Atsushi Yamamuro

Troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non–insulin dependent diabetes mellitus: A serial intravascular ultrasound study

OBJECTIVES The aim of the present study was to determine whether troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non-insulin dependent diabetes mellitus (NIDDM). BACKGROUND Increased in-stent restenosis in patients with diabetes mellitus is due to accelerated neointimal tissue proliferation after coronary stent implantation. Troglitazone inhibits intimal hyperplasia in experimental animal models. METHODS We studied 62 stented lesions in 52 patients with plasma glucose levels (PG) > or = 11.1 mmol/liter at 2 h after 75 g oral glucose load. The study patients were randomized into two groups: the troglitazone group of 25 patients with 29 stents, who were treated with 400 mg of troglitazone, and the control group of 27 patients with 33 stents. All patients underwent oral glucose tolerance tests before and after their six-month treatment period. The sum of PG (sum of PG) and the sum of insulin levels (sum of IRI) were measured. Serial (postintervention and at six-month follow-up) intravascular ultrasound studies were performed. Cross-sectional images within stents were taken at every 1 mm, using an automatic pullback. Stent areas (SA), lumen areas (LA), and intimal areas (IA = SA - LA) were measured and averaged over a number of selected image slices. The intimal index was calculated as intimal index = averaged IA/averaged SA x 100%. RESULTS There were no differences between the two groups before treatment in sum of PG (31.35 +/- 3.07 mmol/liter vs. 32.89 +/- 4.87 mmol/liter, respectively, p = 0.2998) and sum of IRI (219.6 +/- 106.2 mU/liter vs. 209.2 +/- 91.6 mU/liter, respectively, p = 0.8934). However, reductions in sum of PG at the six-month follow-up in the troglitazone group were significantly greater than those in the control group (-21.4 +/- 8.8% vs. -4.5 +/- 7.4%, respectively, p < 0.0001). Likewise, decreases in sum of IRI were greater in the troglitazone-treated group (-31.4 +/- 17.9% vs. -1.9 +/- 15.1%, respectively, p < 0.0001). Although, there were no differences between the two groups in SA at postintervention (7.4 +/- 2.2 mm2 vs. 7.3 +/- 1.7 mm2, respectively, p = 0.9482) and at follow-up (7.3 +/- 2.3 mm2 vs. 7.3 +/- 1.8 mm2, respectively, p = 0.2307), the LA at follow-up in the troglitazone group was significantly greater than that in the control group (5.3 +/- 1.7 mm2 vs. 3.7 +/- 1.7 mm2, respectively, p = 0.0002). The IA at follow-up in the troglitazone group was significantly smaller than that in the control group (2.0 +/- 0.9 mm2 vs. 3.5 +/- 1.8 mm2, respectively, p < 0.0001). This was also true for intimal index (27.1 +/- 11.5% vs. 49.0 +/- 14.4%, respectively, p < 0.0001). CONCLUSIONS Serial intravascular ultrasound assessment shows that administration of troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with NIDDM.

Long-Term Prognosis of Patients With Type A Aortic Intramural Hematoma

Background—The long-term clinical course of patients with type B aortic intramural hematoma (IMH) and predictors for progression remains unknown. The difference of aortic pathology may have a different impact on clinical course compared with classic aortic dissection (AD). The purpose of this study was to investigate long-term clinical course and predictors of progression in patients with type B IMH. Methods and Results—Clinical data were compared retrospectively between 53 patients with acute type B IMH (IMH group) and 57 patients with acute type B AD (AD group). All patients were treated initially with medical therapy. Two patients in IMH group and 14 patients in AD group underwent surgical repair because of aortic enlargement. The in-hospital mortality rate in IMH group was significantly lower than that in AD group (0% and 14%, P =0.006). Mean follow-up periods were 53±43 months, which revealed 3 and 5 late deaths, respectively. Eleven patients with IMH showed progression (development of aortic dissection or aortic enlargement) in follow-up imaging study. The actuarial survival rates in IMH group were 100%, 97%, and 97% at 1, 2, and 5 years, which were significantly higher than those in AD group (83%, 79%, and 79%) (P =0.009). Multivariate analysis identified age >70 years and new appearance of an ulcerlike projection as the strongest predictors of progression in patients with IMH. Conclusions—Patients with type B IMH have better long-term prognosis than patients with AD. Older age and appearance of an ulcerlike projection are predictive for progression in patients with type B IMH.

Pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus: an intravascular ultrasound scanning study

BACKGROUND It has been reported that pioglitazone reduces neointimal hyperplasia after balloon-induced vascular injury in an experimental model. METHODS To determine whether pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus, we studied 44 stented lesions in 44 patients with diabetes mellitus who underwent successful coronary stent implantation. Study patients were randomized into 2 groups: the pioglitazone group (23 patients with 23 lesions) and the control group (21 patients with 21 lesions). All patients underwent serial quantitative coronary angiography and serial intravascular ultrasound scanning studies. With a motorized pullback system, multiple image slices within the stent were obtained at every 1 mm. The stent area and lumen area were measured, and the neointimal area was calculated. Measurements were averaged over the number of selected image slices. The neointimal index was calculated as the averaged neointimal area divided by the averaged stent area multiplied by 100 (%). RESULTS After 6 months of treatment, angiographic in-stent restenosis (17% vs 43%, respectively, P =.0994) and target lesion revascularization (13% vs 38%, respectively, P =.0835) were less frequent in the pioglitazone group than the control group; however, these differences did not reach significance. The intravascular ultrasound scanning study demonstrated that the neointimal index in the pioglitazone group was significantly smaller than that in the control group (28% +/- 9% vs 48% +/- 15%, respectively, P <.0001). CONCLUSION A serial intravascular ultrasound scanning assessment demonstrated that pioglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with type 2 diabetes mellitus.

Relation of Phasic Coronary Flow Velocity Characteristics With TIMI Perfusion Grade and Myocardial Recovery After Primary Percutaneous Transluminal Coronary Angioplasty and Rescue Stenting

BACKGROUND A residual stenosis and/or microvascular damage have been proposed as mechanisms of TIMI 2 flow for acute myocardial infarction. Coronary flow dynamics were assessed in patients with TIMI 2 flow to predict whether additional intervention would improve TIMI grade. METHODS AND RESULTS In 35 patients who had a successfully recanalized anterior acute myocardial infarction using angioplasty or rescue stenting, coronary flow patterns were compared with corresponding TIMI grade and regional left ventricular wall motion (LVWM) 1 month after the intervention. After angioplasty, the time-averaged peak velocity (APV) was lower in patients with TIMI 2 flow (n=22) than in those with TIMI 3 flow (n=13; 7.9+/-3.9 versus 20.6+/-5.1 cm/s; P<0.001). Two different flow patterns were recorded in patients with TIMI 2 flow (versus TIMI 3, P<0.001); patients with type 1 TIMI 2 flow (n=15) had a reduced diastolic APV (8.3+/-4.8 versus 24.2+/-7.4 cm/s), prolonged diastolic deceleration time (1176+/-455 versus 728+/-205 ms), and a small diastolic/systolic APV ratio (1.3+/-0.6 versus 2.1+/-0.7); patients with type 2 TIMI 2 flow (n=7) had systolic flow reversal (systolic APV, -7.9+/-4.6 versus 11. 7+/-4.5 cm/s), a rapid diastolic deceleration time (221+/-84 versus 728+/-205 ms), and a negative diastolic/systolic APV ratio (-2.1+/-1. 4 versus 2.1+/-0.7). A significantly lower mean chord LVWM (-3.0+/-0. 2 versus -1.9+/-0.8; P<0.001) and a greater number of chords <-2SD (50+/-2 versus 28+/-18; P<0.001) were present in patients with type 2 versus type 1 TIMI 2 flow. Stenting increased TIMI 2 flow to TIMI 3 flow more in patients with type 1 than type 2 flow (67% versus 0%; P=0.003). Patients with TIMI 2 flow after stenting continued to demonstrate a type 2 pattern, and they had poor LVWM recovery. CONCLUSIONS The differentiation between 2 types of TIMI 2 flow can predict the improvement of TIMI grade and LVWM recovery after additional stenting.

