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Lancet Glob Health. 2025 Jul;13(7):e1191-e1202. doi: 10.1016/S2214-109X(25)00109-3.

ABSTRACT

BACKGROUND: Stroke, ischaemic heart disease, and dementia share risk factors and influence one another, substantially affecting brain health. Limited health-care resources in Africa might exacerbate the burden of these diseases, with serious brain health consequences. We analysed trends from 1990 to 2021 to inform optimised prevention strategies.

METHODS: Using The Global Burden of Diseases, Injuries, and Risk Factors Study 2021 data, we assessed the burden of these conditions, measured by disability-adjusted life-years (DALYs) lost attributed to 12 risk factors, and their changes from 1990 to 2021. Bayesian modelling generated means and 95% uncertainty intervals (UIs) based on the 2·5th and 97·5th percentiles of 500 posterior distribution draws.

FINDINGS: In Africa in 2021, 17·3 (95% UI 15·5-19·2) million DALYs were lost due to strokes, 17·6 (15·5-19·6) million were lost due to ischaemic heart diseases, and 1·8 (0·8-4·0) million were lost due to dementia. New and prevalent cases doubled from 1990 to 2021, with two-thirds of DALYs occurring before age 70 years. Among five continents, Africa had the highest age-standardised DALY rates per 100 000 population for stroke (2628·1 [2367·4-2893·0]) and ischaemic heart disease (2743·5 [2451·8-3033·6]), and the lowest for dementia (423·4 [190·6-934·6]). Regionally, central and southern Africa showed higher stroke DALY rates, northern Africa had the highest rates for ischaemic heart disease, and central and northern Africa had the highest rates for dementia. Among 12 modifiable risk factors, high systolic blood pressure, unhealthy diet, and air pollution contributed most to DALYs. Stroke DALYs rose prominently due to high BMI, high fasting plasma glucose, high LDL cholesterol, low physical activity, and high systolic blood pressure.

INTERPRETATION: Africa faces substantial challenges from stroke, heart disease, and dementia, including the highest DALY rates globally, with worsening trends over the past three decades, including younger ages of onset. These patterns, coupled with limited health resources, necessitate urgent and targeted strategies to protect, preserve, and promote brain health in Africa.

FUNDING: Weston Family Foundation.

PMID:40580987 | DOI:10.1016/S2214-109X(25)00109-3

Biomed Pharmacother. 2025 Jun 27;189:118296. doi: 10.1016/j.biopha.2025.118296. Online ahead of print.

ABSTRACT

Lipid peroxidation and ferroptosis are critically for the development of cardiac ischaemia-reperfusion (I/R) injury. The proteasome complex is crucial for regulating inflammation and cardiac I/R injury. Proteasome-activating peptide 1 (PAP1) is an activator of the proteasome β5i subunit, but its role in cardiac I/R injury remains unknown. Our results indicate that the administration of PAP1 highly enhanced the expression and activity of the β5i in cardiac tissues possibly by inhibiting of STAT3. Moreover, compared with vehicle control, administration of PAP1 in wild-type mice greatly reversed the I/R-induced decline in myocardial contractility and increases in myocardial infarction, fibrosis, myocyte apoptosis, ROS production and inflammatory response. RNA sequencing revealed that PAP1 mainly affected the genes that were associated with heart contraction, ferroptosis, apoptosis, ROS production and p53. Furthermore, PAP1 clearly decreased the p53 protein and increased the protein levels of SLC7A11 and GPX4 both in mice and cultured cardiomyocytes. Conversely, these protective actions of PAP1 were significantly eliminated in the mice treated with the β5i inhibitor epoxomicin or in the cardiomyocytes transfected with shRNA-β5i but were enhanced by the inhibition of p53 with pifithrin-α. Mechanistically, PAP1 increased the β5i expression, which then bound to p53 and promoted its degradation, resulting in the upregulation of SLC7A11 and GPX4 proteins and the attenuation of oxidative stress and ferroptosis. In summary, our findings suggest that PAP1 can protect against myocardial I/R injury possibly via the β5i-p53-SLC7A11 axis and represent a novel drug candidate for the treating ischaemic heart injury.

PMID:40580875 | DOI:10.1016/j.biopha.2025.118296

Phytomedicine. 2025 Jun 16;145:156994. doi: 10.1016/j.phymed.2025.156994. Online ahead of print.

