Addition of cilostazol to aspirin therapy for secondary prevention of cardiovascular and cerebrovascular disease in patients undergoing percutaneous coronary intervention: A randomized, open-label trial.

BACKGROUND: Patients with established coronary artery disease are at increased risk for future ischemic events and require secondary prevention for systemic vascular disease. We performed a randomized clinical trial to evaluate the impact of cilostazol on cardiovascular and cerebrovascular disease in patients undergoing percutaneous coronary intervention. METHODS: A total of 514 patients who had undergone coronary stent implantation >6 months previously and were thought to no longer need dual antiplatelet therapy with aspirin and a thienopyridine were randomly assigned to receive aspirin plus cilostazol therapy or aspirin therapy alone after discontinuation of thienopyridine therapy. The primary efficacy end point was a composite of all-cause death, myocardial infarction, stroke, or cardiovascular or cerebrovascular revascularization at 2 years after randomization. The main safety end point was major or minor bleeding, according to the Thrombolysis in Myocardial Infarction bleeding definition. RESULTS: At 2 years, follow-up clinical data were available for 98.1% of patients. The primary efficacy end point occurred in 13.9% of the aspirin plus cilostazol group versus 22.1% of the aspirin-only group (hazard ratio 0.61, 95% CI 0.40-0.93, P = .021). The rate of major or minor bleeding was not significantly different between the aspirin plus cilostazol and aspirin-only groups (1.6% and 4.0%, respectively, hazard ratio 0.40, 95% CI 0.13-1.28, P = .12). CONCLUSIONS: In patients who underwent coronary stent implantation, the addition of cilostazol to aspirin therapy was associated with lower rates of cardiovascular and cerebrovascular events at 2 years compared with aspirin monotherapy.

Detailed observation of arterial healing after stent implantation in swine arteries by using optical coherence tomography.

BACKGROUND: Histopathological examination is not suitable for sequential in vivo analysis of arterial healing after stenting because it can be performed only after the animals are killed. Optical coherence tomography (OCT) provides higher resolution than intravascular ultrasound (IVUS). The aim of this study was to compare arterial healing images after stenting on the basis of the findings of histopathological examination, IVUS, and OCT. METHODS: We examined 12 vessels; 12 bare-metal stents were implanted in 6 miniature swine. Histopathological examination, IVUS, and OCT imaging were performed at 1 and 4 weeks after stenting. For quantitative analysis of IVUS and OCT images, we examined cross-sectional frames at 1-mm intervals. For neointimal coverage analysis, the neointimal coverage score was classified into 1 of the 4 categories. A fully covered strut was scored as 3, a partially covered strut was scored as 1 or 2, and an uncovered strut was scored as 0. RESULTS: In IVUS and OCT analyses, the average neointimal thickness increased between 1 and 4 weeks (p < 0.0001). OCT revealed higher scores at 1 and 4 weeks than IVUS did (at week 1, p < 0.0001; at week 4, p < 0.0001). OCT analysis evaluated the neointimal coverage similarly to histopathological examination. CONCLUSIONS: On assessment of arterial healing after stenting, we found that the results of the histological examination were more similar to those of the OCT analysis than to those of the IVUS. An OCT imaging device can be used to precisely and sequentially analyze the arterial healing process after stenting.

Incidence and predictors of plaque rupture in the peripheral arteries.

