Combined sensory, volatilome and transcriptome analyses identify a limonene terpene synthase as a major contributor to the characteristic aroma of a Coffea arabica L. specialty coffee.

BACKGROUND: The fruity aromatic bouquet of coffee has attracted recent interest to differentiate high value market produce as specialty coffee. Although the volatile compounds present in green and roasted coffee beans have been extensively described, no study has yet linked varietal molecular differences to the greater abundance of specific substances and support the aroma specificity of specialty coffees. RESULTS: This study compared four Arabica genotypes including one, Geisha Especial, suggested to generate specialty coffee. Formal sensory evaluations of coffee beverages stressed the importance of coffee genotype in aroma perception and that Geisha Especial-made coffee stood out by having fine fruity, and floral, aromas and a more balanced acidity. Comparative SPME-GC-MS analyses of green and roasted bean volatile compounds indicated that those of Geisha Especial differed by having greater amounts of limonene and 3-methylbutanoic acid in agreement with the coffee cup aroma perception. A search for gene ontology differences of ripening beans transcriptomes of the four varieties revealed that they differed by metabolic processes linked to terpene biosynthesis due to the greater gene expression of prenyl-pyrophosphate biosynthetic genes and terpene synthases. Only one terpene synthase (CaTPS10-like) had an expression pattern that paralleled limonene loss during the final stage of berry ripening and limonene content in the studied four varieties beans. Its functional expression in tobacco leaves confirmed its functioning as a limonene synthase. CONCLUSIONS: Taken together, these data indicate that coffee variety genotypic specificities may influence ripe berry chemotype and final coffee aroma unicity. For the specialty coffee variety Geisha Especial, greater expression of terpene biosynthetic genes including CaTPS10-like, a limonene synthase, resulted in the greater abundance of limonene in green beans, roasted beans and a unique citrus note of the coffee drink.

The feasibility of double stent strategy in left main true bifurcation with small and large angle change between diastole and systole: The Milan and New-Tokyo (MITO) registry.

BACKGROUND: Provisional single stenting strategy (PSS) is a default strategy for percutaneous coronary intervention (PCI) of unprotected left main distal bifurcation lesions (ULMD). Previous study reported that a bifurcation angle change (BAC) between end diastole and systole was associated with outcomes after PCI with double stent strategy (DSS) for ULMD. However, there are no data comparing outcomes after PCI with PSS versus DSS according the degree of BAC. OBJECTIVES: We evaluated outcomes after PCI with PSS versus DSS for true ULMD with small and large BAC. METHODS: We identified 566 patients with true ULMD underwent PCI in three high-volume centers. We calculated the BAC in ULMD between end-diastole and systole before stenting with 2-dimensional quantitative coronary angiographic assessment. We defined small (BAC < 7.0°) and large BAC (≥7.0°) group. We compared clinical outcomes after PCI with PSS versus DSS in each cohort after propensity score adjustment. The primary endpoint was target-lesion failure (TLF), which was defined as a composite of cardiac death, target lesion revascularization, and myocardial infarction. RESULTS: In small BAC cohort, TLF rate was significantly lower in DSS group than in PSS group (12.5% vs. 20.1%, adjusted HR 0.45; 95% CI, 0.26-0.79; p = 0.006). In contrast, in large BAC cohort, TLF rate was significantly higher in DSS group than in PSS group (54.9% vs. 29.0%, adjusted HR 2.25; 95% CI, 1.50-3.38; p < 0.001). CONCLUSIONS: The TLF rate after PCI with DSS was significantly lower in true ULMD with small BAC compared to PSS even after propensity score adjustment. In contrast, it was significantly higher in those with large BAC.

HydroDynamic contrast Recanalization (HDR): Description of a new crossing technique for coronary chronic total occlusions.

