Diagnostic and prognostic utility of bone morphogenetic protein 10 in acute dyspnea: a cohort study

Q: What are the key findings of this study?

Bone morphogenetic protein 10 demonstrated high diagnostic accuracy for acute heart failure (AUC 0.85) but was inferior to and added no incremental value over NT-proBNP (AUC 0.91, p<0.001).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Acute dyspnea (n=933). Intervention: Bone Morphogenetic Protein 10 (BMP10) plasma concentration vs. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Primary outcome: Diagnostic accuracy for acute heart failure (AHF) quantified by area under the receiver operating characteristic curve (AUC) (AUC 0.85 vs 0.91 for NT-proBNP, 95% CI 0.82-0.87, p=<0.001).

Q: What does this research mean for the field?

Bone morphogenetic protein 10 (BMP10) demonstrates high diagnostic accuracy for acute heart failure and predicts adverse outcomes in acute dyspnea, but is inferior to and provides no incremental value over NT-proBNP. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To assess the diagnostic accuracy for acute heart failure and the 720-day prognostic value of bone morphogenetic protein 10 (BMP10) in patients presenting with acute dyspnea.

Justas Simonavičius; Desiree Nadine Wussler; Maria Belkin; Karoline Luening; Pedro López‐Ayala; Ivo Strebel; Samyut Shrestha; Albina Nowak; Eleni Michou; Androniki Papachristou; Codruta Popescu; Nikola Kozhuharov; Zaid Sabti; Zora Reiffer; Elisa Hennings; Tobias Zimmermann; Matthias Diebold; Tobias Breidthardt; Christian Eugen Mueller

doi:10.1007/s00392-024-02584-2

Key result

BMP10 shows high diagnostic accuracy for acute heart failure but remains inferior to NT-proBNP.

AUC 0.85 vs 0.91 for NT-proBNP
95% CI 0.82-0.87
P<0.001
n=933

Figures

Why the study?

The clinical utility of Bone Morphogenetic Protein 10 (BMP10), a novel atrial-specific biomarker, for diagnosing acute heart failure and predicting outcomes in patients presenting with acute dyspnea is incompletely understood.

Does plasma Bone Morphogenetic Protein 10 (BMP10) provide high diagnostic accuracy for acute heart failure and incremental prognostic utility for 720-day mortality compared to NT-proBNP in patients presenting with acute dyspnea?

Key Points

To assess the diagnostic accuracy for acute heart failure and the 720-day prognostic value of bone morphogenetic protein 10 (BMP10) in patients presenting with acute dyspnea.
Multicenter diagnostic cohort study of 933 consecutive patients presenting to the emergency department with acute dyspnea.
Measured concentrations of BMP10, hs-cTnT, and NT-proBNP; the final diagnosis was centrally adjudicated by two independent cardiologists blinded to BMP10.
Primary diagnostic outcome was acute heart failure (AHF) discrimination quantified by AUC; primary prognostic outcome was 720-day all-cause mortality.
AHF was adjudicated in 54% (502 of 933) of patients, who exhibited higher BMP10 concentrations (median 3.34 [IQR 2.55–4.35] ng/mL) than non-AHF patients (2.04 [1.74–2.45] ng/mL, p < 0.001).
The diagnostic AUC of BMP10 was 0.85 (95% CI 0.82–0.87), which was higher than hs-cTnT (0.79, 95% CI 0.76–0.82, p < 0.001) but lower than NT-proBNP (0.91, 95% CI 0.90–0.93, p < 0.001).
Adding BMP10 to NT-proBNP yielded an AUC of 0.92 (95% CI 0.90–0.94, p = 0.64 versus NT-proBNP alone) and provided no incremental prognostic value for 720-day mortality (which occurred in 267 of 933 patients).

Study Design

Type

Cohort (n=933)

Blinding

Final diagnosis centrally adjudicated by two independent cardiologists blinded to BMP10; laboratory personnel and follow-up team blinded

Multicenter

Yes

Structured PICO

Does plasma Bone Morphogenetic Protein 10 (BMP10) provide high diagnostic accuracy for acute heart failure and incremental prognostic utility for 720-day mortality compared to NT-proBNP in patients presenting with acute dyspnea?

P

Population

933 adult patients (median age 76 years, 45% female) presenting with acute dyspnea to emergency departments in Switzerland, excluding those on chronic dialysis, followed for 720 days.

