Heart Failure Syndrome With Preserved Ejection Fraction Is a Metabolic Cluster of Non-resolving Inflammation in Obesity

Figures

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  Figure 1. Evolution of one-dimensional to multidimensional view of cardiovascular disease and heart failure. (A) One-dimensional view of heart failure (HF). Classically, HF emerges in a homogenous population based on geometry, structure, and function. The progress from being a phenotypically normal to abnormal structure accompanied with a decrease or increase in the (cardiomyocyte) heart size due to eccentric or concentric remodeling or following ischemic injury with dilation of the chambers and wall-thinning effect. HF specifically with preserved ejection fraction evolves from one-dimensional view to multidimensional view. (B) Metabolic defects directed the multidimensional view of heart failure with preserved ejection fraction (HFpEF). Heterogeneous metabolic comorbidities are a primary confounder in HFpEF patients like obesity, hypertension, kidney dysfunction, diabetes, aging, etc. The complexity of the HFpEF syndrome resulted in cardiometabolic and cardiorenal defects with signs of suboptimal inflammation without any current treatment.

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  Figure 2. Resolvin D1 and lipoxin receptor-deficient mice (FPR2/ALXKO) complement the criteria of HFpEF with profound age-associated endothelial dysfunction and inflammation in the spleen, heart, and kidneys with signs of chronic inflammation. (A) Left panel indicates the heterogeneous, multidimensional, and multiorgan metabolic defects that contribute to HFpEF. (B) Right panel indicates the dysfunction of the resolution receptor FPR2/ALX in mice that develops spontaneous obesity with diastolic dysfunction along with limited changes in systolic function when obesity is superimposed on aging as signs of preserved ejection fraction. Suboptimal inflammation indicated with profound activation of IL1β gene expression in the heart, kidneys, and lungs in FPR2/ALXKO mice exemplifies the age-associated cardiac strain dysfunction, myocardium dissynchronicity, and amplified inflammation. *p < 0.05 compared to control WT group.

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  Figure 3. Fundamental and lifestyle-associated prime factors that control inflammation (left arm of figure) in contrast to risk factors that drive suboptimal inflammation in HFpEF and integration with lifestyle-associated molecular patterns (LAMPs). The main four aspects of daily life to consider as prime strategy for prevention of HFpEF (diet/nutrient, sleep/wake up rhythm, exercise, and choice of active life and limited sedentary lifestyle). Adoption of optimal age-related lifestyle would be helpful to balance the genesis of LAMPs in cardiovascular disease that will help to limit the progression to heart failure.