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

DOI： 10.30548/vascfail.8.1_1

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OBJECTIVES: The Asian Working Group for Sarcopenia in 2019 (AWGS 2019) emphasized muscle mass measurements. In contrast, the Sarcopenia Definitions and Outcomes Consortium (SDOC) prioritizes functional strength and mobility. Therefore, this study aimed to compare the prognostic utility of the SDOC and AWGS 2019 criteria for all-cause mortality in older patients with heart failure. DESIGN: A post hoc analysis of the FRAGILE-HF study, a prospective, multicenter, observational study. SETTING AND PARTICIPANTS: Patients ≥65 years of age hospitalized for heart failure across 15 hospitals in Japan. METHODS: Sarcopenia was diagnosed according to the AWGS 2019 and SDOC definitions. According to the SDOC criteria and by integrating insights from previous research, patients were categorized into nonsarcopenia, possible sarcopenia, and sarcopenia groups. The primary outcome was 2-year mortality. RESULTS: Of the 1282 study patients, possible sarcopenia and sarcopenia were diagnosed in 357 and 786 individuals, respectively. Kaplan-Meier analysis revealed a significant difference between the groups. Adjusted Cox proportional hazards analysis indicated a significant stepwise association between sarcopenic status and mortality risk (possible sarcopenia: hazard ratio, 1.22; 95% CI, 0.66-2.28; P = .525; sarcopenia: hazard ratio, 1.89; 95% CI, 1.08-3.34; P = .027). When sarcopenia defined by the SDOC and AWGS 2019 criteria was added to the model incorporating conventional risk factors, no significant difference was observed in the prognostic capabilities between the 2 models (net reclassification improvement, -0.009; 95% CI, -0.193 to 0.174; P = .920, with areas under the receiver operating characteristic curve of 0.697 for SDOC and 0.703 for AWGS 2019; P = .675). CONCLUSIONS AND IMPLICATIONS: Among older patients with heart failure, the SDOC criteria for sarcopenia diagnosis are useful for risk stratification and provide prognostic capabilities equivalent to those of the AWGS 2019 criteria.

DOI： 10.1016/j.jamda.2024.105350

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

ABSTRACT

Background

The Asian Working Group for Cachexia (AWGC) proposed a new definition of cachexia; however, its impact on cachexia prevalence and overlaps with other conditions, such as sarcopenia and malnutrition, are unclear. We investigated these aspects and the prognostic value of cachexia based on the AWGC on mortality in older patients with heart failure (HF).

Methods

This study was a secondary analysis of a prospective multicentre cohort, namely, the FRAGILE‐HF cohort study. Older (≥ 65 years) patients who had been hospitalized due to decompensated HF were enrolled. We assessed the presence/absence of cachexia based on the AWGC and Evans' criteria. Sarcopenia and malnutrition based on the Asian Working Group for Sarcopenia 2014 and the Global Leadership Initiative on Malnutrition criteria were also assessed to compare their prevalence and the overlaps between them. Patients were stratified in relation to the presence/absence of cachexia based on the AWGC criteria, and their mortality rates were compared.

Results

Of the 861 enrolled patients (median [interquartile range] age, 80 years [73–85 years]; male, 58.9%), cachexia, as evaluated based on the AWGC and Evans' criteria, sarcopenia and malnutrition, was present in 74.1%, 36.2%, 20.6% and 55.2% of patients, respectively. AWGC‐defined cachexia was most common in the four conditions. All‐cause death events occurred in 153 (18.1%) patients in 2 years. AWGC‐defined cachexia (adjusted hazard ratio [aHRs], 1.442; 95% confidence interval [95% CI], 0.931–2.233; p = 0.101) was not associated with all‐cause mortality in older patients with HF after adjusting for other HF prognosis factors, such as the B‐type natriuretic peptide and the Meta‐Analysis Global Group in Chronic risk score, whereas cachexia evaluated based on Evans's criteria (aHRs, 1.547; 95% CI, 1.118–2.141; p = 0.009), sarcopenia (aHRs, 1.737; 95% CI, 1.214–2.485; p = 0.003), and malnutrition (aHRs, 1.581; 95% CI, 1.094–2.284; p = 0.015) was associated with all‐cause mortality.

Conclusions

Three‐quarters of older patients with HF had cachexia as evaluated by the AWGC criteria, and this was not associated with a worse prognosis. As the new AWGC cachexia criteria will result in a significantly larger proportion of patients being diagnosed with cachexia, the implementation of the criteria in clinical practice requires further consideration.

Trial Registration: UMIN‐CTR unique identifier: UMIN000023929

DOI： 10.1002/jcsm.13610

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OBJECTIVES: The benefits of early rehabilitation for patients with acute heart failure (HF) requiring IV inotropic drugs have yet to be determined. We investigated the association between early rehabilitation and short-term clinical outcomes in patients with acute HF requiring IV inotropic drugs. DESIGN: Retrospective cohort study. SETTING: This study used data including more than 90% of patients at a tertiary emergency hospital in Japan. PATIENTS: This study included patients with acute HF who required IV inotropic drugs within 2 days of admission. INTERVENTIONS: We compared patients who commenced rehabilitation within 2 days of admission (the early rehabilitation group) and those who did not (the control group). MEASUREMENTS AND MAIN RESULTS: Propensity score matching was used to compare in-hospital mortality, 30-day all-cause and HF readmissions, length of stay, and Barthel Index (BI) at discharge between patients who received early rehabilitation and those who did not. Totally, 38,302 patients were eligible for inclusion; of these, 5,127 received early rehabilitation and 5,126 pairs were generated by propensity score matching. After propensity score matching, the patients who received early rehabilitation had a lower in-hospital mortality rate than those who did not (9.9% vs. 13.2%; p < 0.001). The relative risk (95% CI) of early rehabilitation for in-hospital mortality was 0.75 (0.67-0.83). Patients undergoing early rehabilitation exhibited a shorter mean length of stay (25.5 vs. 27.1; p < 0.001), lower 30-day all-cause (14.1% vs. 16.4%; p = 0.001) and HF (8.6% vs. 10.4%; p = 0.002) readmissions, and higher BI scores at discharge (68 vs. 67; p = 0.096). Consistent findings were observed across subgroups, including in patients 80 years old or older, those with a body mass index less than 18.5 kg/m2, and those with BI scores less than 60. CONCLUSIONS: The early prescription of rehabilitation was associated with favorable short-term outcomes even for patients with acute HF requiring IV inotropic drugs.

DOI： 10.1097/CCM.0000000000006462

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Publishing type：Research paper (scientific journal)  

Background: Physical frailty and malnutrition coexist in older patients with heart failure (HF) and form a vicious cycle exacerbating each other and can cause poor clinical outcomes. We aimed to clarify the association of prevalence of physical frailty and malnutrition and clinical outcomes in hospitalized patients with HF. Methods: A total of 862 hospitalized patients aged ≥65 years with HF decompensation were included in this FRAGILE-HF post-hoc sub-analysis. Patients were categorized into Neither, Either, or Both groups based on the prevalence of physical frailty and malnutrition. The primary outcome was all-cause mortality within 1 year after discharge. Prognoses among the groups were compared in the entire cohort and in subgroups with preserved ejection fraction (pEF) and reduced/mildly reduced left ventricular ejection fractions (rEF/mrEF). Results: The Neither, Either, and Both groups comprised 32 %, 40 %, and 28 % respectively. During a 1-year follow-up period, 101 (12 %) patients died. Kaplan–Meier analysis showed significant differences in the primary outcomes among the groups (P < 0.001). The Both group had a higher risk of mortality (HR: 2.47, 95 % CI: 1.38–4.42) than the Neither group, while the Either group showed insignificant risk increase (HR: 1.58, 95 % CI: 0.86–2.90). Similar trends were observed in the pEF and rEF/mrEF subgroups (P = 0.60). Conclusions: Physical frailty and malnutrition coexist in approximately one-quarter of hospitalized older patients with HF and are associated with an increased risk of mortality. Assessing both conditions is crucial for risk stratification and interventions to mitigate their interplay.

DOI： 10.1016/j.ahjo.2024.100467

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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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AIMS: The six-minute walk test (6MWT) is a widely accepted tool for evaluating exercise tolerance and physical capacity, and the six-minute walk distance (6MWD) is an established prognostic factor in patients with heart failure (HF). However, the prognostic implications of post-6MWT dyspnoea remain unknown. We aimed to investigate the prognostic value of Borg scores after the 6MWT in patients with HF. METHODS: Patients hospitalized for HF who underwent the 6MWT before discharge were included. Post-test dyspnoea was assessed using the Borg scale. Patients were stratified into low and high Borg score groups based on the median Borg score. The primary outcome was 2-year mortality. RESULTS: Among 1,185 patients analysed, the median Borg score was 12. The 6MWD was significantly shorter in the high Borg score group than in the low Borg score group. The 2-year mortality rate was 20.2%. In the Kaplan-Meier analysis, the high Borg score group demonstrated an association with 2-year mortality, which remained significant even after adjustment for conventional risk factors, including the 6MWD. Furthermore, Borg scale provided significant net reclassification improvement to the conventional risk model incorporating 6MWD. CONCLUSION: In hospitalized patients with HF, post-6MWT Borg scores were associated with 2-year mortality independent of the 6MWD, providing incremental prognostic value to the 6MWD. Even if patients are able to walk long distances for 6 minutes, it is essential to closely observe dyspnoea immediately thereafter.

DOI： 10.1093/eurjpc/zwae291

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BACKGROUND: Sarcopenia is a substantial therapeutic target, yet the validity of risk stratification values per the latest Asian Working Group for Sarcopenia in 2019 (AWGS 2019) remains unconfirmed in patients with heart failure. We hypothesized that using the 6-minute walk test (6MWT) to assess physical performance improves risk stratification. METHODS: The study included 832 hospitalized patients with heart failure who could walk at discharge. Sarcopenia was diagnosed using both the original AWGS 2019 criteria (AWGS 2019 model) and an alternative method, in which physical performance components were replaced with the 6MWT (modified model). An <300 m 6MWT indicated low physical performance in the modified model. The primary outcome was 2-year mortality. RESULTS: Sarcopenia and severe sarcopenia were identified in 45 and 150 patients with the AWGS 2019 model and in 75 and 108 patients with the modified model, respectively. Over the 2-year follow-up period, 145 (17.4%) deaths occurred. Adjusted Cox proportional hazard analysis showed both sarcopenia and severe sarcopenia were significantly associated with 2-year mortality in the modified model. In the AWGS 2019 model, only severe sarcopenia was significantly related to 2-year mortality. The modified model demonstrated significant net reclassification improvement (NRI) over the AWGS 2019 model (NRI, 0.396; 95% CI, 0.214-0.578; P < 0.001). CONCLUSIONS: In patients with heart failure who were ambulatory at discharge, sarcopenia assessment with the modified AWGS 2019 model using the 6MWT as a physical performance component improved risk stratification compared with the original AWGS 2019 model. Reconsidering the current criteria to improve risk stratification is necessary to ensure timely, appropriate treatment.

DOI： 10.1016/j.cjca.2024.07.031

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

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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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AIMS: In heart failure (HF), inflammation is linked to malnutrition and impaired physical function. In this study, we aimed to assess how novel nutritional-inflammatory markers and lymphocyte-to-C-reactive protein ratio (LCR) and score (LCS) are associated with the nutritional status, physical function, and prognosis of patients with HF. METHODS AND RESULTS: This study was a secondary analysis of the FRAGILE-HF study, a prospective observational study conducted across 15 hospitals in Japan. We included 1212 patients (mean age, 80.2 ± 7.8 years; 513 women) hospitalized with HF, who were classified into three groups according to their LCS score: 0 (n = 498), 1 (n = 533), and 2 (n = 181). Baseline data on physical examination, echocardiography, blood test results (including lymphocyte counts and CRP levels), and oral medication usage were collected in a clinically compensated state before discharge. Nutritional status and physical function were evaluated using several indices and tests. The primary outcome of this study was all-cause death within 2 years. Univariate and multivariate linear regression analyses were performed to evaluate the associations among the nutritional status, physical function, and LCR/LCS. Patients with an LCS score of 2 were older and had a lower body mass index than those in the other two groups. Multivariate linear regression analysis revealed that lower LCR and higher LCS were independently associated with worse nutritional status, lower handgrip strength, shorter physical performance battery score, and shorter 6-min walk distance. At 2 years, all-cause death occurred in 254 patients: 86 (17.6%), 113 (21.5%), and 55 (30.9%) with LCS scores of 0, 1, and 2, respectively (P = 0.001). Cox proportional hazards analysis revealed that LCR and LCS were significantly associated with 2-year mortality even after adjusting for the conventional risk model (LCS score, 0 vs. 2: hazard ratio, 1.64; 95% confidence interval [CI]; 1.14-2.35; P = 0.007; log-transformed LCR: hazard ratio, 0.88; 95% CI, 0.81-0.95; P = 0.002). LCR yielded additional prognostic predictability compared with the conventional risk model (continuous net reclassification improvement, 0.153; 95% CI, 0.007-0.299; P = 0.041). CONCLUSIONS: LCR and LCS emerge as potential predictors of nutritional status, physical function, and prognosis in older patients with HF.

DOI： 10.1002/ehf2.14972

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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: Social factors encompass a broad spectrum of nonmedical factors, including objective (social isolation [SI]) and perceived (loneliness) conditions. Although social factors have attracted considerable research attention, information regarding their impact on patients with heart failure is scarce. We aimed to investigate the prognostic impact of objective SI and loneliness in older patients with heart failure. METHODS AND RESULTS: This study was conducted using the FRAGILE-HF (Prevalence and Prognostic Value of Physical and Social Frailty in Geriatric Patients Hospitalized for Heart Failure; derivation cohort) and Kitasato cohorts (validation cohort), which included hospitalized patients with heart failure aged ≥65 years. Objective SI and loneliness were defined using the Japanese version of Lubben Social Network Scale-6 and diagnosed when the total score for objective and perceived questions on the Lubben Social Network Scale-6 was below the median in the FRAGILE-HF. The primary outcome was 1-year death. Overall, 1232 and 405 patients in the FRAGILE-HF and Kitasato cohorts, respectively, were analyzed. Objective SI and loneliness were observed in 57.8% and 51.4% of patients in the FRAGILE-HF and 55.4% and 46.2% of those in the Kitasato cohort, respectively. During the 1-year follow-up, 149 and 31 patients died in the FRAGILE-HF and Kitasato cohorts, respectively. Cox proportional hazard analysis revealed that objective SI, but not loneliness, was significantly associated with 1-year death after adjustment for conventional risk factors in the FRAGILE-HF. These findings were consistent with the validation cohort. CONCLUSIONS: Objective SI assessed using the Lubben Social Network Scale-6 may be a prognostic indicator in older patients with heart failure. Given the lack of established SI assessment methods in this population, further research is required to refine such methods.

DOI： 10.1161/JAHA.123.032716

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It has not yet been established whether angiotensin II receptor blockers (ARB), statins, and multiple drugs affect the severity of COVID-19. Therefore, we herein performed an observational study on the effects of 1st- and 2nd-generation ARB, statins, and multiple drugs, on COVID-19 in patients admitted to 15 Japanese medical facilities. The results obtained showed that ARB, statins, and multiple drugs were not associated with the primary outcome (odds ratio: 1.040, 95% confidence interval: 0.688-0.571; 0.696, 0.439-1.103; 1.056, 0.941-1.185, respectively), each component of the primary outcome (in-hospital death, ventilator support, extracorporeal membrane oxygenation support, and admission to the intensive care unit), or the secondary outcomes (oxygen administration, disturbed consciousness, and hypotension, defined as systolic blood pressure ≤90 mmHg). ARB were divided into 1st- and 2nd-generations based on their approval for use (before 2000 and after 2001), with the former consisting of losartan, candesartan, and valsartan, and the latter of telmisartan, olmesartan, irbesartan, and azilsartan. The difference of ARB generation was not associated with the primary outcome (odds ratio with 2nd-generation ARB relative to 1st-generation ARB: 1.257, 95% confidence interval: 0.613-2.574). The odd ratio for a hypotension as one of the secondary outcomes with 2nd-generation ARB was 1.754 (95% confidence interval: 1.745-1.763) relative to 1st-generation ARB. These results suggest that patients taking 2nd-generation ARB may be at a higher risk of hypotension than those taking 1st-generation ARB and also that careful observations are needed. Further studies are continuously needed to support decisions to adjust medications for co-morbidities.

DOI： 10.1038/s41440-024-01682-y

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AIMS: The ALIMENT-HF trial aims to determine whether high-calorie and high-protein oral nutritional supplements (ONS) are safe and beneficial for older adult outpatients with heart failure (HF). METHODS AND RESULTS: This multicentre, single-arm, interventional pilot trial is designed to evaluate the tolerance, efficacy, and safety of ONS in older adult outpatients with chronic HF, malnutrition, and anorexia. In total, 80 outpatients with HF regardless of their left ventricular ejection fraction will be treated with ONS, including high-energy (900 kcal/day) and high protein (36 g/day) supplementation, at eight sites in Japan. Inclusion criteria are as follows: age, ≥65 years; outpatients receiving maximally tolerated guideline-directed medical therapy for HF and without change in their diuretic dosage during the last 3 months; outpatients at risk of malnutrition, defined as a Malnutrition Universal Screening Tool score ≥1 point, and anorexia, defined using a Simplified Nutritional Appetite Questionnaire for the Japanese Elderly (SNAQ-JE) score of ≤14 points. Nutritional intervention will continue for up to 120 days, with an observational period lasting for a further 60 days. The primary outcome is a change in body weight between baseline and day 120. CONCLUSIONS: The ALIMENT-HF trial will evaluate the tolerance, efficacy, and safety of high-calorie and high-protein-rich ONS in older outpatients with HF co-morbid with malnutrition and anorexia and will provide insightful information for future randomized controlled trials.

DOI： 10.1002/ehf2.14800

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AIMS: This study aimed to investigate the prevalence, clinical characteristics, and prognostic value of bendopnea in older patients hospitalized for heart failure. METHODS: This post hoc analysis was performed using two prospective, multicenter, observational studies: the FRAGILE-HF (main cohort) and SONIC-HF (validation cohort) cohorts. Patients were categorized based on the presence of bendopnea, which was evaluated before discharge. The primary endpoint was 2-year all-cause mortality after discharge. RESULTS: Among the 1,243 patients (median age, 81 years; 57.2% male) in the FRAGILE-HF cohort and 225 (median age, 79 years; 58.2% men) in the SONIC-HF cohort, bendopnea was observed in 31 (2.5%) and 10 (4.4%) patients, respectively. Over a 2-year follow-up period, all-cause death occurred in 20.8% and 21.9% of the patients in the FRAGILE-HF and SONIC-HF cohorts, respectively. Kaplan-Meier survival curves demonstrated significantly higher mortality rates in patients with bendopnea than in those without bendopnea in the FRAGILE-HF (log-rank P = 0.006) and SONIC-HF cohorts (log-rank P = 0.014). Cox proportional hazard analysis identified bendopnea as an independent prognostic factor for all-cause mortality in both the FRAGILE-HF (hazard ratio [HR] 2.11, 95% confidence interval [CI] 1.18-3.78, P = 0.012) and SONIC-HF cohorts (HR 4.20, 95% CI 1.63-10.79, P = 0.003), even after adjusting for conventional risk factors. CONCLUSIONS: Bendopnea was observed in a relatively small proportion of older patients hospitalized for heart failure before discharge. However, its presence was significantly associated with an increased risk of all-cause mortality.

DOI： 10.1093/eurjpc/zwae128

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BACKGROUND: Although frailty is strongly associated with mortality in patients with heart failure (HF), the risk of which specific cause of death is associated with being complicated with frailty is unclear. We aimed to clarify the association between multidomain frailty and the causes of death in elderly patients hospitalized with HF. METHODS: We analyzed data from the FRAGILE-HF cohort, where patients aged 65 years and older, hospitalized with HF, were prospectively registered between 2016 and 2018 in 15 Japanese hospitals before discharge and followed up for 2 years. All patients were assessed for physical, social, and cognitive dysfunction, and categorized into 3 groups based on their number of frailty domains (FDs, 0-1, 2, and 3). Kaplan-Meier survival analysis was used to evaluate the association between the number of FDs and all-cause mortality, whereas Fine-Gray competing risk regression analysis was used for assessing the impact on cause-specific mortality. RESULTS: We analyzed 1181 patients with HF (81 years old in median, 57.4% were male), 530 (44.9%), 437 (37.0%), and 214 (18.1%) of whom were categorized into the FD 0 to 1, FD 2, and FD 3 groups, respectively. During the 2-year follow-up, 240 deaths were observed (99 HF deaths, 34 cardiovascular deaths, and 107 noncardiovascular deaths), and an increase in the number of FD was significantly associated with mortality (Log-rank: P<0.001). The Fine-Gray competing risk analysis adjusted for age and sex showed that FDs 2 (subdistribution hazard ratio, 1.77 [95% CI, 1.11-2.81]) and 3 (2.78, [95% CI, 1.69-4.59]) groups were associated with higher incidence of noncardiovascular death but not with HF and other cardiovascular deaths. CONCLUSIONS: Although multidomain frailty is strongly associated with mortality in older patients with HF, it is mostly attributable to noncardiovascular death and not cardiovascular death, including HF death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: UMIN000023929.

