Influence of Late Vascular Inflammation on Long-Term Outcomes Among Patients Undergoing Implantation of Drug Eluting Stents: Role of C-Reactive Protein.

BACKGROUND: Elevation of C-reactive protein (CRP) as a marker of vascular inflammation at a late phase of drug-eluting stent (DES) implantation may predict subsequent major adverse cardiac events (MACE). METHODS AND RESULTS: In 1234 consecutive patients undergoing DES implantation, CRP was measured both before (baseline) and 8 to 12 months after (late phase) stenting, and the relationship between elevation of CRP (>2.0 mg/L) and subsequent MACE (all cause death, nonfatal myocardial infarction, target lesion revascularization, and other additional revascularization) was assessed. As results, CRP was elevated in 38.0% of patients at baseline and in 23.6% during late phase (P<0.0001), and hazard ratio (HR) for MACE was 1.52 (95% confidence interval [95% CI] 1.21-1.93, P=0.0004) at baseline versus 4.00 (95% CI 3.16-5.05, P<0.0001) in late phase. By multivariable analysis, late-phase CRP elevation (HR 3.60, 95% CI: 2.78-4.68, P<0.0001), chronic kidney disease (CKD) (HR 1.41, 95% CI: 1.10-1.84, P=0.01), and number of diseased segments (HR 1.19, 95% CI: 1.08-1.30, P=0.0002) were positive predictors of MACE, whereas statin use (HR 0.66, 95% CI 0.50-0.87, P=0.003) was a negative predictor. Propensity score-matched analysis also confirmed the effect of late-phase CRP on MACE (HR 3.39, 95% CI 2.52-4.56, P<0.0001). In prediction of the late-phase CRP elevation, CKD (odds ratio [OR] 1.71, 95% CI 1.24-2.36, P=0.001) and baseline CRP elevation (OR 3.48, 95% CI 2.55-4.74, P<0.0001) were positive predictors, whereas newer generation DES (OR 0.59, 95% CI 0.41-0.84, P=0.003) and statin therapy (OR 0.68, 95% CI 0.47-0.97, P=0.03) were negative predictors. CONCLUSIONS: Monitoring the late-phase CRP may be helpful to identify a high-risk subset for MACE among patients undergoing DES implantation.

Impact of continuous deterioration of kidney function 6 to 8 months after percutaneous coronary intervention for acute coronary syndrome.

Preprocedural chronic kidney disease and contrast-induced acute kidney injury are predictors of in-hospital death and long-term mortality. However, neither the time course of kidney function after percutaneous coronary intervention (PCI) nor the relation between the time course of kidney function and prognosis has been adequately studied. We studied 531 patients who underwent PCI for acute coronary syndrome. The continuous deterioration of kidney function (CDKF) was defined as a >25% increase in serum creatinine level or serum creatinine >0.5 mg/dl above baseline at 6 to 8 months after PCI. CDKF was observed in 87 patients (16.4%). Independent risk factors for CDKF were contrast-induced acute kidney injury, preprocedural hemoglobin level, and proteinuria. Patients with CDKF exhibited significant higher 5-year mortality rate than patients without CDKF (25% vs 9.4%, log-rank p = 0.0006). Independent risk factors for 5-year mortality were age >75 year, anemia, New York Heart Association class III or IV, low ejection fraction, and CDKF. CDKF is associated with an increased risk of all-cause mortality of 5 years in patients with acute coronary syndrome undergoing PCI.

Bleeding risk with triple antithrombotic therapy in patients with atrial fibrillation and drug-eluting stents.

In the era of drug-eluting stents (DES), a long-term dual antiplatelet therapy is required to prevent late stent thrombosis. However, in patients with atrial fibrillation (AF), there is a concern that combining warfarin with dual antiplatelet therapy may increase the risk of bleeding. We analyzed 1274 consecutive patients with coronary artery disease who were treated with coronary intervention from January 2006 through January 2009. Of these, we enrolled 74 AF patients treated with DES and dual antiplatelet therapy as well as warfarin. The primary endpoint was the incidence of major bleeding within 3 years; the predictive factor of major bleeding was also analyzed. To evaluate the efficacy of anticoagulant therapy, time in therapeutic range (TTR) was also measured. The 3-year incidence of major bleeding was 12.2 % (nine of 74 patients). The average observation period was 25.7 ± 20.2 months. Mean TTR value was 44.6 ± 33.0 % and was maintained at a relatively low level. Multivariate analysis revealed that a higher CHADS2 score (2-point more) was an independent predictor of increased risk of major bleeding. Major bleeding in the patients with triple antithrombotic therapy including warfarin occurred at a relatively high rate. Although the higher CHADS2-score indicates a high risk of thrombotic events, it was strongly associated with bleeding complications.

