北原 秀喜

Microvessels within neoatherosclerosis are associated with vulnerability and increase from the early to the very late phase after drug-eluting stent implantation. Microbubble contrast agents have been suggested to enhance tissue microvasculature for optical coherence tomography (OCT) imaging. The present study investigated whether OCT signal intensity of neointima within stented segments was enhanced after intracoronary administration of microbubble contrast agents. A total of 40 patients who underwent follow-up coronary angiography after drug-eluting stent implantation were enrolled. At the time of follow-up coronary angiography, OCT images of the stented segments were recorded before and after intracoronary administration of microbubble contrast agents. Mean OCT signal intensity of neointima after microbubble administration significantly increased [95.5 (85.7, 106.2) vs. 96.5 (88.7, 109.9), p = 0.001]. Multivariate analysis demonstrated the relationship between diabetes and greater neointima enhancement. The change in the OCT signal intensity of neointima following microbubble administration tended to be higher in diabetic patients than in non-diabetic patients [4.6 (0.6, 8.5) vs. 1.4 (- 1.1, 3.0), p = 0.05]. These findings suggest that this methodology may allow identification of neovascularization in neointima and evaluation of vulnerability of neoatherosclerosis. Microvessels in neointima may be a future target of pharmacological and interventional innovations for preventing stent failure.

BACKGROUND: The difference in intraluminal intensity of blood speckle (IBS) on integrated backscatter-intravascular ultrasound (IB-IVUS) across the coronary artery stenosis (i.e., ΔIBS) has been reported to negatively correlate with fractional flow reserve. Fractional flow reserve after coronary stenting is known as a predictor of target vessel revascularization (TVR). However, the relation between ΔIBS and TVR is unclear. METHODS: Seven hundred and three vessels which underwent percutaneous coronary intervention with stents were screened. Vessels without IVUS-guidance and follow-up information were excluded. Intraluminal IBS values were measured using IB-IVUS in cross-sections at the ostium of the target vessel and at the distal reference of implanted stent. ΔIBS was calculated as (distal IBS) - (ostium IBS). RESULTS: A total of 393 vessels were included. Mean ΔIBS at postprocedure was 6.22 ± 5.65. During the follow-up period (11.2 ± 3.1 months), 24 cases (6.1%) had TVR. ΔIBS was significantly greater in the vessels with TVR than in those without (11.10 ± 5.93 vs. 5.90 ± 5.49, P <0.001). In receiver operating characteristic curve analysis, ΔIBS significantly predicted TVR (AUC 0.74, best cut-off value 8.24, P < 0.001). Multiple logistic regression analysis showed use of drug eluting stent and ΔIBS ≥ 8.24 as independent predictors of TVR. CONCLUSIONS: ΔIBS at postprocedure was significantly associated with TVR. IVUS may be able to predict TVR by physiological assessment with measurement of ΔIBS.

We recently reported that preoperative endothelial dysfunction [i.e., reactive hyperemia index (RHI) ≤ 1.64] predicted short-term postoperative adverse events in patients undergoing cardiovascular surgery. However, the relationship between preoperative RHI and long-term cardiovascular risk in these patients is unclear. A total of 195 patients with at least 1-year follow-up who underwent cardiovascular surgery were included. Preoperative endothelial function was assessed by RHI. The primary outcome was a composite of cardiac death, stroke, myocardial infarction, rehospitalization due to heart failure, and any coronary revascularization. Nineteen patients (9.7%) met the primary outcome, including cardiac death (n = 7), stroke (n = 5), heart failure (n = 9), and coronary revascularization (n = 2) during a median follow-up of 20 months. There was no significant difference in the baseline characteristics between patients with RHI ≤ 1.64 (n = 86) and those with RHI > 1.64 (n = 109). The primary outcome occurred in 13 patients with RHI ≤ 1.64 (15.1%) and in 6 patients with RHI > 1.64 (5.5%). Kaplan-Meier analysis demonstrated a significantly higher incidence of the primary outcome in patients with RHI ≤ 1.64 compared to their counterpart (hazard ratio 2.94; 95% confidence interval 1.12-7.75; p = 0.02). Multivariate analysis showed diabetes and RHI ≤ 1.64 as independent predictors for the primary outcome. In conclusion, preoperative endothelial dysfunction assessed by RHI was associated with long-term cardiovascular events in patients undergoing cardiovascular surgery.

