Validation of a Supportive and Palliative Care Indicator Tool among hospitalized patients with heart failure.

BACKGROUND: Palliative care including symptom alleviation and advance care planning is relevant for patients with heart failure (HF). The Supportive and Palliative Care Indicator Tool (SPICT) is a tool for identifying patients who may benefit from palliative care assistance but is not validated in patients hospitalized for HF. METHODS AND RESULTS: Clinical backgrounds, symptom burdens, and outcomes were evaluated using SPICT assessed on admission in consecutive hospitalized patients with HF. SPICT positive was defined as two or more general indicators and a New York Heart Association ≥III were present. Of 601 hospitalized patients with HF (mean age: 79±12 years, male: 314 [52%], and mean left ventricular ejection fraction: 44±18%), 100 (17%) patients were SPICT-positive. SPICT-positive patients were older (85±9 vs. 78±12 years; P<0.001) with higher clinical frailty scale (6±1 vs. 4±1 points; P<0.001), while symptom burdens assessed by the Integrated Palliative care Outcome Scale were not different (17 [13, 28] vs. 20 [11, 26] points; P=0.97) when compared with SPICT-negative. During the median follow-up period of 518 days, 178 patients (30%) died. SPICT positive was independently associated with higher all-cause mortality (hazard ratio: 3.49, 95% confidence interval: 2.41-5.05; P<0.001) after adjusting for age, sex, New York Heart Association class IV, Get-With-The-Guideline risk score, N-terminal pro B-type natriuretic peptide level, and left ventricular ejection fraction. CONCLUSIONS: In patients admitted for HF, SPICT positive was significantly associated with higher all-cause mortality, suggesting the utility of SPICT as an indicator to initiate advance care planning for end-of-life care among hospitalized patients with HF.

Evaluation of fractional flow reserve and atherosclerotic plaque characteristics on coronary non-contrast T1-weighted magnetic resonance imaging.

BACKGROUND AND AIMS: The relationship between high-risk coronary plaque characteristics regardless of the severity of lesion stenosis and myocardial ischemia remains unsettled. High-intensity plaques (HIPs) on non-contrast T1-weighted magnetic resonance imaging (T1WI) have been characterized as high-risk coronary plaques. We sought to elucidate whether the presence of coronary HIPs on T1WI influences fractional flow reserve (FFR) in the distal segment of the vessel. METHODS: We retrospectively analyzed 281 vessels in 231 patients with chronic coronary syndrome who underwent invasive FFR measurement and coronary T1WI using a multicenter registry. The plaque-to-myocardial signal intensity ratio (PMR) of the most stenotic lesion was evaluated; a coronary plaque with PMR ≥1.4 was defined as a HIP. RESULTS: The median PMR of coronary plaques on T1WI in vessels with FFR ≤0.80 was significantly higher than that of plaques with FFR >0.80 (1.17 [interquartile range (IQR): 0.99-1.44] vs. 0.97 [IQR: 0.85-1.09]; p < 0.001). Multivariable analysis showed that an increase in PMR of the most stenotic segment was associated with lower FFR (beta-coefficient, -0.050; p < 0.001). The presence of coronary HIPs was an independent predictor of FFR ≤0.80 (odds ratio (OR), 6.18; 95% confidence interval (CI), 1.93-19.77; p = 0.002). Even after adjusting for plaque composition characteristics based on computed tomography angiography, the presence of coronary HIPs was an independent predictor of FFR ≤0.80 (OR, 4.48; 95% CI, 1.19-16.80; p = 0.026). CONCLUSIONS: Coronary plaques with high PMR are associated with low FFR in the corresponding vessel, indicating that plaque morphology might influence myocardial ischemia severity.

Relationship between 2nd-generation angiotensin receptor blockers and the risk of hypotension in COVID-19 patients admitted to hospital.

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.

Stronger positive correlation of the left ventricular mass index and extracellular volume fraction with diastolic function in diabetic patients without myocardial infarction.

