Direct oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism.

BACKGROUND: Direct oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. METHODS: Using the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N = 88; lower GI cancer: N = 114; non-GI cancer: N = 947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model. RESULTS: The upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4 %, lower GI cancer: 15.4 %, and non-GI cancer: 11.6 %, P = 0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53 %), followed by the lower GI (24 %). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95 %CI, 1.31-3.87, P = 0.003), but that in lower GI cancer was insignificant. CONCLUSIONS: Upper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.

Relationship of interleukin-16 with different phenogroups in acute heart failure with preserved ejection fraction.

AIMS: Interleukin-16 (IL-16) has been reported to mediate left ventricular myocardial fibrosis and stiffening in patients with heart failure with preserved ejection fraction (HFpEF). We sought to elucidate whether IL-16 has a distinct impact on pathophysiology and prognosis across different subphenotypes of acute HFpEF. METHODS AND RESULTS: We analysed 211 patients enrolled in a prospective multicentre registry of acute decompensated HFpEF for whom serum IL-16 levels after stabilization were available (53% female, median age 81 [interquartile range 75-85] years). We divided this sub-cohort into four phenogroups using our established clustering algorithm. The study endpoint was all-cause death. Patients were subclassified into phenogroup 1 ('rhythm trouble' [n = 69]), phenogroup 2 ('ventricular-arterial uncoupling' [n = 49]), phenogroup 3 ('low output and systemic congestion' [n = 41]), and phenogroup 4 ('systemic failure' [n = 52]). After a median follow-up of 640 days, 38 patients had died. Among the four phenogroups, phenogroup 2 had the highest IL-16 level. The IL-16 level showed significant associations with indices of cardiac hypertrophy, diastolic dysfunction, and congestion only in phenogroup 2. Furthermore, the IL-16 level had a significant predictive value for all-cause death only in phenogroup 2 (C-statistic 0.750, 95% confidence interval 0.606-0.863, P = 0.017), while there was no association between the IL-16 level and the endpoint in the other phenogroups. CONCLUSIONS: Our results indicated that the serum IL-16 level had a significant association with indices that reflect the pathophysiology and prognosis of HFpEF in a specific phenogroup in acute HFpEF.

Low-density lipoprotein cholesterol, erythrocyte, and platelet in heart failure with preserved ejection fraction.

AIMS: Low-density lipoprotein cholesterol (LDL-C), anaemia and low platelets have been associated with worse clinical outcomes in heart failure patients. We investigated the relationship between the combination of these three components and clinical outcome in patients with heart failure with preserved ejection fraction (HFpEF). METHODS AND RESULTS: We examined the data of 1021 patients with HFpEF hospitalized with acute decompensated heart failure (HF) from the PURSUIT-HFpEF registry, a prospective, multicenter observational study. The enrolled patients were classified into four groups by an LEP (LDL-C, Erythrocyte, and Platelet) score of 0 to 3 points, with 1 point each for LDL-C, erythrocyte and platelet values less than the cut-off values as calculated by receiver operating characteristic curve analysis. The endpoint, a composite of all-cause death and HF readmission, was evaluated among the four groups. Median follow-up duration was 579 [300, 978] days. Risk of the composite endpoint significantly differed among the four groups (P < 0.001). Kaplan-Meier analysis showed that the groups with an LEP score of 2 had higher risk of the composite endpoint than those with an LEP score of 0 or 1 (P < 0.001, and P = 0.013, respectively), while those with an LEP score of 3 had higher risk than those with an LEP score of 0, 1 or 2 (P < 0.001, P < 0.001 and P = 0.020, respectively). Cox proportional hazards analysis showed that an LEP score of 3 was significantly associated with the composite endpoint (P = 0.030). Kaplan-Meier analysis showed that risk of the composite of all-cause death and HF readmission was significantly higher in low LDL values (less than the cut-off values as calculated by receiver operating characteristic curve analysis) patients with statin use than in those without statin use (log rank P = 0.002). CONCLUSIONS: LEP score, which comprehensively reflects extra-cardiac co-morbidities, is significantly associated with clinical outcomes in HFpEF patients.

The Prognostic Impact of Follow-up Cardiac MIBG Imaging on LV trajectory After Acute Decompensation.

