Left Atrial Function Dynamics During Exercise in Heart Failure: Pathophysiological Implications on the Right Heart and Exercise Ventilation Inefficiency.

Objectives: The hypothesis of this study was that left atrial (LA) dynamic impairment during exercise may trigger right ventricular (RV)-to-pulmonary circulation (PC) uncoupling and ventilation inefficiency.

Background: LA function plays a key role in the hemodynamics of heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Extensive investigation of LA dynamics, however, has been performed exclusively at rest.

Methods: A total of 49 patients with HFrEF, 20 patients with HFpEF, and 32 healthy subjects with normal LA size and reservoir function (LA volume index <34 ml/m and peak left atrial strain [LA-strain] during LA relaxation >23%) were prospectively enrolled. They underwent cardiopulmonary exercise testing and contemporary echo-Doppler assessment of LA-strain and LA-strain rate and of RV-to-PC coupling (pulmonary arterial systolic pressure/tricuspid annular peak systolic excursion ratio), measured at rest, at 40% of predicted peak oxygen consumption, and during recovery.

Results: In control subjects, LA-strain increased during exercise and recovery. Patients with HFpEF exhibited some LA-strain increase during exercise and recovery, whereas no changes occurred in those with HFrEF. The baseline LA-strain rate was greater in control subjects; a significant enhancement during recovery was observed only in this group. In both the HFpEF and HFrEF cohorts, RV-to-PC uncoupling and LA-strain at rest, exercise, and recovery significantly correlated with pulmonary arterial systolic pressure/tricuspid annular peak systolic excursion, as well as ventilation versus carbon dioxide slope, in a continuous fashion across groups (r = -0.63 and r = -0.59, r = -0.65 and r = -0.50, and r = -0.70 and r = -0.53 for control subjects, HFpEF, and HFrEF, respectively; p < 0.05).

Conclusions: In heart failure, an impaired LA-strain response is a key hemodynamic trigger for RV-to-PC uncoupling and exercise ventilation inefficiency with some overlap between HFpEF and HFrEF phenotypes. Reversibility of LA dynamics seems to be an unmet target of specific therapeutic interventions.