Prospective investigation of calcium score in optical coherence tomography-guided revascularization to identify lesions with low risk for stent under expansion: the CORAL study.

The optical coherence tomography (OCT)-based calcium scoring system was developed to guide optimal lesion preparation strategies for percutaneous coronary intervention (PCI) of calcified lesions. However, the score was derived retrospectively, and a prospective investigation is lacking. The CORAL (UMIN000053266) study was a single-arm, prospective, multicenter study that included patients with calcified lesions with OCT-calcium score of 1-2 to investigate whether these lesions could be optimally treated with a balloon-only preparation strategy using a non-compliant/scoring/cutting balloon. The primary endpoint was strategy success (successful stent placement with a final percent diameter stenosis [%DS] < 20% and Thrombolysis In Myocardial Infarction flow grade III without crossover to rotational atherectomy/orbital atherectomy/intravascular lithotripsy [RA/OA/IVL]). A superiority analysis for the primary endpoint was performed by comparing the study cohort with a performance goal of 83.3%. One hundred and eighteen patients with 130 lesions were enrolled. The mean age was 79.0 ± 10.3 years, and 79 patients (66.9%) were male. The OCT-calcium score was 1 for 81 lesions (62.3%) and 2 for 49 lesions (37.7%). The %DS improved from 47.0 ± 14.8% preprocedure to 11.1 ± 5.6% postprocedure. Stent expansion ≥ 70% was achieved in 90.2%. The strategy success rate was 93.1% (95% confidence interval: 87.3-96.8), and superiority against the performance goal was achieved without any crossover to RA/OA/IVL (P = 0.0027). The OCT-calcium score could identify mild/moderately calcified lesions treatable by PCI with the balloon-first strategy using a non-compliant/scoring/cutting balloon for predilatation, with a high strategy success rate. These results support the intravascular imaging-based treatment algorithm for calcified lesions proposed by CVIT.

Quantitative flow ratio versus fractional flow reserve for Heart Team decision-making in multivessel disease: the randomised, multicentre DECISION QFR trial.

BACKGROUND: Vessel-level physiological data derived from pressure wire measurements are one of the important determinant factors in the optimal revascularisation strategy for patients with multivessel disease (MVD). However, these may result in complications and a prolonged procedure time. AIMS: The feasibility of using the quantitative flow ratio (QFR), an angiography-derived fractional flow reserve (FFR), in Heart Team discussions to determine the optimal revascularisation strategy for patients with MVD was investigated. METHODS: Two Heart Teams were randomly assigned either QFR- or FFR-based data of the included patients. They then discussed the optimal revascularisation mode (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) for each patient and made treatment recommendations. The primary endpoint of the trial was the level of agreement between the treatment recommendations of both teams as assessed using Cohen's kappa. RESULTS: The trial included 248 patients with MVD from 10 study sites. Cohen's kappa in the recommended revascularisation modes between the QFR and FFR approaches was 0.73 [95% confidence interval {CI} : 0.62-0.83]. As for the revascularisation planning, agreements in the target vessels for PCI and CABG were substantial for both revascularisation modes (Cohen's kappa=0.72 [95% CI: 0.66-0.78] and 0.72 [95% CI: 0.66-0.78], respectively). The team assigned to the QFR approach provided consistent recommended revascularisation modes even after being made aware of the FFR data (Cohen's kappa=0.95 [95% CI:0.90-1.00]). CONCLUSIONS: QFR provided feasible physiological data in Heart Team discussions to determine the optimal revascularisation strategy for MVD. The QFR and FFR approaches agreed substantially in terms of treatment recommendations.

Geographic disparity of pathophysiological coronary artery disease characteristics: Insights from ASET trials.

