Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Owing to the advent of new generation drug-eluting stents, percutaneous coronary intervention (PCI) outcomes are improving. However, the polymers, which have been the most common type of coatings used in drug-eluting stents, have some issues. The study aim was to evaluate the clinical outcomes of patients undergoing PCI with polymer-free sirolimus- and probucol-eluting stents (NP023). METHODS: This clinical trial was a prospective multicenter single-blind noninferiority randomized study performed at 22 hospitals in Japan. We randomly assigned patients in a 2:1 ratio to undergo PCI with either NP023 or durable polymer-based everolimus-eluting stents (control stents) with a 5-year follow-up. The primary outcome was freedom from target lesion failure (TLF) at 9 months, defined as patient-oriented composite of cardiac death, ischemia-driven target vessel-related myocardial infarction, or ischemia-driven target lesion revascularization. The secondary outcome included adverse outcomes at 5 years following the index procedure. RESULTS: Overall, 432 patients (463 lesions) were treated at 22 sites in Japan [mean age, 68 years; males, 345 (80 %); chronic coronary artery diseases, 322 (74.5 %)]. Of the participants, 91 % completed the 5-year follow-up. The Kaplan-Meier estimates of the percentages of patients who were free from TLF were 95.8 % and 97.3 % with NP023 and control stents, respectively (hazard ratio, 0.98; 95 % confidential interval, 0.80-1.21; p < 0.01 for noninferiority). At the 5-year follow-up, the secondary endpoint for safety was not different between the two groups. CONCLUSIONS: The results of this study showed similar outcomes for polymer-free sirolimus- and probucol-eluting stents and durable polymer-based everolimus-eluting stents regarding freedom from TLF at 9 months and other outcomes at 5 years among patients undergoing PCI.

DOI： 10.1016/j.jjcc.2025.01.018

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Primary percutaneous coronary intervention (pPCI) for ST-segment elevation myocardial infarction (STEMI) is typically performed by experienced operators. Therefore, the safety of pPCI for STEMI performed by less experienced operators with the support of experienced operators remains unknown. We aimed to investigate the long-term outcomes of pPCI for STEMI performed by less experienced operators with the support of experienced operators. In total, 775 STEMI patients were enrolled and divided into groups according to operator experience in PCI: less experienced (n = 384) and experienced (n = 391) operator groups. Experienced operators were defined as those who had performed > 50 elective PCI procedures per year as the first operator or instructional assistant, whereas less experienced operators were defined as others. When less experienced operators performed the pPCI, experienced operators supported them. The primary endpoint was any cardiovascular event, defined as a composite of cardiovascular death, nonfatal myocardial infarction, and unplanned hospitalization for heart failure. In the propensity score-matched analysis, 324 patients were included in each group. The cumulative incidence of the primary endpoint over a median of 5 years in the less experienced operator group was similar to that in the experienced operator group (15% vs. 18%, P = 0.209). In the multivariate Cox proportional hazards model, there was no excess risk for patients operated upon by less experienced operators for the primary endpoint (adjusted hazard ratio, 0.85; 95% confidence interval, 0.58-1.25; P = 0.417). pPCI for STEMI by less experienced operators did not increase the risk of in-hospital mortality or 5-year long-term cardiovascular events if supported by experienced operators.

DOI： 10.1007/s12928-024-01059-5

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AIMS: Pre-existing myocardial fibrosis before aortic valve replacement (AVR) is a major cause of postoperative heart failure (HF). Evaluation of fibrosis by computed tomography extracellular volume (CT-ECV) may allow risk stratification for patients with severe aortic stenosis (AS) scheduled for transaortic AVR (TAVR) or surgical AVR (SAVR). We performed a meta-analysis to determine the prognostic value of CT-ECV for the prediction of adverse events in patients with severe AS scheduled for AVR. METHODS AND RESULTS: Electronic database searches of PubMed, Web of Science Core Collection, Cochrane advanced search, and EMBASE were performed. A comprehensive literature review was conducted to examine the association between CT-ECV and prognosis in patients with severe AS who underwent AVR. The diagnostic performance of CT-ECV for predicting composite adverse events (all-cause death and hospitalization for HF) was assessed using a pooled odds ratio (OR). Data from 902 patients with severe AS were extracted from six studies, including 881 TAVR and 21 SAVR cases. The pooled OR of abnormal CT-ECV for predicting adverse events was 4.53 [95% confidence interval (CI): 3.13-6.57 (I 2 = 10%, P for heterogeneity = 0.50)]. We performed an OR meta-analysis on five studies with only TAVR cases (n = 807). The pooled OR of abnormal CT-ECV for predicting adverse events in TAVR patients was 4.85 [95% CI: 3.26-7.21 (I² = 0%, P < 0.001)]. CONCLUSION: Considering the high prognostic ability and versatility of CT-ECV, it may be used to predict postoperative adverse events in patients with severe AS who underwent AVR.

DOI： 10.1093/ehjopen/oeaf007

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Balloon pulmonary angioplasty (BPA) is an innovative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). We retrospectively examined the clinical outcomes and complications of BPA at Yokohama City University Hospital (YCUH) between 2012 and 2018. In 2012, we began to conduct BPA sessions in 46 patients with inoperable CTEPH; 34 completed the BPA scheme and the follow-up plan. A longitudinal sub-analysis was performed with cohorts 1 and 2 receiving BPA before and after April 2015. Significant improvements in the mean pulmonary arterial pressure, pulmonary vascular resistance, and other parameters were detected after BPA. The total rate of thoracic complications was 25%. Specifically, the increase in SaO2 and home oxygen therapy discontinuation rate, and oral riociguat discontinuation rate was significantly higher in cohort 2 (+ 7.7, 75, and 59%) compared to cohort 1 (+ 3.1, 27, and 10%) (P < 0.05). Moreover, the need for non-invasive positive pressure ventilation was significantly lower: 0% (cohort 2) vs. 7% (cohort 1) (P < 0.05). The BPA sessions conducted at the YCUH resulted in significant improvements in patients with CTEPH. This study demonstrates a clear learning curve regarding the effectiveness of BPA both in normalizing SaO2 and facilitating the cessation of home oxygen therapy, as well as in reducing the incidence of severe complications.

DOI： 10.1007/s12928-024-01076-4

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DOI： 10.1253/circj.CJ-66-0238

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DOI： 10.1253/circj.CJ-66-0237

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Balloon pulmonary angioplasty (BPA) is an innovative treatment for chronic thromboembolic pulmonary hypertension (CTEPH). We retrospectively examined the clinical outcomes and complications of BPA at Yokohama City University Hospital (YCUH) between 2012 and 2018. In 2012, we began to conduct BPA sessions in 46 patients with inoperable CTEPH; 34 completed the BPA scheme and the follow-up plan. A longitudinal sub-analysis was performed with cohorts 1 and 2 receiving BPA before and after April 2015. Significant improvements in the mean pulmonary arterial pressure, pulmonary vascular resistance, and other parameters were detected after BPA. The total rate of thoracic complications was 25%. Specifically, the increase in SaO2 and home oxygen therapy discontinuation rate, and oral riociguat discontinuation rate was significantly higher in cohort 2 (+ 7.7, 75, and 59%) compared to cohort 1 (+ 3.1, 27, and 10%) (P < 0.05). Moreover, the need for non-invasive positive pressure ventilation was significantly lower: 0% (cohort 2) vs. 7% (cohort 1) (P < 0.05). The BPA sessions conducted at the YCUH resulted in significant improvements in patients with CTEPH. This study demonstrates a clear learning curve regarding the effectiveness of BPA both in normalizing SaO2 and facilitating the cessation of home oxygen therapy, as well as in reducing the incidence of severe complications.

DOI： 10.1007/s12928-024-01076-4

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BACKGROUND: Patients with heart failure (HF) are at an increased risk of developing pneumonia, leading to a high mortality. A decrease in muscle strength due to aging or concomitant disease may contribute to the development of pneumonia in older adults. We sought to investigate the relationship between low muscle strength and pneumonia incidence in older patients hospitalized for worsening HF. METHODS: We carried out a subanalysis of the FRAGILE-HF, a prospective multicenter observational study, including 1 266 consecutive older (≥65 years) patients hospitalized with HF (mean age 80.2 ± 7.8 years; 57.4% male; left ventricular ejection fraction 46% ± 17%) and information of incident pneumonia observed after discharge. Patients were followed up for 2 years post-discharge. RESULTS: A total of 88 patients (7.0%) developed pneumonia after discharge, with an incidence of 42.7 per 1 000 person-years. A total of 893 patients with low muscle strength, defined as handgrip strength <28 kg for men and <18 kg for women according to international criteria, were more likely to develop pneumonia than those with normal muscle strength (p < .001; log-rank test). Low muscle strength was a significant predictor of incident pneumonia (adjusted hazard ratio with 95% confidence interval: 2.65 [1.31-5.35], p = .007). Furthermore, the mortality rates were 43.2% in patients who developed pneumonia and 19.3% in those who did not, indicating a heightened risk of death following the onset of pneumonia (adjusted hazard ratio: 4.25 [2.91-6.19], p < .001). CONCLUSIONS: In older patients hospitalized for HF, low muscle strength was associated with incident pneumonia after discharge.

DOI： 10.1093/gerona/glae266

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Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Vascular Failure  

DOI： 10.30548/vascfail.8.1_1

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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BACKGROUND: The importance of prehospital (PH) electrocardiograms (ECG) recorded by emergency medical services (EMS) for diagnosing coronary artery spasm-induced acute coronary syndrome (CS-ACS) remains unclear. METHODS AND RESULTS: We enrolled 340 consecutive patients with ACS who were transported by EMS within 12 h of symptom onset. According to Japanese Circulation Society guidelines, CS-ACS (n=48) was diagnosed with or without a pharmacological provocation test (n=34 and n=14, respectively). Obstructive coronary artery-induced ACS (OC-ACS; n=292) was defined as ACS with a culprit lesion showing 99% stenosis or >75% stenosis with plaque rupture or thrombosis observed via angiographic and intravascular imaging. Ischemic ECG findings included ST-segment deviation (elevation or depression) and negative T and U waves. In CS-ACS, the prevalence of ST-segment deviation decreased significantly from PH-ECG to emergency room (ER) ECG (77.0% vs. 35.4%; P<0.001), as did the prevalence of overall ECG abnormalities (81.2% vs. 45.8%; P<0.001). Conversely, in OC-ACS, there was a similar prevalence on PH-ECG and ER-ECG of ST-segment deviations (94.8% vs. 92.8%, respectively; P=0.057) and abnormal ECG findings (96.9% vs. 95.2%, respectively; P=0.058). Patients with abnormal PH-ECG findings that disappeared upon arrival at hospital without ER-ECG or troponin abnormalities were more frequent in the CS-ACS than OC-ACS group (20.8% vs. 1.0%; P<0.001). CONCLUSIONS: PH-ECG is valuable for detecting abnormal ECG findings that disappear upon arrival at hospital in CS-ACS patients.

DOI： 10.1253/circj.CJ-24-0485

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BACKGROUND: The clinical benefits of optical frequency domain imaging (OFDI)-guided percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. AIMS: We sought to compare intravascular ultrasound (IVUS)- and OFDI-guided PCI in patients with ACS. METHODS: OPINION ACS is a multicentre, prospective, randomised, non-inferiority trial that compared OFDI-guided PCI with IVUS-guided PCI using current-generation drug-eluting stents in ACS patients (n=158). The primary endpoint was in-stent minimum lumen area (MLA), assessed using 8-month follow-up OFDI. RESULTS: Patients presented with ST-segment elevation myocardial infarction (55%), non-ST-segment elevation myocardial infarction (29%), or unstable angina pectoris (16%). PCI procedural success was achieved in all patients, with comparably low periprocedural complications rates in both groups. Immediately after PCI, the minimum stent area (p=0.096) tended to be smaller for OFDI versus IVUS guidance. Proximal stent edge dissection (p=0.012) and irregular protrusion (p=0.03) were significantly less frequent in OFDI-guided procedures than in IVUS-guided procedures. Post-PCI coronary flow, assessed using corrected Thrombolysis in Myocardial Infarction frame counts, was significantly better in the OFDI-guided group than in the IVUS-guided group (p<0.001). The least squares mean (95% confidence interval [CI]) in-stent MLA at 8 months was 4.91 (95% CI: 4.53-5.30) mm2 and 4.76 (95% CI: 4.35-5.17) mm2 in the OFDI- and IVUS-guided groups, respectively, demonstrating the non-inferiority of OFDI guidance (pnon-inferiority<0.001). The average neointima area tended to be smaller in the OFDI-guided group. The frequency of major adverse cardiac events was similar. CONCLUSIONS: Among ACS patients, OFDI-guided PCI and IVUS-guided PCI were equally safe and feasible, with comparable in-stent MLA at 8 months. OFDI guidance may be a potential option in ACS patients. This study was registered in the Japan Registry of Clinical Trials (jrct.niph.go.jp: jRCTs052190093).

DOI： 10.4244/EIJ-D-24-00314

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The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111.

DOI： 10.1016/j.amjcard.2024.07.002

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Language：Japanese   Publisher：(一社)日本集中治療医学会  

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BACKGROUND: The benefit of prehospital 12‑lead electrocardiogram (PH-ECG) performed by emergency medical service personnel at the site of first medical contact (FMC) in patients with ST-segment elevation myocardial infarction (STEMI) with cardiogenic shock (CS-STEMI) remains unclear. This study aimed to investigate the effect of PH-ECG on door-to-device time in patients with CS-STEMI. METHODS: This study enrolled CS-STEMI (Killip class IV) patients who were transferred directly to hospitals by ambulance (n = 517) from the Kanagawa Acute Cardiovascular Registry database. Patients were divided into PH-ECG (+) (n = 270) and PH-ECG (-) (n = 247) groups. Patients who experienced out-of-hospital cardiac arrest, who did not undergo emergent coronary intervention, or whose data were missing were excluded. Patient characteristics, FMC-to-door time, door-to-device time, and in-hospital mortality were compared between the groups. RESULTS: The patient backgrounds of the PH-ECG (+) and PH-ECG (-) groups were comparable. The peak creatinine kinase level was greater in the PH-ECG (+) group than in the PH-ECG (-) group [2756 (1292-6009) IU/ml vs. 2270 (957-5258) IU/ml, p = 0.048]. The FMC-to-door time was similar between the two groups [25 (20-33) min vs. 27 (20-35) min, p = 0.530], while the door-to-device time was significantly shorter in the PH-ECG group [74 (52-103) min vs. 83 (62-111) min, p = 0.007]. In-hospital mortality did not differ between the two groups (18 % vs. 21 %, p = 0.405). Multivariable logistic regression analyses revealed that PH-ECG (+) was independently associated with a door-to-device time < 60 min [odds ratio (95 % confidence intervals): 1.88 (1.24-2.83), p = 0.003]. CONCLUSIONS: PH-ECG was significantly associated with shorter door-to-device times in patients with CS-STEMI. Further studies with larger populations and more defined protocols are required to evaluate the utility of PH-ECG in patients with CS-STEMI.

DOI： 10.1016/j.jjcc.2024.08.004

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Language：Japanese   Publisher：日本肺高血圧・肺循環学会  

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Percutaneous coronary intervention for left main coronary artery disease (LM-PCI) represents a high-risk yet life-saving procedure that has evolved significantly over the years. This review outlines the current state-of-the-art practices for LM-PCI in Japan in detail, emphasizing the integration of coronary physiology and intracoronary imaging alongside with evidence-based standardized technique using latest drug-eluting stents. These advancements enable precise lesion assessment, stent sizing, and optimal deployment, thereby enhancing procedural safety and efficacy. Despite discrepancies between current guidelines favoring coronary artery bypass grafting and real-world practice trends towards increased LM-PCI adoption, particularly in elderly populations with multiple comorbidities, careful patient selection and procedural planning are critical. Future perspectives include further refining LM-PCI through conducting randomized controlled trials integrating advanced techniques and addressing the issue of ostial left circumflex lesions and nationwide standardization of medical care for LM disease.

DOI： 10.1007/s12928-024-01030-4

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The frequency of cardiac amyloidosis potentially present in patients with atrial fibrillation (AF) remains unclear. The purpose of this study is to determine the frequency and clinical characteristics of cardiac amyloidosis latent in AF by performing cardiac magnetic resonance imaging (MRI) in patients scheduled for AF ablation. We retrospectively analyzed 193 consecutive patients who underwent CA and cardiac MRI for atrial fibrillation. The primary endpoint of the study was the frequency of histologically confirmed cardiac amyloidosis or suspected cardiac amyloidosis [positive imaging findings on cardiac MRI strongly suspecting cardiac amyloidosis (diffuse subendocardial late gadolinium enhancement or MRI-derived extracellular volume of > 0.40)]. Among the 193 patients, 8 were confirmed or suspected cases of cardiac amyloidosis, representing a frequency of 4% (8/193 patients). Multivariate analysis identified interventricular septal thickness at end-diastole (LVSd) as an independent and significant predictor of cardiac amyloidosis (OR: 1.72, 95% CI 1.12-2.87, p = 0.020).The optimal cut-off value for IVSd was determined to be > 12.9 mm based on the Youden index. At this cut-off, the sensitivity was 75.0% (95% CI 34.9-96.8%) and the specificity was 92.3% (95% CI 87.4-95.7%), allowing for the identification of patients with definite or suspected cardiac amyloidosis. The frequency of confirmed and suspected cases of cardiac amyloidosis among patients with an IVSd > 12.9 mm was 30% (6/20 patients). In addition, prevalence of biopsy-proven cardiac amyloidosis was 10% (2/20). The prevalence of cardiac amyloidosis in atrial fibrillation patients scheduled for ablation with cardiac hypertrophy is not negligible.

DOI： 10.1007/s00380-024-02447-w

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BACKGROUND: Weight loss is a poor prognostic factor in patients with chronic heart failure (HF). However, whether the same is true for hospitalized patients with HF is unknown, even though hospitalization is the first opportunity for many patients to be diagnosed with HF. This study aimed to investigate the prognostic value of weight loss in patients hospitalized for HF. METHODS: This was a post-hoc analysis of the FRAGILE-HF study, a prospective multi-center, observational study including 1,332 hospitalized older (≥65 years) patients with HF. The primary outcome was all-cause death within two years of discharge. RESULTS: Self-reported body weight data one year prior to hospital admission were available for 1,106 patients (83.0%) and were compared with their weight after decongestion therapy. The median weight change was -6.9% [-2.4 - -11.9] and 86.8% of the overall cohort experienced some weight loss. Whereas patients with weight loss ≥ 5%, which is a well-validated cut-off in chronic HF, had comparable mortality to those with less weight loss (p = 0.96 by log-rank test), patients with weight loss > 12%, the lowest quartile value, had higher mortality than those with less weight loss (p = 0.024 for all-cause mortality, p = 0.028 for non-cardiovascular mortality, and p = 0.28 for cardiovascular mortality, respectively). In a Cox proportional hazard model, > 12% weight loss was associated with high mortality after adjusting for known prognostic factors and history of malignancy (adjusted hazard ratio: 1.485 [1.070-2.062], p=0.018). CONCLUSION: Weight loss derived from patient-reported body weight one year before hospitalization was significantly associated with increased mortality after discharge, mainly due to non-cardiovascular etiology, in elderly patients hospitalized for HF.