BACKGROUND: High on-treatment platelet reactivity (HPR) under clopidogrel treatment is frequently observed in hemodialysis (HD) patients. In such patients, 10mg of prasugrel has reportedly inhibited platelet reactivity more adequately compared with 75mg of clopidogrel. However, the efficacy of 3.75mg prasugrel in Japanese HD patients is largely unknown. METHODS: A total of 41 Japanese coronary artery disease patients under HD who received aspirin and clopidogrel were enrolled. Clopidogrel was switched to 3.75mg prasugrel. At day 14, prasugrel was switched to clopidogrel. Platelet reactivity was measured using VerifyNow assay (Accumetrics, San Diego, CA, USA) at baseline, day 14, and day 28. VerifyNow P2Y12 reaction units (PRU) >208 was defined as HPR. RESULTS: The PRU level on prasugrel therapy was significantly lower than that on clopidogrel therapy before switching (219.1±62.3 PRU vs. 238.2±68.0 PRU, p=0.02). Although the prevalence of HPR was numerically lower on prasugrel therapy compared with clopidogrel therapy before and after switching, the differences did not reach a statistical significance (57.6% vs. 75.7% vs. 74.2%, p=0.13). Even under prasugrel treatment, more than half of patients showed HPR. CONCLUSIONS: Although low-dose prasugrel had somewhat better antiplatelet effect than clopidogrel, it could not significantly improve the prevalence of HPR in Japanese HD patients. Higher doses of prasugrel might be needed to achieve adequate platelet inhibition in this high thrombotic risk population.

Nicorandil has vasodilatory effects on both the epicardial coronary arteries and the coronary microvasculature, thereby increasing coronary blood flow. The objective of the present study was to investigate the effectiveness of intravenous (IV) nicorandil infusion for fractional flow reserve (FFR) measurement. In this crossover randomized study, 49 patients underwent FFR measurement with a consecutive randomized order of patient-blind infusions of continuous IV adenosine administration and a single bolus IV administration of nicorandil. The primary endpoint was the difference between the FFR by nicorandil and the FFR by adenosine, as assessed by the Bland-Altman method. The mean FFR value measured by nicorandil was not significantly different from that measured by adenosine [0.8125 ± 0.1349 vs. 0.7978 ± 0.124; mean difference, 0.0147 (95% confidence interval - 0.0373, 0.0667); P = 0.58]. There was no clinically significant diagnostic discordance, with the FFR by nicorandil > 0.80 and that by adenosine < 0.75. Hyperemia was achieved earlier using nicorandil than adenosine (34 ± 13 vs. 58 ± 15, P < 0.001). The duration of hyperemia after IV nicorandil was variable (6-570 s, mean 89 ± 98 s). IV nicorandil decreased systolic blood pressure by 32 ± 16 mm Hg (24 ± 10%) from baseline. Linear regression analysis showed that the average FFR value and the difference in systolic blood pressure were significantly associated with the bias in the FFR value between the two drugs. In conclusions, the results of the present study suggest that IV nicorandil can achieve maximal hyperemia easily and rapidly, providing an acceptable diagnostic performance for FFR assessment. However, a wide range of variation in hyperemic plateau and a decrease in blood pressure are the major limitations of this method.

BACKGROUND: Vasospastic angina (VSA), which often causes acute coronary syndrome (ACS), can be diagnosed by intracoronary acetylcholine (ACh) provocation test. However, the safety and usefulness of ACh provocation test in ACS patients on emergency coronary angiography (CAG) compared to non-emergency settings are unclear. METHODS: A total of 529 patients undergoing ACh provocation test during emergency or non-emergency CAG were included. Patients with resuscitated cardiac arrest were excluded. The primary endpoint was adverse events defined as a composite of death, ventricular fibrillation or sustained ventricular tachycardia, myocardial infarction, cardiogenic shock, cardiac tamponade, and stroke within 24 h after ACh provocation test. RESULTS: There were no significant differences of the clinical characteristics between the groups of emergency (n = 84) and non-emergency (n = 445) ACh provocation test. The rate of positive ACh provocation test was similar between the 2 groups (50% vs. 49%, p = 0.81). Similarly, the incidence of adverse events in patients with emergency and non-emergency ACh provocation test did not significantly differ (1.2% vs. 1.3%, p = 1.00). CONCLUSION: ACh provocation test can be safely performed in ACS patients with no obstructive culprit lesions on emergency CAG, and may be useful to diagnose VSA in those patients.

BACKGROUND: Due to concern about bleeding complications, a maintenance dose of prasugrel 2.5 mg may be used in elderly or low-body-weight patients in Japan. There is little information, however, on the efficacy and safety of a 2.5-mg maintenance dose of prasugrel. Methods and Results: In this single-center, prospective, open-label, cross-over study, a total of 44 elderly (≥75 years old) or low body-weight (<50 kg) Japanese patients >1 month after percutaneous coronary intervention who were treated with aspirin 81-100 mg and clopidogrel 75 mg were randomized to either prasugrel 2.5 mg or 3.75 mg instead of clopidogrel for 14 days, with a cross-over directly to the alternate treatment for another 14 days. Platelet inhibition was assessed with the VerifyNow assay (Accumetrics, San Diego, CA, USA) at 3 time points: baseline; day 14; and day 28. P2Y12 reaction units (PRU) ≤95 was defined as low on-treatment platelet reactivity (LPR), and PRU ≥262 as high on-treatment platelet reactivity (HPR). The prevalence of LPR was 2.2% in patients treated with clopidogrel, 2.2% in those with prasugrel 2.5 mg, and 22.7% in those with prasugrel 3.75 mg (P<0.001). Clopidogrel resulted in the higher prevalence of HPR compared with 2.5-mg and 3.75-mg prasugrel (40.9% vs. 18.2% vs. 6.8%, P<0.001). CONCLUSIONS: Prasugrel 2.5 mg may be more appropriate in elderly or lower-body-weight Japanese patients.

