Global dyssynchrony correlates with compromised left ventricular filling and stroke volume but not with ejection fraction or QRS duration in HFpEF

Background and Aim: Mechanical global left ventricular (LV) dyssynchrony reflected as prolonged total isovolumic time (t-IVT) has been introduced as a potential mechanism behind compromised stroke volume in heart failure (HF). It has also been shown to be superior to other markers of dyssynchrony in predicting response to cardiac resynchronization therapy (CRT), but its application in HF with preserved ejection fraction (HFpEF) remains unknown. The aim of this study was to assess the role of t-IVT in explaining symptoms in HFpEF. Methods: In 55 symptomatic HFpEF patients (age 60±9 years, NYHA class II-IV; LV EF ≥45%) and 24 age and gender matched controls, a complete Doppler echocardiographic study was performed including mitral annulus peak systolic excursion (MAPSE) and myocardial velocities as well as LV filling, outflow tract velocity time integral (VTI) and stroke volume measurements. Global LV dyssynchrony was assessed by t-IVT [in s/min; calculated as: 60 - (total ejection time + total filling time)], Tei index (t-IVT/ejection time) and pre-ejection time difference between LV and RV. Results: Patients had reduced lateral and septal MAPSE (p=0.009 and p=0.01, respectively) lower lateral and septal s’ (p=0.002 and p=0.04, respectively) and e’ (p<0.001, for both) velocities and higher E/e’ ratio (p=0.01) compared to controls. They also had longer t-IVT (p<0.001), higher Tei index (p=0.04), but similar pre-ejection time difference and LVEF to controls. T-IVT correlated with LV filling time (r=0.44, p<0.001), stroke volume (r=-0.41; p=0.002), MAPSE (lateral: r=-0.36, p=0.007 and septal: r=-0.31; p=0.02), but not with LV mass index, LVEF, E/e’ ratio or QRS duration. Conclusion: Patients with HFpEF have exaggerated global mechanical dyssynchrony shown by prolonged t-IVT, compared with healthy age and gender matched controls. The relationship between t-IVT, LV filling and stroke volume suggests an association, more important than with ejection fraction or electrical dyssynchrony. These results support the importance of the individualistic approach for optimum HFpEF patient management.