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New Approaches in the Management of Sudden Cardiac Death in Patients with Heart Failure—Targeting the Sympathetic Nervous System

1
Dobney Hypertension Cenre, School of Medicine—Royal Perth Hospital Unit, Faculty of Medicine, Dentistry & Health Sciences, The University of Western Australia Level 3, MRF Building, Rear 50 Murray St, Perth 6000, MDBP: M570, Australia
2
Cardiology Division, Department of Medicine, Universidade Federal Fluminense, Niterói, Rio de Janeiro 24033-900, Brazil
3
Harry Perkins Institute of Medical Research and Fiona Stanley Hospital, The University of Western Australia, Perth 6150, Australia
4
Departments of Cardiology and Nephrology, Royal Perth Hospital, Perth 6000, Australia
5
Neurovascular Hypertension & Kidney Disease Laboratory, Baker Heart and Diabetes Institute, Melbourne 3004, Australia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(10), 2430; https://doi.org/10.3390/ijms20102430
Received: 18 April 2019 / Revised: 10 May 2019 / Accepted: 12 May 2019 / Published: 16 May 2019
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Abstract

Cardiovascular diseases (CVDs) have been considered the most predominant cause of death and one of the most critical public health issues worldwide. In the past two decades, cardiovascular (CV) mortality has declined in high-income countries owing to preventive measures that resulted in the reduced burden of coronary artery disease (CAD) and heart failure (HF). In spite of these promising results, CVDs are responsible for ~17 million deaths per year globally with ~25% of these attributable to sudden cardiac death (SCD). Pre-clinical data demonstrated that renal denervation (RDN) decreases sympathetic activation as evaluated by decreased renal catecholamine concentrations. RDN is successful in reducing ventricular arrhythmias (VAs) triggering and its outcome was not found inferior to metoprolol in rat myocardial infarction model. Registry clinical data also suggest an advantageous effect of RDN to prevent VAs in HF patients and electrical storm. An in-depth investigation of how RDN, a minimally invasive and safe method, reduces the burden of HF is urgently needed. Myocardial systolic dysfunction is correlated to neuro-hormonal overactivity as a compensatory mechanism to keep cardiac output in the face of declining cardiac function. Sympathetic nervous system (SNS) overactivity is supported by a rise in plasma noradrenaline (NA) and adrenaline levels, raised central sympathetic outflow, and increased organ-specific spillover of NA into plasma. Cardiac NA spillover in untreated HF individuals can reach ~50-fold higher levels compared to those of healthy individuals under maximal exercise conditions. Increased sympathetic outflow to the renal vascular bed can contribute to the anomalies of renal function commonly associated with HF and feed into a vicious cycle of elevated BP, the progression of renal disease and worsening HF. Increased sympathetic activity, amongst other factors, contribute to the progress of cardiac arrhythmias, which can lead to SCD due to sustained ventricular tachycardia. Targeted therapies to avoid these detrimental consequences comprise antiarrhythmic drugs, surgical resection, endocardial catheter ablation and use of the implantable electronic cardiac devices. Analogous NA agents have been reported for single photon-emission-computed-tomography (SPECT) scans usage, specially the 123I-metaiodobenzylguanidine (123I-MIBG). Currently, HF prognosis assessment has been improved by this tool. Nevertheless, this radiotracer is costly, which makes the use of this diagnostic method limited. Comparatively, positron-emission-tomography (PET) overshadows SPECT imaging, because of its increased spatial definition and broader reckonable methodologies. Numerous ANS radiotracers have been created for cardiac PET imaging. However, so far, [11C]-meta-hydroxyephedrine (HED) has been the most significant PET radiotracer used in the clinical scenario. Growing data has shown the usefulness of [11C]-HED in important clinical situations, such as predicting lethal arrhythmias, SCD, and all-cause of mortality in reduced ejection fraction HF patients. In this article, we discussed the role and relevance of novel tools targeting the SNS, such as the [11C]-HED PET cardiac imaging and RDN to manage patients under of SCD risk. View Full-Text
Keywords: heart failure; positron emission tomography; renal denervation; sudden cardiac death; sympathetic nervous system; ventricular arrhythmias; hypertension heart failure; positron emission tomography; renal denervation; sudden cardiac death; sympathetic nervous system; ventricular arrhythmias; hypertension
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Kiuchi, M.G.; Nolde, J.M.; Villacorta, H.; Carnagarin, R.; Chan, J. .-Y.; Lugo-Gavidia, L.M.; Ho, J.K.; Matthews, V.B.; Dwivedi, G.; Schlaich, M.P. New Approaches in the Management of Sudden Cardiac Death in Patients with Heart Failure—Targeting the Sympathetic Nervous System. Int. J. Mol. Sci. 2019, 20, 2430.

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