Assays Specific for BNP1-32 and NT-proBNP Exhibit a Similar Performance to Two Widely Used Assays in the Diagnosis of Heart Failure.

BACKGROUND: Secretion of cardioprotective B-type natriuretic peptide 1-32 (BNP1-32) is increased proportionately with cardiac dysfunction, but its measurement in plasma is difficult. Therefore, less specific BNP and amino-terminal proBNP (NT-proBNP) assays that detect the precursor molecule proBNP alongside BNP or NT-proBNP metabolites were developed to reflect BNP1-32 secretion and are now mandated in the diagnosis of heart failure (HF). We compared the diagnostic performance of 2 widely used clinical assays: the Roche proBNPII assay, and Abbott BNP assay, against our recently developed in-house assays that measure either intact BNP1-32 or NT-proBNP. METHODS: EDTA plasma samples obtained from patients presenting with breathlessness (n = 195, 60 [31%] with clinically adjudicated HF) were assayed using the Roche NT-proBNP and our specific in-house BNP1-32 and NTBNP assays. A subset (n = 75) were also assessed with the Abbott BNP assay. RESULTS: Roche NT-proBNP was highly correlated with BNP1-32 and NTBNP (Spearman rho = 0.92 and 0.90, respectively, both Ps < 0.001), and all 3 assays similarly discriminated acute HF from other causes of breathlessness (ROC analysis areas under the curve 0.85-0.89). The Abbott BNP assay performed similarly to the other assays. Roche NT-proBNP and BNP1-32 assays had similar sensitivity (83% and 80%), specificity (83% and 84%), positive (70% and 71%) and negative (91% and 90%) predictive values, and accuracy (both 83%) at their optimal cutoffs of 1536 and 12 ng/L, respectively. CONCLUSIONS: Since all assays exhibited similar performance in the diagnosis of HF, currently mandated assays provide a reliable proxy for circulating concentrations of active BNP1-32 in HF diagnosis.

Low miR-19b-1-5p Expression Is Related to Aspirin Resistance and Major Adverse Cardio- Cerebrovascular Events in Patients With Acute Coronary Syndrome.

Background Because of a nonresponse to aspirin (aspirin resistance), patients with acute coronary syndrome (ACS) are at increased risk of developing recurrent event. The in vitro platelet function tests have potential limitations, making them unsuitable for the detection of aspirin resistance. We investigated whether miR-19b-1-5p could be utilized as a biomarker for aspirin resistance and future major adverse cardio-cerebrovascular (MACCE) events in patients with ACS. Methods and Results In this cohort study, patients with ACS were enrolled from multiple tertiary hospitals in Christchurch, Hong Kong, Sarawak, and Singapore between 2011 and 2015. MiR-19b-1-5p expression was measured from buffy coat of patients with ACS (n=945) by reverse transcription quantitative polymerase chain reaction. Platelet function was determined by Multiplate aggregometry testing. MACCE was collected over a mean follow-up time of 1.01±0.43 years. Low miR-19b-1-5p expression was found to be related to aspirin resistance as could be observed from sustained platelet aggregation in the presence of aspirin (-Log-miR-19b-1-5p, [unstandardized beta, 44.50; 95% CI, 2.20-86.80; P<0.05]), even after adjusting for age, sex, ethnicity, and prior history of stroke. Lower miR-19b-1-5p expression was independently associated with a higher risk of MACCE (-Log-miR-19b-1-5p, [hazard ratio, 1.85; 95% CI, 1.23-2.80; P<0.05]). Furthermore, a significant interaction was noted between the inverse miR-19b-1-5p expression and family history of premature coronary artery disease (P=0.01) on the risk of MACCE. Conclusions Lower miR-19b-1-5p expression was found to be associated with sustained platelet aggregation on aspirin, and a higher risk of MACCE in patients with ACS. Therefore, miR-19b-1-5p could be a suitable marker for aspirin resistance and might predict recurrence of MACCE in patients with ACS.

Adrenomedullin 2 increases cardiac sympathetic nerve activity in parallel to heart rate in normal conscious sheep.