BACKGROUND: The geographical disparity in the pathophysiological pattern of coronary artery disease (CAD) among patients undergoing percutaneous coronary intervention (PCI) is unknown. OBJECTIVES: To elucidate the geographical variance in the pathophysiological characteristics of CAD. METHODS: Physiological indices derived from angiography-based fractional flow reserve pullbacks from patients with chronic coronary syndrome enrolled in the ASET Japan (n = 206) and ASET Brazil (n = 201) studies, which shared the same eligibility criteria, were analysed. The pathophysiological patterns of CAD were characterised using Murray law-based quantitative flow ratio (µQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the µQFR pullback pressure gradient index. RESULTS: Significant functional stenoses pre-PCI (µQFR ≤0.80) were more frequent in ASET Japan compared to ASET Brazil (89.9% vs. 67.5%, p < 0.001), as were rates of a post-PCI µQFR <0.91 (22.1% vs. 12.9%, p = 0.013). In the multivariable analysis, pre-procedural µQFR and diffuse disease were independent factors for predicting a post-PCI µQFR <0.91, which contributed to the different rates of post-PCI µQFR ≥0.91 between the studies. Among vessels with a post-PCI µQFR <0.91, a consistent diffuse pattern of CAD pre- and post-PCI occurred in 78.3% and 76.7% of patients in ASET Japan and Brazil, respectively; only 6.3% (Japan) and 10.0% (Brazil) of vessels had a major residual gradient. Independent risk factors for diffuse disease were diabetes mellitus in ASET Japan, and age and male gender in Brazil. CONCLUSIONS: There was geographic disparity in pre-procedural angiography-based pathophysiological characteristics. The combined pre-procedural physiological assessment of vessel µQFR and diffuseness of CAD may potentially identify patients who will benefit most from PCI.

The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise.

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11 C]raclopride, in a multi-experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No-Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. KEY POINTS: Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11 C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.

Preprocedural physiological assessment of coronary disease patterns to predict haemodynamic outcomes post-PCI.

BACKGROUND: Even with intracoronary imaging-guided stent optimisation, suboptimal haemodynamic outcomes post-percutaneous coronary intervention (PCI) can be related to residual lesions in non-stented segments. Preprocedural assessment of pathophysiological coronary artery disease (CAD) patterns could help predict the physiological response to PCI. AIMS: The aim of this study was to assess the relationship between preprocedural pathophysiological haemodynamic patterns and intracoronary imaging findings, as well as their association with physiological outcomes immediately post-PCI. METHODS: Data from 206 patients with chronic coronary syndrome enrolled in the ASET-JAPAN study were analysed. Pathophysiological CAD patterns were characterised using Murray law-based quantitative flow ratio (µQFR)-derived indices acquired from pre-PCI angiograms. The diffuseness of CAD was defined by the pullback pressure gradient (PPG) index. Intracoronary imaging in stented segments after stent optimisation was also analysed. RESULTS: In the multivariable analysis, diffuse disease - defined by the pre-PCI µQFR-PPG index - was an independent factor for predicting a post-PCI µQFR <0.91 (per 0.1 decrease of PPG index, odds ratio 1.57, 95% confidence interval: 1.07-2.34; p=0.022), whereas the stent expansion index (EI) was not associated with a suboptimal post-PCI µQFR. Among vessels with an EI ≥80% and post-PCI µQFR <0.91, 84.0% of those vessels had a diffuse pattern preprocedure. There was no significant difference in EI between vessels with diffuse disease and those with focal disease. The average plaque burden in the stented segment was significantly larger in vessels with a preprocedural diffuse CAD pattern. CONCLUSIONS: A physiological diffuse pattern preprocedure was an independent factor in predicting unfavourable immediate haemodynamic outcomes post-PCI, even after stent optimisation using intracoronary imaging. Preprocedural assessment of CAD patterns could identify patients who are likely to exhibit superior immediate haemodynamic outcomes following PCI.

Reduced-dose prasugrel monotherapy without aspirin after PCI with the SYNERGY stent in East Asian patients presenting with chronic coronary syndromes or non-ST-elevation acute coronary syndromes: rationale and design of the ASET Japan pilot study.

