Sympathetic Activation and Arrhythmogenesis after Myocardial Infarction: Where Do We Stand?

Abstract

Myocardial infarction often leads to progressive structural and electrophysiologic remodeling of the left ventricle. Despite the widespread use of β-adrenergic blockade and implantable defibrillators, morbidity and mortality from chronic-phase ventricular tachyarrhythmias remains high, calling for further investigation on the underlying pathophysiology. Histological and functional studies have demonstrated extensive alterations of sympathetic nerve endings at the peri-infarct area and flow-innervation mismatches that create a highly arrhythmogenic milieu. Such accumulated evidence, along with the previously well-documented autonomic dysfunction as an important contributing factor, has stirred intense research interest for pharmacologic and non-pharmacologic neuromodulation in post-infarction heart failure. In this regard, aldosterone inhibitors, sacubitril/valsartan and sodium-glucose cotransporter type 2 inhibitors have shown antiarrhythmic effects. Non-pharmacologic modalities, currently tested in pre-clinical and clinical trials, include transcutaneous vagal stimulation, stellate ganglion modulation and renal sympathetic denervation. In this review, we provide insights on the pathophysiology of ventricular arrhythmogenesis post-myocardial infarction, focusing on sympathetic activation.

Heart Rate Variability and Cardiovascular Fitness: What We Know so Far

“…However, the chronic character of cardiovascular disease continuously hyperactivates the sympathetic autonomic component, causing long-term impairments. [20][21][22][23] Concomitantly, the literature reveals an increase in stimulation of the renin-angiotensin-aldosterone system, which causes an increase in the concentration angiotensin II and release of reactive oxygen species, favoring oxidative stress and endothelial dysfunction and providing positive feedback on increased SNA. 19,21,24,25 This reorganization corroborates the global reduction in HRV (Figure 1).…”

Research Advances of Injectable Functional Hydrogel Materials in the Treatment of Myocardial Infarction

“…As the infarcted area heals, a new myocardial matrix is gradually established, scarring is formed, the ventricle dilates to maintain cardiac output and cardiac repair transitions to maturity. Healing of the infarct is intertwined with the geometric remodeling of the chamber, with dramatic changes in ventricular geometry, dilation of the chamber, and thinning of the infarcted portion, leading to ventricular remodeling [ 28 ].…”

Stellate Ganglia and Cardiac Sympathetic Overactivation in Heart Failure

“…Stellate ganglion stimulation, including left, right, or bilateral stellate ganglion stimulation, produces distinct patterns of cardiac myocyte repolarization in the normal porcine heart, evaluated by the analysis of epicardial and endocardial electrograms, whereas marked dispersion of cardiac myocyte repolarization does not occur when exogenous norepinephrine is infused (circulating norepinephrine) [ 142 ]. From these data, it has been demonstrated that stellate-ganglion-stimulated dispersion of cardiac myocyte repolarization is highly arrhythmogenic, compared to the more uniform changes in cardiac myocyte repolarization triggered by circulating norepinephrine [ 142 , 143 ]. As described above, cardiac sympathetic denervation, a key approach to the current therapy of HF, highlights the role of cardiac sympathetic remodeling in cardiac sympathetic overactivation, malignant arrhythmias, and cardiac sudden death in HF [ 38 , 42 , 43 ].…”