Cardiovascular Burden and Adverse Events in Patients With Esophageal Cancer Treated With Chemoradiation for Curative Intent

Abstract

Objectives: The aim of this study was to characterize the cardiovascular disease (CVD) profile and describe the incidence and characteristics of cardiovascular (CV) events in patients with esophageal cancer (EC) following chemoradiation and surgery.

Background: Underlying CVD is a concern in patients with EC receiving curative treatment with chemoradiation and surgery.

Methods: Consecutive patients with EC referred for curative treatment were enrolled. Clinical CVD status, ongoing CVD treatment, cardiac function, and physical performance were assessed before chemoradiation. During a 90-day follow-up period, all CV events were noted and classified after in-depth medical record review. CV events were defined by major adverse CV events (transient ischemic attack, imaging-verified new stroke, unstable angina, heart failure or cardiomyopathy) or by Common Terminology Criteria for Adverse Events grade ≥3 (arrhythmia, thromboembolic events, or pericardial effusion requiring pericardiocentesis).

Results: Among 55 patients enrolled (median age 67 years; range: 50-86 years; 89% men), 22% had CVD prior to chemoradiation, and 11% with pre-existing CVD were inadequately treated according to current CV guidelines. Thirteen patients (24%) developed 15 events during follow-up. Pre-existing atrial fibrillation and a dilated left atrium were significantly associated with subsequent CV events. Left ventricular (LV) systolic dysfunction was frequently noted; 51% had impaired LV global longitudinal strain (<18%), and 16% had LV ejection fraction <50%.

Conclusions: A systematic cardiac evaluation prior to chemoradiation in patients with EC revealed a high prevalence of undetected CVD, inadequately treated pre-existing CVD, and a high incidence of CV events after chemoradiation. These findings highlight the need for a systematic baseline cardiac examination in patients with EC to optimize CVD treatment. (Impact of Cancer Therapy on Myocardial Function in Patients With Esophagus Cancer [Heartcheck]; NCT03619317).

Keywords: AF, atrial fibrillation; CTCAE, Common Terminology Criteria for Adverse Events; CV, cardiovascular; CVD, cardiovascular disease; EC, esophageal cancer; GLS, global longitudinal strain; LV, left ventricular; LVEF, left ventricular ejection fraction; MACE, major adverse cardiovascular event(s); METs, metabolic equivalents of task; NT-proBNP, N-terminal pro–B-type natriuretic peptide; Vo2max, peak oxygen consumption; cardiac function; cardiovascular disease; chemoradiation; esophageal cancer.

Conflict of interest statement

This research was supported by the Danish Cancer Society, the Carpenter Jorgen Holm and Wife Elisa F. Hansen’s Memorial Scholarship, and Radiumstationens Research Fund. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

© 2021 The Authors.

Figures

Graphical abstract

Figure 1

Pre-Existing CVD Before Beginning Esophageal Cancer Treatment Proportion of cardiovascular disease (CVD) at the time of cancer diagnosis, as defined by atrial fibrillation (AF), ischemic heart disease (IHD) or heart failure (HF), hypertension or dyslipidemia, and a composite of these elements with either a new diagnosis (ND) or patients not treated optimally according to guidelines (NOGT).

Figure 2

Overall CV Event Rate Time to first major adverse cardiovascular (CV) event or CV event defined by Common Terminology Criteria for Adverse Events grade ≥3.

Figure 3

CV Events: Major Adverse CV Events and CV Events Defined by Common Terminology Criteria for Adverse Events Grade ≥ 3 Cardiovascular (CV) event rate according to the following categories: (A) left ventricular ejection fraction (LVEF); (B) global longitudinal strain (GLS); (C) left atrial volume index (LAVI), and (D) median age.

Central Illustration

Pre-Existing Cardiovascular Disease and Incidence of Cardiovascular Events in Patients With Esophageal Cancer A high prevalence of cardiovascular disease (CVD) was detected prior to cancer treatment with curative intent of patients with esophageal cancer. A substantial proportion of patients presented with a suboptimal medical CVD treatment and undiagnosed CVD. Left ventricular systolic function was impaired in one third of the patients and was associated with mildly reduced peak exercise capacity. A cardiovascular (CV) event rate of 24% was determined over 90 days of follow-up. Atrial fibrillation and the size of the left atrium were associated with CV events.