Role of Early Left Atrial Functional Decline in Predicting Cardiotoxicity in HER2 Positive Breast Cancer Patients Treated With Trastuzumab.

Trastuzumab is widely used in HER2 breast cancer. However, it may cause left ventricular (LV) dysfunction. A decrease in LV global longitudinal strain (GLS) has been previously demonstrated to be a good predictor of subsequent cancer therapy related dysfunction (CTRCD). Left atrial morphological remodeling during Trastuzumab therapy has also been shown. The aim of this study is exploring the relationship between early changes in left atrial function and the development of Trastuzumab-induced cardiotoxicity. Consecutive patients with diagnosis of HER2+non-metastatic breast cancer treated with Trastuzumab were prospectively enrolled. A clinical, conventional, and advanced echocardiographic assessment was performed at baseline and every three months, until a one-year follow-up was reached. One-hundred-sixteen patients completed the 12 months follow-up, 10 (9%) cases of CTRCD were observed, all after the sixth month. GLS and LVEF significantly decreased in the CTRCD group at 6 months of follow-up, with an earlier (3 months) significant worsening in left atrial morpho-functional parameters. Systolic blood pressure, early peak atrial longitudinal strain (PALS), peak atrial contraction (PACS) and left atrial volume (LAVI) changes resulted independent predictors of CTRCD at multivariable logistic regression analysis. Moreover, early changes in PALS and PACS resulted good predictors of CTRCD development (AUC 0.85; p = 0.008, p < 0.001 and 0.77; p = 0.008, respectively). This prospective study emphasizes that the decline in PALS and PACS among trastuzumab-treated patients could possibly increase the accuracy in identifying future CTRCD in non-metastatic HER2 breast cancer cases, adding predictive value to conventional echocardiographic assessment.

Bergamini C ，Niro L ，Springhetti P ，Ferri L ，Trento L ，Minnucci I ，Maffeis C ，Tafciu E ，Rossi A ，Fiorio E ，Benfari G ，Ribichini F ... -  《-》

Left atrial volume in patients with HER2-positive breast cancer: One step further to predict trastuzumab-related cardiotoxicity.

Trastuzumab (TZ) therapy requires careful monitoring of left ventricular (LV) ejection fraction (LVEF) because it can be potentially cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find other variables to predict cardiac dysfunction early. Left atrium (LA) enlargement has proven to be a powerful predictor of adverse outcomes in several disease entities. Baseline LA volume enlargement might predict TZ-related LV dysfunction. HER2-positive breast cancer patients receiving TZ and undergoing transthoracic echocardiography at baseline and at follow-up every 3 months were retrospectively recruited. One-hundred sixty-two patients formed the study population. Baseline LAVI was dilated in 14 patients (8.6%). Mean follow-up was 14 ± 4 months. Cardiotoxicity occurred in 24 patients (14.8%). LAVI was an independent predictor of TZ-induced LV dysfunction in a clinical model, after adjustment for age and hypertension (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.03-1.82, P = 0.03); and in a hemodynamic model, including ventricular sizes and systolic blood pressure level (odds ratio per 5-mL/m2 LAVI increase: 1.34, 95% confidence interval: 1.01-1.81, P = 0.04). The predicted probability of developing cardiotoxicity increased progressively, in parallel with LAVI values. Baseline LA dilatation emerges as a condition associated with the development of cardiotoxicity in HER2-positive breast cancer patients treated with TZ.

Bergamini C ，Dolci G ，Rossi A ，Torelli F ，Ghiselli L ，Trevisani L ，Vinco G ，Truong S ，La Russa F ，Golia G ，Molino A ，Benfari G ，Ribichini FL ... -  《-》

Phenotypes of Myocardial Dysfunction on Serial Echocardiography and CMR in Women With Early-Stage Breast Cancer.

