Assessment of Biomarkers of Myocardial injury, Inflammation, and Renal Function in Heart Failure With Reduced Ejection Fraction: The VICTORIA Biomarker Substudy
Graphical Abstract
Section snippets
Lay Summary
We evaluated 5 blood tests that evaluate heart injury (cardiac troponin T [cTnT]), inflammation, and renal function for associations with outcomes and efficacy of treatment with the drug vericiguat in the VICTORIA study of patients with HFrEF. Higher baseline levels of a measure of cTnT and two measures of inflammation were associated with the primary outcome of cardiovascular death or HF hospitalization. Lower levels of cTnT identified patients when treated with vericiguat had a lower risk of
Study Design and Procedures
The design, baseline characteristics, and primary results of VICTORIA have been published.11,13 The trial included 5050 participants with HFrEF and a left ventricular EF of less than 45%, New York Heart Association functional class of II o higher, HF hospitalization within 6 months or receipt of intravenous diuretics within 3 months, and an elevated BNP (≥300 pg/mL) or NT-proBNP of 1000 pg/mL or higher (≥500 pg/mL and 1600 pg/mL, respectively, for those with atrial fibrillation) within 30 days
Results
Of the 5050 VICTORIA participants, 4652 (92%) had at least 1 biomarker measured. The baseline characteristics of the study patients, coupled with their associated baseline (before randomization) biomarker levels are shown according to their treatment assignment and were well-balanced between placebo and vericiguat (Table 1). The number of participants with each biomarker measured at baseline and with a paired measurement at 16 weeks is shown in Supplemental Fig. 1. The median serum levels of
Discussion
Several findings emerged from this prospectively planned analysis of circulating biomarkers of cardiac injury, systemic inflammation, and renal function in patients with HFrEF treated with vericiguat or placebo. First, the baseline levels of all biomarkers were elevated, as expected in a HF population; however, the levels were higher than those seen in other recent randomized clinical trials in HFrEF.2,3,5,21 This latter observation is consistent with the clinical characteristics and higher
Conclusions
Higher values of baseline hs-cTnT, GDF-15, and IL-6 levels were associated with an increased risk of the primary outcome in the VICTORIA study. These biomarkers, indicative of myocardial injury, inflammation, and renal dysfunction, are elevated in patients with HFrEF and a recent worsening HF event, but were not modified with vericiguat therapy. Uniquely, lower baseline hs-cTnT levels were associated with a lower rate of cardiovascular death but not HF hospitalization after treatment with
Disclosures
deFilippi: Research funding to Inova from Abbott Diagnostics, Roche Diagnostics, Siemens Healthineers, and Ortho Diagnostics; consulting for FujiRebio, Roche Diagnostics, Siemens Healthineers, and Ortho Diagnostics. Alemayehu: Nothing to report. Voors: Research grants from Boehringer Ingelheim and Roche Diagnostics; consulting fees from Merck, Bayer, Amgen, AstraZeneca, Boehringer Ingelheim, Cytokinetics, Myokardia, Novartis, Servier, and Roche Diagnostics. Kaye: Nothing to report. Blaustein:
Proposed Social Media Text
In the VICTORIA biomarker sub-study of vericiguat in HFrEF, cTnT, IL-6 and GDF-15 are prognostic, but cTnT levels also identify patients when treated with vericiguat that had a lower risk of cardiovascular death.
Sources of Funding
Supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Rahway, NJ, and Bayer AG, Wuppertal, Germany. Reagents were donated by Roche Diagnostics (hs-cTnT and GDF-15) and Siemens Healthineers (Cystatin C, hs-CRP and IL-6).
Acknowledgments
The authors acknowledge Elizabeth E.S. Cook of the Duke Clinical Research Institute for editorial assistance and preparation of the manuscript submission.
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Clinical Trial Registration: Clinicaltrials.gov (NCT02861534).