Journal of cardiology最新文献

{"title":"Precision cardiology: Integrating gene therapy, genome editing, and single-cell genomics.","authors":"Tomohiro Nishino, Koh Ono","doi":"10.1016/j.jjcc.2025.09.009","DOIUrl":"10.1016/j.jjcc.2025.09.009","url":null,"abstract":"<p><p>Gene therapy is poised to revolutionize cardiovascular medicine by targeting the molecular roots of disease. This review examines the evolution of gene therapy, highlighting its past progress and future potential with emerging technologies. We first assess foundational gene addition and silencing strategies, noting clinical progress for monogenic cardiomyopathies alongside significant setbacks in multifactorial heart failure, driven mainly by the central challenge of vector delivery. We then discuss the evolution of delivery platforms, from engineered adeno-associated virus capsids to targeted lipid nanoparticles, which are designed to enhance cardiac specificity and safety. Concurrently, the gene editing revolution-progressing from the foundational Clustered Regularly Interspaced Short Palindromic Repeats-Cas9 system to high-fidelity base and prime editors-is enabling the direct correction of pathogenic mutations with increasing precision. Catalyzing these therapeutic platforms is the recent explosion in single-cell genomics, which provides an unprecedented resolution of cardiac pathology, revealing novel cell-specific targets previously obscured by bulk analysis. We conclude that the synergistic convergence of these pillars-genomics-driven discovery, precision genome editing, and targeted delivery-is creating a new paradigm of precision cardiology, moving the field from chronic management towards durable, curative interventions.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Daprodustat for patients with heart failure and renal anemia: A pilot multicenter, open-label, randomized controlled study.","authors":"Yu Suresvar Singh, Yuya Matsue, Takashi Iso, Yudai Fujimoto, Naotake Yanagisawa, Jun Shitara, Satoru Suwa, Shota Miyakuni, Akira Mizukami, Yuki Saito, Yasuo Okumura, Kiyoshi Takasu, Takashi Tokano, Masaru Hiki, Kikuo Isoda, Tadashi Miyazaki, Katsumi Miyauchi, Tohru Minamino","doi":"10.1016/j.jjcc.2025.09.011","DOIUrl":"10.1016/j.jjcc.2025.09.011","url":null,"abstract":"<p><strong>Background: </strong>Anemia and renal failure, common comorbidities in patients with heart failure (HF), are associated with increased mortality. Hypoxia-inducible factor prolyl hydroxylase inhibitors, such as daprodustat, treat renal anemia by stimulating erythropoiesis and enhancing iron availability. However, its efficacy in treating HF with renal anemia remains to be determined.</p><p><strong>Methods: </strong>This pilot, multicenter, open-label, randomized controlled trial was conducted in five hospitals in Japan. Patients with HF, anemia (hemoglobin, 7.5-11 g/dL), and renal impairment (estimated glomerular filtration rate, <60 mL/min/1.73 m²) not requiring hemodialysis were randomized 1:1 to receive daprodustat or standard of care. The primary endpoint was the hemoglobin level at 16 weeks. The secondary endpoints included blood transfusion rates, alleviation of HF symptoms, changes in N-terminal pro-B-type natriuretic peptide and iron-related biomarkers, and cardiac structural and functional changes.</p><p><strong>Results: </strong>Twenty-one patients were randomized between March 2022 and November 2023. At 16 weeks, the mean hemoglobin level was significantly higher in the daprodustat group (12.1 ± 0.73 g/dL) than in the standard of care group (10.3 ± 0.97 g/dL, p < 0.001). Serum iron, ferritin, hepcidin, and transferrin saturation levels were significantly lower, whereas N-terminal pro-B-type natriuretic peptide levels were significantly higher in the daprodustat treatment group. Kansas City Cardiomyopathy Questionnaire Total Symptom Score improvement (44.4 % vs. 55.6 %, p = 0.99) and structural and functional cardiac parameters showed no significant differences.</p><p><strong>Conclusions: </strong>Daprodustat effectively increases hemoglobin levels and modifies iron metabolism by decreasing hepcidin levels and increasing iron utilization in patients with HF and renal anemia.