Usefulness of Renal Autotransplantation for Radiotherapy-induced Renovascular Hypertension.

We experienced a young woman with congestive heart failure (CHF) caused by renovascular hypertension (RVH) and subsequent hypertensive heart disease. She underwent tumor resection and intraoperative radiation therapy because of neuroblastoma at age 2. She was diagnosed with RVH and hypertensive heart disease due to radiation-induced renal artery stenosis at age 12. Thereafter, she was hospitalized with CHF caused by uncontrolled RVH at age 19, and renal autotransplantation with extraction of left kidney was performed after the recovery of CHF. Her blood pressure has been well controlled without CHF readmission during four years of follow-up after the operation.

Feasibility and safety of outpatient cardiac catheterization with intracoronary acetylcholine provocation test.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. Although outpatient coronary angiography has been widely performed in current clinical settings, the feasibility and safety of ACh provocation test in outpatient services are unclear. A total of 323 patients, who electively underwent ACh provocation test in hospitalization and outpatient services, were included. Coronary angiography was performed after insertion of a temporary pacing electrode in the right ventricle. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing accompanied by chest pain and/or ischemic electrocardiographic changes. Cardiac complications defined as composite of death, ventricular fibrillation or sustained ventricular tachycardia, myocardial infarction, cardiogenic shock, and cardiac tamponade, were evaluated. There were 201 patients (62%) in the hospitalization group and 122 patients (38%) in the outpatient group. The incidence of positive ACh provocation test was similar between the 2 groups (47 vs. 54%, p = 0.21). Coronary angiography in the outpatient group was performed through the radial artery, mostly (98%) with a 4 F sheath. Venous access site was not significantly different between the 2 groups, and the sheath size was 5 F in all cases. There were 2 cases (1.0%) of cardiac complications in the hospitalization group, whereas 1 case (0.8%), which led to unexpected hospitalization, occurred in the outpatient group. In conclusion, intracoronary ACh provocation test for the diagnosis of vasospastic angina in outpatient services was feasible and safe in selected patients.

Platelet inhibition after loading dose of prasugrel in patients with ST-elevation and non-ST-elevation acute coronary syndrome.

The PRASFIT-ACS study showed the antiplatelet effect 2-4 h after prasugrel loading. However, there is little information about the antiplatelet effect <2 h after prasugrel loading dose, especially in patients with acute coronary syndrome (ACS). There had not been any comparison between ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE-ACS). Fifty patients with ACS (15 with STEMI and 35 with NSTE-ACS) were enrolled. They received a 20-mg prasugrel loading dose followed by a maintenance dose of 3.75 mg. Platelet reactivity [P2Y12 reaction units (PRU)] was evaluated by the VerifyNow assay at baseline, 30 min, 1, 2, 4, and 6 h, 1 week under prasugrel, and at 1 month after switching to clopidogrel. The primary end point was the change of PRU compared to the baseline. Furthermore, PRU after prasugrel loading between STEMI and NSTE-ACS was compared. A significant reduction in PRU from baseline was observed at ≥2 h after administration of prasugrel. In STEMI patients, a significant reduction in PRU was observed at 4 h after prasugrel loading. STEMI patients had higher PRU compared to NSTE-ACS patients at 2, 4, and 6 h after prasugrel loading. Utilizing >208 PRU as a cutoff value, STEMI patients had a higher prevalence of high on-treatment platelet reactivity at 2-6 h and 1 week after loading. Rapid antiplatelet effect is not achieved by low-dose prasugrel loading in STEMI patients. Platelet inhibition occurs earlier in NSTE-ACS patients, although it takes ≥2 h after loading in the majority of patients.

Relation between severity of myocardial bridge and vasospasm.

