Tadateru Takayama

Safety and Feasibility of an Intravascular Optical Coherence Tomography Image Wire System in the Clinical Setting

Optical coherence tomography (OCT) is a fiber-optic technology that enables high-resolution intracoronary imaging. The aim of this study was to evaluate the safety and feasibility of intracoronary imaging with OCT in the clinical setting; 76 patients with coronary artery disease from 8 centers were enrolled. The OCT imaging system (ImageWire, Light Imaging Inc., Westford, Massachusetts) consists of a 0.006 inch fiber-optic core that rotates within a 0.016 inch transparent sheath. OCT imaging was performed during occlusion of the artery with a compliant balloon and continuous flushing. Intravascular ultrasound (IVUS) imaging was performed in the same segments. We assessed the safety and feasibility of the OCT imaging, compared with IVUS. Vessel occlusion time was 48.3 +/- 13.5 seconds and occlusion-balloon pressure was 0.4 +/- 0.1 atmospheres. Flushing with lactated Ringers solution was performed at a rate of 0.6 +/- 0.4 ml/s. No significant adverse events, including vessel dissection or fatal arrhythmia, were observed. Procedural success rates were 97.3% by OCT and 94.5% by IVUS. The OCT image wire was able to cross 5 of 6 tight lesions that the IVUS catheter was unable to cross. Of the 98 lesions in which both OCT and IVUS were successfully performed, OCT imaging had an advantage over IVUS for visualization of the lumen border. Minimum lumen diameter and area measurements were significantly correlated between OCT and IVUS imaging (r = 0.91, p <0.0001 and r = 0.95, p <0.0001, respectively). In conclusion, this multicenter study demonstrates the safety and feasibility of OCT imaging in the clinical setting.

Effect of fluvastatin on progression of coronary atherosclerotic plaque evaluated by virtual histology intravascular ultrasound.

OBJECTIVES The aim of this study was to evaluate the effect of treatment with statins on the progression of coronary atherosclerotic plaques of a nonculprit vessel by serial volumetric virtual histology (VH) intravascular ultrasound (IVUS). BACKGROUND Recent clinical trials have demonstrated a reduction of atherosclerotic plaque, yet whether statin therapy affects the change in components of plaque remains unknown. METHODS This study was a nonrandomized and nonblinded design. Eighty patients with stable angina pectoris were divided into either the fluvastatin group (n = 40) or the control group (n = 40) according to their total or low-density lipoprotein (LDL) cholesterol level. The volume of each plaque component (dense calcium, fibrous tissue, fibro-fatty, or necrotic core) was evaluated at baseline and at 12-month follow-up. RESULTS The LDL cholesterol and high-sensitivity C-reactive protein (hsCRP) levels in the fluvastatin group were significantly decreased at time of follow-up. In VH IVUS findings, fibro-fatty volume was significantly decreased (baseline 80.1 +/- 57.9 mm(3) vs. follow-up 32.5 +/- 27.7 mm(3), p < 0.0001) and fibrous tissue volume was increased (baseline 146.5 +/- 85.6 mm(3) vs. follow-up 163.3 +/- 94.5 mm(3), p < 0.0001) in the fluvastatin group. In the control group, the volumes of all plaque components without fibrous tissue were significantly increased. Change in fibro-fatty volume has a significant correlation with a change in LDL cholesterol level (R = 0.703, p < 0.0001) and change in hsCRP level (R = 0.357, p = 0.006). CONCLUSIONS One-year lipid-lowering therapy by fluvastatin showed significant regression of plaque volume and alterations in atherosclerotic plaque composition with a significant reduction of fibro-fatty volume.

Influence of Continuous Infusion of Low-Dose Human Atrial Natriuretic Peptide on Renal Function During Cardiac Surgery A Randomized Controlled Study

OBJECTIVES The purpose of this study was to determine the effect of human atrial natriuretic peptide (hANP) in patients who underwent coronary artery bypass grafting (CABG) on renal function. BACKGROUND Acute renal failure after cardiac surgery is associated with high morbidity and mortality. METHODS A total of 504 patients who underwent CABG were divided into 2 groups: 1 group received hANP at 0.02 microg/kg/min from the start of cardiopulmonary bypass (hANP group), and 1 group did not receive hANP (placebo group). Various parameters were measured before and after surgery. RESULTS There was no difference in mortality between the 2 groups, but post-operative complications were less frequent in the hANP group (p = 0.0208). In the hANP group, serum creatinine (Cr) was significantly lower and urinary Cr and Cr clearance were significantly higher from post-operative day 1 to week 1. The maximum post-operative Cr level and percent increase of Cr were significantly lower in the hANP group (p < 0.0001). Patients with Cr exceeding 2.0 mg/dl included 1 in the hANP group and 8 in the placebo group, showing a significant difference (p = 0.0374). Four patients in the placebo group and none in the hANP group required hemodialysis, but the difference was not statistically significant. CONCLUSIONS Continuous infusion of low-dose hANP from the start of cardiopulmonary bypass effectively maintained post-operative renal function. Infusion of hANP prevents early post-operative acute renal failure and helps to achieve safer cardiac surgery. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000001440).

