Accuracy and diagnostic performance of doppler echocardiography to estimate mean pulmonary artery pressure in heart failure.

BACKGROUND: Multiple echocardiographic algorithms have been proposed to estimate mean pulmonary artery pressure (PAPM ) and assess pulmonary hypertension (PH) likelihood. We assessed the accuracy of four echocardiographic approaches to estimate PAPM in heart failure (HF) patients undergoing near-simultaneous right heart catheterization (RHC), and compared diagnostic performance to identify PH with recommendation-advised tricuspid regurgitation peak velocity (TRVmax ). METHODS: We employed four validated echocardiographic algorithms incorporating tricuspid regurgitation peak or mean gradient, pulmonary regurgitation peak gradient, and right ventricular outflow tract acceleration time to estimate PAPM . Echocardiographic estimates of right atrial pressure were incorporated in all algorithms but one. Association and agreement with invasive PAPM were assessed. Diagnostic performance of all algorithms to identify PH was evaluated and compared with the recommended TRVmax cut-off. RESULTS: In 112 HF patients, all echocardiographic algorithms demonstrated reasonable association (r = .41-.65; p < 0.001) and good agreement with invasive PAPM , with relatively lower mean bias and higher precision observed in algorithms that incorporated tricuspid regurgitation peak or mean gradient. All methods demonstrated strong ability to identify PH (AUC = .70-.80; p < 0.001) but did not outperform TRVmax (AUC = .84; p < 0.001). Echocardiographic estimates of right atrial pressure were falsely elevated in 30% of patients. CONCLUSIONS: Echocardiographic estimates demonstrate reasonable association with invasive PAPM and strong ability to identify PH in HF. However, none of the algorithms outperformed recommendation-advised TRVmax . The incremental value of echocardiographic estimates of right atrial pressure may need to be re-evaluated.

Accuracy of echocardiographic estimates of pulmonary artery pressures in pulmonary hypertension: insights from the KARUM hemodynamic database.

Accurate assessment of pulmonary artery (PA) pressures is integral to diagnosis, follow-up and therapy selection in pulmonary hypertension (PH). Despite wide utilization, the accuracy of echocardiography to estimate PA pressures has been debated. We aimed to evaluate echocardiographic accuracy to estimate right heart catheterization (RHC) based PA pressures in a large, dual-centre hemodynamic database. Consecutive PH referrals that underwent comprehensive echocardiography within 3 h of clinically indicated right heart catheterization were enrolled. Subjects with absent or severe, free-flowing tricuspid regurgitation (TR) were excluded. Accuracy was defined as mean bias between echocardiographic and invasive measurements on Bland-Altman analysis for the cohort and estimate difference within ± 10 mmHg of invasive measurements for individual diagnosis. In 419 subjects, echocardiographic PA systolic and mean pressures demonstrated minimal bias with invasive measurements (+ 2.4 and + 1.9 mmHg respectively) but displayed wide limits of agreement (- 20 to + 25 and - 14 to + 18 mmHg respectively) and frequently misclassified subjects. Recommendation-based right atrial pressure (RAP) demonstrated poor precision and was falsely elevated in 32% of individual cases. Applying a fixed, median RAP to echocardiographic estimates resulted in relatively lower bias between modalities when assessing PA systolic (+ 1.4 mmHg; 95% limits of agreement + 25 to - 22 mmHg) and PA mean pressures (+ 1.4 mmHg; 95% limits of agreement + 19 to - 16 mmHg). Echocardiography accurately represents invasive PA pressures for population studies but may be misleading for individual diagnosis owing to modest precision and frequent misclassification. Recommendation-based estimates of RAPmean may not necessarily contribute to greater accuracy of PA pressure estimates.

The peroxisome proliferator-induced cytosolic type I acyl-CoA thioesterase (CTE-I) is a serine-histidine-aspartic acid alpha /beta hydrolase.

Long-chain acyl-CoA thioesterases hydrolyze long-chain acyl-CoAs to the corresponding free fatty acid and CoASH and may therefore play important roles in regulation of lipid metabolism. We have recently cloned four members of a highly conserved acyl-CoA thioesterase multigene family expressed in cytosol (CTE-I), mitochondria (MTE-I), and peroxisomes (PTE-Ia and -Ib), all of which are regulated via the peroxisome proliferator-activated receptor alpha (Hunt, M. C., Nousiainen, S. E. B., Huttunen, M. K., Orii, K. E., Svensson, L. T., and Alexson, S. E. H. (1999) J. Biol. Chem. 274, 34317-34326). Sequence comparison revealed the presence of putative active-site serine motifs (GXSXG) in all four acyl-CoA thioesterases. In the present study we have expressed CTE-I in Escherichia coli and characterized the recombinant protein with respect to sensitivity to various amino acid reactive compounds. The recombinant CTE-I was inhibited by phenylmethylsulfonyl fluoride and diethyl pyrocarbonate, suggesting the involvement of serine and histidine residues for the activity. Extensive sequence analysis pinpointed Ser(232), Asp(324), and His(358) as the likely components of a catalytic triad, and site-directed mutagenesis verified the importance of these residues for the catalytic activity. A S232C mutant retained about 2% of the wild type activity and incubation with (14)C-palmitoyl-CoA strongly labeled this mutant protein, in contrast to wild-type enzyme, indicating that deacylation of the acyl-enzyme intermediate becomes rate-limiting in this mutant protein. These data are discussed in relation to the structure/function of acyl-CoA thioesterases versus acyltransferases. Furthermore, kinetic characterization of recombinant CTE-I showed that this enzyme appears to be a true acyl-CoA thioesterase being highly specific for C(12)-C(20) acyl-CoAs.