Hajer Yaakoubi, Lotfi Boukadida, Marwa Toumia, Anaïs Caillard, Houda Ben Soltane, Rahma Jaballah, Imen Trabelsi, Randa Dhaoui, Asma Zorgati, Hamdi Boubaker, Meriem Khrouf, Zied Mezgar, Houda Ben Salah, Alexandre Mebazaa, Benjamin Deniau, Semir Nouira, Riadh Boukef
Aims
Breathlessness is the primary symptom of decompensated heart failure (HF), but the prevalence and evolution of persistent respiratory distress post-hospitalization remain unclear.
Methods and results
The Longitudinal Observational Study for mIddle Term Follow-up Patients Admitted for Acute Dyspnea in TunIsia (SIDI) study is a prospective and multicentre study on HF patients with preserved ejection fraction admitted for acute dyspnoea. Patients were followed for 6 months. The primary endpoint was to assess the incidence of persistent respiratory distress and factors linked to respiratory recovery at Day 90. The secondary endpoint was rehospitalization and/or death at Day 90 and 180. Among 231 patients, 140 had SpO2 and respiratory rate data at Day 90. Persistent respiratory distress was observed in 97 (69%). Multivariable analysis found no association between respiratory recovery and sex, diabetes, hypertension, kidney disease or NT-proBNP levels. However, intensive follow-up (n = 54) with oral neuroendocrine inhibition significantly improved respiratory parameters at Day 90 (adjusted HR: 5.70 [95% CI 2.13–18.28], P = 0.0001) compared with standard follow-up (n = 86) and reduced rehospitalization and/or death at Day 90 and 180.
Conclusions
Persistent respiratory distress is frequent in the months following HF hospitalization. Optimized guideline-directed therapy and close follow-up improve respiratory recovery. SpO2 and respiratory rate monitoring should be integrated into HF management.
目的：呼吸困难是失代偿性心力衰竭（HF）的主要症状，但住院后持续呼吸窘迫的患病率和演变尚不清楚。方法和结果：突尼斯急性呼吸困难中期随访患者纵向观察研究（SIDI）研究是一项前瞻性多中心研究，研究对象是因急性呼吸困难入院的保留射血分数的HF患者。随访6个月。主要终点是评估第90天持续呼吸窘迫的发生率和与呼吸恢复相关的因素。次要终点是第90天和180天的再住院和/或死亡。在231例患者中，140例患者在第90天有SpO2和呼吸率数据。97例（69%）出现持续呼吸窘迫。多变量分析发现，呼吸恢复与性别、糖尿病、高血压、肾病或NT-proBNP水平无关联。然而，与标准随访（n = 86）相比，口服神经内分泌抑制的强化随访（n = 54）在第90天显著改善了呼吸参数（调整后HR: 5.70 [95% CI 2.13-18.28], P = 0.0001），并减少了第90天和180天的再住院和/或死亡。结论：持续性呼吸窘迫在HF住院后的几个月内是常见的。优化的指导治疗和密切随访可改善呼吸恢复。应将SpO2和呼吸频率监测纳入心衰管理。
{"title":"Intense optimization of oral therapy rapidly restores respiratory function in worsening heart failure patients","authors":"Hajer Yaakoubi, Lotfi Boukadida, Marwa Toumia, Anaïs Caillard, Houda Ben Soltane, Rahma Jaballah, Imen Trabelsi, Randa Dhaoui, Asma Zorgati, Hamdi Boubaker, Meriem Khrouf, Zied Mezgar, Houda Ben Salah, Alexandre Mebazaa, Benjamin Deniau, Semir Nouira, Riadh Boukef","doi":"10.1002/ehf2.15373","DOIUrl":"10.1002/ehf2.15373","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Breathlessness is the primary symptom of decompensated heart failure (HF), but the prevalence and evolution of persistent respiratory distress post-hospitalization remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>The Longitudinal Observational Study for mIddle Term Follow-up Patients Admitted for Acute Dyspnea in TunIsia (SIDI) study is a prospective and multicentre study on HF patients with preserved ejection fraction admitted for acute dyspnoea. Patients were followed for 6 months. The primary endpoint was to assess the incidence of persistent respiratory distress and factors linked to respiratory recovery at Day 90. The secondary endpoint was rehospitalization and/or death at Day 90 and 180. Among 231 patients, 140 had SpO<sub>2</sub> and respiratory rate data at Day 90. Persistent respiratory distress was observed in 97 (69%). Multivariable analysis found no association between respiratory recovery and sex, diabetes, hypertension, kidney disease or NT-proBNP levels. However, intensive follow-up (<i>n</i> = 54) with oral neuroendocrine inhibition significantly improved respiratory parameters at Day 90 (adjusted HR: 5.70 [95% CI 2.13–18.28], <i>P</i> = 0.0001) compared with standard follow-up (<i>n</i> = 86) and reduced rehospitalization and/or death at Day 90 and 180.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Persistent respiratory distress is frequent in the months following HF hospitalization. Optimized guideline-directed therapy and close follow-up improve respiratory recovery. SpO<sub>2</sub> and respiratory rate monitoring should be integrated into HF management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3569-3578"},"PeriodicalIF":3.7,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15373","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Clare J. Taylor, Kathryn S. Taylor, Nicholas R. Jones, Jose M. Ordóñez-Mena, Antoni Bayes-Genis, F.D. Richard Hobbs
Background
European Society of Cardiology (ESC) chronic heart failure (HF) guidelines recommend a single N-terminal pro-B-type natriuretic peptide (NT-proBNP) threshold of ≥125 pg/mL for specialist referral in symptomatic patients; however, natriuretic peptide levels increase with age.
