Preserved and reduced ejection fraction manifest as two unique phenotypes of diastolic dysfunction—a mechanistic study

Diastolic dysfunction is commonplace in patients with preserved (pEF) and reduced (rEF) ejection fraction (EF). Differences in treatment response suggest that these classifications represent two unique phenotypes of diastolic dysfunction. We aimed to evaluate if patients with pEF and rEF would exhibit different mechanics of diastolic dysfunction. Patients with normal EF and normal diastolic function, or grade 2 or 3 diastolic dysfunction with pEF or rEF by echocardiography, were retrospectively identified.

Diastolic function was assessed using the parameterized diastolic filling method, which allows for quantification of key mechanistic properties such as myocardial stiffness and damping using the early mitral inflow pattern of the E-wave from Doppler echocardiography. Patients with diastolic dysfunction and pEF (n = 75) or rEF (n = 75) did not differ in E/e’, tricuspid regurgitation peak velocity, or left atrial volume index (P > 0.05 for all). Ventricular stiffness (mmHg/mL) did not differ between controls [0.13 (0.06–0.20)] and patients with either pEF [0.12 (0.06–0.18)] or rEF [0.11 (0.05–0.17), P > 0.3 for all], while damping (g/s) was increased in pEF [24.1 (20.5–33.2), P < 0.001] but reduced in rEF (16.1 [12.5–19.8], P = 0.005) when compared with controls [19.8 (15.1–24.8)].

Whilst pEF and rEF do not differ in key conventional echocardiographic measures of diastolic dysfunction, they are two unique physiological conditions where diastolic dysfunction manifests fundamentally differently. These findings challenge traditional assumptions about the role of myocardial stiffness in ventricular filling and underscore the importance of damping as a key component of diastolic dysfunction.