Daisuke Shishikura

Indications and outcomes of excimer laser coronary atherectomy: Efficacy and safety for thrombotic lesions—The ULTRAMAN registry

BACKGROUNDnExcimer laser coronary atherectomy (ELCA) recently became available in Japan, but ELCAs effectiveness and safety are not clear.nnnMETHODS AND RESULTSnWe enrolled consecutive patients who underwent ELCA and were registered in the Utility of Laser for Transcatheter Atherectomy-Multicenter Analysis around Naniwa (ULTRAMAN) registry comprising six Japanese medical centers around Naniwa in Japan with patients registered from April 2006 to June 2015. We evaluated the catheter sizes used and compared the success rate, thrombolysis in myocardial infarction (TIMI) flow, blush score, and complications between the rich-thrombus (RT) group [acute coronary syndrome (ACS) and saphenous vein graft (SVG)] and the poor-thrombus (PT) group [in-stent restenosis (ISR), chronic total occlusion (CTO), calcification, and long or bifurcation (L&B) lesions]. Of the 328 patients, 6 (1.8%) were treated for an SVG, 175 (53.4%) were treated for ACS, 18 (5.5%) for CTO, 106 (32.4%) for ISR, 8 (2.4%) for calcification, and 15 for L&B lesions (4.6%). A 1.7-mm (concentric)-diameter ELCA catheter was used most frequently (59.4%). High success rates were achieved in both the RT and PT groups, but the TIMI flow grade and blush score were significantly lower and the complications rate was significantly higher in the RT group (n=181).nnnCONCLUSIONSnIn Japan, the major indications for ELCA have been ACS and ISR. ELCA can provide a safe and effective treatment even for RT lesions.

High-density lipoprotein cholesterol associated with change in coronary plaque lipid burden assessed by near infrared spectroscopy

BACKGROUND AND AIMSnLittle is known about the relation between serum lipid parameters and serial change in plaque composition using inxa0vivo coronary imaging. The aim of this study was to examine the association between serum lipids and change in coronary plaque lipid burden assessed by near-infrared spectroscopy (NIRS).nnnMETHODSnWe performed serial NIRS-intravascular ultrasound studies in 49 patients who underwent coronary angiography for an acute coronary syndrome (ACS) or stable ischemic symptoms. Univariable and multivariable linear regression analyses were applied to evaluate the relationship between serum lipid parameters and change in lipid core burden index at the 4-mm maximal segment (max LCBI4mm).nnnRESULTSnMean patient age was 61xa0±xa09xa0y, 29% were women, 35% had an ACS clinical presentation, 78% received statin therapy at baseline, and median low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), total cholesterol and triglyceride levels were 101, 43, 174 and 133xa0mg/dL, respectively. During a median follow-up period of 13 months, max LCBI4mm significantly decreased from 277 to 194 (pxa0=xa00.001). On univariable analysis, the percent change in HDL-C negatively associated with the change in max LCBI4mm (βxa0=xa0-3.19, pxa0=xa00.004). There were no significant associations between the other lipid parameters and change in max LCBI4mm. On multivariable analysis, percent change in HDL-C remained significantly associated with the change in max LCBI4mm (pxa0=xa00.002).nnnCONCLUSIONSnChange in HDL-C, but not other lipids parameters, associated with changes in coronary plaque lipid burden assessed by NIRS. These findings highlight the potential therapeutic importance of high-density lipoprotein on serial change in plaque composition.

Effect of Evolocumab on Coronary Plaque Composition

BACKGROUNDnIncremental low-density lipoprotein (LDL) cholesterol lowering with the proprotein convertase subtilisin kexin type 9 inhibitor evolocumab regresses coronary atherosclerosis in statin-treated patients.nnnOBJECTIVESnThe purpose of this study was to evaluate the effect of adding evolocumab to statin therapy on coronary plaque composition.nnnMETHODSnA total of 968 statin-treated coronary artery disease patients underwent serial coronary intravascular ultrasound imaging at baseline and following 76xa0weeks of treatment with placebo or evolocumab 420xa0mg monthly. Plaque composition changes were determined in 331 patients with evaluable radiofrequency analysis of the ultrasound backscatter signal.nnnRESULTSnCompared with statin monotherapy, evolocumab further reduced LDL cholesterol (33.5xa0mg/dl vs. 89.9xa0mg/dl; pxa0< 0.0001) and induced regression of percent atheroma volume (-1.2% vs.xa0+0.17%; pxa0< 0.0001) and total atheroma volume (-3.6xa0mm3 vs.xa0-0.8xa0mm3; pxa0=xa00.04). No difference was observed between the evolocumab and placebo groups in changes in calcium (1.0 ± 0.3xa0mm3 vs. 0.6 ± 0.3xa0mm3; pxa0=xa00.49), fibrous (-3.0 ± 0.6xa0mm3 vs.xa0-2.4 ± 0.6xa0mm3; pxa0=xa00.49), fibrofatty (-5.0 ± 1.0xa0mm3 vs.xa0-3.0 ± 1.0xa0mm3; pxa0=xa00.49), and necrotic (-0.6 ± 0.5xa0mm3 vs.xa0-0.1 ± 0.5xa0mm3; pxa0=xa00.49) volumes. An inverse correlation was observed between changes in LDL cholesterol and plaque calcification (r =xa0-0.15; pxa0< 0.001).nnnCONCLUSIONSnThe addition of evolocumab to a statin did not produce differential changes in plaque composition compared with statin monotherapy. This suggests that evaluation of plaque morphology using virtual histology imaging may provide no incremental information about the plaque effects of evolocumab beyond measurement of plaque burden. (GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound [GLAGOV]; NCT01813422).

Evaluation of human coronary vasodilator function predicts future coronary atheroma progression

Objective Coronary vasodilator function and atherosclerotic plaque progression have both been shown to be associated with adverse cardiovascular events. However, the relationship between these factors and the lipid burden of coronary plaque remains unknown. These experiments focus on investigating the relationship between impaired coronary vasodilator function (endothelium dependent (salbutamol) and endothelium independent (glyceryl trinitrate)) and the natural history of atheroma plaque progression and lipid burden using dual modality intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) imaging. Methods 33 patients with stable chest pain or acute coronary syndrome underwent serial assessment of coronary vasodilator function and intracoronary plaque IVUS and NIRS imaging. Coronary segmental macrovascular response (% change segmental lumen volume (ΔSLV)), plaque burden (per cent atheroma volume (PAV)), lipid core (lipid-rich plaque (LRP) and lipid core burden index (LCBI)) were measured at baseline and after an interval of 12–18 months (n=520 segments). Results Lipid-negative coronary segments which develop into LRP over the study time period demonstrated impaired endothelial-dependent function (−0.24±2.96u2009vs 5.60±1.47%, P=0.04) and endothelial-independent function (13.91±4.45u2009vs 21.19±3.19%, P=0.036), at baseline. By multivariate analysis, endothelial-dependent function predicted ∆LCBI (β coefficient: −3.03, 95%u2009CI (−5.81 to −0.25), P=0.033) whereas endothelial-independent function predicted ∆PAV (β coefficient: 0.07, 95%u2009CI (0.04 to 0.10), P<0.0001). Conclusions Epicardial coronary vasodilator function is a determinant of future atheroma progression and composition irrespective of the nature of clinical presentation. Trial registration number ACTRN12612000594820, Post-results.

Intravascular Ultrasound Studies of Plaque Progression and Regression: Impact of Lipid-Modifying Therapies

Application of serial intravascular ultrasound imaging within the coronary arteries enables characterization of the factors associated with progression of atherosclerotic plaque. Integration into clinical trials has enabled determination of the impact of medical therapies on coronary disease. These trials have provided important insights into the effects of lipid-modifying agents currently used in clinical practice and of experimental agents at early stages of clinical development. The results of these trials are reviewed.

