Trasplante cardíaco

Commun Biol. 2025 Oct 1;8(1):1411. doi: 10.1038/s42003-025-08876-1.

ABSTRACT

Three-dimensional (3D) imaging is crucial for elucidating the complex structure of organoid models which involve complex spatial cellular and tissue organization in 3D. While a variety of volume imaging methods, including novel light microscopy tools, are now well established to probe the cellular complexity of organoids in 3D, the gold standard for obtaining a precise morphological picture is histology, a traditionally 2D imaging technique that relies on slicing the specimen and therefore has severe limitations in scalability and volumetric imaging. X-ray phase-contrast tomography (XPCT) has emerged as an imaging modality capable of extending conventional histology into the third dimension. While it has been applied to various types of animal and human tissues, its applicability to organoid systems, however, is yet in its infancy. Here, we use XPCT for 3D histology of unstained and formalin-fixed paraffin-embedded human heart-forming organoids (HFOs) at multiple scales and with isotropic resolution. Derived from human pluripotent stem cells, HFOs are a complex and highly structured in vitro model of early heart, foregut and vasculature development, resembling the early human heart-forming region. Using highly coherent synchrotron radiation, we show that HFOs and their different tissue elements can be visualized in their full three-dimensionality and at subcellular scale.

PMID:41034510 | PMC:PMC12488953 | DOI:10.1038/s42003-025-08876-1

Commun Med (Lond). 2025 Oct 1;5(1):412. doi: 10.1038/s43856-025-01151-8.

ABSTRACT

BACKGROUND: Aortic valve dysfunction is a rare but relevant long-term complication after orthotopic heart transplantation (HTX). Treatment options include surgical (SAVR) and transcatheter (TAVR) aortic valve replacement, but evidence is limited to the level of case reports.

METHODS: A total of 2054 patients underwent HTX between 1986 and 2023 at the Deutsches Herzzentrum der Charité, Berlin, Germany, 16 of them underwent aortic valve replacement (SAVR, N = 7; TAVR, N = 9) after HTX. In this case series we report on the outcomes of these 16 patients (age 29-73 years).

RESULTS: Isolated aortic valve regurgitation occurs in 5 (31%) patients (TAVR N = 1, SAVR N = 4), while 11 patients (69%) suffer from aortic valve stenosis. Severe pre-procedural heart failure is present in 38% of the patients. Thirty-day mortality is 0%, in-hospital mortality is N = 2 (22%) patients due to sepsis, both patients were severely decompensated prior to TAVR. An uneventful postoperative course occurs in 8 (50%) patients, the patient's functional status improves in 12 (75%) cases.

CONCLUSION: TAVR is the increasingly preferred treatment for aortic valve dysfunction after heart transplantation, but SAVR is a feasible alternative for individuals who are ineligible for TAVR. Further information is needed on the appropriate procedural timing in these high-risk patients.

PMID:41034314 | PMC:PMC12488981 | DOI:10.1038/s43856-025-01151-8

Clin Genet. 2025 Oct 1. doi: 10.1111/cge.70078. Online ahead of print.

ABSTRACT

Dilated Cardiomyopathy (DCM) is a genetically heterogeneous condition of left ventricular dilation and systolic dysfunction, leading to heart failure. It is mostly inherited in a dominant pattern. Recessive inheritance has been rarely encountered. This study aims to outline the clinical and genetic characteristics associated with recessively inherited NRAP truncating variants in our highly consanguineous population. Twenty-three cases from 12 unrelated consanguineous families were recruited. Cardiological evaluation and genetic testing with exome sequencing (ES) were conducted in all cases, followed by segregation analysis of first-degree relatives. Genetic analysis with ES identified five unique homozygous truncating variants in NRAP in the affected cases. The segregation analysis detected a total of 23 homozygous and 21 heterozygous individuals. Out of the total homozygous cases, three were asymptomatic, while 20 exhibited symptoms with remarkable inter- and intrafamilial variability of the age of onset (range: 9 months to 47 years, median 10 years), seven of whom died (range: 9 months to 28 years, median 7 years). None of the heterozygous individuals showed symptoms. Of note, three homozygous cases underwent heart transplantation. Our findings show that truncating variants in NRAP are associated with reduced penetrance and clinical variability, suggesting a complex mechanism beyond simple Mendelian inheritance.