BACKGROUND: Plaque rupture may be present in the peripheral arteries of the patients at high risk for cardiovascular events and is possibly associated with vascular vulnerability. METHODS AND RESULTS: One hundred one iliofemoral arteries from 101 patients undergoing angioplasty were studied. Intravascular ultrasound imaging was performed before intervention. Plaque rupture was defined as presence of a cavity that communicated with the lumen with an overlying residual fibrous cap fragment. Incidence, numbers, and location of the plaque rupture were investigated. Plaque rupture was found in 42 of 101 arteries (42%). Patients with plaque rupture had significantly higher prevalence of acute coronary syndrome than did patients without plaque rupture (42% vs 16%, P=0.01). By multivariable logistic regression analysis, acute coronary syndrome (P=0.004) and male sex (P=0.01) were independent clinical correlates of plaque rupture. During follow-up (median, 14.7 months), the incidence of major adverse cardiac or cerebrovascular events (death, myocardial infarction, and ischemic stroke) was similar between the 2 groups. The incidence of major adverse cardiac or cerebrovascular events plus peripheral vascular events (unplanned vascular intervention and amputation) was significantly higher in patients with plaque rupture than in patients without plaque rupture (46% vs 21%, P=0.008). By multivariable Cox regression analysis, plaque rupture (hazard ratio=2.80, 95% CI: 1.23 to 6.37, P=0.01) and Fontaine stage IV (hazard ratio=3.50, 95% CI: 1.58 to 7.71, P=0.002) were independent predictors of major adverse cardiac or cerebrovascular events plus peripheral vascular events. CONCLUSIONS: Ruptured plaque of the iliofemoral arteries is a common finding. Patients with plaque rupture had a higher prevalence of history of acute coronary syndrome and lower major adverse cardiac or cerebrovascular events plus peripheral vascular event-free survival.

Age- and gender-specific changes in the left ventricular relaxation: a Doppler echocardiographic study in healthy individuals.

BACKGROUND: Although left ventricular diastolic function has been shown to deteriorate with advancing age, its gender-specific change is unknown. The aim of this study was to investigate age- and gender-specific changes in tissue Doppler-derived left ventricular diastolic index, E'. METHODS AND RESULTS: A total of 1333 healthy individual without known heart disease or hypertension (mean age, 55 years; range, 10 to 89) were enrolled and studied. Peak early mitral annular velocity (E') and peak late mitral annular velocity (A') were recorded and measured. As an index of the left ventricular relaxation, E' was used. As an index of the left ventricular filling pressure, E/E' was calculated. Although systolic indices poorly correlated with age, diastolic indices correlated well with age. Among those aged 30 to 39 and 40 to 49 years, E' was significantly lower in males than in females. In subjects aged 50 to 59 and 60 to 69 years, E' was similar in both genders. Among those aged 70 to 79 and 80 to 89 years, E' was significantly lower in females than in males. Predictors of the lowest quartile of E' among subjects aged >50 years were age (P<0.0001; chi(2)=66.11; odds ratio, 1.08; 95% CI, 1.058 to 1.097) and female gender (P=0.002; chi(2)=9.23; odds ratio, 1.68; 95% CI, 1.202 to 2.343). CONCLUSIONS: Age-related changes in diastolic indices were gender specific. In the elderly population, diastolic function deteriorated more significantly in the female gender than in the male gender. These results may explain the relatively higher incidence in elderly females among patients with diastolic heart failure and higher cardiovascular mortality in the female gender.

Elevated E/E' predicts prognosis in congestive heart failure patients with preserved systolic function.

BACKGROUND: Although approximately 50% of heart failure patients are reported as heart failure with preserved left ventricular systolic function (HFPSF), echocardiographic prognostic predictors have not been well investigated. Recently, the tissue Doppler-derived index, the ratio of the early transmitral flow velocity and the early mitral annular velocity (E/E'), was reported as useful in predicting prognosis of patients with heart diseases. The purpose of this study was to investigate whether E/E' predicts prognosis in HFPSF. METHODS AND RESULTS: A total of 50 patients with HFPSF (ejection fraction >50%) were consecutively enrolled and studied. Echocardiographic examination was performed on admission and repeated after optimized medical therapy. Cardiac events were defined as death and unplanned hospitalization because of congestive heart failure. Cardiac event-free survival curves from patients with E/E' >15 and E/E' 15 after medical therapy showed significantly lower cardiac event-free survival than patients with E/E' 15 after medical therapy was the only independent predictor of cardiac events (P=0.037, risk ratio=6.1, 95% confidence interval: 1.12-33.3) in patients with HFPSF. CONCLUSIONS: Elevated E/E' after optimized medical therapy may be useful in predicting cardiac events in patients with HFPSF.

Functional mitral regurgitation predicts prognosis independent of left ventricular systolic and diastolic indices in patients with ischemic heart disease.

