Open-Label, Single-Center, Single-Arm Study Evaluating the Efficacy and Safety of Elobixibat for Chronic Constipation in Patients With Heart Failure.

Background: Neither the efficacy nor safety of elobixibat has been investigated in the treatment of chronic constipation in patients with heart failure (HF). Methods and Results: In this prospective, single-center, single-arm study elobixibat (10 mg/day) was administered for 12 weeks to 18 HF patients with chronic constipation defined according to the Rome IV criteria. Spontaneous bowel movement (SBM), stool consistency as measured by the Bristol Stool Form Scale, and degree of straining during defecation were recorded. In addition, biomarkers, blood pressure (BP) measured by ambulatory monitoring, and adverse events were assessed. Although there was no significant difference, the frequency of SBM increased by 2.0/week from baseline to Week 12. Both the degree of straining during defecation and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased at Week 12 (straining, -0.79 [95% confidence interval (CI), -1.40 to -0.17]; LDL-C, -10.4 mg/dL [95% CI, -17.9 to -2.9]). Although not significant, the difference in BP before and after defecation tended to decrease from baseline by approximately 10 mmHg at Week 12. Serious adverse events were not observed. Conclusions: Elobixibat reduced the degree of straining during defecation, and improved the lipid profile in HF patients with chronic constipation.

Prognostic Significance of Soluble PD-L1 on Cardiovascular Outcomes in Patients with Coronary Artery Disease.

AIMS: Programmed cell death-1 (PD-1) and its ligand (PD-L1) regulate T cells, leading to immunotolerance. We previously demonstrated that patients with coronary artery disease (CAD) had increased circulating levels of soluble PD-L1 (sPD-L1). However, the prognostic significance of sPD-L1 on cardiovascular outcomes is unknown. In the present study, we evaluated the association between sPD-L1 and cardiovascular events in patients with CAD. METHODS: We prospectively measured sPD-L1 in patients with CAD admitted to Kumamoto University Hospital between December 2017 and January 2020 and observed their cardiovascular event rate. The primary outcome was a composite of death from non-cardiovascular causes, death from cardiovascular causes, non-fatal myocardial infarction, unstable angina pectoris, revascularization, hospitalization for heart failure, and ischemic stroke. RESULTS: Finally, 627 patients were enrolled, and 35 patients were lost to follow-up. The median follow-up duration was 522 days. In total, 124 events were recorded. The Kaplan-Meier curve showed that the event rate was higher in the higher sPD-L1 group (median ≥ 136 pg/dL) than in the lower sPD-L1 group (25.0% vs. 16.9%; p=0.028, log-rank test). Univariate Cox proportional hazards analysis showed that high-sensitivity C-reactive protein, an estimated glomerular filtration rate of ＜60 mL/min/1.73m2, B-type natriuretic peptide, left ventricular ejection fraction, and sPD-L1 were significantly associated with cardiovascular events. Multivariable Cox proportional hazards analysis of factors that were significant in univariate analysis identified that sPD-L1 was significantly and independently associated with cardiovascular events (hazard ratio: 1.364, 95% confidence interval: 1.018-1.828, p=0.038). CONCLUSIONS: Higher sPD-L1 levels were significantly associated with future cardiovascular events in patients with CAD.

Prognostic impact of diabetes mellitus on in-hospital mortality in patients with acute myocardial infarction complicating renal dysfunction according to age and sex.

BACKGROUND: Patients with acute myocardial infarction (AMI) complicating renal dysfunction (RD) are recognized as being at high risk. Although diabetes mellitus (DM) is a major cause of RD, the prognostic impact of coexisting DM on mortality in patients with AMI complicating RD is ill-defined. This study compared the prognostic impact of coexisting DM in patients with AMI complicating RD according to both age and sex. METHODS: A multicenter retrospective study was conducted on 2988 consecutive patients with AMI complicating RD (estimated glomerular filtration rate <60 mL/min per 1.73 m2). Multivariable Cox regression analysis was performed to investigate the effects of DM on in-hospital mortality. RESULTS: Statistically significant interactions between age and DM and between sex and DM for in-hospital mortality were revealed in the entire cohort. Coexisting DM was identified as an independent risk factor for in-hospital mortality (hazard ratio [HR], 2.543) in young (aged <65 years), but not old (aged ≥65 years), patients. DM was identified as an independent risk factor (HR, 1.469) in male, but not female, patients. Kaplan-Meier survival curves showed that DM correlated with significantly low survival rates in patients that were young or male as compared to those who were old or female. CONCLUSIONS: There were significant differences in the prognostic impact of DM on in-hospital mortality between young and old as well as male and female patients with AMI complicating RD. These results have implications for future research and the management of patients with DM, RD, and AMI comorbidities.

