Domenico Mario Giamundo, Giuliano Cassataro, Stefano Ministrini, Simon F. Stämpfli
Background
Amyloidosis is characterised by the extracellular accumulation of misfolded proteins forming amorphous aggregates called amyloid. Cardiac amyloidosis results from myocardial involvement in systemic amyloidosis, leading to impaired heart function. Besides myocardial involvement, cardiac amyloidosis may also directly and indirectly affect the central nervous system.
Methods
This narrative review summarises current evidence about on central nervous system involvement in cardiac amyloidosis and the pathophysiological mechanisms linking heart and brain in the context of this systemic disease.
Results
Although the pathophysiological relationship between cardiac amyloidosis and cognitive decline remains poorly understood, central nervous system involvement likely results from the complex interplay of direct amyloid deposition, cerebrovascular changes, and cardiac dysfunction.
Conclusion
The growing awareness of cognitive impairment in patients with cardiac amyloidosis highlights the need for further research and supports a multidisciplinary approach in the assessment and management of affected individuals.
{"title":"Central nervous system involvement in cardiac amyloidosis: Redefining the heart-brain axis","authors":"Domenico Mario Giamundo, Giuliano Cassataro, Stefano Ministrini, Simon F. Stämpfli","doi":"10.1111/eci.70122","DOIUrl":"10.1111/eci.70122","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Amyloidosis is characterised by the extracellular accumulation of misfolded proteins forming amorphous aggregates called amyloid. Cardiac amyloidosis results from myocardial involvement in systemic amyloidosis, leading to impaired heart function. Besides myocardial involvement, cardiac amyloidosis may also directly and indirectly affect the central nervous system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This narrative review summarises current evidence about on central nervous system involvement in cardiac amyloidosis and the pathophysiological mechanisms linking heart and brain in the context of this systemic disease.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Although the pathophysiological relationship between cardiac amyloidosis and cognitive decline remains poorly understood, central nervous system involvement likely results from the complex interplay of direct amyloid deposition, cerebrovascular changes, and cardiac dysfunction.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The growing awareness of cognitive impairment in patients with cardiac amyloidosis highlights the need for further research and supports a multidisciplinary approach in the assessment and management of affected individuals.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amir Askarinejad, Tommaso Bucci, Niloofar Asgharzadeh, Zahra Amirjam, Enrico Tartaglia, Michele Rossi, Yang Chen, Yalin Zheng, Gregory Y. H. Lip, Majid Haghjoo
Background
Given the modest performance of available predictive models in estimating the risk of atrial fibrillation (AF) in patients with atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs), this study explores the potential use of machine learning (ML) algorithms in this context.
Purpose
To assess the ability of ML techniques in identifying patients with AHRE at high risk of AF.
Methods
In this prospective study, we enrolled patients without a prior history of AF who experienced at least one AHRE episode detected by CIEDs. ML techniques were applied to predict the 1-year risk of developing new-onset AF based on the following variables: age, BMI, sex, smoking, hypertension, diabetes, coronary artery disease, chronic kidney disease, dyslipidaema, history of stroke or transient ischaemic attack, vascular heart disease, left atrial enlargement (LAE) and congestive heart failure.
Results
Study population consists of 100 patients (48% male, mean age 66.0 ± 18.0 years), of whom 24 developed AF (24%) after 1-year follow-up. The CatBoost ML model achieved the highest AUC (.857, 95% CI .671–.999) when compared to other ML models and all clinical risk scores. The top four most influential predictors of AF in the CatBoost model were LAE, hypertension, diabetes and age.
Conclusions
ML techniques are robust in predicting AF in patients with AHREs. Further validation in larger, independent cohorts is warranted.
