Methods
The study population is part of the Israel Cardio-Oncology Registry
(ICOR) – a prospective registry enrolling all patients evaluated in the
cardio-oncology clinic at Tel Aviv Sourasky Medical Center.
All patients signed an informed
consent at the first visit in the clinic and are then followed
prospectively. The registry was approved by the local ethics committee
(Identifier: 0228-16-TLV) and is registered in clinicaltrials.gov
(Identifier: NCT02818517).
This cohort evaluated patients diagnosed with breast cancer planned for
ANT therapy. All patients underwent at least 2 echocardiographic
evaluations, including GLS; at baseline before chemotherapy (T1) and
during Doxorubicin (a type of ANT) therapy (T2). A 3rdechocardiography exam (T3), was performed within 3 months after the
completion of Doxorubicin therapy.
The exclusion criteria included LVEF<53% at T1 and
significant GLS relative reduction≥15% at T2.
Diastolic strain was measured by the time of lengthening (Dst) (ms) of
the myocardium as specified in the next paragraph (Figure 1). The change
in Dst was assessed between T1 to T2 and its association for GLS
reduction in T3 was evaluated. A clinically significant reduction in GLS
was considered as a relative reduction of ≥15% from T1 to T3, adhered
to the standard benchmark set by previous studies [15].
Three standard apical views (4-chamber, 2-chamber, and 3-chamber) were
recorded using a General Electric system, model Vivid S70 echocardiogram
and were performed by the same vendor, technician and interpreting
cardiologist. Routine Left ventricle (LV) echocardiographic parameters
included LV diameters, and LVEF [16]. Early trans-mitral flow
velocity (E), late atrial contraction (A) velocity, deceleration time
(DT) and early diastolic mitral annular velocity (medial and lateral e’)
were measured in the apical 4-chamber view [17]. The peak E/e’ ratio
was calculated (septal, lateral and average). Images were acquired using
high frame rate (>50 frames/s) [18], and thereafter
stored digitally for offline analysis. GLS was measured using 2D-STE
software and tracking within an approximately 5 mm wide region of
interest. An end-systolic frame was used to initialize LV boundaries
which were then automatically tracked throughout the cardiac cycle.
Manual corrections were performed to optimize boundary tracking as
needed. Optimization of images for endocardial visualization through
adjustment of gain, compress, and time-gain compensation controls was
done prior to acquisition. Dst was
evaluated by measuring manually the time of lengthening (ms) of the
myocardium during diastole. According to past studies, showing
significant association between diastolic strain rate and the time
constant of LV relaxation [11], we evaluated the Dst from the point
of aortic valve closure (AVC) throughout the isovolumic relaxation time
and early diastolic, until the plateau of the curve (Fig. 1),
Dst was assessed in three apical
views (2, 3 and 4-chamber), with 6 segments measured per each view, with
a total of 18 segments per each exam. Dst change between T1 and T2 was
assessed according to the following segments: Average, Anterior,
Inferior, Lateral, Septal, Anteroseptal, Posterior, Apex, Mid and Base,
as specified in Table 2.