Clinical outcomes of catheter ablation for atrial fibrillation, atrial flutter, and atrial tachycardia in wild-type transthyretin amyloid cardiomyopathy: a proposed treatment strategy for catheter ablation in each arrhythmia.

AIMS: Wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is often accompanied by atrial fibrillation (AF), atrial flutter (AFL), and atrial tachycardia (AT), which are difficult to control because beta-blockers and antiarrhythmic drugs can worsen heart failure (HF). This study aimed to investigate the outcomes of catheter ablation (CA) for AF/AFL/AT in patients with ATTRwt-CM and propose a treatment strategy for CA. METHODS AND RESULTS: A cohort study was conducted on 233 patients diagnosed with ATTRwt-CM, including 54 who underwent CA for AF/AFL/AT. The background of each arrhythmia and the details of the CA and its outcomes were investigated. The recurrence-free rate of AF/AFL/AT overall in ATTRwt-CM patients with multiple CA was 70.1% at 1-year, 57.6% at 2-year, and 44.0% at 5-year follow-up, but CA significantly reduced all-cause mortality [hazard ratio (HR): 0.342, 95% confidence interval (CI): 0.133-0.876, P = 0.025], cardiovascular mortality (HR: 0.378, 95% CI: 0.146-0.981, P = 0.045), and HF hospitalization (HR: 0.488, 95% CI: 0.269-0.889, P = 0.019) compared with those without CA. There was no recurrence of the cavotricuspid isthmus (CTI)-dependent AFL, non-CTI-dependent simple AFL terminated by one linear ablation, and focal AT originating from the atrioventricular (AV) annulus or crista terminalis eventually. Twelve of 13 patients with paroxysmal AF and 27 of 29 patients with persistent AF did not have recurrence as AF. However, all three patients with non-CTI-dependent complex AFL not terminated by a single linear ablation and 10 of 13 cases with focal AT or multiple focal ATs originating beyond the AV annulus or crista terminalis recurred even after multiple CA. CONCLUSION: The outcomes of CA for ATTRwt-CM were acceptable, except for multiple focal AT and complex AFL. Catheter ablation may be aggressively considered as a treatment strategy with the expectation of improving mortality and hospitalization for HF.

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.

Writer's Cramps as an Initial Symptom of Spinocerebellar Ataxia Type 14: A Case Report.

Spinocerebellar ataxia type 14 (SCA14) is a rare form of autosomal dominant cerebellar ataxia caused by mutations in PRKCG. We herein report a case of SCA14 presenting with writer's cramp that predated the onset of progressive ataxia by four years. A 47-year-old Japanese woman had an 11-year history of writer's cramps, followed by unsteadiness. Whole-exome sequencing revealed a heterozygous mutation in PRKCG (p.C142S), leading to an SCA14 diagnosis. Therefore, writer's cramp might be a characteristic extracerebellar sign of SCA14 and can precede the onset of cerebellar ataxia.

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.

Evaluation of an Integrin αvß3 Radiotracer, [18F]F-FPP-RGD2, for Monitoring Pharmacological Effects of Integrin αv siRNA in the NASH Liver.

Purpose: Integrin αv is a key regulator in the pathophysiology of hepatic fibrosis. In this study, we evaluated the potential utility of an integrin αvß3 positron emission tomography (PET) radiotracer, 18F-labeled cyclic arginine-glycine-aspartic acid penta-peptide ([18F]F-FPP-RGD2), for detecting hepatic integrin αv and function in nonalcoholic steatohepatitis (NASH) model rats using integrin αv siRNA. Methods: NASH model rats were produced by feeding a choline-deficient, low-methionine, high-fat diet for 8 weeks. PET/computerized tomography imaging and quantification of integrin αv protein, serum aspartate aminotransferase, and alanine aminotransferase were performed 1 week after single intravenous injection of integrin αv siRNA. Results: Integrin αv siRNA (0.1 and 0.5 mg/kg) dose-dependently decreased hepatic integrin αv protein concentrations in control and NASH model rats. The hepatic mean standard uptake value of [18F]F-FPP-RGD2 was decreased dose-dependently by integrin αv siRNA. The mean standard uptake value was positively correlated with integrin αv protein levels in control and NASH model rats. Serum aspartate aminotransferase and alanine aminotransferase concentrations were also decreased by siRNA injection and correlated with liver integrin αv protein expression levels in NASH model rats. Conclusion: This study suggests that [18F]F-FPP-RGD2 PET imaging is a promising radiotracer for monitoring hepatic integrin αv protein levels and hepatic function in NASH pathology.

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.

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.

Placement of catheters without magnetic sensors in the coronary sinus without fluoroscopic guidance: Feasibility and safety evaluation.