PMID:41033658 | DOI:10.1111/cge.70078

Can J Cardiol. 2025 Sep 29:S0828-282X(25)01189-4. doi: 10.1016/j.cjca.2025.09.037. Online ahead of print.

ABSTRACT

Heart transplant recipients are living longer, requiring clinicians to think beyond graft survival and consider long-term challenges and overall well-being. Focus on initial patient survival metrics often overshadows the significant side effects of immunosuppressive therapy. Recipients struggle to overcome physical deconditioning, psychological distress, and issues associated with social reintegration. These burdens may often be considered an expected part of life with transplantation, yet they deeply affect daily living, self-care, and long-term health outcomes. This article reviews the complex realities of life after heart transplantation and recommends a more holistic, patient-centered model, one that prioritizes not just graft survival, but recovery of function, well-being, and quality of life.

PMID:41033438 | DOI:10.1016/j.cjca.2025.09.037

JACC Asia. 2025 Sep 29:S2772-3747(25)00463-6. doi: 10.1016/j.jacasi.2025.08.018. Online ahead of print.

ABSTRACT

BACKGROUND: Early detection and treatment of cardiotoxicity are essential for reducing cardiac events. However, a reliable predictive model for cardiotoxicity in patients with breast cancer receiving chemotherapy is lacking.

OBJECTIVES: In this study, we aimed to develop a risk prediction model and establish effective surveillance for cardiotoxicity in patients with breast cancer undergoing chemotherapy.

METHODS: Patients with breast cancer scheduled for neoadjuvant and/or adjuvant chemotherapy were prospectively screened at 25 participating institutions between August 2017 and March 2020. Cardiotoxicity was defined as a reduction in left ventricular ejection fraction of >10% from baseline to a value <53%.

RESULTS: The study included 559 chemotherapy-naïve female patients. Cardiotoxicity was observed in 46 of 559 patients (8.2%) during a median follow-up period of 366 days (Q1-Q3: 365-367 days). The CHECK HEART (Comprehensive Heart Imaging to Evaluate Cardiac Damage Linked With Chemotherapy in Breast Cancer Patients) score consisted of 6 variables: heart rate, left ventricular global longitudinal strain, left ventricular end-systolic and end-diastolic diameters, right ventricular fractional area change, and treatment with anthracycline and trastuzumab. The time-dependent area under the receiver operating characteristic curve (AUC) at 12 months based on pretreatment data showed acceptable accuracy (AUC: 0.82; 95% CI: 0.76-0.89).

CONCLUSIONS: The developed multivariable risk prediction models can accurately predict cardiotoxicity and support effective surveillance in patients with breast cancer receiving chemotherapy.

PMID:41031980 | DOI:10.1016/j.jacasi.2025.08.018

J Hypertens. 2025 Sep 8. doi: 10.1097/HJH.0000000000004146. Online ahead of print.

ABSTRACT

OBJECTIVES: Flow-mediated slowing (FMS) reflects macrovascular reactivity by quantifying the decline in brachial-radial pulse wave velocity (PWV) during reactive hyperaemia. We identified abnormal FMS response using normal values and integrative algorithms.

METHODS: In this cross-sectional, observational study, 408 community-dwelling individuals underwent FMS testing with 5 min of upper arm occlusion. FMS was assessed at 30 s intervals for 4 min postocclusion. From 76 healthy individuals, we extracted limits of normality for peak FMS, defining an abnormal peak response if PWV slowed by less than 9.4% (if <60 years) or 4.6% (if ≥60 years). Group-based trajectory modelling (GBTM) assigned participants to distinct FMS response groups. Multivariable regression identified clinical correlates of the FMS response groups.

RESULTS: Higher age correlated independently with less decline in PWV in the early phase (P ≤ 0.0076 for 0-30 s), whereas higher SBP and no beta blocker use were linked to less decline overall (SBP: P ≤ 0.048 for 0-210 s; beta blockers: P ≤ 0.014 for 0-180 s). Abnormal peak FMS was associated with higher SBP [adjusted odds ratio (OR): 1.31, P = 0.0017) and less use of beta blockers (adjusted OR: 0.44, P = 0.041). A three-group GBTM model identified a low, moderate and high FMS response group. The risk for a low FMS response increased with age, SBP and no use of beta blockers (P ≤ 0.038 for all).

