Sci Rep. 2025 Oct 1;15(1):34277. doi: 10.1038/s41598-025-16552-x.
ABSTRACT
We aimed to evaluate the prognostic value of octanoyl-carnitine in patients undergoing surgical myocardial revascularization for coronary artery disease. We conducted a retrospective analysis of an existing prospective cohort aimed at studying risk factors for vasoplegia in patients undergoing cardiac surgery with cardiopulmonary bypass. We conducted our study exclusively on patients included in the prospective cohort at Dijon University Hospital in 2021. We included 42 adult patients undergoing coronary artery bypass grafting, either alone or combined with another surgical procedure. We collected plasma samples for each patient from EDTA-anticoagulated tubes, taken as part of routine biological check-ups according to the department protocol, at three time points: preoperatively, immediately postoperatively in the intensive care unit, and on the first postoperative day. Liquid chromatography coupled with tandem mass spectrometry was used to determine plasma levels of acyl-carnitines, including octanoyl-carnitine. The primary endpoint was the occurrence of major postoperative complications (stroke, atrial fibrillation, acute kidney injury, and/or death). Fourteen patients (33%) had major postoperative complications. Octanoyl-carnitine plasma concentration significantly increased during the perioperative period and was significantly associated with major postoperative complications at all three time points in coronary artery bypass grafting patients (T1: 14.2 [11.6; 18.6] vs 21.1 [14.8; 28.0], T2: 20.9 [16.4;27.9] vs 34.8 [21.2;37.2], T3: 22.8 [13.7;30.9] vs 34.4 [30.2;41.2]; p < 0.05; in nmol/l). At baseline, octanoyl-carnitine levels were higher in patients with complications, while other acyl-carnitines showed no significant differences. Octanoyl-carnitine is associated with mitochondrial metabolism and could be evaluated alone or in conjunction with clinical scores.
PMID:41034608 | PMC:PMC12488848 | DOI:10.1038/s41598-025-16552-x
Open Heart. 2025 Sep 30;12(2):e003541. doi: 10.1136/openhrt-2025-003541.
ABSTRACT
BACKGROUND: Aortic stenosis (AS) and coronary artery disease (CAD) frequently coexist, requiring careful revascularisation strategy consideration. While surgical aortic valve replacement (SAVR) plus coronary artery bypass grafting (CABG) is traditional, transcatheter aortic valve replacement (TAVR) plus percutaneous coronary intervention (PCI) is increasingly used. The optimal strategy, particularly regarding residual CAD burden, remains unclear.
OBJECTIVES: This study investigated the impact of residual SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (rSS) on outcomes in men and women with AS and CAD undergoing TAVR+PCI versus SAVR+CABG.
METHODS: In this retrospective study, propensity score-matched cohorts of men and women undergoing either procedure were analysed. Matching variables included age, left ventricular ejection fraction, EuroSCORE II (European System for Cardiac Operative Risk Evaluation II) and CAD severity.
RESULTS: 398 patients (114 women and 284 men) were included. The rSS was predictive of the primary composite endpoint in the TAVR+PCI group (p=0.006 women and p<0.001 men) but not in the SAVR+CABG group. In patients achieving an rSS<8, TAVR+PCI was associated with a lower combined endpoint rate compared with SAVR+CABG, consistent across genders (p=0.02). Furthermore, TAVR+PCI demonstrated significant safety benefits, including lower rates of major bleeding in men (2.1% vs 10.6%) and stroke in women (1.8% vs 12.3%).
CONCLUSIONS: The prognostic importance of the rSS is strategy-dependent. For patients undergoing TAVR+PCI, achieving extensive revascularisation (rSS <8) is a critical procedural goal associated with improved outcomes. For patients undergoing SAVR+CABG, prognosis appears driven more by baseline clinical risk.
PMID:41033711 | PMC:PMC12496072 | DOI:10.1136/openhrt-2025-003541
Open Heart. 2025 Sep 30;12(2):e003317. doi: 10.1136/openhrt-2025-003317.
