Supplementary Material
Table A. Summary of studies that have used advanced myocardial mechanics to illustrate early myocardial injury during cancer chemotherapy
(Studies in adult patients are presented first followed by studies in pediatric patients).
Study
(year)
Echo Method
Cancer
Type
N (age,
years), %
female
78 (52±10),
98.7%
Treatment
Echo Timing
Key Findings
Doxorubicin 81% mean
(range) cumulative dose
238mg/m2 (140-340),
epirubicin 19%,
392mg/m2 (255-572).
68% of HER(-) patients
received radiotherapy. All
HER2(+) received
trastuzumab.
Pre- and 1 week
postanthracycline
(12-18 weeks,
preradiotherapy),
then at 6 & 12
months (only in
HER2-)
GLS fell by 9% by end of
anthracycline (-18.6±2.4% to 17.0±2.2%) in all 78 patients. Also a
2% relative drop in LVEF was seen.
In the HER2(-) patients GLS fell by
7.9% post-anthracycline (-19.0±2.3%
to -17.5±2.3%) but normalized in 84%
by 12 months. Basal and mid LV
segments had significant reduction in
GLS but not apex.
Early diastolic strain-rate fell by 10%
(1.00±0.24% to 0.90±0.22%) postanthracycline. Pre-therapy GLS and
LVEF correlated with post-therapy
diastolic strain (r=-0.35 and -0.54).
GLS data reported in previous study3.
Stoodley et
al 20131‡
STE GLS (2 and 4
chamber)
Breast 28
HER2(+),
50
HER2(-)
Stoodley et
al 20132‡
STE GLS and
diastolic strain
rate (2 and 4
chamber)
Breast,
HER2(+)
and (-)
52 (49 ± 9),
100%
Doxorubicin in 77%,
mean±SD cumulative
dose 236±33 mg/m2,
epirubicin in 23%, dose
408±110mg/m2, no
radiotherapy
Pre-and 1 week
postanthracycline (12
-18 weeks, preradiotherapy or
trastuzumab)
Zhang et al
20124
TDI LSR from the
basal IVS
Breast (no
HER2
data)
60 (54±12),
100%
Epirubicin maximal
cumulative dose
400±40mg/m2 (30
patients randomized to
treatment with salidroside
and 30 to placebo)
Pre, and 7 days
post-reaching
epirubicin doses
of 100,200,300,
and 400mg/m2
Motoki et al
20125
STE LV twist and
untwist
parameters + GLS
(3 apical views),
NHL,
AML,
ALL
25
(58±11),
56%
female
Anthracyclines,
equivalent cumulative
dose 98±59mg/m2 at 1
month and 170±87mg/m2
Pre, 1 and 3
months after start
of anthracycline
Fall in LSR seen in both groups by
200mg/m2 - salidroside 15·5%
(1.68±0.54 to 1.42±0.49/s) placebo
16.0%(1.69 ± 0.64 to 1.35±0.36/s),
LSR returned to normal by 300mg/m2
in the salidroside but not placebo
group. At end of therapy LSR in the
placebo group was lower than
salidroside group (1.40±0.23 vs
1.68±0.29/s). No change in mean
LVEF.
Reduced peak systolic torsion,
twisting rate, untwisting rate by 1
month compared to baseline. GLS
reduced by 1 month, no change in
Vendor,
Reproducibility
GE, Inter GLS COV
9.0%, Intra 9.9%
GE, inter and intra as
mean difference
(SD) for early 0.08
(0.12/s) &
0.01(0.05/s) and late
diastolic SR
0.06(0.12/s) &0.01
(0.08/s), GLS -1.73
(1.0%) and 0.86(0.59%)
Philips, Inter and
intra of LSR as
percentage of mean
of two repeated
measures 10 ± 4%
and 11± 3%.
GE, Inter and intraobserver variability
as bias ±1.96SD for
LV torsion were -
GCS (mid SAX)
at 3 months, no
radiotherapy
Stoodley et
al 20113‡
STE GLS (4
chamber), GRS,
GCS (mid SAX)
and strain-rate
Breast,
HER2(+)
and( -)
52(49±9),
100%
Doxorubin and epirubicin
(mean cumulative dose
236±33mg/m2 and 408
±110mg/m2), radiotherapy
0%
Pre- and 1 week
postanthracycline (12
-18 weeks, preradiotherapy or
trastuzumab)
Cadeddu et
al 20106
TDI LS and LSR
(septum)
Multiple
49
(56±13),
76%
Epirubicin (maximal
cumulative dose
400±20mg//m2) but 25
received telmisartan and
24 placebo, radiotherapy
0%
Pre- and 7 days
post-epirubicin
dose of 100, 200,
300, and 400
mg/m2
Wildiers et
al 20087†
TDI RS and RSR
(SAX mid inferior
lateral wall)
Breast,
HER2(+)
and (-)
TDI LS and LSR
(septum)
Multiple
Liposomal doxorubicin
(cumulative dose
180mg/m2), radiotherapy
0%
Epirubicin cumulative
dose 400mg/m2 (58%)
and 300mg/m2 (42%)
Pre, before 4th
cycle, after 6th
cycle
Mantovani
et al 20088*
16 (median
69, range
65-74),
100%
31
(59±14),
74%
Jurcut et al,
20089†
TDI LS and LSR
(3 apical views,
18 segments), RS
and RSR ( SAX
mid inferior
lateral wall)
Breast,
HER2(+)
and (-)
16
(69.8±3.1),
100%
Liposomal doxorubicin
(cumulative dose
180mg/m2), radiotherapy
0%
Pre- and within
7-14 days after
3rd and 6th cycles
Pre, 7 days post100, 200, 300,
400mg/m2, and
3, 6, 12 &18
months post-last
dose
GCS. All parameters correlated with
anthracycline dose. (No absolute
values). Patients with lower torsion at
baseline had more significant drop in
torsion at 3 months.
Reduced GLS by 8% (-17.8±2.1%to 16.3±2.0%) and GRS by 15%
(40.5±11.4% to 34.3±11.4%), no
change in GCS. LVEF from 58·6
±2.6% to 56.0 ± 2.8%. None had
LVEF drop ≥10%, however those with
an LVEF ≤55% post-therapy had
lower GLS than those with LVEF
>55%. No change in any of the strainrate parameters.
Significant reduction in septal LSR by
200 mg/m2 vs baseline by 20%
(1.78±0.24 to 1.41±0.31/s) in placebo
and 13% in telmisartan (1.83±0.24 to
1.59±0.36/s). LSR recovered in
telmisartan group but not placebo. No
change in strain or LVEF in either
group.
RS and RSR reduced by 34%
(50±12% to 33±8%) and 28%
(4.6±1.2 to 3.3±1.0/s) after 6th cycle.
No significant change in LVEF
Reduced septal LSR after 200 mg/m2
of epirubicin by 19% compared to
baseline (1.79±0·06 to 1.45±0·15/s)
and remained reduced for 18 mos. No
change in LS or drop in LVEF. No
data on LS or LSR predicting changes
in LVEF.
Compared to baseline, RS fell 25%
(50.1±11.6 to 37.7±10.2%) and RSR
20% (4.57±1.18 to 3.64 ±1.52/s) after
3 cycles and GLS 17% (-22.7±2.8 to 18.8±2.8%) and LSR 12% (-1.54±0.19
to -1.36±0.23/s ) after 6 cycles. No
0.26º (1.59) and 0.21º (1.39).
