Prediction of progression of coronary artery disease and clinical outcomes using vascular profiling of endothelial shear stress and arterial plaque characteristics: the PREDICTION Study.

BACKGROUND: Atherosclerotic plaques progress in a highly individual manner. The purposes of the Prediction of Progression of Coronary Artery Disease and Clinical Outcome Using Vascular Profiling of Shear Stress and Wall Morphology (PREDICTION) Study were to determine the role of local hemodynamic and vascular characteristics in coronary plaque progression and to relate plaque changes to clinical events. METHODS AND RESULTS: Vascular profiling, using coronary angiography and intravascular ultrasound, was used to reconstruct each artery and calculate endothelial shear stress and plaque/remodeling characteristics in vivo. Three-vessel vascular profiling (2.7 arteries per patient) was performed at baseline in 506 patients with an acute coronary syndrome treated with a percutaneous coronary intervention and in a subset of 374 (74%) consecutive patients 6 to 10 months later to assess plaque natural history. Each reconstructed artery was divided into sequential 3-mm segments for serial analysis. One-year clinical follow-up was completed in 99.2%. Symptomatic clinical events were infrequent: only 1 (0.2%) cardiac death; 4 (0.8%) patients with new acute coronary syndrome in nonstented segments; and 15 (3.0%) patients hospitalized for stable angina. Increase in plaque area (primary end point) was predicted by baseline large plaque burden; decrease in lumen area (secondary end point) was independently predicted by baseline large plaque burden and low endothelial shear stress. Large plaque size and low endothelial shear stress independently predicted the exploratory end points of increased plaque burden and worsening of clinically relevant luminal obstructions treated with a percutaneous coronary intervention at follow-up. The combination of independent baseline predictors had a 41% positive and 92% negative predictive value to predict progression of an obstruction treated with a percutaneous coronary intervention. CONCLUSIONS: Large plaque burden and low local endothelial shear stress provide independent and additive prediction to identify plaques that develop progressive enlargement and lumen narrowing. CLINICAL TRIAL REGISTRATION: URL: http:www.//clinicaltrials.gov. Unique Identifier: NCT01316159.

S100A12 as a marker to predict cardiovascular events in patients with chronic coronary artery disease.

BACKGROUND: S100A12, a calgranulin family protein released from white blood cells, is involved in inflammatory cardiovascular disease. It was hypothesized that the plasma level of S100A12 can be used to predict outcome in patients with chronic coronary artery disease (CAD). The purpose of this study was to clarify the clinical significance of S100A12 in patients with stable CAD. METHODS AND RESULTS: A total of 652 patients with stable CAD were studied. All patients underwent percutaneous coronary intervention and successful revascularization. Major adverse cardiovascular events (MACE) were defined as a composite of events of CHF, recurrence of angina pectoris, acute myocardial infarction, stroke, critical arrhythmia, intervention to peripheral arteries and cardiac death. The mean follow-up period was 973±639 days. MACE occurred in 108 patients (16.6%). Plasma S100A12 level had a significant positive correlation with high-sensitivity C-reactive protein (hs-CRP) level. On Kaplan-Meier curve analysis the incidence of MACE was significantly different among S100A12 quartiles (P=0.026). The highest S100A12 quartile (Q4) had a significantly higher MACE rate than the lowest quartile (Q1) (P=0.002). In contrast, hs-CRP was not significant for predicting MACE in the present subjects (P=0.074). A Cox proportional hazard model showed that S100A12 was an independent factor for predicting MACE in multivariate models. CONCLUSIONS: S100A12 could be a novel biomarker for predicting cardiovascular events for predicting MACE in patients with stable CAD.

Sirolimus eluting coronary stent implantation in patients on maintenance hemodialysis: the OUCH study (outcome of cypher stent inhemodialysis patients).

