20 Aug 20. Featured Paper

Progression & regression of left ventricular hypertrophy & myocardial fibrosis in a mouse model of hypertension & concomitant cardiomyopathy.

Link to paper on Journal of Cardiovascular Magnetic Resonance

Authors

Jacek Kwiecinski, Ross J. Lennen, Gillian A. Gray, Gary Borthwick, Lyndsey Boswell, Andrew H. Baker, David E. Newby, Marc R. Dweck & Maurits A. Jansen.

Abstract

Background: Myocardial fibrosis is observed in multiple cardiac conditions including hypertension & aortic stenosis.

Excessive fibrosis is associated with adverse clinical outcomes, but longitudinal human data regarding changes in left ventricular remodelling & fibrosis over time are sparse because of the slow progression, thereby making longitudinal studies challenging.

The purpose of this study was to establish & characterize a mouse model to study the development & regression of left ventricular hypertrophy & myocardial fibrosis in response to increased blood pressure & to understand how these processes reverse remodel following normalisation of blood pressure.

Methods: We performed a longitudinal study with serial cardiovascular magnetic resonance (CMR) imaging every 2 weeks in mice (n = 31) subjected to angiotensin II-induced hypertension for 6 weeks & investigated reverse remodelling following normalisation of afterload beyond 6 weeks (n = 9).

Left ventricular (LV) volumes, mass, & function as well as myocardial fibrosis were measured using cine CMR & the extracellular volume fraction (ECV) s.

Results: Increased blood pressure (65 ± 12 vs 85 ± 9 mmHg; p < 0.001) resulted in higher indices of LV hypertrophy (0.09 [0.08, 0.10] vs 0.12 [0.11, 0.14] g; p < 0.001) & myocardial fibrosis (ECV: 0.24 ± 0.03 vs 0.30 ± 0.02; p < 0.001) whilst LV ejection fraction fell (LVEF, 59.3 [57.6, 59.9] vs 46.9 [38.5, 49.6] %; p < 0.001).

We found a strong correlation between ECV & histological myocardial fibrosis (r = 0.89, p < 0.001).

Following cessation of angiotensin II & normalisation of blood pressure (69 ± 5 vs baseline 65 ± 12 mmHg; p = 0.42), LV mass (0.11 [0.10, 0.12] vs 0.09 [0.08, 0.11] g), ECV (0.30 ± 0.02 vs 0.27 ± 0.02) & LVEF (51.1 [42.9, 52.8] vs 59.3 [57.6, 59.9] %) improved but remained impaired compared to baseline (p < 0.05 for all).

There was a strong inverse correlation between LVEF & %ECV during both systemic hypertension (r = − 0.88, p < 0.001) & the increases in ECV observed in the first two weeks of increased blood pressure predicted the reduction in LVEF after 6 weeks (r = − 0.77, p < 0.001).

Conclusions: We have established & characterized angiotensin II infusion & repeated CMR imaging as a model of LV hypertrophy & reverse remodelling in response to systemic hypertension.

Changes in myocardial fibrosis & alterations in cardiac function are only partially reversible following relief of hypertension.

Keywords

• Cardiovascular magnetic resonance 
• ECV
• Hypertension
• T1-mapping