Early-Phase Vascular Healing of Bioabsorbable vs. Durable Polymer-Coated Everolimus-Eluting Stents in Patients With ST-Elevation Myocardial Infarction　- 2-Week and 4-Month Analyses With Optical Coherence Tomography.

BACKGROUND: Despite the revolution of coronary stents, there remain concerns about the risk of stent thrombosis, especially in patients with ST-elevation myocardial infarction (STEMI). The present study compared early vascular healing as a contributing factor to reducing stent thrombosis between Xience everolimus-eluting stents (X-EES) and Synergy everolimus-eluting stents (S-EES) in patients with STEMI. Methods and Results: The present study included 47 patients with STEMI requiring primary percutaneous coronary intervention with X-EES (n=25) or S-EES (n=22). Optical coherence tomography (OCT) assessments of the stented lesions were performed 2 weeks and 4 months after stent implantation. Neointimal strut coverage, malapposition and the frequency of thrombus formation were evaluated. In the 2-week OCT analysis, the proportion of covered struts in S-EES (42.4±15.4%) was significantly higher than in X-EES (26.3±10.1%, P<0.001). In the 4-month OCT analysis, the proportion of covered struts in S-EES (72.2±17.9%) was still significantly higher than in X-EES (62.0±14.9%, P=0.04). CONCLUSIONS: Compared with X-EES, S-EES showed a higher proportion of covered struts in the early phase after stent implantation for STEMI patients.

Association between plaque characteristics and the amount of debris captured by a filter-type distal protection device in patients with acute coronary syndrome.

BACKGROUND AND AIMS: Disruption of atherosclerotic plaque and distal embolism often cause peri-procedural myocardial injury during percutaneous coronary intervention (PCI). In the present study, we evaluate the association between the characteristics of the target lesion and the amount of debris captured by the filter-type distal protection device. METHODS: We enrolled 120 consecutive patients with acute coronary syndrome, who underwent coronary stent implantation with a filter-type distal protection device after integrated backscatter intravascular ultrasound (IB-IVUS) analysis. The amount of debris captured by the protection filter was measured through microscopic evaluation. RESULTS: The lipid and fibrous volume evaluated with IB-IVUS was significantly correlated with the amount of the captured debris (r = 0.657, p < 0.01), (r = 0.322, p < 0.01). The lipid plaque fraction showed a positive correlation (r = 0.335, p < 0.01), while the fibrous plaque fraction was found to be inversely correlated (r = -0.375, p < 0.01) with the amount of captured debris. Multivariate regression analysis showed that lipid volume correlated independently with the amount of captured debris. CONCLUSION: The volume of the lipid-rich plaque was associated with the amount of procedure-related debris released and captured by the filter-type distal protection device.

Tissue characteristics of neointima in late restenosis: integrated backscatter intravascular ultrasound analysis for in-stent restenosis.

Although late restenosis is one of the long-term complications of stent implantation, its pathogenesis has not been fully elucidated. For consecutive patients who developed in-stent restenosis (ISR) after stent implantation, integrated backscatter (IB) intravascular ultrasound was performed for ISR lesions. The tissue characteristics of neointima within the stented segment were compared between lesions with early restenosis and those with late restenosis. Of 73 ISR lesions arising after sirolimus-eluting stent (SES; n = 25) or bare-metal stent (BMS; n = 48) implantation, early and late restenosis were documented in 52 and 21 lesions, respectively. A higher prevalence of late restenosis was observed after SES implantation than after BMS implantation (60.0 vs. 12.5 %; p < 0.001). The duration between stent implantation and late restenosis was significantly shorter after SES implantation than after BMS implantation (57.0 ± 22.1 vs. 124.4 ± 19.6 months; p < 0.001). Percent low-IB volume was significantly higher in the neointima of late restenosis than in that of early restenosis (29.9 ± 9.9 vs. 19.8 ± 11.3 %; p < 0.001). Significantly more low-IB tissue was observed in the neointima of late restenosis than in that of early restenosis, suggesting atherosclerotic progression in late phase after stent implantation as a possible mechanism of late restenosis.

Impact of lesion characteristics on the prediction of optimal poststent fractional flow reserve.

