Koichi Tamita

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.

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.

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.

A Prospective, Multicenter, Randomized Trial to Assess Efficacy of Pioglitazone on In-Stent Neointimal Suppression in Type 2 Diabetes : POPPS (Prevention of In-Stent Neointimal Proliferation by Pioglitazone Study)

OBJECTIVES The aim of this study was to clarify whether pioglitazone suppresses in-stent neointimal proliferation and reduces restenosis and target lesion revascularization (TLR) after percutaneous coronary intervention (PCI). BACKGROUND Previous single-center studies have demonstrated the anti-restenotic effect of a peroxisome proliferator-activated receptor gamma agonist, pioglitazone, after PCI. METHODS A total of 97 patients with type 2 diabetes mellitus (T2DM) undergoing PCI (bare-metal stents only) were enrolled. After PCI, patients were randomly assigned to either the pioglitazone group (n = 48) or the control group (n = 49). Angiographical and intravascular ultrasound (IVUS) imaging were performed at baseline and repeated at 6-month follow-up. Primary end points included angiographical restenosis and TLR at 6 months follow-up. Secondary end point was in-stent neointimal volume by IVUS. RESULTS Baseline glucose level and glycosylated hemoglobin (HbA1c) level were similar between the pioglitazone group and the control group. Angiographical restenosis rate was 17% in the pioglitazone group and 35% in control group (p = 0.06). The TLR was significantly lower in pioglitazone group than in control group (12.5% vs. 29.8%, p = 0.04). By IVUS (n = 56), in-stent neointimal volume at 6 months showed a trend toward smaller in the pioglitazone group than in the control group (48.0 +/- 30.2 mm(3) vs. 62.7 +/- 29.0 mm(3), p = 0.07). Neointimal index (neointimal volume/stent volume x 100) was significantly smaller in the pioglitazone group than in the control group (31.1 +/- 14.3% vs. 40.5 +/- 12.9%, p = 0.01). CONCLUSIONS Pioglitazone treatment might suppress in-stent neointimal proliferation and reduce incidence of TLR after PCI in patients with T2DM.

Prognosis of Retrograde Dissection From the Descending to the Ascending Aorta

Background—Natural history of aortic dissection (AD) with intimal tear in the descending or abdominal aorta and retrograde extension into the ascending aorta (retrograde AD) remains unknown. The purpose of this study was to elucidate medium-term prognosis of patients with retrograde AD. Methods and Results—Study population consisted of 109 patients with acute type A AD. There were 27 patients (25%) with retrograde AD and 82 patients (75%) with intimal tear in the ascending aorta (antegrade AD). In antegrade AD patients, 60 patients underwent surgery and 22 patients were treated medically. In retrograde AD patients, 14 patients showed localized crescentic high attenuation area along the ascending aortic wall without enhancement in computed tomography. Transesophageal echocardiography revealed complete thrombosis of false lumen (FL) in the ascending aorta (retrograde thrombosed). The remaining 13 patients showed incomplete or no thrombosis (retrograde nonthrombosed). All retrograde nonthrombosed AD patients underwent surgery except for 1 patient with stroke, whereas all retrograde thrombosed AD patients were treated medically. In-hospital mortality rate of retrograde AD patients was significantly lower than that of antegrade AD patients (15% versus 38%, P =0.027). The survival rates in retrograde AD patients were all 85% at 1, 2, and 5 years, which were significantly higher than those of antegrade AD patients (63%, 62%, and 57%, respectively)(P =0.009). Conclusions—Patients with type A retrograde AD have better medium-term prognosis than patients with antegrade AD. Retrograde AD patients with thrombosed FL in the ascending aorta could be treated medically with timed surgical repair.

