Pub Date : 2024-11-18DOI: 10.1016/j.jacc.2024.07.059
Nilay S. Shah
Section snippets
Funding Support and Author Disclosures
Dr Shah is funded by grants K23HL157766 from the National Heart, Lung, and Blood Institute and 24CDA1266732 from the American Heart Association. Dr Shah has reported that he has no relationships relevant to the contents of this paper to disclose.
章节片段资金支持和作者披露沙博士获得了美国国家心肺血液研究所（National Heart, Lung, and Blood Institute）的 K23HL157766 号基金和美国心脏协会（American Heart Association）的 24CDA1266732 号基金的资助。据 Shah 博士报告，他没有与本文内容相关的关系需要披露。
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Pub Date : 2024-11-18DOI: 10.1016/j.jacc.2024.11.015
Marianna Fontana, Mathew S. Maurer, Julian D. Gillmore, Shaun Bender, Emre Aldinc, Satish A. Eraly, Patrick Y. Jay, Scott D. Solomon
BACKGROUND
Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a fatal disease, caused by misfolded transthyretin depositing as amyloid fibrils in the heart. Because disease progression is common, practical and sensitive methods are needed to monitor patients and optimize treatment decisions. Outpatient worsening heart failure (HF) (oral loop diuretic intensification or initiation) is simple to assess and has been shown to be prognostic of mortality in patients with ATTR-CM.
OBJECTIVES
We aimed to assess the clinical and prognostic significance of and the effect of vutrisiran treatment on outpatient worsening HF in patients with ATTR-CM from the HELIOS-B trial.
METHODS
Associations between outpatient worsening HF and a composite of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent HF visits), all-cause mortality, and other disease progression-related endpoints were evaluated. The impact of vutrisiran over 36 months on outpatient worsening HF and an expanded composite of all-cause mortality, recurrent CV events, and outpatient worsening HF was also assessed.
RESULTS
Overall, 321 patients (49.1%) had ≥1 outpatient worsening HF, 245 (37.5%) had ≥1 CV event(s), and 120 (18.3%) died; 237 patients (36.2%) had no events. Patients with outpatient worsening HF had an increased risk of all-cause mortality and CV events (hazard ratio [HR]: 2.58; 95% confidence interval [CI]: 2.04-3.27) and all-cause mortality (HR: 2.45; 95% CI: 1.70-3.52), as well as a greater deterioration in 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and a greater increase in N-terminal prohormone of B-type natriuretic peptide. In recurrent event analyses over the double-blind period, vutrisiran versus placebo reduced the rate of outpatient worsening HF (relative rate ratio: 0.66; 95% CI: 0.56-0.78). Vutrisiran also reduced the risk of the composite of all-cause mortality, CV events, and outpatient worsening HF versus placebo (HR: 0.69; 95% CI: 0.57-0.83).
CONCLUSIONS
Outpatient worsening HF was frequent in patients with ATTR-CM in HELIOS-B, and was associated with increased mortality, and reduced by vutrisiran.