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.

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.

BACKGROUND: The aim of this study was to investigate microvascular function in patients with valvular heart disease (VHD), which causes chronic left ventricular volume and/or pressure overload, therefore change in coronary microvascular hemodynamics. PATIENTS AND METHODS: We prospectively enrolled 30 patients with VHD considered for surgery (10 aortic stenosis, 12 aortic regurgitation, and eight mitral regurgitation) and 30 controls. Intracoronary physiological assessments were performed in the unobstructed left anterior descending artery using a pressure-temperature sensor guidewire at rest and hyperemia. RESULTS: The index of microcirculatory resistance (IMR) was similar between the two groups (16.2±6.5 vs. 16.2±8.5, P=0.997), whereas coronary flow reserve (CFR) was lower in the VHD group compared with the controls (3.2±1.4 vs. 4.3±1.7, P=0.005). Resting and hyperemic coronary distal pressure, and hyperemic mean transit time were similar between VHD and controls, whereas resting mean transit time was significantly shorter (0.70±0.29 vs. 0.89±0.39, P=0.035) and baseline resting microvascular resistance was significantly lower in the VHD group compared with the controls (58.1±25.4 vs. 78.1±36.7, P=0.011). Patients with aortic stenosis showed numerically higher IMR values than aortic regurgitation, mitral regurgitation, and controls, although this was not statistically significant (20.4±6.9, P=0.14). CFR was significantly correlated with log high-sensitivity cardiac troponin T levels in patients with VHD (r=-0.523, P=0.004). CONCLUSION: CFR was reduced in patients with VHD compared with controls, despite similar microvascular function as assessed by IMR. This appeared to be mainly because of an increased resting coronary flow accompanied by a decreased resting coronary microvascular resistance rather than microvascular disease.

OBJECTIVES: The aim of this study was to characterize post-procedural intravascular ultrasound (IVUS) findings in the ABSORB Japan trial, specifically stratified by the size of target coronary arteries. BACKGROUND: Despite overall noninferiority confirmed in recent randomized trials comparing bioresorbable vascular scaffolds (BVS) (Absorb BVS) and cobalt-chromium everolimus-eluting metallic stents (CoCr-EES), higher event rates of Absorb BVS have been reported with suboptimal deployment, especially in small coronary arteries. METHODS: In the ABSORB Japan trial, 150 patients (2:1 randomization) were scheduled in the IVUS cohort. Small vessel was defined as mean reference lumen diameter <2.75 mm. Tapered-vessel lesions were defined as tapering index (proximal/distal reference lumen diameter) ≥1.2. RESULTS: Overall, IVUS revealed that the Absorb BVS arm had smaller device expansion than the CoCr-EES arm did, which was particularly prominent in small- and tapered-vessel lesions. Higher tapering index was also associated with higher rates of incomplete strut apposition in Absorb BVS, but not in CoCr-EES. With respect to procedural techniques, small-vessel lesions were treated more frequently with noncompliant balloons at post-dilatation but using significantly lower pressure in the Absorb BVS arm. In contrast, tapered-vessel lesions were post-dilated at equivalent pressure but with significantly smaller balloon catheters in the Absorb BVS arm, compared with the CoCr-EES arm. CONCLUSIONS: The significantly smaller device expansion especially in small vessels may account for the poorer outcomes of Absorb BVS in this lesion type. Appropriate optimization strategy, possibly different between polymeric and metallic devices, needs to be established for bioresorbable scaffold technology. (AVJ-301 Clinical Trial: A Clinical Evaluation of AVJ-301 Absorb™ BVS) in Japanese Population [ABSORB JAPAN]; NCT01844284).

