{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:18:39Z","timestamp":1787807919735,"version":"build-2784847793"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Autonomic nervous system involvement is common in systemic amyloidosis, yet the clinical relevance of heart rate variability (HRV) in immunoglobulin light-chain (AL) amyloidosis remains incompletely defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective cohort study, 56 patients with biopsy-proven AL amyloidosis and 33 age- and sex-comparable healthy controls underwent 24\u2005h Holter monitoring. Time- and frequency-domain HRV parameters were recorded. Associations of HRV with cardiac involvement assessed by cardiac magnetic resonance (CMR), Mayo 2004 stage, and short-term treatment response were evaluated using group comparisons and multivariable regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Compared with controls, patients with AL amyloidosis had significantly higher mean heart rate and lower SDNN, total power (TP), and all frequency-domain components (ULF, VLF, LF, and HF) (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05). Patients with CMR-defined cardiac involvement showed a higher prevalence of HRV abnormalities and lower SDNN, SDANN, pNN50, TP, ULF, VLF, and LF than CMR-negative patients (all nominal\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05). In multivariable models, troponin remained independently associated with CMR-positive status, whereas HRV indices did not retain independent significance. By Mayo 2004 stage (I\/II\/III: 11\/20\/25), SDANN and VLF declined progressively with advancing stage (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&amp;lt;\u20090.05), and SDANN remained independently associated with higher stage after adjustment for troponin. In the exploratory subset with paired follow-up Holter recordings (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200933), most HRV parameters did not change significantly after therapy; however, the coefficient of variation (CV) showed a statistically significant increase following treatment (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.037).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Reduced HRV is a prominent feature of AL amyloidosis and is independently associated with Mayo stage after adjustment for cardiac biomarkers. These findings position HRV as a non-invasive marker of autonomic involvement that complements established cardiac biomarkers in characterising disease severity in AL amyloidosis; whether this translates into independent prognostic value requires evaluation in prospective outcome studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1882210","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:27:21Z","timestamp":1787804841000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Reduced heart rate variability is associated with disease severity in AL amyloidosis: a retrospective cohort study"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiao-hang","family":"Pei","sequence":"first","affiliation":[{"name":"Department of Hematology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-qiong","family":"Zuo","sequence":"additional","affiliation":[{"name":"Department of Hematology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Hematology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong-jun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Hematology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zun-min","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-li","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Hematology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1186\/1750-1172-7-54","article-title":"Al amyloidosis","volume":"7","author":"Desport","year":"2012","journal-title":"Orphanet J Rare Dis"},{"key":"B2","doi-asserted-by":"publisher","first-page":"eaax0914","DOI":"10.1126\/scitranslmed.aax0914","article-title":"Does protein aggregation drive postmitotic tissue degeneration?","volume":"13","author":"Kelly","year":"2021","journal-title":"Sci Transl Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"3517","DOI":"10.1093\/cvr\/cvac119","article-title":"Transthyretin cardiac amyloidosis","volume":"118","author":"Porcari","year":"2023","journal-title":"Cardiovasc Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1186\/s12882-025-04226-9","article-title":"An atypical cause of amyloidosis: a case of combined heavy and light chain amyloidosis","volume":"26","author":"Gonzalez-Hernandez","year":"2025","journal-title":"BMC Nephrol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1186\/s13023-022-02414-6","article-title":"Global epidemiology of amyloid light-chain amyloidosis","volume":"17","author":"Kumar","year":"2022","journal-title":"Orphanet J Rare Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1007\/s11897-019-00446-x","article-title":"Amyloidosis in heart failure","volume":"16","author":"Ihne","year":"2019","journal-title":"Curr Heart Fail Rep"},{"key":"B7","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.cjca.2019.12.033","article-title":"Amyloidosis as a systemic disease in context","volume":"36","author":"Cuddy","year":"2020","journal-title":"Can J Cardiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1001\/jama.2020.5493","article-title":"Systemic amyloidosis recognition, prognosis, and therapy: a systematic review","volume":"324","author":"Gertz","year":"2020","journal-title":"Jama"},{"key":"B9","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1080\/13506129.2021.1994386","article-title":"Tissue biopsy for the diagnosis of amyloidosis: experience from some centres","volume":"29","author":"Benson","year":"2022","journal-title":"Amyloid"},{"key":"B10","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1111\/ejh.13458","article-title":"The value of screening biopsies in light-chain (AL) and transthyretin (ATTR) amyloidosis","volume":"105","author":"Cohen","year":"2020","journal-title":"Eur J