20 Aug 20. Featured Paper
Progression & regression of left ventricular hypertrophy & myocardial fibrosis in a mouse model of hypertension & concomitant cardiomyopathy.
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.
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Featured paper: Progression & regression of left ventricular hypertrophy & myocardial fibrosis in a mouse model of hypertension & concomitant cardiomyopathy. @MarcDweck @EdinUniCVS @EdinUniCinema #Hypertension #CMR