DOI： 10.1093/ehjqcco/qcae058

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BACKGROUND: The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS. OBJECTIVES: This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients. METHODS: The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP. RESULTS: Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP. CONCLUSIONS: The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730).

DOI： 10.1016/j.jacadv.2024.100996

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Background: The prognostic implications of persistent low-grade inflammation in patients with chronic coronary syndrome (CCS) are underexplored. The REAL-CAD (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy with Pitavastatin in Coronary Artery Disease) study demonstrated the benefit of higher intensity pitavastatin in Japanese patients with CCS. Objectives: This prespecified subanalysis of the REAL-CAD study aimed to assess the prognostic effect of the persistent low-grade inflammation represented by high-sensitivity C-reactive protein (hs-CRP) in CCS patients. Methods: The present analysis involved patients without events until 6 months after randomization and whose hs-CRP levels were available at baseline and 6 months (n = 10,460). The primary endpoint was the composite of cardiovascular mortality, myocardial infarction, stroke, and unstable angina hospitalization. Landmark analyses evaluated the prognostic impact of continuous inflammation in 4 groups based on the median levels of hs-CRP (0.5 mg/L for both) at baseline and 6 months. The 4 groups included patient with persistently low, elevated (increased), reduced, and persistently high hs-CRP. Results: Adjusted Cox proportional hazard analyses demonstrated an increased risk of the primary endpoint in the group with persistently high hs-CRP when compared to the group with persistently low hs-CRP as a reference (adjusted HR: 1.48, 95% CI: 1.18-1.89; P = 0.001), but with a similar risk in the group with elevated (HR: 1.07, 95% CI: 0.77-1.49, P = 0.68) and reduced (HR: 0.92; 95% CI: 0.66-1.27; P = 0.60) hs-CRP. Conclusions: The study shows that persistent low-grade inflammation is associated with poor outcomes and underscores the need to address residual inflammatory risk in CCS patients. (Randomized Evaluation of Aggressive or Moderate Lipid Lowering Therapy With Pitavastatin in Coronary Artery Disease [REAL-CAD]; NCT01042730)

DOI： 10.1016/j.jacadv.2024.100996

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DOI： 10.1016/j.ijcard.2024.132197

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DOI： 10.1016/j.jjcc.2024.05.002

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BACKGROUND: A delayed and recurrent complete atrioventricular block (CAVB) is a life-threatening complication of transcatheter aortic valve replacement (TAVR). Post-TAVR evaluation may be important in predicting delayed and recurrent CAVB requiring permanent pacemaker implantation (PPI). The impact of new-onset right bundle-branch block (RBBB) after TAVR on PPI remains unknown. METHODS AND RESULTS: In total, 407 patients with aortic stenosis who underwent TAVR were included in this analysis. Intraprocedural CAVB was defined as CAVB that occurred during TAVR. A 12-lead ECG was evaluated at baseline, immediately after TAVR, on postoperative days 1 and 5, and according to the need to identify new-onset bundle-branch block (BBB) and CAVB after TAVR. Forty patients (9.8%) required PPI, 17 patients (4.2%) had persistent intraprocedural CAVB, and 23 (5.7%) had delayed or recurrent CAVB after TAVR. The rates of no new-onset BBB, new-onset left BBB, and new-onset RBBB were 65.1%, 26.8%, and 4.7%, respectively. Compared with patients without new-onset BBB and those with new-onset left BBB, the rate of PPI was higher in patients with new-onset RBBB (3.4% versus 5.6% versus 44.4%, P<0.0001). On post-TAVR evaluation in patients without persistent intraprocedural CAVB, the multivariate logistic regression analysis showed that new-onset RBBB was a statistically significant predictor of PPI compared with no new-onset BBB (odds ratio [OR], 18.0 [95% CI, 5.94-54.4]) in addition to the use of a self-expanding valve (OR, 2.97 [95% CI, 1.09-8.10]). CONCLUSIONS: Patients with new-onset RBBB after TAVR are at high risk for PPI.

DOI： 10.1161/JAHA.123.032777

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DOI： 10.3390/jvd3020014

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AIMS: The incidence and prognosis of symptomatic heart failure following acute myocardial infarction (AMI) in the primary percutaneous coronary intervention era have rarely been reported in the literature. This study aimed to (i) determine the incidence of heart failure admission among AMI survivors, (ii) compare 1 year outcomes between patients with heart failure admission and those without, and (iii) identify the independent risk factors associated with heart failure admission. METHODS AND RESULTS: The Japan Acute Myocardial Infarction Registry is a prospective multicentre registry from which data on consecutively enrolled patients with AMI from 50 institutions between 2015 and 2017 were obtained. Among the 3411 patients enrolled, 3226 who survived until discharge were included in this study. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiovascular events (defined as cardiovascular mortality, non-fatal myocardial infarction, or non-fatal cerebral infarction) and major bleeding events corresponding to Bleeding Academic Research Consortium Type 3 or 5. Clinical outcomes were compared between the patients who were and were not admitted for heart failure. Over a median follow-up of 12 months, 124 patients (3.8%) were admitted due to heart failure. Independent risk factors for heart failure admission included older age, female sex, Killip class ≥2 on admission, left ventricular ejection fraction <40%, estimated glomerular filtration rate ≤30 mL/min/1.73 m2, a history of malignancy, and non-use of angiotensin-converting enzyme inhibitors at discharge. The cumulative incidence of all-cause mortality was significantly higher in the heart failure admission group than in the no heart failure admission group (11.3% vs. 2.5%, P < 0.001). The rates of major adverse cardiovascular events (16.9% vs. 2.7%, P < 0.001) and major bleeding (6.5% vs. 1.6%, P < 0.001) were significantly higher in the heart failure admission group. Heart failure admission was associated with a higher risk of all-cause mortality, even after adjusting for potential confounders (adjusted hazard ratio: 2.41, 95% confidence interval: 1.33-4.39, P = 0.004). CONCLUSIONS: Utilizing real-world data of the contemporary percutaneous coronary intervention era from the Japan Acute Myocardial Infarction Registry database, this study demonstrates that the heart failure admission of AMI survivors was significantly associated with higher all-cause mortality rates.

DOI： 10.1002/ehf2.14790

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No medications have been reported to inhibit the progression of aortic valve stenosis (AS). The present study aimed to investigate whether evolocumab use is related to the slow progression of AS evaluated by serial echocardiography. This was a retrospective observational study from 2017 to 2022 at Yokohama City University Medical Center. Patients aged ≥ 18 with moderate AS were included. Exclusion criteria were (1) mild AS; (2) severe AS defined by maximum aortic valve (AV) velocity ≥ 4.0 m/s; and/or (3) no data of annual follow-up echocardiography. The primary endpoint was the association between evolocumab use and annual changes in the maximum AV-velocity or peak AV-pressure gradient (PG). A total of 57 patients were enrolled: 9 patients treated with evolocumab (evolocumab group), and the other 48 patients assigned to a control group. During a median follow-up of 33 months, the cumulative incidence of AS events (a composite of all-cause death, AV intervention, or unplanned hospitalization for heart failure) was 11% in the evolocumab group and 58% in the control group (P = 0.012). Annual change of maximum AV-velocity or peak AV-PG from the baseline to the next year was 0.02 (- 0.18 to 0.22) m/s per year or 0.60 (- 4.20 to 6.44) mmHg per year in the evolocumab group, whereas it was 0.29 (0.04-0.59) m/s per year or 7.61 (1.46-16.48) mmHg per year in the control group (both P < 0.05). Evolocumab use was associated with slow progression of AS and a low incidence of AS events in patients with moderate AS.

DOI： 10.1007/s00380-024-02386-6

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AIMS: High platelet-derived thrombogenicity during the acute phase of ST-segment elevation myocardial infarction (STEMI) is associated with poor outcomes; however, the associated factors remain unclear. This study aimed to examine whether acute inflammatory response after STEMI affects platelet-derived thrombogenicity. METHODS: This retrospective observational single-center study included 150 patients with STEMI who were assessed for platelet-derived thrombogenicity during the acute phase. Platelet-derived thrombogenicity was assessed using the area under the flow-pressure curve for platelet chip (PL-AUC), which was measured using the total thrombus-formation analysis system (T-TAS). The peak leukocyte count was evaluated as an acute inflammatory response after STEMI. The patients were divided into two groups: the highest quartile of the peak leukocyte count and the other three quartiles combined. RESULTS: Patients with a high peak leukocyte count (＞15,222/mm3; n=37) had a higher PL-AUC upon admission (420 [386-457] vs. 385 [292-428], p=0.0018), higher PL-AUC during primary percutaneous coronary intervention (PPCI) (155 [76-229] vs. 96 [29-170], p=0.0065), a higher peak creatine kinase level (4200±2486 vs. 2373±1997, p＜0.0001), and higher PL-AUC 2 weeks after STEMI (119 [61-197] vs. 88 [46-122], p=0.048) than those with a low peak leukocyte count (≤ 15,222/mm3; n=113). The peak leukocyte count after STEMI positively correlated with PL-AUC during primary PPCI (r=0.37, p＜0.0001). A multivariable regression analysis showed the peak leukocyte count to be an independent factor for PL-AUC during PPCI (β=0.26, p=0.0065). CONCLUSIONS: An elevated leukocyte count is associated with high T-TAS-based platelet-derived thrombogenicity during the acute phase of STEMI.

DOI： 10.5551/jat.64395

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Language：English   Publisher：(一社)日本循環器学会  

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Language：English   Publisher：(一社)日本循環器学会  

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BACKGROUND: Bleeding rates on dual antiplatelet therapy (DAPT) within 1 month after percutaneous coronary intervention (PCI) remain high in clinical practice, particularly in patients with acute coronary syndrome or high bleeding risk. Aspirin-free strategy might result in lower bleeding early after PCI without increasing cardiovascular events, but its efficacy and safety have not yet been proven in randomized trials. METHODS: We randomly assigned 6002 patients with acute coronary syndrome or high bleeding risk just before PCI either to prasugrel (3.75 mg/day) monotherapy or to DAPT with aspirin (81-100 mg/day) and prasugrel (3.75 mg/day) after loading of 20 mg of prasugrel in both groups. The coprimary end points were major bleeding (Bleeding Academic Research Consortium 3 or 5) for superiority and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) for noninferiority with a relative 50% margin. RESULTS: The full analysis set population consisted of 5966 patients (no-aspirin group, 2984 patients; DAPT group, 2982 patients; age, 71.6±11.7 years; men, 76.6%; acute coronary syndrome, 75.0%). Within 7 days before randomization, aspirin alone, aspirin with P2Y12 inhibitor, oral anticoagulants, and intravenous heparin infusion were given in 21.3%, 6.4%, 8.9%, and 24.5%, respectively. Adherence to the protocol-specified antiplatelet therapy was 88% in both groups at 1 month. At 1 month, the no-aspirin group was not superior to the DAPT group for the coprimary bleeding end point (4.47% and 4.71%; hazard ratio, 0.95 [95% CI, 0.75-1.20]; Psuperiority=0.66). The no-aspirin group was noninferior to the DAPT group for the coprimary cardiovascular end point (4.12% and 3.69%; hazard ratio, 1.12 [95% CI, 0.87-1.45]; Pnoninferiority=0.01). There was no difference in net adverse clinical outcomes and each component of coprimary cardiovascular end point. There was an excess of any unplanned coronary revascularization (1.05% and 0.57%; hazard ratio, 1.83 [95%CI, 1.01-3.30]) and subacute definite or probable stent thrombosis (0.58% and 0.17%; hazard ratio, 3.40 [95% CI, 1.26-9.23]) in the no-aspirin group compared with the DAPT group. CONCLUSIONS: The aspirin-free strategy using low-dose prasugrel compared with the DAPT strategy failed to attest superiority for major bleeding within 1 month after PCI but was noninferior for cardiovascular events within 1 month after PCI. However, the aspirin-free strategy was associated with a signal suggesting an excess of coronary events. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04609111.

DOI： 10.1161/CIRCULATIONAHA.123.066720

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BACKGROUND: Mechanical compression of cardiac conduction system by transcatheter heart valves leads to complete atrioventricular block (CAVB) after transcatheter aortic valve replacement (TAVR). Bulging of ventricular septum in the left ventricular outflow tract (LVOT) may be associated with greater compression of conduction system, leading to irreversible CAVB. OBJECTIVE: This study aimed to investigate the association of ventricular septal bulging with TAVR-related CAVB and permanent pacemaker implantation (PPI). METHODS: Among 294 consecutive patients with severe aortic stenosis who underwent TAVR between July 2017 and February 2023, 271 were included in the analysis. As a quantitative evaluation of bulging of the ventricular septum, the ratio of LVOT area to aortic annulus area (L/A ratio) was measured at the systolic phase of computed tomography images. RESULTS: TAVR-related CAVB occurred in 64 patients (23.6%). Twenty-eight patients (10.3%) required PPI. The optimal thresholds of L/A ratio for predicting TAVR-related CAVB and PPI were 1.0181 and 0.985, respectively. Patients with less than the cut-off values had higher rate of TAVR-related CAVB and PPI than those above (28.3% vs 13.1%, p = 0.0063; 14.7% vs 4.4%, p = 0.0077, respectively). A multivariate analysis showed that L/A ratio < 1.0181 was an independent predictor of TAVR-related CAVB (odds ratio [OR] 2.65, p = 0.011), in addition to prior right bundle branch block (OR 3.76, p = 0.0005), use of a self-expanding valve (OR 1.99, p = 0.030), and short membranous septum length (OR 0.96, p = 0.037). Only L/A ratio < 0.985 was independently associated with PPI (OR 3.70, p = 0.011). CONCLUSION: Low L/A ratio is a predictor of TAVR-related CAVB and PPI.

DOI： 10.1016/j.ijcard.2023.131608

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Background: We retrospectively investigated the effects of the severity and classification of sleep-disordered breathing (SDB) on left ventricular (LV) function in patients with ST-segment elevation myocardial infarction (STEMI). Methods: A total of 115 patients with STEMIs underwent a sleep study using a multichannel frontopolar electroencephalography recording device (Sleep Profiler) one week after STEMI onset. We evaluated LV global longitudinal strain (LV-GLS) using two-dimensional echocardiography at one week and seven months. Patients were classified as no SDB (AHI < 5 events/h), obstructive SDB (over 50% of apnea events are obstructive), and central SDB (over 50% of apnea events are central). Due to the device's limitations in distinguishing obstructive from central hypopnea, SDB classification was based on apnea index percentages. Results: The obstructive apnea index (OAI) was significantly associated with LV-GLS at one week (r = 0.24, p = 0.027) and seven months (r = 0.21, p = 0.020). No such correlations were found for the central apnea index and SDB classification. Multivariable regression analysis showed that the OAI was independently associated with LV-GLS at one week (β = 0.24, p = 0.002) and seven months (β = 0.20, p = 0.008). Conclusions: OAI is associated with persistent LV dysfunction assessed by LV-GLS in STEMI.

DOI： 10.3390/jcm13040986

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Language：English  

UNLABELLED: Coronary obstruction is a rare but life-threatening complication of transcatheter aortic valve implantation (TAVI). This article describes the case of a patient with severe aortic valve stenosis treated with TAVI, during which preventive coronary wiring using a pressure wire was performed for coronary protection. After the deployment of the transcatheter heart valve (THV), the values of the fractional flow reserve (FFR) and resting full-cycle ratio (RFR) remarkably decreased, although the findings of transesophageal echocardiography and coronary angiography did not suggest coronary obstruction. Intravascular ultrasound revealed severe stenosis in the left main trunk due to the displacement of the calcified native leaflets. The decrease in the FFR and RFR values after THV deployment led to a diagnosis of partial coronary obstruction, and percutaneous coronary intervention was successfully performed. In patients at a high risk for coronary obstruction, coronary protection with a pressure wire is useful for the diagnosis and prevention of coronary flow deterioration during TAVI. Functional assessment using a pressure wire before and after TAVI may contribute to the accurate diagnosis of coronary obstruction. LEARNING OBJECTIVE: Accurate diagnosis of coronary obstruction during transcatheter aortic valve implantation (TAVI) is important for successful management. In patients at a high risk for coronary obstruction, coronary protection with a pressure wire is useful for the diagnosis and prevention of coronary flow deterioration during TAVI. The remarkable decrease in the fractional flow reserve and resting full-cycle ratio values after the deployment of the transcatheter heart valve may suggest coronary obstruction.

DOI： 10.1016/j.jccase.2023.10.008

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DOI： 10.1016/j.amjcard.2023.12.013

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Patients with refractory cardiogenic shock (CS) necessitating peripheral veno-arterial extracorporeal membrane oxygenation (VA-ECMO) often require an intra-aortic balloon pump (IABP) or Impella for unloading; however, comparative effectiveness data are currently lacking.Methods and Results: Using Diagnosis Procedure Combination data from approximately 1,200 Japanese acute care hospitals (April 2018-March 2022), we identified 940 patients aged ≥18 years with CS necessitating peripheral VA-ECMO along with IABP (ECMO-IABP; n=801) or Impella (ECPella; n=139) within 48 h of admission. Propensity score matching (126 pairs) indicated comparable in-hospital mortality between the ECPella and ECMO-IABP groups (50.8% vs. 50.0%, respectively; P=1.000). However, the ECPella cohort was on mechanical ventilator support for longer (median [interquartile range] 11.5 [5.0-20.8] vs. 9.0 [4.0-16.8] days; P=0.008) and had a longer hospital stay (median [interquartile range] 32.5 [12.0-59.0] vs. 23.0 [6.3-43.0] days; P=0.017) than the ECMO-IABP cohort. In addition, medical costs were higher for the ECPella than ECMO-IABP group (median [interquartile range] 9.09 [7.20-12.20] vs. 5.23 [3.41-7.00] million Japanese yen; P<0.001). CONCLUSIONS: Our nationwide study could not demonstrate compelling evidence to support the superior efficacy of Impella over IABP in reducing in-hospital mortality among patients with CS necessitating VA-ECMO. Further investigations are imperative to determine the clinical situations in which the potential effect of Impella can be maximized.

