Biomedicines. 2025 May 29;13(6):1335. doi: 10.3390/biomedicines13061335.
ABSTRACT
Background: Right ventricular primary graft dysfunction (RV-PGD) is a rare but serious complication following heart transplantation, associated with a high morbidity and mortality. Temporary mechanical circulatory support is indicated when patients fail to respond to pharmacological therapy. This study aimed to evaluate the outcomes of patients with RV-PGD who received RV mechanical support with the Impella RP Flex device at our institution. Methods: Medical records of patients with RV-PGD supported by the Impella RP Flex device between December 2022 and March 2024 were reviewed retrospectively to assess survival, procedural complications, duration of support, and end organ dysfunction. Results: Of the 20 patients reviewed, 5 met the inclusion criteria. All five patients demonstrated recovery of RV function after a mean support duration of 8.6 ± 3.05 days. One pump showed transient evidence of biologic material ingestion during a weaning trial. No cases of tricuspid valve injury were observed. The most common complications were hemolysis, bleeding, and acute kidney dysfunction, with all patients requiring hemodialysis. Conclusions: Impella RP Flex support is safe and effective for managing primary and isolated RV-PGD without the need for additional blood oxygenation. However, bleeding complications requiring intervention remain a significant concern, and further evaluation of renal recovery is warranted.
PMID:40564056 | PMC:PMC12190657 | DOI:10.3390/biomedicines13061335
Pediatr Transplant. 2025 Aug;29(5):e70123. doi: 10.1111/petr.70123.
ABSTRACT
BACKGROUND: Partial heart transplantation (PHT) is a promising procedure for pediatric patients with irreparable semilunar valve disease. Current immunosuppression regimens mirror orthotopic heart transplant (OHT) protocols. However, semilunar valves may have immune privilege, making true immunosuppressive requirements unclear. This study examines the effect of rejection on semilunar valves in OHT to inform immunosuppression strategies for PHT.
METHODS: We conducted a single-center retrospective case-control study of pediatric OHT recipients from 2008 to 2023. Patients were grouped by the presence or absence of rejection episodes, with further stratification by rejection severity. Semilunar valve function was assessed via echocardiography at baseline, during, and after rejection episodes. Subgroup analysis was performed based on rejection severity and age at transplant (< 1 year of age).
RESULTS: Of 113 eligible OHT recipients, 57 had ≥ 1 rejection episodes (32 high-grade). Baseline valve function was comparable between rejection and non-rejection groups. After a 3.8-year median follow-up, there were no significant differences in aortic or pulmonary valve gradients or in the prevalence of clinically significant regurgitation between groups. Paired analysis during rejection demonstrated no change in valve function compared to pre-rejection assessment. Similar findings were observed in infants transplanted < 1 year of age.
CONCLUSIONS: Over a median follow up of nearly 4 years, semilunar valve function in pediatric OHT recipients remained clinically unaffected by rejection, even in high-grade cases and among younger patients. These findings support the hypothesis of semilunar valve immune privilege and suggest that intensive immunosuppression may not be necessary to preserve valve function after PHT.
PMID:40563161 | PMC:PMC12198430 | DOI:10.1111/petr.70123
BMJ Open. 2025 Jun 25;15(6):e100553. doi: 10.1136/bmjopen-2025-100553.
ABSTRACT
INTRODUCTION: Ischaemia-reperfusion (I/R) injury remains a major challenge in heart transplantation, with mortality risk increasing significantly when allograft ischaemic time exceeds 4 hours. Non-ischaemic heart preservation (NIHP), using continuous hypothermic perfusion, has shown promise in preliminary studies for reducing I/R injury and improving outcomes. This randomised controlled trial aims to compare NIHP with standard static cold storage (SCS) in adult heart transplantation.
METHODS AND ANALYSIS: The trial is a prospective, open-label, multicentre, single-blinded, randomised controlled trial including 66 adult heart transplant recipients across four Swedish hospitals. Participants will be randomised into 1:1 ratio to NIHP or SCS preservation groups and undergo a 12-month follow-up period. The primary outcome is 1-year survival free from acute cellular rejection or retransplantation. Secondary outcomes include quality of life, I/R injury markers, graft function and adverse events. Substudies will evaluate renal function using MRI and continuously monitor physical activity and heart rhythm via wearable devices. Analysis will follow intention-to-treat principles, with time-to-event analysis using Cox proportional hazard models and Kaplan-Meier estimates.