Annular Geometry in Patients With Chronic Ischemic Mitral Regurgitation: Three-Dimensional Magnetic Resonance Imaging Study

Background—Although animal studies showed that annular remodeling may be related to the pathogenesis of chronic ischemic mitral regurgitation (CIMR), little was known in humans. A better understanding of the precise 3D geometry of the mitral valvular-ventricular complex in CIMR is needed to devise a better surgical technique. The purpose of the study was to elucidate mitral annular geometry in patients with CIMR using cardiac MRI. Methods and Results—Thirty-eight patients with previous inferior or posterior myocardial infarction were studied. With the 3D reconstruction of the mitral annulus and subvalvular apparatus from a series of longitudinal cine MRIs, end-systolic mitral annulus dimensions and 3D geometry were calculated. Patients were grouped by mitral regurgitation grade using echocardiography (≥2+, n=15 versus ≤1+, n=23). Both septal-lateral and commissure-commissure mitral annular diameters were significantly greater in CIMR(+) patients (35±5 versus 30±4 mm, P=0.005; 46±6 versus 39±4 mm, P<0.001, respectively). The length of the fibrous annulus was significantly larger in CIMR(+) patients (28±3 versus 24±3 mm; P<0.001). The height of the annular “saddle horn” above a best-fit plane was lower in CIMR(+) patients (4.2±1.2 versus 6.0±1.8 mm; P=0.002), and the annular height to commissural width ratio was significantly lower in CIMR(+) patients (12±3 versus 21±5%; P<0.001). Conclusions—Patients with CIMR had greater septal-lateral and commissure-commissure mitral annular dimension, larger intertrigonal distance, and flattened saddle shape of mitral annulus. These associated geometric alterations may be important in the pathogenesis of CIMR.

Coronary Flow Velocity Pattern Immediately After Percutaneous Coronary Intervention as a Predictor of Complications and In-Hospital Survival After Acute Myocardial Infarction

Background—Recently, it was reported that the degree of microvascular injury and left ventricular functional recovery during the chronic period can be predicted after treatment of the infarct-related artery based on the coronary flow velocity (CFV) pattern assessed using a Doppler guidewire. The aim of this prospective study was to examine whether the CFV pattern may predict complications and in-hospital survival after acute myocardial infarction (AMI). Methods and Results—The study population consisted of 169 consecutive patients with a first anterior AMI successfully treated with percutaneous coronary intervention (PCI). We examined the CFV pattern immediately after PCI using a Doppler guidewire. In accordance with previous findings, we defined severe microvascular injury as a diastolic deceleration time ≤600 ms and the presence of systolic flow reversal. Patients were divided into two groups: those without severe microvascular injury (n=118; group 1) and those with severe microvascular injury (n=51; group 2). All of the patients who had cardiac rupture were in group 2. Congestive heart failure (CHF) was observed more frequently in group 2 than in group 1 (53% versus 8%, P <0.001). The in-hospital cardiac mortality rate was significantly higher in group 2 than in group 1 (18% versus 0%, P <0.001). Nine patients in group 2 died, 5 patients because of CHF and 4 patients because of cardiac rupture. Conclusions—These findings suggest that the CFV pattern is an accurate predictor of the presence or absence of complications and of in-hospital survival after AMI.

Value of acceleration flow and the prestenotic to stenotic coronary flow velocity ratio by transthoracic color Doppler echocardiography in noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty.

OBJECTIVES The study evaluated the value of coronary flow velocity measurement by transthoracic color Doppler echocardiography (TTCDE) for the noninvasive diagnosis of restenosis after percutaneous transluminal coronary angioplasty (PTCA) for left anterior descending coronary artery (LAD) lesions. BACKGROUND Recent advances in TTCDE provide coronary flow velocity measurements in the LAD under the guidance of color flow mapping. METHODS We studied 53 patients who underwent successful PTCA for LAD lesions and follow-up coronary angiography (18 patients with restenosis [Group-R], 35 patients without restenosis [Group-N]). We searched localized color aliasing corresponding to local flow acceleration to obtain coronary flow velocity at PTCA sites in the LAD. When localized aliasing was detected, we measured coronary flow velocity at the aliasing (stenotic site) and the prestenotic site. RESULTS Using TTCDE, it was possible to measure mean diastolic velocity (MDV) in the LAD in 41 (77%) of 53 patients (14 of 18 patients in Group-R; 27 of 35 patients in Group-N). Localized aliasing was displayed by color flow mapping in 14 (100%) of 14 patients in Group-R, and 15 (56%) of 27 patients in Group-N. Stenotic MDV in Group-R was significantly higher than that in Group-N (60.3 +/- 21.1 vs. 35.1 +/- 7.6 cm/s, p < 0.01), although prestenotic MDV did not differ between Group-R and Group-N (20.2 +/- 3.0 vs. 19.6 +/- 2.3 cm/s). There were significant differences in the prestenotic to stenotic MDV ratio between Group-R and Group-N (0.36 +/- 0.10 vs. 0.57 +/- 0.09, p < 0.001). Localized aliasing with the prestenotic to stenotic MDV ratio <0.45 as the optimal cutoff value had a sensitivity of 86% and a specificity of 93% for the presence of restenosis in LAD lesions. CONCLUSIONS Detection of localized color aliasing and measurement of the prestenotic to stenotic MDV ratio in the LAD by TTCDE are useful in the noninvasive diagnosis of restenosis after PTCA for LAD lesions.