背景：鉴于可用的预测模型在估计心房高频率发作（AHREs）患者心房颤动（AF）风险方面的适度表现，本研究探讨了机器学习（ML）算法在这方面的潜在应用。目的：评估ML技术识别AF高风险AHRE患者的能力。方法：在这项前瞻性研究中，我们招募了没有AF病史且至少经历过一次cied检测到的AHRE发作的患者。基于以下变量，应用ML技术预测1年内发生新发房颤的风险：年龄、BMI、性别、吸烟、高血压、糖尿病、冠状动脉疾病、慢性肾脏疾病、血脂异常、中风或短暂性缺血发作史、血管性心脏病、左房扩大（LAE）和充血性心力衰竭。结果：研究人群包括100例患者（男性48%，平均年龄66.0±18.0岁），随访1年后发生房颤24例（24%）。CatBoost ML模型获得了最高的AUC(。857, 95% CI .671-.999)，与其他ML模型和所有临床风险评分相比。在CatBoost模型中，对房颤影响最大的4个预测因子是LAE、高血压、糖尿病和年龄。结论：ML技术在预测AHREs患者房颤方面是可靠的。需要在更大的独立队列中进一步验证。
{"title":"Machine learning-based prediction of atrial fibrillation in patients with atrial high-rate episodes","authors":"Amir Askarinejad, Tommaso Bucci, Niloofar Asgharzadeh, Zahra Amirjam, Enrico Tartaglia, Michele Rossi, Yang Chen, Yalin Zheng, Gregory Y. H. Lip, Majid Haghjoo","doi":"10.1111/eci.70121","DOIUrl":"10.1111/eci.70121","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Given the modest performance of available predictive models in estimating the risk of atrial fibrillation (AF) in patients with atrial high-rate episodes (AHREs) detected by cardiac implantable electronic devices (CIEDs), this study explores the potential use of machine learning (ML) algorithms in this context.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>To assess the ability of ML techniques in identifying patients with AHRE at high risk of AF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this prospective study, we enrolled patients without a prior history of AF who experienced at least one AHRE episode detected by CIEDs. ML techniques were applied to predict the 1-year risk of developing new-onset AF based on the following variables: age, BMI, sex, smoking, hypertension, diabetes, coronary artery disease, chronic kidney disease, dyslipidaema, history of stroke or transient ischaemic attack, vascular heart disease, left atrial enlargement (LAE) and congestive heart failure.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Study population consists of 100 patients (48% male, mean age 66.0 ± 18.0 years), of whom 24 developed AF (24%) after 1-year follow-up. The CatBoost ML model achieved the highest AUC (.857, 95% CI .671–.999) when compared to other ML models and all clinical risk scores. The top four most influential predictors of AF in the CatBoost model were LAE, hypertension, diabetes and age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>ML techniques are robust in predicting AF in patients with AHREs. Further validation in larger, independent cohorts is warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811835/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Megan J. du Preez, Maryke Schoonen, Monray E. Williams, Michelle Bisschoff, Francois H. van der Westhuizen
Background
Congenital myopathies are inherited neuromuscular disorders characterized by early-onset muscle weakness and distinct histopathological features. Although mitochondrial involvement in congenital myopathy is well recognized in its pathophysiology, oxidative phosphorylation (OXPHOS) complex dysfunction, which is associated with primary mitochondrial diseases (MD), is not. This systematic review aimed to evaluate the prevalence and characteristics of reported OXPHOS complex dysfunction in genetically confirmed congenital myopathy cases.
Methods
A systematic literature search was conducted in PubMed, Scopus and Web of Science. The search strategy was developed according to PRISMA guidelines. Two independent reviewers screened the studies for inclusion. Eligible studies reported genetically confirmed congenital myopathy cases or disease models and included diagnostic OXPHOS complex analyses via enzyme kinetic assays and/or protein/RNA expression.
Results
Of 5841 studies screened, 23 publications (2009–2025) met the inclusion criteria, comprising 45 congenital myopathy cases. OXPHOS complex dysfunction was reported in 78% of these cases, including all human cases where OXPHOS enzymology was performed. Nine congenital myopathy-associated genes were involved in the cases, with RYR1 being the most frequent. No definitive genotype–phenotype relationship was established between specific genes and affected complexes.
Conclusions
OXPHOS complex dysfunction in congenital myopathy appears to be more prevalent than previously recognized, challenging the traditional view that associates such dysfunction exclusively with MD. This emerging evidence suggests that mitochondrial involvement in congenital myopathy is not incidental but may represent a meaningful aspect of its pathophysiology. The potential dysregulation of OXPHOS in congenital myopathy has implications for refining diagnostic frameworks for both congenital myopathy and MD.