BACKGROUND: Myocardial bridge (MB) has been reported to induce cardiac complications including coronary vasospasm. Although MB has some anatomical and morphological variations, the association of these variations with vasospasm is unclear. The aim of this study was to investigate the relation between morphological severity of MB and vasospasm induced by acetylcholine (ACh) provocation test. METHODS: A total of 392 patients without coronary stent in the left anterior descending artery (LAD) undergoing intracoronary ACh provocation test were included. Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation. MB was identified on coronary angiography as a milking effect. Total bridged length and maximum percent systolic compression of MB in the LAD were analyzed quantitatively. RESULTS: MBs in the LAD were identified in 140 patients (36%), mostly in the mid segment. Patients with MB in the LAD had greater number of provoked vasospasm in the LAD and positive ACh provocation test compared to those without. The bridged length positively correlated with percent systolic compression of MB (r=0.37, p<0.001). In the receiver operating characteristic curve analysis, both bridged length and percent systolic compression of MB significantly predicted the provoked LAD spasm (AUC 0.74, p<0.001, and AUC 0.68, p<0.001). Multivariate regression analysis demonstrated these factors as independent predictors for provoked LAD spasm. CONCLUSION: MB, especially morphologically severe MB, may induce greater coronary vasospasm.

Comparison of 3-dimensional and 2-dimensional quantitative coronary angiography and intravascular ultrasound for functional assessment of coronary lesions.

BACKGROUND: Three-dimensional quantitative coronary angiography (3D-QCA) reportedly allows more accurate delineation of true vessel geometry when compared with standard two-dimensional (2D) QCA and has been validated by intravascular ultrasound (IVUS). This study sought to compare diagnostic efficiency of 2D- and 3D-QCA, and IVUS in identifying hemodynamically significant coronary stenoses as determined by fractional flow reserve (FFR). METHODS: Forty-two lesions in 40 patients were assessed by FFR, IVUS, and 2D- and 3D-QCA. Correlations between FFR values and anatomical parameters obtained by 2D- and 3D-QCA and IVUS were analyzed. The receiver operating characteristic (ROC) curves were used to compare the diagnostic accuracy of the parameters for predicting FFR≤0.80. RESULTS: Mean FFR value was 0.75±0.13. FFR≤0.80 was observed in 28 lesions (67%). Of IVUS measurements, minimum lumen area (MLA) well correlated with FFR values (r=0.71, p<0.001). Of 3D- and 2D-QCA measurements, minimum lumen diameter (MLD) correlated best with FFR values (r=0.79, p<0.01; r=0.68, p<0.01, respectively), followed by MLA (r=0.76, p<0.01; r=0.67, p<0.01, respectively). The area under the ROC curve for 3D-QCA MLD was greater than those for 2D-QCA MLD (p=0.03) and 2D-QCA MLA (p=0.03). On the other hand, the AUC for 3D-QCA MLD, 3D-QCA MLA, and IVUS MLA were not significantly different. CONCLUSIONS: 3D-QCA is more useful than 2D-QCA and possibly comparable to IVUS in the assessment of functional stenosis severity. When FFR is not available, 3D-QCA MLA and MLD may assist in the assessment of functional severity of intermediate lesions.

Paroxysmal atrial fibrillation during intracoronary acetylcholine provocation test.

Intracoronary acetylcholine (ACh) provocation test is useful to diagnose vasospastic angina. However, paroxysmal atrial fibrillation (AF) often occurs during intracoronary ACh provocation test, leading to disabling symptoms. The aim of this study was to investigate the incidence and predictors of paroxysmal AF during the test. A total of 377 patients without persistent AF who underwent intracoronary ACh provocation test were included. Paroxysmal AF during ACh provocation test was defined as documented AF on electrocardiogram during the procedure. There were 31 patients (8%) with paroxysmal AF during the test. Of these, 11 (35%) required antiarrhythmic drugs, but none received electrical cardioversion. All of them recovered sinus rhythm within 48 h. At procedure, paroxysmal AF occurred mostly during provocation for the right coronary artery (RCA) rather than for the left coronary artery (LCA) (90 vs. 10%). Multivariate logistic regression analysis demonstrated that a history of paroxysmal AF (OR 4.38 CI 1.42-13.51, p = 0.01) and body mass index (OR 0.88 CI 0.78-0.99, p = 0.03) were independent predictors for occurrence of paroxysmal AF during intracoronary ACh provocation test. In conclusions, paroxysmal AF mostly occurs during ACh provocation test for the RCA, especially in patients with a history of paroxysmal AF and lower body mass index. It may be better to initially administer intracoronary ACh in the LCA when the provocation test is performed.