BACKGROUND: Pivotal studies on drug-eluting stents have excluded hemodialysis (HD) patients. No quantitative coronary angiography (QCA) analysis has been reported. METHODS AND RESULTS: The OUtcome of Cypher stent in Hemodialysis patients (OUCH) Study is a prospective non-randomized single-arm registry designed to assess the results of sirolimus-eluting stents in HD patients, with follow-up QCA in an independent core laboratory. The primary endpoint was the occurrence of target-vessel failure (TVF) defined as cardiac death, myocardial infarction (MI), and target-vessel revascularization (TVR) at 1 year. A total of 117 patients were enrolled. The TVF rate was 24.9% (2.6% cardiac death, 1.4% MI, 23.9% TVR), and stent thrombosis was documented in 1 patient (0.9%). Coronary calcification was a predictor of TVF. Late lumen loss (LLL) averaged 0.69±0.93mm. The histogram of LLL showed that a total of 76% of lesions were distributed the same normally as that in normal renal function (average LLL 0.20±0.29mm), but 24% of lesions were outliers (average LLL 2.07±0.62mm). CONCLUSIONS: This report describes different clinical and QCA results in HD patients as higher TVF rate, different predictive factors, and different histogram of LLL compared with normal renal function. The different histogram of LLL was the existence of many outliers with the same average and the same deviation, suggesting the loss of sirolimus had an effect on a significant number of HD patients.

Plasma endoglin as a marker to predict cardiovascular events in patients with chronic coronary artery diseases.

Recent clinical studies have revealed that the expression of endoglin, an accessory protein for the TGF-ß receptor, is increased in patients with atherosclerotic diseases. The plasma endoglin level is thought to represent endothelial activation, inflammation, and senescence. To clarify the significance of plasma endoglin in chronic coronary artery disease. Human umbilical vein endothelial cells (HUVECs) were cultured to examine changes in soluble endoglin (s-endoglin) levels caused by atherogenic stimulation in vitro. We studied 318 patients with stable coronary artery disease who underwent a successful percutaneous coronary intervention (PCI). Patients with acute coronary syndrome were excluded. Major adverse cardiovascular events (MACE) were congestive heart failure, acute myocardial infarction, stroke, and sudden cardiac death. All patients were followed-up to examine MACE after the procedure. We confirmed that the levels of s-endoglin was increased in the culture medium of HUVECs by senescence, tumor necrosis factor-α and hydrogen peroxide. In a clinical study, mean follow-up period was 1055 ± 612 days (49-2136 days) with 27 incidents of MACE (8.5%). We divided patients into three groups according to the plasma s-endoglin levels. Kaplan-Meier curves revealed that the highest endoglin group had a significantly higher MACE rate than the lowest endoglin group (log-rank test, p = 0.009). A Cox proportional hazards model showed that chronic kidney disease, left ventricular ejection fraction and s-endoglin level were significant factors to predict MACE. Plasma endoglin could be a marker to predict cardiovascular events in patients with chronic coronary artery disease after PCI.

A prospective multicenter registry of 0.010-inch guidewire and compatible system for chronic total occlusion: the PIKACHU registry.

OBJECTIVES: The aim of this study was to evaluate the safety and effectiveness of a 0.010-inch guidewire and a balloon catheter for treatment of chronic total occlusion (CTO). BACKGROUND: Pathological studies have shown that 60-70% of CTO lesions have microchannels of sizes equal to or less than 0.010 inch. METHODS: The PIKACHU registry is a prospective, multicenter registry study. A 0.010-inch guidewire had to be used as the first guidewire to attempt to pass the CTO lesion. The primary endpoint was device success using a 0.010 system. RESULTS: A total of 141 patients with 141 lesions were enrolled. The median duration of occlusion was 9 months (range 3-156). Average guiding catheter size was 5.8 +/- 0.7 Fr. and TRI was 76.6 %. CTOs were mostly between 10-20 mm long, observed in 53 occlusions. There were 107 lesions (75.9%) with bending of more than 45 degrees. Calcification was seen in 91 lesions (64.5%). A 0.010-inch guidewire was successfully passed through in 97 of 141 lesions (68.8%). A 0.010-inch guidewire compatible balloon catheter was passed in 87 of the 97 lesions (88.7%) and final PCI success was achieved in all the cases. The overall clinical success rate was 87.9% (124/141). No MACE or bleeding complications were observed. CONCLUSION: The PIKACHU registry data suggest that the 0.010-inch system is safe and practicable for treatment of CTO lesions.

