Success rate and influencing factors of a balloon-push technique: A new technique to remove side branch-jailed struts under three-dimensional optical coherence tomography guidance.

BACKGROUND: Kissing balloon inflation with distal guide wire recross can cause severe stent deformation depending on the stent link location with respect to the carina. The balloon-push technique, by which an inflated balloon is forced into the SB from the proximal main vessel (MV), is a feasible way to remove jailed struts without causing severe stent deformation. AIMS: We investigated the procedural success rate, patterns of jailed strut removal at side branch (SB) orifices, factors related to failure of jailed strut removal, and follow-up angiogram results of the balloon-push technique. METHODS: Between September 2015 and December 2020, 51 bifurcation stenting cases in which the balloon-push technique was used were enrolled. Based on three-dimensional optical coherence tomography images, strut removal with 1 stent crown length was defined as successful. Strut removal patterns were classified into two types: parallel-slide type (stent struts shifted distally into the MV lumen without inversion) and under-carina type (stent struts shifted distally under the carina with strut inversion or strut slide). RESULTS: Procedural success was attained in 39 cases (success rate: 76.5%). Parallel-slide type and under-carina type occurred in 43% and 33% of cases, respectively. Factors related to failure were trifurcation lesions and a smaller pushed balloon-SB artery ratio compared with those in success cases (0.95 ± 0.18 vs. 1.10 ± 0.22, p = 0.032). Follow-up angiography was performed in 37 cases, and 2 cases had binary in-stent restenosis. CONCLUSIONS: Removal of jailed struts with the balloon-push technique was feasible, without severe stent deformation, in bifurcation stentings.

Drug-Coated Balloon for the Treatment of Small Vessel Coronary Artery Disease　- A Randomized Non-Inferiority Trial.

BACKGROUND: Drug-coated balloons (DCB) have shown promising results for the treatment of in-stent restenosis (ISR) and small vessel disease (SVD). However, data comparing the treatment efficacy of different DCBs are limited.Methods and Results: AGENT Japan is a prospective randomized controlled trial that compares the Agent balloon coated with a low-dose formulation of paclitaxel (2 µg/mm2) to the SeQuent Please paclitaxel-coated balloon (3 µg/mm2) for the treatment of SVD. Patients with target lesion length ≤28 mm and reference diameter between ≥2.00 and <3.00 mm were randomized 2 : 1 for treatment with Agent (n=101) or SeQuent Please (n=49). This trial also includes a separate single-arm substudy evaluating the clinical safety and effectiveness of Agent in patients with ISR. The primary endpoint of 6-month target lesion failure (TLF) was observed in 3.0% of Agent and 0.0% of SeQuent Please patients (difference=3.0%; 97.5% upper confidence bound [UCB]=9.57%, which is less than the prespecified margin of 13.2%; Pnon-inferiority=0.0012). There were no deaths or thrombosis, and angiographic and quality-of-life outcomes were comparable between groups. The AGENT Japan ISR substudy (n=30) primary endpoint was met because the one-sided 97.5% UCB for 6-month TLF (3.3%) was significantly less than the study success criterion of 15.1% (97.5% UCB=9.8%; P<0.0001). CONCLUSIONS: Data from this study demonstrate good clinical outcomes with the Agent DCB when used to treat patients with SVD or ISR.

Risk Assessment of Side Branch Compromise After Coronary Bifurcation Stenting　- A Substudy of the 3D-OCT Bifurcation Registry.

BACKGROUND: Side branch (SB) occlusion during bifurcation stenting is a serious complication. This study aimed to predict SB compromise (SBC) using optical coherence tomography (OCT).Methods and Results: Among the 168 patients who enrolled in the 3D-OCT Bifurcation Registry, 111 bifurcation lesions were analyzed to develop an OCT risk score for predicting SBC. SBC was defined as worsening of angiographic SB ostial stenosis (≥90%) immediately after stenting. On the basis of OCT before stenting, geometric parameters (SB diameter [SBd], length from proximal branching point to carina tip [BP-CT length], and distance of the polygon of confluence [dPOC]) and 3-dimensional bifurcation types (parallel or perpendicular) were evaluated. SBC occurred in 36 (32%) lesions. The parallel-type bifurcation was significantly more frequent in lesions with SBC. The receiver operating characteristic curve indicated SBd ≤1.77 mm (area under the curve [AUC]=0.73, sensitivity 64%, specificity 75%), BP-CT length ≤1.8 mm (AUC=0.83, sensitivity 86%, specificity 68%), and dPOC ≤3.96 mm (AUC=0.68, sensitivity 63%, specificity 69%) as the best cut-off values for predicting SBC. To create the OCT risk score, we assigned 1 point to each of these factors. As the score increased, the frequency of SBC increased significantly (Score 0, 0%; Score 1, 8.7%; Score 2, 28%; Score 3, 58%; Score 4, 85%; P<0.0001). CONCLUSIONS: Prediction of SBC using OCT is feasible with high probability.