BACKGROUND: Intraplaque delivery of contrast has been utilized during percutaneous coronary interventions (PCI) of chronic total occlusions (CTO) to delineate anatomy and to facilitate wire crossing. Its utility as a tool to accomplish primary crossing of CTOs has not been described or validated. AIMS: We describe a new technique leveraging the diagnostic and therapeutic roles of intraplaque contrast injection to accomplish primary crossing of CTOs: HydroDynamic contrast Recanalization (HDR). METHODS: HDR is an antegrade crossing method for coronary CTOs based on the synergistic use of contrast microinjections and polymer jacketed wires. We present a retrospective, first-in-man, case series utilizing HDR for CTO PCI in patients with favorable CTO anatomy (visible proximal segment and identifiable distal target). The primary outcome was procedural success. The secondary outcome was any procedural complications. RESULTS: A total of 43 patients with 45 CTOs underwent CTO PCI with HDR. Mean patient age was 64.3 ± 11 years. The mean Japanese CTO and PROGRESS CTO scores were 2.3 ± 0.7 and 1.8 ± 0.7, respectively. CTO complexity was high, with an ambiguous or blunt cap in 34 occlusions (76%); lesion length ≥ 20 mm in 27 occlusions (60%); and moderate/heavy calcification in 36 occlusions (80%). Procedural success using HDR was 100%. There were no complications. CONCLUSIONS: This study shows the utility of HDR in CTO PCI. HDR appears to be a safe and promising new contrast-based primary crossing technique in selected patients. This strategy warrants further evaluation in larger prospective studies.

Predictors of Optical Coherence Tomography-Defined Calcified Nodules in Patients With Acute Coronary Syndrome　- A Substudy From the TACTICS Registry.

BACKGROUND: Recent studies suggest that the presence of calcified nodules (CN) is associated with worse prognosis in patients with acute coronary syndrome (ACS). We investigated clinical predictors of optical coherence tomography (OCT)-defined CN in ACS patients in a prospective multicenter registry. METHODS AND RESULTS: We investigated 695 patients enrolled in the TACTICS registry who underwent OCT assessment of the culprit lesion during primary percutaneous coronary intervention. OCT-CN was defined as calcific nodules erupting into the lumen with disruption of the fibrous cap and an underlying calcified plate. Compared with patients without OCT-CN, patients with OCT-CN (n=28) were older (mean [±SD] age 75.0±11.3 vs. 65.7±12.7 years; P<0.001), had a higher prevalence of diabetes (50.0% vs. 29.4%; P=0.034), hemodialysis (21.4% vs. 1.6%; P<0.001), and Killip Class III/IV heart failure (21.4% vs. 5.7%; P=0.003), and a higher preprocedural SYNTAX score (median [interquartile range] score 15 [11-25] vs. 11 [7-19]; P=0.003). On multivariable analysis, age (odds ratio [OR] 1.072; P<0.001), hemodialysis (OR 16.571; P<0.001), and Killip Class III/IV (OR 4.466; P=0.004) were significantly associated with the presence of OCT-CN. In non-dialysis patients (n=678), age (OR 1.081; P<0.001), diabetes (OR 3.046; P=0.014), and Killip Class III/IV (OR 4.414; P=0.009) were significantly associated with the presence of OCT-CN. CONCLUSIONS: The TACTICS registry shows that OCT-CN is associated with lesion severity and poor clinical background, which may worsen prognosis.

Proteomics associated with coronary high-risk plaques by optical coherence tomography.

Biomarkers are widely used for the diagnosis and monitoring of cardiovascular disease. However, markers for coronary high-risk plaques have not been identified. The aim of this study was to identify proteins specific to coronary high-risk plaques. Fifty-one patients (71.2 ± 11.1 years, male: 66.7%) who underwent intracoronary optical coherence tomography imaging and provided blood specimens for proteomic analysis were prospectively enrolled. A total of 1470 plasma proteins were analyzed per patient using the Olink® Explore 1536 Reagent Kit. In patients with thin-cap fibroatheroma, the protein expression of Calretinin (CALB2), Corticoliberin (CRH) and Alkaline phosphatase, placental type (ALPP) were significantly increased, while the expression of Neuroplastin (NPTN), Folate receptor gamma (FOLR3) and Serpin A12 (SERPINA12) were significantly decreased. In patients with macrophage infiltration, the protein expressions of Fatty acid-binding protein, intestinal (FABP2), and Fibroblast growth factor 21 (FGF21) were significantly decreased. In patients with lipid-rich plaques, the protein expression of Interleukin-17 C (IL17C) was significantly increased, while the expression of Fc receptor-like protein 3 (FCRL3) was significantly decreased. These proteins might be useful markers in identifying patients with coronary high-risk plaques. Clinical Trial Registration: https://www.umin.ac.jp/ctr/ , UMIN000041692.