DOI： 10.1161/CIRCOUTCOMES.123.010416

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

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AIMS: MitraScore is a novel, simple, and manually calculatable risk score developed as a prognostic model for patients undergoing transcatheter edge-to-edge repair (TEER) for mitral regurgitation. As its components are considered prognostic in heart failure (HF), we aimed to investigate the usefulness of the MitraScore in HF patients. METHODS AND RESULTS: We calculated MitraScore for 1100 elderly patients (>65 years old) hospitalized for HF in the prospective multicentre FRAGILE-HF study and compared its prognostic ability with other simple risk scores. The primary endpoint was all-cause deaths, and the secondary endpoints were the composite of all-cause deaths and HF rehospitalization and cardiovascular deaths. Overall, the mean age of 1100 patients was 80 ± 8 years, and 58% were men. The mean MitraScore was 3.2 ± 1.4, with a median of 3 (interquartile range: 2-4). A total of 326 (29.6%), 571 (51.9%), and 203 (18.5%) patients were classified into low-, moderate-, and high-risk groups based on the MitraScore, respectively. During a follow-up of 2 years, 226 all-cause deaths, 478 composite endpoints, and 183 cardiovascular deaths were observed. MitraScore successfully stratified patients for all endpoints in the Kaplan-Meier analysis (P < 0.001 for all). In multivariate analyses, MitraScore was significantly associated with all endpoints after covariate adjustments [adjusted hazard ratio (HR) (95% confidence interval): 1.22 (1.10-1.36), P < 0.001 for all-cause deaths; adjusted HR 1.17 (1.09-1.26), P < 0.001 for combined endpoints; and adjusted HR 1.24 (1.10-1.39), P < 0.001 for cardiovascular deaths]. The Hosmer-Lemeshow plot showed good calibration for all endpoints. The net reclassification improvement (NRI) analyses revealed that the MitraScore performed significantly better than other manually calculatable risk scores of HF: the GWTG-HF risk score, the BIOSTAT compact model, the AHEAD score, the AHEAD-U score, and the HANBAH score for all-cause and cardiovascular deaths, with respective continuous NRIs of 0.20, 0.22, 0.39, 0.39, and 0.29 for all-cause mortality (all P-values < 0.01) and 0.20, 0.22, 0.42, 0.40, and 0.29 for cardiovascular mortality (all P-values < 0.02). CONCLUSIONS: MitraScore developed for patients undergoing TEER also showed strong discriminative power in HF patients. MitraScore was superior to other manually calculable simple risk scores and might be a good choice for risk assessment in clinical practice for patients receiving TEER and those with HF.

DOI： 10.1002/ehf2.14658

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BACKGROUNDS: Frailty is associated with a poor prognosis in older patients with heart failure (HF). However, multi-domain frailty assessment tools have not been established in patients with HF, and the association between the frailty phenotype and the deficit-accumulation frailty index in these patients is unclear. We aimed to understand this relationship and evaluate the prognostic value of the deficit-accumulation frailty index in older patients with HF. METHODS: We retrospectively analyzed the FRAGILE-HF cohort, which consisted of prospectively registered hospitalized patients with HF aged ≥65 years. The frailty index was calculated using 34 health-related items. The physical, social, and cognitive domains of frailty were evaluated using a phenotypic approach. The primary endpoint was all-cause mortality. RESULTS: Among 1,027 patients with HF (median age, 81 years; males, 58.1%; median frailty index, 0.44), a higher frailty index was associated with a higher prevalence in all domains of cognitive, physical, and social frailty defined by the phenotype model. During the two-year follow-up period, a higher frailty index was independently associated with all-cause death even after adjustment for MAGGIC score plus log-BNP (per 0.1 increase: hazard ratio, 1.21; 95% confidence interval, 1.07-1.37, P=0.002). The addition of the frailty index to the baseline model yielded statistically significant incremental prognostic value (net reclassification improvement, 0.165; 95% confidence interval, 0.012-0.318; P=0.034). CONCLUSIONS: A higher frailty index was associated with a higher prevalence of all domains of frailty defined by the phenotype model and provided incremental prognostic information with preexisting risk factors in older patients with HF.

DOI： 10.1016/j.cjca.2023.11.020

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AIMS: Although sarcopenia is common and associated with poor outcomes in patients with heart failure, its simple screening methods remain unclear. We aimed to investigate the predictive value of the Ishii score, which includes age, grip strength, and calf circumference, for sarcopenia and its prognostic predictability in patients with heart failure. METHODS: This was a subanalysis of the FRAGILE-HF study. Receiver operating characteristic curves were used to evaluate the predictive value for sarcopenia. Patients were stratified into the high and low Ishii score groups based on the cutoff values of the Ishii score determined by the Youden index for sarcopenia, and the 1-year mortality rates were compared. RESULTS: Of the 1262 study participants, 936 were evaluated with sarcopenia, and 184 (55 women, 129 men) were diagnosed with sarcopenia. The areas under the receiver operating characteristic curves for sarcopenia were 0.73 and 0.87 for women and men, respectively. The optimal cutoff values for predicting sarcopenia were 165 and 141 for women and men, respectively. Using these cutoff values, the sensitivity and specificity for sarcopenia were 70.9% and 68.5% for women and 88.4% and 69.7% for men, respectively. At 1 year, 151 (low Ishii score group, 98; high Ishii score group, 53) deaths were observed. Adjusted Cox proportional hazards analysis showed that the high Ishii score group was significantly associated with 1-year mortality. CONCLUSION: Among older patients hospitalized for heart failure, the Ishii score is useful for predicting sarcopenia and 1-year mortality. Geriatr Gerontol Int 2023; ••: ••-••.

DOI： 10.1111/ggi.14736

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

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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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BACKGROUND: Cachexia substantially impacts the prognosis of patients with heart failure (HF); however, there is no standard method for cachexia diagnosis. This study aimed to investigate the association of Evans's criteria, consisting of multiple assessments, with the prognosis of HF in older adults. METHODS: This study is a secondary analysis of the data from the FRAGILE-HF study, a prospective multicentre cohort study that enrolled consecutive hospitalized patients aged ≥65 years with HF. Patients were divided into two groups: the cachexia and non-cachexia groups. Cachexia was defined according to Evans's criteria by assessing weight loss, muscle weakness, fatigue, anorexia, a decreased fat-free mass index and an abnormal biochemical profile. The primary outcome was all-cause mortality, as assessed in the survival analysis. RESULTS: Cachexia was present in 35.5% of the 1306 enrolled patients (median age [inter-quartile range], 81 [74-86] years; 57.0% male); 59.6%, 73.2%, 15.6%, 71.0%, 44.9% and 64.6% had weight loss, decreased muscle strength, a low fat-free mass index, abnormal biochemistry, anorexia and fatigue, respectively. All-cause mortality occurred in 270 patients (21.0%) over 2 years. The cachexia group (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.173-1.903; P = 0.001) had a higher mortality risk than the non-cachexia group after adjusting for the severity of HF. Cardiovascular and non-cardiovascular deaths occurred in 148 (11.3%) and 122 patients (9.3%), respectively. The adjusted HRs for cachexia in cardiovascular mortality and non-cardiovascular mortality were 1.456 (95% CI, 1.048-2.023; P = 0.025) and 1.561 (95% CI, 1.086-2.243; P = 0.017), respectively. Among the cachexia diagnostic criteria, decreased muscle strength (HR, 1.514; 95% CI, 1.095-2.093; P = 0.012) and low fat-free mass index (HR, 1.424; 95% CI, 1.052-1.926; P = 0.022) were significantly associated with high all-cause mortality, but there was no significant association between weight loss alone (HR, 1.147; 95% CI, 0.895-1.471; P = 0.277) and all-cause mortality. CONCLUSIONS: Cachexia evaluated by multi-assessment was present in one third of older adults with HF and was associated with a worse prognosis. A multimodal assessment of cachexia may be helpful for risk stratification in older patients with HF.

DOI： 10.1002/jcsm.13291

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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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The effects of high-intensity interval training (HIIT) in patients with heart failure (HF) remain controversial. This systematic review and meta-analysis aimed to examine the efficacy of HIIT versus moderate-intensity continuous aerobic training (MCT) on exercise tolerance in patients with HF. We searched for studies published up to 4 March 2022 in Embase, MEDLINE, PubMed, and the Cochrane Library with no limitations on data, language, or publication status. We included randomized controlled trials comparing the efficacy of HIIT and MCT on peak oxygen uptake (VO2), as a measure of exercise tolerance. We pooled the data on peak VO2, compared HIIT to MCT, and conducted a sub-analysis if there was heterogeneity in the result. We identified 15 randomized controlled trials with 557 patients. Our meta-analysis showed that participants who underwent HIIT achieved a significantly higher peak VO2 than those who underwent MCT (mean difference 1.46 ml/kg/min, 95% confidence interval 0.39 to 2.53; participants = 557; studies = 15; I2 = 65.7%; very low-quality evidence). The meta-regression analysis, conducted as a sub-analysis to explore possible causes of heterogeneity, revealed that the difference in peak VO2 between HIIT and MCT was inversely associated with body mass index (r =  - 0.508, p = 0.028, 95% confidence interval - 0.95 to - 0.07). Our systematic review showed that HIIT achieved a higher peak VO2 than MCT in patients with HF. In addition, HIIT may be more effective in improving exercise tolerance in patients with low body mass index.

DOI： 10.1007/s10741-023-10316-3

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

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

Abstract

Background

Scarce data on factors related to discharge disposition in patients hospitalized for acute heart failure (AHF) were available, and we sought to develop a parsimonious and simple predictive model for non-home discharge via machine learning.

Methods

This observational cohort study using a Japanese national database included 128,068 patients admitted from home for AHF between April 2014 and March 2018. The candidate predictors for non-home discharge were patient demographics, comorbidities, and treatment performed within 2 days after hospital admission. We used 80% of the population to develop a model using all 26 candidate variables and using the variable selected by 1 standard-error rule of Lasso regression, which enhances interpretability, and 20% to validate the predictive ability.

Results

We analyzed 128,068 patients, and 22,330 patients were not discharged to home; 7,879 underwent in-hospital death and 14,451 were transferred to other facilities. The machine-learning-based model consisted of 11 predictors, showing a discrimination ability comparable to that using all the 26 variables (c-statistic: 0.760 [95% confidence interval, 0.752–0.767] vs. 0.761 [95% confidence interval, 0.753–0.769]). The common 1SE-selected variables identified throughout all analyses were low scores in activities of daily living, advanced age, absence of hypertension, impaired consciousness, failure to initiate enteral alimentation within 2 days and low body weight.

Conclusions

The developed machine learning model using 11 predictors had a good predictive ability to identify patients at high risk for non-home discharge. Our findings would contribute to the effective care coordination in this era when HF is rapidly increasing in prevalence.

DOI： 10.1007/s00392-023-02209-0

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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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BACKGROUND: No study with an adequate patients' number has examined the relationship/overlap between sarcopenia and cachexia. We examined the prevalence of the overlap and prognostic implications of sarcopenia and cachexia in older patients with heart failure using well-accepted definitions. METHODS: This was a post-hoc sub-analysis of the FRAGILE-HF study, a prospective, multicenter, observational study conducted at 15 hospitals in Japan. In total, 905 hospitalized older patients were classified into four groups based on the presence or absence of cachexia and/or sarcopenia, which were defined according to the Evans and Asian Working Group for Sarcopenia criteria revised in 2019, respectively. The primary endpoint was 2-year all-cause mortality. RESULTS: Cachexia and sarcopenia prevalence rates were 32.7% and 22.7%, respectively. Patients were classified into the non-cachexia/non-sarcopenia (55.7%), cachexia/non-sarcopenia (21.7%), non-cachexia/sarcopenia (11.6%), and cachexia/sarcopenia (11.0%) groups. During the 2-year follow-up period after discharge, 158 (17.5%) all-cause deaths (124 cardiovascular deaths [CVD] and 34 non-CVD) were observed. The cachexia/sarcopenia group had the lowest body fat mass and exhibited significantly higher mortality rates (log-rank P < 0.001). Cox proportional hazard analysis revealed that cachexia/sarcopenia was an independent prognostic factor after adjusting for known prognostic factors (versus non-cachexia/non-sarcopenia: hazard ratio, 2.78; 95% confidence interval, 1.80-4.29; P < 0.001). Neither cachexia/non-sarcopenia nor non-cachexia/sarcopenia were significantly associated with all-cause mortality compared with non-cachexia/non-sarcopenia. CONCLUSIONS: Cachexia and sarcopenia are prevalent among older hospitalized patients with heart failure; nonetheless, the overlap is not as prominent as previously expected. The presence of cachexia and sarcopenia is a risk factor for all-cause mortality.

DOI： 10.1016/j.ijcard.2023.03.035

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BACKGROUND: The incremental prognostic value of the six-minute walking test over conventional risk factors has not been evaluated in an adequate number of patients with heart failure with preserved ejection fraction (HFpEF). Therefore, we aimed to examine its prognostic significance using data from the FRAGILE-HF study. METHODS AND RESULTS: A total of 513 older patients who were hospitalized for worsening heart failure were examined. Patients were classified according to the tertiles of six-minute walking distance (6MWD): T1 (<166 m), T2 (166-285 m), and T3 (≥285 m). During the 2-year follow-up period after discharge, 90 all-cause deaths occurred. Kaplan-Meier curves showed that the T1 group had significantly higher event rates than the other groups (log-rank p = 0.007). Cox proportional hazard analysis revealed that the T1 group was independently associated with lower survival, even after adjusting for conventional risk factors (T3: hazard ratio 1.79, 95% confidence interval 1.02-3.14, p = 0.042). The addition of the 6MWD to the conventional prognostic model showed a statistically significant incremental prognostic value (net reclassification improvement 0.27, 95% confidence interval 0.04-0.49; p = 0.019). CONCLUSIONS: The 6MWD is associated with survival in patients with HFpEF and has an incremental prognostic value over conventional well-validated risk factors.

DOI： 10.1016/j.ijcard.2023.03.025

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BACKGROUND: Data on the potential benefit of acute-phase rehabilitation initiation in very old (aged ≥90) patients with acute heart failure (AHF) have been scarce. METHODS: We retrospectively analyzed data from the Diagnosis Procedure Combination database, which is a nationwide inpatient database. This study included patients hospitalized for heart failure (HF) from January 2010 to March 2018, those aged ≥90 years, who had a length of stay of ≥3 days, New York Heart Association (NYHA) class of ≥II, and had not undergone major procedures under general anesthesia. Propensity score matching and generalized linear models were used to compare in-hospital mortality, length of stay, 30-day readmission rate due to HF, all-cause 30-day readmission, and improvement in activities of daily living (ADL) between patients with and without an acute-phase rehabilitation initiation, which is defined as the rehabilitation initiation within 2 days after hospital admission. RESULTS: Acute-phase rehabilitation was initiated in 8588 of 41,896 eligible patients. Propensity score matching created 8587 pairs. Patients with acute-phase rehabilitation initiation have lower in-hospital mortality (9.0% vs. 11.2%, p < 0.001). Acute-phase rehabilitation initiation was associated with lower in-hospital mortality (odds ratio, 0.778; 95% confidence interval, 0.704-0.860). Patients with acute-phase rehabilitation initiation have a shorter median length of stay (17 days vs. 18 days, p < 0.001), lower 30-day readmission rate due to HF (5.5% vs. 6.4%, p = 0.011) and all-cause 30-day readmission (10.2% vs. 11.2%, p = 0.036), and better ADL improvement (49.7% vs. 46.9%, p < 0.001). Subgroup analysis revealed consistent results (sex, body mass index, NYHA class, and Barthel Index). CONCLUSIONS: The acute-phase rehabilitation initiation was associated with improved short-term clinical outcomes in patients aged ≥90 years with AHF.

DOI： 10.1111/jgs.18283

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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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AIMS: Frailty is highly prevalent and associated with poor prognoses in elderly patients with heart failure (HF). However, the potential effects of physical frailty on the benefits of HF medications in elderly patients with HF are unclear. We aimed to determine the influence of physical frailty on the prognosis of HF medications in elderly patients with HF with reduced and mildly reduced ejection fraction (HFr/mrEF). METHODS AND RESULTS: From the combined HF database of the FRAGILE-HF and Kitasato cohorts, hospitalized HF patients with a left ventricular ejection fraction < 50% and age ≥ 65 years were analysed. Patients treated with or without renin-angiotensin-aldosterone system inhibitors (RAASi) and beta-blockers at discharge were compared. Physical frailty was defined by the presence of ≥3 items on the Japanese version of the Cardiovascular Health Study criteria. The primary endpoint was all-cause mortality rate. Among the 1021 enrolled patients, 604 patients (59%) received both RAASi and beta-blockers, and 604 patients (59%) were diagnosed as physically frail. Patients receiving both RAASi and beta-blockers showed a significantly lower 1 year mortality than those not receiving either, even after adjusting for covariates (hazard ratio: 0.50, 95% confidence interval: 0.34-0.75). This beneficial effect of both medications on 1 year mortality was comparable between patients with and without physical frailty (hazard ratio: 0.53 and 0.51, respectively; P for interaction = 0.77). CONCLUSIONS: The presence of physical frailty did not interact with the beneficial prognostic impact of RAASi and beta-blocker combination therapy in elderly patients with HFr/mrEF.

DOI： 10.1002/ehf2.14114

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

DOI： 10.1007/s10157-023-02323-3

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BACKGROUND: Although weight loss in heart failure (HF) is a detrimental condition known as cachexia, weight gain caused by fluid retention should also be considered harmful. However, studies with sufficient number of patients examining the impact of weight change and its interval on in-hospital mortality in HF have not been conducted thus far. We sought to elucidate the association of weight change with in-hospital mortality in patients with HF. METHODS: This retrospective observational study used data from the Diagnosis Procedure Combination database, a nationwide inpatient health claims database in Japan. In total, 48 234 patients repeatedly hospitalized for HF (median 82 [74-87] years; 46.4% men) between 2010 and 2018 were included. Weight change was derived from body weight at the first and second admissions. RESULTS: The median weight change and interval between two hospitalizations were -3.1 [-8.3 to -1.8] % and 172 [67-420] days, with 66.9% of overall cohort experiencing any weight loss. As a result of multivariable-adjusted logistic regression analysis, weight loss <-5.0% and weight gain >+5.0% were associated with increased in-hospital mortality (adjusted odds ratio [OR] [95% confidence interval]: 1.46 [1.31-1.62], P < 0.001 and 1.23 [1.08-1.40], P = 0.002, respectively) whereas mild weight loss and gain of 2.0-5.0% were not (OR [95% confidence interval]: 0.96 [0.84-1.10], P = 0.57 and 1.07 [0.92-1.25], P = 0.37, respectively), in comparison with patients with a stable weight (fluctuating no more than -2.0% to +2.0%) used as a reference. Restrictive cubic spline models adjusted for multiple background factors illustrated that higher mortality in patients with weight loss was observed across all subgroups of the baseline body mass index (<18.5, 18.5-24.9 and ≥25.0 kg/m2 ). In patients with short (<90 days) and middle (<180 days) intervals between the two hospitalizations, both weight loss and weight gain were associated with high mortality, whereas the association between weight gain and high mortality was attenuated in those with longer intervals. CONCLUSIONS: Both weight loss and weight gain in patients with repeated hospitalization for HF were associated with high in-hospital mortality, especially weight loss and short/middle-term weight gain. Such patients should be treated with caution in a setting of repeated hospitalization for HF.

