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.