The cardiac phenotype of treatment naive patients with early breast cancer: a precursor to HFpEF?
I Paterson, K Wu, E Pituskin, A Kirkham, S Paterson, L Xu, M Haykowsky, R ThompsonAbstract
Background
Cancer survivors are at high risk for incident cardiovascular disease, even after adjustment for age and other risk factors. We therefore hypothesized that patients with new cancer diagnoses have subclinical cardiac abnormalities with the potential to increase vulnerability to premature heart failure.
Purpose
Characterize the cardiovascular phenotype of patients with early-stage breast cancer prior to the receipt of cancer treatment relative to non-cancer controls.
Methods
We prospectively recruited patients with newly diagnosed stage 0-3 breast cancer (BC) from a tertiary care cancer hospital after excluding those with a history of cardiovascular disease or prior cancer treatment. Patients were stratified into very low, low or moderate/high cardiovascular toxicity risk according to HFA-ICOS criteria. Age and sex-matched healthy controls were included. All participants underwent blood work to evaluate cardiac measures of cardiotoxicity and a cardiac magnetic resonance (CMR) at 1.5T to assess cardiac structure and function and myocardial tissue characterization. Global distress in patients was evaluated using a standardized questionnaire. One way ANOVA or Chi square testing was used to compare demographic, and imaging metrics between healthy controls and patients with BC and Pearson correlation was used to evaluate strength of associations.
Results
186 patients (mean age 52.8±9.5 years) with BC and 55 healthy controls (mean age 52.4±14.4 years) met eligibility criteria for the study. HFA-ICOS criteria identified 82 patients as very low risk (score = 0), 57 as low risk (score = 1) and 47 as moderate or high risk (score 2+). Patients with BC had higher resting heart rate and lower systemic vascular resistance compared to healthy controls, regardless of HFA-ICOS risk score, p<0.001 for each comparison (Table). In patients with BC, there was no correlation between heart rate and patient reported distress or hemoglobin. On CMR, patients with BC had reduced global longitudinal strain relative to healthy controls, with a progressive reduction in function according to increasing HFA-ICOS risk, -22.4±2.0% in controls, -21.1±2.1% in very low risk, -20.5±2.3% in low risk and -19.7±2.7% in moderate to high risk patients, p<0.001. LV mass index was increased in the BC groups compared to controls with similar myocardial tissue characterization on native T1 mapping. Patients with BC had progressively decreased left ventricular (LV) end-diastolic volume and increased LV concentricity according to increasing HFA-ICOS risk.
Conclusions
Patients with newly diagnosed early-stage BC have altered cardiovascular hemodynamics and subclinical abnormalities to cardiac function and structure, even in those at very low risk for cardiotoxicity. Increasing predicted risk of cardiotoxicity is associated with progressive ventricular remodeling and dysfunction akin to the phenotype of heart failure with preserved ejection fraction.