Quantification of Cardiomyocyte Hypertrophy by Cardiac Magnetic Resonance

Abstract

Background Cardiomyocyte hypertrophy is a critical precursor to the development of heart failure. Methods to phenotype cellular hypertrophy non-invasively are limited. The goal was to validate a CMR-based approach for the combined assessment of extracellular matrix expansion and cardiomyocyte hypertrophy. Methods and Results Two murine models of a) hypertension (N=18, with N=15 controls) induced by L-NG-Nitroarginine Methyl Ester (L-NAME) and b) pressure-overload (N=11) from transaortic constriction (TAC), were imaged by CMR at baseline and 7-weeks after L-NAME treatment, or up to 7 weeks following TAC. T1 relaxation times were measured before and after gadolinium contrast. The intracellular lifetime of water (τic), a cell size dependent parameter, and extracellular volume fraction (ECV), a marker of interstitial fibrosis, were determined with a model for transcytolemmal water exchange. Cardiomyocyte diameter and length were measured on FITC-wheat germ agglutinin stained sections. τic correlated strongly with histologic cardiomyocyte volume-to-surface ratio (r=0.78, P<0.001) and cell volume (r=0.75; P<0.001). Histological cardiomyocyte diameters and cell volume were higher in mice treated with L-NAME compared to controls (P<0.001). In the TAC model, CMR and histology showed an cell hypertrophy at two weeks post TAC, without significant fibrosis at this early time point. Mice exposed to TAC demonstrated a significant, longitudinal, and parallel increase in histological cell volume, volume-to-surface ratio, and τic,between 2 and 7 weeks after TAC. Conclusion The intracellular lifetime (τic) measured by contrast-enhanced CMR provides a non-invasive measure of cardiomyocyte hypertrophy. ECV and τic can track myocardial tissue remodeling from pressure overload.

Exercise-Induced Left Ventricular Remodeling Among Competitive Athletes

“…It is noteworthy that the eccentric hypertrophy that developed during CMP was coupled with preservation of supranormal diastolic function, thereby emphasizing the uniquely adaptive nature of EICR in endurance athletes. Future work including the direct measurement of plasma volume and the use of recently developed imaging techniques capable of resolving cellular architecture 25 will be required to confirm these putative mechanisms.…”

Acute Reverse Remodelling After Transcatheter Aortic Valve Implantation: A Link Between Myocardial Fibrosis and Left Ventricular Mass Regression

“…Further study using pre-and post-contrast T1 mapping to estimate extracellular volume and cardiomyocyte size may help to further unravel this potential mechanistic effect [23,24].…”

T1 Mapping in Discrimination of Hypertrophic Phenotypes: Hypertensive Heart Disease and Hypertrophic Cardiomyopathy

“…In compensated LVH because of hypertension-that is before extensive structural and metabolic remodeling with cavity dilatation and functional impairment (eccentric remodeling)-findings reflect physiological adaptations with an increased cellular size because of addition of new, but functional myofibrilles in-parallel and in-series, enabling the ventricle to generate greater forces and to outweigh the increased wall stress. 11,[13][14][15][16][17] Interstitial fibrosis and the expansion of extracellular space in hypertension herald decompensation with eccentric remodeling and heart failure. [12][13][14][15][18][19][20][21][22] In this study, we investigated the ability of CMR to discern hypertrophic phenotypes based on detection of diffuse myocardial disease and regional fibrosis by myocardial T1 mapping and LGE, respectively, first, in overt LVH, and second, in phenotypically subexpressed HCM gene carriers.…”