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.