Prognostic Impact of Calcified Plaque Morphology After Drug Eluting Stent Implantation　- An Optical Coherence Tomography Study.

BACKGROUND: Optical coherence tomography (OCT) has the potential to characterize the detailed morphology of calcified coronary plaques. This study examined the prognostic impact of calcified plaque morphology in patients with coronary artery calcification (CAC) who underwent newer-generation drug-eluting stent (DES) implantation.Methods and Results:In all, 251 patients with moderate to severe CAC who underwent OCT-guided DES implantation were reviewed retrospectively and divided into 3 groups according to OCT findings of the target lesion: 25 patients (10.0%) with calcified nodules (CN), 69 patients (27.5%) with calcified protrusion (CP) without CN, and 157 patients (62.5%) with superficial calcific sheet (SC) without CN and CP. The primary endpoint was major adverse cardiac events (MACE), defined as a composite of cardiac death, myocardial infarction, and target lesion revascularization (TLR). Kaplan-Meier survival analysis revealed that, among the 3 groups, the rates of MACE-free survival (log-rank test, P=0.0117), myocardial infarction (log-rank test, P=0.0103), and TLR (log-rank test, P=0.0455) were significantly worse in patients with CN. Multivariate Cox proportional hazards analysis demonstrated that CN was an independent predictor of MACE (hazard ratio 4.41; 95% confidence interval 1.63-10.8; P=0.0047). CONCLUSIONS: Target lesion CN was associated with higher cardiac event rates in patients who underwent newer-generation DES implantation for lesions with moderate to severe CAC.

Post-Stent Optical Coherence Tomography Findings at Index Percutaneous Coronary Intervention　- Characteristics Related to Subsequent Stent Thrombosis.

BACKGROUND: The association between unfavorable post-stent optical coherence tomography (OCT) findings and subsequent stent thrombosis (ST) remains unclear. This study investigated the ST-related characteristics of post-stent OCT findings at index percutaneous coronary intervention (PCI).Methods and Results:Fifteen patients with ST onset after OCT-guided PCI (ST group) were retrospectively enrolled. Post-stent OCT findings in the ST group were compared with those in 70 consecutive patients (reference group) without acute coronary syndrome onset for at least 5 years after OCT-guided PCI. The incidence of acute myocardial infarction (AMI) was higher in the ST than reference group (60.0% vs. 17.1%, respectively; P=0.0005). The incidence of incomplete stent apposition (93.3% vs. 55.7%; P=0.0064), irregular protrusion (IP; 93.3% vs. 62.8%; P=0.0214), and thrombus (93.3% vs. 51.4%; P=0.0028) was significantly higher in the ST than reference group. The maximum median (interquartile range) IP arc was significantly larger in the ST than reference group (265° [217°-360°] vs. 128° [81.4°-212°], respectively; P<0.0001). In AMI patients, the incidence of a maximum IP arc >180° was significantly higher in the ST than reference group (100% vs. 58.3%, respectively; P=0.0265). CONCLUSIONS: IP with a large arc was a significant feature on post-stent OCT in patients with ST.

Evaluation of the A2B Score for Prediction of Survival in Patients With Heart Failure in a Nationwide Cohort in Japan.

BACKGROUND: Although a tool for sharing patient prognosis among all medical staff is desirable in heart failure (HF) cases, only a few simple HF prognostic scores are available. We previously presented the A2B score, a simple user-friendly HF risk score, and validated it in a small single-center cohort. In the present study, we validated it in a larger nationwide cohort. METHODS AND RESULTS: We examined the 2-year mortality in relation to the A2B scores in 3483 patients from a Japanese nationwide cohort and attempted to stratify their prognoses according to the scores. The A2B score was determined by assigning points for age, anemia, and brain natriuretic peptide (BNP) level at discharge: age (<65 years, 0; 65-74 years, 1; ≥75 years, 2), anemia (hemoglobin ≥12 g/dL, 0; 10-11.9 g/dL, 1; <10 g/dL, 2), and BNP (<200 pg/mL, 0; 200-499 pg/mL, 1; ≥500 pg/mL, 2). Hemoglobin and BNP levels were applied to the data at discharge. The 2-year survival rates for A2B scores 1, 2, 3, 4, 5, and 6 were 94.1%, 83.2%, 74.1%, 63.5%, 51.6%, and 41.5%, respectively; the mortality rate increased by ≈10% for each point increase (c-index, 0.702). The A2B score was applicable in HF cases with reduced or preserved ejection fraction and remained useful when BNP was substituted with N-terminal proBNP (c-index, 0.749, 0.676, and 0.682, respectively). CONCLUSIONS: The A2B score showed a good prognostic value for HF in a large population even when BNP was replaced with N-terminal proBNP.