DOI： 10.1002/jcsm.13170

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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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AIMS: Given the various effects of sacubitril/valsartan in heart failure, a deeper understanding of atrial natriuretic peptide (ANP) actions is warranted. Natriuresis is a fundamental action of ANP in acute heart failure (AHF), whereas the diuretic effect of ANP is different in each patient according to the diversity of renal response to ANP, which is affected by baseline plasma ANP status and deficiency of circulating ANP. Meanwhile, associations between other neuroendocrine hormones and the diuretic response to ANP are unclear. This study investigated the impact of pivotal neuroendocrine hormones on the diuretic effects of exogenous ANP, carperitide. METHODS AND RESULTS: Plasma ANP, renin, aldosterone, and vasopressin levels and the diuretic effect of 0.0125 μg/kg/min of carperitide alone for the first 6 h were prospectively evaluated in 75 patients with AHF. Lower ANP levels were significantly associated with a greater diuretic response to exogenous ANP (r = -0.35, P = 0.002). Additionally, higher vasopressin levels were significantly related to the poor diuretic effects of exogenous ANP (r = -0.54, P < 0.001). Plasma ANP and vasopressin concentrations were not significantly correlated (r = 0.19, P = 0.10). Baseline systolic blood pressure, renal function, and prior use of loop diuretics did not predict the diuretic response to exogenous ANP, whereas vasopressin levels independently predicted a diuretic response to exogenous ANP (P < 0.001), as well as lower plasma ANP levels (P = 0.027). CONCLUSIONS: Vasopressin status was significantly associated with the diuretic response to exogenous ANP in AHF, independent of plasma ANP status. The results may provide a better understanding of the actions of sacubitril/valsartan.

DOI： 10.1002/ehf2.14083

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BACKGROUND: The purpose of this study was to clarify the prevalence, association with frailty and exercise capacity, and prognostic implication of sarcopenic obesity in patients with heart failure. METHODS: The present study included 779 older adults hospitalized with heart failure (median age: 81 years; 57.4% men). Sarcopenia was diagnosed based on the guidelines by the Asian Working Group for Sarcopenia. Obesity was defined as the percentage of body fat mass (FM) obtained by bioelectrical impedance analysis. The FM cut-off points for obesity were 38% for women and 27% for men. The primary endpoint was 1-year all-cause death. We assessed the associations of sarcopenic obesity occurrence with the short physical performance battery (SPPB) score and 6-minute walk distance (6MWD). RESULTS: The rates of sarcopenia and obesity were 19.3 and 26.2%, respectively. The patients were classified into the following groups: non-sarcopenia/non-obesity (58.5%), non-sarcopenia/obesity (22.2%), sarcopenia/non-obesity (15.3%), and sarcopenia/obesity (4.0%). The sarcopenia/obesity group had a lower SPPB score and shorter 6MWD, which was independent of age and sex (coefficient, - 0.120; t-value, - 3.74; P < 0.001 and coefficient, - 77.42; t-value, - 3.61; P < 0.001; respectively). Ninety-six patients died during the 1-year follow-up period. In a Cox proportional hazard analysis, sarcopenia and obesity together were an independent prognostic factor even after adjusting for a coexisting prognostic factor (non-sarcopenia/non-obesity vs. sarcopenia/obesity: hazard ratio, 2.48; 95% confidence interval, 1.22-5.04; P = 0.012). CONCLUSION: Sarcopenic obesity is a risk factor for all-cause death and low physical function in older adults with heart failure. TRIAL REGISTRATION: University Hospital Information Network (UMIN-CTR: UMIN000023929 ).

DOI： 10.1186/s12877-022-03168-3

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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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Language：Japanese   Publisher：日本肺高血圧・肺循環学会・日本小児肺循環研究会  

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BACKGROUND: Identifying predictive factors for coronavirus disease 2019 (COVID-19) is crucial for risk stratification and intervention. Kidney dysfunction contributes to the severity of various infectious diseases. However, the association between on-admission kidney dysfunction and the clinical outcome in COVID-19 patients is unclear. METHODS: This study was a multicenter retrospective observational cohort study of COVID-19 patients, diagnosed by polymerase chain reaction. We retrospectively analyzed 500 COVID-19 patients (mean age: 51 ± 19 years) admitted to eight hospitals in Japan. Kidney dysfunction was defined as a reduced estimated glomerular filtration rate (< 60 mL/min/1.73 m2) or proteinuria (≥ 1 + dipstick proteinuria) on admission. The primary composite outcome included in-hospital death, extracorporeal membrane oxygenation, mechanical ventilation (invasive and noninvasive methods), and intensive care unit (ICU) admission. RESULTS: Overall, 171 (34.2%) patients presented with on-admission kidney dysfunction, and the primary composite outcome was observed in 60 (12.0%) patients. Patients with kidney dysfunction showed higher rates of in-hospital death (12.3 vs. 1.2%), mechanical ventilation (13.5 vs. 4.0%), and ICU admission (18.1 vs. 5.2%) than those without it. Categorical and multivariate regression analyses revealed that kidney dysfunction was substantially associated with the primary composite outcome. Thus, on-admission kidney dysfunction was common in COVID-19 patients. Furthermore, it correlated significantly and positively with COVID-19 severity and mortality. CONCLUSIONS: On-admission kidney dysfunction was associated with disease severity and poor short-term prognosis in patients with COVID-19. Thus, on-admission kidney dysfunction has the potential to stratify risks in COVID-19 patients.

DOI： 10.1007/s10157-022-02240-x

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AIMS: Although evidence suggests that cognitive decline and physical frailty in elderly patients with heart failure (HF) are associated with prognosis, the impact of concurrent physical frailty and cognitive impairment, that is, cognitive frailty, on prognosis has yet to be fully investigated. The current study sought to investigate the prevalence and prognostic impact of cognitive frailty in elderly patients with HF. METHODS AND RESULTS: This study is a sub-analysis of FRAGILE-HF, a prospective multicentre observational study involving patients aged ≥65 years hospitalized for HF. The Fried criteria and Mini-Cog were used to diagnose physical frailty and cognitive impairment, respectively. The association between cognitive frailty and the combined endpoint of mortality and HF rehospitalization within 1 year was then evaluated. Among the 1332 patients identified, 1215 who could be assessed using Mini-Cog and the Fried criteria were included in this study. Among those included, 279 patients (23.0%) had cognitive frailty. During the follow-up 1 year after discharge, 398 combined events were observed. Moreover, cognitive frailty was determined to be associated with a higher incidence of combined events (log-rank: P = 0.0146). This association was retained even after adjusting for other prognostic factors (hazard ratio: 1.55, 95% confidence interval: 1.13-2.13). Furthermore, a sensitivity analysis using grip strength, short physical performance battery, and gait speed to determine physical frailty instead of the Fried criteria showed similar results. CONCLUSIONS: This cohort study found that 23% of elderly patients with HF had cognitive frailty, which was associated with a 1.55-fold greater risk for combined events within 1 year compared with patients without cognitive frailty.

DOI： 10.1002/ehf2.13844

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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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Patients with pulmonary hypertension (PH) suffer from poor exercise tolerance due to impaired oxygenation and/or reduced cardiac output. However, the relationship between exercise tolerance and physical function remains unclear. The purpose of this study was to investigate the relationship between exercise tolerance and physical function in patients with PH. A total of 94 patients without left heart disease (61.3 ± 14.7 years old, 69.1% females, 22/8/60/4 patients with Group 1/3/4/5 PH) were retrospectively analysed. Physical function was measured using muscle strength (grip strength, knee extension muscle strength), balance function (one-leg standing time), and gait speed within 7 days of cardiac catheterization. Exercise tolerance was measured using the 6-min walking distance (6-MWD). A total of 194 6-MWD measurements and the corresponding physical function were evaluated in 94 patients. Multivariable linear regression analysis using adaptive-LASSO methods indicated that the World Health Organization functional classification, pulmonary vascular resistance, mixed venous oxygen saturation, grip strength, and gait speed were independently associated with the 6-MWD. Low grip strength (< 28 kg for males and < 18 kg for females; adjusted odds ratio and 95% confidence interval: 2.06 [1.30-3.26], p = 0.002), and slow gait speed (< 1.0 m/s for both sexes; 13.33 [3.61-49.19], p < 0.001) were independent predictors of poor exercise tolerance (6-MWD < 440 m) in a logistic regression analysis. Grip strength and gait speed as measures of physical function, pulmonary vascular resistance, and mixed venous oxygen saturation were associated with exercise tolerance in patients with PH without left heart disease.

DOI： 10.1007/s00380-022-02091-2

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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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AIMS: A patient's understanding of his or her own comorbidities is part of the recommended patient education for those with heart failure. The accuracy of patients' understanding of their comorbidities and its prognostic impact have not been reported. METHODS AND RESULTS: Patients hospitalized for heart failure (n = 1234) aged ≥65 years (mean age: 80.1 ± 7.7 years; 531 females) completed a questionnaire regarding their diagnoses of diabetes, malignancy, stroke, hypertension, chronic obstructive pulmonary disease (COPD), and coronary artery disease (CAD). The patients were categorized into three groups based on the number of agreements between self-reported comorbidities and provider-reported comorbidities: low (1-2, n = 19); fair (3-4, n = 376); and high (5-6, n = 839) agreement groups. The primary outcome was a composite of all-cause mortality or heart failure rehospitalization at 1 year. The low agreement group had more comorbidities and a higher prevalence of a history of heart failure. The agreement was good for diabetes (κ = 0.73), moderate for malignancy (κ = 0.56) and stroke (κ = 0.50), and poor-to-fair for hypertension (κ = 0.33), COPD (κ = 0.25), and CAD (κ = 0.30). The fair and low agreement groups had poorer outcomes than the good agreement group [fair agreement group: hazard ratio (HR): 1.25; 95% confidence interval (CI): 1.01-1.56; P = 0.041; low agreement group: HR: 2.74: 95% CI: 1.40-5.35; P = 0.003]. CONCLUSIONS: The ability to recognize their own comorbidities among older patients with heart failure was low. Patients with less accurate recognition of their comorbidities may be at higher risk for a composite of all-cause mortality or heart failure rehospitalization.

DOI： 10.1002/ehf2.13824

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Although postural hypotension (PH) is reportedly associated with mortality in the general population, the prognostic value for heart failure is unclear. This was a post-hoc analysis of FRAGILE-HF, a prospective multicenter observational study focusing on frailty in elderly patients with heart failure. Overall, 730 patients aged ≥ 65 years who were hospitalized with heart failure were enrolled. PH was defined by evaluating seated PH, and was defined as a fall of ≥ 20 mmHg in systolic and/or ≥ 10 mmHg in diastolic blood pressure within 3 min after transition from a supine to sitting position. The study endpoints were all-cause death and heart failure readmission at 1 year. Predictive variables for the presence of PH were also evaluated. PH was observed in 160 patients (21.9%). Patients with PH were more likely than those without PH to be male with a New York Heart Association classification of III/IV. Logistic regression analysis showed that male sex, severe heart failure symptoms, and lack of administration of angiotensin-converting enzyme inhibitors were independently associated with PH. PH was not associated with 1-year mortality, but was associated with a lower incidence of readmission after discharge after adjustment for other covariates. In conclusion, PH was associated with reduced risk of heart failure readmission but not with 1-year mortality in older patients with heart failure.

DOI： 10.1038/s41598-022-06760-0

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BACKGROUND: We previously reported on the FREED study, which found that febuxostat reduced the risk of adverse clinical outcome in patients with asymptomatic hyperuricemia without gout. We have now investigated outcomes in subgroups of FREED patients with and without a history of cardiovascular disease (CVD). METHODS: We performed a post hoc subgroup analysis of 1070 patients randomized to the febuxostat or non-febuxostat group and followed for 36 months. RESULTS: At baseline, 234 patients (21.9%) had a history of CVD, including 86 patients with stroke (36.8%), 90 with coronary artery disease (38.5%), 74 with heart failure (31.6%), and 25 with vascular disease (10.7%). The risk for the primary composite endpoint, i.e., cerebral, cardiovascular, and renal events and all deaths, was higher in patients with CVD than in those without CVD (34.2% vs 23.7%; p < 0.001). Treatment with febuxostat lowered rates of the primary composite endpoint in patients with CVD (hazard ratio [HR] 0.601, 95% CI 0.384 to 0.940, p = 0.026), and these effects were consistently observed in subgroups with and without CVD (p = 0.227 for treatment by subgroup interaction). Furthermore, in the subgroup with CVD, all-cause mortality was significantly lower in the febuxostat group than in the non-febuxostat group (HR 0.160, 95% CI 0.047 to 0.547, p = 0.004), with a significant subgroup interaction (p = 0.007 for treatment by subgroup interaction). CONCLUSIONS: In patients with asymptomatic hyperuricemia without gout, febuxostat reduces the risk of the composite of cerebral, cardiovascular, and renal events and death in the secondary prevention setting.

DOI： 10.1016/j.ijcard.2021.11.076

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DOI： 10.1002/jcsm.12883

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BACKGROUND AND AIMS: Frailty and sarcopenia are common and confer poor prognosis in elderly patients with heart failure; however, gender differences in its prevalence or prognostic impact remain unclear. METHODS AND RESULTS: We included 1332 patients aged ≥65 years, who were hospitalized for heart failure. Frailty and sarcopenia were defined using the Fried phenotype model and Asian Working Group for Sarcopenia criteria, respectively. Gender differences in frailty and sarcopenia, and interactions between sex and prognostic impact of frailty/sarcopenia on 1-year mortality were evaluated. Overall, 53.9% men and 61.0% women and 23.7% men and 14.0% women had frailty and sarcopenia, respectively. Although sarcopenia was more prevalent in men, no gender differences existed in frailty after adjusting for age. On Kaplan-Meier analysis, frailty and sarcopenia were significantly associated with 1-year mortality in both sexes. On Cox proportional hazard analysis, frailty was associated with 1-year mortality only in men, after adjusting for confounding factors (hazard ratio [HR], 1.94; 95% confidence interval [CI], 1.19-3.16; P = 0.008 for men; HR, 1.63; 95% CI, 0.84-3.13; P = 0.147 for women); sarcopenia was an independent prognostic factor in both sexes (HR, 1.93; 95% CI, 1.13-3.31; P = 0.017 for men; HR, 3.18; 95% CI, 1.59-5.64; P = 0.001 for women). There were no interactions between sex and prognostic impact of frailty/sarcopenia (P = 0.806 for frailty; P = 0.254 for sarcopenia). CONCLUSIONS: Frailty and sarcopenia negatively affect older patients with heart failure from both sexes. CLINICAL TRIALS: This study was registered at the University Hospital Information Network (UMIN-CTR, unique identifier: UMIN000023929) before the first patient was enrolled.

DOI： 10.1016/j.numecd.2021.10.012

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DOI： 10.1097/MD.0000000000028171

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BACKGROUND: Low physical performance may contribute to reduced exercise capacity in older patients with heart failure (HF). We sought to identify the determinants of exercise capacity out of a plethora of background factors, including measures of physical performance. METHODS: We performed a post-hoc analysis of a cohort study that included 1205 consecutive older (age ≥ 65 years) hospitalized patients (the median age, 80 years; 57.4% males). RESULTS: Low physical performance, defined as ≤1.0 m/s for gait speed, ≥12 s for the 5-time chair stand test, or ≤ 9 points for the Short Physical Performance Battery in both sexes, was seen in 83.9% of the cohort. Multivariate regression analysis revealed that each parameter of physical performance (i.e., gait speed, chair stand test, and balance test) was identified as an independent determinant of lower exercise capacity assessed using the 6-min walking distance. In a logistic regression model, low physical performance predicted short (<300 m) 6-min walking distance (adjusted odds ratio 10.28, 95% CI 6.01-17.60, p < 0.001). No interaction was detected between patients with preserved and reduced ejection fraction. CONCLUSIONS: Low physical performance was prevalent and independently associated with exercise capacity in older patients with HF, irrespective of preserved or reduced ejection fraction.

DOI： 10.1016/j.exger.2021.111626

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

DOI： 10.1016/j.jjcc.2021.10.029

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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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Background Frailty is conceptualized as an accumulation of deficits in multiple areas and is strongly associated with the prognosis of heart failure (HF). However, the social domain of frailty is less well investigated. We prospectively evaluated the clinical characteristics and prognostic impact of social frailty (SF) in elderly patients with HF. Methods and Results FRAGILE-HF (prevalence and prognostic value of physical and social frailty in geriatric patients hospitalized for heart failure) is a multicenter, prospective cohort study focusing on patients hospitalized for HF and aged ≥65 years. We defined SF by Makizako's 5 items, which have been validated as associated with future disability. The primary end point was a composite of all-cause death and rehospitalization because of HF. The impact of SF on all-cause mortality alone was also evaluated. Among 1240 enrolled patients, 825 (66.5%) had SF. During the 1-year observation period after discharge, the rates of the combined end point and all-cause mortality were significantly higher in patients with SF than in those without SF (Log-rank test: both P < 0.05). SF remained as significantly associated with both the combined end point (hazard ratio, 1.30; 95% CI, 1.02-1.66; P = 0.038) and all-cause mortality (hazard ratio, 1.53; 95% CI, 1.01-2.30; P = 0.044), even after adjusting for key clinical risk factors. Furthermore, SF showed significant incremental prognostic value over known risk factors for both the combined end point (net-reclassification improvement: 0.189, 95% CI, 0.063-0.316, P = 0.003) and all-cause mortality (net-reclassification improvement: 0.234, 95% CI, 0.073-0.395, P = 0.004). Conclusions Among hospitalized geriatric patients with HF, two thirds have SF. Evaluating SF provides additive prognostic information in elderly patients with HF. Registration URL: https://upload.umin.ac.jp/. Unique identifier: UMIN000023929.

DOI： 10.1161/JAHA.120.019954

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

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BACKGROUND: Extensive data support the clinical benefit of cardiac rehabilitation (CR) for patients with chronic heart failure (HF). However, whether CR could be beneficial for patients hospitalized for acute heart failure remains unclear. METHODS: We retrospectively analyzed data from the Diagnosis Procedure Combination database, a nationwide inpatient database. We included patients hospitalized for HF, who were aged ≥20 years and with New York Heart Association class ≥II, between January 2010 and March 2018. We excluded patients with length of hospital stay ≤2 days, those undergoing major procedures under general anesthesia, those requiring advanced mechanical supports within 2 days after admission, and those with disturbance of consciousness. Propensity score matching and instrumental variable analyses were conducted to compare clinical outcomes between the patients with and without acute-phase initiation of CR defined as initiation of CR within two days after hospital admission. RESULTS: Among 430,216 eligible patients, 63,470 patients (14.8%) received the acute-phase initiation of CR. Propensity score matching created 63,470 pairs and found that the acute-phase initiation of CR was associated with lower in-hospital mortality (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.73-0.80), shorter hospital stay and lower incidence of 30-day readmission due to HF. The instrumental variable analysis also showed patients with acute-phase initiation of CR was associated with lower in-hospital mortality than those without (OR, 0.73; 95% CI, 0.68-0.79). CONCLUSION: Our analysis suggested a potential benefit of acute-phase initiation of CR for short-term clinical outcomes in hospitalized patients with acute HF.

DOI： 10.1016/j.ijcard.2021.08.041

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Background Recent data suggest that the angiotensin receptor neprilysin inhibitor modulates plasma levels of natriuretic peptides and attenuates the risk of hyperkalemia in patients with heart failure (HF). However, the impact of natriuretic peptides on serum electrolyte abnormalities, especially abnormalities in sodium and potassium levels in patients with HF remains unclear. Methods We performed a post-hoc analysis of a multicenter prospective cohort study in 162 patients with acute HF (74.2 ± 13.3 years, 64.2% male, left ventricular ejection fraction 44 ± 15%) treated with intravenous carperitide, an exogenous atrial natriuretic peptide. Results The dose of carperitide was correlated with urine volume (σ = 0.205, p = 0.009), suggesting a significant diuretic effect. During the initial 48 h, serum sodium level remained unchanged both in 53 patients with carperitide alone (from 140 ± 4 to 140 ± 3 mEq/L, p = 0.653) and 109 patients treated with a combination of carperitide and furosemide (141 ± 4 to 141 ± 4 mEq/L, p = 0.644). On the contrary, serum potassium level was decreased both in patients with carperitide alone (from 4.32 ± 0.70 to 4.08 ± 0.47 mEq/L, p = 0.004) and patients treated with a combination of carperitide and furosemide (4.17 ± 0.55 to 3.98 ± 0.47, p < 0.001), with a significant association between urine volume and change in potassium level in patients treated with carperitide alone (σ = -0.313, p = 0.023). The incidence of hypokalemia at 24 h was higher in patients treated with 20 mg furosemide or more (12.5% vs. 2.8%, p = 0.039). Conclusions Serum potassium level decreased after HF treatment with exogenous atrial natriuretic peptide, with a significant correlation to urine volume. The risk of hypokalemia was low, unless treated with additional furosemide.

