Abstract: BACKGROUND: It is unknown whether adenosine triphosphate disodium (ATP) administration during primary percutaneous coronary intervention (PCI) is useful in anterior acute myocardial infarction (AMI). METHODS: The study was a prospective, non-randomized, open-label trial. Primary PCI was successfully performed in 204 consecutive patients with first anterior AMI. ATP at a mean dose of 117 mug/kg/min for 45 min on an average was infused intravenously during PCI in 100 patients (Group 1). In the other 104 patients, normal saline was administered (Group 2). ST-segment resolution (STR) was estimated 90 min after recanalization. The no-reflow ratio was measured 2 weeks later, using intravenous myocardial contrast echocardiography. Left ventricular ejection fraction (LVEF), LV regional wall motion (LVRWM), and LV end-diastolic volume index (LVEDVI) were measured 6 months later. RESULTS: Baseline patient characteristics of the two groups were similar, including TIMI risk scores. Significant STR (>==50% resolution compared to baseline) (66% versus 50%; Group 1 versus Group 2, p=0.02), no-reflow ratio (24% versus 34%, indicated by mean values, p=0.02), LVEF (61% versus 55%, p=0.0007), LVRWM (-1.56 versus -2.05, using the SD/chord, p=0.0001), and LVEDVI (60 ml/m(2) versus 71 ml/m(2), p=0.0007) were significantly better in Group 1, and the no-reflow ratio, LVEF, LVRWM and LVEDVI were significantly better in ATP-administered patients, regardless of antecedent angina or advanced age. ATP Administration was consistently identified as a significant determinant for STR, no-reflow ratio, LVEF, LVRWM, and LVEDVI. CONCLUSIONS: Intravenous ATP administration during reperfusion is an independent determinant of STR and the no-reflow ratio, and LVEF, LVRWM, and LVEDVI at 6 months after primary PCI.

Abstract: BACKGROUND: The efficacy of sirolimus-eluting stents (SESs) has not been established in dialysis patients. METHODS AND RESULTS: This study was a non-randomized observational single-center registry in a community hospital: data for 80 consecutive dialysis patients who underwent percutaneous coronary intervention (PCI) with SES were compared with those of a historical group of consecutive 124 dialysis patients treated with bare-metal stents (BMS). After 1 year, the cumulative incidence of major adverse cardiac events (MACE), comprising cardiac death, nonfatal myocardial infarction, stent thrombosis, or target lesion revascularization (TLR), was 25.2% in the SES group and 38.2% in the BMS group (p=0.048). In multivariate analysis, use of SES remained an independent predictor of MACE at 1 year after PCI (risk ratio 0.70, 95% confidence interval 0.52-0.93, p=0.015). Rates of TLR were 21.7% in the SES group and 30.9% in the BMS group and (p=0.15). Subgroup analysis showed that use of SES was effective in patients with small vessels, non-diabetic patients, and patients without highly calcified lesions. CONCLUSIONS: In dialysis patients, the implantation of SES was moderately effective in reducing MACE at 1 year after PCI as compared with BMS. However, the TLR rate at 1 year was relatively higher than previously reported.

Abstract: OBJECTIVES: Left ventricular function and prognosis were evaluated in patients with acute myocardial infarction who underwent primary percutaneous coronary intervention supported by intraaortic balloon pumping. METHODS: Fifty-eight consecutive patients with first acute myocardial infarction were treated between July 1999 and April 2006. Twenty-five had cardiogenic shock on admission, whereas 33 did not. Patients with anterior acute myocardial infarction without cardiogenic shock were divided into the prophylactic intraaortic balloon pumping group (Group 1; n=17) and the rescue intraaortic balloon pumping group (Group 2; n=9). RESULTS: Thirty-day in-hospital mortality was 52% in cardiogenic shock patients, and 3% in non-shock patients. Baseline characteristics of non-shock anterior acute myocardial infarction were similar including Thrombolysis in Myocardial Infarction (TIMI) risk scores (5.1 and 5.0) in the two groups. However, average left ventricular ejection fraction in the convalescent stage was superior in Group 1 (48.7% vs. 37.8%, p = 0.03). Thirty-day in-hospital mortality was 0% in Group 1 and 11% in Group 2 (p = 0.34). Cox's hazard ratio in Group 2 to Group 1 was 2.38 (95% confidence intrerval; 0.84-11.1, p = 0.09) in terms of the subsequent major cardiac events. CONCLUSIONS: Prophylactic use of intraaortic balloon pumping starting prior to primary percutaneous coronary intervention preserves the convalescent left ventricular systolic function in patients with high risk for anticipated cardiac events after anterior acute myocardial infarction without cardiogenic shock.