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiovascular-related hospital visits amongst oncology patients receiving immune checkpoint inhibitors: A population-based cohort study.","authors":"Wei Fang Dai, Steven Habbous, Andrew Yan, Husam Abdel-Qadir, Shaun G Goodman, Kelvin K W Chan","doi":"10.1016/j.jjcc.2025.09.010","DOIUrl":"https://doi.org/10.1016/j.jjcc.2025.09.010","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) have substantially improved the clinical outcomes for many cancer patients. However, these treatments are potentially associated with serious cardiovascular adverse events.</p><p><strong>Methods: </strong>We identified a population-based, retrospective cohort of oncology patients who started ICIs treatments between September 1st, 2012 and August 31st, 2019, in Ontario, Canada. The primary outcome was the incidence of cardiovascular-related hospital visits between initiation of ICI to 90 days after the last dose of ICI. Cumulative incidence functions were used to estimate the incidence of cause-specific cardiovascular-related hospital visits, accounting for the competing risks of all-cause mortality.</p><p><strong>Results: </strong>A total of 5725 cancer patients (median age 68 years and 59.4 % male) received ICI, of which 556 (9.7 %) individuals had hospital visits due to cardiovascular-related adverse events. Amongst patients with cardiovascular-related hospital visits, 284 (51 %) were hospitalized and 88 (15.8 %) required intensive care unit monitoring. Of the 0.9 % hospital visits due to myocarditis or pericarditis, the median time from ICI initiation to hospital visits was 63 days (Q1-Q3: 23-128). The one-year cumulative incidence of cardiovascular-related hospital visit was higher for patients with prior cardiovascular history (15.2 %; 95 % CI: 12.2-18.4 %) than those without (8.7 %; 95 % CI: 7.9-9.5 %) (p < 0.001). Amongst the 9.7 % ICI-treated patients with cardiovascular-related hospital visits, the median overall survival was 2.9 months (95 % CI: 2.24-3.52). Patients who required ICU stay had worse survival outcomes (median OS = 2.1 months) compared to those who were not hospitalized for the cardiovascular-related hospital visits (median OS = 2.5 months).</p><p><strong>Conclusion: </strong>In a population-based study, cancer patients treated with ICIs had a high incidence of cardiovascular-related hospital visits. Patients with prior cardiac disease are more likely to have a cardiovascular-related hospital visit. The survival outcomes following cardiovascular-related hospital visits is poor amongst cancer patients treated with ICI.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prodromal symptoms and the care-seeking behavior in patients with acute ST-segment elevation myocardial infarction.","authors":"Akinori Tamura, Hiroki Shiomi, Takeshi Morimoto, Kazuaki Imada, Yutaka Furukawa, Yoshihisa Nakagawa, Kazushige Kadota, Natsuhiko Ehara, Ryoji Taniguchi, Jiro Sakamoto, Makoto Miyake, Toshihiro Tamura, Manabu Ogita, Satoru Suwa, Kenji Ando, Koh Ono, Takeshi Kimura","doi":"10.1016/j.jjcc.2025.09.006","DOIUrl":"10.1016/j.jjcc.2025.09.006","url":null,"abstract":"<p><strong>Background: </strong>The prodromal symptoms perceived by patients before the onset of acute myocardial infarction (AMI) are diverse and not necessarily limited to the typical symptoms of angina.</p><p><strong>Methods: </strong>Among 3959 consecutive patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention within 24 h of the onset of AMI enrolled in the CREDO-Kyoto AMI registry wave-2, the patients were categorized into 3 groups by the symptoms before the onset and within 48 h before the index hospital presentation: (1) prodromal symptoms typical of angina (N = 865, 21.8 %), (2) atypical prodromal symptoms only (N = 156, 3.9 %), and (3) no prodromal symptoms (N = 2938, 74.2 %). We investigated the association between the types of the prodromal symptoms and long-term clinical outcomes as well as the prevalence of seeking medical care for the prodromal symptoms.</p><p><strong>Results: </strong>As compared with patients with no prodromal symptoms, those with typical prodromal symptoms had a lower mortality risk [adjusted hazard ratio (HR): 0.69, 95 % confidence interval (CI): 0.58-0.83, p = 0.0001], whereas those with atypical prodromal symptoms only had a higher mortality risk (HR: 1.53, 95 % CI: 1.17-2.00, p = 0.002). Regarding healthcare-seeking behavior, 162 out of 1021 patients (15.9 %) with the prodromal symptoms sought medical care for the prodromal symptoms. There was no significant difference in the rate of seeking medical care between the patients with typical prodromal symptoms and atypical prodromal symptoms only (15.5 % and 17.9 %, p = 0.44).