Focal myocardial scar/fibrosis is electrically inert but it is surrounded by a “grey zone” where normal cardiomyocytes intermingle with dense bundles of fibrosis.7 Slow impulse conduction in the grey zone allows the establishment of re-entry circuits, leading to VA.7 Dense scar, as well as the surrounding grey zone, can be imaged with LGE-CMR. The gadolinium-based contrast agent accumulates in the expanded extracellular space.8 Inversion recovery images are acquired 10 to 20minutes after gadolinium contrast media administration, and the normal myocardium is nulled by choosing an appropriate inversion time, which provides contrast between areas of gadolinium accumulation (focal scar/fibrosis) and normal tissue.8 Dense scar is distinguished from the grey zone by application of a signal intensity threshold, eg, ≥ 50% for dense scar, 30% to 50% for grey zone and < 30% for normal myocardium.7 Both the presence and extent of LGE (mass or percentage of myocardial volume/mass) have been associated with VA and SCD risk.9

While diffuse myocardial fibrosis causes VA in a manner similar to focal scar/fibrosis, it cannot be visualized with conventional LGE. T1 mapping depicts the time constant of longitudinal spin relaxation of the myocardium on a colour-coded, pixel-by-pixel map. Diffuse fibrosis can be demonstrated on native (without a gadolinium-based contrast agent) and postcontrast T1 maps by means of various CMR sequences, eg, Modified Look-Locker Inversion Recovery (MOLLI) and shortened MOLLI (ShMOLLI).10 Increased diffuse myocardial fibrosis will result in long native T1 values whereas after administration of gadolinium contrast media the T1 values will be shorter compared with normal myocardium. Native T1 mapping has been independently associated with VA in cardiomyopathies of ischemic and nonischemic etiology.11 Furthermore, the extracellular volume fraction (ECV) of the myocardium can be calculated from the pre- and postcontrast T1 values of the blood pool and myocardium. The extracellular volume fraction reflects the size of the extracellular space.12 Since type I collagen is the primary constituent of the extracellular space, in the absence of edema or amyloidosis, ECV is also a marker of diffuse fibrosis.8

Myocardial iron deposition is arrhythmogenic, although the specific mechanism is still debated.13,14 Since iron is paramagnetic, it influences T2* relaxation time by disrupting the magnetic field homogeneity and causing proton spins to dephase, thereby shortening the T2* time. Breath-hold, multiecho gradient echo sequences are employed to construct a T2* relaxation curve with a series of images at increasing echo times.15 An exponential function is then fitted to the data points according to the following formula: y = Ke-TE/T2*, where y is the signal intensity, K is a constant, TE is the echo time and T2* is the T2* relaxation time, which reflects the amount of myocardial iron deposition.15,16

Both focal and diffuse fibrosis lead to myocardial stiffness, which can be demonstrated as abnormal deformation (longitudinal and circumferential strain) by various CMR tagging techniques.17 Circumferential strain abnormalities, demonstrated with tagging, are associated with inducible VA and identification of the grey zone, which plays a pivotal role in arrhythmogenesis.18–20 In contrast to CMR tagging, feature tracking CMR identifies “features” on the epicardial or endocardial borders, and tracks their motion throughout the cardiac cycle.21 No additional sequences are required, and data processing is automated, performed on cine-images, making this an attractive approach.21 Feature tracking analysis has been applied to global longitudinal strain measurement as a risk marker for VA and SCD.22 In addition, LV mechanical dispersion, calculated as the standard deviation of the time-to-peak circumferential strain (feature tracking analysis) of 16 LV segments is a marker of electromechanical inhomogeneity due to myocardial fibrosis/scar, which has been associated with VA and SCD.23,24