Abstract: OBJECTIVE: We tested the hypothesis that simultaneous inhibition of the endothelial integrin alpha(v)beta(3) and the platelet glycoprotein IIb/IIIa receptor will substantially reduce infarct size in a model of acute coronary thrombosis and primary angioplasty. METHODS: Dogs were subjected to thrombus formation in the left anterior descending coronary artery followed by primary angioplasty. Prior to angioplasty, they were randomized into 3 treatment groups. Group 1 (n=7) received saline; Group 2 (n=9) received MK-383 that inhibits only IIb/IIIa; and Group 3 (n=9) received CP-4715, that inhibits both IIb/IIIa and alpha(v)beta(3). RESULTS: There was a 59% reduction in infarct size in dogs receiving CP-4715 compared to controls (p=0.002) and a 37% reduction compared to the dogs receiving MK-383 (p=0.04). Myocardium microthrombi were seen to be reduced similarly with both drugs on post-mortem (99m)Tc-DMP444 autoradiography that reflects in vivo IIb/IIIa receptor activity. In vivo imaging using echistatin-conjugated and leukocyte-targeted microbubbles revealed significant alpha(v)beta(3) inhibition and reduction in active leukocyte recruitment only in Group 3 dogs. Myocardial blood flow and regional function after reperfusion were also significantly better in this group. CONCLUSION: Simultaneous inhibition of IIb/IIIa and alpha(v)beta(3) causes a marked reduction in infarct size in a model of acute coronary thrombosis and primary PTCA that is associated with reduced myocardial microthrombi and inflammation, as well as improved myocardial blood flow and regional function. These results may have important implications in the treatment of acute coronary syndromes.

Abstract: Microthromboemboli (MTE) may contribute to the no-reflow phenomenon in acute myocardial infarction (AMI) either spontaneously or after primary percutaneous transluminal coronary angioplasty (PTCA). We hypothesized that myocardial MTE in acute coronary syndromes can be identified on imaging by in vivo (99m)Tc labeling of the coronary thrombus with a compound that binds to the glycoprotein IIb/IIIa present on activated platelets (DMP-444). METHODS: Fifteen dogs underwent left anterior descending coronary artery (LAD) injury in to produce thrombus, whereas 5 control dogs had LAD ligation. Before recanalization, the risk area (RA) and myocardial blood flow (MBF) were measured, and in vivo thrombus labeling was performed using (99m)Tc-labeled DMP-444. Nine of the 15 LAD injury dogs had occlusive thrombus on angiography and underwent PTCA. MBF measurements were repeated 30 and 60 min after recanalization, and (99m)Tc autoradiography (hot spot imaging) was performed ex vivo to determine the extent and magnitude of MTE. RESULTS: The ratio of hot spot size to RA size was higher in the 9 LAD injury dogs with thrombus compared with the 6 dogs with no thrombus (90% +/- 22% vs. 42% +/- 16%; P = 0.005). In control dogs, this ratio was significantly lower (29% +/- 11%; P = 0.05). (99m)Tc activity within the RA was higher in 8 of the 15 coronary injury dogs with AMI compared with those without AMI (1.8 +/- 0.48 vs. 1.24 +/- 0.22; P = 0.02). CONCLUSION: MTE can be detected and quantified after primary PTCA. The infarct size is proportional to the magnitude and extent of MTE, indicating that MTE may contribute to the AMI. Thus, in vivo thrombus labeling during reperfusion may provide important information in patients with AMI that may lead to better adjuvant therapy during PTCA.

