Targeting aortic elasticity: A promising therapeutic avenue in congestive heart failure and cardiac pumping disorders

• Author Details:   
• Abhilash Santhosh Menon ^*
• Kailash Kumar

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Heart failure (HF), including both preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF) phenotypes, remains a growing global health crisis, affecting over 64 million individuals and contributing significantly to morbidity, mortality, and healthcare burden. Although contemporary HF therapies focus largely on myocardial function and neurohormonal modulation, accumulating evidence suggests that the vascular system-particularly the elastic properties of the aorta-plays a crucial and modifiable role in disease progression. Aortic elasticity is central to maintaining optimal ventriculo-arterial coupling, damping pulsatile load, and ensuring coronary perfusion during diastole. However, age-related changes, hypertension, diabetes, and metabolic syndrome promote vascular stiffening, which increases left ventricular (LV) afterload, exacerbates systolic dysfunction, and impairs diastolic relaxation.
Aortic stiffness, quantified by pulse wave velocity (PWV), has emerged as an independent predictor of cardiovascular events and HF hospitalization. Pharmacologic agents that preserve or restore aortic compliance-including RAAS blockers, calcium channel blockers, statins, SGLT2 inhibitors, soluble guanylate cyclase stimulators, AGE cross-link breakers, and GLP-1 receptor agonists-have demonstrated encouraging vascular benefits in both preclinical and clinical studies. Novel therapies targeting extracellular matrix remodeling, endothelial dysfunction, and oxidative stress hold promise in transforming our approach to HF therapy by shifting focus beyond cardiac contractility to vascular health.
This narrative review comprehensively examines the physiology of aortic elasticity, the pathophysiologic mechanisms linking vascular stiffness to heart failure, and therapeutic strategies aimed at reversing or mitigating arterial stiffening. We highlight key trials, mechanistic insights, and potential research directions to promote integration of vascular-targeted therapies in HF management. Emphasizing aortic compliance as a therapeutic goal may help close the current gap in HFpEF treatment, improve long-term outcomes, and redefine cardiovascular care paradigms.