ETHICS AND DISSEMINATION: The study has been approved by the Swedish Ethical Review Authority. It will be conducted according to the Declaration of Helsinki and relevant local and international regulations. Results will be published in peer-reviewed journals following Consolidated Standards of Reporting Trials guidelines.
TRIAL REGISTRATION NUMBER: NCT04066127.
PMID:40562558 | PMC:PMC12198846 | DOI:10.1136/bmjopen-2025-100553
Rev Esp Cardiol (Engl Ed). 2025 Jun 23:S1885-5857(25)00190-2. doi: 10.1016/j.rec.2025.04.011. Online ahead of print.
ABSTRACT
Introduction and objectives This report presents updated data on heart transplants in Spain, including procedures carried out in 2024. It reviews trends over the past decade (2015-2024) in donor and recipient characteristics, surgical techniques, immunosuppression strategies, and survival rates. Methods Data were drawn from the Spanish heart transplant registry, which is updated annually. The analysis includes 347 transplants performed in 2024, as well as procedures from 2015 to 2023 (n = 2721). Results In 2024, the number of heart transplants increased by 6.8% compared with 2023. There were no significant changes in recipient age or sex, but the proportion of urgent transplants rose to 47.0%. Use of circulatory support devices increased, particularly extracorporeal membrane oxygenation. The average donor age showed a slight increase in 2024, although the long-term trend remained downward. Donation after circulatory death accounted for 29.1% of transplants in 2024. One-year survival rates improved, reaching 85.2% for transplants performed between 2021 and 2023. Conclusions The number of heart transplants continued to grow, nearing historic highs, largely due to the expansion of donation after circulatory death. Improved 1-year survival reflects the maturity of transplant programs, advances in surgical and medical management, and better pretransplant conditions in recipients. Full English text available from: www.revespcardiol.org/en.
PMID:40562161 | DOI:10.1016/j.rec.2025.04.011
J Card Fail. 2025 Jun 23:S1071-9164(25)00284-2. doi: 10.1016/j.cardfail.2025.05.017. Online ahead of print.
ABSTRACT
BACKGROUND: Cytomegalovirus (CMV) infection post heart transplantation (HT) is associated with worse outcomes. Antiviral prophylaxis for at-risk patients is standard of care. Valganciclovir, the most commonly used antiviral, is associated with significant adverse events, particularly leukopenia. Letermovir is a CMV-specific anti-viral with a favorable side effect profile but its efficacy in HT recipients is unclear. This study aims to assess the safety and efficacy of letermovir for CMV prophylaxis in HT recipients.
METHODS: This single-center retrospective analysis included HT recipients at our center from January 2020-September 2023. Patients who were switched to letermovir for CMV prophylaxis for leukopenia/neutropenia on valganciclovir, and 1) remained on letermovir for at least 60 days or 2) developed CMV viremia on letermovir within 60 days of initiation were included. Primary endpoint was incidence of CMV viremia/disease during letermovir therapy. Secondary endpoints included changes in white blood cell (WBC) count, tacrolimus dosing, and clinically significant acute rejection.
RESULTS: Fifty-two patients received letermovir for an average of 8.2 months (range 1 to 35 months). Average time from transplant to letermovir initiation was 9.2 months, (range 0.9 to 77 months). Eight (15.4%) patients developed breakthrough CMV viremia on letermovir with a median viral load of 205 [IQR 142-367.5] copies/mL, and 4 of these patients were converted back to valganciclovir; overall 92.3% of patients completed therapy with letermovir. There were no episodes of suspected or biopsy-proven, CMV disease. Majority of patients (78%) required dose reductions of tacrolimus following letermovir initiation with no episodes of tacrolimus toxicity requiring hospitalization. WBC counts increased, on average, from 2.6 to 5.3 × 103 cells/μL, p <0.001.
CONCLUSIONS: Letermovir holds promise as an effective and safe alternative to valganciclovir for CMV prophylaxis in HT recipients.
PMID:40562091 | DOI:10.1016/j.cardfail.2025.05.017
J Clin Oncol. 2025 Jun 25:JCO2402477. doi: 10.1200/JCO-24-02477. Online ahead of print.