Prognostic impact and predictors of persistent renal dysfunction in acute kidney injury after percutaneous coronary intervention for acute myocardial infarction.

This study aimed to evaluate the prognostic impact and predictors of persistent renal dysfunction in acute kidney injury (AKI) after an emergency percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). A total of 877 patients who underwent emergency PCI for AMI were examined. AKI was defined as serum creatinine (SCr) ≥ 0.3 mg/dL or ≥ 50% from baseline within 48 h after PCI. Persistent AKI was defined as residual impairment of SCr ≥ 0.3 mg/dL or ≥ 50% from baseline 1 month after the procedure. The primary outcome was the composite endpoints of death, myocardial infarction, hospitalization for heart failure, stroke, and dialysis. AKI and persistent AKI were observed in 82 (9.4%) and 25 (2.9%) patients, respectively. Multivariate Cox proportional hazards analysis demonstrated that persistent AKI, but not transient AKI, was an independent predictor of primary outcome (hazard ratio, 4.99; 95% confidence interval, 2.30-10.8; P < 0.001). Age > 75 years, left ventricular ejection fraction < 40%, a high maximum creatinine phosphokinase MB level, and bleeding after PCI were independently associated with persistent AKI. Persistent AKI was independently associated with worse clinical outcomes in patients who underwent emergency PCI for AMI. Advanced age, poor cardiac function, large myocardial necrosis, and bleeding were predictors of persistent AKI.

Heart failure with preserved ejection fraction phenogroup classification using machine learning.

AIMS: Heart failure (HF) with preserved ejection fraction (HFpEF) is a complex syndrome with a poor prognosis. Phenotyping is required to identify subtype-dependent treatment strategies. Phenotypes of Japanese HFpEF patients are not fully elucidated, whose obesity is much less than Western patients. This study aimed to reveal model-based phenomapping using unsupervised machine learning (ML) for HFpEF in Japanese patients. METHODS AND RESULTS: We studied 365 patients with HFpEF (left ventricular ejection fraction >50%) as a derivation cohort from the Nara Registry and Analyses for Heart Failure (NARA-HF), which registered patients with hospitalization by acute decompensated HF. We used unsupervised ML with a variational Bayesian-Gaussian mixture model (VBGMM) with common clinical variables. We also performed hierarchical clustering on the derivation cohort. We adopted 230 patients in the Japanese Heart Failure Syndrome with Preserved Ejection Fraction Registry as the validation cohort for VBGMM. The primary endpoint was defined as all-cause death and HF readmission within 5 years. Supervised ML was performed on the composite cohort of derivation and validation. The optimal number of clusters was three because of the probable distribution of VBGMM and the minimum Bayesian information criterion, and we stratified HFpEF into three phenogroups. Phenogroup 1 (n = 125) was older (mean age 78.9 ± 9.1 years) and predominantly male (57.6%), with the worst kidney function (mean estimated glomerular filtration rate 28.5 ± 9.7 mL/min/1.73 m2 ) and a high incidence of atherosclerotic factor. Phenogroup 2 (n = 200) had older individuals (mean age 78.8 ± 9.7 years), the lowest body mass index (BMI; 22.78 ± 3.94), and the highest incidence of women (57.5%) and atrial fibrillation (56.5%). Phenogroup 3 (n = 40) was the youngest (mean age 63.5 ± 11.2) and predominantly male (63.5 ± 11.2), with the highest BMI (27.46 ± 5.85) and a high incidence of left ventricular hypertrophy. We characterized these three phenogroups as atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups, respectively. At the primary endpoint, Phenogroup 1 demonstrated the worst prognosis (Phenogroups 1-3: 72.0% vs. 58.5% vs. 45%, P = 0.0036). We also successfully classified a derivation cohort into three similar phenogroups using VBGMM. Hierarchical and supervised clustering successfully showed the reproducibility of the three phenogroups. CONCLUSIONS: ML could successfully stratify Japanese HFpEF patients into three phenogroups (atherosclerosis and chronic kidney disease, atrial fibrillation, and younger and left ventricular hypertrophy groups).