Clinical, electrocardiographic, and echocardiographic parameters associated with the development of pacing and implantable cardioverter-defibrillator indication in patients with transthyretin amyloid cardiomyopathy.

AIMS: This study aimed to identify factors for attention leading to future pacing device implantation (PDI) and reveal the necessity of prophylactic PDI or implantable cardioverter-defibrillator (ICD) implantation in transthyretin amyloid cardiomyopathy (ATTR-CM) patients. METHODS AND RESULTS: This retrospective single-center observational study included consecutive 114 wild-type ATTR-CM (ATTRwt-CM) and 50 hereditary ATTR-CM (ATTRv-CM) patients, neither implanted with a pacing device nor fulfilling indications for PDI at diagnosis. As a study outcome, patient backgrounds were compared with and without future PDI, and the incidence of PDI in each conduction disturbance was examined. Furthermore, appropriate ICD therapies were investigated in all 19 patients with ICD implantation. PR-interval ≥220 msec, interventricular septum (IVS) thickness ≥16.9 mm, and bifascicular block were significantly associated with future PDI in ATTRwt-CM patients, and brain natriuretic peptide ≥35.7 pg/mL, IVS thickness ≥11.3 mm, and bifascicular block in ATTRv-CM patients. The incidence of subsequent PDI in patients with bifascicular block at diagnosis was significantly higher than that of normal atrioventricular (AV) conduction in both ATTRwt-CM [hazard ratio (HR): 13.70, P = 0.019] and ATTRv-CM (HR: 12.94, P = 0.002), whereas that of patients with first-degree AV block was neither (ATTRwt-CM: HR: 2.14, P = 0.511, ATTRv-CM: HR: 1.57, P = 0.701). Regarding ICD, only 2 of 16 ATTRwt-CM and 1 of 3 ATTRv-CM patients received appropriate anti-tachycardia pacing or shock therapy, under the number of intervals to detect for ventricular tachycardia of 16-32. CONCLUSIONS: According to our retrospective single-center observational study, prophylactic PDI did not require first-degree AV block in both ATTRwt-CM and ATTRv-CM patients, and prophylactic ICD implantation was also controversial in both ATTR-CM. Larger prospective, multi-center studies are necessary to confirm these results.

Cultural capital and perception of teacher-student relationships: Uncovering inequalities at schools in China.

A long tradition in stratification research argues students with higher cultural capital are likely to be treated by their teachers as possessing the "right culture," which positively affects their academic performance. Nevertheless, the literature has paid little attention to the role of students' perception in this process. Using two waves of the China Educational Panel Survey, we investigate how students' cultural capital affects their own understanding of teacher-student interactions, including its gender difference. Fixed effects regressions show a substantially positive effect of cultural capital on the perceived frequency of teachers praising and calling on students to answer questions across subjects. Nonetheless, we also find the lack of cultural capital is not punished and that the cultural capital's effect varies across its specific components and gender. These findings pave the way for elucidating the entire causal chain of intergenerational social inequality via cultural capital, teacher bias, students' perception, and their educational outcomes.

Japanese high bleeding risk criteria status predicts low thrombogenicity and bleeding events in patients undergoing percutaneous coronary intervention.

Although the Japanese high bleeding risk criteria (J-HBR) were established to predict bleeding risk in patients undergoing percutaneous coronary intervention (PCI), the thrombogenicity in the J-HBR status remains unknown. Here, we examined the relationships among J-HBR status, thrombogenicity and bleeding events. This study was a retrospective analysis of 300 consecutive patients who underwent PCI. Blood samples obtained on the day of PCI were used in the total thrombus-formation analysis system (T-TAS) to investigate the thrombus-formation area under the curve (AUC; PL18-AUC10 for platelet chip; AR10-AUC30 for atheroma chip). The J-HBR score was calculated by adding 1 point for any major criterion and 0.5 point for any minor criterion. We assigned patients to three groups based on J-HBR status: a J-HBR-negative group (n = 80), a low score J-HBR-positive group (positive/low, n = 109), and a high score J-HBR-positive group (positive/high, n = 111). The primary end point was the 1-year incidence of bleeding events defined by the Bleeding Academic Research Consortium types 2, 3, or 5. Both PL18-AUC10 and AR10-AUC30 levels were lower in the J-HBR-positive/high group than the negative group. Kaplan-Meier analysis showed worse 1-year bleeding event-free survival in the J-HBR-positive/high group compared with the negative group. In addition, both T-TAS levels in J-HBR positivity were lower in those with bleeding events than in those without bleeding events. In multivariate Cox regression analyses, the J-HBR-positive/high status was significantly associated with 1-year bleeding events. In conclusion, the J-HBR-positive/high status could reflect low thrombogenicity as measured by T-TAS and high bleeding risk in patients undergoing PCI.