E

Exposure

Plasma Bone Morphogenetic Protein 10 (BMP10) concentration measured at emergency department presentation using a prototype electrochemiluminescence immunoassay on a Roche cobas e601 analyzer

C

Comparator

NT-proBNP (Elecsys NT-proBNP II assay) and high-sensitivity cardiac troponin T (Elecsys hs-cTnT assay) measured upon emergency department presentation

O

Outcome

Diagnostic accuracy for centrally adjudicated acute heart failure (AHF) quantified by the area under the receiver operating characteristic curve (AUC), and 720-day all-cause mortality as the primary prognostic outcomehard clinical

Main Result

Effect estimate: AUC 0.85 vs 0.91 for NT-proBNP (95% CI 0.82-0.87)

Absolute Event Rate: 0.85% vs 0.91%

p-value: p=<0.001

Although the novel atrial-specific biomarker BMP10 shows high diagnostic accuracy for acute heart failure and strong univariable prognostic value in acute dyspnea, it provides no clinically meaningful incremental diagnostic or prognostic benefit over standard NT-proBNP testing.

Limitations

Findings are specific to patients presenting with acute dyspnea to the emergency department and cannot be generalized to primary care.
Potential misclassification of a small proportion of patients despite central adjudication.
Inclusion bias in favor of NT-proBNP because BNP/NT-proBNP measurements were available to adjudicating cardiologists while BMP10 was blinded.
Patients with terminal renal failure on chronic dialysis were excluded.
Underpowered for in-depth insights into overlapping cardiovascular pathologies such as acute coronary syndromes, pulmonary embolism, and pulmonary hypertension.
Findings are specific to emergency department presentations with acute dyspnea and cannot be generalized to primary care settings
Possible misclassification of a small proportion of patients despite central adjudication
Inclusion bias in favor of NT-proBNP because BNP or NT-proBNP concentrations were available during central adjudication while BMP10 was blinded
Patients with terminal renal failure on chronic dialysis were excluded
Not powered for in-depth subgroup analyses of overlapping cardiovascular pathologies like acute coronary syndromes, pulmonary embolism, and pulmonary hypertension

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Implication

BMP10 adds no value to NT-proBNP for acute HF diagnosis; observational data leave open other biomarker roles.

Abstract

Background and aim The possible clinical utility of Bone Morphogenetic Protein 10 (BMP10), a novel atrial-specific biomarker, is incompletely understood. We aimed to test the hypothesis that BMP10 has high diagnostic and prognostic accuracy in patients presenting with acute dyspnea. Methods and results In a multicenter diagnostic study, BMP10, high-sensitivity cardiac troponin T (hs-cTnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations were determined in patients presenting with acute dyspnea to the emergency department. The final diagnosis was centrally adjudicated by two independent cardiologists blinded to BMP10. Diagnostic accuracy for acute heart failure (AHF) was quantified using the area under the receiver operating characteristic curve (AUC). 720-day all-cause mortality and the composite of all-cause mortality or AHF rehospitalization were prognostic endpoints. Among 933 consecutive patients, 54% were adjudicated to have AHF. Patients with AHF had higher BMP10 concentrations (median 3.34 [IQR 2.55–4.35] ng/mL) compared to patients with other causes of acute dyspnea (2.04 [1.74–2.45] ng/mL, p < 0.001). The AUC of BMP10 was 0.85 (95%CI, 0.82–0.87), versus 0.79 (95%CI, 0.76–0.82, p < 0.001) for hs-cTnT and 0.91 (95%CI, 0.90–0.93, p < 0.001) for NT-proBNP. The combination of BMP10 with NT-proBNP (AUC 0.92, 95%CI, 0.90–0.94) did not significantly increase the AUC versus NT-proBNP alone. BMP10 was a powerful predictor of death and AHF rehospitalization, but did not provide incremental value to models including NT-proBNP. Conclusion BMP10 had a high diagnostic accuracy for AHF and high prognostic accuracy for death and AHF rehospitalization. However, it did not provide relevant incremental value to the current gold standard NT-proBNP.

Discussion

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Cite This Study

Simonavičius et al. (2026) conducted a cohort in Acute dyspnea (n=933). Bone Morphogenetic Protein 10 (BMP10) plasma concentration vs. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT) was evaluated on Diagnostic accuracy for acute heart failure (AHF) quantified by area under the receiver operating characteristic curve (AUC) (AUC 0.85 vs 0.91 for NT-proBNP, 95% CI 0.82-0.87, p=<0.001). Bone morphogenetic protein 10 demonstrated high diagnostic accuracy for acute heart failure (AUC 0.85) but was inferior to and added no incremental value over NT-proBNP (AUC 0.91, p<0.001).

synapsesocial.com/papers/6ae682dce432e7a5c4ef378b https://doi.org/10.1007/s00392-024-02584-2

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Diagnostic and prognostic utility of bone morphogenetic protein 10 in acute dyspnea: a cohort study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Diagnostic and prognostic utility of bone morphogenetic protein 10 in acute dyspnea: a cohort study

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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