distressed infants.
PMID:41000549 | PMC:PMC12459967 | DOI:10.1093/jscr/rjaf750