Circumferential strain recovery after human cardiomyocyte transplantation in minipigs using a novel frequency-based method for myocardial tagging quantification.

BACKGROUND

Transplantation of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) is a promising new method for heart remuscularization after infarction. We hypothesized that hPSC-CMs affect heart function by improving local contractility in the infarcted zones. However, there is a need for a precise noninvasive assessment of regional contractile function in the infarcted segments.

METHODS

We describe here a novel approach for rapid and robust quantification of myocardial end-systolic circumferential strain (CS). Linear tags are placed in 60-degree pattern offsets and analyzed via optimized post-processing based on local Fourier transformation of standardized American Heart Association (AHA) myocardial segmentation. This method has been implemented for the first time to evaluate transendocardial hPSC-CMs transplantation in a minipig model of myocardial infarction. Validation of the new frequency-based calculation of myocardial strain was done using two independent approaches as follows: (1) a tag tracking, and (2) feature tracking technique.

RESULTS

In the cell-treated hearts (n=4), mean end-systolic CS in the infarcted segments (anterior and anteroseptal areas combined) at the mid-wall region decreased from -6.69 ± 1.56% (pre-MI) to -1.13 ± 1.96% at 2 weeks post-MI (pre-treatment), with subsequent improvement to -4.00 ± 0.76% by 8 weeks after cell transplantation. Conversely, CS in the infarcted segments in vehicle-control group (n=5) decreased from -5.18 ± 0.97% (pre-MI) to -1.39 ± 1.23% at 2 weeks post-MI and worsened further to 0.33 ± 1.93% by 8 weeks post-vehicle. There was no improvement in the global ejection fraction in the cell-treated group in comparison with control. It was a high correlation of the new method of myocardial strain calculation with the standard tag tracking approach and feature tracking strain analysis across the experimental conditions (normal heart, infarcted, cell/vehicle treated).

CONCLUSIONS

A novel frequency-based technique for assessment of local circumferential strain does not require specialized acquisition protocols, access to k-space data, nor highly optimized reconstruction algorithms or commercial software. It can quickly and precisely assess regional myocardial injury and recovery. Our findings support our hypothesis that transplantation of hPSC-CMs improves regional myocardial strain in infarcted minipig hearts.