C. Lydell

Accuracy and reproducibility of semi-automated late gadolinium enhancement quantification techniques in patients with hypertrophic cardiomyopathy

BackgroundThe presence and extent of late gadolinium enhancement (LGE) has been associated with adverse events in patients with hypertrophic cardiomyopathy (HCM). Signal intensity (SI) threshold techniques are routinely employed for quantification; Full-Width at Half-Maximum (FWHM) techniques are suggested to provide greater reproducibility than Signal Threshold versus Reference Mean (STRM) techniques, however the accuracy of these approaches versus the manual assignment of optimal SI thresholds has not been studied. In this study, we compared all known semi-automated LGE quantification techniques for accuracy and reproducibility among patients with HCM.MethodsSeventy-six HCM patients (51 male, age 54 ±13 years) were studied. Total LGE volume was quantified using 7 semi-automated techniques and compared to expert manual adjustment of the SI threshold to achieve optimal segmentation. Techniques tested included STRM based thresholds of >2, 3, 4, 5 and 6 SD above mean SI of reference myocardium, the FWHM technique, and the Otsu-auto-threshold (OAT) technique. The SI threshold chosen by each technique was recorded for all slices. Bland-Altman analysis and intra-class correlation coefficients (ICC) were reported for each semi-automated technique versus expert, manually adjusted LGE segmentation. Intra- and inter-observer reproducibility assessments were also performed.ResultsFifty-two of 76 (68%) patients showed LGE on a total of 202 slices. For accuracy, the STRM >3SD technique showed the greatest agreement with manual segmentation (ICC =0.97, mean difference and 95% limits of agreement =1.6 ± 10.7 g) while STRM >6SD, >5SD, 4SD and FWHM techniques systematically underestimated total LGE volume. Slice based analysis of selected SI thresholds similarly showed the STRM >3SD threshold to most closely approximate manually adjusted SI thresholds (ICC =0.88). For reproducibility, the intra- and inter-observer reproducibility of the >3SD threshold demonstrated an acceptable mean difference and 95% limits of agreement of -0.5 ± 6.8 g and -0.9 ± 5.6 g, respectively.ConclusionsFWHM segmentation provides superior reproducibility, however systematically underestimates total LGE volume compared to manual segmentation in patients with HCM. The STRM >3SD technique provides the greatest accuracy while retaining acceptable reproducibility and may therefore be a preferred approach for LGE quantification in this population.

Right Ventricular Ejection Fraction Is Incremental to Left Ventricular Ejection Fraction for the Prediction of Future Arrhythmic Events in Patients With Systolic Dysfunction

Background— Left ventricular ejection fraction remains the primary risk stratification tool used in the selection of patients for implantable cardioverter defibrillator therapy. However, this solitary marker fails to identify a substantial portion of patients experiencing sudden cardiac arrest. In this study, we examined the incremental value of considering right ventricular ejection fraction for the prediction of future arrhythmic events in patients with systolic dysfunction using the gold standard of cardiovascular magnetic resonance. Methods and Results— Three hundred fourteen consecutive patients with ischemic cardiomyopathy or nonischemic dilated cardiomyopathy undergoing cardiovascular magnetic resonance were followed for the primary outcome of sudden cardiac arrest or appropriate implantable cardioverter defibrillator therapy. Blinded quantification of left ventricular and right ventricular (RV) volumes was performed from standard cine imaging. Quantification of fibrosis from late gadolinium enhancement imaging was incrementally performed. RV dysfunction was defined as right ventricular ejection fraction ⩽45%. Among all patients (164 ischemic cardiomyopathy, 150 nonischemic dilated cardiomyopathy), the mean left ventricular ejection fraction was 32±12% (range, 6–54%) with mean right ventricular ejection fraction of 48±15% (range, 7–78%). At a median of 773 days, 49 patients (15.6%) experienced the primary outcome (9 sudden cardiac arrest, 40 appropriate implantable cardioverter defibrillator therapies). RV dysfunction was independently predictive of the primary outcome (hazard ratio=2.98; P=0.002). Among those with a left ventricular ejection fraction >35% (N=121; mean left ventricular ejection fraction, 45±6%), RV dysfunction provided an adjusted hazard ratio of 4.2 (P=0.02). Conclusions— RV dysfunction is a strong, independent predictor of arrhythmic events. Among patients with mild to moderate LV dysfunction, a cohort greatly contributing to global sudden cardiac arrest burden, this marker provides robust discrimination of high- versus low-risk subjects.

