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.

Background We hypothesize that a therapy that improves LV pump function early after infarction should decrease the need for compensation through sympathetic activation and dilation, thereby reducing the risk of developing heart failure. The mechanical properties of healing myocardial infarcts are an important determinant of left ventricular (LV) function, yet improving function by altering infarct properties has proven unexpectedly difficult. Using a computational model, we recently predicted that stiffening a large anterior infarct anisotropically (in only one direction) would improve LV function, while isotropic stiffening, the focus of previous studies and therapies, would not. The goal of this study was to test the novel strategy of anisotropic infarct reinforcement. Methods and Results We tested the effects of anisotropic infarct reinforcement in 10 open-chest dogs with large anteroapical infarcts that depressed LV pump function. We measured regional mechanics, LV volumes, and cardiac output at a range of preloads at Baseline, 45 minutes after coronary ligation (Ischemia), and 30 minutes later, following surgical reinforcement in the longitudinal direction (Anisotropic). Ischemia shifted the end-systolic pressure-volume relationship (ESPVR) and cardiac output curves rightward, decreasing cardiac output at matched end-diastolic pressure (EDP) by 44%. Anisotropic reinforcement significantly improved systolic function without impairing diastolic function, recovering half the deficit in overall LV function. Conclusions We conclude that anisotropic reinforcement is a promising new approach to improving LV function following a large myocardial infarction.

Stress echocardiography is an important screening test for coronary artery disease. Currently, cardiologists rely on visual analysis of left ventricular (LV) wall motion abnormalities, which is subjective and qualitative. We previously used finite-element models of the regionally ischemic left ventricle to develop a wall motion measure, 3DFS, for predicting ischemic region size and location from real-time 3D echocardiography (RT3DE). The purpose of this study was to validate these methods against regional blood flow measurements during regional ischemia and to compare the accuracy of our methods to the current state of the art, visual scoring by trained cardiologists. We acquired RT3DE images during 20 brief (<2 min) coronary occlusions in dogs and determined ischemic region size and location by microsphere-based measurement of regional perfusion. We identified regions of abnormal wall motion using 3DFS and by blinded visual scoring. 3DFS predicted ischemic region size well (correlation r 2 =0.64 against microspheres, p<0.0001), reducing error by more than half compared to visual scoring (8±9% vs. 19±14%, p<0.05), while localizing the ischemic region with equal accuracy. We conclude that 3DFS is an objective, quantitative measure of wall motion that localizes acutely ischemic regions as accurately as wall motion scoring while providing superior quantification of ischemic region size.

Significant weight gain is a side effect associated with olanzapine treatment in some patients. We investigated the efficacy of high-dose fluoxetine as a weight-reducing agent for patients who develop early weight gain with olanzapine treatment. Patients that gained X3% of their baseline weight in the initial 8 weeks of olanzapine treatment (n ¼ 31) were randomized to double-blind treatment with placebo or fluoxetine (60 mg/day). Clinical, weight, and weight-related measures were assessed. Fluoxetine failed to demonstrate weight-reducing effects (fluoxetine group: baseline mean 80.5 kg, SD ¼ 19.1, last mean ¼ 83.5 kg, SD ¼ 19.8; placebo group: baseline mean ¼ 77.1 kg, SD ¼ 12.1, last mean ¼ 78.8 kg, SD ¼ 10.6; F ¼ 1.3; df ¼ 1, 18; p ¼ 0.3). There were no differential effects in psychopathology, extrapyramidal side effects or weight-related measures between the placebo and fluoxetine groups. Serotonin reuptake inhibitors are probably not a practical option to counteract weight gain induced by atypical antipsychotics. Atypical-induced weight gain may result from mechanisms other than 5HT reuptake blockade.

Dynamic cardiac metrics, including myocardial strains and displacements, provide a quantitative approach to evaluate cardiac function. However, in current clinical diagnosis, largely 2D strain measures are used despite that cardiac motions are complex 3D volumes over time. Recent advances in 4D ultrasound enable the capability to capture such complex motion in a single image data set. In our previous work, a 4D optical flow based motion tracking algorithm was developed to extract full 4D dynamic cardiac metrics from such 4D ultrasound data. In order to quantitatively evaluate this tracking method, in-vivo coronary artery occlusion experiments at various locations were performed on three canine hearts. Each dog was screened with 4D ultrasound and sonomicrometry data was acquired during each occlusion study. The 4D ultrasound data from these experiments was then analyzed with the tracking method and estimated principal strain measures were directly compared to those recorded by sonomicrometry. Strong agreement was observed independently for the three canine hearts. This is the first validation study of optical flow based strain estimation for 4D ultrasound with a direct comparison with sonomicrometry using in-vivo data.