Beyond exercise oscillatory ventilations: the prognostic impact of loop gain in heart failure

Exercise oscillatory ventilation (EOV) is a strong prognostic marker in patients with heart failure (HF) and left ventricular (LV) dysfunction. This phenomenon can be explained through a single quantitative measurement of ventilatory instability, the loop gain. Therefore, we aimed to evaluate whether loop gain could be a better tool than subjective EOV evaluation to identify HF patients with a higher risk of major cardiovascular complications. This was a single-center retrospective study that included patients with left ventricular ejection fraction (LVEF) <= 50% consecutively referred for cardiopulmonary exercise testing (CPET) from 2016 to 2020. Loop gain was measured through computational evaluation of the minute ventilation graph. Of the 250 patients included, the 66 that presented EOV also had higher values of loop gain, when compared with patients without EOV. Those with both EOV and higher loop gain had more severe HF, with higher NT-proBNP and VE/VCO2 slope as well as lower peak VO2 and LVEF. On multivariable analysis, loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation, or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope, and NT-proBNP. The presence of EOV was not prognostically significant in this analysis. Loop gain is an objective parameter that quantifies ventilatory instability and showed to have a strong prognostic value in a cohort of patients with HF and LVEF <= 50%, outperforming the classification of EOV.Lay Summary Loop gain is an objective parameter that quantifies ventilatory instability and demonstrated strong prognostic value in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) <= 50%. Loop gain was strongly correlated with the composite endpoint of cardiovascular death, urgent heart transplantation, urgent left ventricular assist device implantation, or HF hospitalization, even after correcting for peak VO2, LVEF, VE/VCO2 slope, and NT-proBNP. Presence of exercise oscillatory ventilation was not prognostically significant when added to loop gain measurement.