Potential relationship between high wall shear stress and plaque rupture causing acute coronary syndrome.

The relationship between high wall shear stress (WSS) and plaque rupture (PR) in longitudinal and circumferential locations remains uncertain. Overall, 100 acute coronary syndrome patients whose culprit lesions had PR, documented by optical coherence tomography (OCT), were enrolled. Lesion-specific three-dimensional coronary artery models were created using OCT data. WSS was computed with computational fluid dynamics analysis. PR was classified into upstream-PR, minimum lumen area-PR, and downstream-PR according to the PR's longitudinal location, and into central-PR and lateral-PR according to the disrupted fibrous cap circumferential location. In the longitudinal 3-mm segmental analysis, multivariate analysis demonstrated that higher WSS in the upstream segment was independently associated with upstream-PR, and thinner fibrous cap was independently associated with downstream-PR. In the PR cross-sections, the PR region had a significantly higher average WSS than non-PR region. In the cross-sectional analysis, the in-lesion peak WSS was frequently observed in the lateral (66.7%) and central regions (70%) in lateral-PR and central-PR, respectively. Multivariate analysis demonstrated that the presence of in-lesion peak WSS at the lateral region, thinner broken fibrous cap, and larger lumen area were independently associated with lateral-PR, while the presence of in-lesion peak WSS at the central region and thicker broken fibrous cap were independently associated with central-PR. In conclusion, OCT-based WSS simulation revealed that high WSS might be related to the longitudinal and circumferential locations of PR.

Effect of proximal optimization technique on coronary bifurcation stent failure: Insights from the multicenter randomized PROPOT trial.

OBJECTIVE: We investigated the effect of proximal optimization technique (POT) on coronary bifurcation stent failure (BSF) in cross-over stenting by comparing with the kissing balloon technique (KBT) in a multicenter randomized PROPOT trial. BACKGROUND: POT is recommended due to increased certainty for optimal stent expansion and side branch (SB) wiring. METHODS: We randomized 120 patients treated with crossover stenting into the POT group, which was followed by SB dilation (SBD), and the KBT group. Finally, 52 and 57 patients were analyzed by optical coherence tomography before SBD and at the final procedure, respectively. Composite BSF was defined as a maximal malapposition distance of >400 µm, or malapposed and SB-jailed strut rates of >5.95% and >21.4%, respectively. RESULTS: Composite BSF before SBD in the POT and KBT groups was observed in 29% and 26% of patients, respectively. In the POT group, differences in stent volumetric index between the proximal and distal bifurcation (odds ratio [OR] 60.35, 95% confidential interval [CI] 0.13-0.93, p = 0.036) and between the proximal bifurcation and bifurcation core (OR: 3.68, 95% CI: 1.01-13.40, p = 0.048) were identified as independent risk factors. Composite BSF at final in 27% and 32%, and unplanned additional procedures in 38% and 25% were observed, respectively. Composite BSF before SBD was a risk factor for the former (OR: 6.33, 95% CI: 1.10-36.50, p = 0.039) and the latter (OR: 6.43, 95% CI: 1.25-33.10, p = 0.026) in the POT group. CONCLUSION: POT did not result in a favorable trend in BSF. Insufficient expansion of the bifurcation core after POT was associated with BSF.

Ischemic and Bleeding Events in PENDULUM Patients With High Bleeding Risk and High Platelet Reactivity.