Detection of myocardial bridge by optical coherence tomography.

Myocardial bridge (MB) is less commonly documented by angiography than autopsy. Optical coherence tomography (OCT) may be useful to detect angiographically undetectable MB. To investigate OCT characteristics of MB, 86 LAD vessels were imaged by OCT. MB was defined as presence of intermediate optical intensity, "fine" layer surrounding coronary artery by OCT. Frequency and characteristics of the angio-detectable and angio-undetectable but OCT-detectable MB were investigated. In a subset of patients with angio-detectable MB, cyclic changes in coronary arterial dimensions were analyzed. OCT detected MB in 44 of 86 (51%). Arc of the MB was significantly larger (334.8 ± 58.5° vs. 268.4 ± 92.1°, P = 0.008) and length was significantly longer (22.6 ± 11.7 mm vs. 14.5 ± 8.1 mm, P = 0.014) in angio-detectable MB than OCT-detectable but angio-undetectable MB. Both vessel (6.8 ± 1.5 to 5.3 ± 1.0 mm2, P = 0.035) and lumen area (4.4 ± 1.5 to 3.1 ± 0.7 mm2, P = 0.040) decreased significantly from diastole to systole. Adventitial (0.08 ± 0.03 to 0.08 ± 0.02 mm, P = 0.828) and intima + plaque thickness (0.12 ± 0.05 to 0.10 ± 0.03 mm, P = 0.398) did not change significantly during cardiac cycle. On the other hand, medial thickness increased significantly from diastole to systole (0.08 ± 0.03 to 0.12 ± 0.03 mm, P = 0.022). In conclusion, MB is frequently detected as intermediate intensity, fine layer by OCT. During systole, vessel and lumen size decrease with increased medial thickness. Therefore, we should be careful for OCT interpretation of the coronary arteries with MB.

Incidence and Characteristics of Incomplete Stent Apposition in Calcified Lesions: An Optical Coherence Tomography Study.

BACKGROUND: Persistent or late acquired incomplete stent apposition (ISA) may be associated with late or very late stent thrombosis following drug-eluting stent implantation. Presence of calcium at the target lesion may increase the risk of ISA even after rotational atherectomy (RA) followed by stenting with high pressure balloon inflation. The aim of this study is to examine the incidence and characteristics of ISA in heavily calcified lesions. METHODS: A total of 52 heavily calcified coronary artery lesions requiring RA plus stenting were selected and studied. After successful ablation followed by stent implantation, optical coherence tomography (OCT) was performed to assess stent expansion and apposition. Presence or absence of ISA was examined and maximal stent strut to vessel wall distance (max SV distance) was measured. In lesions with repeated OCT at follow-up, serial changes in ISA were investigated. RESULTS: ISA was documented in 51 of 52 (98%) lesions. Mean max SV distance was 713 ± 371 µm. In lesions with serial OCT images (n = 11), max SV distance decreased significantly (692.1 ± 420.2 to 462.5 ± 387.0 µm, P < 0.01) but persisted in all but 2 lesions (82%). CONCLUSIONS: ISA is frequently documented in heavily calcified lesions requiring RA. Significant ISA still persisted with minimal improvement in SV distance at follow-up. Prognostic impact of the persistent ISA in such calcified lesions needs further investigations.

Clinical Course of Optical Coherence Tomography-Detected Lipid-Rich Coronary Plaque After Optimal Medical Therapy.