Incidence and predictors of the late catch-up phenomenon after drug-eluting stent implantation.

BACKGROUND: Although clinical restenosis within 1 year after percutaneous coronary intervention has been remarkably reduced with the advent of drug-eluting stents (DES), the late catch-up (LCU) phenomenon remains an issue despite medical advances. The aim of this study was to investigate the incidence and predictive factors of the LCU phenomenon in an unselected population treated with first-generation DES. METHODS: A total of 923 patients treated with DES between June 2004 and August 2008 were analyzed. The LCU phenomenon was defined as secondary revascularization 1 year after index stenting. Retreatment for very late stent thrombosis was considered as part of the LCU phenomenon. RESULTS: Incidence of the LCU phenomenon was seen in 33 patients (3.6%). Very late stent thrombosis was observed in 5 patients (0.6%) and very late in-stent restenosis was observed in 28 patients (3.0%). At the 12-month landmark analysis, the cumulative rate of cardiac death was significantly higher in patients with the LCU phenomenon than in those without any target lesion revascularization (9.0% vs. 0.9%, p<0.001). In the multivariate analysis, hemodialysis [odds ratio (OR) 6.07, p=0.003], number of stents (OR 1.58, p=0.02), and coronary bifurcation lesions (OR 2.06, p=0.048) were identified as independent predictors of the LCU phenomenon. CONCLUSION: The LCU phenomenon is associated with serious consequences and adverse events and remains an important issue in modern practice, despite medical advances. DES should be deployed with a minimum number of stents, and special consideration must be given to patients on hemodialysis and those with coronary bifurcation lesions.

A case of paradoxical embolic ST-segment elevation myocardial infarction triggered by sleep apnea.

This report describes an obese 39-year-old man who experienced ST-segment elevation myocardial infarction with total thrombotic occlusion of the right coronary artery. Culprit vessel flow was improved by aspiration. Data suggested that myocardial infarction had resulted from paradoxical embolus via a patent foramen ovale triggered by the Mueller maneuver, which had induced negative intrathoracic pressure following an acute increase of right-heart volume in the context of obesity and sleep-disordered breathing (SDB). Obesity is increasing among younger populations and it represents a risk for SDB and thrombosis. Thus, this mechanism should be included within the differential diagnosis for myocardial infarction in young patients.

Contents of second peak in the circadian variation of acute myocardial infarction in the Japanese population.

BACKGROUND: Circadian variation has been accepted as a factor in acute myocardial infarction (AMI). An increased incidence of cardiac events in the morning has been reported for a long time. Recent reports have indicated that the onset of AMI shows two peaks, which occur in the morning and evening. It has also been demonstrated that circadian pattern of AMI may vary with sex and age. METHODS AND RESULTS: We investigated 522 consecutive patients who underwent primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI) between 2000 and 2010. The patients were classified into 3 age groups: younger (≤59 years old), intermediate (60-79 years old), and older (≥80 years old). Clinical data were investigated, including the age and sex, angiographic characteristics, and time of onset of STEMI. There were two peaks in the onset of STEMI throughout the day, which were at 7:00-10:00 and 19:00-21:00 h, among all patients (male and female). Stratified analysis showed that older females formed the main part of the second peak. CONCLUSIONS: There were two peaks in the onset of STEMI in a Japanese population in Tokyo. The second peak was significantly dominated by the older female group. Age and gender influenced the second peak in the circadian variation of AMI in a Japanese population in Tokyo.

Novel strategy for percutaneous transluminal angioplasty for complex critical hand.

A 60-year-old patient with end-stage renal disease was referred to our institute with ischemic tissue loss and pain at rest of the fourth finger of the left hand. Lesions involved the subclavian artery, the brachial artery, the ulnar artery, the radial artery and the palmer arch. After successful angioplasty with noble technique, patient's symptoms were disappeared immediately and ischemic lesions were healed at only 1-month follow-up. This interesting case report may illustrate a help of treatment strategy of critical hand ischemia with complex lesions.