BACKGROUND: The balance between thrombotic and bleeding risk is of great concern in high bleeding risk (HBR) patients. This study evaluated the relationship between perioperative antiplatelet reactivity and thrombotic and bleeding events in patients at HBR undergoing percutaneous coronary intervention (PCI).Methods and Results: In this post hoc analysis of the PENDULUM (Platelet rEactivity in patieNts with DrUg eLUting stent and balancing risk of bleeding and ischeMic event) registry, patients undergoing PCI were categorized as HBR or non-HBR, and stratified as having high platelet reactivity (HPR; P2Y12reaction unit [PRU] >208) or non-HPR (PRU ≤208). Cumulative incidences of cardiovascular and cerebrovascular events (Journal of the American College of Cardiology expert definitions) and bleeding events (Bleeding Academic Research Consortium criteria) were assessed 12 months after index PCI. The incidence of ischemic and bleeding events was ~3-fold higher in HBR vs. non-HBR patients. Thrombotic/ischemic events were significantly more common in the HPR subgroup in HBR patients (hazard ratio [HR]: 1.59; 95% confidence interval [CI]: 1.11-2.28; P=0.012), but there was no difference in non-HBR patients. After adjustment for covariates, HPR in HBR patients remained an independent factor for thrombotic and ischemic events (HR: 1.69; 95% CI: 1.13-2.54; P=0.011), but not for bleeding events (HR: 1.56; 95% CI: 0.78-3.11; P=0.210). CONCLUSIONS: Maintaining adequate PRU levels during PCI is an important factor in improving clinical outcomes, especially for HBR patients.

Peri-Balloon Leak Flow Velocity Assessed by Intra-Cardiac Echography Predicts Pulmonary Vein Electrical Gap　- Intra-Cardiac Echography-Guided Contrast-Free Cryoballoon Ablation.

BACKGROUND: The use of iodine contrast agents is one possible limitation in cryoballoon ablation (CBA) for atrial fibrillation (AF). This study investigated intracardiac echography (ICE)-guided contrast-free CBA.Methods and Results:The study was divided into 2 phases. First, 25 paroxysmal AF patients (Group 1) underwent CBA, and peri-balloon leak flow velocity (PLFV) was assessed using ICE and electrical pulmonary vein (PV) lesion gaps were assessed by high-density electroanatomical mapping. Then, 24 patients (Group 2) underwent ICE-guided CBA and were compared with 25 patients who underwent conventional CBA (historical controls). In Group 1, there was a significant correlation between PLFV and electrical PV gap diameter (r=-0.715, P<0.001). PLFV was higher without than with an electrical gap (mean [±SD] 127.0±28.6 vs. 66.6±21.0 cm/s; P<0.001) and the cut-off value of PLFV to predict electrical isolation was 105.7 cm/s (sensitivity 0.700, specificity 0.929). In Group 2, ICE-guided CBA was successfully performed with acute electrical isolation of all PVs and without the need for "rescue" contrast injection. Atrial tachyarrhythmia recurrence at 6 months did not differ between ICE-guided and conventional CBA (3/24 [12.5%] vs. 5/25 [20.0%], respectively; P=0.973, log-rank test). CONCLUSIONS: PLFV predicted the presence of an electrical PV gap after CBA. ICE-guided CBA was feasible and safe, and could potentially be performed completely contrast-free without a decrease in ablation efficacy.

Clinical Outcomes After Percutaneous Coronary Intervention in East Asian Patients　- 30-Month Results of the PENDULUM Registry.

BACKGROUND: The 12-month results of the PENDULUM registry showed that after implantation of second-generation drug-eluting stents (DES), high P2Y12reaction unit (HPR) were independently associated with ischemic but not bleeding events.Methods and Results: This study analyzed cumulative incidences of major adverse cardiac and cerebrovascular events (MACCE) and major bleeding (Bleeding Academic Research Consortium type 3 and 5) at 30 months after index percutaneous coronary intervention (PCI) (primary endpoints). Of 6,422 patients undergoing PCI with DES, 5,796 completed the 30-month follow up. The continuation rate of dual antiplatelet therapy decreased to 59.3% at 12 months and 26.4% at 30 months. At 30 months, the cumulative incidence of MACCE increased linearly and reached 9.5% (95% confidence interval 8.8-10.2) and that of major bleeding had the inflection point at 12 months and was 4.4% (3.9-5.0). MACCE and bleeding events were higher in HPR patients (unadjusted P value). After covariate adjustment, P2Y12reactivity units measured immediately after index PCI was not an independent risk factor for MACCE or major bleeding at 30 months. CONCLUSIONS: MACCE consistently increased after 12 months post-PCI, whereas the increase in major bleeding events slowed down after 12 months in Japanese PCI patients in a real-world clinical setting. HPR patients had increased MACCE and bleeding complications, but HPR was not an independent risk factor of events at 30 months.