Impact of chronic kidney disease on platelet inhibition of clopidogrel and prasugrel in Japanese patients.

BACKGROUND: The impact of chronic kidney disease (CKD) on the antiplatelet effect of clopidogrel and low-dose (3.75mg) prasugrel in Japanese patients is largely unknown. METHODS: A total of 53 consecutive Japanese patients with stable coronary artery disease who received aspirin and clopidogrel were enrolled, and categorized by estimated glomerular filtration rate (eGFR): CKD group (n=15, eGFR<60ml/min/1.73m2) and non-CKD group (n=38, eGFR≥60ml/min/1.73m2). Clopidogrel was switched to 3.75mg prasugrel. Platelet reactivity measurement using the VerifyNow P2Y12 assay (Accumetrics, San Diego, CA, USA) was performed at baseline (on clopidogrel) and day 14 (on prasugrel). RESULTS: The VerifyNow P2Y12 reaction units (PRU) during clopidogrel therapy was significantly higher in the CKD group than that in the non-CKD group (185.2±51.1 PRU vs. 224.3±57.0 PRU, p=0.02), whereas, the PRU with the prasugrel therapy in the CKD group and non-CKD group were not significantly different (149.9±51.1 PRU vs. 165.3±61.8 PRU, p=0.36). The PRU was significantly lower with the prasugrel therapy compared to that with the clopidogrel therapy both in the CKD group and in the non-CKD group. CONCLUSIONS: Antiplatelet effect of clopidogrel but not prasugrel is attenuated in patients with CKD. Prasugrel achieves a consistently lower platelet reactivity compared with clopidogrel regardless of the presence of mild to moderate CKD.

Very early tissue coverage after drug-eluting stent implantation: an optical coherence tomography study.

The aim of this study was to evaluate neointimal coverage in the very early phase after second-generation drug-eluting stent (DES) implantation using optical coherence tomography (OCT). Patients who underwent staged percutaneous coronary intervention within 30 days after DES implantation were enrolled. OCT was performed to observe DES previously implanted. The median time interval from implantation to OCT examination was 21.5 days. A total of 10,625 struts of 54 stents (52 everolimus-eluting stents and 2 zotarolimus-eluting stents) in 42 lesions were analyzed. Strut tissue coverage was observed in 71.1 ± 19.2 % of the struts, malapposed struts in 2.56 ± 3.37 %, strut tissue coverage at the side branch orifice in 10.6 ± 17.2 %, and struts with protrusion in 0.95 ± 3.46 %. Mean tissue thickness on the covered struts was 39.8 ± 14.2 µm. The percentage of stent coverage was significantly lower in the overlapping segments than in the non-overlapping segments (48.4 ± 17.5 % vs. 74.4 ± 20.2 %, P < 0.05). Most of the stent struts were covered by tissue within 30 days after second-generation DES implantation. However, the percentage of strut coverage was lower in the overlapping segments than in the non-overlapping segments, suggesting that very early interruption of dual antiplatelet therapy might result in increased risk of stent thrombosis, even in second-generation DES.

Feasibility of omitting provocation test with 50 µg of acetylcholine in left coronary artery.

According to the Japanese Circulation Society guideline of vasospastic angina, incremental doses of acetylcholine (ACh) are prescribed for coronary spasm provocation: 20 and 50 µg for the right coronary artery (RCA), and 20, 50 and 100 µg for the left coronary artery (LCA). However, provocation by low doses of ACh in patients with low vasoreactivity may be less needed, and the requirement of 50 µg of ACh for the LCA in these patients has not been evaluated. In the present study, patients who underwent ACh provocation test for both the RCA and LCA were included. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing (i.e., angiographic coronary artery spasm) accompanied by chest pain and/or ischemic electrocardiographic changes. Coronary artery constriction was visually evaluated and defined as coronary artery diameter reduction <25 or 25-90% in patients without angiographic coronary artery spasm by 20 µg of ACh in the LCA. There were 33 out of 249 patients (13%) with LCA spasm by 20 µg of ACh. In subjects without LCA spasm by 20 µg of ACh, patients with coronary constriction <25% (n = 101) by 20 µg of ACh in the LCA rarely showed coronary artery spasm induced by 50 µg of ACh in the LCA, in comparison to those with coronary constriction 25-90% (n = 115) (2.6 vs. 32.7%, p < 0.001). None of the patients with coronary constriction <25% by 20 µg of ACh in the LCA had cardiac complications associated with administration of ACh. In conclusion, omission of 50 µg of ACh in the LCA may be possible when there is little coronary artery constriction by 20 µg of ACh in the LCA during provocation test, leading to less contrast and shortens overall procedure time.

