Principal strain changes precede ventricular wall thinning during transition to heart failure in a mouse model of dilated cardiomyopathy

This study was performed to elucidate the relation between in viva measurements of two-dimensional principal strains and the progression of left ventricle (LV) wall thinning during development of dilated cardiomyopathy in the protein kinase C-[epsilon] (PKC-[epsilon]) transgenic (TG) overexpressing mouse heart. Principal two-dimensional strains, E1 and E2, were determined in the LV wall of the anesthetized mouse using cardiac MRI tagging at 14.1 T. PKC-[epsilon] TG provided a model of pure dilated cardiomyopathy without evidence of hypertrophy (PKC-[epsilon] TG, n = 6). Ejection fraction, wall thickness, and principal strains were determined at 1-mo intervals in hearts of PKC-[epsilon] TG vs. age-matched, nontransgenic mice (NTG, n = 5) from age 6 to 13 mo. Through the study, PKC-[epsilon] TG displayed lower ejection fraction than NTG. At 7 mo, average principal strain E1 in PKC-[epsilon] TG hearts was lower compared with NTG (PKC-[espilon] TG = 0.14 [+ or -] 0.03, NTG = 0.19 [+ or -] 0.03, P < 0.05). The greatest reductions in regional E1 occurred in the lateral segments. The principal strain E2 did not change significantly in either group. At 9 mo, LV wall thinning occurred in PKC-[epsilon] TG mice (P < 0.01 vs. 8 mo) to 21% below values in NTG (P < 0.001). Average E1 strain diverged between PKC-[epsilon] TG and NTG hearts by 25-43%. These E1 changes preceded LV wall thinning and predated the eventual transition from a compensated circumstance to the dilated phenotype. The findings indicate a near step function in E1 depression that precedes the onset of LV wall thinning and suggest El as a prognostic indicator of dilated cardiomyopathy. protein kinase C; magnetic resonance imaging; ventricular function