Haematol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1093\/ndt\/gfy291","article-title":"AL Amyloidosis: advances in diagnostics and treatment","volume":"34","author":"Ry\u0161av\u00e1","year":"2019","journal-title":"Nephrol Dial Transplant"},{"key":"B12","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/s12968-019-0563-2","article-title":"Characterizing cardiac involvement in amyloidosis using cardiovascular magnetic resonance diffusion tensor imaging","volume":"21","author":"Gotschy","year":"2019","journal-title":"J Cardiovasc Magn Reson"},{"key":"B13","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.ejim.2018.10.013","article-title":"Cardiac troponin T and NT-proBNP as diagnostic and prognostic biomarkers of primary cardiac involvement and disease severity in systemic sclerosis: a prospective study","volume":"60","author":"Bosello","year":"2019","journal-title":"Eur J Intern Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s43044-024-00446-w","article-title":"Cardiovascular biomarkers: exploring troponin and BNP applications in conditions related to carbon monoxide exposure","volume":"76","author":"Taghdiri","year":"2024","journal-title":"Egypt Heart J"},{"key":"B15","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1007\/s40265-022-01830-z","article-title":"Diagnosis and treatment of AL amyloidosis","volume":"83","author":"Palladini","year":"2023","journal-title":"Drugs"},{"key":"B16","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1038\/s41408-021-00486-4","article-title":"Comprehensive review of AL amyloidosis: some practical recommendations","volume":"11","author":"Al Hamed","year":"2021","journal-title":"Blood Cancer J"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1189","DOI":"10.1016\/j.jacc.2018.12.064","article-title":"Autonomic nervous system dysfunction","volume":"73","author":"Goldberger","year":"2019","journal-title":"J Am Coll Cardiol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e13174","DOI":"10.1111\/eci.13174","article-title":"Heart rate variability in atrial fibrillation: the balance between sympathetic and parasympathetic nervous system","volume":"49","author":"Khan","year":"2019","journal-title":"Eur J Clin Investig"},{"key":"B19","doi-asserted-by":"publisher","first-page":"e12749","DOI":"10.1111\/anec.12749","article-title":"Autonomic dysfunction in cardiac amyloidosis assessed by heart rate variability and heart rate turbulence","volume":"25","author":"Yamada","year":"2020","journal-title":"Ann Noninvasive Electrocardiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1053\/euhj.2001.2972","article-title":"Heart rate variability as a predictor of mortality in patients with AA and AL amyloidosis","volume":"23","author":"Reyners","year":"2002","journal-title":"Eur Heart J"},{"key":"B21","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.jcmg.2009.09.023","article-title":"Role of cardiac magnetic resonance imaging in the detection of cardiac amyloidosis","volume":"3","author":"Syed","year":"2010","journal-title":"JACC Cardiovasc Imaging"},{"key":"B22","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1136\/heartjnl-2019-314856","article-title":"Cardiovascular magnetic resonance: applications and practical considerations for the general cardiologist","volume":"106","author":"Arnold","year":"2020","journal-title":"Heart"},{"key":"B23","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1148\/radiol.2018172435","article-title":"Left ventricular myocardial deformation on cine MR images: relationship to severity of disease and prognosis in light-chain amyloidosis","volume":"288","author":"Wan","year":"2018","journal-title":"Radiology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e000029","DOI":"10.1161\/HCI.0000000000000030","article-title":"ASNC\/AHA\/ASE\/EANM\/HFSA\/ISA\/SCMR\/SNMMI expert consensus recommendations for multimodality imaging in cardiac amyloidosis: part 2 of 2\u2014diagnostic criteria and appropriate utilization","volume":"14","author":"Dorbala","year":"2021","journal-title":"Circ Cardiovasc Imaging"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1570","DOI":"10.1161\/CIRCULATIONAHA.115.016567","article-title":"Prognostic value of late gadolinium enhancement cardiovascular magnetic resonance in cardiac amyloidosis","volume":"132","author":"Fontana","year":"2015","journal-title":"Circulation"},{"key":"B26","doi-asserted-by":"publisher","first-page":"8963","DOI":"10.3390\/jcm14248963","article-title":"The vagal link: autonomic nervous system dysfunction in cardiac amyloidosis","volume":"14","author":"Barocelli","year":"2025","journal-title":"J Clin Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1161\/01.CIR.93.5.1043","article-title":"Task force of the European Society of Cardiology and the north American society of pacing and electrophysiology: heart rate variability: standards of measurement, physiological interpretation, and clinical use","volume":"93","year":"1996","journal-title":"Circulation"},{"key":"B28","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1002\/ehf2.14684","article-title":"Progression and prognostic significance of electrocardiographic findings in patients with cardiac amyloidosis","volume":"12","author":"Argir\u00f2","year":"2025","journal-title":"ESC Heart Fail"},{"key":"B29","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/0002-9149(87)90795-8","article-title":"Decreased heart rate variability and its association with increased mortality after acute myocardial infarction","volume":"59","author":"Kleiger","year":"1987","journal-title":"Am J Cardiol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1882210\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T04:27:22Z","timestamp":1787804842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1882210\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,27]]},"references-count":29,"alternative-id":["10.3389\/fmed.2026.1882210"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1882210","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,27]]},"article-number":"1882210"}}