Assessment of Cardiac Sympathetic Innervation in Heart Failure and Lethal Arrhythmias: Therapeutic and Prognostic Implications

Abstract

Sympathetic nerve activities have pivotal roles in pathophysiology and prognosis in patients with heart failure. Among the various available techniques for the analysis of sympathetic nerve function, cardiac neuroimaging with a norepinephrine analogue is a noninvasive, specific and powerful modality that enables in vivo assessment of cardiac sympathetic innervation and activity and has demonstrated pathophysiological alterations at pre-synaptic nerve terminals and their clinical implications. Impaired cardiac metaiodobenzylguanidine (MIBG) activity and, conversely, increased systemic sympathetic function drive closely correlate with clinical outcomes. Cardiac MIBG activities have independent but incremental prognostic values in combination with known clinical determinants in patients with heart failure. Systemic inhibition of sympathetic drive and the rennin-angiotension-aldosterone system can improve cardiac MIBG activity and kinetics together with functional improvement in heart failure patients. Prognostic efficacy of contemporary drug treatment is, however, likely to depend on the severity of the impairment of cardiac MIBG activity. Patients who have impaired cardiac MIBG activity with blunted heart rate variability, an elevated brain natriuretic peptide level or LV dysfunction are likely to have appropriate discharges of an implantable cardioverter defibrillator. Thus, cardiac neuroimaging could enable appropriate selection of patients at greater risk for lethal outcomes, who can probably benefit most from pharmacological and invasive strategies.

Cardiac Mortality Assessment Improved by Evaluation of Cardiac Sympathetic Nerve Activity in Combination with Hemoglobin and Kidney Function in Chronic Heart Failure Patients

“…123 I-MIBG washout kinetics from the heart were calculated as washout rate using a polar-map technique with tomographic data because of the elimination of background activity. The high reproducibility of the quantitative method was confirmed in our previous studies (7)(8)(9).…”

“…Increased norepinephrine spillover, decreased norepinephrine content at nerve endings, and sympathetic denervation in failing hearts can be revealed as an increase in 123 I-MIBG washout rate from the heart or a decrease in 123 I-MIBG activity. Several studies have demonstrated that abnormal 123 I-MIBG kinetics are associated with lethal cardiac events in patients with moderate to severe heart failure (6)(7)(8)(9)(10)(11).…”

Synergistic prognostic values of cardiac sympathetic innervation with left ventricular hypertrophy and left atrial size in heart failure patients without reduced left ventricular ejection fraction: a cohort study

“…[8][9][10][11][12][13] Impaired cardiac sympathetic innervation quantified using cardiac MIBG activity was not only a significant independent predictor of cardiac events but also was additively related to adverse outcomes together with LA size. These findings indicate critical roles of combined use of these quantitative markers on better identification of HF patients with preserved LVEF at increased risk.…”

“…On the other hand, cardiac neuroimaging with idoin-123 metaiodobenzylguanidine (MIBG) has demonstrated that impairment of cardiac sympathetic innervation is closely relate to unfavourable clinical outcomes in HF patients with reduced systolic function not only independently of but also together with LVEF, New York Heart Association functional class, plasma brain natriuretic peptide (BNP) level and coexisting non-cardiac diseases. [8][9][10][11][12][13] In HF patients with preserved LVEF, however, a prognostic value of cardiac sympathetic innervation has not been fully investigated. 14 15 In this study, we hypothesised that quantitatively assessed cardiac echo index and sympathetic innervation marker can contribute to better prognosis assessment of HF patients with preserved LVEF.…”

Predicting the Need for an Implantable Cardioverter Defibrillator Using Cardiac Metaiodobenzylguanidine Activity Together with Plasma Natriuretic Peptide Concentration or Left Ventricular Function

“…The mechanisms underlying impaired cardiac presynaptic sympathetic innervation that are responsible for lethal arrhythmias remain to be investigated. The changes in preand postsynaptic autonomic function in the failing heart are probably dependent on the progression of heart failure and structural myocardial damage (27). Cardiac MIBG activity assessed several hours after tracer injection has been shown to be related to myocardial norepinephrine content, left ventricular systolic function, and New York Heart Association functional status.…”