EXPRESSION OF CONCERN: Cardiomyopathy characterizing and heart failure risk predicting by echocardiography and pathoanatomy in aged male mice

Figures

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  FIGURE 1. Representative echocardiographic images, study protocol, and the 15‐month survival. (a) Echocardiographic short‐axis left ventricular (LV) 2D image‐guided M‐mode traces and the Doppler aortic flow from non‐TG and TG mice. LVDd and LVDs, LV dimension at diastole and systole; h, wall thickness; AVF, aortic flow velocity; ET, ejection time. (b) Diagram depicting the study protocol. Note that all nTG and β2‐TG male mice entering into this study were 12 months old. (c) Kaplan–Meier survival curves of nTG and TG mice. Animals were monitored for a 3‐month period, that is, 12–15 months of age. The survival difference between nTG and TG groups was highly significant (p < 0.0001).

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  FIGURE 2. Cardiomyopathy phenotypes of β2‐AR transgenic mice. (a) Images of hearts and lungs of nTG and TG mice showing the enlarged heart with a thrombus in the left atrium and chronically congested lungs of TG mouse. (b) Hearts (Masson trichrome stain) from TG mice found dead of HF showing cardiomegaly, thinning of left ventricular (LV) walls, organic atrial thrombus (open arrows), patches of myocardial fibrotic scars (→), and the enlarged right ventricle (RV). (c) Histological images (H&E staining) of the enlarged left atrium containing organized thrombi (open arrows) from TG mice. (d) Histological images of lungs (H&E staining) of nTG and TG mice showing in TG mice signs indicating chronic pulmonary congestion, including thickening of alveolar walls, regional cellular proliferation (*), and accumulation of fluid and blood cells within alveolar space or microbronchial tubes (open arrows).

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  FIGURE 3. Histopathology of β2‐AR TG mouse hearts. (a) Histological images of the left ventricle (LV) showing cardiomyocyte hypertrophy (H&E staining) and patches or interstitial myocardial fibrosis (Masson trichrome stain). (b) Quantitative data of cardiomyocyte cross‐sectional area (CSA) or collagen‐positive stained area per view field from nTG (n = 9) and TG (n = 49) groups. Results are presented as individual data points plus mean ± SD. The between‐group differences for both parameters were highly significant (p < 0.0001).

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  FIGURE 4. Correlations between organ weights and differences in the survival or heart failure (HF) incidence in transgenic (TG) mice grouped by fractional shortening (FS) × (h/d) tertiles. (a) Correlation coefficients depicting positive correlations between weights of atria, lungs, and the right ventricle (RV) in TG mice (n = 76), whereas organ weights negatively correlated with FS × (h/d) index. All correlations are highly significant (p < 0.001). (b) Survival or HF incidence in TG mice of FS × (h/d) tertile groups (n = 25–26 per group). Note that mice of the low‐tertile group had very poor survival largely due to a higher incidence of HF and HF death relative to median‐ and high‐tertile groups.