Tatsuhiko Hata

Long-Term (>10 Years) Clinical Outcomes of First-in-Human Biodegradable Poly-l-Lactic Acid Coronary Stents Igaki-Tamai Stents

Background— The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly-l-lactic acid. Methods and Results— Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (>10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121±17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change. Conclusion— Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.

Biodegradable stents as a platform to drug loading.

Despite technical and mechanical improvement in coronary stents the incidence of restenosis caused by in-stent neointimal hyperplasia remains high. Oral administration of numerous pharmacological agents has failed to reduce restenosis after coronary stenting in humans, possibly owing to insufficient local drug concentration. Therefore, drug-eluting stents were developed as a vehicle for local drug administration. The authors developed a new drug-eluting polymer stent that is made of poly-l-lactic acid polymer mixed with tranilast, an anti-allergic drug that inhibits the migration and proliferation of vascular smooth muscle cells induced by platelet-derived growth factor and transforming growth factor->1. Polymer stents might be superior to polymer-coated metallic stents as local drug delivery stents in terms of biodegradation and the amount of loaded drug. Drug-mixed polymer stents can be loaded with a larger amount of drug than can drug-coated metallic stents because the polymer stent struts can contain the drug. Clinical application is required to assess the safety and efficacy of drug-eluting polymer stents against stent restenosis.

Histopathological findings of new in‐stent lesions developed beyond five years

We analyzed 14 cases of new lesions inside implanted bare‐metal stents. In every case, there was no angiographic restenosis within 3 years, but a new lesion was observed inside a stented segment at long‐term follow‐up (>5 years). Fourteen cases were evaluated: 9 with Wiktor stents, 2 with Palmaz‐Schatz stents, and 3 with ACS Multilink stents. The interval from stent implantation to follow‐up angiography was 63–147 months (89 ± 23). Thirteen lesions were treated by percutaneous coronary intervention (PCI) and stenotic tissue was obtained by directional coronary atherectomy (DCA) in 10 cases. All retrieved samples were composed of newly developed atherosclerosis facing the healed neointimal layer, and four samples showed histopathological findings of acute coronary syndrome. Stent struts were retrieved in four cases and no inflammation was observed surrounding them. Qualitative and quantitative analysis of stent struts was performed in two cases that showed no metal corrosion. These findings suggest that new atherosclerotic progression occurred inside the implanted stent without peristrut inflammation.

New technique for superior guiding catheter support during advancement of a balloon in coronary angioplasty: The anchor technique

To get superior guiding catheter support, we tried a new method called the anchor technique. By inflating a balloon in a nontarget vessel and holding its shaft with backward force while advancing another balloon, the anchor effect for the guiding catheter could be obtained and it appeared to be helpful for a balloon or a stent to cross the target lesion. Cathet Cardiovasc Intervent 2003;59:482–488.

Initial and long-term results of angioplasty in unprotected left main coronary artery

Angioplasty of the unprotected left main coronary artery (LMCA) has been controversial. Although recent single-center studies suggest that new devices may change the situation, many questions and problems remain. Therefore, the results of unprotected left main coronary angioplasty of 175 procedures in 107 patients were analyzed to evaluate its feasibility and effectiveness. The treatment of the initial 107 cases included balloon angioplasty (39 cases, 36%), directional coronary atherectomy (53 cases, 50%), and stents (15 cases, 14%). They were divided into 3 major subgroups: (1) acute group (n = 14), in which LMCA angioplasty was performed in patients with acute myocardial infarction; (2) emergency group (n = 10); and (3) elective group (n = 83). In-hospital mortality was higher in the acute (35.7%) and emergency (40.0%) groups than in the elective group (3.6%; p <0.0001). Angiographic follow-up was routinely performed and the restenosis rate including in-hospital restenosis was 70% in the acute group, 37.5% in the emergency group, and 40% in the elective group (p = NS). The mean clinical follow-up period was 2.9 years, and the estimated 5-year survival rates of the acute and emergency groups were 50% and 48.2%, respectively. However the 5-year survival rate of the elective group was higher than that seen in the acute or emergency group (77.5%; p <0.05). Repeat LMCA angioplasty was performed in 37 of 68 patients with 8.8% mortality (38.5% of acute and emergency cases and 1.8% of elective cases). The results indicated that elective unprotected LMCA angioplasty is relatively feasible and effective under scheduled angiographic follow-up.