ABSTRACT

BACKGROUND: Tanshinone I (Tan I) is an essential active ingredient of the traditional cardiovascular medicine Salvia miltiorrhiza Bunge (S. miltiorrhiza). Although the protection of Tan I on cardiomyocyte has been reported, its anti-myocardial ischemia effects and mechanisms remain unknown.

PURPOSE: Systematic evaluation of the role of Tan I in reducing myocardial ischemia (MI) injury and elucidation of the underlying molecular mechanisms by which Tan I improves myocardial fibrosis and ventricular function in mouse MI models.

METHODS: In vivo and in vitro MI models were constructed to substantiate the anti-MI effects of Tan I. Through target fishing, molecular docking, and network pharmacology investigation, the effect mechanisms and potential target proteins of Tan I against MI were predicted further. Tandem mass tags (TMT)-based quantitative proteomics, transforming growth factor beta receptor I (TGFBR1)-overexpressing lentiviral vectors, molecular dynamics (MD) simulations, biolayer interferometry (BLI), cellular thermal shift assay (CETSA), TGFBR1 kinase activity, and drug affinity responsive target stability (DARTS) assay were subsequently used to validate the anti-MI-effect mechanisms and targets of Tan I.

RESULTS: Tan I can markedly increase the survival of oxidative stress cell models, improve intracellular environment, and inhibit the release of intracellular reactive oxygen species. Moreover, it can restore abnormal electrocardiograms, decrease myocardial infarction area, inhibit cardiac fibrosis, and reduce serum levels of key cardiac injury biomarkers in the MI mouse model. Mechanistically, Tan I considerably inhibited the phosphorylation modification levels of TGFBR1 and Smad2 and the aberrant expressions of Collagen I/III, α-smooth muscle actin, Bcl-2, and Bax proteins in MI mice. These findings were further verified in NIH-3T3 cells overexpressing TGFBR1 or activated by TGF-β1. MD simulations, CETSA, and DARTS showed that TGFBR1 binding to Tan I was relatively stable. In addition, BLI indicated that the equilibrium dissociation constant of Tan I binding TGFBR1 was 1.5 × 10-6 M. Based on the kinase activity assay, Tan I restrained TGFBR1 with a half-maximal inhibitory concentration of 739.6 nM.

CONCLUSION: This work reveals for the first time that Tan I can reduce MI injury and fibrosis by modulating the TGF-β signaling pathway via targeting of TGFBR1.

PMID:40580691 | DOI:10.1016/j.phymed.2025.156994

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 28. doi: 10.1007/s00210-025-04409-z. Online ahead of print.

ABSTRACT

PURPOSE: Cardiovascular diseases are one of the leading causes of death worldwide. Vitamin D (VITD) regulates cell proliferation, differentiation, apoptosis and angiogenesis. It boosts glutathione synthesis, reduces reactive oxygen species (ROS), protects tissues and exerts anti-inflammatory effects by lowering proinflammatory cytokines (IL-1β, IL-6, TNF-α) through VITD receptor activation. The aim of this study was to investigate the effects of VITD on liver tissue changes, oxidative stress and inflammation following myocardial infarction (MI) and ischemia/reperfusion (I/R) injury, focusing on its modulation of asprosin (ASP), spexin (SPX) and meteorin-like (METRNL) biomarkers to explore new therapeutic strategies.

METHODS: Rats were divided into four groups (n=7): Control (I), MI (II), VITD (III), and MI + VITD (IV). MI was induced with 200 mg/kg isoproterenol, and VITD (50 IU/day) was administered for 14 days as treatment.

RESULTS: Histopathologically; congestion, sinusoidal dilatation, necrotic hepatocytes and fibrosis, and immunohistochemically; ASP, SPX and METRNL immunoreactivity were examined in the liver tissues of rats. In the immunohistochemical examination of ASP, SPX and METRNL, the histoscore in the MI group was significantly higher compared to the control and VITD groups (p<0.001). The effect size of these differences was large.

CONCLUSION: ASP, SPX, and METRNL can be used as immunohistochemical biomarkers in order to demonstrate ischemia reperfusion injury in the liver of rats with MI. When the findings are evaluated, the application of VITD, a cytoprotective antioxidant, appears to play an effective role in preserving the biochemical and histological properties of hepatocytes. VITD is considered to contribute significantly to the histopathological and biochemical preservation of liver tissue.

PMID:40580311 | DOI:10.1007/s00210-025-04409-z

Proteomics. 2025 Jun;25(11-12):e00087. doi: 10.1002/pmic.202500087.