ABSTRACT
BACKGROUND: Routine invasive management by coronary angiography and revascularisation as appropriate reduces recurrent ischaemic events in non-ST-segment myocardial infarction (NSTEMI), but its mortality benefit is uncertain.
METHODS: Within this state-wide retrospective cohort study, patients with a primary diagnosis of NSTEMI were identified from the New South Wales (NSW) Admitted Patient Data Collection database between 2003 and 2020 and linked to the NSW death registry. Primary outcomes were cardiovascular (CV) and all-cause mortality among NSTEMI patients stratified by in-hospital invasive management.
RESULTS: Among 121 089 patients with NSTEMI (median age 71.4 years; 62.7% men), invasive management increased from 48.8% to 66.8% while all-cause in-hospital mortality decreased from 4.8% to 2.9% between triennial periods of 2003-2005 and 2018-2020, respectively. During the follow-up period (median 8.47 years), 47 304 (39.1%) patients died. CV mortality fell between 2003 and 2020 for those who were and were not invasively managed with greater magnitude in the former (subdistribution HR (sHR)=0.32, 95% CI 0.29 to 0.36; sHR=0.58, 95% CI 0.54 to 0.63, respectively, pinteraction<0.001). For all-cause mortality, the fall was significant for the invasively managed patients, with no plateau evident, but not in patients managed conservatively (adjusted HR (aHR)=0.56, 95% CI 0.52 to 0.61; aHR=1.00, 95% CI 0.95 to 1.06, respectively, pinteraction<0.001).
CONCLUSIONS: In patients presenting to NSW hospitals with NSTEMI between 2003 and 2020, we observed improvements in CV mortality in both invasively and conservatively managed patients while all-cause mortality improved in invasively but not conservatively managed patients. Wider implementation of routine invasive management may further improve long-term mortality among NSTEMI patients in NSW.
PMID:41033709 | PMC:PMC12496111 | DOI:10.1136/openhrt-2025-003317
Am J Case Rep. 2025 Oct 1;26:e947359. doi: 10.12659/AJCR.947359.
ABSTRACT
BACKGROUND Managing acute coronary syndrome in cancer patients poses significant challenges for cardiologists, who often encounter various complications. However, there are multiple therapeutic strategies available. The key lies in identification of the target lesion and early restoration of antegrade blood flow in cases in which it is affected. CASE REPORT We present a case of a 70-year-old man with a medical history of hypertension, type II diabetes mellitus, bioprosthetic aortic valve, coronary artery disease with prior PCI to the LAD, and metastatic prostate cancer who presented with chest pain and shortness of breath. The patient was hemodynamically unstable, with elevated lactates and troponin levels. He was diagnosed with cardiogenic shock secondary to N-STEMI. Coronary angiography revealed a high thrombotic burden at the LM bifurcation, which was managed with balloon angioplasty and medical therapy without stent implantation. Intravascular imaging with IVUS was performed 2 days later, which showed no dissections or significant stenosis. A conservative management strategy was implemented. CONCLUSIONS Cardiogenic shock is a life-threatening complication of N-STEMI, necessitating urgent coronary angiography and immediate revascularization. In certain cases, particularly those involving active malignancy, plain balloon angioplasty combined with optimal medical therapy can be a viable alternative to stent placement. Intravascular imaging assists in making the final decision. Cancer should not be considered a contraindication for invasive treatment in patients presenting with acute coronary syndrome.
PMID:41032480 | PMC:PMC12499628 | DOI:10.12659/AJCR.947359
Catheter Cardiovasc Interv. 2025 Oct 1. doi: 10.1002/ccd.70220. Online ahead of print.
ABSTRACT
BACKGROUND: The comparative outcomes of DEB vs. DES in diabetic patients undergoing PPCI are of significant clinical interest, as these patients often experience higher rates of restenosis and adverse outcomes.
AIMS: This study aimed to compare the outcomes of drug-eluting balloons (DEB) versus drug-eluting stents (DES) in diabetic patients undergoing primary percutaneous coronary intervention (PPCI).
METHODS: We conducted a retrospective analysis of 5668 diabetic patients who underwent PPCI, with 1734 patients in the DEB group and 3934 patients in the DES group. Baseline characteristics, angiographic features, and clinical outcomes, including procedural success, major adverse cardiovascular events (MACE), target lesion revascularization (TLR), restenosis, and bleeding complications, were compared between the two groups.