Prognostic value of transvalvular flow rate in patients with low-gradient severe aortic stenosis: A dobutamine stress echocardiography study.

BACKGROUNDS: There are limited data on the clinical relevance of transvalvular flow rate (Qmean ) at rest (Qrest) and at peak stress (Qstress ) during dobutamine stress echocardiography (DSE) in patients with low-gradient severe aortic stenosis (LG-SAS). METHODS: We retrospectively analyzed the clinical data of patients with LG-SAS who underwent DSE. LG-SAS was defined as an aortic valve (AV) area index of < .6 cm2 /m2 and a mean AV pressure gradient (AVPG) of < 40 mm Hg. The primary endpoint included all-cause death and heart failure hospitalization. RESULTS: Of 100 patients (mean age 79.5 ± 7.3 years; men, 45.0%; resting left ventricular ejection fraction [LVEF] 52.1% ± 15.9%; resting stroke volume index 35.8 ± 7.7 mL/m2 ; Qrest 171.8 ± 34.9 mL/s), the primary endpoint occurred in 51 patients during a median follow-up of 2.84 (interquartile range 1.01-5.21) years. When the study patients were divided into three subgroups based on Qrest and Qstress , the multivariate analysis showed that Qrest < 200 mL/s and Qstress ≥200 mL/s (hazard ratio 3.844; 95% confidence interval 1.143-12.930; p = .030), as well as Qrest and Qstress < 200 mL/s (hazard ratio 9.444; 95% confidence interval 2.420-36.850; p = .001), were significantly associated with unfavorable outcomes with Qrest and Qstress ≥200 mL/s as a reference after adjusting for resting LVEF, resting mean AVPG, chronic kidney disease, New York Heart Association functional class III/IV, and AV replacement. CONCLUSIONS: Flow conditions based on the combination of Qrest and Qstress are helpful for risk stratification in LG-SAS patients.

Usefulness of Vena Contracta for Identifying Severe Secondary Mitral Regurgitation: A Three-Dimensional Transesophageal Echocardiography Study.

Background: In secondary mitral regurgitation (SMR), effective regurgitant orifice area by the proximal isovelocity surface area method ( EROA PISA ) evaluation might cause an underestimation of regurgitant orifice area because of its ellipticity compared with vena contracta area (VCA). We aimed to reassess the SMR severity using VCA-related parameters and EROA PISA . Methods: The three-dimensional transesophageal echocardiography data of 128 patients with SMR were retrospectively analyzed; the following parameters were evaluated: EROA PISA , anteroposterior and mediolateral vena contracta widths (VCWs) of VCA (i.e., VCW AP and VCW ML ), VCW Average calculated as ( VCW AP + VCW ML )/2, and VCA Ellipse calculated as π × ( VCW AP /2) × ( VCW ML /2). Severe SMR was defined as ≥ 0.39 cm 2 . Results: The mean age of the patients was 77.0 ± 8.9 years, and 78 (60.9%) were males. Compared with EROA PISA (r = 0.801), VCW Average (r = 0.940) and VCA Ellipse (r = 0.980) were strongly correlated with VCA. On receiver-operating characteristic curve analysis, VCW Average and VCA Ellipse had C-statistics of 0.981 (95% confidence interval [CI], 0.963-1.000) and 0.985 (95% CI, 0.970-1.000), respectively; these were significantly higher than 0.910 (95% CI, 0.859-0.961) in EROA PISA (p = 0.007 and p = 0.003, respectively). The best cutoff values for severe SMR of VCW Average and VCA Ellipse were 0.78 cm and 0.42 cm 2 , respectively. The prevalence of severe SMR significantly increased with an increase in EROA PISA (38 of 88 [43.2%] patients with EROA PISA < 0.30 cm 2 , 21 of 24 [87.5%] patients with EROA PISA = 0.30-0.40 cm 2 , and 16 of 16 [100%] patients with EROA PISA ≥ 0.40 cm 2 [Cochran-Armitage test; p < 0.001]). Among patients with EROA PISA < 0.30 cm 2 , SMR severity based on VCA was accurately reclassified using VCW Average (McNemar's test; p = 0.505) and VCA Ellipse (p = 0.182). Conclusions: Among patients who had SMR with EROA PISA of < 0.30 cm 2 , suggestive of moderate or less SMR according to current guidelines, > 40% had discordantly severe SMR based on VCA. VCW Average and VCA Ellipse values were useful for identifying severe SMR based on VCA in these patients.