ABSTRACT

As space exploration becomes increasingly accessible, understanding the molecular and pathophysiological consequences of spaceflight on the human body becomes crucial. Space-induced modifications could disrupt multiple signaling pathways, with significant implications for the functional integrity of cardiovascular, nervous, and musculoskeletal systems, among others. In a recent study, Bourdakou et al. have focused on alterations in gene expression profiles linked to cardiovascular disease (CVD), using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) undergoing spaceflight and subsequent postflight conditions. Genes with known associations with CVD and nuclear factor erythroid 2-related factor 2 (NRF2) oxidative stress regulatory network have been identified to present consistent directional expression changes in both spaceflight and postflight. A computational drug repurposing analysis identified ten candidate agents with the potential to reverse observed transcriptomic modifications in spaceflight-exposed cardiomyocytes. These findings highlight the importance of molecular studies and emphasize the need for integrative, multi-omic research efforts to protect human health during and beyond spaceflight.

PMID:40579866 | DOI:10.1002/pmic.202500087

Ann Rheum Dis. 2025 Jun 27:S0003-4967(25)01039-8. doi: 10.1016/j.ard.2025.05.021. Online ahead of print.

ABSTRACT

OBJECTIVES: To establish the long-term impact of cytokine-directed therapies on glucocorticoid use and clinical outcomes in Vacuoles, E1-enzyme, X-linked, Autoinflammatory, Somatic (VEXAS).

METHODS: Patients with VEXAS were prospectively followed for events of transfusion dependence, haematopoietic stem cell transplantation or death. Laboratory results, glucocorticoid exposure and clinical measures were retrospectively assessed in relationship to treatment initiation with interleukin-6-directed therapies (anti-IL6R) or Janus kinase inhibitors (JAKi). Patients were stratified by UBA1 variants and presence of typical clonal haematopoiesis with variant allele fraction ≥ 10% (CHVAF≥10%).

RESULTS: In 71 VEXAS patients (81.7% with anti-IL6R or JAKi exposure), event-free survival differed by genotype and presence of concomitant CHVAF≥10%: p.M41V (HR [95% confidence interval (CI)]: 5.7 [1.5-20.4]) or p.M41L/T with CHVAF≥10% (hazard ratio [HR]: 5.7 [1.6-20.8]) compared to p.M41L. No association between event rates and exposure to anti-IL6R or JAKi was observed. The p.M41V genotype had the highest risk of anaemia, elevated C-reactive protein (CRP) levels, and monocytopenia. Over a median follow-up of 4.8 (interquartile range [IQR] 3.0, 8.1) years, the patients' mean glucocorticoid dose was >15 mg/day prednisone regardless of variant or disease duration. At prospective visits, clinical remission on ≤10 mg/day prednisone was observed in only 2.7% of visits. Treatment with anti-IL6R or JAKi showed no clinically meaningful reduction (<5 mg/day difference) in steroid exposure at 1 year post-treatment. No attenuation in the progression of anaemia was observed in response to anti-IL6R and JAKi.

CONCLUSIONS: Cytokine-directed therapies alone do not alter the risk of haematologic disease progression or significantly reduce glucocorticoid exposure in VEXAS. These data provide benchmarks for future interventional studies.

PMID:40581580 | DOI:10.1016/j.ard.2025.05.021

Phys Med Rehabil Clin N Am. 2025 Aug;36(3):647-662. doi: 10.1016/j.pmr.2025.03.008. Epub 2025 May 24.

ABSTRACT

Hospitalized pediatric heart transplant (PHT) recipients face unique and multifaceted challenges that impact their functional outcomes, including motor skills, activities of daily living, feeding, and communication. Perioperative complications, lengthy hospitalizations, physical deconditioning, and comorbidities associated with complex congenital heart disease are important considerations as they can have a profound impact on their functional abilities and progress of individuals toward achieving independence. This article explores the role of rehabilitation providers in addressing these functional challenges through performance-based outcome measures and aims to support the development of tailored rehabilitation programs to achieve improved quality of life and long-term independence for PHT recipients.

PMID:40581444 | DOI:10.1016/j.pmr.2025.03.008

J Heart Lung Transplant. 2025 Jun 26:S1053-2498(25)02038-8. doi: 10.1016/j.healun.2025.06.012. Online ahead of print.

