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

AIMS: The minute ventilation–carbon dioxide production relationship (VE/VCO(2) 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/VCO(2) 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/VCO(2) slope ≤ 29; VC‐II, 29 < VE/VCO(2) slope < 36; VC‐III, 36 ≤ VE/VCO(2) slope < 45; and VC‐IV, VE/VCO(2) slope ≥ 45. The associations of these VE/VCO(2) 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/VCO(2) 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/VCO(2) slope may offer more refined risk stratification than the current binary approach employed in clinical practice.