DOI： 10.1016/j.jjcc.2021.08.002

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Publishing type：Research paper (scientific journal)   Publisher：Oxford University Press (OUP)  

Abstract

Aims

Functional decline due to skeletal muscle abnormalities leads to poor outcomes in patients with acute heart failure (AHF). The 6-minute walking test (6MWT) reliably evaluates functional capacity, but its technical difficulty for the elderly often limits its benefits. Although the Short Physical Performance Battery (SPPB) is a comprehensive measure of physical performance, its role in AHF remains unclear. This study aimed to examine the prognostic significance of SPPB compared to the 6MWT in elderly patients hospitalized for AHF.

Methods and results

We retrospectively analysed 1192 elderly patients with AHF whose SPPB and 6MWT were measured during the hospitalization. The primary outcome measure was defined as a composite of all-cause death and heart failure readmission until 1 year after discharge. Patients with lower SPPB scores (0–6, n = 373) had significantly poorer outcomes than those with higher SPPB scores (7–12, n = 819) even after multivariable adjustment [adjusted hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01–1.61; P = 0.049], similar to those with shorter 6MWT (&amp;lt;median) than those with longer 6MWT (adjusted HR 1.61, 95% CI 1.27–2.04; P &amp;lt; 0.001). Although both SPPB and 6MWT [net reclassification index (NRI) 0.139, P = 0.036 and NRI 0.350, P &amp;lt; 0.001, respectively] exhibited incremental prognostic value over conventional risk factors of HF, the additive prognostic effect of 6MWT was superior to that of SPPB (NRI 0.300, P &amp;lt; 0.001).

Conclusions

Reduced functional capacity assessed by either the SPPB or 6MWT was associated with worse outcomes in hospitalized elderly patients with AHF. The incremental prognostic value over the conventional risk factors was higher in 6MWT than in SPPB.

Trial Registration

UMIN000023929

DOI： 10.1093/ehjopen/oeab006

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Other Link： https://academic.oup.com/ehjopen/article-pdf/1/1/oeab006/41726318/oeab006.pdf

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AIMS: Although aging is strongly associated with both heart failure and a decline in gait speed, a definition of slowness incorporating an age-related decline has yet to be developed. We aimed to define an event-driven cut-off for the relative decline in gait speed against age-adjusted reference values derived from the general population and evaluate its prognostic implications. METHODS AND RESULTS: Standardized gait speed (SGS) was defined as the median gait speed stratified by age, sex, and height in 3777 elderly (age ≥ 65 years) individuals without a history of cardiovascular diseases (Tokyo Metropolitan Institute of Gerontology-Longitudinal Interdisciplinary Study on Aging: general population cohort). The mortality event-driven optimal cut-off of the SGS ratio (actual gait speed divided by the respective SGS) was defined using FRAGILE-HF cohort data and externally validated using Kitasato cohort data, comprising 1301 and 1247 hospitalized elderly patients with heart failure, respectively. Using FRAGILE-HF data, the optimal SGS ratio cut-off was determined as 0.527. In the Kitasato cohort, SGS ratio < 0.527 was associated with a higher 1 year [hazard ratio (HR): 1.70, 95% confidence interval (CI): 1.07-2.72, P = 0.024] and long-term (HR: 1.46, 95% CI: 1.05-2.02, P = 0.024) mortality rate, independent of pre-existing covariates. CONCLUSIONS: Gait speed was significantly declined in patients with heart failure, even after taking age and sex-related decline into account. A SGS ratio of 0.527 is a validated cut-off for slowness independently associated with mortality in patients with heart failure age ≥65.

DOI： 10.1002/ehf2.13392

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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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Frailty is a common comorbidity associated with adverse events in patients with heart failure, and early recognition is key to improving its management. We hypothesized that the AST to ALT ratio (AAR) could be a marker of frailty in patients with heart failure. Data from the FRAGILE-HF study were analyzed. A total of 1327 patients aged ≥ 65 years hospitalized with heart failure were categorized into three groups based on their AAR at discharge: low AAR (AAR < 1.16, n = 434); middle AAR (1.16 ≤ AAR < 1.70, n = 487); high AAR (AAR ≥ 1.70, n = 406). The primary endpoint was one-year mortality. The association between AAR and physical function was also assessed. High AAR was associated with lower short physical performance battery and shorter 6-min walk distance, and these associations were independent of age and sex. Logistic regression analysis revealed that high AAR was an independent marker of physical frailty after adjustment for age, sex and body mass index. During follow-up, all-cause death occurred in 161 patients. After adjusting for confounding factors, high AAR was associated with all-cause death (low AAR vs. high AAR, hazard ratio: 1.57, 95% confidence interval, 1.02-2.42; P = 0.040). In conclusion, AAR is a marker of frailty and prognostic for all-cause mortality in older patients with heart failure.

DOI： 10.1038/s41598-021-91368-z

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PURPOSE OF REVIEW: With a worldwide aging population, frailty and heart failure (HF) have become issues that need to be addressed urgently in cardiovascular clinical practice. In this review, we outline the clinical implications of frailty in HF patients and the potential therapeutic strategies to improve the clinical outcomes of frail patients with HF. RECENT FINDINGS: Frailty has physical, psychological, and social domains, each of which is a prognostic determinant for patients with HF, and each domain overlaps with the other, although there are no standardized criteria for diagnosing frailty. Frailty can be targeted for treatment with various interventions, and recent studies have suggested that multidisciplinary intervention could be a promising option for frail patients with HF. However, currently, there is limited data, and further research is needed before its clinical implementation. Frailty and HF share a common background and are strongly associated with each other. More comprehensive assessment and therapeutic interventions for frailty need to be developed to further improve the prognosis and quality of life of frail patients with HF.

DOI： 10.1007/s11897-021-00513-2

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DOI： 10.1007/s11897-021-00516-z

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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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Language：Japanese   Publisher：日本肺高血圧・肺循環学会・日本小児肺循環研究会  

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Extensive data on early nutrition support for patients requiring critical care are available. However, whether early initiation of feeding could be beneficial for patients hospitalized for acute heart failure (HF) remains unclear. We sought to compare outcomes of early and delayed initiation of feeding for hospitalized patients with acute HF using a nationwide inpatient database. We retrospectively analyzed data from the Diagnosis Procedure Combination database. We included patients hospitalized for HF between January 2010 and March 2018. We excluded patients with length of hospital stay ≤2 days, those patients who underwent major procedures under general anesthesia, and those requiring advanced mechanical supports within 2 days after admission including intubation, intra-aortic balloon pumping, and extracorporeal membrane oxygenation. Propensity score matching and instrumental variable analyses were conducted to compare in-hospital mortality, complications and length of stay between the early and delayed feeding groups. Among 432,620 eligible patients, 403,442 patients (93%) received early initiation of feeding (within 2 days after admission) and 29,178 patients (7%) received delayed initiation of feeding. Propensity score matching created 29,153 pairs and delayed initiation of feeding was associated with higher in-hospital mortality (odds ratio 1.32; 95% confidence interval 1.26 to 1.39), longer hospital stay and higher incidence of pneumonia and sepsis. The instrumental variable analysis also showed patients with delayed initiation of feeding had higher in-hospital mortality (odds ratio 1.34; 95% confidence interval 1.28 to 1.40). In conclusion, our analysis suggested a potential benefit of early initiation of feeding for in-hospital outcomes in hospitalized patients hospitalized for acute HF. Further investigations are required to confirm our results and to clarify the underlying mechanisms.

DOI： 10.1016/j.amjcard.2020.12.082

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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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OBJECTIVES: We investigated whether the FRAIL scale questionnaire is consistent with the Fried criteria, predicts all-cause mortality, and reflects physical dysfunction in patients with heart failure (HF). DESIGN: Secondary analysis of FRAGILE-HF, a cohort study that enrolled participants from 2016 to 2018 and followed-up for 1-year of discharge. SETTING AND PARTICIPANTS: A prospective multicenter cohort study in which 15 hospitals in Japan (8 university hospitals and 7 nonuniversity teaching hospitals) participated. We prospectively enrolled 1332 consecutive hospitalized patients ≥65 years old with HF and analyzed 1028 patients after excluding 304 patients with missing data on the FRAIL scale. METHODS: The FRAIL scale, the Fried model, and physical function were measured before discharge. The endpoint was all-cause mortality. RESULTS: According to the FRAIL scale, 459 (44.6%) and 491 (47.8%) were classified as frail and prefrail, respectively. The Kappa coefficient between the FRAIL scale and the Fried criteria were 0.39 [95% confidence interval (CI) 0.34-0.44; P < .001]. The area under the receiver-operating characteristic curves for frailty diagnosed by the Fried criteria of the FRAIL scale was 0.74 (95% CI 0.71-0.76; P < .001). A total of 118 deaths occurred during 1 year of follow-up. After adjusting for the MAGGIC risk score and log-BNP, The FRAIL scale predicted all-cause mortality (hazard ratio 1.17; 95% CI 1.01-1.36; P = .035). The FRAIL scale was also associated with various physical dysfunctions that correlated with poor prognosis. CONCLUSIONS AND IMPLICATIONS: The FRAIL scale had moderate consistency with the Fried criteria, predicted all-cause mortality, and reflected clinically important physical dysfunctions.

DOI： 10.1016/j.jamda.2021.02.025

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In the emergency admission due to worsening heart failure (HF) in patients on maintenance hemodialysis, emergent dialysis may be indicated, which increases personnel expenses. To clarify the characteristics and in-hospital management of the patients, we conducted a multicenter retrospective study including 142 patients on maintenance hemodialysis emergently admitted for worsening HF (71.6 ± 9.2 years, 69.0% male, 44.4% HF with preserved [≥50%] ejection fraction). The interval between last hemodialysis and admission was long (median 55 h), suggesting that fluid accumulation triggered HF events. Although most patients (73.9%) were admitted in the nighttime (5 p.m. to 9 a.m.), only 17.9% of them needed nighttime dialysis and were managed medically until the first in-hospital dialysis, with the use of noninvasive positive pressure ventilation in 45.1% and oxygen supplementation in 95.8%. While patients on hemodialysis with worsening HF were frequently admitted in the nighttime, nighttime dialysis was indicated in a limited population.

DOI： 10.1111/1744-9987.13644

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

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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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AIMS: There have been no investigations of the prevalence and clinical implications of coexistence of anaemia and frailty in older patients hospitalized with heart failure (HF) despite their association with adverse health outcomes. The present study was performed to determine the prevalence and prognostic value of the coexistence of anaemia and frailty in hospitalized older patients with HF. METHODS AND RESULTS: We performed post hoc analysis of consecutive hospitalized HF patients ≥65 years old enrolled in the FRAGILE-HF, which was the prospective, multicentre, observational study. Anaemia was defined as haemoglobin < 13 g/dL in men and <12 g/dL in women, and frailty was evaluated according to the Fried phenotype model. The study endpoint was all-cause mortality. Of the total of 1332 patients, 1217 (median age, 81 years; 57.4% male) were included in the present study. The rates of anaemia and frailty in the study population were 65.7% and 57.0%, respectively. The patients were classified into the non-anaemia/non-frail group (16.6%), anaemia/non-frail group (26.4%), non-anaemia/frail group (17.7%), and anaemia/frail group (39.3%). A total of 144 patients died during 1 year of follow-up. In multivariate analyses, only the anaemia/frail group showed a significant association with elevated mortality rate (adjusted hazard ratio, 1.94; 95% confidence interval, 1.02-3.70; P = 0.043), compared with the non-anaemia/non-frail group after adjusting for other covariates. CONCLUSIONS: Coexistence of anaemia and frailty are prevalent in hospitalized older patients with HF, and it has a negative impact on mortality.

DOI： 10.1002/ehf2.13140

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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 & AIMS: Although the Global Leadership Initiative on Malnutrition (GLIM) proposed a consensus scheme for diagnosing malnutrition in adults in clinical settings globally, the prevalence and prognostic value of malnutrition defined by GLIM criteria have yet to be evaluated in elderly patients with heart failure. This study aimed to determine the prevalence and prognostic implication of malnutrition as defined by GLIM criteria in comparison to those for a pre-existing definition of malnutrition, the geriatric nutritional risk index (GNRI), in elderly patients with heart failure METHODS: We evaluated malnutrition by two metrics, the GLIM criteria and geriatric nutritional risk index (GNRI), in 890 hospitalized patients with decompensation of heart failure aged ≥65 years, able to ambulate at discharge. The primary outcome was all-cause death within 1 year of discharge. RESULTS: According to GLIM criteria and GNRI <92, 42.4% and 46.5% of participants, respectively, had malnutrition, with moderate agreement (Cohen's kappa coefficient: 0.46 [95% confidence interval: 0.40-0.51]). During 1 year of follow-up, 101 (11.4%) deaths were observed, and malnutrition defined by either the GLIM criteria or GNRI was associated with a higher mortality rate, independent of other prognostic factors (GNRI: hazard ratio, 1.45, P = 0.031; GLIM: hazard ratio, 1.57, P = 0.016). Although malnutrition defined by either criterion showed additive prognostic value when added to a model incorporating pre-existing prognostic factors, defining malnutrition by GLIM criteria instead of the GNRI yielded a statistically significant improvement in model prognostic predictive ability (net-reclassification improvement, 0.44, P < 0.001; integrated discrimination index, 0.013, P < 0.001). CONCLUSIONS: In elderly patients with heart failure, 42.4% are malnourished according to the GLIM criteria, which is associated with a poor prognosis, independent of known prognostic factors. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN-CTR, https://www.umin.ac.jp/ctr/index.htm, study unique identifier: UMIN000023929).

DOI： 10.1016/j.clnu.2021.01.014

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The aim of the present study was to determine whether urinary 8-hydroxydeoxyguanosine (8-OHdG), which is a marker of oxidative stress, can predict future cardiovascular death in patients with acute coronary syndrome (ACS). A total of 551 consecutive patients with ACS who underwent admission urinary 8-OHdG measurements were enrolled in this study. The patients were divided into 2 groups according to the optimal cutoff value of admission urinary 8-OHdG determined by a receiver-operating characteristics curve for the prediction of cardiovascular death: a high admission urinary 8-OHdG group, 169 patients with admission urinary 8-OHdG ≥ 17.92 ng/mg creatinine; and a low admission urinary 8-OHdG group, 382 patients with admission urinary 8-OHdG < 17.92 ng/mg creatinine. The patients were followed up for a median period of 34 months. The primary and secondary end points were the incidence of cardiovascular death and major cardiovascular events (MACE) composed of cardiovascular death, non-fatal myocardial infarction, or urgent hospitalization for heart failure. Of the 551 patients, cardiovascular deaths and MACE occurred in 14 (2.5%) and 35 (6.4%), respectively. The Kaplan-Meier estimate of the event-free rate revealed cardiovascular deaths and MACE were more likely in the high admission 8-OHdG group than in the low admission 8-OHdG group (log rank, both P < 0.001). Multiple adjusted Cox proportional hazards analysis indicated that high admission urinary 8-OHdG was an independent predictor of cardiovascular death (hazard ratio [HR] 7.642, P = 0.011) and MACE (HR 2.153, P = 0.049). High admission urinary 8-OHdG levels predict cardiovascular mortality after adjustment in patients with ACS.

DOI： 10.1007/s00380-020-01663-4

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

DOI： 10.5551/jat.52282

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AIMS: Sarcopenia, one of the extracardiac factors for reduced functional capacity and poor outcome in heart failure (HF), may act differently between HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF). We sought to investigate the impact of sarcopenia on mortality in HFpEF and HFrEF. METHODS AND RESULTS: We performed a post hoc analysis of a multicentre prospective cohort study, including 942 consecutive older (age ≥65 years) hospitalized patients: 475 with HFpEF (ejection fraction ≥45%, age 81 ± 7 years, 48.8% men) and 467 with HFrEF (ejection fraction <45%, age 78 ± 8 years, 68.1% men). Sarcopenia was diagnosed according to the international criteria incorporating muscle strength (handgrip strength), physical performance (gait speed), and skeletal muscle mass (appendicular skeletal mass). The HFpEF group consisted of fewer patients with low appendicular skeletal muscle mass index measured using bioelectrical impedance analysis [<7.0 kg/m2 (men) and <5.7 (women); 22.1% vs. 31.0%, P = 0.003], and more patients with low handgrip strength [<26 kg (men) and <18 (women); 67.8% vs. 55.5%, P < 0.001], and slow gait speed [<0.8 m/s (both sexes); 54.5% vs. 41.1%, P < 0.001] than the HFrEF group, resulting in a similar sarcopenia prevalence in the two groups (18.1% vs. 21.6%, P = 0.191). Sarcopenia was an independent predictor of 1-year mortality in both HFpEF and HFrEF [hazard ratio (95% confidence interval) 2.42 (1.36-4.32), P = 0.003 in HFpEF and 2.02 (1.08-3.75), P = 0.027 in HFrEF; P for interaction = 0.666] after adjustment for other predictors. CONCLUSIONS: In older patients with HF, sarcopenia contributes to mortality similarly in HFpEF and HFrEF.

DOI： 10.1093/eurjpc/zwaa117

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AIMS: To describe the prevalence, overlap, and prognostic implications of physical and social frailties and cognitive dysfunction in hospitalized elderly patients with heart failure. METHODS AND RESULTS: The FRAGILE-HF study was a prospective multicentre cohort study enrolling consecutive hospitalized patients with heart failure aged ≥65 years. The study objectives were to examine the prevalence, overlap, and prognostic implications of the coexistence of multiple frailty domains. Physical frailty, social frailty, and cognitive dysfunction were evaluated by the Fried phenotype model, Makizako's 5 items, and Mini-Cog, respectively. The primary study outcome was the combined endpoint of heart failure rehospitalization and all-cause death within 1 year. Among 1180 enrolled hospitalized patients (median age, 81 years; 57.4% male), physical frailty, social frailty, and cognitive dysfunction were identified in 56.1%, 66.4%, and 37.1% of the patients, respectively. The number of identified frailty domains was 0, 1, 2, and 3 in 13.5%, 31.4%, 36.9%, and 18.2% of the patients, respectively. During follow-up, the combined endpoint occurred in 383 patients. Adjusted hazard ratios for 1, 2, and 3 domains, with 0 domains as the reference, were 1.38 [95% confidence interval (CI) 0.89-2.13; P = 0.15], 1.60 (95% CI 1.04-2.46; P = 0.034), and 2.04 (95% CI 1.28-3.24; P = 0.003), respectively. Incorporating the number of frailty domains into the pre-existing risk model yielded a 22.0% (95% CI 0.087-0.352; P = 0.001) net reclassification improvement for the primary outcome. CONCLUSIONS: The coexistence of multiple frailty domains is prevalent in hospitalized elderly patients with heart failure. Holistic assessment of multi-domain frailty provides additive value to known prognostic factors.

DOI： 10.1002/ejhf.1926

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Since the beginning of the coronavirus disease 2019 (COVID-19) outbreak initiated on the Diamond Princess Cruise Ship at Yokohama harbor in February 2020, we have been doing our best to treat COVID-19 patients. In animal experiments, angiotensin converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) are reported to suppress the downregulation of angiotensin converting enzyme 2 (ACE2), and they may inhibit the worsening of pathological conditions. We aimed to examine whether preceding use of ACEIs and ARBs affected the clinical manifestations and prognosis of COVID-19 patients. One hundred fifty-one consecutive patients (mean age 60 ± 19 years) with polymerase-chain-reaction proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were admitted to six hospitals in Kanagawa Prefecture, Japan, were analyzed in this multicenter retrospective observational study. Among all COVID-19 patients, in the multiple regression analysis, older age (age ≥ 65 years) was significantly associated with the primary composite outcome (odds ratio (OR) 6.63, 95% confidence interval (CI) 2.28-22.78, P < 0.001), which consisted of (i) in-hospital death, (ii) extracorporeal membrane oxygenation, (iii) mechanical ventilation, including invasive and noninvasive methods, and (iv) admission to the intensive care unit. In COVID-19 patients with hypertension, preceding ACEI/ARB use was significantly associated with a lower occurrence of new-onset or worsening mental confusion (OR 0.06, 95% CI 0.002-0.69, P = 0.02), which was defined by the confusion criterion, which included mild disorientation or hallucination with an estimation of medical history of mental status, after adjustment for age, sex, and diabetes. In conclusion, older age was a significant contributor to a worse prognosis in COVID-19 patients, and ACEIs/ARBs could be beneficial for the prevention of confusion in COVID-19 patients with hypertension.