RESULTS: Both DEB and DES groups demonstrated high procedural success rates (97.6% and 98.4%, respectively), with no significant differences in MACE, death, myocardial infarction, or target vessel revascularization. Restenosis at 6 months occurred in 3.9% of the DEB group and 3.4% of the DES group (p = 0.21). Lesion length, diabetes duration, hypertension, and prior myocardial infarction were identified as significant predictors of adverse outcomes. Use of DES was associated with a higher risk of MACE, but this did not translate into significant differences in clinical outcomes.
CONCLUSION: Both DEB and DES are effective and safe treatment options for diabetic patients undergoing PPCI, with comparable outcomes in terms of procedural success, MACE, and restenosis.
PMID:41031463 | DOI:10.1002/ccd.70220
Cardiovasc Ther. 2025 Sep 22;2025:3713315. doi: 10.1155/cdr/3713315. eCollection 2025.
ABSTRACT
Background: Recently, the combination of rotational atherectomy (RA) with intravascular lithotripsy (IVL), known as "RotaTripsy," has been employed in the treatment of coronary lesions with severe calcification. In this article, we provide an overview of the current evidence regarding this technique, emphasizing the importance of appropriate patient and lesion selection to achieve optimal clinical outcomes, including the primary goal of improvement of stenting and enhancement of short and long-term prognosis. Methods: We performed a systematic literature search using PubMed, Embase, Web of Science, and Cochrane library up to July 2024 for studies that combined RA and IVL for coronary artery calcification lesions that were included. The retrieved articles and references of the primary articles were used to collect the basic information. SPSS 20.0 and Excel statistic software were used to conduct this scoping review. Results: A total of 25 studies consisting of 259 patients were identified. Of all the patients, 208 (80.3%) were male. Patients had an average age of 68.31 years, and 119 (45.95) patients had acute coronary syndrome. In addition, 218 (84.17%) had hypertension, 128 (49.42%) had diabetes mellitus, and 48 (18.53%) had chronic kidney disease. In the ultimate analysis, 252 patients (97.3%) successfully underwent the "RotaTripsy" procedure, with a minimal mortality rate of only 7 individuals (2.7%) during the follow-up period. Conclusions: "RotaTripsy," as an efficacious therapeutic modality, shows its unique potential for severe calcified coronary artery lesions resistant to dilation. Our research findings substantiate its feasibility, safety, and effectiveness in clinic.
PMID:41031101 | PMC:PMC12479158 | DOI:10.1155/cdr/3713315
BMC Cardiovasc Disord. 2025 Sep 30;25(1):708. doi: 10.1186/s12872-025-05136-2.
ABSTRACT
BACKGROUND: Physical activity prior to elective coronary artery bypass grafting (CABG) surgery can potentially improve postoperative outcomes. The aim of the study was to evaluate subjectively and objectively physical activity levels and dose-characteristics in free-living conditions in patients awaiting CABG surgery.
METHODS: A single-centered cross-sectional subanalysis of 32 participants awaiting elective CABG surgery. Physical activity during the preoperative period was assessed subjectively with the SQUASH questionnaire and objectively with the Sensewear activity monitor (accelerometer with physiological sensors). The Wilcoxon signed-rank test was used to assess differences and Bland-Altman plots were used to assess the agreement between the measurement methods. Descriptive statistics were used for the dose-characteristics and Cohen's Kappa for the proportion of participants fulfilling the Dutch guideline for healthy physical activity (NNGB).
RESULTS: Duration of vigorous activity was significantly higher when measured subjectively (120 min/week) than objectively (7 min/week, p = 0.001). Bland-Altman plots showed that differences between the methods increased with longer durations of moderate and total activity. The dose-characteristics of physical activity measured with the SQUASH varied widely among the participants and it consisted mainly of leisure time activities and light household activities. The percentage of participants complying with the NNGB guideline was 74% when measured subjectively and 90% when measured objectively (κ = 0.259, p = 0.089).
