Time course changes of cystatin C and inflammatory and biochemical markers in non-ST-elevation acute coronary syndromes.

BACKGROUND: Serum cystatin C (Cys-C), a good marker of renal function, predicts prognosis in non-ST-elevation acute coronary syndromes (NSTE-ACS). However, no data are available on the time course of Cys-C values after discharge. In this study, Cys-C was measured during admission (ACS sample) and 6 weeks after discharge, and was correlated with troponin (c-TNT), high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6) and the N-terminal portion of the pro-brain natriuretic peptide (proBNP) peptide (NT-proBNP) in a highly selected homogeneous group of NSTE-ACS patients. METHODS: In this prospective, multicentre study, patients with a first NSTE-ACS, single-vessel disease and successful percutaneous coronary interventions (PCIs) had their sera collected, aliquoted and stored at the enrolling site and then shipped for analysis to the clinical chemistry core laboratory. RESULTS: Cys-C values slightly, but significantly, increased from the ACS samples to the 6-week samples. In contrast, hsCRP, NT-proBNP and IL-6 values significantly decreased from the ACS to the 6-week sample. Patients with elevated c-TNT levels had higher hsCRP, NT-proBNP and IL-6 values than patients with normal c-TNT levels in the ACS sample, whereas Cys-C levels were similar in patients with and without elevated c-TNT. Cys-C was highly correlated with estimated glomerular filtration rate in both the ACS and 6-week samples. CONCLUSIONS: In contrast to inflammatory and biochemical stress markers, Cys-C is not affected by the occurrence of myocardial necrosis or by acute left-ventricular impairment, being a reliable marker of renal function during NSTE-ACS.

NT pro-B-type natriuretic peptide levels are related to microvascular reperfusion in patients undergoing direct percutaneous transluminal coronary angioplasty for anterior ST-segment elevation myocardial infarction.

OBJECTIVES: The aim of this study was to describe the time course of NT pro-B-type natriuretic peptide (NT pro-BNP) levels in patients with large anterior ST-segment elevation myocardial infarction (STEMI) treated with primary angioplasty (PPCI) and to investigate the relationship between these values and both microvascular reperfusion and left ventricular (LV) function. BACKGROUND: The clinical efficacy of PPCI is largely dependent on the achievement of microvascular reperfusion. Myocardial blush is an angiographic method to evaluate the presence of effective reperfusion after PPCI. NT pro-BNP is a biomarker of LV stress whose levels are also related to clinical outcome in STEMI. METHODS: We studied 84 patients with large anterior STEMI treated with PPCI. NT pro-BNP was measured at baseline, after 2 days (day 2) and 7 days (day 7). Echocardiographic LV ejection fraction (LVEF) was measured at baseline, day 7 and after 6 months. Myocardial blush was graded immediately after PPCI. RESULTS: NT pro-BNP increased from admission to day 2 and decreased from day 2 to day 7 in patients with significant myocardial blush (grade 2-3) as well as in patients with 0-1 myocardial blush. However, in the latter group median NT pro-BNP levels globally increased from admission to day 7, whereas they decreased in patients with significant myocardial blush. Moreover, in such patients LVEF was higher at all time points than in patients with a grade 0-1 myocardial blush. CONCLUSION: This study shows that the time course of NT pro-BNP in the first week after an anterior STEMI is dependent on the effectiveness of microvascular reperfusion assessed after PPCI and reflects the evolution of LVEF over time.

Significance of total and differential leucocyte count in patients with acute myocardial infarction treated with primary coronary angioplasty.

AIMS: The aim of this study was to correlate total and differential leucocyte (WBC) count with myocardial blush, peak CK levels, and left ventricular (LV) functional recovery at 6 months in 238 consecutive acute myocardial infarction (MI) patients treated with successful primary coronary angioplasty (PCI). METHODS AND RESULTS: Total and differential WBC counts were measured on admission and every 24 h for at least 4 days after PCI. ST-segment resolution and myocardial blush were evaluated immediately after successful primary PCI. LV functional recovery (defined as improvement involving at least two segments, or at least one segment, when only two were asynergic on the basal examination) was obtained through echocardiographic evaluation of LV wall motion at the baseline and at 6 months. Basal CK (P<0.001) and increased neutrophil levels (P<0.001) were the only independent factors related to peak CK, whereas neutrophils and monocytes peaks were related to ST-segment resolution as well as to myocardial blush grade (MBG) 2-3. MBG 2-3 and monocytes number (both as continuous values as well as percentile values) were the only variables independently associated with 6-month LV functional recovery. CONCLUSION: The present study shows that neutrophils and monocytes counts on the first days after acute MI treated with primary PCI are related to markers of effective myocardial reperfusion such as MBG 2-3 and ST-segment resolution. However, only monocytes and MBG are significantly and independently associated with contractile recovery of the infarcted area at 6 months.