STAR procedure becomes SAFER: First-in-man case series of a new antegrade dissection re-entry technique.

INTRODUCTION: Antegrade dissection and re-entry (ADR) is an integral part of the hybrid algorithm, which has allowed for improved outcomes in chronic total occlusion (CTO) coronary intervention (PCI). METHODS: A new ADR method, Subintimal Antegrade FEnestration and Re-entry (SAFER), is described. The results of a first-in-man series are presented. RESULTS: SAFER was performed on seven consecutive patients with angiographic and clinical success in all patients. CONCLUSIONS: This first-in-man study has shown that the SAFER technique is feasible and effective with the possibility of improving the antegrade PCI CTO success rate.

Dual Antiplatelet Therapy Duration After Multivessel Optimal Intravascular Ultrasound-Guided Percutaneous Coronary Intervention.

BACKGROUND: There is a scarcity of data evaluating contemporary real-world dual antiplatelet therapy (DAPT) strategies after percutaneous coronary intervention (PCI).Methods and Results: In the OPTIVUS-Complex PCI study multivessel cohort enrolling 982 patients undergoing multivessel PCI, including left anterior descending coronary artery using intravascular ultrasound (IVUS), we conducted 90-day landmark analyses to compare shorter and longer DAPT. DAPT discontinuation was defined as withdrawal of P2Y12inhibitors or aspirin for at least 2 months. The prevalence of acute coronary syndrome and high bleeding risk by the Bleeding Academic Research Consortium were 14.2% and 52.5%, respectively. The cumulative incidence of DAPT discontinuation was 22.6% at 90 days, and 68.8% at 1 year. In the 90-day landmark analyses, there were no differences in the incidences of a composite of death, myocardial infarction, stroke, or any coronary revascularization (5.9% vs. 9.2%, log-rank P=0.12; adjusted hazard ratio, 0.59; 95% confidence interval, 0.32-1.08; P=0.09) and BARC type 3 or 5 bleeding (1.4% vs. 1.9%, log-rank P=0.62) between the off- and on-DAPT groups at 90 days. CONCLUSIONS: The adoption of short DAPT duration was still low in this trial conducted after the release of the STOPDAPT-2 trial results. The 1-year incidence of cardiovascular events was not different between the shorter and longer DAPT groups, suggesting no apparent benefit of prolonged DAPT in reducing cardiovascular events even in patients who undergo multivessel PCI.

Comparison of the OPTIVUS-Complex PCI Multivessel Cohort With the Historical CREDO-Kyoto Registry Cohort-3.

BACKGROUND: There is a paucity of data on the effect of optimal intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) compared with standard PCI or coronary artery bypass grafting (CABG) in patients with multivessel disease.Methods and Results: The OPTIVUS-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1,021 patients undergoing multivessel PCI including the left anterior descending coronary artery using IVUS aiming to meet the prespecified criteria for optimal stent expansion. We conducted propensity score matching analyses between the OPTIVUS group and historical PCI or CABG control groups from the CREDO-Kyoto registry cohort-3 (1,565 and 899 patients) fulfilling the inclusion criteria for this study. The primary endpoint was a composite of death, myocardial infarction, stroke, or any coronary revascularization. In the propensity score-matched cohort (OPTIVUS vs. historical PCI control: 926 patients in each group; OPTIVUS vs. historical CABG control: 436 patients in each group), the cumulative 1-year incidence of the primary endpoint was significantly lower in the OPTIVUS group than in the historical PCI control group (10.4% vs. 23.3%; log-rank P<0.001) or the historical CABG control group (11.8% vs. 16.5%; log-rank P=0.02). CONCLUSIONS: IVUS-guided PCI targeting the OPTIVUS criteria combined with contemporary clinical practice was associated with superior clinical outcomes at 1 year compared with not only the historical PCI control, but also the historical CABG control.

Layered plaque and plaque volume in patients with acute coronary syndromes.

