Circulating cardiac troponin I levels measured by a novel highly sensitive assay in acute decompensated heart failure: insights from the ASCEND-HF trial

Background: Circulating cardiac troponin levels (cTn), representative of myocardial injury, are commonly elevated in heart failure (HF) and related to adverse clinical events. However, whether cTn represents a spectrum of risk in HF is unclear. Methods: Baseline, 48–72 hour, and 30 day plasma cTnI was measured by a novel highly-sensitive assay in 900 subjects with acute decompensated HF (ADHF) in ASCEND-HF. Multivariable models determined the relationship between cTnI and outcomes. Results: The median(interquartile range) cTnI was 16.4 (9.3-31.6) ng/L at baseline, 14.1 (7.8-29.7) ng/L at 48-72 hours, and 11.6 (6.8-22.5) ng/L at 30 days. After additional adjustment for amino terminal pro-B-type natriuretic peptide (NT-proBNP) to established risk predictors, both baseline and 48-72 hour cTnI were associated with higher risk for death or worsening HF prior to discharge (OR 1.25, P=0.03 and OR 1.43, P=0.001, respectively). However, only cTnI at 30 days was associated 180-day death (HR 1.25, P=0.007). There were no curvilinear associations between changing cTnI and clinical outcomes. Conclusions: Circulating cTnI level was associated with clinical outcomes in ADHF, but these observations diminished with additional adjustment for NT-proBNP. Although they likely represent a spectrum of risk in ADHF, these findings question the implications of changing cTnI levels during treatment

Differential association between the GLP1R gene variants and brain functional connectivity according to the severity of alcohol use

Growing evidence suggests that the glucagon-like peptide-1 (GLP-1) system is involved in mechanisms underlying alcohol seeking and consumption. Accordingly, the GLP-1 receptor (GLP-1R) has begun to be studied as a potential pharmacotherapeutic target for alcohol use disorder (AUD). The aim of this study was to investigate the association between genetic variation at the GLP-1R and brain functional connectivity, according to the severity of alcohol use. Participants were 181 individuals categorized as high-risk (n = 96) and low-risk (n = 85) alcohol use, according to their AUD identification test (AUDIT) score. Two uncommon single nucleotide polymorphisms (SNPs), rs6923761 and rs1042044, were selected a priori for this study because they encode amino-acid substitutions with putative functional consequences on GLP-1R activity. Genotype groups were based on the presence of the variant allele for each of the two GLP-1R SNPs of interest [rs6923761: AA + AG (n = 65), GG (n = 116); rs1042044: AA + AC (n = 114), CC (n = 67)]. Resting-state functional MRI data were acquired for 10 min and independent component (IC) analysis was conducted. Multivariate analyses of covariance (MANCOVA) examined the interaction between GLP-1R genotype group and AUDIT group on within- and between-network connectivity. For rs6923761, three ICs showed significant genotype × AUDIT interaction effects on within-network connectivity: two were mapped onto the anterior salience network and one was mapped onto the visuospatial network. For rs1042044, four ICs showed significant interaction effects on within-network connectivity: three were mapped onto the dorsal default mode network and one was mapped onto the basal ganglia network. For both SNPs, post-hoc analyses showed that in the group carrying the variant allele, high versus low AUDIT was associated with stronger within-network connectivity. No significant effects on between-network connectivity were found. In conclusion, genetic variation at the GLP-1R was differentially associated with brain functional connectivity in individuals with low versus high severity of alcohol use. Significant findings in the salience and default mode networks are particularly relevant, given their role in the neurobiology of AUD and addictive behaviors

Comparison of accuracy of estimation of cardiac output by thermodilution versus the Fick Method using measured oxygen uptake

The thermodilution (TD) method is routinely used for the estimation of cardiac output (Q̇). However, its accuracy, compared with the gold-standard Fick method, where systemic oxygen uptake (V̇O) is directly measured, and Q̇ calculated from V̇O and the arterio-venous oxygen difference ( direct Fick), has not been well validated. The present study determined the agreement between TD and Fick methods in consecutive patients who underwent pulmonary artery catheterization for a broad range of clinical conditions. This is a subanalysis of a previous study comparing the indirect versus Fick method based on a prospective, consecutive patient registry of 253 patients who underwent pulmonary artery catheterization for clinical indications at a single center between 1999 and 2005. We included patients that had an estimation of Q̇ both by the Fick method using measured V̇O by exhaled gas analyses from timed Douglas bag collections and by TD. Cardiac index was classified as low when ≤2.2 L/min/m or normal when \u3e2.2 L/min/m. The median (25th, 75th percentile) age of the cohort was 59 (50,67) years, and 50% were female. A total of 43.5% had normal left ventricular function by ventriculography, and 25.7% had ischemic heart disease. Median overall Fick and TD Q̇ were 4.4 (3.5, 5.5) and 4.3 (3.7, 5.2) L/min, respectively (p = 0.04). The median absolute percent error between Fick and TD Q̇ was 17.5 (7.7, 28.4)%, with a typical error of 0.88 L/min (95% confidence interval [CI] 0.82 to 0.95). Median absolute percent error was comparable in the low (n = 118) and normal Q̇ (n = 135) groups (16.9% vs 18.9%, respectively, p = 0.88). typical error was 0.3 (95% CI 0.27 to 0.33) and 0.49 (95% CI 0.45 to 0.55) L/min/m in that comparison. Percent error \u3e25% between Fick and TD Q̇ was observed in over 30% of patients. Overall, Fick and TD Q̇ modestly correlated (R = 0.64, p \u3c0.001), with a nondirectional error introduced by TD Q̇ [mean bias of 0.21 (-2.2, 2.7) L/min]. There was poor agreement between TD and the gold-standard Fick method, highlighting the limitations of making clinical decisions based on TD