DOI： 10.1253/circj.CJ-23-0758

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Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

DOI： 10.5551/jat.64988

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND AND AIMS: Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and the risk of cardiovascular events partly due to measurement methods that cannot distinguish between uncleaved and furin-cleaved forms of PCSK9. METHODS: This is a prespecified sub-study of the REAL-CAD study which is a prospective, multicenter, randomized trial to compare high- versus low-dose statin in patients with stable coronary artery disease (CAD). The primary endpoint was major adverse cerebrovascular and cardiovascular events (MACCE) defined as a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. In this case-cohort study, serum mature (uncleaved) and furin-cleaved PCSK9 levels obtained at 6 months after randomization were measured among 426 participants who developed MACCE (cases) and 1,478 randomly selected participants (sub-cohort). RESULTS: From 1,478 patients in the sub-cohort, the Cox proportional hazards models with a pseudolikelihood method for case-cohort design revealed that the risk of the primary endpoint in patients with the highest quartile of mature PCSK9 levels was similar to that in the lowest quartile (hazard ratio [HR] 0.809; 95% confidence intervals [CI], 0.541-1.209). Similarly, the HR for the highest to lowest quartiles of furin-cleaved PCSK9 was 0.948 (95% CI, 0.645-1.392) (P = 0.784). Compared to the lowest quartile, neither serum mature nor furin-cleaved PCSK9 levels predicted MACCE. CONCLUSIONS: In a large-scale secondary prevention cohort, serum mature and furin-cleaved PCSK9 levels did not provide useful information for predicting future cardiovascular events in statin-treated patients with stable CAD.

DOI： 10.1016/j.jacl.2024.07.002

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BACKGROUND: This post hoc subanalysis aimed to investigate the impact of polyvascular disease (PolyVD) in patients with acute myocardial infarction (AMI) in the contemporary era of percutaneous coronary intervention (PCI).Methods and Results: The Japan Acute Myocardial Infarction Registry (JAMIR), a multicenter prospective registry, enrolled 3,411 patients with AMI between December 2015 and May 2017. Patients were classified according to complications of a prior stroke and/or peripheral artery disease into an AMI-only group (involvement of 1 vascular bed [1-bed group]; n=2,980), PolyVD with one of the complications (2-bed group; n=383), and PolyVD with both complications (3-bed group; n=48). The primary endpoint was all-cause death. Secondary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and major bleeding. In the 1-, 2-, and 3-bed groups, the cumulative incidence of all-cause death was 6.8%, 17.5%, and 23.7%, respectively (P<0.001); that of MACE was 7.4%, 16.4%, and 33.8% (P<0.001), respectively; and that of major bleeding was 4.8%, 10.0%, and 13.9% (P<0.001), respectively. PolyVD was independently associated with all-cause death (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.48-3.29), MACE (HR 2.07; 95% CI 1.40-3.07), and major bleeding (HR 1.68; 95% CI 1.04-2.71). CONCLUSIONS: PolyVD was significantly associated with worse outcomes, including thrombotic and bleeding events, in the contemporary era of PCI in AMI patients.

DOI： 10.1253/circj.CJ-23-0477

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Immune checkpoint inhibitors (ICIs) have shown significant efficacy in various cancers, including non-small cell lung cancer, small cell lung cancer, melanoma, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, urothelial cancer, and renal cell carcinoma [...].

DOI： 10.3390/cancers15225487

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Circulation Society  

DOI： 10.1253/circj.cj-23-0141

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Language：English   Publishing type：Research paper (scientific journal)  

Background Contradictions between management modalities of type A acute aortic dissection (TAAAD) and ST-elevation-myocardial infarction (STEMI) may result in clinical catastrophe. Therefore, we aimed to explore which 2-dimensional echocardiography (2DE) findings are optimal for differentiating TAAAD from STEMI. Methods and Results This study included 340 patients with STEMI and 340 patients with TAAAD who underwent 2DE in the emergency department between 2012 and 2021. The proximal ascending aorta (PAA) diameter and other echocardiographic parameters were analyzed. PAA diameters were measured at 4 levels in the parasternal view: Valsalva, the sinotubular junction (STJ), the PAA at 1 cm above the STJ, and the PAA at 2 cm above the STJ. Receiver-operating characteristic curve analysis showed that Valsalva, STJ, PAA at 1 cm above the STJ, and PAA at 2 cm above the STJ were significant predictors of TAAAD (areas under the curve: 0.777, 0.924, 0.965, and 0.975, respectively; P<0.001) with the respective cutoff values of 39.4, 38.5, 39.8, and 41.2 mm. Multivariable analysis suggested that all 2DE parameters were significant predictors of TAAAD. Among the 2DE parameters examined, the incorporation of PAA at 2 cm above the STJ to clinical indicators exhibited the most significant diagnostic capability (C-statistics, 0.97; net reclassification improvement, 1.81; integrated discrimination improvement, 0.61). When only TAAAD with coronary malperfusion and STEMI were analyzed, the diagnostic utility of PAA at 1 cm above the STJ was evident (C-statistics, 0.99; net reclassification improvement, 1.79; integrated discrimination improvement, 0.67), with PAA at 2 cm above the STJ ranking second in diagnostic significance (C-statistics, 0.99; net reclassification improvement, 1.12; integrated discrimination improvement, 0.66). Conclusions PAA measurements were the most beneficial for diagnosing TAAAD in all 2DE findings and TAAAD from STEMI.

DOI： 10.1161/JAHA.123.029506

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AIM: Low-density lipoprotein cholesterol (LDL-C) level reduction is highly effective in preventing the occurrence of a cardiovascular event. Contrariwise, an inverse association exists between LDL-C levels and prognosis in some patients with cardiovascular diseases-the so-called "cholesterol paradox." This study aimed to investigate whether the LDL-C level on admission affects the long-term prognosis in patients who develop acute coronary syndrome (ACS) and to examine factors associated with poor prognosis in patients with low LDL-C levels. METHODS: We enrolled 410 statin-naïve patients with ACS, whom we divided into low- and high-LDL-C groups based on an admission LDL-C cut-off (obtained from the Youden index) of 122 mg/dL. Endothelial function was assessed using the reactive hyperemia index 1 week after statin initiation. The primary composite endpoint included all-cause death, as well as myocardial infarction and ischemic stroke occurrences. RESULTS: During a median follow-up period of 6.1 years, 76 patients experienced the primary endpoint. Multivariate Cox regression analysis revealed that patients in the low LDL-C group had a 2.3-fold higher risk of experiencing the primary endpoint than those in the high LDL-C group (hazard ratio, 2.34; 95% confidence interval, 1.29-4.27; p=0.005). In the low LDL-C group, slow gait speed (frailty), elevated chronic-phase high-sensitivity C-reactive protein levels (chronic inflammation), and endothelial dysfunction were significantly associated with the primary endpoint. CONCLUSIONS: Patients with low LDL-C levels at admission due to ACS had a significantly worse long-term prognosis than those with high LDL-C levels; frailty, chronic inflammation, and endothelial dysfunction were poor prognostic factors.

DOI： 10.5551/jat.64368

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Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.

DOI： 10.1161/JAHA.123.030412

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.amjcard.2023.08.043

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jacc.2023.10.013

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Pulmonary hypertension (PH) has recently been described as a complex clinical syndrome affecting multiple organ systems, including the heart, lungs, and skeletal muscle, each of which plays an important role in exercise capacity. However, the relationship between exercise capacity and skeletal muscle abnormalities in patients with PH has not been fully elucidated. METHODS: We retrospectively analysed the exercise capacity and measures of skeletal muscle of 107 patients with PH without left heart disease (mean age 63 ± 15 years, 32.7% males, n = 30/6/66/5 in the clinical classification Group 1/3/4/5). RESULTS: Sarcopenia, low appendicular skeletal muscle mass index, low grip strength, and slow gait speed, determined by international criteria, were found in 15 (14.0%), 16 (15.0%), 62 (57.9%), and 41 (38.3%) patients, respectively. The mean 6-min walk distance of all patients was 436 ± 134 m and was independently associated with sarcopenia (standardised β = -0.292, p < 0.001). All patients with sarcopenia showed reduced exercise capacity defined as 6-min walk distance < 440 m. Multivariable logistic regression analysis showed that each of the components of sarcopenia was associated with reduced exercise capacity (adjusted odds ratio and 95% confidence interval of appendicular skeletal muscle mass index: 0.39 [0.24-0.63] per 1 kg/m2, p = 0.006, grip strength: 0.83 [0.74-0.94] per 1 kg, p = 0.003, and gait speed: 0.31 [0.18-0.51] per 0.1 m/s, p < 0.001). CONCLUSIONS: Sarcopenia and its components are associated with reduced exercise capacity in patients with PH. A multifaceted evaluation may be important in the management of reduced exercise capacity in patients with PH.

DOI： 10.1016/j.ijcard.2023.06.006

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Intravascular ultrasound (IVUS) provides precise anatomic information in coronary arteries including quantitative measurements and morphological assessment. To standardize the IVUS analysis in the current era, this updated expert consensus document summarizes the methods of measurements and assessment of IVUS images and the clinical evidence of IVUS use in percutaneous coronary intervention.

DOI： 10.1007/s12928-023-00957-4

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Other Link： https://link.springer.com/article/10.1007/s12928-023-00957-4/fulltext.html

Language：Japanese   Publisher：日本内科学会-関東地方会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(一社)日本心臓病学会  

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Language：Japanese   Publisher：(NPO)日本高血圧学会  

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Background

New‐generation drug‐eluting stents (DES) achieved technological innovations and reported clinical advantages as compared with first‐generation DES in clinical trials with 3–5 years follow‐up. However, detailed clinical outcome data in very long‐term follow‐up is still scarce.

Objectives

To evaluate 10‐year clinical outcomes after first‐ and new‐generation DES implantation.

Methods

In this extende follow‐up study of the RESET, which is a largest randomized trial comparing everolimus‐eluting stent (EES) with Sirolimus‐eluting stent (SES), the study population consisted of 2892 patients from 84 centers. The primary efficacy and safety endpoints were target lesion revascularization (TLR) and a composite of death or myocardial infarction (MI), respectively. Complete 10‐year follow‐up was achieved in 87.9% of patients.

Results

Cumulative 10‐year incidences of TLR and non‐TLR were not significantly different between EES and SES (13.9% vs. 15.7%, Log‐rank p = 0.20, and 33.4% vs. 31.3%, Log‐rank p = 0.30). The cumulative 10‐year incidence of death/MI was also not significantly different between the groups (32.5% vs. 34.4%, Log‐rank p = 0.18). Cumulative 10‐year incidence of definite stent thrombosis was numerically lower in EES than in SES (1.0% vs. 1.7%, Log‐rank p = 0.16). The lower risk of EES relative to SES was significant for a composite endpoint of target lesion failure (TLF: 19.6% vs. 24.9%, Log‐rank p = 0.001) and target vessel failure (TVF: 26.7% vs. 31.4%, Log‐rank p = 0.006).

Conclusion

During 10‐year of follow‐up, the risks for primary efficacy and safety endpoints were not significantly different between new‐generation EES and first‐generation SES, although EES compared with SES was associated with a lower risk for composite endpoints such as TLF and TVF.

DOI： 10.1002/ccd.30791

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BACKGROUND: This study aimed to investigate the effect of glycemic variability (GV), determined using a continuous glucose monitoring system (CGMS), on left ventricular reverse remodeling (LVRR) after ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 201 consecutive patients with STEMI who underwent reperfusion therapy within 12 h of onset were enrolled. GV was measured using a CGMS and determined as the mean amplitude of glycemic excursion (MAGE). Left ventricular volumetric parameters were measured using cardiac magnetic resonance imaging (CMRI). LVRR was defined as an absolute decrease in the LV end-systolic volume index of > 10% from 1 week to 7 months after admission. Associations were also examined between GV and LVRR and between LVRR and the incidence of major adverse cardiovascular events (MACE; cardiovascular death, acute coronary syndrome recurrence, non-fatal stroke, and heart failure hospitalization). RESULTS: The prevalence of LVRR was 28% (n = 57). The MAGE was independent predictor of LVRR (odds ratio [OR] 0.98, p = 0.002). Twenty patients experienced MACE during the follow-up period (median, 65 months). The incidence of MACE was lower in patients with LVRR than in those without (2% vs. 13%, p = 0.016). CONCLUSION: Low GV, determined using a CGMS, was significantly associated with LVRR, which might lead to a good prognosis. Further studies are needed to validate the importance of GV in LVRR in patients with STEMI.

DOI： 10.1186/s12933-023-01931-3

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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BACKGROUND: The ability to predict secondary cardiovascular events could improve health of patients undergoing statin treatment. Circulating ANGPTL8 (angiopoietin-like protein 8) levels, which positively correlate with proatherosclerotic lipid profiles, activate the pivotal proatherosclerotic factor ANGPTL3. Here, we assessed potential association between circulating ANGPTL8 levels and risk of secondary cardiovascular events in statin-treated patients. METHODS: We conducted a biomarker study with a case-cohort design, using samples from a 2018 randomized control trial known as randomized evaluation of high-dose (4 mg/day) or low-dose (1 mg/day) lipid-lowering therapy with pitavastatin in coronary artery disease (REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease])." From that study's full analysis set (n=12 413), we selected 2250 patients with stable coronary artery disease (582 with the primary outcome, 1745 randomly chosen, and 77 overlapping subjects). A composite end point including cardiovascular-related death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergent admission was set as a primary end point. Circulating ANGPTL8 levels were measured at baseline and 6 months after randomization. RESULTS: Over a 6-month period, ANGPTL8 level changes significantly decreased in the high-dose pitavastatin group, which showed 19% risk reduction of secondary cardiovascular events compared with the low-dose group in the REAL-CAD [Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy With Pitavastatin in Coronary Artery Disease] study. In the highest quartiles, relative increases in ANGPTL8 levels were significantly associated with increased risk for secondary cardiovascular events, after adjustment for several cardiovascular disease risk factors and pitavastatin treatment (hazard ratio in Q4, 1.67 [95% CI, 1.17-2.39). Subgroup analyses showed relatively strong relationships between relative ANGPTL8 increases and secondary cardiovascular events in the high-dose pitavastatin group (hazard ratio in Q4, 2.07 [95% CI, 1.21-3.55]) and in the low ANGPTL8 group at baseline (166 <pmol/L, hazard ratio in Q4: 1.74, [95% CI, 1.04-2.93]). CONCLUSIONS: Monitoring ANGPTL8 levels over time might be useful to assess residual risk of cardiovascular secondary events in patients with cardiovascular disease undergoing statin therapy.

DOI： 10.1161/ATVBAHA.122.318880

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jacasi.2023.03.013

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publisher：(一社)日本心血管インターベンション治療学会  

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: This study aimed to examine whether high-sensitivity cardiac troponin-I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) could predict future major adverse cardiovascular events (MACE) in stable coronary artery disease (CAD) patients with high- or low-dose of pitavastatin. METHODS: This was a case-cohort analysis of the REAL-CAD study, a randomized trial of high- or low-dose (4 or 1 mg/day) pitavastatin therapy in patients with stable CAD. We examined the MACE risk according to the quartile of hsTnI and NT-proBNP at baseline. RESULTS: A total of 1336 and 1396 patients including 582 MACE cases were randomly examined into the hsTnI and NT-proBNP cohort, respectively. Both higher levels of hsTnI and NT-proBNP at baseline were significantly associated with increased risk of MACE (p < 0.001, respectively). When separately analyzed in statin dose, the higher marker levels were significantly associated with higher MACE risk in all cohorts (p < 0.001 in all cohorts). After multivariable adjustment, hsTnI levels were significantly associated with MACE risk in low-dose statin group (HR 2.54, p = 0.0001); however, in high-dose pitavastatin therapy, a significant association was diminished in MACE risk among the quartiles of baseline hsTnI levels (p = 0.154). Conversely in the NT-proBNP cohort, the association between NT-proBNP levels and MACE risk was constantly observed regardless of pitavastatin dose even after multivariable adjustment (both p < 0.0001). CONCLUSIONS: Patients with high hsTnI levels had high risk of MACE in low-dose statin group, but not in high-dose, suggesting that high-dose statin treatment might decrease MACE risk in stable CAD patients with high hsTnI levels.

DOI： 10.1016/j.ijcard.2023.131138

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Language：Japanese   Publisher：日本肺高血圧・肺循環学会  

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Language：Japanese   Publisher：日本肺高血圧・肺循環学会  

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Language：Japanese   Publisher：日本肺高血圧・肺循環学会  

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Objectives Although malignant lymphoma (ML) can occur in every organ, diagnosing cardiac involvement without cardiac manifestations is difficult. We therefore investigated the incidence of cardiac involvement in ML in our hospital and clarified the transthoracic echocardiography (TTE) findings of cardiac involvement. Methods Patients with ML referred to our hospital between January 2013 and December 2019 were retrospectively reviewed. Patients During the study period, 453 patients were identified. The mean age was 64.9 years old, and 54% of the patients were men. Results Diffuse large B-cell lymphoma (DLBCL) was the most common lymphoma, followed by follicular lymphoma. Of the 453 patients, 394 (87.0%) underwent TTE at the initial diagnosis or during the clinical course. The performance rates of TTE in DLBCL, Hodgkin lymphoma, and mantle cell lymphoma were above 90%. Cardiac involvement was detected in 6 (five with DLBCL and one with B-cell lymphoma) (1.5%) of the 394 patients who underwent TTE. The involved lesions of the heart varied, and five patients had pericardial effusion. Five patients had a preserved left ventricular ejection fraction. All patients were treated with chemotherapy, and some were treated with radiation and surgery. Conclusion Cardiac involvement was observed in six (1.5%) of the patients with ML who underwent TTE. B-cell lymphoma, especially DLBCL, is a common ML with cardiac involvement. Although five patients had pericardial effusion, the involved lesions of the heart were not uniform. TTE is a useful imaging modality to noninvasively and repeatedly evaluate the tumor characteristics, response to ML treatment, and cardiac function.