CONCLUSION: Abnormal FMS response was linked to cardiovascular risk factors such as ageing, hypertension and beta blocker use. The FMS response patterns may enable qualitative interpretation of FMS tests, though validation against hard clinical outcomes is warranted.

PMID:41031703 | DOI:10.1097/HJH.0000000000004146

Curr Med Chem. 2025 Sep 30. doi: 10.2174/0109298673377544250714073536. Online ahead of print.

ABSTRACT

BACKGROUND: Endothelins are a family of vasoconstrictive peptides known for their high potency. They are mainly synthesized and secreted by the endothelial cells lining the blood vessels in response to various stimuli. Their main physiological role is the regulation of vascular tone, affecting blood pressure and tissue perfusion.

OBJECTIVE: The aim of this review was to evaluate the importance of Endothelin-1 (ET-1) plasma levels as a marker in diagnosis, disease burden, or development, due to its vascular effects.

METHODS: Data from several studies in different organ systems, collected over the last thirty years, were collected. A statistical analysis was performed to reveal any similarities and differences among them.

RESULTS: ET-1 was found to be increased in arterial and pulmonary hypertension. Plasma ET-1 was elevated in patients with heart failure, autoimmune disease, chronic kidney disease, and liver failure. In all these cases, ET-1 was increased at least twice the maximum of normal plasma concentration in healthy subjects, in a similar pattern, independently of the disease background. More importantly, plasma ET-I levels increased even more according to the severity of the disease, not necessarily in a linear manner.

CONCLUSION: Endothelin-1 appears to increase similarly across various pathological conditions, making it a potential biomarker for overall human physiological status.

PMID:41031504 | DOI:10.2174/0109298673377544250714073536

Front Pharmacol. 2025 Sep 15;16:1663717. doi: 10.3389/fphar.2025.1663717. eCollection 2025.

ABSTRACT

Hyperlipidemia is correlated with the elevation of cholesterol and triglyceride levels in the blood that increase the risk of cardiovascular events, such as heart attacks and strokes. This study aimed to test the hypolipidemic activity and other health benefits of atorvastatin and safflower (Carthamus tinctorius L., family Asteraceae) on rats with induced hypercholesterolemia in a four-week study. 24 male albino rats were divided into four groups (n = 6). The first group (G1) was given a normal basal diet as a negative control, while the other rats received a high-fat diet with 5% cholesterol. The second group (G2) served as the positive control, receiving no treatment. The third group (G3) received 200 mg/kg body weight safflower aqueous extract, and the 4th group (G4) received 20 mg/kg body weight atorvastatin. The induced hypercholesterolemia significantly raised liver function enzymes, lipid peroxidation (14.9 ± 0.11 mg/dL), total cholesterol (273.3 ± 1.1 mg/dL), triglycerides (223.0 ± 4.1 mg/dL), low-density lipoproteins (204.7 ± 0.9 mg/dL), very low-density lipoproteins (44.6 ± 0.8 mg/dL), troponin, creatine kinase (CK), and adrenaline while decreased antioxidant enzymes, high-density lipoprotein (HDL), and vitamin D (11.1 ± 0.5 ng/mL). The liver and heart tissues were also significantly injured by hypercholesterolemia. Administration of atorvastatin and safflower markedly ameliorated the biochemical and histological abnormalities associated with induced hyperlipidemia, restoring them to near-normal levels. Atorvastatin treatment in G4 demonstrated superior efficacy compared to safflower extract in addressing hypercholesterolemia, despite the latter's significant hypolipidemic effect observed in G3.

PMID:41031162 | PMC:PMC12477430 | DOI:10.3389/fphar.2025.1663717

World J Nephrol. 2025 Sep 25;14(3):107415. doi: 10.5527/wjn.v14.i3.107415.

