Sudden Cardiac Death Substrate Imaged by Magnetic Resonance Imaging: From Investigational Tool to Clinical Applications

Abstract

Sudden cardiac death (SCD) is a devastating event afflicting 350 000 Americans annually despite the availability of life-saving preventive therapy, the implantable cardioverter defibrillator. SCD prevention strategies are hampered by over-reliance on global left ventricular ejection fraction <35% as the most important criterion to determine implantable cardioverter defibrillator candidacy. Annually in the United States alone, this results in ≈130 000 implantable cardioverter defibrillator placements at a cost of >$3 billion but only a 5% incidence per year of appropriate firings. This approach further fails to identify individuals who experience the majority, as many as 80%, of SCD events, which occur in the setting of more preserved left ventricular ejection fraction. Better risk stratification is needed to improve care and should be guided by direct pathophysiologic markers of arrhythmic substrate, such as specific left ventricular structural abnormalities. There is an increasing body of literature to support the prognostic value of cardiac magnetic resonance imaging with late gadolinium enhancement in phenotyping the left ventricular to identify those at highest risk for SCD. Cardiac magnetic resonance has unparalleled tissue characterization ability and provides exquisite detail about myocardial structure and composition, abnormalities of which form the direct, pathophysiologic substrate for SCD. Here, we review the evolution and the current state of cardiac magnetic resonance for imaging the arrhythmic substrate, both as a research tool and for clinical applications.

Keywords: arrhythmias, cardiac; cardiomyopathies; death, sudden, cardiac; fibrosis; magnetic resonance imaging; tachycardia, ventricular; ventricular dysfunction, left.

Figure 1. Mechanisms of scar re-entry

Heterogeneously distributed scar forms electrical conduction barriers but also facilitate the formation of critical isthmuses of viable myocytes that support re-entrant circuits (Panels A and B, collagen bundles shown in blue on Masson’s trichrome staining). Panel C: Wavefronts can enter the proximal end of the isthmus (entrance), exiting from the distal end (exit) and then propagating throughout the ventricle to form the QRS complex. The wavefront can re-enter the isthmus from channels within the infarct (inner loop) or via an outer loop at the border of the infarct zone with the normal myocardium. Reprinted with permission from: Danciu M. and Ajijola A. et al.

Figure 2. Ischemic scar (between arrows)

Panel A: non-transmural scar of the inferior and inferoseptal walls. Panel B: thinned transmural scar in the territory of the left anterior descending coronary artery. Panel C: two subendocardial infarcts of the anterolateral and inferolateral walls. Panel D: chronic inferior infarct with wall thinning (left image) and quantification (right image) of core (red) and peri-infarct, gray regions (yellow) using the FWHM method.

Figure 3. Pathologic correlates of LGE post-MI

The region of LGE closely matches the extent of infarction determined by pathology at all stages of infarct healing. Panels A (1 day post-MI) and B (3 days post-MI) show pathologic cross-sections stained with tetrazolium chloride (TTC) in which the pale regions represent regions of infarction and corresponding CMR-LGE images. Panel C (6 weeks post-MI) shows Masson’s trichrome staining in which collagenous scar appears blue and corresponding CMR-LGE images. Reprinted from Kim et al. and Zhang et al. with permission.

Figure 4. Nonischemic scar (between arrows)

Panel A: CMR images showing basal septal scar in a 45 year-old woman with strong family history of ventricular arrhythmia and SCD. EPS showed inducible monomorphic VT with right bundle, inferior axis morphology. An ICD was placed and subsequently discharged for monomorphic VT. Panel B: patchy inferior, inferoseptal and inferolateral LGE in a 65 year-old with NICM and multiple episodes of VT. Panel C: septal and inferior RV insertion LGE sparing the endocardium (top image) with quantification (lower image) of core (red) and gray regions (yellow) using the FWHM method.

Figure 5. Pathologic correlates of nonischemic scar

Panels A (pre-transplant CMR-LGE), B (post-transplant gross macroscopic cross-section) and C (post-transplant microscopic cross-section with fibrotic bundles, blue arrow) showing that the LGE with a midwall, near-circumferential pattern mirrors the distribution of pathologic replacement fibrosis. Panel D (pre-transplant CMR-LGE) shows diffuse LGE corresponding to regions of fibrosis confirmed by Masson’s trichrome staining (in green) on post-transplant histopathology (Panel E). E Reprinted from Iles et al. and Halliday et al. with permission of the publishers.

Figure 6. HCM

Two patients (Panels A and B) with HCM. Panel A: focal fibrosis (arrows) in non-coronary territories. Panel B: extensive, diffusely distributed LGE (arrows).

Figure 7. Cardiac sarcoidosis

33-year-old who presented with intermittent third degree heart block and CMR-LGE demonstrating extensive cardiac involvement and sarcoidosis on lymph node biopsy. Panel A (4 chamber apical view): patchy LV lateral wall LGE and LGE of the right ventricular side of the ventricular septum with endocardial sparing (blue arrows). There is also LGE (red arrowheads) of the epicardium and pericardium of the basal to mid RV free wall; atria; and LV pericardium. Panels B (mid-ventricular short axis slice) and C (apical short axis slice): extensive epicardial and pericardial (red arrowheads) LGE. Despite steroid therapy, he subsequently developed VT storm.

Figure 8. Acute and chronic myocarditis

Panels A and B: 29-year-old who presented with acute myocarditis with peak troponin-I 72 ng/mL; peak creatine phosphokinase 2742 U/L, CK-MB 331μg/L. LVEF was mildly reduced (Video 1) but he was asymptomatic from the arrhythmia and HF standpoint during a 6 day hospitalization. Panel A: mid-septal and lateral epicardial wall LGE (arrows) and pericardial enhancement. Panel B: T2 weighted edema imaging with extensive edema (arrowheads). He died suddenly at home 2 days post-discharge. Panel C: 22 year-old with documented acute myocarditis 15 months previously. CMR-LGE showed LGE of the distal segments of the LV with endocardial sparing (arrows) and pericardium. LV function was normal with no regional wall motion abnormalities (Video 2). Two years later, the patient developed palpitations and syncope with large burden of multifocal PVCs on Holter (>5%). EPS showed easily inducible monomorphic and polymorphic VT. An ICD was implanted and subsequently fired multiple times for MVT at 250 beats per minute.