AIMS: Cardiac metaiodobenzylguanidine (MIBG) imaging provides prognostic information in patients with heart failure. Recently, the trajectory of left ventricular ejection fraction (LVEF) has been a focus in patients with reduced LVEF admitted for acute decompensated heart failure (ADHF). We sought to investigate the prognostic value of follow-up cardiac MIBG imaging in ADHF patients with reduced LVEF in relation to LVEF trajectory. METHODS AND RESULTS: We prospectively studied 145 ADHF patients with reduced LVEF<40%. The cardiac MIBG heart-to-mediastinum ratio (late HMR) was measured on the delayed image at discharge and at the 6-month follow-up (6FUP). At 6 months after discharge, 54 (37%) patients had complete recovery of LVEF≥50% (HFcorEF), and 43 (30%) patients had partial recovery of LVEF: 40%-50% (HFparEF), while the remaining 48 (33%) patients had no functional recovery of LVEF (HFnorEF). The late HMR at 6 FUP in HFcorEF patients was significantly greater than that in HFparEF and HFnorEF patients. During a follow-up period of 4.3 ± 2.6 years, 43 patients had cardiac events, defined as the composite of readmission for worsening HF and cardiac death. Patients with lower late HMR at 6 FUP had a greater risk of cardiac events than those with higher late HMR at 6 FUP in the group with recovered LVEF, especially HFparEF, which was not observed in the HFnorEF subgroup. CONCLUSION: Follow-up MIBG imaging after discharge could provide additional prognostic information in ADHF patients with recovered left ventricular function.

Renal Endocytic Regulation of Vitamin D Metabolism during Maturation and Aging in Laying Hens.

Egg-laying hens undergo a specific and dramatic calcium metabolism to lay eggs with eggshells composed of calcium carbonate. Calcium metabolism is mainly regulated by vitamin D3. Although vitamin D3 metabolism is closely related to the deterioration of eggshell quality associated with aging and heat stress, the details of the mechanisms regulating vitamin D3 metabolism are not clear. In mammals, the vitamin D3 metabolite (25(OH)D3) produced in the liver binds to the vitamin binding protein (DBP), is subsequently taken up by renal proximal tubular cells via the endocytic receptors megalin (Meg) and cubilin (CUB), and is metabolized to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Therefore, the present study aimed to examine the expression and localization of Meg and CUB in the kidneys of immature chicks and mature and aged laying hens to prevent eggshell quality deterioration. As a result, we showed that as circulating 1,25(OH)2D3 concentrations increased from 156.0 ± 13.5 pg/mL to 815.5 ± 61.4 pg/mL with maturation in immature chicks, relative expression levels (arbitrary units; AU) of Meg and CUB mRNA in the kidneys of mature hens significantly increased 1.92- and 2.75-fold, respectively, compared to those in immature chicks. On the other hand, the Meg mRNA expression levels of mature hens did not change with age, while CUB mRNA expression levels (1.03 ± 0.11 AU) were significantly decreased compared to mature hens (2.75 ± 0.24 AU). Immunohistochemical observations showed that Meg and CUB proteins were localized to the apical membrane of renal proximal tubular epithelial cells in immature chicks, mature hens, and aged hens, and that DBP protein was observed as granular endosomes in the cytoplasm of proximal tubular cells from the apical membrane to the cell nucleus. Especially in mature hens, the endosomes were larger and more numerous than those in immature chicks. In contrast, in aged hens, DBP-containing endosomes were smaller and limited to the apical cytoplasm. These results indicate that with maturation, the expression of Meg and CUB is promoted in the renal proximal tubules of laying hens, facilitating the uptake of the 25(OH)D3-DBP complex and its conversion to 1,25(OH)2D3, and regulating calcium metabolism in eggshell formation. On the other hand, it is suggested that the age-related decrease in CUB expression suppresses the uptake of the 25(OH)D3-DBP complex in the kidney, resulting in a deterioration of eggshell quality.

The WATCH-DM risk score estimates clinical outcomes in type 2 diabetic patients with heart failure with preserved ejection fraction.

