北原 秀喜

BACKGROUND: There are limited data regarding whether anemia is associated with adverse clinical outcomes in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). METHODS: Patients with AF undergoing PCI at 15 institutions between January 2015 and March 2021 were included in this analysis. Based on the baseline hemoglobin levels, moderate to severe anemia was defined as hemoglobin levels <11 g/dL, and mild anemia was defined as hemoglobin levels 11-12.9 g/dL for men and 11-11.9 g/dL for women. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, stent thrombosis, and stroke) and major bleeding events (BARC 3 or 5), were compared among patients with moderate/severe anemia, mild anemia, and no anemia. RESULTS: In a total of 746 enrolled patients, 119 (16.0%) and 168 (22.5%) patients presented with moderate/severe and mild anemia. The incidence of MACE (22.5%, 11.0%, and 9.1%, log-rank p < 0.001), all-cause death (20.0%, 7.2%, and 4.8%, log-rank p < 0.001), and major bleeding events (10.7%, 6.5%, and 2.7%, log-rank p < 0.001) were the highest in the moderate/severe anemia group compared with the mild and no anemia groups. Multivariable Cox regression analyses determined moderate/severe anemia as an independent predictor for MACE (p = 0.008), all-cause death (p = 0.005), and major bleeding events (p = 0.031) at 1 year after PCI. CONCLUSION: Moderate/severe anemia was significantly associated with the higher incidence of MACE and all-cause death as well as major bleeding events compared with mild and no anemia in AF patients undergoing PCI.

The diagnosis of vasospastic angina (VSA) according to Japanese guidelines involves an initial intracoronary acetylcholine (ACh) provocation test in the left coronary artery (LCA) followed by testing in the right coronary artery (RCA). However, global variations in test protocols often lead to the omission of ACh provocation in the RCA, potentially resulting in the underdiagnosis of VSA. This study assessed the validity of the LCA-only ACh provocation approach for the VSA diagnosis and whether vasoreactivity in the LCA aids in determining further provocation in the RCA. A total of 273 patients who underwent sequential intracoronary ACh provocation testing in the LCA and RCA were included. Patients with a positive ACh provocation test in the LCA were excluded. Relations between vasoreactivity in the LCA and ACh test outcomes (positivity and adverse events) in the RCA were evaluated. In patients with negative ACh test results in the LCA, subsequent ACh testing was positive in the RCA in 23 of 273 (8.4%) patients. In patients with minimal LCA vasoconstriction (<25%), only 3.0% had a positive ACh test in the RCA, whereas the ACh test in the RCA was positive in 13.5% of those with LCA constriction of 25% to 90% (p = 0.002). No major adverse events occurred during ACh testing in the RCA. In conclusion, for the VSA diagnosis, the omission of ACh provocation in the RCA may be clinically acceptable, particularly when vasoconstriction induced by ACh injection was minimal in the LCA. Further studies are needed to define ACh provocation protocols worldwide.

Background: We previously developed a risk-scoring system for heart failure (HF) in patients with acute myocardial infarction (MI), namely "HF time-points (HFTPs)". In the original HFTPs, the presence of HF on admission, during hospitalization, and at short-term follow-up was individually scored. This study examined whether the revised HFTPs, with additional scoring of previous HF, provide better predictivity. Methods: This multicenter registry included a total of 1331 patients with acute MI undergoing percutaneous coronary intervention. HF was evaluated at four time-points before and after acute MI onset: (1) a history of HF; (2) elevated natriuretic peptide levels on admission; (3) in-hospital HF events; and (4) elevated natriuretic peptide levels at a median of 31 days after the onset. When HF was present at each time-point, one point was assigned to a risk scoring system, namely the original and revised HFTPs, ranging from 0 to 3 and from 0 to 4. The primary endpoint was a composite of cardiovascular death and HF rehospitalization after discharge. Results: Of the 1331 patients, 65 (4.9%) had the primary outcome events during a median follow-up period of 507 (interquartile range, 335-1106) days. The increase in both original and revised HFTPs was associated with an increased risk of the primary outcomes in a stepwise fashion with similar diagnostic ability. Conclusions: The original and revised HFTPs were both predictive of long-term HF-related outcomes in patients with acute MI undergoing percutaneous coronary intervention. Yet, the original HFTPs may be sufficient to estimate HF risks after MI.

Patients with previous atherosclerotic cardiovascular disease (ASCVD) are typically managed by secondary prevention modalities; however, they may experience recurrent events. In acute myocardial infarction (MI), the prognostic effect of preexisting ASCVD on the short- and long-term outcomes remains uncertain. This retrospective, multicenter registry included 2,475 patients with acute MI who underwent percutaneous coronary intervention. Previous ASCVD was defined as a history of ischemic events in the coronary, cerebral, and peripheral arterial territories. Patients were divided into 2 groups according to preexisting ASCVD. The primary end point was major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular death, recurrent MI, and ischemic stroke during hospitalization and after discharge. The bleeding outcomes were also evaluated. Of the 2,475 patients, 475 (19.2%) had previous ASCVD. Patients with previous ASCVD were older and likely to have more co-morbidities than those without ASCVD. During hospitalization, the MACE rates were higher in the ASCVD group than in the non-ASCVD group (16.4% vs 9.6%, p <0.001). Similarly, during a median follow-up of 542 days after discharge, patients with previous ASCVD had an increased risk of MACEs than those without ASCVD (13.4% vs 5.6%, p <0.001). The multivariable analyses identified previous ASCVD as a factor that was significantly associated with MACEs after discharge. Major bleeding events occurred more frequently in the ASCVD group than in the non-ASCVD group. In conclusion, preexisting ASCVD was often observed in patients with acute MI and was particularly associated with long-term ischemic outcomes after discharge; thus, further clinical investigations are needed in this vulnerable patient subset.

Background: Coronary artery calcification score (CACS) on electrocardiography (ECG)-gated computed tomography (CT) is used for risk stratification of atherosclerotic cardiovascular disease, which requires dedicated analytic software. In this study, we evaluated the diagnostic ability of manual calcification length assessment on non-ECG-gated CT for epicardial coronary artery disease (CAD). Methods: A total of 100 patients undergoing both non-ECG-gated plain CT scans with a slice interval of 1.25 mm and invasive coronary angiography were retrospectively included. We manually measured the length of the longest calcified lesions of coronary arteries on each branch. The relationship between the number of coronary arteries with the length of coronary calcium > 5, 10, or 15 mm and the presence of epicardial CAD on invasive angiography was evaluated. Standard CACS was also evaluated using established software. Results: Of 100 patients, 49 (49.0%) had significant epicardial CAD on angiography. The median standard CACS was 346 [7, 1965]. In both manual calcium assessment and standard CACS, the increase in calcium burden was progressively associated with the presence of epicardial CAD on angiography. The receiver operating characteristic curve analysis showed similar diagnostic abilities of the two diagnostic methods. The best cut-off values for CAD were 2, 1, and 1 for the number of vessels with calcium > 5, 10, and 15 mm, respectively. Overall, the diagnostic ability of manual calcium assessment was similar to that of standard CACS > 400. Conclusions: Manual assessment of coronary calcium length on non-ECG-gated plain CT provided similar diagnostic ability for the presence of significant epicardial CAD on invasive angiography, as compared to standard CACS.