CONCLUSIONS: Surprisingly, both measurement methods suggest that the majority of patients awaiting CABG surgery met the recommendations of the NNGB guideline. The agreement between the methods however decreased with higher physical activity levels. Despite its limitations, the study suggests the complementary value of a subjective and objective measurement of physical activity in free-living conditions among CABG patients.
PMID:41029232 | PMC:PMC12482120 | DOI:10.1186/s12872-025-05136-2
J Imaging Inform Med. 2025 Sep 30. doi: 10.1007/s10278-025-01667-4. Online ahead of print.
ABSTRACT
This study aims to develop and assess an optimized three-dimensional convolutional neural network model (3D CNN) for predicting major cardiac events from coronary computed tomography angiography (CCTA) images in patients with suspected coronary artery disease. Patients undergoing CCTA with suspected coronary artery disease (CAD) were retrospectively included in this single-center study and split into training and test sets. The endpoint was defined as a composite of all-cause death, myocardial infarction, unstable angina, or revascularization events. Cardiovascular risk assessment relied on Morise score and the extent of CAD (eoCAD). An optimized 3D CNN mimicking the DenseNet architecture was trained on CCTA images to predict the clinical endpoints. The data was unannotated for presence of coronary plaque. A total of 5562 patients were assigned to the training group (66.4% male, median age 61.1 ± 11.2); 714 to the test group (69.3% male, 61.5 ± 11.4). Over a 7.2-year follow-up, the composite endpoint occurred in 760 training group and 83 test group patients. In the test cohort, the CNN achieved an AUC of 0.872 ± 0.020 for predicting the composite endpoint. The predictive performance improved in a stepwise manner: from an AUC of 0.652 ± 0.031 while using Morise score alone to 0.901 ± 0.016 when adding eoCAD and finally to 0.920 ± 0.015 when combining Morise score, eoCAD, and CNN (p < 0.001 and p = 0.012, respectively). Deep learning-based analysis of CCTA images improves prognostic risk stratification when combined with clinical and imaging risk factors in patients with suspected CAD.
PMID:41028565 | DOI:10.1007/s10278-025-01667-4
Exp Mol Med. 2025 Oct 1. doi: 10.1038/s12276-025-01549-3. Online ahead of print.
ABSTRACT
Therapeutic interventions to replenish lost cardiomyocytes and recover myocardium functions following ischemic myocardial infarction (MI) remain major goals in the cardiac regeneration field. Clinical trials harnessing autologous or allogeneic cell therapy approaches from both cardiac and noncardiac cells sources, thus far, demonstrate marginal improvement. Moreover, complications such as arrythmias and graft rejections associated with cellular or organ-based therapies continue to prevail. Extracellular vesicles, on the other hand, are cell-derived, nano-sized, cargo-containing biomolecules that have emerged as potent alternatives to cell-based cardiac regeneration/replacement therapy. Recent studies demonstrate that most stem-cell-derived extracellular vesicles (Stem-EVs) are nonimmunogenic and carry cardioprotective therapeutic cargos. Moreover, administration of multiple Stem-EV types in animal models of acute MI results in reduced inflammation, apoptosis, smaller infarct size and improved cardiac functionality. With recent developments, engineered Stem-EVs with enhanced cardiac targeting, prolonged circulation and recombinant therapeutic cargos may tilt the cardiac regeneration field toward these novel cell-free biologics. Here we provide a brief overview of current approaches to repair and replenish damaged cardiomyocytes following MI via cell therapy and in vivo reprogramming, and we delve deeply into the therapeutic potentials of Stem-EVs in cardiac repair and regeneration.
PMID:41034526 | DOI:10.1038/s12276-025-01549-3
Circ Res. 2025 Oct 1. doi: 10.1161/CIRCRESAHA.125.326522. Online ahead of print.
ABSTRACT
BACKGROUND: Induction of cardiomyocyte proliferation in situ represents a promising strategy for myocardial regeneration following injury. However, cardiomyocytes possess intrinsic inhibitory mechanisms that attenuate pro-proliferative signaling and constrain their expansion. We hypothesized that cell-cell contact is a key suppressor of cardiomyocyte proliferation. We aimed to delineate the underlying molecular pathways to enable sustained proliferation in 3-dimensional contexts.
