Advanced Echocardiography in the Evaluation of Chemotherapy Patients Juan Carlos Plana, MD, FACC, FASE Co-Director, Cardio-Oncology Center Section of Cardiovascular Imaging Department of Cardiovascular Medicine Cleveland Clinic
Outlook Introduction with a case presentation Early detection of cardio-toxicity using 2D- based strain imaging Extended prediction of cardio-toxicity using 2D-based strain imaging Optimal myocardial deformation index and cut-off values Putting it all together Conclusions
1.Introduction with a case study
Case study 47 year old female Invasive ductal carcinoma (ER-, PR-, Her2-neu+) Docetaxel, Carboplatinum and Trastuzumab followed by mastectomy Baseline EF=65% EF=58% 3 months later while on Trastuzumab What to do?
LVEF which is widely used to monitor cardiac systolic function during and after chemotherapy, fails to detect subtle alterations in LV function. Once the LVEF has decreased in patients treated with cardio-toxic agents, it may be too late to reverse the course of the cardiomyopathy Introduction More sensitive and specific markers of chemotherapy-induced injury and subsequent dysfunction, may allow for better adaptation of oncologic and cardiac
Mor-Avi, et al.jase 2011;24:277-313
2. Early detection and prediction of cardiotoxicity
Objective To evaluate whether sensitive echocardiographic measurements and biomarkers could predict later cardiac dysfunction in chemotherapy-treated patients
Methods and results 43 patients Anthracyclines followed by Trastuzumab Echocardiograms and biomarkers were measured at baseline / after anthracyclines (3 months) / 6 months Cardiotoxicity: Symptomatic drop of 5 points of EF to an EF <55%, asymptomatic drop of 10 points to EF <55%
Variables measured LVEF Markers of diastolic function Peak longitudinal and radial strain NT - pro BNP c Tn I
Results 9 patients (21%) developed cardio-toxicity (1 at 3 months, 8 at 6 months) 2 patients developed symptomatic CHF
Univariate Analysis of Predictors of Cardiotoxicity Cardiotoxicity P value (prediction No Yes of Variable (N=34) (N=9) Cardiotoxicity) OR CI Change in left ventricular ejection fraction at 3 months (%) 1.2 ± 9 5.6 ± 8 0.19 5.5 0.45-100 Change in longitudinal strain at 3 months (%) 3 ± 10 15 ± 8 0.01 500 6.7-0.11x10 6 Change in radial strain at 3 months (%) 2 ± 23 22 ± 22 0.02 250 4-0.4x10 5 Change in N-terminal pro B type natriuretic peptide at 3 months (%) 46 ± 240 56 ± 190 0.91 1 0.65-1.4 Elevation high sensitivity cardiac Troponin I at 3 months 6 (18%) 6 (67%) 0.006 9 1.8-50
Univariate Analysis of Cardiotoxicity - Diastolic Indices Cardiotoxicity P Value No Yes Prediction of Variable (N=34) (N=9) Cardiotoxicity) OR CI ΔLAD at 3 months, mm 0.01 ± 0.12 0.05 ± 0.11 0.19 0.01 8.68x10-6 6.90 ΔE, at 3 months, % 5 ± 20 1 ± 21 0.47 4.57 0.12 201.2 ΔE/A at 3 months, % 2 ± 24 10 ± 41 0.28 4.05 0.31 61.47 ΔE at 3 months, % 6 ± 16 7 ± 17 0.80 0.53 0.003 7.59 ΔE/E at 3 months, % 3 ± 25 15 ± 31 0.25 0.17 0.007 3.39
Sensitivity, Specificity, Positive and Negative Value of the Predictors of Cardiotoxicity Sensitivity Specificity PPV NPV 10% decrease long strain 7/9 (78%) 27/34 (79%) 7/14 (50%) 27/29 (93%) Increased ctnl at 3 months 6/9 (67%) 28/34 (82%) 6/12 (50%) 28/31 (90%) 10% decrease long strain and increased ctnl at 3 months 5/9 (55%) 33/34 (97%) 5/6 (83%) 33/37 (89%) 10% decrease long strain or increased ctnl at 3 months 8/9 (89%) 22/34 (65%) 8/20 (40%) 22/23 (97%)
3. Extended prediction of cardiotoxicity
Objective To evaluate the long term predictive value of these measurements in a larger cohort
Results 81 consecutive patients 26 patients developed cardio-toxicity (32%) 3 at the end of anthracyclines, 23 while on Trastuzumab 5 (6%) of the patients were symptomatic
1 1 2 1
Results LVEF measured at the completion of anthracyclines was not predictive of later cardio-toxicity ( P=0.075) Change in EF was not predictive (continuous (P=0.081)/ discrete 8 (P=0.23)or 10%(P=0.34)cut offs Peak GLS was predictive of cardiotoxicity (P=0.0003) Neither radial nor circumferential were predictive (P=0.25 and 0.67
26(32%) 9 (11%)
EF < 50% 15 patients developed EF < 50% 5 patients had EF<50% at end of follow up (6%).