DOI： 10.2169/internalmedicine.1902-23

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BACKGROUND: Several stent expansion criteria derived from the intravascular ultrasound (IVUS) evaluation have been proposed to predict future clinical outcomes, but optimal stent expansion criteria as a guide during percutaneous coronary intervention (PCI) are still controversial. There are no studies evaluating the utility of stent expansion criteria along with the clinical and procedural factors in predicting target lesion revascularization (TLR) after contemporary IVUS-guided PCI. METHODS: OPTIVUS-Complex PCI study (Optimal Intravascular Ultrasound Guided Complex Percutaneous Coronary Intervention) multivessel cohort was a prospective multicenter study enrolling 961 patients undergoing multivessel PCI including left anterior descending coronary artery using IVUS with an intention to meet the prespecified criteria for optimal stent expansion. We compared several stent expansion criteria (minimum stent area [MSA], MSA/distal or average reference lumen area, MSA/distal or average reference vessel area, OPTIVUS criteria, IVUS-XPL [Impact of Intravascular Ultrasound Guidance on Outcomes of Xience Prime Stents in Long Lesions] criteria, ULTIMATE [Intravascular Ultrasound Guided Drug Eluting Stents Implantation in "All-Comers" Coronary Lesions] criteria, and modified MUSIC [Multicenter Ultrasound Stenting in Coronaries Study] criteria) as well as clinical, angiographic, and procedural characteristics between lesions with and without TLR. RESULTS: Among 1957 lesions, the cumulative 1-year incidence of lesion-based TLR was 1.6% (30 lesions). Hemodialysis, treatment of proximal left anterior descending coronary artery lesions, calcified lesions, small proximal reference lumen area, and small MSA had univariate associations with TLR, while all of the stent expansion criteria except for MSA were not associated with TLR. The independent risk factors of TLR were calcified lesions (hazard ratio, 2.34 [95% CI, 1.03-5.32]; P=0.04) and small proximal reference lumen area (Tertile 1: hazard ratio, 7.01 [95% CI, 1.45-33.93]; P=0.02; and Tertile 2: hazard ratio, 5.40 [95% CI, 1.17-24.90]; P=0.03). CONCLUSIONS: In contemporary IVUS-guided PCI practice, the 1-year incidence of TLR was very low. MSA, but not other stent expansion criteria, had univariate association with TLR. Independent risk factors of TLR were calcified lesions and small proximal reference lumen area, although the findings should be interpreted with caution due to small number of TLR events, limited lesion complexity, and short duration of follow-up.

DOI： 10.1161/CIRCINTERVENTIONS.123.012922

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BACKGROUNDS: Recently, there has been increasing awareness that bleeding may lead to adverse outcomes. Endothelial dysfunction is associated with increased risk of cardiovascular and bleeding events. This study aimed to investigate the association of endothelial dysfunction with major bleeding and specific causes of death in addition to major adverse cardiovascular events in patients with acute coronary syndrome. METHODS: This single-centre retrospective observational study was conducted at a tertiary-care hospital; patients with acute coronary syndrome were included between June 2010 and November 2014 (median follow-up, 6.1 years). The reactive hyperaemia index was assessed before their discharge; reactive hyperaemia index <1.67 was defined as endothelial dysfunction. The main outcomes were the incidence of major bleeding, all-cause death, cardiovascular death, non-cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, and hospitalisation for heart failure. RESULTS: Among the included 674 patients with acute coronary syndrome, 264 (39.2%) had endothelial dysfunction. Multivariable Cox-hazard analyses revealed an independent predictive value of endothelial dysfunction for major bleeding (hazard ratio 2.29, 95% confidence interval 1.17-4.48, P = 0.016) and major adverse cardiovascular events (hazard ratio 2.04, 95% confidence interval 1.43-2.89, P < 0.001). The endothelial dysfunction group patients had a 2.5-fold greater risk of cardiovascular death; however, no association was found with non-cardiovascular death. CONCLUSION: Endothelial dysfunction assessed using reactive hyperaemia index predicted future major cardiovascular event as well as major bleeding and cardiovascular death in patients with acute coronary syndrome.

DOI： 10.1016/j.ijcard.2023.01.079

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.iccl.2022.10.003

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BACKGROUND: Intravascular ultrasound (IVUS) was only rarely used in landmark trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel disease. OBJECTIVES: The authors aimed to evaluate clinical outcomes after optimal IVUS-guided PCI in patients undergoing multivessel PCI. METHODS: The OPTIVUS (OPTimal IntraVascular UltraSound)-Complex PCI study multivessel cohort was a prospective multicenter single-arm study enrolling 1,021 patients undergoing multivessel PCI, including left anterior descending coronary artery using IVUS, aiming to meet the prespecified criteria (OPTIVUS criteria: minimum stent area > distal reference lumen area [stent length ≥28mm], and minimum stent area >0.8 × average reference lumen area [stent length <28mm]) for optimal stent expansion. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE) (death/myocardial infarction/stroke/any coronary revascularization). The predefined performance goals were derived from the CREDO-Kyoto (Coronary REvascularization Demonstrating Outcome study in Kyoto) PCI/CABG registry cohort-2 fulfilling the inclusion criteria in this study. RESULTS: In this study, 40.1% of the patients met OPTIVUS criteria in all stented lesions. The cumulative 1-year incidence of the primary endpoint was 10.3% (95% CI: 8.4%-12.2%), which was significantly lower than the predefined PCI performance goal of 27.5% (P < 0.001), and which was numerically lower than the predefined CABG performance goal of 13.8%. The cumulative 1-year incidence of the primary endpoint was not significantly different regardless of meeting or not meeting OPTIVUS criteria. CONCLUSIONS: Contemporary PCI practice conducted in the OPTIVUS-Complex PCI study multivessel cohort was associated with a significantly lower MACCE rate than the predefined PCI performance goal, and with a numerically lower MACCE rate than the predefined CABG performance goal at 1 year.

DOI： 10.1016/j.jacasi.2022.12.009

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.7759/cureus.36446

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Language：English   Publishing type：Research paper (scientific journal)  

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

DOI： 10.1253/circj.CJ-22-0837

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DOI： 10.1007/s10157-023-02323-3

Web of Science

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There are 3 main reasons to promote the practical application of IVUS during PCI. First reason is to understand the mechanism of vessel dilatation. Even if angiographic stenoses are similar, their pathophysiologies are different. It is important to understand what can happen by dilating coronary artery with balloon/stent, and to develop a strategy to achieve the maximum effect. Second reason is to anticipate possible complications and to reduce them in advance. In that case, we can deal with it as calmly as possible. Third reason is to validate the PCI performed. This should lead to further improvements of the procedures, which in turn will lead to improved short- and long-term prognosis. Then, high-quality PCI could be possible. This review summarizes the standard usage of IVUS in routine clinical practice and the use of IVUS in specific situations, especially complex lesions.

DOI： 10.1007/s12928-022-00892-w

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DOI： 10.1007/s12928-022-00894-8

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BACKGROUND: The optimal endpoint after balloon angioplasty remains poorly defined. This study aimed to characterize post-balloon angioplasty anatomical and physiological indexes by quantitative flow ratio (QFR) and to compare their prognostic impacts on long-term clinical outcomes. METHODS: This retrospective study included 106 lesions from 106 patients who underwent percutaneous coronary interventions with drug-coated-balloon (n = 69) or plain-old-balloon-angioplasty (n = 37). Analyses measured minimum lumen diameter (MLD) and percent diameter stenosis (%DS) as anatomical indexes; QFR of target vessel (QFR-vessel) and QFR-gradient (ΔQFR between proximal and distal segments of the lesion) as physiological indexes. Primary endpoint was target lesion revascularization (TLR) after the index procedure. RESULTS: TLR occurred in 21 (20 %) lesions. TLR group showed significantly smaller QFR-vessel (0.79 ± 0.12 vs. 0.85 ± 0.12, p = 0.03), as well as greater QFR-gradient (0.12 ± 0.07 vs. 0.04 ± 0.03, p < 0.0001) at post-procedure compared with non-TLR group. The percentage of angiographically significant dissection was also more frequently observed in TLR group compared with non-TLR group (47.6 % vs. 14.1 %, p < 0.0001 for log-rank). In the multivariate analysis, angiographically significant dissection and QFR-gradient at post-procedure was significantly associated with TLR. In the receiver-operating characteristics curve analysis, the area under the curve for predicting post-procedural TLR was significantly greater for QFR-gradient than for MLD and residual %DS (p < 0.0001 for MLD and p = 0.0003 for residual %DS at post-procedure). The best cut-off value of post-procedural QFR-gradient for predicting TLR was 0.08. CONCLUSIONS: Post-procedural QFR-gradient across the lesion was a statistically independent and stronger predictor of TLR, compared with anatomical indexes.

DOI： 10.1016/j.jjcc.2022.07.007

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Publishing type：Research paper (scientific journal)   Publisher：Ovid Technologies (Wolters Kluwer Health)  

Background:

Rapidly progressive, extensive myocardial injury/infarction (RPEMI) beyond the concept of wave-front phenomenon can be observed even when achieving timely reperfusion; however, the pathogenesis of RPEMI remains unknown. This retrospective study investigated clinical and lesion characteristics of RPEMI, focusing on culprit-lesion morphology (CLM).

Methods:

Among patients with extensive anterior-wall ST-segment elevation myocardial infarction due to proximal left anterior descending artery lesions who had reperfusion within 3 hours of symptom onset, 60 patients undergoing both intravascular ultrasound and cardiac magnetic resonance imaging were enrolled. Myocardial injury/infarction before reperfusion therapy was assessed by QRS scores at hospitalization electrocardiogram, and the extent of myocardial injury/infarction was evaluated by cardiac magnetic resonance imaging, which measured area at risk, infarct size, myocardial salvage index, microvascular obstruction, and left ventricular ejection fraction. RPEMI was defined as lower left ventricular ejection fraction (less median value) with microvascular obstruction.

Results:

Despite comparable onset-to-door and onset-to-reperfusion times and area at risk, patients with RPEMI showed higher QRS scores at hospitalization (5 [4.3–6] versus 3 [2–4], P &lt;0.001) and infarct size (26.5±9.1 versus 20.4±10.5%, P =0.04), and a tendency toward lower myocardial salvage index (0.27±0.14 versus 0.36±0.20, P =0.10) compared with those without. Patients with versus without RPEMI more frequently observed specific CLM on intravascular ultrasound, characterized by the combination of vulnerable plaques, plaque ruptures, and/or large thrombi. When stratified by CLM-score composed of these 3 criteria, higher CLM-scores were or tended to be associated with higher QRS scores and incidence of RPEMI. In multivariate analyses including no-reflow phenomenon and final coronary-flow deterioration, increased CLM-score (≥2) was independently associated with high QRS scores and RPEMI (odd ratio 11.25 [95% CI, 2.43–52.00]; P =0.002).

Conclusions:

Vulnerable CLM was a consistent determinant of advanced myocardial injury/infarction both before and after reperfusion therapy and may play a pivotal role in the development of RPEMI.

DOI： 10.1161/circimaging.122.014497

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AIMS: Reduced skeletal muscle mass is a major component of sarcopenia, associated with impaired exercise capacity and poor prognosis in patients with heart failure (HF). Measurement of skeletal muscle mass by dual-energy X-ray absorptiometry may be affected by fluid retention, typically in the patients' lower extremities. The aim of the present study was to elucidate the association between upper and lower extremity skeletal muscle mass (USM and LSM) and all-cause mortality in hospitalized patients with HF, after discharge. METHODS: This was a single-centre observational cohort study of 418 patients (59% were men) admitted with a diagnosis of HF (71 ± 13 years), with a left ventricular ejection fraction of 39 ± 16%. USM and LSM were measured by dual-energy X-ray absorptiometry with patients in a stable state after decongestion therapy. RESULTS: The USM and LSM were 5.29 ± 1.18 and 13.78 ± 3.20 kg for men and 3.37 ± 0.68 and 9.19 ± 1.80 kg for women. A positive correlation was obtained between USM and LSM with mid-upper arm circumference (r = 0.684, P < 0.001) and calf circumference (r = 0.822, P < 0.001), respectively. During a median follow-up of 37 months, 92 (22.0%) of the 418 patients died. A Kaplan-Meier analysis revealed that sex-specific quartiles of USM/height2 and LSM/height2 were associated with all-cause mortality (both P < 0.001 by the log-rank test). In Cox models adjusted by age, sex, creatinine, haemoglobin, NYHA class, and height2 , the hazard ratio with 95% confidence intervals for all-cause mortality was 0.557 [0.393-0.783] (P < 0.001) for USM per 1 kg, and 0.783 [0.689-0.891] (P < 0.001) for LSM per 1 kg. The receiver-operator-characteristic curve analysis showed a comparable area under the curve between the USM/height2 and LSM/height2 (0.557 vs. 0.568, P = 0.562) in predicting all-cause mortality. The ratio of USM to LSM was significantly lower in 37 patients with residual leg oedema than in the 360 patients without oedema (36.1% vs. 38.1%, P = 0.004), suggesting the influence of oedema on measured LSM. CONCLUSIONS: Both USM and LSM had a prognostic implication on mortality after discharge in HF, even though LSM may have been affected by leg oedema. These findings indicate that clinicians should not ignore a patient's USM or LSM in the prognostication of patients with HF.

DOI： 10.1002/ehf2.14195

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BACKGROUND: Statins have been shown to prevent microvascular dysfunction that may cause periprocedural myocardial infarction after percutaneous coronary intervention (PCI). Evolocumab has more potent lipid-lowering properties than statins. AIMS: The aims of this study were to investigate whether evolocumab pretreatment on top of statin therapy could prevent periprocedural microvascular dysfunction. METHODS: This study included 100 patients with stable coronary artery disease who were scheduled to undergo PCI and had high low-density lipoprotein cholesterol (LDL-C) under statin therapy. Patients were randomised to receive evolocumab 140 mg every 2 weeks for 2 to 6 weeks before PCI (evolocumab group: N=54) or not (control group: N=46). The primary endpoint was the index of microvascular resistance (IMR) after PCI. Troponin T was measured before and 24 hours after PCI. RESULTS: Geometric mean LDL-C was 94.1 (95% confidence interval [CI]: 86.8-102.1) mg/dl and 89.4 (95% CI: 83.5-95.7) mg/dl at baseline, and 25.6 (95% CI: 21.9-30.0) mg/dl and 79.8 (95% CI: 73.9-86.3) mg/dl before PCI, in the evolocumab group and in the control group, respectively. PCI was performed 22.1±8.5 days after allocation. Geometric mean IMR was 20.6 (95% CI: 17.2-24.6) in the evolocumab group and 20.6 (95% CI: 17.0-25.0) in the control group (p=0.98). There was no significant difference in the geometric mean of post-PCI troponin T (0.054, 95% CI: 0.041-0.071 ng/ml vs 0.054, 95% CI: 0.038-0.077 ng/ml; p=0.99) and in the incidence of major periprocedural myocardial infarction between the 2 groups (44.4% vs 44.2%; p=1.00). CONCLUSIONS: Evolocumab pretreatment did not prevent periprocedural microvascular dysfunction in patients on modern medical management with statins.

DOI： 10.4244/EIJ-D-22-00269

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DOI： 10.1253/circj.CJ-22-0417

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AIM: We investigated the relationship between small dense low-density cholesterol (sdLDL-C) and risk of major adverse cardiovascular events (MACE) in patients treated with high- or low-dose statin therapy. METHODS: This was a prospective case-cohort study within the Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study, a randomized trial of high- or low-dose (4 or 1 mg/d pitavastatin, respectively) statin therapy, in patients with stable coronary artery disease (CAD). Serum sdLDL-C was determined using an automated homogenous assay at baseline (randomization after a rule-in period, ＞1 month with 1 mg/d pitavastatin) and 6 months after randomization, in 497 MACE cases, and 1543 participants randomly selected from the REAL-CAD study population. RESULTS: High-dose pitavastatin reduced sdLDL-C by 20% than low-dose pitavastatin (p for interaction ＜0.001). Among patients receiving low-dose pitavastatin, baseline sdLDL-C demonstrated higher MACE risk independent of LDL-C (hazard ratio [95% confidence interval], 4th versus 1st quartile, 1.67 [1.04-2.68]; p for trend=0.034). High-dose (versus low-dose) pitavastatin reduced MACE risk by 46% in patients in the highest baseline sdLDL-C quartile (＞34.3 mg/dL; 0.54 [0.36-0.81]; p=0.003), but increased relative risk by 40% in patients with 1st quartile (≤ 19.5 mg/dL; 1.40 [0.94-2.09]; p=0.099) and did not alter risk in those in 2nd and 3rd quartiles (p for interaction=0.002). CONCLUSIONS: These findings associate sdLDL-C and cardiovascular risk, independent of LDL-C, in statin-treated CAD patients. Notably, high-dose statin therapy reduces this risk in those with the highest baseline sdLDL-C.

DOI： 10.5551/jat.63229

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Since optical coherence tomography (OCT) was first performed in humans two decades ago, this imaging modality has been widely adopted in research on coronary atherosclerosis and adopted clinically for the optimization of percutaneous coronary intervention. In the past 10 years, substantial advances have been made in the understanding of in vivo vascular biology using OCT. Identification by OCT of culprit plaque pathology could potentially lead to a major shift in the management of patients with acute coronary syndromes. Detection by OCT of healed coronary plaque has been important in our understanding of the mechanisms involved in plaque destabilization and healing with the rapid progression of atherosclerosis. Accurate detection by OCT of sequelae from percutaneous coronary interventions that might be missed by angiography could improve clinical outcomes. In addition, OCT has become an essential diagnostic modality for myocardial infarction with non-obstructive coronary arteries. Insight into neoatherosclerosis from OCT could improve our understanding of the mechanisms of very late stent thrombosis. The appropriate use of OCT depends on accurate interpretation and understanding of the clinical significance of OCT findings. In this Review, we summarize the state of the art in cardiac OCT and facilitate the uniform use of this modality in coronary atherosclerosis. Contributions have been made by clinicians and investigators worldwide with extensive experience in OCT, with the aim that this document will serve as a standard reference for future research and clinical application.

DOI： 10.1038/s41569-022-00687-9

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BACKGROUND: The role of left atrial (LA) function in the long-term prognosis of ST-elevation acute myocardial infarction (STEMI) is still unclear.Methods and Results: Percutaneous coronary intervention (PCI) was performed in 433 patients with the first episode of STEMI within 12 h of onset. The patients underwent echocardiography 24 h after admission. LA reservoir strain and other echocardiographic parameters were analyzed. Follow up was performed for up to 10 years (mean duration, 91 months). The primary endpoint was major adverse cardiovascular events (MACE): cardiac death or hospitalization due to heart failure (HF). MACE occurred in 90 patients (20%) during the follow-up period. Multivariate Cox hazard analyses showed LA reservoir strain, global longitudinal strain (GLS), age and maximum B-type natriuretic peptide (BNP) were the significant predictors of MACE. Kaplan-Meier curves demonstrated that LA reservoir strain <25.8% was a strong predictor (Log rank, χ2=76.7, P<0.0001). Net reclassification improvement (NRI) demonstrated that adding LA reservoir strain had significant incremental effect on the conventional parameters (NRI and 95% CI: 0.24 [0.11-0.44]) . When combined with GLS >-11.5%, the patients with LA reservoir strain <25.8% were found to be at extremely high risk for MACE (Log rank, χ2=126.3, P<0.0001). CONCLUSIONS: LA reservoir strain immediately after STEMI onset was a significant predictor of poor prognosis in patients, especially when combined with GLS.

