Background Anthracyclines are cardiotoxic; however, there are limited data characterizing the serial changes in cardiac structure and function after anthracyclines. The aim of this study was to use cardiac magnetic resonance (CMR) to characterize anthracycline-induced cardiotoxicity (AIC) in mice. Methods and Results This was a longitudinal CMR and histological study of 45 wild-type male mice randomized to doxorubicin (DOX, n=30, 5 mg/kg of DOX/week for 5 weeks) or placebo (n=15). A CMR was performed at baseline and at 5, 10 and 20 weeks after randomization. Measures of primary interest included left ventricular ejection fraction (LVEF), myocardial edema (multi-echo short-axis spin-echo acquisition) and myocardial fibrosis (Look-Locker gradient-echo). In DOX-treated mice vs. placebo, there was an increase in myocardial edema at 5 weeks (T2 values of 32±4 vs. 21±3 msec, P < 0.05); followed by a reduction in LVEF (54±6 vs. 63±5%, P < 0.05) and an increase in myocardial fibrosis (extracellular volume of 0.34±0.03 vs. 0.27±0.03, P < 0.05) at 10 weeks. There was a strong association between the early (5 weeks) increase in edema and the sub-acute (10 weeks) increase in fibrosis (r = 0.90, P < 0.001). Both the increase in edema and fibrosis predicted the late DOX-induced mortality in mice (P < 0.001). Conclusions Our data suggest that, in mice, AIC is associated with an early increase in cardiac edema and a subsequent increase in myocardial fibrosis. The early increase in edema and sub-acute increase in fibrosis are strongly linked and are both predictive of late mortality.

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OBJECTIVES To investigate the impact of transcatheter intervention on left ventricular (LV) function and aortic hemodynamics in patients with mild coarctation of the aorta (COA). BACKGROUND The optimal method and timing of transcatheter intervention for COA remains unclear, especially when the severity of COA is mild (peak-to-peak trans-coarctation pressure gradient, PKdP < 20 mmHg). Debate rages regarding the risk/benefit ratio of intervention vs. long-term effects of persistent minimal gradient in this heterogeneous population with differing blood pressures, ventricular function and peripheral perfusion. METHODS We developed a unique computational fluid dynamics and lumped parameter modeling framework based on patient-specific hemodynamic input parameters and validated it against patient-specific clinical outcomes (pre- and post-intervention). We used clinically measured hemodynamic metrics and imaging of the aorta and the LV in thirty-four patients with mild COA to make these correlations. RESULTS Despite dramatic reduction in trans-coarctation pressure gradient (catheter and Doppler echocardiography pressure gradients reduced 75% and 47.3%,), there was only modest effect on aortic flow and no significant impact on aortic shear stress (maximum time-averaged wall shear stress in descending aorta was reduced 5.1%). In no patient did transcatheter intervention improve LV function (e.g., stroke work and normalized stroke work were reduced by only 4.48% and 3.9%). CONCLUSIONS Transcatheter intervention which successfully relieves mild COA pressure gradients does not translate to decrease myocardial strain. The effects of intervention were determined to the greatest degree by ventricular-vascular coupling hemodynamics, and provide a novel valuable mechanism to evaluate patients with COA which may influence clinical practice.