Cardiopulmonary exercise testing predicts risk of progressive heart failure and long term mortality in ambulatory patients awaiting isolated heart transplant
Authors: Afoke J , Daly R , Dearani J , Villavicencio M , Spencer P J , Stephens E H , Tang P , Todd A , Briggs C , Patel K , Martinez Aguilar M , Kushwaha S , Allison T G 
Published: October 2024

Abstract

Introduction
Cardiopulmonary exercise testing (CPET) parameters such as peak VO2 ≤ 14ml/kg/min, percentage predicted peak VO2 (ppVO2) ≤ 50% and ventilation equivalent of carbon dioxide (Ve/VCO2) &gt;35 l/min/l/min are recommended thresholds to list for isolated heart transplant. There is minimal data on clinical events after listing to guide clinical management or priority in organ allocation.

Purpose
To assess the effect of peak VO2, ppVO2, Ve/VCO2 on clinical events after listing for isolated heart transplant.

Methods
In a single centre retrospective study, we identified patients who were status 6 or status 2 prior to 2018 at time of listing for isolated heart transplant between 2007 and 2021. Clinical data were collected by chart review. Primary outcome of progressive heart failure was defined as death or upgrade in transplant priority status (new inotropes or mechanical circulatory support). Comparison was made between peak VO2 strata (&gt; 14 vs ≤ 14 ml/kg/min), ppVO2 strata (&gt; 50% vs 40-50% vs &lt;40%) and Ve/VCO2 strata (&lt;35 vs &gt;35 l/min/l/min). Secondary outcome was time dependent survival after listing for heart transplant.

Results
We identified 141 patients of which 133 underwent CPET and follow up was available for 130 who were included in the analysis. Median age was 53 years (interquartile range 41-59 years), 29.1% of patients were female. Median peak VO2 was 14.0 ml/kg/min (11.2-15.7), ppVO2 was 44% (36-52), Ve/VCO2 slope was 34.0 (31.0-37.0) and RER was 1.1 (1.1-1.2).
87 patients had progressive heart failure consisting of 34 deaths and 83 patients having upgrade in priority status. There was a significant difference in risk of progressive heart failure comparing peak VO2 strata (Figure 1) (freedom from event at one year 71.4% with peak VO2 &gt; 14 vs 46.5% with peak VO2 ≤ 14, p=0.00061) and ppVO2 strata (Figure 2) (freedom from event at one year 75.0% with ppVO2 &gt;50% vs 61.2% with ppVO2 40-50% vs 42.6% with ppVO2 &lt;40%, p=0.0015). There was no significant difference with Ve/VCO2 strata (freedom from event at one year 59.8% with Ve/VCO2 &lt;34 vs 54.9% with Ve/VCO2 &gt;34, p=0.52).
There were 34 deaths before transplant and 23 deaths after transplant. 87 patients underwent transplant. In a time dependent survival analysis, age, gender and ppVO2&lt;50% (HR 1.65 (0.87-3.12)) were not significant predictors of mortality. Both early transplant (defined as &lt; 1 year after listing, HR 0.14 (0.06-0.34) and late transplant (defined as &gt; 1 year after listing, HR 0.16 (0.08-0.32)) were significant predictors of lower mortality whilst Ve/VCO2&gt;35 (HR 2.09 (1.19-3.68)) was a significant predictor of higher mortality.

Conclusions
Peak VO2 and ppVO2 stratify risk of progressive heart failure in ambulatory patients awaiting isolated heart transplant. However, Ve/VCO2 is a predictor of significantly higher mortality. These findings should affect clinical management and transplant priority status; and influence revision of future guidelines.Freedom from event by peak VO2 strataFreedom from event by ppVO2 strata