Differential effects of overweight/obesity depending on the severity of heart failure complicating acute myocardial infarction in Japan.

BACKGROUND: The existence of a paradoxical association between overweight/obesity and survival benefits, the so-called obesity paradox, in heart failure (HF) as well as coronary artery disease (CAD) remains contentious. Previously, we reported that a past history of CAD negated the obesity paradox in the general population with acute HF. Herein, we further focused on HF complicating acute myocardial infarction (AMI) and compared the prognostic effects of overweight/obesity with respect to the severity of HF. METHODS: We conducted a multicenter retrospective study of 7265 consecutive patients with AMI. The severity of HF was categorized according to the Killip classification. Overweight/obesity was defined as a body mass index (BMI) of ≥25 kg/m2. The interaction between overweight/obesity and the Killip classification for in-hospital mortality was tested in the entire cohort. Multivariable logistic regression analyses were performed to examine the effects of overweight/obesity on in-hospital mortality. RESULTS: Across the entire study cohort, 1931 patients had HF. Overweight/obesity had a significant association with reductions in in-hospital mortality in patients with mild HF (Killip class II; odds ratio [OR], 0.284; P = 0.019). Conversely, overweight/obesity was a significant risk factor for in-hospital mortality in patients with severe HF (Killip class IV; OR, 2.152; P = 0.001). The effects of overweight/obesity on in-hospital mortality in patients with moderate HF (Killip class III) were intermediate between those with mild HF and severe HF. CONCLUSION: Opposing effects of overweight/obesity on in-hospital mortality in patients with mild HF versus severe HF were demonstrated, suggesting a balance between beneficial and deleterious effects of overweight/obesity may be inclined toward the latter with the severity of HF complicating AMI.

Effect of the ALDH2 Variant on the Prevalence of Atrial Fibrillation in Habitual Drinkers.

Background: Alcohol-a risk factor for atrial fibrillation (AF)-is metabolized by aldehyde dehydrogenase 2 (ALDH2). Dysfunctional alleles of ALDH2 (ALDH2-deficient variants) are prevalent among East Asians. Objectives: Because the prevalence of AF is estimated to be high in ALDH2-deficient variant carriers, we investigated the correlation between AF and ALDH2-deficient variant carriers, including the association with habitual alcohol consumption. Methods: A total of 656 consecutive patients were included in this investigation. ALDH2 genotypes were divided into ALDH2 homozygous wild-type (∗1/∗1), ALDH2 heterozygous-deficient allele (∗1/∗2), and ALDH2 homozygous-deficient allele (∗2/∗2). Multivariate analyses were applied to determine the correlation between ALDH2 genotype and AF. Results: ALDH2∗1/∗2 and ALDH2∗2/∗2 carriers who were ALDH2-deficient variant carriers comprised 199 (30.3%) and 27 (4.1%) patients, respectively. Among these patients, the proportions of habitual alcohol consumption were 26.1% and 0%, respectively. Multivariate analysis revealed that ALDH2∗1/∗2 itself was not a risk factor for AF (odds ratio [OR]: 1.28; P = 0.21). However, habitual alcohol consumption in ALDH2∗1/∗2 carriers was an independent risk factor of AF (OR: 4.13; P = 0.001). Contrary to expectations, ALDH2∗2/∗2 itself had a lower incidence of AF among other risk factors (OR: 0.37; P = 0.03). Conclusions: Although the ALDH2∗1/∗2 itself was not associated with AF, ALDH2∗1/∗2 carriers with habitual alcohol consumption could experience AF because of slow alcohol metabolism. In contrast, ALDH2∗2/∗2 itself had a lower incidence of AF. This might be related to the absence to habitual alcohol consumption in ALDH2∗2/∗2 carriers because of the negligible activity of ALDH2. Thus, abstaining from alcohol consumption might prevent the development of AF in patients who are ALDH2∗1/∗2 carriers.

