{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:28:58Z","timestamp":1784334538005,"version":"3.55.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"am","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["10.55776\/PAT8668424"],"award-info":[{"award-number":["10.55776\/PAT8668424"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>This study aimed to characterize circulating renin\u2013angiotensin\u2013aldosterone system (RAAS) profiles in transthyretin amyloid cardiomyopathy (ATTR-CM), examine their relationship with clinical and echocardiographic parameters and determine their prognostic value.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this prospective study, ATTR-CM patients underwent serum quantification of classical (angiotensin I\u2013IV, aldosterone) and alternative (angiotensin 1\u20137, angiotensin 1\u20135) RAAS peptides and angiotensin-converting enzyme 2 (ACE2) activity using mass spectrometry. RAAS inhibitor use was recorded. Associations of RAAS peptides with N-terminal pro brain natriuretic peptide (NT-proBNP) and echocardiographic parameters were analysed. Prognostic associations with the composite endpoint of HF hospitalization or cardiac death were assessed using Kaplan\u2013Meier curves stratified by median peptide values.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 137 patients, RAAS inhibitor use included ACEi (21.2%), ARBs (34.3%), ARNIs (7.3%), and none (26.0%). RAAS profiles were consistent with the expected effects of the respective RAAS inhibitors. During a median follow-up of 1.6 years, 49 patients (36%) experienced the composite endpoint. Patients with adverse cardiac events had higher ACE2 activity (P &amp;lt; .001) and alternative RAAS peptides (angiotensin 1\u20137: P = .007; angiotensin 1\u20135: P &amp;lt; .001). Higher ACE2 activity was associated with higher NT-proBNP (P &amp;lt; .001) and more advanced echocardiographic parameters of biventricular dysfunction. In Kaplan\u2013Meier analysis, ACE2 above median predicted adverse cardiac outcomes (P = .017), while classical RAAS peptides were not predictive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ATTR-CM patients exhibit distinct RAAS profiles, with increased ACE2 activity and a shift towards the alternative RAAS axis in more advanced disease. Higher ACE2 activity is associated with higher NT-proBNP, biventricular dysfunction and adverse cardiac outcomes, suggesting that ACE2 may represent a promising marker for risk stratification in ATTR-CM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ejhf\/xuag102","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T12:46:30Z","timestamp":1774701990000},"source":"Crossref","is-referenced-by-count":2,"title":["Insights into the renin\u2013angiotensin\u2013aldosterone system in transthyretin amyloid cardiomyopathy"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3866-3710","authenticated-orcid":false,"given":"Christina","family":"Kronberger","sequence":"first","affiliation":[{"name":"Department of Internal Medicine II, Division of Cardiology, Medical University of Vienna , Waehringer Guertel 18-20, Vienna 1090 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