In the international guidelines, higher thrombolysis in myocardial infarction frame count (TFC) is indicated as evidence of coronary microvascular dysfunction (CMD). However, the association of TFC with invasively measured coronary physiologic parameters such as coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) remains unclear. Patients without significant epicardial coronary lesions underwent invasive coronary physiologic assessment using a thermodilution method in the left anterior descending artery. Corrected TFC (cTFC) was evaluated on coronary angiography. The cut-off values of CFR and IMR were defined as ≤2.0 and >25, and patients with abnormal CFR and/or IMR were defined as having CMD. This study aimed to assess whether cTFC >25, a cut-off value in the guidelines, was diagnostic of the presence of CMD. Of the 137 patients, 34 (24.8%) and 32 (23.3%) had cTFC >25 and CMD, respectively. The rate of CMD was not significantly different between patients with and without cTFC >25. cTFC was weakly correlated with at rest and hyperemic mean transit time and IMR, whereas no significant correlation was observed between cTFC and CFR. The receiver operating characteristic curve analysis showed the poor diagnostic ability of cTFC for abnormal CFR and IMR and the presence of CMD. In conclusion, in patients without epicardial coronary lesions, cTFC as a continuous value and with the cut-off value of 25 was not diagnostic of abnormal CFR and IMR and the presence of CMD. Our results did not support the use of cTFC in CMD evaluation.

Background and Objectives: An interventional diagnostic procedure (IDP), including intracoronary acetylcholine (ACh) provocation and coronary physiological testing, is recommended as an invasive diagnostic standard for patients suspected of ischemia with no obstructive coronary arteries (INOCA). Recent guidelines suggest Thrombolysis In Myocardial Infarction frame count (TFC) as an alternative to wire-based coronary physiological indices for diagnosing coronary microvascular dysfunction. We evaluated trajectories of TFC during IDP and the impact of ACh provocation on TFC. Materials and Methods: This was a single-center, retrospective study. Patients who underwent IDP to diagnose INOCA were included and divided into two groups according to the positive or negative ACh provocation test. Wire-based invasive physiological assessment was preceded by ACh provocation tests and intracoronary isosorbide dinitrate (ISDN). We evaluated TFC at three different time points during IDP; pre-ACh, post-ISDN, and post-hyperemia. Results: Of 104 patients, 58 (55.8%) had positive ACh provocation test. In the positive ACh group, resting mean transit time (Tmn) and baseline resistance index were significantly higher than in the negative ACh group. Post-ISDN TFC was significantly correlated with resting Tmn (r = 0.31, p = 0.002). Absolute TFC values were highest at pre-ACh, followed by post-ISDN and post-hyperemia in both groups. All between-time point differences in TFC were statistically significant in both groups, except for the change from pre-ACh to post-ISDN in the positive ACh group. Conclusions: In patients suspected of INOCA, TFC was modestly correlated with Tmn, a surrogate of coronary blood flow. The positive ACh provocation test influenced coronary blood flow assessment during IDP.

OBJECTIVES: We aimed to investigate the regional variations in the number of interventions and surgeries for peripheral artery disease (PAD) and explore the major determinants of the variations. DESIGN: Cross-sectional study. SETTING: The Japanese Ministry of Health, Labour and Welfare National Database and Diagnostic Procedure Combination database in 2018. DATA: The rates of endovascular treatment (EVT), bypass surgery per 100 000 individuals in the population were calculated for all 47 prefectures in Japan. The total annual changes in the rates of EVT and bypass surgery in Japan from 2012 to 2019 were calculated. ANALYSIS: A linear regression model was developed with rates of EVT and bypass surgery as dependent variables and regional medical supply in each prefecture as explanatory variables. These regional factors included the rate of percutaneous coronary intervention (PCI) for angina, the numbers of cardiovascular specialists, specialists in cardiac surgery, interventional radiology (IVR) training facilities and cardiovascular surgery training facilities, per 100 000, respectively. RESULTS: There was a 5.7-fold difference (143 and 25 per 100 000 individuals aged ≥40 years) in the highest and lowest EVT rates. The highest and lowest rates of bypass surgery were 34 and <10 per 100 000 individuals aged ≥40 years in a prefecture, respectively. The rate of PCI contributed most significantly positive to the rate of EVT (p<0.001). However, the numbers of IVR and cardiovascular surgery training facilities had significant positive and negative relationships, respectively, with the rate of EVT. The numbers of specialists in cardiac surgery and cardiovascular specialists had significant positive (p=0.01) and negative (p=0.01) correlations, respectively, with the rate of bypass surgery. CONCLUSIONS: Considerable regional variations in the rates of revascularisation for PAD were found. Unbalanced presence of medical resources, preference of suppliers and the training system had larger effects on the regional variation in Japan.

The effect of prehospital factors on favorable neurological outcomes remains unclear in patients with witnessed out-of-hospital cardiac arrest (OHCA) and a shockable rhythm. We developed a decision tree model for these patients by using prehospital factors. Using a nationwide OHCA registry database between 2005 and 2020, we retrospectively analyzed a cohort of 1,930,273 patients, of whom 86,495 with witnessed OHCA and an initial shockable rhythm were included. The primary endpoint was defined as favorable neurological survival (cerebral performance category score of 1 or 2 at 1 month). A decision tree model was developed from randomly selected 77,845 patients (development cohort) and validated in 8650 patients (validation cohort). In the development cohort, the presence of prehospital return of spontaneous circulation was the best predictor of favorable neurological survival, followed by the absence of adrenaline administration and age. The patients were categorized into 9 groups with probabilities of favorable neurological survival ranging from 5.7 to 70.8% (areas under the receiver operating characteristic curve of 0.851 and 0.844 in the development and validation cohorts, respectively). Our model is potentially helpful in stratifying the probability of favorable neurological survival in patients with witnessed OHCA and an initial shockable rhythm.

BACKGROUND: The efficacy and safety of dual antithrombotic therapy (DAT) with oral anticoagulant and P2Y12 inhibitors (P2Y12i) in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) have not been well investigated. The purpose of this study was first to evaluate clinical outcomes of DAT with P2Y12i compared with triple antithrombotic therapy (TAT), and then to compare DAT with low-dose prasugrel and DAT with clopidogrel, in patients with AF undergoing PCI. METHODS: This study was a multicenter, non-interventional, prospective and retrospective registry. A total of 710 patients with AF undergoing PCI between January 2015 and March 2021 at 15 institutions were analyzed. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE) and major bleeding events (BARC 3 or 5) were compared between patients receiving DAT (n = 239) and TAT (n = 471), and then, compared among prasugrel-DAT (n = 82), clopidogrel-DAT (n = 157), and TAT. RESULTS: The DAT group showed significantly lower incidence of MACE and major bleeding events compared with the TAT group (log-rank p = 0.013 and 0.047). In the multivariable Cox regression analyses, DAT (p = 0.028), acute coronary syndrome (p = 0.025), and anemia (p = 0.015) were independently associated with MACE. In addition, anemia (p = 0.022) was independently associated with, and DAT (p = 0.056) and thrombocytopenia (p = 0.051) tended to be associated with, major bleeding events. When analyzed among the prasugrel-DAT, clopidogrel-DAT, and TAT groups, there were no significant differences in clinical outcomes between the prasugrel-DAT and clopidogrel-DAT groups, and similar trends were observed for both 2 groups in comparison with the TAT group. CONCLUSIONS: In AF patients undergoing PCI, DAT was associated with lower incidence of MACE and major bleeding events compared with TAT. In comparison of P2Y12i, there might be no significant difference in the incidence of MACE and bleeding events between prasugrel-based DAT and clopidogrel-based DAT.

Although coronary artery perforation can be a fatal complication during percutaneous coronary intervention, it is rarely observed in in-stent restenotic lesions. We present a case with coronary artery perforation after balloon dilatation for a recurrent in-stent restenotic lesion with calcified nodule inside the double-layered stents that were previously implanted. (Level of Difficulty: Advanced.).

BACKGROUND: Intracoronary acetylcholine (ACh) provocation test and coronary physiological assessment are useful interventional diagnostic procedures for evaluating ischemia with no obstructive coronary arteries (INOCA). However, the appropriate sequential order of the diagnostic procedures has been a matter of debate. We investigated the impact of preceding ACh provocation on following coronary physiological assessment. METHODS: Patients suspected of INOCA underwent invasive coronary physiological assessment using thermodilution method and were divided into two groups according to the implementation of ACh provocation test. The ACh group was further divided into the positive and negative ACh groups. In the ACh group, intracoronary ACh provocation was performed before the invasive coronary physiological assessment. The main interest of this study was to compare coronary physiological indices among the no ACh, negative ACh, and positive ACh groups. RESULTS: Of 120 patients, the no ACh, and negative and positive ACh groups included 46 (38.3 %), 36 (30.0 %), and 38 (31.7 %), respectively. Fractional flow reserve was lower in the no ACh group than in the ACh group. Resting mean transit time was significantly longer in the positive ACh group, followed by the no ACh and negative ACh groups (1.22 ± 0.55 vs. 1.00 ± 0.46 vs. 0.74 ± 0.36 s, p < 0.001). Index of microcirculatory resistance and coronary flow reserve did not differ significantly among the three groups. CONCLUSIONS: Preceding ACh provocation influenced following physiological assessment, particularly when ACh test was positive. Further studies are warranted to determine which interventional diagnostic procedure, ACh provocation or physiological assessment, should be preceded in the invasive evaluation of INOCA.

Background Chronic systemic inflammatory diseases (CSIDs) such as rheumatoid arthritis (RA) are reportedly associated with an increased risk of ischemic cardiovascular events including acute myocardial infarction (MI). However, data are limited on clinical characteristics and ischemic and bleeding outcomes after acute MI in patients with CSIDs. Methods This bi-center registry included a total of 1001 patients with acute MI undergoing percutaneous coronary intervention. CSIDs included inflammatory rheumatological conditions (RA, systemic lupus erythematosus, vasculitis, etc.) and organ-specific diseases (chronic hepatitis, psoriasis, inflammatory bowel disease, etc.). The primary endpoint was net adverse clinical events (NACE), a composite of ischemic (all-cause death, MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events, during hospitalization and after discharge. Results Of the 1001 patients, 58 (5.8%) had CSIDs. The proportion of women was higher in patients with CSIDs than those without (37.9% vs. 22.1%, p = 0.009). During the hospitalization, no significant differences in the primary endpoint of NACE were observed between patients with and without CSIDs (10.3% vs. 12.7%, p = 0.84). During the median follow-up of 42.6 months after discharge, patients with CSIDs had a higher risk of NACE (22.5% vs. 10.1%, p = 0.01) than those without, mainly driven by an increased risk of ischemic events (18.4% vs. 8.4%, p = 0.03). Conclusions A small but significant proportion of patients with acute MI (5.8%) had CSIDs. While the incidence of in-hospital events was similar, patients with CSIDs had worse outcomes after discharge, suggesting that further clinical investigations and therapeutic approaches are needed in this patient subset.

The Japanese version of high bleeding risk (J-HBR) criteria was domestically proposed to identify patients at HBR after percutaneous coronary intervention (PCI). The applicability of J-HBR on bleeding events has been validated, while whether J-HBR predicts ischemic events is uncertain. This bi-center registry included 904 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were stratified by the J-HBR major (1 point) and minor (0.5 point) criteria. Patients with J-HBR ≥ 1 point were diagnosed as having HBR. The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiovascular death, recurrent MI, and ischemic stroke, after discharge. Of the 904 patients, 451 (49.9%) had the J-HBR. The primary endpoint more frequently occurred in patients with J-HBR than in those without (10.9% vs. 4.9%, p < 0.001) during the median follow-up period of 522 days. Probability of MACE was progressively increased with the increase in the number of J-HBR major and minor criteria, in which severe anemia, severe chronic kidney disease, prior heart failure, peripheral artery disease, and prior ischemic stroke were identified as significant factors associated with MACE. In patients with acute MI undergoing PCI, the J-HBR criteria were predictive for ischemic outcomes after discharge, suggesting that the J-HBR criteria may be useful to identify patients at high bleeding and ischemic risks.

BACKGROUND: Extracellular volume fraction (ECV) on magnetic resonance imaging can predict prognosis after aortic valve replacement in patients with aortic stenosis (AS). However, the usefulness of ECV on computed tomography (CT) for patients who have undergone transcatheter aortic valve replacement (TAVR) is unclear, so we investigated whether ECV analysis on CT is associated with clinical outcomes in TAVR candidates.Methods and Results: We analyzed 127 patients with severe AS who underwent preoperative CT for TAVR. We evaluated the utility of ECV analysis on single-energy CT for predicting patient prognosis after TAVR. The primary outcome was a composite of all-cause death and hospitalization due to heart failure (HF) after TAVR. 15 patients (12%) had composite outcomes: 4 deaths and 11 hospitalizations due to HF. In multivariate survival analysis using the Cox proportional hazard model, atrial fibrillation (AF) (hazard ratio (HR), 7.86; 95% confidence interval (CI), 2.57-24.03; P<0.001), history of congestive HF (HR, 4.91; 95% CI, 1.49-16.2; P=0.009) and ECV ≥32.6% on CT (HR, 6.96; 95% CI, 1.92-25.12; P=0.003) were independent predictors of composite outcomes. On Kaplan-Meier analysis, the higher ECV group (≥32.6%) had a significantly greater number of composite outcomes than the lower ECV group (P<0.001). CONCLUSIONS: ECV on CT is an independent predictor of prognosis after TAVR.

Fractional flow reserve derived from coronary CT (FFR-CT) is a noninvasive physiological technique that has shown a good correlation with invasive FFR. However, the use of FFR-CT is restricted by strict application standards, and the diagnostic accuracy of FFR-CT analysis may potentially be decreased by severely calcified coronary arteries because of blooming and beam hardening artifacts. The aim of this study was to evaluate the utility of deep learning (DL)-based coronary computed tomography (CT) data analysis in predicting invasive fractional flow reserve (FFR), especially in cases with severely calcified coronary arteries. We analyzed 184 consecutive cases (241 coronary arteries) which underwent coronary CT and invasive coronary angiography, including invasive FFR, within a three-month period. Mean coronary artery calcium scores were 963 ± 1226. We evaluated and compared the vessel-based diagnostic accuracy of our proposed DL model and a visual assessment to evaluate functionally significant coronary artery stenosis (invasive FFR < 0.80). A deep neural network was trained with consecutive short axial images of coronary arteries on coronary CT. Ninety-one coronary arteries of 89 cases (48%) had FFR-positive functionally significant stenosis. On receiver operating characteristics (ROC) analysis to predict FFR-positive stenosis using the trained DL model, average area under the curve (AUC) of the ROC curve was 0.756, which was superior to the AUC of visual assessment of significant (≥ 70%) coronary artery stenosis on CT (0.574, P = 0.011). The sensitivity, specificity, positive and negative predictive value (PPV and NPV), and accuracy of the DL model and visual assessment for detecting FFR-positive stenosis were 82 and 36%, 68 and 78%, 59 and 48%, 87 and 69%, and 73 and 63%, respectively. Sensitivity and NPV for the prediction of FFR-positive stenosis were significantly higher with our DL model than visual assessment (P = 0.0004, and P = 0.024). DL-based coronary CT data analysis has a higher diagnostic accuracy for functionally significant coronary artery stenosis than visual assessment.

BACKGROUND: Although guidelines recommend intracoronary administration of acetylcholine (ACh) with incremental doses of 20, 50, and 100 μg into the left coronary artery (LCA) during spasm provocation test for diagnosing vasospastic angina, 50 μg of ACh rarely induced significant coronary vasospasm when no vasoconstriction was observed with 20 μg of ACh in a previous report. The aim of this study was to evaluate the safety and feasibility of omitting 50 μg according to the vasoreactivity by 20 μg of ACh in the LCA. METHODS: A total of 556 patients undergoing ACh provocation test with 20 μg followed by 50 and/or 100 μg were retrospectively included. Injection of 50 μg of ACh was primarily omitted when vasoconstriction <25 % was observed with 20 μg, which was left to operator's discretion. Adverse events were defined as a composite of ventricular fibrillation, sustained ventricular tachycardia, and cardiogenic shock during ACh test in the LCA. RESULTS: Positive ACh test in the LCA was observed in 245 (44.1 %) patients. Overall, patients with LCA constriction <25 % by 20 μg of ACh had a lower rate of positive ACh test than their counterpart (24.0 % vs. 88.4 %, p < 0.001). In patients with LCA constriction ≥25 % by 20 μg, the incidence of adverse events was significantly higher than in those with LCA constriction <25 % during the provocation test at doses of 50 and 100 μg (2.3 % vs. 0 %, p = 0.009). CONCLUSIONS: Omitting 50 μg of ACh in the LCA may be safe and feasible when little vasoconstriction was observed with preceding injection of 20 μg of ACh during spasm provocation test for diagnosing vasospastic angina. However, we believe that 50 μg of ACh should not be omitted when 20 μg of ACh induced LCA constriction ≥25 %.

BACKGROUND: We investigated the influence of concomitant mitral regurgitation (MR) in patients undergoing transcatheter aortic valve implantation on the 1-year outcome using Japan Transcatheter Valve Therapy (J-TVT) registry data. METHODS: The patients who underwent the transcatheter aortic valve implantation for aortic stenosis performed from August 2013 to December 2019 in Japan were included. History of previous valve surgery and dialysis patients were excluded. A total of 24,979 patients were included, and 1-year follow-up data were obtained from the registry (follow-up rate 98.5 %). Propensity-score matching, using multivariable logistic regression and 1:1 matching without replacement, was performed between the patients with grade 3-4 MR (MR 3-4 group) and those with grade 0-2 MR (MR 0-2 group). All-cause death and the composite outcome of death and/or heart failure events were compared. RESULTS: After propensity score matching, 3920 cases (1960 cases each in MR 0-2 group and MR 3-4 group) were extracted. The procedure success rate was 96.4 % in MR 0-2 and 96.0 % in MR 3-4 group (p = 0.56) and the surgical conversion rate was 0.7 % in MR 0-2 group and 0.8 % in MR 3-4 group (p = 0.58). Cox regression model showed no statistical difference in 1-year survival rate between MR 0-2 group (89.4 %) and MR 3-4 group (89.6 %) (p = 0.80). However, freedom from 1-year death and/or heart failure event was lower in MR 3-4 (86.3 %) than in MR 0-2 group (88.9 %) (p = 0.01). This trend was also found in the subgroup of New York Heart Association (NYHA) class 1-2 but not in the subgroup of NYHA class 3-4. CONCLUSIONS: One-year survival rate was not different between groups but freedom from death and/or heart failure events was lower in patients with preoperative MR grade 3-4 than in patients with preoperative MR grade 0-2 after transcatheter aortic valve replacement.

The role of the incomplete form of Kawasaki disease in future cardiovascular risk is unknown. The present case demonstrates that even a healthy young man with only a history of incomplete Kawasaki disease can develop endothelial dysfunction and suffer myocardial infarction. We did not obtain ethical/institutional review board approval for our submission because this is not a clinical study, but the patient gave written informed consent to publish the case. (Level of Difficulty: Advanced.).

It is well known that patients with acute myocardial infarction (AMI) have delayed vessel healing despite accelerated endothelial progenitor cells (EPC) mobilization. The COMBO stent is a unique biodegradable-polymer sirolimus-eluting stent with an anti-CD34 antibody coating which captures EPC and potentially promotes vessel healing. However, there are limited data about strut tissue coverage at the very short-term period after COMBO stent implantation. This was a prospective study to investigate strut tissue coverage within 1 month after COMBO stent implantation using optical coherence tomography (OCT). Struts fully covered with tissue were defined as covered, and struts with distance from lumen surface longer than strut plus polymer thickness were defined as malapposed. Mean tissue thickness was measured only in apposed struts. A total of 8173 struts of 33 lesions in 32 patients were analyzed at an average of 19.8 ± 4.6 days after COMBO stent implantation. In lesion-level analysis, the rate of covered struts was 89.6 ± 7.2%, the rate of malapposed struts was 0.9 ± 2.0% and mean tissue thickness was 46.8 ± 14.3 µm. In comparison between AMI (n = 12) and non-AMI (n = 21) patients, there were no significant differences in the rate of covered struts (88.4 ± 8.4% vs. 90.2 ± 6.6%, p = 0.48) and mean tissue thickness (46.8 ± 13.7 µm vs. 46.9 ± 15.0 µm, p = 0.98). Multivariable analysis demonstrated that time from implantation to OCT imaging was significantly associated with mean tissue thickness. The COMBO stent had substantial tissue coverage at the very short-term period after implantation even in AMI patients, and follow-up time had an impact on vessel healing.

A 74-year-old woman with a history of interstitial pneumonia, who had been taking oral corticosteroids for the past 9 years, was diagnosed with severe aortic stenosis. The patient underwent transfemoral transcatheter aortic valve replacement (TAVR) with a balloon-expandable valve under local anesthesia. After deploying a 26-mm SAPIEN 3 valve with 1.5 ml less balloon inflation, transesophageal echocardiography revealed a hemorrhage in the aortic annulus. Intraoperative angiography revealed a small contrast leakage around the ascending aorta. Emergent surgical aortic valve replacement was performed successfully, with a tear at the non-left commissure closed using interrupted sutures. The patient was discharged on postoperative day 14 with no paravalvular leakage. Chronic corticosteroid use may be a risk factor for annular ruptures during TAVR. Careful balloon dilation may be necessary, especially when balloon-expandable valves are used in patients receiving long-term corticosteroids.

OBJECTIVES: This study aimed to explore the impact of myocardial bridging (MB) on early development of cardiac allograft vasculopathy and long-term graft survival after heart transplantation. BACKGROUND: MB has been reported to be associated with acceleration of proximal plaque development and endothelial dysfunction in native coronary atherosclerosis. However, its clinical significance in heart transplantation remains unclear. METHODS: In 103 heart-transplant recipients, serial (baseline and 1-year post-transplant) volumetric intravascular ultrasound (IVUS) analyses were performed in the first 50 mm of the left anterior descending (LAD) artery. Standard IVUS indices were evaluated in 3 equally divided LAD segments (proximal, middle, and distal segments). MB was defined by IVUS as an echolucent muscular band lying on top of the artery. The primary endpoint was death or re-transplantation, assessed for up to 12.2 years (median follow-up: 4.7 years). RESULTS: IVUS identified MB in 62% of the study population. At baseline, MB patients had smaller intimal volume in the distal LAD than non-MB patients (p = 0.002). During the first year, vessel volume decreased diffusely irrespective of the presence of MB. Intimal growth diffusely distributed in non-MB patients, whereas MB patients demonstrated significantly augmented intimal formation in the proximal LAD. Kaplan-Meier analysis revealed significantly lower event-free survival in patients with versus without MB (log-rank p = 0.02). In multivariate analysis, the presence of MB was independently associated with late adverse events [hazard ratio 5.1 (1.6-22.2)]. CONCLUSION: MB appears to relate to accelerated proximal intimal growth and reduced long-term survival in heart-transplant recipients.