Coronary artery disease is the most common cause of SCD, due to the arrhythmogenicity of postinfarct scar.7 Evidence linking both the presence and burden of LGE and VA/SCD in the chronic, postinfarct setting, originates from multiple studies (Table 1, Figure 1).7,25–30 In 195 patients with suspected coronary artery disease who underwent CMR, the presence of LGE was independently associated with outcome, including VA requiring appropriate ICD discharge (hazard ratio [HR], 5.98; 95% confidence interval [95%CI], 2.68-13.3; P < .0001).30 The LGE burden (calculated as scar mass) was independently associated with appropriate ICD therapy in 66 patients with chronic coronary artery disease (HR, 3.15; 95%CI, 1.35-7.33; P < .001).25 Late gadolinium enhancement is also associated with VA and SCD in the acute, postinfarct context.31,32 The ratio between the peri-infarct zone and the core infarct (as a measure of the grey zone: dense scar) was found to be independently associated with sustained VA and appropriate ICD therapy in a cohort of patients with coronary artery disease (HR, 2.01; 95%CI, 1.17-3.44; P = .01).28 In postinfarct patients, abnormalities of circumferential strain (on tagging sequences) are associated with inducible VA and characterizes the peri-infarct grey zone.18–20 Left ventricular mechanical dispersion was independently associated with mortality and SCD, including VA and appropriate ICD therapy (HR, 1.39; 95%CI, 1.20-1.62; P < .001) in a cohort of 130 patients after ST-segment elevation myocardial infarction (Figure 1).23

Figure 1.

Feature tracking cardiac magnetic resonance to assess LVMD. LVMD is defined as the standard deviation of time-to-peak circumferential strain, expressed as a percentage of the cardiac cycle length. The midventricular, short-axis slice of the left ventricle of a healthy individual, demonstrating absence of LGE is shown in panel A. A normal LVMD is demonstrated in patient (A) by synchronous deformation of the different LV segments (colour-coded) and time-to-peak circumferential strain, indicated by white arrows (B). In panel C, thinning and extensive LGE of the interventricular septum and anterior LV wall after myocardial infarction is shown (arrow). Increased LVMD (11.8%) in patient (C), reflecting dyssynchronous LV segments (D). LVMD > 9.79% is associated with ventricular arrhythmias and sudden cardiac death risk postinfarct. LGE, late gadolinium enhancement; LV, left ventricular; LVMD, left ventricular mechanical dispersion.

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Dilated cardiomyopathy (DCM) is characterized by LV or biventricular dilation and dysfunction that are not explained by abnormal loading conditions or coronary artery disease.33 A multitude of genetic and environmental etiologies have been identified, including more than 50 pathogenic genes.33 Fibrosis (both focal and diffuse) causes scar-related re-entry and VA.34–37 Late gadolinium enhancement-related VA and SCD risk has been extensively documented in this heterogeneous group of patients (Table 2).9,24,34,35,38–46 Different LGE patterns have been described, with some studies correlating midwall LGE with greater risk, while this finding was not apparent in others (Table 2).35,41,43,44,47,48 The prognostic implications of LGE for VA/SCD has been shown in certain specific, genetic DCMs, eg, lamin A/C mutations, Duchenne and Becker muscular dystrophy.49,50 Prognostic evidence for LGE presence and extent has accumulated for “nonischemic cardiomyopathy” in various studies, which overlaps with DCM.36,38,48,51,52 Extracellular volume was also found to be an independent predictor of a combined endpoint (including VA) in nonischemic DCM (Figure 2A).12,53 In Becker muscular dystrophy, an increased ECV has been associated with VA (odds ratio [OR], 1.97; 95%CI, 1.21-32.22; P = .032).54 Impaired LV global longitudinal strain (HR, 1.27; 95%CI, 1.06-1.52; P < .02), assessed with feature tracking analysis, was independently associated with a combined endpoint, including VA and SCD, in a study of 210 patients with DCM (Figure 2B-2D).22

Figure 2.