Results of low-dose human atrial natriuretic peptide infusion in nondialysis patients with chronic kidney disease undergoing coronary artery bypass grafting: the NU-HIT (Nihon University working group study of low-dose HANP Infusion Therapy during cardiac surgery) trial for CKD.

OBJECTIVES The purpose of this comparative study is to prove the efficacy of the human atrial natriuretic peptide (hANP) in patients with chronic kidney disease (CKD) undergoing coronary artery bypass graft surgery (CABG). BACKGROUND CKD is an important risk factor for cardiac surgery. METHODS This was a randomized controlled study of 303 patients with CKD who underwent CABG, and were divided into a group who received carperitide infusion and another group without carperitide. The primary endpoints were: 1) the post-operative dialysis-free rate; and 2) serum creatinine (sCr) and estimated glomerular filtration rate. The secondary endpoints were: 1) the early post-operative outcome; 2) outcome at 1 year post-operatively; 3) the maximum sCr, the rate of increase of sCr, and an increase of sCr by ≥ 0.3 mg/dl compared with the pre-operative value; and 4) ANP and cyclic-guanosine monophosphate levels. RESULTS The post-operative sCr was significantly lower in the hANP group not only in the post-operative acute stage but also in the first year. The maximum Cr and Cr increase rate were significantly lower in the hANP group (p = 0.00665, p < 0.0001). There was no difference in mortality rate in the first year post-operatively, and fewer cardiac events and patients going on dialysis were found in the hANP group (p < 0.0001 and p = 0.0014, respectively). CONCLUSIONS In the post-operative acute stage, carperitide showed cardiorenal protective effects that prevented post-operative cardiac events and initiation of dialysis. Thus, perioperative infusion of low-dose carperitide may have a significant role in management of patients with renal dysfunction undergoing on-pump CABG. (Effectiveness of hANP for Cardiac Surgery in Patients With Moderate to Severe Preoperative Renal Dysfunction Without Dialysis [NU-HIT for CRF]; UMIN000001462).

Continuous Low-Dose Infusion of Human Atrial Natriuretic Peptide in Patients With Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting: The NU-HIT (Nihon University working group study of low-dose Human ANP Infusion Therapy during cardiac surgery) for Left Ventricular Dysfunction

OBJECTIVES Continuous low-dose infusion of human atrial natriuretic peptide (hANP) in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) inhibits the renin-angiotensin-aldosterone system and compensates for the adverse effects of CPB. BACKGROUND We examined the influence of hANP infusion on cardiac and renal function in patients with left ventricular dysfunction undergoing coronary artery bypass grafting (CABG). METHODS The subjects were 133 patients who underwent CABG and had a pre-operative ejection fraction < or =35%. They were randomized to receive 0.02 microg/kg/min of hANP from the initiation of CPB (hANP group) or placebo (saline) infusion. RESULTS Early post-operative mortality did not show a significant difference between the 2 groups, but perioperative complications were significantly less frequent in the hANP group (p = 0.015). Long-term all-cause mortality showed no difference, but the cardiac death-free rate at 5 or 8 years post-operatively was 98.5% in the hANP group and 85.5% in the placebo group (p = 0.0285). Post-operative ejection fraction was significantly larger and the post-operative brain natriuretic peptide level was significantly lower in the hANP group. Serum creatinine was significantly lower in the hANP group than the placebo group at 1 month, 6 months, and 1 year post-operatively, whereas the estimated glomerular filtration rate was significantly higher in the hANP group at these times. CONCLUSIONS In patients with left ventricular dysfunction undergoing CABG, hANP showed renal- and cardio-protective effects and reduced post-operative complications. It also improved the long-term prognosis. We suggest that hANP should be considered as part of perioperative management of patients with cardiac dysfunction undergoing cardiac surgery. (NU-HIT trial for LVD; UMIN000001652).

Antiischemic effects of nicorandil during coronary angioplasty in humans

SummaryThe present study was undertaken on 10 patients with angina undergoing percutaneous transluminal coronary angioplasty. The angioplasty procedure consisted of two successive 30-second balloon inflations at 5 minute intervals. After the first inflation, nicorandil (0.1 mg/kg) was given intravenously over a 2-minute period. The second inflation was then performed 3 minutes after the completion of drug administration. Myocardial ischemia was measured as the magnitude of ST-segment elevation on the intracoronary electrocardiogram (intracoronary ECG) recorded from the guidewire. Nicorandil significantly reduced the magnitude of ST-segment elevation. Nicorandil did not change the heart rate-blood pressure product, nor the oxygen saturation of the blood sampled from the great cardiac vein, nor the velocity of coronary blood flow in those patients with no evidence of collaterals. These results favor the conclusion that nicorandil prolongs the intrinsic ability of cardiac myocyte to withstand oxygen deprivation. This salutary effect is possibly due to a direct cellular mechanism because nicorandil did not modify the peripheral and coronary hemodynamic parameters that govern myocardial oxygen consumption.