AIM OF THE STUDY: Defibrillation plays a crucial role in early return of spontaneous circulation (ROSC) and survival of patients with out-of-hospital cardiac arrest (OHCA) and shockable rhythm. Prehospital adrenaline administration increases the probability of prehospital ROSC. However, little is known about the relationship between number of prehospital defibrillation attempts and neurologically favourable survival in patients treated with and without adrenaline. METHODS: Using a nationwide Japanese OHCA registry database from 2006 to 2020, 1,802,084 patients with OHCA were retrospectively analysed, among whom 81,056 with witnessed OHCA and initial shockable rhythm were included. The relationship between the number of defibrillation attempts before hospital admission and neurologically favourable survival rate (cerebral performance category score of 1 or 2) at 1 month was evaluated with subgroup analysis for patients treated with and without adrenaline. RESULTS: At 1 month, 18,080 (22.3%) patients had a cerebral performance category score of 1 or 2. In the study population, the probability of prehospital ROSC and favourable neurological survival rate were inversely associated with number of defibrillation attempts. Similar trends were observed in patients treated without adrenaline, whereas a greater number of defibrillation attempts was counterintuitively associated with favourable neurological survival rate in patients treated with prehospital adrenaline. CONCLUSIONS: Overall, a greater number of prehospital defibrillation attempts was associated with lower neurologically favourable survival at 1 month in patients with OHCA and shockable rhythm. However, an increasing number of shocks (up to the 4th shock) was associated with better neurological outcomes when considering only patients treated with adrenaline.

Coronary microvascular dysfunction (CMD) is described as an important subset of ischemia with no obstructive coronary artery disease. Resistive reserve ratio (RRR) and microvascular resistance reserve (MRR) have been proposed as novel physiological indices evaluating coronary microvascular dilation function. The aim of this study was to explore factors associated with impaired RRR and MRR. Coronary physiological indices were invasively evaluated in the left anterior descending coronary artery using the thermodilution method in patients suspected of CMD. CMD was defined as a coronary flow reserve <2.0 and/or index of microcirculatory resistance ≥25. Of 117 patients, 26 (24.1%) had CMD. RRR (3.1 ± 1.9 vs. 6.2 ± 3.2, p < 0.001) and MRR (3.4 ± 1.9 vs. 6.9 ± 3.5, p < 0.001) were lower in the CMD group. In the receiver operating characteristic curve analysis, RRR (area under the curve 0.84, p < 0.001) and MRR (area under the curve 0.85, p < 0.001) were both predictive of the presence of CMD. In the multivariable analysis, previous myocardial infarction, lower hemoglobin, higher brain natriuretic peptide levels, and intracoronary nicorandil were identified as factors associated with lower RRR and MRR. In conclusion, the presence of previous myocardial infarction, anemia, and heart failure was associated with impaired coronary microvascular dilation function. RRR and MRR may be useful to identify patients with CMD.

The GRACE risk score is established to predict thrombotic events in patients with acute coronary syndrome (ACS). Although thrombotic events including myocardial infarction after ACS are mainly attributable to vulnerable plaque formation, whether the GRACE score correlates with coronary lipid-rich plaque is unclear. A total of 54 patients with ACS undergoing primary percutaneous coronary intervention under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance were included in a prospective manner. Patients were divided into two groups according to the median of the GRACE risk score. Coronary lipid plaques in the target vessel were assessed by NIRS-IVUS with lipid core burden index (LCBI) and a maximum LCBI in 4 mm (maxLCBI4mm). The receiver operating characteristics (ROC) curve analysis was performed based on the major adverse cardiovascular events as an exploratory analysis. The GRACE risk score was significantly and positively correlated with LCBI (r = 0.31, p = 0.03) and maxLCBI4mm (r = 0.38, p = 0.006). LCBI (111.7 ± 85.7 vs. 169.0 ± 83.5, p = 0.02) and maxLCBI4mm (428.5 ± 227.1 vs. 600.6 ± 227.7, p = 0.009) in the target vessel were significantly higher in the high GRACE risk score group than their counterpart. In the ROC curve analysis, LCBI and maxLCBI4mm were predictive for clinical events. In conclusion, the higher GRACE risk score may serve as a discriminator of risk comprising more lipid-rich plaques as an underlying mechanism of an increased risk of thrombotic events after ACS. In patients with ACS, the higher GRACE risk score was significantly and modestly associated with greater coronary lipid plaques in the target vessel.

[This corrects the article DOI: 10.1371/journal.pone.0272140.].

Objective The Patterns of Non-adherence to Anti-platelet Regimen in Stented Patients (PARIS) and Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) thrombotic and bleeding risk scores were established to predict ischemic and bleeding events in patients undergoing percutaneous coronary intervention (PCI). However, whether or not the combination of these risk scores is predictive of clinical outcomes is unclear. Methods This bicenter registry included a total of 1,098 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were divided into three groups according to the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores. The study endpoints included the rates of both ischemic (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events at two years. Results Two years after primary PCI, ischemic and major bleeding events occurred in 17.3% and 10.2% of patients, respectively. The higher-risk categories of PARIS and CREDO-Kyoto scores were associated with increased risks of ischemic and bleeding events. The rates of ischemic and major bleeding events progressively increased with the increase in risk categories in the two risk scoring systems. In the receiver operating characteristic curve analysis, the addition of CREDO-Kyoto thrombotic and bleeding risk scores to PARIS scores significantly improved diagnostic ability in predicting ischemic (area under the curve: 0.59 vs. 0.63, p=0.01) and bleeding (area under the curve: 0.65 vs. 0.68, p=0.01) events. Conclusion The combinations of the PARIS and CREDO-Kyoto risk scores might be useful for evaluating ischemic and bleeding risks in patients with acute MI undergoing primary PCI.

AIMS: Several scoring systems, including the ABCD-GENE and HHD-GENE scores incorporating clinical and genetic factors, have been developed to identify patients likely to have high platelet reactivity on P2Y12 inhibitors, leading to increased risks of ischemic events. However, genetic testing is not widely available in daily practice. We aimed to evaluate the differential impact of clinical factors in the scores on ischemic outcomes in patients treated with clopidogrel and prasugrel. METHODS: This bi-center registry included 789 patients with acute myocardial infarction (MI) undergoing percutaneous coronary intervention and treated with either clopidogrel or prasugrel at discharge. The relations of the number of clinical factors included in the ABCD-GENE (age ≥ 75 years, body mass index ＞30 kg/m2, chronic kidney disease, and diabetes) and HHD-GENE (hypertension, hemodialysis, and diabetes) scores to the primary endpoint of major cardiovascular events after discharge, a composite of death, recurrent MI, and ischemic stroke, were evaluated. RESULTS: The number of clinical factors in the ABCD-GENE score was not predictive of ischemic outcomes after discharge in patients treated with clopidogrel and/or prasugrel, while the increase in the number of clinical factors of the HHD-GENE score was associated with an increased risk of the primary endpoint in a stepwise manner in patients on a P2Y12 inhibitor. CONCLUSIONS: Clinical factors listed in the HHD-GENE score may help stratify ischemic risks in patients with acute MI treated with clopidogrel and prasugrel, whereas risk stratification without genetic testing in patients treated with clopidogrel may be challenging.

BACKGROUND: Limited data are available for clinical outcomes in patients who underwent urgent or emergency transcatheter aortic valve implantation (TAVI). This study investigated in-hospital and 1-year outcomes and explored prognostic covariates in urgent/emergency TAVI using nationwide registry data.Methods and Results: Among 26,775 patients who underwent TAVI between August 2013 and December 2019, 25,495 with 1-year follow-up information were analyzed in this study. Baseline and procedural characteristics, as well as clinical adverse events, were compared between the urgent/emergency and elective TAVI groups. The primary outcome was all-cause mortality within 1 year after TAVI. Multivariable Cox regression models were constructed to identify independent predictors after urgent or emergency TAVI. Urgent or emergency TAVI was performed in 578 (2.3%) patients. The Society of Thoracic Surgeons score was significantly higher in the urgent/emergency than elective TAVI group (13.3% vs. 6.0%; P<0.001). Device success rate was comparable between the 2 groups. All-cause death-free survival within 1 year was lower in the urgent/emergency than elective TAVI group (77.2% vs. 92.2%; log rank P<0.001). Malignancy, albumin and creatinine concentrations, ejection fraction, and mean pressure gradient were associated with 1-year mortality in the urgent/emergency TAVI group. CONCLUSIONS: Despite higher surgical risk and more comorbidities, the procedure was successfully performed in patients undergoing urgent/emergency TAVI, although it should be noted that prognosis was worse than for elective TAVI.

