Mien-g Chen

Serial Changes in Platelet Activation in Patients After Ischemic Stroke Role of Pharmacodynamic Modulation

Background and Purpose— Enhanced platelet activity has previously been reported in the acute phase after ischemic stroke. We tested the hypothesis that activated platelets (expressed by CD62p) are substantially increased in the acute stage after a stroke and decrease thereafter, and that antiplatelet therapies can suppress CD62p expression. Methods— We serially examined platelet CD62p expression using flow cytometry after acute ischemic stroke in 87 consecutive patients. The CD62p expression was also evaluated in 20 healthy volunteers and 33 at-risk control subjects. Results— CD62p expression was significantly higher in the acute phase after ischemic stroke than in normal and at-risk control subjects (both P < 0.0001). CD62p expression decreased to a significantly lower level on day 21, and to a substantially lower level on day 90. CD62p expression was not significantly suppressed by warfarin. However, CD62p expression was significantly suppressed by aspirin treatment (P = 0.024) and more substantially suppressed by clopidogrel (P < 0.0001) on day 90. Furthermore, only clopidogrel treatment (P = 0.0016) was significantly independently associated with decreased CD62p expression on day 90. Conclusions— Platelet activation was significantly increased in acute ischemic stroke and substantially decreased thereafter. The lesser long-term pharmacodynamic potency of aspirin relative to clopidogrel raises the prospect of the need for more effective antiplatelet agents or a synergistic combination therapy for stroke prevention in the future.

Risk Stratification of In-Hospital Mortality in Patients Hospitalized for Chronic Congestive Heart Failure Secondary to Non-Ischemic Cardiomyopathy

The study population consisted of 234 consecutive patients hospitalized for acute exacerbation of congestive heart failure secondary to non-ischemic cardiomyopathy. Of the 234 patients, there were 55 in-hospital deaths. Their medical records were deliberatively reviewed and the association of 38 clinical, hemodynamic and biochemical variables with in-hospital mortality was evaluated by multiple stepwise logistic regression analysis. The following variables were statistically associated with in-hospital mortality: profound cardiogenic shock, severe hyponatremia, the presence of ventricular arrhythmias, history of stroke, the presence of acute renal failure, and requirement of dobutamine therapy. In stratified analyses, the rates of in-hospital mortality rose rapidly as the number of risk factors increased: 0 risk factors, 2.5%; 1 risk factor, 5.1%; 2 risk factors, 36.4%; 3 risk factors, 75%, and no less than 4 risk factors, 100%. In conclusion, our study identified 6 variables that correlated with in-hospital death in patients with heart failure secondary to non-ischemic cardiomyopathy. The identification of these variables may allow more accurate risk stratification of individuals at risk of in-hospital mortality in this clinical setting.

Link between Platelet Activity and Outcomes after an Ischemic Stroke

Background: Platelets play an important role in atherosclerosis and thromboembolic events. We examined the relationship between platelet activity and outcomes after an ischemic stroke. Methods: Using flow cytometry, we serially measured the fractions of circulating platelet activity (CD62p expression) after an ischemic stroke in early (<48 h), recent (day 7), convalescent (day 21) and chronic (day 90) phases in 92 consecutive patients with an ischemic stroke. Patients were classified into high (CD62p expression >3.16%) and low (CD62p expression ≤3.16%) platelet activity groups according to the median value of CD62p expression in the early phase of a stroke. Results: The composite end point – death, recurrent stroke and severe neurological impairment (alive in care), defined as a score of >13 on the National Institutes of Health Stroke Scale – within the first 30 days and at an interval of 8.2 ± 1.5 months of follow-up was determined for each group. In the first 30 days, the composite end point occurred in 37.0% of patients in the high platelet activity group as compared with 6.5% in the low platelet activity group (p = 0.0004). At a mean follow-up of 8.2 ± 1.5 months, the composite end point occurred in 36.6% of patients in the high platelet activity group as compared with 10.9% in the low platelet activity group (p = 0.0044). Multiple stepwise logistic regression analysis displayed that high platelet activity (p = 0.011), age (p = 0.013) and the presence of coronary artery disease (p = 0.021) were independently associated with adverse outcomes at the intermediate-term follow-up. Conclusions: Results of this study showed that high platelet activity is strongly associated with adverse clinical outcomes after an early ischemic stroke.

Clinical features and outcome of coronary artery aneurysm in patients with acute myocardial infarction undergoing a primary percutaneous coronary intervention.