Anomalous coronary arteries in adults detected by multislice computed tomography: presentation of cases from multicenter registry and review of the literature

Anomalous coronary arteries are a rare condition, but they may cause myocardial ischemia, heart failure, and sudden death. We evaluated the prevalence and multislice computed tomographic (MSCT) findings of anomalous coronary arteries in a large number of patients from the multicenter registry. At four institutes, 29 (0.74%) out of 3910 patients were found to have anomalous coronary arteries by MSCT. They consisted of 15 patients with anomalous origins of the right coronary artery, 1 with right-sided origin of the left circumflex artery, 1 with right-sided origin of the left main coronary artery, 2 with double right coronary arteries, 2 with the absence of the left circumflex artery, 1 with absence of the right coronary artery, 6 with coronary artery fistulas, and 1 with Bland-White-Garland syndrome. Multislice computed tomography findings were consistent with those obtained by conventional coronary angiography in all 14 patients undergoing both diagnostic procedures. Multislice computed tomography permits three-dimensional comprehension of coronary arteries, which is suitable for the diagnosis of anomalous coronary arteries.

Plaque Morphology at Coronary Sites With Focal Spasm in Variant Angina

In the present study, the intravascular ultrasound (IVUS) morphologic appearance of coronary atherosclerotic plaque associated with focal spasm was prospectively studied in 45 patients with or without focal coronary spasm provoked by ergonovine or acetylcholine. The percent plaque area and plaque arc were determined from the IVUS images at the sites of spasm. Calcified lesion was defined as the presence of high-intensity echo with acoustic shadowing. Twenty-three patients had focal coronary spasm defined as angiographic narrowing >75% and IVUS demonstrated atherosclerotic plaque in these 23 sites. In the 22 patients without focal spasm, IVUS demonstrated 18 atherosclerotic lesions in 17 patients and the remaining 5 patients did not have significant lesions. There was no difference in the percent plaque area and plaque arc between plaque lesions with (47+/-10%, 298+/-71 degrees ) and without (39+/-15%, 249+/-83 degrees ) coronary spasm. Interestingly, calcified lesion was less frequently present at the sites with than at those without spasm (p<0.05). These results indicate that the presence of plaque without calcification is likely to be related to the occurrence of focal vasospasm, although the severity and distribution of the disease did not differ between each patient group.

Efficacy of Aggressive Lipid Controlling Therapy for Preventing Saphenous Vein Graft Disease

BACKGROUND We assessed the efficacy of aggressive lipid controlling therapy (ALCT), which maintains low-density lipoprotein cholesterol (LDL-C) below to 80 mg/dL and LDL/high-density lipoprotein cholesterol (HDL-C) ratio less than 1.5 for preventing postcoronary bypass (CABG) saphenous vein graft (SVG) diseases by using intracoronary angioscopy. METHODS Twenty-one patients after CABG were divided into two groups: group I consisted of 10 patients whose serum LDL-C level and LDL/HDL could be controlled less than 80 mg/dL and 1.5, respectively, by rosuvastatin for about one year; group II consisted of 11 patients whose LDL-C level and LDL/HDL have been higher than 100 mg/dL and 2.5, respectively, regardless of having medication of pravastatin. Twenty-seven SVGs were assessed by intravascular ultrasound (IVUS) and angioscopy on postoperative 12 to 16 months. RESULTS The serum LDL-C level (I: 64.1 vs II: 130.2 mg/dL) and LDL/HDL (I: 1.36 vs II: 2.64), and high sensitive C-reactive protein (I: 0.045 +/- 0.100 vs II: 0.116 +/- 0.020 mg/dL) were significantly lower in group I. In group II, IVUS detected eccentric plaques in 11 (78.6%) of 14 SVGs. Furthermore the angioscope showed yellow plaque in all 14 SVGs (100%) and 11 (78.6%) of them had thrombi. On the other hand, in group I, all 13 SVGs had no eccentric, yellow plaques or thrombi and the intima was entirely clear white. CONCLUSIONS Prophylactic treatment for yellow plaque and thrombus formation are extremely important in the development of early and late SVG disease. Aggressive lipid controlling therapy is quite attractive to avoid post CABG SVG disease and may be effective to maintain the long-term graft patency.

Stent thrombosis and drug-eluting stents.

Coronary stents have been used for the treatment of patients with coronary artery disease (CAD), and significantly improved procedural safety and are associated with a lower rate of restenosis compared with balloon angioplasty alone. Drug-eluting stents (DES) have been dominant for the treatment of CAD with efficacy in significantly reducing both restenosis and target lesion revascularization. However, late and very late stent thrombosis have become a major concern in DES-implanted arteries compared with those treated with bare-metal stents (BMS). This review focuses on the feature of DES thrombosis and pathological examination and dual antiplatelet therapy for prevention of stent thrombosis. Currently, the incidence of stent thrombosis associated with first-generation and second-generation DES remains unclear in data from real-world cohort registry studies. Further studies of larger multicenter trials would give us insight into the specific mechanisms of stent thrombosis among different generations of DES.