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Previous data suggested a lower native T1 value in spite of a higher LV mass and higher extracellular volume fraction (ECV) value in wild-type transthyretin amyloidosis (ATTRwt) compared to light-chain amyloidosis (AL)\u2014resulting in the still unsolved \u201cnative T1 vs. ECV paradox\u201d in CA. The purpose of this study was to address this paradox. The present study comprised N\u2009=\u200990 patients with ATTRwt and N\u2009=\u200930 patients with AL who underwent multi-parametric CMR studies prior to any specific treatment. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging as well as T2-mapping and pre-\/post-contrast T1-mapping allowing to measure myocardial ECV. Left ventricular ejection fraction (LV-EF), left ventricular mass index (LVMi) and left ventricular wall thickness (LVWT) were significantly higher in ATTRwt in comparison to AL. Indexed ECV (ECVi) was also higher in ATTRwt (<jats:italic>p<\/jats:italic>\u2009=\u20090.041 for global and <jats:italic>p<\/jats:italic>\u2009=\u20090.001 for basal septal). In contrast, native T1- [1094\u00a0ms (1069\u20131127\u00a0ms) in ATTRwt vs. 1,122\u00a0ms (1076\u20131160\u00a0ms) in AL group, <jats:italic>p<\/jats:italic>\u2009=\u20090.040] and T2-values [57\u00a0ms (55\u201360\u00a0ms) vs. 60\u00a0ms (57\u201364\u00a0ms); <jats:italic>p<\/jats:italic>\u2009=\u20090.001] were higher in AL. Considering particularities in myocardial density, \u201ctotal extracellular mass\u201d (TECM) was substantially higher in ATTRwt whereas \u201ctotal intracellular mass\u201d (TICM) was rather similar between ATTRwt and AL. Consequently, the \u201cratio TICM\/TECM\u201d was lower in ATTRwt compared to AL (0.58 vs. 0.83; <jats:italic>p<\/jats:italic>\u2009=\u20090.007). Our data confirm the presence of a \u201cnative T1 vs. ECV paradox\u201d with lower native T1 values in spite of higher myocardial mass and ECV in ATTRwt compared to AL. Importantly, this observation can be explained by particularities regarding myocardial density that result in a lower TICM\/TECM \u201cratio\u201d in case of ATTRwt compared to AL\u2014since native T1 is determined by this ratio.<\/jats:p>","DOI":"10.1038\/s41598-022-26216-9","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T10:05:55Z","timestamp":1671185155000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["A compartment-based myocardial density approach helps to solve the native T1 vs. ECV paradox in cardiac amyloidosis"],"prefix":"10.1038","volume":"12","author":[{"given":"Bishwas","family":"Chamling","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Bietenbeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanos","family":"Drakos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Korthals","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Vehof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Stalling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Meier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Yilmaz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"26216_CR1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1182\/blood-2016-01-629790","volume":"128","author":"G Palladini","year":"2016","unstructured":"Palladini, G. & Merlini, G. 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