This study was a secondary analysis of previously published results from a National Institutes of Health–funded cohort (R01CA167821) of patients scheduled to receive potentially cardiotoxic chemotherapy (1). We sought to determine the utility of mid-cancer treatment assessments of left ventricular (LV) volumes for forecasting 2-year post-cancer treatment measurements of LV ejection fraction (EF) in those <55 or ≥55 years in age. This prospective cohort study was approved by the Institutional Review Board of the Wake Forest School of Medicine, and all participants provided written informed consent.
Seventy-one subjects completed pre-therapy, 3 months into therapy, and 24-month post-treatment assessments of previously published, reproducible measures of LV end-diastolic volume and LV end-systolic volume (LVESV) (2) and LVEF using cardiac magnetic resonance (1). Baseline to 24 months’ decline in LVEF ≥5% were identified along with assessments of heart failure (3).
Participants were 68% women, 82% White, and averaged 54 ± 15 years in age. The weight and body mass index averaged 84.2 ± 19 kg and 30 ± 6 kg/m2, respectively. The percentage of individuals with hypertension, history of smoking, diabetes, and previously receiving radiation were 51%, 12%, 17%, and 35%. Of the 71 participants, 29 had a history of breast cancer, 37 of lymphoma, and 5 of sarcoma. Twenty-two participants took 1 cardioprotective drug, 9 participants took 2 cardioprotective drugs, and 3 participants took 3 cardioprotective drugs; these included angiotensin-converting enzyme inhibitors, betablockers, and statins.
Patients were categorized as receiving or not receiving anthracycline-based chemotherapy and whether they were younger or older than the median age of 55 years. Forty-two percent of patients experienced a >5% decline (average drop of 11.4%) in LVEF over 2 years. Patients age ≥55 years receiving an anthracycline were more likely to experience a 24-month post-treatment decline in LVEF relative to those <55 years of age or not receiving an anthracycline (Fisher exact test; p = 0.022). For those <55 years of age or those not receiving an anthracycline, after accounting for sex or the presence of hypertension, diabetes, smoking, coronary artery disease, or hyperlipidemia, 3-month adverse LV volume changes (that included previously published increases in LVESV >3 ml or 10 ml decline in LV end-diastolic volume with no decline in LVESV [1]) forecasted a 24-month post-cancer treatment decline in LVEF >5% (Fisher exact test; p = 0.011). There was no relationship between measurements of LV function 3 months into treatment and symptoms associated with heart failure (p = 0.22).
In this study, those patients <55 years of age or not receiving an anthracycline received additional prognostic information from comparing a pre-treatment to 3 months into treatment assessment of LV function in terms of predicting a 24-month post-treatment more long-term decline in LVEF. As such, these data support several societies’ recommendations regarding mid-treatment assessments of subclinical cardiac injury in those at risk for long-term decline in LV function (4,5). This includes younger individuals even though symptoms of heart failure associated with mid-cancer treatment may not be present.
Acknowledgments
This research was supported in part by National Institutes of Health grants 1R01CA167821, R01CA199167, and R01HL118740. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
REFERENCES
- 1.Suerken CK, D’Agostino RB, Jordan JH, et al. Simultaneous left ventricular volume and strain changes during chemotherapy associate with 2-year post chemotherapy measures of left ventricular ejection fraction. J Am Heart Assoc 2020;9:e015400. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Jordan JH, Bunyapon S, Meléndez GC, et al. Early myocardial strain changes during potentially cardiotoxic chemotherapy may occur due to reductions in LV end diastolic volume: the need to interpret LV strain with volumes. Circulation 2017;135:2575–7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Jones DN, Jordan JH, Melendez GC, et al. Frequency of transition from stage A to stage B heart failure after initiating potentially cardiotoxic chemotherapy. J Am Coll Cardiol HF 2018;6:1023–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practical guidelines. J Clin Oncol 2017;8:893–911. [DOI] [PubMed] [Google Scholar]
- 5.Plana JC, Galderisi M, Barac A, et al. Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2014;27: 911–39. [DOI] [PubMed] [Google Scholar]