Kaname Takizawa

Local Drug Delivery via a Coronary Stent With Programmable Release Pharmacokinetics

Background—Fixed drug release kinetics and vessel wall partitioning may limit the effectiveness of drug-eluting stents. We report preliminary experience using a new coronary stent with programmable pharmacokinetics. Methods and Results—A newly designed metallic stent contains honeycombed strut elements with inlaid stacked layers of drug and polymer. In vitro studies evaluated recipes for loading paclitaxel to establish the parameters for controlling drug release. Manipulation of the layers of biodegradable polymer and drug allowed varying of the initial 24-hour burst release of paclitaxel from 69% to 8.6% (P <0.0001). Late release of drug could be adjusted dependently or independently of early burst release. A biphasic release profile was created by the addition of blank layers of polymer within the stack. In the 30-day porcine coronary model (n=17 pigs), there was a 70% reduction in late loss (0.3±0.5 versus 1.0±0.5 mm, P =0.04), a 28% increase in luminal volume (132±12 versus 103±21 mm3, P =0.02), and a 50% decrease in histological neointimal area (2.0±0.5 versus 4.0±1.6 mm2;P <0.001) compared with bare metal controls. Temporal and regional variations in vascular healing were seen histologically. Conclusions—Layered polymer/drug inlay stent technology permits flexible and controllable pharmacokinetic profiles. Programmable, complex chemotherapy using this approach may be feasible for the treatment of cardiovascular disease.

Effectiveness of right or left radial approach for coronary angiography

The transradial approach for catheterization is becoming increasingly more popular. At present, the choice of the right or left radial artery depends on the operators preference. We examined how the laterality influenced the effectiveness of the approach. Employing Judkins‐type catheters, we performed coronary angiography in 232 patients with the left approach and in 205 patients with the right approach. Although access time did not differ between the two groups of patients, the duration of catheter manipulation was shorter in the left‐ than in the right‐approach group (11.7 ± 5.9 vs. 9.8 ± 4.4 min; P < 0.001). Because of the shorter duration of catheter manipulation, the total procedural duration was shorter in the left‐approach group (13.7 ± 6.4 vs. 11.4 ± 4.8 min; P < 0.001). The fluoroscopy time was shorter in the left‐ than in the right‐approach group (3.7 ± 2.5 vs. 5.0 ± 3.3 min; P < 0.001). The amount of contrast material did not differ between the groups (79 ± 27 vs. 83 ± 25 ml). The rate of guidewire usage to engage the coronary ostium was higher in the right‐ than in the left‐approach group because of the severe tortuosity of the right subclavian artery (20/205 vs. 0/232; P < 0.001). Thus, for operators with significant experience, the left radial approach may provide increased procedural efficacy for coronary angiography compared to the right radial approach. Catheter Cardiovasc Interv 2004;61:333–337.

Outcome of Percutaneous Intrapericardial Fibrin-Glue Injection Therapy for Left Ventricular Free Wall Rupture Secondary to Acute Myocardial Infarction

Left ventricular free wall rupture (LVFWR) is a fetal complication of acute myocardial infarction. This study was conducted to test the feasibility of percutaneous intrapericardial fibrin-glue injection therapy (PIFIT) for LVFWR after acute myocardial infarction and to assess its clinical outcome. From January 2000 to December 2004, LVFWR was confirmed by echocardiography in 22 patients. Thirteen patients showing abrupt hemodynamic collapse failed to recover from resuscitation maneuvers and died <2 hours after LVFWR. The remaining 9 patients (5 women, mean age 73 +/- 10 years) underwent PIFIT. Pericardiocentesis was performed from the subxiphoid process, and a 6Fr pigtail catheter was introduced into the pericardial space. After bloody fluid was drained from the catheter, the fibrin glue was injected into the pericardial space. There were no complications relating to pericardiocentesis and PIFIT. One patient underwent surgical repair on the day of PIFIT because of uncontrollable bleeding from pericardial drainage. In-hospital death as a result of rerupture occurred in 2 patients on days 4 and 7 after PIFIT. Echocardiography during follow-up revealed no evidence of pseudoaneurysm or left ventricular restriction. On follow-up at a median of 4.0 years (interquartile range 3.1 to 4.8), 1 noncardiac death occurred at 3.3 months. The other 5 patients were free of cardiovascular events and in New York Heart Association functional class I. In conclusion, PIFIT is a simple, effective, and less invasive technique for the management of LVFWR and thus can be an alternative to surgical repair for LVFWR after acute myocardial infarction.