Absence of circadian variation of acute coronary syndrome onset in chronic kidney disease patients.

BACKGROUND: Several studies have reported on the circadian variation in acute coronary syndrome (ACS) onset. The influence of morning blood pressure surge, platelet aggregation and sympathetic activity is believed to cause this circadian variation. At the same time, a high frequency of ACS and sympathetic nerve hyperactivity has been reported in chronic kidney disease (CKD). Therefore, we investigated the relationship between CKD and the circadian variation in ACS. METHODS: This study included 460 consecutive patients undergoing primary percutaneous coronary intervention for ACS between 2003 and 2009. Patients undergoing hemodialysis were excluded. The subjects were divided into two groups according to the value of estimated glomerular filtration rate (eGFR): CKD group [eGFR ≤ 60 ml/min/1.73 m2 by Modification of Diet in Renal Disease (MDRD) equation] and No CKD group (eGFR > 60 ml/min/1.73 m2 by MDRD equation). Clinical and angiographic characteristics, as well as the time distribution of ACS, were compared between the two groups. RESULTS: There were no significant differences in clinical and angiographic characteristics between the two groups. A significant increase in morning coronary events was observed in the No CKD group. This increase was absent in the CKD group. CONCLUSIONS: The existence of CKD affected the circadian variation associated with the more frequent ACS onset observed in the No CKD group patients. Probably, these data may suggest the cause of frequent cardiovascular events in CKD patients.

Relation of coronary plaque composition determined by 64-slice multidetector computed tomography in patients with suspected coronary heart disease.

Sixty-four-slice multidetector row computed tomography is a noninvasive method of assessing coronary artery stenosis and plaque composition. The aim of this study was to clarify the relation between plaque composition and coronary heart disease. Three hundred sixty consecutive patients and 1,085 plaques were evaluated using 64-slice multidetector row computed tomography. On axial or cross-sectional multiplanar reconstruction images, 3 regions of interest were randomly selected within each plaque. Soft plaques and calcified plaques were defined as having computed tomographic densities <50 and >130 Hounsfield units, respectively. The association between coronary risk factors and plaque composition was analyzed. The number of plaques and the mean computed tomographic density of plaques were significantly higher in men than in women (p = 0.002 and p = 0.04, respectively). Coronary plaques were more frequent in patients with stroke, diabetes, hypertension, and dyslipidemia than in patients without these conditions (all p values <0.001). Calcified plaques were more frequent in patients with hypertension (p = 0.02), and patients with calcified plaques also had significantly lower low-density lipoprotein cholesterol levels (p <0.001). Soft plaques were more frequent in patients with dyslipidemia (p <0.001). Patients with soft plaques had significantly higher low-density lipoprotein cholesterol levels (p = 0.02) and lower high-density lipoprotein cholesterol levels (p <0.001) than those without soft plaques. In conclusion, 64-slice multidetector row computed tomography is a useful noninvasive method for quantifying coronary plaques.

Higher body mass index at the time of acute myocardial infarction is associated with a favorable long-term prognosis (8-year follow-up).

Obesity is an important public health problem, especially among patients with cardiovascular disease. However, little is known about the impact of obesity on the long-term prognoses of patients with acute myocardial infarction (AMI). Major adverse cardiac and cerebrovascular events (MACCE) consist of all causes of death, stroke, target lesion revascularization, target vessel revascularization, non-fatal myocardial infarction, and hospitalization. From January 2001 to March 2005, we analyzed 121 patients who survived >30 days after suffering their first AMI of the left anterior descending artery for MACCE. The mean follow-up period for this study was 59 ± 26 months. Seventy-five patients presented with normal weight (BMI <25 kg/m(2)) and 46 were obese (BMI >25 kg/m(2)). During the follow-up period, 56 patients presented MACCE, including 18 deaths, 11 strokes, and seven non-fatal myocardial infarctions. Normal weight was significantly associated with the occurrence of MACCE (p = 0.012). Grouping of the patients by BMI and homeostasis model assessment ratio (HOMA-R) indicated that the combination of a higher BMI (>25) and lower insulin resistance (HOMA-R < 2.0) provided the best prognosis (p = 0.0006). Kaplan-Meier curves stratified to the four groups, sorted by diabetes mellitus and BMI at admission, showed that the normal weight patients with diabetes mellitus presented the highest risk of MACCE (p < 0.0001). Patients with higher BMI and no insulin resistance or diabetes mellitus present better long-term outcomes following anterior AMI.