BACKGROUND: The structural and functional characteristics of the heart in patients with diabetes mellitus (DM) and without myocardial infarction (MI) are not fully understood. METHODS: We retrospectively analysed the data of patients with left ventricular ejection fraction (LVEF) ≥ 40% who underwent contrast-enhanced cardiac magnetic resonance imaging (CMR), which was also used to exclude MI, at two hospitals. Volumetric data and extracellular volume fraction (ECVf) of the myocardium evaluated using CMR were compared between patients with and without DM, and their association with diastolic function was evaluated. RESULTS: Among 322 analysed patients, 53 had DM. CMR revealed that the left ventricular mass index (LVMi) and ECVf were increased while LVEF was decreased in patients with DM after adjusting for patient characteristics (all P < 0.05). A stronger positive correlation was observed between LVMi and the early diastolic transmitral flow velocity to early diastolic mitral annular velocity ratio (E/e') in patients with DM than in those without DM (correlation coefficient [R] = 0.46, p = 0.001; R = 0.15, p = 0.021, respectively; p for interaction = 0.011). ECVf correlated with E/e' only in patients with DM (R = 0.61, p = 0.004). CONCLUSIONS: Patients with DM have increased LVMi and ECVf. Importantly, there was a difference between patients with and without DM in the relationship between these structural changes and E/e', with a stronger relationship in patients with DM. Furthermore, DM is associated with mildly reduced LVEF even in the absence of MI.

Multicentre, open-label, randomised, controlled trial to compare early intervention with calcimimetics and conventional therapy in preventing coronary artery calcification in patients with secondary hyperparathyroidism (UPCOMING): a study protocol.

INTRODUCTION: Coronary artery and heart valve calcification is a risk factor for cardiovascular death in haemodialysis patients, so calcification prevention should be started as early as possible. Treatment with concomitant calcimimetics and low-dose vitamin D receptor activators (VDRAs) is available, but not enough evidence has been obtained on the efficacy of this regimen, particularly in patients with short dialysis duration. Therefore, this study will evaluate the efficacy and safety of early intervention with upacicalcet, a calcimimetic used to prevent coronary artery calcification in this patient population. METHODS AND ANALYSIS: This multicentre, open-label, randomised, parallel-group controlled study will compare an early intervention group, which received upacicalcet and a low-dose VDRA, with a conventional therapy group, which received a VDRA. The primary endpoint is a change in log coronary artery calcium volume score from baseline to 52 weeks. The main inclusion criteria are as follows: (1) age 18 years or older; (2) dialysis is planned or dialysis duration is less than 60 months; (3) intact parathyroid hormone (PTH) >240 pg/mL or whole PTH level>140 pg/mL; (4) serum-corrected calcium≥8.4 mg/dL and (5) Agatston score >30. The main exclusion criteria are as follows: (1) history of parathyroid intervention or fracture in the past 12 weeks; (2) history of myocardial infarction, stroke or leg amputation in the past 12 weeks; (3) history of coronary angioplasty and (4) heart failure of New York Heart Association class III or worse. ETHICS AND DISSEMINATION: The study will comply with the Declaration of Helsinki and the Japanese Clinical Trials Act. The study protocol has been approved by the Fujita Health University Certified Review Board (file no. CR22-052). Written informed consent will be obtained from all participants. Study results will be presented in academic meetings and peer-reviewed academic journals. TRIAL REGISTRATION NUMBER: jRCTs041220126.

Association between intraoperative blood salvage and coagulation disorder after cardiopulmonary bypass.

BACKGROUND: This study investigated whether intraoperative blood salvage was associated with coagulation disorder diagnosed by conventional coagulation tests and thromboelastography (TEG) after cardiopulmonary bypass (CPB). STUDY DESIGN AND METHODS: This was a prospective, observational study. Ninety-two patients who underwent cardiovascular surgery with CPB were enrolled. We evaluated coagulation function in patients with or without cell salvage blood transfusion at the following time points: before CPB, just after protamine administration, and 1 h after protamine administration. We evaluated platelet count, fibrinogen concentration, and TEG parameters. Patients were considered to have coagulation disorder if one or more of the following criteria were present: (1) residual heparin, (2) low platelet count, (3) low fibrinogen level, (4) low clotting factor level, and (5) hyperfibrinolysis. RESULTS: Fifty-three of 92 patients (57.6%) received intraoperative cell salvage. Coagulation disorder was observed in 56 of 92 patients (60.9%) after CPB. There was no significant difference between patients with or without intraoperative blood salvage in terms of the incidence of coagulation disorder (p = 0.542) or the total volume of blood from the drain after CPB (p = 0.437). Intraoperative blood salvage was not associated with coagulation disorder diagnosed by either TEG or conventional coagulation tests (odds ratio 1.329, 95% confidence interval: 0.549-3.213, p = 0.547). There were no significant interactions between patients with or without intraoperative blood salvage regarding coagulation parameters derived from TEG. CONCLUSIONS: The incidence of coagulation disorder and the total blood volume from the drain after CPB did not differ significantly between patients with or without intraoperative blood salvage.

