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%). While only 2 (3%) patients had ischemic heart
disease, 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.
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 underwent 2D-STE assessment at T1 and T2 and 50 patients
underwent 2D-STE assessment at T3 as well. 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 significant reduction of
LVEF≥10% (Table 1) (7).
The mean baseline Dst (ms) of all 69 patients was 217.01±28.77ms and is
presented in Supplementary Table S1according to each segment. When
comparing the values of baseline Dst between patients with vs. without
cardiac disease or cardiac risk factors, we observed longer Dst values
among the latter (Supplementary Table S2). When comparing the Dst change
between T1 and T2 we observed a longer values of Dst at T2 among the
group of patients that developed GLS reduction at T3 (Supplementary
Table S3), which was not consistent among the group of patients that did
not developed GLS reduction (Supplementary Table S4).
When comparing the association between Dst to e’ average, significant
inverse correlations were noted in average, anteroseptal, apical and
middle segments. When comparing the association of Dst and E/e’ average,
significant positive correlations were seen in average, lateral,
posterior and basal segments (Table 2).
Using logistic models to assess the predictive ability of the relative
Dst change from T1 to T2, the only measurement that showed significant
prediction capabilities for significant GLS reduction, was the basal
segment time (OR 1.09 for every 1% increase in basal diastolic time,
p=0.03, Table 3). 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 T1 and T3, with covariates including
baseline cardiac risk factors, cardiotoxic cancer therapy and
cardioprotective medication, 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 4)
The predictive ability of basal Dst for significant GLS reduction
between T1 and T3 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.