Scoping Review of Screening and Assessment Tools for Social Determinants of Health in the Field of Cardiovascular Disease.

BACKGROUND: Despite the importance of implementing the concept of social determinants of health (SDOH) in the clinical practice of cardiovascular disease (CVD), the tools available to assess SDOH have not been systematically investigated. We conducted a scoping review for tools to assess SDOH and comprehensively evaluated how these tools could be applied in the field of CVD.Methods and Results: We conducted a systematic literature search of PubMed and Embase databases on July 25, 2023. Studies that evaluated an SDOH screening tool with CVD as an outcome or those that explicitly sampled or included participants based on their having CVD were eligible for inclusion. In addition, studies had to have focused on at least one SDOH domain defined by Healthy People 2030. After screening 1984 articles, 58 articles that evaluated 41 distinct screening tools were selected. Of the 58 articles, 39 (67.2%) targeted populations with CVD, whereas 16 (27.6%) evaluated CVD outcome in non-CVD populations. Three (5.2%) compared SDOH differences between CVD and non-CVD populations. Of 41 screening tools, 24 evaluated multiple SDOH domains and 17 evaluated only 1 domain. CONCLUSIONS: Our review revealed recent interest in SDOH in the field of CVD, with many useful screening tools that can evaluate SDOH. Future studies are needed to clarify the importance of the intervention in SDOH regarding CVD.

Prognostic Impact of Reduced Left Ventricular Ejection Fraction After Endovascular Therapy for Lower Extremities.

BACKGROUND: The mechanism underlying a poor prognosis in patients with lower-extremity artery disease (LEAD) with heart failure is unknown. We examined the prognostic impact of the left ventricular ejection fraction (LVEF) in patients with LEAD who underwent endovascular therapy (EVT).Methods and Results: From August 2014 to August 2016, 2,180 patients with LEAD (mean age, 73.2 years; male, 71.9%) underwent EVT and were stratified into low-LVEF (LVEF <40%; n=234, 10.7%) and not-low LVEF groups. In the low- vs. not-low LVEF groups, there was a higher prevalence of heart failure (i.e., history of heart failure hospitalization or New York Heart Association functional class III or IV symptoms) (44.0% vs. 8.3%, respectively), diabetes mellitus, chronic kidney disease, below-the-knee lesion, critical limb ischemia, and incidence of major cardiovascular and cerebrovascular events (MACCEs) and major adverse limb events (MALEs) (P<0.001, all). Low LVEF independently predicted MACCEs (hazard ratio: 2.23, 95% confidence interval: 1.63-3.03; P<0.001) and MALEs (hazard ratio: 1.85, 95% confidence interval: 1.15-2.96; P=0.011), regardless of heart failure (P value for interaction: MACCEs: 0.27; MALEs: 0.52). CONCLUSIONS: Low LVEF, but not symptomatic heart failure, increased the incidence of MACCEs and MALEs. Intensive cardiac dysfunction management may improve LEAD prognosis after EVT.

Awareness of Being Prescribed Antihypertensive Medications and Cardiovascular Outcomes.

BACKGROUND: Hypertension is a major cause of cardiovascular disease (CVD). In patients with hypertension, unawareness of the disease often results in poor blood pressure control and increases the risk of CVD. However, data in nationwide surveys regarding the proportion of unaware individuals and the implications of such on their clinical outcomes are lacking. We aimed to clarify the association between unawareness of being prescribed antihypertensive medications among individuals taking antihypertensive medications and the subsequent risk of developing CVD.Methods and Results: This retrospective cohort study analyzed data from the JMDC Claims Database, including 313,715 individuals with hypertension treated with antihypertensive medications (median age 56 years). The primary endpoint was a composite of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Overall, 19,607 (6.2%) individuals were unaware of being prescribed antihypertensive medications. During the follow-up period, 33,976 composite CVD endpoints were documented. Despite their youth, minimal comorbidities, and the achievement of better BP control with a reduced number of antihypertensive prescriptions, unawareness of being prescribed antihypertensive medications was associated with a greater risk of developing composite CVD. Hazard ratios of unawareness of being prescribed antihypertensive medications were 1.16 for myocardial infarction, 1.25 for angina pectoris, 1.15 for stroke, 1.36 for heart failure, and 1.28 for atrial fibrillation. The results were similar in several sensitivity analyses, including the analysis after excluding individuals with dementia. CONCLUSIONS: Among individuals taking antihypertensive medications, assessing the awareness of being prescribed antihypertensive medications may help identify those at high risk for CVD-related events.