SIRT7 Deficiency Protects against Aging-Associated Glucose Intolerance and Extends Lifespan in Male Mice.

Sirtuins (SIRT1-7 in mammals) are evolutionarily conserved nicotinamide adenine dinucleotide-dependent lysine deacetylases/deacylases that regulate fundamental biological processes including aging. In this study, we reveal that male Sirt7 knockout (KO) mice exhibited an extension of mean and maximum lifespan and a delay in the age-associated mortality rate. In addition, aged male Sirt7 KO mice displayed better glucose tolerance with improved insulin sensitivity compared with wild-type (WT) mice. Fibroblast growth factor 21 (FGF21) enhances insulin sensitivity and extends lifespan when it is overexpressed. Serum levels of FGF21 were markedly decreased with aging in WT mice. In contrast, this decrease was suppressed in Sirt7 KO mice, and the serum FGF21 levels of aged male Sirt7 KO mice were higher than those of WT mice. Activating transcription factor 4 (ATF4) stimulates Fgf21 transcription, and the hepatic levels of Atf4 mRNA were increased in aged male Sirt7 KO mice compared with WT mice. Our findings indicate that the loss of SIRT7 extends lifespan and improves glucose metabolism in male mice. High serum FGF21 levels might be involved in the beneficial effect of SIRT7 deficiency.

Validation of the obesity paradox by body mass index and waist circumference in patients undergoing percutaneous coronary intervention.

BACKGROUND: The paradoxical association of obesity with mortality, named the "obesity paradox", has been inconsistent, possibly due to a difference between body mass index (BMI) and central obesity, estimated by waist circumference (WC) as patterns of adiposity. SUBJECTS/METHODS: We enrolled 8513 participants from the Kumamoto Intervention Conference Study, a multicenter registry that included consecutive patients undergoing percutaneous coronary intervention (PCI) at 18 centers between 2008 and 2017 in Japan. Patients were divided into quartiles in ascending order of the BMI or WC. The primary endpoints were all-cause mortality and cardiovascular death within a year. RESULTS: There were 186 deaths (case fatality rate, 22.1/1000 person-years) during the follow-up period. The lowest group (1st quartile) of BMI or WC had the worst prognosis among the quartiles (1st quartile, 4.2%; 2nd quartile, 1.9%; 3rd quartile, 1.5%; 4th quartile, 1.1%; P < 0.001 (χ2) and 1st quartile, 4.1%; 2nd quartile, 2.3%; 3rd quartile, 1.2%; 4th quartile, 1.5%; P < 0.001 (χ2), respectively). Similar results were obtained for cardiovascular death. In a multivariable analysis adjusted by nine conventional factors, the lowest group (1st quartile) of BMI (hazards ratio, 2.748; 95% confidence interval [CI], 1.712-4.411) and WC (hazards ratio, 2.340; 95% CI, 1.525-3.589) were independent prognostic factors for all-cause mortality. By dividing the participants into two groups according to either the BMI or WC based on the National Cholesterol Education Program Adult Treatment Panel III and World Health Organization classification, the highest mortality was observed in the lower group. However, the C-statistic after adding BMI (quartile) to conventional factors was found to be slightly higher than BMI (two categories) and WC (two categories) (0.735 vs. 0.734). CONCLUSIONS: The obesity paradox was observed in patients after PCI, and single-use of BMI (or WC) was sufficient to predict the prognosis of patients after PCI.

The Resilience Divide Among Older Adults Under Uncertainty: A Positive Sociological Study of Life Satisfaction During the COVID-19 Crisis.

While recent research has detected older adults' resilience during the global pandemic, its unequal distribution is inadequately examined. Using the panel survey data in Japan (N = 3,725), this positive sociological study investigated who were more/less resilient under COVID-19, with attention to the heterogeneity in life satisfaction (LS). It was first confirmed that older adults' LS had substantially improved during the pandemic, indicating their resilience on average. However, the multinomial logistic regression and the fixed effects model revealed that the shift in LS was associated with age, gender, income, family/social relationships, and heath in a nuanced way. This suggests, while older adults who have access to economic, social, and health-related resources can maintain/enhance their LS under the global crisis, those without such assets face the risk of being penalized. In these uncertain times, it is therefore imperative to shed light on the resilience divide among older adults alongside their average strength.