The coexistence of heart failure is frequent and associated with higher mortality in patients with type 2 diabetes (T2DM), and its management is a critical issue. The WATCH-DM risk score is a tool to predict heart failure in patients with type 2 diabetes mellitus (T2DM). We investigated whether it could estimate outcomes in T2DM patients with heart failure with preserved ejection fraction (HFpEF). The WATCH-DM risk score was calculated in 418 patients with T2DM hospitalized for HFpEF (male 49.5%, age 80 ± 9 years, HbA1c 6.8 ± 1.0%), and they were divided into the "average or lower" (≤ 10 points), "high" (11-13 points) and "very high" (≥ 14 points) risk groups. We followed patients to observe all-cause death for 386 days (median). We compared the area under the curve (AUC) of the WATCH-DM score for predicting 1-year mortality with that of the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score and of the Barcelona Bio-Heart Failure Risk (BCN Bio-HF). Among the study patients, 108 patients (25.8%) had average or lower risk scores, 147 patients (35.2%) had high risk scores, and 163 patients (39.0%) had very high risk scores. The Cox proportional hazard model selected the WATCH-DM score as an independent predictor of all-cause death (HR per unit 1.10, 95% CI 1.03 to 1.19), and the "average or lower" risk group had lower mortality than the other groups (p = 0.047 by log-rank test). The AUC of the WATCH-DM for 1-year mortality was 0.64 (95% CI 0.45 to 0.74), which was not different from that of the MAGGIC score (0.72, 95% CI 0.63 to 0.80, p = 0.08) or that of BCN Bio-HF (0.70, 0.61 to 0.80, p = 0.25). The WATCH-DM risk score can estimate prognosis in T2DM patients with HFpEF and can identify patients at higher risk of mortality.

A Rare Case of a Common Inferior Pulmonary Vein Presumed to Be a Remnant of the Common Pulmonary Vein.

A 74-year-old woman with an implanted physiological DDD pacemaker visited our department complaining of palpitations due to atrial fibrillation (AF). Catheter ablation therapy for AF was scheduled. Preoperative multidetector computed tomography showed that the inferior pulmonary vein (PV) was a common trunk, and the left and right superior PVs branched from the center of the left atrial roof. In addition, mapping of the left atrium before AF ablation revealed no potential in either the inferior PV or common trunk. We performed left and right superior PV and posterior wall isolation. After ablation, AF was not observed on pacemaker recordings.

Renal transcriptome analysis of uninephrectomized db/db mice identified a mechanism for the transition to severe diabetic nephropathy.

Diabetic nephropathy (DN), included in diabetic kidney disease (DKD), is a primary driver of end-stage renal disease (ESRD) leading to dialysis treatment. To develop new therapeutic drugs to prevent ESRD and avoid dialysis treatment, insight into DKD pathophysiology and animal models suitable for drug efficacy testing are needed. In this study, transcriptome analysis of kidneys from 26-week-old and 35-week-old uninephrectomized (UNX) db/db mice was used to identify the pathways that affect the deterioration of renal function in db/db mice. Differentially expressed genes suggested that there was increased interferon (IFN)-γ signaling during the 26 to 35-week period. Modules that changed between 26 and 35 weeks of age extracted by weighted gene co-expression network analysis (WGCNA) suggested increased the tumor necrosis factor (TNF)-α and nuclear factor-kappa B (NF-κB) signaling pathway in component cells of glomeruli. The protein-protein interaction (PPI) network analysis identified Cxcl16 as a hub gene for those signaling pathways, and it was shown that the pathways in this module changed when the glomerular filtration rate decreased in patients with DN. These results suggested the possibility that signaling mediated by Cxcl16 induced by IFN-γ and TNF-α between 26 and 35 weeks of age leads to renal fibrosis, resulting in severe disease. Drugs that target such pathways can be options for developing drugs for DN. We also think that the uninephrectomized db/db mouse can be used as an animal model of severe DKD and to evaluate efficacy in patients with DN.

The clinical relevance of mild cognitive impairment in acute heart failure: A comparison with cognitive impairment.