Sex Differences in Cardiovascular Disease-Related Hospitalization and Mortality in Japan　- Analysis of Health Records From a Nationwide Claim-Based Database, the Japanese Registry of All Cardiac and Vascular Disease (JROAD).

BACKGROUND: The prevalence of cardiovascular disease (CVD) is rising in Japan with its aging population, but there is a lack of epidemiological data on sex differences in CVD, including acute coronary syndrome (ACS), acute heart failure (AHF), and acute aortic disease.Methods and Results: This retrospective study analyzed data from 1,349,017 patients (January 2012-December 2020) using the Japanese Registry Of All Cardiac and Vascular Diseases database. ACS patients were youngest on average (70.5±12.9 years) and had the lowest female proportion (28.9%). AHF patients had the oldest mean age (79.7±12.0 years) and the highest proportion of females (48.0%). Acute aortic disease had the highest in-hospital mortality (26.1%), followed by AHF (11.5%) and ACS (8.9%). Sex-based mortality differences were notable in acute aortic disease, with higher male mortality in Stanford Type A acute aortic dissection (AAD) with surgery (males: 14.2% vs. females: 10.4%, P<0.001) and similar rates in Type B AAD (males: 6.2% vs. females: 7.9%, P=0.52). Aging was a universal risk factor for in-hospital mortality. Female sex was a risk factor for ACS and acute aortic disease but not for AHF or Types A and B AAD. CONCLUSIONS: Sex-based disparities in the CVD-related hospitalization and mortality within the Japanese national population have been highlighted for the first time, indicating the importance of sex-specific strategies in the management and understanding of these conditions.

Feedbacks Using behaviOral econOmic theories on STEP countS in Cardiovascular Disease Patients (FOOTSTEPS) Using Novel Daily Step Counts Retrieving System.

The effectiveness of gamification-based feedback systems that utilize non-monetary points to promote exercise among cardiovascular disease (CVD) patients has not been fully evaluated. This study aimed to evaluate the effectiveness of a gamification program using non-monetary points on the daily step counts in CVD patients. We collected 30 patients with a history of heart failure or myocardial infarction at a single tertiary center between January 9, 2023, and April 13, 2023. The primary outcome was the change in daily step counts. The baseline step counts were compared with those during the 4-week gamification and the 1-week follow-up period. A total of 29 participants with a mean age of 64.6 years were finally enrolled, and 8 (27.6%) were female. Among them, 23 (79.3%) had a history of old myocardial infarction, and 9 (31.0%) had a history of chronic heart failure. During the intervention period, the average daily step counts increased significantly from baseline in weeks 1-5 (week 1: 1165 steps; 95% CI, 319-2011; P = 0.009, week 2: 1508; 635-2382; P = 0.001, week 3: 1321; 646-1996; P < 0.001, week 4: 1436; 791-2081; P < 0.001, week 5:1148; 436-1860; P < 0.001). Higher body mass index was statistically associated with the smaller difference in step counts from the baseline, and the lower proportion of achievement of step count goals. Female sex was significantly associated with the higher proportion of achievement of step count goals. In conclusion, this pilot prospective interventional study demonstrated the effectiveness of gamification-based feedback systems that utilize non-monetary points to increase daily step counts in CVD patients.

Wearable Devices to Monitor and Reduce the Risk of Cardiovascular Disease: Evidence and Opportunities.

There is a growing interest in using wearable devices to improve cardiovascular risk factors and care. This review evaluates how wearable devices are used for cardiovascular disease monitoring and risk reduction. Wearables have been evaluated for detecting arrhythmias (e.g., atrial fibrillation) as well as monitoring physical activity, sleep, and blood pressure. Thus far, most interventions for risk reduction have focused on increasing physical activity. Interventions have been more successful if the use of wearable devices is combined with an engagement strategy such as incorporating principles from behavioral economics to integrate social or financial incentives. As the technology continues to evolve, wearable devices could be an important part of remote-monitoring interventions but are more likely to be effective at improving cardiovascular care if integrated into programs that use an effective behavior change strategy.