Coronary flow reserve (CFR) represents entire coronary compensatory capacity. While CFR assessment is recommended to identify patients at an increased risk of cardiovascular events and coronary microvascular dysfunction, invasive CFR measurement is often technically challenging. Although not well validated yet, pressure-bounded CFR (pbCFR) has been proposed as a simple surrogate to estimate impaired CFR. In this study, we evaluated coronary physiological characteristics of low pbCFR using detailed invasive assessment. Invasive physiological assessment including resting ratio of distal coronary pressure to aortic pressure (Pd/Pa), fractional flow reserve (FFR), resting and hyperemic mean transit time, index of microcirculatory resistance (IMR), CFR, resistive reserve ratio, and microvascular resistance reserve (MRR) was performed in 107 patients in the left anterior descending coronary artery. pbCFR was calculated only with resting Pd/Pa and FFR. Patients were divided into low pbCFR and non-low pbCFR groups. Of 107 patients, 50 (46.7%) had low pbCFR. FFR (0.90 ± 0.05 vs. 0.83 ± 0.05, p < 0.001), hyperemic mean transit time (0.27 ± 0.17 vs. 0.21 ± 0.12, p = 0.04), and IMR (20.4 ± 13.2 vs. 15.0 ± 9.1, p = 0.01) were significantly higher in the low pbCFR group than their counterpart. While directly measured CFR did not differ significantly (4.4 ± 2.3 vs. 5.1 ± 2.8, p = 0.18), MRR was lower in the low pbCFR group (5.4 ± 3.0 vs. 6.8 ± 3.8, p = 0.047). The rates of CFR < 2.0 and IMR ≥ 25 were not significantly different between the 2 groups. In conclusion, although CFR did not differ significantly, IMR and MRR were impaired in patients with low pbCFR, suggesting pbCFR as a potential surrogate of coronary microvascular function in clinical practice.

BACKGROUND: In patients with acute myocardial infarction (AMI), elevated natriuretic peptide (NP) concentrations are reportedly associated with worse clinical outcomes. This study evaluated the prognostic value of NP concentrations and in-hospital heart failure (HF) events after AMI.Methods and Results: The present bicenter registry included 600 patients with AMI undergoing percutaneous coronary intervention. HF was evaluated at 3 different time points after AMI: on admission, during hospitalization, and at the short-term follow-up at 1 month. When HF was present at each time point, 1 point was assigned to the "HF time points" (HFTP) risk scoring system; possible total scores on this system ranged from 0 to 3. The primary endpoint was a composite of all-cause death and HF rehospitalization after discharge. Among the 600 patients who survived to discharge, the primary outcome occurred in 69 (11.5%) during a mean follow-up period of 488 days. HF on admission, during hospitalization, and at the short-term follow-up were all significantly associated with subsequent clinical outcomes. Higher scores on the HFTP scoring system were related to an increased risk of the primary endpoint. Multivariable analysis indicated scores of 2 and 3 were independently associated with outcome events in a stepwise manner. CONCLUSIONS: Among patients with AMI, HF evaluation at different time points was useful in stratifying risks of mortality and HF rehospitalization after discharge.

Among patients with acute myocardial infarction (MI) complicated by cardiogenic shock (CS), in-hospital mortality remains high. In the present study, we aimed to identify factors associated with clinical outcomes of acute MI patients with CS in a contemporary setting. A total of 1102 patients with acute MI undergoing primary percutaneous coronary intervention were included, among whom 196 (17.8%) were complicated by CS. The primary outcome was all-cause death during hospitalization, and factors associated with in-hospital mortality were explored in patients with acute MI and CS. Of the 196 patients with acute MI complicated by CS, 77 (39.3%) died during hospitalization. The rates of non-ST-segment elevation MI (NSTEMI) (33.8% vs. 19.3%, p = 0.02) and culprit lesion in the left main or left anterior descending coronary artery (68.8% vs. 47.9%, p = 0.004) were higher, while left ventricular ejection fraction (LVEF) was lower (24.4 ± 11.7% vs. 39.7 ± 13.8%, p &lt; 0.001) in non-survivors than in survivors. Multivariable analysis identified NSTEMI presentation and lower LVEF as independent predictors of in-hospital death. In conclusion, NSTEMI and low LVEF were identified as factors associated with higher in-hospital mortality. The identification of even higher-risk subsets and targeted therapeutic strategies may be warranted to improve survival of patients with acute MI and CS.

Background and Objectives: Although previous studies showed that an activity of xanthine oxidoreductase (XOR), a rate-limiting enzyme in purine metabolism, beyond the serum uric acid level, was associated with the development of coronary artery disease (CAD), the underlying mechanisms are unclear. Because endothelial dysfunction and a greater blood pressure (BP) variability may play a role, we investigated the relations among the endothelial function, XOR, and BP variability. Materials and Methods: This was a post-hoc study using pooled data of patients with a stable CAD from two prospective investigations, in which the systemic endothelial function was assessed with the reactive hyperemia index (RHI) and the XOR activity was measured. The BP variability was evaluated using BP measurements during the three- and four-day hospitalization. Results: A total of 106 patients with a stable CAD undergoing a percutaneous coronary intervention were included. Of the 106 patients, 46 (43.4%) had a systemic endothelial dysfunction (RHI &lt; 1.67). The multivariable analysis identified a higher body mass index (BMI), female gender, and diabetes as factors associated with an endothelial dysfunction. A higher BMI was also related to an elevated XOR activity, in addition to current smoking. No significant correlation was observed between the RHI and XOR activity. Similarly, the in-hospital BP variability was associated with neither the endothelial function nor XOR. Conclusions: Among patients with a stable CAD, several factors were identified as being associated with a systemic endothelial dysfunction or an elevated XOR activity. However, no direct relations between the endothelial function, XOR, and BP variability were found.

BACKGROUND: This study aims to clarify whether myocardial bridge (MB) could influence atherosclerotic plaque characteristics assessed using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) imaging. METHODS: One hundred and sixteen patients who underwent percutaneous coronary intervention (PCI) using NIRS-IVUS imaging were included. MB was defined as an echo-lucent band surrounding left anterior descending artery (LAD). In MB patients, LAD was divided into three segments: proximal, MB, and distal segments. In non-MB patients, corresponding three segments were defined based on the average length of the above segments. Segmental maximum plaque burden and lipid content derived from NIRS-IVUS imaging in the section of maximum plaque burden were evaluated in each segment. Lipid content of atherosclerotic plaque was evaluated as lipid core burden index (LCBI) and maxLCBI4mm. LCBI is the fraction of pixels indicating lipid within a region multiplied by 1000, and the maximum LCBI in any 4-mm region was defined as maxLCBI4mm. RESULTS: MB was identified in 42 patients. MB was not associated with maximum plaque burden in proximal segment. LCBI and maxLCBI4mm were significantly lower in patients with MB than those without in proximal segment. Multivariable analysis demonstrated both MB and maximum plaque burden in proximal segment to be independent predictors of LCBI in proximal segment. CONCLUSIONS: Lipid content of atherosclerotic plaque assessed by NIRS-IVUS imaging was significantly smaller in patients with MB than those without. MB could be considered as a predictor of lipid content of atherosclerotic plaque when assessed by NIRS-IVUS imaging.