Differentiation of physiologic versus pathologic basal septal fibrosis: Proposed diagnostic criteria and associations with clinical and CMR-based markers of cardiovascular disease

Background Abnormal late gadolinium enhancement (LGE) is commonly identified in the basal septum of patients with dilated cardiomyopathy, hypertrophic cardiomyopathy and sarcoidosis, and has been associated with major adverse events. However, basal septal LGE may also be seen in otherwise normal individuals (Figure 1) and may be “physiologic”. No diagnostic criteria to differentiate the latter have been established, and both its prevalence and clinical significance remain uncertain. In this study we propose such criteria and examine its prevalence and association with markers of cardiovascular disease.

Clinical feasibility and validation of 3D principal strain analysis from cine MRI: comparison to 2D strain by MRI and 3D speckle tracking echocardiography

Two-dimensional (2D) strain analysis is constrained by geometry-dependent reference directions of deformation (i.e. radial, circumferential, and longitudinal) following the assumption of cylindrical chamber architecture. Three-dimensional (3D) principal strain analysis may overcome such limitations by referencing intrinsic (i.e. principal) directions of deformation. This study aimed to demonstrate clinical feasibility of 3D principal strain analysis from routine 2D cine MRI with validation to strain from 2D tagged cine analysis and 3D speckle tracking echocardiography. Thirty-one patients undergoing cardiac MRI were studied. 3D strain was measured from routine, multi-planar 2D cine SSFP images using custom software designed to apply 4D deformation fields to 3D cardiac models to derive principal strain. Comparisons of strain estimates versus those by 2D tagged cine, 2D non-tagged cine (feature tracking), and 3D speckle tracking echocardiography (STE) were performed. Mean age was 51 ± 14 (36% female). Mean LV ejection fraction was 66 ± 10% (range 37–80%). 3D principal strain analysis was feasible in all subjects and showed high inter- and intra-observer reproducibility (ICC range 0.83–0.97 and 0.83–0.98, respectively—p < 0.001 for all directions). Strong correlations of minimum and maximum principal strain were respectively observed versus the following: 3D STE estimates of longitudinal (r = 0.81 and r = −0.64), circumferential (r = 0.76 and r = −0.58) and radial (r = −0.80 and r = 0.63) strain (p < 0.001 for all); 2D tagged cine estimates of longitudinal (r = 0.81 and r = −0.81), circumferential (r = 0.87 and r = −0.85), and radial (r = −0.76 and r = 0.81) strain (p < 0.0001 for all); and 2D cine (feature tracking) estimates of longitudinal (r = 0.85 and −0.83), circumferential (r = 0.88 and r = −0.87), and radial strain (r = −0.79 and r = 0.84, p < 0.0001 for all). 3D principal strain analysis is feasible using routine, multi-planar 2D cine MRI and shows high reproducibility with strong correlations to 2D conventional strain analysis and 3D STE-based analysis. Given its independence from geometry-related directions of deformation this technique may offer unique benefit for the detection and prognostication of myocardial disease, and warrants expanded investigation.

Relative influence of peak strain delay and peak strain amplitude of non-scarred myocardium in response to cardiac resynchronization therapy: insights from segmental 4D strain analysis

Background The burden and location of replacement fibrosis by Late Gadolinium Enhancement (LGE) MRI is a recognized predictor of non-response in patients undergoing cardiac resynchronization therapy (CRT). However, the capacity of the non-scarred tissue to respond favorably is felt to be dependent upon incremental factors. In this study we explored the utility of 4D strain analysis of non-scarred myocardial tissue to predict response to CRT.