The Acetyl Salicylic Elimination Trial (ASET) Japan pilot study is a multicentre, single-arm, open-label, proof-of-concept study with a stopping rule based on the occurrence of definite stent thrombosis. This study aims to demonstrate the feasibility and safety of low-dose prasugrel monotherapy following percutaneous coronary intervention (PCI) in Japanese patients presenting with chronic coronary syndromes (CCS) or non-ST-elevation acute coronary syndromes (NSTE-ACS). Four hundred patients with a SYNTAX score <23 requiring PCI due to CCS or NSTE-ACS will be screened and considered eligible for the study. The enrolment is planned in two phases: 1) 200 patients presenting with CCS, followed by 2) 200 patients presenting with NSTE-ACS. After optimal PCI with implantation of a SYNERGY (Boston Scientific) stent, patients will be enrolled and loaded with prasugrel 20 mg, followed by a maintenance dose of prasugrel 3.75 mg once daily without aspirin continued for 3 months in Phase 1 (CCS patients), and for 12 months in Phase 2 (NSTE-ACS patients). After these follow-up periods, prasugrel will be replaced by standard antiplatelet therapy according to local practice. The primary endpoint is a composite of cardiac death, target vessel myocardial infarction, or definite stent thrombosis after the index procedure. The primary bleeding endpoint is any Bleeding Academic Research Consortium type 3 or 5 bleeding occurring within 3 months of the index PCI for CCS patients, or 12 months for NSTE-ACS patients. The ASET Japan study is designed to demonstrate the feasibility and safety of reduced-dose prasugrel monotherapy after PCI in East Asian patients with acute and chronic coronary syndromes.

Prasugrel Monotherapy After Percutaneous Coronary Intervention With Biodegradable-Polymer Platinum-Chromium Everolimus Eluting Stent for Japanese Patients With Chronic Coronary Syndrome (ASET-JAPAN).

BACKGROUND: P2Y12 inhibitor monotherapy without aspirin immediately after percutaneous coronary intervention (PCI) has not been tested in East Asian patients, so in this study we aimed to assess the safety and feasibility of reduced dose (3.75 mg/day) prasugrel monotherapy in Japanese patients presenting with chronic coronary syndrome (CCS).Methods and Results: ASET-JAPAN is a prospective, multicenter, single-arm pilot study that completed enrolment of 206 patients from 12 Japanese centers in September 2022. Patients with native de-novo coronary lesions and a SYNTAX score <23 were treated exclusively with biodegradable-polymer platinum-chromium everolimus-eluting stent(s). Patients were loaded with standard dual antiplatelet therapy (DAPT) and following successful PCI and optimal stent deployment, they received low-dose prasugrel (3.75 mg/day) monotherapy for 3 months. The primary ischemic endpoint was a composite of cardiac death, spontaneous target-vessel myocardial infarction, or definite stent thrombosis. The primary bleeding endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5. At 3-month follow-up, there were no primary bleeding or ischemic events, or any stent thrombosis. CONCLUSIONS: This pilot study showed the safety and feasibility of prasugrel monotherapy in selected low-risk Japanese patients with CCS. This "aspirin-free" strategy may be a safe alternative to traditional DAPT following PCI.

Revisiting the Aortic Valve Calcium Score in Evaluating the Severity of Aortic Stenosis in Japanese Patients　- A Single-Center Study.

Background: In patients with aortic stenosis (AS), measurement of aortic valve calcification (AVC) using computed tomography (CT) is recommended in cases where echocardiographic measurements are inconclusive. However, sex-specific AVC thresholds proposed in the guidelines for predicting severe AS (women: 1,200 arbitrary units [AU]; men: 2,000 AU) are based on studies from Western countries. Methods and Results: We retrospectively included 512 Japanese patients with at least moderate AS who underwent transthoracic echocardiography and CT. AVC was quantified using the Agatston method. AVC was positively correlated with peak aortic jet velocity and mean transvalvular gradient (mPG), and negatively correlated with aortic valve area (AVA) and the AVA index (AVAi). In 257 patients with concordant AS grading (152 severe AS [AVAi ≤0.6 cm2/m2, mPG ≥40 mmHg], 105 moderate AS [AVAi >0.6 cm2/m2, mPG <40 mmHg]), receiver operating characteristic curve analysis of AVC predicting severe AS yielded an area under the curve of 0.91 (95% confidence interval [CI] 0.87-0.95; P<0.001) in women and 0.86 (95% CI 0.75-0.98; P<0.001) in men. The optimal thresholds (women: 1,379 AU; men: 1,802 AU) were close to those proposed in the guidelines. The diagnostic accuracy of the thresholds in the guidelines was similar to that of the optimal thresholds. Conclusions: The sex-specific AVC thresholds proposed in international guidelines can be applied to Japanese AS patients, yielding similar diagnostic accuracy as the optimal cut-off derived from the study patients.