Prolonged delirium during hospitalization is associated with worse long-term and short-term outcomes in patients with acute heart failure.

BACKGROUND: The association between prolonged delirium during hospitalization and long-term prognosis in patients with acute heart failure (AHF) admitted to the cardiac intensive care unit (CICU) has not been fully elucidated. METHODS: We conducted a prospective registry study of patients with AHF admitted to the CICU at 2 hospitals from 2013 to 2021. We divided study patients into 3 groups according to the presence or absence of delirium and prolonged delirium as follows: no delirium, resolved delirium, or prolonged delirium. Main outcomes were in-hospital mortality and 3-year mortality after discharge. RESULTS: A total of 1555 patients with AHF (median age, 80 years) were included in the analysis. Of these, 406 patients (26.1%) developed delirium. We divided patients with delirium into 2 groups: the resolved delirium group (n = 201) or the prolonged delirium group (n = 205). Multivariate Cox proportional hazards models for long-term prognosis demonstrated that the prolonged delirium group had a higher incidence of all-cause death (hazard ratio [HR], 1.52; 95% CI, 1.08 to 2.14) and non-cardiovascular death (HR, 1.84; 95% CI, 1.21 to 2.78) than the resolved delirium group. Regarding in-hospital outcomes, multivariate logistic regression modeling showed that prolonged delirium is associated with all-cause death (odds ratio [OR], 9.55; 95% confidential interval [CI], 2.99 to 30.53) and cardiovascular death (OR, 13.02; 95% CI, 2.86 to 59.27) compared with resolved delirium. CONCLUSIONS: Prolonged delirium is associated with worse long-term and short-term outcomes than resolved delirium in patients with AHF.

Ten-year national trends in in-hospital mortality and functional outcomes after intracerebral hemorrhage by age in Japan: J-ASPECT study.

INTRODUCTION: National-level data on trends in the prognosis of age-stratified patients with intracerebral hemorrhage (ICH) are lacking. This study aimed to assess time trends in in-hospital mortality and functional outcomes of ICH patients by sex and age, and to explore factors associated with changes in in-hospital mortality trend. PATIENTS AND METHODS: Using the largest nationwide, J-ASPECT stroke database in Japan, this serial cross-sectional study included ICH patients aged ⩾18 years who were hospitalized for non-traumatic ICH from April 2010 to March 2020. We examined trends in in-hospital mortality and functional outcomes using the modified Rankin Scale at discharge, as well as differences in in-hospital mortality change between age groups. RESULTS: Among 262,399 ICH patients from 934 hospitals, crude in-hospital mortality showed a significant decreasing time trend (from 19.5% to 16.7%), and this trend was consistent across sex and age groups. In addition, differences in in-hospital mortality change over the 10-year study period were significant between male patients aged ⩾75 years and those aged ⩽64 years (-3.9% [95% confidence interval, -5.4 to -2.4] for 75-84 years; -4.1% [-6.3 to -1.9] for ⩾85 years). On the other hand, the proportion of dependent patients (mRS 3-5) at discharge increased from 52.0% to 54.9% over the 10-year study period. CONCLUSION: The in-hospital mortality of ICH patients improved, whereas the proportion of patients with dependent functional outcome at discharge increased, over the 10-year study period. Elucidating the mechanism underlying differences in in-hospital mortality reduction in men may provide insights into effective interventions in the future.

High pillow and spontaneous vertebral artery dissection: A case-control study implicating "Shogun pillow syndrome".