BACKGROUND: Layered plaque is a signature of previous subclinical plaque destabilization and healing. Following plaque disruption, thrombus becomes organized, resulting in creation of a new layer, which might contribute to rapid step-wise progression of the plaque. However, the relationship between layered plaque and plaque volume has not been fully elucidated. METHODS: Patients who presented with acute coronary syndromes (ACS) and underwent pre-intervention optical coherence tomography (OCT) and intravascular ultrasound (IVUS) imaging of the culprit lesion were included. Layered plaque was identified by OCT, and plaque volume around the culprit lesion was measured by IVUS. RESULTS: Among 150 patients (52 with layered plaque; 98 non-layered plaque), total atheroma volume (183.3 mm3[114.2 mm3 to 275.0 mm3] vs. 119.3 mm3[68.9 mm3 to 185.5 mm3], p = 0.004), percent atheroma volume (PAV) (60.1%[54.7-60.1%] vs. 53.7%[46.8-60.6%], p = 0.001), and plaque burden (86.5%[81.7-85.7%] vs. 82.6%[77.9-85.4%], p = 0.001) were significantly greater in patients with layered plaques than in those with non-layered plaques. When layered plaques were divided into multi-layered or single-layered plaques, PAV was significantly greater in patients with multi-layered plaques than in those with single-layered plaques (62.1%[56.8-67.8%] vs. 57.5%[48.9-60.1%], p = 0.017). Layered plaques, compared to those with non-layered pattern, had larger lipid index (1958.0[420.9 to 2502.9] vs. 597.2[169.1 to 1624.7], p = 0.014). CONCLUSION: Layered plaques, compared to non-layered plaques, had significantly greater plaque volume and lipid index. These results indicate that plaque disruption and the subsequent healing process significantly contribute to plaque progression at the culprit lesion in patients with ACS. CLINICAL TRIAL REGISTRATION: http://www. CLINICALTRIALS: gov , NCT01110538, NCT03479723, UMIN000041692.

The estimation of coronary artery calcium thickness by computed tomography angiography based on optical coherence tomography measurements.

Optical coherence tomography (OCT) is recommended to be the most appropriate modality in assessing calcium thickness, however, it has limitations associated with infrared attenuation. Although coronary computed tomography angiography (CCTA) detects calcification, it has low resolution and hence not recommended to measure the calcium size. The aim of this study was to devise a simple algorithm to estimate calcium thickness based on the CCTA image. A total of 68 patients who had CCTA for suspected coronary artery disease and subsequently went on to have OCT were included in the study. 238 lesions of them divided into derivation and validation dataset at 2:1 ratio (47 patients with 159 lesions and 21 with 79, respectively) were analyzed. A new method was developed to estimate calcium thickness from the maximum CT density within the calcification and compared with calcium thickness measured by OCT. Maximum Calcium density and measured calcium-border CT density had a good correlation with a linear equation of y = 0.58x + 201 (r = 0.892, 95% CI 0.855-0.919, p < 0.001). The estimated calcium thickness derived from this equation showed strong agreement with measured calcium thickness in validation and derivation dataset (r2 = 0.481 and 0.527, 95% CI 0.609-0.842 and 0.497-0.782, p < 0.001 in both, respectively), more accurate than the estimation by full width at half maximum and inflection point method. In conclusion, this novel method provided the estimation of calcium thickness more accurately than conventional methods.

Semiquantitative assessed proteinuria and risk of heart failure: analysis of a nationwide epidemiological database.