Nitric-oxide mediated effects of transdermal capsaicin patches on the ischemic threshold in patients with stable coronary disease.

BACKGROUND: Capsaicin has been shown to exert direct vasodilating effects through increased calcitonin gene-related peptide (CGRP) release. However, no data exist on its effect following systemic administration in humans. METHODS: Twelve male patients with stable coronary disease and a persistently positive exercise were selected for study. According to a double blind, placebo-controlled, cross-over study, patients were randomized to placebo or 3 g oleic capsaicin-containing patches, on 2 different days and with a 2-day interval between treatments. Patients performed treadmill exercise testing according to the Bruce protocol. Time to 1 mm ST segment depression and to peak exercise, maximal ST segment depression, and the number of ECG leads showing diagnostic changes were also measured. Blood samples for nitric oxide (NO) and CGRP were drawn at baseline, 2, 6, and 24 hours after exercise. RESULTS: On placebo, all patients had a positive ECG during exercise test. Only 1 patient experienced angina, on both treatments. With capsaicin, 1 patient had a negative exercise, while 8 patients significantly increased time to 1 mm ST depression from 328 +/- 167 to 401 +/- 174 seconds (P = 0.01). Of the remaining patients, 1 did not show any changes and 2 showed a worse ischemic threshold when on capsaicin. CGRP levels were not significantly different between placebo and capsaicin treatment. Conversely, when on capsaicin, NO significantly increased at 6 hours. CONCLUSIONS: Transdermal capsaicin may improve ischemic threshold in patients with stable coronary disease, probably through arteriolar vasodilation. Increased capsaicin-induced NO availability could represent the principal mechanism of action.

Tezosentan. Actelion/Genentech.

Tezosentan is an endothelin receptor antagonist in development by Actelion Ltd and Genentech Inc for the potential treatment of cardiovascular disorders, including acute heart failure (AHF) and congestive heart failure. Actelion has conducted a phase III study of tezosentan in AHF patients, however, following disappointing trial results a new phase III study in AHF was planned using lower doses of the compound. By January 2003, Actelion anticipated that the first results of a two-year phase III study evaluating mortality/morbidity would be available by early 2005.

High prevalence of (99m)tc-tetrofosmin reverse perfusion pattern in patients with myocardial infarction and angiographically smooth coronary arteries.

BACKGROUND: There are no published data in the literature on the scintigraphic perfusion pattern in patients with myocardial infarction (MI) and normal coronary arteries (NCA). OBJECTIVES: To evaluate myocardial perfusion imaging in a series of patients with MI and NCA. METHODS: Twenty-seven patients who had developed a MI and had NCA were studied. As a control group we included 27 patients with a recent MI and coronary artery disease (CAD). All patients underwent stress/rest tetrofosmin myocardial perfusion SPECT within 6 months from MI. RESULTS: In patients with NCA tetrofosmin stress images revealed 41 hypoperfused segments in 17 patients (63%). On rest images, 13 segments remained unchanged, 4 showed partial reperfusion, 10 normalized and 14 worsened. Additionally, there were 18 new hypoperfused segments in nine patients. Therefore, perfusion worsened at rest in 18 patients (67%) (32 segments). Overall, at rest there were 49 hypoperfused segments in 22 patients (81%). In patients with CAD, stress images revealed 71 hypoperfused segments. On rest images, 39 segments remained unchanged, 16 showed partial reperfusion and 12 normalized. Four segments worsened at rest and only four patients (15%) showed new perfusion defects at rest. CONCLUSIONS: Myocardial perfusion with tetrofosmin might appear considerably worse at rest than at stress in patients with MI and NCA. Specifically, a reverse perfusion pattern in the infarct area is a frequent finding and is likely to be due to residual tissue viability. We postulate that in these patients the hyperemic response to exercise may mask resting underperfusion areas.