Noninvasive Assessment of Myocardial Viability by Positron Emission Tomography With 11C Acetate in Patients With Old Myocardial Infarction Usefulness of Low-Dose Dobutamine Infusion

BACKGROUND When patients with severely depressed left ventricular function are treated, it is crucial to know in advance how much functional recovery is expected from coronary revascularization. METHODS AND RESULTS We compared the results of 11C acetate positron emission tomography (PET) with dobutamine infusion with changes in regional wall motion evaluated by left ventriculography in 28 patients with old Q-wave anterior myocardial infarctions. Dysfunctional but viable myocardium (group A, n = 13) was separated from nonviable myocardium (group B, n = 15) by echocardiographic assessments of regional wall motion before and after successful coronary revascularization. 11C acetate PET was performed to characterize normalized myocardial blood flow and oxidative metabolism (the clearance rate constant, k mono). While the baseline k monos of the infarct areas of the two groups were different with overlap, the responses to dobutamine infusion were directionally different. In addition, relative perfusion by 11C acetate PET could predict recovery of left ventricular function as well as or better than dobutamine 11C acetate kinetics. The extent of the increase in k monos of the infarct area with dobutamine infusion correlated well (P < .01) with the degree of the increase in the percentage of systolic segment shortening in the infarct area (left ventriculography) after coronary revascularization. CONCLUSIONS 11C acetate PET with dobutamine infusion can predict not only the reversibility of dysfunctioning myocardium after coronary revascularization but also the extent of improvement of regional wall motion in patients with old Q-wave infarction.

Intravascular ultrasound-guided directional coronary atherectomy for unprotected left main coronary stenoses with distal bifurcation involvement

Stent implantation in unprotected left main coronary artery (LMCA) bifurcation lesions may improve procedural and late clinical outcomes. However, concerns regarding stent-related complications, such as stent jail, subacute thrombosis, and in-stent restenosis remain. Optimal debulking by directional coronary atherectomy (DCA) with intravascular ultrasound (IVUS) guidance may be effective in this complex lesion subset, but this strategy has not yet been established. Our objective was to evaluate the safety and efficacy of IVUS-guided DCA for unprotected LMCA stenoses with distal bifurcation involvement. A total of 67 consecutive patients were included in this study and procedural success was achieved in all cases. Two cardiac deaths (2.9%) were noted and 3 patients (4.5%) underwent repeat angioplasty during hospitalization. There was no Q-wave myocardial infarction or emergency bypass surgery. Non-Q-wave myocardial infarction (creatine kinase-MB >3 times normal) occurred in 13.4% of patients. Stent implantation was necessary in 17 cases (25.4%) to achieve an optimal result. IVUS showed an improved lumen cross-sectional area and a low plaque burden in the LMCA after intervention. All-cause mortality, angiographic restenosis, and the target lesion revascularization rates at 6 months were 7.4%, 23.8%, and 20.0%, respectively. With IVUS guidance, aggressive DCA can be performed safely in unprotected LMCA bifurcation lesions, and optimal angiographic and IVUS results can be achieved with low residual plaque burden, which leads to a low restenosis rate. Optimal lesion debulking by DCA does not necessarily need adjunctive stenting in this specific anatomic subset.

Comparative study of201Tl-scintigraphic image and myocardial pathologic findings in patients with dilated cardiomyopathy

