ECHO 2013 / Cancer Treatment Related Cardiotoxicity
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Definition of Cardiotoxicity
•Asymptomatic reduction of the LVEF of
≥10% to <55%
•Reduction of LV EF of ≥ 5% to <55% with symptoms of heart failure
Seidman A, et al. JCO 2002
Cardiac Monitoring and Detection
•Pre-Treatment:
–Early identification of patients at risk for developing heart failure or LV dysfunction
•During Treatment:
–EF by 2D is inadequate. Drop in EF represents a relatively late stage of systolic impairment, after the myocardium has lost considerable functional reserve.
–Use a sensitive method that can detect early subclinical changes of cardiac function.
•Post Treatment:
–Regular cardiac surveillance for late effects.
•No formal guideline due to lack of high quality evidence-based data
2D Strain Imaging
Detection of Subclinical Disease
• Superior to EF in the assessment of myocardial contractile function.
• A stronger predictor of outcome in the general population.
• Able to detect early changes in myocardial function and identify
subclinical LV dysfunction.
2D Strain Imaging
Detection of Cardiotoxicity
•Neilan TG, et al. Eur Heart J 2005;27:1868-1875
•Ganame J, et al. J Am Soc Echocardiogr 2007;20:1351-1358
•Jurcut R, et al. J Am Soc Echocardiogr 2008;21:1283-1289
•Mercurio G, et al. Oncologist 2007;12:1124-1133
•Hare J, et al. Am Heart J 2009;158:294-301
•Ho E, et al. Heart 2009;96:701-707
•Cheung Y, et al. Heart 2010;96:1137-1141
•Tsai, HR, et al. Am J Cardiol 2011;107:472-477
•Fallah-Rad, et al. J Am Coll Cardiol 2011;57:2263-70
•Sawaya H, et al. Circ Cardiovasc Imaging 2012;5:596-603
Early Sign of Cardiotoxicity
Subclinical LV Dysfunction: Strain Imaging
Baseline
2 mos therapy
Marwick, et al. Am Heart J 2009; 158:294
Prevalence of LV Systolic Dysfunction in
Survivors of Childhood Cancer
N= 135
* EF = Ejection Fraction, FS= Fractional Shortening, GLS= Global Longitudinal Strain
Raikhelkar J, Liu, JE. JACC, 2012; 59
Predictors of Cardiotoxicity: Biomarkers
Troponin and BNP
•Persistent elevation of cTnI immediately after and at 1 month after chemotherapy is associated with early cardiac events (asymptomatic LVEF reduction - >25 % from baseline, overt heart failure, life-threating arrhythmias or cardiac death; N= 703 patients).
•Elevated levels of BNP correlated with impairment of LV systolic function during anthracycline therapy.
Cardinale et al, JACC 2000;36:517-22
Cardinale et al, Circulation 2004;109:2749-2754
Lenihan DJ et al. J Card Fail 2007;13 (suppl 2);S151
Predictors of cardiotoxicity: strain and biomarkers
69 breast cancer patients receiving Anthracyclines followed by Taxanes and Trastuzumab
Time course of the LVEF, longitudinal strain and ultrasensitive troponin
Only longitudinal strain <19 at 3 mos predictive of subsequent cardiotoxicity.
Sawaya et al. Circ CV Imaging 2012
Predictors of cardiotoxicity: strain and biomarkers
69 breast cancer patients receiving anthracyclines followed by taxanes and trastuzumab
Predictors* |
Sensitivity |
Specificity |
PPV |
NPV |
|
(%) |
(%) |
(%) |
(%) |
Long strain <19% |
74 |
73 |
53 |
87 |
usTnI>30 pg/ml |
48 |
73 |
44 |
77 |
Long strain <19% and |
35 |
93 |
67 |
77 |
usTnI>30 pg/ml |
|
|
|
|
Long strain <19% or |
87 |
53 |
43 |
91 |
usTnI>30 pg/ml |
|
|
|
|
*measured at the completion of anthracyclines
Sawaya et al. Circ CV Imaging 2012
Case
•57 year old woman with HTN, DM and hyperlipidemia
• Breast cancer with high risk recurrence - high grade invasive ductal CA, ER/PR (-) HER2 (+)
•Recommended treatment:
–Mastectomy
–Radiotherapy
–Adriamycin, Cytoxan, Taxol
–Trastuzumab (1 year treatment)