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 : 2026-02-01DOI: 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 : 2026-02-01DOI: 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}
Pub Date : 2026-02-01DOI: 10.1016/j.jchf.2025.03.008
Ahmad Masri MD, MS , Martin S. Maron MD , Theodore P. Abraham MD , Michael E. Nassif MD , Roberto Barriales-Villa MD , Ozlem Bilen MD , Caroline J. Coats MD, PhD , Perry Elliott MBBS, MD , Pablo Garcia-Pavia MD, PhD , Daniele Massera MD , Iacopo Olivotto MD , Artur Oreziak MD, PhD , Anjali Tiku Owens MD , Sara Saberi MD, MS , Scott D. Solomon MD , Albree Tower-Rader MD , Stephen B. Heitner MD , Daniel L. Jacoby MD , Chiara Melloni MD, MS , Jenny Wei PhD , Mark Zenker
<div><h3>Background</h3><div>Disopyramide, used in obstructive hypertrophic cardiomyopathy (oHCM) for its negative inotropic properties mediated by its reduction in cytosolic calcium, has been recommended for decades as an option to relieve resistant obstruction. Aficamten is a selective cardiac myosin inhibitor that reduces hypercontractility directly by reducing myosin-actin interaction.</div></div><div><h3>Objectives</h3><div>This study aims to investigate the safety and efficacy of concomitant use and withdrawal of disopyramide in patients with symptomatic oHCM receiving aficamten.</div></div><div><h3>Methods</h3><div>Patients with oHCM enrolled in REDWOOD-HCM Cohort 3 (open-label), SEQUOIA-HCM (placebo-controlled), and FOREST-HCM (open-label) were analyzed. The authors identified 4 groups, each with patients symptomatic despite background therapy with disopyramide who received: 1) disopyramide plus aficamten and subsequent aficamten withdrawal per protocol (Diso-Afi Withdrawal); 2) disopyramide plus placebo (Diso-Pbo); 3) aficamten plus disopyramide with subsequent disopyramide withdrawal (Afi-Diso Withdrawal); and 4) continued both disopyramide and aficamten (Diso+Afi Continuous). Assessments were performed at baseline, after aficamten or placebo add-on therapy, and after washout (except at week 24 for Diso+Afi Continuous group).</div></div><div><h3>Results</h3><div>Overall, 50 unique patients from 3 trials enrolled, resulting in 93 subjects (segments) across 4 groups: Diso-Afi Withdrawal (n = 29), Diso-Pbo (n = 20), Afi-Diso Withdrawal (n = 17), and Diso+Afi Continuous (n = 27); mean disopyramide dose was 331 ± 146 mg/d. The addition of aficamten to disopyramide alleviated left ventricular outflow tract (LVOT) obstruction (resting: change [Δ] in least squares mean −27.0 ± 3.6, Valsalva: Δ least squares mean −39.2 ± 5.0, both <em>P <</em> 0.0001), symptoms (≥1 NYHA functional class improvement: 77.8% [95% CI: 61.0-94.5]; <em>P <</em> 0.0001; Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score: 12.3 ± 3.3 [<em>P <</em> 0.001]), and reduced N-terminal pro–B-type natriuretic peptide ratio: 0.35 [95% CI: 0.26-0.48]; <em>P <</em> 0.0001, and there was no significant change with placebo. Withdrawal of aficamten while on disopyramide resulted in return of LVOT obstruction, worsening of symptoms, and increase in NT-proBNP to baseline values. Conversely, withdrawal of disopyramide while on aficamten did not impact efficacy. There were no safety events associated with aficamten or disopyramide withdrawal, and no episodes of atrial fibrillation after disopyramide withdrawal.</div></div><div><h3>Conclusions</h3><div>In this cohort of patients with symptomatic oHCM with persistent LVOT obstruction, combination therapy with aficamten and disopyramide was safe and well tolerated but did not enhance clinical efficacy vs aficamten alone. For such oHCM patients, aficamten treatment may be considered with an option to discontinue disop
{"title":"Concomitant Aficamten and Disopyramide in Symptomatic Obstructive Hypertrophic Cardiomyopathy","authors":"Ahmad Masri MD, MS , Martin S. Maron MD , Theodore P. Abraham MD , Michael E. Nassif MD , Roberto Barriales-Villa MD , Ozlem Bilen MD , Caroline J. Coats MD, PhD , Perry Elliott MBBS, MD , Pablo Garcia-Pavia MD, PhD , Daniele Massera MD , Iacopo Olivotto MD , Artur Oreziak MD, PhD , Anjali Tiku Owens MD , Sara Saberi MD, MS , Scott D. Solomon MD , Albree Tower-Rader MD , Stephen B. Heitner MD , Daniel L. Jacoby MD , Chiara Melloni MD, MS , Jenny Wei PhD , Mark Zenker","doi":"10.1016/j.jchf.2025.03.008","DOIUrl":"10.1016/j.jchf.2025.03.008","url":null,"abstract":"<div><h3>Background</h3><div>Disopyramide, used in obstructive hypertrophic cardiomyopathy (oHCM) for its negative inotropic properties mediated by its reduction in cytosolic calcium, has been recommended for decades as an option to relieve resistant obstruction. Aficamten is a selective cardiac myosin inhibitor that reduces hypercontractility directly by reducing myosin-actin interaction.