INTRODUCTION: The underlying causes of spontaneous vertebral artery dissection (sVAD) remain insufficiently understood. This study aimed to determine whether high-pillow usage is associated with an increased risk of sVAD and evaluate the frequency of sVAD attributable to high-pillow usage. PATIENTS AND METHODS: This case-control study identified patients with sVAD and age- and sex-matched non-sVAD controls (case-to-control ratio: 1:1) treated at a certified comprehensive stroke center in Japan between 2018 and 2023. The pillow height used at the onset of the index disease was measured and classified into three categories between 12 and 15 cm boundaries. Univariable logistic regression was performed to assess the odds ratio (OR) with a 95% confidence interval (CI) of high-pillow usage for sVAD development. A subgroup of sVAD attributable to high-pillow usage was defined with the following three conditions: high-pillow usage (⩾12 or ⩾15 cm); no minor preceding trauma; and wake-up onset. RESULTS: Fifty-three patients with sVAD and 53 non-sVAD controls (42% women, median age: 49 years) were identified. High-pillow usage (⩾12 and ⩾15 cm) was more common in the sVAD group than in the non-sVAD group (34 vs 15%; OR = 2.89; 95%CI = 1.13-7.43 and 17 vs 1.9%; OR = 10.6; 95%CI = 1.30-87.3, respectively). The subgroup of sVAD attributed to high-pillow usage (⩾12 and ⩾15 cm) was found in 11.3% (95%CI = 2.7%-19.8%) and 9.4% (95%CI = 1.5%-17.3%), respectively. CONCLUSION: High-pillow usage was associated with an increased risk of sVAD and accounted for approximately 10% of all sVAD cases. This tentative subgroup of sVAD may represent a distinct spectrum of disease-Shogun pillow syndrome.

Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease: A Novel Analysis of the VITAL Trial Using Win Ratio and Hierarchical Composite Outcomes.

This study aimed to investigate whether n-3 fatty acid supplementation reduced cardiovascular disease (CVD) events in a novel analysis using hierarchical composite CVD outcomes based on win ratio in the VITamin D and OmegA-3 TriaL (VITAL). This was a secondary analysis of our VITAL randomized trial, which assessed the effects of marine n-3 fatty acids (1 g/day) and vitamin D3 on incident CVD and cancer among healthy older adults (n = 25,871). The primary analysis estimated win ratios of a composite of major CVD outcomes prioritized as fatal coronary heart disease, other fatal CVD including stroke, non-fatal myocardial infarction (MI), and non-fatal stroke, comparing n-3 fatty acids to placebo. The primary result was a nonsignificant benefit of this supplementation for the prioritized primary CVD outcome (reciprocal win ratio [95% confidence interval]: 0.90 [0.78-1.04]), similar to the 0.92 (0.80-1.06) hazard ratio in our original time-to-first event analysis without outcome prioritization. Its benefits came from reducing MI (0.71 [0.57-0.88]) but not stroke (1.01 [0.80 to 1.28]) components. For the primary CVD outcome, participants with low fish consumption at baseline benefited (0.79 [0.65-0.96]) more than those with high consumption (1.05 [0.85-1.30]). These results are consistent with, but slightly stronger than, those without outcome prioritization.

Effect of postoperative delirium after cardiovascular surgery on 5-year mortality.

INTRODUCTION: Postoperative delirium is a common complication after cardiovascular surgery. A meta-analysis revealed that postoperative delirium was associated with cognitive decline and dementia, which may affect long-term mortality. However, few studies have reported the association between postoperative delirium after cardiovascular surgery and long-term postoperative mortality. Therefore, we investigated the effect of postoperative delirium on 5-year survival rates of patients who underwent cardiovascular surgery. METHODS: We retrospectively reviewed the records of patients who underwent cardiovascular surgery with cardiopulmonary bypass from January 2016 to December 2019. Postoperative delirium was defined as an Intensive Care Delirium Screening score ≥ 3, which might include subclinical delirium. Cox proportional hazards modeling was performed to assess the association between postoperative delirium and mortality. Postoperative mortality in patients with and without delirium was assessed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Postoperative delirium was observed in 562 (31.9%) of 1731 patients. There were more elderly patients, more emergent surgery procedures, longer operative time, and larger transfusion volume in the postoperative delirium group. Cox regression analyses showed that delirium (hazard ratio (HR), 1.501; 95% confidence interval (CI), 1.053-2.140; p = 0.025) and emergent surgery (HR, 3.380; 95% CI, 2.231-5.122; p < 0.001) are significantly associated with 5-year mortality. Among patients who underwent elective surgery, postoperative delirium (HR, 1.987; 95% CI, 1.135-3.481; p = 0.016) is significantly associated with 5-year mortality. Kaplan-Meier survival analysis revealed that patients with postoperative delirium had significantly higher 5-year mortality. CONCLUSIONS: Patients with postoperative delirium after cardiovascular surgery have significantly higher 5-year mortality.

Cognitive transitions based on functional status in older adults with heart failure: a population-based study.