Efficacy of intravenous nicorandil for fractional flow reserve assessment: study protocol for a crossover randomised trial.

INTRODUCTION: Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. Intravenous administration of nicorandil can be applicable for fractional flow reserve (FFR) measurement as a hyperaemic agent and a possible alternative to adenosine. However, the effectiveness of intravenous nicorandil infusion for FFR measurement is largely unclear. METHODS AND ANALYSIS: This crossover randomised study is being performed to investigate the efficacy of intravenous administration of nicorandil for FFR measurement. Patients with an intermediate coronary artery stenosis who satisfy the eligibility criteria undergo FFR measurement with a consecutive randomised order of patient-blind infusions of continuous intravenous administration of adenosine and a single bolus intravenous administration of nicorandil. The primary end point of the study is the agreement between the FFR values obtained by the intravenous nicorandil and those obtained by the intravenous adenosine. Recruitment of this trial started in November 2015 and will end in March 2017, or until a total of 50 participants have been recruited. ETHICS AND DISSEMINATION: The protocol was approved by the Institutional Review Board at Chiba University Hospital. Study findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: UMIN000019309; Pre-results.

Predictive value of coronary artery dilation response to nitrate for a positive intracoronary acetylcholine provocation test.

BACKGROUND: Baseline coronary artery diameter and coronary artery dilation response to nitrate are associated with coronary vasoreactivity. OBJECTIVES: The present study investigated the predictive value of coronary artery tone for a positive intracoronary acetylcholine (ACh) provocation test. METHODS: A total of 197 patients who underwent an ACh provocation test in the right coronary artery were included. A positive ACh provocation test was defined as transient total or subtotal occlusion of a coronary artery with signs/symptoms of myocardial ischemia. The segment, from the ostium to the bifurcation, of the right coronary artery was analyzed quantitatively. Coronary artery dilation response to isosorbide dinitrate (ISDN) was defined as the mean lumen diameter after an intracoronary injection of ISDN divided by the diameter before administration of ACh (i.e. baseline coronary artery diameter). RESULTS: After the administration of ACh, 49 patients (24.9%) had a positive ACh provocation test. Smaller baseline right coronary artery diameter (2.35±0.45 vs. 2.73±0.48 mm, P<0.001) and greater right coronary artery dilation response to ISDN (1.34±0.12 vs. 1.15±0.11, P<0.001) were observed in patients with a positive ACh provocation test. The receiver operating characteristic curve for baseline coronary artery diameter poorly predicted the occurrence of a positive ACh provocation test (area under the curve 0.71). The predictive values of dilation response of the right coronary artery to ISDN for the occurrence of a positive ACh provocation test (area under the curve 0.87) was significantly better compared with that of baseline right coronary artery diameter (P<0.001). CONCLUSION: Coronary artery dilation response to nitrate is a more accurate predictor of a positive intracoronary ACh provocation test compared with baseline coronary artery diameter.

Intracoronary Acetylcholine Provocation Testing　- Omission of the 20-µg Dose Is Feasible in Patients Without Coronary Artery Spasm in the Other Coronary Artery.

