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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., Competing Interests: Declarations. Conflict of interest: The authors have no competing interests to declare., (© 2024. The Author(s).)

Background: Trimethylamine N-oxide (TMAO) has been associated with cardiovascular outcomes. However, the diagnostic value of TMAO and its precursors have not been assessed for functionally relevant coronary artery disease (fCAD) and its prognostic potential in this setting needs to be evaluated., Methods: Among 1726 patients with suspected fCAD serum TMAO, and its precursors betaine, choline and carnitine, were quantified using liquid chromatography tandem mass spectrometry. Diagnosis of fCAD was performed by myocardial perfusion single photon emission tomography (MPI-SPECT) and coronary angiography blinded to marker concentrations. Incident all-cause death, cardiovascular death (CVD) and myocardial infarction (MI) were assessed during 5-years follow-up., Results: Concentrations of TMAO, betaine, choline and carnitine were significantly higher in patients with fCAD versus those without (TMAO 5.33 μM vs 4.66 μM, p < 0.001); however, diagnostic accuracy was low (TMAO area under the receiver operating curve [AUC]: 0.56, 95% CI [0.53-0.59], p < 0.001). In prognostic analyses, TMAO, choline and carnitine above the median were associated with significantly (p < 0.001 for all) higher cumulative events for death and CVD during 5-years follow-up. TMAO remained a significant predictor for death and CVD even in full models adjusted for renal function (HR = 1.58 (1.16, 2.14), p = 0.003; HR = 1.66 [1.07, 2.59], p = 0.025). Prognostic discriminative accuracy for TMAO was good and robust for death and CVD (2-years AUC for CVD 0.73, 95% CI [0.65-0.80])., Conclusion: TMAO and its precursors, betaine, choline and carnitine were significantly associated with fCAD, but with limited diagnostic value. TMAO was a strong predictor for incident death and CVD in patients with suspected fCAD., Clinical Trial Registration: NCT01838148., (© 2022. The Author(s).)

Background: Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity., Methods: This was a prospective multicentre study. AHF diagnosis and phenotype were centrally adjudicated by two independent cardiologists among patients presenting to the emergency department with acute dyspnoea. Adrenomedullin system activity was quantified using the biologically active component, bioactive adrenomedullin (bio-ADM), and a prohormone fragment, midregional proadrenomedullin (MR-proADM). Bio-ADM and MR-proADM concentrations were measured in a blinded fashion at presentation and at discharge. Interaction with specific treatments at discharge and the utility of these biomarkers on predicting outcomes during 365-day follow-up were assessed., Results: Among 1886 patients with adjudicated AHF, 514 patients (27.3%) died during 365-day follow-up. After adjusting for age, creatinine, and treatment at discharge, patients with bio-ADM plasma concentrations above the median (> 44.6 pg/mL) derived disproportional benefit if treated with diuretics (interaction p values < 0.001). These findings were confirmed when quantifying adrenomedullin system activity using MR-proADM (n = 764) (interaction p values < 0.001). Patients with bio-ADM plasma concentrations above the median were at increased risk of death (hazard ratio 1.87, 95% CI 1.57-2.24; p < 0.001). For predicting 365-day all-cause mortality, both biomarkers performed well, with MR-proADM presenting an even higher predictive accuracy compared to bio-ADM (p < 0.001)., Conclusions: Quantifying the adrenomedullin's system activity may help to personalise post-discharge diuretic treatment and enable accurate risk-prediction in AHF., (© 2021. The Author(s).)

Background: The impact of obesity on the incidence of perioperative myocardial infarction/injury (PMI) and mortality following non-cardiac surgery is not well understood., Methods: We performed a prospective diagnostic study enrolling consecutive patients undergoing non-cardiac surgery, who were considered at increased cardiovascular risk. All patients were screened for PMI, defined as an absolute increase from preoperative to postoperative sensitive/high-sensitivity cardiac troponin T (hs-cTnT) concentrations. The body mass index (BMI) was classified according to the WHO classification (underweight< 18 kg/m 2 , normal weight 18-24.9 kg/m 2 , overweight 25-29.9 kg/m 2 , obesity class I 30-34.9 kg/m 2 , obesity class II 35-39.9 kg/m 2 , obesity class III > 40 kg/m 2 ). The incidence of PMI and all-cause mortality at 365 days, both stratified according to BMI., Results: We enrolled 4277 patients who had undergone 5413 surgeries. The median BMI was 26 kg/m 2 (interquartile range 23-30 kg/m 2 ). Incidence of PMI showed a non-linear relationship with BMI and ranged from 12% (95% CI 9-14%) in obesity class I to 19% (95% CI 17-42%) in the underweight group. This was confirmed in multivariable analysis with obesity class I. showing the lowest risk (adjusted OR 0.64; 95% CI 0.49-0.83) for developing PMI. Mortality at 365 days was lower in all obesity groups compared to patients with normal body weight (e.g., unadjusted OR 0.54 (95% CI 0.39-0.73) and adjusted OR 0.52 (95% CI 0.38-0.71) in obesity class I)., Conclusion: Obesity class I was associated with a lower incidence of PMI, and obesity in general was associated with a lower all-cause mortality at 365 days.

Background: Myocardial scar is associated with adverse cardiac outcomes. The Selvester QRS-score was developed to estimate myocardial scar from the 12-lead ECG, but its manual calculation is difficult. An automatically computed QRS-score would allow identification of patients with myocardial scar and an increased risk of mortality., Objectives: To assess the diagnostic and prognostic value of the automatically computed QRS-score., Methods: The diagnostic value of the QRS-score computed automatically from a standard digital 12-lead was prospectively assessed in 2742 patients with suspected myocardial ischemia referred for myocardial perfusion imaging (MPI). The prognostic value of the QRS-score was then prospectively tested in 1151 consecutive patients presenting to the emergency department (ED) with suspected acute heart failure (AHF)., Results: Overall, the QRS-score was significantly higher in patients with more extensive myocardial scar: the median QRS-score was 3 (IQR 2-5), 4 (IQR 2-6), and 7 (IQR 4-10) for patients with 0, 5-20 and > 20% myocardial scar as quantified by MPI (p < 0.001 for all pairwise comparisons). A QRS-score ≥ 9 (n = 284, 10%) predicted a large scar defined as > 20% of the LV with a specificity of 91% (95% CI 90-92%). Regarding clinical outcomes in patients presenting to the ED with symptoms suggestive of AHF, mortality after 1 year was 28% in patients with a QRS-score ≥ 3 as opposed to 20% in patients with a QRS-score < 3 (p = 0.001)., Conclusions: The QRS-score can be computed automatically from the 12-lead ECG for simple, non-invasive and inexpensive detection and quantification of myocardial scar and for the prediction of mortality. TRIAL-REGISTRATION: http://www.clinicaltrials.gov . Identifier, NCT01838148 and NCT01831115.