Shigeru Ikeguchi

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.

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.

Electrophysiological effects of amiodarone on isolated rabbit heart muscles.

We studied the electrophysiological effects of amiodarone on isolated rabbit heart muscles by conventional microelectrode techniques. It significantly suppressed not only sinus node functions (basic cycle length, sinus recovery time, and corrected sinus recovery time) but also atrioventricular node functions (AH interval, effective refractory period, and functional refractory period) by both superfusion (10 μg/ml amiodarone in Tyrode solution) and long-term oral administration (50 mg/day for 2 weeks, then 25 mg/day for 4–6 weeks). On the other hand, oral administration significantly lengthened the action potential duration and effective refractory period of the left atrium and the right ventricle, while superfusion did not. The maximum rate of depolarization, action potential amplitude, and diastolic resting potential were not changed by either route of administration. It is thought that the action of amiodarone on the sinus node and on the atrioventricular node is mainly due to its noncompetitive sympathetic inhibition, and that its action on the left atrium and on the right ventricle is mainly due to reduction of serum triiodothyronine, which requires long-term administration of amiodarone.

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.

Decade of Histological Follow-Up for a Fully Biodegradable Poly-l-lactic Acid Coronary Stent (Igaki-Tamai Stent) in Humans Are Bioresorbable Scaffolds the Answer?

An 83-year-old male with a history of angina pectoris presented with massive intracranial hemorrhage in June 2011, and he died 2 days after admission. Previously, he was included in the first in-human feasibility study of biodegradable poly- l -lactic acid (PLLA) coronary stents: the Igaki-Tamai stents (Kyoto Medical Planning Co Ltd, Kyoto, Japan).1,2 To assess the long-term behavior of PLLA coronary stents in humans, postmortem examination of his coronary arteries was performed. In November 1999, he was diagnosed with stable angina pectoris, and coronary angiography disclosed a single lesion at the middle part of left anterior descending coronary artery (Figure 1A). One Igaki-Tamai stent had been implanted with successful result (Figure 1B). He received …

Combined effect of disopyramide and bethanechol: use of bethanechol to prevent anticholinergic side effects of disopyramide without reduction of antiarrhythmic efficacy.

Because bethanechol chloride (B) relieves the anticholinergic side effects of disopyramide (D), we examined the combined effects of D and B on the heart and urinary bladder. B was confirmed to counteract dose dependently the effect of D on the dog bladder. In the ventricular muscle, the combined electrophysiological effects (D + B) were additive, with no reduction in the effect of D. With the control value set as 100%, the decrease in the maximum rate of depolarization with 5 × 10−6 g/ml D (90 ± 6%) was not affected by the same dose of B (D + B: 84 ± 14%). Moreover, the effective refractory period (ERP) was larger with D + B (128 ± 12%) than with either B (109 ± 9%, p < 0.01) or D (115 ± 11%, p < 0.05). In contrast, in the atrial muscle and AV and SA nodes, B had marked acetylcholine-like effects. These were completely suppressed by the addition of D except for the atrial ERP with the highest tested concentration of B (5 × 10−6 g/ml). In the latter case, the prolongation of ERP was minimal (B + D: 105 ± 14%) as compared with D alone (130 ± 15%). Since the plasma concentration of B after oral administration of a clinical dose is expected to be on the order of 10−7 g/ml, no practical effect is anticipated. We conclude that B can be expected to counteract urination disorders caused by D without reducing Ds antiarrhythmic efficacy.

Risk stratification for major adverse cardiac events and ventricular tachyarrhythmias by cardiac MRI in patients with cardiac sarcoidosis

Background The presence of myocardial fibrosis by cardiac MRI has prognostic value in cardiac sarcoidosis, and localisation may be equally relevant to clinical outcomes. Objective We aimed to analyse cardiac damage and function in detail and explore the relationship with clinical outcomes in patients with cardiac sarcoidosis using cardiac MRI. Methods We included 81 consecutive patients with cardiac sarcoidosis undergoing cardiac MR. Left ventricular mass and fibrosis mass were calculated, and localisation was analysed using a 17-segment model. Participants underwent follow-up through 2015, and the development of major adverse cardiac events including ventricular tachyarrhythmias was recorded. Results Increased left ventricular fibrosis mass was associated with increased prevalence of ventricular tachyarrhythmias (p<0.001). When localisation was defined as the sum of late gadolinium enhancement in the left ventricular basal anterior and basal anteroseptal areas, or the right ventricular area, it was associated with ventricular tachyarrhythmias (p<0.001). Kaplan-Meier analysis during a median follow-up of 22.1 months showed that both the mass and localisation groupings for fibrosis were significantly associated with major adverse cardiac events or ventricular tachyarrhythmias and that when combined, the risk stratification was better than for each variable alone (p<0.001, respectively). By Cox-proportional hazard risk analysis, the localisation grouping was an independent predictor for the both. Conclusions In patients with cardiac sarcoidosis, both fibrosis mass and its localisation to the basal anterior/anteroseptal left ventricle, or right ventricle was associated with the development of major adverse cardiac events or ventricular tachyarrhythmias. Cardiac MR with late gadolinium enhancement may be useful for improving risk stratification in patients with cardiac sarcoidosis.

Rare case of cardiac hemangioma causing massive pericardial effusion: can a left atrial tumor produce pericardial effusion?

A 35-year-old woman presented to the emergency room with a 2-month history of general malaise and anasarca. The chest x-ray showed cardiomegaly, and transthoracic echocardiography revealed massive pericardial effusion leading to cardiac tamponade (Figure 1A and 1B). Immediately, 1400 mL pericardial effusion (yellow exudate) was removed by needle pericardiocentesis. After the procedure, transthoracic echocardiography showed an immobile, heterogeneous tumor in the left atrium (LA) (Figure 1C and Movie I in the online-only Data Supplement). Figure 1. Multimodality imaging of the left atrial (LA) tumor. Transthoracic echocardiography revealed massive pericardial effusion leading to cardiac tamponade ( A and B ). After removal of the pericardial effusion, the immobile, heterogeneous tumor was observed in the LA ( C and Movie I in the online-only Data Supplement). Cardiac computed tomography (CT) showed a well-circumscribed tumor located in the LA wall near the origin of the left pulmonary veins ( D and …

Electrophysiological effects of melperone on isolated rabbit heart muscles

1 Electrophysiological effects of melperone on isolated atrial and ventricular muscle preparations of the rabbit were studied by a conventional microelectrode technique. 2 Melperone (3.3 μm) prolonged the action potential duration and effective refractory period of the atrial preparations without affecting the maximum rate of depolarization (). These effects of melperone on action potential duration and effective refractory period were inhibited by a low potassium perfusate (2.7 mm). 3 A high concentration of melperone (16.6 μm) decreased of atrial preparations. In ventricular muscles, melperone at either concentration decreased , although the increase in action potential duration was greater than in the atrium. 4 Depression of of ventricular muscles by melperone was found to be augmented by an increase of stimulation frequency and drug concentration. 5 The rate of onset of rate‐dependent block of in ventricle was increased with drug concentration and frequency of stimulation. However, the time constant of recovery from rate‐dependent block was almost constant. The kinetics of rate‐dependent block of by melperone were approximately similar to those of quinidine and disopyramide. Consequently it is concluded that melperone possesses class la antiarrhythmic activity as well as class 3 activity.

Long-term use of carvedilol in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention

Background Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI). Methods and results In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06) Conclusion Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI. Trial registration CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.