{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:44:44Z","timestamp":1790318684547,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2015,11,18]],"date-time":"2015-11-18T00:00:00Z","timestamp":1447804800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000145","name":"Alberta Innovates - Health Solutions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000145","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004411","name":"Heart and Stroke Foundation of Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The molecular and cellular determinants of ventricular tachycardia (<jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content>) in patients with nonischaemic dilated cardiomyopathy (<jats:styled-content style=\"fixed-case\">NIDCM<\/jats:styled-content>) remain poorly defined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>We examined 20 <jats:styled-content style=\"fixed-case\">NIDCM<\/jats:styled-content> hearts where <jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content> was reported in 10 cases and <jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content> was absent in 10 cases, using a double\u2010blinded case\u2013control study design, and assessed the molecular and cellular features of the adverse myocardial remodelling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Explanted hearts from patients with <jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content> showed greater hypertrophic changes based on cardiomyocyte cross\u2010sectional area and expression of disease markers, and increased myocardial fibrosis which extended into the left ventricular and right ventricular outflow tract regions. The <jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content> group also showed increased oxidative stress with reduction in reduced glutathione levels. Connexin 43 levels in the intercalated discs showed increased levels in the <jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content> group with reduced phosphorylation. Microarray <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> analysis of gene expression in the left ventricle (<jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content>) free wall revealed several families of genes which were differentially upregulated or downregulated in hearts with documented <jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content> compared to hearts without <jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content>. Notably, we identified reduced expression of the Ca<jats:sup>2+<\/jats:sup>\u2010activated K<jats:sup>+<\/jats:sup> channel (<jats:styled-content style=\"fixed-case\">KCNN<\/jats:styled-content>2) and increased expression of the transient receptor potential cation channel 7 (<jats:styled-content style=\"fixed-case\">TRPM<\/jats:styled-content>7) and intracellular chloride channel 3. Western blot analysis on <jats:styled-content style=\"fixed-case\">LV<\/jats:styled-content> membrane fractions showed reduced <jats:styled-content style=\"fixed-case\">KCNN<\/jats:styled-content>2 and increased <jats:styled-content style=\"fixed-case\">TRPM<\/jats:styled-content>7 levels in hearts with <jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In explanted human hearts with <jats:styled-content style=\"fixed-case\">NIDCM<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> VT<\/jats:styled-content> is associated with greater hypertrophy, oxidative stress and myocardial fibrosis, differential gene expression, and altered ion channel levels indicative of a distinctive adverse myocardial remodelling process associated with clinically significant <jats:styled-content style=\"fixed-case\">VT<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.12549","type":"journal-article","created":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T17:38:41Z","timestamp":1444239521000},"page":"1286-1296","source":"Crossref","is-referenced-by-count":33,"title":["Determinants of ventricular arrhythmias in human explanted hearts with dilated cardiomyopathy"],"prefix":"10.1111","volume":"45","author":[{"given":"Nirmal","family":"Parajuli","sequence":"first","affiliation":[{"name":"Division of Cardiology Department of Medicine University of Alberta Edmonton Canada"},{"name":"Mazankowski Alberta Heart Institute University of Alberta Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Valtuille","sequence":"additional","affiliation":[{"name":"Division of Cardiology Department of Medicine University of Alberta Edmonton Canada"},{"name":"Mazankowski Alberta Heart Institute University of Alberta Edmonton 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