BACKGROUND: Although mild cognitive impairment (MCI) has received much attention as a precursor of dementia, its prognostic role has not been fully clarified in patients with heart failure (HF). METHODS AND RESULTS: We studied 274 patients admitted for acute decompensated HF. Cognitive function was evaluated using Mini Mental State Examination (MMSE). According to the previous definition, MMSE of 0-23, 24-27, and 28-30 were classified as CI (n = 132), MCI (n = 81), and normal cognitive function (n = 61). The primary endpoint was cardiac events, defined as the composite of unplanned HF hospitalization and cardiovascular mortality. During a mean follow-up period of 4.9 ±â€¯3.1 years, 145 patients experienced cardiac events. Multivariable logistic regression analysis showed that hypertension (p = 0.043), low cardiac index (p = 0.022), and low serum albumin level (p = 0.041) had a significant association with cognitive abnormalities. Both CI and MCI were significantly associated with cardiac events after Cox multivariable adjustment [CI: p = 0.001, adjusted HR 2.66 (1.48-4.77); MCI: p = 0.025, adjusted HR 1.90 (1.09-3.31), normal cognitive function group: reference]. Patients with MCI had a significantly higher risk of unplanned HF hospitalization [p = 0.033, adjusted HR 1.91 (1.05-3.47)], but not all-cause mortality (p = 0.533) or cardiovascular mortality (p = 0.920), while CI was significantly associated with all-cause mortality (p = 0.025) and cardiovascular mortality (p = 0.036). CONCLUSION: Even MCI had a significant risk of cardiac events in patients with acute decompensated HF. This risk was mainly derived from unplanned HF hospitalization.

Pathophysiological insights into machine learning-based subphenotypes of acute heart failure with preserved ejection fraction.

OBJECTIVE: The heterogeneous pathophysiology of the diverse heart failure with preserved ejection fraction (HFpEF) phenotypes needs to be examined. We aim to assess differences in the biomarkers among the phenotypes of HFpEF and investigate its multifactorial pathophysiology. METHODS: This study is a retrospective analysis of the PURSUIT-HFpEF Study (N=1231), an ongoing, prospective, multicentre observational study of acute decompensated HFpEF. In this registry, there is a predefined subcohort in which we perform multibiomarker tests (N=212). We applied the previously established machine learning-based clustering model to the subcohort with biomarker measurements to classify them into four phenotypes: phenotype 1 (n=69), phenotype 2 (n=49), phenotype 3 (n=41) and phenotype 4 (n=53). Biomarker characteristics in each phenotype were evaluated. RESULTS: Phenotype 1 presented the lowest value of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive C reactive protein, tumour necrosis factor-α, growth differentiation factor (GDF)-15, troponin T and cystatin C, whereas phenotype 2, which is characterised by hypertension and cardiac hypertrophy, showed the highest value of these markers. Phenotype 3 showed the second highest value of GDF-15 and cystatin C. Phenotype 4 presented a low NT-proBNP value and a relatively high GDF-15. CONCLUSIONS: Distinctive characteristics of biomarkers in HFpEF phenotypes would indicate differential underlying mechanisms to be elucidated. The contribution of inflammation to the pathogenesis varied considerably among different HFpEF phenotypes. Systemic inflammation substantially contributes to the pathophysiology of the classic HFpEF phenotype with cardiac hypertrophy. TRIAL REGISTRATION NUMBER: UMIN-CTR ID: UMIN000021831.

Changing Trends in Mechanical Circulatory Support Use and Outcomes in Patients Undergoing Percutaneous Coronary Interventions for Acute Coronary Syndrome Complicated With Cardiogenic Shock: Insights From a Nationwide Registry in Japan.

