Pub Date : 2026-02-07DOI: 10.1016/j.jchf.2026.102948
Nir Uriel, Gabriel T Sayer, Boaz Elad, Justin A Fried, Jayant K Raikhelkar, Dor Lotan, Daniel J Goldstein, Ulrich P Jorde, Joseph C Cleveland, Mandeep R Mehra, Stavros G Drakos, Katherine L Wood, John D Henderson, Fei San Lee, Manreet K Kanwar, Kevin J Clerkin
Background: Younger patients (18-49 years of age) with advanced heart failure (HF) face unique challenges in decision-making for advanced HF therapies. Although heart transplantation (HT) offers excellent survival, it is associated with finite graft longevity. The HeartMate 3 (HM3) left ventricular assist device (LVAD) has demonstrated promising outcomes, but direct comparisons with those listed for or undergoing HT in this age group remain limited.
Objectives: This study sought to compare survival and adverse event (AE) outcomes between younger patients receiving HM3 LVAD support and those listed for or undergoing HT.
Methods: The authors analyzed patients 18-49 years of age from the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) portfolio (HM3 cohort; n = 420) and the UNOS (United Network for Organ Sharing) registry (HT listing cohort; n = 1,955) (HT recipients; n = 1,176) from 2014-2018. Propensity score matching was performed to adjust for baseline differences. Outcomes included 2-year survival from time of treatment or time of listing, freedom from death or delisting for deterioration, and 1-year incidence of major AEs (ie, stroke, renal dysfunction, infection).
Results: After propensity score matching, 2-year survival from treatment was similar for HM3 and HT (88.7% vs 90.2%; HR: 1.18; P = 0.53). When comparing outcomes from time of transplant listing vs LVAD implantation, HM3 was associated with higher freedom from death compared with freedom from death or delisting due to deterioration in UNOS (90.1% vs 76.7%; HR: 0.38; P < 0.0001). AE analysis showed lower 1-year rates of renal dysfunction requiring dialysis (5.0% vs 10.4%; P = 0.016) and fewer infection-related hospitalizations (24.8% vs 34.2%; P = 0.012) in HM3 recipients, but a higher incidence of debilitating stroke (3.4% vs 0.3%; P = 0.027).
Conclusions: Contemporary data suggest that durable LVAD therapy may offer survival outcomes comparable to HT in adults <50 years of age. These findings support the consideration of an LVAD-first strategy as a viable initial approach to heart replacement therapy in appropriately selected patients. (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 Investigational Device Exemption [MOMENTUM 3 IDE]; NCT02224755) (MOMENTUM 3 Continued Access Protocol [MOMENTUM 3 CAP]; NCT02892955).
背景：患有晚期心力衰竭（HF）的年轻患者（18-49岁）在晚期心力衰竭治疗决策方面面临独特的挑战。虽然心脏移植（HT）提供了良好的生存，但它与有限的移植寿命有关。HeartMate 3 （HM3）左心室辅助装置（LVAD）已显示出良好的结果，但与该年龄组中列出的或正在接受HT的患者的直接比较仍然有限。目的：本研究旨在比较接受HM3 LVAD支持的年轻患者与接受或正在接受HT治疗的患者之间的生存和不良事件（AE）结果。方法：作者分析了2014-2018年来自MOMENTUM 3（磁浮技术在接受心脏伴侣3机械循环支持治疗的患者中的多中心研究）组合（HM3队列，n = 420）和UNOS（联合器官共享网络）登记（HT列表队列，n = 1955） （HT接受者，n = 1176）的18-49岁患者。进行倾向评分匹配以调整基线差异。结果包括从治疗时间或上市时间算起的2年生存率，免于死亡或因恶化而退市，以及1年内主要不良事件（即中风、肾功能不全、感染）的发生率。结果：倾向评分匹配后，HM3和HT治疗后的2年生存率相似（88.7% vs 90.2%; HR: 1.18; P = 0.53）。当比较移植上架时间与LVAD植入时间的结果时，与因UNOS恶化而死亡或退架的自由相比，HM3与更高的死亡自由相关（90.1% vs 76.7%; HR: 0.38; P < 0.0001）。AE分析显示，HM3受者1年内需要透析的肾功能不全发生率较低（5.0%对10.4%,P = 0.016），感染相关住院率较低（24.8%对34.2%,P = 0.012），但衰弱性卒中发生率较高（3.4%对0.3%,P = 0.027）。结论：当代数据表明，持久的左心室辅助器治疗可能提供与成人HT相当的生存结果