Background: While coronary artery aneurysm is an uncommon anatomic disorder and has various forms, its clinical features and outcome and its impact on thrombus formation and the no-reflow phenomenon in the clinical setting of acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (p-PCI) have not been discussed. The purpose of this study was to evaluate whether this anatomic disorder predisposes to a high burden of thrombus formation, and subsequently leads to the no-reflow phenomenon and untoward clinical outcome in patients with AMI undergoing p-PCI. Methods and Results: In our hospital, emergency p-PCI was performed in 924 consecutive patients with AMI between May 1993 and July 2001. Of these 924 patients, 24 patients (2.6%) who had an infarct-related artery (IRA) with aneurysmal dilatation were retrospectively registered and constituted the patient population of this study. Angiographic findings demonstrated that the ectasia type (defined as diffuse dilatation of 50% or more of the length of the IRA) was found most frequently (70%), followed by the fusiform type (20%; defined as a spindle-shaped dilatation in the IRA) and the saccular type (10%; defined as a localized spherical-shaped dilatation in the IRA). The right coronary artery was the most frequently involved vessel (54.2%), followed by the left anterior descending (25.0%) and the left circumflex arteries (20.8%). Coronary angiography revealed that all of these aneurysmal IRA filled with heavy thrombus (indicated as high-burden thrombus formation). The no-reflow phenomenon (defined as ≤TIMI-2 flow) and distal embolization after p-PCI were found in 62.5 and 70.8% of the IRA, respectively. The incidence of cardiogenic shock and the 30-day mortality rate were 25 and 8.3%, respectively. The survival rate was 90.9% (20/22) during a mean follow-up of 19 ± 30 months. Conclusions: While aneurysmal dilatation of an IRA is an uncommon angiographic finding in the clinical setting of AMI, it is frequently associated with high-burden thrombus formation and has a significantly lower incidence of successful reperfusion. However, the long-term survival of these patients is excellent.

Left Atrial Platelet Activity With Rheumatic Mitral Stenosis: Correlation Study of Severity and Platelet P-Selectin Expression by Flow Cytometry

BACKGROUND Previous studies have demonstrated that platelet activation, evaluated by measuring the secretory substances of platelets (ie, platelet factor 4 and beta-thromboglobulin), occurs in the peripheral blood of patients with rheumatic mitral stenosis (MS). However, the differences in platelet activation between peripheral and atrial blood, and the relationship between regional left atrial platelet P-selectin expression and the severity of MS have never been investigated. METHODS AND RESULTS A total of 16 patients with symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty were studied (group 1). The fractions of platelets expressing P selectin in the prevalvuloplasty left atrial, right atrial, peripheral venous, and arterial blood were determined by flow cytometry. The mitral valve area was calculated by means of the Doppler pressure half-time method. Peripheral venous platelet activity also was evaluated in 23 control patients (including 15 healthy volunteers who were in sinus rhythm [group 2] and 8 patients who had chronic lone atrial fibrillation [group 3]). The fraction of peripheral venous platelets expressing P selectin among group 1 patients was significantly higher than that of group 2 or 3 patients (p = 0.008). In group 1 patients, the fraction of platelets expressing P selectin in the left atrium was significantly higher than that in the right atrium, the femoral vein, or the femoral artery (p < 0.01). Correlation analysis demonstrated that there was a significantly direct relationship between the severity of MS and the fraction of left atrial platelets expressing P selectin (p = 0.01; r = -0.620). The fraction of peripheral venous platelets expressing P selectin among group 2 patients did not differ from that of group 3 patients CONCLUSIONS In patients with rheumatic MS, increased regional left atrial platelet P-selectin expression had a significantly direct relationship with the severity of MS. The increased regional left atrial platelet P-selectin expression was not reflected in peripheral venous blood samples.

Clinical InvestigationsCARDIOLOGYLeft Atrial Platelet Activity With Rheumatic Mitral Stenosis*: Correlation Study of Severity and Platelet P-Selectin Expression by Flow Cytometry

