Synopsis

At present, hypertensive left ventricular hypertrophy (LVH) is generally considered to be an adaptive hypertrophy of cardiomyocytes due to an increase in left ventricular afterload. However, recent studies have shown that myocardial interstitial fibrosis may play an important role in cardiac hypertrophy. This study aims to investigate the relationship between extracellular volume (ECV) fraction and left ventricular remodeling in hypertension by prospective randomized controlled swine model of hypertension, and explain its internal mechanism based on pathology.

Background: The mechanism of left ventricular hypertrophy (LVH) in the setting of hypertension is currently thought to be an adaptive hypertrophy of cardiomyocytes in response to hypertension. However, recent studies have shown that extracellular interstitial fibrosis, which can be detected by extracellular volume (ECV) fraction on CMR, also plays an important role in LVH.

Aim: To quantitatively evaluate the dynamic changes of ECV in normal and hypertensive pigs over time and determine whether ECV quantification by cardiac magnetic resonance (CMR) can demonstrate left ventricle (LV) extracellular interstitial fibrosis in a hypertensive (HTN) swine model. To determine the significance of extracellular interstitial fibrosis in left ventricular remodeling and hypertrophy secondary to hypertension.

Methods: Ten adult male Chinese miniature pigs aged 6-12 months were divided into two groups: 7 pigs were in the hypertensive (HTN) group and 3 pigs were in the normal control group. Both groups of pigs underwent cardiac MR imaging before and 1week, 1 month, 3 months, 6 months after induction of hypertension in the HTN group. The systolic and diastolic pressure of HTN group was gradually increased from 111.20/68.00 mmHg to 167.67/109.33mmHg. ECV quantification was prospectively performed in both groups at all imaging time points. Systolic function of the left ventricle (LV) was calculated from the cine images. Individual and segmental ECV were compared to the late gadolinium enhancement (LGE) images. Histopathologic examination of the heart was performed after sacrifice.

Results: The control group ECV was 24.21±4.0%. The mean ECV fraction was higher in the HTN model group than the control group ECV fraction at 3 months (25.79±5.81; p=0.009) and 6 months (26.88±4.87; p=0.019). The LGE of both HTN and NC groups were all negative. There were no differences between the HTN group and control group in terms of LV ejection fraction (mean, 61.38±6.64 vs 63.67±4.51; P =0 .99).

Conclusion: ECV fraction calculation from CMR imaging can identify LV abnormalities secondary to myocardial fibrosis at an early stage in a HTN model before LGE abnormalities are evident. As the hypertensive disease progresses, the ECV fraction increases. These abnormalities reflect diffuse myocardial fibrosis. Extrapolation of this finding from animal models to human subjects suggests that ECV measured by CMR could be a robust sensitive parameter in HTN patients to detect fibrosis. These results provide scientific basis for relevant basic and clinical research, especially for drug therapy targeting increased extracellular matrix synthesis in HTN patients.

Acknowledgements

References

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