Sympathetic drive stimulating diastolic dysfunction?

Abstract

Diastolic heart failure accounts for half of the heart failure population and its pathophysiology remains an area of active research. The renin angiotensin and aldosterone axis has been the focus of clinical trials to treat patients with heart failure with preserved ejection fraction, however with limited yield in terms of clinical success. Sympathetic activity has been considered a plausible cause for the molecular changes that lead to diastolic dysfunction. Based on this understanding the study by Gimelli et al uses MIBG to evaluate for association between diastolic dysfunction and sympathetic denervation. The results of this study set the stage for a follow up study for evaluation of sympathetic denervation in isolated diastolic dysfunction

Heart rate variability is associated with left ventricular systolic, diastolic function and incident heart failure in the general population

“…HRV has mostly been associated with adverse outcomes in patients with reduced LVEF, establishing a link between autonomic derangement and systolic dysfunction. More recently, evidence on the role of increased sympathetic activity on the development of diastolic dysfunction in HF has emerged [ 7 – 9 ]. Increase in collagen and elastic fibers with aging can result in pathologic changes in the sinoatrial node, resulting in sinus node dysfunction [ 25 , 26 ].…”

“…Increase in collagen and elastic fibers with aging can result in pathologic changes in the sinoatrial node, resulting in sinus node dysfunction [ 25 , 26 ]. Collagen over-expression is linked to diastolic dysfunction in HF with preserved LVEF [ 7 ]. But these associations have not been extensively studied in the general population before.…”

“…HRV has mostly been associated with adverse outcomes in HF patients with reduced left ventricular ejection fraction (LVEF), establishing a link between autonomic derangement and systolic dysfunction. More recently, evidence on the role of increased sympathetic activity on the development of diastolic dysfunction in HF has emerged [ 7 – 9 ]. Inconclusive studies for therapies in patients with HF with preserved LVEF highlight the need for a better understanding of the pathophysiology of the sympathetic nervous system in LV function [ 7 ].…”

“…More recently, evidence on the role of increased sympathetic activity on the development of diastolic dysfunction in HF has emerged [ 7 – 9 ]. Inconclusive studies for therapies in patients with HF with preserved LVEF highlight the need for a better understanding of the pathophysiology of the sympathetic nervous system in LV function [ 7 ]. Despite few studies showing an association between HRV and incident HF in the elderly [ 2 ] or postmenopausal women [ 10 ], HRV before the onset of clinical symptoms of HF has not been extensively studied and data on the link between HRV and systolic and diastolic function prior to onset of HF are sparse.…”

Predominance of Heart Failure With Preserved Ejection Fraction in Postmenopausal Women: Intra- and Extra-Cardiomyocyte Maladaptive Alterations Scaffolded by Estrogen Deficiency

“…However, hyperactivity of the sympathetic nervous system (SNS) during stress upregulates circulating catecholamines, which overstimulates βARs, causing the receptors to become dysfunctional, leading to their desensitization and downregulation ( Adzika et al, 2019 ). Unfortunately, the calcium handling proteins, such as the L-type calcium channel (LTCC), which ensure homeostatic levels of Ca 2+ in cardiomyocytes for proper cardiac contractions, are downstream of the βARs ( Aikawa et al, 2017 ; Ahmad and Gerson, 2018 ; Morimoto et al, 2020 ). Hence, the dysfunctionalities of the receptors during chronic catecholamine stress disrupts the intracellular Ca 2+ and cardiac contractility.…”