</p><p><strong>Conclusions: </strong>Compared to patients with no prodromal symptoms before STEMI, long-term mortality outcome was better in patients with typical prodromal symptoms, but worse in those with atypical prodromal symptoms.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early outcomes in patients undergoing heart re-transplantation in the era of HCV-viremic donors.","authors":"Matylda Mazur, Barbara Pisani, Andres Carmona Rubio, Howard J Eisen, Geetha Bhat, Marina Núñez","doi":"10.1016/j.jjcc.2025.09.005","DOIUrl":"10.1016/j.jjcc.2025.09.005","url":null,"abstract":"<p><strong>Background: </strong>The use of hepatitis C virus (HCV) viremic donors has increased the heart donor pool and reduced waitlist time and mortality among first-time single-organ heart transplant (HT) candidates without compromising their post-transplant survival. The outcomes of heart re-transplantation (re-HT) using HCV-viremic donor grafts have not been investigated.</p><p><strong>Methods: </strong>Using the United Network for Organ Sharing Registry, we analyzed adult patients who underwent re-HT in the USA between January 1, 2016, and December 31, 2023. HCV-viremic donors were defined by a positive nucleic acid amplification test.</p><p><strong>Results: </strong>Of 25,836 HTs performed, 509 (2 %) were single-organ re-HT: 21 and 488 from HCV-viremic and nonviremic donors, respectively. Among the two recipient groups, there were no significant differences in age, body mass index, blood type, diabetes or stroke rates, creatinine or bilirubin levels, time from the first HT, hemodynamics, use of inotropic/mechanical circulatory support, listing status, and waitlist time. Ischemic time, cytomegalovirus, donor/recipient gender mismatch rates, and calculated panel reactive antibodies levels were comparable across the two groups. There were no significant differences in demographics or comorbidities between HCV-viremic and HCV-nonviremic donors. At 1 year post-re-HT, rates of acute rejection and cardiac allograft vasculopathy were comparable across the two groups. Short-term survival rates were similar at 30 days (95.2 % vs. 91.8 %), 1 year (95.2 % vs. 84.4 %), and 2 years (95.2 % vs. 80.7 %) for recipients of HCV-viremic and nonviremic donor grafts, respectively (p = 0.3).</p><p><strong>Conclusion: </strong>This study provides preliminary evidence that short-term post-re-HT outcomes of recipients of HCV-viremic donor grafts are comparable to those of recipients of HCV-nonviremic donor grafts.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bereaved family members-reported distressing symptoms in terminally ill patients with heart disease.","authors":"Ryo Nakamaru, Takashi Kohno, Atsushi Mizuno, Yoko Nakazawa, Mitsunori Miyashita, Tatsuya Morita, Yasuyuki Okumura, Yoshiyuki Kizawa, Shohei Kawagoe, Hiroshi Yamamoto, Emi Takeuchi, Risa Yamazaki, Asao Ogawa","doi":"10.1016/j.jjcc.2025.09.007","DOIUrl":"10.1016/j.jjcc.2025.09.007","url":null,"abstract":"<p><strong>Background: </strong>Family members' (FMs) perceptions play a crucial role in understanding distressing symptoms in terminally ill patients. However, research on FM-reported physical distress and the corresponding care settings and caregiver burdens remain sparse across the spectrum of heart diseases.</p><p><strong>Methods: </strong>This retrospective study utilized a nationwide mortality follow-up survey completed by bereaved FMs of patients with heart failure, ischemic heart disease (IHD), or other heart diseases. FMs retrospectively rated distress from 11 patient symptoms experienced 1 week prior to death using the Memorial Symptom Assessment Scale-Short Form (5-point scale). Patient and FMs profiles were compared among three groups according to the number of symptoms rated \"a little bit\" or more distressing: minimal (0 symptoms), mild-moderate (1-5 symptoms), and severe physical distress (6-11 symptoms).</p><p><strong>Results: </strong>Among 5003 patients (61.2 % women; mean age, 86.7 ± 9.7 years), 23.3 %, 44.1 %, and 32.6 % were classified as having minimal, mild-moderate, and severe physical distress, respectively. The most frequent FM-reported symptom was feeling drowsy (52.8 %). Patients with severe distress were more likely to have received care at hospitals. The proportion of patients perceived as receiving palliative care was 5.8 %, 11.2 %, and 16.1 % for those with minimal, mild-moderate, and severe distress, respectively. FMs of patients with severe distress reported more frequent caregiving and worse physical and psychological conditions. The proportion of patients with minimal physical distress was consistently low regardless of primary diagnosis (heart failure, 20.6 %; IHD, 27.3 %; other diseases, 23.8 %).