Publications

INTRODUCTION: Nonuniformities in depolarization and repolarization morphology are critical factors in ventricular arrhythmogenesis. METHODS AND RESULTS: We assessed interlead R-wave heterogeneity (RWH) and T-wave heterogeneity (TWH) in standard 12-lead electrocardiograms (ECGs) using second central moment analysis. This technique quantifies variance about the mean morphology of beats in adjoining precordial leads, V4 , V5 , and V6 in this study. The study was conducted in 120 consecutive patients without an apparent reversible trigger for ventricular tachycardia (VT), recent myocardial infarction, or active ischemia, who presented for electrophysiologic study, implantable cardioverter defibrillator (ICD) placement, or generator change at our institution from 2008 to 2011. Primary outcome was sustained VT/ventricular fibrillation (VF) or appropriate ICD therapies. Secondary outcome was arrhythmic death or resuscitated cardiac arrest. Cutpoints for elevated RWH (>160 μV) and TWH (>80 μV) identified 67% of primary outcome cases and 85% of secondary outcome cases. Cardiomyopathy patients who met the primary outcome (n = 42) had significantly higher TWH than those who did not (n = 28) (TWH: 95 ± 11 μV vs. 44 ± 9 μV, P < 0.002). Likewise, cardiomyopathy patients who met secondary outcome (N = 13) had VT/VF during follow-up and also had significantly higher TWH than survivors (N = 57) (TWH: 105 ± 24 μV vs. 67 ± 8 μV, P < 0.002). Kaplan-Meier analysis revealed significant differences in arrhythmia-free survival (P = 0.012) and total survival (P = 0.011) among cardiomyopathy patients with (n = 37) compared to without (n = 33) elevated RWH and/or TWH independent of age, sex, and left ventricular ejection fraction (LVEF). CONCLUSION: Interlead RWH and TWH in 12-lead ECGs predict sustained ventricular arrhythmia, appropriate ICD therapies, and arrhythmic death or cardiac arrest in cardiomyopathy patients independent of LVEF and other standard variables.

BACKGROUND: Most patients with implantable cardioverter-defibrillator (ICD) implantation fail to utilize the device resulting in increasing societal costs and patient exposure to device morbidity. We sought to determine whether volumetric cardiovascular magnetic resonance (CMR) left ventricular (LV) spherical remodeling predicts future ventricular arrhythmias in primary ICD patients with reduced LV ejection fraction (EF). METHODS: Sixty-eight consecutive patients with transthoracic echocardiographic LVEF <35% referred for CMR prior to ICD implantation for primary prevention of sudden death were identified. Sphericity index was measured as the ratio of LV end-diastolic volume (from cine short axis stack) to the volume of a sphere with a LV end-diastolic 4-chamber length diameter. RESULTS: During a median follow-up of 55 months (interquartile range; 28-88), 15 patients (22%) received appropriate ICD therapy. Multivariable Cox's proportional hazard modeling identified increased CMR-derived sphericity index as the strongest independent predictor of appropriate ICD therapy (hazard ratio [HR], 1.09; 95% confidence interval [CI], 1.02 to 1.16; p = 0.007). In addition, dichotomized volumetric CMR-derived sphericity index ≥0.57 carried a 4-fold hazard risk for appropriate ICD therapy, controlling for age and LVEF (HR, 4.49; 95% CI, 1.53 to 13.21; p = 0.006). When sphericity index, LVEF and mass index were used in combination, important incremental prognostic information was achieved (net reclassification improvement, 0.42; 95% CI, 0.06 to 0.77). CONCLUSIONS: The combined assessment of LV geometry, mass index and systolic function may provide incremental prognostic information regarding ventricular arrhythmia requiring appropriate ICD therapy in primary prevention patients with reduced LVEF.

PURPOSE: To study the relationship between diffuse myocardial fibrosis and complex ventricular arrhythmias (ComVA) in patients with nonischemic dilated cardiomyopathy (NICM). We hypothesized that NICM patients with ComVA would have a higher native myocardial T1 time, suggesting more extensive myocardial diffuse fibrosis. MATERIALS AND METHODS: We prospectively enrolled NICM patients with a history of ComVA (n = 50) and age-matched NICM patients without ComVA (n = 57). Imaging was performed at 1.5T with a protocol that included cine magnetic resonance imaging (MRI) for left ventricular (LV) function, late gadolinium enhancement (LGE) for focal scar, and native T1 mapping for diffuse fibrosis assessment. RESULTS: Global native T1 time was significantly higher in patients with NICM with ComVA when compared to patients with NICM without ComVA (1131 ± 42 vs. 1107 ± 45 msec, P = 0.006), and this finding remained after excluding segments with scar on LGE (1124 ± 36 vs. 1102 ± 44 msec, P = 0.006). Native T1 was similar in NICM patients with and without the presence of LGE (1121 ± 39 vs. 1117 ± 48 msec, P = 0.68) and mildly correlated with LV end-diastolic volume index (r = 0.27, P = 0.005), LV end-systolic volume index (r = 0.24, P = 0.01), and LV ejection fraction (r = -0.28, P = 0.003). Native T1 value for each 10-msec increment was an independent predictor of ComVA (odds ratio 1.14, 95% confidence interval 1.03-1.25; P = 0.008) beyond LV function and LGE. CONCLUSION: NICM patients with ComVA have higher native T1 compared to NICM without any documented ComVA. Native myocardial T1 is independently associated with ComVA, after adjusting for LV function and LGE. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2017. In memoriam: The authors are grateful for Dr. Josephson's inspiring guidance and contributions to this study.

Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR). Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV). These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water). Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment. There is a multitude of technical approaches and potential applications. This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.