Objectives
We aimed to assess NT-proBNP test performance at age-adjusted thresholds recently proposed by the ESC Heart Failure Association (HFA).
Methods
Diagnostic accuracy study using linked primary and secondary care data (2004–2018) in England. NT-proBNP test performance at ESC HFA age-adjusted rule-in thresholds (≥125 pg/mL, ≥250 pg/mL and ≥500 pg/mL for <50 years, 50–74 years and ≥75 years, respectively) and a high-risk threshold (≥2000 pg/mL) was assessed overall, by sex and body mass index (BMI) with ESC's suggested threshold reductions for obesity.
Results
Of 155 347 patients with NT-proBNP tests performed, 14 585 (9.4%) were diagnosed with HF. Current ESC single threshold of ≥125 pg/mL had sensitivity 94.6% [95% confidence interval (CI) 94.2–95.0] and specificity 50.0% (49.7–50.3). Age-adjusted thresholds had reduced sensitivity (83.5%, 88.5%, 84.4%) but increased specificity (77.6%, 67.8%, 63.5%) across the respective age groups. The high-risk threshold had sensitivity 38.9% (38.1–39.7) and specificity 96.1% (96.0–96.2). A high BMI was associated with lower sensitivity at each age-adjusted threshold, which improved with adjustment by obesity category. Test performance was similar in women and men.
Conclusions
At ESC HFA age-adjusted thresholds, the number of referrals required for HF diagnostic assessment are substantially reduced, but with some (likely lower risk) cases initially being undetected. Lower thresholds for patients with obesity are needed to avoid missing HF cases, but there is no need for adjustment by sex.
{"title":"Age-adjusted natriuretic peptide thresholds for a diagnosis of heart failure in the community: Diagnostic accuracy study","authors":"Clare J. Taylor, Kathryn S. Taylor, Nicholas R. Jones, Jose M. Ordóñez-Mena, Antoni Bayes-Genis, F.D. Richard Hobbs","doi":"10.1002/ehf2.15383","DOIUrl":"10.1002/ehf2.15383","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>European Society of Cardiology (ESC) chronic heart failure (HF) guidelines recommend a single N-terminal pro-B-type natriuretic peptide (NT-proBNP) threshold of ≥125 pg/mL for specialist referral in symptomatic patients; however, natriuretic peptide levels increase with age.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>We aimed to assess NT-proBNP test performance at age-adjusted thresholds recently proposed by the ESC Heart Failure Association (HFA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Diagnostic accuracy study using linked primary and secondary care data (2004–2018) in England. NT-proBNP test performance at ESC HFA age-adjusted rule-in thresholds (≥125 pg/mL, ≥250 pg/mL and ≥500 pg/mL for <50 years, 50–74 years and ≥75 years, respectively) and a high-risk threshold (≥2000 pg/mL) was assessed overall, by sex and body mass index (BMI) with ESC's suggested threshold reductions for obesity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of 155 347 patients with NT-proBNP tests performed, 14 585 (9.4%) were diagnosed with HF. Current ESC single threshold of ≥125 pg/mL had sensitivity 94.6% [95% confidence interval (CI) 94.2–95.0] and specificity 50.0% (49.7–50.3). Age-adjusted thresholds had reduced sensitivity (83.5%, 88.5%, 84.4%) but increased specificity (77.6%, 67.8%, 63.5%) across the respective age groups. The high-risk threshold had sensitivity 38.9% (38.1–39.7) and specificity 96.1% (96.0–96.2). A high BMI was associated with lower sensitivity at each age-adjusted threshold, which improved with adjustment by obesity category. Test performance was similar in women and men.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>At ESC HFA age-adjusted thresholds, the number of referrals required for HF diagnostic assessment are substantially reduced, but with some (likely lower risk) cases initially being undetected. Lower thresholds for patients with obesity are needed to avoid missing HF cases, but there is no need for adjustment by sex.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3552-3568"},"PeriodicalIF":3.7,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15383","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dan Liu, Kai Hu, Vera Schimpf, Victoria Sokalski, Friederike Hermann, Björn Daniel Lengenfelder, Georg Ertl, Stefan Frantz, Peter Nordbeck
Aims
This study evaluated the prognostic value of the relative apical sparing pattern (RASP) of longitudinal strain (LS) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) and investigated whether its combination with pre-procedural biomarkers enhances risk stratification.
Methods and results
This retrospective study included 598 patients (mean age 81.7 ± 5.7 years, 48.8% male) with severe AS undergoing TAVR. Two-dimensional speckle-tracking echocardiography was used to assess LS. RASP was defined as an apical-to-basal LS ratio >3.0 in ≥3 out of six left ventricular walls. The primary endpoint was 2-year cardiovascular (CV) mortality. RASP was present in 19.2% of patients and independently predicted 2-year CV mortality (hazard ratio [HR] 2.01, 95% CI 1.22–3.29, P = 0.006). Low serum albumin (<4.0 g/dL; HR 2.40, 95% CI 1.50–3.84, P < 0.001) and low BMI (≤25.5 kg/m2; HR 1.71, 95% CI 1.07–2.73, P = 0.025) were also independent predictors. A composite risk score (0–3 points) was constructed using these three factors. Two-year CV mortality increased progressively with higher scores: 6.3% for score 0, 11.4% for score 1, 27.2% for score 2 and 35.3% for score 3 (log-rank P < 0.001). High-risk patients (score ≥2) had a more than threefold increase in adjusted mortality risk (HR 3.42, 95% CI 2.14–5.48, P < 0.001).