Increased thrombogenicity is associated with revascularization outcomes in patients with chronic limb-threatening ischemia.

OBJECTIVES: Clinically driven target lesion revascularization (CD-TLR) frequently occurs after endovascular therapy (EVT) in patients with chronic limb-threatening ischemia (CLTI). The total thrombus-formation analysis system (T-TAS) can quantitatively evaluate thrombogenicity. Therefore, we aimed to elucidate the association of the T-TAS parameters with CD-TLR. METHODS: We analyzed 34 patients with CLTI and 62 patients without CLTI who had undergone EVT. Blood samples collected on the day of EVT were used in the T-TAS to compute the thrombus formation area under the curve for the first 10 minutes for the platelet chip tested at a flow rate of 24 µL/min (PL24-AUC10) and area under the curve for the first 30 minutes for the atheroma chip tested at a flow rate of 10 µL/min (AR10-AUC30). After EVT, clinical follow-up was performed, and the presence of CD-TLR was assessed. RESULTS: During the follow-up period (median, 574 days), 10 patients (29%) in the CLTI group and 11 (18%) in the non-CLTI group had required CD-TLR. In the CLTI group, the patients with CD-TLR had had a higher AR10-AUC30 vs those without (median, 1694 [interquartile range, 1657-1799] vs median, 1561 [interquartile range, 1412-1697]; P = .01). In contrast, the PL24-AUC10 showed no significant differences when stratified by CD-TLR in either group. For the CLTI patients, multivariable Cox regression analysis using propensity score matching revealed that the AR10-AUC30 was an independent predictor of CD-TLR even after adjusting for baseline demographics, lesion characteristics, and anticoagulant use (hazard ratio, 2.04; 95% confidence interval, 1.18-3.88; P = .01; per 100-unit increase). In contrast, for those without CLTI, neither the AR10-AUC30 nor the PL24-AUC10 was significantly associated with CD-TLR. Receiver operating characteristics curve analysis identified an AR10-AUC30 level of 1646 as an optimal cutoff value to predict for CD-TLR (AUC, 0.85; sensitivity, 0.93; specificity, 0.56). CONCLUSIONS: For patients with CLTI, but not for those without CLTI, the AR10-AUC30 showed potential to predict for CD-TLR. This finding suggests that hypercoagulability might play a predominant role in the progression of CLTI and that anticoagulant therapy might be useful in preventing revascularization.

Utility of left atrial and ventricular strain for diagnosis of transthyretin amyloid cardiomyopathy in aortic stenosis.

AIMS: To clarify the usefulness of left atrial (LA) function and left ventricular (LV) function obtained by two-dimensional (2D) speckle tracking echocardiography to diagnose concomitant transthyretin amyloid cardiomyopathy (ATTR-CM) in patients with aortic stenosis (AS). METHODS AND RESULTS: We analysed 72 consecutive patients with moderate to severe AS who underwent 99m Tc-pyrophosphate (PYP) scintigraphy at Kumamoto University Hospital from January 2012 to September 2020. We divided these 72 patients into 2 groups based on their 99m Tc-PYP scintigraphy positivity or negativity. Among 72 patients, 16 patients (22%) were positive, and 56 patients (78%) were negative for 99m Tc-PYP scintigraphy. In clinical baseline characteristics, natural logarithm troponin T was significantly higher in the 99m Tc-PYP scintigraphy-positive than scintigraphy-negative group (-2.9 ± 0.5 vs. -3.5 ± 0.8 ng/mL, P < 0.05). In conventional echocardiography, the severity of AS was not significantly different between these two groups. In 2D speckle tracking echocardiography, the relative apical longitudinal strain (LS) index (RapLSI) [apical LS/ (basal LS + mid LS)] was significantly higher (1.09 ± 0.49 vs. 0.78 ± 0.23, P < 0.05) and the peak longitudinal strain rate (LSR) in LA was significantly lower in the 99m Tc-PYP scintigraphy-positive than scintigraphy-negative group (0.36 ± 0.14 vs. 0.55 ± 0.20 s-1 , P < 0.05). Multivariable logistic analysis revealed the peak LSR in LA and RapLSI were significantly associated with 99m Tc-PYP scintigraphy positivity. Receiver operating characteristic analysis showed that the area under the curve (AUC) of the peak LSR in LA for 99m Tc-PYP scintigraphy positivity was 0.79 and that the best cut-off value of the peak LSR in LA was 0.47 s-1 (sensitivity: 78.6% and specificity: 72.3%). The AUC of RapLSI for 99m Tc-PYP scintigraphy positivity was 0.69, and the cut-off value of RapLSI was decided as 1.00 (sensitivity: 43.8% and specificity: 87.5%) according to the previous report. The 99m Tc-PYP scintigraphy positivity in patients with RapLSI ≥ 1.0 and the peak LSR in LA ≤ 0.47 s-1 was 83.3% (5/6), and the 99m Tc-PYP scintigraphy negativity in patients with RapLSI < 1.0 and the peak LSR in LA > 0.47 s-1 was 96.6% (28/29). CONCLUSIONS: Left atrial and LV strain analysis were significantly associated with 99m Tc-PYP scintigraphy positivity in ATTR-CM patients with moderate to severe AS. The combination of the peak LSR in LA and RapLSI might be a useful predictor of the presence of ATTR-CM in patients with moderate to severe AS.