GE, mean (SD) inter
and intra for GLS 1.73(1.0%) & 0.86(0.59%). GRS
5.0 (7.8%) & 3.4
(12.4%). GCS 1.48
(1.24%) & 1.62
(1.10%)
Toshiba, no data
GE, no data
Toshiba, No data.
GE, mean relative
intraobserver
variability was 8.3%
of strain and 9.1%
for strain rate
change in LVEF.
Mercuro et
al 2007 10*
TDI – LS and
LSR (septum)
Multiple
16
(56±3),
81%
Epirubicin cumulative
dose of upto 400mg/m2
Pre-therapy and
after 200, 300,
and 400 mg/m2
Poterucha et
al 201211
STE GLS (3
apical views)
Various
pediatric
19
(15·3±3),
37%. 19
controls
Mean cumulative
anthracycline dose 296
±103mg/m2, doxorubicin
(89%), idarubicin (32%),
danorubicin (5%),
radiotherapy 0%
Before, 4, and 8
months after
starting
anthracycline
Al-Biltagi et
al 201212
STE GLS (3
apical views)
ALL
25 (9±2.6),
48%, 30
controls
Doxorubicin 30mg/m2 (as
part of induction therapy).
No radiotherapy.
Pre- and within 1
week of starting
doxorubicin
Ganame et
al 200713
TDI – LS and
LSR (entire
septum) and RS
and RSR (SAX
mid inferior
lateral wall)
Multiple
13
(10.7±3.8),
23%
Danorubicin (30 or
40mg/m2), doxorubicin
(60-75mg/m2), or
Idarubicin 10mg/m2
Before first dose,
then post-1, 2,
and 3rd doses
Reduced septal LSR after 200 mg/m2
of epirubicin by 20% versus baseline
(1.82±0.57 to 1.45±0.44/s). No change
in LS, LVEF.
GLS fell by 9% by 4 months vs pretherapy (-19.9 ±2.1% to -18.1±2.5 %),
remained reduced at 8 months (18.1±2.8%). Also GLS fell compared
with controls (-20.5±1.5%) at both
time points. LVEF did not change
until 8 months (62±3% to 59±3%).
Correlation between fall in LVEF
between pre-therapy and 8 months and
the fall in average mid (r=-0.49) and
apical (r=-0.48) segmental LS was
reported but no data on early change
in strain predicting LVEF drop.
Pre-therapy, patients had lower GLS (18.7±4.5% vs -21.5± 2.2%) than
controls. Post-treatment the GLS fell
further by 19% to -15.1 ± 2.5%.
Fractional shortening also fell
(40±4.9% to 33.5± 6.6%).
RS and RSR fell by 24% (74±14% to
56±11%) and 15% (5.4±0.9 to
4.6±0.8/s) and LS and LSR fell by
15% (-27±5% to -23±7%) and 9% (2.2±0.4% to -2.0±0.4%) after first
dose and remained reduced. LVEF
change significant by second dose
(71±4% to 66±4%)
Toshiba, no data
GE, GLS COV Inter
7.2%, Intra 10%.
GE, no data
GE, mean difference
(95% CI): intra /
inter LS 2.67(3.69%)
/ 5.14 (3.73%), LSR
0.13(0.13/s) / 0.44
(0.41/s), RS
2.03(2.81%)
/6.44(8.98)%, RSR
0.44 (0.36/s) / 0.50
(0.33/s)
STE, speckle-tracking echocardiography; TDI, tissue-doppler imaging, GCS, global circumferential strain; GCSR, global circumferential strain-rate; GLS, global
longitudinal strain; GLSR, global longitudinal strain-rate; GRS, global radial strain; GRSR, global radial strain-rate – the word global was used for all STE-based
strain as multiple segments were used; for TDI strain, unless multiple segments were used, the character G is removed to illustrate that this is not “global” strain;
GE, General electric; IVS, interventricular septum; SAX, short axis; NHL, Non-Hodgkin’s Lymphoma; ALL, Acute Lymphoblastic Leukemia, AML; Acute
Myelogenous Leukemia; COV, coefficient of variance. *‡study from same group with likely overlap in the patients; †study of the same patients.
Table B. Summary of studies that have used early changes in advanced myocardial mechanics to predict subsequent cardiotoxicity (Studies in
adult patients are presented first followed by studies in pediatric patients).
Study
(year)
Echo Method
Cancer
Type
N (age,
years), %
female
74
(51±11),
58%, 37
controls
Treatment
Echo Timing
Key Findings
Prognosis
Anthracycline
equivalent
cumulative dose
118±43mg/m2 at 6
weeks and
178±58mg/m2 at 12
weeks. Total
cumulative dose
259±52mg/m2, no
data on radiotherapy
Preanthracycline,
immediately
post, 6, 12,
24, and 52
weeks later
By 6 weeks GLS fell
10.4% (-21.2±2·5 to 19.0±2·4), GRS 14.0%
(47.8±5.3% to 41.1±5.4%),
apical rotation 16%
(8.1±1.4% to 6.8±1.3%),
twist 10.8% (13.8±1.7% to
12.3±1.7%), and GLS x
twist by 19.9% (-297±68 to
-238±57). No separate data
for cardiotoxicity group.
Significant GLS fall of
11.4% (-20.7±2.6% to 18.3±2.1%), GLSR 12.8%
(-1.17±0.24 to 1.00±0.15/s)
and GLSRE-E 11.9%
(1.36±0.28 to 1.20±0.28/s)
at 6 months in patients
with cardiotoxicity at 12
months. GCS and GRS
changes not significant. No
data for whole group
For the whole group GLS
fell 6.9% (-20.3±2.7% to
18.9±2.5%) at 3 months,
and GRS 5.6% (53.1±4%
to 50±3.9) at 4 months . In
patients with cardiotoxicity
fall in GLS and GRS at 3
months by 20.1% (20.4±3·0% to 16.3±2·4%)
and 5.5% (54±2% to
51±4%) and at 4 months
by 22.0%(to -15.9±1·7%)
13% cardiotoxicity (CREC
criteria). Best predictors of
cardiotoxicity between 24
and 52 weeks were change
between pre-therapy and 6
weeks in GLS x twist –
cut-off of 71% x o had
sensitivity 90%, specificity
82% and GLS – cut-off of
2.77% (13·1% relative)
had sensitivity 79% and
specificity 73%.
30% cardiotoxicity (EF fall
≥ 10%). Relative GLS
change ≥11% between preand 6 months had
sensitivity 65% and
specificity 95% to predict
cardiotoxicity at 12
months. Absolute GLS >20·5 at 6 months also
predictive (sensitivity 96%,
specificity 66%)
19.4% cardiotoxicity
(CREC criteria) by 6
months. Relative GLS fall
≥15% at 3 months had
sensitivity 86% and
specificity 86% and GRS
≥10% at 4 months had
sensitivity 86% and
specificity 69% for
cardiotoxicity.
Combination of both
sensitivity 71%, specificity
Mornos et
al, 201314
STE GLS (3
apical views),
twist (basal and
apical slices),
and GRS (mid
SAX)
Breast
(HER2-),
lymphoma,
ALL,
AML,
osteosarcoma
Negishi et al
201315
STE GLS,
GLSR, early
diastolic GLSR
(GLSR-E) - 3
apical views,