AIMS: Cognitive impairment and functional status are both important determinants of poor outcomes in heart failure (HF). However, little is known about how functional status impacts the changes in cognitive status during the disease course. This study aimed to describe the cognitive transitions in patients with HF and assess the relationship of these transitions to functional status, which was assessed by the dependency of activities of daily living (ADL). METHODS AND RESULTS: This retrospective cohort study included 1764 patients with an International Classification of Diseases-10 code of HF (≥65 years, mean age 82.3 ± 7.9 years, 39% male) from a long-term care and medical insurance database from Nobeoka city, a rural city of south-western Japan. Cognitive status at baseline and 6, 12, 18, and 24 month time points was collected, and participants were stratified based on ADL status at baseline. Generalized estimating equations and multi-state modelling were used to examine associations between ADL dependency and cognitive changes/mortality. Transition probabilities were estimated using multi-state modelling. At baseline, there were 1279 (73%) and 485 (27%) patients with independent and dependent ADL, respectively. In overall patients, 1656 (93.9%) patients had normal/mild cognitive status and 108 (6%) patients had a moderate/severe cognitive status at baseline. The majority [104 (96%) patients] of patients with moderate/severe cognitive status at baseline had dependent ADL. In patients with moderate/severe cognitive status, the number of patients with dependent ADL always outnumbered that of the independent ADL throughout the follow-up. Multi-state modelling estimated that patients with dependent ADL and normal/mild cognitive status at baseline had 47% probability of maintaining the same cognitive status at 24 months, while the probability of maintaining the same cognitive status was 86% for those with independent ADL. Patients with normal/mild cognitive status in the dependent ADL group at baseline had a higher risk of experiencing a transition to moderate/severe cognitive status at any time point during 24 months compared with those with independent ADL [hazard ratio 5.24 (95% confidence interval 3.47-7.90)]. CONCLUSIONS: In older patients with HF, the prevalence of cognitive impairment was always higher for those with reduced functional status. Despite having a normal/mild cognitive status at baseline, patients with dependent ADL are at high risk of experiencing cognitive decline over 24 months with substantially less chance of maintaining their cognitive status. ADL dependency was an important risk factor of cognitive decline in patients with HF.

Periodic discharges plus fast activity on electroencephalogram predict worse outcomes in poststroke epilepsy.

OBJECTIVE: Postseizure functional decline is a concern in poststroke epilepsy (PSE). However, data on electroencephalogram (EEG) markers associated with functional decline are scarce. Thus, we investigated whether periodic discharges (PDs) and their specific characteristics are associated with functional decline in patients with PSE. METHODS: In this observational study, patients admitted with seizures of PSE and who had scalp EEGs were included. The association between the presence or absence of PDs and postseizure short-term functional decline lasting 7 days after admission was investigated. In patients with PD, EEG markers were explored for risk stratification of short-term functional decline, according to the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology. The association between EEG markers and imaging findings and long-term functional decline at discharge and 6 months after discharge, defined as an increase in the modified Rankin Scale score compared with the baseline, was evaluated. RESULTS: In this study, 307 patients with PSE (median age = 75 years, range = 35-97 years, 64% males; hemorrhagic stroke, 47%) were enrolled. Compared with 247 patients without PDs, 60 patients with PDs were more likely to have short-term functional decline (12 [20%] vs. 8 [3.2%], p < .001), with an adjusted odds ratio (OR) of 4.26 (95% confidence interval [CI] = 1.44-12.6, p = .009). Patients with superimposed fast-activity PDs (PDs+F) had significantly more localized (rather than widespread) lesions (87% vs. 58%, p = .003), prolonged hyperperfusion (100% vs. 62%, p = .023), and a significantly higher risk of short-term functional decline than those with PDs without fast activity (adjusted OR = 22.0, 95% CI = 1.87-259.4, p = .014). Six months after discharge, PDs+F were significantly associated with long-term functional decline (adjusted OR = 4.21, 95% CI = 1.27-13.88, p = .018). SIGNIFICANCE: In PSE, PDs+F are associated with sustained neuronal excitation and hyperperfusion, which may be a predictor of postseizure short- and long-term functional decline.

Changes in neurological outcomes of out-of-hospital cardiac arrest during the COVID-19 pandemic in Japan: a population-based nationwide observational study.