Prognostic value of right ventricular global longitudinal strain in transthyretin amyloid cardiomyopathy.

BACKGROUND: This study was performed to investigate whether right ventricular global longitudinal strain (RV-GLS) provides prognostic information in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). METHODS AND RESULTS: Among 129 patients who were diagnosed with ATTRwt-CM at Kumamoto University Hospital from December 2002 to December 2019, 111 patients who had enough information for two-dimensional speckle tracking imaging were retrospectively analyzed. During a median follow-up of 615 days, 26 cardiovascular deaths occurred. Compared with patients in the non-event group, those in the cardiovascular death group were significantly older (81.1 ±â€¯7.4 years vs. 78.2 ±â€¯6.2 years, p = 0.009) and had significantly higher interventricular septal thickness in diastole (16.6 ±â€¯3.1 mm vs. 15.3 ±â€¯2.4 mm, p = 0.048), lower RV-GLS (10.9 ±â€¯2.7% vs. 12.8 ±â€¯3.5%, p = 0.010), and lower right ventricular free wall longitudinal strain (RVFWLS) (13.1 ±â€¯3.3% vs. 15.5 ±â€¯3.8%, p = 0.004). In the univariate Cox proportional hazard analysis, age, left atrial volume index (LAVI), RV-GLS, and RVFWLS were significantly associated with cardiovascular death [age, hazard ratio (HR), 1.10; 95% confidence interval (CI), 1.02-1.19, p = 0.010; LAVI, HR, 1.02; 95% CI, 1.00-1.03, p = 0.009; RV-GLS, HR, 0.86; 95% CI, 0.75-0.97, p = 0.017; RVFWLS, HR 0.89; 95% CI, 0.79-1.00; p = 0.041]. Multivariable Cox proportional hazard analysis showed RV-GLS was significantly and independently associated with cardiovascular death in patients with ATTRwt-CM (HR, 0.86; 95% CI, 0.74-0.99; p = 0.038). Receiver operating characteristic analysis showed that the area under the curve of RV-GLS for cardiovascular death was 0.668 and that the best cut-off value of RV-GLS was 11.59% (sensitivity, 69.2%; specificity, 63.5%). In the Kaplan-Meier analysis, patients with ATTRwt-CM who had low RV-GLS (<11.59%) had a significantly higher probability of total cardiovascular death (p = 0.004) and heart failure-related hospitalization (p = 0.013). CONCLUSION: RV-GLS has significant prognostic value in patients with ATTRwt-CM and provides greater prognostic power than conventional echocardiographic findings.

Cardiac computed tomography-derived myocardial tissue characterization after anthracycline treatment.

AIMS: Understanding cardiac function after anthracycline administration is very important from the perspective of preventing the onset of heart failure. Although cardiac magnetic resonance and echocardiography are recognized as the 'gold standard' for detecting cardiotoxicity, they have many shortcomings. We aimed to investigate whether cardiac computed tomography (CCT) could replace these techniques, assessing serial changes in cardiac tissue characteristics as determined by CCT after anthracycline administration. METHODS AND RESULTS: We prospectively investigated 15 consecutive breast cancer patients who were scheduled to receive anthracycline therapy. We performed echocardiography and CCT before and 3, 6, and 12 months after anthracycline treatment. The mean cumulative administered anthracycline dose was 269.9 ± 14.6 mg/m2 (doxorubicin-converted dose). Of the 15 enrolled patients who received anthracycline treatment for breast cancer, none met the definition of cardiotoxicity. The CCT-derived extracellular volume fraction tended to continue to increase after anthracycline treatment and had relatively similar dynamics to the left ventricular ejection fraction and global longitudinal strain as determined by echocardiography. CONCLUSIONS: Our findings indicated that CCT could provide adequate information about the characteristics of myocardial tissue after anthracycline administration. CCT may improve the understanding of cardiotoxicity by compensating for the weaknesses of echocardiography. This technique could be useful for understanding cardiac tissue characterization as a 'one-stop shop' evaluation, providing new insight into cardiooncology.

