Faculty Bibliography

BACKGROUND:Echocardiography (echo)-quantified LV stroke volume (SV) is widely used to assess systolic performance after acute myocardial infarction (AMI). This study compared 2 common echo approaches - predicated on flow (Doppler) and linear chamber dimensions (Teichholz) - to volumetric SV and global infarct parameters quantified by cardiac magnetic resonance (CMR). METHODS:Multimodality imaging was performed as part of a post-AMI registry. For echo, SV was measured by Doppler and Teichholz methods. Cine-CMR was used for volumetric SV and LVEF quantification, and delayed-enhancement (DE) CMR for infarct size. RESULTS:Overall, 142 patients underwent same day echo and CMR. On echo, mean SV by Teichholz (78 ± 17 mL) was slightly higher than Doppler (75 ± 16 mL; Δ = 3 ± 13 mL; P = 0.02). Compared to SV on CMR (78 ± 18 mL), mean difference by Teichholz (Δ = -0.2 ± 14; P = 0.89) was slightly smaller than Doppler (Δ = -3 ± 14; P = 0.02), but limits of agreement were similar between CMR and echo methods (Teichholz: -28, 27 mL, Doppler: -31, 24 mL). For Teichholz, differences with CMR SV were greatest among patients with anteroseptal or lateral wall hypokinesis (P < 0.05). For Doppler, differences were associated with aortic valve abnormalities or root dilation (P = 0.01). SV by both echo methods decreased stepwise in relation to global LV injury as assessed by CMR-quantified LVEF and infarct size (P < 0.01). CONCLUSIONS:Teichholz and Doppler calculated SV yield similar magnitude of agreement with CMR. Teichholz differences with CMR increase with septal or lateral wall contractile dysfunction, whereas Doppler yields increased offsets in patients with aortic remodeling.

Key requirements for cardiac tissue engineering include the maintenance of cell viability and function and the establishment of a perfusable vascular network in millimeters thick and compact cardiac constructs upon implantation. We investigated if these requirements can be met by providing an intrinsic vascularization stimulus (via sustained action of VEGF secreted at a controlled rate by transduced myoblasts) to a cardiac patch engineered under conditions of effective oxygen supply (via medium flow through channeled elastomeric scaffolds seeded with neonatal cardiomyocytes). We demonstrate that this combined approach resulted in increased viability, vascularization and functionality of the cardiac patch. After implantation in a mouse model of myocardial infarction, VEGF-expressing patches displayed significantly improved engraftment, survival and differentiation of cardiomyocytes, leading to greatly enhanced contractility as compared to controls not expressing VEGF. Controlled VEGF expression also mediated the formation of mature vascular networks, both within the engineered patches and in the underlying ischemic myocardium. We propose that this combined cell-biomaterial approach can be a promising strategy to engineer cardiac patches with intrinsic and extrinsic vascularization potential.

The capability of currently available echocardiography-based strain estimation techniques to fully map myocardial abnormality at early stages of myocardial ischemia is yet to be investigated. In this study, myocardial elastography (ME), a radio-frequency (RF)-based strain imaging technique that maps the full 2D transmural angle-independent strain tensor in standard echocardiographic views at both high spatial and temporal resolution is presented. The objectives were to (1) evaluate the performance of ME on mapping the onset, extent and progression of myocardial ischemia at graded coronary constriction levels (from partial to complete coronary flow reduction), and (2) validate the accuracy of the strain estimates against sonomicrometry (SM) measurements. A non-survival canine ischemic model (n = 5) was performed by gradually constricting the left anterior descending (LAD) coronary blood flow from 0% (baseline blood flow) to 100% (zero blood flow) at 20% increments. An open-architecture ultrasound system was used to acquire RF echocardiograms in a standard full short-axis view at the frame rate of 211 fps, at least twice higher than what is typically used in conventional echocardiographic systems, using a previously developed, fully automated composite technique. Myocardial deformation was estimated by ME and validated against sonomicrometry. ME estimates and maps transmural (1) 2D displacements using RF cross-correlation and recorrelation; and (2) 2D polar (radial and circumferential) strains, derived from 2D (i.e. both lateral and axial) displacement components, at high accuracy. Full-view strain images were shown and found to reliably depict decreased myocardial function in the region at risk at increased levels of coronary flow reduction. The ME radial strain was deemed to be a more sensitive, quantitative, regional measure of myocardial ischemia as a result of coronary flow reduction when compared to the conventional wall motion score index and ejection fraction. Good agreement (0.22% strain bias, 95% limits of agreement) using Bland-Altman analysis and good correlation (r = 0.84) were found between the ME and SM measurements. These findings demonstrate for the first time that ME could map angle-independent strains to non-invasively detect, localize and characterize the early onset of myocardial ischemia, i.e. at 40%, and possibly as low as 20%, LAD flow reduction, which could be further associated with the severity of coronary stenosis.

Cardiac conduction abnormalities remain a major cause of death and disability worldwide. However, as of today, there is no standard clinical imaging modality that can noninvasively provide maps of the electrical activation. In this paper, electromechanical wave imaging (EWI), a novel ultrasound-based imaging method, is shown to be capable of mapping the electromechanics of all four cardiac chambers at high temporal and spatial resolutions and a precision previously unobtainable in a full cardiac view in both animals and humans. The transient deformations resulting from the electrical activation of the myocardium were mapped in 2D and combined in 3D biplane ventricular views. EWI maps were acquired during five distinct conduction configurations and were found to be closely correlated to the electrical activation sequences. EWI in humans was shown to be feasible and capable of depicting the normal electromechanical activation sequence of both atria and ventricles. This validation of EWI as a direct, noninvasive, and highly translational approach underlines its potential to serve as a unique imaging tool for the early detection, diagnosis, and treatment monitoring of arrhythmias through ultrasound-based mapping of the transmural electromechanical activation sequence reliably at the point of care, and in real time.