A new 0.010-inch guidewire and compatible balloon catheter system: the IKATEN registry.

OBJECTIVE: To evaluate the safety and feasibility of a new 0.010-inch guidewire and a specialized balloon catheter for the 0.010-inch guidewire in routine percutaneous coronary intervention (PCI). BACKGROUND: Several reports have shown that a new 0.010-inch system is effective for specific situations where reduction of catheter size may be necessary. However, the safety of this system in routine PCI is unknown. METHODS: The IKATEN registry is a prospective, multicenter, nonrandomized registry study. Patients who underwent elective PCI with a 0.010-inch guidewire and its associated balloon catheter as primary devices were enrolled. The coprimary endpoints were clinical success and device success rates. The secondary endpoints were major adverse cardiac events (MACE) and bleeding complications. RESULTS: A total of 133 patients with 148 lesions were enrolled. The majority were male (75.3%), and mean age was 68 +/- 10 years. Type B2/C lesions comprised 60% of the lesions, prevalence of chronic total occlusion (CTO) was 16.9%, and bifurcation lesions were found in 22.3% of patients. A transradial approach was used in 79.7% of patients, and the average guiding catheter size was 5.1 +/- 0.4 Fr. Clinical success rate was 99.2%, and device success rate was 99.3%. Device failure occurred only in one case of chronic total occlusion because of unsuccessful guidewire passage. No MACE or bleeding complications were reported except for a small hematoma at the puncture site in one patient. Stent delivery success rate on 0.010-inch guidewire was 93.9% because of failure of stent balloon to pass eight lesions. CONCLUSION: The IKATEN registry data suggest that the 0.010-inch system is safe and its use is feasible in routine PCI including bifurcation and CTO lesions.

Determinants of thrombin generation, fibrinolytic activity, and endothelial dysfunction in patients on dual antiplatelet therapy: involvement of factors other than platelet aggregability in Virchow's triad.

AIMS: The aim of the study was to assess mechanisms and clinical backgrounds in order to determine residual platelet aggregability in dual antiplatelet therapy and to ascertain whether platelet aggregability is involved in systemic thrombogenicity. METHODS AND RESULTS: A cross-sectional study was conducted in 85 consecutive patients who underwent dual antiplatelet therapy (aspirin and thienopyridine/cilostazol) after percutaneous coronary intervention (PCI). Although serum thromboxane B(2) and dephosphorylation of vasodilator-stimulated phosphoprotein were significantly abolished, the platelet aggregation tests showed inter-individual differences that could be partly explained by plasma glucose levels. Platelet aggregability was not related to other factors involved in thrombogenicity. Thrombin generation assessed by soluble fibrin was independently associated with total cholesterol (beta = 0.349, P < 0.001), brain natriuretic peptide (beta = 0.222, P = 0.018), and ankle-brachial index (beta = -0.330, P = 0.001). Plasminogen activator inhibitor-1 was associated with the apnea-hypopnea index (beta = 0.300, P = 0.006). E-selectin was correlated with diabetes mellitus (beta = 0.279, P = 0.008) and body mass index (beta = 0.323, P = 0.002). CONCLUSION: Although dual antiplatelet therapy effectively inhibited its pharmacological targets, thrombin generation, inhibition of fibrinolytic activity, and endothelial dysfunction were determined by other clinical backgrounds. Our data suggested that some patients remain at risk of thrombotic complications after PCI and that these may benefit from anticoagulant treatment despite adequate dual antiplatelet therapy.

Can ischemic stroke be caused by acute reduction of blood pressure in the acute phase of cardiovascular disease?