Early P2Y12 Inhibitor Single Antiplatelet Therapy for High-Bleeding Risk Patients After Stenting　- PENDULUM Mono 24-Month Analysis.

BACKGROUND: In PENDULUM mono, Japanese patients with high bleeding risk (HBR) received short-term dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) with prasugrel after percutaneous coronary intervention (PCI). One-year data from PENDULUM mono showed better outcomes with prasugrel monotherapy after short-term DAPT compared with matched patients in the PENDULUM registry with longer DAPT durations according to guidelines at that time. This study presents 2-year results.Methods and Results: We compared 24-month data from PENDULUM mono (n=1,107; de-escalation strategy group) and the PENDULUM registry (n=2,273; conventional strategy group); both were multicenter, non-interventional, prospective registry studies, using the inverse probability of treatment weighting (IPTW) method. In the PENDULUM mono group, the cumulative incidence of clinically relevant bleeding (CRB) at 24 months post-PCI (primary endpoint) was 6.8%, and that of major adverse cardiac and cerebrovascular events (MACCE) was 8.9%. After IPTW adjustment, the cumulative incidence of CRB was 5.8% and 7.2% in PENDULUM mono and the PENDULUM registry, respectively (hazard ratio [HR] 0.77; 95% confidence interval [CI] 0.57-1.04; P=0.086), and that of MACCE was 8.0% and 9.5%, respectively (HR 0.77; 95% CI 0.59-1.01; P=0.061). CONCLUSIONS: Japanese PCI patients with HBR prescribed prasugrel SAPT after short-term DAPT had a lower ischemic event risk than those prescribed long-term DAPT, and this was particularly relevant for ischemic events after 1 year.

Real-world clinical outcomes of percutaneous transluminal septal myocardial ablation for patients with drug-refractory hypertrophic obstructive cardiomyopathy: results from a retrospective multicenter registry of non-high-volume centers.

Percutaneous transluminal septal myocardial ablation (PTSMA) is a well-established interventional therapy for drug-refractory hypertrophic obstructive cardiomyopathy (HOCM) as an alternative to surgical myectomy. Although guidelines recommend that PTSMA should be performed in institutions with extensive experience, it is not centralized to such high-volume centers in real-world clinical practice. Thus, this study aimed to assess the feasibility of PTSMA in non-high-volume centers. We retrospectively examined patients with HOCM who underwent PTSMA between August 2012 and May 2020 at four institutions that experienced fewer than 20 cases of PTSMA procedures. The primary clinical endpoint was a composite of safety (all-cause death, electrical defibrillation for ventricular tachycardia or fibrillation, cardiac tamponade, permanent pacemaker implantation, and repeated interventions) and efficacy endpoints (repeated interventions [PTSMA or surgical myectomy]). Fifty-eight consecutive patients were enrolled. During the 30-day follow-up, no major clinical adverse events were noted except three patients (5.2%) requiring permanent pacemaker implantation for complete atrioventricular block. The percentage of patients with New York Heart Association functional class 1 or 2 significantly increased from 8.6 to 100% (p < 0.001). In the Cox proportional hazard model, left ventricular outflow tract pressure gradient at rest ≥ 30 mmHg (hazard ratio [HR] 6.56; 95% confidence interval [CI] 1.44-29.90; p = 0.015) and mitral regurgitation grade ≥ 3 (HR 10.75; 95% CI 1.81-63.79; p = 0.009) at the 30-day follow-up were associated with a composite of major clinical adverse events. The current study demonstrated that 58 patients who underwent PTSMA in non-high-volume centers had favorable 30-day clinical outcomes, with a primary composite endpoint rate of 5.2%. A prospective study with a larger sample size and longer follow-up is warranted to verify the safety and efficacy of PTSMA in non-high-volume centers.

Relationship between platelet aggregation and stroke risk after percutaneous coronary intervention: a PENDULUM analysis.