BACKGROUND: Recently, the impact of the lack of standard modifiable risk factors, including hypertension, diabetes, dyslipidaemia, and current smoking, has been investigated in ST-segment elevation myocardial infarction (MI). The present study aimed to evaluate clinical characteristics and prognosis of the patients with no standard risk factors in acute MI. METHODS: This bi-centre registry included 1,093 patients with acute MI undergoing percutaneous coronary intervention. The participants were divided into two groups: patients having at least one of the four standard risk factors and those having none of the risk factors. The study endpoints included major adverse cardiovascular events (MACE) (death, recurrent MI, and stroke) and major bleeding events during hospitalisation. Any MACE and major bleeding events after discharge were also evaluated as an exploratory analysis. RESULTS: Of 1,093 patients, 64 (5.9%) had none of the four standard risk factors. The patients with no standard risk factors were likely to present with Killip class IV and cardiac arrest. The rate of in-hospital MACE was higher in patients with no risk factors than in their counterparts (25.0% vs 9.9%; p<0.001), whereas the incidence of in-hospital major bleeding was not significantly different between the two groups (9.4% vs 6.7%; p=0.44). Active cancer and autoimmune/inflammatory diseases were often found in patients with no standard risk factors. After discharge, no significant differences were observed in the risks of MACE and major bleeding events between the two groups. CONCLUSIONS: No standard modifiable risk factors were not uncommon and were associated with poor short-term outcomes in patients with acute MI.

BACKGROUND: Dialysis patients have strong intracoronary calcification, accelerated by secondary hyperparathyroidism as well as atherosclerosis. We evaluated the association of intact parathyroid hormone (iPTH) level with intracoronary calcification evaluated by intravascular ultrasound (IVUS), and its impact on both stent expansion after percutaneous coronary intervention (PCI) and long-term clinical outcomes, in dialysis patients with coronary artery disease (CAD).Methods and Results: A total of 116 patients on dialysis, who underwent PCI with IVUS guidance between March 2012 and December 2020, were enrolled. Patients were divided into 2 groups based on their median iPTH level. The degree of intracoronary calcification was evaluated by calcification score using grayscale IVUS in the target lesions. Preprocedural calcification scores were significantly higher in the high iPTH group compared with the low iPTH group (2.9±1.1 vs. 2.1±0.7, P<0.001). After PCI, the high iPTH group had a significantly lower stent expansion index (0.6±0.2 vs. 0.7±0.1, P<0.001) and stent symmetry index (0.5±0.1 vs. 0.7±0.1, P<0.001) compared with the low iPTH group. The incidence of major adverse cardiac or cerebrovascular events within 3 years was significantly higher in the high iPTH group (log-rank P<0.05). CONCLUSIONS: High iPTH level is likely to increase intracoronary calcification, and cause inadequate stent expansion, which may be associated with increased risk of future adverse events in dialysis patients with CAD requiring PCI.

We treated a female patient known to have a double-chambered right ventricle (DCRV) who presented with symptoms of an acute myocardial infarction (AMI). Emergent coronary artery catheterization revealed acute right coronary artery (RCA) occlusion and proximal left anterior descending (LAD) stenosis. We performed percutaneous coronary intervention (PCI) for the RCA occlusion. Right heart catheterization revealed a pressure gradient across the mid-RV of 58 mmHg. Computed tomography and magnetic resonance imaging revealed no other congenital cardiac abnormalities. She underwent surgical repair of the RV stenosis and coronary artery bypass surgery for LAD stenosis.

BACKGROUND: Coronary flow reserve (CFR) represents entire coronary compensatory capacity, while fractional flow reserve (FFR) is a standard to evaluate functional severity of epicardial coronary artery disease (CAD). ΔFFR, a decrease in a ratio of mean distal coronary pressure to aortic pressure (Pd/Pa) at rest to FFR, is conceptually associated with coronary microvascular function. This study aimed to evaluate the relation of ΔFFR to CFR in patients with stable CAD. METHODS: We performed resting Pd/Pa and FFR measurements in a total of 309 vessels with intermediate coronary artery stenosis in 242 patients. ΔFFR was defined as (resting Pd/Pa - FFR), and pressure bounded-CFR was calculated to estimate low CFR. Vessels were divided as the low CFR and non-low CFR groups. RESULTS: Of 309 vessels, low CFR was observed in 101 (32.7 %). While FFR values were similar (0.78 ± 0.11 vs. 0.78 ± 0.09, p = 0.84), resting Pd/Pa (0.85 ± 0.08 vs. 0.93 ± 0.04, p < 0.001) and ΔFFR (0.07 ± 0.06 vs. 0.15 ± 0.06, p < 0.001) were significantly lower in the low CFR group than in the non-low CFR group. The receiver operating characteristic curve analysis indicated that ΔFFR was predictive for low CFR (area under the curve 0.84, best cut-off value 0.08, p < 0.001). Multivariable analysis identified lower ΔFFR, the left anterior descending coronary artery, and lower hemoglobin and higher brain natriuretic peptide levels as factors associated with low CFR. CONCLUSIONS: In patients with stable CAD, lower ΔFFR was significantly associated with low CFR in intermediate coronary stenosis in patients with stable CAD. ΔFFR may be a simple, practical, and useful surrogate to identify patients with impaired CFR.

This study aims to clarify the impact of myocardial bridge (MB) on the presence and progression of atherosclerosis in left descending coronary artery (LAD) in patients with acute coronary syndrome (ACS). Ninety-eight patients who underwent percutaneous coronary intervention with the diagnosis of ACS and follow-up coronary angiography but had no significant stenosis in the LAD were included. MB was defined based on coronary angiography. Quantitative coronary angiography was performed to determine the segments where MB was present and proximal to the MB (proximal segment) in patients with MB. In patients without MB, a corresponding region was quantitatively analyzed. The primary endpoint was changes in minimum lumen diameter (MLD) and percentage of diameter stenosis (%DS) in the proximal segment from baseline to follow-up angiography, namely ΔMLD and Δ%DS. MB was identified in 29 (29.6%) patients. Patients with MB had larger MLD and smaller %DS in the proximal segment than their counterpart. During the mean follow-up period of 12.9 ± 5.7 months, MLD and %DS in the proximal segment did not change significantly from baseline to follow-up in patients with and without MB. No significant between-group differences were observed in ΔMLD and Δ%DS. Baseline MLD was identified as the only factor associated with ΔMLD in the proximal segment. ACS patients who had MB but no significant stenosis in the LAD had larger MLD and smaller %DS at the segment proximal to MB compared to those without. In this selected population, serial lumen changes assessed by ΔMLD were not associated with the presence of MB in the LAD.

BACKGROUND: Resting full-cycle ratio (RFR), a non-hyperemic pressure ratio, is alternative to fractional flow reserve (FFR) for the evaluation of coronary artery stenoses. Although FFR and RFR results are often discordant using the cut-off values (0.80 and 0.89), factors associated with the discordance are unclear. The aim of this study was to explore factors related to the discordant results. METHODS: We performed FFR and RFR measurements in a total of 408 vessels with intermediate coronary artery stenosis in 277 patients. Positive FFR and RFR were defined based on the cut-off values of 0.80 and 0.89. The discordance was determined as positive FFR and negative RFR (FFR ≤0.80 and RFR >0.89) or negative FFR and positive RFR (FFR >0.80 and RFR ≤0.89). RESULTS: Overall, FFR and RFR were significantly correlated (r = 0.76, p < 0.001), while positive FFR and negative RFR and negative FFR and positive RFR were observed in 44 (10.8%) and 45 (11.0%) of 408 vessels, respectively. Smaller body surface area, diabetes, chronic kidney disease including hemodialysis, severe aortic stenosis, higher E/e', and lower left ventricular ejection fraction on echocardiography, and lower hemoglobin and higher brain natriuretic peptide levels were identified as factors associated with the negative FFR and positive RFR discordance. CONCLUSIONS: Discordant results between FFR and RFR were often found in more than 20% of vessels with intermediate coronary stenosis. Clinical characteristics such as renal function, heart failure, and anemia may be considered in clinical decision-making when using FFR and RFR.