BACKGROUND Previous studies have demonstrated that platelet activation, evaluated by measuring the secretory substances of platelets (ie, platelet factor 4 and beta-thromboglobulin), occurs in the peripheral blood of patients with rheumatic mitral stenosis (MS). However, the differences in platelet activation between peripheral and atrial blood, and the relationship between regional left atrial platelet P-selectin expression and the severity of MS have never been investigated. METHODS AND RESULTS A total of 16 patients with symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty were studied (group 1). The fractions of platelets expressing P selectin in the prevalvuloplasty left atrial, right atrial, peripheral venous, and arterial blood were determined by flow cytometry. The mitral valve area was calculated by means of the Doppler pressure half-time method. Peripheral venous platelet activity also was evaluated in 23 control patients (including 15 healthy volunteers who were in sinus rhythm [group 2] and 8 patients who had chronic lone atrial fibrillation [group 3]). The fraction of peripheral venous platelets expressing P selectin among group 1 patients was significantly higher than that of group 2 or 3 patients (p = 0.008). In group 1 patients, the fraction of platelets expressing P selectin in the left atrium was significantly higher than that in the right atrium, the femoral vein, or the femoral artery (p < 0.01). Correlation analysis demonstrated that there was a significantly direct relationship between the severity of MS and the fraction of left atrial platelets expressing P selectin (p = 0.01; r = -0.620). The fraction of peripheral venous platelets expressing P selectin among group 2 patients did not differ from that of group 3 patients CONCLUSIONS In patients with rheumatic MS, increased regional left atrial platelet P-selectin expression had a significantly direct relationship with the severity of MS. The increased regional left atrial platelet P-selectin expression was not reflected in peripheral venous blood samples.

Increased Plasma Levels of Soluble P-Selectin in Rheumatic Mitral Stenosis*

BACKGROUND Previous studies have demonstrated that platelet activation occurs in peripheral blood of patients with rheumatic mitral stenosis (MS). However, in patients with MS, the plasma level of soluble P-selectin (a marker of platelet activation) remains unsettled. METHODS AND RESULTS A total of 20 patients with symptomatic MS undergoing percutaneous transluminal mitral valvuloplasty (PTMV) were studied (group 1; 16 patients in permanent atrial fibrillation, and 4 patients in sinus rhythm). The plasma levels of soluble P-selectin in the femoral vein and artery, and right and left atria before PTMV and those in the peripheral venous blood at the 1-week and 4-week follow-ups after PTMV were determined by solid-phase, sandwich, enzyme-linked immunosorbent assay. The mitral valve area was calculated by means of the Doppler pressure half-time method. In addition, we measured plasma concentrations of soluble P-selectin in the peripheral venous blood samples obtained from 22 control patients (including 14 healthy volunteers in sinus rhythm [group 2] and 8 patients in permanent lone atrial fibrillation [group 3]). The plasma levels of soluble P-selectin were significantly elevated in group 1 patients (49.78 +/- 37.72 ng/mL) [mean +/- SD] compared with group 2 (25.52 +/- 15.38 ng/mL) and group 3 patients (32.17 +/- 14.18 ng/mL) [p < 0.005]. In group 1 patients, the plasma levels of soluble P-selectin in the left atrium did not significantly differ from those in the right atrium, femoral vein, or femoral artery (p = 0.05). The area of mitral valve increased significantly after PTMV (1.06 +/- 0.17 cm(2) vs 1.48 +/- 0.32 cm(2), p < 0.0001). The mean left atrial pressure fell significantly and immediately after PTMV (23.0 +/- 5.1 mm Hg vs 17.6 +/- 5.9 mm Hg, p < 0.0001). The peripheral venous plasma levels of soluble P-selectin obtained before PTMV did not significantly fall after PTMV (before, 49.8 +/- 37.7 ng/mL; 10 min after, 39.8 +/- 19.1 ng/mL; 1 week after, 46.1 +/- 20.8 ng/mL; and 4 weeks after, 41.2 +/- 15.9 ng/mL; p = 0.145). CONCLUSIONS The venous plasma levels of soluble P-selectin in patients with moderate-to-severe MS were significantly higher than those in healthy volunteers or patients with lone atrial fibrillation. In addition, in patients with MS, there was no difference in the plasma levels of soluble P-selectin between the left and right atrial blood and between peripheral and atrial blood. Moreover, there was no change in soluble P-selectin levels as a result of PTMV.

Transradial application of PercuSurge GuardWire device during primary percutaneous intervention of infarct-related artery with high-burden thrombus formation.

