{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:58:38Z","timestamp":1792155518483,"version":"4.4.0"},"reference-count":39,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,10]],"date-time":"2024-11-10T00:00:00Z","timestamp":1731196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MCW Advancing a Healthier Wisconsin Endowment","award":["UL1TR001436"],"award-info":[{"award-number":["UL1TR001436"]}]},{"name":"MCW Advancing a Healthier Wisconsin Endowment","award":["1TL1TR001437"],"award-info":[{"award-number":["1TL1TR001437"]}]},{"name":"MCW Advancing a Healthier Wisconsin Endowment","award":["T32-GM080202"],"award-info":[{"award-number":["T32-GM080202"]}]},{"name":"MCW Department of Surgery, and the Herma Heart Institute. MQA is a member of the MCW Medical Scientist Training Program","award":["UL1TR001436"],"award-info":[{"award-number":["UL1TR001436"]}]},{"name":"MCW Department of Surgery, and the Herma Heart Institute. MQA is a member of the MCW Medical Scientist Training Program","award":["1TL1TR001437"],"award-info":[{"award-number":["1TL1TR001437"]}]},{"name":"MCW Department of Surgery, and the Herma Heart Institute. MQA is a member of the MCW Medical Scientist Training Program","award":["T32-GM080202"],"award-info":[{"award-number":["T32-GM080202"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: MYH6 variants are the most well-known genetic risk factor (10%) for hypoplastic left heart syndrome (HLHS) and are associated with decreased cardiac transplant-free survival. MYH6 encodes for \u03b1-myosin heavy chain (\u03b1-MHC), a contractile protein expressed in the neonatal atria. We therefore assessed atrial function in HLHS patients with MYH6 variants. Methods: We performed a retrospective, blinded assessment of pre-stage I atrial function using 2D speckle-tracking echocardiography (2D-STE). Variant carriers were control-matched based on AV valve anatomy, sex, and birth year. Studies were obtained postnatally from awake patients prior to surgical intervention. Right atrial (RA) and right ventricular (RV) strain and strain rate (SR) were measured from the apical four-chamber view. Results: A total of 19 HLHS patients with MYH6 variants had echocardiograms available; 18 were matched to two controls each, and one had a single control. RA active strain (ASct) was decreased in variant carriers (\u22121.41%, IQR \u22122.13, \u22120.25) vs. controls (\u22123.53%, IQR \u22125.53, \u22121.28; p = 0.008). No significant differences were identified in RV strain between the groups. RA reservoir strain (ASr) and conduit strain (AScd) positively correlated with heart rate (HR) in MYH6 variant carriers only (ASr R = 0.499, p = 0.029; AScd R = 0.469, p = 0.043). RV global longitudinal strain (GLS) as well as RV systolic strain (VSs) and strain rate (VSRs) correlated with HR in controls only (GLS R = 0.325, p = 0.050; VSs R = 0.419, p = 0.010; VSRs R = 0.410, p = 0.012). Conclusions: We identified functional consequences associated with MYH6 variants, a known risk factor for poor outcomes in HLHS. MYH6 variant carriers exhibit impaired RA contractility despite there being no differences in RV function between variant carriers and controls. MYH6 variants are also associated with an ineffective RA reservoir and conduit function at high heart rates, despite preserved RV diastolic function. RA dysfunction and reduced atrial \u201ckick\u201d may therefore be a significant contributor to RV failure and worse clinical outcomes in HLHS patients with MYH6 variants.<\/jats:p>","DOI":"10.3390\/genes15111449","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"1449","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["MYH6 Variants Are Associated with Atrial Dysfunction in Neonates with Hypoplastic Left Heart Syndrome"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9878-4223","authenticated-orcid":false,"given":"Melissa","family":"Quintanilla Anfinson","sequence":"first","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Creighton","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pippa M.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Division of Quantitative Health Sciences, Department of Biostatistics, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne M.","family":"James","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Mercy Kansas City, Kansas City, MO 64108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phoebe","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Frommelt","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics, Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoy","family":"Tomita-Mitchell","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA"},{"name":"Division of Congenital Cardiac Surgery, Divisions of Thoracic and Cardiac Surgery, Department of Surgery, Children\u2019s Wisconsin, Milwaukee, WI 53226, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1161\/CIRCULATIONAHA.116.022816","article-title":"Current Therapy for Hypoplastic Left Heart Syndrome and Related Single Ventricle Lesions","volume":"134","author":"Ohye","year":"2016","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e234","DOI":"10.1161\/CIR.0000000000000696","article-title":"Evaluation and Management of the Child and Adult With Fontan Circulation: A Scientific Statement From the American Heart Association","volume":"140","author":"Rychik","year":"2019","journal-title":"Circulation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1093\/ejcts\/ezu547","article-title":"Results of heart transplantation following failed staged palliation of hypoplastic left heart syndrome and related single ventricle anomalies","volume":"48","author":"Alsoufi","year":"2015","journal-title":"Eur. 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