Abstract: We tested the hypothesis that when acute coronary occlusion is caused by thrombus, part of the no-reflow phenomenon may result from spontaneous or coronary angioplasty-induced microthromboemboli, and that this phenomenon may be partly or wholly reversible. Accordingly, a thrombus was created in the left anterior descending coronary artery of 6 dogs and was labeled in vivo with (99m)Tc-DMP-444 that binds to the IIb/IIIa platelet receptor. Angioplasty was then performed to obtain thrombolysis in myocardial infarction grade-3 flow. Myocardial contrast echocardiography was performed 15 and 60 minutes after recanalization to define perfusion defect size. (99m)Tc-autoradiography and infarct size (IS) measurement were performed postmortem. An additional 5 dogs with coronary artery ligation followed by reperfusion served as control animals. These dogs also underwent myocardial contrast echocardiography and in vivo labeling with (99m)Tc-DMP-44. (99m)Tc uptake was significantly higher in the reperfused bed in dogs with thrombus compared with control dogs (2.7 +/- 0.9 vs 1.4 +/- 0.3 counts/pixel(-1)/min(-1), P =.01) indicating the presence of microthromboemboli. Perfusion defect size early (15 minutes) after recanalization was smaller than the hot spot on autoradiography and overestimated IS in dogs with thrombus. Perfusion defect size decreased with time and was closer to IS 60 minutes after recanalization. The dogs with thrombi demonstrated larger IS/risk area ratios compared with the 5 control dogs (46 +/- 6% vs 27 +/- 12%, P =.04). We conclude that part of the no-reflow phenomenon seen after angioplasty in acute coronary thrombosis is a result of microthromboemboli and is mostly reversible. No reflow late after reperfusion is a result of tissue necrosis. The thrombus burden also affects ultimate IS.

Abstract: OBJECTIVES: To elucidate the relationship between the infarct-related coronary artery and the right ventricular function before and after successful recanalization. METHODS: Hemodynamics and right ventricular function were measured using a REF-1 thermodilution catheter before and shortly after recanalization and during the convalescent stage in 35 patients, 17 with anteroseptal and 18 with inferior acute myocardial infarction. RESULTS: Pulmonary arterial pressure significantly decreased in both anteroseptal and inferior myocardial infarction patients after recanalization. Right ventricular volume index in patients with anteroseptal myocardial infarction increased after recanalization, but again decreased during convalescence. The right ventricle became enlarged in patients with inferior myocardial infarction to maintain the right ventricular stroke volume constant. Right ventricular ejection fraction (RVEF) did not significantly change in patients with inferior myocardial infarction during convalescence (38 +/- 13%, 38 +/- 13%, 46 +/- 9%), whereas RVEF in patients with anteroseptal myocardial infarction temporarily decreased after recanalization, and then increased during convalescence (37 +/- 10%, 31 +/- 12%, 41 +/- 7%). Patients with inferior myocardial infarction were divided into two groups, patients with increased RVEF (n = 6) and decreased RVEF (n = 12) shortly after recanalization. Patients with increased RVEF showed significantly improved RVEF during convalescence (49 +/- 7% vs 37 +/- 6%, p < 0.05). The increase in RVEF shortly after recanalization in patients with inferior myocardial infarction was an independent factor for predicting RVEF during convalescence. CONCLUSIONS: Patients with anteroseptal myocardial infarction showed a different pattern of change in the right ventricular function during the acute and convalescent stages. An early change in RVEF in patients with inferior myocardial infarction can predict RVEF in the convalescent stage.

Abstract: The objective of this study was to determine the optimal time to assess microvascular integrity within the risk area for myocardial infarction in order to predict unfavorable left ventricular remodeling (LVR) after successful primary coronary angioplasty. Fifty-three patients who underwent myocardial contrast echocardiography (MCE) just before recanalization, shortly after and 1 day (Day 2) and 3 weeks after recanalization were studied. The no- and low-reflow ratio (LR ratio) was analyzed at each stage. The wall-thinning ratio within the risk area was determined using magnetic resonance imaging performed 3-4 weeks after the recanalization. Thirteen of the 53 patients showed LVR 3-8 months after recanalization. The optimal time to predict LVR was found to be Day 2 based on the receiver operating characteristic curves. The LR ratio on Day 2 (chi2=7.39, p=0.007) and the collateral circulation before recanalization (chi2=4.57, p=0.03) were chosen as independent variables for predicting LVR. Patients with greater than 0.43 in the LR ratio on Day 2 showed a lower wall-thinning ratio (58+/-19% vs 72+/-20%, p=0.05). This study shows that the optimal time to estimate the microvascular integrity for predicting LVR is 1 day after recanalization, which is neither shortly after recanalization nor during the convalescent stage.

