Magnetic Resonance Imaging in the Assessment of the Risk of Sudden Death in Cardiac Sarcoidosis: What Is Extensive or Significant Late Gadolinium Enhancement?

Abstract

Background: Cardiac sarcoidosis involves a significant but difficult-to-define risk of sudden cardiac death (SCD). Current guidelines recommend consideration of an implantable cardioverter defibrillator for patients with extensive or significant myocardial late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging. However, extensive/significant LGE is not defined.

Methods: A nationwide cardiac sarcoidosis registry was screened for patients entered before 2020 with cardiac magnetic resonance imaging done before or <3 months after diagnosis. Available studies were re-analyzed for LGE mass as a percentage of left ventricular (LV) mass and the number of LGE-positive LV segments in a 17-segment model. The occurrence of fatal or aborted SCD and ventricular tachycardia (VT) prompting therapy was recorded until the end of 2020 and subjected to cumulative incidence analyses, including competing events (LV assist device implantations, heart transplantations, and fatalities other than SCD). The predictors of SCD/VT were assessed using Fine and Gray modeling and time-dependent receiver operating characteristic analysis.

Results: Altogether, 305 patients (66% women, median age 51) with clinically manifest, definite (45%) or probable cardiac sarcoidosis (55%) were analyzed. On follow-up (median, 4.0 years), 21 SCDs, 60 VTs, and 14 competing events were noted. Both LGE mass and the number of LGE segments predicted the composite of SCD/VT (P<0.001), with receiver operating characteristic analyses identifying LGE mass ≥9.9% and ≥6 LGE segments as discriminative thresholds. At presentation, 70 patients were free of class I and class IIa implantable cardioverter defibrillator indications unrelated to LGE. Their 5-year rate of SCD/VT was 6.3% (0.0-14.8%) with LGE mass <9.9% versus 21.5% (6.5-36.6%) with higher LGE mass, and 6.9% (0.0-16.3%) with <6 LGE segments versus 20.5% (5.9-35.2%) with ≥6 segments.

Conclusions: In cardiac sarcoidosis, myocardial LGE making up ≥9.9% of LV mass or affecting ≥6 LV segments may suggest prognostically significant LV involvement and a high risk of SCD. However, prospective validation of the thresholds is needed.

Keywords: contrast media; gadolinium; incidence; magnetic resonance imaging; sarcoidosis; sudden death.

Figure 1.

Contrast-enhanced magnetic resonance imaging phenotypes of cardiac sarcoidosis featuring the distribution of late gadolinium enhancement (LGE). The images present short-axis views of both ventricles. A, Demonstrates ring-like LGE^, with continuous subepicardial enhancement in the basal anterior and anteroseptal left ventricular segments (arrows), extending into parts of the inferoseptal and anterolateral segments. B, Shows right ventricular free-wall LGE (asterisk), the hook-sign LGE at septal insertions (yellow arrows), as well as septal and subepicardial LGE (white arrows), demonstrating multifocal myocardial involvement and thus all 4 features of pathology-frequent LGE.^20.

Figure 2.

Overlap across the distribution phenotypes and the extent of late gadolinium enhancement (LGE) in cardiac sarcoidosis. Venn diagrams demonstrate how patients with (A), ring-like LGE; (B) the hook sign; (C) right ventricular (RV) free-wall LGE; and (D) 4 of 4 features of pathology-frequent LGE overlap with groups having ≥6 LGE-positive left ventricular segments out of 17 or an LGE mass ≥9.9%. E, Shows the extent of overlap across groups of patients with different LGE imaging phenotypes. Numbers in the lower right corners represent the number of patients outside all circles (groups or phenotypes).

Figure 3.

The composite incidence of sudden cardiac death (SCD) or ventricular tachycardia (VT) in cardiac sarcoidosis by the extent of late gadolinium enhancement (LGE) and the type of cardiac presentation. A, Shows the incidence of SCD/VT in patients who presented without ventricular tachyarrhythmia and had no indication for a secondary prevention implantable cardioverter defibrillator (ICD; n=226), while (B) refers to patients without either ventricular tachyarrhythmia or ejection fraction ≤35% (n=191), and (C) represents patients without any current class I or class II ICD indication independent of LGE (n=70). The patients are stratified by the thresholds of LGE mass and the number of LGE-positive segments.