</p><p><strong>Conclusions: </strong>A substantial proportion of FMs reported terminally ill patients with heart disease experiencing physical distress. Nevertheless, the proportion of patients perceived as receiving palliative care was low. FMs of those with severe physical distress reported greater caregiving burden. These findings highlight an unmet need for more comprehensive palliative interventions for both patients and their families in advanced stages of heart disease.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase angle as a predictor of congestion, muscle wasting, and malnutrition in cardiovascular surgery patients.","authors":"Ikuko Shibasaki, Taira Fukuda, Suguru Hirose, Yusuke Takei, Shigeru Toyoda, Hirotsugu Fukuda, Toshiaki Nakajima","doi":"10.1016/j.jjcc.2025.09.004","DOIUrl":"10.1016/j.jjcc.2025.09.004","url":null,"abstract":"","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiothoracic ratio as a prognostic marker in heart failure with preserved ejection fraction.","authors":"Masato Okada, Koichi Inoue, Toshinari Onishi, Nobuaki Tanaka, Katsuomi Iwakura, Masahiro Seo, Takaharu Hayashi, Masamichi Yano, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Yoshio Yasumura, Takahisa Yamada, Shungo Hikoso, Daisuke Sakamoto, Katsuki Okada, Daisaku Nakatani, Yohei Sotomi, Yasushi Sakata","doi":"10.1016/j.jjcc.2025.09.008","DOIUrl":"10.1016/j.jjcc.2025.09.008","url":null,"abstract":"<p><strong>Background: </strong>The cardiothoracic ratio (CTR), derived from chest X-ray, is an established metric for quantifying cardiac size and has prognostic value in acquired heart disease. However, its association with echocardiographic parameters and clinical outcomes in heart failure with preserved ejection fraction (HFpEF) remains inadequately characterized.</p><p><strong>Methods: </strong>This analysis was performed using the PURSUIT-HFpEF registry, a prospective multicenter observational study for HFpEF. Among 1238 patients registered, 1195 with CTR data at discharge were included. Patients were categorized into three groups: CTR <50 % (N = 199), 50-59 % (N = 631), and ≥60 % (N = 365). Associations of CTR with echocardiographic indices and clinical outcomes were evaluated.</p><p><strong>Results: </strong>The median CTR at discharge was 56 % (interquartile range: 51-61 %). Increased CTR was associated with impaired hemodynamics on Doppler echocardiography but not with the left ventricular (LV) end-diastolic or end-systolic volume indices. Conversely, CTR demonstrated moderate correlations with the left atrial volume index (r = 0.39), indexed right ventricular diameter (r = 0.28), inferior vena cava end-expiratory diameter (r = 0.30), and LV mass index (r = 0.18) (all p < 0.001). During a 36-month follow-up, 687 patients experienced the composite of death or rehospitalization for heart failure. Event rates increased with the CTR category (<50 %: 44.2 % vs. 50-59 %: 57.2 % vs. ≥60 %: 65.2 %; log-rank p < 0.001). Compared with CTR <50 %, CTR ≥60 % independently predicted the composite endpoint (hazard ratio, 1.47; 95 % confidence interval, 1.09-1.98; p = 0.011) after multivariable adjustment.</p><p><strong>Conclusions: </strong>In patients with HFpEF, increased CTR reflected hemodynamic compromise, along with enlargement of the left atrium and right-sided chambers without LV cavity dilatation. CTR ≥60 % independently predicted adverse clinical outcomes, supporting its value for risk stratification in this population.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145075322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2i with ARNi versus RASi in heart failure with reduced ejection fraction: Improved survival and reduced hyperkalemia risk in a real-world cohort study.","authors":"Jian-Rong Peng, Tien-Hsing Chen, Dong-Yi Chen, Yuan Lin, Tien-Shin Chou, Ning-I Yang, Chao-Yung Wang, Ming-Lung Tsai","doi":"10.1016/j.jjcc.2025.09.002","DOIUrl":"10.1016/j.jjcc.2025.09.002","url":null,"abstract":"<p><strong>Background: </strong>The management of heart failure with reduced ejection fraction (HFrEF) has advanced with the introduction of sodium-glucose cotransporter-2 inhibitors (SGLT2i) and angiotensin receptor-neprilysin inhibitors (ARNi). However, direct comparisons between combination therapies using SGLT2i plus ARNi versus SGLT2i plus conventional renin-angiotensin system inhibitors (RASi) remain limited.