ABSTRACT

Chikungunya, a vector-borne viral disease, has become a critical global health issue due to its capacity for widespread outbreaks, especially in tropical and subtropical regions, and its recent global expansion. The resurgence of Chikungunya virus (CHIKV) in Karachi, Pakistan, has amplified public health challenges, driven by factors such as urbanization, climate change, and socioeconomic vulnerabilities, including limited healthcare infrastructure. Clinically, the disease primarily manifests with fever, rash, and debilitating joint pain, which often leads to prolonged discomfort and decreased quality of life. However, emerging evidence points to atypical and severe complications affecting the neurological, cardiac, and kidney systems, increasing the risk of morbidity and mortality. Kidney involvement in Chikungunya is of particular concern, with acute kidney injury being identified as a critical complication. Timely diagnosis of the infection and early identification of individuals at heightened risk of progressing to severe kidney dysfunction is crucial to improving patient outcomes. Such individuals often include those with pre-existing kidney conditions or other underlying comorbidities, making them more susceptible to complications. This narrative review aims to synthesize and expand upon the current understanding of the mechanisms underlying CHIKV-induced kidney injury. These mechanisms encompass direct viral invasion of kidney tissue, immune-mediated inflammatory responses that inadvertently damage the kidneys, and the aggravation of pre-existing kidney pathologies. Furthermore, the complex interplay between the virus and the host's immune system may exacerbate kidney complications, highlighting the multifaceted nature of CHIKV pathophysiology.

PMID:41030918 | PMC:PMC12477685 | DOI:10.5527/wjn.v14.i3.107415

Respir Med Case Rep. 2025 Sep 16;58:102291. doi: 10.1016/j.rmcr.2025.102291. eCollection 2025.

ABSTRACT

This case report describes a 45-year-old female with HHT type 1 (ENG mutation) and congenital heart disease (sinus venosus atrial septal defect and partial anomalous pulmonary venous return), diagnosed with severe PAH at age 16. Despite long-term treatment with epoprostenol, treprostinil, macitentan, and tadalafil, her condition progressed, leading to evaluation for lung transplantation. In May 2024, sotatercept, a novel TGF-β superfamily ligand trap, was initiated, resulting in significant improvement in exertional capacity and quality of life. The patient experienced increased epistaxis frequency (2-4 episodes/week), though hemoglobin levels rose from 13.0 to 15.4 g/dL. No new telangiectasias or other adverse events were noted. This is the first reported case of sotatercept use in PAH with HHT, highlighting its potential efficacy but also the need for careful monitoring due to increased bleeding risk.

PMID:41030324 | PMC:PMC12477927 | DOI:10.1016/j.rmcr.2025.102291

Nat Med. 2025 Sep 30. doi: 10.1038/s41591-025-03956-5. Online ahead of print.

ABSTRACT

Critical care syndromes such as sepsis, acute respiratory distress syndrome (ARDS) and trauma continue to have unacceptably high morbidity and mortality, with progress limited by the inherent heterogeneity within syndromic illnesses. Although numerous immune endotypes have been proposed for sepsis and critical care, the similarities and differences between these endotypes remain unclear, hindering clinical translation. The SUBSPACE consortium is an international consortium that aims to advance precision medicine in critical care through the sharing of transcriptomic data. Here, evaluating the overlap of existing immune endotypes in sepsis across >7,074 samples from 37 independent cohorts, we developed cell-type-specific gene expression signatures to quantify dysregulation within immune compartments. Myeloid and lymphoid dysregulation were associated with disease severity and mortality across all cohorts. Importantly, this dysregulation was also observed in patients with ARDS, trauma and burns, suggesting a conserved mechanism across various critical illness syndromes. Moreover, analysis of randomized controlled trial data revealed that myeloid and lymphoid dysregulation are associated with differential mortality in patients treated with anakinra in the SAVE-MORE trial (n = 452) and corticosteroids in the VICTAS (n = 89) and VANISH (n = 117) trials, underscoring their prognostic and therapeutic implications. In conclusion, our proposed immunology-based framework for quantifying cellular compartment dysregulation offers a potentially valuable tool for understanding immune dysregulation in critical illness with prognostic and therapeutic significance.

PMID:41028543 | DOI:10.1038/s41591-025-03956-5

Nat Med. 2025 Sep 30. doi: 10.1038/s41591-025-03933-y. Online ahead of print.