BACKGROUND: Poststent fractional flow reserve (FFR) is a useful indicator of optimal percutaneous coronary intervention, and higher poststent FFR is associated with favorable long-term clinical outcome. However, little is known about the factors influencing poststent FFR. The purpose of this study was to determine the impact of lesion characteristics on poststent FFR. METHODS: For patients who had scheduled stent implantation for stable angina, FFR measurements at maximum hyperemia were performed before and after coronary stent implantation. As one of lesion characteristics, the FFR pressure drop pattern was evaluated and classified as either an abrupt or a gradual pattern according to the pullback curve of FFR. RESULTS: A total of 205 lesions with physiological significant stenosis were evaluated. Fractional flow reserve value increased from 0.67±0.10 to 0.87±0.07 after stent implantation. Optimal poststent FFR was achieved in 75 lesions (36.6%). Logistic regression analysis demonstrated that optimal poststent FFR was positively correlated with an abrupt pressure drop pattern (hazard ratio [HR] 2.11, 95% CI 1.06-4.15, P=.03) and prestent FFR (HR 1.04, 95% CI 1.03-2.04, P=.03; per 0.1 increase), and negatively correlated with lesion localization to the left anterior descending artery (HR 0.18, 95% CI 0.09-0.36, P<.0001). The c statistic for predicting optimal poststent FFR was 0.763 (95% CI 0.702-0.819). CONCLUSION: Abrupt pressure drop patterns, prestent FFR, and lesion localization to the left anterior descending artery were independent predictors of optimal poststent FFR.

Safety and efficacy of intracoronary nicorandil as hyperaemic agent for invasive physiological assessment: a patient-level pooled analysis.

AIMS: Our aim was to evaluate the safety and efficacy of intracoronary (IC) nicorandil as an alternative choice of hyperaemic agent for invasive physiologic studies. METHODS AND RESULTS: A total of 480 intermediate coronary lesions from 429 patients enrolled from six Japanese and Korean centres were analysed. IC nicorandil showed earlier achievement of hyperaemia (time to the lowest FFR: 18.0 s [1st and 3rd quartile value 15.6-21.5] vs. 44.0 s [36.0-60.0], p<0.001) with similar hyperaemic efficacy, compared with intravenous (IV) adenosine/ATP (FFR 0.82 [0.75-0.87] vs. 0.82 [0.74-0.88], p=0.207). FFR measurements with both agents showed excellent correlation and classification agreement (CA) for FFR ≤0.80 (r=0.941, ICC 0.980, CA 90.8%, kappa=0.814, AUC of nicorandil 0.980, all p<0.001). Only three patients (0.7%) showed changes in classification across the grey zone (0.75-0.80). IC nicorandil produced fewer changes in blood pressure (BP) and heart rate (HR) and showed less chest pain than IV adenosine/ATP (all p<0.001). When comparing ΔFFR according to ΔBP or ΔHR between IV adenosine/ATP and IC nicorandil, there were no correlations, either between ΔFFR and ΔBP (r=-0.114, p=0.091), or between ΔFFR and ΔHR (r=1.000, p=0.151). CONCLUSIONS: Nicorandil IC bolus injection is a simple, safe and effective hyperaemic method for FFR measurement and can be used as a substitute for adenosine.

Influence of plaque characteristics on fractional flow reserve for coronary lesions with intermediate to obstructive stenosis: insights from integrated-backscatter intravascular ultrasound analysis.

The aim of this study was to determine the correlation between the fractional flow reserve (FFR) values and volumetric intravascular ultrasound (IVUS) parameters derived from classic gray-scale IVUS and integrated backscatter (IB)-IVUS, taking into account known confounding factors. Patients with unstable angina pectoris with the frequent development of vulnerable plaques often showed the discrepancy between the FFR value and the quantitative coronary angiography findings. Our target population was 107 consecutive subjects with 114 isolated lesions who were scheduled for elective coronary angiography. The FFR was calculated as the mean distal coronary pressure divided by the mean aortic pressure during maximal hyperemia. Various volumetric parameters such as lipid plaque volume (LPV) and percentage of LPV (%LPV) were measured using IB-IVUS. Simple and multivariate linear regression analysis was employed to evaluate the correlation between FFR values and various classic gray-scale IVUS and IB-IVUS parameters. The Akaike information criterion (AIC) was used to compare the goodness of fit in an each model. Both the %LPV (r = -0.24; p = 0.01) and LPV (r = -0.40; p < 0.01) were significantly correlated with the FFR value. Only the LPV (AIC = -147.0; p = 0.006) and %LPV (AIC = -152.9; p = 0.005) proved to be independent predictors for the FFR value even after the adjustment of known confounding factors. The volumetric assessment by IB-IVUS could provide better information in terms of the relationship between plaque morphology and the FFR values as compared to the classic IVUS 2-dimensional gray-scale analysis.