Assessment of diffuse myocardial fibrosis and functional consequences with cardiac magnetic resonance in patients with DCM. Elevated ECV of 37% in a patient with nonischemic DCM (A). An elevated ECV is associated with ventricular arrhythmias in nonischemic DCM.12 Epi- and endocardial LV contours in a horizontal long axis, steady state free precession image of a patient with idiopathic DCM (LVEF < 10%) from which global longitudinal strain is calculated with feature tracking (B). Polar map of LV segmental, longitudinal strain in patient (B), demonstrating impaired global longitudinal strain (4.4%). LV segments are coded in shades of blue (darker hues denote better segmental strain) and green (worse segmental strain) (C). Global longitudinal strain greater than 12.5% is associated with sudden cardiac death in nonischemic DCM, independent of LVEF.22 Surface-rendered display of LV segmental strain from (B), with blue/white segments representing better strain, compared with red/yellow segments (worse strain) (D). DCM, dilated cardiomyopathy; ECV, extracellular volume fraction; LV, left ventricular; LVEF, left ventricular ejection fraction. Panel A reproduced with permission from Schelbert et al.53.

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Hypertrophic cardiomyopathy is a genetic cardiomyopathy, identified by an unexplained increase in LV wall thickness with a nondilated chamber.55 More than 1400 mutations have been described, which are accompanied by a range of phenotypes.55 Left ventricular wall thickening is most commonly observed in the LV basal septum, but also occurs in apical and midventricular patterns (Figure 3D). Left ventricular wall thickening ≥ 30mm in any segment is a risk factor for SCD (Figure 3D).56 Apical aneurysm formation is associated with midventricular obstruction, likely because of chronic exposure of the LV apex to high wall stress from increased systolic pressure.57,58 This leads to ischemia and focal replacement fibrosis of the LV apex.58 Midventricular obstruction with a gradient ≥ 30mmHg (HR, 3.19; 95%CI, 1.62-6.29; P < .001) with and without apical aneurysm formation was an independent determinant of VA and SCD in a study of 490 Japanese patients.58 Multiple studies have furnished evidence for the association of LGE with VA and SCD (Table 3).59–73 Not only the presence, but also the extent of LGE, is linked to VA/SCD risk (Figure 3A-3B).59,61,62,66,67,70,71 Furthermore, the pattern of LGE has prognostic implications: while LGE at the right ventricular insertion points is typical for the diagnosis of HCM, it does not appear to portend a higher risk of SCD (Figure 3C).74

Figure 3.

Focal fibrosis in hypertrophic cardiomyopathy. Short axis, left ventricular slices (A-C) and an apical, long-axis slice (D) demonstrating different patterns of LGE and LV wall thickening in hypertrophic cardiomyopathy. Basal, septal LV thickening and co-localized LGE (A). More extensive basal, septal LGE, which represents a higher SCD risk (B). LGE at the anterior and inferior right ventricular LV attachments, which is not associated with an increased SCD risk (C). Midventricular pattern of LV thickening, with the interventricular septum measuring 33mm (D). Both midventricular hypertrophy and LV thickening ≥ 30mm are risk markers for SCD. LGE, late gadolinium enhancement; LV, left ventricular; SCD, sudden cardiac death.

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Degenerative mitral valve disease may involve leaflet thickening, redundancy, chordal elongation, annular dilatation, and abnormal annular dynamics.95,96 Mechanical forces, exerted by prolapsing leaflets and chords, possibly cause repetitive damage to the papillary muscle and underlying myocardium, eventually leading to myocardial scarring.95 Late gadolinium enhancement at the papillary muscle and inferobasal LV wall correlates with the occurrence of VA.95 Papillary muscle LGE (especially at the tips, adjacent to chordal insertion) is present in 63% of patients with mitral valve prolapse and is associated with VA (Figure 6).4,97

Figure 6.

Late gadolinium enhancement on cardiac magnetic resonance in patients with mitral valve prolapse. Horizontal long axis steady state free precession image, demonstrating bileaflet prolapse of the mitral valve (A). Short axis view, with late gadolinium enhancement of the papillary muscle tips (B), which has been linked to ventricular arrhythmias.95 Reproduced with permission from van der Bijl et al.4.

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