DOI： 10.1253/circj.CJ-21-0907

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BACKGROUND: The aim of this study was to create a risk scoring model to differentiate obstructive coronary artery (CA) from CA spasm in the etioology of acute coronary syndrome (ACS).Methods and Results: We included 753 consecutive patients with ACS without persistent ST-segment elevation (p-STE). The exclusion criteria were: (1) out-of-hospital cardiac arrest; (2) cardiogenic shock; (3) hemodialysis; (4) atrial fibrillation/flutter; (5) severe valvular disease; (6) no coronary angiography; (7) non-obstructive coronary artery without "definite" vasospastic angina definition; and/or (8) missing data. From the multivariate logistic regression analysis for prediction of obstructive CA, an integer score of 2 to each 0.5 increment in odds ratio was given, and values were divided into quartiles according to the total score. The scores were as follows: age >70 years (6 points), non-STE myocardial infarction (9 points), diabetes mellitus (5 points), B-type natriuretic peptide >90 pg/mL (7 points), neutrophil to lymphocyte ratio >2 (5 points), and high-density lipoprotein cholesterol <50 mg/dL (5 points). CA spasm-induced ACS occurred in 50.0% in Quartile 1 (total score: 0-13), 20.5% in Quartile 2 (total score: 14-19), 4.9% in Quartile 3 (total score: 20-26), and 2.2% in Quartile 4 (total score: 27-37) (P<0.001), indicating that a total score of <20 was a potential clinical indicator of CA spasm-induced ACS. CONCLUSIONS: CA spasm-induced ACS should be suspected if a total score of <20, and a spasm provocation test was being considered.

DOI： 10.1253/circj.CJ-22-0096

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OBJECTIVE: This study aimed to investigate the possible influence of arterial stiffness assessed by the cardio-ankle vascular index (CAVI) on chronic-phase left ventricular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: A total of 208 consecutive patients with first STEMI (age, 64 ± 11 years; 86% men) who underwent reperfusion therapy within 12 h of onset were enrolled. We analysed arterial stiffness by measuring CAVI in a stable phase after admission and performed two-dimensional echocardiography at baseline and 7 months' follow-up. Subsequently, we assessed left ventricular global longitudinal strain (LV-GLS) to evaluate left ventricular function. A total of 158 (75.9%) patients underwent baseline cardiac magnetic resonance (CMR). We estimated left ventricular infarct size by measuring peak levels of creatine kinase-myocardial band (CK-MB), and CMR-late gadolinium enhancement (LGE). RESULTS: On the basis of the median CAVI value, the patients were allocated into high CAVI (CAVI ≥ 8.575) and low CAVI (CAVI < 8.575) groups. The groups showed no statistically significant differences in LV-GLS at baseline (-13.5% ± 3.1 vs. -13.9% ± 2.7%, P  = 0.324). However, LV-GLS was significantly worse in the high CAVI group than in the low-CAVI group at 7 months (-14.0% ± 2.9 vs. -15.6% ± 3.0%, P  < 0.001). Stratified by CAVI and peak CK-MB or LGE, the four groups showed significant differences in LV-GLS at 7 months after STEMI (both P  < 0.001). Multivariate linear regression analysis with the forced inclusion model showed that CAVI was an independent predictor of LV-GLS at 7 months ( P  = 0.015). CONCLUSION: CAVI early after STEMI onset was significantly associated with chronic-phase LV-GLS. In addition, combining CAVI with CK-MB or LGE improves its predictive ability for evaluation of chronic-phase LV-GLS. Thus, the arterial stiffness assessment by CAVI was an important factor related to chronic-phase left ventricular dysfunction after the first STEMI.

DOI： 10.1097/HJH.0000000000003165

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The early and mid-term arterial healing profile of biodegradable polymer-coated everolimus-eluting stents (BP-EES) is unclear, especially in ST-segment elevation myocardial infarction (STEMI) culprit lesions. This study aimed to compare early- and mid-term arterial healing between durable polymer-coated everolimus-eluting stents (DP-EES) and BP-EES in STEMI patients. In a prospective, multicenter, non-inferiority trial, STEMI patients were randomized to receive BP-EES (n = 60) or DP-EES (n = 60). The primary endpoint of this study was the mean percentage of covered struts (%covered struts) on FD-OCT 2 weeks post-PCI. Key secondary endpoints included the percentage of uncovered struts, frequency of abnormal intra-stent tissue, and percentage of malapposed struts by FD-OCT 2 weeks and 12 months post-PCI. They underwent serial frequency-domain optical coherence tomography (FD-OCT) evaluations immediately after percutaneous coronary intervention, and at 2 weeks and at 12 months after the procedure. The primary endpoint of %covered struts at 2 weeks was 71.4% in BP-EES and 72.3% in DP-EES [risk difference - 0.94%, lower limit of one-sided 95% confidence interval (CI) - 5.6; Pnon-inferiority = 0.0756]. At 12 months, the mean percentage of uncovered struts was significantly lower [1.73% (95% CI 0.28-3.17) vs. 4.81% (95% CI 3.52-6.09); p = 0.002], and the average malapposed volume was significantly smaller in the BP-EES group than in the DP-EES group (p = 0.002). At 12 months, BP-EES had a significantly larger average neointimal area with a significantly smaller average intra-stent tissue unevenness score than DP-EES, suggesting more uniform neointimal coverage with BP-EES. Strut coverage was comparable between BP-EES and DP-EES at 2 weeks. Non-inferiority could not be proven because of an insufficient sample size. The significantly better arterial healing with BP-EES at 12 months suggests a safer profile for STEMI culprit lesions.Trial registration: jRCTs022180024 https://jrct.niph.go.jp/en-latest-detail/jRCTs022180024.

DOI： 10.1007/s12928-022-00879-7

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Balloon aortic valvuloplasty (BAV) was developed as a technique to treat aortic stenosis (AS) and is associated with significant improvements in aortic valve area and trans-aortic valve gradient in the early and immediate periods after the procedure. BAV is commonly performed using a trans-femoral retrograde approach; however, trans-femoral access is associated with frequent access-site bleeding. Among 146 patients with symptomatic severe AS who were treated with BAV in our institution, 123 patients received BAV treatment via a trans-radial approach using a 7-Fr Glidesheath. The balloon size was 16-20 mm for all patients. Echocardiograms were obtained before and after BAV. Patients who received BAV alone (n = 119) were followed up for 3 months, and major adverse events (stroke, re-hospitalization for heart failure, and death) and procedural complications were recorded. At post-procedural echocardiography, the mean trans-valvular gradient (49.7 ± 21.5-42.5 ± 17.6 mmHg; p < 0.0001) was reduced significantly. All patients in this study did not die or require valve surgery within the first 7 days after BAV. Successful BAV was obtained in 45.6% of the patients. No patients had severe aortic insufficiency or BAV access-site bleeding. Three patients died suddenly and 4 patients were readmitted for heart failure. Trans-radial BAV is safe and may be useful as a bridging therapy for trans-catheter aortic valve replacement or surgical aortic valve replacement.

DOI： 10.1007/s12928-021-00825-z

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DOI： 10.1016/j.jjcc.2022.07.002

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Background: The role of left ventricular (LV) mechanical dispersion estimated after an ST elevation acute myocardial infarction (STEMI) remains unclear. Methods: The study participants were 208 consecutive patients (152 men, age = 72 years) presenting with STEMI for the first time who underwent primary percutaneous coronary intervention (PCI) within 12 h of STEMI onset. Within 48 h of PCI (mean = 24 h), 2D and 3D speckle-tracking echocardiography were performed. The global longitudinal strain (GLS) was calculated using 3D (3D-GLS) and 2D (2D-GLS) speckle tracking. Mechanical dispersion was defined using the standard deviation (SD) of the time to regional peak longitudinal strain (LS) for all 16 segments for both 2D-STE and 3D-STE (2D-LS-SD, 3D-LS-SD). Infarct size was estimated by Tc99m-sestamibi as the total area of < 50% of the uptake area at 2 weeks. The patients were followed up for a longer period of time (median118months) and checked for major adverse cardiac events (MACE: cardiac death, heart failure). Results: During follow-up, 55 patients experienced MACE. The cut-off values were determined using receiver operating characteristic curves. The multivariate analysis revealed that a 3D-LS-SD > 56.7 ms was a significant predictor of MACEs (hazard ratio = 1.991, 95% confidence interval 1.033-3.613, p = 0.03), but 2D-LS-SD > 58.1 ms was not an independent predictor of MACEs (hazard ratio = 1.577, 95% confidence interval 0.815-3.042, p = 0.1). Furthermore, the combination of 3D-GLS and 3D-LS-SD had accurate predictability for MACE, as shown by the Kaplan-Meier curves (log rank, χ2 = 94.1, p < 0.0001). Conclusions: LV mechanical dispersion besides 3D-GLS assessed by 3D-STE immediately after PCI can predict long-term prognosis.

DOI： 10.1016/j.ijcha.2022.101028

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Whether free fatty acids (FFAs), which are generators of reactive oxygen species and substrates of cytotoxic lipid peroxidation products in proximal tubules of the kidney, can be a predictor of worsening renal function (WRF) is not fully elucidated. A total of 110 patients with ST-segment elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention within 24 h after symptom onset were included. The exclusion criteria were out-of-hospital cardiac arrest, vasospastic angina, hemodialysis, and/or lack of data. FFAs and serum cystatin C were measured on admission, and urinary liver-type fatty acid-binding protein (L-FABP) was measured 3 h after admission. WRF, defined as an increase in serum creatinine by ≥ 0.3 mg/dL for 2-year follow-up, was observed in 16 patients (15%). A multivariate logistic regression analysis (a stepwise algorithm) revealed that the FFA level was an independent predictor of WRF (P = 0.024). The FFA level was associated with WRF adjusted after serum cystatin C (odds ratio [OR]: 1.378 per 1 mEq/L, P = 0.017), L-FABP (OR: 1.370 per 1 mEq/L, P = 0.016), or the Mehran contrast-induced nephropathy (CIN) risk score (OR: 1.362 per 1 mEq/L, P = 0.021). The FFA level was inversely associated with the change in estimated glomerular filtration rate level for 2 years (R2 = 0.051, P = 0.018). The FFA level on admission was associated with the mid-term WRF in patients with STEMI.

DOI： 10.1007/s00380-021-01982-0

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IMPORTANCE: Clopidogrel monotherapy after short dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has not yet been fully investigated in patients with acute coronary syndrome (ACS). OBJECTIVE: To test the hypothesis of noninferiority of 1 to 2 months of DAPT compared with 12 months of DAPT for a composite end point of cardiovascular and bleeding events in patients with ACS. DESIGN, SETTING, AND PARTICIPANTS: This multicenter, open-label, randomized clinical trial enrolled 4169 patients with ACS who underwent successful PCI using cobalt-chromium everolimus-eluting stents at 96 centers in Japan from December 2015 through June 2020. These data were analyzed from June to July 2021. INTERVENTIONS: Patients were randomized either to 1 to 2 months of DAPT followed by clopidogrel monotherapy (n = 2078) or to 12 months of DAPT with aspirin and clopidogrel (n = 2091). MAIN OUTCOMES AND MEASURES: The primary end point was a composite of cardiovascular (cardiovascular death, myocardial infarction [MI], any stroke, or definite stent thrombosis) or bleeding (Thrombolysis in MI major or minor bleeding) events at 12 months, with a noninferiority margin of 50% on the hazard ratio (HR) scale. The major secondary end points were cardiovascular and bleeding components of the primary end point. RESULTS: Among 4169 randomized patients, 33 withdrew consent. Of the 4136 included patients, the mean (SD) age was 66.8 (11.9) years, and 856 (21%) were women, 2324 (56%) had ST-segment elevation MI, and 826 (20%) had non-ST-segment elevation MI. A total of 4107 patients (99.3%) completed the 1-year follow-up in June 2021. One to 2 months of DAPT was not noninferior to 12 months of DAPT for the primary end point, which occurred in 65 of 2058 patients (3.2%) in the 1- to 2-month DAPT group and in 58 of 2057 patients (2.8%) in the 12-month DAPT group (absolute difference, 0.37% [95% CI, -0.68% to 1.42%]; HR, 1.14 [95% CI, 0.80-1.62]; P for noninferiority = .06). The major secondary cardiovascular end point occurred in 56 patients (2.8%) in the 1- to 2-month DAPT group and in 38 patients (1.9%) in the 12-month DAPT group (absolute difference, 0.90% [95% CI, -0.02% to 1.82%]; HR, 1.50 [95% CI, 0.99-2.26]). The major secondary bleeding end point occurred in 11 patients (0.5%) in the 1- to 2-month DAPT group and 24 patients (1.2%) in the 12-month DAPT group (absolute difference, -0.63% [95% CI, -1.20% to -0.06%]; HR, 0.46 [95% CI, 0.23-0.94]). CONCLUSIONS AND RELEVANCE: In patients with ACS with successful PCI, clopidogrel monotherapy after 1 to 2 months of DAPT failed to attest noninferiority to standard 12 months of DAPT for the net clinical benefit with a numerical increase in cardiovascular events despite reduction in bleeding events. The directionally different efficacy and safety outcomes indicate the need for further clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT02619760 and NCT03462498.

DOI： 10.1001/jamacardio.2021.5244

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In this updated expert consensus document, the methods for the quantitative measurement and morphological assessment of optical coherence tomography (OCT)/optical frequency domain imaging images (OFDI) are briefly summarized. The focus is on the clinical application and the clinical evidence of OCT/OFDI to guide percutaneous coronary interventions.

DOI： 10.1007/s12928-022-00845-3

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The purpose of this study was to assess early and late vascular healing in response to bioresorbable-polymer sirolimus-eluting stents (BP-SESs) for the treatment of patients with ST-elevation myocardial infarction (STEMI) and stable coronary artery disease (CAD). A total of 106 patients with STEMI and 101 patients with stable-CAD were enrolled. Optical frequency-domain images were acquired at baseline, at 1- or 3-month follow-up, and at 12-month follow-up. In the STEMI and CAD cohorts, the percentage of uncovered struts (%US) was significantly and remarkably decreased during early two points and at 12-month (the STEMI cohort: 1-month: 18.75 ± 0.78%, 3-month: 10.19 ± 0.77%, 12-month: 1.80 ± 0.72%; p < 0.001, the CAD cohort: 1-month: 9.44 ± 0.78%, 3-month: 7.78 ± 0.78%, 12-month: 1.07 ± 0.73%; p < 0.001 respectively). The average peri-strut low-intensity area (PLIA) score in the STEMI cohort was significantly decreased during follow-up period (1.90 ± 1.14, 1.18 ± 1.25, and 1.01 ± 0.72; p ≤ 0.001), whereas the one in the CAD cohort was not significantly changed (0.89 ± 1.24, 0.67 ± 1.07, and 0.64 ± 0.72; p = 0.59). In comparison with both groups, differences of %US and PLIA score at early two points were almost disappeared or close at 12 months. The strut-coverage and healing processes in the early phase after BP-SES implantation were significantly improved in both cohorts, especially markedly in STEMI patients. At 1 year, qualitatively and quantitatively consistent neointimal coverage was achieved in both pathogenetic groups.

DOI： 10.1007/s12928-021-00777-4

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BACKGROUND: Two-dimensional (2D) and three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) can predict the prognosis. This study investigated the clinical significance of a serial 3D-STE can predict the prognosis after onset of STEMI.Methods and Results:This study enrolled 272 patients (mean age, 65 years) with first-time STEMI treated with reperfusion therapy. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Within 1 year, 19 patients who experienced major adverse cardiac events (MACE; cardiac death, heart failure requiring hospitalization) were excluded. Among the 253 patients, 248 were examined with follow-up echocardiography. The patients were followed up for a median of 108 months (interquartile range: 96-129 months). The primary endpoint was the occurrence of a MACE; 45 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 2D-global longitudinal strain (GLS) and 3D-GLS at 1-year indices were significant predictors of MACE. The Kaplan-Meier curve demonstrated that a 3D-GLS of >-13.1 was an independent predictor for MACE (log-rank χ2=165.5, P<0.0001). The deterioration of 3D-GLS at 1 year was a significant prognosticator (log-rank χ2=36.7, P<0.0001). CONCLUSIONS: The deterioration of 3D-GLS measured by STE at 1 year after the onset of STEMI is the strongest predictor of long-term prognosis.

DOI： 10.1253/circj.CJ-21-0815

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The complete blood cell count is one of the most frequently ordered laboratory tests, and many parameters, including red blood cell distribution width (RDW) and mean platelet volume (MPV), are available. The purpose of this study was to investigate the usefulness of the combination of RDW and MPV in patients with ST-segment elevation myocardial infarction (STEMI). Patients with STEMI who underwent primary percutaneous coronary intervention were retrospectively enrolled (n = 229). The association between RDW as well as MPV and cardiovascular events was investigated. The median age was 67 years, and males made up 85% of the sample. Median RDW was 13.6%, and median MPV was 8.2 fL. During a median follow-up period of 528 days (IQR 331.5-920.5), 41 patients died or experienced major adverse cardiac and cerebrovascular events (MACCEs). Patients with RDW ≧ 13.7% had more deaths or MACCEs with marginal significance (p = 0.0799). Patients with MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0283). Patients with RDW ≧ 13.7% and MPV ≧ 8.3 fL had significantly more deaths or MACCEs (p = 0.0185). MPV was significantly associated with death or adverse events in patients with STEMI who were treated with primary PCI. RDW had only a weak association with death or adverse events. The results of the combination of MPV and RDW were similar to those of MPV.