GCS, GRS (mid
SAX)
Breast
HER2(+)
81
(50 ± 11),
100%
100% trastuzumab,
46% doxorubicin
<240mg/m2 or
epirubicin
<600mg/m2,
radiotherapy 62%.
Pretrastuzumab,
6, and 12
months later
Baratta et al
201316
STE – GLS (2
and 4 chamber
basal and mid
segments), GRS
(mid SAX)
Breast
(HER2+
and -)
(n=16),
lymphoma/
leukemia
(n=11),
other
(n=9),
36 (47 ±
16), 58%
Doxorubicin in 58%
(mean
294±122mg/m2 in
those with
cardiotoxicity and
102±124mg/m2 in
those without),
trastuzumab in 22%.
No data on
radiotherapy
Pre, 2,3,4,
and 6 months
after start of
therapy
Vendor,
Reproducibility
GE, Intra ICC
(COV) for GLS x
twist 0.94(2.9%),
GLS 0.95 (2.6%),
LV twist 0.93
(3.1%), GRS 0.91
(2.9%). Inter 0.90
(4.3%), 0.91
(3.9%), 0.89
(4.8%), 0.84
(5.1%)
GE, Intra ICC
(95% CI) for GLS
0.85 (0.54-0.96%),
GLSR 0.91 (0.700.98/s), GLSR-E
0.90 (0.66-0.97/s).
Inter 0.71 (0.230.92%), 0.85 (0.280.97/s), 0.87 (0.560.97/s).
GE, mean (SD)
absolute difference
inter / intra GLS
0.6 (1.4%) / 0.2
(1.1%), GRS 3.4
(7.1%) / 3.2 (6.6%)
Sawaya et
al, 201217
STE GLS (basal
and mid
segments of
4CH and 2CH
views), GCS,
GRS (mid
SAX)
Breast
HER2(+)
81
(50±10),
100%
Cumulative
doxorubicin
240mg/m2 or
epirubin 300mg/m2,
then paclitaxel and
trastuzumab,
radiotherapy 60%.
Preanthracycline,
3 months
(pretrastuzumab),
then at, 6, 9,
12, 15
months
Sawaya et
a,.201118
STE GLS (basal
and mid
segments of
4CH and 2CH
views), GCS,
and GRS (mid
SAX)
Breast
HER2(+)
43
(49 ± 10),
100%
Doxorubicin
240mg/m2 or
epirubicin
300mg/m2, taxanes
and trastuzumab,
radiotherapy 11.6%
Preanthracycline,
3, 6 months
Fallah-Rad
et al 201119
STE GLS (3
apical views),
GRS (mid
SAX)
Breast,
HER2(+)
42
(47 ± 9),
100%
FEC 6 cycles in
88% (max
epirubicin
600mg/m2), AC 4
cycles in 12% (max
doxorubicin
240mg/m2) then
trastuzumab (no
taxanes),
radiotherapy 98%.
Preanthracycline,
Pretrastuzumab,
3, 6, 9, 12
months
thereafter
Hare et al,
200920
TDI LS and
LSR (6 basal
segments)
STE GLS,
Breast
HER 2(+)
35
(51±8),
100%
Doxorubicin or
epirubicin use in
91%, taxane 89%,
and trastuzumab
Baseline (preand/or postanthracycline
) and at 3
and 14.8% (to 46±2%).
Significant fall in GLS of
10% (-21±2% to -19±2%),
GRS 6% (53±15% to
50±17%), GCS 11% (18±4% to -16±4%) for the
whole group by 3 months
compared to baseline. GLS
fell by a maximum of
15±3% for the group with
cardiotoxicity
Significant fall in GLS by
5·8% (-20.5±2.2% to 19.3±2.4%), GCS by
16.7% (18±4% to 15±4%)
for whole group by 3
months compared to
baseline. GRS fall not
significant by 3 months.
GLS fell by 15±8% and
GRS 22±22% in group
with cardiotoxicity.
GLS fell by 18% (19.8±1.8% to -16.4±1.1%)
and GRS by 19%
(41.4±15.2% to
34.5±15.2%) at 3 months
into trastuzumab (versus
pre-trastuzumab) in
patients with
cardiotoxicity. No data for
group as whole.
TDI LS – no change, LSR
13% fall (-1.32±0.28 to 1.15±0.27/s) by 3-6
months. STE GLSR fell by
97%.
32% cardiotoxicity (CREC
criteria). Fall in absolute
GLS at 3 months to < -19%
predicted subsequent
cardiotoxicity sensitivity
74%, specificity 73%, PPV
53%, NPV 87%. Relative
fall in GLS of 10% also
predictive.
GE, same
variability as in
previous study18.
21% cardiotoxicity (CREC
criteria). A 10% relative
fall of GLS by 3 months
had sensitivity 78%,
specificity 79%, PPV 50%,
and NPV 93% to predict
cardiotoxicity at 6 months.
GE, intra as
absolute mean
error (SD) GLS 0.14(1.1%), inter
0.5 (1.5%). GRS 2
(5%), 2.2
(7.5%).GCS 0.53
(2.82%), 3.3
(3.5%).
24% cardiotoxicity (Fall in
LVEF ≥10% to <55%,
signs or symptoms of CHF,
discontinuation of drug).
Absolute GLS fall of 2·0%
(~10.1% relative) had
sensitivity 79%, specificity
82%, PPV 60%, and NPV
92% and absolute GRS
fall of 0.8% (~1.9%
relative) sensitivity 86%,
specificity 81%, PPV 60%,
and NPV 95% to predict
cardiotoxicity.
Amongst 14 patients who
had a drop in 2D GLSR
>1SD during therapy 2
(14%) and had follow-up, a
GE, Intra as ICC
(COV) GLS 0.94
(3.5%), GRS 0.91
(3.2%). Inter 0.90
(5.2%), 0.82(5.4%)
GE, Intra / Inter as
ICC for 2D GLS
0.94 / 0.91, GLSR
0.94 / 0.91, GRS
GLSR (3 apical
views) GRS and
GRSR (mid
SAX)
Mavinkurve
-Groothuis
et al, 201321
STE, GLS
(4CH), for GRS
and GCS (mid
SAX) and
strain-rate for
all
ALL
60 (49
with
complete
f/u), age 6
(2.2-15.4),
38%. 60
controls.
100%, radiotherapy
77%
month
intervals after
start of
trastuzumab
Anthracycline
equivalent
cumulative dose –
120mg/m2 to
300mg/m2,
radiotherapy 100%
Preanthracycline,
10 weeks and
12 months
later
5% by 3 months (1.30±0.21 to -1.24±0.18/s)
and RSR by 13% by 6-9
months (2.02±0.61 to
1.75±0.41/s). A fall ≥1SD
in LSR and RSR seen in
51% and 37% of patients.
No fall in GLS or GRS. No
separate data on
cardiotoxicity group
By 12 months significant
fall in GLS by 8·2% (18.2±3.1% to -16.7±5·2%),
GLSR 16.7% (-1.44±0·3 to
-1.20±0.4/s), GRS 17.3%
(66.8±1% to 55.2±16%),
GCS 12.9% (-19.4±4.3%
to -16.9±3.1%). At 12
months compared to
controls, all strain and
strain-rate except GRS
were lower by 7.7 to
32.4%.
drop in LVEF >10%
(cardiotoxicity) from
baseline as seen at a mean
follow-up of 22± 6 months.
0.86 / 0.50, GRSR
0.83/0.65. TDI LS
0.99/0.64, LSR
0.96/0.77
0% cardiotoxicity (Fall in
FS > 10%). Early strain
values were not predictive
of decrease in LV
fractional shortening by 12
months. But a decrease in
FS >10% was seen in 23%
although not into abnormal
range.
GE, no data.
Please see abbreviations from Table A. FS, fractional shortening; FEC, 5-fluorouracil, epirubicin, cyclophosphamide; AC, Adriamycin,
cyclophosphamide. 4CH, 4 chamber
APPENDIX TABLE C: Guidelines and Position Statements on Monitoring of Chemotherapy-induced
Cardiotoxicity
ESC Heart Failure Guidelines (2012)22

