Life-Threatening Ventricular Arrhythmias: Current Role of Imaging in Diagnosis and Risk Assessment

Abstract

Sudden cardiac arrest continues to be a major cause of death from cardiovascular disease but our ability to predict patients at the highest risk of developing lethal ventricular arrhythmias remains limited. Left ventricular ejection fraction is inversely related to the risk of sudden death but has a low sensitivity and specificity for the population at risk. Nevertheless, it continues to be the main variable considered in identifying patients most likely to benefit from implantable defibrillators to prevent sudden death. Imaging myocardial sympathetic innervation with PET and SPECT as well as imaging characteristics of myocardial infarcts using gadolinium-enhanced cardiac magnetic resonance are emerging as imaging modalities that may further refine patient selection beyond ejection fraction. This review will primarily focus on employing advanced imaging approaches to identify patients with left ventricular dysfunction that are most likely to develop lethal arrhythmias and benefit from inserting a primary prevention implantable cardiac defibrillator. While not yet tested in prospective studies, we will review risk prediction models incorporating quantitative imaging and biomarkers that have been developed that appear promising to identify those at highest risk of sudden death.

Keywords: 11C-hydroxyephedrine; 123I-metaiodobenzylguanidine; Sudden cardiac arrest; gadolinium MRI; risk stratification.

Figures

Figure 1. Schematic of Sympathetic Transmission

Schematic of sympathetic transmission and neuronal uptake of 11C-HED (11C-meta-Hydroxyephedrine) and 123I-mIBG (123I-Metaiodobenzyguanidine) for imaging of sympathetic neuronal innervation. Norepinephrine (NE) is synthesized and packaged in the presynaptic sympathetic nerve terminals and released into the synaptic cleft. Released NE binds to post synaptic receptors, is taken up via the presynaptic norepinephrine transporter (NET) for repackaging or is released into the circulation and exits the heart through the coronary venous circulation (not show). Both 11C-HED and 123I-mIBG are taken up into the presynaptic nerve terminals using the NET-dependent mechanism. VMAT= vesicular monoamine transporter, DOPA = 3,4-dihydroxyphenylalanine. Modified and reproduced with permission from Malhotra et al.(56).

Figure 2. Imaging of Myocardial Flow, Viability, and Sympathetic Innervation with Positron Emission Tomography

Reconstructed images summarizing retention of each isotope. Upper panel (A) shows a subject who experienced SCA. Infarct size (18F-2-deoxyglucose, 18 FDG) which was smaller than the volume of sympathetic denervation (reduced 11C-HED). Within the region of viable but denervated myocardium (mismatch between reduced 11C-HED and preserved 18FDG) there was reduced perfusion (13NH3-ammonia) indicating hibernating myocardium. In contrast, the lower panel (B) shows a subject with fairly closely matched reductions in flow, infarct volume and sympathetic denervation. (ANT – anterior; INF – inferior; LAT – lateral; SEP – Septum). Reproduced with permission from Fallavollita et al.(55).

Figure 3. Late Gadolinium Enhanced Cardiac Magnetic Resonance from a Patient with Ischemic Cardiomyopathy and Sustained Ventricular Tachycardia

Late gadolinium enhanced cardiac magnetic resonance depicts patchy myocardial scar (between red chevrons and white arrows) in the lateral wall of the left ventricle.

Figure 4. Prediction of Arrhythmic Events by the ADMIRE-HF Score Risk Model

ADMIRE-HF risk score comprised of LVEF

Figure 5. Sudden Cardiac Arrest Risk Factor Model from PAREPET

PAREPET risk score based on retrospective analysis using the four independent risk parameters from multivariate analysis. These included the percent of the left ventricle that was denervated, left ventricular end-diastolic volume index, serum creatinine and the inability to take in angiotensin-converting enzyme inhibitor. Cut points were obtained from univariate models for each continuous parameter or the presence or absence of angiotensin inhibition therapy. Kaplan-Meier curves demonstrate highly significant differences in the incidence of SCA in relation to the number of risk factors present (p