{"title":"Heart Replacement Therapy in Young Patients: A Comparative Analysis of HeartMate 3 LVAD and Heart Transplant Using MOMENTUM 3 and UNOS Registry.","authors":"Nir Uriel, Gabriel T Sayer, Boaz Elad, Justin A Fried, Jayant K Raikhelkar, Dor Lotan, Daniel J Goldstein, Ulrich P Jorde, Joseph C Cleveland, Mandeep R Mehra, Stavros G Drakos, Katherine L Wood, John D Henderson, Fei San Lee, Manreet K Kanwar, Kevin J Clerkin","doi":"10.1016/j.jchf.2026.102948","DOIUrl":"10.1016/j.jchf.2026.102948","url":null,"abstract":"<p><strong>Background: </strong>Younger patients (18-49 years of age) with advanced heart failure (HF) face unique challenges in decision-making for advanced HF therapies. Although heart transplantation (HT) offers excellent survival, it is associated with finite graft longevity. The HeartMate 3 (HM3) left ventricular assist device (LVAD) has demonstrated promising outcomes, but direct comparisons with those listed for or undergoing HT in this age group remain limited.</p><p><strong>Objectives: </strong>This study sought to compare survival and adverse event (AE) outcomes between younger patients receiving HM3 LVAD support and those listed for or undergoing HT.</p><p><strong>Methods: </strong>The authors analyzed patients 18-49 years of age from the MOMENTUM 3 (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3) portfolio (HM3 cohort; n = 420) and the UNOS (United Network for Organ Sharing) registry (HT listing cohort; n = 1,955) (HT recipients; n = 1,176) from 2014-2018. Propensity score matching was performed to adjust for baseline differences. Outcomes included 2-year survival from time of treatment or time of listing, freedom from death or delisting for deterioration, and 1-year incidence of major AEs (ie, stroke, renal dysfunction, infection).</p><p><strong>Results: </strong>After propensity score matching, 2-year survival from treatment was similar for HM3 and HT (88.7% vs 90.2%; HR: 1.18; P = 0.53). When comparing outcomes from time of transplant listing vs LVAD implantation, HM3 was associated with higher freedom from death compared with freedom from death or delisting due to deterioration in UNOS (90.1% vs 76.7%; HR: 0.38; P < 0.0001). AE analysis showed lower 1-year rates of renal dysfunction requiring dialysis (5.0% vs 10.4%; P = 0.016) and fewer infection-related hospitalizations (24.8% vs 34.2%; P = 0.012) in HM3 recipients, but a higher incidence of debilitating stroke (3.4% vs 0.3%; P = 0.027).</p><p><strong>Conclusions: </strong>Contemporary data suggest that durable LVAD therapy may offer survival outcomes comparable to HT in adults <50 years of age. These findings support the consideration of an LVAD-first strategy as a viable initial approach to heart replacement therapy in appropriately selected patients. (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 Investigational Device Exemption [MOMENTUM 3 IDE]; NCT02224755) (MOMENTUM 3 Continued Access Protocol [MOMENTUM 3 CAP]; NCT02892955).</p>","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":" ","pages":"102948"},"PeriodicalIF":11.8,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1016/j.jchf.2026.102950
Robert M A van der Boon, Lida Feyz
{"title":"From Signals to Decisions: The Need for Standardized Reporting in Heart Failure Remote Monitoring.","authors":"Robert M A van der Boon, Lida Feyz","doi":"10.1016/j.jchf.2026.102950","DOIUrl":"https://doi.org/10.1016/j.jchf.2026.102950","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":" ","pages":"102950"},"PeriodicalIF":11.8,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1016/j.jchf.2026.102953
Carsten Tschöpe, W H Wilson Tang
{"title":"Parvovirus B19 in Pediatric Myocarditis: When Context Becomes Clinical Action.","authors":"Carsten Tschöpe, W H Wilson Tang","doi":"10.1016/j.jchf.2026.102953","DOIUrl":"https://doi.org/10.1016/j.jchf.2026.102953","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":" ","pages":"102953"},"PeriodicalIF":11.8,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146131707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-02DOI: 10.1016/j.jchf.2026.102939
Stephen J Greene, Haolin Xu, Karen Chiswell, G Michael Felker, Sabra C Lewsey, Punag H Divanji, Hans-Peter Goertz, Stephen B Heitner, Javed Butler, Gregg C Fonarow
{"title":"Residual Risk Despite Quadruple Medical Therapy for Men vs Women Hospitalized for Heart Failure With Reduced Ejection Fraction.","authors":"Stephen J Greene, Haolin Xu, Karen Chiswell, G Michael Felker, Sabra C Lewsey, Punag H Divanji, Hans-Peter Goertz, Stephen B Heitner, Javed Butler, Gregg C Fonarow","doi":"10.1016/j.jchf.2026.102939","DOIUrl":"10.1016/j.jchf.2026.102939","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":" ","pages":"102939"},"PeriodicalIF":11.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146105567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-02DOI: 10.1016/j.jchf.2026.102938
Misato Chimura, Alasdair D Henderson, Pardeep S Jhund, Brian L Claggett, Akshay S Desai, Gerasimos Filippatos, Grzegorz Gajos, Meike Brinker, Flaviana Amarante, James Lay-Flurrie, Katja Rohwedder, Carolyn S P Lam, Naoki Sato, Michele Senni, Adriaan A Voors, Faiez Zannad, Mehmet B Yilmaz, Bertram Pitt, Muthiah Vaduganathan, Scott D Solomon, John J V McMurray
Background: Given that mineralocorticoid receptor antagonists have the potential to impair renal function and induce hyperkalemia, close monitoring of estimated glomerular filtration rate (eGFR) and serum potassium levels is essential to ensure the safe administration of this therapy.
Objectives: In this prespecified analysis, the authors evaluated the efficacy and safety of the kidney function-based finerenone dosing strategy used in the FINEARTS-HF trial.
Methods: In FINEARTS-HF, patients with an eGFR of 25 to 60 mL/min/1.73 m2 at baseline were stratified at randomization to the low-dose group and started on 10 mg of finerenone once daily (titrated to a maximum 20 mg/d) or matching placebo, whereas those with an eGFR >60 mL/min/1.73 m2 at baseline were stratified to the high-dose group and started on 20 mg of finerenone once daily (titrated to a maximum 40 mg/d) or matching placebo. The primary outcome was the composite of total (first and recurrent) heart failure events and cardiovascular death.
Results: Among 5,986 (99.8%) analyzable patients, 3,159 were assigned to the higher eGFR/high-dose stratum and 2,827 to the lower eGFR/low-dose stratum group. The mean ± SD achieved dose was 32.3 ± 9.1 mg (finerenone) and 34.4 ± 7.8 mg (placebo) in the higher eGFR/high-dose stratum, and 15.6 ± 4.3 mg (finerenone) and 16.7 ± 4.0 mg (placebo) in the lower eGFR/low-dose stratum. The effect of finerenone on the primary outcome was consistent across the 2 dosing strata (higher eGFR/high-dose stratum: rate ratio: 0.77 [95% CI: 0.63-0.94] vs lower eGFR/low-dose stratum: rate ratio: 0.87 [95% CI: 0.74-1.03]; P for interaction = 0.34). Consistent benefits were observed for the components of the primary outcome and all-cause death. Safety was also consistent between dosing strata, except for hypokalemia, where the reduction in the odds of hypokalemia with finerenone compared to placebo was greater in the higher eGFR/high-dose stratum (P-interaction < 0.01).
Conclusions: In FINEARTS-HF, an eGFR-based dosing strategy allowed effective and safe use of finerenone in patients with heart failure with mildly reduced ejection fraction/ heart failure with preserved ejection fraction with a baseline eGFR as low as 25 mL/min/1.73 m2. We recommend that clinicians implement the trial-validated dosing strategy and incorporate appropriate uptitration to the target dose to ensure optimal therapeutic outcomes. (FINEARTS-HF [Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40%; NCT04435626).
{"title":"Efficacy and Safety of the Kidney Function-Based Finerenone Dosing Strategy Used in FINEARTS-HF.","authors":"Misato Chimura, Alasdair D Henderson, Pardeep S Jhund, Brian L Claggett, Akshay S Desai, Gerasimos Filippatos, Grzegorz Gajos, Meike Brinker, Flaviana Amarante, James Lay-Flurrie, Katja Rohwedder, Carolyn S P Lam, Naoki Sato, Michele Senni, Adriaan A Voors, Faiez Zannad, Mehmet B Yilmaz, Bertram Pitt, Muthiah Vaduganathan, Scott D Solomon, John J V McMurray","doi":"10.1016/j.jchf.2026.102938","DOIUrl":"https://doi.org/10.1016/j.jchf.2026.102938","url":null,"abstract":"<p><strong>Background: </strong>Given that mineralocorticoid receptor antagonists have the potential to impair renal function and induce hyperkalemia, close monitoring of estimated glomerular filtration rate (eGFR) and serum potassium levels is essential to ensure the safe administration of this therapy.</p><p><strong>Objectives: </strong>In this prespecified analysis, the authors evaluated the efficacy and safety of the kidney function-based finerenone dosing strategy used in the FINEARTS-HF trial.</p><p><strong>Methods: </strong>In FINEARTS-HF, patients with an eGFR of 25 to 60 mL/min/1.73 m<sup>2</sup> at baseline were stratified at randomization to the low-dose group and started on 10 mg of finerenone once daily (titrated to a maximum 20 mg/d) or matching placebo, whereas those with an eGFR >60 mL/min/1.73 m<sup>2</sup> at baseline were stratified to the high-dose group and started on 20 mg of finerenone once daily (titrated to a maximum 40 mg/d) or matching placebo. The primary outcome was the composite of total (first and recurrent) heart failure events and cardiovascular death.</p><p><strong>Results: </strong>Among 5,986 (99.8%) analyzable patients, 3,159 were assigned to the higher eGFR/high-dose stratum and 2,827 to the lower eGFR/low-dose stratum group. The mean ± SD achieved dose was 32.3 ± 9.1 mg (finerenone) and 34.4 ± 7.8 mg (placebo) in the higher eGFR/high-dose stratum, and 15.6 ± 4.3 mg (finerenone) and 16.7 ± 4.0 mg (placebo) in the lower eGFR/low-dose stratum. The effect of finerenone on the primary outcome was consistent across the 2 dosing strata (higher eGFR/high-dose stratum: rate ratio: 0.77 [95% CI: 0.63-0.94] vs lower eGFR/low-dose stratum: rate ratio: 0.87 [95% CI: 0.74-1.03]; P for interaction = 0.34). Consistent benefits were observed for the components of the primary outcome and all-cause death. Safety was also consistent between dosing strata, except for hypokalemia, where the reduction in the odds of hypokalemia with finerenone compared to placebo was greater in the higher eGFR/high-dose stratum (P-interaction < 0.01).</p><p><strong>Conclusions: </strong>In FINEARTS-HF, an eGFR-based dosing strategy allowed effective and safe use of finerenone in patients with heart failure with mildly reduced ejection fraction/ heart failure with preserved ejection fraction with a baseline eGFR as low as 25 mL/min/1.73 m<sup>2</sup>. We recommend that clinicians implement the trial-validated dosing strategy and incorporate appropriate uptitration to the target dose to ensure optimal therapeutic outcomes. (FINEARTS-HF [Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone in Participants With Heart Failure and Left Ventricular Ejection Fraction (Proportion of Blood Expelled Per Heart Stroke) Greater or Equal to 40%; NCT04435626).</p>","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":" ","pages":"102938"},"PeriodicalIF":11.8,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146124897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-05DOI: 10.1016/j.jchf.2025.102889
João Pedro Ferreira MD, PhD , Milton Packer MD , Javed Butler MD, MPH, MBA , Francisco Vasques-Nóvoa MD , Pedro Marques MD , Stuart Pocock PhD , Gerasimos Filippatos MD, PhD , Faiez Zannad MD, PhD , Stefan D. Anker MD, PhD
Background
Magnesium plays a central role in maintaining cellular homeostasis. Limited data exist on the clinical implications of magnesium derangements and the influence of sodium-glucose cotransporter 2 inhibitors on magnesium levels in heart failure with mildly reduced or preserved ejection fraction.
Objectives
Using the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) population, the authors aimed to study the association of serum magnesium with outcomes, assess the impact of empagliflozin on serum magnesium levels, and explore the influence of serum magnesium on the effect of empagliflozin on the study outcomes.
Methods
Patients with heart failure with mildly reduced or preserved ejection fraction were randomized to receive placebo or empagliflozin 10 mg daily. Laboratory results were available at baseline; week 4; weeks 12, 32, and 52; and every 24 weeks thereafter. The median follow-up time was 26.2 months. The primary outcome was a composite of cardiovascular death or heart failure hospitalization.
Results
A total of 5,988 patients were included. The mean serum magnesium levels at baseline were 0.82 ± 0.11 mmol/L. The corresponding magnesium quintiles were as follows: Q1 = 0.67 ± 0.07 mmol/L (n = 1,291), Q2 = 0.78 ± 0.02 (n = 1,189), Q3 = 0.83 ± 0.01 (n = 1,378), Q4 = 0.88 ± 0.01 (n = 1,078), and Q5 = 0.96 ± 0.05 (n = 1,052). Patients with higher magnesium levels were older, had lower estimated glomerular filtration rate, and higher prevalence of atrial fibrillation. Conversely, patients with lower serum magnesium had diabetes and used thiazide-type diuretic agents more frequently. Placebo-treated patients experienced a higher risk of primary outcome events with higher magnesium levels (Q5). Empagliflozin (vs placebo) was associated with a more pronounced reduction of primary outcome events at higher baseline magnesium levels: Q1, HR: 1.05 [95% CI: 0.77-1.39]; Q2, HR: 0.85 [95% CI: 0.63-1.14]; Q3, HR: 0.88 [95% CI: 0.66-1.17]; Q4, HR: 0.62 [95% CI: 0.45-0.86]; Q5, HR: 0.60 [95% CI: 0.45-0.79]; interaction P-trend = 0.030. At week 4, empagliflozin had increased magnesium levels by 0.05 mmol/L, reaching a steady state thereafter.
Conclusions
In EMPEROR-Preserved, higher serum magnesium levels were associated with a higher risk of primary outcome events among patients treated with placebo but not among patients treated with empagliflozin who experienced pronounced benefit. (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction [EMPEROR-Preserved]; NCT03057951)
{"title":"Serum Magnesium, Outcomes, and the Effect of Empagliflozin in Heart Failure With Mildly Reduced and Preserved Ejection Fraction","authors":"João Pedro Ferreira MD, PhD , Milton Packer MD , Javed Butler MD, MPH, MBA , Francisco Vasques-Nóvoa MD , Pedro Marques MD , Stuart Pocock PhD , Gerasimos Filippatos MD, PhD , Faiez Zannad MD, PhD , Stefan D. Anker MD, PhD","doi":"10.1016/j.jchf.2025.102889","DOIUrl":"10.1016/j.jchf.2025.102889","url":null,"abstract":"<div><h3>Background</h3><div>Magnesium plays a central role in maintaining cellular homeostasis. Limited data exist on the clinical implications of magnesium derangements and the influence of sodium-glucose cotransporter 2 inhibitors on magnesium levels in heart failure with mildly reduced or preserved ejection fraction.</div></div><div><h3>Objectives</h3><div>Using the EMPEROR-Preserved (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction) population, the authors aimed to study the association of serum magnesium with outcomes, assess the impact of empagliflozin on serum magnesium levels, and explore the influence of serum magnesium on the effect of empagliflozin on the study outcomes.</div></div><div><h3>Methods</h3><div>Patients with heart failure with mildly reduced or preserved ejection fraction were randomized to receive placebo or empagliflozin 10 mg daily. Laboratory results were available at baseline; week 4; weeks 12, 32, and 52; and every 24 weeks thereafter. The median follow-up time was 26.2 months. The primary outcome was a composite of cardiovascular death or heart failure hospitalization.</div></div><div><h3>Results</h3><div>A total of 5,988 patients were included. The mean serum magnesium levels at baseline were 0.82 ± 0.11 mmol/L. The corresponding magnesium quintiles were as follows: Q1 = 0.67 ± 0.07 mmol/L (n = 1,291), Q2 = 0.78 ± 0.02 (n = 1,189), Q3 = 0.83 ± 0.01 (n = 1,378), Q4 = 0.88 ± 0.01 (n = 1,078), and Q5 = 0.96 ± 0.05 (n = 1,052). Patients with higher magnesium levels were older, had lower estimated glomerular filtration rate, and higher prevalence of atrial fibrillation. Conversely, patients with lower serum magnesium had diabetes and used thiazide-type diuretic agents more frequently. Placebo-treated patients experienced a higher risk of primary outcome events with higher magnesium levels (Q5). Empagliflozin (vs placebo) was associated with a more pronounced reduction of primary outcome events at higher baseline magnesium levels: Q1, HR: 1.05 [95% CI: 0.77-1.39]; Q2, HR: 0.85 [95% CI: 0.63-1.14]; Q3, HR: 0.88 [95% CI: 0.66-1.17]; Q4, HR: 0.62 [95% CI: 0.45-0.86]; Q5, HR: 0.60 [95% CI: 0.45-0.79]; interaction <em>P</em>-trend = 0.030. At week 4, empagliflozin had increased magnesium levels by 0.05 mmol/L, reaching a steady state thereafter.</div></div><div><h3>Conclusions</h3><div>In EMPEROR-Preserved, higher serum magnesium levels were associated with a higher risk of primary outcome events among patients treated with placebo but not among patients treated with empagliflozin who experienced pronounced benefit. (Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Preserved Ejection Fraction [EMPEROR-Preserved]; <span><span>NCT03057951</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102889"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145902532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-10-16DOI: 10.1016/j.jchf.2025.102712
Barry A. Borlaug MD , Cecilie Holse MD , Mette Holme Jung MD, PhD , A. Michael Lincoff MD , Sharon L. Mulvagh MD , Jacob Stærk-Østergaard PhD , Katherine R. Tuttle MD , Mark C. Petrie MD
Background
Systemic inflammation contributes to the pathophysiology of heart failure (HF). Inflammation in heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) has been linked to cardiovascular-kidney-metabolic conditions, whereas inflammation in heart failure and reduced ejection fraction (HFrEF) is thought to develop secondary to cardiac stress and circulatory derangements.
Objectives
This study aims to characterize the prevalence and correlates of systemic inflammation across the spectrum of HF.
Methods
Patients with HF participating in 3 large outcome trials (SELECT, SOUL, and FLOW) were examined to identify the prevalence of systemic inflammation, defined as elevated high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L. Clinical characteristics associated with elevated hsCRP were examined by HF subtype and across the HF spectrum.
Results
Across the 3 trials, 3,204 patients had HFpEF, 1,246 had HFmrEF, and 1,018 had HFrEF. Elevated hsCRP was observed in 2,335 patients (52.5%) with HFpEF/HFmrEF and 503 patients (49.4%) with HFrEF. Compared with patients with lower hsCRP levels, those with higher hsCRP levels were more likely to be female and have obesity, diabetes, lower estimated glomerular filtration rate, higher albuminuria, and chronic obstructive pulmonary disease, without meaningful differences by HF subtype. hsCRP level was unrelated to ejection fraction (R2 < 0.001; P = 0.73) but increased linearly with the number of comorbidities for all HF subtypes (R2 = 0.94; P < 0.001).
