Background:
The interaction between regional left ventricular (LV) myocardial work and metabolism in remodeled hearts has not yet been well established. Our aim was to investigate the effect of inhomogeneous LV work distribution on regional metabolism and remodeling in our animal model with reversible dyssynchrony due to pacing.
Methods:
In 12 sheep, 8 weeks of right atrial and right ventricular free wall (DDD) pacing lead to LV dilatation, a thinned septum, and thickened lateral wall. Left bundle branch block–like dyssynchrony caused by DDD pacing could be acutely reverted by right atrial pacing (AAI) only. Invasive hemodynamics and echocardiography were used to assess regional work by stress-strain loop area and compared with regional glucose metabolism measured by
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F-fluorodeoxyglucose positron emission tomography with and without improved spatial resolution by motion and anatomy correction on gated reconstructions.
Results:
Glucose metabolism by positron emission tomography with anatomic correction on gated positron emission tomography reconstruction showed a different regional distribution than with clinical reconstructions and correlated best and significantly with regional myocardial work. At baseline, work was homogeneously distributed with normal conduction (AAI pacing), whereas during dyssynchrony (DDD pacing), the lateral wall was more loaded, and the septum was unloaded. After 8 weeks of remodeling under DDD pacing, however, an almost homogeneous work distribution was found with DDD pacing, whereas with AAI pacing, the thin septum showed exaggerated loading and the lateral walls a low load. Our experimental observations were confirmed in 5 patient responders to cardiac resynchronization therapy.
Conclusions:
Regional LV glucose metabolism closely correlates with regional work. Our data indicate that regionally different LV remodeling after exposure to inhomogeneous loading conditions, such as during LV dyssynchrony, is an adaptive process that helps to equilibrate work distribution. Correction of the inhomogeneous loading conditions, such as during cardiac resynchronization therapy, then triggers a reverse LV remodeling through the same mechanism.
Dys-synchronous myocardial shortening is related to thinning of early and thickening of late activated segments in heart failure with conduction delay. Correction of dys-synchrony leads to regression of inhomogeneity towards more evenly distributed wall thickness. Regional differences in myocardial work load that are homogenized by successful CRT are considered as the underlying pathophysiological mechanism.
The results indicated that high TH17/Treg ratio exists inrheumatic MVD. This imbalance may play a role in the pathogenesis, and TH17/Treg balance may be a promising therapeutic approach in RHD.
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