Increased Expression of Macrophage Colony–Stimulating Factor After Coronary Artery Balloon Injury Is Inhibited by Intracoronary Brachytherapy

Background—The mechanisms underlying the reduced neointimal proliferation (NP) by intracoronary brachytherapy (ICBT) are unknown. We hypothesized that ICBT inhibits NP by reducing expression of macrophage colony–stimulating factor (M-CSF). Methods and Results—Thirty coronary arteries from 10 pigs were divided into 3 groups of 10 each: control (C), balloon injury (BI), and BI followed by ICBT (16 Gy at 0.5-mm tissue depth with a 32P balloon system). Pigs were killed at 24 hours (n=3) and at 7 (n=4) and 14 (n=3) days. Expression of M-CSF was assessed by Western blot, ELISA, and quantitative immunostaining. Persistently increased levels of M-CSF after BI (to 1.4±0.2 nmol/L [ELISA] and 29.4±4.9% of cross-sectional area stained [immunocytochemistry];P < 0.001 versus control for both) were observed in the injured arteries. Treatment of BI arteries with ICBT reduced M-CSF expression compared with BI alone (to 0.7±0.1 nmol/L [ELISA] and 13.5±2.9% of cross-sectional area stained [immunocytochemistry];P <0.001 versus BI and P =NS versus control for both) and remained similar to control M-CSF expression for the 14-day study period. Neointimal thickness increased after BI (to 4.8±2.9 mm2;P <0.001 versus control), but this was reduced by ICBT (1.4±0.4 mm2;P <0.001 versus BI). Conclusions—In porcine coronary arteries, BI is associated with increased expression of M-CSF and NP, but neither occurs after ICBT. The beneficial effects of ICBT on NP involve inhibition of M-CSF expression.

Intracoronary beta-irradiation enhances balloon-injury-induced tissue factor expression in the porcine injury model.

Intracoronary brachytherapy (ICBT) effectively reduces restenosis but is associated with late thrombosis. Since tissue factor (TF) is an important mediator of arterial thrombosis, we tested the hypothesis that ICBT results in persistently augmented TF expression. Coronary arteries from 12 pigs were randomized to: control (C; no injury), oversized balloon injury (BI), or BI followed by ICBT. Animals were sacrificed at 1, 7, 14, or 60 days postprocedure, and coronary arteries collected for expression analyses and immunostaining. ICBT‐treated arteries had higher TF antigen and activity at all time‐points compared to BI arteries (Western blot: 16 571 ± 2090 vs 10 135 ± 2939 densitometric units, p = 0.001; ELISA: 0.42 ± 0.13 nM vs 0.25 ± 0.14 nM, p = 0.001; TF activity assay: 0.303 ± 0.11 nM vs 0.18 ± 0.07 nM, p = 0.01; immunohistochemical staining: 30.6 ± 6.6% vs 11.5% ± 3.2%, p = 0.01). TF expression increased following BI, increased further following ICBT, and persisted for the duration of the study. We conclude that TF expression increases after BI, but is further increased and persists for a longer duration following ICBT, suggesting that a TF‐mediated mechanism may play a role in late thrombosis following ICBT. (Int J Cardiovasc Intervent 2004; 1: 20–27)

Elution of everolimus and sirolimus from a biodegradable polymer coated stent inhibits neointimal hyperplasia without inflammation or toxicity