Bilateral spontaneous renal artery dissection.

Spontaneous renal artery dissection is a rare condition that precedes renal infarction. We describe a 48-year-old, normotensive healthy woman presenting with left flank pain of sudden onset. Enhanced abdominal computed tomography demonstrated a dissecting intimal flap of the left renal artery complicating renal infarction. Doppler ultrasonography, selective angiography, and intravascular ultrasound revealed a dissecting intimal flap, with a large false lumen and narrow true lumen, of the renal artery bilaterally. Conservative management was undertaken with anticoagulant and analgesic therapy, and the patient was discharged after an uneventful clinical course.

Combined assessment of chronic kidney disease and subclinical peripheral artery disease used to predict future cardiac events.

BACKGROUND: Both the presence of peripheral arterial disease and chronic kidney disease has been reported to be independent risk factors associating with poor prognosis. However, the impact of combination of peripheral arterial disease and chronic kidney disease remains unknown. METHODS: The long-term outcome in 715 consecutive patients who had undergone coronary angiogram for the evaluation of chest pain was analyzed. Patients on haemodialysis were excluded from this analysis. Cohort patients were divided into four groups according to the Ankle Brachial Index (ABI <0.9) and glomerular filtration rate (GFR <60 mL/min per m(2)): group A (n= 498; ABI >0.9, GFR >60); B (n = 65, ABI <0.9, GFR >60); C (n = 99; ABI >0.9, GFR <60); and D (n = 53; ABI <0.9, GFR <60). The mean follow-up period was 620 +/- 270 days and evaluated the major cardiac adverse events included survival, stroke, acute coronary syndrome and heart failure. RESULTS: The mean follow-up period was 620 +/- 270 days. Total long-term event was present in 89 patients (groups A-D were 9.4%, 18.5%, 15.2% and 28.3%, respectively). Long-term event rate was 28.3% for patients with the presence of peripheral arterial disease and chronic kidney disease, compared to 9.4% for those without peripheral arterial disease and chronic kidney disease (P < 0.0001). Kaplan-Meier event-free survival curves also showed that the combination of peripheral arterial disease and chronic kidney disease predicted long-term event rate. CONCLUSION: The combination of chronic kidney disease and ABI of less than 0.9 undergoing coronary angiogram is strongly associated with long-term event rate.

Acute compartment syndrome of the forearm that occurred after transradial intervention and was not caused by bleeding or hematoma formation.

Recently, transradial angiography and intervention have been performed with high success rates and low rates of vascular complications. The incidence of compartment syndrome after the transradial approach seems to be very low. However, bleeding in the arm can occur and may lead to the devastating complication of compartment syndrome of the forearm, which if not treated early, can evolve into a disability of the arm. In fact, most cases of such complications are caused by guidewire- or catheter-induced damage to small arterial branches that are considerably proximal to the puncture site. However, we encountered a case of compartment syndrome that was not caused by bleeding or hematoma formation and required urgent fasciotomy for its treatment. The forearm wounds were left open to allow the edema to resolve and closed after 1 week. The patient recovered and was discharged, with full movement of his forearm and hand. We suspect that an arterial spasm induced by the radial sheath or catheter resulted in ischemia of the forearm muscles. To our knowledge, this is the first reported case in which acute compartment syndrome of the forearm occurred after transradial intervention and was not due to bleeding or hematoma formation.

Aggressive statin therapy in multicenter and effectiveness for the reduction of intra-myocardial damage caused by non-ST elevation acute coronary syndrome: AMERICA study.

