Vo2peak in Adult Survivors of Hodgkin Lymphoma: Rate of Decline, Sex Differences, and Cardiovascular Events

Raheel Rizwan; Kimberlee Gauvreau; Cheryl Vinograd; Jessica M Yamada; Christina Mangano; Andrea K Ng; Mark E Alexander; Ming Hui Chen

doi:10.1016/j.jaccao.2021.04.010

Vo₂peak in Adult Survivors of Hodgkin Lymphoma: Rate of Decline, Sex Differences, and Cardiovascular Events

JACC CardioOncol. 2021 Jun 15;3(2):263-273. doi: 10.1016/j.jaccao.2021.04.010. eCollection 2021 Jun.

Authors

Raheel Rizwan¹, Kimberlee Gauvreau^{2

3}, Cheryl Vinograd⁴, Jessica M Yamada¹, Christina Mangano¹, Andrea K Ng^{5

6}, Mark E Alexander^{2

3}, Ming Hui Chen^{1

2

3}

Affiliations

¹ Department of Pediatrics, Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA.
² Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts, USA.
³ Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Pediatrics, New York University Grossman School of Medicine, New York, New York, USA.
⁵ Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
⁶ Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

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 Vo₂ (ppVo₂peak), and clinical outcomes, as well as the rate of ppVo₂peak 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 ppVo₂peak was 91% (range 58% to 138%). ppVo₂peak 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 ppVo₂peak decline. However, women had a lower ppVo₂peak at all times, and they developed abnormal ppVo₂peak (≤85%) on average earlier than men (24.1 years vs 47.0 years after RT). Patients with abnormal ppVo₂peak vs normal ppVo₂peak (>85%), had an increased risk of CV events (59% vs 16%). Abnormal ppVo₂peak 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 Vo₂peak 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 ppVo₂peak more than 2 decades earlier than male survivors. Abnormal ppVo₂peak was associated with an increased risk of CV events in this group of patients.

Keywords: BCH, Boston Children’s Hospital; CPET, cardiopulmonary exercise testing; CV, cardiovascular; HL, Hodgkin lymphoma; Hodgkin lymphoma; LSM, least squares mean; RER, respiratory exchange ratio; RT, radiation therapy; Vo2; cardiac events; cardiopulmonary test; ppVo2peak, percent-predicted peak volume oxygen; radiation; sex; women.