DOI： 10.1038/s41440-020-00535-8

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Adiponectin (APN) has cardioprotective properties and bisoprolol has been reported to increase myocardial APN expression and reduce myocardial damage. Administration of landiolol, which has a higher cardio-selectivity and shorter half-life than bisoprolol, during the percutaneous coronary intervention (PCI) may increase serum APN and high-molecular weight (HMW)-APN, an active form of APN, in patients with stable angina pectoris (SAP). We recruited 70 patients with SAP and randomized them to intravenous landiolol during PCI (N = 35) or control group (N = 35). The primary endpoint was serum APN and HMW-APN level 3 days after PCI. There was no difference in the primary endpoint between the landiolol and control groups (8.93 ± 5.24 vs. 10.18 ± 5.81 μg/mL, p = 0.35 and 3.36 ± 2.75 vs. 4.28 ± 3.13 μg/mL, p = 0.20) for APN and HMW-APN levels, respectively. APN and HMW-APN level were significantly decreased 1 day after PCI [-0.55 ± 0.92 μg/mL (9.87-9.32 μg/mL), p < 0.001 and -0.20 ± 0.45 μg/mL (3.89-3.69 μg/mL), p < 0.001, respectively]. Additionally, the absolute change in HMW-APN was significantly smaller in the landiolol group compared to the control group (-0.08 ± 0.27 vs. -0.31 ± 0.55 μg/mL, p = 0.031). Multiple linear regression analysis showed that use of landiolol was an independent predictor of change in HMW-APN (β = 0.276, p = 0.014). Serum APN and HMW-APN level 3 days after PCI were similar between patients treated with and without landiolol. APN and HMW-APN decreased 1 day after PCI in the SAP and landiolol mitigated decrease in HMW-APN.

DOI： 10.1007/s00380-020-01637-6

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AIMS: Exogenous atrial natriuretic peptide (ANP) may be a logical treatment for heart failure (HF) patients with ANP deficiency. Lower ANP concentrations may result from HF with preserved ejection fraction (HFpEF), which also results in lower brain natriuretic peptide levels in HFpEF relative to HF with reduced ejection fraction (HFrEF), although clinical features regarding circulating ANP in HFpEF and HFrEF have not been fully investigated during acute HF. Here, we characterized the differential regulation of circulating ANP and the efficacy of exogenous ANP (carperitide) in patients with acute HF, especially HFpEF. METHODS AND RESULTS: Serum ANP levels before treatment and the diuretic effect of 0.0125 μg/kg/min of carperitide alone for the first 6 h were prospectively evaluated in 113 patients with acute HF who were divided into two groups: HFpEF vs. HFrEF. We mainly analysed the impact of baseline ANP levels and the presence of HFpEF on the diuretic effect of exogenous ANP. There was an inverse relationship between ANP levels and the diuretic effect of exogenous ANP (r2  = 0.19, P < 0.001). Patients with HFpEF had lower ANP levels (P < 0.001) and a greater diuretic effect of exogenous ANP than patients HFrEF (P < 0.001). HFpEF was an independent predictor of greater diuretic effect of exogenous ANP (P = 0.003), as with a lower baseline ANP level (P = 0.004). CONCLUSIONS: Patients with HFpEF might have an aspect of ANP deficiency and represent a promising therapeutic target for modulating circulating ANP.

DOI： 10.1002/ehf2.13042

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

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BACKGROUND: Lipoprotein (a) [Lp(a)] has been reported to be a residual risk factor in patients who have achieved target lipid levels. The aim of the present study was to investigate the associations of Lp(a) with plaque progression and major cardiovascular events in patients with acute coronary syndromes (ACS). METHODS: The Yokohama-ACS study included 102 patients with ACS who underwent intravascular ultrasound (IVUS) at baseline and at 10-month follow-up after percutaneous coronary intervention (PCI). The patients were randomly assigned to receive either moderate- or low-intensity statin therapy. IVUS was performed to measure the plaque volume at non-culprit lesions. We enrolled 76 patients for whom Lp(a) levels at 10-month follow-up were available. RESULTS: The patients were divided into 2 groups according whether their Lp(a) levels were ≤20 mg/dl [low Lp(a) group; n = 49] or >20 mg/dl [high Lp(a) group; n = 27]. Baseline characteristics and low-density lipoprotein cholesterol levels at 10-month follow-up were similar in the low Lp(a) group and high Lp(a) group (87 ± 29 mg/dl vs. 93 ± 27 mg/dl, p = 0.42). The low Lp(a) group had significant plaque regression, whereas the high Lp(a) group showed slight plaque progression (-6.8% vs. 2.5%, p = 0.02). Ninety-five percent of the prognostic data were obtained 5 years after PCI. The cumulative event-free survival rate was significantly lower in the high Lp(a) group (p = 0.02; log-rank test). CONCLUSIONS: Lp(a) levels may be an alternative predictor of further plaque regression and the likelihood of major adverse cardiovascular events in statin-treated ACS patients.

DOI： 10.1016/j.jjcc.2020.01.005

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

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There are few reports investigating the relationship between bronchial asthma (BA) and heart failure (HF). We hypothesized BA may have impact on prognosis in patients with HF. Among 323 consecutive outpatients with HF, 191 patients without chronic obstructive pulmonary disease were analyzed. Twenty patients had BA, most of whom (80.0%) had preserved left ventricular ejection fraction (LVEF ≥ 50%). The use of β-blockers was less frequent (55.0% vs 83.0%. p = 0.01), systolic blood pressure (133 ± 22 vs 120 ± 17 mmHg, p = 0.003), and heart rate (83 ± 14 vs 74 ± 15 bpm, p = 0.02) were higher in patients with BA than those without BA. During median follow up of 24 months, 45 (23.6%) experienced primary outcome defined as a composite of all-cause death, nonfatal myocardial infarction, nonfatal ischemic stroke, and unexpected hospitalization due to HF. Multivariate Cox regression analysis revealed that the presence of BA was independently associated with the occurrence of primary outcome (hazard ratio 3.08, 95% CI 1.42-6.71, p = 0.004). In the subgroup analysis of patients with preserved LVEF, patients with BA exhibited worse outcomes (p = 0.03 by log-rank). Patients with HF complicated by BA, most of whom had preserved LVEF, exhibited worse outcomes than those without BA.

DOI： 10.1007/s00380-020-01555-7

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BACKGROUND: Low population density may be associated with high mortality in acute myocardial infarction (AMI) patients. The purpose of this study was to investigate the effect of population density and hospital primary percutaneous coronary intervention (PCI) volume on AMI in-hospital mortality in Japan.Methods and Results:This is a retrospective study of 64,414 AMI patients transported to hospital by ambulances. The main outcome measure was in-hospital mortality. The median population density was 1,147 (interquartile range, 342-5,210) persons/km2. There was a significant negative relationship between population density and in-hospital mortality (OR for a quartile down in population density 1.086, 95% CI 1.042-1.132, P<0.001). Patients in less densely populated areas were more often transported to hospitals with a lower primary PCI volume, and they had a longer distance to travel. By using multivariable analysis, primary PCI volume was found to be significantly associated with in-hospital mortality, but distance to hospital was not. When divided into the low- and high-volume hospitals, using the cut-off value of 115 annual primary PCI procedures, the increase in in-hospital mortality associated with low population density was observed only in patients hospitalized in the low-volume hospitals. CONCLUSIONS: Increased in-hospital mortality related to low population density was observed only in AMI patients who were transported to the low primary PCI volume hospitals, but not in those who were transported to high-volume hospitals.

DOI： 10.1253/circj.CJ-19-0869

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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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BACKGROUND: There is little evidence regarding social and geographic factors in patients with heart failure (HF). We sought to investigate the association between in-hospital mortality of patients with HF and population density of the patients' area of residence in Japan. METHODS: The present study is a retrospective cohort analysis of the nationwide claim-based database, the Japanese Registry Of All cardiac and vascular Diseases-Diagnostic Procedure Combination (JROAD-DPC). We selected data of 196,286 hospitalized patients with HF (median age of 81 years and 51.8% males). RESULTS: In-hospital mortality was 14.2%, 11.8%, and 9.5% in the lower, middle, and upper tertiles of population density, respectively. Age sub-analysis showed the largest absolute rural-urban disparity in mortality was 4.6% in the oldest subgroup (≥80 years). Multivariate analysis using mixed logistic regression model revealed that higher population density was associated with lower in-hospital mortality: multivariable-adjusted odds ratio (OR): 0.785, 95% confidence interval (CI): (0.713-0.864), p < 0.001 and 0.687, 95% CI: (0.623-0.757), p < 0.001 in the middle and upper tertiles, in comparison with the lower tertile as a reference, after adjustment for age, sex, the New York Heart Association class, comorbidities, and hospital volume. The same tendency was observed in propensity score analysis using 62,291 (in the lower vs. middle tertile) and 57,228 (in the lower vs. upper tertile) matched pairs (OR: 0.797, 95% CI: 0.725-0.877, p < 0.001 and OR: 0.695, 95% CI: 0.634-0.762, p < 0.001 in the middle and upper tertile, respectively). CONCLUSIONS: Higher population density was associated with lower in-hospital mortality in HF. More research is needed to gain insight into causality.

DOI： 10.1016/j.jjcc.2019.09.008

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

The Diamondback 360® coronary orbital atherectomy system (OAS) can safely debulk calcified lesions by pullback of the crown, if the crown is advanced to the distal of the lesion. The aim of this study was to compare crossability with two types of crown in OAS. Thirty-six consecutive severely calcified lesions in 33 patients who underwent percutaneous coronary intervention with the coronary OAS were included. The micro crown was used in 18 consecutive lesions from April 2018 to February 2019, and the classic crown with the glide assist was used in 18 consecutive lesions from March 2019 to August 2019. Good crossability was defined as the ability to cross the lesion before orbital atherectomy or to cross the lesion with a first session of orbital atherectomy. We also tried to elucidate whether the crown could cross the lesion without using the glide assist in 13 consecutive lesions at the end of the classic crown cases. Good crossability was more often observed in cases with the classic crown (17 of 18 lesions, 94%) than the micro crown (6 of 18 lesions, 33%) (P < 0.001). In 13 consecutive lesions at the end of the classic crown cases, the crown could cross the lesion in 4 lesions (31%) without use of the glide assist or orbital atherectomy, and in 11 lesions (85%) with only use of the glide assist (P = 0.005). The classic crown with the glide assist is superior to the micro crown in terms of crossability for severely calcified lesions.

DOI： 10.1007/s12928-020-00640-y

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Language：Japanese   Publisher：日本成人先天性心疾患学会  

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

DOI： 10.1253/circrep.cr-19-0076

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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：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：(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：(一社)日本心臓病学会  

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

DOI： 10.1038/s41598-019-48246-6

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Other Link： http://www.nature.com/articles/s41598-019-48246-6

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© 2019 Elsevier Inc. We presented a case of acute anterior myocardial infarction caused by left anterior descending artery occlusion in a patient with pectus carinatum. The electrocardiogram (ECG)on admission showed counterclockwise rotation and T wave inversion only in leads V1–V2. Computed tomography revealed that this patient with pectus carinatum had greater septal angle. Electrocardiographic counterclockwise rotation due to greater septal angle in pectus carinatum led to atypical ECG findings of acute myocardial infraction.

DOI： 10.1016/j.jelectrocard.2019.04.004

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

DOI： 10.1253/circj.CJ-18-1236

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

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Background: Thinning of the fibrous cap of atherosclerotic plaque is a major component of plaque vulnerability. The high resolution of optical coherence tomography (OCT) provides an accurate measurement of fibrous-cap thickness. Endothelial dysfunction is associated with inflammation and enhanced local expression of matrix metalloproteinases. We investigated the association between endothelial dysfunction and OCT-derived thin-cap fibroatheroma (TCFA) in patients with acute coronary syndromes (ACS). Methods: Seventy-four patients with ACS, who underwent both OCT examinations of the culprit lesion before percutaneous coronary intervention and peripheral endothelial function assessment as assessed by logarithmic value of reactive hyperemia index (Ln_RHI), were enrolled. Age-, sex-, hypertension-, and diabetes-matched non-coronary artery disease (non-CAD) patients were also enrolled (n=15). Results: Ln_RHI levels were significantly lower in ACS patients compared with non-CAD patients (0.56±0.26 vs 0.74±0.22, P=0.01). Furthermore, the Ln_RHIs of ACS patients with TCFA (n=44) were significantly lower than those of ACS patients without TCFA (n=30) (0.50±0.24 vs 0.65±0.26, P=0.01). There was a weak but significant positive correlation between Ln_RHI and fibrous-cap thickness (Spearman's ρ=0.25, P=0.03). Multivariate logistic regression analysis identified lower Ln_RHI as an independent factor associated with TCFA in ACS patients (OR per 0.1 increase in Ln_RHI: 0.78 [95% CI: 0.62-0.98], P=0.03). Conclusion: Advanced endothelial dysfunction significantly correlates with a thin fibrous cap of coronary plaques in patients with ACS.

DOI： 10.2147/TCRM.S184457

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Background: The aim of this study was to clarify the clinical impact of activities of daily living (ADL) using the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC) database. Methods and Results: From April 2012 to March 2014, the JROAD-DPC database included 206,643 patients with acute coronary syndrome (ACS; n=49,784), heart failure (HF; n=136,878), or aortic aneurysm/dissection (Aorta; n=19,981). We divided them into 3 categories with regard to age (low, 20-59 years; middle, 60-79 years; high, ≥80 years) and admission ADL (low, Barthel index [BI] 0-70; middle, BI 75-95; high, BI 100). ACS, HF, and Aorta patients with low ADL had higher in-hospital mortality rates (18.3%, 16.7%, and 33.4%) than those with middle or high ADL (P<0.001, χ2 test). On multivariable analysis, BI on admission was associated with in-hospital mortality of ACS (OR, 0.986 per 1 BI; P<0.001), HF (OR, 0.986 per 1 BI; P<0.001), and Aorta (OR, 0.986 per 1 BI; P<0.001), adjusted for gender, age, body mass index, hypertension, diabetes mellitus, dyslipidemia, and the Charlson comorbidity index. Moreover, patients with low age and low ADL had a higher in-hospital mortality rate than those with high age and high ADL in regard to HF (8.6% vs. 6.0%). Conclusions: According to JROAD-DPC data, assessment of admission ADL is important in patients with cardiovascular disease.

DOI： 10.1253/circrep.CR-18-0009

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

DOI： 10.1016/j.cjca.2018.08.023

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Language：Japanese   Publisher：(NPO)日本冠疾患学会  

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

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

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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)   Publisher：BMC  

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.

DOI： 10.1186/s12933-018-0761-5

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

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BACKGROUND: Sleep-disordered breathing (SDB) is associated with cardiovascular complications. However, the effect of SDB on renal function in patients with acute coronary syndrome (ACS) treated by percutaneous coronary intervention (PCI) remains unclear. METHODS: We enrolled 154 consecutive ACS patients without heart failure. A sleep study was performed immediately after PCI. RESULTS: The mean apnea-hypopnea index (AHI) was 16.4±13.1, and 33 patients (21%) had severe SDB, defined as AHI≥25. Estimated glomerular filtration rate (eGFR) values on admission (60±12mL/min/1.73m2 vs. 67±17mL/min/1.73m2, p=0.046) and at discharge (54±15mL/min/1.73m2 vs. 63±15mL/min/1.73m2, p=0.002) were lower in patients with severe SDB than in those patients without severe SDB. Multiple linear regression analysis showed that AHIs were significantly correlated with absolute changes in eGFR values from admission to discharge (β=0.201, p=0.004). Median 24-h urinary noradrenaline excretion measured on the same day of the sleep study was higher [297 (interquartile range {IQR}: 232-472) vs. 174 (IQR: 107-318)μg/day, p=0.021] in patients with severe SDB. On multivariate logistic regression analysis, the presence of severe SDB was a significant predictor (adjusted odds ratio 3.76, 95% confidence interval 1.06-13.9, p=0.047) for eGFR of less than 45mL/min/1.73m2 at discharge. This association was independent of age, eGFR on admission, and a presentation of ST-segment elevation myocardial infarction. CONCLUSION: In patients with ACS who undergo PCI, severe SDB is associated with impaired renal function on admission and its deterioration during hospitalization. Further studies will be needed to conclude that SDB would be a therapeutic target in ACS.

DOI： 10.1016/j.jjcc.2017.07.017

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

Background: Worsening renal function, indicated by increased serum creatinine (SCr), is a common complication of percutaneous coronary procedures. Risk factors for increased SCr overlap with coronary risk factors involved in endothelial dysfunction. We hypothesized that endothelial dysfunction, measured using the reactive hyperemia peripheral arterial tonometry index (RHI), can predict periprocedure-increased SCr.
Methods: RHI was assessed before elective coronary procedures in 316 consecutive stable patients with a preserved estimated glomerular filtration rate (eGFR, &gt;60 mL/min/1.73 m(2)). SCr was measured before and 2 days after procedures.
Results: There was no significant correlation between natural logarithmic transformations of RHI (Ln-RHI) and basal Ln-eGFR. Periprocedure increase in SCr was observed in 148 (47%) patients. The increased SCr group had significantly lower Ln-RHI [0.48 (0.36, 0.62) vs. 0.59 (0.49, 0.76), p &lt; 0.001]. Multivariate linear regression analysis identified body mass index (BMI) (beta = 0.148, p = 0.005) and Ln-RHI (beta = -0.365, p &lt; 0.001) as significant determinants of percent changes in SCr. Multivariate logistic regression analysis identified Ln-RHI (per 0.1) [odds ratio (OR) 0.672, 95% confidence interval (95% CI) 0.586-0.722; p &lt; 0.001], Ln-B-type natriuretic peptide (OR: 1.484, 95% CI: 1.130-1.974; p = 0.004), current smoking (OR: 2.563, 95% CI: 1.379-4.763, p = 0.003), BMI (OR: 1.113, 95% CI: 1.031-1.203; p = 0.007), coronary intervention (OR: 1.736, 95% CI: 1.036-2.909; p = 0.036), and Ln-hemoglobin A1c (OR: 6.728, 95% CI: 1.093-41.392, p = 0.040) as independent determinants of increased SCr. Receiver operating characteristics curve analysis showed that Ln-RHI correlated significantly with increased SCr (area under the curve, 0.684, 95% CI: 0.626-0.742, p &lt; 0.001). The optimum cut-off point of Ln-RHI for the periprocedure increased SCr was 0.545.
Conclusions: Pre-procedure measurement of endothelial function by RHI is an effective strategy to assess the patient's risk conditions for worsening renal function after percutaneous coronary procedures. (C) 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2017.03.004

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

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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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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)   Publisher：ELSEVIER IRELAND LTD  

Background: Myostatin, a negative regulator of skeletal muscle mass, is up-regulated in the myocardiumof heart failure (HF) and increasedmyostatin is associatedwithweight loss in animal models with HF. Although there are disparities in pathophysiology and epidemiology between male and female patients with HF, it remains unclear whether there is gender difference in myostatin expression and whether it is associated with weight loss in HF patients.
Methods: Heart tissue sampleswere collected frompatientswith advanced heart failure (n= 31, female n= 5) as well as healthy control donors (n= 14, female n= 6). Expression levels of myostatin and its related proteins in the heart were evaluated by western blotting analysis.
Results: Body mass index was significantly lower in female HF patients than inmale counterparts (20.0 +/- 4.2 in female vs 25.2 +/- 3.8 in male, p= 0.04). In female HF patients, both mature myostatin and pSmad2 were significantly up-regulated by 1.9 fold (p= 0.05) and 2.5 fold (p &lt; 0.01) respectively compared to female donors, while expression of pSmad2was increased by 2.8 times inmale HF patients compared to male healthy subjects, but that of myostatinwas not. Therewas no significant difference in protein expression related tomyostatin signaling between male and female patients.
Conclusion: In this study, myostatin and pSmad2 were significantly up-regulated in the failing heart of female patients, but notmale patients, and female patients displayed lower body mass index. Enhancedmyostatin signaling in female failing heart may causally contribute to pathogenesis of HF and cardiac cachexia. (C) 2017 Elsevier B. V. All rights reserved.