Conclusions
Systemic inflammation is present in one-half of patients with HF, and is associated with excess body fat, chronic kidney disease, albuminuria, and diabetes, and increases with comorbidity burden. These relationships are not specific to HFpEF/HFmrEF but are also common to HFrEF (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity [SELECT]; NCT03574597; A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153; A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes [SOUL]; NCT03914326)
背景：全身性炎症有助于心衰（HF）的病理生理。心力衰竭伴轻度射血分数降低（HFmrEF）或心力衰竭伴保留射血分数（HFpEF）的炎症与心血管-肾脏-代谢状况有关，而心力衰竭伴射血分数降低（HFrEF）的炎症被认为是继发于心脏应激和循环紊乱。目的：本研究旨在描述HF全身性炎症的患病率及其相关因素。方法参与3个大型结局试验（SELECT、SOUL和FLOW）的HF患者进行检查，以确定全身性炎症的患病率，定义为高敏感性c反应蛋白（hsCRP）升高≥2mg /L。与hsCRP升高相关的临床特征通过HF亚型和整个HF谱进行了检查。结果在这3项试验中，3204例患者患有HFpEF， 1246例患有HFmrEF， 1018例患有HFrEF。在2335例HFpEF/HFmrEF患者（52.5%）和503例HFrEF患者（49.4%）中观察到hsCRP升高。与hsCRP水平较低的患者相比，hsCRP水平较高的患者更有可能是女性，并且有肥胖、糖尿病、肾小球滤过率较低、蛋白尿较高和慢性阻塞性肺疾病，而HF亚型之间没有显著差异。hsCRP水平与射血分数无关（R2 < 0.001; P = 0.73），但与所有HF亚型共病数量呈线性增加（R2 = 0.94; P < 0.001）。结论：半数心衰患者存在全身性炎症，与体脂过多、慢性肾病、蛋白尿和糖尿病相关，并伴有合并症负担增加。这些关系不是HFpEF/HFmrEF所特有的，但在HFrEF中也很常见（Semaglutide对超重或肥胖患者心脏病和卒中的影响[SELECT]； NCT03574597；一项研究研究Semaglutide与安慰剂相比在2型糖尿病和慢性肾脏疾病患者中的作用[FLOW]； NCT03819153； Semaglutide在2型糖尿病患者中的心脏病研究[SOUL]； NCT03914326）。
{"title":"Prevalence and Associations of Systemic Inflammation in Heart Failure Across the Spectrum of Ejection Fraction","authors":"Barry A. Borlaug MD , Cecilie Holse MD , Mette Holme Jung MD, PhD , A. Michael Lincoff MD , Sharon L. Mulvagh MD , Jacob Stærk-Østergaard PhD , Katherine R. Tuttle MD , Mark C. Petrie MD","doi":"10.1016/j.jchf.2025.102712","DOIUrl":"10.1016/j.jchf.2025.102712","url":null,"abstract":"<div><h3>Background</h3><div>Systemic inflammation contributes to the pathophysiology of heart failure (HF). Inflammation in heart failure with mildly reduced ejection fraction (HFmrEF) or heart failure with preserved ejection fraction (HFpEF) has been linked to cardiovascular-kidney-metabolic conditions, whereas inflammation in heart failure and reduced ejection fraction (HFrEF) is thought to develop secondary to cardiac stress and circulatory derangements.</div></div><div><h3>Objectives</h3><div>This study aims to characterize the prevalence and correlates of systemic inflammation across the spectrum of HF.</div></div><div><h3>Methods</h3><div>Patients with HF participating in 3 large outcome trials (SELECT, SOUL, and FLOW) were examined to identify the prevalence of systemic inflammation, defined as elevated high-sensitivity C-reactive protein (hsCRP) ≥2 mg/L. Clinical characteristics associated with elevated hsCRP were examined by HF subtype and across the HF spectrum.</div></div><div><h3>Results</h3><div>Across the 3 trials, 3,204 patients had HFpEF, 1,246 had HFmrEF, and 1,018 had HFrEF. Elevated hsCRP was observed in 2,335 patients (52.5%) with HFpEF/HFmrEF and 503 patients (49.4%) with HFrEF. Compared with patients with lower hsCRP levels, those with higher hsCRP levels were more likely to be female and have obesity, diabetes, lower estimated glomerular filtration rate, higher albuminuria, and chronic obstructive pulmonary disease, without meaningful differences by HF subtype. hsCRP level was unrelated to ejection fraction (<em>R</em><sup>2</sup> < 0.001; <em>P =</em> 0.73) but increased linearly with the number of comorbidities for all HF subtypes (<em>R</em><sup>2</sup> = 0.94; <em>P</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>Systemic inflammation is present in one-half of patients with HF, and is associated with excess body fat, chronic kidney disease, albuminuria, and diabetes, and increases with comorbidity burden. These relationships are not specific to HFpEF/HFmrEF but are also common to HFrEF (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity [SELECT]; <span><span>NCT03574597</span><svg><path></path></svg></span>; A Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; <span><span>NCT03819153</span><svg><path></path></svg></span>; A Heart Disease Study of Semaglutide in Patients With Type 2 Diabetes [SOUL]; <span><span>NCT03914326</span><svg><path></path></svg></span>)</div></div>","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102712"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145296193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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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