BACKGROUND: While preprocedural statin treatment for acute coronary syndrome (ACS) is widely regarded as beneficial, there has been no prospective randomized multicenter trial of patients with non-ST elevation ACS in the Japanese population to examine the efficacy of preprocedural aggressive statin use. The aim of this study was to confirm this effect by prospective randomized multicenter design. METHODS: Fifty patients who presented with non-ST elevation ACS were enrolled, and randomly assigned to aggressive statin administration before percutaneous coronary intervention (PCI). Troponin-T (TnT), creatine phosphokinase (CK), CK-myocardial band (CK-MB), high-sense C-reactive protein (hs-CRP), and brain natriuretic peptide (BNP) were measured at baseline and/ or after procedure. RESULTS: Three days after PCI, the statin group had significantly less CK elevation compared with the nonstatin group (84+/-17 IU/l versus 180+/-68 IU/l, respectively, p = 0.02). CK-MB elevation also tended to be lower in the statin group than in the nonstatin group (3.2+/-1.9 versus. 7.0+/-3.0, respectively, p = 0.07), as was BNP level (3.2+/-1.9 versus 7.0+/-3.0 pg/ml, respectively, p = 0.07). The change of serum LDL cholesterol was significantly correlated with CK (p = 0.01) and TnT (p = 0.02) at 1 day after PCI. CONCLUSIONS: Aggressive statin usage before PCI to Japanese patients with non-ST elevation ACS appears to reduce myocardial damage after procedure. The degree of serum lipid level reduction may reflect the vulnerability of atheromatous plaques that could cause cardiac damage after PCI.

Comparison of the in vitro performance of 6 and 7 French aspiration catheters.

OBJECTIVE: A comparison of aspiration catheters that have been approved for real-world use was carried out in vitro. BACKGROUND: Myocardial damage occurs during therapeutic aspiration of thrombus. The relative efficiency of aspiration may be important in this regard. METHODS: Using saline and human clot, nine aspiration catheters were compared Thrombuster III(R)N (6 Fr and 7 Fr), ZEEK (6 Fr), Rebirth (7 Fr), Eliminate (6 Fr and 7 Fr), Pronto (6 Fr), and Export(R) (6 Fr and 7 Fr). Tracking was assessed from the resistance required to pass the catheter through a vessel model. Pushability was determined from the difference between the load at the hand piece and tip of the catheter during advancement through the vessel model. RESULTS: The Thrombuster III(R)N (6 Fr and 7 Fr) showed significantly better aspiration performance, although the ranking order of the catheters was not the same for saline and clot. The Thrombuster III(R)N also showed the best tracking with low resistance and was the easiest catheter to advance, as evaluated based on pushability. CONCLUSIONS: In the present in vitro evaluation system, the Thrombuster III(R)N performed better than other catheters.

Comparison of coronary arterial finding by intravascular ultrasound in patients with "transient no-reflow" versus "reflow" during percutaneous coronary intervention in acute coronary syndrome.

Previous studies have shown that transient no-reflow during coronary intervention but with Thrombosis in Myocardial Infarction (TIMI) grade 3 flow at the completion of the procedure is associated with increased in-hospital and 6-month mortality. We hypothesized that the use of intravascular ultrasound before intervention could identify morphologic features that were predictive of transient no-reflow in patients who had acute coronary syndrome (ACS). We analyzed 220 patients with ACS who had suitable intravascular ultrasound images that were acquired before intervention. We defined "transient no-reflow" as TIMI grade 0, 1, or 2 flow during the procedure and TIMI grade 3 flow at the completion of the procedure. We defined "reflow" as good coronary flow (TIMI grade 3 flow) during and after the procedure. Patients were categorized to a transient no-reflow group (n = 20) or a reflow group (n = 200). In the transient no-reflow group, vessel area and amount of plaque burden in the culprit lesion were significantly greater than in the reflow group (vessel 20.8 +/- 5.4 vs 16.4 +/- 6.2 mm(2), p < 0.01; plaque burden 0.90 +/- 0.03 vs 0.83 +/- 0.08, p < 0.001). The presence of ruptured plaque, lipid pool-like images, and thrombus formation were significantly higher in the transient no-reflow group than in the reflow group. Multivariate analysis identified the presence of thrombus formation (odds ratio 4.53, 95% confidence interval 1.03 to 20.0, p = 0.04) and larger plaque burden (odds ratio 1.79, 95% confidence interval 1.01 to 3.23, p = 0.05) as independent predictors of transient no-reflow. In conclusion, lesion morphologies are different for transient no-reflow and reflow. These findings suggest that the presence of thrombus formation and large plaque burden increase the risk for developing transient no-reflow during coronary intervention for ACS.