Background: Earfy clinical trials with drug eluting stents have suggested limitations including edge restenosis and malaposition. Persistent bio-stable polymer and/or drug may be causal. Biodegradable polymers hold potential advantage if they are metabolized prior to tissue toxicity and deliver drug during the optimal window. Local delivery of active drug from a slowly biodegradable, high molecular weight polylactic acid (PLA) coated stent could lead to inhibition of intimal hyperplasia without impaired healing. Methods: We compared PLA polymer containing 160 or 220 ug of Everolimus(E), 180 ug Sirolimus(S), and bare metal stent. 40 stents were deployed in coronary artehes of 19 pigs with sacrifice at 28 days. Endpoints were assessed by quantitative coronary angiog raphy @CA), histomorphometry, and histology at 28 and 90 days. Results:There was reduction of intimal hyperplasia as assessed by QCA and histomorphometry by both E and S (Table 1). At both 28 and 90 days, there was complete reendothelialization and ho difference in inflammation or fibrin between the bare stent and druglpolymer groups. Conclusion: Everolimus and Sirolimus delivered via stent and thin layer biodegradable polymer are equally effective at inhibition of intimal hyperplasia. At follow-up evaluation. complete healing without toxic or inflammatory reaction was seen. A clinical trial to determine safety and efficacy of the Everolimus coated stent has commenced.

Role of Coronary Calcium Scoring in the Assessment of Physiological Ischemia in Patients with Intermediate Stenosis.

Although coronary artery calcium (CAC) is an established marker of coronary atherosclerosis, whether it also reflects the physiological significance is unknown. This study aims to evaluate if CAC could indicate physiological ischemia in intermediate stenosis defined by an invasive fractional flow reserve (FFR). CAC score (CACS) derived from either whole coronary arteries or individual arteries was measured by computed tomography among patients with intermediate de novo lesions (percent diameter stenosis from 30% to less than 70%). All stenoses were evaluated by invasive FFR; lesions with an FFR ≤ 0.80 were considered significant. We enrolled 119 patients with 143 lesions. Of these, 42 lesions (29.4%) demonstrated significant ischemia by FFR measurement. FFR values had modest but significant correlations with CACS in individual arteries with intermediate stenosis (r = - 0.290; p < 0.001). A receiver operating characteristic curve analysis showed that CACS of individual arteries with intermediate stenosis had 71.4% sensitivity and 67.3% specificity as a predictor of significant ischemia at a cut off value of 145.9. Multivariable analysis showed that percent diameter stenosis and CACS in individual arteries with intermediate stenosis were independent predictors for significant ischemia. By net reclassification improvement analysis, CACS in individual arteries with intermediate stenosis provided incremental prediction for significant ischemia over minimum lumen diameter, percent diameter stenosis, and lesion length. CACS measured in each artery, but not the total CACS, provides additional information as to whether an angiographically intermediate stenosis within the artery is significant enough to cause myocardial ischemia.

Interatrial mechanical dyssynchrony shown by tissue doppler imaging during atrial flutter

Although regular supraventricular tachycardia is traditionally classified on the basis of P‐wave morphology, diagnostic accuracy is limited to information obtained from surface electrocardiography. Intracardiac electrophysiology is a conclusive although invasive diagnostic method. We report a case of regular supraventricular tachycardia with a heart rate of 162 bpm. M‐mode echocardiography of the interatrial septum clarified both the atrial rate and the ventricular response ratio. Tissue Doppler M‐mode imaging demonstrated the delay between the posterior wall motion of the left and right atrium. Although it deserves further study, transthoracic echocardiography may provide useful information in addition to electrocardiography.

Three-dimensional relationship between the conus branch and the precordial leads confirmed by 64–multidetector-row computed tomography

A 65-year-old man with effort angina pectoris underwent percutaneous coronary intervention of the proximal right coronary artery. The lesion was dilated with a bare-metal stent under wire protection of the conus branch (CB). However, the jailed CB was occluded. Electrocardiogram with conventional precordial leads (V(1) through V(6)) accompanied with the supplementary leads (V(1) through V(6)) positioned 1 intercostal space higher showed marked ST elevation in V(1) through V(3) that was more prominent in V(1) through V(3). The 64-multidetector-row computed tomographic coronary angiography showed recanalization of the CB located just in the center of the V(1), V(2), V(1), and V(2) electrodes.

THE PREDICTORS AND CLINICAL IMPACT OF FAILURE OF TRANSRADIAL APPROACH FOR PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN STEMI PATIENTS IN THE SINGLE-CENTER REGISTRY

Transradial approach (TRA) improves clinical outcomes driven by less hemorrhagic complications in patients with ST-elevation acute myocardial infarction (STEMI), as compared to transfemoral approach (TFA). However, TRA is sometimes avoided in clinical practice due to its procedural complexity, which