Abstract: OBJECTIVES: The aim of the study was to determine whether coronary stenosis can be detected and myocardial viability assessed after myocardial infarction from a single venous bolus injection of BR14, a new ultrasound contrast agent. BACKGROUND: BR14 is an ultrasound contrast agent that, like (201)Tl, demonstrates redistribution. Whether this principle can be used to determine myocardial viability is not known. METHODS: Non-critical (n = 6) or flow-limiting (n = 4) stenoses were placed on coronary arteries of 10 open-chest dogs, which then underwent 2 h of coronary occlusion followed by reperfusion through the stenosis. Hyperemia was induced to create flow mismatch in the dogs with non-critical stenosis. Hyperemia was not induced in dogs with reduced resting coronary blood flow. All dogs were given 2 ml of BR14 as a bolus injection and serial images were obtained. Myocardial blood flow (MBF) was measured using radiolabeled microspheres. At the end of the experiment, tissue staining was performed to determine infarct size and topography. RESULTS: Initial images demonstrated flow mismatch between the normal bed and that subtended by the stenosis (during hyperemia in dogs without critical stenosis and during rest in those with reduced resting MBF). The perfusion defect size correlated well with radiolabeled microsphere-derived hypoperfused zone (r = 0.89). Regions within the hypoperfused zone that had not undergone necrosis showed redistribution, whereas the necrotic regions showed a persistent defect, the size of which correlated well with infarct size (r = 0.80). CONCLUSIONS: Because of its ability to redistribute, BR14 can define regions of relative hypoperfusion and also discriminate between infarcted and viable tissue within the hypoperfused zone after a single venous injection. This property lends itself to assessing myocardial perfusion during exercise stress.

Abstract: Although regional myocardial perfusion can be currently quantified with myocardial contrast echocardiography (MCE) by using intermittent harmonic imaging (IHI), the method is tedious and time-consuming in the clinical setting. We hypothesized that regional myocardial perfusion can be quantified and the severity of coronary stenosis determined during hyperemia with MCE using real-time imaging (RTI) where microbubbles are not destroyed. Six open-chest dogs were studied during maximal hyperemia induced by adenosine in the absence or presence of coronary stenoses varying from mild to severe. Myocardial blood flow (MBF) was measured at each stage by using radiolabeled microspheres. MCE was performed using both IHI and RTI. Data for the latter were acquired in both end-systole and end-diastole. No differences were found between myocardial flow velocity (MFV) derived from IHI and RTI when end-systolic frames were used for the latter. MFV was consistently higher for RTI (P <.01) when end-diastolic frames were used. A linear relation was noted between MFV and radiolabeled microsphere-derived MBF ratios from the stenosed and the normal beds when end-systolic frames were used for RTI (r = 0.78, P <.001), whereas no relation was found when end-diastolic frames were used (r = 0.08, P =.78). The scatter for assessing MBF (A.beta) was minimal for IHI and RTI (9%-10%) with end-systolic frames, whereas that for RTI with end-diastolic frames was large (30%). Furthermore the correlation with radiolabeled microsphere-derived MBF was significantly (P <.01) weaker with RTI when end-diastolic frames were used (r = 0.53) than when end-systolic frames (r = 0.94) or IHI was used (r = 0.99). Data acquisition for IHI was 10 minutes, whereas it was 8 seconds for RTI. Thus, RTI can be used to quantify regional myocardial perfusion and stenosis severity during MCE. Only end-systolic frames, however, provide accurate data. RTI offers a rapid and easy means of assessing regional myocardial perfusion with MCE.

Abstract: This study sought to elucidate serial changes in microvascular integrity during papaverine-induced hyperemia in the risk area for myocardial infarction. In addition, we attempted to determine the optimal time for predicting myocardial viability. Seventy-two patients who underwent serial myocardial contrast echocardiography (MCE) before and shortly after (day 1), 1 day (day 2), and 3 weeks (day 21) after recanalization were studied. In 18 of 72 patients, MCE was performed at baseline and during hyperemia using selective intracoronary infusion of papaverine. Both the peak grayscale ratio (PGSR) within the risk area, and the no- and low-reflow ratio (LR ratio) were analyzed in each stage. Left ventricular regional wall motion (RWM) was determined 6 months after recanalization. The correlation coefficient between PGSR with papaverine on day 1 and that on day 2 was 0.54 (p = 0.02); it was 0.50 (p = 0.04) between day 1 and day 21, and 0.82 (p = 0.001) between day 2 and day 21. On day 1, the correlation coefficient between the LR ratio with papaverine and RWM was 0.60 (p = 0.02), which changed to 0.72 (p = 0.003) on day 2 and 0.54 (p = 0.04) on day 21, respectively. The best time to predict viable myocardium was established on day 2 by receiver operating characteristics curves. ST-segment re-elevation, elapsed time from onset to recanalization, and antecedent angina pectoris were independent factors for PGSR on day 2 using stepwise and multiple linear regression analysis. This study suggests that the optimal time to estimate microvascular integrity for predicting myocardial viability might be 1 day after recanalization, which is neither shortly after recanalization nor during the convalescent stage.