Pre- and post-evaluation of EF in patients receiving cardiotoxic chemotherapy
Heart Failure Association of the ESC (2011)23

Regular cardiovascular evaluation in patients receiving treatment known to be associated with cardiotoxicity

Follow-up beyond the completion of chemotherapy should be considered in those receiving high doses of
anthracyclines
ESMO Clinical Practice Guidelines (2010)24

Baseline assessment with echocardiography in patients undergoing treatment with anthracyclines or
monoclonal antibodies if:
a)
>60 years old
b) Cardiovascular risk factors
c)

Documented cardiomyopathy or previous thoracic radiotherapy
Further evaluations of LVEF are recommended according to the following schedule:
a)
After administration of half the planned dose of anthracycline
b) After administration of a cumulative dose of doxorubicin 300 mg/m2, epirubicin 450 mg/m2 or
mitoxantrone 60 mg/m2
c)
After administration of a cumulative dose of doxorubicin of 240 mg/m 2 or epirubicin 360 mg/m2 in
patients <15 years or >60 years
d) Before every next administration of anthracycline
e)
After 3, 6, and 12 months from the end of therapy with anthracycline

Assess LV diastolic function for early signs of LV dysfunction before the onset of reduction in LVEF

Periodic monitoring every 12 weeks for those receiving monoclonal antibodies

Assessment of cardiac function is recommended 4 and 10 years after anthracycline in patients who were treated
at <15 years, or even at age >15 years but with cumulative dose of doxorubicin >240 mg/m 2 or epirubicin >360
mg/m2

LVEF reduction of ≥20% from baseline despite normal function or LVEF decline to <50% necessitate
reassessment or discontinuation of therapy
Children’s Oncology Group Long-Term Follow-up Guidelines from Children’s Oncology Group Late Effects
Committee and Nursing Discipline (Version 3.0 – 10/08)25
Age at treatment < 1 year

With chest radiation, any anthracycline dose, LVEF every year

No chest radiation, total anthracycline dose <200mg/m2, LVEF every 2 years

No chest radiation, total anthracycline dose≥200 mg/m2, LVEF every year
Age at treatment 1-4 years

Chest radiation, any anthracycline dose, LVEF every year

No chest radiation, total anthracycline dose <100 mg/m2, LVEF every 5 years

No chest radiation, total anthracycline dose ≥100 mg/m2 to <300mg/ m2 LVEF every 2 years

No chest radiation, total anthracycline dose ≥300mg/ m2 LVEF every year
Age at treatment ≥5 years

Chest radiation, total anthracycline dose <300mg/ m2, LVEF every 2 years

Chest radiation, total anthracycline dose ≥300 mg/m2, LVEF every year

No chest radiation, total anthracycline dose <200 mg/m2, LVEF every 5 years

No chest radiation, total anthracycline dose ≥200 mg/m2 to <300mg/ m2 LVEF every 2 years