Enduring Relevance of the Stages of Change Model for Transforming Lifestyle Behaviors.

BACKGROUND: The applicability of the Stages of Change model for cardiovascular disease-related behaviors, such as smoking, exercise, diet, and sleep quality, is unclear.Methods and Results: Using a large-scale epidemiological dataset, we found that baseline behavior change intention, as per the transtheoretical model, was associated with modifications of unhealthy lifestyles including cigarette smoking, physical inactivity, skipping breakfast, and poor sleep quality. CONCLUSIONS: Our results suggest that an individual's motivation to change assessed by a general questionnaire may contribute to lifestyle modification and potentially prevent subsequent cardiovascular disease.

End-of-Life Discussions and Their Timing for Patients With Cardiovascular Diseases　- From the Perspective of Bereaved Family Members.

BACKGROUND: Enhanced discussions regarding end-of-life (EOL) are crucial to provide appropriate care for seriously ill patients. However, the current status of EOL discussions, especially their timing and influencing factors, among patients with cardiovascular diseases (CVD) remains unknown.Methods and Results: We conducted a cross-sectional questionnaire survey of bereaved family members of CVD patients who died at 10 tertiary care institutes in Japan. In all, 286 bereaved family members (38.2% male; median age 66.0 [interquartile range 58.0-73.0] years) of CVD patients were enrolled; of these, 200 (69.9%) reported that their families had had EOL discussions with physicians. The major topic discussed was resuscitation (79.0%), and 21.5% discussed the place of EOL care. Most discussions were held during hospitalization of the patient (88.2%). More than half (57.1%) the discussions were initiated less than 1 month before the patient died, and 22.6% of family members felt that this timing of EOL discussions was late. Bereaved family members' perception of late EOL discussions was associated with the family members aggressive attitude towards life-prolonging treatment, less preparedness for bereavement, and less satisfaction with EOL care. CONCLUSIONS: Approximately 70% of bereaved family members of CVD patients had EOL discussions, which were often held shortly before the patient died. Further research is required to establish an ideal approach to EOL discussions at an appropriate time, which may improve the quality of EOL care.

Prognostic impact of atrial fibrillation on the outcomes of peripheral artery disease according to preoperative symptoms for endovascular revascularization.

Peripheral artery disease (PAD) and atrial fibrillation (AF) are associated with major cardiovascular and cerebrovascular events (MACCE). However, outcomes stratified according to the preoperative symptoms of PAD in patients with AF have not been sufficiently investigated. This was a retrospective study of prospectively collected data pertaining to 2237 patients (1179 patients with intermittent claudication [IC] and 1058 patients with critical limb-threatening ischemia [CLTI]) who underwent endovascular therapy at 34 hospitals between August 2014 and August 2016. AF was present in 91 (7.7%) patients with IC and 150 (14.2%) patients with CLTI. In the CLTI group, patients with AF had a higher event rate of MACCE and all-cause death than those without AF (1-year rates of freedom from MACCE: 0.66 and 0.81 in patients with and without AF, respectively, p < 0.001). In contrast, in the IC group, there was no statistically significant difference in the rates of MACCE between patients with and without AF. In the Cox multivariate analysis, AF was a significant predictor of MACCE in patients with CLTI but not in patients with IC, even after adjusting for covariates. The impact of AF on the outcome of patients with PAD was greater in those with CLTI. Further studies are needed to clarify the possible mechanisms underlying these differences.

Differences in major limb outcomes by indication for lower extremity endovascular revascularization in patients receiving hemodialysis.

