Left Ventricular Mass Change After Anthracycline Chemotherapy

Abstract

Background: Myocardial atrophy and left ventricular (LV) mass reductions are associated with fatigue and exercise intolerance. The relationships between the receipt of anthracycline-based chemotherapy (Anth-bC) and changes in LV mass and heart failure (HF) symptomatology are unknown, as is their relationship to LV ejection fraction (LVEF), a widely used measurement performed in surveillance strategies designed to avert symptomatic HF associated with cancer treatment.

Methods and results: We performed blinded, serial assessments of body weight, LVEF and mass, LV-arterial coupling, aortic stiffness, and Minnesota Living with Heart Failure Questionnaire measures before and 6 months after initiating Anth-bC (n=61) and non-Anth-bC (n=15), and in 24 cancer-free controls using paired t and χ² tests and multivariable linear models. Participants averaged 51±12 years, and 70% were women. Cancer diagnoses included breast cancer (53%), hematologic malignancy (42%), and soft tissue sarcoma (5%). We observed a 5% decline in both LVEF (P<0.0001) and LV mass (P=0.03) in the setting of increased aortic stiffness and disrupted ventricular-arterial coupling in those receiving Anth-bC but not other groups (P=0.11-0.92). A worsening of the Minnesota Living with Heart Failure Questionnaire score in Anth-bC recipients was associated with myocardial mass declines (r=-0.27; P<0.01) but not with LVEF declines (r=0.11; P=0.45). Moreover, this finding was independent of LVEF changes and body weight.

Conclusions: Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.

Keywords: anthracyclines; atrophy; heart failure; leukemia; sarcoma.

Figure 1.. Six-month change in cardiovascular magnetic resonance (CMR)–derived left ventricular (LV) remodeling measurements after anthracycline-based chemotherapy.

Six-month change in CMR-derived measurements of left ventricular remodeling in adults treated with anthracycline-based chemotherapy (Anth-bC, orange), non–Anth-bC (purple) for breast cancer or hematologic malignancy and cancer-free comparators of similar age (white). Compared with cancer-free comparators, those receiving Anth-bC had a significant decrease in LV ejection fraction (LVEF; A; P<0.01) and LV myocardial mass (B; P=0.03) that occurred concurrently with increased end-systolic wall stress index (C; P<0.01) and reduced ventricular-arterial coupling (D; P<0.01). Changes among patients with cancer who received non–Anth-bC were not statistically different than those observed in noncancer comparators (P>0.15 for all). Data shown as mean±SEM.*P<0.05 for change from baseline. †P<0.05 vs change in controls.

Figure 2.. Associations of cardiovascular magnetic resonance–derived changes in left ventricular (LV) remodeling with worsening Minnesota Living With Heart Failure Questionnaire in patients with cancer treated with anthracyclines.

Subclinical declines in LV ejection fraction (LVEF; A) were not associated with worsening of total Minnesota Living With Heart Failure Questionnaire (MLHFQ) score (P=0.45). Instead, atrophic remodeling (reduced myocardial mass; B) was associated with worsening total MLHFQ score (P<0.01) 6 mo after initiation of cancer treatment. Correlation of variables in (A) and (B) with P values for model adjusted for baseline MLHFQ score.