In patients undergoing percutaneous coronary intervention (PCI) with a stent, high on-treatment platelet reactivity may be associated with an increased risk of stroke. This post hoc analysis of the PENDULUM registry compared the risk of post-PCI stroke according to on-treatment P2Y12 reaction unit (PRU) values. Patients aged ≥ 20 years who underwent PCI were stratified by baseline PRU (at 12 and 48 h post-PCI) as either high (HPR, > 208), optimal (OPR, > 85 to ≤ 208), or low on-treatment platelet reactivity (LPR, ≤ 85). The incidences of non-fatal ischemic and non-ischemic stroke through to 12 months post-PCI were recorded. Almost all enrolled patients (6102/6267 [97.4%]) had a risk factor for ischemic stroke, and most were receiving dual antiplatelet therapy. Of the 5906 patients with PRU data (HPR, n = 2227; OPR, n = 3002; LPR, n = 677), 47 had a non-fatal stroke post-PCI (cumulative incidence: 0.68%, ischemic; 0.18%, non-ischemic stroke). Patients with a non-fatal ischemic stroke event had statistically significantly higher post-PCI PRU values versus those without an event (P = 0.037). The incidence of non-fatal non-ischemic stroke was not related to PRU value. When the patients were stratified by PRU ≤ 153 versus > 153 at 12-48 h post-PCI, a significant difference was observed in the cumulative incidence of non-fatal stroke at 12 months (P = 0.044). We found that patients with ischemic stroke tended to have higher PRU values at 12-48 h after PCI versus those without ischemic stroke.Clinical trial registration: UMIN000020332.

Single Antiplatelet Therapy With Prasugrel vs. Dual Antiplatelet Therapy in Japanese Percutaneous Coronary Intervention Patients With High Bleeding Risk.

BACKGROUND: Outcomes with prasugrel single antiplatelet therapy (SAPT) vs. dual antiplatelet therapy (DAPT) in Japanese percutaneous coronary intervention (PCI) patients with high bleeding risk (HBR) are currently unknown.Methods and Results:Data from 1,173 SAPT and 2,535 DAPT patients from the PENDULUM mono and PENDULUM registry studies (respective median DAPT durations: 108 vs. 312 days) were compared. The adjusted cumulative incidence of Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding from 1 to 12 months after PCI (primary endpoint) was 2.8% (95% confidence interval [CI], 1.9-4.2) and 4.1% (95% CI, 3.3-5.1), respectively (hazard ratio [HR], 0.69; 95% CI, 0.45-1.06; P=0.090). The adjusted cumulative incidences of BARC 2, 3, or 5 bleeding from 0 to 12 months after PCI (secondary endpoint) were 3.8% (95% CI, 2.7-5.3) and 5.6% (95% CI, 4.7-6.7), respectively (HR, 0.68; 95% CI, 0.47-0.98; P=0.039). There was no significant difference in major adverse cardiac and cerebrovascular events (MACCE) from 1 to 12 months after PCI (HR, 0.93; 95% CI, 0.63-1.37; P=0.696) and at 12 months after PCI (HR, 0.85; 95% CI, 0.61-1.19; P=0.348) between the groups. CONCLUSIONS: Prasugrel SAPT may reduce BARC 2, 3, or 5 bleeding, without increasing MACCE, in Japanese patients with HBR.

Impact of the Antithrombotic Effects of Prasugrel on Mid-Term Vascular Healing in Acute Coronary Syndrome vs. Stable Coronary Artery Disease.

BACKGROUND: The impact of antiplatelet drug effects on mid-term local arterial responses following percutaneous coronary intervention (PCI) remains uncertain. We evaluated the impact of the platelet reactivity of prasugrel on mid-term vascular healing between acute coronary syndrome (ACS) and stable coronary artery disease (CAD).Methods and Results:We conducted a prospective, 12-center study in 125 patients with ACS and 126 patients with stable CAD who underwent PCI with an everolimus-eluting stent (EES) and received dual antiplatelet therapy (DAPT) with prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed immediately after PCI and at the 9-month follow-up to assess the association of P2Y12reaction units (PRU) with the frequency of malapposed or uncovered struts and intrastent thrombi (IST). The incidence of abnormal mid-term OCT findings did not different between the ACS and CAD arms, regardless of clinical presentation, except that uncovered struts were more frequent in the ACS than CAD arm. PRU at PCI was significantly associated with the frequency of IST at follow-up, but not with uncovered and malapposed struts. PRU at PCI was the only independent predictor of IST detected at follow-up (odds ratio 1.009). CONCLUSIONS: In patients undergoing EES implantation and receiving prasugrel, achieving an adequate antiplatelet effect at the time of stent implantation may regulate thrombus formation throughout the follow-up period.

