Vincenzo B. Polsinelli , Karen Hanley-Yanez , Charles F. McTiernan , Kalgi Modi , Jennifer Haythe , Hal Skopicki , Uri Elkayam , Leslie T. Cooper Jr , James D. Fett , Dennis M. McNamara , for the IPAC investigators
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McNamara , for the IPAC investigators","doi":"10.1016/j.ahjo.2024.100489","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>Evaluate the relationship of cathepsin-D (CD) on disease severity and clinical outcomes for women with peripartum cardiomyopathy.</div></div><div><h3>Background</h3><div>Cathepsin-D is a protease released during oxidative stress that cleaves prolactin (PRL) generating a 16 kDa fragment that is pro-apoptotic, anti-angiogenic, and has been implicated in the pathogenesis of peripartum cardiomyopathy (PPCM).</div></div><div><h3>Methods</h3><div>In 99 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study, CD levels were assessed by ELISA from serum obtained at study entry. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6, and 12-months. CD levels were compared to healthy PP and non-PP controls. Survival free from major cardiovascular events (death, transplantation, or left ventricular assist device) was determined up to 12 months post-partum (PP).</div></div><div><h3>Results</h3><div>Mean age was 30 ± 6 years, with a baseline LVEF of 34 % ± 10. Cathepsin-D levels were higher in PPCM women (278 ± 114 ng/ml) than in healthy PP (190 ± 74, <em>p</em> = 0.02) and healthy non-PP controls (136 ± 79, <em>p</em> < 0.001). There was no association of CD with age, breastfeeding status, or time from delivery to the presentation. Cathepsin-D levels were higher in women with higher New York Heart Association (NYHA) functional class (<em>p</em> = 0.001). Higher tertiles of CD levels were associated with lower event-free survival (<em>p</em> = 0.008).</div></div><div><h3>Conclusions</h3><div>In this prospective cohort of women with PPCM, higher CD levels at the time of diagnosis were associated with worse symptoms, less recovery of LVEF, and worse clinical outcomes. Circulating CD may contribute to the development of PPCM and influence disease severity, myocardial recovery, and clinical outcomes.</div></div>","PeriodicalId":72158,"journal":{"name":"American heart journal plus : cardiology research and practice","volume":"49 ","pages":"Article 100489"},"PeriodicalIF":1.3000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731516/pdf/","citationCount":"0","resultStr":"{\"title\":\"Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC\",\"authors\":\"Vincenzo B. Polsinelli , Karen Hanley-Yanez , Charles F. McTiernan , Kalgi Modi , Jennifer Haythe , Hal Skopicki , Uri Elkayam , Leslie T. Cooper Jr , James D. Fett , Dennis M. McNamara , for the IPAC investigators\",\"doi\":\"10.1016/j.ahjo.2024.100489\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><div>Evaluate the relationship of cathepsin-D (CD) on disease severity and clinical outcomes for women with peripartum cardiomyopathy.</div></div><div><h3>Background</h3><div>Cathepsin-D is a protease released during oxidative stress that cleaves prolactin (PRL) generating a 16 kDa fragment that is pro-apoptotic, anti-angiogenic, and has been implicated in the pathogenesis of peripartum cardiomyopathy (PPCM).</div></div><div><h3>Methods</h3><div>In 99 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study, CD levels were assessed by ELISA from serum obtained at study entry. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6, and 12-months. CD levels were compared to healthy PP and non-PP controls. Survival free from major cardiovascular events (death, transplantation, or left ventricular assist device) was determined up to 12 months post-partum (PP).