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

Hari K Narayan; Wei Wei; Ziding Feng; Daniel Lenihan; Ted Plappert; Virginia Englefield; Michael Fisch; Bonnie Ky

doi:10.1136/openhrt-2016-000524

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

Open Heart. 2017 Jan 16;4(1):e000524. doi: 10.1136/openhrt-2016-000524. eCollection 2017.

Authors

Hari K Narayan¹, Wei Wei², Ziding Feng², Daniel Lenihan³, Ted Plappert⁴, Virginia Englefield⁴, Michael Fisch⁵, Bonnie Ky⁶

Affiliations

¹ Division of Cardiology, Department of Pediatrics , The Children's Hospital of Philadelphia , Philadelphia, Pennsylvania , USA.
² Department of Biostatistics , The University of Texas MD Anderson Cancer Center , Houston, Texas , USA.
³ Department of Medicine , Vanderbilt University Medical Center , Nashville, Tennessee , USA.
⁴ Department of Medicine, Division of Cardiovascular Medicine , The University of Pennsylvania , Philadelphia, Pennsylvania , USA.
⁵ Department of General Oncology , The University of Texas MD Anderson Cancer Center , Houston, Texas , USA.
⁶ Department of Medicine, Division of Cardiovascular Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA; Department of Biostatistics and Epidemiology, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Abstract

Background: Our objective was to determine the relevance of changes in myocardial mechanics in diagnosing and predicting cancer therapeutics-related cardiac dysfunction (CTRCD) in a community-based population treated with anthracyclines.

Methods: Quantitative measures of cardiac mechanics were derived from 493 echocardiograms in 165 participants enrolled in the PREDICT study (A Multicenter Study in Patients Undergoing AnthRacycline-Based Chemotherapy to Assess the Effectiveness of Using Biomarkers to Detect and Identify Cardiotoxicity and Describe Treatment). Echocardiograms were obtained primarily at baseline (prior to anthracyclines), 6 and 12 months. Predictors included changes in strain; strain rate; indices of contractile function derived from the end-systolic pressure-volume relationship (end-systolic elastance (Ees_sb) and the left ventricular (LV) volume at an end-systolic pressure of 100 mm Hg (V₁₀₀)); total arterial load (effective arterial elastance (Ea)) and ventricular-arterial coupling (Ea/Ees_sb). Logistic regression models determined the diagnostic and prognostic associations of changes in these measures and CTRCD, defined as a LV ejection fraction decline ≥10 to <50%.

Results: By 12 months, 31 participants developed CTRCD. Longitudinal and circumferential strain and strain rate, V₁₀₀, Ea, and Ea/Ees_sb each demonstrated significant diagnostic associations, with a 1-7% increased odds of CTRCD (p<0.05). Changes in longitudinal strain rate (area under the curve (AUC) 0.719 (95% CI 0.595 to 0.843)), V₁₀₀ (AUC 0.796 (95% CI 0.686 to 0.903)) and Ea (AUC 0.742 (95% CI 0.632 to 0.852)) from baseline to 6 months were individually predictive of CTRCD at 12 months.

Conclusions: Changes in non-invasively derived measures of myocardial mechanics are diagnostic and predictive of cardiac dysfunction with anthracycline chemotherapy in community populations. Our findings support the non-invasive assessment of measures of myocardial mechanics more broadly in clinical practice and emphasise the role of serial assessments of these measures during and after cardiotoxic cancer therapy.

Trial registration number: NCT01032278; Pre-results.

Keywords: HEART FAILURE.

Publication types

Research Support, N.I.H., Extramural

Associated data

ClinicalTrials.gov/NCT01032278

Abstract

Publication types

Associated data

Grants and funding