**4. Influence of ANS in heart failure and myocardial infarction**

Besides electrical abnormalities, ANS also correlates with ischemic heart disease. Following a transmural myocardial infarction (MI), sympathetic fibers within the scar become denervated and die. However, denervation also occurs in the noninfarcted sites distal to the infarction early after occlusion, resulting in a neurotransmission disruption, nerve sprouting, and denervation supersensitivity even in the viable myocardium cells. Not all sites are denervated equally, this disruption leads to a heterogeneous change of effective refractory period (ERP). Together with decreased protection from vagal denervation, this leads to ventricular arrhythmias [4].

As with heart failure, myocardial dysfunction caused by cardiac insult activates neurohormonal mechanisms, including activation of the sympathetic system and the renin-angiotensin-aldosterone system (RAAS) axis. Increased activation of the sympathetic system causes an increase in NE delivery to myocardial cells. High local catecholamine level leads to ventricular hypertrophy and increase susceptibility to arrhythmia, which worsens the heart's function and, in turn, further increases sympathetic tone [15]. This activation is initially essential to compensate for the weakened myocardial function; however, in the long term, this activation leads to further deterioration of cardiac function, worsening heart failure, and cardiac

decompensation. Besides sympathetic activation, there has been evidence of reduced parasympathetic function, which further worsens heart failure. Heart failure can also cause denervation, creating nerve sprouting and electrical remodeling, leading to ventricular arrhythmia and sudden cardiac death [4, 16].