Fulminant fatal cardiotoxicity following cyclophosphamide therapy

A 59-year-old male with an abdominal mass that showed a diffuse large B cell lymphoma underwent extirpation of the tumor and chemotherapy. He subsequently received high-dose chemotherapy containing cyclophosphamide (1.5 g/m(2)/day x 2 days), followed by autologous peripheral blood stem cell transplantation. He developed congestive heart failure 5 days after administration of cyclophosphamide. His electrocardiogram showed extremely low voltage with ST segment change and echocardiogram showed diffusely increased left ventricular wall thickness, an increase in myocardial echogenicity, pericardial effusion, and generally decreased systolic function. Congestive heart failure progressed rapidly and he died the following day. Post-mortem examination of the heart revealed myocardial hemorrhage, yellowish brown pericardial effusion, and fibrinous pericarditis. His liver was atrophic and focal necrosis was observed histologically. Cyclophosphamide-induced cardiotoxicity occurred, even though the patient had both shown normal cardiac function before high-dose chemotherapy and had received a lower dose of cyclophosphamide. Concomitant administration of cytarabine might have affected his liver function and there might have been interaction between the drugs.

Newly diagnosed glucose intolerance and prognosis after acute myocardial infarction: comparison of post-challenge versus fasting glucose concentrations

Background Recent studies have demonstrated that newly diagnosed glucose intolerance is common among patients with acute myocardial infarction (AMI). The purpose of this study was to assess the long-term clinical cardiovascular outcomes in participants with AMI with abnormal fasting glucose compared with normal fasting glucose and an abnormal oral glucose tolerance test (OGTT) compared with a normal OGTT. Methods A prospective study was performed in 275 consecutive patients with AMI, 85 of whom had pre-diagnosed diabetes mellitus (DM). Those without DM were divided into two groups based on the 75 g OGTT at the time of discharge. Abnormal glucose tolerance (AGT) was defined as 2 h glucose ≥140 mg/dl; 78 patients had normal glucose tolerance (NGT) and 112 had AGT. The same patients were also reclassified into the normal fasting glucose group (NFG; n=168) or the impaired fasting glucose group (IFG; n=22). The association between the glucometabolic status and long-term major adverse cardiovascular event rates was evaluated. Results Kaplan–Meier survival curves showed that the AGT group had a worse prognosis than the NGT group and an equivalent prognosis to the DM group (p<0.0005). Cox proportional hazard model analysis showed that the HR of AGT to NGT for major adverse cardiovascular event rates was 2.65 (95% CI 1.37 to 5.15, p=0.004) while the HR of DM to NGT was 3.27 (1.68 to 6.38, p=0.0005). However, Cox HR of IFG to NFG for major adverse cardiovascular event rates was 1.83 (0.86 to 3.87), which was not significant. Conclusion In patients with AMI, an abnormal OGTT is a better risk factor for future adverse cardiovascular events than impaired fasting blood glucose.

Detection of severe stenosis and total occlusion in the left anterior descending coronary artery with transthoracic Doppler echocardiography in the emergency room.

Background: The noninvasive measurement of coronary flow velocity in the left anterior descending artery (LAD) has recently been realized by using the transthoracic Doppler echocardiography (TTDE). A couple of investigations demonstrated that the diastolic‐to‐systolic peak velocity ratio (DSVR) by TTDE is a simple and noninvasive method for the detection of severe stenosis in the elective settings. However, the usefulness of DSVR by TTDE in the emergency settings has not been evaluated. Objective: The purpose of this study was to assess the clinical feasibility to document the LAD flow by TTDE in emergency patients who complained of chest pain. Methods: We studied 49 consecutive patients with acute coronary syndrome who were going to undergo emergency coronary angiography (CAG) for the anatomical diagnosis and the facilitated percutaneous coronary intervention (PCI). Prior to CAG, we recorded the LAD flow by TTDE and measured the diastolic peak velocity (DVp), systolic peak velocity (SVp), and their ratio, DSVR (DVp/SVp) of LAD flow. Results: By CAG, the culprit lesions actually resided in the proximal LAD in 36 patients. Among the 36 patients, we detected the Doppler LAD flow in 29. Five out of 7 patients who were unable to detect the LAD flow revealed total occlusions by CAG. DSVR of the LAD is significantly lower in 17 patients who showed severe stenoses (>90%) than those in the rest of 12 patients who did not show such critical stenoses (1.44 ± 0.16 vs 2.10 ± 0.26, P < 0.0001). Conclusion: In the emergency settings, a noninvasive assessment of the LAD flow by TTDE accurately estimates the critical stenotic lesions of the LAD.