Background-The diagnosis of cardiac necrosis such as myocardial infarction can be difficult and relies on the use of circulating protein markers like troponin. However, there is a clear need to identify circulating, specific biomarkers that can detect cardiac ischemia without necrosis. Methods and Results-Using specific immunoassay and tandem mass spectrometry, we show that a fragment derived from the signal peptide of B-type natriuretic peptide (BNPsp) not only is detectable in cytosolic extracts of explant human heart tissue but also is secreted from the heart into the circulation of healthy individuals. Furthermore, plasma levels of BNPsp in patients with documented acute ST-elevation myocardial infarction (nϭ25) rise to peak values (Ϸ3 times higher than the 99th percentile of the normal range) significantly earlier than the currently used biomarkers myoglobin, creatine kinase-MB, and troponin. Preliminary receiver-operating characteristic curve analysis comparing BNPsp concentrations in ST-elevation myocardial infarction patients and other patient groups was positive (area under the curveϭ0.97; PϽ0.001), suggesting that further, more rigorous studies in heterogeneous chest pain patient cohorts are warranted. Key Words: acute coronary syndrome Ⅲ biomarkers Ⅲ ischemia Ⅲ myocardial infarction Ⅲ signal peptide A cute coronary syndromes encompass a spectrum of cardiac ischemic events ranging from unstable angina to acute myocardial infarction. However, a significant proportion of patients who present with suspected acute coronary syndromes do not have a cardiac cause for their symptoms or have equivocal findings on history and ECG. This places a heavy emphasis on using circulating biomarker concentrations for accurate diagnosis. 1 A number of biomarkers have been proposed for this purpose, including creatine kinase-MB (CK-MB), troponin T, troponin I (TnI), and myoglobin. However, time to detectable or abnormal elevation of plasma cardiac biomarkers in acute myocardial infarction can be 6 to 12 hours, imposing a delay on a precise diagnosis and treatment. Furthermore, myoglobin, CK, and to a lesser degree CK-MB lack specificity and can be secreted from extracardiac sources, especially during trauma or surgery. Accurate early diagnosis of acute myocardial infarction facilitates prompt introduction of effective percutaneous or thrombolytic revascularization and adjunctive anticoagulant and antiplatelet therapy. Such treatments are progressively less effective at reducing mortality and morbidity with each hour of delay in diagnosis and management. 2 Given the need for accelerated decision making in this clinical situation, there is considerable interest in the identification of new circulating biomarkers that provide early and specific diagnosis of acute cardiac injury. Conclusion-Our Editorial see p 229 Clinical Perspective on p 264Signal peptides (SPs) perform the function of directing nascent preproproteins through the process of translation into the endoplasmic reticulum (ER) and eventual secretion from Received ...
We report results of a retrospective review of intra-aortic balloon pump (IABP) use in two Australasian centres and evaluate the effect of final IABP tip position on outcome. Indications for counterpulsation, patient demographics and in-hospital outcomes and complications were retrospectively collected. The chest X-ray reports provided the 'final' position of the IABP tip. The position was defined as acceptable (tip was seen just below the aortic arch, at T2-T5 vertebrae), malpositioned (tip >5 cm below aortic arch or at T5-T6) or severely malpositioned (tip >10 cm below aortic arch or at T7 or below). Major complications were considered a composite of death secondary to IABP, major limb ischaemia, major IABP malfunction, balloon rupture or haemorrhage, severe renal dysfunction (rise in creatinine >200 µmol/l), stroke and mesenteric ischaemia. Six hundred and forty-five cases were reviewed. The overall major complication rate was 26.2% and 24.3%. Severe renal impairment was the most common complication (16.6%), and second, severe catheter dysfunction (5.4%). Final IABP position was acceptable in 39.9%, malpositioned in 11.1%, severely malpositioned in 6.7% and unavailable for 42.4%. Logistic regression analysis showed IABP tip malposition (compared with satisfactory position odds ratio=3.9 [95% confidence interval=2.0-7.6, P <0.001] and severely malpositioned odds ratio=13.0 [95% confidence interval=5.3-31.7, P <0.001]) were associated with major complications more than the presence of shock (odds ratio=3.8, confidence interval 2.1-6.8 P <0.001). The acceptance of a less than ideal final position was highly predictive of morbidity directly related to IABP device therapy.
BACKGROUND New biomarkers are needed to assist clinical decision making in cardiovascular disease. We have recently shown that signal peptides may represent a novel biomarker target in cardiovascular diseases. METHODS We developed a novel immunoassay for the signal peptide of preproANP (ANPsp) and used it to document cardiac tissue levels of ANPsp in explant human hearts (n = 9), circulating venous concentrations of ANPsp in healthy volunteers (n = 65), temporal ANPsp concentrations in patients with ST-elevation myocardial infarction (STEMI) <4 h after chest pain onset (n = 23), and regional plasma ANPsp concentrations in patients undergoing clinically indicated catheterization (n = 10). We analyzed the structure and sequence of circulating ANPsp by tandem mass spectrometry (MS/MS). RESULTS ANPsp levels in human heart tissue were 50–1000 times lower than those of ANP/NT-proANP. ANPsp was detectable in control human plasma at concentrations comparable with ANP itself (approximately 20 ng/L). In STEMI patients, plasma concentrations of ANPsp rose to peak values at 5 h after symptom onset, significantly earlier than myoglobin, creatine kinase-MB, and troponin (P < 0.001). There were significant arteriovenous increases in ANPsp concentrations (P < 0.05) across the heart and kidney; arterial and coronary sinus concentrations of ANPsp both negatively correlated with systolic and mean arterial blood pressures (both P < 0.01). MS/MS verified circulating ANPsp to be preproANP(16–25) and preproANP(18–25). CONCLUSIONS ANPsp is a novel circulating natriuretic peptide with potential to act as a cardiovascular biomarker. The rapid increase of plasma ANPsp in STEMI and its significant relationship with blood pressure encourage further study of its potential clinical utility.
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