Heart Failure with Reduced Ejection Fraction (HFrEF)

(A) Representative ECG waveforms; (B) Body weight data; (C) Survival rate following surgery. Deaths typically occurred within 7 days post LAD surgery.

(A) Parasternal B-/M-mode images. (B) Echo data: Structural (IVSd/s, LVPWd/s), dimensional (LVIDd/s, LVEDV/ESV), and functional (EF, FS, SV, CO) parameters. The LAD group shows anterior wall thinning, LV dilation, and systolic dysfunction.

(A) Parasternal B-/M-mode images. (B) Echo data: Structural (IVSd/s, LVPWd/s), dimensional (LVIDd/s, LVEDV/ESV), and functional (EF, FS, SV, CO) parameters. The LAD group shows anterior wall thinning, LV dilation, and systolic dysfunction.

(A) Parasternal B-/M-mode images. (B) Echo data shows ventricular dilation, systolic dysfunction (reduced EF/FS), and arrhythmias. Parameters: wall thickness (IVSd/s, LVPWd/s), dimensions (LVIDd/s, LVEDV/ESV), and function (SV, CO).

(A) Gross morphology shows ventricular wall thinning and LV dilation. Heart weight/body weight (HW/BW) and HW/tibia length (HW/TL) ratios are elevated. (B) TTC staining: white indicates infarct region. (C) Masson's trichrome blue indicates fibrotic scars.

Mice received Entresto (Sac/Val) for 2 weeks post-modeling. Treatment slowed HF progression, primarily by reducing LV dilation (LVIDd/s, LVEDV, LVESV) and improving systolic function (EF, FS).

Entresto (Sac/Val) treatment demonstrated a cardioprotective effect, significantly reducing the infarct area. Quantification was performed using the midline method on multi-sectional Masson's trichrome-stained images (shown, apical to base), which demarcate fibrotic scars (blue).

Sham vs. MIRI groups at baseline (0h) and 24h post-op. MIRI shows significantly impaired systolic function (↓EF, FS, SV, CO), ventricular dilation (↑LVID;s/d, LVEDV, LVESV), and altered wall thickness at 24h (*p<0.05, **p<0.01).

Echo panel comparing Sham (●) and MIRI (◆) groups at baseline and 7 days post-op. MIRI shows significant systolic dysfunction (↓EF, FS, CO), ventricular dilation (↑LVEDV, LVESV, LVID;d), and altered wall thickness (IVS;d, LVPW;d) vs. Sham at 7dpa (ns, *, ,*). Data: mean±SEM.

Transverse heart sections (base to apex) from Sham and MIRI (14 days post-op) mice. Sham myocardium is uniformly brick-red (viable). MIRI hearts show extensive pale, unstained areas across sections, indicating transmural infarction.

After 28G TAC surgery: 2-3 weeks shows compensatory ventricular hypertrophy (↑IVSd/s, LVPWd/s, LV dMass). By 4 weeks, ventricular dilation (↑LVIDd/s, LVEDV/ESV) and systolic dysfunction (↓EF, SV) develop, worsening over time.

(A) HW/BW and HW/TL ratios are significantly increased. (B) Coronal sections show enlarged hearts, thickened walls, dilated chambers, and marked fibrosis (replacement, perivascular, interstitial).

After 6-week Entresto (Sac/Val) treatment starting 4 weeks post-TAC (28G), phenotypes of ventricular dilation (↓LVESV) and systolic dysfunction (↑EF) were reversed, with a slight reduction in wall hypertrophy (trend in IVSd/s, LV dMass).

(A) Representative ECG waveforms and (B) statistical analysis from mice treated with ISO (30/50 mpk, osmotic pump). Increasing ISO concentration significantly prolonged the QT interval and elevated the ST segment and T wave.

Echocardiography shows that increasing ISO concentration elevates LV mass (indicating hypertrophy/edema) while significantly decreasing EF% and FS%, demonstrating impaired systolic function and pump failure.

Masson staining reveals 30 mpk ISO causes compensatory ventricular wall thickening. The 50 mpk dose leads to extensive cardiomyocyte death, resulting in wall thinning, ventricular cavity enlargement, and increased fibrosis.