Discussion
As speckle tracking echocardiography technology continues to increase in frequency of usage and demonstrate its value, a more complete understanding of its capabilities becomes ever more necessary. Past studies have shown that reduced GLS is associated with LVEF reduction among patients with cancer [19]; however, limited data is available regarding diastolic strain. It has also been shown that diastolic strain rate is associated with cardiovascular morbidity and mortality [12], but information is still lacking in cancer patient populations [20]. In this study, new methods were highlighted by measuring Ds lengthening time to gain direct insight into the relaxation of the ventricles rather than indirect measurements of filling pressures, used more conventionally, to help understand the relationship between diastolic changes and overall cardiac dysfunction and its predictive value among patients with breast cancer.
Dst was found to be significantly associated with common diastolic parameters including average e’ and average E/e’, showing that worse diastolic function by common measurements is associated with longer diastolic time. These correlations suggest that the measurement of Dst can be used as measurements of diastolic function. This poses an advantage due to the inherent limitations of using conventional measurements (e’, E/e’), such as load and angle dependence [21], while it is postulated that global Dsr would circumvent these limitations [21, 22, 23]. Diastolic dysfunction detection’s importance is apparent when considering its role in its association with increased all-cause mortality of heart failure (HF) patients [24] but the early detection and usefulness of 2D-STE measurement techniques among cancer patients have not been well-defined and require further study.
With the use of both a univariate and a multivariate analyses, it was found that the change in basal Dst from T1 to T2 appeared to be significantly associated with a clinically significant GLS reduction at T3 (p<0.04). When building ROC curves the predictive ability of basal Dst was moderate with an AUC of 0.732, while the entire model including basal Dst showed an excellent predictive ability with an AUC of 0.950 a significantly high positive NRI showed that added to the other variables in the regression basal Dst was overall significantly beneficial to its predictive ability.
In line with previous studies [19, 25], we found that treatment with Pertuzumab emerged also as significantly associated with GLS reduction. Since treatment with Pertuzumab is considered to be less cardiotoxic as compared to Transuzumab [1], we believe that future studies focusing on Pertuzumab are required.
The usefulness in predicting the development of cardiac dysfunction can affect treatment course and clinical decision-making as it has been shown that reversing cardiotoxicity can be achieved with early detection and implementation of modern HF treatment [26]. Currently, many methods in assessing heart function are considered to be inaccurate, leading to misguidance in therapy and possible premature termination [27], yet speckle tracking has emerged as having the highest sensitivity in detecting early LV changes associated with future dysfunction [28, 29, 30]. The measurement of Dst can contribute to the clinician’s predictive capabilities and clinical picture of the cancer patients’ heart functioning.
To our knowledge, our study is the first to report the evaluation of Dst. Moreover, data evaluating diastolic strain and its association with systolic dysfunction among cancer patients are limited [20].
Our study has several limitations. First, it was a single center study, however, its strength is the prospective nature following a homogenous population and the unity of all echocardiography performed by the same vendor, technician and interpreting cardiologist. Second, the relatively short period of follow up did not allow us to assess development of LVEF reduction, cardiac morbidity and all-cause mortality. Finally, having many comparisons may increase the chances of having a statistically significant result by chance. However, a physiologic mechanism and consistency in the results make this new method of cardiac function estimation very promising as being another tool in a cardiologist arsenal for risk estimation. A larger cohort with a longer echocardiography follow-up is planned and will allow us to determine the impact of Ds change on the development of LV dysfunction and symptomatic heart failure.
Using a novel measurement method of Dst from 2-D STE yielded significant findings. A high correlation was found between diastolic parameters and Dst. Moreover, a relative prolongation of Ds basal time acted as a significant independent early predictor for clinically significant systolic dysfunction as measured by GLS reduction. Introducing parameters capable of early detection of cardio toxicity in cancer patients, may allow treatment with cardio-protective regimens and the prevention of LV dysfunction.