背景：先天性肌病是一种以早发性肌肉无力和明显的组织病理学特征为特征的遗传性神经肌肉疾病。虽然线粒体参与先天性肌病在病理生理学上得到了很好的认识，但与原发性线粒体疾病（MD）相关的氧化磷酸化（OXPHOS）复合物功能障碍却没有得到很好的认识。本系统综述旨在评估遗传证实的先天性肌病病例中报告的OXPHOS复杂功能障碍的患病率和特征。方法：系统检索PubMed、Scopus和Web of Science的文献。搜索策略是根据PRISMA指南制定的。两名独立审稿人筛选了纳入的研究。符合条件的研究报告了遗传证实的先天性肌病病例或疾病模型，并包括通过酶动力学测定和/或蛋白质/RNA表达进行诊断OXPHOS复合物分析。结果：在筛选的5841项研究中，23篇出版物（2009-2025）符合纳入标准，包括45例先天性肌病病例。这些病例中有78%报告了OXPHOS复杂功能障碍，包括所有进行OXPHOS酶学研究的人类病例。9个先天性肌病相关基因与病例有关，其中RYR1最为常见。特异性基因和受影响的复合物之间没有确定的基因型-表型关系。结论：先天性肌病中的OXPHOS复合物功能障碍似乎比以前认识到的更为普遍，挑战了将这种功能障碍仅与MD联系在一起的传统观点。这一新证据表明，线粒体参与先天性肌病不是偶然的，而是其病理生理学的一个有意义的方面。先天性肌病中OXPHOS的潜在失调对完善先天性肌病和MD的诊断框架具有重要意义。
{"title":"OXPHOS complex deficiency in congenital myopathy: A systematic review","authors":"Megan J. du Preez, Maryke Schoonen, Monray E. Williams, Michelle Bisschoff, Francois H. van der Westhuizen","doi":"10.1111/eci.70114","DOIUrl":"10.1111/eci.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Congenital myopathies are inherited neuromuscular disorders characterized by early-onset muscle weakness and distinct histopathological features. Although mitochondrial involvement in congenital myopathy is well recognized in its pathophysiology, oxidative phosphorylation (OXPHOS) complex dysfunction, which is associated with primary mitochondrial diseases (MD), is not. This systematic review aimed to evaluate the prevalence and characteristics of reported OXPHOS complex dysfunction in genetically confirmed congenital myopathy cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature search was conducted in PubMed, Scopus and Web of Science. The search strategy was developed according to PRISMA guidelines. Two independent reviewers screened the studies for inclusion. Eligible studies reported genetically confirmed congenital myopathy cases or disease models and included diagnostic OXPHOS complex analyses via enzyme kinetic assays and/or protein/RNA expression.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 5841 studies screened, 23 publications (2009–2025) met the inclusion criteria, comprising 45 congenital myopathy cases. OXPHOS complex dysfunction was reported in 78% of these cases, including all human cases where OXPHOS enzymology was performed. Nine congenital myopathy-associated genes were involved in the cases, with <i>RYR1</i> being the most frequent. No definitive genotype–phenotype relationship was established between specific genes and affected complexes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>OXPHOS complex dysfunction in congenital myopathy appears to be more prevalent than previously recognized, challenging the traditional view that associates such dysfunction exclusively with MD. This emerging evidence suggests that mitochondrial involvement in congenital myopathy is not incidental but may represent a meaningful aspect of its pathophysiology. The potential dysregulation of OXPHOS in congenital myopathy has implications for refining diagnostic frameworks for both congenital myopathy and MD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yao Du, Yuwen Zeng, Sixin Xu, Qiwei Shen, Jinzhu Hu, Gregory Y. H. Lip
Background
Patients with atrial fibrillation (AF) with end-stage renal failure on renal replacement therapy are at high risk of stroke and bleeding, but the optimal oral anticoagulation (OAC) strategy is uncertain. To investigate the most effective OAC therapy for patients with AF on long-term dialysis.
Methods
PubMed, EMBASE and Web of Science databases were systematically searched from inception to 9 October 2024 to identify relevant studies on OAC strategy for patients with AF on long-term dialysis. The effectiveness outcomes were ischaemic stroke and/or systemic thromboembolism, all-cause mortality and the safety endpoint was major bleeding.
