Discussion
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, to help understand the relationship between diastolic strain
changes and overall cardiac dysfunction in patients with breast cancer.
Dst was found to be significantly associated with average e’ and average
E/e’, showing that worse diastolic function by the routine measurements
is associated with longer Dst. These correlations suggest that Dst can
be used as measurements of diastolic function with an advantage of
circumvent the inherent limitations of the routine measurements, such as
load and angle dependence [21,22, 23]. The association of longer Dst
and cardiac damage was also supported by the longer Dst values observed
among patients with vs. without cardiac disease or cardiac risk factors
and among patients developing significant GLS reduction. The importance
of detection of diastolic dysfunction is apparent when considering its
association with increased all-cause mortality in heart failure (HF)
patients [24]. However, 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, highlights 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 cardio-protective treatment [26]. Currently,
many methods in assessing heart function are considered to be
inaccurate, leading to misguidance in therapy and possible premature
termination [27].2D-STE 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 yielded significant findings.
A high correlation was found
between the routine 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. Future studies are
needed in order to strengthen the validity of this new measurement and
assessing whether this early marker may play a role in introducing
cardio-protective regimens in order to prevent LV dysfunction.