ABSTRACT

BACKGROUND: Lung transplantation offers life-saving benefits for patients with end-stage lung disease, however, long-term outcomes remain poor, with a median survival of 6.5 years. Identifying patients at risk for poor post-transplant lung function is crucial for improving outcomes. While peri-operative and demographic factors have previously been studied, the impact of donor-specific antibodies (DSA) on longitudinal post-transplant lung function remains unclear. This study examines the effects of DSA on post-transplant lung function and the risk of baseline lung allograft dysfunction (BLAD).

RESEARCH QUESTION: Is DSA development linked to worse longitudinal lung function, higher BLAD rates, and poorer survival compared to DSA-negative patients regardless of the development of clinical AMR?

METHODS: The study included lung transplant recipients from two prospective cohort studies, comparing DSA+ and DSA- patients. All participants underwent serial surveillance and clinically-indicated bronchoscopy, pulmonary function tests, and DSA testing. Statistical analysis included linear mixed models for longitudinal lung function data, multivariable logistic regression for BLAD, and survival analysis using Cox Proportional Hazard models.

RESULTS: We analyzed 213 patients with a median follow-up of 48.1 months. Among them, 50.7% developed DSA. DSA+ patients showed significantly lower rates of post-transplant spirometric improvement compared to DSA- patients (p=0.008 for %FVC; p=0.02 for %FEV1). After DSA diagnosis, there was a significant decrease in the slopes of %FVC and %FEV1 (p=0.0008 and p=0.0006, respectively). DSA+ patients had a higher risk of developing BLAD (OR 2.14, 95% CI [1.45, 3.17], p=0.0001). Additionally, DSA+ patients had a higher risk of death (HR 2.98, 95% CI [1.79, 4.99], p<0.0001). These findings were consistent even when excluding patients with clinical antibody-mediated rejection (AMR).

INTERPRETATION: Our study demonstrates that DSA development significantly impairs post-transplant lung function and increases the risk of BLAD even in the absence of clinical AMR. These findings suggest that DSA may serve as a biomarker of BLAD, and could potentially aid in risk stratification following lung transplantation.

PMID:40581272 | DOI:10.1016/j.healun.2025.06.012

J Heart Lung Transplant. 2025 Jun 26:S1053-2498(25)02055-8. doi: 10.1016/j.healun.2025.06.019. Online ahead of print.

ABSTRACT

PURPOSE: Early referral for lung transplantation in patients with pulmonary arterial hypertension (PAH) is recommended by multiple professional societies. We sought to use the Pulmonary Hypertension Association Registry (PHAR) to describe the current landscape of referrals for lung transplantation in patients with PAH.

METHODS: PHAR is a 72-center US-based registry of patients with PAH. Participants were followed longitudinally with repeat assessments of clinical parameters, including referrals for transplantation. We compared clinical parameters between those referred for transplantation at any point, with those never referred. Next, we tested whether various clinical parameters predicted time to referral, using cox-proportional hazards modeling and stepwise backward elimination.

RESULTS: Of 1671 participants analyzed with 4607 person-years of follow up, 199 (12%) were referred for transplantation. Of those referred, 30% underwent transplantation and 21% died without transplantation. Only 18-29% of participants with functional class 4 disease, REVEAL Lite 2 high-risk disease, or 2022 ESC/ERS high-risk disease were referred for transplant. Rates of referral did not increase in sensitivity analyses restricting the cohort to participants without obvious contraindications based on body mass index or age. In multivariate modeling accounting for death as a competing risk, a diagnosis of pulmonary veno-occlusive disease, higher REVEAL Lite 2 Scores, and parenteral prostacyclin use were associated with increased likelihood of referral, while older age and higher body mass index were associated with decreased likelihood of referral.

CONCLUSION: Rates of referral for lung transplantation in patients with PAH remain unacceptably low and occur too late. Increased awareness of the benefit of early referral is necessary, even at expert centers.

PMID:40581270 | DOI:10.1016/j.healun.2025.06.019

J Geriatr Oncol. 2025 Jun 27;16(7):102303. doi: 10.1016/j.jgo.2025.102303. Online ahead of print.

ABSTRACT

INTRODUCTION: The clinical uptake of validated chemotherapy toxicity predictor tools for older adults with cancer remains low. In this qualitative study, we sought to evaluate oncologist perspectives on the acceptability, appropriateness, and feasibility of the Cancer and Aging Research Group (CARG) chemotherapy toxicity predictor tool.