Results
The present study encompassed a comprehensive analysis of 33 studies involving a total of 137,574 patients with AF on long-term dialysis. All OACs, including warfarin (hazard ratio [HR], .963; 95% confidence interval [CI], .841–1.104), did not show a statistically significant decrease in the risk of ischaemic stroke and/or systemic thromboembolism compared to no anticoagulant therapy. Only apixaban 5 mg twice daily was associated with a lower risk of all-cause mortality compared to non-OAC use (HR, .671; 95% CI, .490–.919). Dabigatran (HR, 2.140; 95% CI, 1.734–2.642) and phenprocoumon (HR, 2.419; 95% CI, 1.241–4.713) were associated with a significantly higher risk of major bleeding than non-OAC use.
Conclusions
All OACs were not associated with a reduced risk of ischaemic stroke and/or systemic thromboembolism in patients with AF on long-term dialysis. Only apixaban 5 mg twice daily was associated with a decrease in all-cause mortality when compared with non-OAC use.
{"title":"Oral anticoagulant therapy for patients with atrial fibrillation on long-term dialysis: A network meta-analysis of 137,574 patients","authors":"Yao Du, Yuwen Zeng, Sixin Xu, Qiwei Shen, Jinzhu Hu, Gregory Y. H. Lip","doi":"10.1111/eci.70120","DOIUrl":"10.1111/eci.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Patients with atrial fibrillation (AF) with end-stage renal failure on renal replacement therapy are at high risk of stroke and bleeding, but the optimal oral anticoagulation (OAC) strategy is uncertain. To investigate the most effective OAC therapy for patients with AF on long-term dialysis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>PubMed, EMBASE and Web of Science databases were systematically searched from inception to 9 October 2024 to identify relevant studies on OAC strategy for patients with AF on long-term dialysis. The effectiveness outcomes were ischaemic stroke and/or systemic thromboembolism, all-cause mortality and the safety endpoint was major bleeding.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The present study encompassed a comprehensive analysis of 33 studies involving a total of 137,574 patients with AF on long-term dialysis. All OACs, including warfarin (hazard ratio [HR], .963; 95% confidence interval [CI], .841–1.104), did not show a statistically significant decrease in the risk of ischaemic stroke and/or systemic thromboembolism compared to no anticoagulant therapy. Only apixaban 5 mg twice daily was associated with a lower risk of all-cause mortality compared to non-OAC use (HR, .671; 95% CI, .490–.919). Dabigatran (HR, 2.140; 95% CI, 1.734–2.642) and phenprocoumon (HR, 2.419; 95% CI, 1.241–4.713) were associated with a significantly higher risk of major bleeding than non-OAC use.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>All OACs were not associated with a reduced risk of ischaemic stroke and/or systemic thromboembolism in patients with AF on long-term dialysis. Only apixaban 5 mg twice daily was associated with a decrease in all-cause mortality when compared with non-OAC use.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 12","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014146","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}
Nicolò Gilardi, Massimo Ballabio, Francesco Ravera, Lorenzo Ferrando, Mario Stabile, Andrea Bellodi, Giovanni Talerico, Benedetta Cigolini, Carlo Genova, Federico Carbone, Fabrizio Montecucco, Christian Bracco, Alberto Ballestrero, Gabriele Zoppoli
This pilot study evaluated the influence of medical background on the diagnostic quality of ChatGPT-4's responses in Internal Medicine. Third-year students, residents and specialists summarised five complex NEJM clinical cases before querying ChatGPT-4. Diagnostic ranking, assessed by independent experts, revealed that residents significantly outperformed students (OR 2.33, p = .007); though overall performance was low. These findings indicate that user expertise and concise case summaries are critical for optimising AI diagnostics, highlighting the need for enhanced AI training and user interaction strategies.
