Pro–B-Type Natriuretic Peptide1–108 Circulates in the General Community Plasma Determinants and Detection of Left Ventricular Dysfunction

ObjectivesThe purpose of this study was to investigate circulating pro–B-type natriuretic peptide (proBNP1–108) in the general community and evaluate its ability to detect left ventricular (LV) dysfunction.BackgroundThe current concept for cardiac endocrine function is that, in response to cardiac stress, the heart secretes B-type natriuretic peptide (BNP1–32) and amino-terminal pro–B-type natriuretic peptide (NT-proBNP1–76) after intracardiac cleavage of their molecular precursor, proBNP1–108. We hypothesized that proBNP1–108 circulates in normal human subjects and that it is a useful biomarker for LV dysfunction.MethodsOur population-based study included a cohort of 1,939 adults (age ≥45 years) from Olmsted County, Minnesota, with 672 participants defined as healthy. Subjects underwent in-depth clinical characterization, detailed echocardiography, and measurement of proBNP1–108. Independent factors associated with proBNP1–108 and test characteristics for the detection of LV dysfunction were determined.ResultsProBNP1–108 in normal humans was strongly influenced by sex, age, heart rate, and body mass index. The median concentration was 20 ng/l with a mean proBNP1–108 to NT-proBNP1–76 ratio of 0.366, which decreased with heart failure stage. ProBNP1–108 was a sensitive (78.8%) and specific (86.1%) biomarker for detecting LV systolic dysfunction, which was comparable to BNP1–32, but less than NT-proBNP1–76, in several subsets of the population.ConclusionsProBNP1–108 circulates in the majority of healthy humans in the general population and is a sensitive and specific biomarker for the detection of systolic dysfunction. The proBNP1–108 to NT-proBNP1–76 ratio may provide insights into altered proBNP1–108 processing during heart failure progression. Thus, this highly specific assay for proBNP1–108 provides important new insights into the biology of the BNP system

MRI findings in patients with acute coronary syndrome and unobstructed coronary arteries

PURPOSE:The underlying diagnosis in patients with acute coronary syndrome (ACS) and unobstructed coronary arteries remains a diagnostic challenge. We analyzed the value of magnetic resonance imaging (MRI) in this clinical setting.METHODS:A total of 213 patients with ACS and unobstructed coronary arteries underwent MRI within a median of 2 days after initial presentation. Clinical, laboratory, and MRI data were analyzed. A consensus diagnosis was established for each case by an independent panel after reviewing the individual clinical, laboratory, and MRI data. Standardized interviews to determine patient outcomes were carried out after a median follow-up of 24 months. Clinical events were defined as a composite of death, stroke, myocardial infarction or recurrence of Takotsubo syndrome (TTS), new onset of heart failure with a left ventricular ejection fraction (LVEF) <30%, and occurrence of a new left ventricular thrombus formation.RESULTS:Final diagnoses included acute myocardial infarction (AMI) (40%), acute myocarditis (24%) and TTS (33%). In 3% of patients, nonspecific findings lead to an indeterminate diagnosis. Patients with TTS showed a significantly impaired LVEF during the index event (50% vs. 60% in AMI and 60% in myocarditis, P = 0.001). The extent of myocardial edema was most pronounced in patients with TTS (13.4%±11.4 vs. 4.6%±7.9 in AMI and 1.8%±2.7 in myocarditis, P < 0.001). TTS patients had the highest event rate (16.9%).CONCLUSION:Our study emphasizes the diagnostic utility of timely MRI in patients with ACS and unobstructed coronary arteries. We found a high prevalence of TTS patients, who had poorer outcomes compared with patients with a final diagnosis of AMI or myocarditis