Predictor analysis of 1-year restenosis after percutaneous transluminal angioplasty for femoropopliteal stenotic lesions using intravascular ultrasound.

This retrospective, single-center study evaluated the patency rate and predictors of restenosis after percutaneous transluminal angioplasty (PTA) for femoropopliteal stenotic lesions using intravascular ultrasound. We assessed 78 de novo femoropopliteal stenotic lesions (64 patients; mean age, 73.6 ± 9.4 years; average lesion length, 59.8 mm) that underwent PTA under intravascular ultrasound guidance. The primary endpoint was 1-year primary patency. The 1-year primary patency rate was 63%. The frequency of insulin use was significantly greater (44% vs. 12%, p = 0.005), and lesions were significantly longer (77.8 mm vs. 49.2 mm, p = 0.047) in the restenosis group than in the non-restenosis group. The pre-intervention reference lumen area and minimum lumen area (MLA) were significantly smaller in the restenosis group (reference lumen area: 19.7 ± 6.7 mm2 vs. 23.7 ± 7.4 mm2, p = 0.017; MLA 3.9 ± 2.8 mm2 vs. 5.7 ± 3.9 mm2, p = 0.026; respectively). The MLA was significantly smaller and the maximum angle of dissection was significantly larger in the restenosis group (MLA 9.3 mm2 vs. 12.3 mm2, p = 0.013; maximum angle of dissection: 104.1° vs. 69.6°, p = 0.003; respectively) among post-intervention parameters. Multivariate analysis revealed that the independent predictors of 1-year restenosis were the large post-intervention maximum angle of dissection and insulin use. Per receiver operating curve analysis, the best cut-off value of the post-intervention maximum angle of dissection that predicted 1-year restenosis was 70.2° (sensitivity 72.4%, specificity 63.3%, area under the curve 0.70, p = 0.004). In conclusion, the 1-year primary patency rate after PTA for relatively short stenotic femoropopliteal lesions was 63%. The large post-intervention maximum angle of dissection, measured using intravascular ultrasound, and insulin use were independent predictors of restenosis after PTA.

Efficacy of optical frequency domain imaging in detecting peripheral artery disease: the result of a multi-center, open-label, single-arm study.

Optical frequency domain imaging (OFDI) is a high-resolution intracoronary imaging modality with fast automated longitudinal pullback. We aimed to evaluate the ability of performing OFDI from the superficial femoral artery (SFA) to the below-knee (BK) artery. This clinical trial was a multi-center, single-arm, open-label study. The primary endpoint was to obtain a clear image of the intra-vascular lumen from the SFA to the BK artery, specifically > 270° visualization of the blood vessel lumen with > 16/21 cross sections. The proportion of the clear image (≥ 85%) was regarded as confirmatory of the ability of OFDI to visualize the vessel lumen. Overall, 20 patients were enrolled. The proportion of the primary endpoint was 90% (18/20), and the pre-specified criterion was successfully attained. The proportion of the clear image assessed by the operator was 100% (20/20), and an additional statistical analysis for the proportion of the visualization, > 270°, of the blood vessel lumen revealed a significantly higher cut-off value than that for the pre-specified criterion, 85% (p = 0.0315). There were three adverse events not related to OFDI. OFDI achieved acceptable visualization of the vessel lumen without any adverse event related to it. After regulatory approval based on the present study, OFDI will be available as a new option of endovascular imaging for peripheral artery diseases in daily practiceTrial registration: This study was registered in the Japanese Registry of Clinical Trials (jRCT 2052190025, https://jrct.niph.go.jp/latest-detail/jRCT2052190025 ).

Positive effect of dapagliflozin on left ventricular longitudinal function for type 2 diabetic mellitus patients with chronic heart failure.

