Rationale High-sensitivity in vivo phenotyping of cardiac function is essential for evaluating genes of interest and novel therapies in small animal models of cardiovascular disease. Transthoracic echocardiography is the principal method currently used for assessing cardiac structure and function; however, standard echocardiographic techniques are relatively insensitive to early or subtle changes in cardiac performance, particularly in mice. Objective To develop and validate an echocardiographic strain imaging methodology for sensitive and rapid cardiac phenotyping in small animal models. Methods and Results Herein, we describe a modified echocardiographic technique that utilizes speckle-tracking based strain analysis for the non-invasive evaluation of cardiac performance in adult mice. This method is found to be rapid, reproducible, and highly sensitive in assessing both regional and global left ventricular (LV) function. Compared to conventional echocardiographic measures of LV structure and function, peak longitudinal strain and strain rate were able to detect changes in adult mouse hearts at an earlier time point following myocardial infarction (post-MI) and predicted the later development of adverse LV remodeling. Moreover, speckle-tracking based strain analysis was able to clearly identify subtle improvement in LV function that occurred early in response to standard post-MI cardiac therapy. Conclusions Our results highlight the utility of speckle-tracking based strain imaging for detecting discrete functional alterations in mouse models of cardiovascular disease in an efficient and comprehensive manner. Echocardiography speckle-tracking based strain analysis represents a method for relatively high-throughput and sensitive cardiac phenotyping, particularly in evaluating emerging cardiac agents and therapies in mice.

No abstract

R ight ventricular (RV) function is closely coupled with subsequent morbidity and mortality in patients with diseases affecting the right heart chambers. [1][2][3][4][5][6][7] The most common cause of RV dysfunction is chronic left-sided heart failure. Complex factors such as pulmonary hypertension, intrinsic myocardial involvement, ventricular interdependence, and myocardial ischemia lead to RV dysfunction. 1 Therefore, assessment of RV function is clinically important in almost all patients with heart disease. However, the complex geometry of the RV poses a significant limitation to the reliable quantitation of RV volumes and ejection fraction (RVEF) using 2-dimensional transthoracic echocardiography. Although cardiac magnetic resonance (CMR) imaging is the gold standard for the evaluation of RV volumes and RVEF, 8,9 factors such as cost, portability, time consumption, and contraindications hinder its routine use in every patient. Three-dimensional transthoracic echocardiography (3DTTE) has the advantage of full-volume acquisition of the entire right ventricle, which may overcome the technical and clinical limitations of 2-dimensional transthoracic echocardiography. [10][11][12] Recent studies have validated the accuracy of 3DTTE-determined RV volumes and RVEF against CMR 13,14 and determined the reference values of RV volumes and RVEF in healthy subjects. 15,16 However, the prognostic value of RVEF is largely unknown. We hypothesized that RVEF assessed by 3DTTE (3DRVEF) would offer incremental value over left ventricular (LV) functional parameters for predicting future cardiac events. See Editorial by Fernández-Golfín and Zamorano See Clinical PerspectiveAccordingly, the aims of this study were (1) to validate the accuracy of 3DTTE-determined RV volumes and RVEF against CMR reference and (2) to evaluate the prognostic value of 3DRVEF to predict future cardiac death and major adverse cardiac events (MACEs) in a large number of patients.Background-Cardiac magnetic resonance is the gold standard for the evaluation of right ventricular (RV) volumes, but it is impractical to perform in every patient. Although reference values of RV volumes and RV ejection fraction by 3D transthoracic echocardiography (3DTTE) have been established, their prognostic values have not been elucidated yet. We hypothesized that RV ejection fraction measured by 3DTTE (3DRVEF) predicts future cardiovascular events. Methods and Results-In protocol 1, we determined the accuracy of RV volumes and RV ejection fraction measurements by 3DTTE against cardiac magnetic resonance in 60 subjects. In protocol 2, 3DRVEF was measured in 446 patients with various cardiovascular diseases. Study subjects were followed up to record cardiac death and major adverse cardiovascular events. In protocol 1, 3DTTE-determined RV end-diastolic volume, end-systolic volume, and RV ejection fraction had good correlations to those by cardiac magnetic resonance (r=0.74-0.90). In protocol 2, 38 cardiac deaths and 88 major adverse cardiovascular events occurred during a med...