BACKGROUND: Based on the Japanese Circulation Society guideline of vasospastic angina, incremental doses of acetylcholine (ACh) are prescribed for coronary spasm provocation: 20 and 50 µg for the right coronary artery (RCA), and 20, 50 and 100 µg for the left coronary artery (LCA). However, the requirement for each dose of ACh has not been fully evaluated. METHODS AND RESULTS: A total of 249 patients who underwent ACh provocation test for both the RCA and LCA were included. The positive diagnosis of intracoronary ACh provocation test was defined as total or subtotal coronary artery narrowing accompanied by chest pain and/or ischemic ECG changes. Positive ACh provocation test was observed in 116 patients (47%). Patients without vasospasm in the LCA had a lower incidence of vasospasm in the RCA induced by 20 µg of ACh compared with those with vasospasm in LCA (0.8% vs. 27.5%, P<0.001). Similarly, vasospasm in the LCA induced by 20 µg of ACh was observed less frequently in patients without than with vasospasm in the RCA (6.1% vs. 26.7%, P<0.001). In all patients without vasospasm in the other coronary artery, intracoronary administration of 50 µg of ACh was performed without any complications. CONCLUSIONS: Skipping the provocation test with 20 µg of ACh in patients without coronary artery spasm in the other coronary artery may be possible. (Circ J 2016; 80: 1820-1823).

Efficacy of combined administration of intracoronary papaverine plus intravenous adenosine 5'-triphosphate in assessment of fractional flow reserve.

BACKGROUND: Inducing maximal coronary hyperemia is important to measure fractional flow reserve (FFR) accurately. Intravenous adenosine and adenosine 5'-triphosphate (ATP) have been used to achieve maximal hyperemia. However, they may not induce maximal hyperemia in all patients. The present study evaluated the combined effect of intracoronary papaverine and intravenous ATP on FFR measurements. METHODS: FFR measurements with administration of intracoronary papaverine (12mg in the left coronary artery and 8mg in the right coronary artery), intravenous ATP (140µg/kg/min), and combined administration of intracoronary papaverine and intravenous ATP were performed in 51 patients with 57 intermediate lesions. RESULTS: The mean FFR after intravenous ATP was higher compared to intracoronary papaverine and intravenous ATP plus intracoronary papaverine (0.76±0.13 vs. 0.75±0.13 vs. 0.75±0.13, p=0.01). FFR-positive lesions (FFR ≤0.80) were observed more frequently with intravenous ATP plus intracoronary papaverine compared to intravenous ATP (64.9% vs. 47.4%, p=0.02). Of 32 and 25 FFR-negative lesions with intravenous ATP and intracoronary papaverine, 11 (34%) and 7 (28%) had positive FFR after administration of intravenous ATP plus intracoronary papaverine. No ventricular tachycardia or ventricular fibrillation was observed after administration of intracoronary papaverine. CONCLUSIONS: Maximal hyperemia may not be induced with intravenous ATP in all lesions. When sufficient hyperemia is doubtful during intravenous infusion of ATP, additional intracoronary administration of papaverine may be a possible option.

Protective effect of angiotensin II receptor blocker and calcium channel blocker on endothelial vasomotor function after everolimus-eluting stent implantation.

BACKGROUND: Endothelial dysfunction after drug-eluting stent implantation has been demonstrated. It may be associated with adverse cardiovascular events during follow-up. Olmesartan, an angiotensin II receptor antagonist, ameliorates endothelial dysfunction. The present study evaluated the protective effect of olmesartan on endothelial function after everolimus-eluting stent (EES) implantation. METHODS: A total of 40 patients who underwent EES implantation were randomly assigned to the olmesartan group (20 patients with 30 lesions) or the non-olmesartan group (20 patients with 32 lesions). Endothelial function was estimated by measuring the coronary vasoreactivity in the segments 15mm proximal and distal to EES in response to intracoronary infusion of acetylcholine (Ach; 10(-8) and 10(-7)mol/L) at 9-month follow-up. Endothelium-independent vasomotion was assessed after an intracoronary bolus of isosorbide dinitrate. RESULTS: In both groups, Ach infusion did not induce significant vasoconstriction in the segment either proximal or distal to the EES. The changes in coronary diameter in response to 10(-8)mol/L (-2.0±4.4% vs. -0.6±4.1%, p=0.33) and 10(-7)mol/L (-1.8±7.9% vs. -0.3±7.6%, p=0.57) Ach infusion in the segment proximal to EES were not significantly different between the olmesartan group and the non-olmesartan group. There were no significant differences in vasoconstriction in response to 10(-8)mol/L (-0.8±5.8% vs. -0.9±7.0%, p=0.96) and 10(-7)mol/L (1.8±9.7% vs. -1.8±9.7%, p=0.16) Ach infusion in the segment distal to EES between the 2 groups. Endothelium-independent vasodilation after nitrate infusion did not differ between the 2 groups. CONCLUSIONS: Endothelial dysfunction is not observed after EES implantation. Olmesartan does not improve endothelial function after EES implantation.