背景转甲状腺素淀粉样变性伴有心肌病（ATTR-CM）是一种致命疾病，由错误折叠的转甲状腺素以淀粉样纤维的形式沉积在心脏中引起。由于疾病的进展很常见，因此需要实用而灵敏的方法来监测患者并优化治疗决策。门诊心力衰竭（HF）恶化（口服襻利尿剂加强或开始）的评估很简单，而且已被证明是ATTR-CM患者死亡率的预后指标。目的我们旨在评估HELIOS-B试验中ATTR-CM患者门诊HF恶化的临床和预后意义以及武曲西兰治疗的效果。方法评估了门诊恶化性高血压与全因死亡率、复发性心血管（CV）事件（CV 住院和紧急高血压就诊）、全因死亡率和其他疾病进展相关终点之间的关系。结果总体而言，321名患者（49.1%）≥1次门诊恶化HF，245名患者（37.5%）≥1次CV事件，120名患者（18.3%）死亡；237名患者（36.2%）未发生任何事件。门诊恶化型心房颤动患者发生全因死亡和心血管事件的风险增加（危险比[HR]：2.58；95% 置信区间[CI]：2.04-3.27），全因死亡的风险增加（HR：2.45；95% 置信区间[CI]：1.70-3.52），6 分钟步行测试距离和堪萨斯城心肌病问卷-综合评分的恶化程度更大，B 型钠尿肽 N 端前体的增加程度更大。在双盲期间的复发事件分析中，武曲西兰与安慰剂相比降低了门诊患者HF恶化的比率（相对比率比：0.66；95% CI：0.56-0.78）。结论在HELIOS-B中，ATTR-CM患者经常出现门诊恶化性心房颤动，这与死亡率升高有关，武曲西兰可降低门诊恶化性心房颤动的发生率。
{"title":"Outpatient Worsening Heart Failure in Patients with Transthyretin Amyloidosis with Cardiomyopathy in the HELIOS-B Trial","authors":"Marianna Fontana, Mathew S. Maurer, Julian D. Gillmore, Shaun Bender, Emre Aldinc, Satish A. Eraly, Patrick Y. Jay, Scott D. Solomon","doi":"10.1016/j.jacc.2024.11.015","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.11.015","url":null,"abstract":"<h3>BACKGROUND</h3>Transthyretin amyloidosis with cardiomyopathy (ATTR-CM) is a fatal disease, caused by misfolded transthyretin depositing as amyloid fibrils in the heart. Because disease progression is common, practical and sensitive methods are needed to monitor patients and optimize treatment decisions. Outpatient worsening heart failure (HF) (oral loop diuretic intensification or initiation) is simple to assess and has been shown to be prognostic of mortality in patients with ATTR-CM.<h3>OBJECTIVES</h3>We aimed to assess the clinical and prognostic significance of and the effect of vutrisiran treatment on outpatient worsening HF in patients with ATTR-CM from the HELIOS-B trial.<h3>METHODS</h3>Associations between outpatient worsening HF and a composite of all-cause mortality and recurrent cardiovascular (CV) events (CV hospitalizations and urgent HF visits), all-cause mortality, and other disease progression-related endpoints were evaluated. The impact of vutrisiran over 36 months on outpatient worsening HF and an expanded composite of all-cause mortality, recurrent CV events, and outpatient worsening HF was also assessed.<h3>RESULTS</h3>Overall, 321 patients (49.1%) had ≥1 outpatient worsening HF, 245 (37.5%) had ≥1 CV event(s), and 120 (18.3%) died; 237 patients (36.2%) had no events. Patients with outpatient worsening HF had an increased risk of all-cause mortality and CV events (hazard ratio [HR]: 2.58; 95% confidence interval [CI]: 2.04-3.27) and all-cause mortality (HR: 2.45; 95% CI: 1.70-3.52), as well as a greater deterioration in 6-minute walk test distance and Kansas City Cardiomyopathy Questionnaire-Overall Summary score, and a greater increase in <em>N</em>-terminal prohormone of B-type natriuretic peptide. In recurrent event analyses over the double-blind period, vutrisiran versus placebo reduced the rate of outpatient worsening HF (relative rate ratio: 0.66; 95% CI: 0.56-0.78). Vutrisiran also reduced the risk of the composite of all-cause mortality, CV events, and outpatient worsening HF versus placebo (HR: 0.69; 95% CI: 0.57-0.83).<h3>CONCLUSIONS</h3>Outpatient worsening HF was frequent in patients with ATTR-CM in HELIOS-B, and was associated with increased mortality, and reduced by vutrisiran.","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"168 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665354","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 : 2024-11-18DOI: 10.1016/j.jacc.2024.06.052
Kristjan Norland, Daniel J. Schaid, Mohammadreza Naderian, Jie Na, Iftikhar J. Kullo
Background
Social determinants of health (SDOH) influence the risk of common diseases such as coronary heart disease (CHD).
Objectives
This study sought to test the associations of self-reported race/ethnicity, SDOH, and a polygenic risk score (PRS), with CHD in a large and diverse U.S. cohort.
Methods
In 67,256 All of Us (AoU) participants with available SDOH and whole-genome sequencing data, we ascertained self-reported race/ethnicity and 22 SDOH measures across 5 SDOH domains, and we calculated a PRS for CHD (PRSCHD, PGS004696). We developed an SDOH score for CHD (SDOHCHD). We tested the associations of SDOH and PRSCHD with CHD in regression models that included clinical risk factors.