本初步研究评估了医学背景对ChatGPT-4在内科诊断质量的影响。在查询ChatGPT-4之前，三年级学生、住院医师和专家总结了五个复杂的NEJM临床病例。由独立专家评估的诊断排名显示，住院医生的表现明显优于学生（OR 2.33, p = .007）；尽管整体表现不佳。这些发现表明，用户专业知识和简明的案例摘要对于优化人工智能诊断至关重要，强调了加强人工智能培训和用户交互策略的必要性。
{"title":"Influence of medical educational background on the diagnostic quality of ChatGPT-4 responses in internal medicine: A pilot study","authors":"Nicolò Gilardi, Massimo Ballabio, Francesco Ravera, Lorenzo Ferrando, Mario Stabile, Andrea Bellodi, Giovanni Talerico, Benedetta Cigolini, Carlo Genova, Federico Carbone, Fabrizio Montecucco, Christian Bracco, Alberto Ballestrero, Gabriele Zoppoli","doi":"10.1111/eci.70113","DOIUrl":"10.1111/eci.70113","url":null,"abstract":"<p>This pilot study evaluated the influence of medical background on the diagnostic quality of ChatGPT-4's responses in Internal Medicine. Third-year students, residents and specialists summarised five complex NEJM clinical cases before querying ChatGPT-4. Diagnostic ranking, assessed by independent experts, revealed that residents significantly outperformed students (OR 2.33, <i>p</i> = .007); though overall performance was low. These findings indicate that user expertise and concise case summaries are critical for optimising AI diagnostics, highlighting the need for enhanced AI training and user interaction strategies.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marco Tomasino, Ravi Vazirani, Jorge Salamanca, Sergio Raposeiras-Roubin, Clara Fernández-Cordón, Miguel Corbí-Pascual, Oscar Vedia, Agustín C. Martín-García, Emilia Blanco-Ponce, Manuel Almendro Delia, Alberto Piserra-López, Jaime Francisco Larre Guerra, Francisco Gonzalez-Santorum, Carmen Lluch-Requerey, Marta Guillén-Marzo, Alberto Pérez-Castellanos, Francisco Ridocci-Soriano, Javier Lopez-País, Rut Andrea, Alessandro Sionis, Iván J. Núñez-Gil, Aitor Uribarri
Background
Age-related differences in Takotsubo Syndrome (TTS) have been described, but there is limited information regarding TTS patients who develop cardiogenic shock (CS).
Methods and Results
We analysed data from 408 CS-TTS patients in the RETAKO registry. Patients were stratified into three age groups: ≤50 years (9%), 51–74 years (48%), and ≥75 years (43%). In the youngest group, compared to the middle-aged and the oldest groups, patients were more likely to be male (35% vs. 16% and 14%, p = .01), have a physical trigger (65% vs. 43% and 49%, p = .04), exhibit atypical echocardiographic patterns (27% vs. 11% and 11%, p = .02), and experienced a higher incidence of ventricular arrhythmias (24% vs. 8% and 7%, p = .01). In-hospital mortality rates were 5% in younger patients, 12% in middle-aged patients, and 15% in older patients (p = .15). Older age independently predicted both in-hospital mortality (OR 2.33, 95% CI 1.05–5.17; reference: middle-aged) and 5-year mortality (HR 3.69, 95% CI 1.77–7.67), regardless of shock severity.
Conclusions
In CS-TTS, younger patients exhibit distinct clinical features but have better outcomes. Older age is associated with higher in-hospital and long-term mortality, regardless of comorbidities and shock severity. These findings underscore the need for age-specific management strategies and further research into the mechanisms underlying age-related differences in CS-TTS.