ABSTRACT
In REACH3 (ClinicalTrials.gov identifier: NCT03112603), ruxolitinib was investigated versus best available therapy (BAT) for 3 years in patients with steroid-refractory/dependent chronic graft-versus-host-disease (SR/D-cGVHD). Patients received ruxolitinib (10 mg twice daily) or BAT for 24 weeks; thereafter (weeks 24-156), patients continued randomized treatment, entered long-term survival follow-up, or crossed over from BAT to ruxolitinib. In 329 randomly assigned patients (ruxolitinib: 165; BAT: 164), the median failure-free survival (FFS) was 38.4 months for ruxolitinib versus 5.7 months for BAT (hazard ratio, 0.36 [95% CI, 0.27 to 0.49]). Median duration of response (DOR) was not reached for ruxolitinib versus 6.4 months for BAT. Ruxolitinib-treated patients had a higher probability of FFS (ruxolitinib: 56.5%; BAT: 18.2%) and maintaining a response (ruxolitinib: 59.6%; BAT: 26.7%) at 36 months. Median overall survival was not reached. Nonrelapse mortality and malignancy relapse/recurrence events were low. In 70 patients who crossed over to ruxolitinib, the overall response rate (50.0%) at week 24 and best overall response (81.4%) during the crossover period were consistent with the primary analysis of randomly assigned patients. No new safety signals were observed. Ruxolitinib provided longer FFS and DOR than BAT, demonstrating sustained efficacy and manageable safety over 3 years of follow-up in patients with SR/D-cGVHD.
PMID:40561385 | DOI:10.1200/JCO-24-02477
Eur Heart J Qual Care Clin Outcomes. 2025 Jun 25:qcaf052. doi: 10.1093/ehjqcco/qcaf052. Online ahead of print.
ABSTRACT
There is increasing recognition that social determinants of health affect outcomes in individuals with congenital heart disease and cause health disparities. This scientific statement from the European Association of Preventive Cardiology of the European Society of Cardiology provides an outline of the existing disparities from a global perspective in this population. We review the current knowledge on racial and ethnic patterns and the role of deprivation status, food insecurity, built environment, financial strain, psychological health and parental distress and education and literacy in creating inequities. Finally, we provide future directions for policy, research and clinical practice in achieving health equity in the congenital heart disease population.
PMID:40561137 | DOI:10.1093/ehjqcco/qcaf052
Transplantation. 2025 Jun 24. doi: 10.1097/TP.0000000000005435. Online ahead of print.
ABSTRACT
The rising prevalence of heart failure, global donor heart shortages, and limitations of current assist devices have driven innovation in bioartificial hearts (BAHs) and cardiac constructs. This systematic review aims to give an overview of new developments in BAHs, engineered myocardium, and biohybrid ventricular assist devices research, evaluating their clinical readiness and outcomes while addressing strengths and limitations. Significant variability in study designs and outcomes highlights both advancements and ongoing challenges in this field. Although the development of BAHs and larger cardiac tissue constructs remains in preclinical stages, progress has been achieved in the development of cardiac patches, with 2 approved for clinical use. Several critical challenges continue to hinder the successful clinical translation of bioengineered cardiac solutions. Achieving meaningful myocardial contraction remains a complex task, as well as ensuring adequate vascularization and electrical integration. Biocompatibility limits the progression of bioengineered cardiac constructs toward clinical applications. Innovations in 3-dimensional bioprinting, shape-memory materials, adhesives, microfabrication techniques, and soft and stretchable bioelectronics are driving advancements in this field. However, outcomes regarding hemodynamic performance of BAHs or constructs are marginal at best. Cardiac patches show promising results in preclinical studies, with the paracrine effect of the patches being the most plausible explanation of these results. Importantly, from very little clinical experience thus far, we cannot conclude that cardiac patches have any beneficial effects nor that they are safe. The path toward developing a fully functional BAH or even parts of a functional myocardium appears to be long, complex, and perhaps even unattainable.
PMID:40561089 | DOI:10.1097/TP.0000000000005435
Cell Transplant. 2025 Jan-Dec;34:9636897251348566. doi: 10.1177/09636897251348566. Epub 2025 Jun 25.