Noninvasive mathematical analysis of spectral electrocardiographic components for coronary lesions of intermediate to obstructive stenosis severity-relationship with classic and functional SYNTAX score.

OBJECTIVES: The aim of this study was to evaluate the relationship between the multifunction cardiogram (MCG), and SYNTAX score (SS) and functional SYNTAX score (FSS) in detecting the presence of intermediate to obstructive coronary lesions. BACKGROUND: Performing coronary angiography (CAG) and measuring fractional flow reserve (FFR) to calculate the SS and FSS is inherently invasive and adds complexity. METHODS: The MCG was obtained and analyzed before performing CAG in 87 consecutive subjects with suspected coronary artery disease who were scheduled for elective CAG. The patients were divided into three groups according to risk based on high, borderline, and low MCG scores. The SS was determined, as well as FSS but only by counting lesions prone to functional ischemia (FFR ≤ 0.8). The relationship between the MCG and the SS and FSS was evaluated. RESULTS: The MCG was the only test significantly associated with the SS (odds ratio, 2.92 [1.60 - 5.31], P < 0.001) and FSS (odds ratio, 3.66 [1.95 - 6.87], P < 0.001). A high MCG score had a specificity of 92.6% (89.0-96.2%) and 92.3% (89.0-95.6%), and a predictive accuracy of 72.4% (67.6-77.2%) and 82.8% (78.7-86.8%) for the prediction of SS and FSS, respectively. CONCLUSIONS: The MCG showed high specificity and predictive accuracy especially for the FSS, suggesting that it is useful not only in identifying functionally significant ischemia but also in reducing unnecessary CAGs.

Severity of morphological lesion complexity affects fractional flow reserve in intermediate coronary stenosis.

BACKGROUND: Although functional ischemia identification is important when determining revascularization, angiographic assessment alone is challenging in intermediate coronary stenosis. Previous studies have reported that lesion-specific characteristics affected the fractional flow reserve (FFR). However, the relationship between morphological lesion complexity and FFR has not yet been fully evaluated. This study aimed to evaluate the impact of morphological lesion complexity on FFR in intermediate coronary stenosis. METHODS: A total of 109 consecutive patients with 136 intermediate coronary stenoses (visually estimated diameter stenosis: 40-70%) were assessed via quantitative coronary angiography, lesion-specific characteristics, and FFR. Indexed lesions were assessed according to 6 morphological lesion characteristics: eccentricity, bend, irregularity, calcification, bifurcation, and diffuse. The lesions were then classified into 3 groups according to the morphological severity count represented by the number of present characteristics (mild-complex: 0-1, moderate-complex: 2-3, and severe-complex: 4-6), and their functional severities were evaluated. Lesions with an FFR <0.80 were considered functionally significant coronary stenoses. RESULTS: Of the 136 lesions, 51% were located in the left anterior descending artery (LAD) and 47% had an FFR <0.80. The FFR differed significantly among the 3 lesion complexity groups (0.84±0.10 vs. 0.79±0.10 vs. 0.73±0.07, for mild-, moderate-, and severe-complex, respectively; p<0.01). In a multivariate logistic analysis, LAD lesions, moderate- and severe-complex, and diameter stenosis were independently associated with an FFR <0.80 [odds ratio (OR): 5.65, 95% confidence interval (CI): 2.50-12.80, p<0.01; OR: 2.96, 95% CI: 1.30-6.72, p<0.01; OR: 7.11, 95% CI: 1.25-40.37, p=0.03, and OR: 2.65, 95% CI: 1.04-6.72, p=0.04, respectively]. CONCLUSIONS: Both indexed vessels and the degree of diameter stenosis affected the FFR. In addition, the severity of morphological lesion complexity correlated with the degree of functional severity in intermediate coronary stenosis.

Variability of fractional flow reserve according to the methods of hyperemia induction.

