Early myocardial oedema can predict subsequent cardiomyopathy in high-dose anthracycline therapy.

Abstract

This study aims to assess subclinical changes in functional and morphologic myocardial MR parameters very early into a repetitive high-dose anthracycline treatment (planned cumulative dose >650mg/m2 ), which may predict subsequent development of anthracycline-induced cardiomyopathy (aCMP). Thirty sarcoma patients with previous exposition of 300-360mg/m2 doxorubicin-equivalent chemotherapy who were planned for a second treatment of anthracycline-based chemotherapy (360mg/m2 doxorubicin-equivalent) were recruited. Enrolled individuals received three CMR studies (before treatment, 48h after first anthracycline treatment and upon completion of treatment). Native T1 mapping (MOLLI 5s(3s)3s), T2 mapping, and extracellular volume (ECV) maps were acquired in addition to a conventional CMR with SSFP-cine imaging at 1.5T. Patients were given 0.2mmol/kg gadoteridol for ECV quantification and LGE imaging. Blood samples for cardiac biomarkers were obtained before each scan. Development of relevant aCMP was defined as drop of left ventricular ejection fraction (LVEF) by >10% compared with baseline. Twenty-three complete datasets were available for analysis. Median treatment time was 20.7±3.0weeks. Eight patients developed aCMP with LVEF reduction >10% until end of chemotherapy. Baseline LVEF was not different between patients with and without subsequent aCMP. Patients with aCMP had decreased LV mass upon completion of therapy (99.4±26.5g vs. 90.3±24.8g; P=0.02), whereas patients without aCMP did not show a change in LV mass (91.5±20.0g vs. 89.0±23.6g; P>0.05). On strain analysis, GLS (-15.3±1.3 vs. -13.4±1.6; P=0.02) and GCS (-16.7±2.1 vs. -14.9±2.6; P=0.04) were decreased in aCMP patients upon completion of therapy, whereas non-aCMP individuals showed no change in GLS (-15.4±3.3 vs. -15.4±3.4; P=0.97). When assessed 48h after first dose of anthracyclines, patients with subsequent aCMP had significantly elevated myocardial T2 times compared with before therapy (53.0±2.8ms vs. 49.3±5.2ms, P=0.02) than patients who did not develop aCMP (50.7±5.1ms vs. 51.1±3.9ms, P>0.05). Native T1 times decreased at 48h after first dose irrespective of development of subsequent aCMP (1020.2±28.4ms vs. 973.5±40.3ms). Upon completion of therapy, patients with aCMP had increased native T1 compared with baseline (1050.8±17.9ms vs. 1022.4±22.0ms; P=0.01), whereas non-aCMP patients did not (1034.5±46.6ms vs. 1018.4±29.7ms; P=0.15). No patient developed new myocardial scars or compact myocardial fibrosis under chemotherapy. Cardiac biomarkers were elevated independent of development of aCMP. With high cumulative anthracycline doses, early increase of T2 times 48h after first treatment with anthracyclines can predict the development of subsequent aCMP after completion of chemotherapy. Early drop of native T1 times occurs irrespective of development of aCMP in high-dose anthracycline therapy.