</div></div><div><h3>Results</h3><div>Mean age was 30 ± 6 years, with a baseline LVEF of 34 % ± 10. Cathepsin-D levels were higher in PPCM women (278 ± 114 ng/ml) than in healthy PP (190 ± 74, <em>p</em> = 0.02) and healthy non-PP controls (136 ± 79, <em>p</em> < 0.001). There was no association of CD with age, breastfeeding status, or time from delivery to the presentation. Cathepsin-D levels were higher in women with higher New York Heart Association (NYHA) functional class (<em>p</em> = 0.001). Higher tertiles of CD levels were associated with lower event-free survival (<em>p</em> = 0.008).</div></div><div><h3>Conclusions</h3><div>In this prospective cohort of women with PPCM, higher CD levels at the time of diagnosis were associated with worse symptoms, less recovery of LVEF, and worse clinical outcomes. Circulating CD may contribute to the development of PPCM and influence disease severity, myocardial recovery, and clinical outcomes.</div></div>\",\"PeriodicalId\":72158,\"journal\":{\"name\":\"American heart journal plus : cardiology research and practice\",\"volume\":\"49 \",\"pages\":\"Article 100489\"},\"PeriodicalIF\":1.3000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731516/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American heart journal plus : cardiology research and practice\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2666602224001320\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CARDIAC & CARDIOVASCULAR SYSTEMS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American heart journal plus : cardiology research and practice","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2666602224001320","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0
摘要
目的:探讨组织蛋白酶- d (CD)与围生期心肌病患者病情严重程度及临床预后的关系。背景:Cathepsin-D是一种在氧化应激过程中释放的蛋白酶,可裂解催乳素(PRL),产生一个16kda的促凋亡、抗血管生成片段,并与围产期心肌病(PPCM)的发病机制有关。方法:入选妊娠相关心肌病调查(IPAC)研究的99名新诊断PPCM的妇女,在研究开始时通过ELISA检测血清中的CD水平。左心室射血分数(LVEF)在入院、6个月和12个月时通过超声心动图评估。将健康PP组和非PP组的CD水平进行比较。无主要心血管事件(死亡、移植或左心室辅助装置)的生存期直至产后12个月(PP)。结果:平均年龄30±6岁,基线LVEF为34%±10。PPCM妇女的Cathepsin-D水平(278±114 ng/ml)高于健康PP组(190±74,p = 0.02)和健康非PP组(136±79,p = 0.001)。较高的CD水平与较低的无事件生存率相关(p = 0.008)。结论:在这个PPCM女性的前瞻性队列中,诊断时较高的CD水平与更严重的症状、更少的LVEF恢复和更差的临床结果相关。循环CD可能促进PPCM的发展,影响疾病严重程度、心肌恢复和临床结果。
Cathepsin-D and outcomes in peripartum cardiomyopathy: Results from IPAC
Objective
Evaluate the relationship of cathepsin-D (CD) on disease severity and clinical outcomes for women with peripartum cardiomyopathy.
Background
Cathepsin-D is a protease released during oxidative stress that cleaves prolactin (PRL) generating a 16 kDa fragment that is pro-apoptotic, anti-angiogenic, and has been implicated in the pathogenesis of peripartum cardiomyopathy (PPCM).
Methods
In 99 women with newly diagnosed PPCM enrolled in the Investigation in Pregnancy Associated Cardiomyopathy (IPAC) study, CD levels were assessed by ELISA from serum obtained at study entry. Left ventricular ejection fraction (LVEF) was assessed by echocardiography at entry, 6, and 12-months. CD levels were compared to healthy PP and non-PP controls. Survival free from major cardiovascular events (death, transplantation, or left ventricular assist device) was determined up to 12 months post-partum (PP).
Results
Mean age was 30 ± 6 years, with a baseline LVEF of 34 % ± 10. Cathepsin-D levels were higher in PPCM women (278 ± 114 ng/ml) than in healthy PP (190 ± 74, p = 0.02) and healthy non-PP controls (136 ± 79, p < 0.001). There was no association of CD with age, breastfeeding status, or time from delivery to the presentation. Cathepsin-D levels were higher in women with higher New York Heart Association (NYHA) functional class (p = 0.001). Higher tertiles of CD levels were associated with lower event-free survival (p = 0.008).
Conclusions
In this prospective cohort of women with PPCM, higher CD levels at the time of diagnosis were associated with worse symptoms, less recovery of LVEF, and worse clinical outcomes. Circulating CD may contribute to the development of PPCM and influence disease severity, myocardial recovery, and clinical outcomes.