</p><p><strong>Methods: </strong>This retrospective cohort study included 2985 HFrEF patients receiving SGLT2i with either ARNi (n = 1542) or RASi (n = 1443) between 2016 and 2022. Inverse probability of treatment weighting was applied to balance baseline characteristics. The primary outcomes included all-cause mortality, cardiovascular death, heart failure hospitalization (HFH), and renal function decline.</p><p><strong>Results: </strong>Over a median follow-up of 1.1 years, SGLT2i + ARNi was associated with significantly lower all-cause mortality compared to SGLT2i + RASi [hazard ratio (HR): 0.81; 95 % confidence interval (CI): 0.67-0.97]. Risk of cardiovascular death (HR: 0.95; 95 % CI: 0.85-1.0), HFH (subdistribution HR: 0.95; 95 % CI: 0.85-1.06), and renal function decline (subdistribution HR: 0.96; 95 % CI: 0.82-1.13) were comparable between groups. The incidence of hyperkalemia was significantly lower with SGLT2i + ARNi (subdistribution HR: 0.38; 95 % CI: 0.27-0.54). Subgroup analysis revealed a more pronounced survival benefit of SGLT2i + ARNi among patients without heart failure hospitalization in the prior year (HR = 0.58 vs. 0.87; p for interaction = 0.041).</p><p><strong>Conclusion: </strong>Among patients with HFrEF receiving SGLT2i therapy, concomitant use of ARNi was associated with a significant reduction in all-cause mortality, comparable cardiovascular and renal outcomes, and a lower risk of hyperkalemia compared to RASi. These findings support the preferential use of ARNi over RASi as background therapy in SGLT2i-treated HFrEF patients.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"11β-HSD1 inhibitor alleviates sepsis-induced cardiac dysfunction by regulating macrophage polarization via the AMPK/mTOR autophagy pathway.","authors":"Zheng Zhang, Binghui Yin, Dongmei Zhu, Danying Wu, Min Huang, Suming Zhou","doi":"10.1016/j.jjcc.2025.09.003","DOIUrl":"10.1016/j.jjcc.2025.09.003","url":null,"abstract":"<p><strong>Objectives: </strong>Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SIMD) is often associated with an excessive inflammatory response within the cardiac tissue. Targeted inhibition of the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) attenuates local tissue inflammatory responses. We investigated the efficacy of 11β-HSD1 blockade as a potential new treatment in SIMD.</p><p><strong>Methods: </strong>In mice, sepsis was established by intraperitoneally injecting lipopolysaccharide (LPS, 10 mg/kg). Subsequently, the effects of 11β-HSD1 selective inhibitor BVT.2733 administration on LPS-triggered cardiac dysfunction, macrophage infiltration, and spleen inflammation in mice were investigated. In in vitro studies, the macrophage cell line RAW264.7 was used to assess the effect and molecular mechanism of BVT.2733 (50 or 100 μM) on LPS-induced polarization and inflammation. Furthermore, the supernatant of macrophages was collected after intervention and co-cultured with the H9C2 cell line to assess cardiomyocyte apoptosis and injury.</p><p><strong>Results: </strong>The preventive administration of BVT.2733 can ameliorate cardiac dysfunction, M1 macrophage infiltration, and cardiac inflammation induced by LPS. The findings also demonstrated that BVT.2733 exhibited a mitigating effect on spleen pathological injury and inflammatory responses. Subsequently, BVT.2733 demonstrated the ability to inhibit M1 polarization of macrophages and attenuate inflammatory response in vitro. Meanwhile, our findings showed that BVT.2733 administration effectively mitigated inflammation and apoptosis in H9C2 cells in the proinflammatory environment produced by macrophages. Mechanistic studies revealed that BVT.2733 elevated autophagy levels by activating the AMPK/mTOR signaling pathway.</p><p><strong>Conclusion: </strong>The 11β-HSD1 selective inhibitor BVT.2733 demonstrates potential in ameliorating cardiac dysfunction and myocardial injury in septic mice induced by LPS. This beneficial effect is likely attributed to the modulation of macrophage polarization through the AMPK/mTOR autophagy pathway.</p>","PeriodicalId":15223,"journal":{"name":"Journal of cardiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145053598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}