Background
Predicting a favorable cardiac resynchronization therapy (CRT) response holds great
clinical importance.
Objective
The purpose of this study was to examine proteins from broad biological pathways and
develop a prediction tool for response to CRT.
Methods
Plasma was collected from patients before CRT (SMART-AV [SmartDelay Determined AV
Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization
Therapy] trial). A CRT response was prespecified as a ≥15-mL reduction in left ventricular
end-systolic volume at 6 months, which resulted in a binary CRT response (responders
52%, nonresponders 48%; n = 758).
Results
Candidate proteins (n = 74) were evaluated from the inflammatory, signaling, and structural
domains, which yielded 12 candidate biomarkers, but only a subset of these demonstrated
predictive value for CRT response: soluble suppressor of tumorgenicity-2, soluble
tumor necrosis factor receptor-II, matrix metalloproteinase-2, and C-reactive protein.
These biomarkers were used in a composite categorical scoring algorithm (Biomarker
CRT Score), which identified patients with a high/low probability of a response to
CRT (P <.001) when adjusted for a number of clinical covariates. For example, a Biomarker
CRT Score of 0 yielded 5 times higher odds of a response to CRT compared to a Biomarker
CRT Score of 4 (P <.001). The Biomarker CRT Score demonstrated additive predictive value when considered
against a composite of clinical variables.
Conclusion
These unique findings demonstrate that developing a biomarker panel for predicting
individual response to CRT is feasible and holds potential for point-of-care testing
and integration into evaluation algorithms for patients presenting for CRT.
Keywords
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Article info
Publication history
Published online: November 23, 2018
Footnotes
This work was supported by National Institutes of Health Grant HL095608 (FGS), a Merit Award from the Veterans’ Affairs Health Administration to Dr Spinale, and an unrestricted grant from Boston Scientific to Dr Spinale. Dr Meyer, Dr Stolen, Mr Wold, and Dr Stein are employees of Boston Scientific. ClinicalTrials.gov Identifier: NCT00677014.
Identification
Copyright
© 2018 Heart Rhythm Society. All rights reserved.
