Faculty Bibliography

OBJECTIVES: We sought to evaluate the feasibility and validity of a new method to quantify the hyperemic response of the forearms that can be incorporated into a rest myocardial perfusion protocol. BACKGROUND: Evaluation of the hyperemic response could provide useful clinical information in the detection and risk stratification of atherosclerotic vascular disease. METHODS: Patients with proven coronary artery disease (CAD) (n = 46) were compared with low-risk subjects without such evidence (n = 47). A regular dose of Myoview was injected after 5 min of right arm ischemia. Three dimensionless parametric ratios (right/left) were derived from the analysis of activity-time curves of the hyperemic right forearm and that of the contralateral left forearm. RESULTS: The maximal ingress upslope ratio was 40% lower in the CAD group (3.0 +/- 0.2 vs. 4.2 +/- 0.3, p < 0.0005), and the integral to peak ratio was also lower (23 +/- 4 vs. 52 +/- 11, p < 0.01), whereas the peak activity ratio was nonsignificantly lower (3.0 +/- 0.3 vs. 3.8 +/- 0.3, p = 0.07). Using a value of 3.55 for the maximal upslope ratio, this approach could predict the presence of CAD with a sensitivity of 0.70 and a specificity of 0.60. CONCLUSIONS: This simple and noninvasive method is feasible and can discriminate between patients with known CAD and those at low risk of atherosclerosis. Refinements of this approach and its inclusion in larger clinical trials are needed to determine whether it could provide additional value to myocardial scintigraphic imaging

BACKGROUND: Endothelin-1 (ET-1) levels are elevated in congestive heart failure (CHF) in relation with the severity of pulmonary hypertension. We evaluated whether a reduced pulmonary ET-1 clearance could contribute to this elevation. METHODS AND RESULTS: We determined pulmonary ET-1 clearance in 24 patients with CHF in relation with hemodynamics, plasma ET-1, and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Pulmonary ET-1 extraction, measured by the single bolus indicator-dilution technique, was reduced to 32 +/- 14% in comparison to historic controls (47 +/- 7%). Plasma ET-1 clearance by the lungs (924 +/- 588 mL/min) was also much lower than in controls (1424 +/- 79 mL/min). Clearance correlated inversely with mean pulmonary artery pressure (PAP, r = -.47, P = .017) and pulmonary capillary wedge pressure (r = -.47, P = .017) and positively with the rate of left ventricular (LV) relaxation LV -dP/dt (r = .593, P = .004). After multivariate analysis, only mean PAP and LV -dP/dt were independently correlated with ET-1 clearance (r = -.40, P = .03, and r = .55, P = .005, respectively). Plasma ET-1 levels did not correlate with clearance (r = .038, P = .86), and there was no significant arteriovenous ET-1 gradient. There was a mild nonsignificant correlation between plasma ET-1 and pulmonary artery systolic pressure (r = .38, P = .06), but a strong correlation with right atrial pressure (r = .696, P < .0001) and NT-proBNP levels (r = .51, P = .001), which were maintained after multivariate linear regression (r = .60, P = .001, and r = .32, P = .04, respectively). CONCLUSION: Pulmonary ET-1 clearance is reduced in CHF in relation with the severity of pulmonary hypertension. This reduced clearance does not significantly modulate plasma ET-1 levels. Whether this is only a marker of secondary pulmonary hypertension or could modulate pulmonary vascular tone will require further studies

There has been great interest in the possibility of identifying plaques that might be the site of future acute coronary events. These plaques are termed vulnerable and the majority are lipid-rich with an abundance of inflammatory cells and a thin fibrous cap. Several techniques developed to identify these plaques are in various stages of development and in the near future, one might employ a strategy to potentially identify and therapeutically modify such lesions during percutaneous intervention to avoid future acute events. Although this approach of identifying the vulnerable plaque seems promising, there are significant potential limitations. The natural history of a vulnerable plaque is unknown and clinical trials utilizing this strategy of identification and therapeutic intervention are lacking. Moreover, in any given patient, multiple vulnerable plaques are likely to be present. This article reviews some of the techniques for identifying a vulnerable plaque and discusses the potential advantages and limitations of this strategy

Percutaneous closure of atrial septal defects (ASD) is increasingly performed in pediatric and adult patients. This study reports a single-center experience with the use of the Amplatzer Septal Occluder for percutaneous ASD closure in adults. One hundred and seventeen consecutive patients were prospectively included in the database. The procedure was successful in 106 patients (90.6%). The mean age was 50 years. Eighty-four percent of the patients had a Qp:Qs > 1.5. Other indications included a history of thromboembolism, decreased exercise tolerance, atrial arrhythmias, evidence of pulmonary hypertension or right heart overload. Mean procedure time was 44 minutes, and mean fluoroscopy time was 13 minutes. The mean defect diameter was 17.2 mm (range, 5 30 mm). There was no residual shunting at the end of the procedure in 75% of the patients. Shunting was minimal in all but 2 of the remaining 25 patients (1.8%). No major complications were observed at a mean follow-up of 19 months. Patients in whom the procedure failed had larger defects (mean, 25.0 mm versus 18.3 mm; p < 0.001), larger right ventricles (44.1 mm versus 38.2 mm; p = 0.03) and more significant shunting (Qp:Qs, 3.5 versus 2.1; p < 0.001). New York Heart Association functional class improved in all but 1 patient. Percutaneous ASD closure using ASO is safe and mid-term results compare favorably with those reported with surgical ASD closure. It can therefore be recommended as the first line of treatment in adult patients with secundum ASD

Angiotensin-converting enzyme (ACE) is present on the luminal surface of the coronary vessels, mostly on capillary endothelium. ACE is also expressed on coronary smooth muscle cells and on plaque lipid-laden macrophages. Excessive coronary circulation (CC)-ACE activity might be linked to plaque progression. Here we used the biologically inactive ACE substrate (3)H-labeled benzoyl-Phe-Ala-Pro ([(3)H]BPAP) to quantify CC-ACE activity in 10 patients by means of the indicator-dilution technique. The results were compared with atherosclerotic burden determined by coronary angiography. There was a wide range of CC-ACE activity as revealed by percent [(3)H]BPAP hydrolysis (30-74%). The atherosclerotic extent scores ranged from 0.0 to 66.97, and the plaque area scores ranged from 0 to 80 mm(2). CC-ACE activity per unit extracellular space (V(max)/K(m)V(i)), an index of metabolically active vascular surface area, was correlated with myocardial blood flow (r = 0.738; P = 0.03) but not with measures of the atherosclerotic burden. These results show that CC-ACE activity can be safely measured in humans and that it is a good marker of the vascular area of the perfused myocardium. It does not, however, reflect epicardial atherosclerotic burden, suggesting that local tissue ACE may be more important in plaque development