背景：Takotsubo综合征（TTS）的年龄相关差异已被描述，但关于TTS患者发生心源性休克（CS）的信息有限。方法和结果：我们分析了RETAKO登记处408例CS-TTS患者的数据。患者分为三个年龄组：≤50岁（9%）、51-74岁（48%）和≥75岁（43%）。与中年组和老年组相比，最年轻组的患者更有可能是男性(35%对16%和14%，p =。01)，有物理触发(65%对43%和49%，p =。2004)，表现出非典型超声心动图模式(27%对11%和11%，p =。2002年)，室性心律失常发生率较高（24%比8%和7%，p = 0.01）。住院死亡率年轻患者为5%，中年患者为12%，老年患者为15% （p = .15）。无论休克严重程度如何，老年人独立预测住院死亡率（OR 2.33, 95% CI 1.05-5.17；参考：中年人）和5年死亡率（HR 3.69, 95% CI 1.77-7.67）。结论：在CS-TTS中，年轻患者表现出明显的临床特征，但预后较好。无论合并症和休克严重程度如何，年龄越大，住院死亡率和长期死亡率越高。这些发现强调了针对年龄的管理策略和进一步研究CS-TTS年龄相关差异机制的必要性。
{"title":"Age-related differences in cardiogenic shock secondary to Takotsubo syndrome","authors":"Marco Tomasino, Ravi Vazirani, Jorge Salamanca, Sergio Raposeiras-Roubin, Clara Fernández-Cordón, Miguel Corbí-Pascual, Oscar Vedia, Agustín C. Martín-García, Emilia Blanco-Ponce, Manuel Almendro Delia, Alberto Piserra-López, Jaime Francisco Larre Guerra, Francisco Gonzalez-Santorum, Carmen Lluch-Requerey, Marta Guillén-Marzo, Alberto Pérez-Castellanos, Francisco Ridocci-Soriano, Javier Lopez-País, Rut Andrea, Alessandro Sionis, Iván J. Núñez-Gil, Aitor Uribarri","doi":"10.1111/eci.70119","DOIUrl":"10.1111/eci.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Age-related differences in Takotsubo Syndrome (TTS) have been described, but there is limited information regarding TTS patients who develop cardiogenic shock (CS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>We analysed data from 408 CS-TTS patients in the RETAKO registry. Patients were stratified into three age groups: ≤50 years (9%), 51–74 years (48%), and ≥75 years (43%). In the youngest group, compared to the middle-aged and the oldest groups, patients were more likely to be male (35% vs. 16% and 14%, <i>p</i> = .01), have a physical trigger (65% vs. 43% and 49%, <i>p</i> = .04), exhibit atypical echocardiographic patterns (27% vs. 11% and 11%, <i>p</i> = .02), and experienced a higher incidence of ventricular arrhythmias (24% vs. 8% and 7%, <i>p</i> = .01). In-hospital mortality rates were 5% in younger patients, 12% in middle-aged patients, and 15% in older patients (<i>p</i> = .15). Older age independently predicted both in-hospital mortality (OR 2.33, 95% CI 1.05–5.17; reference: middle-aged) and 5-year mortality (HR 3.69, 95% CI 1.77–7.67), regardless of shock severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In CS-TTS, younger patients exhibit distinct clinical features but have better outcomes. Older age is associated with higher in-hospital and long-term mortality, regardless of comorbidities and shock severity. These findings underscore the need for age-specific management strategies and further research into the mechanisms underlying age-related differences in CS-TTS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12811834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Response to the comment on ‘Branched-chain amino acids and all-cause mortality in patients with liver cirrhosis, and the onset of diabetes in liver transplant recipients’","authors":"Yakun Li, Robin P. F. Dullaart","doi":"10.1111/eci.70118","DOIUrl":"10.1111/eci.70118","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991948","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}
López-Baizán J, Ruiz Ortiz M, Delgado Ortega M, et al. Risk scores for predicting incident heart failure admission in patients with chronic coronary syndromes: Validation in a prospective, monocentric, long-term, cohort study. Eur J Clin Invest. 2023;53: e13941. doi: 10.1111/eci.13941.
The following affiliations are incomplete:
1Cardiology Department, Reina Sofia University Hospital, Córdoba, Spain.
2Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, Córdoba, Spain.
These should have read as follows:
1Cardiology Department, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain.
2Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, University of Córdoba, Córdoba, Spain.