BACKGROUND: The effect of sodium glucose cotransporter type 2 (SGLT2) inhibitor on left ventricular (LV) longitudinal myocardial function in type 2 diabetes mellitus (T2DM) patients with heart failure (HF) has remained unclear. METHODS: We analyzed data from our previous prospective multicenter study, in which we investigated the effect of the SGLT2 inhibitor dapagliflozin on LV diastolic functional parameters of T2DM patients with stable HF at five institutions in Japan. Echocardiography was performed at baseline and 6 months after administration of dapagliflozin. LV diastolic function was defined as the ratio of mitral inflow E to mitral e' annular velocities (E/e'). LV longitudinal myocardial function was assessed as global longitudinal strain (GLS), which in turn was determined as the averaged peak longitudinal strain from standard LV apical views. RESULTS: E/e' significantly decreased from 9.3 to 8.5 cm/s 6 months after administration of dapagliflozin (p = 0.020) as previously described, while GLS showed significant improvement from 15.5 ± 3.5% to 16.9 ± 4.1% (p < 0.01) 6 months after administration of dapagliflozin. Furthermore, improvement of GLS in HF with preserved ejection fraction patients was more significant from 17.0 ± 1.9% to 18.7 ± 2.0% (p < 0.001), compared to that in HF with mid-range ejection fraction and HF with reduced ejection fraction patients from 14.4 ± 2.4% to 15.5 ± 1.8% (p = 0.06) and from 8.1 ± 1.5% to 7.8 ± 2.1% (p = 0.44), respectively. It was noteworthy that multiple regression analysis showed that the change in GLS after administration of dapagliflozin was the only independent determinant parameters for the change in E/e' after administration of dapagliflozin. CONCLUSION: Dapagliflozin was found to be associated with improvement of LV longitudinal myocardial function, which led to further improvement of LV diastolic function of T2DM patients with stable HF. GLS-guided management may thus lead to improved management of T2DM patients with stable HF.

Vascular Response Occurring at 3 Months After Everolimus-Eluting Cobalt-Chromium Stent Implantation in Patients With ST-Segment Elevation Myocardial Infarction vs. Stable Coronary Artery Disease.

BACKGROUND: Second-generation drug-eluting stents (DES) reduce the incidence of stent thrombosis, even in patients with ST-segment elevated myocardial infarction (STEMI). However, the early local vascular healing after DES implantation in STEMI lesions, which mainly concerns stent thrombosis, is still unclear.Methods and Results:We attempted to determine early local vascular healing 3 months after cobalt-chromium everolimus-eluting stent (CoCr-EES) implantation in STEMI lesions relative to stable coronary artery disease (CAD) lesions. This prospective, multicenter study analyzed 96 total lesions (STEMI=49, stable CAD=51) by frequency domain-optical coherence tomography (FD-OCT) performed post-procedure and at the 3-month follow-up. Although CoCr-EES implanted in STEMI were almost entirely covered at 3 months, they had a relatively high incidence of uncovered struts compared with stable CAD (5.5% vs. 1.6%, P<0.001). Intrastent thrombus in the 2 groups was primarily resolved at the 3-month follow-up (STEMI: 91.7%→26.5%, stable CAD: 74.5%→11.8%). Regarding irregular protrusion, complete resolution was observed in stable CAD (21.6%→0%), while a few stents remained in STEMI (79.2%→8.2%). Although there were almost no changes for the serial change of average lumen area in STEMI, there were slight but significant decreases in stable CAD [STEMI 0.08 (-0.44, 0.55) mm2, stable CAD -0.35 (-0.55, 0.11) mm2; P=0.009]. CONCLUSIONS: Although strut coverage after CoCr-EES implantation for STEMI lesions was slightly delayed, the healing process appeared to be acceptable in both STEMI and stable CAD.

Questionnaire in patients with aborted sudden cardiac death due to coronary spasm in Japan.