Conclusions
RASP, particularly when combined with hypoalbuminemia and low BMI, identifies a high-risk phenotype associated with adverse outcomes after TAVR. This integrated risk model may assist in guiding pre-procedural assessment and individualized management.
目的：本研究评估纵向应变（LS）相对根尖保留模式（RASP）在严重主动脉瓣狭窄（AS）行经导管主动脉瓣置换术（TAVR）患者中的预后价值，并探讨其与术前生物标志物的联合是否能增强风险分层。方法与结果：本回顾性研究纳入598例重度AS患者（平均年龄81.7±5.7岁，男性48.8%）行TAVR。二维斑点跟踪超声心动图评价LS。RASP定义为6个左室壁中≥3个左室壁顶端与基底的LS比值bbb3.0。主要终点是2年心血管（CV）死亡率。19.2%的患者存在RASP，独立预测2年CV死亡率（风险比[HR] 2.01, 95% CI 1.22-3.29, P = 0.006）。低血清白蛋白(2)；HR 1.71, 95% CI 1.07-2.73, P = 0.025)也是独立预测因子。使用这三个因素构建一个综合风险评分（0-3分）。2年CV死亡率随着评分的升高而逐渐增加：评分为0分的为6.3%，评分为1分的为11.4%，评分为2分的为27.2%，评分为3分的为35.3% （log-rank P）。结论：RASP，特别是当合并低白蛋白血症和低BMI时，确定了与TAVR后不良结局相关的高风险表型。这种综合风险模型有助于指导程序前评估和个性化管理。
{"title":"Prognostic value of longitudinal strain relative apical sparing in severe aortic stenosis patients undergoing TAVR","authors":"Dan Liu, Kai Hu, Vera Schimpf, Victoria Sokalski, Friederike Hermann, Björn Daniel Lengenfelder, Georg Ertl, Stefan Frantz, Peter Nordbeck","doi":"10.1002/ehf2.15365","DOIUrl":"10.1002/ehf2.15365","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This study evaluated the prognostic value of the relative apical sparing pattern (RASP) of longitudinal strain (LS) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) and investigated whether its combination with pre-procedural biomarkers enhances risk stratification.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>This retrospective study included 598 patients (mean age 81.7 ± 5.7 years, 48.8% male) with severe AS undergoing TAVR. Two-dimensional speckle-tracking echocardiography was used to assess LS. RASP was defined as an apical-to-basal LS ratio >3.0 in ≥3 out of six left ventricular walls. The primary endpoint was 2-year cardiovascular (CV) mortality. RASP was present in 19.2% of patients and independently predicted 2-year CV mortality (hazard ratio [HR] 2.01, 95% CI 1.22–3.29, <i>P</i> = 0.006). Low serum albumin (<4.0 g/dL; HR 2.40, 95% CI 1.50–3.84, <i>P</i> < 0.001) and low BMI (≤25.5 kg/m<sup>2</sup>; HR 1.71, 95% CI 1.07–2.73, <i>P</i> = 0.025) were also independent predictors. A composite risk score (0–3 points) was constructed using these three factors. Two-year CV mortality increased progressively with higher scores: 6.3% for score 0, 11.4% for score 1, 27.2% for score 2 and 35.3% for score 3 (log-rank <i>P</i> < 0.001). High-risk patients (score ≥2) had a more than threefold increase in adjusted mortality risk (HR 3.42, 95% CI 2.14–5.48, <i>P</i> < 0.001).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>RASP, particularly when combined with hypoalbuminemia and low BMI, identifies a high-risk phenotype associated with adverse outcomes after TAVR. This integrated risk model may assist in guiding pre-procedural assessment and individualized management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3537-3551"},"PeriodicalIF":3.7,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15365","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144717748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart failure (HF) is a steadily increasing health problem associated with a high mortality rate. Lymphocytopenia is common and reportedly associated with poor clinical outcomes in patients with HF. Alterations in circulating lymphocyte subsets have not been examined. The current study focused on the CD19 cell count, B cells and examined whether alteration of lymphocyte subsets can predict clinical outcomes in patients with HF.
Methods
Three hundred ninety-five consecutive patients with HF were enrolled (mean age 73, 59.6% men). Circulating lymphocyte subset counts (CD3 cells: T cells; CD19 cells: B cells; and CD56 cells: NK cells) were evaluated. All patients were prospectively followed for a median period of 374 days. The primary and secondary endpoints were all-cause mortality and HF-related events, respectively.
Results
Simple linear analysis indicated that circulating CD19 B cell counts negatively correlated with heart-type fatty acid-binding protein levels (r = −0.3669; P < 0.0001). The C-index of the CD19 B cell count for all-cause mortality was the highest among the lymphocyte subset counts (C-index 0.73085 vs. 0.69063, 0.65312, 0.60117). Multivariate Cox proportional hazard regression analysis demonstrated that the CD19 B cell count was an independent predictor of all-cause mortality and HF-related events after adjusting for confounding risk factors [hazard ratio (HR) 0.57; confidence interval (CI) 0.45–0.71; P < 0.0001 for all-cause mortality; HR 0.79; CI 0.64–0.98; P = 0.0293 for HF-related events], but not for other subset counts. Adding the CD19 B cell count to the basic risk factors significantly improved the C-index for all-cause mortality, with a significant net reclassification index and integrated discrimination improvement (C-index 0.8000 vs. 0.7609; P = 0.0256).
Conclusions
Circulating CD19 B cell counts correlated with myocardial injury and could be a feasible marker for clinical outcomes in patients with HF.
{"title":"Circulating CD19 B cell count, myocardial injury and clinical outcomes in patients with heart failure","authors":"Yuta Kobayashi, Yoichiro Otaki, Tetsu Watanabe, Ryuhei Yamaguchi, Hiroe Ono, Shingo Tachibana, Junya Sato, Naoaki Hashimoto, Masahiro Wanezaki, Daisuke Kutsuzawa, Takanori Arimoto, Masafumi Watanabe","doi":"10.1002/ehf2.15382","DOIUrl":"10.1002/ehf2.15382","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Heart failure (HF) is a steadily increasing health problem associated with a high mortality rate. Lymphocytopenia is common and reportedly associated with poor clinical outcomes in patients with HF. Alterations in circulating lymphocyte subsets have not been examined. The current study focused on the CD19 cell count, B cells and examined whether alteration of lymphocyte subsets can predict clinical outcomes in patients with HF.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Three hundred ninety-five consecutive patients with HF were enrolled (mean age 73, 59.6% men). Circulating lymphocyte subset counts (CD3 cells: T cells; CD19 cells: B cells; and CD56 cells: NK cells) were evaluated. All patients were prospectively followed for a median period of 374 days. The primary and secondary endpoints were all-cause mortality and HF-related events, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Simple linear analysis indicated that circulating CD19 B cell counts negatively correlated with heart-type fatty acid-binding protein levels (<i>r</i> = −0.3669; <i>P</i> < 0.0001). The C-index of the CD19 B cell count for all-cause mortality was the highest among the lymphocyte subset counts (C-index 0.73085 vs. 0.69063, 0.65312, 0.60117). Multivariate Cox proportional hazard regression analysis demonstrated that the CD19 B cell count was an independent predictor of all-cause mortality and HF-related events after adjusting for confounding risk factors [hazard ratio (HR) 0.57; confidence interval (CI) 0.45–0.71; <i>P</i> < 0.0001 for all-cause mortality; HR 0.79; CI 0.64–0.98; <i>P</i> = 0.0293 for HF-related events], but not for other subset counts. Adding the CD19 B cell count to the basic risk factors significantly improved the C-index for all-cause mortality, with a significant net reclassification index and integrated discrimination improvement (C-index 0.8000 vs. 0.7609; <i>P</i> = 0.0256).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Circulating CD19 B cell counts correlated with myocardial injury and could be a feasible marker for clinical outcomes in patients with HF.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3512-3523"},"PeriodicalIF":3.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15382","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amanda Ochoa-Espinosa, Lucile Genty, Lifen Xu, Asli Akin, Katharina Glatz, Sarah Decembrini, Christian Mueller, Albert Neutzner, Rajesh Jayachandran, Felix Mahfoud, Jean Pieters, Beat A. Kaufmann
Aims
Dilated cardiomyopathy (DCM) caused by viral myocarditis and autoimmune processes is a frequent cause for heart failure. CD4+ T cells are indispensable for autoimmune myocarditis. Coronin 1 is required for peripheral T cell survival. We therefore hypothesized that deficiency in coronin 1 protects mice from experimental autoimmune myocarditis (EAM).
Methods
EAM was induced in coronin 1-deficient and wild-type (WT) mice. WT CD4+ T cells isolated from spleens were transferred to coronin 1-deficient mice in a subset of animals; IL-10 was blocked in another subset before EAM induction. On day 21 mice underwent echocardiography and were sacrificed. Myocarditis severity was scored (Grades 0–4) on histology. Leukocyte fractions in blood and heart tissue were characterized. Plasma cytokines including interleukin (IL)-10 were measured and RNA sequencing of myocardial tissue was performed.
Results
The severity of myocarditis was lower in coronin 1-deficient versus WT mice [median 0 (25th–75th percentile 0–2) vs. 4 (3–4), P < 0.0001]. Coronin 1-deficient animals showed significant reductions of inflammatory cells in the myocardium [median 2.5% (25th–75th percentile 1.5%–7.0%) vs. 28.3% (14.5%–54.8%), P < 0.0001]. IL-10 was selectively increased in the plasma of coronin 1-deficient mice [median 3.0 pg/mL (25th–75th percentile 1.3–5.2 pg/mL) vs. 0.4 pg/mL (0–2.0 pg/mL), P < 0.05]. Transfer of WT CD4+ T cells but not blocking of IL-10 restored EAM. Left ventricular mass was increased, but effects of myocarditis on left ventricular function were evident only on the RNA level.
Conclusions
Deficiency in coronin 1 protects from the development of EAM by reducing CD4+ T cells. This protection resulted in less structural alterations of the left ventricular myocardium. IL-10 was selectively increased in the plasma of coronin 1-deficient mice, but blocking of IL-10 was not sufficient to restore EAM.
{"title":"Coronin 1 deficiency protects from the development of autoimmune myocarditis by reducing CD4+ T cells","authors":"Amanda Ochoa-Espinosa, Lucile Genty, Lifen Xu, Asli Akin, Katharina Glatz, Sarah Decembrini, Christian Mueller, Albert Neutzner, Rajesh Jayachandran, Felix Mahfoud, Jean Pieters, Beat A. Kaufmann","doi":"10.1002/ehf2.15384","DOIUrl":"10.1002/ehf2.15384","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Dilated cardiomyopathy (DCM) caused by viral myocarditis and autoimmune processes is a frequent cause for heart failure. CD4+ T cells are indispensable for autoimmune myocarditis. Coronin 1 is required for peripheral T cell survival. We therefore hypothesized that deficiency in coronin 1 protects mice from experimental autoimmune myocarditis (EAM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>EAM was induced in coronin 1-deficient and wild-type (WT) mice. WT CD4+ T cells isolated from spleens were transferred to coronin 1-deficient mice in a subset of animals; IL-10 was blocked in another subset before EAM induction. On day 21 mice underwent echocardiography and were sacrificed. Myocarditis severity was scored (Grades 0–4) on histology. Leukocyte fractions in blood and heart tissue were characterized. Plasma cytokines including interleukin (IL)-10 were measured and RNA sequencing of myocardial tissue was performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The severity of myocarditis was lower in coronin 1-deficient versus WT mice [median 0 (25th–75th percentile 0–2) vs. 4 (3–4), <i>P</i> < 0.0001]. Coronin 1-deficient animals showed significant reductions of inflammatory cells in the myocardium [median 2.5% (25th–75th percentile 1.5%–7.0%) vs. 28.3% (14.5%–54.8%), <i>P</i> < 0.0001]. IL-10 was selectively increased in the plasma of coronin 1-deficient mice [median 3.0 pg/mL (25th–75th percentile 1.3–5.2 pg/mL) vs. 0.4 pg/mL (0–2.0 pg/mL), <i>P</i> < 0.05]. Transfer of WT CD4+ T cells but not blocking of IL-10 restored EAM. Left ventricular mass was increased, but effects of myocarditis on left ventricular function were evident only on the RNA level.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Deficiency in coronin 1 protects from the development of EAM by reducing CD4+ T cells. This protection resulted in less structural alterations of the left ventricular myocardium. IL-10 was selectively increased in the plasma of coronin 1-deficient mice, but blocking of IL-10 was not sufficient to restore EAM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3524-3536"},"PeriodicalIF":3.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15384","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144689656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maximilian Leo Müller, Phillip Suwalski, Finn Wilke, Ekaterina Latinova, Gamze Satilmis, Nicolas Musigk, Anna Brand, Isabel Mattig, Fabian Knebel, Daniel Messroghli, Katrin Hahn, Sebastian Spethmann, Ulf Landmesser, Bettina Heidecker
Aims
Myocardial inflammation is increasingly recognized for its association with impaired clinical outcomes in cardiac amyloidosis but a trend towards less invasive diagnosis impedes its detection. The aim of this study was to assess magnetocardiography (MCG) as a potential non-invasive method to diagnose myocardial inflammation in patients with cardiac amyloidosis.
Methods and results
This retrospective proof-of-concept study included 27 patients with cardiac amyloidosis who had undergone MCG and endomyocardial biopsy as part of their diagnostic workup. Immunohistopathological evaluation identified myocardial inflammation in 10 patients (37.0%). Patients with myocardial inflammation had significantly higher magnetocardiography vector (VMCG) values than those without (0.093 [IQR 0.058–0.183] vs. 0.052 [IQR 0.039–0.073]; P = 0.01). With an area under the curve of 0.785 (95% CI 0.600–0.970; P < 0.01), VMCG had significant diagnostic value for myocardial inflammation in cardiac amyloidosis when tested against a non-informative random classifier in receiver operating characteristic analysis. Youden's index identified VMCG ≥0.078 as the optimal cut-off to discriminate between patients with and without myocardial inflammation, yielding a sensitivity of 60.0%, a specificity of 88.2%, a positive predictive value of 75.0% and a negative predictive value of 78.9%.
Conclusions
This proof-of-concept study provides initial evidence for the potential of MCG as a non-invasive method to identify myocardial inflammation in patients with cardiac amyloidosis. These findings require validation in larger prospective studies but could substantially contribute to the optimization of personalized management in patients diagnosed with cardiac amyloidosis via non-invasive pathways in the future.
目的：心肌炎症越来越被认为与心脏淀粉样变性患者的临床预后受损有关，但微创诊断的趋势阻碍了其检测。本研究的目的是评估心脏磁图（MCG）作为一种潜在的无创方法来诊断心肌淀粉样变性患者的心肌炎症。方法和结果：这项回顾性的概念验证研究包括27例心脏淀粉样变性患者，他们接受了MCG和心内膜肌活检作为诊断检查的一部分。10例（37.0%）患者经免疫组织病理学检查发现心肌炎症。心肌炎症患者的心磁矢量（VMCG）值明显高于无炎症患者（0.093 [IQR 0.058 ~ 0.183] vs. 0.052 [IQR 0.039 ~ 0.073]; P = 0.01）。曲线下面积为0.785 （95% CI 0.600-0.970； P）结论：这项概念验证性研究为MCG作为无创方法识别心脏淀粉样变性患者心肌炎症的潜力提供了初步证据。这些发现需要在更大规模的前瞻性研究中得到验证，但可以在未来通过非侵入性途径对诊断为心脏淀粉样变性的患者进行个性化管理的优化。
{"title":"Magnetocardiography for the non-invasive diagnosis of myocardial inflammation in cardiac amyloidosis: A proof-of-concept study","authors":"Maximilian Leo Müller, Phillip Suwalski, Finn Wilke, Ekaterina Latinova, Gamze Satilmis, Nicolas Musigk, Anna Brand, Isabel Mattig, Fabian Knebel, Daniel Messroghli, Katrin Hahn, Sebastian Spethmann, Ulf Landmesser, Bettina Heidecker","doi":"10.1002/ehf2.15377","DOIUrl":"10.1002/ehf2.15377","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Myocardial inflammation is increasingly recognized for its association with impaired clinical outcomes in cardiac amyloidosis but a trend towards less invasive diagnosis impedes its detection. The aim of this study was to assess magnetocardiography (MCG) as a potential non-invasive method to diagnose myocardial inflammation in patients with cardiac amyloidosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>This retrospective proof-of-concept study included 27 patients with cardiac amyloidosis who had undergone MCG and endomyocardial biopsy as part of their diagnostic workup. Immunohistopathological evaluation identified myocardial inflammation in 10 patients (37.0%). Patients with myocardial inflammation had significantly higher magnetocardiography vector (VMCG) values than those without (0.093 [IQR 0.058–0.183] vs. 0.052 [IQR 0.039–0.073]; <i>P</i> = 0.01). With an area under the curve of 0.785 (95% CI 0.600–0.970; <i>P</i> < 0.01), VMCG had significant diagnostic value for myocardial inflammation in cardiac amyloidosis when tested against a non-informative random classifier in receiver operating characteristic analysis. Youden's index identified VMCG ≥0.078 as the optimal cut-off to discriminate between patients with and without myocardial inflammation, yielding a sensitivity of 60.0%, a specificity of 88.2%, a positive predictive value of 75.0% and a negative predictive value of 78.9%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This proof-of-concept study provides initial evidence for the potential of MCG as a non-invasive method to identify myocardial inflammation in patients with cardiac amyloidosis. These findings require validation in larger prospective studies but could substantially contribute to the optimization of personalized management in patients diagnosed with cardiac amyloidosis via non-invasive pathways in the future.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3755-3760"},"PeriodicalIF":3.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15377","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144947213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kati Valtola, Päivi Pietilä-Effati, Jonna M. E. Männistö, Susanne Walls, Ilkka Kantola, Johanna Kuusisto
Aims
To investigate the genetics, cardiac phenotype and cardiovascular outcomes of Finnish Fabry patients.
Methods and results
Among the 109 patients with Fabry disease (FD) diagnosed in Finland by 2018, 97 (89%; 32 males and 65 females, mean ages 42 and 52 years) were followed for a mean of 12 years. Data on genetics, phenotypes, cardiac imaging and cardiovascular outcomes were collected from the Fabry Registry and medical records. The 26 families with FD harboured 22 different hemi−/heterozygous GLA variants, most commonly p.R227X, p.A143T or p.P409A. The Fabry phenotype in males was classic in 19 (59%), late-onset in 10 (31%) and intermediate in 3 (9%) patients. Among the females, 62 (95%) were symptomatic. Fabry cardiomyopathy (FC, maximal left ventricular wall thickness ≥13 mm, or an increased cardiac mass and decreased T1 time, or typical late gadolinium enhancement (LGE) in CMR) was present in 21 (66%) males manifesting since their 20s, and in 32 (49%) females since their 40s. LGE in CMR was detected in most subjects with cardiomyopathy, particularly in females. Among the 53 patients with FC, 16 (30%) developed atrial fibrillation, 17 (32%) stroke, 14 (26%) heart failure (HF) and 3 (6%) end-stage renal disease. Nine patients died during the follow-up at mean ages of 48 (males) and 75 years (females), three of whom died from HF and three from stroke. Eight of those who died had cardiomyopathy.
Conclusions
In Finland, FD is caused by multiple GLA variants. Classic phenotype is more common. Contrasting previous studies, most women are symptomatic. Cardiomyopathy is very common also in women since their 40s and associates with atrial fibrillation, HF, stroke and death, emphasizing the malignant natural course of FC. Our findings highlight the need for even more diligent monitoring of cardiac manifestations also in females with FD by regular cardiac imaging with CMR.
{"title":"Genetics, cardiac phenotype and cardiovascular outcomes in Fabry disease patients in Finland","authors":"Kati Valtola, Päivi Pietilä-Effati, Jonna M. E. Männistö, Susanne Walls, Ilkka Kantola, Johanna Kuusisto","doi":"10.1002/ehf2.15387","DOIUrl":"10.1002/ehf2.15387","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>To investigate the genetics, cardiac phenotype and cardiovascular outcomes of Finnish Fabry patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>Among the 109 patients with Fabry disease (FD) diagnosed in Finland by 2018, 97 (89%; 32 males and 65 females, mean ages 42 and 52 years) were followed for a mean of 12 years. Data on genetics, phenotypes, cardiac imaging and cardiovascular outcomes were collected from the Fabry Registry and medical records. The 26 families with FD harboured 22 different hemi−/heterozygous <i>GLA</i> variants, most commonly p.R227X, p.A143T or p.P409A. The Fabry phenotype in males was classic in 19 (59%), late-onset in 10 (31%) and intermediate in 3 (9%) patients. Among the females, 62 (95%) were symptomatic. Fabry cardiomyopathy (FC, maximal left ventricular wall thickness ≥13 mm, or an increased cardiac mass and decreased T1 time, or typical late gadolinium enhancement (LGE) in CMR) was present in 21 (66%) males manifesting since their 20s, and in 32 (49%) females since their 40s. LGE in CMR was detected in most subjects with cardiomyopathy, particularly in females. Among the 53 patients with FC, 16 (30%) developed atrial fibrillation, 17 (32%) stroke, 14 (26%) heart failure (HF) and 3 (6%) end-stage renal disease. Nine patients died during the follow-up at mean ages of 48 (males) and 75 years (females), three of whom died from HF and three from stroke. Eight of those who died had cardiomyopathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>In Finland, FD is caused by multiple <i>GLA</i> variants. Classic phenotype is more common. Contrasting previous studies, most women are symptomatic. Cardiomyopathy is very common also in women since their 40s and associates with atrial fibrillation, HF, stroke and death, emphasizing the malignant natural course of FC. Our findings highlight the need for even more diligent monitoring of cardiac manifestations also in females with FD by regular cardiac imaging with CMR.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3502-3511"},"PeriodicalIF":3.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15387","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We commend the authors of the RED-HEART study for their valuable contribution detailing real-world use of sodium–glucose co-transporter 2 inhibitors (SGLT2is) in heart failure patients.1 Their identification of factors influencing SGLT2i prescription provides important clinical insights.