{"title":"Correction to “Risk scores for predicting incident heart failure admission in patients with chronic coronary syndromes: Validation in a prospective, monocentric, long-term, cohort study”","authors":"","doi":"10.1111/eci.70116","DOIUrl":"10.1111/eci.70116","url":null,"abstract":"<p>López-Baizán J, Ruiz Ortiz M, Delgado Ortega M, et al. Risk scores for predicting incident heart failure admission in patients with chronic coronary syndromes: Validation in a prospective, monocentric, long-term, cohort study. <i>Eur J Clin Invest</i>. 2023;53: e13941. doi: 10.1111/eci.13941.</p><p>The following affiliations are incomplete:</p><p><sup>1</sup>Cardiology Department, Reina Sofia University Hospital, Córdoba, Spain.</p><p><sup>2</sup>Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, Córdoba, Spain.</p><p>These should have read as follows:</p><p><sup>1</sup>Cardiology Department, Reina Sofia University Hospital, University of Córdoba, Córdoba, Spain.</p><p><sup>2</sup>Maimonides Institute for Biomedical Research of Córdoba, IMIBIC, University of Córdoba, Córdoba, Spain.</p><p>We apologize for this error.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comment on “Branched-chain amino acids and all-cause mortality in patients with liver cirrhosis, and the onset of diabetes in liver transplant recipients”","authors":"Rachana Mehta, Ranjana Sah","doi":"10.1111/eci.70117","DOIUrl":"10.1111/eci.70117","url":null,"abstract":"","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"55 11","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947845","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}
Heart failure (HF) and pulmonary hypertension (PH) due to left heart disease (PH-LHD) are complex and heterogeneous syndromes with diverse underlying mechanisms and variable clinical courses. Despite significant progress in clinical management, current diagnostic and prognostic approaches often fail to capture the underlying molecular diversity of these conditions. Unbiased serum proteomics offers a promising solution to enable novel biomarkers and pathophysiological pathways directly from patient samples. Using high-throughput mass spectrometry (MS) and aptamer-based platforms, proteomic profiling enables the simultaneous quantification of thousands of proteins across a wide dynamic range, offering a multidimensional perspective on disease mechanisms. In HF, proteomic signatures differentiate phenotypes such as HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) through distinct inflammatory, metabolic and remodelling pathways, supporting more accurate diagnosis and risk assessment. In PH-LHD, dysregulated protein networks reflect pressure overload, atrial remodelling and right ventricular adaptation, supporting more refined phenotypic stratification. Integrating proteomic data with clinical, imaging and genomic variables enhances predictive accuracy and opens new avenues for individualized therapy. However, challenges remain, including pre-analytical variability, data interpretation and the need for rigorous validation across independent cohorts. This review discusses current advances in serum proteomics applied to HF and PH-LHD, methodological strengths and limitations and outlines the translational potential of proteomic findings to improve patient outcomes and support precision medicine.
{"title":"Unbiased serum proteomics in heart failure and associated pulmonary hypertension: From biomarkers discovery to precision medicine","authors":"Matteo Santi, Rosalinda Madonna","doi":"10.1111/eci.70115","DOIUrl":"10.1111/eci.70115","url":null,"abstract":"<p>Heart failure (HF) and pulmonary hypertension (PH) due to left heart disease (PH-LHD) are complex and heterogeneous syndromes with diverse underlying mechanisms and variable clinical courses. Despite significant progress in clinical management, current diagnostic and prognostic approaches often fail to capture the underlying molecular diversity of these conditions. Unbiased serum proteomics offers a promising solution to enable novel biomarkers and pathophysiological pathways directly from patient samples. Using high-throughput mass spectrometry (MS) and aptamer-based platforms, proteomic profiling enables the simultaneous quantification of thousands of proteins across a wide dynamic range, offering a multidimensional perspective on disease mechanisms. In HF, proteomic signatures differentiate phenotypes such as HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) through distinct inflammatory, metabolic and remodelling pathways, supporting more accurate diagnosis and risk assessment. In PH-LHD, dysregulated protein networks reflect pressure overload, atrial remodelling and right ventricular adaptation, supporting more refined phenotypic stratification. Integrating proteomic data with clinical, imaging and genomic variables enhances predictive accuracy and opens new avenues for individualized therapy. However, challenges remain, including pre-analytical variability, data interpretation and the need for rigorous validation across independent cohorts. This review discusses current advances in serum proteomics applied to HF and PH-LHD, methodological strengths and limitations and outlines the translational potential of proteomic findings to improve patient outcomes and support precision medicine.</p>","PeriodicalId":12013,"journal":{"name":"European Journal of Clinical Investigation","volume":"56 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947867","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}
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