Usefulness of ventilatory inefficiency in predicting prognosis across the heart failure spectrum

Abstract

Aims: The minute ventilation-carbon dioxide production relationship (VE/VCO₂ slope) is widely used for prognostication in heart failure (HF) with reduced left ventricular ejection fraction (LVEF). This study explored the prognostic value of VE/VCO₂ slope across the spectrum of HF defined by ranges of LVEF.

Methods and results: In this single-centre retrospective observational study of 1347 patients with HF referred for cardiopulmonary exercise testing, patients with HF were categorized into HF with reduced (HFrEF, LVEF < 40%, n = 598), mid-range (HFmrEF, 40% ≤ LVEF < 50%, n = 164), and preserved (HFpEF, LVEF ≥ 50%, n = 585) LVEF. Four ventilatory efficiency categories (VC) were defined: VC-I, VE/VCO₂ slope ≤ 29; VC-II, 29 < VE/VCO₂ slope < 36; VC-III, 36 ≤ VE/VCO₂ slope < 45; and VC-IV, VE/VCO₂ slope ≥ 45. The associations of these VE/VCO₂ slope categories with a composite outcome of all-cause mortality or HF hospitalization were evaluated for each category of LVEF. Over a median follow-up of 2.0 (interquartile range: 1.9, 2.0) years, 201 patients experienced the composite outcome. Compared with patients in VC-I, those in VC-II, III, and IV demonstrated three-fold, five-fold, and eight-fold increased risk for the composite outcome. This incremental risk was observed across HFrEF, HFmrEF, and HFpEF cohorts.

Conclusions: Higher VE/VCO₂ slope is associated with incremental risk of 2 year all-cause mortality and HF hospitalization across the spectrum of HF defined by LVEF. A multilevel categorical approach to the interpretation of VE/VCO₂ slope may offer more refined risk stratification than the current binary approach employed in clinical practice.

Keywords: Cardiopulmonary exercise test; Heart failure; Heart failure hospitalization; VE/VCO2 slope; Ventilatory efficiency.