Key result
TAC-spared non-hypertrophied segments linked to ~17-point lower LVEF in murine pressure overload.
Why the study?
Growing evidence suggests myocardium responds to chronic pressure overload in a spatially heterogeneous manner rather than traditional uniform concentric hypertrophy.
p-value: p=<0.001
Multiparametric cardiac MRI identifies spatial heterogeneity in myocardial adaptation to pressure overload, revealing a 'spared hypertrophy' segment linked to early regional and global functional decline.
Spared hypertrophy segments associate with lower EF in TAC mice; hypothesis-generating for regional remodeling heterogeneity but leaves open human relevance.
Cardiac adaptation to chronic pressure overload is traditionally viewed as a uniform concentric hypertrophy; however, growing evidence suggests that the myocardium responds in a spatially heterogeneous manner. This study aimed to systematically map regional and temporal adaptation patterns of the left ventricle (LV) under experimental pressure overload using high-resolution multiparametric cardiac MRI, with the hypothesis that distinct regional adaptation phenotypes contribute to both local functional differences and global ventricular dysfunction. Thirty-seven male 129/SvEv mice underwent transverse aortic constriction (TAC) surgery and were followed longitudinally over 7 weeks. Cine imaging, T1- and T2-mapping were performed at baseline, 3 days, 4 weeks and 7 weeks using a 9.4 T small-animal scanner. A 200-sector LV segmentation enabled quantitative regional analysis of wall thickness, fractional shortening (FS) and relaxation times. Global and regional imaging parameters were correlated with histological and biochemical indices at study termination, and statistical analyses were performed using the Mann-Whitney test and correlation modelling, with p < 0.05 considered significant. All TAC animals developed global LV hypertrophy and an early increase in LV mass (+62% ± 15% at Week 7, p < 0.001). Unexpectedly, in 18 animals (49%), a discrete basolateral LV segment failed to hypertrophy (spared hypertrophy, SH) despite uniform pressure elevation. This region exhibited markedly reduced regional FS (10.2% ± 3.1% vs. 24.9% ± 2.2%, p = 0.01) and was associated with lower global ejection fraction (32.5% ± 1.8% vs. 49.8% ± 4.1%, p < 0.05) and LV dilatation. Parametric MRI revealed distinct tissue signatures: T1 increased in hypertrophied sectors (+22.6% ± 1.1%), whereas it decreased in SH sectors (-5.1% ± 1.7%, p < 0.01) over the 7-week observation period. Sector-wise correlations linked T1 shortening with reduced FS (R² = 0.58, p = 0.002), suggesting maladaptive regional remodeling. In conclusion, pressure overload elicits diverse regional adaptation, and failure to hypertrophy identifies myocardial territories prone to early dysfunction and global decline. Recognizing hypertrophy as an essential adaptive mechanism shifts the paradigm of pressure-overload remodeling. Multiparametric MRI provides a translational platform for detecting regional vulnerability and guiding early intervention.
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Koch et al. (2026) studied Pressure overload-induced cardiac hypertrophy (n=37). Transverse aortic constriction (TAC) vs. Baseline (longitudinal follow-up) was evaluated on Change in left ventricular (LV) mass at 7 weeks (p=<0.001). Transverse aortic constriction induced global LV hypertrophy, but 49% of mice showed a spared, non-hypertrophied segment associated with lower global ejection fraction (32.5% vs 49.8%, p<0.05).
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