BACKGROUND: In vivo assessment of bioresorbable scaffold (BRS) is of growing clinical interest. The novel 60MHz high-definition intravascular ultrasound (HD-IVUS) has been developed to overcome the limitations of conventional 40 MHz IVUS. This study aimed to evaluate the performance and limitations of 60 MHz HD-IVUS compared with 40 MHz IVUS with respect to polymeric-strut visualization, quantitative and qualitative analysis, and feasibility of high-speed pullback in the assessment of BRS. METHODS AND RESULTS: In a bench-test model, 361 struts were analyzed to evaluate the influence of ultrasound-beam angles and proximity of adjacent struts on IVUS visualization of BRS struts. Various settings were created by deforming the BRS and positioning the transducer offcenter. In an in vivo swine coronary model, scaffold and lumen areas, degree of visible external elastic membrane, incomplete strut apposition, and strut fracture were evaluated in 59 matched cross-sections obtained at conventional (0.5 mm/sec) and high speed (10 mm/sec) pullbacks. Both studies utilized optical coherence tomography (OCT) as reference. Overall, 60 MHz HD-IVUS demonstrated significantly improved visualization of polymeric struts compared with 40 MHz IVUS (well-visualized: 84.5% vs 62.3%, not visible: 4.4% vs 13.9%, respectively. P < 0.001), which was less affected by the beam angle and adjacent strut proximity. In the in vivo model, 60-MHz HD-IVUS showed better agreement of area measurements and strut abnormalities with OCT than 40 MHz IVUS. These findings were also confirmed on high-speed pullback images of 60 MHz HD-IVUS. CONCLUSION: As referenced to OCT, this study showed superiority of 60 MHz HD-IVUS over 40 MHz IVUS in the assessment of BRS with feasibility of high-speed pullback imaging.

Left ventricular outflow tract (LVOT) obstruction is sometimes observed in patients with severe aortic stenosis (AS). It is still controversial how to manage the remaining severe AS, when LVOT obstruction is well-controlled by medical therapy. We report a case with acute recurrence of LVOT obstruction requiring emergent alcohol septal ablation (ASA) after transcatheter aortic valve implantation (TAVI), even in a stable state on beta-blockers. For the ASA procedure, transesophageal echocardiography was useful to clearly observe the perfusion area of the target septal branch by injecting microbubble contrast. Since it took some time to cause the recurrence of LVOT obstruction in this case, careful evaluation should be done after TAVI in high-risk patients for LVOT obstruction before terminating the TAVI procedure.

BACKGROUND: Cardiovascular surgery is one of the highest risk procedures in the field of surgery. Preoperative assessment of endothelial function has been reported as useful for predicting postoperative adverse events (AEs). The aim of this study was to investigate the relationship between endothelial function assessed by reactive hyperemia index (RHI) and AEs after cardiovascular surgery.Methods and Results:A prospective observational study of 197 patients who underwent cardiovascular surgery was conducted. RHI was measured before the surgery. The primary endpoint was a composite of postoperative death, reoperation, stroke, newly required dialysis, deep sternum infection, and prolonged ventilation within 30 days. The secondary endpoint was new-onset atrial fibrillation (AF) within 30 days. Following cardiovascular surgery, 19 patients (9.6%) had AEs. New-onset AF was documented in 42 (25.9%) of 162 patients without a prior history of AF. In the receiver-operating characteristic curve analysis, RHI significantly predicted AEs (area under the curve [AUC] 0.67, best cutoff value 1.64, P=0.03), whereas RHI did not predict new-onset AF (AUC 0.53, P=0.93). Patients with RHI ≤1.64 had more AEs than those with RHI >1.64 (16.3% vs. 4.5%, P=0.005). Multiple logistic regression analysis showed the number of surgical procedures and RHI ≤1.64 as significant predictors of AEs. CONCLUSIONS: Preoperative endothelial dysfunction assessed by RHI was associated with postoperative AEs in patients with cardiovascular surgery.

BACKGROUND: Prevalence of myocardial bridging of the left anterior descending coronary artery (LAD) in patients with takotsubo syndrome (TTS) has been demonstrated. However, the impact of myocardial bridging on in-hospital outcome has not been fully evaluated. METHODS: A total of 144 consecutive patients with TTS were enrolled. Coronary angiography and left ventriculography were performed in all patients and absence of obstructive coronary disease explaining the left ventricular contraction abnormality was confirmed. Myocardial bridging was diagnosed when a dynamic compression in systole, so-called "milking effect", was observed in the LAD. We evaluated differences in the clinical characteristics and in-hospital outcome between patients with and without myocardial bridging. Furthermore, multiple logistic regression analysis was performed to predict in-hospital death. RESULTS: Myocardial bridging was observed in 33 patients (23%). In-hospital death was more frequent in patients with myocardial bridging (21% vs. 6%, p=0.02), which was due mainly to a higher non-cardiac death in those patients (15% vs. 5%, p=0.049). Multiple logistic regression analysis demonstrated myocardial bridging (odds ratio=12.0, 95% CI=2.52-78.5, p<0.01) as one of the independent predictors of in-hospital death. CONCLUSION: Myocardial bridging is an independent predictor of in-hospital death in patients with TTS.

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.

