Age Differences in Cardiopulmonary Exercise Testing Parameters in Heart Failure with Reduced Ejection Fraction

Abstract

Background and Objectives: Cardiopulmonary exercise testing (CPET) is a cornerstone of risk stratification in heart failure with reduced ejection fraction (HFrEF). However, there is a paucity of evidence on its predictive power in older patients. The aim of this study was to evaluate the prognostic power of current heart transplantation (HTx) listing criteria in HFrEF stratified according to age groups. Materials and Methods: Consecutive patients with HFrEF undergoing CPET between 2009 and 2018 were followed-up for cardiac death and urgent HTx. Results: CPET was performed in 458 patients with HFrEF. The composite endpoint occurred in 16.8% of patients ≤50 years vs. 14.1% of patients ≥50 years in a 36-month follow-up. Peak VO₂ (pVO₂), VE/VCO₂ slope and percentage of predicted pVO₂ were strong independent predictors of outcomes. The International Society for Heart and Lung Transplantation thresholds of pVO₂ ≤ 12 mL/kg/min (≤14 if intolerant to β-blockers), VE/VCO₂ slope > 35 and percentage of predicted pVO₂ ≤ 50% presented a higher overall diagnostic effectiveness in younger patients (≤50 years). Specific thresholds for each age subgroup outperformed the traditional cut-offs. Conclusions: Personalized age-specific thresholds may contribute to an accurate risk stratification in HFrEF. Further studies are needed to address the gap in evidence between younger and older patients.

Keywords: VE/VCO2 slope; age; cardiopulmonary exercise testing; heart failure with reduced ejection fraction; heart transplantation; peak oxygen consumption.

Figure 1

Study flowchart. * in patients intolerant to β-blockers. HFrEF: Heart failure with reduced ejection fraction; CPET: Cardiopulmonary exercise test; HTx: Heart transplantation; LVEF: Left ventricular ejection fraction; NYHA: New York Heart Association; ISHLT: International Society for Heart and Lung Transplantation; pVO₂: Peak oxygen consumption; VE/VCO₂ slope: Minute ventilation–carbon dioxide production ratio.

Figure 2

ROC curves for the composite endpoint in a 36-month follow up are presented in blue. The diagonal reference line is presented in green. (a) Peak oxygen consumption (pVO₂) in patients under 50 years old. (b) pVO₂ in patients over 50 years old. (c) Minute ventilation–carbon dioxide production ratio (VE/VCO₂ slope) in patients under 50 years old. (d) VE/VCO₂ slope in patients over 50 years old.

Figure 3

Kaplan–Meier survival analysis for the composite endpoint in a 36-month follow-up stratified according to the International Society for Heart and Lung Transplantation (ISHLT) guidelines in patients under 50 years old and patients over 50 years old. (a) Peak oxygen consumption (pVO₂) ≤12 mL/Kg/min (≤14 mL/kg/min if intolerant to β-blockers [βB]). (b) Minute ventilation–carbon dioxide production ratio (VE/VCO₂ slope) of >35.

Figure 4

Kaplan–Meier analysis for the composite endpoint in patients under 50 years old and patients over 50 years old stratified according to (a) Peak oxygen consumption (pVO₂) of ≤14 mL/Kg/min. (b) Minute ventilation–carbon dioxide production ratio (VE/VCO₂ slope) of >32 and >33, respectively.