Background: The aim of this study was to evaluate optical coherence tomography (OCT)-detected lipid-rich coronary plaques (LRCPs) with coronary computed tomography angiography (CCTA) 10 months after optimal medical therapy (OMT). Methods and Results: Baseline OCT detected 28 LRCPs in non-culprit lesions. High-risk plaque features (HRPFs), such as positive remodeling, very low attenuation plaques, napkin-ring sign, and spotty calcification, were observed in 67.9%, 67.9%, 21.4%, and 64.3% of LRCPs, respectively, at the 10-month follow-up CCTA. Lesions with ≥3 HRPFs were defined as high-risk LRCPs (n=12); the remaining were defined as low-risk LRCPs (n=16). The maximum lipid arc on baseline OCT was larger in high- than low-risk LRCPs (221±62° vs. 179±44°, respectively; P=0.04). Receiver operating characteristic curve analysis indicated that a maximum lipid arc >154° on baseline OCT was the optimal cut-off value to predict high-risk LRCPs 10 months after OMT. Patients with high-risk LRCPs had worse clinical outcomes, defined as a composite of cardiac death, target lesion-related myocardial infarction, and target lesion-related revascularization, during follow-up than those with low-risk LRCPs (33.3% vs. 0%; P=0.01). Conclusions: A high-risk LRCP at follow-up CCTA was correlated with a larger maximum lipid arc on baseline OCT. Further aggressive treatment for patients with large LRCPs may reduce vulnerable plaque features and prevent future cardiac events.

Prediction of optical coherence tomography-detected calcified nodules using coronary computed tomography angiography.

Diagnosis of calcified nodules (CNs) is critical in the proper management of coronary artery disease, but CNs can be detected only using intracoronary imaging modalities. This study aimed to investigate the ability of coronary computed tomography angiography (CCTA) in predicting CNs detected using optical coherence tomography (OCT). From 138 patients who underwent OCT-guided percutaneous coronary intervention (PCI) after CCTA evaluation, 141 PCI target vessels were retrospectively enrolled and classified into CN (12 vessels/11 patients; CNs in the PCI culprit lesion) and non-CN (129 vessels/127 patients; without CNs) groups based on the OCT analysis. Retrospective CCTA analysis revealed significantly higher coronary artery calcification score (CACS), calcified plaque volume (CPV), and maximum calcified plaque area (MCPA) of the target vessel in the CN group than in the non-CN group. Receiver operating characteristic curve indicated that CACS ≥ 162 (area under the ROC curve (AUC 0.76, sensitivity 83.3%, specificity 54.2%), CPV ≥ 20.1 mm3 (AUC 0.83, sensitivity 100%, specificity 57.3%), and MCPA ≥ 4.51 mm2 (AUC 0.87, sensitivity 91.7%, specificity 78.3%) were the best cutoff values for predicting CNs. MCPA showed the highest AUC among all the CCTA parameters. In conclusion, CCTA is useful for predicting OCT-detected CNs in PCI target vessels.

Clinical Impact of Irregular Protrusion Angle After Coronary Stenting at Culprit Lesions With ST-Elevation Myocardial Infarction　- An Intravascular Optical Coherence Tomography Study.

Background: A recent optical coherence tomography (OCT) registry showed that the presence of irregular protrusion (IP) after coronary stenting was a predictor of worse 1-year cardiovascular events. This study evaluated the clinical impact of OCT-detected IP after coronary stenting at ST-elevation myocardial infarction (STEMI) culprit lesions. Methods and Results: In all, 139 consecutive STEMI patients with OCT-detected IP after stenting were analyzed retrospectively. The maximum IP angles were measured and patients with IP were divided into 2 groups (large IP, maximum IP angle ≥180°; small IP, 0°

Visualization of the improvement of myocardial perfusion after coronary intervention using motorized fractional flow reserve pullback curve.