Results
SDOH across 5 domains, including food insecurity, income, educational attainment, health literacy, neighborhood disorder, and loneliness, were associated with CHD. SDOHCHD was highest in self-reported Black and Hispanic people. Self-reporting as Blacks had higher odds of having CHD than Whites but not after adjustment for SDOHCHD. SDOHCHD and PRSCHD were weakly correlated. In the test set (n = 33,628), 1-SD increases in SDOHCHD and PRSCHD were associated with CHD in models that adjusted for clinical risk factors (OR: 1.32; 95% CI: 1.23-1.41 and OR: 1.36; 95% CI: 1.28-1.44, respectively). SDOHCHD and PRSCHD were associated with incident CHD events (n = 52) over a median follow-up of 214 days (Q1-Q3: 88 days).
Conclusions
Increased odds of CHD in people who self-report as Black are likely due to a higher SDOH burden. SDOH and PRS were independently associated with CHD. Our findings suggest that including both PRS and SDOH in CHD risk models could improve their accuracy.
{"title":"Associations of Self-Reported Race, Social Determinants of Health, and Polygenic Risk With Coronary Heart Disease","authors":"Kristjan Norland, Daniel J. Schaid, Mohammadreza Naderian, Jie Na, Iftikhar J. Kullo","doi":"10.1016/j.jacc.2024.06.052","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.06.052","url":null,"abstract":"<h3>Background</h3>Social determinants of health (SDOH) influence the risk of common diseases such as coronary heart disease (CHD).<h3>Objectives</h3>This study sought to test the associations of self-reported race/ethnicity, SDOH, and a polygenic risk score (PRS), with CHD in a large and diverse U.S. cohort.<h3>Methods</h3>In 67,256 All of Us (AoU) participants with available SDOH and whole-genome sequencing data, we ascertained self-reported race/ethnicity and 22 SDOH measures across 5 SDOH domains, and we calculated a PRS for CHD (PRS<sub>CHD</sub>, PGS004696). We developed an SDOH score for CHD (SDOH<sub>CHD</sub>). We tested the associations of SDOH and PRS<sub>CHD</sub> with CHD in regression models that included clinical risk factors.<h3>Results</h3>SDOH across 5 domains, including food insecurity, income, educational attainment, health literacy, neighborhood disorder, and loneliness, were associated with CHD. SDOH<sub>CHD</sub> was highest in self-reported Black and Hispanic people. Self-reporting as Blacks had higher odds of having CHD than Whites but not after adjustment for SDOH<sub>CHD</sub>. SDOH<sub>CHD</sub> and PRS<sub>CHD</sub> were weakly correlated. In the test set (n = 33,628), 1-SD increases in SDOH<sub>CHD</sub> and PRS<sub>CHD</sub> were associated with CHD in models that adjusted for clinical risk factors (OR: 1.32; 95% CI: 1.23-1.41 and OR: 1.36; 95% CI: 1.28-1.44, respectively). SDOH<sub>CHD</sub> and PRS<sub>CHD</sub> were associated with incident CHD events (n = 52) over a median follow-up of 214 days (Q1-Q3: 88 days).<h3>Conclusions</h3>Increased odds of CHD in people who self-report as Black are likely due to a higher SDOH burden. SDOH and PRS were independently associated with CHD. Our findings suggest that including both PRS and SDOH in CHD risk models could improve their accuracy.","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"38 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665355","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 : 2024-11-18DOI: 10.1016/j.jacc.2024.07.061
Adam Hartley, Nasser Alshahrani, Ramzi Y. Khamis
No Abstract
无摘要
{"title":"Reply: Answering the Call: Enhancing Telemedicine Reach With Artificial intelligence Integration","authors":"Adam Hartley, Nasser Alshahrani, Ramzi Y. Khamis","doi":"10.1016/j.jacc.2024.07.061","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.07.061","url":null,"abstract":"No Abstract","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"248 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665358","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 : 2024-11-18DOI: 10.1016/j.jacc.2024.06.051
