{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:50:11Z","timestamp":1784130611488,"version":"3.55.0"},"reference-count":35,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"24","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2022,12,20]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiomegaly caused by left ventricular hypertrophy is a risk factor for development of congestive heart failure, classically associated with decreased systolic and\/or diastolic ventricular function. Less attention has been given to the phenotype of left ventricular hypertrophy with enhanced ventricular function and increased cardiac output, which is potentially associated with high\u2010output heart failure. Lack of recognition may pose diagnostic ambiguity and management complexities.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We sought to systematically characterize high\u2010output cardiac hypertrophy in subjects with Cantu syndrome (CS), caused by gain\u2010of\u2010function variants in\n              <jats:italic>ABCC9<\/jats:italic>\n              , which encodes cardiovascular K\n              <jats:sub>ATP<\/jats:sub>\n              (ATP\u2010sensitive potassium) channel subunits. We studied the cardiovascular phenotype longitudinally in 31 subjects with CS with confirmed\n              <jats:italic>ABCC9<\/jats:italic>\n              variants (median [interquartile range] age 8\u2009years [3\u201332\u2009years], body mass index 19.9 [16.5\u201322.9], 16 male subjects). Subjects with CS presented with significant left ventricular hypertrophy (left ventricular mass index 86.7 [57.7\u2013103.0] g\/m\n              <jats:sup>2<\/jats:sup>\n              in CS, n=30; 26.6 [24.1\u201332.8] g\/m\n              <jats:sup>2<\/jats:sup>\n              in controls, n=17;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001) and low blood pressure (systolic 94.5 [90\u2013103] mm\u2009Hg in CS, n=17; 109 [98\u2013115] mm\u2009Hg in controls, n=17;\n              <jats:italic>P<\/jats:italic>\n              =0.0301; diastolic 60 [56\u201366] mm\u2009Hg in CS, n=17; 69 [65\u201372] mm\u2009Hg in control, n=17;\n              <jats:italic>P<\/jats:italic>\n              =0.0063). Most (21\/31) subjects with CS exhibited eccentric hypertrophy with normal left ventricular wall thickness. Congestive heart failure symptoms were evident in 4 of the 5 subjects with CS aged &gt;40\u2009years on long\u2010term follow\u2010up.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">The data define the natural history of high\u2010output cardiac hypertrophy resulting from decreased systemic vascular resistance in subjects with CS, a defining population for long\u2010term consequences of high\u2010output hypertrophy caused by low systemic vascular resistance, and the potential for progression to high\u2010output heart failure.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.122.027363","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T11:38:14Z","timestamp":1671017894000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["A Unique High\u2010Output Cardiac Hypertrophy Phenotype Arising From Low Systemic Vascular Resistance in Cantu Syndrome"],"prefix":"10.1161","volume":"11","author":[{"given":"Gautam K.","family":"Singh","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Pediatrics Washington University School of Medicine St. Louis MO"},{"name":"Center for the Investigation of Membrane Excitability Diseases (CIMED) Washington University School of Medicine St. Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0859-3854","authenticated-orcid":false,"given":"Conor","family":"McClenaghan","sequence":"additional","affiliation":[{"name":"Center for the Investigation of Membrane Excitability Diseases (CIMED) Washington University School of Medicine St. Louis MO"},{"name":"Department of Cell Biology and Physiology Washington University School of Medicine St. Louis 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MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7425-6322","authenticated-orcid":false,"given":"Dorothy K.","family":"Grange","sequence":"additional","affiliation":[{"name":"Center for the Investigation of Membrane Excitability Diseases (CIMED) Washington University School of Medicine St. Louis MO"},{"name":"Department of Pediatrics, Division of Genetics Washington University School of Medicine St. Louis MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4929-2134","authenticated-orcid":false,"given":"Colin G.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Center for the Investigation of Membrane Excitability Diseases (CIMED) Washington University School of Medicine St. Louis MO"},{"name":"Department of Cell Biology and Physiology Washington University School of Medicine St. Louis 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