No chest radiation, total anthracycline dose ≥300mg/ m2 LVEF every year
ASCO Clinical Evidence Review on the Ongoing Care of Adult Cancer Survivors (2007) 26

No approved surveillance recommendation for long-term cardiotoxicity in asymptomatic cancer survivors due
to the lack of high quality evidence
ACC/AHA Heart Failure Guidelines (2005)27

Monitor closely for the development of cardiac dysfunction
ACC/AHA/ASE Clinical application of echocardiography guidelines (2003) 28
 Class I indication to use echocardiography for baseline and re-evaluation examinations of patients receiving
cardiotoxic chemotherapeutic agents.
TABLE D: Summary of studies that have used advanced myocardial mechanics parameters to demonstrate subclinical myocardial injury in
patients who previously received cancer chemotherapy (Studies in adult patients are presented first followed by studies in pediatric patients).
Study
(year)
Echo Method
Cancer
Type
N (age,
years), %
female
70
(54±8),
100%, 50
controls
Echo Timing
Key Findings
Anthracycline
(mean range
402[312-580mg/m2)
with (n=19) and
without (n=51)
trastuzumab,
radiotherapy (55±9
Gy) 80%
Anthracyclines,
mean cumulative
dose of 229mg/m2
(range 40–644
mg/m2)
Mean of
4.2±1.8 years
postanthracycline
or 3.1± 1.9
years posttrastuzumab for
breast cancer
Median of 7·2
years (2.4-16.4
years) after
completion of
anthracycline
Reduced global LS compared to control
by 7.7% (-18.1±2·2% versus 19·6±1·8%). 26% had GLS below
lower limit of values for control group.
No differences in radial strain or
LVEF. Number of patients with LV
dysfunction not provided.
GE, Intra / Inter as
ICC (COV) GLS
0.97(3.1%) / 0.95
(4.8%), GRS 0.97
(2.9%) / 0.97 (5.0%)
Compared to control, LVEF reduced by
7·5%(60.1±4.2 vs 55.6±4.2), 3D global
by 21% (44.7±7.8 vs 35.4±7.5), twist
by 33% (9.9±3.2 vs 6.6±2.5), torsion
32%(1.9±0.7 vs 1.3±0.5), GPI by
67%(20.2±10·6 vs 6.7±3.9).
Cumulative anthracycline dose
correlated with 3D LV global strain
(r=-0.32), GPI (r=-0.32)
Compared with control: Reduced GRS
of the mid-papillary level inner and
outer layers, and the apical inner layers
(11.6-20.6%). Lower transmural GCS
gradients at all 3 LV levels (9.919.2%). Reduced rotation, PSTV and
PDUV of both subendocardial and
supepicardial layers of the base and
subendocardial layer only of the apex
(exact values not provided). Reduction
in the apical transmural rotation
gradient by 41.3% (2.7 ± 1.7 vs 4.6 ±
2.4º). No reduction in GLS. Number of
patients with LV dysfunction not
provided.
LS and LSR were significantly lower in
the basal RV, LV septal, lateral, and
inferior walls. No values provided.
Toshiba, Intra / Inter
as COV 3D strain
7.3% / 8.2%, twist
7.5% / 10.3%, torsion
7.7% / 10.7%
Ho et al
2010 29
STE – GLS (3
apical views) and
GRS (mid SAX)
Breast
Yu et al
201330*
3D STE global
systolic strain, LV
twist, torsion,
global performance
index (GPI) =
global 3D strain x
torsion/systolic
dyssynchrony
index)
STE - GLS (4 CH),
GRS GCS and
rotation parameters
(basal, mid, and
apical SAX). Layer
specific strain
analysis
Multiple
pediatric
53
(18.6±5.1),
30%, 38
controls
Multiple
pediatric
32
(19.3±5.4),
34%, 28
controls
Anthracyclines,
mean cumulative
dose of 220mg/m2
(range 120–470
mg/m2)
Median of 6.9
years (2.2-14.4
years) after
completion of
anthracycline
TDI – LS and LSR
from 4 basal LV
segments (4 and 2
Multiple
pediatric
19, (median
age 14), 32%.
17 controls
Doxorubicin,
daunorubicin, or
epirubicin dose ≥
Median of 67
months (range
8-142
Yu et al
201331*
YagciKupeli et al
201232
Vendor,
Reproducibility
Treatment
Toshiba, Inter and
intra reported as COV
for all parameters.
Intra ranged from
2.49% to 6.29%, and
inter from 2.86% to
13.35%
GE, no data.
Cheung et al
201133
chamber views)
and one RV lateral
wall segment
STE - LV torsion
parameters (basal
and mid SAX)
ALL
(childhood
survivors)
36
(15.6 ± 5.5),
47%, 20
controls
350mg/m2 (range
350-480 mg/m2),
radiotherapy 10·5%
Doxorubicin or
daunorubicin, mean
(range) cumulative
dose 240mg/m2
(120-470 mg/m2)
months)postanthracyclines
Three patients had LV dysfunction
Median of 7
years (3.1-24.3
years) after last
anthracycline
dose
Reduced peak LV systolic torsion by
32% (8.0±4.1degrees vs 11.8 ±
4.5degrees), systolic twisting velocity
by 25% (68.1 ± 20.3(degree/sec vs
91·0 ± 22·3 (degree/sec), and diastolic
untwisting velocity by 18% (-90.1 ±
34.3(degree/sec vs -109.6 ±
33.4(degree/sec ) compared to control.
This was a reflection of reduction in
apical rotational parameters. Patients
had lower LVEF than controls but 78%
had LVEF ≥ 50%.
Reduced global LS, CS, RS, and CSR
compared to controls reductions of 7%
(-17.6 ± 3.0% vs -19.0± 2.2%) , 17% (14.5 ±2.9% vs -17.4 ± 4.3%), 20%
(40.1 ± 15.6% vs 50.0 ± 16.4%), and
15% (0.90 ± 0.21/s vs 1.06 ± 0.28/s)
respectively. No reductions in GLSR.
Cumulative anthracyline dose
correlated with LSR (r=-0.33) and CSR
(-0.32). None with LV dysfunction.
Compared to controls all strain and
strain-rate values were significantly
reduced. GLS 6.6% (-19.8±2.6% vs 21.2±1.6%), GLSR 12.9% (-1.22
±0.19/s vs -1.40 ± 0.08/s), GRS 14.0%
(49±12% vs 57±5%), GRSR
48·9%(1.75±0.35/s vs 3.43±0.36/s),
GCS 29.6% (-15.9±6.7% vs 22.6±2.1%), GCSR 19.1%(1.48±0.42/s vs -1.83±0.17/s). Number
of patients with LV dysfunction not
provided.
Cheung et al
201034
STE - LV GLS,
GLSR (4CH),
GCS, GCSR, GRS
(mid SAX)
ALL
45
(15.3±5.8),
38%, 44
controls
Doxorubicin or
daunorubicin
median (range)
cumulative dose
240mg/m2 (120470mg/m2),
radiotherapy 0%
Median 6.3