Acute-phase cardiovascular disease (CVD) frequently presents with markedly elevated blood pressure (BP) levels and often requires fairly rapid lowering of BP. On the other hand, aggressive lowering of systemic BP to the point that the cerebral BP decreases below a certain threshold may result in ischemic stroke. The authors retrospectively studied 192 consecutive patients with CVD who had markedly elevated BP and end-organ damage. Ischemic stroke was noted in 12 of these patients during BP-lowering therapy. The incidence of ischemic stroke did not differ significantly between a standard BP-lowering group, in which the target BP reduction was within the parameters of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure guidelines, and a rapid BP-lowering group, in which the target BP was below these guidelines (7.1% vs 2.6%, respectively; P=.27, not significant). In stepwise multiple regression analysis, diabetes mellitus (beta=0.203, P=.008) and acute pulmonary edema (beta=0.228, P=.003) remained significant factors associated with the incidence of stroke. Thus, acute pulmonary edema and diabetes were the most important factors related to ischemic stroke during BP reduction in patients with marked elevations of BP regardless of the rapidity of BP lowering.

Life- and limb-saving endovascular therapy in a patient with acute abdominal aortic occlusion.

A 79-year-old man developed severe bilateral ischemic symptoms in the lower limbs. Chest-abdominal-pelvic contrast computed tomography (CT) showed acute occlusion involving the abdominal aorta, and endovascular therapy (EVT) was used as emergency treatment. Two self-expandable stents placed in the thrombus area resulted in restoration of blood flow to the lower limbs, despite limited stent expansion, and movement of these limbs. Follow-up CT showed good stent expansion. The patient had a favorable recovery without additional surgery. This case suggests that EVT might be an additional option for acute abdominal aortic occlusion if surgery or thrombolytic therapies are not possible.

A Prospective Multicenter Study Using a Virtual 3 Fr Percutaneous Coronary Intervention System: The V3 Registry.

OBJECTIVES: To evaluate the safety and feasibility of virtual 3 Fr (V3), sheathless 5 Fr percutaneous coronary intervention (PCI). BACKGROUND: A small-diameter guiding catheter (GC) makes less-invasive PCI possible. The V3 is an extremely slender PCI system; however, the outcome of using this system has not yet been determined. METHODS: The V3 registry is a prospective, multicenter, non-randomized study that enrolled patients who underwent elective V3-PCI. The primary endpoint was clinical success rate, and the secondary endpoints were PCI success rate in all cases, major adverse cardiac and cerebrovascular event (MACCE) at 30 days, and access-site complications. RESULTS: A total of 260 patients with 321 lesions were enrolled. Of this group, 70% were male and the mean age was 70.8 ± 10.0 years. Type B2/C lesions comprised 50.7% of the total. The clinical success rate was 95.8%, and the PCI success rate was 99.2%. PCI failure was reported in 2 chronic total occlusion cases. No MACCE was reported. Although there was no major bleeding, hematoma occurred at the puncture site in 12.7% of cases. There was a single radial artery occlusion (0.4%) without symptoms. CONCLUSIONS: PCI with the V3 was safe and feasible. Radial artery occlusion and major bleeding complications were extremely low. However, access-site hematoma frequently complicated catheter exchange.

Exercise at ventilatory threshold aggravates left ventricular remodeling in patients with extensive anterior acute myocardial infarction.