Abstract: OBJECTIVES: This study sought to determine whether microvascular integrity in the risk area (RA) for myocardial infarction (MI) one day after recanalization predicts the outcome in patients with first acute MI. BACKGROUND: Immediately after recanalization, microcirculation in the RA is modified by both hyperemic response and microvascular impairment. METHODS: Fifty consecutive patients who underwent serial myocardial contrast echocardiography before and one day after recanalization (day 2) were studied. All patients had a completely occluded lesion in the left anterior descending coronary artery alone, and underwent successful reperfusion therapy. The relative size of the initial RA (RA ratio) and peak gray scale ratio (PGSR) within the RA on day 2 were determined. Patients were followed for a median of 22 months to evaluate clinical outcome. RESULTS: On day 2, PGSR was a median of 0.46. Study patients were subdivided into two groups, group A of 24 patients with acceptable opacification (PGSR > 0.46 on day 2) and group B of 26 patients without it. Major cardiac events (cardiac death, nonfatal MI and repeat admission for congestive heart failure) were more frequently observed in group B (28% vs. 4%, Cox hazard ratio=8.5, p=0.05, 95% confidence interval [CI] 1.03 to 69.9). The median value of the RA ratio was 0.45. Patients (n=15) with RA ratio > 0.45 on day 1 and PGSR on day 2 < or = 0.46 exhibited a 10.7-fold relative risk for major cardiac events (p=0.005, 95% CI 2.06 to 55.8) and a 3.69-fold relative risk for composite cardiac events (major cardiac events and target lesion revascularizations) after the initial intervention (p=0.004, 95% CI 1.51 to 9.04). CONCLUSIONS: The assessment of both the size of the initial RA and microvascular integrity on day 2 enables precise determination of the efficacy of reperfusion therapy and prediction of the short- and intermediate-term prognoses of patients with recanalized MI.

Abstract: Serial myocardial contrast echocardiograms were recorded to investigate the time course of microvascular integrity in the risk area for first acute myocardial infarction. Serial changes in the risk area were categorized into 4 main types according to the potential for recovery from microvascular impairment.

Abstract: This study evaluated the correlation between the acute course and prognosis of patients with acute myocardial infarction complicated by heart failure. Heart failure was defined as a mean pulmonary capillary wedge pressure equal to or greater than 20 mmHg with radiographic evidence of pulmonary congestion during hospitalization in the coronary care unit. A total of 77 heart failure patients underwent primary percutaneous transluminal coronary angioplasty or thrombolysis. Twelve patients who died within the first 3 days (group I) had a higher incidence of unsuccessful reperfusion (50 vs 19%, p < 0.05) and cardiogenic shock (64 vs 4%, p < 0.01), compared with the 65 patients who survived at least the initial 4 days (group II). These 65 patients were classified into three subgroups according to the course of heart failure: early regression type (group IIA, n = 38); prolonged type (group IIB, n = 18); delayed-onset type (group IIC, n = 9). Patients in group IIB had a higher incidence of multivessel disease than group IIA. Patients in group IIC had a higher incidence of unsuccessful reperfusion. Cardiac index in group IIB was lower than in group IIA (2.50 +/- 0.70 vs 1.91 +/- 0.39 l/min/m2). Changes in left ventricular ejection fraction were 4.1 +/- 9.2% in group IIA, -6.6 +/- 16.8% in group IIB, and 0.9 +/- 7.3% in group IIC. The hospital mortality rate was 0% in group IIA, 11% in group IIB, and 33% in group IIC, the reinfarction rate was 0, 17 and 22%, and sustained arterial patency was demonstrated in 81, 62 and 43%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)