years (2.7-19.8
years) postanthracycline
Mavinkurve
-Groothuis
et al 201035
STE- GLS, GLSR
(4CH), GCS,
GCSR, GRS,
GRSR (mid SAX)
Multiple
pediatric
111(20[5.637.4], 49%,
107 controls
Doxorubicin or
daunorubicin,
cumulative dose
median (range)
180mg/m2(50-600),
radiotherapy 6.3%
Median of 13.2
years (5.0-29.2
years posttherapy
GE, intra / inter as
mean (SD) difference
for LV torsion 0.9º
(5.0) / 4.0 º (7.1), peak
systolic twisting
velocity 0.0 º/sec (9.5)
/ -2.1 º/sec (10.8),
peak diastolic
untwisting velocity 1.7 º/sec (11.2) / -2.0
º/sec (14.4)
GE, no data.
GE, no data.
Park et al
200936
STE – GLS and
GLSR using VVI
(4CH)
Multiple
pediatric
14 (age 6 to
17), 50%, 14
controls
Anthracyclines
cumulative dose
between 90342mg/m2
> 3 years posttherapy
Ganame et
al 200737
TDI – LS and LSR
(basal, mid, and
apical septum,
lateral wall, RV
free wall) and RS
and RSR (inferior
lateral wall).
Pediatric,
ALL,
lymphoma,
solid
tumour, or
AML
56
(median 12.7
[4-28]), 61%,
32 controls
Doxorubicin,
daunorubicin, or
idarubicin. Median
cumulative dose
240mg/m2, range
(90-300mg/m2)
Median 5.2
years (2.0-15.2
years) after last
dose of
anthracycline.
Although systolic strain, strain-rate,
and diastolic strain-rate were lower in
patients, it was not statistically
significant. However compared to
controls longitudinal peak systolic
strain-rate fell by 12.2%(-1.89 ± 0.63/s
vs -1.66 ± 0.27/s) and diastolic strain
by 19.6% (2.38 ± 0.77% vs 2.96 ±
1.26%) in the septum. None had LV
dysfunction.
Reduced RS and RSR by 15-20%.
Reduction in LS and LSR in each of the
6 LV segments (numbers not provided).
Significant drop in LSR in the basal
RV segment only by 17.5% (-33 ± 13%
vs -40 ± 16%). Mean LVEF normal but
3 patients had abnormal fractional
shortening.
*study from same group with likely overlap in the patients, Please see Tables A and B for abbreviations.
Siemens, intra as mean
absolute difference
(95% CI) GLS 0.99
(4.08%), GLSR 0.13
(0.53/s), diastolic
strain rate 0.18
(0.72/s)
GE, intra / inter as
absolute mean
difference (95% CI)
LS 2.56 (3.72%) /
3.48%(3.89%), LSR
0.11(0.12/s) /
0.41(0.42/s), RS 2.79
(2.91%) /
6.03(8.57%), RSR
0.52 (0.47/s), 0.53
(0.59/s)
TABLE E: Summary or studies used advanced myocardial mechanics to detect early myocardial injury from radiation therapy
Study
(year)
Erven et
al, 201338
Echo
Method
TDI – GLS (
3 apical
views)
Cancer
Type
Breast
HER2(+)
and (-)
N (age, years),
% female
75 (no age),
100%. 51 left
sided and 24
right sided caner.
Total strain
follow-up in 63
patients
Treatment
Echo Timing
Key Findings
Doxorubicin or
epirubicin (in 100%),
RT (50Gy) mean heart
and LV doses were
9±4Gy for L sided
breast cancer and 4±4
and 1±0.4Gy for R
sided. 20% received
trastuzumab
Before RT,
immediately after
50Gy, 8 months,
14 months
Erven et
al, 201139
TDI – GLS
and GLSR (3
apical views)
Breast
HER2(+)
and (-)
30 (no age),
100%. 20 left
sided and 10
right sided
cancer. Complete
follow-up in 20
Epirubicin (100mg/m2,
in 53%), RT (50Gy)
mean LV dose was
6.7±6Gy for L sided
RT and 0.6±0.1Gy for
R sided RT. 16.7%
received trastuzumab.
Before RT,
immediately after
50Gy, 2 months
Tsai et al,
201140
STE – GLS
(3 apical
views) and
GCS (mid
SAX)
Hodgkin’s
Lymphom
a
47
(51±9), 66%
RT (mean 41Gy) with
(n=27) and without
doxorubicin
(n=20)(309 ±92mg).
Controls (N=20)
22±2 years after
therapy
Chang et
TDI –
Lung
40 (48·7 ± 3·2),
RT only. Dose
1-2 days pre-RT,
GLS fell immediately after RT by
9.8% (-19.4±2.4% to -17.5±1.9%),
lowest strain at 8 months with 14.4%
reduction (-16.6±1.4%). Strain-rate
fell by 12.8% (-1.4±0.26/s to
1.22±0.15/s immediately postRT).Strain and strain-rate remained
reduced to 14 months. Changes were
only seen in women with L sided RT
and involved the anterior wall and not
the inferior wall. No change in LVEF.
GLS fell in patients with left sided RT
by 10.2% (from -19.5±2.1% to 17.6±1.5%) immediately post-RT, and
remained reduced at 2 months. No
change in overall GLSR. Strain drop
was significant in the apical LV
segments only, there was a reduction
in GLSR in the apical segments only.
The strain drop was limited to
myocardial segments receiving >3Gy.
No change in right sided radiation
patients. LVEF reduction immediately
post-rad in left sided breast cancer
patients by 4·6% (absolute).
GLS reduced by 8% in radiotherapy
with anthracyclines versus no
anthracyclines (-16.1±1.9% vs 17.5±1.7%). No difference in GCS or
LVEF. In radiotherapy with and
without anthracyclines reduced GLS
(21% and 14% respectively) and GCS
(19% and 21% respectively)
compared to control (-20.4±1.7% and
-22.5±2.2%). Patients had lower
LVEF than controls.
Compared to those imaged pre-
Vendor,
Reproducibility
GE, no data.
GE, no data.
GE, Intra and
inter Cronbach α
were 0.98 and
0.97
Philips, no data
al, 200941
systolic and
early and late
diastolic
strain-rate
(n=27),
breast
(n=13)
40%
between 30-60Gy
after week 3
(30Gy), 4 (40Gy),
5 (50Gy), or 6
(60Gy)
Wang et
al, 200642
TDI –
systolic and
early and late
diastolic
strain-rate
Lung (19),
esophagea
l (12),
thymic
(5),
lymphoma
(4)
40 (48±3·2),
55% female
RT only. Doses
between 26-60Gy.
1-3 days before
RT, after 2·5-3
weeks (26-30Gy),
or 5-6 weeks (5060Gy)
Please see Tables A and B for abbreviations.
therapy the systolic and early diastolic
strain-rate were lower in the anterior
septum, and anterior and posterior
wall in patients who received 50 and
60Gy of radiation but not with lower
doses. Reduction was higher at 60Gy
than 50Gy. At 60Gy reduction in