ABSTRACT
Mesenchymal stem cells (MSCs) are considered to be effective treatments for various diseases, and a wide variety of clinical studies have been performed worldwide. However, substantial obstacles remain before they can be approved and disseminated as treatments. A major bottleneck is the elucidation of their mechanisms of action, and the molecules that are essential for their efficacy have not been fully characterized. In this paper, I review the studies that attempted to identify the key mediators of MSCs that are involved in their effects on disease using in vivo models. More specifically, studies are discussed in which reductions in the efficacy of MSCs in animal models of disease were induced by the absence of key mediators. The target diseases were lung, joint, cerebral nerve, or cardiac diseases and graft-versus-host disease (GVHD). The following molecules were identified and are discussed herein: TSG-6, VEGF, KGF, HGF, claudin-4, ANXA1, MANF, PYCR1, integrin β1, PDGFRβ, type-II collagen, CD151, TIMP3, TGF-β1, BDNF, COX-2, Botch, IL-1β, CTRP3, CXCR4, miR-34c, FSTL1, IDO, iNOS, IFNγR1, PGES, Chi3l1, and IL-6. These are key mediators of the efficacy of MSCs in vivo.
PMID:40560652 | PMC:PMC12198582 | DOI:10.1177/09636897251348566
J Cardiovasc Dev Dis. 2025 May 29;12(6):205. doi: 10.3390/jcdd12060205.
ABSTRACT
INTRODUCTION: Pediatric heart transplantation (HTX) remains the only therapeutic option for end-stage heart failure not amenable to conventional surgical or catheter interventions. We reviewed our pediatric HTX outcomes according to primary diagnosis.
PATIENTS AND METHODS: Sixty-two patients underwent HTX between 01/2007 and 12/2022. Patients were divided into congenital heart disease (CHD, n = 20) and cardiomyopathy (CMP, n = 42) groups. All potential variables relevant to patient recovery and long-term survival with endpoints of retransplantation or death were analyzed.
RESULTS: CHD patients underwent HTX after significantly more multiple major cardiac surgeries per patient (2.5 [0-5]) than CMP patients (0.5 [0-2], p < 0.01), without notable allosensitization. Post-HTX recovery was longer in CHD (mean mechanical ventilation 7 vs. 3 days, p = 0.001), likely due to longer surgical time (468 vs. 375 min, p = 0.037). There were no significant differences in the frequency of rejections between the two groups (4/20 vs. 9/42). Midterm survival was slightly better (85/70% p = NS) in CMP (median follow-up 44.5 [0-177] months).
CONCLUSION: Our study confirmed good short- and long-term outcomes of pediatric HTX in both CMP and CHD. The longer postoperative recovery in CHD did not lead to higher mortality. No higher pretransplant hypersensitization was observed, possibly explaining the lack of difference in the number and severity of rejections.
PMID:40558640 | PMC:PMC12194210 | DOI:10.3390/jcdd12060205
Curr Opin Cardiol. 2025 Jun 23. doi: 10.1097/HCO.0000000000001238. Online ahead of print.
ABSTRACT
PURPOSE OF REVIEW: There are several multifactorial risk assessment tools used to predict mortality in patients with pulmonary arterial hypertension (PAH). These tools are also used to guide clinical decision-making including changes in therapy and referrals for transplantation. While the prominent driver of morbidity and mortality in PAH is right ventricular failure, most available risk assessment tools do not include parameters specific to right ventricular structure or function. Several cardiac imaging parameters are known to be associated with survival and may enhance the predictive ability of existing risk scores.
RECENT FINDINGS: This review compiles the existing literature surrounding the improved predictive power of existing risk assessment tools when combined with echocardiographic and cardiac magnetic resonance imaging findings. The review also discusses scenarios in which imaging findings may influence clinical decision making outside of risk scores.
SUMMARY: Decision making in PAH is complex and multifaceted. Cardiac imaging is an important component in the management of PAH and should be considered carefully and in conjunction with existing risk assessment tools.
PMID:40557914 | DOI:10.1097/HCO.0000000000001238
ESC Heart Fail. 2025 Jun 25. doi: 10.1002/ehf2.15353. Online ahead of print.
ABSTRACT
AIMS: Following HeartMate 3 (HM3) LVAD implantation, acute right heart failure necessitating temporary right ventricular assist device (tRVAD) support has not been extensively described. We examined clinical outcomes in patients with HM3 LVAD stratified by the need for tRVAD support.
