Mechanistic validation of the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging Guidelines for the assessment of diastolic dysfunction in heart failure with reduced ejection fraction

Background: The American Society for Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI) 2016 guidelines for assessment of diastolic dysfunction (DD) are based primarily on the effects of diastolic dysfunction on left ventricular filling hemodynamics. However, these measures do not provide quantifiable mechanistic information about diastolic function. The Parameterized Diastolic Filling (PDF) formalism is a validated theoretical framework that describes DD in terms of the physical properties of left ventricular filling. Aims: We hypothesized that PDF analysis can provide mechanistic insight into the mechanical properties governing higher grade DD. Methods: Patients referred for echocardiography showing reduced left ventricular ejection fraction (< 45%) were prospectively classified into DD grade according to 2016 ASE/EACVI guidelines. Serial E-waves acquired during free breathing using pulsed wave Doppler of transmitral blood flow were analyzed using the PDF formalism. Results: Higher DD grade (grade 2 or 3, n = 20 vs grade 1, n = 30) was associated with increased chamber stiffness (261 ± 71 vs 169 ± 61 g/s², p < 0.001), increased filling energy (2.0 ± 0.9 vs 1.0 ± 0.5 mJ, p < 0.001) and greater peak forces resisting filling (median [interquartile range], 18 [15–24] vs 11 [8–14] mN, p < 0.001). DD grade was unrelated to chamber viscoelasticity (21 ± 4 vs 20 ± 6 g/s, p = 0.32). Stiffness was inversely correlated with ejection fraction (r = − 0.39, p = 0.005). Conclusions: Higher grade DD was associated with changes in the mechanical properties that determine the physics of poorer left ventricular filling. These findings provide mechanistic insight into, and independent validation of the appropriateness of the 2016 guidelines for assessment of DD.