The incidence of lower extremity artery disease (LEAD) in patient receiving hemodialysis is remarkably higher than the general population. The treatment strategy and prognosis for LEAD patients differs depending on whether a patient has intermittent claudication (IC) or critical limb-threatening ischemia (CLTI). However, the distinction between the prognosis in HD-dependent patients with IC and CLTI has not been fully elucidated. This study is to determine whether indication of PAD has a distinct impact on major adverse cardiovascular and cerebrovascular events (MACCE) and limb events in patients receiving hemodialysis. The current study included 2321 prospectively enrolled patients from the Tokyo taMA peripheral vascular intervention research ComraDE registry (UMIN-CTR no. UMIN000015100) between September 2014 and December 2016. Out of the enrolled patients, 1644 were not receiving hemodialysis (non-HD patients) and 603 were receiving hemodialysis (HD patients). A composite of all-cause death, myocardial infarction, and stroke events defined as MACCE; while limb events were defined as a composite of unscheduled major amputation, unscheduled major lower limb surgery, acute limb ischemia, unscheduled endovascular treatment, and target lesion revascularization. Propensity score matching was applied among the non-HD and HD patients, in whole group, IC subgroup, and CLTI subgroup. Kaplan-Meier analysis was used for the analysis of outcomes for the whole group, IC subgroup, and the CLTI subgroup. CLTI accounted for 75.5% of the HD patients, whereas IC was 63.4% in the non-HD patients. The HD patients exhibited more frequent below-the-knee lesions than those in the non-HD patients in both IC (p = 0.01) and CLTI (p < 0.001) subgroups. Overall, HD patients exhibited a significantly higher rate of MACCE at 24 months. This trend was similar for limb events in whole group and CLTI subgroup. In contrast, no significant differences in outcomes for limb events were found in IC subgroup. Although, prognosis after EVT in HD patients were significantly worse than non-HD patients, comparable outcome with non-HD patients was observed in the patients treated for IC. Clinical trial registration: This study was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR No. UMIN000015100).

Comparison of the incidence of depression before and after endovascular treatment in patients with lower limb peripheral artery disease.

Depression is a chronic illness that affects mood, physical health, and overall vitality and quality of life. Depression has been associated with an increased risk of all-cause and cardiovascular mortality among patients with peripheral arterial disease (PAD). Therefore, this study aimed to compare the incidence of depression before and after endovascular treatment in patients with lower limb PAD. This is an important clinical issue considering the worldwide increase in PAD with the aging population and the known negative impact of depression on recovery. This was a retrospective sub-analysis of data from the Tokyo Peripheral Vascular Intervention Study using the TOMA-CODE registry. The presence and extent of depressive symptoms were evaluated using the patient health questionnaire (PHQ-9), with a depressive tendency score of ≥ 5. The PHQ-9 score was evaluated before endovascular treatment (EVT) and at 4 (± 1) weeks after EVT. The study population consisted of 87 patients who completed the PHQ-9 before EVT, with 76 completing the post-EVT PHQ-9. Of these 76, 19 had a pre-EVT score ≥ 5. Overall, there was no difference in the pre- and post-EVT scores (P = 0.091). There was no significant change in the 19 patients with a pre-EVT score ≥ 5 (mean 9.2 ± 4.4); however, there was a tendency to improve in the pre- to post-EVT score (mean, 6.9 ± 5.2; P = 0.059). Diabetes was a significant negative factor for pre- to post-EVT score improvement (P = 0.023). Overall, symptoms of depression showed the tendency to improve at 30 days post-EVT. However, diabetes was associated with lower improvement in symptoms.

The relationship between coronary stent strut thickness and the incidences of clinical outcomes after drug-eluting stent implantation: A systematic review and meta-regression analysis.