The objective of the present study was to characterize the production of201Tl myocardial perfusion defects, the relation between the201Tl multiple small defects and the myocardial damage indicated by myocardial fibrosis shown histopathologically in patients with dilated cardiomyopathy (DCM).Rest201Tl scintigraphy was performed in thirty-seven patients with myocardial tissue fibrosis by endomyocardial biopsy, and without stenosis of the coronary artery.201Tl myocardial SPECT images were visually classified into 4 grades according to the severity of inhomogeneous perfusion defects (IPD), 0: none, 1: slight, 2: moderate, 3: severe.201Tl uptake, defect regions (DR), and coefficient of variation % (CV%) were also quantified by Bull’s eye quantification in nineteen patients. During cardiac catheterization, three biopsy specimens were obtained from the lateral wall to the apical region of the left ventricle and the amount of fibrosis was assessed by means of light microscopic morphometry. The myocardial fibrosis was also classified into 4 grades by a pointcounting method. Autopsy study was also assessed in six patients.201Tl perfusion defects were observed in 35 (94.6%) patients, of whom 29 (78.4%) showed inhomogeneous perfusion defects. Twenty-four (64.9%) showed Stage 0 and 1201Tl findings, and 21 (62.2%) had myocardial fibrosis in stage 1. Clinically, the correlation between the grades of the IPD, %201Tl uptake, DR and CV% of myocardial uptake, which were calculated semiquantitatively by Bull’s eye image, and the histological grades of fibrosis were also good (IPD vs. fibrosis: r = 0.7014; %201Tl uptake vs. fibrosis: r = −0.6542; DR vs. fibrosis: r = 0.7027; CV% vs. fibrosis: r = 0.6985). The201Tl SPECT findings were in close agreement with the severity of myocardial fibrosis confirmed by autopsy, but the grading of the IPD was not related to the ejection fraction or left ventricular diameter.It showed a higher rate of inhomogeneous201Tl myocardial perfusion defects (78.4%) in patients with DCM. This result may contribute to the clinical evaluation of DCM or differentiation from other diseases. Furthermore, the grading of201Tl inhomogeneous perfusion defects related to the myocardial fibrosis of left ventricular myocardium may contribute to speculation of the myocardial degenerative stage in clinical settings.

Comparison of the self-expanding Radius stent and the balloon-expandable Multilink stent for elective treatment of coronary stenoses: a serial analysis by intravascular ultrasound.

We compared the outcome of the self‐expanding Radius stent and the balloon‐expandable Multilink stent serially by angiography and intravascular ultrasound. Successful stent deployment was achieved in 66 lesions of 56 stable angina patients (34 lesions with Radius stents and 32 lesions with Multilink stents). At follow‐up, there were no significant differences in minimal lumen diameter or percent diameter stenosis between the groups, nor in restenosis rates, although the Radius stent group rate was slightly lower (23.5% vs. 31.3%). In the Radius stent group, stent cross‐sectional area (CSA) increased gradually after implantation until the 6‐month follow‐up (8.37 ± 1.83 to 10.16 ± 2.59 mm2; n = 15), giving a larger CSA (P = 0.03) than the Multilink stent group, which decreased (9.00 ± 2.05 to 8.27 ± 2.15 mm2; n = 17). The lumen CSA was also slightly larger (6.82 ± 3.06 vs. 5.84 ± 1.85 mm2; P = 0.29) in the Radius stent group. These findings indicated that the Radius stent enlarged progressively after implantation, which might be useful for prevention of restenosis. Cathet Cardiovasc Intervent 2002;56:40–45.

Long-Term (>10 Years) Clinical Outcomes of First-In-Man Biodegradable Poly-l-lactic Acid Coronary Stents: Igaki-Tamai Stents

Background— The purpose of this study was to evaluate the long-term safety of the Igaki-Tamai stent, the first-in-human fully biodegradable coronary stent made of poly-l-lactic acid. Methods and Results— Between September 1998 and April 2000, 50 patients with 63 lesions were treated electively with 84 Igaki-Tamai stents. Overall clinical follow-up (>10 years) of major adverse cardiac events and rates of scaffold thrombosis was analyzed together with the results of angiography and intravascular ultrasound. Major adverse cardiac events included all-cause death, nonfatal myocardial infarction, and target lesion revascularization/target vessel revascularization. During the overall clinical follow-up period (121±17 months), 2 patients were lost to follow-up. There were 1 cardiac death, 6 noncardiac deaths, and 4 myocardial infarctions. Survival rates free of all-cause death, cardiac death, and major adverse cardiac events at 10 years were 87%, 98%, and 50%, respectively. The cumulative rates of target lesion revascularization (target vessel revascularization) were 16% (16%) at 1 year, 18% (22%) at 5 years, and 28% (38%) at 10 years. Two definite scaffold thromboses (1 subacute, 1 very late) were recorded. The latter case was related to a sirolimus-eluting stent, which was implanted for a lesion proximal to an Igaki-Tamai stent. From the analysis of intravascular ultrasound data, the stent struts mostly disappeared within 3 years. The external elastic membrane area and stent area did not change. Conclusion— Acceptable major adverse cardiac events and scaffold thrombosis rates without stent recoil and vessel remodeling suggested the long-term safety of the Igaki-Tamai stent.