MATERIALS AND METHODS: We conducted semi-structured qualitative interviews with 18 medical oncologists in the M Health Fairview system to understand barriers to CARG tool use and implementation solutions. A trained researcher conducted interviews, and two coders analyzed interview transcripts to identify themes. Using an implementation science framework, we categorized oncologist perspectives into the outcomes of acceptability, appropriateness, and feasibility.

RESULTS: We identified four themes: (1) current methods for assessing chemotoxicity risk, (2) acceptability - perceptions of the CARG tool, (3) appropriateness - perceptions of the CARG tool in practice, and (4) appropriateness - integration of the CARG tool into oncologist workflow. Participants highlighted the relevance of the CARG questions but noted that certain treatment regimens required additional information (e.g., cardiac function or pre-existing neuropathy). They also noted that the topline results lack nuance and are difficult to interpret, with concern about the tool keeping up with the rapid pace of oncology advances. They pointed out that the tool was not applicable for every patient, especially newer treatments, and questioned the benefit over standard of care. However, they emphasized that a trusted colleague who could be a champion could aid buy-in, and a workflow priority was a seamless integration into the electronic health record.

DISCUSSION: Practicing academic and community-based medical oncologists noted several implementation considerations for the CARG tool. These data have implications for health systems and policymakers who wish to implement chemotoxicity predictor tools into routine practice, and for researchers and learning health systems in designing and conducting pragmatic trials.

PMID:40580678 | DOI:10.1016/j.jgo.2025.102303

Ann Indian Acad Neurol. 2025 Jun 28. doi: 10.4103/aian.aian_74_25. Online ahead of print.

ABSTRACT

Chronic kidney disease is a global public health problem. Emphasis has been placed on uremic peripheral neuropathy (PN) in nondiabetic chronic hemodialysis (HD) patients. This complication could affect the quality of life. We aimed to determine the prevalence and risk factors of PN. This was a cross-sectional study. Evaluation of PN was made by clinical examination and electroneuromyogram. The prevalence of PN was 30.3%. The most common symptoms were paresthesia and burning. Neuropathic pain was symmetrical in the majority of cases and localized to the lower limb (60%). All patients had axonal type PN. In univariate analysis, the risk factors for PN were advanced age (P = 0.012), hypertension (P = 0.007), ischemic heart disease (P = 0.036), high C-reactive protein (microinflammation) (P = 0.002), low urea reduction ratio (P = 0.013), and high ß2 microglobulin (P = 0.002). Since PN is common in nondiabetic chronic HD patients, it becomes necessary to diagnose it and correct its risk factors.

PMID:40580435 | DOI:10.4103/aian.aian_74_25

Phys Med Rehabil Clin N Am. 2025 Aug;36(3):647-662. doi: 10.1016/j.pmr.2025.03.008. Epub 2025 May 24.

ABSTRACT

Hospitalized pediatric heart transplant (PHT) recipients face unique and multifaceted challenges that impact their functional outcomes, including motor skills, activities of daily living, feeding, and communication. Perioperative complications, lengthy hospitalizations, physical deconditioning, and comorbidities associated with complex congenital heart disease are important considerations as they can have a profound impact on their functional abilities and progress of individuals toward achieving independence. This article explores the role of rehabilitation providers in addressing these functional challenges through performance-based outcome measures and aims to support the development of tailored rehabilitation programs to achieve improved quality of life and long-term independence for PHT recipients.

PMID:40581444 | DOI:10.1016/j.pmr.2025.03.008

J Pediatr Surg. 2025 Jun 26:162427. doi: 10.1016/j.jpedsurg.2025.162427. Online ahead of print.

ABSTRACT

AIM: To describe the collective experience of six international tertiary paediatric surgery centres performing thoracoscopic salvage surgery for oesophageal atresia.

METHODS: Retrospective review of all neonates undergoing thoracoscopic repair of oesophageal atresia following a previous failed repair via thoracotomy, from September 2018 - May 2024, at 6 international tertiary paediatric surgery centres. Data collected included demographics, co-morbidities, operative details and post-operative clinical course. Results are presented as median with range.

RESULTS: 24 babies were included. Median gestational age was 34 weeks (26-40), birthweight was 1858g (780-3300). 19 were Gross type C (79%), 4 type B (17%), with 1 type A (4%). 7/24 (29%) had thoracoscopic traction sutures, and 2/24 (8%) had a cervical oesophagostomy formed prior to thoracoscopic repair. Definitive thoracoscopic repair was undertaken at 23 weeks (7-116) after initial thoracotomy, at 6 months of age (1-26) and weight of 5340g (1050-1100). Operative time was 245 minutes (120-585). 23/24 (96%) were completed thoracoscopically. Follow-up was 36 months (7-130). 17/24 (71%) developed an oesophageal stricture requiring a median of 5 dilatations (1-45). 2/24 (8%) developed a fistula to the airway. 2/24 (8%) developed significant gastro-oesophageal reflux disease requiring a fundoplication. One patient required an aortopexy and re-do aortopexy for management of tracheomalacia. There was 1 death at 11 months of age (2 months post definitive repair) in a patient with complex congenital cardiac disease. 22/23 (96%) patients are feeding exclusively orally.

CONCLUSION: thoracoscopic salvage surgery in oesophageal atresia when undertaken by experienced surgeons is feasible, safe and with good clinical outcomes.

PMID:40581151 | DOI:10.1016/j.jpedsurg.2025.162427

Eur J Cardiothorac Surg. 2025 Jun 19:ezaf205. doi: 10.1093/ejcts/ezaf205. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate gender authorship in two cardio-thoracic surgical journals.

METHODS: We performed a bibliometric analysis of all articles published from 2017 to 2022 in the European Journal of Cardio-Thoracic Surgery and the Interdisciplinary Cardiovascular and Thoracic surgery. For each article, the gender and academic rank of the first, senior and corresponding author was verified by Internet search, email contact or use of the application Genderize.io. Articles were categorized based on topic, type and country of origin. The Cochran-Armitage test was used to evaluate gender authorship trend over time.

RESULTS: 5243 articles were included in the analysis. Women represented 18% of first authors, 7% of senior authors and 13% of corresponding authors and no trend was seen over time. Women represented 16% of first authors and 7% of senior authors in adult cardiac surgery, 23% of first authors and 9% of senior authors in congenital cardiac surgery, and 19% of first authors and 8% of senior authors in thoracic surgery. Male first authors were more frequently full professor (17% vs 5%) and associate professor (16% vs 8%) and male senior authors were more frequently full professor (48% vs 31%) and associate professor (16% vs 8%) compared to female.

CONCLUSIONS: The proportion of female authors is significantly lower than that of male authors in highest-impact European cardio-thoracic surgery journals and no significant increase in female authorship has been demonstrated in recent years. Increasing awareness of gender disparities is essential to facilitate equal career opportunities and academic advancement for women in cardio-thoracic surgery.

PMID:40581079 | DOI:10.1093/ejcts/ezaf205

J Thorac Cardiovasc Surg. 2025 Jun 26:S0022-5223(25)00543-4. doi: 10.1016/j.jtcvs.2025.06.023. Online ahead of print.

ABSTRACT

OBJECTIVE: Our study aims to compare long-term survival and clinical outcomes of ring and band prostheses for annuloplasty repair of functional mitral regurgitation (FMR).

METHODS: From 3/2005 to 11/2017, 160 patients with moderate to severe FMR underwent undersized annuloplasty using semirigid complete ring (CR, N=69) or partial band (PB, N=91) prostheses of the same material and manufacturer. Primary outcomes were long-term survival and clinical outcomes, while secondary outcomes included comparison of postoperative echocardiography data.

RESULTS: Both groups had comparable baseline characteristics, cardiac function, FMR severity, and perioperative complications. CR and PB experienced equivalent 10-year freedom from CV mortality(65.2% vs 68.3%, P=.39), and FMR recurrence (78.5% vs 71.4%, P=.27).At mean follow-up of 58±46 months, both groups had parallel increase in ejection fraction (+7±16 vs +5±15%, P=.35) and reduction of left ventricle internal diameter end-diastole (-0.5±0.8 vs -0.4±0.9 cm, P=.61). CR had greater reduction in left ventricle internal diameter end-systole (-0.6±0.9 vs -0.2±0.9 cm, P=.007) but higher mean (5.6±3.4 vs 5.0±7 mmHg, P=.025) and peak (16.7±19.4 vs 12.9±10.7 mmHg, P=.048) transvalvular pressure gradients (TPG). Mean TPG predicted postoperative mortality at 10-years (HR 1.19[CI 95% (1.0037-1.357)], P=.013).

CONCLUSION: CR and PB annuloplasty for FMR confer equivalent 10-year survival and MR recurrence. CR repair was associated with increased LV reverse remodeling yet higher long-term valvular gradients.

PMID:40581290 | DOI:10.1016/j.jtcvs.2025.06.023

J Am Heart Assoc. 2025 Jul;14(13):e040848. doi: 10.1161/JAHA.124.040848. Epub 2025 Jun 27.

ABSTRACT

BACKGROUND: The fibrosis-4 index (FIB-4) score, a noninvasive marker of subclinical liver fibrosis, has shown prognostic utility in general surgical populations. Current risk assessment models for patients with coronary artery disease undergoing percutaneous coronary intervention or coronary artery bypass grafting do not account for liver dysfunction apart from overt liver cirrhosis. We analyzed the distribution of the baseline FIB-4 score and its association with all-cause death in patients with coronary artery disease using data from the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial.

METHODS: The baseline FIB-4 score was calculated for all ISCHEMIA randomized participants with laboratory data (platelet count, aspartate aminotransferase, and alanine aminotransferase). The primary outcome was the association between baseline FIB-4 and all-cause death. Secondary outcomes were cardiovascular death, heart failure, myocardial infarction, and stroke. Multivariable Cox regression was performed adjusting for key risk factors.

RESULTS: The FIB-4 score was calculated for 3735 participants. Baseline FIB-4 score was significantly associated with an increased risk of all-cause (hazard ratio [HR], 1.19 [95% CI, 1.07-1.32]; P=0.001) and cardiovascular death (HR, 1.19 [95% CI, 1.04-1.36]; P=0.011). This association was consistent across the overall population and within subgroups of patients treated with percutaneous coronary intervention, coronary artery bypass grafting, and medical therapy. There was no significant association regarding heart failure, myocardial infarction, and stroke.

CONCLUSIONS: The FIB-4 score may be a significant predictor of death in patients with coronary artery disease. Preprocedural hepatic assessment should be considered to stratify risk in patients undergoing invasive cardiac procedures.

PMID:40576034 | DOI:10.1161/JAHA.124.040848

Ann Nucl Med. 2025 Jun 27. doi: 10.1007/s12149-025-02077-w. Online ahead of print.

ABSTRACT

PURPOSE: The study aimed to assess the prognostic value of non-perfusion parameters for gated myocardial perfusion imaging (MPI) performed using Cadmium-Zinc-Telluride (CZT) single-photon emission computed tomography (SPECT) for individuals with normal myocardial perfusion.

METHODS: We analyzed data from consecutive patients who underwent thallium-201 MPI SPECT with normal perfusion. Major adverse cardiovascular events (MACEs) were recorded during a 2-year follow-up. Non-perfusion parameters were evaluated as predictors of MACEs.

RESULTS: Among 1570 patients with normal SPECT perfusion, 80 (5.1%) experienced MACEs over a mean follow-up of 22.5 ± 10.8 months: 12 (0.8%) had cardiac death, and 68 (4.3%) underwent coronary revascularization due to significant coronary artery disease. Independent predictors of MACEs included worsening post-stress ejection fraction (HR: 1.971; p = 0.008), and increased lung-to-heart ratio (HR: 2.207; p = 0.001). Kaplan-Meier analysis showed the highest MACEs' incidence in patients with two of these factors (p < 0.001). Among patients with normal resting ejection fraction, EF worsening (OR: 2.16; p = 0.004) and increased lung-to-heart ratio (OR: 1.91; p = 0.0013) both remained strong predictors.

CONCLUSIONS: Although normal myocardial perfusion typically indicates low risk for obstructive coronary artery disease, worsening post-stress ejection fraction and increased lung-to-heart ratio are crucial prognostic indicators. Importantly, these non-perfusion parameters retain their prognostic value even in patients without clinical heart failure, highlighting their relevance in comprehensive risk stratification beyond perfusion assessment alone.

PMID:40576735 | DOI:10.1007/s12149-025-02077-w

J Am Heart Assoc. 2025 Jul;14(13):e038770. doi: 10.1161/JAHA.124.038770. Epub 2025 Jun 27.

ABSTRACT

BACKGROUND: In patients presenting with acute coronary syndromes (ACS), impaired coronary blood flow (CBF) after percutaneous coronary interventions (PCI) is linked to mortality. We developed a novel angiography-based approach for blood flow quantification using automatic contrast bolus tracking. Therefore, this study aimed to investigate the clinical impact of angiography-based blood flow quantification on major adverse cardiovascular events (MACE) after PCI in patients with ACS.

METHODS: Prospective, multicenter, nested case-control study of patients presenting ACS. A propensity score was used to match patients with and without MACE at 1 year of follow-up. MACE was defined as cardiovascular death, myocardial infarction, hospitalization for heart failure, or ischemia-driven revascularization. CBF was measured automatically from angiograms after PCI.

RESULTS: One hundred sixty-two patients were included. The mean age was 68.3±13.0 years, 83% were male, and 33% had diabetes. Overall, 66% of patients presented with ST-segment-elevation myocardial infarction. CBF after PCI was lower after ST-segment-elevation myocardial infarction compared with other clinical presentations (74.1±47.0 mL/min ST-segment-elevation myocardial infarction, 89.1±45.8 mL/min, non-ST-segment-elevation myocardial infarction, 95.7±48.8 mL/min, unstable angina, P=0.046). Patients with low post-PCI CBF (<54.3 mL/min) had an increased risk of MACE (hazard ratio, 2.11 [95% CI, 1.35-3.28], P=0.001).

CONCLUSIONS: After PCI, automatic quantification of CBF using angiography was associated with MACE in patients with ACS. Risk stratification using post-PCI CBF-derived angiography may enable tailored management strategies for individuals with ACS.

PMID:40576041 | DOI:10.1161/JAHA.124.038770

Catheter Cardiovasc Interv. 2025 Jun 27. doi: 10.1002/ccd.31724. Online ahead of print.

ABSTRACT

BACKGROUND: Coronary calcified nodules (CNs) are a challenging subset of calcific lesions associated with adverse procedural outcomes. While rotational atherectomy (RA) and balloon angioplasty (BA) have been traditionally used, orbital atherectomy (OA) offers a unique mechanism of plaque modification that may be advantageous in the treatment of CNs. Data on OA in CNs remains limited.

OBJECTIVES: To evaluate procedural success, periprocedural safety, in-hospital and long-term outcomes of retrograde OA in the treatment of CNs.

METHODS: We conducted a retrospective analysis of all patients who underwent OA for angiographically identified coronary calcification between January 1, 2022 and March 31, 2024. A total of 312 patient underwent OA during this period, of whom 57 had a CN identified. Baseline demographics, lesion characteristics, procedural details, and outcomes were assessed. CNs were defined by angiographic or intravascular ultrasound appearance.

RESULTS: The mean age was 71, 71.9% were male, 71.9% had diabetes, 40.3% had CKD and 15.8% had prior coronary artery bypass. The majority of lesions involved the left anterior descending artery (49.1%). Retrograde treatment using a 1.25 mm burr at 80,000 rpms was exclusively used. Angiographic success was achieved in 100% of cases. No perforations or flow-limiting dissections were observed. During an average follow-up of 325.57 ± 233.45 days, there were no cases of early or late stent thrombosis, with one case of very late stent thrombosis. Major adverse cardiac events (MACE) occurred in 5.26% (three patients), comprising myocardial infarction in 3.51% (two patients) and target vessel revascularization in 1.75% (one patient).

CONCLUSIONS: In this real-world, single-center, retrospective analysis, OA was safe and effective in treating coronary CNs, achieving high angiographic success with minimal periprocedural complications. These findings support the use of OA as a viable strategy for CNs, though further studies are warranted.

PMID:40576015 | DOI:10.1002/ccd.31724

Zhongguo Yi Liao Qi Xie Za Zhi. 2025 May 30;49(3):269-275. doi: 10.12455/j.issn.1671-7104.240595.

ABSTRACT

This study investigated a novel coronary knobby scoring balloon through finite element analysis (FEA) and in vitro anti-slippage testing, evaluating its dilation process under various vascular conditions and comparing it with other balloons. The FEA results indicated that in the cases of healthy artery and diseased artery with different stenosis rates, the stress on the vessels caused by the knobby scoring balloon was significantly smaller than that of the scoring balloon, and was close to that of the plain balloon. In vitro anti-slippage testing showed that the slippage distance of a plain balloon was 0.11±0.06 mm, and there was no slippage for knobby scoring balloon under nominal pressure. Knobby scoring balloon can effectively expand calcified lesion while providing anti-slippage function, and has a lower risk of vascular injury.

PMID:40574436 | DOI:10.12455/j.issn.1671-7104.240595