OBJECTIVE: The purpose of this study was to investigate the prognostic impact of functional mitral regurgitation (FMR) and tissue Doppler-derived index of left ventricular filling pressure, E/E', on long-term clinical outcome in a broad spectrum of ischemic heart disease. BACKGROUND: FMR has been shown to predict prognosis in patients with myocardial infarction. METHODS: A total of 524 patients with ischemic heart disease were enrolled. Patients were categorized according to the presence (n = 58) or absence (n = 466) of severe FMR. RESULTS: Patients with severe FMR were significantly older. By echocardiography, ejection fraction was significantly lower (43.0% +/- 14.6% vs. 56.4% +/- 12.8%, P < .01) and E/E' was significantly higher (21.3 +/- 9.0 vs. 14.6 +/- 6.4, P < .01) in patients with FMR than without FMR. Event-free (death and congestive heart failure) survival was significantly lower in patients with FMR than in those without (log-rank P < .0001). By multivariate logistic regression analysis, E/E' greater than 15 (relative risk [RR] 3.49; 95% confidence interval [CI] 2.08-5.88, P < .0001), ejection fraction less than 50% (RR 3.33; 95% CI 1.96-5.64, P < .0001), and severe FMR (RR 2.34; 95% CI 1.22-2.48, P = .01) were independent echocardiographic predictors of cardiac events. In further analysis of 116 patients matched by a propensity score, severe FMR remained associated with reduced event-free survival (log-rank P = .004). CONCLUSION: FMR is a strong predictor of cardiac events independently of left ventricular systolic and diastolic indices in patients with ischemic heart disease.

Impact of statin therapy on systemic inflammation, left ventricular systolic and diastolic function and prognosis in low risk ischemic heart disease patients without history of congestive heart failure.

OBJECTIVES: The aim of this study was to investigate the impact of statin on systemic inflammation, left ventricular systolic and diastolic function and prognosis in low risk ischemic heart disease (IHD) patients. METHODS: A total of 430 consecutive IHD patients without congestive heart failure were enrolled. One hundred and thirty-two patients (31%) were treated with statin (statin group) and 298 patients (69%) were not (no statin group). Echocardiographic indices, high sensitivity CRP, and prognosis were compared. RESULTS: Ejection fraction (EF) was significantly higher in the statin group (p<0.01). The ratio of the early transmitral flow velocity to early diastolic velocity of the mitral annulus (E/E') was significantly lower in the statin group than in the no statin group (p<0.01). Although LDL-cholesterol level did not differ, high sensitivity CRP level was significantly lower in the statin group (0.3+/-0.5 vs. 1.1+/-2.3 mg/dl, p=0.005). Cardiac event-(cardiac death and congestive heart failure)free survival rate was significantly higher in the statin group than in no statin group (Log-rank p<0.0001). By multivariate logistic regression analysis, E/E' > 15 (p=0.002), EF < 50% (p=0.003), lack of statin use (p=0.009), left atrial dimension (p=0.02), use of diuretics (p=0.03) and lack of beta-blockers (p=0.04) were independent predictors of cardiac events. In 248 patients matched by propensity scores, statin remained associated with better event-free survival (Log-rank p=0.006). CONCLUSION: Statin may improve left ventricular function and thus improve the prognosis in low risk patients with IHD.

Method analysis for optimal continuous imaging using intravascular optical coherence tomography.

OBJECTIVES: Optical coherence tomography(OCT)is a high-resolution imaging method that can clearly visualize vessels through the displacement of blood with flushing agents. Continuous imaging methods have not been established. This study investigated optimal methods for continuous OCT imaging. METHODS: Thirty-four arteries with stent implantation (24 peripheral and 10 coronary arteries)in 14 pigs were examined using OCT with a motorized pullback device. Two imaging methods (flush alone by liquid substance and flush with occlusion) were compared. Adequate image acquisition was defined as the entire circumferential intimal layer being detectable within continuous segments. To investigate factors that could influence image quality, stented regions were divided into 4-5 mm segments. RESULTS: The flush with occlusion method provided better OCT images compared to flush alone (flush with occlusion: 60.9%, flush alone: 8.7%, p = 0.0002). Using the flush with occlusion method, the rate of adequate image acquisition was 64.4% and visualization of > 75% intimal circumference was 83.5%. Intravascular ultrasound could detect all stented regions. Segmental analyses found more adequate images were detected in smaller vessels (adequate segment: 3.8 +/- 0.4 mm, inadequate segment: 4.2 +/- 0.8 mm, p < 0.0001) or with centered image wire position (adequate segment: center 35%, inadequate segment: center 14%, p = 0.003). In addition, side branches did not affect image quality. CONCLUSIONS: To acquire continuous OCT images, the flush with occlusion method was more effective compared to flush alone. Moreover, image quality is affected by vessel size and imaging wire position. These results suggest that optimized OCT imaging can provide continuous vessel detection.

