Elsevier

Journal of Nuclear Cardiology

Volume 23, Issue 6, December 2016, Pages 1380-1398
Journal of Nuclear Cardiology

Review Article
The role of nuclear cardiac imaging in risk stratification of sudden cardiac death

https://doi.org/10.1007/s12350-016-0599-8Get rights and content

Abstract

Sudden cardiac death (SCD) represents a significant portion of all cardiac deaths. Current guidelines focus mainly on left ventricular ejection fraction (LVEF) as the main criterion for SCD risk stratification and management. However, LVEF alone lacks both sensitivity and specificity in stratifying patients. Recent research has provided interesting data which supports a greater role for advanced cardiac imaging in risk stratification and patient management. In this article, we will focus on nuclear cardiac imaging, including left ventricular function assessment, myocardial perfusion imaging, myocardial blood flow quantification, metabolic imaging, and neurohormonal imaging. We will discuss how these can be used to better understand SCD and better stratify patient with both ischemic and non-ischemic cardiomyopathy.

Introduction

Sudden cardiac death (SCD) currently accounts for up to 60% of all cardiac death in the adult population in the United States.1,2 Despite recent advances in our understanding of cardiovascular disease and in cardiac care, effective primary prevention of SCD in the general population is still an aspiration.3,4 The final common pathway in most cases is malignant ventricular arrhythmia.5 Although the fundamental pathophysiology is complex, an underlying anatomical substrate can be identified in the majority of patients,6 with the most frequent being attributed to ischemic heart disease, idiopathic dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM).7

Current guidelines focus on the left ventricular ejection fraction (LVEF) as the primary measure for SCD risk stratification and patient management.8,9 One-third of all SCD occur in patients with moderate to severe left ventricular (LV) systolic dysfunction (LVEF ≤ 35%).10 In this group, primary prevention with an implantable cardioverter defibrillator (ICD) significantly prolongs survival.11,12 However, numerous patients with higher LVEF are still at risk of SCD, but would not qualify for ICD placement according to current guidelines. Furthermore, only 35% of patients randomized for ICD placement in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) received appropriate shock therapy over a 3-year follow-up.13 Taken together, these facts underscore the lack of sensitivity and specificity of LVEF alone in identifying patients who will suffer from SCD and the need for better markers for SCD.

Emerging data support the potential of cardiac imaging to understand the mechanisms of SCD beyond simple LVEF measurement.14 In this review, we will focus on the possible benefits that nuclear cardiology imaging (including myocardial perfusion imaging (MPI), LV function assessment, accurate flow quantification, metabolic imaging and neurohormonal imaging) offers us to improve risk stratification of SCD in patients with ischemic and non-ischemic cardiomyopathy.

Section snippets

Mechanisms of Sudden Cardiac Death

By definition “sudden,” the acute event is not often witnessed, and therefore SCD is difficult to study. In most cases, it is accepted that the final pathway is malignant ventricular arrhythmia.15,16 The underlying mechanisms of ventricular arrhythmogenesis are complex but can simply be considered as the interaction between a structural or anatomic substrate (myocardial scar from prior myocardial infarction) and a functional trigger, such as ischemia.5,6 In the adult population, most SCD occurs

Left Ventricular Function

LVEF is currently the most studied and most commonly used cardiac imaging marker to assess risk for SCD and is used to guide appropriate therapy in both ischemic and non-ischemic cardiomyopathies. Many studies, dating back to the 1980s, quickly established that LVEF is a strong predictor for overall cardiac mortality.24, 25, 26 Not surprisingly, this led to the use of LVEF as a criterion of enrollment in the large clinical trials for the evaluation of ICDs in primary prevention of SCD in the

Ischemia

Ischemia is a well-recognized trigger for ventricular arrhythmias.40,41 Current ICD therapy guidelines recommend optimal revascularization before ICD therapy.31 Moreover, coronary revascularization has been proven to reduce SCD risk.42, 43, 44 Hachamovitch et al, in a large study with 5183 patients who underwent rest/stress dual-isotope (Thallium-201 and Technetium-99m Sestamibi) SPECT MPI, demonstrated that the presence of ischemia yields incremental prognostic data for predicting cardiac

Myocardial Scar and Hibernating Myocardium

Myocardial scar is a complex and powerful substrate for arrhythmogenesis. Changes in tissue composition following an infarct create a heterogeneous zone that leads to depolarization abnormalities, autonomic dysfunction, and repolarization disruption; the presence of viable myocardium adjacent to scar tissue often forms the anatomic substrate for reentrant ventricular tachycardia (VT).55,56 Studies have shown that the extent of scar on SPECT MPI is related to the risk of cardiac death.

Sympathetic Innervation Imaging

Cardiac sympathetic innervation is another novel imaging target in the search for better prediction and prevention of SCD. It plays an important role in cardiac function and may play an important role in future stratification strategies.

The most widely available and studied non-invasive method to assess cardiac sympathetic innervation is currently Iodine-123-metaiodobenzylguanidine (MIBG). MIBG is a guanethidine analog initially developed in the 1980s to study adrenal medulla tumors and other

Idiopathic Dilated Cardiomyopathy (DCM)

According to some studies, SCD accounts for up to 30% of overall death in patients with DCM,96 which accounts for a significant fraction of overall SCD.6 Current guidelines recommend ICD therapy in patients with non-ischemic cardiomyopathy with LVEF ≤ 35% and NYHA class II-III HF,29 while it may be considered in patients with NYHA class I. Evaluation of LV function is thus indicated in these patients. Additionally, studies have shown that sympathetic innervation abnormalities are present in

Future Outlook

Although 11C-HED shows great promise, its use and adoption remain limited because of its short half-life which requires an onsite cyclotron. LMI1195 is a Fluorine-18-based PET tracer with a design similar to MIBG, which could theoretically solve this problem thanks to its longer half-life which allows delivery from a regional cyclotron. Preliminary studies are promising,134,135 and the relationship between myocardial denervation and SCD, along with the potential for an effective

Conclusion

Correctly identifying patients who are at high risk for SCD is of paramount importance since appropriate therapy can be life-saving. While modern medicine has made significant progress in the diagnosis and management of CAD, this is one area where recent progress remains limited. Our current screening process for SCD relies heavily on LVEF assessment, which lacks both sensitivity and specificity. Recent advances in our understanding of the underlying pathophysiology, combined with advances in

Acknowledgments

RSB is a career investigator supported by the Heart and Stroke Foundation of Ontario, a Tier 1 Research Chair supported by the University of Ottawa, and the University of Ottawa Heart Institute Vered Chair in Cardiology. DJ is a Cardiac Imaging Fellow at the University of Ottawa Heart Institute supported by a grant from the CHUM and CHUM Foundation. JK is supported by the Centre of Excellence of Cardiovascular and Metabolic Disease, Academy of Finland.

Disclosures

RSB is or has been a consultant for and

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