Gender and age normalization and ventilation ef fi ciency during exercise in heart failure with reduced ejection fraction

Aims Ventilation vs. carbon dioxide production (VE/VCO 2 ) is among the strongest cardiopulmonary exercise testing prognostic parameters in heart failure (HF). It is usually reported as an absolute value. The current de fi nition of normal VE/VCO 2 slope values is inadequate, since it was built from small groups of subjects with a particularly limited number of women and elderly. We aimed to de fi ne VE/VCO 2 slope prediction formulas in a sizable population and to test whether the prognostic power of VE/VCO 2 slope in HF was different if expressed as a percentage of the predicted value or as an absolute value. results We calculated the linear regressions between age and VE/VCO 2 slope in 1136 healthy subjects ( 68 % male, age 44 . 9 ± 14 . 5 , range 13 – 83 years). We then applied age-adjusted and sex-adjusted formulas to predict VE/VCO 2 slope to HF patients included in the metabolic exercise test data combined with cardiac and kidney indexes score database, which counts 6112 patients ( 82 % male, age 61 . 4 ± 12 . 8 , left ventricular ejection fraction 33 . 2 ± 10 . 5 %, peakVO 2 14 . 8 ± 4 . 9 , mL/min/ kg, VE/VCO 2 slope 32 . 7 ± 7 . 7 ) from 24 HF centres. Finally, we evaluated whether the use of absolute values vs. percentages of events/ 1000 pts/year) HF. In the healthy population, we obtained the following equations: female, VE/VCO 2 = 0 . 052 × Age + 23 . 808 ( r = 0 . 192 ); male, VE/VCO 2 = 0 . 095 × Age + 20 . 227 ( r = 0 . 371 ) ( P = 0 . 007 ). We applied these formulas to calculate the percentages of predicted VE/VCO 2 values. The 2 -year survival prognostic power of VE/VCO 2 slope was strong, and it was similar if expressed as absolute value or as a percentage of predicted value (AUCs 0 . 686 and 0 . 690 , respectively). In contrast, in severe HF patients, AUCs signi fi cantly differed between absolute values ( 0 . 637 ) and percentages of predicted values ( 0 . 650 , P = 0 . 0026 ). Moreover, VE/VCO 2 slope expressed as a percentage of predicted value allowed to reclassify 6 . 6 % of peakVO 2 < 14 mL/min/kg patients (net reclassi fi cation improvement = 0 . 066 , P = 0 . 0015 ). Conclusions The percentage of predicted VE/VCO 2 slope value strengthens the prognostic power of VE/VCO 2 in severe HF patients, and it should be preferred over the absolute value for HF prognostication. Furthermore, the widespread use of VE/VCO 2 slope expressed as percentage of predicted value can improve our ability to identify HF patients at high risk, which is a goal of utmost clinical relevance.