OBJECTIVES: We investigated the medical or mechanical therapy, and the present knowledge of Japanese cardiologists about aborted sudden cardiac death (ASCD) due to coronary spasm. METHODS: A questionnaire was developed regarding the number of cases of ASCD, implantable cardioverter-defibrillator (ICD), and medical therapy in ASCD patients due to coronary spasm. The questionnaire was sent to the Japanese general institutions at random in 204 cardiology hospitals. RESULTS: The completed surveys were returned from 34 hospitals, giving a response rate of 16.7%. All SCD during the 5 years was observed in 5726 patients. SCD possibly due to coronary spasm was found in 808 patients (14.0%) and ASCD due to coronary spasm was observed in 169 patients (20.9%). In 169 patients with ASCD due to coronary spasm, one or two coronary vasodilators was administered in two-thirds of patients [113 patients (66.9%)], while more than 3 coronary vasodilators were found in 56 patients (33.1%). ICD was implanted in 117 patients with ASCD due to coronary spasm among these periods including 35 cases with subcutaneous ICD. Majority of cause of ASCD was ventricular fibrillation, whereas pulseless electrical activity was observed in 18 patients and complete atrioventricular block was recognized in 7 patients. Mean coronary vasodilator number in ASCD patients with ICD was significantly lower than that in those without ICD (2.1 ± 0.9 vs. 2.6 ± 1.0, p < 0.001). Although 16 institutions thought that the spasm provocation tests under the medications had some clinical usefulness of suppressing the next fatal arrhythmias, spasm provocation tests under the medication were performed in just 4 institutions. CONCLUSIONS: In the real world, there was no fundamental strategy for patients with ASCD due to coronary spasm. Each institution has each strategy for these patients. Cardiologists should have the same strategy and the same knowledge about ASCD patients due to coronary spasm in the future.

Clinical Impact of Coronary Computed Tomography Angiography-Derived Fractional Flow Reserve on Japanese Population in the ADVANCE Registry.

BACKGROUND: Coronary computed tomography angiography (cCTA)-derived fractional flow reserve (FFRCT) is a promising diagnostic method for the evaluation of coronary artery disease (CAD). However, clinical data regarding FFRCTin Japan are scarce, so we assessed the clinical impact of using FFRCTin a Japanese population.Methods and Results:The ADVANCE registry is an international prospective FFRCTregistry of patients suspected of CAD. Of 5,083 patients, 1,829 subjects enrolled from Japan were analyzed. Demographics, symptoms, cCTA, FFRCT, treatment strategy, and 90-day major cardiovascular events (MACE) were assessed. Reclassification of treatment strategy between cCTA alone and cCTA+FFRCToccurred in 55.8% of site investigations and in 56.9% in the core laboratory analysis. Patients with positive FFR (FFRCT≤0.80) were less likely to have non-obstructive disease on invasive coronary angiography than patients with negative FFR (FFRCT>0.80) (20.5% vs. 46.1%, P=0.0001). After FFRCT, 67.0% of patients with positive results underwent revascularization, whereas 96.1% of patients with negative FFRCTwere medically treated. MACE occurred in 5 patients with positive FFRCT, but none occurred in patients with negative FFRCTwithin 90 days. CONCLUSIONS: In this Japanese population, FFRCTmodified the treatment strategy in more than half of the patients. FFRCTshowed potential for stratifying patients suspected of CAD properly into invasive or non-invasive management pathways.

Impact of dual antiplatelet therapy with adjusted-dose prasugrel on mid-term vascular response in patients undergoing elective percutaneous coronary intervention with everolimus-eluting stents.

The impact of dual antiplatelet therapy (DAPT) with adjusted-dose (3.75 mg/day) prasugrel for Japanese patients has not been fully investigated in terms of local arterial healing following the elective percutaneous coronary intervention (PCI). The ROUTE-01 elective study was a prospective, 12-center and single-arm registry that enrolled 123 patients who underwent elective PCI with everolimus-eluting stents (EESs) under DAPT with a combination of adjusted-dose prasugrel and aspirin. Serial optical coherence tomography (OCT) was performed at the index PCI and 9-month follow-up to assess the relationship between in-stent thorombus (IST) and residual platelet reactivity measuring platelet reactivity unit (PRU). The patients were classified as extensive, intermediate, and poor metabolizers by cytochrome P450 2C19 (CYP2C19) loss-of-function polymorphisms. The prevalence of IST was 9.0% by 9-month OCT, with no difference amongst the three groups (p = 0.886). The incidences of malapposed and uncovered struts were not different among the groups. PRU was not statistically different among the groups. In multivariate logistic regression analysis, the independent predictor for IST on 9-month OCT was irregular protrusion (odds ratio = 8.952, p = 0.037) on post-PCI OCT, not CYP2C19 loss-of-function polymorphisms. An adequate anti-thrombotic effect with an acceptable incidence of IST was observed irrespective of CYP2C19 loss-of-function polymorphisms. Our data suggests that adjusted-dose prasugrel and aspirin is a feasible treatment option in Japanese patients treated with EESs in elective PCI.