{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:35:37Z","timestamp":1791974137306,"version":"4.4.0"},"reference-count":24,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,4,14]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Sarcomere gene variants are a key cause of hypertrophic cardiomyopathy (HCM), and have been associated with worse prognosis. However, it is unclear how comorbidities influence clinical trajectories, the timing of events, and causes of death in sarcomeric and nonsarcomeric HCM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We conducted a multicenter longitudinal cohort study of genotyped patients with HCM in the Sarcomeric Human Cardiomyopathy registry (SHaRe). Patients were classified as sarcomeric HCM (pathogenic\/likely pathogenic sarcomere variant) or nonsarcomeric HCM (genetically elusive). The influence of genetic classification and comorbidities on the sequence of cardiovascular events were assessed in time-varying Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Among 6120 patients (40% women; 87% probands; 50% sarcomeric HCM), followed for a median of 5.3 years, sarcomeric HCM (n=3082) was associated with a younger age at diagnosis (median 38.1 versus 54.3 years;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), a higher proportion of women and less obesity, hypertension, and left ventricular (LV) obstruction. After age standardization, sarcomeric HCM was associated with a higher burden of atrial fibrillation (age-standardized incidence [ASI] ratio, 1.28 [CI, 1.16\u20131.40]), LV systolic dysfunction (ASI ratio, 1.31 [CI, 1.15\u20131.48]), and ventricular arrhythmias (ASI ratio, 1.37 [CI, 1.17\u20131.52]) than nonsarcomeric HCM. All-cause mortality was similar (10.4% versus 9.4%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.20); however, patients with sarcomeric HCM died younger (mean 7.8 years;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001), with model-based survival-analysis estimating 3.5 life-years lost between ages 44 and 85. Sarcomeric HCM was also associated with higher HCM-related mortality (hazard ratio [HR], 1.61 [CI, 1.18\u20132.20]). Temporal analysis identified atrial fibrillation as the strongest disease-modifier, increasing the risk of LV systolic dysfunction (HR, 2.54 [CI 2.07\u20133.11]), ventricular arrhythmias (HR, 3.13 [CI, 2.36\u20134.20]), and mortality (HR, 1.94 [CI, 1.64\u20132.31]) in both groups. Genotype-interaction analyses demonstrated a larger impact of atrial fibrillation and LV systolic dysfunction on adverse outcomes in sarcomeric versus nonsarcomeric HCM, with effect ratios up to 1.98 for severe heart failure and 2.01 for mortality (both\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>Genotype can refine risk stratification and inform clinical management in HCM. Sarcomeric HCM is associated with worse prognosis and may benefit from more vigilant surveillance for arrhythmias and systolic dysfunction, with a lower threshold for advanced therapies. Comorbidities, including hypertension and obesity, may be modifiable risk factors for patients with nonsarcomeric HCM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.076036","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:00:54Z","timestamp":1773050454000},"page":"1104-1116","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":10,"title":["Differences in Disease Trajectory, Comorbidities, and Mortality in Sarcomeric and Nonsarcomeric Hypertrophic Cardiomyopathy"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0834-206X","authenticated-orcid":true,"given":"Christoffer R.","family":"Vissing","sequence":"first","affiliation":[{"name":"Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark (C.R.V., A.A.R., H.B.)."},{"name":"Department of Cardiology, Hvidovre Hospital, Copenhagen University Hospital, Denmark (C.R.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-3309","authenticated-orcid":true,"given":"Anna","family":"Axelsson Raja","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark (C.R.V., A.A.R., H.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0234-6430","authenticated-orcid":true,"given":"Adam S.","family":"Helms","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor (A.S.H., S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4473-6725","authenticated-orcid":true,"given":"Sara","family":"Saberi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor (A.S.H., S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9669-8495","authenticated-orcid":true,"given":"Anjali T.","family":"Owens","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Pennsylvania, PA (A.T.O., S.M.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-0673","authenticated-orcid":true,"given":"Joseph W.","family":"Rossano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5266-2805","authenticated-orcid":true,"given":"Dominic J.","family":"Abrams","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Genetics, Department of Cardiology, Boston Children\u2019s Hospital &amp; Harvard Medical School, Boston, MA (D.J.A)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4846-7676","authenticated-orcid":true,"given":"Jodie","family":"Ingles","sequence":"additional","affiliation":[{"name":"Genomics and Inherited Disease Program, Garvan Institute of Medical Research and University of New South Wales, Sydney, Australia (J.I.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9966-0329","authenticated-orcid":true,"given":"Belinda","family":"Gray","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health, The University of Sydney, Australia, Department of Cardiology, Royal Prince Alfred Hospital, Sydney, Australia (B.G)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3313-0939","authenticated-orcid":true,"given":"Rachel","family":"Lampert","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (R.L, J.C.S)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1568-9280","authenticated-orcid":true,"given":"John C.","family":"Stendahl","sequence":"additional","affiliation":[{"name":"Department of Medicine, Section of Cardiovascular Medicine, Yale School of Medicine, New Haven, CT (R.L, J.C.S)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6458-5421","authenticated-orcid":true,"given":"Neal K.","family":"Lakdawala","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.L.C, N.K.L., C.Y.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6110-5880","authenticated-orcid":true,"given":"James S.","family":"Ware","sequence":"additional","affiliation":[{"name":"Royal Brompton &amp; Harefield Hospitals, Guy\u2019s and St. Thomas\u2019 NHS Foundation Trust, London, United Kingdom (J.S.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5138-5559","authenticated-orcid":true,"given":"Victoria N.","family":"Parikh","sequence":"additional","affiliation":[{"name":"Center for Inherited Cardiovascular Disease, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA (V.N.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6432-0431","authenticated-orcid":true,"given":"Michelle","family":"Michels","sequence":"additional","affiliation":[{"name":"Cardiovascular Institute, Thoraxcenter, Department of Cardiology, Thoraxcenter, Erasmus Medical Center Rotterdam, the Netherlands (M.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8739-6527","authenticated-orcid":true,"given":"Lia","family":"Crotti","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy (L.C.)."},{"name":"IRCCS, Istituto Auxologico Italiano, Department of Cardiology, San Luca Hospital, Cardiomyopathy Unit, Milan, Italy (L.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4237-576X","authenticated-orcid":true,"given":"Thomas D.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH; Division of Cardiology, The Heart Institute, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH (E.M., T.D.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1751-9266","authenticated-orcid":true,"given":"Iacopo","family":"Olivotto","sequence":"additional","affiliation":[{"name":"Meyer Children\u2019s Hospital IRCCS, Florence, Italy (I.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9802-7188","authenticated-orcid":true,"given":"Sharlene M.","family":"Day","sequence":"additional","affiliation":[{"name":"Division of Cardiology, University of Pennsylvania, PA (A.T.O., S.M.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-7049","authenticated-orcid":true,"given":"Henning","family":"Bundgaard","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Denmark (C.R.V., A.A.R., H.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1748-4340","authenticated-orcid":true,"given":"Brian L.","family":"Claggett","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.L.C, N.K.L., C.Y.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7334-7924","authenticated-orcid":true,"given":"Carolyn Y.","family":"Ho","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Boston, MA (B.L.C, N.K.L., C.Y.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvv025"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2022.1061"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2024.08.011"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.117.033200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.113.000331"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circgen.123.004200"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2017.79"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.116.001620"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1136\/heartjnl-2014-306387"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-018-0039-z"},{"key":"e_1_3_3_13_2","unstructured":"Vissing CR. Comparing clinical course of hypertrophic cardiomyopathy in sarcomere variant carriers and non-carriers. 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