METHODS AND RESULTS: This was a single-centre, retrospective study of patients who underwent primary HM3 implantation from 2018 to 2022. Patients were placed on tRVAD (concomitant or delayed) support due to clinical deterioration. The primary outcome was 1-year all-cause mortality following HM3 implantation using competing risk analysis with heart transplantation acting as the competing event. A matched cohort analysis was also performed to evaluate the primary outcome of patients with and without tRVAD support. Secondary outcomes included an analysis of risk of LVAD-related adverse events stratified by the presence of tRVAD. Of the 192 patients (median age 60 [49-68] years, 74% male, 37% white), 51 (26%) required tRVAD support. Compared with those with HM3 alone, the tRVAD group had a higher percentage of INTERMACS profile 1 or 2 (49% vs. 27%, P = 0.0005) and had higher rates of pre-operative VA-ECMO (28% vs. 5%, P < 0.0001). The tRVAD group had a higher 1-year all-cause mortality (33% vs. 3%, adjusted HR [95%CI]: 32.4 [9.51-110], P < 0.0001) compared with the HM3 alone group. In-hospital mortality for patients with tRVAD was 26% compared with 1% in patients with HM3 alone (P < 0.0001). In the matched cohort analysis, significantly higher risk of both stroke (HR [95% CI]: 5.75 [1.55-21.3], P = 0.009) and dialysis (HR [95% CI]: 13.4 (3.96-45.5), P < 0.0001) was observed in the tRVAD cohort. Compared with concomitant tRVAD support, the delayed tRVAD group did not have a significantly higher risk of adverse events.
CONCLUSIONS: In this large single-centre experience, patients undergoing HM3 LVAD requiring tRVAD support had significantly higher risks of adverse clinical outcomes.
PMID:40557852 | DOI:10.1002/ehf2.15353
Int J Artif Organs. 2025 Jun 25:3913988251351116. doi: 10.1177/03913988251351116. Online ahead of print.
ABSTRACT
BACKGROUND: Ongoing donor-organ shortage has limited transplantation making LVADs an effective alternative therapy for patients with end-stage heart failure. When LVAD-associated complications arise device exchange is a feasible and safe alternative. This study addresses the factors that impact survival post-LVAD exchange.
METHODS: Our decoded database was constructed retrospectively. Surgical details, device features, and re-intervention information were studied. The primary outcome was mortality. Kaplan-Meier estimators were used for post-pump exchange survival analysis. Pairwise log-rank tests compare the survivals between different groups within each variable. p-Value <0.05 was considered significant. Backward-stepwise regression was used to construct the multivariable model using a subset of variables, retaining only variables with a p-value <0.1. Hazard ratios, their 95% confidence intervals, and p-values of the significant variables were reported.
RESULTS: Analysis of factors impacting survival post-pump exchange study showed a poor survival probability of only primary midline-sternotomy/redo (p = 0.005). Multivariable analysis showed that bridging with ECMO was protective with a hazard ratio of 0.16 (0.03-0.86, p = 0.03).
CONCLUSIONS: The overall survival probability is 50% at 4 years post-pump exchange. This study highlights the differences in post-exchange outcomes depending on the device types and surgical approaches used. LVAD exchange for device-related complications can be performed in high-risk patients as a viable alternative to heart transplantation in the setting of the current heart allocation prioritization systems.
PMID:40557755 | DOI:10.1177/03913988251351116
Clin Transplant. 2025 Jul;39(7):e70193. doi: 10.1111/ctr.70193.
ABSTRACT
BACKGROUND: Days alive and out of the hospital (DAOH) is an increasingly used patient-centered outcome in studies of patients with heart failure, but has not been well studied in heart transplantation (HT). We sought to examine predictors of DAOH at 1-year post-discharge from HT in a diverse population at a large volume HT center.
METHODS: Adult recipients who underwent HT between January 1, 2005 and December 31, 2022 at our institution were included. Baseline demographics were collected as well as psychosocial factors including primary insurance, education, primary language, and socioeconomic status (SES) index as determined by the American Community Survey using patient zip code data. The primary outcome was DAOH at 1 year from HT, accounting for hospital readmissions and time spent in rehabilitation facilities. For patients who died on index admission, DAOH was considered 0.
RESULTS: A total of 1141 patients (26% female, 16% Hispanic, 24% Black) were included in the primary analysis. Seventy-two patients (6.3%) died during the index HT hospitalization. Mean DAOH was 306 (± 87) days. Among those who survived to hospital discharge, 56% were readmitted at least once in the first year after HT. After adjustment for clinical and psychosocial variables, older age, chronic kidney disease, post-2018 allocation change, and greater length of stay at the index hospitalization were associated with significantly fewer DAOH.
