Revisiting the 12 mL/kg/min threshold: contemporary data challenge heart transplant criteria

Abstract Background Current guidelines recommend referring ambulatory heart failure (HF) patients for heart transplantation (HTX) when peak oxygen uptake (peak VO2) is 12 mL/kg/min. This threshold, however, is based on decades-old data. As HF management has significantly improved, the relevance of this criterion in today’s clinical practice is uncertain. Methods We retrospectively selected 1,218 ambulatory patients with HF and reduced or improved ejection fraction (HFrEF or HFimpEF) from the MECKI score registry, with peak VO2 12 mL/kg/min. Patients were enrolled between 2010 and 2022. Clinical and cardiopulmonary exercise testing (CPET) variables were recorded, with a primary composite outcome of death, LVAD implantation, or HTX. Kaplan-Meier survival curves were compared to contemporary data from heart transplant recipients in the ISHLT registry. We stratified patients by VE/VCO2 slope (34 vs. ≤34) and presence/absence of periodic breathing (PB). Sensitivity analyses included adjustment for % predicted peak VO2 and subgroup evaluation in non-maximal CPET (RER 1.05). Results Over a median follow-up of 2.3 years, 400 events occurred. Fig. 1A compares the survival of the study population with the survival of HTX recipients. Patients with VE/VCO2 ≤34 (n=446) had significantly lower 10-year event rates than those with VE/VCO2 34 (26.2% vs. 37.2%, p0.001). Survival in the VE/VCO2 ≤34 group exceeded that of HTX recipients until year 4 (Fig. 1B). Similarly, absence of PB (n=884) was associated with improved outcomes (29.4% vs. 42.7%, p0.001), with survival crossing HTX at year 3. Combining VE/VCO2 and PB defined four distinct prognostic groups. Patients with both VE/VCO2 ≤34 and no PB had the most favorable outcomes (10-year event rate 23.3%), surpassing HTX recipients at year 5 (Fig. 1C). Prognostic differences persisted after adjustment for % predicted peak VO2 and were evident even in patients with RER 1.05. Conclusions In a contemporary cohort, a peak VO2 12 mL/kg/min alone no longer identifies ambulatory HF patients with a high enough short-term mortality to justify transplant listing. Incorporating VE/VCO2 slope and PB into CPET interpretation provides significantly improved risk stratification. These findings suggest that current HTX referral criteria might need revision to avoid premature listing of low-risk patients and target optimize organ allocation to patients with very poor prognosis.Figure 1For image description, please refer to the figure legend and surrounding text.