Acute myocardial infarction: clinical characteristics and plaque morphology between expansive remodeling and constrictive remodeling by intravascular ultrasound.

BACKGROUND: According to recent intravascular ultrasound (IVUS) studies, expansive remodeling (ER) at the culprit lesion has been observed in almost 50% of patients with acute coronary syndrome and constrictive remodeling (CR) in 30%. The purpose of this study is to investigate the difference between ER and CR at the culprit lesion in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Preinterventional IVUS images of 73 patients with AMI were identified. The remodeling index (RI) was defined as the ratio of the external elastic membrane (EEM) areas at the culprit lesion to the EEM areas at the proximal reference site. Expansive remodeling was defined as an RI > 1.05; CR, as an RI < 0.95. In patients with AMI, 40 patients (55%) showed ER on IVUS, whereas CR was observed in 18 patients (25%). Patients with ER were significantly older than those with CR (P < .005). The frequency of the presence of calcifications was higher in patients with ER than in those with CR (P < .0005). In patients with AMI with ER, soft plaque with small calcium was the most frequent (58%). Multivariate analysis revealed that age and the presence of calcifications remained as independent predictors of ER. CONCLUSIONS: These findings suggest that ER relates to old age and calcification, and CR may contribute to early plaque progression than ER in patients with AMI.

Quadricuspid aortic valve: report of three cases.

Quadricuspid aortic valve (QAV) is a very rare congenital malformation. We have encountered three patients with QAV, of whom one patient may be the eldest reported patient with this particular anatomical abnormality. In another of our patients, there was aortic regurgitation, aortic stenosis, and healed infective endocarditis, with adhesion of the tips of the cusps. In all three patients, the cusps were all of equal size. Until now, there has been very little documented evidence about the anatomical variations in QAV or its relationship with infective endocarditis. From the available literature, we conclude that the anatomical variations in patients with QAV are similar to those in patients with quadricuspid pulmonary valve, and infective endocarditis may not be an uncommon complication.

Impact of HMG-CoA reductase inhibitors for non-treated coronary segments.

BACKGROUND: HMG-CoA reductase inhibitors (statin) have been reported to decrease coronary artery events in several angiographic studies. However, the mechanism by which statin achieve this is still unclear. The purpose of this study was to identify the effect of statin on coronary plaque using serial intravascular ultrasound analysis. METHODS AND RESULTS: In this study, 48 patients with 48 lesions were divided into the prescribed group (statin group, n = 22) or the non-prescribed group (control group, n = 26) after successful coronary artery stenting. IVUS images were obtained at consecutive 5 mm segments, 5 mm from the proximal stent edge, immediately after stenting and at 6 months follow up. External elastic membrane volume (EEMV), lumen volume (LV) and plaque volume (PV) were measured using Simpson's method. The control group revealed no significant serial change in EEMV, PV, and LV during 6 months. On the other hand, the statin group revealed significant reductions of PV (35.5 +/- 12.7 mm3 vs 30.9 +/- 15.6 mm3, p = 0.001), resulting in increase of LV (47.7 +/- 19.8 mm3 vs 52.5 +/- 22.2 mm3, p = 0.003) without EEMV change (82.8 +/- 21.8 mm3 vs 83.9 +/- 25.7 mm3, p = NS). Although percent EEMV and percent LV changes showed no differences between the two groups, a larger percent PV change was observed in the statin group compared to the control group (control; 5.8 +/- 20.3% vs statin; -20.4 +/- 21.8%, p = 0.02). CONCLUSION: The results of this study suggest that statin administration for 6 months reduces coronary plaque without positive vessel remodeling.