Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents

Figure 1. PRISMA flowchart of the study selection process.

Figure 2. Results of the risk of bias assessment (N = 194 studies) according to the SYRCLE Risk of Bias strategy [203].

Figure 3. The percentage of reviewed experimental protocols used to evaluate the therapeutic efficacy of pharmacological agents according to the therapeutic group/pharmacological class (a) and according to the particular animal model of heart failure (b,c). The minimal percentage of interventions was 0.5.

Figure 4. The contribution of comorbid conditions to HF development indicated by individual animal models. Any alterations in parameters associated with heart failure (Vehicle vs. healthy animals) are given as functions of the baseline body weight (systolic blood pressure, glycemia) in bubble plots; meta-regression lines have been fitted to indicate effect size. Overall active diastolic function (active relaxation) did not significantly correlate with body weight gain (a), or alterations in systolic blood pressure (b); however, it significantly decreased in animals with elevated glucose level (c). In addition, a decrease in passive diastolic function significantly correlated with BW gain (d) and higher glucose levels (f), but not with elevated systolic blood pressure (e). An increase in left ventricular end-diastolic value significantly correlated with BW gain (g) and higher glucose levels (i), but not with elevated systolic blood pressure (h). In HF models, LV hypertrophy insignificantly correlated with animal BW gain (j) or increased glucose levels (l), and more significantly, with SBP elevation (k) (N = 74 studies). Changes in BW (SBP, glycemia) were calculated as differences in the…

Figure 5. The relationship between improvement in particular HF-related parameters by tested medicine agents and baseline LVEF values in Vehicle (animals with induced heart failure). Meta-regression lines have been fitted to indicate effect size. The differences in overall passive diastolic, and fibrosis levels between animals with HF treated with pharmacological agents and those receiving placebo correlated slightly, but non-significantly, with the following: decreased baseline ejection fraction (b,g). The impact of treatment on the normalization of active diastolic function (a), left ventricular end-diastolic value (c), left ventricular end-systolic value (d), pulmonary edema/lung congestion (e), left ventricle hypertrophy (f) was correlated significantly with decreased baseline ejection fraction—LVEF%. (N = 131 studies). The overall diastolic active function was defined by such parameters as dP/dtmin, E/A, tau; and passive stiffness—by LVEDP and EDPVR slope or LVEDP/LVDd ratio. NS—non significant.