DOI： 10.1016/j.ijcard.2017.03.153

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Objectives: Skeletal muscle wasting, also known as sarcopenia, has recently been identified as a serious comorbidity in patients with heart failure (HF). We aimed to assess the impact of sarcopenia on endothelial dysfunction in patients with HF with reduced ejection fraction (HFrEF) and with preserved ejection fraction (HFpEF).
Design: Cross-sectional study.
Setting: Ambulatory patients with HF were recruited at Charite Medical School, Campus Virchow-Klinikum, Berlin, Germany.
Participants: We assessed peripheral blood flow (arm and leg) in 228 patients with HF and 32 controls who participated in the Studies Investigating Comorbidities Aggravating HF (SICA-HF).
Measurements: The appendicular skeletal muscle mass of the arms and the legs combined was assessed by dual energy x-ray absorptiometry (DEXA). Sarcopenia was defined as the appendicular muscle mass two standard deviations below the mean of a healthy reference group of adults aged 18 to 40 years, as suggested for the diagnosis of muscle wasting in healthy aging. All patients underwent a 6-minute walk test and spiroergometry testing. Forearm and leg blood flow were measured by venous occlusion plethysmography. Peak blood flow was assessed after a period of ischemia in the limbs to test endothelial function.
Results: Sarcopenia was identified in 37 patients (19.5%). Patients with sarcopenia presented with lower baseline forearm blood flow (2.30 +/- 1.21 vs. 3.06 +/- 1.49 vs. 4.00 +/- 1.66 mL min(-1) 100 mL(-1); P = .02) than those without sarcopenia or controls. The group of patients with sarcopenia showed similar baseline leg blood flow (2.06 +/- 1.62 vs. 2.39 +/- 1.39 mL min(-1) 100 mL(-1); P = .11) to those without but lower values when compared to controls (2.06 +/- 1.62 vs. 2.99 +/- 1.28 mL min(-1) 100 mL(-1); P = .03). In addition, patients with and without sarcopenia presented with lower peak flow in the forearm when compared to controls (18.37 +/- 7.07 vs. 22.19 +/- 8.64 vs. 33.63 +/- 8.57 mL min(-1) 100 mL(-1); P &lt; .001). A similar result was observed in the leg (10.89 +/- 5.61 vs. 14.66 +/- 7.19 vs. 21.37 +/- 13.16 mL min(-1) 100 mL(-1); P &lt; .001). Peak flow in the forearm showed a significant correlation with exercise capacity (relative peak VO2: R = 0.47; P &lt; .001; absolute peak VO2: R = 0.35; P &lt; .001; and 6-min walk distance: R = 0.20; P &lt; .01). Similar correlations were observed between peak flow in the leg and exercise capacity (absolute peak VO2: R = 0.42, P &lt; .001; relative peak VO2: R = 0.41, P &lt; .001; and 6-min walk test: R = 0.33; P &lt; .001). Logistic regression showed peak flow in the leg to be independently associated with the 6-min walk distance adjusted for age, hemoglobin level, albumin, creatinine, presence of sarcopenia, and coronary artery disease (hazard ratio, 0.903; 95% confidence interval, 0.835-0.976; P = .01).
Conclusion: Patients with HF associated with sarcopenia have impaired endothelial function. Lower vasodilatation had a negative impact on exercise capacity, particularly prevalent in patients with sarcopenia. (C) 2016 AMDA - The Society for Post-Acute and Long-Term Care Medicine.

DOI： 10.1016/j.jamda.2016.09.006

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE CIRCULATION SOC  

Background: Kynurenine is a circulating metabolite from the essential amino acid tryptophan. Accelerated degradation of kynurenine in skeletal muscle has been reported to provide an anti-inflammatory effect. The aim of this study was to investigate the association between blood kynurenine and muscle mass/function in patients with heart failure (HF), in whom diseased muscle mass/function plays a pathophysiological role.
Methods and Results: Plasma kynurenine was assessed in 249 patients with HF (67 +/- 11 years, 21% women) and in 45 controls from the SICA-HF study. Kynurenine was higher in 173 HF patients with reduced ejection fraction (EF) and in 76 patients with preserved EF than controls (3.5 +/- 1.5, 3.4 +/- 1.3, and 2.4 +/- 1.1 mu mol/L, P&lt;0.001). In HF patients, kynurenine had an inverse association with handgrip strength (r=-0.26, P&lt;0.01), peak oxygen consumption (r=-0.29, P&lt;0.01), 6-min walk distance (r=-0.23, P&lt;0.01), and had a positive association with kidney and liver function parameters. No correlation was observed between kynurenine and lean mass. On multivariable linear regression analysis, a significant association was noted between kynurenine and peak oxygen consumption even after adjustment for age, gender, BMI, and hemoglobin (beta-0.23, P&lt;0.001). Patients with higher kynurenine were at higher risk of death (adjusted HR, 1.46 per 1 mu mol/L, P&lt;0.01).
Conclusions: In stable HF patients, plasma kynurenine was inversely correlated with muscle strength and functional capacity as well as with liver and kidney function.

DOI： 10.1253/circj.CJ-16-0791

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Language：English   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

The health status of older people is frequently complicated by one or more chronic diseases. Some conditions might have a different meaning in certain groups of elderly subjects, like in frail people or older patients with heart failure. Cut-off values defining these conditions may require adjustment in such groups. Indeed, several such conditions (e.g. obesity and hypercholesterolemia) have been discussed recently in light of so-called paradoxical situations, which are - counter-intuitively - associated with better outcome instead of a negative impact on survival in the general population. Therefore, different cut-off values may be needed in some groups of older subjects. The pathophysiological mechanisms for these paradoxical situations need to be understood in at least two different ways, causal and non-causal. The aim of this review is to provide an overview of a variety of conditions (obesity, dyslipidaemia, hypertension, and diabetes) in which new cut-offs may have diagnostic, clinical, or prognostic value, focusing on heart failure as a chronic disease, which is frequently observed in older patients. Haemoglobin concentration may need a different cut-off in heart failure for a reason other than paradox. Namely, underlying iron deficiency itself, both in those with or without anaemia, can have effects on symptoms and quality of life. Further studies will be needed for re-defining cut-off values in heart failure and maybe in the other chronic illnesses. (C) 2016 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.exger.2016.10.010

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Even though most clinical data on cachexia have been reported from Western countries, cachexia may be a growing problem in Asia as well, as the population in this area of the world is considerably larger. Considering the current definitions of obesity and sarcopenia in Japan, which are different from the ones in Western countries, the lack of a distinct cachexia definition in Japan is strinking. Only one epidemiological study has reported the prevalence of cachexia using weight loss as part of the definition in patients with stage III or IV non-small cell lung cancer. Although the reported prevalence of 45.6% is within the range of that in Western countries (28-57% in advanced cancer), we cannot compare the prevalence of cachexia in other types of cancer, heart failure, chronic obstructive pulmonary disease (COPD), and kidney disease (CKD) between Japan and Western countries. In patients with heart failure, one third of Japanese patients has a body mass index &lt;20.3kg/m(2) whereas the prevalence of underweight is 13.6% in reports from Western countries. These results may suggest that there are more cachectic heart failure patients in Japan, or that using the same definition like Western countries leads to gross overestimation of the prevalence of cachexia in Japan. The rate of underweight patients in COPD has been reported as 31-41% in COPD and seems to be high in comparison to the prevalence of cachexia in Western countries (27-35%). The reported lowest quartile value of BMI (19.6 kg/m(2)) in CKD may match with the prevalence of cachexia in Western countries (30-60%). The number of clinical trials targeting cachexia is very limited in Japan so far.

DOI： 10.1002/jcsm.12117

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

Inadequate nutritional status has been linked to poor outcomes in patients with heart failure (HF). Skeletal muscle wasting affects about 20% of ambulatory patients with HF. The impact of nutritional intake and appetite on skeletal muscle wasting has not been investigated so far. We sought to investigate the impact of nutritional status on muscle wasting and mortality in ambulatory patients with HF.
We studied 130 ambulatory patients with HF who were recruited as a part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) program. Muscle wasting was defined according to criteria of sarcopenia, i.e., appendicular skeletal muscle mass two standard deviations below the mean of a healthy reference group aged 18-40 years. Nutritional status was evaluated using the Mini-Nutritional Assessment-Short Form (MNA-SF). Functional capacity was assessed as peak oxygen consumption (peak VO2) by cardiopulmonary exercise testing, 6aEurominute walk testing, and the Short Physical Performance Battery (SPPB).
At baseline, 19 patients (15%) presented with muscle wasting. Patients with muscle wasting had significantly lower values of peak VO2, 6aEurominute walk distance, SPPB, and MNA-SF score than patients without (all p &lt; 0.05). In multivariate analysis, MNA-SF remained an independent predictor of muscle wasting after adjustment for age and New York Heart Association class (odds ratio [OR] 0.66; confidence interval [CI] 0.50-0.88; p &lt; 0.01). A total of 16 (12%) patients died during a mean follow-up of 21 months. In Cox regression analysis, MNA-SF (OR 0.80, CI 0.64-0.99, p = 0.04), left ventricular ejection fraction (OR 0.93, CI 0.86-0.99, p = 0.05), and peak VO2 (OR 0.78, CI 0.65-0.94, p = 0.008) were predictors of death.
MNA-SF is an independent predictor of muscle wasting and mortality in ambulatory patients with HF. Nutritional screening should be included as a fundamental part of the overall assessment of these patients.

DOI： 10.1007/s00508-016-1112-8

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Language：English   Publisher：ELSEVIER IRELAND LTD  

DOI： 10.1016/j.ijcard.2016.09.128

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DOI： 10.1016/j.ijcard.2016.08.289

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BACKGROUND: An early IV beta blocker during primary percutaneous coronary intervention (PCI) has been shown to reduce infarct size in ST-segment elevation acute myocardial infarction (STEMI), although the underlying mechanism is unknown. The aim of this study was to investigate the efficacy of early infusion of landiolol, the short-acting beta-1 adrenergic receptor blocker, on the reperfusion status in a STEMI. METHODS: We conducted a prospective, single-group trial of landiolol during the primary PCI for a STEMI. Landiolol was started intravenously just before reperfusion. The reperfusion status and outcomes in 55 treated patients were compared with those in 60 historical controls treated without landiolol. The optimal reperfusion was assessed by an ST-segment resolution (STR), coronary flow, and myocardial brush grade (MBG) after reperfusion. RESULTS: Patients in the landiolol group achieved a higher rate of an STR (64% vs. 42%, p=0.023) and MBG 2/3 (64% vs. 45%, p=0.045), whereas coronary flow was comparable between the two groups. A multivariate analysis showed that landiolol use was an independent predictor of an STR (odds ratio 2.99, 95% confidence interval 1.25-7.16, p=0.014). The incidence of non-sustained ventricular tachycardia (27% vs. 50%, p=0.014), hypotension (15% vs. 32%, p=0.046), and progression to Killip class grade III or IV (0% vs. 10%, p=0.028) were lower in the landiolol group. CONCLUSION: Early infusion of landiolol during the primary PCI was associated with optimal reperfusion and a lower incidence of adverse events in comparison with the control group.

DOI： 10.1016/j.ijcard.2016.07.076

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Background: Erythropoietin administration, which is clinically used in cancer patients with cancer-induced anemia, has also potentially beneficial effects on nonhematopoietic organs. We assessed the effects of erythropoietin on cancer cachexia progression and cardiac wasting compared with placebo using the Yoshida hepatoma model.
Methods: Wistar rats were divided in a sham group (n = 10) and a tumor-bearing group (n = 60). The tumor-bearing group was further randomized to placebo (n = 28), 500 Unit/kg/day (n = 16) or 5000 Unit/kg/day of erythropoietin (n = 16). Body composition was measured using nuclear magnetic resonance spectroscopy, cardiac function using echocardiography, physical activity using infrared monitoring system.
Results: Tumor-bearing rats with high dose erythropoietin led to a significant improvement on survival compared with placebo (hazard ratio: 0.43, 95% CI: 0.20-0.92, p = 0.030), though low dose erythropoietin did not reach significance (hazard ratio: 0.46, 95% CI: 0.22-1.02, p = 0.056). Loss of body weight, wasting of lean mass, fat mass, and reduced physical activity were ameliorated in rats treated with both low and high doses of erythropoietin (p &lt; 0.05, all). Moreover, reduced left ventricularmass and left ventricular systolic function were also ameliorated in rats treated with low and high doses of erythropoietin (p &lt; 0.05, respectively).
Conclusions: Overall, the present data support that cardiac wasting induced by cancer cachexia plays an important rolewhich leads to impaired survival, provided that the erythropoietin could be an effective therapeutic approach for cancer cachexia progression and cardiac wasting. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2016.05.008

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DOI： 10.1002/ehf2.12103

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Language：English   Publisher：BIOMED CENTRAL LTD  

Research and development of new drugs requires both long time and high costs, whereas safety and tolerability profiles make the success rate of approval very low. Drug repurposing, applying known drugs and compounds to new indications, has been noted recently as a cost-effective and time-unconsuming way in developing new drugs, because they have already been proven safe in humans. In this review, we discuss drug repurposing of approved cardiovascular drugs, such as aspirin, beta-blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, cardiac glycosides and statins. Regarding anti-tumor activities of these agents, a number of experimental studies have demonstrated promising pleiotropic properties, whereas all clinical trials have not shown expected results. In pathological conditions other than cancer, repurposing of cardiovascular drugs is also expanding. Numerous experimental studies have reported possibilities of drug repurposing in this field and some of them have been tried for new indications ('bench to bedside'), while unexpected results of clinical studies have given hints for drug repurposing and some unknown mechanisms of action have been demonstrated by experimental studies ('bedside to bench'). The future perspective of experimental and clinical studies using cardiovascular drugs are also discussed.

DOI： 10.1186/s12967-016-1031-5

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Language：English   Publisher：WILEY-BLACKWELL  

DOI： 10.1002/jcsm.12125

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE CIRCULATION SOC  

Background: Target lesion calcification is known to influence percutaneous coronary intervention. We evaluated the effects of rotational atherectomy (RA) and subsequent balloon angioplasty on calcified coronary lesions using optical coherence tomography (OCT).
Methods and Results: Thirty-seven calcified lesions in 36 patients were treated with RA followed by balloon angioplasty and stent implantation. In all patients, serial OCT images obtained after RA, after balloon angioplasty, and after stent implantation were analyzed at 1-mm intervals. The arc and thickness of the calcium component were measured after RA. The formation of calcium cracks was assessed after balloon angioplasty. A total of 625 segments were analyzed. The formation of calcium crack after balloon angioplasty was associated with greater stent crosssectional area (7.38 +/- 1.92 vs. 7.13 +/- 1.68 mm(2), P=0.035) as well as greater lumen gain (3.89 +/- 1.53 vs. 3.40 +/- 1.46 mm(2), P&lt;0.001). Segments with calcium cracks after angioplasty had a larger median calcium arc (360, IQR, 246-360 vs. 147, IQR, 118-199, P&lt;0.001) and a thinner calcium thickness (0.53 +/- 0.28 vs. 1.02 +/- 0.42 mm, P&lt;0.001) than those without. The optimal thresholds of calcium arc and calcium thickness for the prediction of cracks were 227 and 0.67 mm, respectively.
Conclusions: Larger calcium arc and thinner calcium thickness were associated with formation of calcium crack. Presence of calcium crack was the important determinant of optimal stent expansion.

DOI： 10.1253/circj.CJ-15-1059

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Background: Polyvascular disease (PolyVD) refers to the coexistence of coronary artery disease (CAD), peripheral arterial disease (PAD), and/or cerebrovascular disease (CVD), and carries a high risk of cardiovascular mortality. Endothelial dysfunction plays a crucial role in cardiovascular pathophysiology. This study investigated the association between PolyVD and the presence of microvascular endothelial dysfunction.
Methods: Consecutive stable patients (n = 533) with diabetes mellitus and/or multiple cardiovascular risk factors were enrolled. Peripheral microvascular endothelial function in the finger microvasculature was assessed using the reactive hyperemia peripheral arterial tonometry index (RHI), and ankle-brachial index was measured for diagnosis of lower-extremity PAD prior to coronary angiography. Diagnosis of CVD was based on clinical symptoms, carotid ultrasound, and magnetic resonance imaging. PolyVD was defined as two or more coexisting vascular diseases from CAD, lower-extremity PAD, and CVD.
Results: Natural logarithmic transformations of RHI (Ln-RHI) were significantly attenuated in 93 patients with PolyVD (0.44 +/- 0.20) compared with those in 440 patients without PolyVD (0.56 +/- 0.19; p &lt; 0.001) or in 299 patients with a single vascular disease (0.54 +/- 0.19; p &lt; 0.001). There was an independent correlation between Ln-RHI (per 0.1) and the presence of PolyVD in all high-risk patients [odds ratio (OR): 0.724; 95% confidence interval (CI): 0.610-0.859; p &lt; 0.001] and one or more vascular diseases (OR: 0.724; 95% CI: 0.605-0.867, p &lt; 0.001). Receiver-operating characteristics curve analysis showed that Ln-RHI correlated significantly with PolyVD (area under the curve, 0.682, 95% CI: 0.625-0.740, p &lt; 0.001). The optimum cut-off point of Ln-RHI for the existence of PolyVD was 0.479.
Conclusions: Microvascular endothelial dysfunction is significantly associated with the presence of PolyVD. Severe impairment of endothelial function in peripheral microvasculature may be an important pathophysiological component of PolyVD. (C) 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2015.07.003

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Language：English   Publisher：WILEY-BLACKWELL  

DOI： 10.1002/jcsm.12123

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DOI： 10.1002/jcsm.12119

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As malnutrition is often present in cachexia, nutritional intervention has been one of the widely accepted strategies. A literature review of cachexia models with dietary interventions in the present issue of this journal pointed out that the majority of nutrient intervention studies were of n-3 fatty acid, mainly eicosapentaenoic acid and docosahexaenoic acid. Effect on protein catabolism and anti-inflammation are most pronounced benefits of n-3 fatty acid. The effectiveness of n-3 fatty acid may depend on control diet or even be attributed to the polyunsaturated fatty acid deficiency inadvertently produced in control group. However, there is not enough clinical evidence to support a benefit of n-3 fatty acid substitution in patients with cachexia. The second important result from this review is that the majority of studies did not provide information about dietary design or did not standardize design, content, source, and overall composition. To guide dietary design for researchers in preclinical studies, a model has been proposed in this review, which may be useful to predict the efficacy of new dietary intervention in cachexia science. From a clinical point of view, the limited effectiveness of nutritional support in cachexia may partly be explained by the multifactorial nature of this condition. Cachexia differs from malnutrition inasmuch as malnutrition can be reversed by adequate nutrition and/or by overcoming problems of absorption or utilization of nutrients, but cachexia cannot be successfully treated by nutrition alone. Multidisciplinary approach including the assessment and intervention in feeding, appetite, swallowing, exercise, psychosocial, and psychological issue may be needed to improve nutrition in patients with cachexia.

DOI： 10.1002/jcsm.12111

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Background: The relationship between plasma glucagon-like peptide-1 (GLP-1) and coronary plaque characteristics in humans remains unclear.
Methods and Results: A total of 85 culprit coronary vessels excluding the 10-mm culprit segments in non-diabetic patients with acute coronary syndrome (ACS) were examined using integrated backscatter intravascular ultrasound, performed using a 40-MHz intravascular catheter before PCI. All patients underwent 75-g oral glucose tolerance test (OGTT), and the plasma GLP-1 response was evaluated on the basis of the area under the GLP-1 concentration-time curve (GLP-1 AUC) from 0 to 120 min. Patients in the low GLP-1 AUC tertile had a significantly greater percentage lipid area than did patients in the intermediate and high tertiles (low tertile vs. intermediate tertile vs. high tertile: 57.3+/-12.1% vs. 47.2+/-15.4% vs. 46.3+/-12.7%, P&lt;0.01, ANOVA) and a smaller percentage fibrosis area (38.1+/-9.4% vs. 44.6+/-11.5% vs. 45.7+/-9.0%; P=0.01, ANOVA). On multiple regression analysis, low GLP-1 AUC tertile was independently associated with percentage lipid area.
Conclusions: Low plasma GLP-1 during 75-g OGTT is associated with increased lipid content in non-diabetic patients with ACS, suggesting that plaque vulnerability is increased in this subgroup of patients.