The difference in the intraluminal intensity of blood speckle (IBS) on integrated backscatter-intravascular ultrasound (IB-IVUS) across a coronary artery stenosis (i.e., ΔIBS) has previously shown a negative correlation with fractional flow reserve, reflecting an impaired coronary blood flow. Periprocedural myocardial injury (PMI) after coronary stenting has also been associated with coronary circulatory dysfunction. The aim of this study was to investigate the relation between ΔIBS after coronary stenting and PMI. A total of 180 patients who underwent elective coronary stenting under IVUS guidance for a single lesion were included. Intraluminal IBS was measured using IB-IVUS in cross sections at the ostium of the target vessel and at the distal reference of the stent. ΔIBS was calculated as (distal IBS value) - (ostium IBS value). PMI was defined as an elevation of troponin I >5 times the 99th percentile upper reference limit (>0.45 ng/ml) within 24 hours after the procedure. The mean ΔIBS after coronary stenting was 6.52 ± 5.71. There was a significantly greater use of the rotational atherectomy, the number of stents, the total stent length, and ΔIBS in patients with PMI than those without. In the receiver operating characteristic curve analysis, ΔIBS significantly predicted PMI (area under the curve 0.64, best cut-off value 7.88, p = 0.001). Multiple logistic regression analysis determined that the total stent length, the use of rotational atherectomy, and ΔIBS were independent predictors of PMI. In conclusion, greater ΔIBS assessed by IB-IVUS was significantly associated with PMI after coronary stenting in patients with a stable coronary artery disease.

BACKGROUND: Although significant undersizing often results in incomplete stent apposition or underexpansion, the possible impact of oversized stent implantation on arterial wall injury has not been systematically investigated with drug-eluting stents. The aim of this study was to investigate the impact of stent oversizing on acute and long-term outcomes after drug-eluting stents implantation in de novo coronary lesions. METHODS AND RESULTS: Serial (baseline and 6-12 months) coronary angiography and intravascular ultrasound were performed in 2931 lesions treated with drug-eluting stents (355 sirolimus, 846 paclitaxel, 1387 zotarolimus, and 343 everolimus). The percentage of stent oversizing to angiographic reference vessel diameter (RVD) was calculated as (nominal stent diameter-RVD)/RVD×100 (%). Clinical outcomes, including target lesion revascularization and stent thrombosis, were followed for 1 year. Overall, smaller preintervention RVD was associated with higher percentage of stent oversizing (P<0.001). The significant oversizing group underwent less post-dilatation (P=0.002) but achieved greater stent expansion (P<0.001) and less incomplete stent apposition (P<0.001) without increase of edge dissection after procedure. When stratified by vessel size and stent oversizing, progressive decreases of restenosis (P=0.002) and target lesion revascularization rates (P=0.007) were found in favor of larger vessel size and oversized stents. Stent thrombosis was observed the most in small RVD with low percentage of stent oversizing group among the subgroups (P=0.040). CONCLUSIONS: The positive impact of stent oversizing was documented on procedural and clinical outcomes. In particular, small vessels treated with smaller stents were associated with greater adverse events, suggesting that aggressive selection of larger stents, with appropriate attention to edge effects, may optimize long-term outcomes, even in drug-eluting stents implantation.

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.

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.

BACKGROUND AND AIMS: The aim of this study was to investigate the impact of attenuated-signal plaque (ASP) observed by intravascular ultrasound (IVUS) on vessel response after drug-eluting stent implantation. METHODS: Data were derived from the IVUS cohort of the J-DESsERT trial comparing paclitaxel- and sirolimus-eluting stents. Serial IVUS analysis (pre- and post-intervention, and 8-month follow-up) was performed in 136 non-AMI lesions. ASP was defined as hypoechoic plaque with ultrasound attenuation without calcification. Calcified plaque (CP) was defined as brightly echoreflective plaque with acoustic shadowing. ASP and CP scores were calculated by grading their measured angle as 0 to 4 for 0°, <90°, 90-180°, 180-270° and >270°, respectively. The entire stented segment was analyzed at 1-mm intervals. RESULTS: At pre-intervention, ASP was observed in 40.4% of lesions, and this group had greater % neointimal volume (%NIV) at follow-up than the no-ASP group (p = 0.011). ASP score at pre-intervention positively correlated with %NIV (p = 0.023). During the follow-up, ASP score significantly decreased (p < 0.001), and CP score significantly increased (p < 0.001), with a negative correlation between them (p < 0.001). A decrease in the ASP score was associated with less %NIV in PES (p = 0.031), but not in SES (p = 0.229). CONCLUSIONS: The greater extent of plaque with IVUS-signal attenuation at pre-intervention and its persistence during follow-up were associated with neointimal proliferation, possibly representing sustained inflammatory status, depending on the type of DES used.

