Abstract Body (Do not enter title and authors here): Introduction: Myocardial injury is a hallmark of the syndrome of heart failure (HF). It is unknown whether established (e.g. troponin) or novel biomarkers of myocardial injury (e.g. cardiac myosin-binding protein C [cMyBP-C]) offer additive diagnostic value to natriuretic peptide concentrations in patients presenting in the community with signs and symptoms suggestive of HF.
Methods: Community-based patients with suspected HF and elevated NT-proBNP levels were recruited into a multicenter, prospective, observational study conducted at 5 outpatient sites (NCT04724200). Venous blood collection was performed at the time of transthoracic echocardiography. A HF diagnosis was made according to left ventricular ejection fraction (LVEF) phenotypes: HF with reduced ejection fraction (HFrEF) = ≤40%, HF with mildly reduced ejection (HFmrEF) = 41-49%, and HF with preserved ejection fraction (HFpEF) = ≥50% and HFA-PEFF score ≥5. NT-proBNP (Roche Elecsys assay), high-sensitivity cardiac troponin T (cTnT-hs, Roche Elecsys assay) and cMyBP-C (Roche precommercial assay) were analyzed. The diagnostic accuracy of each biomarker alone and in combination was examined using the area under the receiver operating characteristic curve (AUROC).
Results: Of the 867 patients enrolled, 751 (87%) had a measurable LVEF and available biomarker data. Of these, 43 (6%) had HFrEF, 75 (10%) HFmrEF, and 278 (37%) HFpEF. Median NT-proBNP levels were highest in those with HFrEF compared to other HF phenotypes and patients without HF (n=355, 47%). Similar results were seen for hsTnT and cMyBP-C. The Spearman correlations between biomarkers and echocardiographic parameters are displayed in Table 1. When considering a diagnosis of HF vs. no HF, the combination of NT-proBNP and cMyBP-C had the highest AUROC of 0.77 (95%CI 0.73-0.80) vs. NT-proBNP alone (0.74 [0.71-0.78]), p for comparison=0.003 - Figure 1. After exclusion of those with HFmrEF/HFpEF, the AUROC to detect HFrEF (vs. no HF) was 0.90 (0.86-0.95) for the combination of NT-proBNP and cMyBP-C, vs. 0.85 (0.80-0.90) for NT-proBNP alone (p=0.006) - Figure 2.
Conclusion: The measurement of cMyBP-C, a novel biomarker of chronic myocardial injury, improved the diagnostic accuracy of NT-proBNP in patients with suspected HF in the community. The additive value was greatest in the detection of HFrEF. The measurement of cMyBP-C, in addition to NT-proBNP, may help in the prioritization of echocardiography for those with suspected HF in the community.