Ioannis Skalidis, Niccolo Maurizi, George Dangas, Yiannis S. Chatzizisis
No Abstract
无摘要
{"title":"Answering the Call: Enhancing Telemedicine Reach With Artificial intelligence Integration","authors":"Ioannis Skalidis, Niccolo Maurizi, George Dangas, Yiannis S. Chatzizisis","doi":"10.1016/j.jacc.2024.06.051","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.06.051","url":null,"abstract":"No Abstract","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"99 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665356","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 : 2024-11-18DOI: 10.1016/j.jacc.2024.08.081
Sarah Crook, Brett R. Anderson
No Abstract
无摘要
{"title":"Reply: Revealing the Hidden Layers: Focus on Social and Psychological Determinants in Congenital Heart Surgery Prognosis","authors":"Sarah Crook, Brett R. Anderson","doi":"10.1016/j.jacc.2024.08.081","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.08.081","url":null,"abstract":"No Abstract","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"12 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665362","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 : 2024-11-18DOI: 10.1016/s0735-1097(24)10255-0
No Abstract
无摘要
{"title":"Audio Summary","authors":"","doi":"10.1016/s0735-1097(24)10255-0","DOIUrl":"https://doi.org/10.1016/s0735-1097(24)10255-0","url":null,"abstract":"No Abstract","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"55 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665564","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 : 2024-11-18DOI: 10.1016/j.jacc.2024.08.080
Irene Santos-Pardo, Mikael Andersson Franko, Thomas Nyström
No Abstract
无摘要
{"title":"Reply: Glycemic Control and Coronary Stent Failure in Patients With Type 2 Diabetes Mellitus","authors":"Irene Santos-Pardo, Mikael Andersson Franko, Thomas Nyström","doi":"10.1016/j.jacc.2024.08.080","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.08.080","url":null,"abstract":"No Abstract","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"1 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665577","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 : 2024-11-18DOI: 10.1016/j.jacc.2024.11.014
Mikhail N. Kosiborod, David Z.I. Cherney, Akshay S. Desai, Jeffrey M. Testani, Subodh Verma, Khaja Chinnakondepalli, David Dolling, Shachi Patel, Magnus Dahl, James M. Eudicone, Lovisa Friberg, Mario Ouwens, Murillo O. Antunes, Kim A. Connelly, Vagner Madrini, Luca Kuthi, Anuradha Lala, Miguel Lorenzo, Patrícia O. Guimarães, Marta Cobo Marcos, Mark C. Petrie
Background
Mineralocorticoid receptor antagonists (MRA) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF) but are underused in clinical practice. Observational data suggest that hyperkalemia is the leading obstacle for the suboptimal use of MRA.
Objectives
We evaluated the effects of sodium zirconium cyclosilicate (SZC) in optimizing use of spironolactone among participants with HFrEF and hyperkalemia.
Methods
REALIZE-K (NCT04676646) was a prospective, double-blind, randomized- withdrawal trial in participants with HFrEF (NYHA II–IV; left ventricular ejection fraction ≤40%), optimal guideline-directed therapy (except MRA), and prevalent or incident MRA- induced hyperkalemia. During open-label run-in, participants underwent spironolactone titration (target: 50 mg/daily); those with hyperkalemia started SZC. Participants with normokalemia (potassium 3.5–5.0 mEq/L) on SZC and spironolactone ≥25 mg/daily were randomized to continued SZC or placebo for 6 months. The primary endpoint was optimal treatment response (normokalemia on spironolactone ≥25 mg/daily without rescue therapy for hyperkalemia [months 1–6]). The five key secondary endpoints were tested hierarchically. Exploratory endpoints included a composite of adjudicated cardiovascular death or worsening HF events (hospitalizations and urgent visits).