BACKGROUND: Drug-eluting stents (DESs) have been developed with thinner stent struts, and more biocompatible polymers and anti-proliferative drugs to improve the clinical performance. However, it remains unclear whether thinner struts are associated with favorable short- and long-term clinical outcomes such as target lesion revascularization (TLR), periprocedural myocardial infarction (PMI), and stent thrombosis (ST). METHODS: We searched MEDLINE, Embase and other online sources for randomized controlled trials (RCTs) comparing clinical outcomes between a DES and other stent(s), with independent clinical event adjudication. We investigated stent-related events (TLR, PMI, and ST) in 5 years. Each outcome was analyzed with random-effects meta-regression model against strut thickness, then adjusted for DES generation and patient and lesion characteristics. RESULTS: We identified 49 RCTs enrolling 97,465 patients, of which strut thickness ranged from 60 to 140 µm. Incidences of 1-year TLR, PMI, and early ST were reduced with thinner stent struts, when adjusted for stent generation (adjusted relative risk [RR] per 10 µm increase 1.12 [95% CI 1.04-1.21], 1.15 [95% CI 1.05-1.26], and 1.15 [95% CI 1.06-1.25], respectively). Strut thickness was not independently associated with incidences of 5-year TLR, late and very late ST. In addition, early DESs contributed to a higher incidence of very late ST (adjusted RR 2.97 [95% CI 1.36-6.50]). CONCLUSIONS: In this meta-regression analysis, a thinner strut thickness was associated with reduced incidences of early stent-related adverse events (1-year TLR, PMI, and early ST), but not with later events (5-year TLR, late ST, and very late ST).

Impact of Tweeting Summaries by the Japanese Circulation Society Official Account on Article Viewership　- Pilot Trial.

BACKGROUND: The impact of promotional tweets from the official journal account (forCirculation JournalandCirculation Reports) on article viewership has not been thoroughly evaluated.Methods and Results:We retrospectively collected journal viewership data forCirculation JournalandCirculation Reportsfrom March 2021 to August 2021. We compared viewership between articles with (n=15) and without (n=250) tweets. After 1 : 4 propensity score matching (15 tweeted articles and 60 non-tweeted matched controls), journal viewership metrics within 7 days of the tweeting date (and the hypothetical tweeting date), was larger in tweeted articles than non-tweeted articles (median [interquartile range] Abstract page views 89 [60-104] vs. 18 [8-41]). CONCLUSIONS: This pilot study suggests a positive relationship between journal-posted promotional tweets and article viewership.

Quality Indicators in Patient Referral Documents for Heart Failure in Japan.

This study examined quality indicators (QIs) for heart failure (HF) in patients' referral documents (PRDs).We conducted a nationwide questionnaire survey to identify information that general practitioners (GPs) would like hospital cardiologists (HCs) to include in PRDs and that HCs actually include in PRDs. The percentage of GPs that desired each item included in PRDs was converted into a deviation score, and items with a deviation score of ≥ 50 were defined as QIs. We rated the quality of PRDs provided by HCs based on QI assessment.We received 281 responses from HCs and 145 responses from GPs. The following were identified as QIs: 1) HF cause; 2) B-type natriuretic peptide (BNP) or N-terminal pro-BNP concentration; 3) left ventricular ejection fraction or echocardiography; 4) body weight; 5) education of patients and their families on HF; 6) physical function, and 7) functions of daily living. Based on QI assessment, only 21.7% of HCs included all seven items in their PRDs. HCs specializing in HF and institutions with many full-time HCs were independently associated with including the seven items in PRDs.The quality of PRDs for HF varies among physicians and hospitals, and standardization is needed based on QI assessment.

Prognostic Implications of Reductions in Heart Rates in Patients With Acute Heart Failure and Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia in patients with acute heart failure (AHF). Heart rate (HR) also changes significantly over time. However, the association between changes in HR in AF patients and prognosis is uncertain.Methods and Results:We investigated the association between HR reduction in AF achieved within 48 h of admission and 60-day mortality in patients with AHF from the REALITY-AHF study. The percentage HR (%HR) reduction was calculated as (baseline HR-HR at 48 h) / baseline HR × 100. The primary endpoint was 60-day all-cause mortality. In 468 patients with confirmed AF at both admission and 48 h after admission, the median HR at these time points was 105±31 and 84±18 beats/min, respectively. The median %HR reduction was 15.4% (interquartile range 2.2-31.4%). During the 60 days of admission, 39 deaths (8.3%) were recorded, and the %HR reduction within 48 h was significantly associated with 60-day mortality in the unadjusted model (hazard ratio [HR] 0.85; 95% confidence interval [CI] 0.77-0.95; P=0.005) and after adjusting for other covariates (HR 0.81; 95% CI 0.68-0.96; P=0.016).Furthermore, the %HR reduction was associated with a significant reduction in 60-day mortality in patients with higher baseline HR. CONCLUSIONS: %HR reduction is associated with a better short-term prognosis in patients with AHF presenting with AF, particularly in those with a rapid ventricular response.