A large infarct‐related artery (IRA), which mostly contains high‐burden thrombus formation (HBTF) and lipid pool‐like plaque contents, has been suggested to play a pivotal role in the no‐reflow phenomenon during primary percutaneous coronary intervention (p‐PCI). To reduce the thrombus burden of the IRA using the PercuSurge GuardWire device before intervention may be of crucial importance to preventing no‐reflow. The purposes of this study were to test the transradial application (TRA) of this new mechanical device and to determine its impact on prevention of no‐reflow during p‐PCI. From May to September 2002, the PercuSurge GuardWire device was utilized in 42 consecutive patients with acute myocardial infarction and large IRA (vessel size ≥ 3.5 mm with HBTF; group 1). From January to December 2000, p‐PCI was performed in large IRA (vessel size ≥ 3.5 mm) with HBTF using tranfemoral arterial approach in 101 consecutive patients (group 2). The angiographic and clinical outcomes of the two groups were compared in a chronologically consecutive manner. Successful reperfusion (final TIMI‐3 flow) was significantly higher in group 1 than in group 2 patients (95.2% vs. 79.1%; P = 0.005). Moreover, the combined incidence of vascular complications, post‐PCI thromboembolisms (defined as a distal embolism and a post‐PCI residual thrombus score of ≥ 3), and combined 30‐day major adverse cardiac events were significantly lower in group 1 than in group 2 patients (all P values < 0.05). In group 1 patients, post‐p‐PCI myocardial blush (MB) of ≥ 2 grades was found to be more than 88.0%. Furthermore, when compared with preintervention, thrombus scores were significantly reduced after aspiration (P = 0.0001), whereas the minimal lumen diameter (P = 0.0001), TIMI flow grade (P = 0.0001), and MB grade (P = 0.0001) had all significantly increased after aspiration using Export Aspiration Catheter. There were no significant differences in corrected TIMI frame count (P = 0.42), TIMI flow grade (P > 0.5), or MB grade (all P values > 0.5) between postaspiration and post‐PCI. The TRA of the PercuSurge GuardWire device during primary intervention of large IRA with HBTF was safe and feasible and provided benefits to patients. The initial successful reduction of the thrombus burden with this mechanical device before intervention can be translated into increased final TIMI‐3 flow, a combined MB of ≥ 2 grades, and fewer final thromboembolic events. Catheter Cardiovasc Interv 2004;61:503–511.

Short- and long-term outcomes after percutaneous transluminal coronary angioplasty in chronic hemodialysis patients

The aim of this study was to obtain data on the outcomes of chronic hemodialysis patients who underwent percutaneous transluminal coronary angioplasty (PTCA). A retrospective chart analysis identified 31 such patients between August 1992 and October 1996. The mean follow‐up period was 12.4 ± 11.7 months. Angiographic success was achieved in 39 of 41 (95.1%) stenoses attempted. There were three in‐hospital deaths. Clinical success was achieved in 28 of 31 patients (90%). Two of the 28 survivors were lost to follow‐up. Recurrent angina developed within 6 months in 14 of 26 patients (53.8%). Eleven and 17 of the 26 patients (42.3% and 65.4%) died within 6 and 14 months, respectively, after the PTCA procedure. Ten of the 17 deaths (58.8%) were due to cardiovascular events. Our study suggests that PTCA is technically feasible with high angiographic success rate in chronic hemodialysis patients. In‐hospital mortality rate and rate of recurrent angina are high. Long‐term prognosis is poor. Cathet. Cardiovasc. Intervent. 47:430–433, 1999.

Balance between plasma levels of tumor necrosis factor-α and interleukin-10 in rheumatic mitral stenosis

The study population consisted of 16 patients with rheumatic mitral stenosis undergoing percutaneous transluminal mitral valvuloplasty (group 1). The plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) in the femoral vein and the right and left atria before valvuloplasty were determined by ELISA. Additionally, we measured plasma concentrations of TNF-α and IL-10 in the venous blood obtained from 19 control patients, including 12 healthy volunteers in sinus rhythm (group 2) and 7 patients in permanent lone atrial fibrillation (group 3). The venous plasma levels of TNF-α were significantly elevated in group 1 patients compared with group 2 patients (p < 0.002). Correlation analysis demonstrated that there was a significantly direct relationship between the plasma TNF-α and IL-10 concentrations in the left atrial, right atrial and peripheral venous blood (p < 0.008, r = 0.640; p < 0.04, r = 0.538; p< 0.03, r = 0.571, respectively). In conclusion, the plasma concentrations of TNF-α of patients with rheumatic mitral stenosis were significantly higher than those of healthy volunteers. In addition, there was a significantly direct relationship between the soluble TNF-α and IL-10 concentrations in the atrial and peripheral venous blood, indicating a balance between circulating TNF-α and IL-10 levels in patients with rheumatic mitral stenosis.