Clinical outcomes of sirolimus-eluting stenting after rotational atherectomy.

BACKGROUND: The efficacy of drug-eluting stents after rotational atherectomy (ROTA) has not been clarified. METHODS AND RESULTS: The 704 consecutive patients who underwent percutaneous coronary intervention (PCI) with a sirolimus-eluting stent (SES) (79 with and 625 without ROTA) were enrolled. The 2-year clinical outcome of these patients was compared with that of a group of 1,123 consecutive patients treated with bare-metal stents (BMS) (144 with and 979 without ROTA). At 2 years after index PCI, the use of SES after ROTA was associated with a lower crude incidence of major adverse cardiac events (MACE) than were BMS after ROTA (30.1% vs 43.1%, P=0.024). The difference was mainly derived from the reduction in target lesion revascularization (TLR) (25.0% vs 39.1%, P=0.022). After adjusting for confounders, ROTA-SES was associated with a reduction in MACE and TLR, with a similar hazard ratio to the non-ROTA group only with SES implantation. In a subgroup of dialysis patients, the incidence of TLR after ROTA with SES and BMS was similarly high. CONCLUSIONS: The use of SES after ROTA is an appropriate method for selected hard lesions, but has a limited effect in dialysis patients, even after lesion preparation with ROTA.

Simultaneous integrin alphavbeta3 and glycoprotein IIb/IIIa inhibition causes reduction in infarct size in a model of acute coronary thrombosis and primary angioplasty.

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.

Detection of coronary stenosis and myocardial viability using a single intravenous bolus injection of BR14.

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.

Molecular imaging identifies regions with microthromboemboli during primary angioplasty in acute coronary thrombosis.

UNLABELLED: 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.

Further insights into the no-reflow phenomenon after primary angioplasty in acute myocardial infarction: the role of microthromboemboli.

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.

Exogenous adenosine triphosphate disodium administration during primary percutaneous coronary intervention reduces no-reflow and preserves left ventricular function in patients with acute anterior myocardial infarction: a study using myocardial contrast echocardiography.

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 microg/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 (> or =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.

Intravenous administration of adenosine triphosphate disodium during primary percutaneous coronary intervention attenuates the transient rapid improvement of myocardial wall motion, not myocardial stunning, shortly after recanalization in acute anterior myocardial infarction.

BACKGROUND AND PURPOSE: Administration of adenosine attenuates myocardial stunning after reperfusion in a canine experimental ischemic model. However, it is unknown whether administration of adenosine triphosphate disodium (ATP) during reperfusion can attenuate myocardial stunning after coronary recanalization in patients with acute myocardial infarction (MI). Therefore, we sought to elucidate the effects of ATP administration on serial changes of left ventricular systolic function before and after coronary recanalization. METHODS: In 27 patients with first ST-elevation acute anterior MI, in whom primary percutaneous coronary intervention (PCI) was completed within 10 h after symptom onset, ATP at a mean rate of 103 microg/kg/min (n=16) or normal saline (n=11) was intravenously administered for 1 h during reperfusion. Left ventricular regional wall motion within the initially severely ischemic region was serially analyzed using the standard wall motion score index (WMSI) by transthoracic echocardiography. RESULTS: Means of WMSIs were similar shortly before primary PCI in both groups (2.79 in ATP group and 2.69 in controls). They changed to 2.56 and 2.22 shortly after PCI, 2.49 and 2.39 on day 2, 2.34 and 2.30 on day 3, 2.19 and 2.25 on day 10, and 1.85 and 2.02, 6 months later, respectively. Transient improved regional wall motion within the initially severely ischemic region was observed shortly after PCI in controls (10.3% of observed segments); however, it was significantly suppressed in the ATP group (2.55%). The percent recovery of WMSI on day 10, which was defined as WMSI on day 10 normalized by improvement of WMSI for 6 months, was 63.8% in ATP group and 65.7% in controls, implying ATP administration could not reduce myocardial stunning by day 10 after primary PCI. CONCLUSIONS: The high-dose administration of ATP during primary PCI prevented transient improved wall motion shortly after coronary recanalization rather than preventing left ventricular stunning. These results suggest that ATP can prevent reperfusion injury during primary PCI.

One-year clinical outcomes of dialysis patients after implantation with sirolimus-eluting coronary stents.

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.

[Prophylactic intraaortic balloon pumping preserves left ventricular systolic function in acute anterior myocardial infarction without cardiogenic shock].

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.

[Serial assessment of right ventricular function in the acute and convalescent stages after successful reperfusion: relationship to infarct-related coronary artery].

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.

Optimal time for predicting left ventricular remodeling after successful primary coronary angioplasty in acute myocardial infarction using serial myocardial contrast echocardiography and magnetic resonance imaging.

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.