This study aimed to evaluate the feasibility and utility of using motorized pullback of the pressure guidewire to provide a graphic assessment and prediction of the benefits of coronary intervention. Fractional flow reserve (FFR) measurements were performed with motorized pullback imaging in 20 patients who underwent successful percutaneous coronary intervention (PCI) of the left anterior descending artery. Physiological lesion length (PLL) was calculated using frame counts to determine stent length. FFR area was calculated by integrating the FFR values recorded during pullback tracing (FFRarea). The percentage increase in FFR area (%FFRarea) was defined as the ratio of the difference between the pre- and post-intervention FFRarea to the total frame count. The average FFR values were enhanced following PCI, from 0.64 to 0.82, and the median value of the difference between pre- and post-interventional FFR values (D-FFR) and %FFRarea were 0.13 and 10.6%, respectively. The %FFRarea demonstrated a significant positive correlation with D-FFR (R 2, 0.61; p < 0.01). PLL tended to be longer and the %FFRarea was smaller in lesions with a gradual pressure-drop pattern than those with an abrupt pressure-drop pattern (35.37 vs. 20.40 mm, p = 0.07; 5.78 vs. 16.21%, p < 0.05, respectively). Motorized pullback tracing was able to identify the extent and location of stenosis and help in appropriate stent implantation, in addition to visualizing and quantifying the improvement in FFR following PCI.

Cholesterol crystal depth in coronary atherosclerotic plaques: A novel index of plaque vulnerability using optical frequency domain imaging.

BACKGROUND: The involvement of cholesterol crystals (CCs) in plaque progression and destabilization of atherosclerotic plaques has been recently recognized. This study aimed to evaluate the association between the intraplaque localization of CCs and plaque vulnerability. METHODS: We investigated 55 acute coronary syndrome (ACS) and 80 stable angina pectoris (stable AP) lesions using optical frequency domain imaging (OFDI) prior to percutaneous coronary intervention. The distance between CCs and the luminal surface of coronary plaques was defined as CC depth. RESULTS: Although the incidence of CCs had similar frequencies in the ACS and stable AP groups (95% vs. 89%, p = 0.25), CC depth was significantly less in patients with ACS than in those with stable AP (median [25th to 75th percentile]: 68 µm [58 to 92 µm] vs. 152 µm [115 to 218 µm]; p < 0.001). The incidences of plaque rupture, thrombus, lipid-rich plaques, and thin-cap fibroatheroma were significantly greater in patients with ACS than in those with stable AP (62% vs. 18%, p < 0.001; 67% vs. 16%, p < 0.001; 84% vs. 57%, p < 0.01; and 56% vs. 19%, p < 0.001, respectively). CONCLUSION: OFDI analysis revealed that CCs were found in the more superficial layers within the coronary atherosclerotic plaques in patients with ACS than in those with stable AP, suggesting that CC depth is associated with plaque vulnerability. CC depth, a novel OFDI-derived parameter, could be potentially used as an alternative means of evaluating plaque vulnerability in coronary arteries.

Usefulness of the novel risk estimation software, Heart Risk View, for the prediction of cardiac events in patients with normal myocardial perfusion SPECT.

BACKGROUND: Myocardial perfusion single-photon emission-computed tomography (SPECT) can predict cardiac events in patients with coronary artery disease with high accuracy; however, pseudo-negative cases sometimes occur. Heart Risk View, which is based on the prospective cohort study (J-ACCESS), is a software for evaluating cardiac event probability. OBJECTIVES: We examined whether Heart Risk View was useful to evaluate the cardiac risk in patients with normal myocardial perfusion SPECT (MPS). METHODS AND RESULTS: We studied 3461 consecutive patients who underwent MPS to detect myocardial ischemia and those who had normal MPS were enrolled in this study (n = 698). We calculated cardiac event probability by Heart Risk View and followed-up for 3.8 ± 2.4 years. The cardiac events were defined as cardiac death, non-fatal myocardial infarction, and heart failure requiring hospitalization. During the follow-up period, 21 patients (3.0 %) had cardiac events. The event probability calculated by Heart Risk View was higher in the event group (5.5 ± 2.6 vs. 2.9 ± 2.6 %, p < 0.001). According to the receiver-operating characteristics curve, the cut-off point of the event probability for predicting cardiac events was 3.4 % (sensitivity 0.76, specificity 0.72, and AUC 0.85). Kaplan-Meier curves revealed that a higher event rate was observed in the high-event probability group by the log-rank test (p < 0.001). CONCLUSION: Although myocardial perfusion SPECT is useful for the prediction of cardiac events, risk estimation by Heart Risk View adds more prognostic information, especially in patients with normal MPS.