OBJECTIVES: We performed this study to evaluate the variability of fractional flow reserve (FFR) values which were measured from various methods of hyperemia induction. BACKGROUND: Concerns have been raised regarding the variability of FFR due to different routes for hyperemic agent administration and different hyperemic agents targeting different receptors to induce maximal hyperemia. METHODS: A total of 656 intermediate coronary lesions from 628 patients with coronary artery disease were analyzed. Among them, 238 lesions underwent FFR measurement with hyperemia induced by both intravenous (IV) and intracoronary (IC) adenosine administration, 318 by IV adenosine/adenosine triphosphate (ATP) and IC nicorandil injection, and 100 by IV adenosine and regadenoson infusion. RESULTS: Excellent correlation and close classification agreement (FFR ≤ 0.80) were observed between IV vs. IC adenosine (r = 0.980, CA = 92.9%, Cohen's Kappa = 0.887, P < 0.001), between IV adenosine/ATP vs. IC nicorandil (r = 0.962, CA = 91.2%, Cohen's Kappa = 0.817, P < 0.001), and between IV adenosine vs. regadenoson (r = 0.990, CA = 100%, Cohen's Kappa = 1.000, P < 0.001). When changes in blood pressure (ΔBP) or heart rate (ΔHR) were compared with changes in FFR (ΔFFR) between IV adenosine/ATP and IC nicorandil administration, there were no significant correlations between ΔBP and ΔFFR nor between ΔHR and ΔFFR (r = -0.122, P = 0.076; r = 0.036, P = 0.605, respectively). CONCLUSIONS: This study suggests that the measurement of FFR is reproducible regardless of the hemodynamic changes, hyperemic agents used, or the route of administration.

Effects of eicosapentaenoic acid on peri-procedural (type IVa) myocardial infarction following elective coronary stenting.

OBJECTIVES: The aim of this study was to assess the effect of eicosapentaenoic acid (EPA) on peri-procedural (type IVa) myocardial infarction (MI) following elective percutaneous coronary intervention (PCI). METHODS AND RESULTS: We analyzed data from 165 of 178 consecutive patients with stable angina pectoris who underwent de novo successful stent implantation in the native coronary artery. Patients were assigned to receive statin therapy in combination with 1800mg/day of EPA or statin alone. Post-procedural index of microcirculatory resistance (IMR) values were calculated for 30 patients in the EPA group and 32 controls. In the multivariate logistic model, EPA administration, low kidney function, and the presence of slow flow/no reflow were significantly and independently associated with type IVa MI. Post-procedural IMR values were significantly lower in the EPA group [19.8 (6.4, 51.1) vs. 27.8 (8.2, 89.3), p=0.003] compared to the control group. CONCLUSIONS: Pre-treatment with EPA in addition to statins significantly reduced the incidence of type IVa MI compared to statin therapy only, which may be attributed to the ability of EPA to reduce microvascular dysfunction induced by PCI.

Feasibility and safety of intracoronary nicorandil infusion as a novel hyperemic agent for fractional flow reserve measurements.

Fractional flow reserve (FFR) is a useful modality to assess the functional significance of coronary stenoses. Although adenosine triphosphate (ATP) is generally used as the hyperemic stimulus, we sometimes encounter adverse events like hypotension during FFR measurement. Nicorandil, an ATP-sensitive potassium channel opener, recognized as an epicardial and resistance vessel dilator, has not been fully evaluated as a possible alternative hyperemic agent. The aim of this study was to evaluate the feasibility and safety of intracoronary nicorandil infusion compared to intravenous ATP for FFR measurement in patients with coronary artery disease. A total of 102 patients with 124 intermediate lesions (diameter stenosis >40 and <70% by visual assessment) were enrolled. All vessels underwent FFR measurements with both ATP (150 µg/kg/min) and nicorandil (2.0 mg) stimulus. FFR, hemodynamic values, and periprocedural adverse events between the two groups were evaluated. A strong correlation was observed between FFR with ATP and FFR with nicorandil (r = 0.954, p < 0.001). The agreement between the two sets of measurements was also high, with a mean difference of 0.01 ± 0.03. The mean aortic pressure drop during pharmacological stimulus was significantly larger with ATP compared to nicorandil (9.6 ± 9.6 vs. 5.5 ± 5.8 mmHg, p < 0.001). During FFR measurement, transient atrioventricular block was frequently observed with ATP compared to nicorandil (4.0 vs. 0%, p = 0.024). This study suggests that intracoronary nicorandil infusion is associated with clinical utility and safety compared to ATP as an alternative hyperemic agent for FFR measurement.

Impact of cigarette smoking on coronary plaque composition.

