Results
From July 2016 to March 2019, 72 patients were evaluated, of which 3
patients were excluded due to significant GLS reduction at T2, leaving
69 patients for analysis, with a mean age of 52±13 years and female
predominance (97%). Cardiac comorbidities included 2 (3%) patients
with ischemic heart disease of whom 1 (1%) was post myocardial
infarction and cardiovascular risk factors (hypertension, hyperlipidemia
and diabetes mellitus) were relatively common ranging from 12 to 30
percent of the patients. Due to comorbidities 21 patients (30%) were
treated with either angiotensin
converting enzyme inhibitor (ACEI),
angiotensin II receptor blocker
(ARB) or beta blockers (BB) and 11
(16%) with statins. All baseline characteristics are summarized on
Table-1.
All patients were diagnosed with breast cancer, of whom 9 (13%) were
metastatic. Cancer therapy, other than ANT (100%), included paclitaxel
(88%), and the recombinant humanized monoclonal antibodies against HER2
Trastuzumab (21%) and Pertuzumab (19%) (Table 1).
All patients performed speckle strain at T1 and T2 echocardiography
assessment and 50 patients performed speckle strain also at T3. All
patients had normal baseline LVEF (mean 60±1%) and normal GLS (mean
-21±2%). Clinically significant reduction of GLS was observed in 10
(20%) patients at T3, however only 2 (3%) patients showed a reduction
of 10% in LVEF (Table 1), which considered to be clinically significant
(7).
When comparing the association between Dst to e’ average, significant
inverse correlations were noted in anteroseptal, apical and middle
segments (B between -20.8 to -15.2, p<0.008) and in the
average of all LV segments (B=-14.9, p=0.045). When comparing the
association of Dst and E/e’ average, significant positive correlations
were seen in the lateral, posterior and basal segments (B between 12.1
to 20.2, p< 0.04) as well as the average of all segments
(B=19.2, p=0.024). These associations show that poorer diastolic
function by common measurements, is associated with longer diastolic
time. (Table 2)
Using logistic models to assess the predictive ability of the relative
change between the various diastolic strain parameters in T2 and T1, the
only Dst measurement that was able to show significant prediction
capabilities for significant GLS reduction, was the one for the basal
segment time (OR 1.09 for every 1% increase in basal diastolic time,
p=0.03, supplementary Table-S1). Therefore, we continued investigation
of this predictor only, in a multivariate fashion.
After construction of a multivariate logistic regression model of
significant GLS reduction between T3 and T1, with covariates of relative
basal Dst change between T2 and T1, relative GLS reduction between T2
and T1, baseline cardiac risk factors, cardiotoxic cancer therapy used
and cardioprotective medication used, and application of a model
selection algorithm as described in the methods section we ended up with
a final multivariate model that included relative change in basal Dst,
relative change in GLS, hypertension, hyperlipidemia and Pertuzumab
therapy. Of those, the only significant predictors were the relative
change in the basal Dst (OR 1.3 per 1% change, p=0.022, and Pertuzumab
treatment (OR 159.1, p=0.035). (Table-S2)
The predictive ability of basal Dst for significant GLS reduction
between T3 and T1 was moderate with a Youden index of 0.38 and an AUC of
0.732 (95% CI 0.523-0.940). When building a ROC curve for the
prediction of the multivariate logistic model, predictive ability was
better with a Youden index of 0.8 and an AUC of 0.950 (95% CI 0.888- 1)
(p for AUC comparison = 0.05, Fig. 2). The net reclassification index
(NRI) for basal Dst added to the multivariate logistic model was 0.48
(95% CI of 0.10 to 0.0.86) composed of a positive NRI of 0.50 (95% CI
0.12 to 0.87) and a negative NRI of -0.02 (95% CI -0.08 to 0.00)
showing that adding the basal Dst to the multivariate model was overall
significantly beneficial to its predictive ability.