The authors rightly acknowledge as a limitation that their study included only patients managed in cardiology outpatient clinics. However, this limitation also represents a missed opportunity to explore how multidisciplinary care models might address the underuse of SGLT2is, particularly in patients with chronic kidney disease or diabetes. These populations often require co-management by nephrologists and endocrinologists, specialists with considerable experience prescribing SGLT2is.
Recent heart failure guidelines emphasize the importance of integrated, team-based approaches to optimize guideline-directed medical therapy. Multidisciplinary clinics and shared-care pathways have been shown to reduce therapeutic inertia and improve medication uptake in complex patients. The absence of analysis or discussion of multidisciplinary care as a potential enabler of higher SGLT2i use leaves a gap in interpreting the real-world barriers and solutions.
Future studies should evaluate how collaborative care models involving cardiology, nephrology and endocrinology influence the implementation of SGLT2 inhibitors in routine practice. Such research may help overcome barriers identified in RED-HEART and improve equitable access to these life-saving therapies.
{"title":"Multidisciplinary care: A missing solution to SGLT2 inhibitor underuse in heart failure","authors":"Wahab Khawar Siddiqui","doi":"10.1002/ehf2.15372","DOIUrl":"10.1002/ehf2.15372","url":null,"abstract":"<p>We commend the authors of the RED-HEART study for their valuable contribution detailing real-world use of sodium–glucose co-transporter 2 inhibitors (SGLT2is) in heart failure patients.<span><sup>1</sup></span> Their identification of factors influencing SGLT2i prescription provides important clinical insights.</p><p>The authors rightly acknowledge as a limitation that their study included only patients managed in cardiology outpatient clinics. However, this limitation also represents a missed opportunity to explore how multidisciplinary care models might address the underuse of SGLT2is, particularly in patients with chronic kidney disease or diabetes. These populations often require co-management by nephrologists and endocrinologists, specialists with considerable experience prescribing SGLT2is.</p><p>Recent heart failure guidelines emphasize the importance of integrated, team-based approaches to optimize guideline-directed medical therapy. Multidisciplinary clinics and shared-care pathways have been shown to reduce therapeutic inertia and improve medication uptake in complex patients. The absence of analysis or discussion of multidisciplinary care as a potential enabler of higher SGLT2i use leaves a gap in interpreting the real-world barriers and solutions.</p><p>Future studies should evaluate how collaborative care models involving cardiology, nephrology and endocrinology influence the implementation of SGLT2 inhibitors in routine practice. Such research may help overcome barriers identified in RED-HEART and improve equitable access to these life-saving therapies.</p><p>Sincerely,</p><p>Dr. Wahab Khawar Siddiqui</p><p>Jinnah Sindh Medical University</p><p><span>[email protected]</span></p><p>None.</p>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":""},"PeriodicalIF":3.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15372","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lisa-Maria Rosenthal, Oliver Miera, Annemarie Krauss, Friederike Danne, Felix Berger, Peter Kramer
Aims
Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has shown clinical benefits in adults with heart failure (HF), improving cardiac function, reducing HF-related hospitalizations and enhancing survival rates. While extensively studied in adult HF, data on its efficacy and safety in paediatric HF patients remain limited. We aimed to evaluate the use of dapagliflozin in addition to optimized therapy in paediatric HF patients regarding safety, clinical outcomes and adverse events.
Methods and results
We conducted a single-centre retrospective analysis of 37 paediatric HF patients (median age 9.0 years, range 0.2–17.1 years) treated with dapagliflozin at our institution between April 2022 and February 2025. Clinical outcomes, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), NT-proBNP levels and estimated glomerular filtration rate (eGFR) were analysed at baseline, 3–6 months and the latest follow-up. The most frequent diagnoses among paediatric HF patients treated with dapagliflozin were dilated cardiomyopathy (43.2%, 56% of those with acute myocarditis), heart transplant recipients (18.9%) and single ventricle heart defects (16.2%). The median duration of dapagliflozin treatment was 189 days (Q1, Q3: 381, 596). Dapagliflozin was well tolerated, with no severe adverse effects observed. During follow-up, four patients required ventricular assist device (VAD) implantation, five underwent heart transplantation and one patient died. In six patients, the VAD could be explanted due to myocardial recovery. Overall, LVEF significantly improved from 40% at baseline to 51% at 3–6 months and further to 57% at latest follow-up (P = 0.016). GLS significantly improved from −9.2% to −14.7% from baseline to latest follow-up (P = 0.023). Heart failure classification significantly improved from baseline to latest follow-up (P = 0.004). NT-proBNP levels decreased during follow-up, without reaching statistical significance.
Conclusions
Dapagliflozin in addition to optimized HF therapy was safe and well tolerated in paediatric HF patients, with improvements in functional class, left ventricular contractility and heart failure symptoms. The study's limitations, including its small sample size and retrospective design, highlight the need for larger, multicentre, prospective trials to confirm these findings.
