Left Ventricular Geometry as a Major Determinant of Left Ventricular Ejection Fraction: Physiological Considerations and Clinical Implications

The limited myocardial fibre thickening and shortening alone cannot explain the marked left ventricular (LV) volume reduction during LV ejection. This can only be achieved with LV helical (spiral) orientation of myocardial fibres, which is determined by the non-contractile LV myocardial components (intrasarcomeric and extrasarcomeric cytoskeleton, extracellular matrix). Preservation of LV ejection fraction (LVEF) in heart failure (HF) is due to the presence of normal ellipsoid LV configuration and spiral myocardial fibre orientation. Conversely, reduction of LVEF in HF results from spherical LV configuration associated with impaired myocardial fibre orientation. These mechanisms are supported by the fact that biomarkers of inflammation and fibrosis are strong predictors of LV reverse remodelling in HF with reduced LVEF (HFrEF) and therapeutic interventions in HFrEF that retard or inhibit extracellular matrix remodelling are effective, whereas those that increase myocardial contractility are ineffective. Thus, current classification of HF, based on LVEF, should be revised, and future therapy in HF should focus on interventions affecting the non-contractile LV myocardial components rather than on LV myocardial contractility.