No-reflow protection and long-term efficacy for acute myocardial infarction with Tongxinluo： a randomized double-blind placebo- controlled multicenter clinical trial （ENLEAT Trial）

Background No-reflow after emergency percutaneous coronary intervention （PCI） for acute ST segment elevation myocardial infarction （STEMI） is related to the severe prognosis. The aim of this study was to evaluate the efficacy of Tongxinluo, a traditional Chinese medicine, on no-reflow and the infarction area after emergency PCI for STEMI.Methods A total of 219 patients （female 31, 14%） undergoing emergency PCI for STEMI from nine clinical centers were consecutively enrolled in this randomized, double-blind, placebo-controlled, multicenter clinical trial from January 2007 to May 2009. All patients were randomly divided into Tongxinluo group （n=108） and control group （n=111）, given Tongxinluo or placebo in loading dose 2.08 g respectively before emergency PCI with asprin 300 mg and clopidogrel 300 mg together, then 1.04 g three times daily for six months after PCI. The ST segment elevation was recorded by electrocardiogram at hospitalization and 1, 2, 6, 12, 24 hours after coronary balloon dilation to evaluate the myocardial no-flow; myocardial perfusion scores of 17 segments were evaluated on day 7 and day 180 after STEMI with static single-photon emission computed tomography （SPECT） to determine the infarct area.Results There was no statistical significance in sex, age, past history, chest pain, onset-to-reperfusion time, Killip classification, TIMI flow grade just before and after PCI, either in the medication treatment during the follow up such as statin, β-blocker, angiotensin converting enzyme inhibitor （ACEI） or angiotensin receptor blocker （ARB） between two groups. There was significant ST segment restoration in Tongxinluo group compared to the control group at 6 hours （（-0.22±0.18） mV vs. （-0.18±0.16） mV, P=0.0394）, 12 hours （（-0.24 ± 0.18） mV vs. （-0.18±0.15） mV, P=0.0158） and 24 hours （（-0.27±0.16） mV vs. （-0.20±0.16） mV, P=0.0021） reperfusion; and the incidence of myocardial no-reflow was also reduced significantly at 24-hour reperfusion （34.3% vs. 54.1%, P=0.0031）. The myocardial perfusion scores of 17 segments evaluated by static SPECT was improved significantly on day 7 and day 180 after STEMI in Tongxinluo group compared to the control group （0.61±0.40 vs. 0.76±0.42, P=0.0109 and 0.51 ±0.42 vs. 0.66±0.43, P=0.0115, respectively）.There was no significant difference in severe adverse events between two groups.Conclusion Tongxinluo as a kind of traditional Chinese medicine could reduce myocardial no-reflow and infarction area significantly after emergency PCl for STEMI with conventional medicine therapy.

N-terminal pro-B-type natriuretic peptide and diastolic function measurements by adenosine stress echocardiography in prediction of coronary stenosis in patients

Background Stress echocardiography is mainly used in detection of coronary artery disease （CAD） and to assess risk.This study aimed to use adenosine stress echocardiography （ASE） and N-terminal pro-B-type natriuretic peptide （NT-proBNP） to noninvasively assess coronary stenosis in patients with chest pain syndromes or anginal equivalent.Methods NT-proBNP was measured after overnight fast in fifty patients, 42 males and 8 females, who were （57＋11）years old. They then underwent echocardiography before and during adenosine administration. Left ventricular （LV）diastolic function analyzed included mitral annular early （E＇） and late velocity （A＇） both at the mitral septal and lateral level and the mitral inflow to annulus ratio （E/E＇）. Coronary angiography was performed the following day after which patients were assigned to three groups： normal results （16 patients）, stenosis 50%-69%（17 patients） and stenosis≥70% （17 patients）.Results NT-proBNP levels in the groups of stenosis 50%-69% and≥ 70% were significantly higher than that in the group with normal results （P=0.014 and P=0.040）. During adenosine stress, the E/E＇ in the group of stenosis≥70% was higher than in the group of normal results （P=0.024）. E＇lateral/A＇lateral in the group of stenosis 50%-69% and E＇septal/A＇septal and E＇lateral/A＇lateral in the group of stenosis≥70% were also decreased during stress compared with baseline （P=0.003,P=0.001, P=0.022）. The variation of E＇septal/A＇septal before and during adenosine stress （△E＇septal/A＇septal） between the groups of normal results and stenosis ≥70% were significantly different （P=0.001）. By receiver operating characteristic （ROC）, the specificity of △E＇septal/A＇septal ≥0.037 predicting coronary stenosis ＜70% was 94%. The sensitivity and specificity of NT-proBNP≥544.6 fmol/ml in predicting coronary stenosis ≥70% were 93% and 75%, respectively.NT-proBNP inversely correlated with E＇lateral/A＇lateral （r=-0.390, P=0.014） and positively correlated with E/E＇lateral（r=0.550,P=0.001）.Conclusions Adenosine might induce diastolic dysfunction in patients with coronary stenosis more than 70% and NT-proBNP could reflect LV diastolic function to a certain extent. We support the prediction that most patients having chest pain syndromes or anginal equivalent with NT-proBNP＜544.6 fmol/ml and in ASE AE＇septal/A＇septal≥0.037 might be spared coronary angiography.