DOI： 10.1253/circj.CJ-15-0718

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

Background: Heart failure (HF) is associated with adverse metabolic influences and provokes fat loss as well as bone and muscle loss at the terminal stages. Pericardial fat is an ectopic fat depot that can potentially affect the myocardium, but the role of pericardial fat in HF is unclear. We sought to characterize pericardial fat in HF, particularly in association with bone tissue using cardiac computed tomography (CT).
Methods: In 61 consecutive hospitalized HF patients with left ventricular ejection fraction &lt;= 50%, pericardial fat volume (PFV), CT density in the thoracic vertebrae, and ectopic calcification in the aortic valve were assessed simultaneously using electrocardiogram-gated non-contrast-enhanced CT.
Results: The mean PFV was 93.5 +/- 50.6 cm(3), which might reflect the total body fat measured with dual energy X-ray absorptiometry (Pearson's r = 0.48, p = 0.01). The PFV index, defined as the PFV/body surface area, was significantly higher among older patients (&gt;65 years; 63.5 +/- 30.6 cm(3)/m(2) vs. 42.7 +/- 17.1 cm3/m2, p &lt; 0.01) and among patients with atrial fibrillation (AF; 70.9 +/- 36.4 cm(3)/m(2) vs. 48.8 +/- 21.2 cm(3)/m(2), p &lt; 0.01) and hypertension (60.7 +/- 29.3 cm(3)/m(2) vs. 41.5 +/- 18.2 cm(3)/m(2), p &lt; 0.01) compared to patients without these conditions. The PFV indices were comparable between the patients with and without ischemic etiology, diabetes, and renal dysfunction. Patients with increased PFV indices (above the median) exhibited lower CT density in the thoracic vertebrae (134 +/- 41 Hounsfield units vs. 161 +/- 57 Hounsfield units, p = 0.04), and were more likely to have aortic valve calcification (48% vs. 18%, p = 0.02) and N-telopeptide (bone resorption marker; 20.7 +/- 5.2 nmol BCE/mmol Cr vs. 25.5 +/- 5.9 nmol BCE/mmol Cr, p = 0.03) levels than those without increased PFV indices.
Conclusions: We simultaneously assessed the pericardial fat and bone tissue of HF patients with CT and successfully characterized AF, hypertension, and advanced age as factors that are associated with increased PFV. PFV was correlated with bone tissues and alterations in bone turnover. (C) 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2015.03.016

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Loss of muscle mass arises from an imbalance of protein synthesis and protein degradation. Potential triggers of muscle wasting and function are immobilization, loss of appetite, dystrophies and chronic diseases as well as aging. All these conditions lead to increased morbidity and mortality in patients, which makes it a timely matter to find new biomarkers to get a fast clinical diagnosis and to develop new therapies. This mini-review covers current developments in the field of biomarkers and drugs on cachexia and sarcopenia. Here, we reported about promising markers, e.g. tartrate-resistant acid phosphatase 5a (TRACP5a), and novel substances like Epigallocatechin-3-gallate (EGCg). In summary, the progress to combat muscle wasting is in full swing and perhaps diagnosis of muscle atrophy and of course patient treatments could be soon supported by improved and more helpful strategies. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.ijcard.2015.10.033

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Eleven biosurfactant-producing strains were newly isolated from environmental samples using a drop-collapse assay and thin-layer chromatography (TLC). According to the TLC analysis, the separation patterns of the glycolipid spots of nine dominant strains corresponded to that of the sophorolipids produced by a Starmerella bombicola type strain. The retention factor values of the spot patterns of two strains were less than those of the others. Two representative major products were purified, and their molecular structures were determined. The major products were identified as diacetylated lactonic and acidic sophorolipids. The fatty acid moieties of both compounds were estimated to be 17-hydroxymethyl hexadecenoic acid. The amounts of glycolipids ranged from 5.0 to 22.9g/L after 4 d of cultivation. According to a phylogenetic analysis, the strains were identified as Starmerella bombicola and Candida floricola.

DOI： 10.1080/09168451.2016.1191332

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DOI： 10.1002/jcsm.12080

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DOI： 10.1002/ehf2.12073

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Language：English   Publisher：WILEY-BLACKWELL  

Loss of muscle mass arises from an imbalance of protein synthesis and protein degradation. Potential triggers of muscle wasting and function are immobilization, loss of appetite, dystrophies, and chronic diseases as well as aging. All these conditions lead to increased morbidity and mortality in patients, which makes it a timely matter to find new biomarkers to get a fast clinical diagnosis and to develop new therapies. This mini-review covers current developments in the field of biomarkers and drugs on cachexia and sarcopenia. Here, we reported about promising markers, e.g. tartate-resistant acid phosphatase 5a, and novel substances like epigallocatechin-3-gallate. In summary, the progress to combat muscle wasting is in full swing, and perhaps diagnosis of muscle atrophy and of course patient treatments could be soon support by improved and more helpful strategies.

DOI： 10.1002/jcsm.12082

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DOI： 10.1002/jcsm.12085

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DOI： 10.1002/jcsm.12081

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DOI： 10.1002/jcsm.12084

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DOI： 10.1517/17460441.2015.1041914

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Background Activity of xanthine oxidase is induced in cancer cachexia, and its inhibition by allopurinol or oxypurinol improves survival and reduces wasting in the Yoshida hepatoma cancer cachexia model. Here, we tested the effects of the second-generation xanthine oxidase inhibitor febuxostat compared with placebo in the same model as used previously by our group.
Methods Wistar rats (similar to 200g) were treated daily with febuxostat at 5mg/kg/day or placebo via gavage for a maximum of 17days. Weight change, quality of life, and body composition were analysed. After sacrifice, proteasome activity in the gastrocnemius muscle was measured. Muscle-specific proteins involved in metabolism were analysed by western blotting.
Results Treatment of the tumour-bearing rats with febuxostat led to a significantly improved survival compared with placebo (hazard ratio: 0.45, 95% confidence interval: 0.22-0.93, P=0.03). Loss of body weight was reduced (-26.312.4g) compared with placebo (-50.2 +/- 2.1g, P&lt;0.01). Wasting of lean mass was attenuated (-12.7 +/- 10.8g) vs. placebo (-31.9 +/- 2.1g, P&lt;0.05). While we did not see an effect of febuxostat on proteasome activity at the end of the study, the pAkt/Akt ratio was improved by febuxostat (0.94 +/- 0.09) vs. placebo (0.41 +/- 0.05, P&lt;0.01), suggesting an increase in protein synthesis.
Conclusions Febuxostat attenuated cachexia progression and improved survival of tumour-bearing rats.

DOI： 10.1002/jcsm.12017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Objective: Mitochondrial dysfunction plays an important role in cellular senescence and impaired function of vascular endothelium, resulted in cardiovascular diseases. Telmisartan is a unique angiotensin II type I receptor blocker that has been shown to prevent cardiovascular events in high risk patients. AMP-activated protein kinase (AMPK) plays a critical role in mitochondrial biogenesis and endothelial function. This study assessed whether telmisartan enhances mitochondrial function and alters cellular functions via AMPK in human coronary artery endothelial cells (HCAECs).
Methods and results: In cultured HCAECs, telmisartan significantly enhanced mitochondrial activity assessed by mitochondrial reductase activity and intracellular ATP production and increased the expression of mitochondria related genes. Telmisartan prevented cellular senescence and exhibited the anti-apoptotic and pro-angiogenic properties. The expression of genes related anti-oxidant and pro-angiogenic properties were increased by telmisartan. Telmisartan increased endothelial NO synthase and AMPK phosphorylation. Peroxisome proliferator-activated receptor gamma signaling was not involved in telmisartan-induced improvement of mitochondrial function. All of these effects were abolished by inhibition of AMPK.
Conclusions: Telmisartan enhanced mitochondrial activity and exhibited anti-senescence effects and improving endothelial function through AMPK in HCAECs. Telmisartan could provide beneficial effects on vascular diseases via enhancement of mitochondrial activity and modulating endothelial function through AMPK activation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2015.01.037

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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/j.jacc.2014.11.043

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DOI： 10.1016/j.ijcard.2014.07.221

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Language：Japanese   Publisher：(一社)日本内分泌学会  

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

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Background: Venous thromboembolism (VTE) is a common and sometimes lethal postoperative complication of arthroplasty. Endothelial dysfunction is important in the pathogenesis of thrombus formation. Reactive hyperemia-peripheral arterial tonometry (RH-PAT) can noninvasively evaluate endothelial function. This study investigated the predictive value of RH-PAT for deep vein thrombosis (DVT) after lower limb arthroplasty.
Methods and Results: A prospective observational study of 126 osteoarthritic patients who underwent total knee arthroplasty (TKA) or hip arthroplasty (THA) was conducted. The RH-PAT index (RHI) was measured on the day before surgery, and presence of DVT was checked by ultrasonography or phlebography before and after surgery. Following arthroplasty, DVT was diagnosed in 51 patients (40.5%). RHI in the DVT group (0.58 +/- 0.25) was significantly lower than in the non-DVT group (0.71 +/- 0.25, P=0.004). RHI was a significant and independent predictor of postoperative DVT in multivariate logistic regression analyses and improved a net reclassification index (23.8%, P=0.022). Subgroup analyses according to operation site with adjustment for Qthrombosis score demonstrated that RHI significantly predicted postoperative DVT in the THA group (odds ratio per 0.1, 0.77; 95% confidence interval 0.60-0.98; P=0.03), but did not reach statistical significance in the TKA group.
Conclusions: Low RHI was significantly associated with DVT after lower limb arthroplasty. Endothelial dysfunction, as assessed by RH-PAT, is potentially useful for identifying patients at high risk for VTE especially after THA.

DOI： 10.1253/circj.CJ-13-1325

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Language：Japanese   Publisher：(一社)日本血栓止血学会  

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BACKGROUND:  Acute pulmonary edema (APE) often occurs without remarkable fluid retention, and the benefits of diuretics are unclear in such patients. Although aggressive diuresis induces an increase in intravascular substances including hemoglobin (Hb), acute changes in Hb level remain to be investigated. METHODS AND RESULTS:  We analyzed 237 consecutive acute heart failure patients (74±12 years; 60.8% men) without shock, hemodialysis, bleeding, or urgent coronary angiography. APE was defined as acute onset of dyspnea within the preceding 6h and radiographic alveolar edema requiring immediate airway intervention. At admission, Hb level was higher in APE (n=29) than non-APE patients (n=208; 13.4±2.2 vs 12.2±2.1g/dl, P<0.01). Although diuretic therapy was performed in 232 patients (97.9%), hemoconcentration (ie, any increase in Hb) was observed in only 64 patients (27.0%) at 24h after admission. Conversely, Hb level decreased in both groups and the difference was larger in APE patients (-1.8±1.1 in APE and -0.5±1.0g/dl in non-APE patients, P<0.001). APE was significantly related to a greater decrease in Hb after adjusting for baseline Hb (β=-1.08g/dl, SE=0.20, P<0.001, ANCOVA). CONCLUSIONS:  APE patients had higher Hb level at admission and a more remarkable decline in 24h than did those without APE. Acute change in Hb might be caused by factors other than diuresis-induced hemoconcentration. The present findings may be useful in the selection of diuretic strategies.

DOI： 10.1253/circj.CJ-13-1163

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Background-Endothelial dysfunction is a key component of vascular vulnerability. Reactive hyperemia index (RHI), as assessed by the peripheral arterial tonometry, can noninvasively evaluate endothelial function. This study was designed to determine the additional prognostic value of endothelial function to the Synergy Between PCI With Taxus and Cardiac Surgery Score (SYNTAXsc) and the Framingham Risk Score (FRS) in predicting cardiovascular events in high-risk patients.
Methods and Results-We undertook a two-center prospective study in 528 stable patients at high-risk for cardiovascular events from the years 2006-2011. The RHI was measured before coronary angiography and coronary complexity was assessed by SYNTAXsc. After optimal therapies including coronary revascularization, there was follow-up with patients until August 2012. Cardiovascular events consist of cardiovascular death, myocardial infarction, unstable angina, ischemic stroke, coronary revascularization, heart failure-induced hospitalization, aortic disease, and peripheral arterial disease. During 1468 person-years of follow-up, 105 patients developed cardiovascular events. Multivariate Cox proportional hazards analysis identified B-type natriuretic peptide (BNP), SYNTAXsc, and RHI as independent cardiovascular event predictors (hazard ratio [95% confidence interval]: natural logarithm of BNP per 0.1: 1.019 [1.002 to 1.037]; P=0.023, SYNTAXsc per tertile: 2.426 [1.825 to 3.225]; P&lt;0.0001, RHI per 0.1: 0.761 [0.673 to 0.859]; P&lt;0.0001). When RHI was added to the FRS, BNP, and SYNTAXsc, net reclassification index was significantly improved (27.5%; P&lt;0.0001), with a significant increase in the C-statistic (from 0.728 [0.679 to 0.778] to 0.766 [0.726 to 0.806]; P=0.031).
Conclusions-Advanced endothelial dysfunction significantly correlated with near future cardiovascular events in high-risk patients. This physiological vascular measurement improved risk discrimination when added to the FRS, BNP, and SYNTAXsc.

DOI： 10.1161/JAHA.113.000426

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPANESE CIRCULATION SOC  

Background: Simple office-based counseling for diet and exercise does not appear to positively affect success rates in metabolic syndrome (MetS) patients. The utility of the lifestyle modification self-assessment score (Self-AS) in the improvement of endothelial function by office-based counseling for patients with MetS was investigated.
Methods and Results: Patients with MetS (n=207) and age- and sex-matched individuals without MetS (n=124) were enrolled in this cross-sectional study. Endothelial function was assessed using reactive hyperemia-peripheral arterial tonometry index (RHI). Patients with MetS had significant endothelial dysfunction compared with those without MetS (RHI, 0.502+/-0.178 vs. 0.614+/-0.229; P&lt;0.001). Seventy MetS patients participating in the prospective interventional study received simple office-based lifestyle modification counseling that was accompanied by Self-AS questionnaire after 10 months. RHI was significantly improved following lifestyle modifications (from 0.452+/-0.136 to 0.547+/-0.202, P&lt;0.001). Reductions in waist circumference (R2=0.094, P=0.01) and increased high-density lipoprotein cholesterol (R-2=0.227, P&lt;0.001) independently correlated with improved RHI. Self-AS significantly correlated with changes in waist circumference (r=-0.57, P&lt;0.001) and RHI (r=0.30, P=0.02). Patients with a good achievement of lifestyle modifications (higher Self-AS) had significant improvement in endothelial function compared with those with lower scores (% change in RHI, +48.7+/-61.6 vs. +7.8+/-35.1, P=0.001).
Conclusions: Good achievement of lifestyle modifications as evaluated on Self-AS significantly improved endothelial function with concomitant reductions in waist circumferences in MetS patients.

DOI： 10.1253/circj.CJ-13-0549

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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)日本脈管学会  

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Language：Japanese   Publisher：(一社)日本脈管学会  

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

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Language：Japanese   Publisher：(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：(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：(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：(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：(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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OBJECTIVES: This study sought to determine the additional clinical value of gait speed to Framingham risk score (FRS), cardiac function, and comorbid conditions in predicting cardiovascular events in patients with ST-segment elevation myocardial infarction. BACKGROUND: There is growing evidence that gait speed is inversely associated with all-cause mortality, particularly cardiovascular mortality, among the elderly. METHODS: We undertook a single-center prospective observational study of gait speed in 472 patients with ST-segment elevation myocardial infarction in Japan, between 2001 and 2008. Gait speeds were measured using a 200-m course before discharge in all patients, and we followed up cardiovascular events, which consist of cardiovascular deaths, nonfatal myocardial infarctions, and nonfatal ischemic strokes. RESULTS: During the 2,596 person-years of follow-up, 83 patients (17.6%) experienced cardiovascular events. Cardiovascular events increased across decreasing tertiles of gait speed (fastest tertile: n = 5, 3.2%; middle tertile: n = 20, 12.6%; slowest tertile, n = 58, 36.7%). By multiple adjusted Cox proportional hazards analysis, gait speed was a significant and independent predictor of cardiovascular events (hazard ratio for increasing 0.1 m/s of gait speed: 0.71, 95% confidence interval [CI]: 0.63 to 0.81, p < 0.001). The addition of gait speed to the model incorporating FRS, B-type natriuretic peptide levels, and comorbidity index improved reclassification (net reclassification index: 32.8%, 95% CI: 17.4 to 48.3, p < 0.001) and the C-statistics with a reasonable global fit and calibration (C-statistics: from 0.703 [95% CI: 0.636 to 0.763] to 0.786 [95% CI: 0.738 to 0.829]). CONCLUSIONS: Among patients with ST-segment elevation myocardial infarction, slow gait speed was significantly associated with an increased risk of cardiovascular events. (Gait Speed for Predicting Cardiovascular Events After Myocardial Infarction; NCT01484158).

DOI： 10.1016/j.jacc.2013.02.020

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BACKGROUND: Cardiac troponin is a specific biomarker for cardiomyocyte necrosis in acute coronary syndromes. Troponin release from the coronary circulation remains to be determined because of the lower sensitivity of the conventional assay. We sought to determine basal and angina-induced troponin release using a highly sensitive troponin assay. METHODS AND RESULTS: The cardiac troponin T levels in serum sampled from the peripheral vein (PV), the aortic root (AO), and the coronary sinus (CS) were measured in 105 consecutive stable patients with coronary risk factor(s) and suspected coronary artery disease (CAD) and in 33 patients without CAD who underwent an acetylcholine provocation test. At baseline, there was a significant increase in the troponin levels from AO [9.0 (6.4, 13.1) pg/mL for median (25(th), 75(th) percentiles)] to CS [10.3 (7.3, 15.5) pg/mL, p<0.001] in 96 (91.4%) patients and the difference was 1.1 (0.4, 2.1) pg/mL, which reflected basal transcardiac troponin release (TTR). TTR was positively correlated with PV levels (r = 0.22, p = 0.03). Male sex, left ventricular hypertrophy determined by echocardiography, T-wave inversion, and CAD correlated with elevated TTR defined as above: median, 1.1 pg/mL. A significant increase in TTR was noted in 17 patients with coronary spasms [0.6 (0.2, 1.2) pg/mL, p<0.01] but not in 16 patients without spasms [0.0 (-0.5, 0.9) pg/mL, p = 0.73] after the acetylcholine provocation. CONCLUSION: Basal TTR in the coronary circulation was observed in most of the patients with suspected CAD and risk factor(s). This sensitive assay detected myocardial ischemia-induced increases in TTR caused by coronary spasms.

DOI： 10.1371/journal.pone.0060163

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Language：Japanese   Publisher：(NPO)日本冠疾患学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Background-Angina without significant stenosis, or nonobstructive coronary artery disease, attracts clinical attention. Microvascular coronary artery spasm (microvascular CAS) can cause nonobstructive coronary artery disease. We investigated the clinical features of microvascular CAS and the therapeutic efficacy of calcium channel blockers.
Methods and Results-Three hundred seventy consecutive, stable patients with suspected angina presenting nonobstructive coronary arteries (&lt;50% diameter) in coronary angiography were investigated with the intracoronary acetylcholine provocation test, with simultaneous measurements of transcardiac lactate production and of changes in the quantitative coronary blood flow. We diagnosed microvascular CAS according to lactate production and a decrease in coronary blood flow without epicardial vasospasm during the acetylcholine provocation test. We prospectively followed up the patients with calcium channel blockers for microvascular coronary artery disease. We identified 50 patients with microvascular CAS who demonstrated significant impairment of the endothelium-dependent vascular response, which was assessed by coronary blood flow during the acetylcholine provocation test. Administration of isosorbide dinitrate normalized the abnormal coronary flow pattern in the patients with microvascular CAS. Multivariate logistic regression analysis indicated that female sex, a lower body mass index, minor-borderline ischemic electrocardiogram findings at rest, limited-baseline diastolic-to-systolic velocity ratio, and attenuated adenosine triphosphate-induced coronary flow reserve were independently correlated with the presence of microvascular CAS. Receiver-operating characteristics curve analysis revealed that the aforementioned 5-variable model showed good correlation with the presence of microvascular CAS (area under the curve: 0.820). No patients with microvascular CAS treated with calcium channel blockers developed cardiovascular events over 47.8 +/- 27.5 months.
Conclusions-Microvascular CAS causes distinctive clinical features and endothelial dysfunction that are important to recognize as nonobstructive coronary artery disease so that optimal care with calcium channel blockers can be provided.