systolic strain ranged from 27.4% to
39.5%, and diastolic strain from
31.8% to 37.9%.
Compared to those pre-therapy
systolic strain-rate and early diastolic
strain-rate significantly reduced in the
5-6 weeks group in the basal and mid
anterior wall, anterior septum, and
posterior wall. Systolic strain-rate
reduction ranged from 30·3% to
42·5% and diastolic strain-rate
between 32·9%-44·0%.
Philips, no data
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Stoodley PW, Richards DA, Boyd A, et al. Left ventricular systolic function in
HER2/neu negative breast cancer patients treated with anthracycline chemotherapy: A
comparative analysis of left ventricular ejection fraction and myocardial strain imaging
over 12 months. Eur J Cancer 2013; 49(16): 3396-403.
Stoodley PW, Richards DA, Boyd A, et al. Altered left ventricular longitudinal diastolic
function correlates with reduced systolic function immediately after anthracycline
chemotherapy. European heart journal cardiovascular Imaging 2013; 14(3): 228-34.
Stoodley PW, Richards DA, Hui R, et al. Two-dimensional myocardial strain imaging
detects changes in left ventricular systolic function immediately after anthracycline
chemotherapy. European Journal of Echocardiography 2011; 12(12): 945-52.
Zhang H, Shen WS, Gao CH, Deng LC, Shen D. Protective effects of salidroside on
epirubicin-induced early left ventricular regional systolic dysfunction in patients with
breast cancer. Drugs in R&D 2012; 12(2): 101-6.
Motoki H, Koyama J, Nakazawa H, et al. Torsion analysis in the early detection of
anthracycline-mediated cardiomyopathy. European heart journal cardiovascular
Imaging 2012; 13(1): 95-103.
Cadeddu C, Piras A, Mantovani G, et al. Protective effects of the angiotensin II receptor
blocker telmisartan on epirubicin-induced inflammation, oxidative stress, and early
ventricular impairment. Am Heart J 2010; 160(3): 487 e1-7.
Wildiers H, Jurcut R, Ganame J, et al. A pilot study to investigate the feasibility and
cardiac effects of pegylated liposomal doxorubicin (PL-DOX) as adjuvant therapy in
medically fit elderly breast cancer patients. Critical reviews in oncology/hematology
2008; 67(2): 133-8.
Mantovani G, Madeddu C, Cadeddu C, et al. Persistence, up to 18 months of follow-up,
of epirubicin-induced myocardial dysfunction detected early by serial tissue Doppler
echocardiography: correlation with inflammatory and oxidative stress markers.
Oncologist 2008; 13(12): 1296-305.
Jurcut R, Wildiers H, Ganame J, et al. Strain Rate Imaging Detects Early Cardiac Effects
of Pegylated Liposomal Doxorubicin as Adjuvant Therapy in Elderly Patients with Breast
Cancer. Journal of the American Society of Echocardiography 2008; 21(12): 1283-9.
Mercuro G, Cadeddu C, Piras A, et al. Early epirubicin-induced myocardial dysfunction
revealed by serial tissue Doppler echocardiography: correlation with inflammatory and
oxidative stress markers. Oncologist 2007; 12(9): 1124-33.
Poterucha JT, Kutty S, Lindquist RK, Li L, Eidem BW. Changes in left ventricular
longitudinal strain with anthracycline chemotherapy in adolescents precede subsequent
decreased left ventricular ejection fraction. Journal of the American Society of
Echocardiography 2012; 25(7): 733-40.
Al-Biltagi M, Abd Rab Elrasoul Tolba O, El-Shanshory MR, Abd El-Aziz El-Shitany N,
El-Sayed El-Hawary E. Strain echocardiography in early detection of Doxorubicininduced left ventricular dysfunction in children with acute lymphoblastic leukemia. ISRN
pediatrics 2012; 2012: 870549.
Ganame J, Claus P, Eyskens B, et al. Acute cardiac functional and morphological
changes after Anthracycline infusions in children. Am J Cardiol 2007; 99(7): 974-7.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
Mornos C, Petrescu L. Early detection of anthracycline-mediated cardiotoxicity: The
value of considering both global longitudinal left ventricular strain and twist. Can J
Physiol Pharmacol 2013; 91(8): 601-7.
Negishi K, Negishi T, Hare JL, Haluska BA, Plana JC, Marwick TH. Independent and
incremental value of deformation indices for prediction of trastuzumab-induced
cardiotoxicity. J Am Soc Echocardiogr 2013; 26(5): 493-8.
Baratta S, Damiano M, Marchese M, et al. Serum markers, conventional Doppler
echocardiography and two-dimensional systolic strain in the diagnosis of chemotherapyinduced myocardial toxicity. Rev Argent Cardiol 2013; 81(2): 151-8.
Sawaya H, Sebag IA, Plana JC, et al. Assessment of echocardiography and biomarkers
for the extended prediction of cardiotoxicity in patients treated with anthracyclines,
taxanes, and trastuzumab. Circ Cardiovasc Imaging 2012; 5(5): 596-603.
Sawaya H, Sebag IA, Plana JC, et al. Early detection and prediction of cardiotoxicity in
chemotherapy-treated patients. Am J Cardiol 2011; 107(9): 1375-80.
Fallah-Rad N, Walker JR, Wassef A, et al. The utility of cardiac biomarkers, tissue
velocity and strain imaging, and cardiac magnetic resonance imaging in predicting early
left ventricular dysfunction in patients with human epidermal growth factor receptor IIpositive breast cancer treated with adjuvant trastuzumab therapy. J Am Coll Cardiol
2011; 57(22): 2263-70.
Hare JL, Brown JK, Leano R, Jenkins C, Woodward N, Marwick TH. Use of myocardial
deformation imaging to detect preclinical myocardial dysfunction before conventional
measures in patients undergoing breast cancer treatment with trastuzumab. Am Heart J
2009; 158(2): 294-301.
Mavinkurve-Groothuis AM, Marcus KA, Pourier M, et al. Myocardial 2D strain