OBJECTIVES: Cigarette smoking is associated with atherosclerosis and is an important risk factor for cardiovascular disease. We evaluated the impact of cigarette smoking on coronary plaque composition using integrated backscatter intravascular ultrasound (IB-IVUS). METHODS: A total of 143 consecutive patients undergoing percutaneous coronary intervention were enrolled. A history of illness, as well as smoking habits, was obtained by interview. Participants were asked to report whether they were current smokers, had quit smoking, or had never smoked. According to interview results, patients were divided into the following three groups: current, former, and never smokers. Conventional and IB-IVUS tissue characterization analyses were carried out. Three-dimensional analyses were carried out to determine plaque volume and the volume of each plaque component (lipid, fibrous, and calcified). RESULTS: IB-IVUS analysis indicated that the patients in the current smoker group had significantly increased percent lipid volume and significantly decreased percent fibrous volume (P=0.01 and 0.03). Logistic regression analysis showed that the current smoking state (odds ratio 3.51, 95% confidence interval 1.02-12.10, P=0.04) was independently associated with the presence of lipid-rich plaques, which was defined as the upper 75th percentile of the study population. CONCLUSION: Smoking is independently associated with lipid-rich plaques, contributing to the increasing risk for plaque vulnerability.

Effects of polyunsaturated fatty acids on periprocedural myocardial infarction after elective percutaneous coronary intervention.

AIMS: The aim of this study was to address the association of lipid profiles with periprocedural myocardial infarction (pMI) after elective percutaneous coronary intervention (PCI). METHODS AND RESULTS: Of the 302 consecutive patients who received elective PCI at the Chubu Rosai Hospital, Nagoya, Japan between June 2009 and December 2010, data from 231 native coronary lesions were analysed. Various biomarkers including serum troponin T (TnT), eicosapentaenoic acid (EPA), arachidonic acid (AA), and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were measured at baseline and at 18 hrs after PCI. pMI was defined as a post-procedural increase of TnT >3 times above the upper normal limit. Patients with pMI had significantly lower EPA/AA (0.25 [0.19-0.28] vs. 0.45 [0.21-0.62], p<0.001) and higher LDL/HDL cholesterol (3.00±1.05 vs. 2.36±0.90, p=0.008) than patients without pMI. On multivariate logistic analysis, EPA/AA per 0.1 increase (hazard ratio [HR] 0.62, 95% CI: 0.43-0.88, p=0.007), LDL/HDL (HR 1.92, 95% CI: 1.15-3.19, p=0.012), stented length (HR 1.40, 95% CI: 1.07-1.83, p=0.015), and the presence of unstable angina pectoris (UAP) (HR 8.89, 95% CI: 2.83-27.9, p<0.001) were significantly and independently associated with the incidence of pMI. CONCLUSIONS: EPA/AA and LDL/HDL were significantly associated with pMI after PCI, creating the possibility of a new therapeutic target of pMI.

Clustering of metabolic syndrome components attenuates coronary plaque regression during intensive statin therapy in patients with acute coronary syndrome: the JAPAN-ACS subanalysis study.

BACKGROUND: The JAPAN-ACS (Japan Assessment of Pitavastatin and Atorvastatin in Acute Coronary Syndrome) trial showed that intensive statin therapy could induce significant coronary plaque regression in acute coronary syndrome (ACS). We evaluated the impact of metabolic syndrome (MetS) and its components on coronary plaque regression in the JAPAN-ACS patients. METHODS AND RESULTS: Serial intravascular ultrasound measurements over 8-12 months were performed in 242 ACS patients receiving pitavastatin or atorvastatin. Patients were divided into groups according to the presence of MetS or the number of MetS components. Although the percent change in plaque volume (%PV) was not significantly different between the MetS (n=119) and non-MetS (n=123) groups (P=0.50), it was significantly associated with an increasing number of MetS components (component 0: -24.0%, n=7; components 1: -20.8%, n=31; components 2: -16.1%, n=69; components 3: -18.7%, n=83; components 4: -13.5%, n=52; P=0.037 for trend). The percent change in body mass index (%BMI) significantly correlated with %PV (r=0.15, P=0.021), especially in the MetS components 4 group (r=0.35, P=0.017). In addition, %BMI was an independent predictor of plaque regression after adjustment for the changes of low- and high-density lipoprotein cholesterol, triglycerides and HbA(1c). CONCLUSIONS: The clustering of MetS components, but not the presence of MetS itself, could attenuate coronary plaque regression during intensive statin therapy in ACS patients. Therefore, to achieve a greater degree of plaque regression, it is necessary to treat to each MetS component and use lifestyle modification.