Results
Overall, 203 participants were randomized (SZC 102, placebo 101). Higher percentage of SZC- versus placebo-treated participants had optimal response (71% vs 36%; OR 4.45 [95% CI 2.89–6.86]; p<0.001). SZC (versus placebo) improved the first four key secondary endpoints: normokalemia on randomization dose of spironolactone and without rescue therapy (58% vs 23%; OR 4.58 [2.78–7.55]; p<0.001), receiving spironolactone ≥25 mg/daily (81% vs 50%; OR 4.33 [2.50–7.52]; p<0.001), time to hyperkalemia (HR 0.51 [0.37–0.71]; p<0.001), time to decrease/discontinuation of spironolactone due to hyperkalemia (HR 0.37 [0.17–0.73]; p=0.006). There was no between-group difference in KCCQ-CSS at 6 months (-1.01 points [-6.64–4.63]; p=0.72). Adverse events (64% vs 63%) and serious adverse events (23% vs 22%) were balanced between SZC and placebo, respectively. Composite of CV death or worsening HF occurred in 11 (11%) participants in the SZC group (1 with CV death, 10 with HF events) and 3 (3%) participants in the placebo group (1 with CV death, 2 with HF events; log-rank nominal p=0.034).
Conclusions
In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalaemia and down-titration/discontinuation of spironolactone.Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making.
背景矿物皮质激素受体拮抗剂（MRA）可改善射血分数降低型心力衰竭（HFrEF）患者的预后，但在临床实践中使用不足。目的 我们评估了环硅酸锆钠（SZC）在优化 HFrEF 和高钾血症患者使用螺内酯方面的效果。方法REALIZE-K（NCT04676646）是一项前瞻性、双盲、随机撤消试验，参加者均为高频低氧血症患者（NYHA II-IV；左心室射血分数≤40%），接受过最佳指南指导治疗（MRA除外），并存在或发生过由 MRA 引起的高钾血症。在开放标签试运行期间，参与者接受螺内酯滴定（目标值：50 毫克/天）；出现高钾血症者开始服用 SZC。服用 SZC 且螺内酯≥25 毫克/天的正常血钾患者（血钾 3.5-5.0 mEq/L）被随机分配至继续服用 SZC 或安慰剂，为期 6 个月。主要终点是最佳治疗反应（服用螺内酯≥25 毫克/天后无高钾血症抢救治疗的正常血钾[第 1-6 个月]）。对五个关键次要终点进行了分层测试。探索性终点包括判定的心血管死亡或HF恶化事件（住院和急诊）的复合终点。与安慰剂相比，SZC治疗参与者中获得最佳应答的比例更高（71% vs 36%；OR 4.45 [95% CI 2.89-6.86]；p<0.001）。SZC（与安慰剂相比）改善了前四个关键次要终点：服用随机剂量螺内酯且未接受抢救治疗的正常血钾（58% vs 23%；OR 4.58 [2.78-7.55]；p<0.001）、接受螺内酯≥25 mg/天（81% vs 50%；OR 4.33 [2.50-7.52]；p<0.001）、高钾血症发生时间（HR 0.51 [0.37-0.71]；p<0.001）、因高钾血症减少/停止使用螺内酯时间（HR 0.37 [0.17-0.73]；p=0.006）。6个月时的KCCQ-CSS没有组间差异（-1.01分[-6.64-4.63]；P=0.72）。SZC和安慰剂的不良事件发生率（64% vs 63%）和严重不良事件发生率（23% vs 22%）分别均衡。SZC组有11人（11%）发生冠心病死亡或HF恶化（1人发生冠心病死亡，10人发生HF事件），安慰剂组有3人（3%）发生冠心病死亡或HF恶化（1人发生冠心病死亡，2人发生HF事件；log-rank名义P=0.034）。结论 在患有高频低氧血症和高钾血症的参与者中，SZC可大幅提高在服用最佳螺内酯剂量时出现正常血钾的参与者比例，并降低高钾血症和螺内酯降量/停药的风险。虽然临床结果的馈源不足，但使用SZC发生高频事件的参与者多于使用安慰剂的参与者，临床决策时应考虑到这一点。
{"title":"Sodium Zirconium Cyclosilicate for Management of Hyperkalemia During Spironolactone Optimization in Patients with Heart Failure","authors":"Mikhail N. Kosiborod, David Z.I. Cherney, Akshay S. Desai, Jeffrey M. Testani, Subodh Verma, Khaja Chinnakondepalli, David Dolling, Shachi Patel, Magnus Dahl, James M. Eudicone, Lovisa Friberg, Mario Ouwens, Murillo O. Antunes, Kim A. Connelly, Vagner Madrini, Luca Kuthi, Anuradha Lala, Miguel Lorenzo, Patrícia O. Guimarães, Marta Cobo Marcos, Mark C. Petrie","doi":"10.1016/j.jacc.2024.11.014","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.11.014","url":null,"abstract":"<h3>Background</h3>Mineralocorticoid receptor antagonists (MRA) improve outcomes in patients with heart failure and reduced ejection fraction (HFrEF) but are underused in clinical practice. Observational data suggest that hyperkalemia is the leading obstacle for the suboptimal use of MRA.<h3>Objectives</h3>We evaluated the effects of sodium zirconium cyclosilicate (SZC) in optimizing use of spironolactone among participants with HFrEF and hyperkalemia.