CONCLUSIONS: The integration of patient-centered metrics such as DAOH should be a continued priority in our transplant community as it may better convey health-related quality of life.
PMID:40557739 | DOI:10.1111/ctr.70193
Circ Arrhythm Electrophysiol. 2025 Jun 25:e013670. doi: 10.1161/CIRCEP.124.013670. Online ahead of print.
ABSTRACT
BACKGROUND: Differences in cardiac sarcoidosis between racial groups remain understudied. Therefore, this study aims to explore race differences in patients with cardiac sarcoidosis.
METHODS: We analyzed data from the Cardiac Sarcoidosis Consortium, an international registry including over 25 centers. The primary clinical outcome was a composite end point of all-cause mortality, left ventricular assist device implantation, heart transplantation, or implantable cardioverter defibrillator therapy.
RESULTS: A total of 619 patients were included in the study (362 White, 193 Black, and 64 other races). Black patients were diagnosed with cardiac sarcoidosis at a younger age (50.5±11.8 versus 53.7±10.5 years old; P=0.010) compared with White patients. Left ventricular ejection fraction was significantly lower in Black patients (44.6±15.4 versus 48.3±14.0; P=0.008). In addition, extracardiac involvement in the lungs (80.3% versus 72.7%; P=0.046), skin (22.8% versus 12.4%; p=0.002), and eyes (13.5% versus 5.5%; P=0.001) was more prevalent in Black patients. Patients had significantly higher rates of hypertension (69.9% versus 50.6%; P<0.001), diabetes (37.8% versus 21.0%; P<0.001), smoking (40.9% versus 26.8%; P<0.001), chronic obstructive pulmonary disease or emphysema (15.5% versus 4.1%; P<0.001), and chronic kidney disease (25.9% versus 12.4%; P<0.001). The treatment patterns including glucocorticoid (71% versus 74.3%; P=0.4), glucocorticoid-sparing (53.4% versus 59.9%; P=0.14), and implantable cardioverter defibrillator or cardiac resynchronization implantation (75.6% versus 73.8%; P=0.63), were similar. No significant differences were found in the primary outcome (29.5% in Black versus 28.5% in White; P=0.79). Subgroup analysis of the primary outcome also revealed no significant differences in both the left ventricular ejection fraction >35% group (24.1% in Black versus 25.9% in White; P=0.72) and the left ventricular ejection fraction ≤35% group (51% versus 42.5%; P=0.35).
CONCLUSIONS: Black patients with cardiac sarcoidosis exhibited significantly higher rates of lung, skin, and eye involvement and comorbidities, but had similar cardiac clinical outcomes and all-cause mortality compared with White patients. Nonetheless, ascertainment bias cannot be excluded.
PMID:40557494 | DOI:10.1161/CIRCEP.124.013670
Ann Surg Open. 2025 Jun 13;6(2):e582. doi: 10.1097/AS9.0000000000000582. eCollection 2025 Jun.
ABSTRACT
OBJECTIVE: To assess the outcomes of a pair of kidneys from a single donor used for simultaneous heart-kidney transplantation (SHKT) or kidney after heart transplantation (KAH).
BACKGROUND: An Increase in kidney dysfunction among heart transplant candidates has led to an increased need for SHKT and KAH. The risk of early kidney graft loss and mortality is higher in SHKT compared with kidney-alone recipients.
METHODS: Among adult kidney transplant recipients from Oct 2014 to Oct 2022, outcomes were compared between paired kidney-alone vs SHKT and kidney-alone vs KAH. Paired kidney models were used to mitigate differences among donor risk factors. Differential graft years were calculated using restricted mean survival analysis.
RESULTS: A total of 1220 pairs of kidney-alone and SHKT recipients and 441 pairs of kidney-alone and KAH recipients were identified. Among the paired donor kidneys, graft survival was significantly lower in SHKT recipients compared with kidney-alone recipients at 1-year post-transplant (96.1% vs 89.3%; P < 0.001) and at 3-year post-transplant (83.9% vs 78.8%; P < 0.001). This resulted in lower mean graft years [SHKT (3.98 years, standard error = 0.06) vs kidney-alone (4.55 years, standard error = 0.04); P < 0.001] and an additional loss of 57 kidney graft years per 100 transplants (P < 0.01) during the study period. There was no difference in graft survival of paired kidneys in kidney-alone vs KAH recipients with additional loss of 17 kidney graft years per 100 transplants (P = 0.20).