Background: There is growing interest in the indirect negative effects of coronavirus disease 2019 (COVID-19) on mortality. We aimed to assess its indirect effect on out-of-hospital cardiac arrest (OHCA) outcomes. Methods: We analysed a prospective nationwide registry of 506,935 patients with OHCA between 2017 and 2020. The primary outcome was favourable neurological outcome (Cerebral Performance Category 1 or 2) at 30 days. The secondary outcomes were public access defibrillation (PAD) and bystander-initiated chest compression. We performed an interrupted time series (ITS) analysis to assess changes in the trends of these outcomes around the declaration of a state of emergency (April 7 - May 25, 2020). We also performed a subgroup analysis stratified by infection spread status. Findings: We identified 21,868 patients with OHCA witnessed by a bystander who had an initial shockable heart rhythm. ITS analysis showed a drastic decline in PAD use (relative risk [RR], 0.60; 95% confidence interval [CI], 0.49-0.72; p < 0.0001) and a reduction in favourable neurological outcomes (RR, 0.79; 95% CI, 0.68-0.91; p = 0.0032) all over Japan after the state of emergency was declared when compared with the equivalent time period in previous years. The decline in favourable neurological outcomes was more pronounced in areas with COVID-19 spread than in areas without spread (RR, 0.70; 95% CI, 0.58-0.86 vs. RR, 0.87; 95% CI, 0.72-1.03; p for effect modification = 0.019). Interpretation: COVID-19 is associated with worse neurological outcomes and less PAD use in patients with OHCA. Funding: None.

Tolvaptan's Association with Low Risk of Acute Kidney Injury in Patients with Advanced Chronic Kidney Disease and Acute Decompensated Heart Failure.

INTRODUCTION: Furosemide, a loop diuretic, is often empirically used to treat acute decompensated heart failure (ADHF) initially. Conversely, decongestion using tolvaptan, an aquaretic, is thought to maintain renal function compared to furosemide. However, it has not been investigated in patients with advanced chronic kidney disease (CKD) at high risk of developing acute kidney injury (AKI). This study aimed to investigate AKI incidence using tolvaptan add-on treatment, compared to increased furosemide treatment for patients with ADHF complicated by advanced CKD. METHODS: We retrospectively studied patients with advanced CKD (estimated glomerular filtration rate [eGFR] <45 mL/min/1.73 m2) who developed ADHF under outpatient furosemide treatment. The exposure was set to tolvaptan add-on treatment, and the control was set to increased furosemide treatment. RESULTS: Of the 163 patients enrolled, 79 were in the tolvaptan group and 84 in the furosemide group. The mean age was 71.6 years, the percentage of males was 63.8%, the mean eGFR was 15.7 mL/min/1.73 m2, and patients with CKD stage G5 were 61.9%. AKI incidence was 17.7% in the tolvaptan group and 42.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.13-0.86], p = 0.023 in multivariate logistic regression analysis). Persistent AKI incidence was 11.8% in the tolvaptan group and 32.9% in the furosemide group (odds ratio [95% confidence interval]: 0.34 [0.10-1.06], p = 0.066 in the multinomial logit analysis). CONCLUSION: This study suggests that tolvaptan may be better than furosemide in patients with ADHF experiencing complicated advanced CKD.

Association Between Genetic Diagnosis and Clinical Outcomes in Patients With Heritable Thoracic Aortic Disease.

Background Differences in the clinical course of heritable thoracic aortic disease based on the disease-causing gene have not been fully evaluated. To clarify the clinical relevance of causative genes in heritable thoracic aortic disease, we assessed the clinical course of patients categorized based on genetic diagnosis. Methods and Results We investigated cardiovascular events and mortality in 518 genetically diagnosed patients in 4 groups: Group 1, FBN1 (n=344); Group 2, TGFBR1, TGFBR2, SMAD3, or TGFB2 (n=74); Group 3, COL3A1 (n=60); and Group 4, ACTA2 or MYH11 (n=40). The median age at the first cardiovascular event ranged from 30.0 to 35.5 years (P=0.36). Patients with gene variants related to transforming growth factor-ß signaling had a significantly higher rate of subsequent events than those with FBN1 variants (adjusted hazard ratio, 2.33 [95% CI, 1.60-3.38]; P<0.001). Regarding the incidence of aortic dissection, there were no significant differences among the 4 groups in male patients (36.3%, 34.3%, 21.4%, and 54.2%, respectively; P=0.06). Female patients with COL3A1 variants had a significantly lower incidence than female patients in the other 3 groups (34.2%, 59.0%, 3.1%, and 43.8%, respectively; P<0.001). Conclusions Gene variants related to transforming growth factor-ß signaling are associated with a higher incidence of subsequent cardiovascular events than FBN1 variants. COL3A1 variants might be related to a lower incidence of aortic dissection than other gene variants in women only. Identifying the genetic background of patients with heritable thoracic aortic disease is important for determining appropriate treatment.