BACKGROUND: Temporal trends in the management of acute coronary syndrome complicated with cardiogenic shock after the revision of guideline recommendations for intra-aortic balloon pump (IABP) use and the approval of the Impella require further investigation, because their impact remains uncertain. METHODS AND RESULTS: Using the Japanese Percutaneous Coronary Intervention (J-PCI) registry database from 2019 to 2021, we identified 12 171 patients undergoing percutaneous coronary intervention for acute coronary syndrome complicated with cardiogenic shock under mechanical circulatory support. The patients were stratified into 3 groups: (1) IABP alone, (2) Impella, and (3) venoarterial extracorporeal membrane oxygenation (VA-ECMO); the VA-ECMO group was further stratified into (3a) VA-ECMO alone, (3b) VA-ECMO in combination with IABP, and (3c) VA-ECMO in combination with Impella. The quarterly prevalence and outcomes were reported. The use of IABP alone decreased significantly from 63.5% in the first quarter of 2019 to 58.3% in the fourth quarter of 2021 (P for trend=0.01). Among 4245 patients requiring VA-ECMO, the use of VA-ECMO in combination with IABP decreased significantly from 78.7% to 67.3%, whereas the use of VA-ECMO in combination with Impella increased significantly from 4.2% to 17.0% (P for trend <0.001 for both). After adjusting for the confounders, the risk difference in the fourth quarter of 2021 relative to the first quarter of 2019 for in-hospital mortality was not significant (adjusted odds ratio, 0.84 [95% CI, 0.69-1.01]). CONCLUSIONS: Our study revealed substantial changes in the use of different mechanical circulatory support modalities in acute coronary syndrome complicated with cardiogenic shock, but they did not significantly improve the outcomes.

Human leukocyte antigen-DQ risk heterodimeric haplotypes of left ventricular dysfunction in cardiac sarcoidosis: an autoimmune view of its role.

Cardiac sarcoidosis (CS) is the scarring of heart muscles by autoimmunity, leading to heart abnormalities and patients with sarcoidosis with cardiac involvements have poor prognoses. Due to the small number of patients, it is difficult to stratify all patients of CS by human leukocyte antigen (HLA) analysis. We focused on the structure of antigen-recognizing pockets in heterodimeric HLA-class II, in addition to DNA sequences, and extracted high-affinity combinations of antigenic epitopes from candidate autoantigen proteins and HLA. Four HLA heterodimer-haplotypes (DQA1*05:03/05:05/05:06/05:08-DQB1*03:01) were identified in 10 of 68 cases. Nine of the 10 patients had low left ventricular ejection fraction (< 50%). Fourteen amino-acid sequences constituting four HLA anchor pockets encoded by the HLA haplotypes were all common, suggesting DQA1*05:0X-DQB1*03:01 exhibit one group of heterodimeric haplotypes. The heterodimeric haplotypes recognized eight epitopes from different proteins. Assuming that autoimmune mechanisms might be activated by molecular mimicry, we searched for bacterial species having peptide sequences homologous to the eight epitopes. Within the peptide epitopes form the SLC25A4 and DSG2, high-homology sequences were found in Cutibacterium acnes and Mycobacterium tuberculosis, respectively. In this study, we detected the risk heterodimeric haplotypes of ventricular dysfunction in CS by searching for high-affinity HLA-class II and antigenic epitopes from candidate cardiac proteins.

ß-blockers may be detrimental in frail patients with heart failure with preserved ejection fraction.

BACKGROUND: The effectiveness of ß-blocker in patients with heart failure with preserved ejection fraction (HFpEF) remains to be determined. We aimed to clarify the association between the use of ß-blocker and prognosis according to the status of frailty. METHODS: We compared prognosis between HFpEF patients with and without ß-blockers stratified with the Clinical Frailty Scale (CFS), using data from the PURSUIT-HFpEF registry (UMIN000021831). RESULTS: Among 1159 patients enrolled in the analysis (median age, 81.4 years; male, 44.7%), 580 patients were CFS ≤ 3, while 579 were CFS ≥ 4. Use of ß-blockers was associated with a worse composite endpoint of all-cause death and heart failure readmission in patients with CFS ≥ 4 (adjusted hazard ratio (HR) 1.43, 95% CI 1.10-1.85, p = 0.007), but was not significantly associated with this endpoint in those with CFS ≤ 3 (adjusted HR 0.95, 95% CI 0.71-1.26, p = 0.719) in multivariable Cox proportional hazard models. These results were confirmed in a propensity-matched analysis (HR in those with CFS ≥ 4: 1.42, 95% CI 1.05-1.90, p = 0.020; that in those with CFS ≤ 3: 0.83, 95% CI 0.60-1.14, p = 0.249), and in an analysis in which patients were divided into CFS ≤ 4 and CFS ≥ 5. CONCLUSIONS: Use of ß-blockers was significantly associated with worse prognosis specifically in patients with HFpEF and high CFS, but not in those with low CFS. Use of ß-blockers in HFpEF patients with frailty may need careful attention.

