Noninvasive Measures of Ventricular-Arterial Coupling and Circumferential Strain Predict Cancer Therapeutics–Related Cardiac Dysfunction

Abstract

Structured Abstract Objective The objective of this study was to determine the relationships between echocardiography-derived measures of myocardial mechanics and cancer therapeutics-related cardiac dysfunction (CTRCD). Background Doxorubicin and trastuzumab are highly effective breast cancer therapies, but have a substantial risk of CTRCD. There is a critical need for the early detection of patients at increased risk of toxicity. Methods We performed a prospective, longitudinal cohort study of breast cancer participants undergoing doxorubicin and/or trastuzumab therapy. Echocardiography was performed prior to therapy initiation (baseline) and at standardized follow-up intervals during and after completion of therapy. Ejection fraction (EF), strain, strain rate, and ventricular-arterial coupling (Ea/Eessb) were quantitated. CTRCD was defined as a ≥10% reduction in EF from baseline to <50%. Multivariable logistic regression models were used to determine the associations between baseline levels and changes from baseline in echocardiographic measures and CTRCD. Receiver operating characteristic curves were used to evaluate the predictive ability of these measures. Results In total, 135 participants contributed 517 echocardiograms to the analysis. Over a median follow-up time of 1.9 years (Interquartile range 0.9, 2.4), 21 participants (15%) developed CTRCD. In adjusted models, baseline levels and changes in Ea/Eessb, circumferential strain, and circumferential strain rate were associated with 21 to 38% increased odds of CTRCD (p<0.001). Changes in longitudinal strain (p=0.037), radial strain (p=0.015), and radial strain rate (p=0.006) were also associated with CTRCD. Ea/Eessb [Area under the curve (AUC) 0.703 (95% confidence interval (CI) 0.583–0.807)] and circumferential strain [AUC 0.655 (95% CI 0.517–0.767)] demonstrated the greatest predictive utility. Sensitivity analyses using an alternative CTRCD definition did not impact our results. Conclusions Over an extended follow-up time, ventricular-arterial coupling and circumferential strain were strongly predictive of CTRCD. Our findings suggest a noninvasive strategy to identify high-risk patients prior to, during, and after cardiotoxic cancer therapy.

Cardiac mechanics and dysfunction with anthracyclines in the community: results from the PREDICT study

“…While a number of prior investigations in tertiary care centres have suggested a role for myocardial mechanics in cardio-oncology,13 22–25 our data provide external validity to the relevance of non-invasively derived measures of myocardial mechanics to community-based populations treated with anthracyclines. Moreover, our findings emphasise the critical importance of assessing change over time in imaging measures with cancer therapy.…”

“…Our prior data in a tertiary-referral breast cancer population first suggested that Ea, Ea/Ees sb as well as longitudinal and circumferential strain and strain rate hold important diagnostic and prognostic relevance 13. This current study suggests that these indices are also valid in community-based populations.…”

“…24 27 We also found diagnostic associations between longitudinal and circumferential strain and cardiac dysfunction 13. However, we did not find changes in longitudinal or circumferential strain to be predictive of subsequent outcomes 13…”

“…The quantitation and derivation of these parameters have been previously described and are further summarised below 911 13…”

Evaluation and Long-Term Outcomes of Cardiac Toxicity in Paediatric Cancer Patients

“…While EF is an adequate gross marker of cardiac function, it may not be sensitive enough to detect early cardiac dysfunction [13][14][15]. Zito et al demonstrated that there is enough variability in EF measurements that it is not sensitive to detect a decrease in EF less than 10% [7].…”