DEFINING RISK ASSOCIATED WITH LEFT VENTRICULAR HYPERTROPHY PATTERNS AS ASSESSED BY CARDIAC MAGNETIC RESONANCE IMAGING

Background: Left ventricular hypertrophy (LVH) is a well-established risk factor for the development of cardiovascular complications. However, the pattern of LVH based on LV mass, LV dilation, and concentricity may have incremental prognostic implications. We investigated associations between LVH

Abnormal Lymphatic Channels Detected by T2-Weighted MR Imaging as a Substrate for Ventricular Arrhythmia in HCM

Hypertrophic cardiomyopathy (HCM) is a common genetic disorder associated with elevated risk of lethal ventricular arrhythmias. While the absence of myocardial fibrosis on late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) appears to identify lower risk individuals, approximately two

4-dimensional strain imaging of the right ventricle: application in patients with severe pulmonary hypertension

Background The risk stratification of patients with pulmonary hypertension (PHTN) using non-invasive techniques is challenging. 4D analysis techniques of right ventricular (RV) strain may provide unique opportunities for the identification of high-risk individuals. However, conventional strain metrics, developed for left ventricular geometry, pose limitations for RV geometry and its associated fibre orientations. In this study we examine a novel 4D strain analysis tool affording calculation of axis-independent Principal strains for the assessment of right ventricular mechanics. Patients with mild-moderate and severe PHTN were studied in comparison to a young healthy volunteer cohort.

Prognostic significance of the extent of septal fibrosis quantified on late gadolium enhanced images in patients with nonischemic cardiomyopathy

Background Midwall septal fibrosis on late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) imaging has been shown to be an independent predictor of adverse events in patients with non-ischemic dilated cardiomyopathy (NICM). Recent studies in other cardiomyopathy cohorts, such as Hypertrophic Cardiomyopathy, suggest that LGE extent provides incremental prognostic value over its binary presence or absence. The objective of this study was to investigate the prognostic value of septal LGE quantification for the prediction of arrhythmic events among patients with NICM.

Three-dimensional thoracic aorta principal strain analysis from routine ECG-gated computerized tomography: feasibility in patients undergoing transcatheter aortic valve replacement

BackgroundFunctional impairment of the aorta is a recognized complication of aortic and aortic valve disease. Aortic strain measurement provides effective quantification of mechanical aortic function, and 3-dimenional (3D) approaches may be desirable for serial evaluation. Computerized tomographic angiography (CTA) is routinely performed for various clinical indications, and offers the unique potential to study 3D aortic deformation. We sought to investigate the feasibility of performing 3D aortic strain analysis in a candidate population of patients undergoing transcatheter aortic valve replacement (TAVR).MethodsTwenty-one patients with severe aortic valve stenosis (AS) referred for TAVR underwent ECG-gated CTA and echocardiography. CTA images were analyzed using a 3D feature-tracking based technique to construct a dynamic aortic mesh model to perform peak principal strain amplitude (PPSA) analysis. Segmental strain values were correlated against clinical, hemodynamic and echocardiographic variables. Reproducibility analysis was performed.ResultsThe mean patient age was 81±6 years. Mean left ventricular ejection fraction was 52±14%, aortic valve area (AVA) 0.6±0.3 cm2 and mean AS pressure gradient (MG) 44±11 mmHg. CTA-based 3D PPSA analysis was feasible in all subjects. Mean PPSA values for the global thoracic aorta, ascending aorta, aortic arch and descending aorta segments were 6.5±3.0, 10.2±6.0, 6.1±2.9 and 3.3±1.7%, respectively. 3D PSSA values demonstrated significantly more impairment with measures of worsening AS severity, including AVA and MG for the global thoracic aorta and ascending segment (p<0.001 for all). 3D PSSA was independently associated with AVA by multivariable modelling. Coefficients of variation for intra- and inter-observer variability were 5.8 and 7.2%, respectively.ConclusionsThree-dimensional aortic PPSA analysis is clinically feasible from routine ECG-gated CTA. Appropriate reductions in PSSA were identified with increasing AS hemodynamic severity. Expanded study of 3D aortic PSSA for patients with various forms of aortic disease is warranted.