1348591 - The effect of aortic coarctation on cardiac contractility: a preclinical CMR study

Aortic coarctation (CoA) is a congenital cardiovascular disease characterized by severe narrowing of the proximal descending thoracic aorta, which affects 5,000-8,000 births annually in USA. The long-term morbidity that persists in many patients despite successful surgical correction can be explained on the basis of abnormal cardiac function and hemodynamics. However, morbidity from CoA is difficult to study clinically; therefore, data are limited following correction and using less severe clinically representative blood pressure gradients (BPG). In this study, we used CMR to investigate the impact of coarctations within the range of BPG seen clinically on cardiac contractility using rabbit models of treated and untreated CoA.

Methods:

New Zealand white rabbits underwent CoA of the proximal descending thoracic aorta when they were ~10-weeks of age to produce peak-to-peak BPGs (BPGpp) of ≤10, 11-20 , or >20 mmHg for 1, 4 or 20 weeks (Figure 1). A control group was also established. Anesthetized rabbits (n=3-10/group) were scanned at 32 weeks on a GE 3T MRI scanner using an 18-channel knee coil. Both cine and tagged images were acquired to obtain short-axis and long-axis slices covering the heart. The cine images were analyzed using the cvi42 software to measure ejection fraction (EF) and mass. The tagged images were analyzed using the SinMod method to measure myocardial circumferential (Ecc) and longitudinal (Ell) strains. Data were presented as mean ± standard error of the mean (SEM).

Results:

The results showed some differences in CMR parameters between groups. LV mass was only statistically elevated for the most severe CoA (6.0±0.7 g) versus Control (3.9±0.3 g) group. Other CMR parameters including EF, circumferential and longitudinal strains, and percent LV thickening were not statistically different between groups. For example, Ell and Ecc were similar between groups regardless of the severity or duration of CoA vs Control (Table 1). For the BPGpp 11-20 mmHg group, Ell / Ecc for 1-week = -20±3% / -17±4%; 4-weeks = -22±4% / -20±4%; and 20-weeks = -22±2% / -19±1% vs. control -21±2% / -25±3%. The corresponding EF for 1-week = 55±3%; 4-weeks = 57±6%; and 20-weeks = 61±3% vs. control 56±3%. However, the corresponding mass for 1-week = 4.0±0.2 g; 4-weeks = 4.3±0.4 g; and 20-weeks = 4.4±0.3 g vs. control 3.9±0.3 g.

Conclusion:

These findings suggest that the current putative treatment guideline referencing a BPGpp >20 mmHg may be reasonable to avoid LV remodeling. CMR imaging of the rabbit model developed here for treated and untreated CoA provides valuable information about global and regional cardiac function in controlled settings resembling patients with aortic CoA. The results showed that cardiovascular parameters can normalize in mild CoA (severity or duration) as compared to the most severe case. These findings may inform future guidelines of BPGpp values for avoiding long-term morbidity.