Background: A three-dimensional (3D) mapping system is essential to reduce radiation exposure during catheter ablation. When using the CARTO 3D mapping system, only the catheter with magnetic sensor can visualize its location. However, once target chamber matrix is created using the catheter, even the catheters without magnetic sensors (CWMS) can enable visualization. We aimed to investigate the feasibility and safety of placing a CWMS in the coronary sinus (CS) without fluoroscopic guidance. Methods: The study group comprised 88 consecutive patients who underwent catheter ablation. CWMS placement was performed without fluoroscopic guidance in 47 patients and with fluoroscopic guidance in 41 patients. Placement without fluoroscopic guidance was performed after creating a visualization matrix of the CS, right atrium, and superior vena cava using a catheter with a magnetic sensor. Feasibility and safety were compared between the two groups. Results: Successful catheter placement was achieved in all patients without fluoroscopic guidance, with no inter-group difference in the median procedure time: with guidance, 120.0 [96.0-135.0] min, and without guidance, 110.0 [97.5-125.0] min; p = .22. However, radiation exposure was significantly shorter, and the effective dose was lower without fluoroscopic guidance (0 [0-17.5] s and 0 [0-0.004] mSv, respectively) than with fluoroscopic guidance (420.0 [270.0-644.0] s and 0.73 mSv [0.36-1.26], respectively); both p < .001. Conclusions: CWMS placement without fluoroscopic guidance is feasible, safe to perform, and does not involve complications. Our technique provides an option to decrease radiation exposure during catheter ablation and electrophysiological testing.

Usefulness of 18F-FPP-RGD2 PET in pathophysiological evaluation of lung fibrosis using a bleomycin-induced rat model.

PURPOSE: Integrins αv are key molecules in the pathogenesis of fibrosis in multiple organs. To assess the potential utility of integrin αvß3 imaging for idiopathic pulmonary fibrosis (IPF), we evaluated an 18F-FPP-RGD2 PET probe in a rat model of bleomycin-induced lung fibrosis. METHODS: Pulmonary fibrosis was induced by single intratracheal instillation of bleomycin (3 mg/rat). Positron emission tomography (PET)/computerized tomography scans were performed 4 weeks after bleomycin administration using 18F-FPP-RGD2. Total distribution volume (VT) was estimated using one-tissue/two-compartment, two-tissue/three-compartment models, and Logan graphical analysis (Logan plot; t* = 30 min). Plasma-free fractions were estimated from images of the left ventricle. Correlation between Logan VT and lung pathology was assessed by Spearman's rank correlation. RESULTS: Histopathological evaluation demonstrated the development of fibrosis in IPF-model group. Integrin αv protein expression and lung radioactivity were higher in IPF-model group compared with control group. The lung radioactivity of 18F-FPP-RGD2 rapidly reached the peak after administration and then gradually decreased, whereas left ventricular radioactivity rapidly disappeared. Logan graphical analysis was found to be suitable for 18F-FPP-RGD2 kinetic analysis in the IPF-model lung. Logan VT values for 18F-FPP-RGD2 were significantly higher in IPF rats compared with control rats and strongly correlated with lung fibrosis, pathology, integrin αv protein expression, and oxygen partial pressure. CONCLUSION: Our findings demonstrate that the integrin αvß3 PET probe 18F-FPP-RGD2 can detect pathophysiological changes in lungs, including fibrosis accompanying upregulated integrin αv of IPF-model rats. These findings support the utility of 18F-FPP-RGD2 PET imaging for the pathophysiological evaluation of pulmonary fibrosis.

Laparoscopic and Robot-Assisted Hepatic Surgery: An Historical Review.

Hepatic surgery is a rapidly expanding component of abdominal surgery and is performed for a wide range of indications. The introduction of laparoscopic cholecystectomy in 1987 was a major change in abdominal surgery. Laparoscopic surgery was widely and rapidly adopted throughout the world for cholecystectomy initially and then applied to a variety of other procedures. Laparoscopic surgery became regularly applied to hepatic surgery, including segmental and major resections as well as organ donation. Many operations progressed from open surgery to laparoscopy to robot-assisted surgery, including colon resection, pancreatectomy, splenectomy thyroidectomy, adrenalectomy, prostatectomy, gastrectomy, and others. It is difficult to prove a data-based benefit using robot-assisted surgery, although laparoscopic and robot-assisted surgery of the liver are not inferior regarding major outcomes. When laparoscopic surgery initially became popular, many had concerns about its use to treat malignancies. Robot-assisted surgery is being used to treat a variety of benign and malignant conditions, and studies have shown no deterioration in outcomes. Robot-assisted surgery for the treatment of malignancies has become accepted and is now being used at more centers. The outcomes after robot-assisted surgery depend on its use at specialized centers, the surgeon's personal experience backed up by extensive training and maintenance of international registries. Robot-assisted hepatic surgery has been shown to be associated with slightly less intraoperative blood loss and shorter hospital lengths of stay compared to open surgery. Oncologic outcomes have been maintained, and some studies show higher rates of R0 resections. Patients who need surgery for liver lesions should identify a surgeon they trust and should not be concerned with the specific operative approach used. The growth of robot-assisted surgery of the liver has occurred in a stepwise approach which is very different from the frenzy that was seen with the introduction of laparoscopic cholecystectomy. This approach allowed the identification of areas for improvement, many of which are at the nexus of engineering and medicine. Further improvements in robot-assisted surgery depend on the combined efforts of engineers and surgeons.