BACKGROUND: The effects of physical training on ventricular remodeling after extensive anterior acute myocardial infarction (AMI) have not yet been defined. This randomized controlled study examines whether exercise aggravates left ventricular (LV) remodeling in patients with extensive anterior AMI. METHODS: Forty-eight consecutive patients with a first extensive anterior AMI and an LV ejection fraction (EF) of <45% assessed with left ventriculography (LVG) within 3 days of onset were randomly allocated to a training group (n = 24) or a control group (n = 24). Exercise intensity was determined by the heart rate of each patient at ventilatory threshold (VT). Three weeks after onset, a second LVG was performed, followed by a supervised exercise program at VT for 12 weeks. The LVG was reassessed after the exercise program. We then calculated the global LV volume (end-diastolic volume index [EDVI], end-systolic volume index [ESVI]) and systolic expansion volume index (SEVI), a new parameter for measuring the infarction site expansion at the end-systolic phase. RESULTS: Both EDVI and ESVI significantly decreased in the control group from 1 to 4 months after onset (91.2 +/- 26.1 to 83.3 +/- 24.0 mL/m2, P <.05; 52.4 +/- 22.5 to 45.7 +/- 18.8 mL/m2, P <.01, respectively), but not in the exercise group. The SEVI also significantly decreased in the control group from 1 to 4 months (33.1 +/- 16.9 to 25.7 +/- 13.9 mL/m2, P <.05), but not in the training group (34.2 +/- 12.9 to 36.5 +/- 15.5 mL/m2, P = not significant). CONCLUSION: Exercise while healing in patients with extensive anterior AMI, even at the VT level, induces LV enlargement and thus might aggravate LV remodeling. Therefore, in these patients, clinicians should consider withholding exercise training for at least 8 weeks, versus the 3-week period used in this trial.

Comparison of frequency of radial artery occlusion after 4Fr versus 6Fr transradial coronary intervention (from the Novel Angioplasty USIng Coronary Accessor Trial).

The frequency of radial artery occlusion was compared between patients receiving 4Fr versus 6Fr transradial coronary interventions (TRIs) in an open-label randomized trial (ClinicalTrials.gov identifier: NCT00815997). The primary outcome measure was radial artery occlusion on the day after TRI. The secondary outcome measures were the procedural success, major advanced cardiac events, access site-related complications, procedural times, fluoroscopy times, and contrast dye usage. A total of 160 patients were included. The procedure was successful in 79 of 80 patients (99%) in both groups. Whereas the 4Fr group showed no access site-related complications, the 6Fr developed 5 (6%), including 3 radial artery occlusions and 2 bleedings (1 radial artery perforation and 1 massive hematoma; p = 0.02). Although the radial artery occlusion rate was lower in the 4Fr versus the 6Fr groups, the difference was not significant (0% vs 4%, p = 0.08). The mean hemostasis time was significantly shorter in the 4Fr than in the 6Fr groups (237 ± 105 vs 320 ± 238 minutes, p = 0.007). In conclusion, these findings suggest that 4Fr TRI may become a less invasive alternative to 6Fr TRI in treating coronary artery diseases.

High-sensitivity troponin T is a prognostic marker for patients with aortic stenosis after valve replacement surgery.

BACKGROUND: Aortic stenosis (AS) is recognized as a cause of sudden cardiac death. Recently, the measurement of high-sensitivity troponin T (hs-TnT) has become possible. Several studies have clarified that hs-TnT is a marker to indicate mortality of cardiovascular diseases. OBJECTIVES: To examine whether hs-TnT can be used as a prognostic marker to predict the operative outcome of AS. METHODS: We enrolled 60 patients with AS (mean age=68.7 ± 9.6 years, male/female=30/30). Cardiac catheterization and echocardiography were performed to evaluate the severity of AS. Aortic valve replacement surgery was performed in all patients. We defined major adverse cardiac events (MACE) as composite events of heart failure, fatal arrhythmia, and all causes of death. RESULTS: We followed up the patients for 922 ± 800 days. Mean left ventricular ejection fraction was 60.0 ± 1.8%. Mean aortic valve area was 0.61 ± 0.03 cm(2). MACE occurred in 11 patients (18%), including 5 sudden cardiac deaths. We divided the patients into three groups based on the percentile of the plasma levels of hs-TnT. Kaplan-Meier curve revealed a statistically significant difference in MACE rate among the groups (log-rank test, χ(2)=13.0, p=0.002). We conducted a Cox proportional hazard analysis with a model including age, sex, estimated glomerular filtration rate, and hs-TnT tertile as explanatory variables to predict MACE. We found that hs-TnT tertile to be a significant factor to predict MACE (hazard ratio: 3.71, p=0.03). CONCLUSIONS: hs-TnT can be a prognostic marker for patients with AS after valve replacement surgery.