METHODS: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured at varying plating densities to examine the impact of cell-cell contact on cell cycle activity. Phosphoproteomic profiling was performed in sparse versus dense cultures to identify signaling alterations. Conditioned media from sparse cultures were interrogated using a human growth factor array to identify secreted pro-proliferative factors.
RESULTS: hiPSC-CM proliferation increased proportionally with plating density until intercellular contacts were established, at which point proliferation was suppressed. Dense cultures exhibited enhanced adherens junction assembly, sarcomeric organization, and contractile function. Increased cell-cell contact in dense conditions attenuated nuclear translocation of β-catenin and reduced TCF/LEF transcriptional activity, providing a mechanistic basis for the reduced hiPSC-CM proliferation. Disruption of adherens junctions or sarcomere assembly via siRNA-mediated knockdown of N-cadherin or α-actinin, respectively, resulted in increased cell cycle activation of hiPSC-CMs, but this was not sufficient to drive division of hiPSC-CMs. Additional screening for putative secreted growth factors in the conditioned media from sparsely plated hiPSC-CMs revealed the enrichment of IGFBP2, which was sufficient to drive hiPSC-CM division in the presence of cell-cell contact in 3-dimensional constructs.
CONCLUSIONS: Our findings demonstrate that cell-cell contact inhibits hiPSC-CM proliferation through adherens junction formation, sarcomeric assembly, and reduced IGFBP2 secretion. Importantly, exogenous supplementation of IGFBP2 can overcome cell contact-mediated inhibition of hiPSC-CM proliferation and facilitate the growth of 3-dimensional cardiac tissue. These insights provide valuable implications for advancing cardiac tissue engineering and regenerative therapies.
PMID:41031396 | DOI:10.1161/CIRCRESAHA.125.326522
Int J Biol Macromol. 2025 Sep 29;330(Pt 1):148001. doi: 10.1016/j.ijbiomac.2025.148001. Online ahead of print.
ABSTRACT
Ganoderma lucidum polysaccharides (GLPs) are a diverse class of bioactive compounds abundantly present in the mycelia, fruiting bodies, and spores of Ganoderma lucidum (G. lucidum). In recent years, GLPs have attracted considerable attention owing to their broad pharmacological activities and favorable safety profile. Despite advances in therapeutic approaches that have improved survival rate, cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. CVDs are characterized by a complex pathogenesis and multiple risk factors, including hyperglycemia, lipid metabolism disturbances, and chronic inflammation. Accumulating evidence has demonstrated that GLPs exhibit remarkable anti-inflammatory and antioxidant properties, while also exerting regulatory effects on glucose and lipid homeostasis. Additionally, GLPs have demonstrated therapeutic potential in ameliorating endothelial dysfunction, modulating angiogenesis, attenuating atherosclerosis, and mitigating chemical-induced cardiotoxicity. This review summarizes the fundamental pharmacological activities of GLPs and discusses their potential mechanisms in cardiovascular diseases, with the aim of providing a valuable reference for future research and clinical application.
PMID:41033521 | DOI:10.1016/j.ijbiomac.2025.148001
Xenobiotica. 2025 Oct 1:1-12. doi: 10.1080/00498254.2025.2567470. Online ahead of print.
