Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 May 15;8(5):57.
doi: 10.3390/jcdd8050057.

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

Konstantinos C Zekios  1   2 , Eleni-Taxiarchia Mouchtouri  2   3 , Panagiotis Lekkas  3 , Dimitrios N Nikas  1 , Theofilos M Kolettis  1   2   3
Affiliations
Review

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

Konstantinos C Zekios et al. J Cardiovasc Dev Dis. .

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.

Keywords: myocardial infarction; sympathetic activation; ventricular tachyarrhythmias.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Sympathetic activation post-infarction triggers delayed afterdepolarizations and polymorphic ventricular tachycardia; and (A) facilitates reentrant mechanisms via (B) altering the conduction properties of the peri-infarct tissue.
Figure 2
Figure 2
The normal sympathetic nerve distribution (upper panel) is replaced by sympathetic nerve remodeling post-infarct (lower panel), characterized by areas of increased (red circle) sympathetic nerve density, mediated by inflammatory responses; decreased (green circle) nerve density also occurs, characterized by norepinephrine overspill, activating β1 and β2 adrenergic receptors.
Figure 3
Figure 3
Transcutaneous vagal stimulation, (1) stellate ganglion modulation, and (2) renal sympathetic denervation are (3) currently investigated in nonpharmacologic autonomic modulation post-infarction.
See this image and copyright information in PMC

References

    1. Jenca D., Melenovsky V., Stehlik J., Stanek V., Kettner J., Kautzner J., Adamkova V., Wohlfahrt P. Heart failure after myocardial infarction: Incidence and predictors. ESC Heart Fail. 2021;8:222–237. doi: 10.1002/ehf2.13144. - DOI - PMC - PubMed
    1. Waks J.W., Buxton A.E. Risk stratification for sudden cardiac death after myocardial infarction. Annu. Rev. Med. 2018;69:147–164. doi: 10.1146/annurev-med-041316-090046. - DOI - PubMed
    1. Turitto G., El-Sherif N. Cardiac resynchronization therapy: A review of proarrhythmic and antiarrhythmic mechanisms. Pacing Clin. Electrophysiol. 2007;30:115–122. doi: 10.1111/j.1540-8159.2007.00585.x. - DOI - PubMed
    1. Gatzoulis K.A., Sideris A., Kanoupakis E., Sideris S., Nikolaou N., Antoniou C.K., Kolettis T.M. Arrhythmic risk stratification in heart failure: Time for the next step? Ann. Noninvasive Electrocardiol. 2017;22:e12430. doi: 10.1111/anec.12430. - DOI - PMC - PubMed
    1. Paranskaya L., Akin I., Chatterjee T., Ritz A., Paranski P., Rehders T., Ince H., Schneider H., Nienaber C.A., Bansch D. Ventricular tachycardia and sudden death after primary PCI-reperfusion therapy: Impact on primary prevention of sudden cardiac death. Herzschrittmacherther. Elektrophysiol. 2011;22:243–248. doi: 10.1007/s00399-011-0160-z. - DOI - PubMed

LinkOut - more resources