Heart Team risk assessment with angiography-derived fractional flow reserve determining the optimal revascularization strategy in patients with multivessel disease: Trial design and rationale for the DECISION QFR randomized trial.

In patients with multivessel disease (MVD), functional information on lesions improves the prognostic capability of the SYNTAX score. Quantitative flow ratio (QFR®) is an angiography-derived fractional flow reserve (FFR) that does not require a pressure wire or pharmacological hyperemia. We aimed to investigate the feasibility of QFR-based patient information in Heart Teams' discussions to determine the optimal revascularization strategy for patients with MVD. We hypothesized that there is an acceptable agreement between treatment recommendations based on the QFR approach and recommendation based on the FFR approach. The DECISION QFR study is a prospective, multicenter, randomized controlled trial that will include patients with MVD who require revascularization. Two Heart Teams comprising cardiologists and cardiac surgeons will be randomized to select a revascularization strategy (percutaneous coronary intervention or coronary artery bypass graft) according to patient information either based on QFR or on FFR. All 260 patients will be assessed by both teams with reference to the anatomical and functional SYNTAX score/SYNTAX score II 2020 derived from the allocated physiological index (QFR or FFR). The primary endpoint of the trial is the level of agreement between the treatment recommendations of both teams, assessed using Cohen's κ. As of March 2022, the patient enrollment has been completed and 230 patients have been discussed in both Heart Teams. The current trial will indicate the usefulness of QFR, which enables a wireless multivessel physiological interrogation, in the discussions of Heart Teams to determine the optimal revascularization strategy for MVD.

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) update 2022.

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Interventional and Therapeutics (CVIT) society proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018. Updated guidelines for the management of AMI were published by the European Society of Cardiology (ESC) in 2017 and 2020. Major changes in the guidelines for STEMI patients included: (1) radial access and drug-eluting stents (DES) over bare-metal stents (BMS) were recommended as a Class I indication, (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. In 2020, updated guidelines for Non-ST-Elevation Myocardial Infarction (NSTEMI) patients, the followings were changed: (1) an early invasive strategy within 24 h is recommended in patients with NSTEMI as a Class I indication, (2) complete revascularization in NSTEMI patients without cardiogenic shock is considered as Class IIa recommendation, and (3) in patients with atrial fibrillation following a short period of triple antithrombotic therapy, dual antithrombotic therapy (e.g., DOAC and single oral antiplatelet agent preferably clopidogrel) is recommended, with discontinuation of the antiplatelet agent after 6 to 12 months. Furthermore, an aspirin-free strategy after PCI has been investigated in several trials those have started to show the safety and efficacy. The Task Force on Primary PCI of the CVIT group has now proposed the updated expert consensus document for the management of AMI focusing on procedural aspects of primary PCI in 2022 version.

Investigation of the role and quantitative impact of breast cancer resistance protein on drug distribution into brain and CSF in rats.