CONCLUSIONS: Optimal recipient selection for kidney after heart transplant under the new safety-net policy may help mitigate the significant risk of kidney graft failure among SHKT recipients.
PMID:40557359 | PMC:PMC12185088 | DOI:10.1097/AS9.0000000000000582
J Investig Med. 2025 Jun 24:10815589251355173. doi: 10.1177/10815589251355173. Online ahead of print.
ABSTRACT
Lung transplantation (LTx) is a vital treatment option for patients with end-stage lung diseases, significantly enhancing survival rates and quality of life. Nonetheless, chronic lung allograft dysfunction (CLAD) remains the primary cause of long-term morbidity and mortality in LTx recipients, posing substantial challenges to patient outcomes and healthcare systems. Despite progress in surgical methods and immunosuppressive treatments, CLAD management is complicated by its multifaceted, potentially irreversible nature. This review delves into critical aspects such as short telomere syndrome (STS), innovations in early detection, and adjunctive therapeutic approaches, offering insights into strategies that may extend the survival of LTx recipients. STS exacerbates CLAD by accelerating cellular aging and hindering tissue repair, necessitating a multidisciplinary approach involving pulmonologists, geneticists, hepatologists, and hematologists to devise comprehensive care plans. The review emphasizes dynamic magnetic resonance imaging as a promising tool for early CLAD detection, enhancing patient monitoring capabilities. Additionally, it examines the roles of extracorporeal photopheresis (ECP), total lymphoid irradiation (TLI), and anti-thymocyte globulins as adjunctive therapies, advocating for their inclusion in standard treatment protocols. This could lead to broader adoption and insurance coverage. Furthermore, we attempt to provide a framework to help decide which adjunctive treatments should be pursued based on the available evidence. By assessing these strategies and highlighting the importance of personalized care, this review aims to guide future research and clinical practice, ultimately improving CLAD management in lung transplant recipients.
PMID:40556056 | DOI:10.1177/10815589251355173
J Cardiothorac Surg. 2025 Jun 24;20(1):272. doi: 10.1186/s13019-025-03505-8.
ABSTRACT
OBJECTIVE: To explore the application and effect of aortic annulus reconstruction (AAR) with bovine pericardium during surgical aortic valve replacement (SAVR) for severe calcific aortic stenosis (AS).
METHODS: We retrospectively reviewed 12 patients with severe calcified AS who underwent bovine pericardium aortic annulus reconstruction between January 2021 to December 2023. The average age of the patients was 58 ± 8.8 years. All patients were diagnosed with severe AS, along with aortic valve and annulus calcification, through chest computed tomography (CT) and transthoracic echocardiography (TTE) prior to surgery. After the resection of severely calcified aortic annulus tissue, all patients were given a bovine pericardial patch to repair the annular defect, and five of these patients underwent Y-incision aortic annular enlargement (AAE). The patients were followed up for a duration of 0.5 to 2 years.
RESULTS: A total of 12 patients undergoing SAVR were enrolled, and all received bovine pericardial patches to repair the annular defects, with a mean preoperative indexed effective orifice area (iEOA) of 0.58 ± 0.098 cm²/m². The average extracorporeal circulation time during the operation was 150.83 ± 34.5 min, and the average cross-clamp time was 95.42 ± 17.46 min. Postoperative evaluations indicated that the structural integrity of the valve annulus remained intact, demonstrating hemodynamic stabilization without any recorded fatalities among participants. Compared to preoperative levels, the aortic valve mean gradient (4.67 ± 1.15 vs. 59.67 ± 17.94 mmHg, P < 0.001), peak gradient (13 [10-15.75] vs. 92 [82.25-110.25] mmHg, P < 0.001), mean aortic jet velocity (99.67 ± 15.44 vs. 367.17 ± 58.13 cm/s, P < 0.001), and peak aortic jet velocity (182.25 ± 23.40 vs. 495.67 ± 61.74 cm/s, P < 0.001) significantly decreased after 0.5 years of follow-up. There were no complications such as hemolysis, perivalvular leakage, thrombosis or endocarditis during follow-up.
