a,b, M-mode echocardiography (a) reveals that left-ventricular fractional shortening (LVFS) percentage (b), a measure of cardiac function, is decreased in TV-Dhet mice compared to WT and VclVFS/+ mice at 58 weeks. c–f, Trichrome sections of mouse hearts (c,d) and echocardiographic measurements of left ventricular internal dimension in diastole (LVIDd; e) reveal that TV-Dhet mouse hearts are not significantly dilated compared to WT; in addition, the heart-to-body-weight ratios (HW:BW; f) do not differ significantly between genotypes at 58 weeks. In b,e and f, filled and open squares indicate 15 and 58 week timepoints, respectively. g,h, M-mode echocardiography of pre-TAC (14–16 weeks) and (g) post-TAC (one week following TAC surgery) mouse hearts reveals that the LVFS (h) is significantly reduced in TV-Dhet post-TAC mice when compared with WT post-TAC mice. i–k, Trichrome sections and LVIDd measurements of post-TAC mouse hearts show increased chamber size in TV-Dhet mice compared with WT mice. l, Post-TAC heart-to-body-weight ratios are also increased in mice with TEK and/or VFS variants compared to WT mice. Data are presented as interquartile range (box), around the mean (horizontal line), with whiskers representing the minimum and maximum of the dataset, with the individual data points superimposed. *P < 0.05; **P < 0.01; ***P < 0.001; n.s., no statistically significant comparisons; one-sided ANOVA with Tukey multiple correction test alpha. n, number of biologically independent mice of each genotype used for each study. Scale bars, 2 mm. The complete echocardiography data are available in Supplementary Tables 6 and 7.