ABSTRACT

Lack of reliable diagnostics for the presence, type and severity of infection in patients presenting to emergency departments with non-specific symptoms poses considerable challenges. We developed TriVerity, which uses isothermal amplification of 29 mRNAs and machine learning algorithms on the Myrna instrument to determine likelihoods of bacterial infection, viral infection and need for critical care interventions within 7 days. To validate TriVerity, the SEPSIS-SHIELD study enrolled 1,222 patients with clinically adjudicated infection status and need for critical care intervention within 7 days as endpoints. The TriVerity Bacterial and Viral scores had higher accuracy than C-reactive protein, procalcitonin or white blood cell count for the diagnosis of bacterial infection with area under the receiver operating characteristic (AUROC) of 0.83, and viral infection (AUROC = 0.91). The TriVerity Severity score had an AUROC of 0.78 for predicting illness severity and allowed reclassification of risk for critical care interventions compared to clinical assessment (quick Sequential Organ Failure Assessment) alone. Each of the three scores had rule-in specificity >92% and rule-out sensitivity >95%. Comparison of antibiotics administration at presentation with post-follow-up adjudication found that TriVerity could potentially reduce false positives and false negatives for inappropriate antibiotics use by 60-70%. Further clinical testing in an interventional setting is needed to prove actionability and clinical benefit of TriVerity.

PMID:41028541 | DOI:10.1038/s41591-025-03933-y

Br J Haematol. 2025 Sep 30. doi: 10.1111/bjh.70167. Online ahead of print.

ABSTRACT

Evolution of acute myeloid leukaemia (AML) treatments and transplantation procedures may affect outcomes after second haematopoietic stem cell transplantation (HSCT2) for relapsed paediatric AML. We analysed 345 paediatric patients reported to the European Society for Bone Marrow Transplantation (EBMT) registry for HSCT2 performed for AML relapse post-HSCT between 2000 and 2022. Multivariable analyses were adjusted for sex, age, transplant period, donor, disease status pre-HSCT2, cytogenetics, conditioning, total body irradiation (TBI) and post-first haematopoietic stem cell transplantation (HSCT1) remission duration. At three years leukaemia-free survival (LFS), overall survival (OS), non-relapse mortality (NRM), relapse incidence (RI) and graft-versus-host disease (GVHD)/relapse-free survival (GRFS) were 30.2%, 37.5%, 19.1%, 50.7% and 20.7% respectively. Compared with the 2000-2013 period, HSCT2 performed in 2014-2022 had better LFS (hazard ration [HR]: 0.66, 95% confidence interval [95% CI]: 0.48-0.90; 3-year: 34.3% vs. 26.3%), OS (HR: 0.60, 95% CI: 0.42-0.84; 3-year: 42.9% vs. 32.8%), RI (HR: 0.66, 95% CI: 0.46-0.98; 3-year: 46.0% vs. 54.7%) and GRFS (HR: 0.65, 95% CI: 0.48-0.90; 3-year: 25.3% vs. 16.1%) while NRM and GVHD incidence were stable. Relapse >6 months post-HSCT1 and remission pre-HSCT2 were associated with better LFS, OS and RI. Conditioning and cytogenetics did not influence outcomes. Mismatched unrelated donor negatively affected OS. These results highlight the improving survival after HSCT2 and support it in selected patients, particularly those relapsing later and in remission at HSCT2.

PMID:41027844 | DOI:10.1111/bjh.70167

J Card Fail. 2025 Sep 28:S1071-9164(25)00435-X. doi: 10.1016/j.cardfail.2025.09.021. Online ahead of print.

NO ABSTRACT

PMID:41027506 | DOI:10.1016/j.cardfail.2025.09.021

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

ABSTRACT

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

PMID:41026944 | DOI:10.32725/jab.2025.014

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

ABSTRACT

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

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

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

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

PMID:41026898 | DOI:10.1093/eurjpc/zwaf593

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

ABSTRACT

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

PMID:41026891 | DOI:10.1093/ehjqcco/qcaf117

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

ABSTRACT

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

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

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

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

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

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

ABSTRACT

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

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

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

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

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

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

ABSTRACT

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

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

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

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

PMID:41025556 | DOI:10.1056/NEJMoa2508170