Objectives Using cardiac magnetic resonance (CMR), we sought to evaluate the relative influences of mechanical, electrical, and scar properties at the left ventricular (LV) lead position (LVLP) on CRT response and clinical events. Background CMR cine displacement encoding with stimulated echoes (DENSE) provides high quality strain for overall dyssynchrony (circumferential uniformity ratio estimate [CURE, 0–1]) and timing of onset of circumferential contraction at the LVLP. CMR DENSE, late gadolinium enhancement, and electrical timing together could improve upon other imaging modalities for evaluating the optimal LVLP. Methods Patients had complete CMR studies and echocardiography before CRT. CRT response was defined as a 15% reduction in LV end-systolic volume. Electrical activation was assessed as the time from QRS-onset-to-LVLP-electrogram (QLV). Patients were then followed for clinical events. Results In 75 patients, multivariable logistic modeling accurately identified the 40 (53%) of patients with CRT response (AUC=0.95 [p<0.0001]) based on CURE (OR 2.59/0.1 decrease), delayed circumferential contraction onset at LVLP (OR 6.55), absent LVLP scar (OR 14.9), and QLV (OR 1.31/10 ms increase). The 33% of patients with CURE<0.70, absence of LVLP scar, and delayed LVLP contraction onset had a 100% response rate, whereas those with CURE≥0.70 had a 0% CRT response rate and a 12-fold increased risk of death, and the remaining patients had a mixed response profile. Conclusions Mechanical, electrical, and scar properties at the LVLP together with CMR mechanical dyssynchrony are strongly associated with echocardiographic CRT response and clinical events after CRT. Modeling these findings holds promise for improving CRT outcomes.

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Purpose To use singular value decomposition (SVD) in heart failure (HF) to reveal primary spatiotemporal strain patterns in the left ventricle (LV), then develop and test a time-independent metric of cardiac dyssynchrony on the basis of the circumferential uniformity ratio estimate (CURE) computed with SVD (CURE-SVD) in both a canine model of HF with or without left bundle branch block (LBBB) and a clinical cohort referred for cardiac resynchronization therapy (CRT). Materials and Methods The research was approved by the institutional review board and conformed with HIPAA requirements. All subjects provided informed consent. In both the canine model (n = 13) and the clinical cohort (80 CRT candidates; mean age, 65.2 years; range, 18.5–86.9 years), regional strains were derived by using cardiac magnetic resonance (MR) displacement encoding with stimulated echoes. CURE-SVD was compared with the standard CURE (averaged over systolic phases). Statistical methods included the Wilcoxon rank-sum test, Hodges-Lehmann estimator, Bland-Altman test, multivariable logistic regression, and receiver operating characteristic analysis. Results In the canine model, the median difference in CURE-SVD (range, 0–1) for LBBB-HF group versus narrow-QRS–HF group (−0.40; 95% confidence interval [CI]: −0.79, −0.31) was similar to that for CURE (−0.43; 95% CI: −0.72, −0.34]). In 80 CRT candidates, CURE-SVD and CURE were highly correlated (r = 0.90; P < .0001). The multivariable model for CRT response with CURE-SVD demonstrated excellent performance without the need for time averaging over cardiac phases (area under the receiver operating characteristic curve = 0.96, P < .0001). Conclusion SVD of circumferential strain in HF identifies primary LV spatiotemporal contraction patterns with minimal user input, while the time-independent CURE-SVD parameter has excellent performance in a canine model of dyssynchrony and is strongly associated with CRT response in patients with HF.

Radiation exposure can increase the risk for many non-malignant physiological complications, including cardiovascular disease. We have previously demonstrated that ionizing radiation can induce endothelial dysfunction, which contributes to increased vascular stiffness. In this study, we demonstrate that gamma radiation exposure reduced endothelial cell viability or proliferative capacity using an in vitro aortic angiogenesis assay. Segments of mouse aorta were embedded in a Matrigel-media matrix 1 day after mice received whole-body gamma irradiation between 0 and 20 Gy. Using three-dimensional phase contrast microscopy, we quantified cellular outgrowth from the aorta. Through fluorescent imaging of embedded aortas from Tie2GFP transgenic mice, we determined that the cellular outgrowth is primarily of endothelial cell origin. Significantly less endothelial cell outgrowth was observed in aortas of mice receiving radiation of 5, 10, and 20 Gy radiation, suggesting radiation-induced endothelial injury. Following 0.5 and 1 Gy doses of whole-body irradiation, reduced outgrowth was still detected. Furthermore, outgrowth was not affected by the location of the aortic segments excised along the descending aorta. In conclusion, a single exposure to gamma radiation significantly reduces endothelial cell outgrowth in a dose-dependent manner. Consequently, radiation exposure may inhibit re-endothelialization or angiogenesis after a vascular injury, which would impede vascular recovery.

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