DOI： 10.1161/JAHA.112.002485

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Objectives The purpose of this study was to investigate whether peripheral endothelial dysfunction could predict the occurrence of cardiovascular events in patients with heart failure (HF) with normal left ventricular ejection fraction (HFNEF).
Background Endothelial dysfunction plays an important role in HF, but the relation between peripheral endothelial dysfunction and prognosis in HFNEF remains unknown.
Methods We conducted a prospective cohort study of 321 patients with HFNEF. We evaluated cardiac function by echo-cardiography measuring the ratio of early transmitral flow velocity to tissue Doppler early diastolic mitral annular velocity (E/e'), noninvasively assessed peripheral endothelial function by reactive hyperemia-peripheral arterial tonometry (RH-PAT) as the RH-PAT index (RHI), and followed cardiovascular events.
Results A total of 59 patients had a cardiovascular event. Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in the low RHI group than in the high RHI group (mean follow-up: 20 months; log-rank test: p &lt; 0.001). Multivariate Cox hazard analysis identified RHI (per 0.1) (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.67 to 0.94; p = 0.007), E/e' (Ln[E/e'] [per 0.1]) (HR: 1.15; 95% CI: 1.04 to 1.26; p = 0.006), and B-type natriuretic peptide (BNP) (Ln[BNP] [per picogram/milliliter]) (HR: 1.81; 95% CI: 1.44 to 2.28; p &lt; 0.001) as independent predictors of cardiovascular events. The C-statistics for cardiovascular events substantially increased when the RHI was added to the HFNEF prognostic 5 factors (PF5)-age, diabetes, New York Heart Association classification, HF hospitalization history, and left ventricular ejection fraction-which were identified in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction Study) (PF5 alone: 0.671; PF5 + RHI: 0.712). The net reclassification index was significant after addition of the RHI (19.0%, p = 0.01).
Conclusions Peripheral endothelial dysfunction independently correlated with future cardiovascular events, adding incremental clinical significance for risk stratification in patients with HFNEF. (Endothelial Dysfunction Assessed by Reactive Hyperemia Peripheral Arterial Tonometry and Heart Failure with Preserved Left Ventricular Ejection Fraction; UMIN000002640) (J Am Coll Cardiol 2012; 60: 1778-86) (C) 2012 by the American College of Cardiology Foundation

DOI： 10.1016/j.jacc.2012.07.036

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Background: Left ventricular diastolic dysfunction (LVDD) plays an important role in heart failure with normal left ventricular ejection fraction (LVEF). Obesity is one of the major comorbid conditions of LVDD. Pericardial fat (PF) is an ectopic fat depot with possible paracrine or mechanical effects on the coronary circulation and myocardial function.
Methods: We measured PF volume on 64 slice computed tomography and analyzed echocardiographic parameters to confirm LVDD in 229 consecutive patients suspected of coronary artery disease with LVEF of more than 50% and no symptomatic heart failure (59% men, 67 +/- 12 years). LVDD was defined as the ratio of transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e') &gt; 10.
Results: PF volume correlated significantly with E/e' (r = 0.21, p &lt; 0.01), left ventricular mass index (r = 0.23, p &lt; 0.001), and left atrial diameter (r = 0.32, p &lt; 0.001). The mean PF volume was significantly greater in patients with LVDD (184 +/- 61 cm(3), n = 141) than in those without LVDD (154 +/- 58, n=88, p &lt; 0.001). Multivariate logistic regression analysis indicated that PF volume correlated significantly with the presence of LVDD (odds ratio: 2.00 per 100 cm(3) increase in PF volume, p = 0.02) independent of age, gender, abdominal obesity, hypertension, and diabetes.
Conclusions: PF volumes are significantly associated with LVDD, independent of other factors such as hypertension or diabetes. PF may be implicated in the pathogenesis of LVDD in patients with normal LVEF. (C) 2012 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jjcc.2012.01.006

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Objectives The aim of this study was to investigate the antiatherogenic effects of the dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin (DFS).
Background The new class of anti-type 2 diabetes drugs, dipeptidyl peptidase-4 inhibitors, improves glucose metabolism by increasing levels of active glucagon-like peptide (GLP)-1.
Methods Endothelial function was examined by acetylcholine-induced endothelium-dependent vasorelaxation using aortic rings and atherosclerotic lesion development in the entire aorta in apolipoprotein E-deficient mice fed a high-fat diet with or without DFS, and the antiatherogenic effects of DFS were investigated in cultured human macrophages and endothelial cells. Plasma levels of active GLP-1 were measured in patients with or without coronary artery disease.
Results DFS significantly improved endothelial dysfunction (89.9 +/- 3.9% vs. 79.2 +/- 4.3% relaxation at 10(-4) mol/l acetylcholine, p &lt; 0.05) associated with increased endothelial nitric oxide synthase phosphorylation and reduced atherosclerotic lesion area (17.7% [15.6% to 25.8%] vs. 24.6% [19.3% to 34.6%], p &lt; 0.01) compared with vehicle treatment. In cultured human macrophages, DFS significantly increased GLP-1-induced cytosolic levels of cyclic adenosine monophosphate compared with GLP-1 alone, resulted in inhibiting phosphorylation of c-jun N-terminal kinase and extracellular signal-regulated kinase 1/2 and nuclear factor-kappa B p65 nuclear translocation through the cyclic adenosine monophosphate/protein kinase A pathway, and suppressed proinflammatory cytokines (i.e., interleukin-1-beta, interleukin-6, and tumor necrosis factor-alpha) and monocyte chemoattractant protein-1 production in response to lipopolysaccharide. DFS-enhanced GLP-1 activity sustained endothelial nitric oxide synthase phosphorylation and decreased endothelial senescence and apoptosis compared with GLP-1 alone. In the human study, fasting levels of active GLP-1 were significantly lower in patients with coronary artery disease than those without (3.10 pmol/l [2.40 to 3.62 pmol/l] vs. 4.00 pmol/l [3.10 to 5.90 pmol/l], p &lt; 0.001).
Conclusions A DPP-4 inhibitor, DFS, exhibited antiatherogenic effects through augmenting GLP-1 activity in macrophages and endothelium. (J Am Coll Cardiol 2012;59:265-76) (C) 2012 by the American College of Cardiology Foundation

DOI： 10.1016/j.jacc.2011.07.053

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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：(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：(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：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Objectives This study investigated the clinical significance of plasma pentraxin 3 (PTX3) levels in patients with heart failure with normal ejection fraction (HFNEF) and whether PTX3 is produced from coronary circulation.
Background Pentraxin 3 is a novel inflammatory marker and a member of pentraxin superfamily including C-reactive protein (CRP). The relationship between inflammatory markers and HFNEF remains unclear.
Methods We measured peripheral blood levels of PTX3, high-sensitivity CRP, tumor necrosis factor-alpha, and interleukin-6 in 323 patients comprising 82 HFNEF, 70 heart failure (HF) with reduced EF, and 171 non-HF patients. Levels of PTX3 were also measured at the aortic root and the coronary sinus in 75 patients.
Results The levels of PTX3, tumor necrosis factor-alpha, and interleukin-6, but not high-sensitivity CRP, were significantly higher in HFNEF patients than in non-HF patients. Multivariate logistic regression analysis identified only high levels of PTX3 as the independent inflammatory marker correlated with the presence of HFNEF in patients with normal left ventricular (LV) EF (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.11 to 1.98, p &lt; 0.01) and with the presence of left ventricular diastolic dysfunction (LVDD) in non-HF patients (OR: 1.23, 95% CI: 1.02 to 1.50, p &lt; 0.05). Levels of PTX3 at the coronary sinus were significantly higher than at the aortic root in HFNEF patients (p &lt; 0.05) and in non-HF patients with LVDD (p &lt; 0.01), but not different in non-HF patients without LVDD (p = 0.33).
Conclusions Pentraxin 3 is significantly elevated in HFNEF patients and produced in the coronary circulation in patients with LVDD. Pentraxin 3, but not high-sensitivity CRP, is an independent inflammatory marker correlated with the presence of LVDD and HFNEF. (The Clinical Significance of Plasma Pentraxin 3 levels for Patients with Diastolic Heart Failure; UMIN000002170) (J Am Coll Cardiol 2011; 57: 861-9) (C) 2011 by the American College of Cardiology Foundation

DOI： 10.1016/j.jacc.2010.10.018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

Aim: Increased coronary plaque burden, which could be involved in the pathogenesis of athero-thrombotic events, is difficult to evaluate in the three major coronary arteries. The purpose of this study was to quantify coronary plaque volume using 64-slice computed tomography (CT).
Methods: We measured coronary plaque volume with our new protocol in 23 consecutive patients (48% men; 66 +/- 11 years old) who underwent cardiac CT for suspicion of coronary artery disease and had noncalcified plaques. We counted the total pixel volume of noncalcified plaques in the three major coronary arteries.
Results: The coronary plaque volume was 1.29 +/- 0.56 cm(3) in the right coronary artery, 1.29 +/- 0.42cm(3) in the left main coronary artery and left anterior descending artery, and 0.88 +/- 0.32 cm(3) in the left circumflex artery. The total coronary plaque burden (TCPB) was 3.45 +/- 1.02 cm(3)/patient and had a positive correlation with waist circumference (r = 0.44, p&lt;0.05) and insulin resistance (r = 0.46, p&lt;0.05). TCPB was significantly greater in men (3.89 +/- 1.07 cm(3) vs. 3.06 +/- 0.82 cm(3) in women, p&lt;0.05), patients with diabetes or impaired glucose tolerance (3.77 +/- 0.94 cm(3) vs. 2.86 +/- 0.92 cm(3) in non-diabetics, p&lt;0.05), and patients with metabolic syndrome (3.91 +/- 0.95 cm(3) vs. 3.03 +/- 0.91 cm(3) in patients without metabolic syndrome, p&lt;0.05).
Conclusions: Cardiac CT can provide a noninvasive assessment of TCPB, which was significantly associated with metabolic syndrome and its components. Measuring TCPB by CT could be an important strategy for identifying high-risk patients with suspected coronary artery disease.

DOI： 10.5551/jat.8953

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Objectives: We sought to assess the association between inflammation in pericardial fat (PF) and coronary artery disease (CAD) by pathological examination and clinical evaluation with cardiac computed tomography (CT).
Background: Inflammation of adipose tissue is involved in cardio-metabolic disorders and shows high density in CT.
Methods: We quantified, by immunohistochemical means, the PF inflammation in 39 autopsy cases by counting leukocyte common antigen (LCA)-positive cells. We then measured the CT density of PF in 39 patients with acute coronary syndromes and 69 patients suspected of CAD.
Results: Pericoronary PF had significantly more LCA-positive cells in CAD autopsy cases (n = 21) than non-CAD cases (n = 18) (44 +/- 21 vs. 24 +/- 22 cells/mm(2), p = 0.006). The CT density of PF around culprit lesions was significantly higher than non-culprit lesions in patients with acute coronary syndromes (-72 +/- 11 vs. -82 +/- 14 HU, p = 0.002), which may reflect PF inflammation. Among patients suspected of CAD, the pericardial CT density gradient (PDG; difference in CT density between pericoronary PF and PF apart from coronary arteries) was significantly greater in CAD patients (n = 30) than non-CAD patients (n = 39) (22 +/- 16 vs. 16 +/- 10 HU, p = 0.046). Multiple logistic regression analysis demonstrated that the PF inflammation index (PFI; PDG x PF volume, which could be the integrated index of inflammatory activity and abundance of PF) was significantly associated with the presence of CAD (odds ratio [95% confidence interval]; 1.234 [1.012-1.503] per 1000HUcm(3), p = 0.037) independent of other metabolic risk factors such as hypertension, dyslipidemia, and diabetes.
Conclusions: Active inflammation in PF correlates with CAD. PF inflammation may be involved in pathogenesis of CAD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2010.10.007

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Language：Japanese   Publisher：(NPO)日本冠疾患学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Heart failure (HF) is associated with endothelial dysfunction. Endothelium-derived microparticles (EMPs) are a novel quantitative plasma marker of endothelial dysfunction. We investigated whether plasma levels of EMPs can predict future cardiovascular events in patients with HF.
We enrolled 169 consecutive HF patients (70 ischaemic, 99 non-ischaemic HF) with New York Heart Association (NYHA) class I or more. Plasma CD144-positive EMP levels were measured by flow cytometry in the HF patients and in 31 healthy subjects. We followed the HF patients for mean 30 months. Endpoints were: a composite of cardiovascular events (myocardial infarction, stroke, re-hospitalization for HF, and cardiovascular death) and all-cause mortality. Endothelium-derived microparticle levels increased significantly with NYHA functional class [EMP median (range): healthy, 0.325 (0.164-0.354) x10(6)/mL; NYHA I, 0.484 (0.426-0.575); II, 0.646 (0.439-0.795); and III/IV, 0.786 (0.569-1.026), P &lt; 0.001]. A total of 33 cardiovascular events and 22 all-cause deaths were registered. Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in the high-EMP group, but there was only a borderline difference for all-cause mortality (above median; log rank test P = 0.01, P = 0.053, respectively). Multivariate Cox regression analysis adjusted for clinical factors, identified high-EMP levels as an independent predictor of future cardiovascular events, but not for all-cause mortality in HF patients [hazard ratio (95% confidence interval): 2.423 (1.034-5.681), P = 0.04 for cardiovascular events; and 2.095 (0.825-5.323), P = 0.12 for all-cause mortality].
Endothelial dysfunction assessed by plasma levels of EMPs can independently predict future cardiovascular events in patients with HF. Endothelium-derived microparticles are a potentially useful biomarker of endothelial dysfunction in HF risk stratification.

DOI： 10.1093/eurjhf/hfq145

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER IRELAND LTD  

Objectives: The purpose of this study was to examine the association of pericardial fat with the presence of coronary plaques.
Background: Waist circumference, reflecting abdominal obesity, is a risk factor of metabolic syndrome and coronary artery disease (CAD). Adipose tissue secretes many factors implicated in atherogenesis, however, the role of pericardial fat (ectopic visceral fat around coronary arteries) in the pathogenesis of CAD is not clear.
Methods: We measured total pericardial fat volume (PFV) and determined presence and characteristics of coronary plaques using 64-slice computed tomography in 171 consecutive patients suspected of CAD (101 men; mean age, 66 +/- 11 years, +/-SD).
Results: PFV correlated with age (p &lt; 0.05), body mass index (p &lt; 0.05), waist circumference (p &lt; 0.01), and high-density lipoprotein cholesterol (p &lt; 0.01) by multivariate regression analysis. PFV was significantly larger in patients with coronary plaques, even nonstenotic or noncalcified ones, than those without plaques (any plaques, n = 123; 201 +/- 71 cm(3), nonstenotic plaques, n = 51; 192 +/- 63, noncalcified plaques, n = 32; 196 +/- 56 vs. no plaque, n = 48; 144 +/- 45, p &lt; 0.001, respectively). Multivariate backward logistic regression analysis demonstrated that PFV, but not waist circumference, significantly associated with the presence of any coronary plaques (odds ratio [OR]; 2.876, 95% confidence interval [95% CI]; 1.614-5.125, p &lt; 0.001), nonstenotic plaques confirmed by coronary angiography (OR; 3.423, 95% CI; 1.764-6.642, p &lt; 0.001), and noncalcified plaques (OR; 3.316, 95% CI; 1.435-7.661, p &lt; 0.01).
Conclusions: PFV correlated significantly with the presence of nonstenotic and noncalcified coronary plaques assessed by multislice computed tomography. Pericardial fat is more highly associated with early development of CAD than simple anthropometric measures of abdominal obesity. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.atherosclerosis.2009.10.008

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Objectives We investigated the utility of digital reactive hyperemia peripheral arterial tonometry (RH-PAT) in predicting ischemic heart disease (IHD), including obstructive coronary artery disease (CAD) and nonobstructive coronary artery disease (NOCAD), in women.
Background IHD is the leading cause of mortality, and its pathogenesis is diverse in women. Fingertip RH-PAT is a new device that provides noninvasive, automatic, and quantitative evaluation of endothelial dysfunction.
Methods RH-PAT was measured using Endo-PAT2000 (Itamar Medical, Caesarea, Israel) before cardiac catheterization in 140 stable women scheduled for hospitalization to examine chest pain. NOCAD was diagnosed by angiography with measurement of coronary blood flow and cardiac lactate production during intracoronary acetylcholine provocation test and cardiac scintigraphy with stress tests.
Results Sixty-eight women (49%) had obstructive CAD and 42 women (30%) had NOCAD. RH-PAT indexes were significantly attenuated in both obstructive CAD and NOCAD as compared with non-IHD (n = 30) (obstructive CAD: median 1.57, interquartile range [IQR] 1.42 to 1.76; NOCAD: median 1.58, IQR 1.41 to 1.78; non-IHD: median 2.15, IQR 1.85 to 2.48, p &lt; 0.001). By multivariate logistic regression analysis, only RH-PAT index was significantly associated with IHD, including obstructive CAD and NOCAD (odds ratio 0.51; 95% confidence interval: 0.38 to 0.68; p &lt; 0.001). In receiver-operating characteristic analysis, RH-PAT index was a significant predictor of IHD (area under the curve 0.86; p &lt; 0.001). Furthermore, only RH-PAT was useful for the prediction of NOCAD after excluding obstructive CAD (area under the curve 0.85; p &lt; 0.001; RH-PAT index of &lt;1.82 had 81% sensitivity and 80% specificity).
Conclusions RH-PAT indexes were significantly attenuated in women with IHD. Digital RH-PAT can predict patients with IHD, especially NOCAD before angiography. RH-PAT is potentially useful for identifying high-risk women for IHD. (Endothelial Dysfunction and Coronary Artery Spasm; NCT00619294) (J Am Coll Cardiol 2010;55:1688-96) (C) 2010 by the American College of Cardiology Foundation

DOI： 10.1016/j.jacc.2009.10.073

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN ATHEROSCLEROSIS SOC  

Aim: A recent clinical study using coronary intravascular ultrasound showed that rimonabant, a cannabinoid 1 (CB1) receptor antagonist, significantly reduced total atheroma volume, suggesting that CB1 receptor blockade could be beneficial in anti-atherogenic therapy. The reverse cholesterol transport (RCT) system plays important roles in atherogenesis. We investigated whether CB1 receptor blockade could modulate atherogenesis in mice.
Methods and Results: Oral administration of rimonabant (8 mg/kg/day) to apolipoprotein E-deficient mice for 3 months significantly reduced the relative area of atherosclerotic lesions in the aorta (vehicle; 12.6 +/- 4.0% vs. rimonabant; 9.7 +/- 2.3, n = 12 each, p&lt;0.05) with an increase in serum adiponectin levels (15.6 +/- 2.3 mu g/mL vs. 12.2 +/- 2.1, n = 12 each, p&lt;0.001), without affecting body weight or serum cholesterol levels. Rimonabant tended to increase serum high-density lipoprotein cholesterol (HDL-C) (p=0.05). The relative area of atherosclerotic lesions in the aorta correlated inversely with serum HDL-C levels (r=-0.45, n = 24, p&lt;0.05). Rimonabant upregulated the mRNA expression levels of various components of the RCT system on THP-1 cell-derived macrophages (scavenger receptor B1: 1.15 +/- 0.12 fold, n = 6; p&lt;0.05, ATP-binding cassette [ABC] transporter G1: 1.23 +/- 0.11 fold, n = 6; p&lt;0.01), but not ABCA1 (1.13 +/- 0.20 fold, n = 6; p = 0.13).
Conclusion: CB1 receptor blockade reduced atherosclerosis in apoE-deficient mice through an increase in serum adiponectin levels and activation of the RCT system. CB1 receptor blockade may be therapeutically beneficial for atherogenesis by increasing the serum adiponectin level and enhancing of the RCT system.

DOI： 10.5551/jat.2865

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DOI： 10.1016/S0735-1097(19)31095-2

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DOI： 10.1016/j.jacc.2018.08.2016

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DOI： 10.1016/j.cardfail.2016.07.348

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DOI： 10.1016/S0735-1097(15)60251-0

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DOI： 10.1016/j.cardfail.2014.07.173

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DOI： 10.1016/j.cardfail.2014.07.209

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DOI： 10.1016/S0735-1097(14)60175-3

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DOI： 10.1016/S0735-1097(14)60545-3

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DOI： 10.1016/S0735-1097(14)60249-7

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