Development and validation of a new CMR-derived risk prediction model in excessive trabeculation of the left ventricle

Abstract Background Excessive trabeculation of the left ventricle (ETLV) is a controversial entity with inconsistent outcomes. Cardiovascular magnetic resonance (CMR) may help in risk stratification. Purpose To develop and validate a CMR prediction model of major adverse cardiovascular events (MACE) in ETLV. Methods Retrospective longitudinal international study. A total of 589 patients with ETLV from 17 centers across Europe and North America were recruited, 412 (70%) were assigned to the development cohort and 177 (30%) to the validation cohort. Core-lab CMR analysis was performed, including functional parameters (LVEF, strain, burden of LGE, etc.) and morphological variables (NC/C ratio, trabeculated mass and fractal dimension). MACE was defined as a composite of heart failure, ventricular arrhythmias, systemic embolisms and all-cause death. The prediction model with the highest Harrell’s C was chosen, initially including only functional variables, and subsequently incorporating morphological variables. Patients were divided according to terciles of score punctuation. The score was converted into a nomogram and a decision tree was developed. Results Among the development cohort, age was 43.4 (18.2) years and 45% were women. LVEF was 48.0 (14.1) and 12% exhibited LGE. During a median follow-up of 2.8 years (IQR 0.99 – 5.55) years, MACE occurred in 77 (19%) patients. Most functional CMR variables were associated with MACE in univariate analysis, while most morphologic variables were not associated. The best prediction model including only functional parameters resulted to be a combination of indexed LV end-diastolic volume (iLVEDV) (HR 1.01, 95% CI 1.00 - 1.01, p = 0.033), LV global circumferential strain (GCS) (HR 1.09, 95% CI 1.04 - 1.15, p 0.001), and percentage of LGE (HR 1.06, 95% CI 1.03 - 1.08, p 0.001). The risk score had a Harrell’s C of 0.77 in the development cohort, and 0.70 in the validation cohort. Patients in terciles of score punctuation showed significant survival differences (log-rank p 0.001). Patients with an iLVEDV 119 ml/m2, an LV-GCS -19% and an LGE 2% showed a MACE rate of only 3%, while those with more dilated LV, worse LV-GCS or more extensive LGE experienced progressively higher risks of MACE. Conclusions We developed and validated a CMR-based score for precise risk stratification in patients with excessive trabeculation of the LV. Functional variables (LV dilatation and dysfunction and extension of fibrosis) seem to carry the main prognostic value, while morphologic variables (quantification of trabeculation) have only a modest additional role, underscoring the importance of the underlying phenotype in ETLV. Patients with no major CMR functional abnormalities show a benign prognosis, suggesting they do not have an actual cardiomyopathy. Our results could be used for individualized management.