OBJECTIVES: The difference in intraluminal intensity of blood speckle (IBS) on integrated backscatter intravascular ultrasound (IVUS) across the coronary stenosis was reportedly correlated with fractional flow reserve (FFR) in the left descending coronary artery. The aim of this study was to investigate the novel physiological assessment using IVUS in all coronary arteries. PATIENTS AND METHODS: Fifty-four patients with 57 coronary lesions underwent both FFR and IVUS. Intraluminal IBS was analyzed using integrated backscatter IVUS in cross-sections at the ostium and the distal site of the target vessel. ΔIBS was calculated as: (distal IBS)-(ostium IBS). RESULTS: Both ΔIBS (r=-0.50, P<0.01) and minimum lumen area (MLA) (r=0.55, P<0.01) showed significant correlations with FFR. There were significant correlations between FFR and ΔIBS in the right and left descending coronary arteries (r=-0.60, P=0.02, and r=-0.58, P<0.01), but not in the left circumflex (r=0.30, P=0.44). In receiver operating characteristic curve analyses, ΔIBS predicted FFR less than or equal to 0.80 (area under the curve=0.82, P<0.01, best cutoff value=6.78), as with MLA (area under the curve=0.83, P<0.01, best cutoff value=2.38). FFR progressively decreased in association with ΔIBS greater than or equal to 6.78 and MLA less than or equal to 2.38, and was the lowest when these were combined. CONCLUSION: ΔIBS was correlated with FFR in right and left descending coronary arteries. IVUS may assess coronary artery stenosis anatomically and physiologically.

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.

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.

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.

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.

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.

BACKGROUND: Although cardiac allograft vasculopathy (CAV) is typically characterized by diffuse coronary intimal thickening with pathological vessel remodeling, plaque instability may also play an important role in CAV. Previous studies of native coronary atherosclerosis have demonstrated associations between attenuated-signal plaque (ASP), plaque instability, and adverse clinical events. OBJECTIVES: This study's aim was to characterize the association between ASP and long-term mortality post-heart transplantation. METHODS: In 105 heart transplant recipients, serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in the first 50 mm of the left anterior descending artery. The ASP score was calculated by grading the measured angle of attenuation from grades 0 to 4 (specifically, 0°, 1° to 90°, 91° to 180°, 181° to 270°, and >270°) at 1-mm intervals. The primary endpoint was all-cause death or retransplantation. RESULTS: At 1-year post-transplant, 10.5% of patients demonstrated ASP progression (newly developed or increased ASP). Patients with ASP progression had a higher incidence of acute cellular rejection during the first year (63.6% vs. 22.3%; p = 0.006) and tendency for greater intimal growth (percent intimal volume: 9.2 ± 9.3% vs. 4.4 ± 5.3%; p = 0.07) than those without. Over a median follow-up of 4.6 years, there was a significantly lower event-free survival rate in patients with ASP progression at 1-year post-transplant compared with those without. In contrast, maximum intimal thickness did not predict long-term mortality. CONCLUSIONS: ASP progression appears to reflect chronic inflammation related to acute cellular rejection and is an independent predictor of long-term mortality after heart transplantation. Serial assessments of plaque instability may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

BACKGROUND: Because it is difficult to distinguish between focal takotsubo cardiomyopathy and aborted myocardial infarction, there is little information about the prevalence and clinical features of focal takotsubo cardiomyopathy. METHODS AND RESULTS: Our cardiac catheterization databases were queried to identify patients with focal takotsubo cardiomyopathy and other types of takotsubo cardiomyopathy. We defined focal takotsubo cardiomyopathy as hypo-, a- or dyskinesis in both anterolateral and septal segments without obstructive coronary artery disease explaining the wall motion abnormality. A total of 10 patients were diagnosed with focal takotsubo cardiomyopathy. The control group comprised patients with takotsubo cardiomyopathy with apical, mid-ventricular, or basal ballooning. Clinical features and in-hospital outcomes were compared between patients with focal takotsubo cardiomyopathy and those with other types of takotsubo cardiomyopathy. Among the 144 patients with takotsubo cardiomyopathy, the apical, mid-ventricular, basal, and focal types occurred in 85 (59.0%), 49 (34.0%), 0 (0%), and 10 patients (6.9%), respectively. The left ventricular ejection fraction was significantly higher in the focal group compared with the apical and mid-ventricular group (56±13 vs. 45±13 vs. 46±12%, P=0.03). In-hospital outcome was not significantly different among the 3 groups. CONCLUSIONS: Focal takotsubo cardiomyopathy is not rare. Biplane left ventriculography is useful for its diagnosis. (Circ J 2016; 80: 1824-1829).

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).

AIMS: Our aim was to evaluate stent expansion and acute recoil at deployment and post-dilatation, and the impact of post-dilatation strategies on final stent dimensions. METHODS AND RESULTS: Optical coherence tomography (OCT) was performed on eight bare metal platforms of drug-eluting stents (3.0 mm diameter, n=6 for each) during and after balloon inflation in a silicone mock vessel. After nominal-pressure deployment, a single long (30 sec) vs. multiple short (10 sec x3) post-dilatations were performed using a non-compliant balloon (3.25 mm, 20 atm). Stent areas during deployment with original delivery systems were smaller in stainless steel stents than in cobalt-chromium and platinum-chromium stents (p<0.001), whereas subsequent acute recoil was comparable among the three materials. At post-dilatation, acute recoil was greater in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001), resulting in smaller final stent areas in cobalt-chromium and platinum-chromium stents than in stainless steel stents (p<0.001). In comparison between conventional and latest-generation cobalt-chromium stents, stent areas were not significantly different after both deployment and post-dilatation. With multiple short post-dilatations, acute recoil was significantly improved from first to third short inflation (p<0.001), achieving larger final area than a single long inflation, despite stent materials/designs (p<0.001). CONCLUSIONS: Real-time OCT revealed significant acute recoil in all stent types. Both stent materials/designs and post-dilatation strategies showed a significant impact on final stent expansion.