Differences in Priorities for Heart Failure Management Between Cardiologists and General Practitioners in Japan.

BACKGROUND: The purpose of this study was to clarify the current status and issues of community collaboration in heart failure (HF) using a nationwide questionnaire survey.Methods and Results:We conducted a survey among hospital cardiologists and general practitioners (GPs) using a web-based questionnaire developed with the Delphi method, to assess the quality of community collaboration in HF. We received responses from 46 of the 47 prefectures in Japan, including from 281 hospital cardiologists and 145 GPs. The survey included the following characteristics and issues regarding community collaboration. (1) Hospital cardiologists prioritized medical intervention for preventing HF hospitalization and death whereas GPs prioritized supporting the daily living of patients and their families. (2) Hospital cardiologists have not provided information that meets the needs of GPs, and few regions have a community-based system that allows for the sharing of information about patients with HF. (3) In the transition to home care, there are few opportunities for direct communication between hospitals and community staff, and consultation systems are not well developed. CONCLUSIONS: The current study clarified the real-world status and issues of community collaboration for HF in Japan, especially the differences in priorities for HF management between hospital cardiologists and GPs. Our data will contribute to the future direction and promotion of community collaboration in HF management.

Use of PCR in the diagnosis of pericardial amebiasis: a case report and systematic review of the literature.

BACKGROUND: Entamoeba histolytica (E. histolytica) is rarely identified as a cause of amebic pericarditis. We report a case of amebic pericarditis complicated by cardiac tamponade, in which the diagnosis was missed initially and was made retrospectively by polymerase chain reaction (PCR) testing of a stored sample of pericardial fluid. Furthermore, we performed a systematic review of the literature on amebic pericarditis. CASE PRESENTATION: A 71-year-old Japanese man who had a history of sexual intercourse with several commercial sex workers 4 months previously, presented to our hospital with left chest pain and cough. He was admitted on suspicion of pericarditis. On hospital day 7, he developed cardiac tamponade requiring urgent pericardiocentesis. The patient's symptoms temporarily improved, but 1 month later, he returned with fever and abdominal pain, and multiple liver lesions were found in the right lobe. Polymerase chain reaction of the aspiration fluid of the liver lesion and pericardial and pleural fluid stored from the previous hospitalization were all positive for E. histolytica. Together with the positive serum antibody for E. histolytica, a diagnosis of amebic pericarditis was made. Notably, the diagnosis was missed initially and was made retrospectively by performing PCR testing. The patient improved with metronidazole 750 mg thrice daily for 14 days, followed by paromomycin 500 mg thrice daily for 10 days. CONCLUSIONS: This case suggests that, although only 122 cases of amebic pericarditis have been reported, clinicians should be aware of E. histolytica as a potential causative pathogen. The polymerase chain reaction method was used to detect E. histolytica in the pericardial effusion and was found to be useful for the diagnosis of amebic pericarditis in addition to the positive results for the serum antibody testing for E. histolytica. Because of the high mortality associated with delayed treatment, prompt diagnosis should be made.

Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death globally. Recently, dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) were approved for treating people with type 2 diabetes mellitus. Although metformin remains the first-line pharmacotherapy for people with type 2 diabetes mellitus, a body of evidence has recently emerged indicating that DPP4i, GLP-1RA and SGLT2i may exert positive effects on patients with known CVD. OBJECTIVES: To systematically review the available evidence on the benefits and harms of DPP4i, GLP-1RA, and SGLT2i in people with established CVD, using network meta-analysis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and the Conference Proceedings Citation Index on 16 July 2020. We also searched clinical trials registers on 22 August 2020. We did not restrict by language or publication status. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) investigating DPP4i, GLP-1RA, or SGLT2i that included participants with established CVD. Outcome measures of interest were CVD mortality, fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, all-cause mortality, hospitalisation for heart failure (HF), and safety outcomes. DATA COLLECTION AND ANALYSIS: Three review authors independently screened the results of searches to identify eligible studies and extracted study data. We used the GRADE approach to assess the certainty of the evidence. We conducted standard pairwise meta-analyses and network meta-analyses by pooling studies that we assessed to be of substantial homogeneity; subgroup and sensitivity analyses were also pursued to explore how study characteristics and potential effect modifiers could affect the robustness of our review findings. We analysed study data using the odds ratios (ORs) and log odds ratios (LORs) with their respective 95% confidence intervals (CIs) and credible intervals (Crls), where appropriate. We also performed narrative synthesis for included studies that were of substantial heterogeneity and that did not report quantitative data in a usable format, in order to discuss their individual findings and relevance to our review scope. MAIN RESULTS: We included 31 studies (287 records), of which we pooled data from 20 studies (129,465 participants) for our meta-analysis. The majority of the included studies were at low risk of bias, using Cochrane's tool for assessing risk of bias. Among the 20 pooled studies, six investigated DPP4i, seven studied GLP-1RA, and the remaining seven trials evaluated SGLT2i. All outcome data described below were reported at the longest follow-up duration. 1. DPP4i versus placebo Our review suggests that DPP4i do not reduce any risk of efficacy outcomes: CVD mortality (OR 1.00, 95% CI 0.91 to 1.09; high-certainty evidence), myocardial infarction (OR 0.97, 95% CI 0.88 to 1.08; high-certainty evidence), stroke (OR 1.00, 95% CI 0.87 to 1.14; high-certainty evidence), and all-cause mortality (OR 1.03, 95% CI 0.96 to 1.11; high-certainty evidence). DPP4i probably do not reduce hospitalisation for HF (OR 0.99, 95% CI 0.80 to 1.23; moderate-certainty evidence). DPP4i may not increase the likelihood of worsening renal function (OR 1.08, 95% CI 0.88 to 1.33; low-certainty evidence) and probably do not increase the risk of bone fracture (OR 1.00, 95% CI 0.83 to 1.19; moderate-certainty evidence) or hypoglycaemia (OR 1.11, 95% CI 0.95 to 1.29; moderate-certainty evidence). They are likely to increase the risk of pancreatitis (OR 1.63, 95% CI 1.12 to 2.37; moderate-certainty evidence). 2. GLP-1RA versus placebo Our findings indicate that GLP-1RA reduce the risk of CV mortality (OR 0.87, 95% CI 0.79 to 0.95; high-certainty evidence), all-cause mortality (OR 0.88, 95% CI 0.82 to 0.95; high-certainty evidence), and stroke (OR 0.87, 95% CI 0.77 to 0.98; high-certainty evidence). GLP-1RA probably do not reduce the risk of myocardial infarction (OR 0.89, 95% CI 0.78 to 1.01; moderate-certainty evidence), and hospitalisation for HF (OR 0.95, 95% CI 0.85 to 1.06; high-certainty evidence). GLP-1RA may reduce the risk of worsening renal function (OR 0.61, 95% CI 0.44 to 0.84; low-certainty evidence), but may have no impact on pancreatitis (OR 0.96, 95% CI 0.68 to 1.35; low-certainty evidence). We are uncertain about the effect of GLP-1RA on hypoglycaemia and bone fractures. 3. SGLT2i versus placebo This review shows that SGLT2i probably reduce the risk of CV mortality (OR 0.82, 95% CI 0.70 to 0.95; moderate-certainty evidence), all-cause mortality (OR 0.84, 95% CI 0.74 to 0.96; moderate-certainty evidence), and reduce the risk of HF hospitalisation (OR 0.65, 95% CI 0.59 to 0.71; high-certainty evidence); they do not reduce the risk of myocardial infarction (OR 0.97, 95% CI 0.84 to 1.12; high-certainty evidence) and probably do not reduce the risk of stroke (OR 1.12, 95% CI 0.92 to 1.36; moderate-certainty evidence). In terms of treatment safety, SGLT2i probably reduce the incidence of worsening renal function (OR 0.59, 95% CI 0.43 to 0.82; moderate-certainty evidence), and probably have no effect on hypoglycaemia (OR 0.90, 95% CI 0.75 to 1.07; moderate-certainty evidence) or bone fracture (OR 1.02, 95% CI 0.88 to 1.18; high-certainty evidence), and may have no impact on pancreatitis (OR 0.85, 95% CI 0.39 to 1.86; low-certainty evidence). 4. Network meta-analysis Because we failed to identify direct comparisons between each class of the agents, findings from our network meta-analysis provided limited novel insights. Almost all findings from our network meta-analysis agree with those from the standard meta-analysis. GLP-1RA may not reduce the risk of stroke compared with placebo (OR 0.87, 95% CrI 0.75 to 1.0; moderate-certainty evidence), which showed similar odds estimates and wider 95% Crl compared with standard pairwise meta-analysis. Indirect estimates also supported comparison across all three classes. SGLT2i was ranked the best for CVD and all-cause mortality. AUTHORS' CONCLUSIONS: Findings from both standard and network meta-analyses of moderate- to high-certainty evidence suggest that GLP-1RA and SGLT2i are likely to reduce the risk of CVD mortality and all-cause mortality in people with established CVD; high-certainty evidence demonstrates that treatment with SGLT2i reduce the risk of hospitalisation for HF, while moderate-certainty evidence likely supports the use of GLP-1RA to reduce fatal and non-fatal stroke. Future studies conducted in the non-diabetic CVD population will reveal the mechanisms behind how these agents improve clinical outcomes irrespective of their glucose-lowering effects.