</div></div><div><h3>Objectives</h3><div>This study aims to investigate the safety and efficacy of concomitant use and withdrawal of disopyramide in patients with symptomatic oHCM receiving aficamten.</div></div><div><h3>Methods</h3><div>Patients with oHCM enrolled in REDWOOD-HCM Cohort 3 (open-label), SEQUOIA-HCM (placebo-controlled), and FOREST-HCM (open-label) were analyzed. The authors identified 4 groups, each with patients symptomatic despite background therapy with disopyramide who received: 1) disopyramide plus aficamten and subsequent aficamten withdrawal per protocol (Diso-Afi Withdrawal); 2) disopyramide plus placebo (Diso-Pbo); 3) aficamten plus disopyramide with subsequent disopyramide withdrawal (Afi-Diso Withdrawal); and 4) continued both disopyramide and aficamten (Diso+Afi Continuous). Assessments were performed at baseline, after aficamten or placebo add-on therapy, and after washout (except at week 24 for Diso+Afi Continuous group).</div></div><div><h3>Results</h3><div>Overall, 50 unique patients from 3 trials enrolled, resulting in 93 subjects (segments) across 4 groups: Diso-Afi Withdrawal (n = 29), Diso-Pbo (n = 20), Afi-Diso Withdrawal (n = 17), and Diso+Afi Continuous (n = 27); mean disopyramide dose was 331 ± 146 mg/d. The addition of aficamten to disopyramide alleviated left ventricular outflow tract (LVOT) obstruction (resting: change [Δ] in least squares mean −27.0 ± 3.6, Valsalva: Δ least squares mean −39.2 ± 5.0, both <em>P <</em> 0.0001), symptoms (≥1 NYHA functional class improvement: 77.8% [95% CI: 61.0-94.5]; <em>P <</em> 0.0001; Kansas City Cardiomyopathy Questionnaire–Clinical Summary Score: 12.3 ± 3.3 [<em>P <</em> 0.001]), and reduced N-terminal pro–B-type natriuretic peptide ratio: 0.35 [95% CI: 0.26-0.48]; <em>P <</em> 0.0001, and there was no significant change with placebo. Withdrawal of aficamten while on disopyramide resulted in return of LVOT obstruction, worsening of symptoms, and increase in NT-proBNP to baseline values. Conversely, withdrawal of disopyramide while on aficamten did not impact efficacy. There were no safety events associated with aficamten or disopyramide withdrawal, and no episodes of atrial fibrillation after disopyramide withdrawal.</div></div><div><h3>Conclusions</h3><div>In this cohort of patients with symptomatic oHCM with persistent LVOT obstruction, combination therapy with aficamten and disopyramide was safe and well tolerated but did not enhance clinical efficacy vs aficamten alone. For such oHCM patients, aficamten treatment may be considered with an option to discontinue disop","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102441"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018970","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}
{"title":"Inflammation and the Need for Biology-Driven Care in Heart Failure","authors":"Abhinav Sharma MD, PhD , Virginia Anagnostopoulou MD , Anique Ducharme MD, MSc","doi":"10.1016/j.jchf.2025.102834","DOIUrl":"10.1016/j.jchf.2025.102834","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102834"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680592","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 : 2026-02-01DOI: 10.1016/j.jchf.2025.102891
Jeffrey M. Testani MD, MTR , Zachary L. Cox PharmD , Javed Butler MD
{"title":"Could Mineralocorticoid Receptor Antagonists Be Harmful in Some Patients With Heart Failure?","authors":"Jeffrey M. Testani MD, MTR , Zachary L. Cox PharmD , Javed Butler MD","doi":"10.1016/j.jchf.2025.102891","DOIUrl":"10.1016/j.jchf.2025.102891","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102891"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098872","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 : 2026-02-01DOI: 10.1016/j.jchf.2025.102707
Diana de Oliveira-Gomes MD , Rachel M. Drazner MD, MPH , Michelle Dimza DO , Colby Ayers MS , Angela Duvalyan MD , Tiffany L. Brazile MD , Robert Morlend MD , Faris Araj MD , E. Ashley Hardin MD , Nicholas Hendren MD , Justin L. Grodin MD, MPH , Jennifer T. Thibodeau MD, MSCS , Mark H. Drazner MD, MSc
{"title":"Novel 4-Stage Classification to Estimate Right Atrial Pressure by Point-of-Care Ultrasound of Neck Vasculature","authors":"Diana de Oliveira-Gomes MD , Rachel M. Drazner MD, MPH , Michelle Dimza DO , Colby Ayers MS , Angela Duvalyan MD , Tiffany L. Brazile MD , Robert Morlend MD , Faris Araj MD , E. Ashley Hardin MD , Nicholas Hendren MD , Justin L. Grodin MD, MPH , Jennifer T. Thibodeau MD, MSCS , Mark H. Drazner MD, MSc","doi":"10.1016/j.jchf.2025.102707","DOIUrl":"10.1016/j.jchf.2025.102707","url":null,"abstract":"","PeriodicalId":14687,"journal":{"name":"JACC. Heart failure","volume":"14 2","pages":"Article 102707"},"PeriodicalIF":11.8,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145277198","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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