The relationship between segmental wall shear stress and lipid core plaque derived from near-infrared spectroscopy

BACKGROUND AND AIMSnWall shear stress (WSS) has an important role in the natural history of coronary atherosclerosis. The aim of this study is to investigate the relationship between WSS and the lipid content of atherosclerotic plaques as assessed by near-infrared spectroscopy (NIRS).nnnMETHODSnWe performed serial NIRS and intravascular ultrasound (IVUS) upon Doppler coronary flow guidewire of coronary plaques at baseline and after 12-18 months in 28 patients with <30% angiographic stenosis, who presented with coronary artery disease. Segmental WSS, plaque burden and NIRS-derived lipid rich plaque (LRP) were evaluated at both time-points in 482 consecutive 2-mm coronary segments.nnnRESULTSnSegments with LRP at baseline (nu202f=u202f106) had a higher average WSS (1.4u202f±u202f0.6u202fN/m2), compared to those without LRP (nu202f=u202f376) (1.2u202f±u202f0.6u202fN/m2, p<0.001). In segments without baseline LRP, WSS was higher in those who subsequently developed new LRP (nu202f=u202f35) than those who did not (nu202f=u202f341) (1.4u202f±u202f0.8 vs. 1.1u202f±u202f0.6u202fN/m2, p=0.002). Conversely, in segments with baseline LRP, WSS was lower in those who had regression of lipid content (nu202f=u202f41) than those who did not (nu202f=u202f65) (1.2u202f±u202f0.4 vs. 1.6u202f±u202f0.7u202fN/m2, p=0.007). Segments with the highest tertile of WSS displayed greater progression of LCBI irrespective of baseline lipid content (p<0.001). Multivariate analysis revealed that baseline WSS (p=0.017), PAV (p<0.001) and LCBI (p<0.001) were all independent predictors of change in LCBI over time.nnnCONCLUSIONSnCoronary segments with high WSS associate with progression of lipid content over time, which may indicate transformation to a more vulnerable phenotype.

The Effect of Bromodomain and Extra-Terminal Inhibitor Apabetalone on Attenuated Coronary Atherosclerotic Plaque: Insights from the ASSURE Trial

BackgroundApabetalone is a selective bromodomain and extra-terminal (BET) inhibitor which modulates lipid and inflammatory pathways implicated in atherosclerosis. The impact of apabetalone on attenuated coronary atherosclerotic plaque (AP), a measure of vulnerability, is unknown.MethodsThe ApoA-1 Synthesis Stimulation and intravascular Ultrasound for coronary atheroma Regression Evaluation (ASSURE; NCT01067820) study employed serial intravascular ultrasound (IVUS) measures of coronary atheroma in 281 patients treated with apabetalone or placebo for 26xa0weeks. AP was measured at baseline and follow-up. Factors associated with changes in AP were investigated.ResultsAP was observed in 31 patients (11%) [27 (13.0%) in the apabetalone group and four (5.5%) in the placebo group]. The apabetalone group demonstrated reductions in AP length by −xa01xa0mm [interquartile range (IQR) −xa04, 1] (pu2009=u20090.03), AP arc by −xa037.0° (IQR −xa059.2, 8.2) (pu2009=u20090.003) and the AP index by −xa034.6xa0mm° (IQR −xa052.6, 10.1) (pu2009=u20090.003) from baseline. The change in AP index correlated with on-treatment concentration of high-density lipoprotein (HDL) particles (ru2009=u2009−xa00.52, pu2009=u20090.006), but not HDL cholesterol (ru2009=u2009−xa00.11, pu2009=u20090.60) or apolipoprotein A-1 (ru2009=u2009−xa00.16, pu2009=u20090.43). Multivariable analysis revealed that on-treatment concentrations of HDL particles (pu2009=u20090.03) and very low-density lipoprotein particles (pu2009=u20090.01) were independently associated with changes in AP index.ConclusionsApabetalone favorably modulated ultrasonic measures of plaque vulnerability in the population studied, which may relate to an increase in HDL particle concentrations. The clinical implications are currently being investigated in the phase 3 major adverse cardiac event outcomes trial BETonMACE.