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.

Highlights

  • Over the last two decades, cardiovascular (CV) mortality has reduced in high-income countries [5] due to the implementation of protective actions to decrease the impact of coronary artery disease (CAD) and heart failure (HF)

  • sudden cardiac death (SCD) risk is more significant in male than in female patients, and the risk growths according to age, mainly due to the increased prevalence of CAD in the aged population [15]

  • Left ventricular ejection fraction (LVEF) is the single predictor that has reliably presented a relationship with higher risk of SCD in subjects presenting with myocardial infarction (MI) and left ventricular (LV) dysfunction [21,22]

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Summary

Epidemiology of Sudden Cardiac Death

Cardiovascular diseases (CVDs) have been considered the most predominant causes of death and one of the most critical public health issues worldwide [1]. Over the last two decades, cardiovascular (CV) mortality has reduced in high-income countries [5] due to the implementation of protective actions to decrease the impact of coronary artery disease (CAD) and heart failure (HF). In spite of these promising outcomes, CVDs provoke ~17 million deaths per year globally of which ~25% are due to sudden cardiac death (SCD) [6]. Recent recommendations for managing ventricular arrhythmias (VAs) report that SCD in the young has an expected incidence of 0.46–3.7 episodes per 100,000 individual years [16,17,18], equivalent to a ~1,100–9,000 deaths in Europe, and from 800 to 6200 deaths every year in the US [19]

Treatment Indication
Prognosis
Pathophysiology of HF and Sympathetic Nerve Activity Synonym
Findings
Relevant Diagnostic Approaches
Full Text
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