BACKGROUND: Heart failure (HF) is increasing in prevalence worldwide. We explored whether adults with trace and positive proteinuria were at a high risk for incident HF compared with those with negative proteinuria using a nationwide epidemiological database. METHODS: This is an observational cohort study using the JMDC Claims Database collected between 2005 and 2020. This is a population-based sample [n = 1 021 943; median age 44 years (interquartile range 37-52); 54.8% men]. No participants had a known history of cardiovascular disease (CVD). Each participant was categorized into three groups according to the urine dipstick test results: negative proteinuria (n = 902 273), trace proteinuria (n = 89 599) and positive proteinuria (≥1+; n = 30 071). The primary outcome was HF. The secondary outcomes were myocardial infarction (MI), stroke and atrial fibrillation (AF). We performed multivariable Cox regression analyses to identify the association between the proteinuria category and incident HF and other CVD events. RESULTS: Over a mean follow-up of 1150 ± 920 days, 17 182 incident HF events occurred. After multivariable adjustment, hazard ratios for HF events were 1.09 [95% confidence interval (CI) 1.03-1.15] and 1.59 (95% CI 1.49-1.70) for trace proteinuria and positive proteinuria versus negative proteinuria, respectively. This association was present irrespective of clinical characteristics. A stepwise increase in the risk of MI, stroke and AF with proteinuria category was also observed. Our primary results were confirmed in participants after multiple imputations for missing values and in those having no medications for hypertension, diabetes mellitus and dyslipidemia. The discriminative predictive value for HF events improved by adding the results of urine dipstick tests to traditional risk factors [net reclassification improvement 0.0497 (95% CI 0.0346-0.0648); P < 0.001]. CONCLUSIONS: Not only positive proteinuria, but also trace proteinuria was associated with a greater incidence of HF in the general population. Semiquantitative assessment of proteinuria would be informative for the risk stratification of HF.

Prevention of Contrast-Induced Nephropathy After Cardiovascular Catheterization and Intervention With High-Dose Strong Statin Therapy in Japan　- The PREVENT CINC-J Study.

BACKGROUND: Previous studies have reported that high-dose strong statin therapy reduces the incidence of contrast-induced nephropathy (CIN) in statin naïve patients; however, the efficacy of high-dose strong statins for preventing CIN in real-world clinical practice remains unclear. The aim of this study was to evaluate the efficacy of strong statin therapy in addition to fluid hydration for preventing CIN after cardiovascular catheterization.Methods and Results: This prospective, multicenter, randomized controlled trial included 420 patients with chronic kidney disease who underwent cardiovascular catheterization. They were assigned to receive high-dose pitavastatin (4 mg/day × 4 days) on the day before and of the procedure and 2 days after the procedure (Statin group, n=213) or no pitavastatin (Control group, n=207). Isotonic saline hydration combined with a single bolus of sodium bicarbonate (20 mEq) was scheduled for administration to all patients. In the control group, statin therapy was continued at the same dose as that before randomization. CIN was defined as a ≥0.5 mg/dL increase in serum creatinine or ≥25% above baseline at 48 h after contrast exposure. Before randomization, 83% of study participants were receiving statin treatment. The statin group had a higher incidence of CIN than the control group (3.0% vs. 0%, P=0.01). The 12-month rate of major adverse cardiovascular events was similar between the 2 groups. CONCLUSIONS: High-dose pitavastatin increases the incidence of CIN in this study population.

Potent platelet inhibition with peri-procedural tirofiban may attenuate progression of atherosclerosis in patients with acute coronary syndromes.

Organization of platelet-rich thrombus at the site of plaque disruption may contribute to rapid progression of atherosclerosis. This study was conducted to investigate if potent platelet inhibition therapy in patients with acute coronary syndromes (ACS) mitigates plaque progression. Patients enrolled in the EROSION study who presented with ACS caused by plaque erosion and underwent serial imaging of the culprit lesion by optical coherence tomography at baseline, 1 month, and 1 year were included. Among 49 patients, 32 (65.3%) patients were treated with glycoprotein IIb/IIIa inhibitor (GPI) in addition to aspirin and ticagrelor. The increase in area stenosis from baseline to 1-year follow-up was significantly smaller in patients treated with GPI, compared to those without GPI therapy (4.8% [- 1.6 to 10.9] vs. 9.6% [4.0 to 21.3], p = 0.031). The cohort was divided into 2 groups based on culprit lesion phenotype at 1 year: Group A, new layer formation at 1-year that was not present at baseline (n = 18); Group B, no new layer formation (n = 31). A new layer was less frequently found at 1 year in patients treated with GPI than in those without GPI (25.0% vs. 58.8%, p = 0.019). Group A, compared to Group B, was associated with a greater increase in area stenosis (19.0 ± 16.4% vs. 3.7 ± 7.1%; p < 0.001). Potent platelet inhibition with GPI in patients with ACS caused by plaque erosion was associated with lower incidence of new layer formation and less plaque progression.

Biomarkers associated with coronary high-risk plaques.

