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ASSESSMENT OF LEFT VENTRICULAR SYSTOLIC
DYSFUNCTION BY TISSUE DOPPLER IMAGING
SHOWS EVIDENCE OF SUBCLINICAL
CARDIOMYOPATHY EARLY AFTER
ATHRACYCLINE THERAPY
M. LOTRIONTE1, R. NATALI1, G. PALAZZONI1,
G. BIONDI-ZOCCAI2, G. COMERCI1,
M. SAVINO1, F. LOPERFIDO1
(1)
Catholic University, Rome, Italy ([email protected])
(2)
University of Turin, Turin, Italy
1
BACKGROUND
• Anthracycline (ANT) chemotherapy for
breast cancer, while associated with high
response rates, is fraught by risks of
irreversible cardiotoxicity
• Unfortunately, means to detect such
cardiotoxicity early on and at a sublinical
stage are lacking
2
OBJECTIVES
• We aimed to evaluate early and late effects of
ANT-chemotherapy in patients with breast
cancer using standard and systolic tissue
Doppler imaging (TDI) echocardiography
• We appraised changes from baseline to followup of TDI-derived LV systolic parameters, and
explored whether these TDI-parameters could
be used to detect myocardial dysfunction
before conventional echocardiographic
indexes
3
METHODS
• Consecutive patients undergoing ANT-chemotherapy for
breast cancer at our Institution, who were routinely referred
for standard echocardiography at baseline and after
chemotherapy (usually 6 to 12 months after beginning
antineoplastic treatment) were enrolled between May 2004
and September 2006
• Comprehensive transthoracic echocardiography was
performed using a commercially available ultrasound
system with TDI capabilities (Sonos 5500, Philips Medical
System, Italy) with a 3.5 MHz phased-array ultrasound
probe, by operators unaware of individual chemotherapy
schemes
4
METHODS
• TDI measurements were acquired using a 5-10 mm
sample volume placed at the lateral and septal mitral
annular margins, and at the lateral annulus of the tricuspid
valve in the 4-chamber view
• We measured the TDI peak systolic (Sm), early and late
diastolic velocities in the LV lateral and septum wall, as
well as in the lateral wall of the right ventricle (RV)
• All images were stored onto magneto-optical disc and were
measured offline after the completion of the
echocardiogram by a single experienced investigator
unaware of individual chemotherapy schemes, and with
measurements averaged over 3 cycles
5
METHODS
• LVEF was considered abnormal if <50%
• We a priori decided to stratify patients according to the
pattern of systolic TDI remodelling from baseline to followup as follows:
– group 1 (no LV TDI systolic worsening) including patients without
any evidence of significant LV systolic dysfunction at follow-up;
– group 2 (minor LV TDI systolic worsening) including subjects with
evidence of significant LV systolic remodelling at follow-up in only one
of the LV regions (ie either in the basal lateral wall or in the basal
septum, but not in both);
– group 3 (major LV TDI systolic worsening) including those with
evidence of significant LV systolic remodelling at follow-up in both the
LV lateral wall and the septum
6
RESULTS
• We enrolled a total of 56 patients (55 females), and
followed them all for 8.8±5.7 months (range 6-24)
• All patients but one with atrial fibrillation had normal
sinus rhythm (80±18) at the time of the ultrasound
examination
• Notably, no patient had abnormal LVEF or evidence of
significant LV TDI systolic dysfunction at baseline
• Stratification according to pattern of LV TDI systolic
remodelling allocated 29 (51.8%) patients to group 1,
17 (30.4%) to group 2, and 10 (17.9%) to group 3
7
RESULTS
• No significant increase in major or minor bleedings
(respectively p=0.55 and p=0.98) was found in patients
treated with a high clopidogrel dose
• Sensitivity analysis restricted to randomized trials
confirmed the superiority of a high loading dose regimen
on risk of death or infarction (p=0.001)
• Meta-regression disclosed a significant interaction
between event rate and benefits of high loading dose
(p=0.005), suggesting that the higher the underlying risk,
the greater the favorable impact of high loading
8
PATIENT CHARACTERISTICS
9
CHANGES IN ECHOGRAPHIC
DATA AT FOLLOW-UP
10
CHANGES IN TDI DATA
AT FOLLOW-UP
11
CHANGES IN END-DIASTOLIC
DIAMETER AT FOLLOW-UP
12
CHANGES IN END-SYSTOLIC
DIAMETER AT FOLLOW-UP
13
CHANGES IN TELEDIASTOLIC
DIAMETER AT FOLLOW-UP
14
CONCLUSIONS
• Subclinical systolic dysfunction occurs in almost
50% of patients early after chemotherapy for
breast cancer
• A more adverse by LV-TDI remodelling implies a
more pronounced deterioration of standard
echocardiographic parameters
• TDI monitoring could thus be envisaged to
identify at an earlier stage post-chemotherapy
cardiomyopathy, in order to tailor management
strategies
15
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