Relation of Lipid Content of Coronary Plaque to Level of Serum Uric Acid.

Elevated serum uric acid (SUA) level is known to be a prognostic factor in patients with acute coronary syndrome (ACS). However, the pathogenesis of the relation between SUA level and coronary plaque characteristics has not been fully evaluated. The aim of this study was to investigate the relation between SUA level and plaque composition of nonculprit lesions in patients with ACS. A total of 81 patients with ACS who underwent intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were included. They were classified into 3 groups according to tertiles of SUA level. Using integrated backscatter (IB)-IVUS system, tissue components were classified into 4 categories: calcium deposits, dense fibrosis, fibrosis, and lipid. Tertiles of SUA level were as follows: low tertile <5.0 mg/dl; intermediate tertile 5.0 to 6.4 mg/dl; and high tertile >6.4 mg/dl. There was a trend toward greater vessel volume in the high tertile group than in the low and intermediate tertile groups (19.4 ± 3.7 vs 17.4 ± 4.4 vs 16.7 ± 4.1 mm(3)/mm, p = 0.05). There was no significant difference in lumen volume between the 3 groups. Plaque volume was significantly greater in the high than in the low tertile group (8.6 ± 2.4 vs 6.7 ± 2.2 mm(3)/mm, p = 0.01). IB-IVUS analysis demonstrated greater lipid (59.1 ± 9.1% vs 49.7 ± 10.9% vs 51.1 ± 9.3%, p = 0.001) and less fibrous components (36.8 ± 7.8% vs 44.3 ± 7.8% vs 43.2 ± 6.7%, p <0.001) in the high than in the low and intermediate tertile groups. Multivariate analysis showed high SUA as an independent predictor of increasing lipid volume. In conclusion, elevated SUA level is associated with greater lipid content of coronary plaque in patients with ACS than in patients with normal levels.

Increased platelet inhibition after switching from maintenance clopidogrel to prasugrel in Japanese patients with stable coronary artery disease.

BACKGROUND: The pharmacodynamic effects of changing from standard-dose clopidogrel to low-dose (3.75 mg) prasugrel in Japanese patients are largely unknown. METHODS AND RESULTS: A total of 53 consecutive Japanese patients with stable coronary artery disease (CAD) who received aspirin and clopidogrel were enrolled. Clopidogrel was switched to 3.75 mg prasugrel. At day 14, prasugrel was switched to 75 mg clopidogrel. Platelet reactivity was measured using the VerifyNow assay at baseline, day 14, and day 28. VerifyNow P2Y12 reaction units (PRU) >208 was defined as high on-treatment platelet reactivity (HPR). The prevalence of HPR (18.9% vs. 41.5% vs. 44.2%, P<0.001) and the PRU level (154.3±54.2 vs. 196.2±55.5 vs. 194.6±55.8, P<0.001) were significantly lower on prasugrel maintenance therapy compared with the clopidogrel therapy before and after switching. The CYP2C19 genotypes that account for the 3 phenotypes (ie, extensive metabolizer, intermediate metabolizer, and poor metabolizer) had a significant impact on platelet reactivity with clopidogrel (174.9±54.0 vs. 193.1±56.5 vs. 240.6±25.4 PRU, P<0.001) but not prasugrel (147.0±51.9 vs. 147.5±58.3 vs. 184.4±38.3 PRU, P=0.15). CONCLUSIONS: Low-dose prasugrel achieves stronger platelet inhibition than clopidogrel in Japanese patients with stable CAD.

Efficacy and safety of low-dose clopidogrel in Japanese patients after drug-eluting stent implantation: a randomized pilot trial.