{"title":"Initial clinical experience with dapagliflozin in addition to optimized medical therapy in paediatric heart failure patients","authors":"Lisa-Maria Rosenthal, Oliver Miera, Annemarie Krauss, Friederike Danne, Felix Berger, Peter Kramer","doi":"10.1002/ehf2.15386","DOIUrl":"10.1002/ehf2.15386","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has shown clinical benefits in adults with heart failure (HF), improving cardiac function, reducing HF-related hospitalizations and enhancing survival rates. While extensively studied in adult HF, data on its efficacy and safety in paediatric HF patients remain limited. We aimed to evaluate the use of dapagliflozin in addition to optimized therapy in paediatric HF patients regarding safety, clinical outcomes and adverse events.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>We conducted a single-centre retrospective analysis of 37 paediatric HF patients (median age 9.0 years, range 0.2–17.1 years) treated with dapagliflozin at our institution between April 2022 and February 2025. Clinical outcomes, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), NT-proBNP levels and estimated glomerular filtration rate (eGFR) were analysed at baseline, 3–6 months and the latest follow-up. The most frequent diagnoses among paediatric HF patients treated with dapagliflozin were dilated cardiomyopathy (43.2%, 56% of those with acute myocarditis), heart transplant recipients (18.9%) and single ventricle heart defects (16.2%). The median duration of dapagliflozin treatment was 189 days (Q1, Q3: 381, 596). Dapagliflozin was well tolerated, with no severe adverse effects observed. During follow-up, four patients required ventricular assist device (VAD) implantation, five underwent heart transplantation and one patient died. In six patients, the VAD could be explanted due to myocardial recovery. Overall, LVEF significantly improved from 40% at baseline to 51% at 3–6 months and further to 57% at latest follow-up (<i>P</i> = 0.016). GLS significantly improved from −9.2% to −14.7% from baseline to latest follow-up (<i>P</i> = 0.023). Heart failure classification significantly improved from baseline to latest follow-up (<i>P</i> = 0.004). NT-proBNP levels decreased during follow-up, without reaching statistical significance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Dapagliflozin in addition to optimized HF therapy was safe and well tolerated in paediatric HF patients, with improvements in functional class, left ventricular contractility and heart failure symptoms. The study's limitations, including its small sample size and retrospective design, highlight the need for larger, multicentre, prospective trials to confirm these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3494-3501"},"PeriodicalIF":3.7,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15386","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144682173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christoph Knosalla, Gloria Färber, Andreas J. Rieth, Rolf Wachter, Marius Placzek, Wolfgang Albert, Gerd Hasenfuß, Volkmar Falk, Tim Friede, for the VAD-DZHK3 Investigators
Aims
Bridge to transplantation (BTT) with durable, continuous-flow left ventricular assist devices (LVAD) of patients is a well-established treatment concept in patients awaiting heart transplantation (HTx). However, the role of elective LVAD implantation in patients with less advanced HF, but increased risk of decompensation remains uncertain.
Methods and results
The VAD-DZHK3 trial is an investigator-initiated, randomized controlled trial designed to assess whether an early strategy of elective LVAD implantation improves outcomes compared with a conventional approach involving optimal medical therapy and delayed device implantation only after clinical deterioration. Eligible patients are those with end-stage HF listed for cardiac transplantation. This is an event-driven study, that is, the study is completed once 120 events of the primary composite endpoint have been observed and all patients have at least 1 year of follow-up unless they died earlier. Patients meeting inclusion criteria who decline randomization are enrolled in a parallel observational registry reflecting standard care. The primary efficacy endpoint is survival free from high urgent cardiac transplantation, disabling stroke and HF hospitalizations (including emergency room HF visits >6 h).
Conclusions
The VAD-DZHK3 trial will provide guidance on the optimal timing and patient selection for LVAD implantation in heart transplant candidates, potentially redefining current standards of care.
{"title":"Rationale and design of the randomized ‘early ventricular assist device’—Trial (VAD-DZHK3)","authors":"Christoph Knosalla, Gloria Färber, Andreas J. Rieth, Rolf Wachter, Marius Placzek, Wolfgang Albert, Gerd Hasenfuß, Volkmar Falk, Tim Friede, for the VAD-DZHK3 Investigators","doi":"10.1002/ehf2.15376","DOIUrl":"10.1002/ehf2.15376","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Bridge to transplantation (BTT) with durable, continuous-flow left ventricular assist devices (LVAD) of patients is a well-established treatment concept in patients awaiting heart transplantation (HTx). However, the role of elective LVAD implantation in patients with less advanced HF, but increased risk of decompensation remains uncertain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>The VAD-DZHK3 trial is an investigator-initiated, randomized controlled trial designed to assess whether an early strategy of elective LVAD implantation improves outcomes compared with a conventional approach involving optimal medical therapy and delayed device implantation only after clinical deterioration. Eligible patients are those with end-stage HF listed for cardiac transplantation. This is an event-driven study, that is, the study is completed once 120 events of the primary composite endpoint have been observed and all patients have at least 1 year of follow-up unless they died earlier. Patients meeting inclusion criteria who decline randomization are enrolled in a parallel observational registry reflecting standard care. The primary efficacy endpoint is survival free from high urgent cardiac transplantation, disabling stroke and HF hospitalizations (including emergency room HF visits >6 h).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>The VAD-DZHK3 trial will provide guidance on the optimal timing and patient selection for LVAD implantation in heart transplant candidates, potentially redefining current standards of care.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11864,"journal":{"name":"ESC Heart Failure","volume":"12 5","pages":"3731-3740"},"PeriodicalIF":3.7,"publicationDate":"2025-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ehf2.15376","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144674122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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