Impact of Structural Abnormalities in Left Ventricle and Left Atrium on Clinical Outcomes in Heart Failure with Preserved Ejection Fraction.

Two key echocardiographic parameters, left ventricular mass index (LVMI) and left atrial volume index (LAVI), are important in assessing structural myocardial changes in heart failure (HF) with preserved ejection fraction (HFpEF). However, the differences in clinical characteristics and outcomes among groups classified by LVMI and LAVI values are unclear.We examined the data of 960 patients with HFpEF hospitalized due to acute decompensated HF from the PURSUIT-HFpEF registry, a prospective, multicenter observational study. Four groups were classified according to the cut-off values of LVMI and LAVI [LVMI = 95 g/m2 (female), 115 g/m2 (male) and LAVI = 34 mL/m2]. Clinical endpoints were the composite of HF readmission and all-cause death. Study endpoints among the 4 groups were evaluated. The composite endpoint occurred in 364 patients (37.9%). Median follow-up duration was 445 days. Kaplan-Meier analysis revealed significant differences in the composite endpoint among the 4 groups (P < 0.001). Cox proportional hazards analysis demonstrated that patients with increased LAVI alone were at significantly higher risk of HF readmission and the composite endpoints than those with increased LVMI alone (P = 0.030 and P = 0.024, respectively). Age, male gender, systolic blood pressure at discharge, atrial fibrillation (AF) hemoglobin, renal function, and LAVI were significant determinants of LVMI and female gender, AF, hemoglobin, and LVMI were significant determinants of LAVI.In HFpEF patients, increased LAVI alone was more strongly associated with HF readmission and the composite of HF readmission and all-cause death than those with increased LVMI alone.

A Case of Cardiac Undifferentiated Pleomorphic Sarcoma With Right Ventricular Outflow Tract Obstruction.

Malignant tumors originating from the heart are extremely rare. Here, we report a case of severe right ventricular outflow tract (RVOT) stenosis in a 67 year-old woman caused by a massive intimal sarcoma that required venous-arterial extracorporeal membrane oxygenation to support systemic circulation. Surgical resection and RVOT reconstruction with tricuspid and pulmonary valve replacement were performed. The pathological diagnosis was cardiac undifferentiated pleomorphic sarcoma. Although the patient was discharged 65 days after surgery in good condition, she subsequently died from multiple metastases detected in the early phase after surgery.

Trends in Mechanical Circulatory Support Use and Outcomes of Patients With Cardiogenic Shock in Japan, 2010 to 2020 (from a Nationwide Inpatient Database Study).

Little is known about the impact of the downgrade of guideline recommendations for intra-aortic balloon pump (IABP) use and the approval of the Impella in Japan, where IABPs have been predominantly used. This study aimed to describe the annual trends in the mechanical circulatory support (MCS) use and outcomes in patients with cardiogenic shock (CS) requiring MCS. Using the Japanese Diagnosis Procedure Combination database from July 2010 to March 2021, we identified inpatients with CS requiring MCS. The patients were stratified into 3 groups: (1) IABP alone, (2) Impella alone, and (3) extracorporeal membrane oxygenation (ECMO), regardless of IABP or Impella use. The patient characteristics and outcomes were reported by the fiscal year. Of the 160,559 eligible patients, 117,599 (73.2%) used IABP alone, 1,465 (0.9%) Impella alone, and 41,495 (25.8%) ECMO. The prevalence of the use of an IABP alone significantly decreased from 80.5% in 2010 to 65.3% in 2020 (p for trend <0.001), whereas the prevalence of the use of an Impella alone significantly increased from 0.0% to 5.0% and ECMO from 19.5% to 29.6% (p for trend <0.001 for both). In-hospital mortality significantly increased from 29.3% in 2010 to 32.6% in 2020 in the overall patients with CS requiring MCS but significantly decreased in those requiring ECMO from 73.7% to 64.1% (p for trend <0.001 for both). In conclusion, there were significant annual changes in the patterns of MCS use and clinical outcomes in patients with CS requiring MCS.