A case of Takayasu arteritis with repeated coronary artery restenosis after drug-eluting stent implantation successfully treated with a combination of steroids.

A 52-year-old woman with Takayasu arteritis developed acute coronary syndrome and received percutaneous coronary intervention (PCI). The patient experienced restenosis three times even with drug-eluting stent (DES) implantation. We started steroid administration after the fourth PCI to reduce inflammation due to autoimmunity. With DES and a steroid combination, the patient remained free of chest pain, and a follow-up angiography demonstrated good patency of the stent site. Since in-stent restenosis may result from a complicated combination of neointimal proliferation and autoimmune mechanisms, physicians should consider a combination of DES and a steroid for the treatment of coronary artery disease in Takayasu arteritis.

Lack of association between serum paraoxonase-1 activity and residual platelet aggregation during dual anti-platelet therapy.

High residual platelet aggregability during thienopyridine treatment occurs because of low levels of the active drug metabolite, and is associated with an increased rate of major adverse cardiovascular events. Recent findings suggest that paraoxonase-1 (PON1) is a major determinant for clopidogrel efficacy. The aim of this study was to assess the impact of serum PON1 activity on platelet aggregability in thienopyridine-treated patients. In 72 patients receiving treatment with aspirin and ticlopidine after acute coronary syndrome, various laboratory data including the formation of platelet aggregations induced by agonists were compared with serum PON1 activities, measured as paraoxonase and homocysteine thiolactone hydrolase (HTLase). Serum paraoxonase activity was significantly associated with HTLase activity (R=0.4487, P<0.0001). These PON1 activities were not correlated with any parameters for platelet aggregation, hypertension, sleep apnea, and diabetes mellitus. In contrast, serum PON1 activities seemed to be involved in cardiac function, with brain natriuretic peptide and ejection fraction being significantly correlated with serum HTLase activity (R=-0.2767, P=0.0214) and paraoxonase activity (R=0.2558, P=0.0339), respectively. Paraoxonase activity also demonstrated a significant association with increased levels of ankle-brachial index (R=0.267, P=0.0255). Serum PON1 activities did not influence platelet aggregability during treatment with thienopyridine. However, they might modulate cardiac function after acute coronary syndrome and progression of atherosclerosis.

Roles of ghrelin in left-ventricular remodelling after acute myocardial infarction.

OBJECTIVE: The purpose of this study was to elucidate the role of ghrelin after acute myocardial infarction (AMI) in left ventricular (LV) remodelling. DESIGN: Prospective observational study. SETTING: Jichi Medical University Hospital. PATIENTS: Fifty consecutive patients experiencing their first AMI. INTERVENTIONS: Ghrelin was measured on the day of admission, day 7, day 14 and 6 months after AMI. Patients were treated by percutaneous coronary intervention, and successful myocardial reperfusion was accomplished within 12 h after onset. To analyse LV remodelling, the authors performed left ventriculographies on the day of admission and 6 months after AMI. MAIN OUTCOME MEASURES: Changes in LV volume. RESULTS: Plasma ghrelin increased significantly after AMI (admission: 40.9±7.3; day 7: 89.5±11.0; day 14: 92.6±11.8 fmol/ml, p<0.0001). There was a significant correlation between ghrelin on day 14 and changes in LV volume over 6 months (r=+0.46, p<0.001). Multivariate regression analysis showed that ghrelin on day 14 is a significant predictor of LV remodelling after AMI (ß=+0.44, p=0.001). CONCLUSION: To our knowledge, this is the first report that shows a relation between circulating ghrelin after AMI and the progression of LV remodelling in the chronic phase. The elevation of ghrelin after AMI might be a compensatory mechanism to attenuate LV remodelling.