Both adrenomedullin 2 (AM2) and sympathetic nerve activity (SNA) have been shown to be involved in regulating cardiovascular activity, but whether any interaction between these two systems exists remains to be determined. In this study, we examine the effects of intravenous AM2 infusions on SNA directed toward the heart (cardiac SNA (CSNA)) in healthy sheep studied in the conscious state. In response to AM2, arterial pressure was reduced (P = 0.005) with both heart rate (P < 0.001) and cardiac output (P < 0.001) increased compared with vehicle control response. CSNA burst frequency (bursts/min) and burst area/min both increased during infusion of AM2 (both P < 0.001). However, correcting CSNA indices for concurrent heart rate changes resulted in CSNA burst incidence (bursts/100 beats) and burst area incidence (area/100 beats) being not significantly different between AM2 and control treatments. There were no significant differences demonstrated in plasma epinephrine or norepinephrine levels between the two study days. In conclusion, AM2 administered systemically to normal conscious sheep increases both CSNA and heart rate. However, correction for heart rate responses abrogates the rise in CSNA. It remains unclear whether AM2's primary effect is to act via the central nervous system to directly stimulate CSNA with resultant increase in heart rate, or to induce a rise in heart rate by other mechanisms.

A Risk Assessment Score and Initial High-sensitivity Troponin Combine to Identify Low Risk of Acute Myocardial Infarction in the Emergency Department.

OBJECTIVES: Early discharge of patients with presentations triggering assessment for possible acute coronary syndrome (ACS) is safe when clinical assessment indicates low risk, biomarkers are negative, and electrocardiograms (ECGs) are nonischemic. We hypothesized that the Emergency Department Assessment of Chest Pain Score (EDACS) combined with a single measurement of high-sensitivity cardiac troponin (hs-cTn) could allow early discharge of a clinically meaningful proportion of patients. METHODS: We pooled data from four patient cohorts from New Zealand and Australia presenting to an emergency department with symptoms suggestive of ACS. The primary outcome was major adverse cardiac events (MACE) within 30 days of presentation. In patients with a nonischemic ECG we evaluated the sensitivity for MACE and percentage low risk of every combination of high-sensitivity cardiac troponin T (hs-cTnT) concentration and high-sensitivity cardiac troponin I (hs-cTnI) concentration with EDACS. We used a standard smoothing technique on the probability density function for hs-cTn and EDACS and applied bootstrapping to determine the optimal threshold combinations, namely, the combination that maximized the percentage low risk with ≥98.5% sensitivity for MACE. RESULTS: From 2,536 patients, 2,258 presented without an ischemic ECG of whom 272 (12.1%) had a MACE within 30 days. The optimal threshold for hs-cTnI was 7 ng/L combined with an EDACS threshold of 16 (36.8% patients low risk). The optimal thresholds for hs-cTnT were 8 ng/L combined with an EDACS threshold of 15 (30.2% patients low risk). CONCLUSION: Single measurements of both hs-cTnI and hs-cTnT at presentation combined with EDACS to identify over 30% of patients as low risk and therefore eligible for safe early discharge after only one blood draw.

Concentraciones plasmáticas de neprilisina: ¿un nuevo marcador pronóstico en la insuficiencia cardiaca? / Plasma neprilysin concentrations: a new prognostic marker in heart failure?

No disponible

Urocortin 2 protects heart and kidney structure and function in an ovine model of acute decompensated heart failure: Comparison with dobutamine.

BACKGROUND: Renal dysfunction is a frequent complication and crucial determinant of outcome in acute decompensated heart failure (ADHF). The aim of the study was to assess urocortin 2 (Ucn2) as a short-term therapy in ADHF with a focus on its renal effects. Comparison was made with dobutamine to distinguish effects beyond pure inotropism. METHODS: Sheep with ADHF received a 2-day infusion of a vehicle-control, Ucn2 or dobutamine (n=6/grp). RESULTS: Compared to controls, Ucn2 and dobutamine produced matched improvements in cardiac contractility and output and arterial pressure, whereas reductions in central venous and left atrial pressures were greater with Ucn2. Both agents comparably repressed ADHF-activated hormone systems with the exception of the natriuretic peptides, which fell significantly during dobutamine but not Ucn2. While Ucn2 and dobutamine increased creatinine clearance and urine volume similarly, only Ucn2 induced a significant natriuresis. Ucn2 also decreased collagen deposition in the heart and kidney and suppressed gene expression of collagen-1, transforming growth factor-ß1, components of the angiotensin system (angiotensinogen, angiotensin-converting enzyme, type-1 receptor) and markers of hypertrophy (GATA binding protein-4, ß-myosin heavy chain), apoptosis (caspase3) and inflammation/injury (interleukin-18, cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1) in these tissues, while increasing cardiac natriuretic peptide mRNA. In contrast, dobutamine produced reduced or opposite effects on expression of these factors. CONCLUSIONS: Ucn2 administration in ADHF has favorable effects on hemodynamics, the natriuretic peptides and tissue mediators of inflammation, fibrosis, apoptosis and hypertrophy that stand in contrast to dobutamine. These data support Ucn2's potential as a renoprotective therapeutic in this setting.