Trends in Treatment Patterns and Outcomes of Patients With Pulmonary Embolism in Japan, 2010 to 2020: A Nationwide Inpatient Database Study.

Background The impact of major changes in the treatment practice of pulmonary embolism (PE), such as limited indications for systemic thrombolysis and the introduction of direct oral anticoagulants, is not well documented. This study aimed to describe annual trends in the treatment patterns and outcomes in patients with PE. Methods and Results Using the Japanese Diagnosis Procedure Combination inpatient database from April 2010 to March 2021, we identified hospitalized patients with PE. Patients with high-risk PE were defined as those admitted for out-of-hospital cardiac arrest or who received cardiopulmonary resuscitation, extracorporeal membrane oxygenation, vasopressors, or invasive mechanical ventilation on the day of admission. The remaining patients were defined as patients with non-high-risk PE. The patient characteristics and outcomes were reported with fiscal year trend analyses. Of 88 966 eligible patients, 8116 (9.1%) had high-risk PE, and the remaining 80 850 (90.9%) had non-high-risk PE. Between 2010 and 2020, in patients with high-risk PE, the annual proportion of extracorporeal membrane oxygenation use significantly increased from 11.0% to 21.3%, whereas that of thrombolysis use significantly decreased from 22.5% to 15.5% (P for trend <0.001 for both). In-hospital mortality significantly decreased from 51.0% to 43.7% (P for trend=0.04). In patients with non-high-risk PE, the annual proportion of direct oral anticoagulant use increased from 0.0% to 38.3%, whereas that of thrombolysis use significantly decreased from 13.7% to 3.4% (P for trend <0.001 for both). In-hospital mortality significantly decreased from 7.9% to 5.4% (P for trend <0.001). Conclusions Substantial changes in the PE practice and outcomes occurred in patients with high-risk and non-high-risk PE.

Effectiveness of systemic thrombolysis on clinical outcomes in high-risk pulmonary embolism patients with venoarterial extracorporeal membrane oxygenation: a nationwide inpatient database study.

BACKGROUND: Current guidelines recommend systemic thrombolysis as the first-line reperfusion treatment for patients with high-risk pulmonary embolism (PE) who present with cardiogenic shock but do not require venoarterial extracorporeal membrane oxygenation (VA-ECMO). However, little is known about the optimal reperfusion treatment in high-risk PE patients requiring VA-ECMO. We aimed to evaluate whether systemic thrombolysis improved high-risk PE patients' outcomes who received VA-ECMO. METHODS: This was a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database from July 2010 to March 2021. We identified patients who were diagnosed with PE and received VA-ECMO on the day of admission. Patients who received systemic thrombolysis with monteplase or urokinase within two days of initiating VA-ECMO were defined as the thrombolysis group and the remaining patients as the control group. The primary outcome was in-hospital mortality and secondary outcomes were favorable neurological outcomes, length of hospital stay, VA-ECMO duration, total hospitalization cost, major bleeding, and blood transfusion volume. Propensity-score inverse probability of treatment weighting (IPTW) was performed to compare the outcomes between the groups. RESULTS: Of 1220 eligible patients, 432 (35%) received systemic thrombolysis within two days of initiating VA-ECMO. Among the unweighted cohort, patients in the thrombolysis group were less likely to have poor consciousness at admission, out-of-hospital cardiac arrest, and left heart catheterization. After IPTW, the patient characteristics were well-balanced between the two groups The crude in-hospital mortality was 52% in the thrombolysis group and 61% in the control group. After IPTW, in-hospital mortality did not differ significantly between the two groups (risk difference: - 3.0%, 95% confidence interval: - 9.6% to 3.5%). There were also no significant differences in the secondary outcomes. Sensitivity analyses showed a significant difference in major bleeding between the monteplase and control groups (risk difference: 6.9%, 95% confidence interval: 1.7% to 12.1%), excluding patients who received urokinase. There were no significant differences in the other sensitivity and subgroup analyses except for the total hospitalization cost. CONCLUSIONS: Systemic thrombolysis was not associated with reduced in-hospital mortality or increased major bleeding in the high-risk PE patients receiving VA-ECMO. However, systemic thrombolysis with monteplase was associated with increased major bleeding.