Purpose High-quality images can be obtained with 320-slice computed tomography (CT) with model-based iterative reconstruction (MBIR). We therefore investigated the diagnostic accuracy of 320-slice CT with MBIR for detecting significant coronary artery stenosis. Methods This was a retrospective study of 160 patients who underwent coronary CT and invasive coronary angiography (ICA). The first 100 consecutive patients (Group 1) underwent 320-slice CT without MBIR or small-focus scanning. The next 60 consecutive patients (Group 2) underwent 320-slice CT with both MBIR and small-focus scanning. Patients who underwent coronary artery bypass surgery were excluded. The diagnostic performance of 320-slice CT without MBIR or small-focus scanning and 320-slice CT with both of them, with ICA regarded as a reference standard, was compared to detect significant coronary artery stenosis (≥70% on CT, ≥75% on ICA). Results In a patient-based analysis, the sensitivity, specificity, and overall accuracy of detection of significant stenosis on CT against ICA were 95%, 85%, and 91% in Group 1, and 93%, 83%, and 90% in Group 2, respectively. No significant differences were observed between the two groups in the patient- and segment-based analyses. However, among cases with a severe coronary artery calcium score >400 (31 cases in Group 1 and 28 in Group 2), the specificity and overall accuracy were significantly higher (all p<0.01) in Group 2 than in Group 1 according to the segment-based analysis. Conclusion The diagnostic accuracy of the detection of coronary artery stenosis on CT was improved using 320-slice CT with MBIR.

BACKGROUND: In acute myocardial infarction (MI), the prognosis has been improved, and the length of hospital stay has been shortened. In the present study, we aimed to evaluate the potential of identifying low-risk patients for early discharge after acute MI using the GRACE and CADILLAC risk scores. METHODS: This bi-center registry included 797 patients with acute MI undergoing primary percutaneous coronary intervention. Patients were divided into 3 groups according to the tertiles and pre-defined thresholds of the GRACE and CADILLAC scores. The primary endpoint was a composite of in-hospital major adverse events (all-cause death, sustained ventricular arrhythmia, recurrent MI, heart failure requiring intravenous treatment, stroke, and major bleeding events). RESULTS: Of 797 patients, 271 (34.0%) and 316 (39.7%) had low GRACE and CADILLAC risk scores. During the hospitalization, 251 (31.5%) patients had major adverse events. Higher GRACE and CADILLAC scores were associated with longer length of stay and higher in-hospital adverse event rates. In patients with low GRACE and/or CADILLAC risk scores, 16 (5.9%) and 16 (5.1%) had in-hospital adverse events, most of which occurred within 3 days. Only 1 (0.4% and 0.3%) patient had major adverse events on day 4 or later in the low GRACE and CADILLAC risk score groups. CONCLUSION: In patients with acute MI with low GRACE and/or CADILLAC risk scores who were free from acute events within 3 days, early discharge after primary percutaneous coronary intervention may be feasible and safe.

BACKGROUND: Although glucose variability (GV) is reportedly associated with coronary plaque vulnerability, namely lipid-rich plaque, details are not fully understood. The aim of this study was to evaluate relations of GV after discharge to vulnerable plaque formation assessed by near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) in patients with and without diabetes. METHODS: A total of 40 patients undergoing percutaneous coronary intervention under NIRS-IVUS guidance were included, among whom 13 (33%) had diabetes and 20 (50%) presented with acute myocardial infarction (MI). GV was evaluated by a flush glucose monitoring system, primarily with mean amplitude of glycemic excursion (MAGE). Lipid-rich plaque was assessed by maximum lipid core burden index in 4 mm (maxLCBI4mm) in the target lesion using NIRS-IVUS. RESULTS: Mean MAGE and maxLCBI4mm were 69.7 ± 25.6 mg/dl and 508.0 ± 294.9. Intra-day GV was not significantly associated with maxLCBI4mm in the entire study population, while MAGE was correlated with maxLCBI4mm in non-diabetic patients (r = 0.46, p = 0.02). In patients with and without acute MI presentation, no significant relations were found between MAGE and maxLCBI4mm. CONCLUSION: GV was associated with lipid core plaque formation, especially in non-diabetic patients.

Patients with epicardial coronary vasospastic angina (VSA) may be likely to have coronary microvascular dysfunction, although mixed results have been reported. The aim of this study was to evaluate coronary microvascular function in detail using novel invasive physiologic indices, such as resistive reserve ratio (RRR) and microvascular resistance reserve (MRR). A total of 45 patients undergoing intracoronary acetylcholine (ACh) provocation test and invasive coronary circulatory evaluation using a thermodilution method were prospectively included. VSA was diagnosed as angiographic vasospasm accompanied by chest pain and/or ischemic electrocardiographic changes by intracoronary injection of ACh. Coronary circulation was assessed with physiologic indices including fractional flow reserve, resting and hyperemic mean transit time (Tmn), coronary flow reserve (CFR), basal resistance index, index of microcirculatory resistance (IMR), RRR, and MRR. Of 45 patients, 23 (51.1%) were diagnosed as having VSA. Patients with positive ACh test had longer resting Tmn (slower coronary flow velocity), higher basal resistance index, and greater RRR and MRR than those without, while fractional flow reserve, CFR, and IMR did not differ significantly between the two groups. In conclusion, although conventional measures such as CFR and IMR failed to show significant differences, RRR and MRR, novel invasive coronary physiologic indices, provided counterintuitive insights that coronary microvascular dilation function was better preserved in patients with VSA than those without.

This study sought to investigate the relationship between physiological severity and plaque vulnerability of intermediate coronary artery stenoses as assessed by fractional flow reserve (FFR) and near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). We included vessels where both FFR and NIRS-IVUS were performed. A positive FFR was defined as FFR ≤ 0.80. Lipid core burden index of the entire target vessel (TV-LCBI), maximum LCBI in 4 mm (maxLCBI4mm), and maximum plaque burden (PB) were evaluated using NIRS-IVUS. A vulnerable plaque was defined as a lipid-rich plaque (maxLCBI4mm ≥ 400) with large PB (≥ 70%). A total of 59 vessels of 45 patients were included. Median FFR value was 0.75 [interquartile 0.72, 0.82]. An FFR value of ≤ 0.80 was observed in 42 vessels (71%). TV-LCBI (correlation coefficient [CC] = - 0.331, p = 0.011), lesion length (CC = - 0.350, p = 0.007), and PB (CC = - 0.230, p = 0.080) negatively correlated with FFR value, while maxLCBI4mm did not (CC = - 0.156, p = 0.24). The prevalence of vulnerable plaques (26.2% vs. 29.4%, p > 0.99) and mean TV-LCBI, maxLCBI4mm, and PB values were not significantly different between the vessels with FFR ≤ 0.80 and those with FFR > 0.80. In multivariable logistic models, diabetes mellitus (p = 0.003) and hemoglobin A1c (p = 0.012) were associated with the presence of a vulnerable plaque. In conclusion, the results of the present study suggested that FFR may reflect total lipid burden but not necessarily plaque vulnerability. In patients with coronary artery disease and a high likelihood of rapid atherosclerosis progression, such as diabetes mellitus patients, assessing plaque vulnerability in addition to the functional severity of coronary artery lesions may help stratify better the risk of future events.