A simple staging system using biomarkers for wild-type transthyretin amyloid cardiomyopathy in Japan.

AIMS: It has been reported that a staging system combining N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T (hs-cTnT) or estimated glomerular filtration rate (eGFR) is useful in patients with wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM). However, these studies were mainly conducted in Western countries, and their usefulness for the Japanese population is unclear. We examined and validated the staging system using hs-cTnT, eGFR, and B-type natriuretic peptide (BNP) in Japanese patients with ATTRwt-CM. METHODS AND RESULTS: We retrospectively evaluated 176 patients with ATTRwt-CM. The cut-off values of hs-cTnT and eGFR were selected as 0.05 ng/mL and 45 mL/min/1.73 m2 , respectively, based on a previous report. The optimal cut-off value of BNP was 255.6 pg/mL to predict all-cause mortality (sensitivity, 75%; specificity, 58%; area under the curve, 0.69; 95% confidence interval [CI], 0.61-0.78; P < 0.001) based on a receiver operating characteristic curve. We defined the cut-off value of BNP as 250 pg/mL. Increased hs-cTnT (>0.05 ng/mL) and BNP (>250 pg/mL) and decreased eGFR (<45 mL/min/1.73 m2 ) were significant predictors of poor prognosis (P < 0.05). We calculated the score by adding 1 point if hs-cTnT and BNP levels increased or eGFR decreased by more than the cut-off value. The hazard ratio of all-cause death adjusted by age and sex, using score 0 as a reference, was 0.44 (95% CI 0.08-2.49, P = 0.44) for score 1, 3.69 (95% CI 1.21-11.21, P = 0.02) for score 2, and 5.40 (95% CI 1.57-18.54, P = 0.007) for score 3. We divided patients into a low score group (0-1 point) and high score group (2-3 points). Kaplan-Meier analyses revealed significant differences in all-cause death and rehospitalization for heart failure (log rank test; P < 0.001), and after adjusting for sex and age, the hazard ratio of all-cause death was 6.96 (95% Cl 2.88-16.83, P < 0.001) and that for rehospitalization for heart failure was 4.27 (95% Cl 2.26-8.07, P < 0.001) in the high-risk group, compared with those in the low-risk group. The median survival period was 32.0 months in the high-risk group. CONCLUSIONS: This simple staging system, which combines hs-cTnT, BNP, and eGFR, was useful for predicting prognosis in Japanese patients with ATTRwt-CM. This system can objectively evaluate the disease progression of ATTRwt-CM and may be useful for patient selection for disease-modifying therapy.

Malnutrition-associated high bleeding risk with low thrombogenicity in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Although antithrombotic treatments are established for coronary artery disease (CAD), they increase the bleeding risk, especially in malnourished patients. The total thrombus-formation analysis system (T-TAS) is useful for the assessment of thrombogenicity in CAD patients. Here, we examined the relationships among malnutrition, thrombogenicity and 1-year bleeding events in patients undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: This was a retrospective analysis of 300 consecutive CAD patients undergoing PCI. Blood samples obtained on the day of PCI were used in the T-TAS to compute the thrombus formation area under the curve. We assigned patients to two groups based on the geriatric nutritional risk index (GNRI): 102 patients to the lower GNRI group (≤98), 198 patients to the higher GNRI group (98<). The primary endpoint was the incidence of 1-year bleeding events defined by Bleeding Academic Research Consortium criteria types 2, 3, or 5. The T-TAS levels were lower in the lower GNRI group than in the higher GNRI group. Kaplan-Meier analysis showed worse 1-year bleeding event-free survival in the lower GNRI group compared with the higher GNRI group. The combined model of the GNRI and the Academic Research Consortium for High Bleeding Risk (ARC-HBR) had good calibration and discrimination for bleeding risk prediction. In addition, having a lower GNRI and ARC-HBR positivity was associated with 1-year bleeding events. CONCLUSION: A lower GNRI could reflect low thrombogenicity evaluated by the T-TAS and determine bleeding risk in combination with ARC-HBR positivity.