DOI： 10.1007/s00380-021-01936-6

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Language：English   Publisher：(一社)日本心臓病学会  

経皮的冠動脈インターベンション(PCI)で生じる微小血管損傷をエボロクマブは予防できるか検証した。本稿では、そのEVOCATION試験(経皮的冠動脈インターベンション施行患者におけるエボロクマブの周術期微小循環障害に対する軽減効果を検討する臨床研究;jRCTs051180022)のデザインについて記述した。本試験の目的は、安定型冠動脈疾患の患者に対し、エボロクマブによる前治療を行っておくことで、PCI施行後の微小血管抵抗指数(IMR)を低下させられるか評価することとする。デザインは、多施設共同無作為化非盲検プラセボ対照並行群間の探索的な医師主導の臨床研究とする。研究対象集団は、スタチン薬の最大耐量を少なくとも2週間投与されても低比重リポ蛋白質(LDL)コレステロールが高値であった安定型冠動脈疾患の患者で、PCI施行予定の100名で構成する。適格患者は、PCI前の2〜6週間に亘り標準治療にエボロクマブ(140mg、2週毎)を上乗せする群か、標準治療のみ行う群へ、1:1の比率で無作為に割り付ける。主要評価項目はPCI施行後のIMRとする。

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AIM: The association between high-density lipoprotein cholesterol (HDL-C) level after statin therapy and cardiovascular events in patients with stable coronary artery disease (CAD) remains unclear. Thus, in this study, we sought to determine how HDL-C level after statin therapy is associated with cardiovascular events in stable CAD patients. METHODS: From the REAL-CAD study which had shown the favorable prognostic effect of high-dose pitavastatin in stable CAD patients with low-density lipoprotein cholesterol (LDL-C) ＜120 mg/dL, 9,221 patients with HDL-C data at baseline and 6 months, no occurrence of primary outcome at 6 months, and reported non-adherence for pitavastatin, were examined. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission after 6 months of randomization. Absolute difference and ratio of HDL-C levels were defined as (those at 6 months-at baseline) and (absolute difference/baseline)×100, respectively. RESULTS: During a median follow-up period of 4.0 (IQR 3.2-4.7) years, the primary outcome occurred in 417 (4.5%) patients. The adjusted risk of all HDL-C-related variables (baseline value, 6-month value, absolute, and relative changes) for the primary outcome was not significant (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.91-1.08, HR 1.03, 95% CI 0.94-1.12, HR 1.05, 95% CI 0.98-1.12, and HR 1.08, 95% CI 0.94-1.24, respectively). Furthermore, adjusted HRs of all HDL-C-related variables remained non-significant for the primary outcome regardless of on-treatment LDL-C level at 6 months. CONCLUSIONS: After statin therapy with modestly controlled LDL-C, HDL-C level has little prognostic value in patients with stable CAD.

DOI： 10.5551/jat.59881

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Intravascular ultrasound (IVUS) provides precise anatomic information in coronary arteries including quantitative measurements and morphological assessment. To standardize the IVUS analysis in the current era, this updated expert consensus document summarizes the methods of measurements and assessment of IVUS images and the clinical evidence of IVUS use in percutaneous coronary intervention.

DOI： 10.1007/s12928-021-00824-0

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DOI： 10.1007/s12928-021-00834-y

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Percutaneous coronary intervention (PCI) is a standard treatment in patients with stable coronary artery disease (CAD); however, periprocedural myocardial infarction (PMI) remains a common complication of PCI. Aggressive lipid-lowering therapy with statin has shown to reduce the incidence of PMI by preventing coronary microvascular dysfunction. It is unclear whether evolocumab, a potent lipid-lowering agent, could diminish microvascular damage after PCI. The EVOCATION trial (jRCTs051180022) is a multicenter, randomized, open-label, active-controlled, parallel-group, exploratory, investigator-initiated clinical study to evaluate whether pretreatment with evolocumab could decrease the index of microvascular resistance (IMR) after PCI in patients with stable CAD. This study population consists of 100 patients with stable CAD who will undergo PCI and have high low-density lipoprotein cholesterol levels despite administration of maximum tolerated dose of statins for at least 2 weeks. Eligible patients are randomized in a 1:1 ratio to receive either evolocumab 140 mg every 2 weeks in addition to standard of care treatment or standard of care treatment only for 2-6 weeks before PCI. The primary endpoint is IMR after PCI. The EVOCATION trial will evaluate whether pretreatment with evolocumab reduces periprocedural microvascular damage in patients with stable CAD undergoing PCI.

DOI： 10.1016/j.jjcc.2021.08.024

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BACKGROUND: Landiolol enables us to treat the patients with rapid atrial fibrillation (AF) with acute decompensated heart failure (ADHF) efficiently. We sought to determine the role of echocardiography in predicting the prognosis. METHODS: Among 314 patients, a total 115 ADHF patients with reduced ejection fraction and rapid AF were enrolled. They received landiolol treatment to decrease the heart rate (HR) to <110 bpm and change HR (ΔHR) of >20% within 24 h. The dose of landiolol was increased every 2 h; then, we performed echocardiography repeatedly, at baseline, 2 h, and 24h. We followed the patients after discharge for 180 days, and checked cardiac death and HF hospitalization as major adverse cardiac events (MACE). RESULTS: During initial hospitalization, 5 patients (4%) died. During 180 days after discharge, 19 (16%) out of 115 patients experienced MACE (2 cardiac death, 17 HF rehospitalization, 5 in-hospital death). Multivariate analysis showed that the change in left ventricular outflow tract-velocity time integral (LVOT-VTI) at 2 h was the most significant predictor for MACE (hazard ratio =1.21, 95% confidence interval: 1.10-1.83, p=0.0001). Kaplan-Meier curves demonstrated the patients with deteriorated LVOT-VTI at minimum dose landiolol suggested the high-risk patients for MACE (χ2=30.9, p<0.0001). CONCLUSIONS: During landiolol treatment, the patients with deteriorated LVOT-VTI predicted the poor prognosis. We may detect the high-risk patients by two-point echocardiography. UMIN000020084. Registered 1 November 2013 - prospective study https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&language=J&recptno=R000023203.

DOI： 10.1016/j.jjcc.2021.09.008

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To explore the biological and immunological basis of human rheumatoid arthritis and human atherosclerosis, we planned and reported a detailed design and rationale for Orencia Atherosclerosis and Rheumatoid Arthritis Study (ORACLE Arthritis Study) using highly sensitive, high-throughput, human autoantibody measurement methods with cell-free protein synthesis technologies. Our previous study revealed that subjects with atherosclerosis had various autoantibodies in their sera, and the titers of anti-Th2 cytokine antibodies were correlated with the severity of atherosclerosis. Because rheumatoid arthritis is a representative autoimmune disease, we hypothesized that both rheumatoid arthritis and atherosclerosis are commonly developed by autoantibody-mediated autoimmune processes, leading to incessant inflammatory changes in both articular joint tissues and vessel walls. We planned a detailed examination involving carotid artery ultrasonography, measurements of adhesion molecules, such as ICAM-1 (intercellular adhesion molecule 1) and VCAM-1 (vascular cell adhesion molecule 1) for the evaluation of atherosclerosis progression, and high-throughput, high-sensitivity, autoantibody analyses using cell-free technologies, with detailed examinations of the disease activity of rheumatoid arthritis. Analyses of correlations and associations between biological markers and degrees of carotid atherosclerosis over time under consistent conditions may enable us to understand the biological and humoral immunity background of human atherosclerosis and autoimmune diseases.

DOI： 10.3390/mps4040083

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BACKGROUND: The efficacy and bleeding complications of direct oral anticoagulant (DOAC) therapy for isolated distal deep vein thrombosis (IDDVT) associated with cancer in routine clinical practice remain unclear. Moreover, prior studies on prolonged therapy for IDDVT are limited. METHODS: This retrospective study enrolled 1641 consecutive patients with acute venous thromboembolism (VTE) who had received oral anticoagulant therapy, including warfarin or DOAC, between April 2014 and September 2018 in our institutions. In these patients, 200 patients with cancer-associated IDDVT were evaluated. RESULTS: Mean follow-up period was 780 ± 593 days. Major bleeding and VTE recurrence were observed in 22 (11.0%) and 11 (5.5%) patients, respectively. In multivariate analysis, statistically significant factors correlated with major bleeding were advanced cancer stage, high performance status, stomach cancer, and gallbladder cancer; those correlated with all-cause death were advanced cancer stage, high performance status, liver dysfunction, pancreatic cancer, and major bleeding. Cumulative events of major bleeding and recurrence between patients with prolonged DOAC therapy (≥90 days) and those with nonprolonged therapy were not significantly different. CONCLUSIONS: Preventing major bleeding is important because it is a significant risk factor for all-cause death. Major bleeding and recurrent events were comparable between prolonged and nonprolonged therapy.

DOI： 10.3390/jcm10204648

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DOI： 10.1007/s12928-020-00718-7

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DOI： 10.1007/s12928-020-00741-8

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BACKGROUND: It has not yet been established whether higher-dose statins have beneficial effects on cardiovascular events in patients with stable coronary artery disease (CAD) and renal dysfunction. METHODS: The REAL-CAD study is a prospective, multicenter, open-label trial. As a substudy, we categorized patients by an estimated glomerular filtration rate (eGFR) as follows: eGFR ≥60 (n = 7,768); eGFR ≥45 and <60 (n = 3,176); and eGFR <45 mL/Min/1.73 m2 (n = 1,164), who were randomized to pitavastatin 4mg or 1mg therapy. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina, and was assessed by the log-rank test and Cox proportional hazards model. RESULTS: The baseline characteristics and medications were largely well-balanced between two groups. The magnitude of low-density lipoprotein cholesterol (LDL-C) reduction at 6 months in high- and low-dose pitavastatin groups was comparable among all eGFR categories. During a median follow-up of 3.9 years, high- compared with low-dose pitavastatin significantly reduced cardiovascular events in patients with eGFR ≥60 (hazard ratio (HR) 0.73; 95% confidence interval (CI) 0.58-0.91; P = .006), and reduced but not significant for patients with eGFR ≥45 and <60 (HR 0.85; 95% CI, 0.63-1.14; P = .27) or eGFR <45 mL/Min/1.73 m2 (HR 0.90; 95% CI 0.62-1.33; P = .61). An interaction test of treatment by eGFR category was not significant (P value for interaction = .30). CONCLUSION: Higher-dose pitavastatin therapy reduced LDL levels and cardiovascular events in stable CAD patients irrespective of eGFR level, although the effect on events appeared to be numerically lower in patients with lower eGFR.

DOI： 10.1016/j.ahj.2021.06.009

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BACKGROUND AND AIMS: Both low appendicular skeletal muscle index (ASMI) and specific abdominal fat composition [i.e., increased visceral to subcutaneous (V/S) fat ratio] have been associated with cardiovascular events. However, the combined impact of these 2 components on long-term outcomes remains unclear, especially in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: In 303 patients with STEMI, ASMI and V/S fat ratio were assessed using dual-energy X-ray absorptiometry and abdominal computed tomography. Based on the criteria of the Asian Working Group for Sarcopenia and median of V/S fat ratio, sarcopenic obesity (SO) pattern was defined as low ASMI with high V/S fat ratio. The primary endpoint was composite outcomes of all-cause death, myocardial infarction, ischemic stroke, hospitalization for heart failure and unplanned revascularization. RESULTS: During a median follow-up of 3.9 years, primary endpoint occurred in 67 patients. Patients with an SO pattern showed significantly lower event-free survival rate compared with those without (p=0.006 by log-rank). Notably, when stratified by median age (67 years), this trend was particularly prominent in the younger-age group (p <0.001), but not significant in the older-age group (p=0.38). In the younger-age group, the multivariate analysis revealed that patients with SO pattern had a 2.97 (1.10-7.53) fold higher risk for primary endpoints compared with those without. CONCLUSIONS: Low ASMI with high V/S fat ratio, or so-called sarcopenic obesity, was associated with poor prognosis after STEMI, particularly in younger-age patients. The combined assessment of skeletal muscle with abdominal fat distribution may help stratify the risk among patients with STEMI, rather than each component alone.

DOI： 10.1016/j.atherosclerosis.2021.08.038

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The ultra-short dual antiplatelet therapy (DAPT) followed by P2Y12 inhibitor monotherapy might be promising after percutaneous coronary intervention (PCI). However, CYP2C19 loss-of-function (LOF) alleles have been reported to diminish the effect of clopidogrel, and clopidogrel monotherapy has a concern about the increased ischemic risk for patients with such alleles. STOPDAPT-2 is the multicenter prospective open-label, but adjudicator-blinded randomized control study comparing 1-month DAPT followed by clopidogrel monotherapy with the standard 12-month DAPT after PCI with cobalt-chromium everolimus-eluting stents. Among the participants of STOPDAPT-2, selected patients participated in a substudy of the CYP2C19 gene test. Patients with two CYP2C19*2 or *3 alleles were defined as the poor metabolizer (PM), one allele as the intermediate metabolizer (IM), and no allele as the extensive metabolizer (EM). The primary endpoint was the composite of cardiovascular and bleeding events, as defined in STOPDAPT-2. Among 750 (24.9%) patients with known CYP2C19 genotypes, 129 (17.2%) were PM, 367 (49.0%) were IM, and 254 (33.9%) were EM. The hazard ratios of 1-month DAPT relative to 12-month DAPT for the primary endpoint in PM, IM, and EM strata were 0.66 (95% CI 0.11-3.94), 1.94 (95% CI 0.60-6.31), and 0.21 (95% CI 0.02-1.78), respectively (P interaction = 0.17), and those for cardiovascular composite endpoint were 1.00 (95% CI 0.14-7.10), 6.10 (95% CI 0.75-49.55), and 0.26 (95% CI 0.03-2.34), respectively (P interaction = 0.12). In conclusion, for the selected patients in STOPDAPT-2 trial, CYP2C19 LOF alleles had no significant, consistent interaction with the effect of 1-month DAPT relative to 12-month DAPT for clinical outcomes, although the study was overtly underpowered. TRIAL REGISTRY: STOPDAPT-2 ClinicalTrials.gov number, NCT02619760.

DOI： 10.1007/s12928-020-00719-6

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BACKGROUND: Three-dimensional (3D) speckle tracking echocardiography (STE) after ST-elevation acute myocardial infarction (STEMI) is associated with left ventricular (LV) remodeling and 1-year prognosis. This study investigated the clinical significance of 3D-STE in predicting the long-term prognosis of patients with STEMI.Methods and Results:A total of 270 patients (mean age 64.6 years) with first-time STEMI treated with reperfusion therapy were enrolled. At 24 h after admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-STE and 3D-STE were calculated. Patients were followed up for a median of 119 months (interquartile range: 96-129 months). The primary endpoint was occurrence of a major adverse cardiac event (MACE: cardiac death, heart failure with hospitalization), and 64 patients experienced MACEs. Receiver operating characteristic curves and Cox hazard multivariate analysis showed that the 3D-STE indices were stronger predictors of MACE compared with those of 2D-STE. Additionally, 3D-global longitudinal strain (GLS) was the strongest predictor for MACE followed by 3D-global circumferential strain (GCS). The Kaplan-Meier curve demonstrated that 3D-GLS >-11.0 was an independent predictor for MACE (log-rank χ2=132.2, P<0.0001). When combined with 3D-GCS >-18.3, patients with higher values of 3D-GLS and 3D-GCS were found to be at extremely high risk for MACE. CONCLUSIONS: Global strain measured by 3D-STE immediately after the onset of STEMI is a clinically significant predictor of 10-year prognosis.

DOI： 10.1253/circj.CJ-21-0183

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We encountered a case of ST-segment elevation myocardial infarction (STEMI) as the first clinical manifestation of essential thrombocythemia (ET). Platelet function tests revealed high thrombogenicity during primary percutaneous coronary intervention compared with general cardiovascular patients, whereas the platelet function two weeks after admission was effectively suppressed by dual antiplatelet therapy. The patient, who lacked cytoreduction, suffered from recurrent STEMI because of poor compliance with antiplatelet drugs. The risk of acute coronary occlusion may be high during the acute phase of STEMI in ET patients because of high thrombogenicity. Insufficient antiplatelet therapy and no cytoreduction are also risk factors for recurrent coronary events.

DOI： 10.2169/internalmedicine.6095-20

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BACKGROUND: This analysis aimed to evaluate the clinical impact of high bleeding risk (HBR) on adverse events after percutaneous coronary intervention (PCI). METHODS: We retrospectively analyzed 1695 patients in the MODEL U-SES study, which was a multicenter, open-label, prospective observational study evaluating safety of 3-month dual antiplatelet therapy (DAPT) after Ultimaster stent (Terumo Corporation, Tokyo, Japan) implantation at 65 sites in Japan. Patients were divided into 2 groups (HBR/Non-HBR) according to modified Academic Research Consortium-HBR criteria. Ischemic/thrombotic event (cardiovascular death, myocardial infarction, ischemic stroke, and stent thrombosis) and bleeding event (Bleeding Academic Research Consortium 3 or 5) at 1 year were evaluated. RESULTS: Of 1695 patients, 840 patients were categorized as HBR and 855 patients were Non-HBR. One-year follow-up was completed in 95.3%. During 1-year follow-up, ischemic/thrombotic events were observed in 31 cases (1.8%) and bleeding events occurred in 21 cases (1.2%). Presence of HBR was significantly associated with higher incidence of ischemic/thrombotic events as compared to Non-HBR (adjusted hazard ratio, 0.16; 95% confidence interval, 0.05 to 0.50), whereas the incidence of bleeding events did not reach statistical significance between HBR and Non-HBR. In comparison of monotherapy after DAPT, P2Y12 inhibitor monotherapy after DAPT had comparable ischemic/thrombotic and bleeding events with aspirin monotherapy after DAPT in both HBR and Non-HBR. CONCLUSION: In contemporary PCI practice, nearly half of patients had HBR and presence of HBR significantly increased risk of ischemic/thrombotic events. Both aspirin and P2Y12 inhibitor monotherapy following short DAPT had low and comparable ischemic/bleeding events.

DOI： 10.1016/j.jjcc.2021.03.015

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Background: The significance of late diastolic velocity (a') obtained by tissue Doppler imaging (TDI), which reveals atrial function, in ST-elevation myocardial infarction (STEMI) remains unclear. This study evaluated the association of TDI parameters determined either immediately or 2 weeks after percutaneous coronary intervention (PCI) with long-term outcomes. Methods and Results: In all, 740 patients with first-time STEMI underwent immediate PCI (i.e., within 12 h of onset). Echocardiography was performed in 307 patients 2 weeks after onset (Group A; mean age 64 years, 249 males), in 277 patients immediately after PCI (Group B; mean age 65 years, 229 males), and in 156 patients twice (i.e., immediately and 2 weeks after PCI; Group C; mean age 65 years, 135 males). Patients were followed-up for up to 10 years (mean 81 months). The primary endpoints were cardiac death or heart failure hospitalization. Major adverse cardiovascular events (MACE) occurred in 143 patients (19%) during the follow-up period. Both univariate and multivariate Cox hazard analyses were used to determine predictors of MACE. At 24 h and 2 weeks after STEMI onset, a' and E/e' were the strongest predictors of MACE, respectively. Conclusions: TDI parameters have different implications depending on the timing of echocardiography after a first-time STEMI. Based on the results of this study, atrial dysfunction measured by TDI 24 h after STEMI onset may indicate a poor prognosis.

DOI： 10.1253/circrep.CR-21-0056

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Skeletal muscle function has been studied to determine its effect on glucose metabolism; however, its effect on glycemic variability (GV), which is a significant glycemic marker in patients with coronary artery disease, is unknown. The aim of the present study was to elucidate the association between skeletal muscle mass and GV. Two hundred and eight consecutive ST-segment elevation myocardial infarction (STEMI) patients who underwent continuous glucose monitoring to evaluate mean amplitude of glycemic excursion (MAGE) as GV and a dual-energy X-ray absorptiometry (DEXA) to evaluate skeletal muscle mass were enrolled. Skeletal muscle index (SMI) level was calculated as skeletal muscle mass divided by height squared (kg/m2). SMI level in men had a weak inverse correlation with Log MAGE level by the linear regression model in diabetes mellitus (DM) patients (R2 = 0.139, P = 0.004) and even in non-DM patients (R2 = 0.068, P = 0.004). Multivariate linear regression analysis with a stepwise algorithm (age, male sex, body mass index [BMI], hemoglobin A1c [HbA1c], fasting glucose, HOMA-IR, and SMI; R2 = 0.203, P < 0.001) demonstrated that HbA1c level (B = 0.077, P < 0.001) and SMI level (B = - 0.062, P < 0.001) were both independently associated with Log MAGE level. This association was also confirmed in limited non-DM patients with a subgroup analysis. SMI level was associated with Log MAGE level (B = - 0.055, P = 0.001) independent of BMI or HbA1c level. SMI level was inversely associated with MAGE level independent of glucose metabolism in STEMI patients, suggesting the significance of skeletal muscle mass as blood glucose storage for glucose homeostasis to reduce GV.

DOI： 10.1007/s00380-021-01781-7

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Other Link： https://link.springer.com/article/10.1007/s00380-021-01781-7/fulltext.html

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND: Cachexia, characterized by loss of muscle with or without loss of fat mass, is a poor prognostic factor in patients with heart failure (HF). However, there is limited investigation on the prognostic impact of muscle and fat mass separately in HF. We hypothesized that muscle and fat mass have different effects on the prognosis of HF. METHODS: This was an observational cohort study of 418 patients (59% were men) admitted with a diagnosis of HF (71 ± 13 years [mean ± standard deviation]), with left ventricular ejection fraction (LVEF) of 39 ± 16%, including 31.3%, 14.8%, and 53.8% of patients with preserved LVEF (LVEF ≥ 50%), mid-range LVEF (40-50%), and reduced (<40%) LVEF, respectively. Dual-energy X-ray absorptiometry was performed with the patients in the stable state after decongestion therapy. RESULTS: The mean body mass index of patients was 22.1 ± 4.6 kg/m2 , and the mean appendicular skeletal mass (ASM) index was 6.88 ± 1.23 kg/m2 in men and 5.59 ± 0.92 in women; 54.1% of the patients showed reduced muscle mass defined by the international cut-off value (7.0 kg/m2 for men and 5.4 for women). The mean fat mass was 20.4 ± 7.2% in men and 27.2 ± 8.6% in women. During a median follow-up of 37 months, 92 (22.0%) of 418 patients with HF died (1 and 3 year mortality: 8.4% and 17.3%, respectively). Lower values of both skeletal muscle and fat mass were independently associated with increased risk of mortality adjusted for age, sex, haemoglobin, New York Heart Association functional class, and height squared (hazard ratio with 95% confidence interval of 0.825 [0.747-0.908] per 1 kg increase of ASM, P < 0.001, and 0.954 [0.916-0.993] per 1 kg increase of fat mass, P = 0.018, respectively). CONCLUSIONS: More than half of the patients with HF showed reduced muscle mass. Lower values of both muscle and fat mass were associated with higher mortality in HF.

DOI： 10.1002/jcsm.12702

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jcsm.12702

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

BACKGROUND: This study aimed to simultaneously investigate diagnostic performance and limitation of quantitative flow reserve (QFR) for assessing functionally significant coronary stenosis, focusing on factors affecting diagnostic accuracy of QFR. METHODS: This study evaluated 1) QFR diagnostic accuracy compared with fractional flow reserve (FFR) in patients with stable coronary artery disease (Cohort-A, n = 95) and 2) QFR reproducibility for non-culprit lesions (NCLs) assessment between acute and staged (14±5 days later) procedures in patients with ST-segment elevation myocardial infarction (STEMI) (Cohort-B, n = 65). All coronary angiography image acquisition was performed before the introduction of QFR system into our institution. RESULTS: Cohort-A showed good correlation (r = 0.80, p<0.0001) between QFR and FFR; diagnostic accuracy of QFR for FFR ≤0.80 was 85.2% (sensitivity 80.4%, specificity 91.0%, positive predictive value 91.1%, negative predictive value 80.0%). There were 14 lesions showing discordance between QFR and FFR, which was primarily attributable to inadequate lesion visualization due to vessel overlap/tortuosity and/or insufficient intra-coronary contrast-media injection. In Cohort-B, there was also excellent correlation between acute and staged QFR; classification agreement of acute and staged QFR was 92.3%. Five lesions showed discordance between acute and staged QFR, 4 were due to limited image acquisition and/or high coronary flow velocity at acute phase of STEMI and 1 was borderline ischemia. CONCLUSIONS: QFR-derived physiological assessment of intermediate coronary stenosis is feasible, even in the acute setting of STEMI. Adjusting some technical factors may further improve the diagnostic performance of QFR.

DOI： 10.1016/j.jjcc.2020.11.002

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This study aimed to evaluate the characteristics and prognosis of patients with vasospastic angina (VSA) diagnosed by a provocation test with a secondary prevention implantable cardioverter defibrillator (ICD), compared with patients with organic coronary stenosis. We retrospectively evaluated 309 consecutive patients who received an ICD implantation between January 2010 and March 2018 in our institutions. Of these patients, 206 were implanted with an ICD for secondary prevention. In these 206 patients, 40 with VSA and 72 with organic coronary stenosis were evaluated. Patients with VSA were characterized by younger age (56.1 ± 13.1 versus 69.2 ± 9.5 years, respectively), and a lower prevalence of diabetes (15.0% versus 40.3%, respectively) and heart failure (2.5% versus 26.4%, respectively) than patients with organic coronary stenosis (P < 0.001). Using the Kaplan-Meier analysis, with the VSA group as the reference, the incidence of appropriate ICD shock was similar between the two groups (hazard ratio, 0.85; 95% confidence interval, 0.341-2.109; P = 0.722). The incidence of ventricular fibrillation was significantly higher in the VSA group (hazard ratio, 0.22; 95% confidence interval, 0.057-0.814; P = 0.024), whereas the incidence of major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, hospitalization for unstable angina pectoris, and heart failure, was significantly higher in the organic coronary stenosis group (hazard ratio, 13.1; 95% confidence interval, 1.756-98.17; P = 0.012). In conclusion, patients with VSA with an ICD implanted for secondary prevention have a higher risk of ventricular fibrillation and lower risk of major adverse cardiac events than patients with organic coronary stenosis.

DOI： 10.1536/ihj.20-360

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DOI： 10.1007/s12928-020-00651-9

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DOI： 10.1253/circj.CJ-20-0449

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BACKGROUND: This study evaluated the safety of 3-month dual antiplatelet therapy (DAPT) after implantation of a bioresorbable polymer sirolimus-eluting stent (BP-SES) and compared P2Y12inhibitor with aspirin monotherapy 3 months after DAPT.Methods and Results:Patients who underwent percutaneous coronary intervention using BP-SES were enrolled and followed for 1 year. Patients with a history of stent thrombosis were excluded. The primary endpoint was a composite of all-cause death, myocardial infarction, stroke (ischemic and hemorrhagic), definite or probable stent thrombosis, and severe bleeding at 12 months. The BP-SES arm of the CENTURY II trial was used as a conventional DAPT group for comparison. After DAPT, patients were maintained on either aspirin (n=846) or a P2Y12inhibitor (n=674 patients).In all, 1,695 patients were enrolled in the study across 65 centers. The primary endpoint occurred in 4.3% of patients at 1 year. After propensity score adjustment, the incidence of the primary endpoint was not inferior in those receiving DAPT for 3 months compared with conventional DAPT (5.5%; Pnon-inferiority<0.0001). The incidence of the primary endpoint and severe bleeding did not differ between the aspirin and P2Y12inhibitor monotherapy groups. CONCLUSIONS: After adjustment, 3-month DAPT was not inferior to longer DAPT after BP-SES implantation in terms of net adverse clinical events. There was no difference in bleeding and thrombotic events between P2Y12inhibitor and aspirin monotherapy after 3 months DAPT.

DOI： 10.1253/circj.CJ-20-0644

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AIM: The importance of sarcopenia in cardiovascular diseases has been recently demonstrated. This study aims to examine whether skeletal muscle mass (SMM), an important component of sarcopenia, is associated with an increased risk of poor outcome in patients after ST-segment elevation myocardial infarction (STEMI). METHODS: We measured SMM in 387 patients with STEMI using dual-energy X-ray absorptiometry. Patients were divided into low- and high-appendicular skeletal mass index (ASMI: appendicular SMM divided by height squared (kg/m2)) groups using the first quartile of ASMI (≤ 6.64 kg/m2 for men and ≤ 5.06 kg/m2 for women). All patients were followed up for the primary composite outcome of all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke, hospitalization for congestive heart failure, and unplanned revascularization. RESULTS: Low-ASMI group was older and had a more complex coronary lesion, a lower left ventricular ejection fraction, and a higher prevalence of Killip classification ≥ 2 than high-ASMI group. During a median follow-up of 33 months, the event rate was significantly higher in low-ASMI group than in high-ASMI group (24.7% vs 13.4%, log-rank p=0.001). Even after adjustment for patients' background, low ASMI was independently associated with the high risk of primary composite events (adjusted hazard ratio 2.06, 95% confidence interval 1.01- 4.19, p=0.04). In the subgroup analyses of male patients (n=315), the optimal cutoff point of ASMI for predicting primary composite outcome was 6.75 kg/m2, which was close to its first quartile value. CONCLUSIONS: Low ASMI is independently associated with poor outcome in patients with STEMI.

DOI： 10.5551/jat.52282

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本循環器学会  

Background Myocardial bridge (MB), common anatomic variant, is generally considered benign, while previous studies have shown associations between MB and various cardiovascular pathologies. This study aimed to investigate for the first time possible impact of MB on long-term outcomes in patients with implantable cardioverter defibrillator, focusing on life-threatening ventricular arrhythmia (LTVA). Methods and Results This retrospective analysis included 140 patients with implantable cardioverter defibrillator implantation for primary (n=23) or secondary (n=117) prevention of sudden cardiac death. Angiographically apparent MB was identified on coronary angiography as systolic milking appearance with significant arterial compression. The primary end point was the first episode(s) of LTVA defined as appropriate implantable cardioverter defibrillator treatments (antitachyarrhythmia pacing and/or shock) or sudden cardiac death, assessed for a median of 4.5 (2.2-7.1) years. During the follow-up period, LTVA occurred in 37.9% of patients. Angiographically apparent MB was present in 22.1% of patients; this group showed younger age, lower rates of coronary risk factors and ischemic cardiomyopathy, higher prevalence of vasospastic angina and greater left ventricular ejection fraction compared with those without. Despite its lower risk profiles above, Kaplan-Meier analysis revealed significantly lower event-free rates in patients with versus without angiographically apparent MB. In multivariate analysis, presence of angiographically apparent MB was independently associated with LTVA (hazard ratio, 4.24; 95% CI, 2.39-7.55; P<0.0001). Conclusions Angiographically apparent MB was the independent determinant of LTVA in patients with implantable cardioverter defibrillator. Although further studies will need to confirm our findings, assessment of MB appears to enhance identification of high-risk patients who may benefit from closer follow-up and targeted therapies.

DOI： 10.1161/JAHA.120.017455

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BACKGROUND: The early mitral inflow velocity to mitral early diastolic velocity ratio (E/e') and electrocardiogram (ECG) determination of QRS score are useful for risk stratification in patients with ST-elevation myocardial infarction (STEMI).Methods and Results:In this study, 420 consecutive patients (357 male; mean [±SD] age 63.6±12.2 years) with first-time STEMI who successfully underwent primary percutaneous coronary intervention within 12 h of symptom onset were followed-up for 5 years (median follow-up 67 months). Echocardiography, ECG, and blood samples were obtained 2 weeks after onset. Infarct size was estimated by the QRS score after 2 weeks (QRS-2wks) and creatine phosphokinase-MB concentrations (peak and area under the curve). The primary endpoint was death from cardiac causes or rehospitalization for heart failure (HF). During follow-up, 21 patients died of cardiac causes and 62 had HF. Multivariate Cox proportional hazard analysis showed that mean E/e' (hazard ratio [HR] 1.152; 95% confidence interval [CI] 1.088-1.215; P<0.0001), QRS-2wks (HR 1.153; 95% CI 1.057-1.254; P<0.0001), and hypertension (HR 1.702; 95% CI 1.040-2.888; P=0.03) were independent predictors of the primary endpoint. Kaplan-Meier curve analysis showed that patients with QRS-2wks >4 and mean E/e' >14 were at an extremely high risk of cardiac death or HF (log rank, χ2=116.3, P<0.0001). CONCLUSIONS: In patients with STEMI, a combination of QRS-2wks and mean E/e' was a simple but useful predictor of cardiac death and HF.

DOI： 10.1253/circj.CJ-20-0486

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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.

DOI： 10.1253/circj.CJ-20-0264

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AIMS: In patients with ST-segment elevation myocardial infarction (STEMI), predicting left ventricular (LV) remodelling (LVR) and prognosis is important. We explored the clinical usefulness of three-dimensional (3D) speckle-tracking echocardiography to predict LVR and prognosis in STEMI. METHODS AND RESULTS: The study group comprised 255 first STEMI patients (65 years; 210 men) treated with primary percutaneous coronary intervention between April 2008 and May 2012 at Yokohama City University Medical Center. Baseline global longitudinal strain (GLS) was measured with two-dimensional (2D) and 3D speckle-tracking echocardiography. Within 48 of admission, standard 2D echocardiography and 3D full-volume imaging were performed, and 2D-GLS and 3D-GLS were calculated. Infarct size was estimated by 99mTc-sestamibi single-photon emission computed tomography. Echocardiography was performed at 1 year repeatedly in 239 patients. The primary endpoint was LVR, defined as an increase of 20% of LV end-diastolic volume index and major adverse cardiac and cerebrovascular events (MACE: cardiac death, non-fatal MI, heart failure, and ischaemic stroke) at 1 year, and the secondary endpoint was cardiac death and heart failure. Patients were followed for 1 year; 64, 25, and 16 patients experienced LVR, MACE, and the secondary endpoint, respectively. Multivariate analysis revealed that 3D-GLS was the strongest predictor of LVR (odds ratio = 1.437, 95% CI: 1.047-2.257, P = 0.02), MACE (odds ratio = 1.443, 95% CI: 1.240-1.743, P = 0.0002), and the secondary end point (odds ratio = 1.596, 95% CI: 1.17-1.56, P < 0.0001). Receiver-operating characteristic curve analysis showed that 3D-GLS was superior to 2D-GLS in predicting LVR and 1-year prognosis. CONCLUSION: 3D-GLS obtained immediately after STEMI is independently associated with LVR and 1-year prognosis.

DOI： 10.1093/ehjci/jeaa241

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DOI： 10.1536/ihj.20-141

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DOI： 10.1016/j.jjcc.2020.03.010

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DOI： 10.1007/s40256-019-00384-y

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DOI： 10.1002/ccd.28612

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DOI： 10.1007/s00380-020-01663-4

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DOI： 10.1016/j.jjcc.2020.01.005

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DOI： 10.1016/j.numecd.2020.03.017

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DOI： 10.1253/circj.CJ-19-0869

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DOI： 10.1016/j.jccase.2020.02.009

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DOI： 10.1007/s12928-019-00585-x

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DOI： 10.1007/s12928-020-00653-7

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Background: The present article describes two cases of patients with coronary arteritis (CA) whose identification of CA diagnosis (late vs. early) resulted in different clinical courses and outcomes. Case summary: Case 1 is a 53-year-old woman with multiple coronary risk factors who was admitted with acute coronary syndrome (ACS) and significant stenosis in the left main trunk (LMT). Although clues suggested arteritis (LMT lesion without any other stenosis, occlusion of left internal thoracic artery, etc.), the diagnosis of CA (coronary involvement of unclassified arteritis) was delayed and revascularization, including coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI), was performed under uncontrolled inflammatory status. As a result, Case 1 experienced repeated ACS episodes due to graft failure and in-stent restenosis, and repeatedly underwent PCI. Case 2 is a 76-year-old woman with no significant coronary risk factors who was admitted with ACS. This patient was successfully diagnosed with coronary involvement of Takayasu arteritis before revascularization. Coronary artery bypass grafting was performed after stabilizing inflammation with prednisolone, and the patient remains angina-free beyond 1-year post-CABG. In both cases, intravascular imaging clearly identified the localization and degree of inflammation related to CA by demonstrating specific findings (ambiguous typical three-layer structure of arterial wall and extended low-echoic areas within adventitia). Discussion: Accurate and early diagnosis with meticulous diagnostic and therapeutic strategies appear to be important for favourable clinical outcomes in the medical treatment of patients with coronary involvement of arteritis. Intravascular imaging has the potential to contribute to optimizing clinical management of CA.

DOI： 10.1093/ehjcr/ytaa011

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DOI： 10.1007/s12928-019-00625-6

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DOI： 10.1007/s12928-019-00626-5

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DOI： 10.1253/circj.CJ-20-0084

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DOI： 10.1371/journal.pone.0227612

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DOI： 10.1253/circj.CJ-19-1043

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DOI： 10.1161/CIRCULATIONAHA.119.043613

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DOI： 10.1038/s41598-019-48246-6

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DOI： 10.15420/icr.2019.16.R1

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DOI： 10.1016/j.cjca.2019.07.633

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DOI： 10.1016/j.jjcc.2019.04.011

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Background: We investigated the clinical usefulness of landiolol for rapid atrial fibrillation (AF) in patients with acute decompensated heart failure (ADHF) and identify the patients eligible for landiolol. Methods and Results: A total of 101 ADHF patients with reduced ejection fraction (HFrEF) with rapid AF were enrolled. Immediately after admission, an initial dose of landiolol was given (1 μg/kg-1/min-1), and then the dose was increased to decrease heart rate (HR) to <110 beats/min and change HR (∆HR) >20% in ≤24 h. Thirty-seven were monitored using right heart catheterization at 3 points (baseline, 1 μg/kg-1/min-1, and maximum dose). We checked the major adverse events (MAE) during initial hospitalization, which included cardiac death, HF prolongation (required i.v. treatment at 30 days), and worsening renal function. The average maximum dose of landiolol was 3.8±2.3 μg/kg-1/min-1. HR (P<0.0001) and pulmonary capillary wedge pressure (P=0.0008) decreased safely. MAE occurred in 39 patients. The patients with left ventricular (LV) end-diastolic volume index <84.0 mL/m2 and mean blood pressure (mean BP) >97 mmHg had less frequent MAE (P<0.0001). Conclusions: Landiolol was effective for safely controlling rapid AF in patients with HFrEF with ADHF, leading to hemodynamic improvement and avoidance of short-term MAE, especially in patients with relatively smaller LV and higher BP.