Vascular inflammation, lipid metabolism, and thrombogenicity play a key role not only in atherogenesis but also in the development of acute coronary syndromes. Biomarkers associated with coronary high-risk plaques defined according to intravascular imaging have not been systematically studied. A total of 69 patients with coronary artery disease who underwent both optical coherence tomography and intravascular ultrasound imaging, and who provided blood specimens were included. Comprehensive biomarkers for inflammation, lipid, and coagulation were analyzed. Composite models sought biomarker patterns associated with thin-cap fibroatheroma (TCFA) and "high-risk plaques" (TCFA and large plaque burden). Two different composite models were developed for TCFA, based on the finding that high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1, fibrinogen, IL-6, homocysteine and amyloid A levels were elevated, and high-density lipoprotein cholesterol (HDL) and bile acid levels were decreased in these patients. Both composite models were highly accurate for detecting patients with TCFA (area under curve [AUC]: 0.883 in model-A and 0.875 in model-B, both p < 0.001). In addition, creatinine, hsCRP, fibrinogen, tumor necrosis factor-α, IL-6, homocysteine, amyloid A, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques". Two composite models were highly accurate for detection of patients with "high-risk plaques" (AUC: 0.925 in model-A and 0.947 in model-B, both p < 0.001). Biomarkers useful for detection of patients with high-risk coronary plaques defined according to intravascular imaging have been identified. These biomarkers may be useful to risk stratify patients and to develop targeted therapy.Clinical Trial Registration https://www.umin.ac.jp/ctr/ , UMIN000041692. Biomarkers and high-risk plaques hsCRP, PAI-1, fibrinogen, IL-6, homocysteine, amyloid A, HDL, and bile acid were useful for detecting patients with TCFA. hsCRP, fibrinogen, IL-6, homocysteine, amyloid A, creatinine, TNFα, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques" (plaque which has both TCFA and large plaque burden). White arrowhead denotes TCFA. Red and green dashed lines denote lumen area and external elastic membrane area, respectively.

The impact of chronic kidney disease severity on clinical outcomes after current generation drug-eluting stent implantation for left main distal bifurcation lesions: the Milan and New-Tokyo registry.

Objectives. The impact of chronic kidney disease (CKD) on clinical outcomes after percutaneous coronary intervention (PCI) for unprotected left main distal bifurcation lesions (ULMD) is not fully understood in current generation drug eluting stent (cDES) era. We assessed clinical outcomes after PCI using cDES for ULMD according to CKD severity based on estimated glomerular filtration rate (eGFR). Design. We identified 720 consecutive patients who underwent PCI using cDES for ULMD at three high volume centers between January 2005 and December 2015. We divided those patients to the following five groups according to eGFR. Each group was defined as follows: no CKD (60 mL/min/1.73 m2 ≤ eGFR), mild CKD (45 ≤ eGFR < 60 mL/min/1.73 m2), moderate CKD (30 ≤ eGFR < 45 mL/min/1.73 m2), severe CKD (15 ≤ eGFR < 30 mL/min/1.73 m2) and hemodialysis (HD). The primary endpoint was target lesion failure (TLF) at 3 years. TLF was defined as a composite of cardiac death, target lesion revascularization (TLR) and myocardial infarction (MI). Results. TLF occurred more frequently in severe CKD and HD group compared with other three groups. Conclusions. The patients who have severe CKD or are on HD, were extremely associated with worse clinical outcomes after PCI for ULMD even with cDES.

Impact of directional coronary atherectomy followed by drug-coated balloon strategy to avoid the complex stenting for bifurcation lesions.