4. Optimal myocardial deformation index and cut-off values
Objectives We sought the optimal myocardial deformation index for prediction of cardio-toxicity at 12 months
Methods 100 women (51±12 y) receiving chemotherapy 46 received simultaneous anthracycline and trastuzumab. Conventional echo (mitral annular s and e velocity) and myocardial deformation indices (global longitudinal peak systolic strain [GLS], strain rate [SR-s] and early diastolic strain rate [SR-e]) from speckle tracking were measured at baseline, 6 and 12m. Cardiotoxicity was defined by a decrement of EF >10%.
JACC 3/27/2012 E1245
Cut-off (%) Sen (%) Spe (%) ΔGLSR-S -12.3 75 72 ΔGLS -12.1 69 76 ΔGLSR-E 10.0 69 69 Δs -3.4 100 34
Study Cut-off Sensitivity Specificity MDACC/M GH -19% 77% 71% CCF/Brisba ne -12.1% change 69% 76%
5. Putting it all together
Early detection of Type II toxicity during F/U using strain EF Cardiotoxicity Cardioprotection No criteria by EF Baseline strain available Drop >12% as ompared to baseline Baseline strain un-available Strain -19% or better No Yes No Yes Continue therapy Sub-clinical LV dysfunction Consider cardio-protection Continue therapy
Change in strain: 25-5 - 19 / 25.5 =25%
Early detection of Type II toxicity during F/U using strain EF Cardiotoxicity Cardioprotection o criteria by EF (Asymptomatic drop of 7 points) Baseline strain available Drop >12%(25.5%) as compared to Baseline strain un-available Strain -19% or better No baseline Yes No Yes Continue therapy Sub-clinical LV dysfunction Consider cardio-protection Continue therapy
Conclusions GLS and Troponin I measured at the completion of anthracyclines are useful in the prediction of subsequent cardiotoxicity and may help guide treatment to avoid cardiac side effects
Thanks for your attention
Circulation 2011;124(10021):A13998
Baseline: -20.1% F/U: -17% (15.4% drop)
Breast cancer pts n=100 Baseline echo & trastuzumab initiation exclude Pts taking BB before chemo n=8 Early follow-up visit GLS >12% decrease or EF decrease BB start n=8 GLS no change n=59 GLS >12% decrease n=25 BB(+) BB(-) Follow-up echo 45
BB(-) BB(+) Delta GLS BB(-) :-1.6±2.5 BB(+):-3.3±1.4 p=0.008 p=0.028 p=0.005 Baseline 6m 12m -20.8±2.1-16.8±2.4-18.4±2.7 BB(-) Delta EF BB(-) :0.1±4.6 BB(+):4.5±6.0 p=0.861 p=0.098
Thanks for your attention.
A retrospective look Prospectively entered data in EPIC 197 patients with or without anthracycline regimen 2005-2010 14 patients new diagnosis of CHF (7.1%) 72 patients developed LV dysfunction (36.54%)
Study Follow up LV dysfunction CHF Cochrane metaanalysis CCF retrospectiv e MDACC/M GH CCF/Brisba ne 3 years 11% 2.6% up to 4y 36% 7.1% 18 months 32% 6% 12 months 20% -