Understanding phenotypic variations in left ventricular (LV) dysfunction during cancer therapy may allow for tailored surveillance and prevention. This study sought to determine LV dysfunction phenotypes during cancer therapy and their interrelated-ness and association with cancer therapy-related cardiac dysfunction (CTRCD), myocardial tissue changes, and blood biomarkers. This is a secondary analysis of the EMBRACE-MRI (Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI) study in which women with early-stage HER2+ breast cancer were recruited prospectively. High-sensitivity troponin I, B-type natriuretic peptide, and echocardiography were obtained pre-anthracycline and every 3 months with measurement of systolic and diastolic function and left atrial reservoir strain (LARS). Cardiac magnetic resonance (CMR) was performed at baseline and follow-ups with quantification of myocardial T1, T2, and extracellular volume (ECV). Diastolic dysfunction (DD) was graded using American Society of Echocardiography guidelines ("conventional") and regraded by replacing left atrial volume with LARS <24% ("modified"). Relative reduction in global longitudinal strain (GLS) >15% was considered "worsening GLS," and CTRCD was defined using CMR-derived left ventricular ejection fraction. Among 136 women (age 51.1 ± 9.2 years), CTRCD developed in 37 of 136 (27%) and worsening GLS in 53 of 126 (42%) with analyzable studies. Incident DD occurred in 25 (19.4%) of 129 and 19 (14.4%) of 132 patients by conventional and modified grading, respectively. Using LARS improved the ability to classify DD. Transition state analysis demonstrated that the first abnormal state during cancer therapy could be worsening GLS, DD, CTRCD, or a combination. A greater proportion of patients who first transition to DD vs worsening GLS developed subsequent CTRCD (5 of 8 [63%]) vs 7 of 39 [18%]). Worsening DD was associated with higher odds of subsequent CTRCD (OR: 20.9, 95% CI: 3.4-129.5) vs worsening GLS (OR: 4.9, 95% CI: 2.6-9.4). DD was significantly associated with radiation dose and ECV but not with blood biomarkers. Patients receiving breast cancer therapy can develop significant GLS change, DD, or CMR-defined CTRCD that can occur in isolation, concurrently, or sequentially. Development of DD is associated with ECV and higher risk for subsequent CTRCD. (Evaluation of Myocardial Changes During BReast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).

Huang F ，Rankin K ，Sooriyakanthan M ，Signorile M ，Steve Fan CP ，Thampinathan B ，Marwick TH ，Osataphan N ，Yu C ，Koch CA ，Amir E ，Hanneman K ，Abdel-Qadir H ，Wintersperger BJ ，Thavendiranathan P ... -  《-》

Early diastolic strain rate measurements by cardiac MRI in breast cancer patients treated with trastuzumab: a longitudinal study.

Gong IY ，Ong G ，Brezden-Masley C ，Dhir V ，Deva DP ，Chan KKW ，Graham JJ ，Chow CM ，Thavendiranathan P ，Dai D ，Ng MY ，Barfett JJ ，Connelly KA ，Yan AT ... -  《-》

Diagnostic and Prognostic Value of Myocardial Work Indices for Identification of Cancer Therapy-Related Cardiotoxicity.

Echocardiographic global longitudinal strain (GLS) is a useful measure for detection of cancer treatment-related cardiac dysfunction (CTRCD) but is influenced by blood pressure changes. This limitation may be overcome by assessment of myocardial work (MW), which incorporates blood pressure into the calculation. This work aims to determine whether myocardial work indices (MWIs) can help diagnose or prognosticate CTRCD. In this prospective cohort study, 136 women undergoing anthracycline and trastuzumab treatment for HER2+ breast cancer, underwent serial echocardiograms and cardiac magnetic resonance pre- and post-anthracycline and every 3 months during trastuzumab. GLS, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency were measured. CTRCD was defined with cardiac magnetic resonance. Generalized estimating equations quantified the association between changes in GLS and MWIs and CTRCD at the current (diagnosis) and subsequent visit (prognosis). Regression tree analysis was used to explore the combined use of GLS and MW for the diagnostic/prognostic assessment of CTRCD. Baseline left ventricular ejection fraction (LVEF) was 63.2 ± 4.0%. Thirty-seven (27.2%) patients developed CTRCD. An absolute change in GLS (standardized odds ratio [sOR]: 1.97 [95% CI: 1.07-3.66]; P = 0.031) and GWI (sOR: 1.73 [95% CI: 1.04-2.85]; P = 0.033) were associated with concurrent CTRCD. An absolute change in GLS (sOR: 1.79 [95% CI: 1.22-2.62]; P = 0.003), GWI (sOR: 1.67 [95% CI: 1.20-2.32]; P = 0.003), and GCW (sOR: 1.65 [95% CI: 1.17-2.34]; P = 0.005) were associated with subsequent CTRCD. Change in GWI and GCW demonstrated incremental value over GLS and clinical factors for the diagnosis of concurrent CTRCD. In a small group with a GLS change <3.3% (absolute), and a >21 mm Hg reduction in systolic blood pressure, worsening of GWI identified patients with higher probability of concurrent CTRCD (24.0% vs 5.2%). MWIs did not improve identification of subsequent CTRCD beyond knowledge of GLS change. GLS can be used to diagnose and prognosticate cardiac magnetic resonance (CMR) defined CTRCD, with additional value from MWIs in selected cases. (Evaluation of Myocardial Changes During Breast Adenocarcinoma Therapy to Detect Cardiotoxicity Earlier With MRI [EMBRACE-MRI]; NCT02306538).

Calvillo-Argüelles O ，Thampinathan B ，Somerset E ，Shalmon T ，Amir E ，Steve Fan CP ，Moon S ，Abdel-Qadir H ，Thevakumaran Y ，Day J ，Woo A ，Wintersperger BJ ，Marwick TH ，Thavendiranathan P ... -  《-》