BACKGROUND: This study investigated the relationship between periarterial neovascularization, development of cardiac allograft vasculopathy (CAV), and long-term clinical outcomes after heart transplantation. Proliferation of the vasa vasorum is associated with arterial inflammation. The contribution of angiogenesis to the development of CAV has been suggested. METHODS: Serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in 102 heart transplant recipients. Periarterial small vessels (PSV) were defined as echolucent luminal structures <1 mm in diameter, located ≤2 mm outside of the external elastic membrane. The signal void structures were excluded when they connected to the coronary lumen (considered as side branches) or could not be followed in ≥3 contiguous frames. The number of PSV was counted at 1-mm intervals throughout the first 50 mm of the left anterior descending artery, and the PSV score was calculated as the sum of cross-sectional values. Patients with a PSV score increase of ≥ 4 between baseline and 1-year post-transplant were classified as the "proliferative" group. Maximum intimal thickness was measured for the entire analysis segment. RESULTS: During the first year post-transplant, the proliferative group showed a greater increase in maximum intimal thickness (0.33 ± 0.36 mm vs 0.10 ± 0.28 mm, p < 0.001) and had a higher incidence of acute cellular rejection (50.0% vs 23.9%, p = 0.025) than the non-proliferative group. On Kaplan-Meier analysis, cardiac death-free survival rate over a median of 4.7 years was significantly lower in the proliferative group than in the non-proliferative group (hazard ratio, 3.10; p = 0.036). CONCLUSIONS: The increase in PSV, potentially representing an angioproliferative response around the coronary arteries, was associated with early CAV progression and reduced survival after heart transplantation.

Clopidogrel resistance is associated with stent thrombosis. Prasugrel achieves greater platelet inhibition with less variability among patients than does clopidogrel. Thus, a patient who had stent thrombosis due to clopidogrel resistance may receive prasugrel to prevent repeated episodes of stent thrombosis. This case report describes a case of repetitive stent thrombosis in which resistance not only to clopidogrel, but also to prasugrel, was observed. <Learning objective: In the face of clopidogrel resistance, prescribing prasugrel may be an acceptable treatment option. However, cross-unresponsiveness may be observed between clopidogrel and prasugrel. Thus, platelet function assay should be performed in patients with stent thrombosis, even when clopidogrel is replaced with prasugrel.>.

No systematic validation study is available with optical frequency domain imaging (OFDI), directly compared with frequency domain optical coherence tomography (FD-OCT) and intravascular ultrasound (IVUS). Controversy also remains about the impact of different stent contour tracing methods by OFDI/FD-OCT. In vitro: coronary phantom models (1.51-5.04 mm) were imaged with OFDI, FD-OCT, and IVUS, demonstrating excellent quantitative precision with a slight overestimation of mean lumen diameter (difference 0.01-0.02 mm). In vivo: corresponding 64 OFDI/IVUS images of stented coronary segments from 20 swines were analyzed. Minimum lumen area by OFDI was larger than IVUS at baseline (P < 0.001), whereas it was smaller than IVUS at follow-up. When stent was traced at leading edges of struts by OFDI, minimum stent area was similar between OFDI and IVUS (P = 0.60). When traced at the highest intensity points of struts by OFDI, it was significantly larger in OFDI than in IVUS (P < 0.001). Three modalities have clinically acceptable precision across the wide range of lumen diameters. In vivo measurements by OFDI and IVUS could slightly be discrepant depending on the parameters and time points. In stent assessment by OFDI, the 2 methods led to a small but systematic difference; therefore, consistency in methodology is advised for comparative studies.

BACKGROUND: In drug-eluting stents (DESs), the theoretical drug dose exposed to the vessel wall per stent surface area may vary due to the fixed loading dose and differences in the stent surface area once expanded in varying vessel sizes. The aim of this study was to evaluate the potential effects of different dose intensities, as estimated by 3D-IVUS dosimetry, on vascular response after DES implantation. METHODS: Follow-up (6-9 months) 3D-IVUS was performed in 840 coronary lesions treated with a single DES of the following types: sirolimus (SES, n=148), paclitaxel (PES, n=162), Endeavor zotarolimus (E-ZES, n=233), Resolute zotarolimus (R-ZES, n=147), and everolimus (EES, n=150). Volume index (volume/length, mm(3)/mm) was obtained for vessel, lumen, plaque, stent, and neointima. In each lesion, exposed dose intensity was calculated as known loading dose divided by measured luminal surface area of the stented segment. Lesions were divided into tertiles based on the exposed dose intensity: high, medium, and low dose groups. RESULTS: The exposed dose intensity ranged 0.74-1.76 μg/mm(2) for SES, 0.41-1.18 μg/mm(2) for PES, 0.71-1.57 μg/mm(2) for E-ZES, 0.72-1.63 μg/mm(2) for R-ZES, and 0.40-0.99 μg/mm(2) for EES. All types of DES showed no significant difference in neointimal hyperplasia among the 3 groups, except that E-ZES showed significantly less neointimal hyperplasia in the high dose group. CONCLUSIONS: Detailed 3D-IVUS revealed significant lesion-to-lesion variability in dose intensity exposed to the vessel wall following DES implantation. However, the major types of DES appear to yield equally effective neointimal suppression, despite the varying dose intensity, except for E-ZES.

