Breast Cancer Therapy-Related Cardiac Dysfunction Likely Diagnosed More Accurately With Combined Testing

By Marilynn Larkin

February 22, 2022

NEW YORK (Reuters Health) - In a cohort of women with HER2-positive breast cancer, combined sequential use of echocardiographic 3-D left ventricular ejection fraction (LVEF) with 2-D global longitudinal strain (GLS) and global circumferential strain (GCS) provided a more timely and accurate diagnosis of cancer therapy-related cardiac dysfunction (CTRCD) than when these measures were used individually.

"We have often relied on individual measures to identify CTRCD (e.g., 3D echocardiography LVEF) or risk of future CTRCD (e.g., GLS, GCS, troponin, BNP). However, despite using these techniques, we still miss patients with CTRCD," Dr. Paaladinesh Thavendiranathan of Toronto General Hospital, University Health Network, told Reuters Health by email.

"Furthermore," he said, "although 3D echocardiography LVEF is suggested as the best echocardiography method...to identify CTRCD in guidelines, prior studies have not compared its accuracy to a gold standard (i.e., cardiac MRI) specifically for the diagnosis of CTRCD."

"Our findings provide a new approach for clinicians to consider when they now think of CTRCD," he said. "Instead of thinking of a single measure, they should think of these measures in combination to help determine which patients have a high probability of CTRCD versus low probability. This is a new way of thinking."

As reported in JAMA Cardiology, Dr. Thavendiranathan and colleagues analyzed data from 136 breast cancer patients (mean age, 51) who underwent echocardiography; high-sensitivity troponin I (hsTnI); B-type natriuretic peptide (BNP); and cardiovascular magnetic resonance (CMR) studies every three months before and after anthracycline therapy, and during and after trastuzumab therapy.

Echocardiographic measures included 2-dimensional (2-D) LVEF; 3-D LVEF, peak systolic GLS; and GCS.

LVEF CTRCD was defined as a greater than 15% relative change, and abnormal hsTnI and BNP as greater than 26 pg/mL and 35 pg/mL or more, respectively, at any follow-up point.

CTRCD occurred in 27% of patients by CMR; 23% by 2-D LVEF; 22% by 3-D LVEF; 42% by GLS; 50% by GCS; 24% by BNP; 10% by hsTnI.

As a single measure, 3-D LVEF had greater sensitivity and specificity for CMR CTRCD than 2-D LVEF, whereas GLS had greater sensitivity than 2-D or 3-D LVEF.

Regression tree analysis identified a sequential algorithm using 3-D LVEF, GLS, and GCS for an optimal CTRCD diagnosis (area under the receiver operating characteristic curve, 89.3%).

The probability of CTRCD when results for all three tests were negative was 1.0%.

Dr. Thavendiranathan said, "Realizing some centers will not be able to measure 3D-LVEF, we also substituted 2D-LVEF for 3D-LVEF in the algorithm we developed. When 2D-LVEF is used with GLS and GCS, we were still able to reliably identify patients at the lowest probability of current CTRCD. This was a surprising finding, as we did not expect this combined approach to work as well as it did. Now, our approach can be used more globally even in centers that do not have access to 3D-LVEF."

"If 2D or 3D LVEF, GLS, and GCS are all normal, (clinicians) can be quite confident that the patient does not have CTRCD, re-assure the patient, and continue cancer therapy," he concluded.

Dr. N. Lynn Henry, Disease Lead, Breast Oncology at the University of Michigan Rogel Cancer Center in Ann Arbor commented on the study in an email to Reuters Health. "The authors propose a new algorithm incorporating multiple assessment modalities...to optimally assess cardiac dysfunction in a timely manner."

"However, as the authors noted, the algorithm requires validation in an independent cohort," she said. "Importantly, the clinical utility of this new methodology has also not yet been investigated. It remains unknown whether use of this algorithm for patient monitoring, compared to the current standard-of care-monitoring, will translate into better cardiac outcomes for patients, including less permanent cardiac dysfunction."

"Studies examining the impact of the implementation of the algorithm in routine clinical practice will also be important," she added. "This is especially true if the new assessment technology is more costly than the current standard monitoring approach."

"At this time, it is reasonable to continue to monitor cardiac function according to current guidelines, and to refer patients with findings consistent with cardiac dysfunction to cardiologists or, if available, cardio-oncologists," Dr. Henry concluded.

SOURCE: https://bit.ly/3rWJPrt JAMA Cardiology, online February 9, 2022.

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