Impact of troglitazone on coronary stent implantation using small stents in patients with type 2 diabetes mellitus

In summary, troglitazone reduces angiographic in-stent restenosis and target lesion revascularization rates after coronary stent implantation using 2.5-mm stents in patients with type 2 DM. Serial IVUS assessment demonstrates that the reduction in neointimal tissue proliferation in the troglitazone group is associated with the angiographic results.

Clinical Outcomes of Medical Therapy and Timely Operation in Initially Diagnosed Type A Aortic Intramural Hematoma: A 20-Year Experience

Background— The management of aortic intramural hematoma (IMH) involving the ascending aorta (type A) has not been well-established. The purpose of this study was to clarify the long-term clinical outcomes of patients with type A IMH who were treated with medical therapy and timely operation. Methods and Results— Clinical data including operative mortality, IMH-related events, and long-term survival were retrospectively reviewed in 66 patients with type A IMH, who were admitted to our institution from 1986 to 2006. Emergent surgical repair was performed in 16 (24%) patients because of severe complications, whereas 50 patients were treated with initial medical therapy. In medically treated patients, 15 (30%) patients who demonstrated progression to classic dissection or increase in hematoma size within 30 days underwent surgical repair except for 2 patients who refused surgery. The 30-day mortality rate was 6% with emergent surgery and 4% with supportive medial therapy. There were 7 late deaths and the actuarial survival rates of all patients were 96±3%, 94±3%, and 89±5% at 1, 5, and 10 years, respectively. In medically treated patients, maximum aortic diameter was the only predictor of early and late progression of ascending IMH (hazard ratio, 4.43; 95% CI, 2.04–9.64; P<0.001). Aortic diameter ≥50 mm predicted progression of ascending IMH with the positive and negative value of 83% and 84%, respectively. Conclusions— Combination of medical therapy and timely operation resulted in favorable long-term clinical outcomes in patients with type A IMH.

Hyperinsulinemia during oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients : A serial intravascular ultrasound study

OBJECTIVES The purpose of this study was to determine whether hyperinsulinemia during the oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients. BACKGROUND Although hyperinsulinemia induces increased vascular smooth muscle cell proliferation in experimental models, it has not been determined whether hyperinsulinemia is associated with increased neointimal tissue proliferation after coronary stent implantation. METHODS Serial (postintervention and six-month follow-up) intravascular ultrasound (IVUS) was used to study 67 lesions treated with Palmaz-Schatz stents in 55 nondiabetic patients. Cross-sectional images within stents were taken at every 1 mm, using an automatic pullback, and a neointimal index was calculated as the ratio between the averaged neointimal area and averaged stent area. All patients underwent a 75-g oral glucose tolerance test. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were measured at baseline and 1 and 2 h after the glucose load. The sum of PGs (sigmaPG) and the sum of IRIs (sigmaIRI) were calculated. Body mass index (BMI), lipid levels, and glycosylated hemoglobin levels were measured. RESULTS There were 27 patients with normal glucose tolerance, and 28 patients with impaired glucose tolerance (IGT). The neointimal index in patients with IGT was greater than that in patients with normal glucose tolerance (42.9 +/- 14% vs. 24.9 +/- 8.3%, respectively, p < 0.0001). Linear regression analysis showed that the neointimal index at follow-up correlated well with sigmaPG (p < 0.0001), fasting IRI (p < 0.0001), sigmaIRI (p < 0.0001), triglyceride level (p = 0.018), and BMI (p < 0.0001). Multiple regression analysis revealed that sigmaIRI (p = 0.0002) and sigmaPG (p = 0.0034) were the best predictors of the greater neointimal index at follow-up. CONCLUSIONS Serial IVUS assessment shows that hyperinsulinemia during an oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients.