記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Aortic atherosclerosis can affect the strategy and outcomes of transcatheter aortic valve replacement (TAVR). Limited investigation exists into how aortic atheroma morphology influences outcomes post-TAVR. OBJECTIVES: This study aimed to assess the influence of protruding and ulcerated aortic atheromas on periprocedural ischemic stroke post-TAVR. METHODS: This analysis included 977 patients who underwent TAVR between February 2010 and May 2019, with available contrast-enhanced computed tomography data. Protruding aortic atheroma was defined as atheroma of ≥3 mm thickness with protruding components. Ulcerated aortic atheroma was defined as atheroma with ulcer-like intimal disruption. The primary endpoint was periprocedural ischemic stroke within 30 days post-TAVR. RESULTS: In total, 43 (4.4%) experienced periprocedural ischemic stroke. Patients with protruding or ulcerated aortic atheroma had a significantly higher incidence of periprocedural stroke compared with those without (8.0% [95% CI: 4.9%-12.2%] vs 3.2% [95% CI: 2.1%-4.8%]; P = 0.003). Protruding or ulcerated atheroma (adjusted OR [aOR]: 2.55 [95% CI: 1.37-4.74]), particularly in the aortic arch (aOR: 3.86 [95% CI: 1.69-8.83]), independently increased periprocedural stroke risk. Among patients undergoing transfemoral TAVR with self-expandable valves (n = 315, 32%), protruding or ulcerated atheroma in the aortic arch was independently associated with periprocedural stroke (aOR: 9.04 [95% CI: 1.59-51.4]), whereas it was not among those with balloon-expandable valves (n = 580, 59%) (aOR: 2.85 [95% CI: 0.92-8.84]). CONCLUSIONS: Protruding and ulcerated aortic atheromas are associated with a higher risk of periprocedural ischemic stroke post-TAVR. Careful selection of TAVR strategy, including valve type and procedural approach, is essential for patients with such aortic lesions.

DOI： 10.1016/j.jacasi.2024.10.020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIMS: Atrial fibrillation (AF), the most common cardiac arrhythmia favouring ischemic stroke and heart failure involves left atrial remodelling, fibrosis and a complex interplay between cardiovascular risk factors. This study examined whether activated factor X (FXa) induces pro-remodelling and pro-fibrotic responses in atrial endothelial cells (AECs) and human atrial tissues and determined the underlying mechanisms. METHODS AND RESULTS: AECs collected from porcine hearts and human right atrial appendages (RAA) from patients undergoing heart surgery. Protein expression levels were assessed by Western blot and immunofluorescence staining, mRNA levels by RT-qPCR, formation of reactive oxygen species (ROS) and NO using fluorescent probes, thrombin and angiotensin II generation by specific assays, fibrosis by Sirius red staining and senescence by senescence-associated beta-galactosidase (SA-β-gal) activity. In AECs, FXa increased ROS formation, senescence (SA-β-gal activity, p53, p21), angiotensin II generation and the expression of pro-inflammatory (VCAM-1, MCP-1), pro-thrombotic (tissue factor), pro-fibrotic (TGF-β and collagen-1/3a) and pro-remodelling (MMP-2/9) markers whereas eNOS levels and NO formation were reduced. These effects were prevented by inhibitors of FXa but not thrombin, protease-activated receptors antagonists (PAR-1/2) and inhibitors of NADPH oxidases, ACE, AT1R, SGLT1/SGLT2. FXa also increased expression levels of ACE1, AT1R, SGLT1/2 proteins which were prevented by SGLT1/2 inhibitors. Human RAA showed tissue factor mRNA levels that correlated with markers of endothelial activation, pro-remodelling and pro-fibrotic responses and SGLT1/2 mRNA levels. They also showed protein expression levels of ACE1, AT1R, p22phox, SGLT1/2, and immunofluorescence signals of nitrotyrosine and SGLT1/2 colocalized with those of CD31. FXa increased oxidative stress levels which were prevented by inhibitors of the AT1R/NADPH oxidases/SGLT1/2 pathway. CONCLUSION: FXa promotes oxidative stress triggering premature endothelial senescence and dysfunction associated with pro-thrombotic, pro-remodelling and pro-fibrotic responses in AECs and human RAA involving the AT1R/NADPH oxidases/SGLT1/2 pro-oxidant pathway. Targeting this pathway may be of interest to prevent atrial remodelling and the progression of atrial fibrillation substrate.

DOI： 10.1093/cvr/cvae101

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記述言語：英語  

DOI： 10.1016/j.cjca.2024.02.026

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

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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掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Atherosclerosis Society  

DOI： 10.5551/jat.64988

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記述言語：英語   出版者・発行元：(一社)日本心血管インターベンション治療学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

BACKGROUND AND AIMS: Anti-atherosclerotic effects of early intervention with dipeptidyl peptidase-4 inhibitors remain poorly defined. METHODS: In a prospective, single-center, randomized trial, 66 patients with acute coronary syndrome (ACS) and mild dysglycemia (HbA1c 6.0 (5.7, 6.3)%, 58% of impaired glucose tolerance) were randomly assigned to receive alogliptin (n = 33) or placebo (n = 33) in addition to standard treatments. Serial intravascular ultrasound (IVUS) was performed at baseline and 10 months to evaluate changes in coronary percent plaque volumes (%PV) and plaque tissue components of non-culprit lesions (NCLs). RESULTS: Baseline clinical and IVUS characteristics, as well as decreases in HbA1c and lipid variables during 10 months, did not differ significantly between the 2 groups. In contrast, with respect to vascular responses, the alogliptin group showed significantly greater decreases in plaque volumes (-0.3 ± 0.6 vs. -0.04 ± 0.7 mm3/mm, p = 0.03) and %PV (-0.9 ± 2.8 vs. 1.2 ± 3.6%, p = 0.01), with a tendency toward smaller lumen loss (-0.1 ± 0.7 vs. -0.4 ± 0.8 mm3/mm, p = 0.07) compared with the placebo group. Significantly decreased percent necrotic volumes (%NV) (-1.9 ± 3.8 vs. 0.3 ± 3.7%, p = 0.03) and increased fibrotic volumes (2.5 ± 5.0 vs. -0.3 ± 5.3%, p = 0.05) were or tended to be seen in alogliptin versus placebo groups at 10 months. In multiple regression analysis, alogliptin use was a statistically significant determinant of changes in %PV (β = -0.33, p = 0.004) and %NV (β = -0.28, p = 0.03) at 10 months. CONCLUSIONS: Alogliptin treatment, independently of glycemic and lipid status, resulted in significant plaque regression and stabilization in NCLs in patients with ACS and mild dysglycemia, suggesting the potential utility of early intervention with incretin-based treatments for this patients' subset.

DOI： 10.1016/j.atherosclerosis.2022.09.005

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1253/circj.CJ-22-0417

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記述言語：英語   出版者・発行元：(一社)日本循環器学会  

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Endothelial dysfunction is reportedly associated with worse outcomes in patients with chronic heart failure. Ubiquinol is a reduced form of coenzyme Q10 (CoQ10) that may improve endothelial function. OBJECTIVE: We assessed the hypothesis that ubiquinol improves peripheral endothelial function in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: In this randomized, double-blind, placebo-controlled, crossover pilot study, 14 patients with stable HFrEF were randomly and blindly allocated to ubiquinol 400 mg/day or placebo for 3 months. After a 1-month washout period, patients were crossed over to the alternative treatment. Before and after each treatment, we assessed peripheral endothelial function using the reactive hyperemia index (RHI) and analyzed it using the natural logarithm of RHI (LnRHI). RESULTS: Peripheral endothelial function as assessed by LnRHI tended to improve with ubiquinol 400 mg/day for 3 months (p = 0.076). Original RHI values were also compared, and RHI significantly improved with ubiquinol treatment (pre-RHI 1.57 [interquartile range (IQR) 1.39-1.80], post-RHI 1.74 [IQR 1.63-2.02], p = 0.026), but not with placebo (pre-RHI 1.67 [IQR 1.53-1.85], post-RHI 1.51 [IQR 1.39-2.11], p = 0.198). CONCLUSIONS: Ubiquinol 400 mg/day for 3 months led to significant improvement in peripheral endothelial function in patients with HFrEF. Ubiquinol may be a therapeutic option for individuals with HFrEF. Large-scale randomized controlled trials of CoQ10 supplementation in patients with HFrEF are needed. CLINICAL TRIAL REGISTRATION: Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000012604.

DOI： 10.1007/s40256-019-00384-y

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記述言語：英語  

The incidence of acute complications is high in patients presenting late with acute myocardial infarction (AMI). We describe the case of a patient who presented late with anterior AMI that was complicated by left ventricular (LV) thrombus and electrical storm (ES). Temporary right ventricular pacing suppressed ES under extracorporeal membrane oxygenation support but reduced cardiac function. Immediately after returning to sinus rhythm (i.e. increase in cardiac function), free-floating LV thrombus was detected by echocardiography, resulting in cerebral embolism. Rapid improvement in cardiac function related to mechanical hemodynamic support may become a trigger for embolization in patients with LV thrombus. <Learning objective: Patients presenting late with acute myocardial infarction have a high incidence of complications. In patients with severe left ventricular (LV) dysfunction who require venoarterial extracorporeal membrane oxygenation, right ventricular (RV) pacing can advocate cardiac dysfunction with insufficient aortic valve opening. When patients have LV thrombus in this situation, rapid improvement in cardiac function by the interruption of RV pacing can dislodge LV thrombus, leading to systematic embolism.>.

DOI： 10.1016/j.jccase.2020.02.009

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Prompt and potent antiplatelet effects are important aspects of management of ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). We evaluated the association between platelet-derived thrombogenicity during PPCI and enzymatic infarct size in STEMI patients.Methods and Results:Platelet-derived thrombogenicity was assessed in 127 STEMI patients undergoing PPCI by: (1) the area under the flow-pressure curve for the PL-chip (PL18-AUC10) using the total thrombus-formation analysis system (T-TAS); and (2) P2Y12reaction units (PRU) using the VerifyNow system. Patients were divided into 2 groups (High and Low) based on median PL18-AUC10during PPCI. PRU levels during PPCI were suboptimal in both the High and Low PL18-AUC10groups (median [interquartile range] 266 [231-311] vs. 272 [217-317], respectively; P=0.95). The percentage of final Thrombolysis in Myocardial Infarction (TIMI) 3 flow was lower in the High PL18-AUC10group (75% vs. 90%; P=0.021), whereas corrected TIMI frame count (31.3±2.5 vs. 21.0±2.6; P=0.005) and the incidence of slow-flow/no-reflow phenomenon (31% vs. 11%, P=0.0055) were higher. The area under the curve for creatine kinase (AUCCK) was greater in the High PL18-AUC10group (95,231±7,275 IU/L h vs. 62,239±7,333 IU/L h; P=0.0018). Multivariate regression analysis identified high PL18-AUC10during PPCI (β=0.29, P=0.0006) and poor initial TIMI flow (β=0.37, P<0.0001) as independent determinants of AUCCK. CONCLUSIONS: T-TAS-based high platelet-derived thrombogenicity during PPCI was associated with enzymatic infarct size in patients with STEMI.

DOI： 10.1253/circj.CJ-19-1043

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語  

DOI： 10.1016/j.jacc.2019.08.984

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記述言語：英語  

DOI： 10.1016/j.jacc.2019.08.215

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Trimethylamine N-oxide (TMAO), a metabolite derived from the gut microbiota, is proatherogenic and associated with cardiovascular events. However, the change in TMAO with secondary prevention therapies for ST-segment elevation acute myocardial infarction (STEMI) remains unclear. The purpose of this study was to investigate the sequential change in TMAO levels in response to the current secondary prevention therapies in patients with STEMI and the clinical impact of TMAO levels on cardiovascular events We included 112 STEMI patients and measured plasma TMAO levels at the onset of STEMI and 10 months later (chronic phase). After the chronic-phase assessment, patients were followed up for cardiovascular events. Plasma TMAO levels significantly increased from the acute phase to the chronic phase of STEMI (median: 5.63 to 6.76 μM, P = 0.048). During a median period of 5.4 years, 17 patients experienced events. The chronic-phase TMAO level independently predicted future cardiovascular events (adjusted hazard ratio for 0.1 increase in log chronic-phase TMAO level: 1.343, 95% confidence interval 1.122-1.636, P = 0.001), but the acute-phase TMAO level did not. This study demonstrated the clinical importance of the chronic-phase TMAO levels on future cardiovascular events in patients after STEMI.

DOI： 10.1038/s41598-019-48246-6

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.jelectrocard.2019.04.004

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

Some experimental studies have shown that direct oral anticoagulants (DOACs) have anti-inflammatory effects. However, the interval changes in inflammatory markers in patients with non-valvular atrial fibrillation (AF) who receive DOACs remain unknown. Between July 2013 and April 2014, a total of 187 AF patients randomly assigned to receive rivaroxaban (n = 91) or dabigatran (n = 96) were assessed for eligibility. The levels of the following inflammatory markers were serially evaluated: high-sensitivity C-reactive protein, pentraxin-3, interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α, monocyte chemotactic protein-1, growth and differentiation factor-15, and soluble thrombomodulin (sTM). The aim in this study was to evaluate the anti-inflammatory effects of rivaroxaban and dabigatran in patients with AF, in addition to the impact of markers on bleeding events. Finally, 117 patients (rivaroxaban: n = 55, dabigatran: n = 62) were included in the analysis at 12 months. Although the interval changes in sTM levels tended to be greater in the dabigatran group [0.3 (0-0.7) vs. 0.5 (0-1.0) FU/ml, p = 0.061], there were no significant differences in the interval changes in any inflammatory marker between 2 groups. There were no significant differences in bleeding events between 2 groups. The interval changes in sTM levels were significantly greater in patients with bleeding compared with those without [0.8 (0.5-1.3) vs. 0.4 (- 0.1-0.8) FU/ml, p = 0.017]. There were no significant differences in the interval changes in any inflammatory marker between rivaroxaban and dabigatran treatments in patients with AF. The increased levels of sTM after DOACs treatment might be related to bleeding events.

DOI： 10.1007/s00380-018-01324-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Few reports have evaluated the total antithrombotic effect of multiple antithrombotic agents. Methods and Results: Thrombus formation was evaluated with the Total Thrombus-formation Analysis System (T-TAS®) using 2 types of microchips in 145 patients with stable coronary artery disease receiving oral anticoagulants plus single- or dual-antiplatelet therapy. The PL-chip coated with collagen is designed for analysis of the platelet thrombus formation process under shear stress condition (18 µL/min). The AR-chip coated with collagen and tissue thromboplastin is designed for analysis of the fibrin-rich platelet thrombus formation process under shear stress condition (4 µL/min). The results were expressed as an area under the flow pressure curve (PL18-AUC10and AR4-AUC30, respectively). Bleeding events occurred in 43 patients during a 22-month follow-up. AR4-AUC30was significantly lower in patients with bleeding events than in those without (584 [96-993] vs. 1,028 [756-1,252], P=0.0003). Multivariate logistic regression analysis identified AR4-AUC30(odds ratio 3.18) as a significant predictor of bleeding events, in addition to baseline anemia and usage of the standard dose of direct oral anticoagulants. However, PL18-AUC10was not significantly related to bleeding events. CONCLUSIONS: A lower AR4-AUC30level was associated with increasing risk of subsequent bleeding complications in patients with stable coronary artery disease who received multiple antithrombotic agents.

DOI： 10.1253/circj.CJ-18-1236

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

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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記述言語：英語  

DOI： 10.1016/j.jacc.2018.08.2016

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記述言語：日本語   出版者・発行元：医学図書出版(株)  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00001&link_issn=&doc_id=20181003460008&doc_link_id=%2Faa6icutc%2F2018%2F004208%2F009%2F0542-0546%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Faa6icutc%2F2018%2F004208%2F009%2F0542-0546%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：日本語   出版者・発行元：(公財)日本心臓財団  

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その他リンク： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00679&link_issn=&doc_id=20180813190015&doc_link_id=%2Fah2sinzd%2F2018%2F005008%2F016%2F0934-0940%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fah2sinzd%2F2018%2F005008%2F016%2F0934-0940%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

記述言語：英語  

Management of in-stent restenosis (ISR) remains challenging even in the drug-eluting stent era. We report the case of a Japanese female with repeated ISR after primary percutaneous coronary intervention (PCI) for acute coronary syndrome. We observed ISR tissue with "black hole" on intravascular ultrasound, which appeared to be heterogeneous tissue on optical frequency-domain imaging (OFDI). Paclitaxel-coated balloon dilatation of the ISR lesion with "black hole" was ineffective. The morphological assessment of ISR tissue using OFDI might be important to treat ISR lesions by PCI. OFDI is a novel tool to observe the difference in the in-stent tissue characteristics. <Learning objective: In-stent restenosis (ISR) remains a clinical problem even in the drug-eluting stent (DES) era. The morphological assessment of ISR tissue using optical frequency-domain imaging (i.e. homogeneous, heterogeneous, and layered types) might be important to treat ISR lesions by percutaneous coronary intervention since the reaction to DES and drug-coating balloon seems to be different according to the in-stent tissue characteristics.>.

DOI： 10.1016/j.jccase.2017.10.006

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: The purpose of this study is to evaluate whether prone myocardial perfusion single-photon emission computed tomography (MPS) with thallium-201 acquired through a variable-focus collimator (IQ-SPECT) can correct for soft-tissue attenuation. METHODS: Thirty-nine patients underwent thallium-201 stress MPS with IQ-SPECT. Delayed images acquired with the patients in the prone position were compared with delayed images obtained with the patients in the supine position with computed tomography-derived attenuation correction (CTAC) (S-CTAC images) or without CTAC (S-NCTAC images). Quantitative tracer uptake (QTU) and semi-quantitative defect scores were determined for the 17 standard myocardial segments. Segments were categorized into anterior-anteroseptal, lateral, inferior, and apex, and areas with defect decision were determined by using the defect scores. RESULTS: Image quality in the prone images was similar to that of S-NCTAC and S-CTAC images. In male patients, QTU in prone images was equivalent to that in S-CTAC images in the anterior-anteroseptal area, but was significantly lower than that in S-CTAC images in the inferior area. In female patients, QTU in prone images was similar to that in S-CTAC images in the anterior-anteroseptal, lateral, and inferior areas. In male and in female patients, QTU in the apex was significantly greater in the prone images than that in the S-CTAC images. In the combined male and female patient group, the defect decision for prone images was similar to that for S-CTAC images in the anterior-anteroseptal, lateral, and inferior areas. Apical defects were observed more frequently in S-CTAC images than in prone or S-NCTAC images. CONCLUSIONS: Fewer artificial defects were observed in the apex of images acquired by prone imaging than by S-CTAC imaging. Prone images improved attenuation and had similar defect decision as S-CTAC images in the anterior-anteroseptal, lateral, and inferior areas.

DOI： 10.1007/s12149-015-1019-x

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVE: IQ-SPECT (Siemens AG, Munich, Germany) is a highly sensitive single-photon-emission computed tomography (SPECT) myocardial perfusion imaging (MPI) system that uses a multifocal collimator. We searched for a suitable protocol for short-time imaging by IQ-SPECT in thallium-201 (Tl-201) MPI by evaluating phantom images and also by comparing human IQ-SPECT images with conventional SPECT images as reference standards. METHODS: We assessed the image quality using the normalized mean square error (NMSE) and drew up count profiles in Tl-201 SPECT images acquired with IQ-SPECT in a phantom study. We also performed Tl-201 stress myocardial SPECT/CT in 21 patients and compared delayed images acquired by using IQ-SPECT with 36 or 17 views per head with images obtained by using conventional SPECT. RESULTS: The NMSE of SPECT images from IQ-SPECT with 36 views was approximately one-fifth of that with 17 views. The myocardial count profile of images with 17 views was lower than those of images with 36 or 104 views in some regions. Defect scores were significantly lower, and image quality scores higher, in images from conventional SPECT than in those from IQ-SPECT with 17 views. Defect scores and image quality scores were equivalent in images from conventional SPECT and those from IQ-SPECT with 36 views. Agreement with the results of conventional SPECT in terms of coronary artery territory-based defect judgment was the best in IQ-SPECT with 36 views with computed tomography-derived attenuation correction (CTAC): the kappa values for IQ-SPECT with 36 views were 0.76 (without CTAC) and 0.83 (with CTAC), and those for IQ-SPECT with 17 views were 0.62 (without CTAC) and 0.59 (with CTAC). The difference in quantitative tracer uptake between conventional SPECT images and IQ-SPECT images was significantly greater for IQ-SPECT images with 17 views than for those with 36 views. CONCLUSIONS: Scanning with 36 views per head with CTAC may be appropriate for Tl-201 MPI using IQ-SPECT, because it provides images equivalent to those using conventional SPECT.

DOI： 10.1007/s12149-014-0880-3

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