Predictive Value of VO2peak in Adult Congenital Heart Disease in Comparison with Heart Failure with Reduced Ejection Fraction

BACKGROUNDPeak oxygen consumption ([V]O2peak) is used to predict outcomes and the timing of transplantation in patients with heart failure with reduced ejection fraction (HFrEF); [V]O2peak also has predictive utility in patients with adult congenital heart disease (ACHD). However, the predictive value of a given [V]O2peak in patients with ACHD compared to those with HFrEF, especially after adjustment for age and sex, is not clear. METHODSTo address this, we performed a longitudinal cohort study comparing patients with ACHD to patients with HFrEF. The ACHD and HFrEF cohorts were matched for sex and age (+/- 10 y). [V]O2peak tests were conducted between 1993 and 2012. Events were defined as death, cardiac transplantation, or left ventricular assist device placement. Outcome data were obtained via electronic medical record, Social Security Death Index, and phone interview. Cox proportional-hazard regressions were used to evaluate relationships of event-free survival with predictor variables. RESULTSPatients with ACHD (N=137) and HFrEF (N=137) with a median follow-up time of 14.5 (13.4-15.6) y in the ACHD cohort and 19 (14.8-21.1) y in the HFrEF cohort. Higher [V]O2peak was associated with lower risk for a cardiac outcome, independent of age and sex, in both ACHD (HR 0.89, 95% CI 0.83-0.96, P=0.002) and HFrEF (HR 0.85, 95% CI 0.81-0.89, P <0.001Male sex was associated with greater risk of a cardiac outcome (P=0.001) in ACHD (HR 3.34) and HFrEF (HR 1.83). After multivariable adjustment (that included age, sex, and [V]O2peak) having ACHD conferred a 66% lower risk of a cardiovascular event compared to a HFrEF diagnosis (HR 0.34, 95% CI 0.22-0.53, P<0.001). CONCLUSIONS[V]O2peak independently predicts event-free survival among adults with ACHD or HFrEF and has clinical utility in the outpatient setting. Patients with ACHD, however, have a better prognosis for any given [V]O2peak compared to those with HFrEF. WHAT IS NEW?O_LIIn an age- and sex-matched longitudinal cohort study with over 7 y of follow-up, adults with congenital heart disease (ACHD) were found to have a better event-free (no transplant or LVAD) survival than adults with heart failure with reduced ejection fraction (HFrEF) even after multivariable adjustment that included age, sex, and [V]O2peak. Thus, for any given [V]O2peak a better event-free survival would be expected in ACHD compared with HFrEF. For both groups, a higher [V]O2peak did still confer an improved event-free survival and male sex conferred a worse event-free survival. C_LI WHAT ARE THE CLINICAL IMPLICATIONS?Patients with HFrEF commonly undergo [V]O2peak testing to evaluate clinical status, exercise capabilities, and timing for transplantation. Less commonly, patients with ACHD undergo [V]O2peak testing. This study confirmed that a higher [V]O2peak is still an excellent predictor of freedom from cardiac events and survival in both groups; however, for a given [V]O2peak, a patient with ACHD would be expected to have a markedly improved event-free survival vs. a patient with HFrEF even after adjusting for age and sex. Moreover, our analysis adds to the understanding of how much of an advantage a higher [V]O2peak confers for each mL{middle dot}min-1{middle dot}kg-1 confers in each group, with a slightly greater incremental benefit for the ACHD group. This finding has implications for timing of referral to cardiac transplantation for patients with ACHD. Future studies are needed to determine the optimal [V]O2peak cut-off for transplantation for those with ACHD. Furthermore, more studies are needed to investigate the potential mechanism(s) for the ACHD survival advantage.