CONCLUSION: In patients with severe calcified AS, the AAR technique using bovine pericardium during SAVR is safe and effective, with stable hemodynamic performance and satisfactory clinical outcomes.
PMID:40556029 | PMC:PMC12186314 | DOI:10.1186/s13019-025-03505-8
Cell Death Differ. 2025 Jun 24. doi: 10.1038/s41418-025-01540-5. Online ahead of print.
ABSTRACT
Activation of the intrinsic regenerative potential of adult mammalian hearts by promoting cardiomyocyte proliferation holds great potential in heart repair. CAND1 (Cullin-associated and neddylation-dissociated protein 1) functions as a critical regulator of cellular protein homeostasis by fine-tuning the ubiquitinated degradation of specific abnormally expressed protein substrates. Here, we identified that cardiac-specific transgenic overexpression of CAND1 reduced the infarct size, restored cardiac function, and promoted cardiomyocyte proliferation after myocardial infarction in juvenile (7-day-old) and adult (8-week-old) mice. Conversely, CAND1 deficiency blunted the regenerative capacity of neonatal hearts after apex resection. MS and functional verification demonstrated that CAND1 enhanced the assembly of Cullin1, FBXW11(F-box/WD repeat-containing protein 11), and Mob1b (Mps one binder kinase activator 1b) complexes, and thus promotes the degradation of Mob1b. The ubiquitination of Mob1b occurred at K108 and was linked by K48 of ubiquitin. Mob1b deletion partially rescued the loss of regenerative capacity in neonatal hearts induced by CAND1 deficiency and improved cardiac function in adult mice post-MI. Moreover, CAND1 promoted the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our data demonstrate that CAND1 promotes cardiomyocyte proliferation via FBXW11-mediated K48-linked ubiquitination degradation of Mob1b, and improves heart regeneration after cardiac injury. The findings provide a novel strategy to promote cardiac regeneration and repair. Schematic diagram of the role of CAND1 in regulating ubiquitination and degradation of Mob1b and cardiomyocyte proliferation and heart regeneration. Under CAND1-High condition, CAND1 promotes the incorporation of Cullin1, FBXW11, and Mob1b complexes, and accelerates SCFFBXW11-mediated K48-linked ubiquitination of Mob1b at the K108 site, which leads to the degradation of Mob1b and thus suppresses the Hippo signaling pathway and facilitates cardiomyocyte proliferation and heart regeneration post-MI.
PMID:40555744 | DOI:10.1038/s41418-025-01540-5
Exp Mol Med. 2025 Jun 24. doi: 10.1038/s12276-025-01472-7. Online ahead of print.
ABSTRACT
Barth syndrome (BTHS) is an ultrarare, infantile-onset, X-linked recessive mitochondrial disorder that primarily affects males, owing to mutations in TAFAZZIN, which catalyzes the remodeling of cardiolipin, a mitochondrial phospholipid required for oxidative phosphorylation. Mitochondrial transplantation is a novel technique to treat mitochondrial dysfunction by delivering healthy mitochondria to diseased cells or tissues. Here we explored the possibility of using stem-cell-derived cardiomyocytes as a source of mitochondrial transplantation to treat BTHS. We established induced pluripotent stem (iPS) cells from healthy individuals and from patients with BTHS and differentiated them into cardiomyocytes. The iPS-cell-differentiated cardiomyocytes (CMs) derived from patients with BTHS exhibited less expression of cardiomyocytes markers, such as α-SA, cTnT and cTnI, and smaller cell size than normal iPS-cell-derived CMs. Multielectrode array analysis revealed that BTHS CMs exhibited shorter beat period and longer field potential duration than normal CMs. In addition, mitochondrial morphology and function were impaired and mitophagy was decreased in BTHS CMs compared with normal CMs. Transplantation of mitochondria isolated from normal CMs induced mitophagy in BTHS CMs, mitigated mitochondrial dysfunction and promoted mitochondrial biogenesis. Furthermore, mitochondrial transplantation stimulated cardiac maturation and alleviated cardiac arrhythmia of BTHS CMs. These results suggest that normal CMs are useful for allogeneic transplantation in the treatment of mitochondrial diseases, including BTHS.
PMID:40555742 | DOI:10.1038/s12276-025-01472-7