Although the simple single stenting rather than complex double stenting is recommended on percutaneous coronary intervention (PCI) for bifurcation lesions, double stenting cannot always be avoided. We investigated the impact of directional coronary atherectomy (DCA), followed by drug-coated balloon (DCB) treatment to reduce the number of stents and avoid complex stenting in PCI for bifurcation lesions and short-term patency. DCA treatment without stents was attempted for 27 bifurcation lesions in 25 patients, of those, 26 bifurcation lesions in 24 patients were successfully treated and 3-month follow-up angiography and optical coherence tomography (OCT) were performed. Sixteen lesions (59.3%) were related to left main trunk distal bifurcations, and 7 (25.9%) were true bifurcation lesions. Among the true bifurcation lesions, 4 lesions (57.1%) needed 1 stent, and the other 3 lesions (42.9%) needed no stents. Among the non-true bifurcation lesions, 1 lesion (5.0%) needed bailout stent and other lesions (95.0%) needed no stents. According to DCA followed by DCB treatment, the angiographic mean diameter stenosis improved from 65.5 ± 15.0% to 7.8 ± 9.8%, and the mean plaque area in intravascular ultrasound improved from 80.4 ± 10.5% to 39.0 ± 11.5%, respectively. Angiographic and OCT late lumen loss values were 0.2 ± 0.6 mm and 1.4 ± 1.9 mm, respectively. No patient had in-hospital major adverse cardiac events (MACE) and 3-month MACE. In conclusion, compared with standard provisional side branch stenting strategy, DCA followed by DCB treatment might reduce the number of stents, avoid complex stenting for major bifurcation lesions and provide good short-term outcomes.

The importance of proximal optimization technique with intravascular imaging guided for stenting unprotected left main distal bifurcation lesions: The Milan and New-Tokyo registry.

OBJECTIVES: This study evaluated the 5-years outcomes of intracoronary imaging-guided proximal optimization technique (POT) for percutaneous coronary intervention (PCI) in patients with unprotected left main distal bifurcation lesions (ULMD). BACKGROUND: The long-term effects of POT with intracoronary imaging guide in PCI for ULMD have been unclear. METHODS: Between January 2005 and December 2015, we identified 1832 consecutive patients who underwent DES implantation for ULM distal bifurcation lesions. Of them, 780 (56.1%) patients underwent POT with intravascular imaging guidance (optimal expansion group). Residual 611 (43.9%) patients did not undergo either POT or intravascular imaging or both (suboptimal expansion group). Analysis using propensity score adjustment was performed. The primary endpoint was target lesion failure (TLF) defined as a composite of cardiac death, target lesion revascularization (TLR), and myocardial infarction. RESULTS: TLF rate at 5 years was significantly lower in optimal expansion group than that in suboptimal expansion group [adjusted HR 0.65, 95% CI (0.48-0.87), p = 0.004]. Cardiac mortality was significantly lower in optimal expansion group than that in suboptimal expansion group [adjusted HR 0.46, 95% CI (0.27-0.79), p = 0.004]. The multivariable analysis identified POT with intravascular imaging guide [adjusted HR 0.65, 95% CI (0.48-0.87), p = 0.004] as an independent predictor of TLF. CONCLUSIONS: Intravascular imaging guided POT was strongly associated with the reduced risk of TLF at 5 years after PCI for ULMD, mainly driven by reducing cardiac mortality.

Clinical outcomes of double stent strategy for unprotected left main distal bifurcation lesions using current generation drug eluting stent comparing to early generation drug eluting stent; The Milan and New Tokyo (MITO) registry.

BACKGROUND: There are only little data available on the comparison of clinical outcomes between a early generation drug eluting stent (eDES) and a current generation drug eluting stent (cDES) for percutaneous coronary intervention (PCI) with double stent strategy (DSS) for unprotected distal left main disease (ULMD). METHODS: Between April 2005 and December 2015, we recruited 452 consecutive ULMD patients treated with DSS (eDES, 236 patients; cDES, 216 patients). In this study, eDES included Cipher, Taxus, and Endeavor and cDES included Ultimaster, Resolute family, Xience family, Promus family, Synergy, and Nobori. The primary endpoint was target lesion failure (TLF) defined as a composite of cardiac death, target lesion revascularization (TLR) and myocardial infarction (MI) during the median follow-up period of 1,809(IQR: 1,190-2,510) days. RESULTS: In entire population, the rate of overall TLR was significantly lower in cDES group than that in eDES group (adjusted HR 0.62, 95% CI 0.40-0.96, p = .032). The rate of TLR for the ostium of LCX was significantly lower in cDES group than that in eDES group (adjusted HR 0.63, 95% CI 0.39-0.99, p = .047). Cardiac mortality, the rate of TLR for LM-LAD, MI and definite/probable ST did not significantly differ between both groups. The results were preserved in the propensity adjusted population. CONCLUSIONS: cDES significantly improved the clinical outcomes in population treated with DSS mainly driven by the reduction of TLR for the ostium of LCX.