Differences in aggressive treatments during the actively dying phase in patients with cancer and heart disease: an exploratory study using the sampling dataset of the National Database of Health Insurance Claims.

Despite the recent attention given to palliative care for patients with heart disease, data about the treatments in their actively dying phase are not sufficiently elaborated. In this study, we used the sampling dataset of a national database to compare the aggressive treatments performed in patients with cancer and those with heart disease. We only included patients deceased in January or July from 2011 to 2015, using the Diagnosis Procedure Combination sampling dataset of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Patients who were discharged within the first 10 days of each month were excluded. We explored and compared aggressive treatments such as cardiopulmonary resuscitation and intensive care utilization, performed within seven days before death in cancer patients. We used 10,637 (0.4% of the dataset) deceased target population (40.0% female), with 7844 (73.7%) and 2793 (26.3%) being the proportion of cancer and heart disease patients, respectively. Aggressive treatments and procedures such as cardiopulmonary resuscitation (18.4%), intensive care utilization (5.4%), use of inotropes (43.4%), use of respirators (29.1%), and dialysis (4.5%) were frequently observed in heart disease patients. These associations remained after adjusting for age, sex, and disease severity. This study indicates the possible use of an NDB sampling dataset to evaluate the aggressive treatments and procedures in the actively dying phase in both heart disease and cancer patients. Our results showed the differences in aggressive treatment strategies in the actively dying phase between patients with cancer and those with heart disease.

Realization and personalization by facing fatality: A grounded theory of developing the view of dying in people with heart failure.

AIM: To explore how people with heart failure develop and change their views of dying and death. DESIGN: A Straussian grounded theory approach. METHODS: Purposive and theoretical sampling were used. Data collection and analysis were repeated until reaching data saturation using the constant comparative method. We conducted semi-structured interviews between January 2019 and July 2020 with 24 people with heart failure from a university and a community hospital in Japan. RESULTS: Initially, participants' views of dying and death were unrelated to their disease. After the first turning point, namely the confirmation of the deterioration and incurability of the disease, their views became related to their own disease, adding to the suffering caused by the exacerbated symptoms. After the second turning point, namely when participants became tormented by the inevitability of death, they added their struggles with physical, psychological, and spiritual pain owing to medical interventions to their views of dying and death. Only a few participants reached the last stage of this process as it was emotionally distressing; some chose not to proceed to the next stage. CONCLUSION: Participants develop their views of dying and death gradually and in stages while they experience two turning points. Healthcare providers need to address this process while keeping in mind that proceeding this process requires some turning points, and it can be painful. IMPACT: This study provides a theoretical framework on the development of the views regarding dying and death of people with heart failure; it showed that these people need some turning points and to pass through stages to develop/individualize their views, and that this process is inherently distressing. This theory provides a cornerstone for healthcare professionals to understand the disease-specific transition in views of dying and psychological readiness, and it may help establish a therapeutic relationship that includes advance care planning.