OBJECTIVES: This study investigated the association between arterial remodeling and geographic distribution of cardiac allograft vasculopathy (CAV), and outcomes after heart transplantation. BACKGROUND: CAV is characterized by a combination of coronary intimal thickening and pathological vessel remodeling, which varies at different locations in coronary arteries. METHODS: In 100 transplant recipients, serial volumetric intravascular ultrasonography (IVUS) was performed at baseline and 1 year post-transplantation in the first 50 mm of the left anterior descending artery (LAD). IVUS indices were evaluated in the entire segment and 3 equally divided LAD segments. Paradoxical vessel remodeling was defined as [Δvessel volume/Δintimal volume <0]. RESULTS: After 1 year, death or re-transplantation occurred in 20 patients over a median follow-up period of 4.7 years. Paradoxical vessel remodeling was observed in 57%, 41%, 50%, and 40% for the entire vessel, proximal, middle, and distal LAD segments, respectively. Kaplan-Meier analysis revealed a significantly lower event-free rate of survival in patients with paradoxical vessel remodeling involving the proximal LAD segment, which was not present when involving the entire LAD or mid and distal LAD segments. In multivariate analysis, paradoxical vessel remodeling of the proximal LAD segment was independently associated with death or re-transplantation (hazard ratio [HR]: 11.18; 95% confidence interval [CI]: 2.39 to 83.23; p = 0.0015). CONCLUSIONS: Despite the diffuse nature of CAV, paradoxical vessel remodeling of the proximal LAD segment at 1 year was the primary determinant of long-term mortality or re-transplantation. Assessment of arterial remodeling combined with coronary intimal thickening may enhance identification of high-risk patients who may benefit from closer follow-up and targeted medical therapies.

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.

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.

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.

OBJECTIVES: The present study evaluated the mechanism of edge restenosis after sirolimus-eluting stent (SES) implantation using serial (post-intervention and follow-up) intravascular ultrasound (IVUS) analysis. BACKGROUND: There is little information about the mechanism of edge restenosis after SES implantation. METHODS: Serial IVUS analysis was performed at 5 mm reference segments immediately proximal and distal to the SES in 25 lesions with edge restenosis. Proximal and distal reference segments were divided into 1 mm subsegments. RESULTS: Between post-intervention and follow-up IVUS studies, a decrease in external elastic membrane area was observed at the proximal edge. There was a significant increase in plaque & media area in the subsegment closest to the proximal edge. On the other hand, there was an increase in plaque & media area at the distal edge, with no change in external elastic membrane area. CONCLUSIONS: There may be different mechanisms between proximal and distal edge restenosis after SES implantation. Negative remodeling plays a major role in proximal edge restenosis. On the other hand, intimal hyperplasia may mainly contribute to distal edge restenosis.

Previous studies have demonstrated endothelial dysfunction after sirolimus-eluting stent (SES) implantation. The present study evaluated the effect of pioglitazone on endothelial dysfunction after SES implantation in nondiabetic patients. A total of 50 nondiabetic patients who had undergone SES implantation were randomly assigned to the pioglitazone group (n = 25) or the control group (n = 25). Endothelial function was estimated by measuring the coronary vasoreactivity in the reference segment within 15 mm proximal and distal to the SES in response to intracoronary acetylcholine infusion (10(-8) and 10(-7) mol/L) at 9 months of follow-up. Endothelium-independent vasomotion was assessed after an intracoronary bolus of nitroglycerin. Changes in the coronary diameter in response to 10(-8) and 10(-7) mol/L acetylcholine in the segment proximal to the SES were not significantly different between the pioglitazone and control groups. In contrast, in the segment distal to the SES, vasoconstrictions to 10(-8) (-3.0 ± 2.8% vs -7.1 ± 4.5%, p <0.01) and 10(-7) mol/L acetylcholine (-6.2 ± 8.0% vs -13.1 ± 8.9%, p <0.01) were attenuated in the pioglitazone group compared to the control group. Endothelium-independent vasodilation to nitrate did not differ between the 2 groups. Multivariate analysis showed that pioglitazone was an independent predictor improving endothelial dysfunction after SES implantation. In conclusion, pioglitazone might improve endothelial dysfunction after SES implantation in nondiabetic patients.