ABSTRACT
Phytopharmacology has become a key approach for developing new therapeutic strategies by utilizing the diverse bioactive properties of plant-derived compounds to treat complex diseases, including cardiovascular disorders.Myocardial ischemia-reperfusion (I/R) injury presents a major challenge in the management of acute myocardial infarction by worsening myocardial damage through oxidative stress, apoptosis, and cellular senescence.Carvacrol, a monoterpenoid phenol present in plants such as Origanum vulgare, possesses potent antioxidant and anti-inflammatory properties.This study investigates carvacrol's cardioprotective effects in an H9C2 cardiac myoblast model of I/R injury.Cardiac myoblast cells were exposed to an ischemic buffer to simulate I/R conditions, with carvacrol administered at a sub-cytotoxic dose of 12.5 µg/ml prior to exposure. Carvacrol significantly enhanced cell viability by 77.37% restoration, reduced lactate dehydrogenase (LDH) release (from 330.5 ± 25.3 to 160.8 ± 15.7 U/ml, p < 0.01), suppressed reactive oxygen species (ROS) production, inhibited caspase-3 and -8 activities, and mitigated cellular senescence as evidenced by reduced β-galactosidase staining. Additionally, carvacrol restored the expression of the myogenin gene, which was downregulated by ischemic injury.These findings highlight carvacrol's antioxidant, anti-apoptotic, anti-senescence, and gene-regulatory properties, positioning it as a promising therapeutic candidate for mitigating myocardial I/R injury.
PMID:41030227 | DOI:10.1080/00498254.2025.2567470
Cardiovasc Diabetol. 2025 Sep 30;24(1):370. doi: 10.1186/s12933-025-02900-8.
ABSTRACT
BACKGROUND: Combination therapy with glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), and/or finerenone offers a strategy to reduce the risk of adverse cardiovascular and renal outcomes. This study aimed to quantify the cardiorenal benefits of combination regimens with GLP-1RA, SGLT2i, and/or finerenone versus corresponding monotherapies.
METHODS: MEDLINE and Embase were systematically searched, yielding four post hoc analyses of randomized controlled trials (RCTs) and ten observational studies that met prespecified inclusion criteria. Among RCTs, a random-effects meta-regression was performed to assess whether the effect of GLP-1RAs on cardiorenal outcomes differed based on baseline SGLT2i use. Additionally, for observational studies, random-effects meta-analyses were performed to estimate the effect of combination therapy versus monotherapy on the risk of cardiorenal outcomes.
RESULTS: Across RCTs, p for interaction was > 0.05 for major adverse cardiac events (MACE) (p = 0.730), cardiovascular (CV) mortality (p = 0.889), non-fatal myocardial infarction (MI) (p = 0.237), non-fatal stroke (p = 0.696), all-cause mortality (p = 0.682), heart failure (HF) hospitalization (p = 0.257), and renal composite outcome (p = 0.890), supporting that GLP-1RAs result in a consistent reduction in outcomes irrespective of baseline SGLT2i use. In observational trials, compared to SGLT2i monotherapy, GLP-1RA and SGLT2i combination therapy significantly reduced MACE (HR 0.59, 95% CI 0.47-0.75), MI (HR 0.73, 95% CI 0.61-0.88), stroke (HR 0.72, 95% CI 0.53-0.97), all-cause mortality (HR 0.57, 95% CI 0.48-0.67), and HF hospitalization/events (HR 0.71, 95% CI 0.59-0.86). Compared to GLP-1RA monotherapy, SGLT2i and GLP-1RA combination therapy significantly reduced CV mortality (HR 0.35, 95% CI 0.15-0.81), MI (HR 0.93, 95% CI 0.88-0.97), stroke (HR 0.92, 95% CI 0.88-0.96), all-cause mortality (HR 0.59, 95% 0.49-0.70), HF hospitalization/events (HR 0.84, 95% CI 0.81-0.88), and serious renal events (HR 0.43, 95% CI 0.23-0.80). Compared to either SGLT2i or finerenone monotherapy, SGLT2i and finerenone combination therapy significantly reduced all-cause mortality and major adverse kidney events.
CONCLUSION: Combination therapy with GLP-1RA, SGLT2i, or finerenone confers cardiorenal protection beyond monotherapy in T2D, as supported by concordant evidence from RCTs and large real-world cohorts. These findings support broader clinical adoption of dual-agent strategies but also underscore the need for dedicated prospective trials powered to assess hard clinical outcomes with dual-agent strategies.
PMID:41029853 | PMC:PMC12487346 | DOI:10.1186/s12933-025-02900-8
J Cardiothorac Surg. 2025 Sep 30;20(1):353. doi: 10.1186/s13019-025-03625-1.
NO ABSTRACT
PMID:41029744 | PMC:PMC12487582 | DOI:10.1186/s13019-025-03625-1
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