IMPACT OF CHEMOTHERAPY EXPOSURE ON RIGHT VENTRICULAR CONTRACTILE FUNCTION: A 12-MONTH SERIAL EVALUATION BY CARDIOVASCULAR MAGNETIC RESONANCE IMAGING

Abstract

Adverse effects of chemotherapy on left ventricular (LV) performance is receiving intense exploration. However, the relative impact of these therapies on right ventricular (RV) function remains poorly studied. Given emerging evidence supporting prognostic significance for RV function in patients with cardiomyopathy, we aimed to prospectively study the relative impact of cardiotoxic chemotherapies on the RV over a 12-month exposure to Anthracycline-containing (Anthr) or Trastuzumab-alone (Tr) chemotherapy. Baseline, 3-, 6- and 12-month cardiovascular magnetic resonance (CMR) imaging was performed in 57 patients (total 288 CMR studies) referred for curative chemotherapy (Anthr=40, Tr=17) of either Breast cancer (N=52) or Lymphoma (N=5). The CMR imaging protocol included multi-axial cine imaging to allow for standardized, core-laboratory based analyses of LV and RV volumes and ejection fraction for all study time points. Interval changes (versus baseline) were established for chamber volumes and systolic function and analyzed for the entire population and for both of the Anthr and Tr sub-groups. The mean age was 52 ± 11 years (53 female). LVEF was 65.0± 5.3% with RV EF 60.2±5.1% at time of baseline evaluation. A ≥10% drop in LVEF occurred during follow-up in 28% of the Anthr group and 24% of the Tr group. A corresponding ≥10% drop in RVEF occurred in 43% of the Anthr group and 35% of the Tr group. Anthr patients showed an immediate and significant reduction in RVEF at the three-month study visit with a mean change of -4.6±6.1% (p<0.001) that persisted to 12 months. In the same group the LVEF dropped progressively over the 12-month period (-3.0±6.1% at three months, -3.9±6.1% at 6 months, and -4.2±6.1% at 12 months, p<0.001). Tr patients showed a modest reduction in RVEF at three months (-2.8±4.9%, p<0.05) followed by progressive recovery out to 12 months (-0.7±6.7%, p=0.7). In the same group the LVEF dropped progressively until six months (-5.2±5.0%, p=0.001) followed by recovery at 12 months (-2.4±4.9%, p=0.06). This study provides strong evidence for the RV having greater sensitivity to Anthracycline-based chemotherapy with earlier and a higher prevalence of contractile dysfunction versus the LV, each persisting out to 12 months. Trastuzumab monotherapy was associated with more modest and transient reductions. The prognostic significance of RV dysfunction in patients receiving Anthracycline based chemotherapy warrants expanded investigation.