Mitoxantrone-Induced Cardiotoxicity in Acute Myeloid Leukemia-A Velocity Vector Imaging Analysis.
BACKGROUND
The purpose of this investigation was to: (1) determine incidence and predictors of mitoxantrone-induced early cardiotoxicity and (2) study left ventricular mechanics before and after receiving mitoxantrone.


RESULTS
We retrospectively analyzed 80 subjects diagnosed with acute myeloid leukemia (AML) who underwent chemotherapy with bolus high-dose mitoxantrone. Echocardiographic measurements were taken at baseline and at a median interval of 55 days after receiving mitoxantrone. Thirty-five (44%) of the patients developed clinically defined early cardiotoxicity, 29 (36%) of which developed heart failure. There was a significant decrease in the ejection fraction (EF) not only in the cardiotoxicity group (17.6 ± 14.8%, P < 0.001) but also in the noncardiotoxicity group (5.3 ± 8.4%, P < 0.001). Decrease in global longitudinal strain (GLS) (-3.7 ± 4.5, P < 0.001 vs. -2.4 ± 4.3, P = 0.01) and global circumferential strain (GCS) (-5.6 ± 9, P = 0.003 vs. -5.3 ± 8.7, P < 0.001) was significant in both the cardiotoxicity and noncardiotoxicity group, respectively. A multivariate model including baseline left ventricular end-systolic diameter, baseline pre-E/A ratio, and baseline pre-E/e' ratio was found to be the best-fitted model for prediction of mitoxantrone-induced early clinical cardiotoxicity.


CONCLUSIONS
High-dose mitoxantrone therapy is associated with an excellent remission rate but with a significantly increased risk of clinical and subclinical early cardiotoxicity and heart failure. Mitoxantrone-induced systolic dysfunction is evident from reduction in EF, increase in Tei index, and significant reduction in GLS and GCS. Baseline impaired ventricular relaxation evident from higher E/e' ratio and lower E/A ratio independently predicts increased risk of mitoxantrone-induced early cardiotoxicity.
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
Amir Y
AY
Shaikh
Department of Medicine, Providence Holy Cross Medical Center, Mission Hills, California.
Sourabh
S
Suryadevara
Division of Hematology-Oncology, Baystate Medical Center, Springfield, Massachusetts.
Abhishek
A
Tripathi
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Cardiology, University of Massachusetts Medical School, Worcester, Massachusetts.
Mohamed
M
Ahmed
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Cardiology, University of Massachusetts Medical School, Worcester, Massachusetts.
Jennifer L
JL
Kane
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.
Jorge
J
Escobar
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Hematology-Oncology, University of Massachusetts Medical School, Worcester, Massachusetts.
Jan
J
Cerny
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Hematology-Oncology, University of Massachusetts Medical School, Worcester, Massachusetts.
Rajneesh
R
Nath
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Cardiology, University of Massachusetts Medical School, Worcester, Massachusetts.
David D
DD
McManus
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Cardiology, University of Massachusetts Medical School, Worcester, Massachusetts.
Jeffrey
J
Shih
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Cardiology, University of Massachusetts Medical School, Worcester, Massachusetts.
Matthew E
ME
McGuiness
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Cardiology, University of Massachusetts Medical School, Worcester, Massachusetts.
Dennis A
DA
Tighe
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Cardiology, University of Massachusetts Medical School, Worcester, Massachusetts.
Theo E
TE
Meyer
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Hematology-Oncology, University of Massachusetts Medical School, Worcester, Massachusetts.
Muthalagu
M
Ramanathan
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts.|Division of Cardiology, University of Massachusetts Medical School, Worcester, Massachusetts.
Gerard P
GP
Aurigemma
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D015984:Causality; D015897:Comorbidity; D004452:Echocardiography / Q000379:methods / Q000706:statistics & numerical data; D054459:Elasticity Imaging Techniques / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000401:mortality; D006801:Humans; D015994:Incidence; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008942:Mitoxantrone / Q000009:adverse effects* / Q000627:therapeutic use; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013318:Stroke Volume / Q000187:drug effects; D015996:Survival Rate; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging* / Q000401:mortality*
D000970:Antineoplastic Agents; D008942:Mitoxantrone
Tei index; anthracyclines; chemotherapy; diastolic dysfunction; dyssynchrony; heart failure; leukemia; myocardial performance index; strain