<h3>Methods</h3>REALIZE-K (NCT04676646) was a prospective, double-blind, randomized- withdrawal trial in participants with HFrEF (NYHA II–IV; left ventricular ejection fraction ≤40%), optimal guideline-directed therapy (except MRA), and prevalent or incident MRA- induced hyperkalemia. During open-label run-in, participants underwent spironolactone titration (target: 50 mg/daily); those with hyperkalemia started SZC. Participants with normokalemia (potassium 3.5–5.0 mEq/L) on SZC and spironolactone ≥25 mg/daily were randomized to continued SZC or placebo for 6 months. The primary endpoint was optimal treatment response (normokalemia on spironolactone ≥25 mg/daily without rescue therapy for hyperkalemia [months 1–6]). The five key secondary endpoints were tested hierarchically. Exploratory endpoints included a composite of adjudicated cardiovascular death or worsening HF events (hospitalizations and urgent visits).<h3>Results</h3>Overall, 203 participants were randomized (SZC 102, placebo 101). Higher percentage of SZC- versus placebo-treated participants had optimal response (71% vs 36%; OR 4.45 [95% CI 2.89–6.86]; p<0.001). SZC (versus placebo) improved the first four key secondary endpoints: normokalemia on randomization dose of spironolactone and without rescue therapy (58% vs 23%; OR 4.58 [2.78–7.55]; p<0.001), receiving spironolactone ≥25 mg/daily (81% vs 50%; OR 4.33 [2.50–7.52]; p<0.001), time to hyperkalemia (HR 0.51 [0.37–0.71]; p<0.001), time to decrease/discontinuation of spironolactone due to hyperkalemia (HR 0.37 [0.17–0.73]; p=0.006). There was no between-group difference in KCCQ-CSS at 6 months (-1.01 points [-6.64–4.63]; p=0.72). Adverse events (64% vs 63%) and serious adverse events (23% vs 22%) were balanced between SZC and placebo, respectively. Composite of CV death or worsening HF occurred in 11 (11%) participants in the SZC group (1 with CV death, 10 with HF events) and 3 (3%) participants in the placebo group (1 with CV death, 2 with HF events; log-rank nominal p=0.034).<h3>Conclusions</h3>In participants with HFrEF and hyperkalemia, SZC led to large improvements in the percentage of participants with normokalemia while on optimal spironolactone dose, and reduced risk of hyperkalaemia and down-titration/discontinuation of spironolactone.Although underpowered for clinical outcomes, more participants had HF events with SZC than placebo, which should be factored into the clinical decision making.","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"12 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665353","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 : 2024-11-18DOI: 10.1016/j.jacc.2024.08.079
Jaimie Coburn, Pieter A. Neef, Simon Hobson, Jonathan R. Dalzell
No Abstract
无摘要
{"title":"Clinical Signs of Congestion in Younger Patients With Decompensated Heart Failure","authors":"Jaimie Coburn, Pieter A. Neef, Simon Hobson, Jonathan R. Dalzell","doi":"10.1016/j.jacc.2024.08.079","DOIUrl":"https://doi.org/10.1016/j.jacc.2024.08.079","url":null,"abstract":"No Abstract","PeriodicalId":17187,"journal":{"name":"Journal of the American College of Cardiology","volume":"8 1","pages":""},"PeriodicalIF":24.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665370","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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