Breast cancer resistance protein (BCRP) expressed in the blood-brain barrier plays a major role in limiting drug distribution into the central nervous system (CNS). However, functional involvement of BCRP in drug distribution into the brain and cerebrospinal fluid (CSF) remains unclear. The aim of present study was to reveal the role and quantitative impact of BCRP on CNS distribution. The brain-to-plasma unbound concentration ratio (Kp,uu,brain) and CSF-to-plasma unbound concentration ratio (Kp,uu,CSF) values of BCRP-specific substrates were determined in rats. The Kp,uu,brain values decreased, as the in vitro BCRP corrected flux ratio (CFR) increased. The Kp,uu,CSF values of BCRP-specific substrates were greater than the Kp,uu,brain values. Increase in the Kp,uu,brain values induced by co-administration of BCRP inhibitor correlated with the in vitro BCRP CFR and were greater than the increase in Kp,uu,CSF values induced by BCRP inhibitor except nebicapone. The contribution of BCRP to the brain and CSF distribution of the dual P-glycoprotein/BCRP substrates, imatinib and prazosin, was similar to that of BCRP-specific substrates. Thus, we revealed that the impact of in vivo BCRP on CNS distribution is correlated with in vitro BCRP CFR, and that BCRP limits drug distribution into the brain more strongly than into the CSF.

Online three-dimensional OFDI-guided versus angiography-guided PCI in bifurcation lesions: design and rationale of the randomised OPTIMUM trial.

AIMS: The feasibility of offline optical coherence tomography (OCT) guidance in bifurcation (with either two-dimensional or three-dimensional images) and its potential benefits have been demonstrated in retrospective studies; however, these have not yet been investigated prospectively. The aim of this trial is to determine the superiority of online three-dimensional optical frequency domain imaging (3D-OFDI)-guided stenting to angiography-guided percutaneous coronary intervention (PCI) in terms of incomplete stent apposition (ISA) at the bifurcation segment. METHODS AND RESULTS: The OPTIMUM trial is a randomised, superiority, multicentre clinical trial. The primary endpoint of this trial is the post-procedural percentage of malapposed struts assessed by OFDI in the main branch bifurcation region after final kissing balloon dilatation (FKBD). A total of 106 patients will be randomly allocated to either 3D-OFDI guidance or angiography guidance PCI. Bifurcation lesions will be treated with a provisional single-stent strategy using the Ultimaster sirolimus-eluting stent. Patients randomised to the 3D-OFDI guidance arm will undergo OFDI assessment in the main branch (MV) after rewiring into the jailed side branch following stent implantation, while in the angiography guidance arm re-crossing of a wire into the side branch will be performed using conventional fluoroscopic/angiographic guidance. In patients in the 3D-OFDI guidance arm, if the position of the wire is not located in the optimal cell, further attempts to redirect the wire to the optimal cell will be performed, with subsequent OFDI acquisitions to confirm the re-crossing position. The proximal optimisation technique and FKBD are mandatory in this trial. The study will provide a 90% power to show superiority of 3D-OFDI guidance PCI compared with angiography-guided PCI. CONCLUSIONS: The OPTIMUM trial will be the first prospective, randomised trial to evaluate the efficacy and safety of online 3D-OFDI-guided PCI in bifurcation lesions. ClinicalTrials.gov Identifier: NCT02972489.

Neointimal hyperplasia of ultra-thin stents with microcrystalline sirolimus or durable polymer everolimus-eluting stents: 6- and 24-month results of the DESSOLVE III OCT study.

AIMS: The DESSOLVE III OCT substudy aimed to compare serially neointimal hyperplasia volume obstruction (%VO) between the thin-strut MiStent with early polymer elimination and nine-month sustained drug release from microcrystalline sirolimus and the durable polymer-coated everolimus-eluting XIENCE stent at six and 24 months after implantation. METHODS AND RESULTS: The efficacy endpoint was %VO, calculated as abluminal neointimal volume/stent volume. Thirty-six patients (MiStent 16 patients, 16 lesions; XIENCE 20 patients, 22 lesions) underwent serial OCT evaluation at both six and 24 months. At six months, mean abluminal %VO was significantly lower in the MiStent group than in the XIENCE group (14.54±3.70% vs 19.11±6.70%; p=0.011), whereas the difference in %VO between the two groups decreased at 24 months (20.88±5.72% vs 23.50±7.33%; p=0.24). There was no significant difference in percentage malapposed struts and percentage uncovered struts between the two groups at both time points. CONCLUSIONS: In the serial comparative OCT analysis of the MiStent versus the XIENCE, the MiStent showed a more favourable efficacy for preventing neointimal formation with comparable strut tissue coverage, as compared with the XIENCE at six months, but this difference in %VO decreased at 24 months so that the difference in neointima at 24 months was no longer significant.

Site vs. core laboratory variability in computed tomographic angiography-derived SYNTAX scores in the SYNTAX III trial.

AIMS: To investigate the variability between site and core laboratory (CL) calculation of the anatomical SYNTAX score (SS) based on coronary computed tomography angiography (CTA) alone and functional SS based on coronary CTA and fractional flow reserve derived from computed tomography (FFRCT) in the SYNTAX III trial. METHODS AND RESULTS: The SYNTAX III trial was a multicentre, international study that included 223 patients with three-vessel disease with or without left main involvement. Functional SS was computed by subtracting non-flow limiting stenoses (FFRCT > 0.80) from anatomical SS. SS was combined with clinical information to generate the SYNTAX score II (SS II) that provides treatment recommendations. The mean anatomical SS based on coronary CTA alone was 33.4 ± 12.7 by sites and 37.1 ± 13.4 by CL (P < 0.001). The mean functional SS based on coronary CTA and FFRCT was 30.5 ± 13.0 by sites and 33.3 ± 13.6 by CL (P < 0.001). The intraclass correlation coefficient was 0.49 [95% confidence interval (CI) 0.37-0.59) in anatomical SS and 0.62 (95% CI 0.52-0.70) in functional SS. The Cohen's κ comparing treatment recommendation between sites and CL was 0.68 (95% CI 0.58-0.78) based on anatomical SS and 0.71 (95% CI 0.60-0.82) based on functional SS. CONCLUSION: The mean anatomical SS derived from coronary CTA alone and functional SS based on coronary CTA and FFRCT were higher when assessed by the CL than by the sites themselves. However, substantial agreement in treatment recommendation by SS II between sites and CL was demonstrated. CLINICAL TRIALS.GOV IDENTIFIER: NCT02385279.

A Prospective Multicenter Randomized Trial to Assess the Effectiveness of the MagicTouch Sirolimus-Coated Balloon in Small Vessels: Rationale and Design of the TRANSFORM I Trial.

AIMS: The objective of the study is to assess the efficacy and safety of the novel Magic Touch sirolimus coated-balloon (SCB) when compared to the SeQuent Please Neo paclitaxel coated balloon (PCB) for the treatment of de-novo small vessel coronary artery diseases (SVD). STUDY DESIGN: The TRANSFORM I study is a randomized, multicenter, non-inferiority trial with the intent to enroll a total of 114 patients with a de-novo SVD (≤2.5 mm). Vessel size will be pre-screened by on-line QCA. After successful pre-dilatation without major coronary dissections (type C-F) nor Thrombolysis In Myocardial Infarction trial [TIMI] grade flow ≤2, patients will be enrolled in a 1:1 randomization to receive treatment with either the novel SCB balloon or the comparative PCB balloon. The balloon sizing will be selected according to the lumen-based approach derived from optical coherence tomography (OCT). The primary endpoint is 6-month mean net lumen diameter gain (6-month minimum lumen diameter [MLD] minus baseline MLD) assessed by quantitative coronary analysis (QCA) with non-inferiority margin of 0.3 mm in per-protocol analysis. The clinical follow-up will be conducted up to 1 year. The enrollment started in September 2020 and will complete in April 2021. CONCLUSIONS: The TRANSFORM I trial will assess the efficacy of novel SCB in terms of non-inferiority to conventional PCB with a novel OCT measurement approach in patients with a de-novo SVD. Clinical Trial Registration URL: https://clinicaltrials.gov. Unique identifier: NCT03913832.

A Randomized Trial Evaluating Online 3-Dimensional Optical Frequency Domain Imaging-Guided Percutaneous Coronary Intervention in Bifurcation Lesions.