In Japan, a lower maintenance dose of ticlopidine is used than in the United States and Europe. Therefore a lower maintenance dose of clopidogrel may also be considered appropriate in Japanese patients. The present randomized pilot study evaluated the efficacy and safety of 50 mg clopidogrel in Japanese patients who underwent drug-eluting stent (DES) implantation. A total of 200 patients with 277 lesions who underwent intravascular ultrasound-guided DES implantation were enrolled. The subjects were allocated to the 50- or 75-mg clopidogrel group. All patients received 100 mg aspirin daily before the procedure, and this continued indefinitely. The duration of clinical follow-up was 21.8 ± 5.7 months in the 75-mg group and 21.9 ± 6.1 months in the 50-mg group (P = 0.96). During follow-up, no cardiac death, myocardial infarction, or stent thrombosis was observed in either group. Side effects of clopidogrel were observed in 4 patients (4.0 %) in the 75-mg group and in 4 patients (4.0 %) in the 50-mg group. Following this randomized pilot study, it may be justified to perform a large-scale randomized study comparing 50- and 75-mg dosing of clopidogrel in Japanese patients undergoing coronary stent implantation.

Effects of stem cell mobilization by granulocyte colony-stimulating factor on endothelial function after sirolimus-eluting stent implantation: a double-blind, randomized, placebo-controlled clinical trial.

BACKGROUND: Stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) has been shown to enhance endothelial healing after spontaneous or iatrogenic arterial disruption. Granulocyte colony-stimulating factor treatment might attenuate endothelial dysfunction after sirolimus-eluting stent (SES) implantation that may be associated with adverse cardiac events during follow-up. This prospective, double-blind, randomized, placebo-controlled study investigated whether G-CSF improved endothelial dysfunction after SES implantation. METHODS: One hundred patients who underwent SES implantation were randomly assigned to the G-CSF (n = 50) or the placebo group (n = 50). They received daily subcutaneous injection of 300 µg G-CSF or saline for 5 days. Endothelial function was estimated by measuring the coronary vasoreactivity in the segments 15 mm proximal and distal to SES in response to intracoronary infusion of acetylcholine (10(-8) and 10(-7) mol/L) at 9-month follow-up. RESULTS: Follow-up angiography was performed in 41 G-CSF patients (82%) and 46 placebo patients (92%) (P = .14). Changes in coronary diameter in response to acetylcholine infusion in the proximal segment were not significantly different between the 2 groups. However, vasoconstriction in the distal segment in response to 10(-8) mol/L (-3.9% ± 6.4% vs -7.0% ± 8.1%, P < .05) and 10(-7) mol/L (-8.8% ± 11.0% vs -15.2% ± 7.6%, P < .01) acetylcholine infusion was attenuated in the G-CSF group. Endothelium-independent vasodilatation after nitrate infusion did not differ between the 2 groups. CONCLUSION: Granulocyte colony-stimulating factor attenuates endothelial dysfunction after SES implantation.

Recovery of endothelial function after sirolimus-eluting stent implantation: a pilot study.

Whether endothelial dysfunction after sirolimus-eluting stent (SES) implantation is persistent has not been fully evaluated. Endothelial function was evaluated in 152 lesions that underwent follow-up coronary angiography after SES implantation. Lesions were classified into 2 groups according to the duration between SES implantation and follow-up: ≤12 months (n = 95) and >12 months (n = 57). Changes in coronary diameter in response to 10(-8) mol/L (-2.4% ± 6.3% vs -4.9% ± 3.8%, P < .01) and 10(-7) mol/L acetylcholine (Ach; -4.6% ± 7.6% vs -10.7% ± 9.1%, P < .001) in segment proximal to SES were significantly attenuated in the >12-month group than in the ≤12-month group. There were less changes in coronary diameter in response to 10(-8) mol/L (-2.3% ± 4.6% vs -6.9% ± 5.0%, P < .001) and 10(-7) mol/L Ach (-6.5% ± 11.4% vs -16.8% ± 10.5%, P < .001) in segment distal to SES in the >12-month group. Endothelial dysfunction may diminish long after SES implantation.