Impact of cerebrovascular comorbidity on prognosis in Japanese patients undergoing PCI: 1-year data from Japanese multicenter registry (KICS).

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases.

Incidence, clinical characteristics, and diagnostic approach in transthyretin amyloid cardiomyopathy: The Kumamoto Cardiac Amyloidosis Survey.

BACKGROUND: In recent years, transthyretin amyloid cardiomyopathy (ATTR-CM) has received increasing attention; however, the epidemiology of ATTR-CM in Japan is not yet understood. In the Kumamoto Cardiac Amyloid Survey, we evaluated the current incidence, clinical characteristics, diagnostic approaches, and treatment strategies for ATTR-CM and compared tafamidis-prescription hospitals with regional hospitals. METHODS: We conducted a retrospective multicenter observational cohort study. The registry included patients with ATTR-CM diagnosed in two tafamidis-prescription hospital institutes [Japanese Circulation Society (JCS)-certified facilities] and 15 regional cardiovascular facilities in Kumamoto between January 2018 and December 2020. RESULTS: In total, 174 patients were diagnosed with ATTR-CM. The incidence of ATTR-CM was estimated to be approximately 1 per 10,000 person-years in the elderly population (>65 years old) in Kumamoto. Compared with that in the JCS-certified facilities cohort (n=115), age at diagnosis was significantly older (84.5 ± 5.6 vs. 77.5 ± 6.3 years old; p<0.01) in the regional hospitals cohort (n=59). Histological (25% vs. 81%; p<0.01) and genetic diagnosis (7% vs. 82%) were also less frequently performed. Probable (as indicated by positive bone scintigraphy findings with confirmation of monoclonal protein absence) and possible (as indicated by positive bone scintigraphy findings without confirmation of monoclonal protein absence) ATTR-CM accounted for the majority of cases (75% vs. 19%; p<0.01) in the regional hospitals cohort compared to the JCS-certified facilities cohort. There were no cases of hereditary ATTR-CM among the patients who underwent TTR genetic testing (n=98). CONCLUSIONS: We confirmed the incidence of ATTR-CM in Kumamoto and the diagnostic approach used in patients with ATTR-CM. Further prospective studies with a larger sample are needed to validate our results and to further shed light on the epidemiology of ATTR-CM in Japan.

Increased soluble programed cell death-ligand 1 is associated with acute coronary syndrome.

BACKGROUND: Programmed cell death (PD)-1 and its ligand (PD-L1) plays crucial roles in T-cell tolerance as immune checkpoint. Previous studies reported that increased serum levels of soluble PD-L1 (sPD-L1) reflect myocardial and vascular inflammation. However, little is known about the clinical relationship between sPD-L1 and acute coronary syndrome (ACS). We investigated the relation of sPD-L1 and ACS. METHODS: We prospectively measured serum levels of sPD-L1 using a commercially available enzyme-linked immunosorbent assay kit in patients with coronary artery disease (CAD) and continuous non-CAD admitted to Kumamoto University Hospital between December 2017 and June 2019. All malignant diseases, patients who underwent hemodialysis, active collagen diseases, and severe infectious diseases were excluded. RESULTS: Totally, 446 CAD patients [ACS, n = 124; chronic coronary syndrome (CCS), n = 322] and 24 non-CAD patients were analyzed. The levels of sPD-L1 were significantly higher in patients with ACS than those both with non-CAD and CCS {ACS, 188.7 (111.0-260.8) pg/mL, p < 0.001 vs. non-CAD [83.5 (70.8-130.4) pg/mL]; and p = 0.009 vs. CCS [144.2 (94.8-215.5) pg/mL], respectively}. Univariate logistic regression analysis identified that sPD-L1 was significantly associated with ACS [odds ratio (OR): 1.459, 95% confidence interval (CI): 1.198-1.778, p < 0.001]. Multivariable logistic regression analysis with nine significant factors identified from the univariate analysis revealed that sPD-L1 was significantly and independently associated with ACS (OR: 1.561, 95% CI: 1.215-2.006, p < 0.001). CONCLUSIONS: This is the first clinical study to demonstrate the increased level of sPD-L1 in patients with CAD, and the significant association with ACS.