Plasma TMAO levels among patients presenting with chest pain predict both near- and long-term risks of incident cardiovascular events, and may thus provide clinical utility in risk stratification among subjects presenting with suspected ACS.

Background-Significant left main coronary artery stenosis is an accepted indication for surgical revascularization. The potential of angiography to evaluate the hemodynamic severity of a stenosis is limited. The aims of the present study were to assess the long-term clinical outcome of patients with an angiographically equivocal left main coronary artery stenosis in whom the revascularization strategy was based on fractional flow reserve (FFR) and to determine the relationship between quantitative coronary angiography and FFR. Methods and Results-In 213 patients with an angiographically equivocal left main coronary artery stenosis, FFR measurements and quantitative coronary angiography were performed. When FFR was Ն0.80, patients were treated medically or another stenosis was treated by coronary angioplasty (nonsurgical group; nϭ138). When FFR was Ͻ0.80, coronary artery bypass grafting was performed (surgical group; nϭ75). The 5-year survival estimates were 89.8% in the nonsurgical group and 85.4% in the surgical group (Pϭ0.48). The 5-year event-free survival estimates were 74.2% and 82.8% in the nonsurgical and surgical groups, respectively (Pϭ0.50). Percent diameter stenosis at quantitative coronary angiography correlated significantly with FFR (rϭϪ0.38, PϽ0.001), but a very large scatter was observed. In 23% of patients with a diameter stenosis Ͻ50%, the left main coronary artery stenosis was hemodynamically significant by FFR. Conclusions-In patients with equivocal stenosis of the left main coronary artery, angiography alone does not allow appropriate individual decision making about the need for revascularization and often underestimates the functional significance of the stenosis. The favorable outcome of an FFR-guided strategy suggests that FFR should be assessed in such patients before a decision is made "blindly" about the need for revascularization. (Circulation. 2009;120:1505-1512.)

Objectives Aims were to investigate 1) relationships between serum ST2 levels and hemodynamic/neurohormonal variables; 2) myocardial ST2 production; 3) expression of ST2, membrane-anchored ST2L, and its ligand, IL-33, in myocardium, endothelium and leukocytes from patients with LV pressure overload and congestive cardiomyopathy. Background Serum levels of ST2 are elevated in heart failure. Relationship of ST2 with hemodynamic variables, source of ST2, and expression of ST2L and IL-33 in the cardiovascular system are unknown. Methods Serum ST2 (pg/mL; median [25th-75th]) was measured in patients with LV hypertrophy (aortic stenosis, AS, N=45), congestive cardiomyopathy (CCM N=53), and Controls (N=23). ST2 was correlated to NT-pro BNP, CRP and hemodynamic variables. Coronary sinus and arterial blood sampling determined myocardial gradient (production) of ST2. ST2, ST2L and IL-33 were measured (RT-PCR) in myocardial biopsies and leukocytes; ST2 protein production was evaluated in human endothelial cells. IL-33 protein expression was determined (immunohistochemistry) in coronary artery endothelium Results ST2 was elevated in AS (103[65-165], p<0.05) and CCM (194[69-551], p<0.01) vs. Controls (49[4-89]) and correlated with BNP (r=0.5; p<0.05), CRP (r=0.6; p<0.01) and LV EDP (r=0.38, p<0.03). LV ST2 mRNA was similar in AS and CCM vs. Control (NS). No myocardial ST2 protein gradient was observed. Endothelial cells secreted ST2. IL-33 protein was expressed in coronary artery endothelium. Leukocyte ST2L and IL-33 levels were highly correlated (r=0.97, p<0.001). Conclusions In human hypertrohy and failure, serum ST2 correlates with diastolic load. Though the heart, endothelium, and leukocytes express components of ST2/ST2L/IL-33 pathway, the source of circulating serum ST2 is extra-myocardial.

FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

During the acute phase of acute coronary syndromes, the severity of nonculprit coronary artery stenoses can reliably be assessed by FFR. This allows a decision about the need for additional revascularization and might contribute to a better risk stratification.