Vo(2)peak in Adult Survivors of Hodgkin Lymphoma: Rate of Decline, Sex Differences, and Cardiovascular Events

BACKGROUND: Adult survivors of Hodgkin lymphoma (HL) are at increased risk of cardiovascular (CV) events secondary to mediastinal radiation therapy (RT). OBJECTIVES: In this group of patients, we assessed the association between cardiopulmonary exercise testing (CPET), as determined by percent-predicted peak Vo(2) (ppVo(2)peak), and clinical outcomes, as well as the rate of ppVo(2)peak decline and sex differences. METHODS: All survivors of HL who were >10 years post chest RT and who underwent ≥1 CPET were enrolled from a single center. Traditional CV and treatment risk factors, along with CV events, were ascertained. RESULTS: A total of 64 patients (67% female; median age 51 years [range 26 to 70 years]) with a median follow-up time after RT of 23 years (range 11 to 41 years), and 141 CPET studies, were included. Median initial ppVo(2)peak was 91% (range 58% to 138%). ppVo(2)peak in survivors declined by 7.5 percentage points every 10-year period after RT, as compared with age- and sex-based norms (P = 0.001), even after adjusting for hypertension and history of anthracycline. Both male and female patients had a similar rate of ppVo(2)peak decline. However, women had a lower ppVo(2)peak at all times, and they developed abnormal ppVo(2)peak (≤85%) on average earlier than men (24.1 years vs 47.0 years after RT). Patients with abnormal ppVo(2)peak vs normal ppVo(2)peak (>85%), had an increased risk of CV events (59% vs 16%). Abnormal ppVo(2)peak was independently associated with the risk of CV events (adjusted HR: 6.37; 95% CI: 2.06-19.80; P = 0.001). CONCLUSIONS: Percent-predicted Vo(2)peak in long-term survivors of HL who were treated with chest RT progressively declined as compared with population- and sex-based norms. Importantly, women developed abnormal ppVo(2)peak more than 2 decades earlier than male survivors. Abnormal ppVo(2)peak was associated with an increased risk of CV events in this group of patients.