Taxifolin for Cognitive Preservation in Patients with Mild Cognitive Impairment or Mild Dementia.

BACKGROUND: The development of numerous disease-modifying drugs for age-related dementia has been attempted based on the amyloid-ß (Aß) hypothesis without much success. Taxifolin (TAX), a natural bioactive flavonoid, shows pleiotropic neuroprotective effects with inhibition of Aß aggregation, production, and glycation, antiinflammatory effects, and amelioration of the waste clearance system. We hypothesized that TAX intake is associated with the suppression of cognitive deterioration. OBJECTIVE: To investigate associations between TAX intake and cognitive changes. METHODS: We retrospectively identified patients who orally took TAX 300 mg/day and regularly underwent Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog) and Montreal Cognitive Assessment (MoCA) and compared the temporal changes in ADAS-Cog and MoCA between the non-treatment (pre-TAX) period (180±100 days) and following treatment (on-TAX) period (180±100 days) from June 2020 to November 2021. Since some additional patients underwent the Mini-Mental State Examination (MMSE) instead of the MoCA at the beginning of the pre-TAX period, the same comparison was performed using the MoCA total score converted from MMSE as a sensitivity analysis. RESULTS: Sixteen patients were identified. TAX intake was associated with significantly higher interval changes in the MoCA subscale scores of visuospatial/executive function (p = 0.016), verbal fluency (p = 0.02), and the total score (p = 0.034), but not with ADAS-Cog (total score, p = 0.27). In the sensitivity analysis, 29 patients were included. TAX intake was associated with a significantly higher interval change in the total MoCA score (p = 0.004) but not with ADAS-Cog (p = 0.41). CONCLUSION: Our findings provide a basis for TAX as a novel strategy for maintaining brain health during aging. A prospective cohort study is required to confirm these findings.

National trends in the outcomes of subarachnoid haemorrhage and the prognostic influence of stroke centre capability in Japan: retrospective cohort study.

OBJECTIVES: To examine the national, 6-year trends in in-hospital clinical outcomes of patients with subarachnoid haemorrhage (SAH) who underwent clipping or coiling and the prognostic influence of temporal trends in the Comprehensive Stroke Center (CSC) capabilities on patient outcomes in Japan. DESIGN: Retrospective study. SETTING: Six hundred and thirty-one primary care institutions in Japan. PARTICIPANTS: Forty-five thousand and eleven patients with SAH who were urgently hospitalised, identified using the J-ASPECT Diagnosis Procedure Combination database. PRIMARY AND SECONDARY OUTCOME MEASURES: Annual number of patients with SAH who remained untreated, or who received clipping or coiling, in-hospital mortality and poor functional outcomes (modified Rankin Scale: 3-6) at discharge. Each CSC was assessed using a validated scoring system (CSC score: 1-25 points). RESULTS: In the overall cohort, in-hospital mortality decreased (year for trend, OR (95% CI): 0.97 (0.96 to 0.99)), while the proportion of poor functional outcomes remained unchanged (1.00 (0.98 to 1.02)). The proportion of patients who underwent clipping gradually decreased from 46.6% to 38.5%, while that of those who received coiling and those left untreated gradually increased from 16.9% to 22.6% and 35.4% to 38%, respectively. In-hospital mortality of coiled (0.94 (0.89 to 0.98)) and untreated (0.93 (0.90 to 0.96)) patients decreased, whereas that of clipped patients remained stable. CSC score improvement was associated with increased use of coiling (per 1-point increase, 1.14 (1.08 to 1.20)) but not with short-term patient outcomes regardless of treatment modality. CONCLUSIONS: The 6-year trends indicated lower in-hospital mortality for patients with SAH (attributable to better outcomes), increased use of coiling and multidisciplinary care for untreated patients. Further increasing CSC capabilities may improve overall outcomes, mainly by increasing the use of coiling. Additional studies are necessary to determine the effect of confounders such as aneurysm complexity on outcomes of clipped patients in the modern endovascular era.