echocardiography and cardiac biomarkers in children during and shortly after
anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study.
European heart journal cardiovascular Imaging 2013; 14(6): 562-9.
McMurray JJ, Adamopoulos S, Anker SD, et al. ESC guidelines for the diagnosis and
treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and
Treatment of Acute and Chronic Heart Failure 2012 of the European Society of
Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the
ESC. European journal of heart failure 2012; 14(8): 803-69.
Eschenhagen T, Force T, Ewer MS, et al. Cardiovascular side effects of cancer therapies:
a position statement from the Heart Failure Association of the European Society of
Cardiology. European journal of heart failure 2011; 13(1): 1-10.
Bovelli D, Plataniotis G, Roila F, Group EGW. Cardiotoxicity of chemotherapeutic
agents and radiotherapy-related heart disease: ESMO Clinical Practice Guidelines. Ann
Oncol 2010; 21 Suppl 5: v277-82.
Children's Oncology Group. Long-term follow-up guidelines for survivors of childhood,
adolescent and young adiult cancers, Version 3.0. 2008.
http://www.survivorshipguidelines.org/pdf/LTFUGuidelines.pdf (accessed Nov 22, 2013
2013).
Carver JR, Shapiro CL, Ng A, et al. American Society of Clinical Oncology clinical
evidence review on the ongoing care of adult cancer survivors: cardiac and pulmonary
late effects. J Clin Oncol 2007; 25(25): 3991-4008.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
Hunt SA, American College of C, American Heart Association Task Force on Practice G.
ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart
failure in the adult: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines (Writing Committee to Update the 2001
Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol
2005; 46(6): e1-82.
Cheitlin MD, Armstrong WF, Aurigemma GP, et al. ACC/AHA/ASE 2003 guideline
update for the clinical application of echocardiography--summary article: a report of the
American College of Cardiology/American Heart Association Task Force on Practice
Guidelines (ACC/AHA/ASE Committee to Update the 1997 Guidelines for the Clinical
Application of Echocardiography). J Am Coll Cardiol 2003; 42(5): 954-70.
Ho E, Brown A, Barrett P, et al. Subclinical anthracycline- and trastuzumab-induced
cardiotoxicity in the long-term follow-up of asymptomatic breast cancer survivors: A
speckle tracking echocardiographic study. Heart 2010; 96(9): 701-7.
Yu HK, Yu W, Cheuk DK, Wong SJ, Chan GC, Cheung YF. New three-dimensional
speckle-tracking echocardiography identifies global impairment of left ventricular
mechanics with a high sensitivity in childhood cancer survivors. J Am Soc Echocardiogr
2013; 26(8): 846-52.
Yu W, Li SN, Chan GC, Ha SY, Wong SJ, Cheung YF. Transmural strain and rotation
gradient in survivors of childhood cancers. European heart journal cardiovascular
Imaging 2013; 14(2): 175-82.
Yagci-Kupeli B, Varan A, Yorgun H, Kaya B, Buyukpamukcu M. Tissue Doppler and
myocardial deformation imaging to detect myocardial dysfunction in pediatric cancer
patients treated with high doses of anthracyclines. Asia Pac J Clin Oncol 2012; 8(4): 36874.
Cheung YF, Li SN, Chan GC, Wong SJ, Ha SY. Left ventricular twisting and untwisting
motion in childhood cancer survivors. Echocardiography 2011; 28(7): 738-45.
Cheung YF, Hong WJ, Chan GC, Wong SJ, Ha SY. Left ventricular myocardial
deformation and mechanical dyssynchrony in children with normal ventricular shortening
fraction after anthracycline therapy. Heart 2010; 96(14): 1137-41.
Mavinkurve-Groothuis AM, Groot-Loonen J, Marcus KA, et al. Myocardial strain and
strain rate in monitoring subclinical heart failure in asymptomatic long-term survivors of
childhood cancer. Ultrasound in medicine & biology 2010; 36(11): 1783-91.
Park JH, Kim YH, Hyun MC, Kim HS. Cardiac functional evaluation using vector
velocity imaging after chemotherapy including anthracyclines in children with cancer.
Korean circulation journal 2009; 39(9): 352-8.
Ganame J, Claus P, Uyttebroeck A, et al. Myocardial Dysfunction Late After Low-Dose
Anthracycline Treatment in Asymptomatic Pediatric Patients. Journal of the American
Society of Echocardiography 2007; 20(12): 1351-8.
Erven K, Florian A, Slagmolen P, et al. Subclinical cardiotoxicity detected by strain rate
imaging up to 14 months after breast radiation therapy. International Journal of
Radiation Oncology Biology Physics 2013; 85(5): 1172-8.
Erven K, Jurcut R, Weltens C, et al. Acute radiation effects on cardiac function detected
by strain rate imaging in breast cancer patients. International Journal of Radiation
Oncology, Biology, Physics 2011; 79(5): 1444-51.
40.
41.
42.
Tsai HR, Gjesdal O, Wethal T, et al. Left ventricular function assessed by twodimensional speckle tracking echocardiography in long-term survivors of hodgkin's
lymphoma treated by mediastinal radiotherapy with or without anthracycline therapy.
American Journal of Cardiology 2011; 107(3): 472-7.
Chang HF, Jiang ZR, Wang XF, Wang ZN. Strain rate imaging in assessment of the
relationship between the dose of thoracic radiotherapy and the radiotherapy-induced
myocardial damage. [Chinese]. Chinese Journal of Medical Imaging Technology 2009;
25(6): 1032-5.
Wang YA, Li GS, Cui HY, Xia DZ. Strain rate imaging in early assesment of thoracic
radiotherapy-induced myocardial damage. [Chinese]. Chinese Journal of Medical
Imaging Technology 2006; 22(8): 1194-6.