Comparison of new point-of-care troponin assay with high sensitivity troponin in diagnosing myocardial infarction.

OBJECTIVES: The aim of this study is to compare a new improved point of care cardiac troponin assay (new POC-cTnI) with 1. its predecessor (old POC-cTnI) and 2. a high sensitivity assay (hs-cTnI) for the diagnosis of acute myocardial infarction (AMI) and for major adverse cardiac events (MACE) by 30 days. METHODS: This is a single centre observational study, set in Christchurch Hospital, New Zealand. Patients presenting to the emergency department with non-traumatic chest pain underwent blood sampling at 0 h and 2h post presentation for analysis with the 3 cTnI assays for the outcome of AMI and for analysis using an accelerated diagnostic protocol (ADP-normal 2h troponins, normal electrocardiograms and Thrombolysis In Myocardial Infarction (TIMI) score of 0 or ≤ 1) for 30 day MACE. RESULTS: Of 962 patients, 220 (22.9%) had AMI. Old POC-cTnI was least sensitive at 70.0% (65.4-73.9%) by 2h (p<0.001). New POC-cTnI, sensitivity 93.6% (89.9-96.2%) had similar sensitivity to hs-cTnI, sensitivity 95.0% (91.5-97.3%) (p = 0.508). There were 231 (24.0%) patients with 30 day MACE. When used as part of the ADP, all assays had 100% (98.0-100%) sensitivity using TIMI = 0. Sensitivities of new POC-cTnI ADP, 98.3% (95.4-99.4%), old POC-cTnI, 96.5% (93.2-98.4%) and hs-cTnI, 98.7% (96.0-99.7%) were similar (p = 0.063-0.375) using TIMI ≤ 1. CONCLUSIONS: A new POC-cTnI has improved sensitivity for AMI and MACE compared with its predecessor and comparable sensitivity to a high sensitivity assay. Now that sensitivities of the POC assay are improved, the new assay may be a useful alternative to central laboratory assays when rapid turn-around times are not possible.

Nuevos biomarcadores en la insuficiencia cardiaca: aplicaciones en el diagnóstico, pronóstico y pautas de tratamiento / New biomarkers in heart failure: applications in diagnosis, prognosis and guidance of therapy

No disponible

No disponible

Adrenomedullin 2 attenuates the pressor but not adrenal responses to angiotensin II in conscious sheep.

Biological actions attributed to the adrenomedullin (AM) peptides, AM and AM2, include reduction of arterial pressure and peripheral resistance. While AM has been shown to reduce aldosterone secretion from the adrenal, little information is available regarding possible actions of AM2 on aldosterone. Evidence suggests that AM may act as a functional antagonist to angiotensin II (Ang II) but such a role has not been investigated for AM2. Accordingly, we have examined hemodynamic and adrenal responses to stepped Ang II infusions with or without co-infusions of AM2 (33ng/(kgmin)) in conscious sheep under controlled conditions of a low sodium intake. The dose-dependent pressor response (5-50mmHg) of Ang II was both delayed and attenuated (p<0.001) by AM2 which also stimulated heart rate (p<0.001) and cardiac output (p<0.001). AM2 prevented Ang II-induced increases in peripheral resistance (p<0.001). In contrast, plasma aldosterone responses to Ang II were not significantly altered by concomitant AM2 infusion. In conclusion, low dose infusion of AM2 administered to conscious sheep on a low salt diet clearly antagonized the vasopressor action of administered Ang II while stimulating cardiac output and heart rate. In contrast to AM, AM2 had no restraining influence on the aldosterone response to Ang II. The data suggest a possible role for AM2 in cardiovascular homeostasis in part through antagonism of the vasopressor action of Ang II.