DOI： 10.1253/circrep.cr-19-0076

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DOI： 10.1007/s00380-019-01368-3

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DOI： 10.1016/j.jelectrocard.2019.04.004

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DOI： 10.1007/s00380-018-1320-4

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DOI： 10.1001/jama.2019.8145

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DOI： 10.1371/journal.pone.0218096

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DOI： 10.1016/j.jcin.2019.01.234

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DOI： 10.1007/s10554-018-1476-0

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DOI： 10.1007/s12928-017-0507-4

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DOI： 10.2147/TCRM.S184457

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DOI： 10.5551/jat.47621

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DOI： 10.1253/circj.CJ-18-1236

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DOI： 10.1016/j.jcin.2018.10.028

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A 28-year-old man without coronary risk factors was admitted to the hospital with acute coronary syndromes (ACS). The angiogram and intravascular ultrasound revealed myocardial bridge (MB) in the mid-left anterior descending artery and flow-limiting plaque located 15.4 mm proximal to MB. The culprit lesion was treated only with drug-coated balloon, considering the patient's extremely young age. This case suggests that an accelerated formation of plaque caused by MB appeared to contribute to the development of ACS; thus, MB should be considered as an important cause of ACS in young patients with low cardiovascular risk.

DOI： 10.1016/j.cjca.2018.08.023

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BACKGROUND: Impaired glucose metabolism is an established risk factor for coronary artery disease. Previous studies revealed that glycemic variability (GV) is also important for glucose metabolism in patients with acute coronary syndrome (ACS). We explored the association between GV and prognosis in patients with ACS. METHODS: A total of 417 patients with ACS who received reperfusion wore a continuous glucose monitoring system (CGMS) in a stable phase after admission and were monitored for at least 24 consecutive h. The mean amplitude of glycemic excursion (MAGE) was calculated as a marker of GV. We divided into two groups based on the highest tertile levels of MAGE (MAGE = 52 mg/dl). The groups were followed up for a median of 39 months [IQR 24-50 months]. The primary endpoint was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE). RESULT: During follow-up, 66 patients experienced MACCE (5 patients had cardiovascular death, 14 had recurrence of ACS, 27 had angina requiring revascularization, 8 had acute decompensated heart failure, and 16 had a stroke). MACCE was more frequently observed in the high MAGE group (23.5% vs. 11.6%, p = 0.002). In multivariate analysis, high MAGE was an independent predictive factor of poor prognosis for MACCE (odds ratio, 1.84; 95% confidence interval, 1.01-3.36; p = 0.045). CONCLUSION: Glycemic variability determined with a CGMS is a predictor of prognosis in patients with ACS without severe DM. Trial registration UMIN 000010620. Registered April 1st 2012.

DOI： 10.1186/s12933-018-0761-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese College of Cardiology (Nippon-Sinzobyo-Gakkai)  

DOI： 10.1016/j.jjcc.2018.01.005

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OBJECTIVES: The aim of this study was to evaluate the utility of distal protection during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes at high risk for distal embolization. BACKGROUND: The results of previous clinical trials indicated that the routine use of distal protection in patients with ST-segment elevation myocardial infarction did not improve clinical outcomes. However, selective use of distal protection by means of a filter-based distal protection system has not been evaluated. METHODS: Two hundred patients with acute coronary syndromes who had native coronary artery lesions and attenuated plaque with longitudinal length ≥5 mm on pre-PCI intravascular ultrasound were randomly assigned to undergo PCI with distal protection or conventional treatment. RESULTS: The primary endpoint (no-reflow phenomenon) occurred in 26 patients (26.5%) in the distal protection group and 39 patients (41.7%) in the conventional treatment group (p = 0.026), and the corrected TIMI (Thrombolysis In Myocardial Infarction) frame count after revascularization was significantly lower in the distal protection group (23 vs. 30.5; p = 0.0003). The incidence of cardiac death, cardiac arrest, cardiogenic shock after revascularization requiring defibrillation, cardiopulmonary resuscitation, or extracorporeal membrane oxygenation was significantly lower in the distal protection group than in the conventional treatment group (0% vs. 5.2%; p = 0.028). CONCLUSIONS: The use of distal embolic protection applied with a filter device decreased the incidence of the no-reflow phenomenon and was associated with fewer serious adverse cardiac events after revascularization than conventional PCI in patients with acute coronary syndromes with attenuated plaque ≥5 mm in length. (Assessment of Distal Protection Device in Patients at High Risk for Distal Embolism in Acute Coronary Syndrome [ACS] [VAMPIRE3]; NCT01460966).

DOI： 10.1016/j.jcin.2018.03.021

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DOI： 10.1016/j.jjcc.2017.11.013

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DOI： 10.1016/j.ijcha.2018.04.005

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DOI： 10.1161/JAHA.118.008718

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BACKGROUND: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population. METHODS: In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention. RESULTS: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group (P<0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; P=0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73-0.93; P=0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups. CONCLUSIONS: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730.

DOI： 10.1161/CIRCULATIONAHA.117.032615

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Large-scale clinical trials in patients in Western countries with coronary artery disease (CAD) have found that aggressive lipid-lowering therapy using high-dose statins reduces cardiovascular (CV) events further than low-dose statins. However, such evidence has not yet been fully established in Asian populations, including in Japan. The Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study addresses whether intensification of statin therapy improves clinical outcomes in Japanese patients with CAD.REAL-CAD is a prospective, multicenter, randomized, open-label, blinded-endpoint, physician-initiated phase 4 trial in Japan. The study will recruit up to 12,600 patients with stable CAD. Patients are assigned to receive either pitavastatin 1 mg/day or pitavastatin 4 mg/day. LDL-C levels are expected to reach approximate mean values of 100 mg/dL in the low-dose pitavastatin group and 80 mg/dL in the high-dose group. The primary endpoint is the time to occurrence of a major CV event, including CV death, non-fatal myocardial infarction, non-fatal ischemic stroke, and unstable angina requiring emergency hospitalization during an average of 5 years. The large number of patients and the long follow-up period in the REAL-CAD study should ensure that there is adequate power to definitively determine if reducing LDL-C levels to approximately 80 mg/dL by high-dose statin can provide additional clinical benefit.After the study is completed, we will have categorical evidence on the optimal statin dose and target LDL-C level for secondary prevention in Japanese patients.

DOI： 10.1536/ihj.17-557

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DOI： 10.1016/j.jccase.2017.10.006

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DOI： 10.1016/j.jcmg.2017.06.021

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BACKGROUND: Despite its recommendation by the current guidelines, the role of long-term oral beta-blocker therapy has never been evaluated by randomized trials in uncomplicated ST-segment elevation myocardial infarction (STEMI) patients without heart failure, left ventricular dysfunction or ventricular arrhythmia who underwent primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: In a multi-center, open-label, randomized controlled trial, STEMI patients with successful primary PCI within 24 hours from the onset and with left ventricular ejection fraction (LVEF) ≥40% were randomly assigned in a 1-to-1 fashion either to the carvedilol group or to the no beta-blocker group within 7 days after primary PCI. The primary endpoint is a composite of all-cause death, myocardial infarction, hospitalization for heart failure, and hospitalization for acute coronary syndrome. Between August 2010 and May 2014, 801 patients were randomly assigned to the carvedilol group (N = 399) or the no beta-blocker group (N = 402) at 67 centers in Japan. The carvedilol dose was up-titrated from 3.4±2.1 mg at baseline to 6.3±4.3 mg at 1-year. During median follow-up of 3.9 years with 96.4% follow-up, the cumulative 3-year incidences of both the primary endpoint and any coronary revascularization were not significantly different between the carvedilol and no beta-blocker groups (6.8% and 7.9%, P = 0.20, and 20.3% and 17.7%, P = 0.65, respectively). There also was no significant difference in LVEF at 1-year between the 2 groups (60.9±8.4% and 59.6±8.8%, P = 0.06). CONCLUSION: Long-term carvedilol therapy added on the contemporary evidence-based medications did not seem beneficial in selected STEMI patients treated with primary PCI. TRIAL REGISTRATION: CAPITAL-RCT (Carvedilol Post-Intervention Long-Term Administration in Large-scale Randomized Controlled Trial) ClinicalTrials.gov.number, NCT 01155635.

DOI： 10.1371/journal.pone.0199347

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DOI： 10.1253/circj.CJ-17-0649

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DOI： 10.1253/circj.CJ-17-0598

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DOI： 10.1253/circj.CJ-17-0746

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DOI： 10.1093/eurheartj/ehx351

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BACKGROUND: The biphasic inflammation after ST-segment elevation myocardial infarction (STEMI) plays an important role in myocardial healing and progression of systemic atherosclerosis. The purpose of this study is to investigate the impact of fever during the first and second phases of post-STEMI inflammation on long-term cardiac outcomes. METHODS AND RESULTS: A total of 550 patients with STEMI were enrolled in this study. Axillary body temperature (BT) was measured and maximum BTs were determined for the first (within 3 days: max-BT1-3d) and second (from 4 to 10 days after admission: max-BT4-10d) phases, respectively. Patients were followed for cardiac events (cardiovascular death, acute coronary syndrome, and rehospitalization for heart failure) for a median 5.3 years. During the follow-up period, 80 patients experienced cardiac events. A high max-BT4-10d was strongly associated with long-term cardiac events (hazard ratio, 95% CI) for a 1°C increase in the max-BT4-10d: 2.834 (2.017-3.828), P<0.0001, whereas the max-BT1-3d was not associated with cardiac events (1.136 [0.731-1.742], P=0.57). Even after adjustment for coronary risk factors, estimated glomerular filtration rate, infarct size, pericardial effusion, and medications on discharge, fever during the second phase (max-BT4-10d ≥37.1°C) was significantly associated with future cardiac events (hazard ratio [95% CI] 2.900 [1.710-5.143], P<0.0001). CONCLUSIONS: Fever during the second phase but not the first phase of post-STEMI inflammation was a strong associated factor with worse long-term cardiac outcomes in patients after STEMI, suggesting the need to consider the optimal timing for anti-inflammatory strategies after STEMI.

DOI： 10.1161/JAHA.116.005463

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DOI： 10.1016/j.jjcc.2016.04.014

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DOI： 10.1016/j.jjcc.2016.02.013

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Contrast-induced nephropathy (CIN) and chronic kidney disease (CKD) are associated with poor outcomes after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI); however, its combined prognostic significance remains unclear. We enrolled 577 patients with AMI undergoing primary PCI within 12 h after symptom onset and measured serum creatinine on admission and the next 3 days. CKD was defined as admission estimated glomerular filtration rate <60 ml/min/1.73 m2, and CIN was defined as creatinine increase ≥0.5 mg/dl or ≥25 % from baseline within the first 72 h. Patients were stratified according to the presence or absence of CKD and CIN. In patients with no CKD and no CIN (n = 244), no CKD but CIN (n = 152), CKD but no CIN (n = 127), and both CKD and CIN (n = 54), the 3-year major adverse cardiovascular events (MACE: a combination of all-cause mortality, nonfatal reinfarction, or heart failure requiring rehospitalization) were 8, 9, 13, and 35 %, respectively (p < 0.001). Multivariate analysis showed that as compared with no CKD and no CIN, hazard ratios (95 % CI) for MACE associated with no CKD but CIN, CKD but no CIN, and both CKD and CIN were 0.91 (0.44-1.84; p = 0.79), 1.11 (0.5-2.23; p = 0.77), and 2.98 (1.48-6.04; p = 0.002), respectively. In patients with AMI undergoing primary PCI, the combination of CKD and CIN is significantly associated with adverse long-term outcomes.

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DOI： 10.1161/JAHA.116.003202

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DOI： 10.1253/circj.CJ-15-0718

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Dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated anti-inflammatory and anti-atherogenic effects in an animal model. However, the clinical usefulness of DPP-4 inhibitors, particularly its effects on coronary atherosclerosis, has not been evaluated thus far. Therefore, in this study, we evaluated the effects of sitagliptin, a DPP-4 inhibitor, on coronary atherosclerosis using integrated backscatter (IB)-intravascular ultrasound (IVUS) in patients with type 2 diabetes. This trial was a prospective, open-labeled, randomized, multicenter study. Twenty-eight patients with type 2 diabetes who underwent elective percutaneous coronary intervention (PCI) were randomly assigned to either the sitagliptin group (group S) or the control group (group C). Non-PCI lesions were evaluated using IB-IVUS at the time of PCI and at the 48-week follow-up. The primary endpoint was the percentage change in plaque volume measured using grayscale IVUS, and the secondary endpoint was changes in plaque composition evaluated using IB-IVUS. Grayscale IVUS analysis demonstrated that plaque volume tended to decrease in both groups (group S: -1.7±8.5%; group C: -3.2±12.2%), but a between-group difference was not observed. A decrease in the lipid plaque volume (group S: from 200.1±116.2 to 179.8±121.0 mm3, P = 0.02; group C: from 298.3±363.0 to 256.6±386.1 mm3, P = 0.1) and an increase in the calcified plaque volume (group S: from 2.1±0.9 to 3.2±1.8 mm3, P = 0.06; group C: from 2.3±1.7 to 4.8±3.5 mm3, P = 0.04) was observed on IB-IVUS analysis. Univariate and multivariate regression analyses showed that the percentage change in serum non-high-density lipoprotein (HDL) cholesterol level was an independent and significant predictor of a reduction in lipid plaque volume (β = 0.445, P = 0.04). In conclusions, sitagliptin did not significantly reduce coronary plaque volume in patients with type 2 diabetes. However, a decrease in the lipid plaque volume was observed in the sitagliptin group. A decrease in non-HDL cholesterol level was associated with a reduction in the lipid volume of coronary artery plaques.

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AIMS: Non-invasive positive pressure ventilation rapidly improves the symptoms of acute heart failure (AHF). A portion of patients, however, are forced to be intubated even though intubation is associated with serious complications, and hypercapnia is often observed in AHF requiring intubation. The purpose of this study is to examine the clinical profile and management of hypercapnia in AHF patients. METHODS AND RESULTS: We examined the arterial blood gas analysis in 193 consecutive AHF patients (73 ± 12 years, 61% men) at admission. Many patients (n = 129, 66.8%) had already been treated with oxygen by the ambulance staff. Hypercapnia (PaCO2 at admission >45 mmHg) and hypocapnia (PaCO2  < 35 mmHg) were observed in 33.7% and 32.6%, respectively. Whereas 16 (24.6%) hypercapnic patients were intubated, there were only one (1.5%) normocapnic and no hypocapnic patients intubated. Patients with hypercapnia are more likely to be in the New York Heart Association Class IV (96.9% vs. 78.9%, P < 0.001), to have acute onset within 6 h (50.8% vs. 25.0%, P < 0.001), and to have radiographic pulmonary oedema (84.6% vs. 57.8%, P < 0.001) than those with hypo-normocapnia. Hypercapnia was more frequent in patients with acute cardiogenic pulmonary oedema than in those with acute decompensated heart failure (51.9% vs. 23.6%, P < 0.001). At discharge, hypercapnia was observed in 17.8% of patients who were hypercapnic at admission. CONCLUSION: Hypercapnia emerged in AHF acutely and transiently, was associated with immediate airway intervention, and was possibly involved in the pathophysiology of acute pulmonary oedema. Patients with acute onset dyspnoea should have their respiratory status carefully managed. These pathophysiological findings are expected to be utilized in treating or preventing AHF.

DOI： 10.1002/ehf2.12023

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DOI： 10.1016/S0735-1097(15)61228-1

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DOI： 10.1093/ehjci/jeu173

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DOI： 10.1007/s00380-013-0453-8

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DOI： 10.1253/circj.CJ-14-1044

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BACKGROUND: Although rapid progression (RP) of coronary artery disease (CAD) has been shown to be a powerful predictor of cardiovascular events, predictors of RP are not fully understood in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: We prospectively investigated the clinical impact of glycemic variability (GV), as determined on continuous glucose monitoring system (CGMS), on RP of non-culprit lesions in 88 patients with ACS. RP was defined as ≥10% diameter reduction in a pre-existing stenosis ≥50%; ≥30% diameter reduction in a stenosis <50%; development of a new stenosis ≥30% in a previously normal segment; or progression of any stenosis to total occlusion. Patients were classified into 2 groups according to the presence (progressor, n=20) or absence (non-progressor, n=68) of RP. All patients were equipped with a CGMS during the stable phase, and mean amplitude of glycemic excursion (MAGE) was calculated as a marker of GV. Mean MAGE was significantly higher in progressors than in non-progressors (55±19 mg/dl vs. 37±18 mg/dl, P<0.01). On multiple logistic regression analysis, MAGE was an independent predictor of RP (odds ratio, 1.06 per 1 mg/dl; P<0.01). CONCLUSIONS: MAGE early after the onset of ACS is a predictor of RP of non-culprit lesions.

DOI： 10.1253/circj.CJ-15-0496

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BACKGROUND: Impaired glucose metabolism plays an important role in patients with acute myocardial infarction, but the clinical significance of glycemic variability (GV) early after the onset of ST-segment elevation myocardial infarction (STEMI) remains to be fully elucidated. METHODS AND RESULTS: We prospectively investigated the clinical impact of GV, as determined by a continuous glucose monitoring system (CGMS), on left ventricular remodeling (LVR) assessed by cardiac magnetic resonance imaging (CMR) in 69 patients (63±13 years, 59 men) with a first reperfused STEMI within 12 h of onset. All patients were equipped with a CGMS when in a stable phase after admission and underwent repeat CMR at baseline and 7 months follow-up. Patients were divided into 2 groups according to the mean amplitude of glycemic excursions (MAGE). Patients in the upper tertile of MAGE were categorized as group High (H) and the other two-thirds as group Low (L). LVR was defined as an absolute increase in left ventricular end-diastolic volume index of ≥20%. LVR more frequently occurred in group H than in group L (56% vs. 11%, P<0.001). Multivariate analysis showed the higher MAGE group was an independent predictor of LVR in the chronic phase (odds ratio, 13.999; 95% confidence interval, 3.059 to 64.056; P=0.001). CONCLUSIONS: MAGE early after the onset of STEMI identified patients with LVR in the chronic phase.

DOI： 10.1253/circj.CJ-14-1226

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DOI： 10.1016/j.ijcard.2014.07.221

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DOI： 10.1016/j.jacc.2014.07.396

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ireland Ltd  

DOI： 10.1016/j.ijcme.2014.07.002

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DOI： 10.1016/j.jacc.2014.07.441

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