BACKGROUND: Clinical implications of online 3-dimensional optical frequency domain imaging (3D-OFDI)-guided stenting for bifurcation lesions have not been investigated in the randomized controlled trials. The purpose of this study was to determine whether online 3D-OFDI-guided stenting is superior to angiography-guided percutaneous coronary intervention (PCI) in terms of incomplete stent apposition at the bifurcation segment. METHODS: The OPTIMUM trial (Online 3-Dimensional Optical Frequency Domain Imaging to Optimize Bifurcation Stenting Using UltiMaster Stent) was a randomized, multicenter clinical trial. Eligible patients had an angiographically significant stenosis in the bifurcation lesion treated with a provisional single stent strategy using the Ultimaster sirolimus eluting stent. Patients were randomly allocated to either online 3D-OFDI-guided or angiography-guided PCI. Patients randomized to 3D-OFDI guidance underwent online 3D-OFDI assessment after rewiring into the jailed side branch after stenting and proximal optimization technique, while in the angiography guidance arm, rewiring was performed using conventional fluoroscopic/angiographic guidance. The primary end point of this trial was the postprocedural average percentage of malapposed struts per lesion assessed by OFDI in the confluence zone of the main and side branches. RESULTS: Between June 8, 2017 and September 26, 2018, 110 patients with 111 bifurcation lesions were randomized at 4 Japanese centers. Of these, 56 patients with 57 lesions were treated with 3D-OFDI-guided PCI, whereas 54 patients with 54 lesions were treated with angiography-guided PCI. In the 3D-OFDI guidance arm, the feasibility of online 3D-OFDI was 98.2%. The average percentage of incomplete stent apposition per lesion at bifurcation was lower in the 3D-OFDI guidance arm than that in the angiography guidance arm (19.5±15.8% versus 27.5±14.2%, P=0.008). The superiority of the 3D-OFDI guidance arm was also confirmed in the strut level analysis (odds ratio: 0.54 [95% CI, 0.36-0.81]; P=0.003). CONCLUSIONS: Online 3D-OFDI-guided bifurcation PCI was superior to angiography-guided bifurcation PCI in terms of acute incomplete stent apposition at bifurcation. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02972489.

Endothelial shear stress and vascular remodeling in bioresorbable scaffold and metallic stent.

BACKGROUND AND AIMS: The impact of endothelial shear stress (ESS) on vessel remodeling in vessels implanted with bioresorbable scaffold (BRS) as compared to metallic drug-eluting stent (DES) remains elusive. The aim of this study was to determine whether the relationship between ESS and remodeling patterns differs in BRS from those seen in metallic DES at 3-year follow-up. METHODS: In the ABSORB II randomized trial, lesions were investigated by serial coronary angiography and intravascular ultrasound (IVUS). Three-dimensional reconstructions of coronary arteries post-procedure and at 3 years were performed. ESS was quantified using non-Newtonian steady flow simulation. IVUS cross-sections in device segment were matched using identical landmarks. RESULTS: Paired ESS calculations post-procedure and at 3 years were feasible in 57 lesions in 56 patients. Post-procedure, median ESS at frame level was higher in BRS than in DES, with marginal statistical significance (0.97 ± 0.48 vs. 0.75 ± 0.39 Pa, p = 0.063). In the BRS arm, vessel area and lumen area showed larger increases in the highest tercile of median ESS post-procedure as compared to the lowest tercile. In contrast, in DES, no significant relationship between median ESS post-procedure and remodeling was observed. In multivariate analysis, smaller vessel area, larger lumen area, higher plaque burden post-procedure, and higher median ESS post-procedure were independently associated with expansive remodeling in matched frames. Only in BRS, younger age was an additional significant predictor of expansive remodeling. CONCLUSIONS: In a subset of lesions with large plaque burden, shear stress could be associated with expansive remodeling and late lumen enlargement in BRS, while ESS had no impact on vessel dimension in metallic DES.