Regulation mechanisms of the dual ATPase in KaiC.

KaiC is a dual adenosine triphosphatase (ATPase), with one active site in its N-terminal domain and another in its C-terminal domain, that drives the circadian clock system of cyanobacteria through sophisticated coordination of the two sites. To elucidate the coordination mechanism, we studied the contribution of the dual-ATPase activities in the ring-shaped KaiC hexamer and these structural bases for activation and inactivation. At the N-terminal active site, a lytic water molecule is sequestered between the N-terminal domains, and its reactivity to adenosine triphosphate (ATP) is controlled by the quaternary structure of the N-terminal ring. The C-terminal ATPase activity is regulated mostly by water-incorporating voids between the C-terminal domains, and the size of these voids is sensitive to phosphoryl modification of S431. The up-regulatory effect on the N-terminal ATPase activity inversely correlates with the affinity of KaiC for KaiB, a clock protein constitutes the circadian oscillator together with KaiC and KaiA, and the complete dissociation of KaiB from KaiC requires KaiA-assisted activation of the dual ATPase. Delicate interactions between the N-terminal and C-terminal rings make it possible for the components of the dual ATPase to work together, thereby driving the assembly and disassembly cycle of KaiA and KaiB.

Elucidation of master allostery essential for circadian clock oscillation in cyanobacteria.

Spatiotemporal allostery is the source of complex but ordered biological phenomena. To identify the structural basis for allostery that drives the cyanobacterial circadian clock, we crystallized the clock protein KaiC in four distinct states, which cover a whole cycle of phosphor-transfer events at Ser431 and Thr432. The minimal set of allosteric events required for oscillatory nature is a bidirectional coupling between the coil-to-helix transition of the Ser431-dependent phospho-switch in the C-terminal domain of KaiC and adenosine 5'-diphosphate release from its N-terminal domain during adenosine triphosphatase cycle. An engineered KaiC protein oscillator consisting of a minimal set of the identified master allosteric events exhibited a monophosphorylation cycle of Ser431 with a temperature-compensated circadian period, providing design principles for simple posttranslational biochemical circadian oscillators.

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.

HFA-PEFF scores: prognostic value in heart failure with preserved left ventricular ejection fraction.

BACKGROUND/AIMS: The Heart Failure Association (HFA)-PEFF score is recognized as a simple method to diagnose heart failure (HF) with preserved ejection fraction (HFpEF). This study aimed to evaluate the relationship between HFA-PEFF scores and cardiovascular outcomes in HFpEF patients. METHODS: A total of 502 consecutive HFpEF patients were prospectively observed for up to 1,500 days. Cardiovascular outcomes were compared between two groups of patients, defined by their HFA-PEFF scores: those who scored 2-4 (the intermediate-score group) and those who scored 5-6 group (the high-score group). Overall, 236 cardiovascular events were observed during the follow-up period (median, 1,159 days). RESULTS: Kaplan-Meier analysis showed that there were significant differences in composite cardiovascular events and HF-related events between the intermediate-score group and the high-score group (p = 0.003 and p < 0.001, respectively). Multivariate Cox proportional hazards analysis showed that the HFA-PEFF scores significantly predicted future HF-related events (hazard ratio, 1.66; 95% confidence interval [CI], 1.11 to 2.50; p = 0.014); receiver operating characteristic analysis confirmed this relationship (area under the curve, 0.633; 95% CI, 0.574 to 0.692; p < 0.001). The cutoff HFA-PEFF score for the identification of HF-related events was 4.5. Decision curve analysis revealed that combining the HFA-PEFF score with conventional prognostic factors improved the prediction of HF-related events. CONCLUSION: HFA-PEFF scores may be useful for predicting HF-related events in HFpEF patients.

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.