Prognostic impact of heart failure admission in survivors of acute myocardial infarction.

AIMS: The incidence and prognosis of symptomatic heart failure following acute myocardial infarction (AMI) in the primary percutaneous coronary intervention era have rarely been reported in the literature. This study aimed to (i) determine the incidence of heart failure admission among AMI survivors, (ii) compare 1 year outcomes between patients with heart failure admission and those without, and (iii) identify the independent risk factors associated with heart failure admission. METHODS AND RESULTS: The Japan Acute Myocardial Infarction Registry is a prospective multicentre registry from which data on consecutively enrolled patients with AMI from 50 institutions between 2015 and 2017 were obtained. Among the 3411 patients enrolled, 3226 who survived until discharge were included in this study. The primary endpoint was all-cause mortality. The secondary endpoints were major adverse cardiovascular events (defined as cardiovascular mortality, non-fatal myocardial infarction, or non-fatal cerebral infarction) and major bleeding events corresponding to Bleeding Academic Research Consortium Type 3 or 5. Clinical outcomes were compared between the patients who were and were not admitted for heart failure. Over a median follow-up of 12 months, 124 patients (3.8%) were admitted due to heart failure. Independent risk factors for heart failure admission included older age, female sex, Killip class ≥2 on admission, left ventricular ejection fraction <40%, estimated glomerular filtration rate ≤30 mL/min/1.73 m2, a history of malignancy, and non-use of angiotensin-converting enzyme inhibitors at discharge. The cumulative incidence of all-cause mortality was significantly higher in the heart failure admission group than in the no heart failure admission group (11.3% vs. 2.5%, P < 0.001). The rates of major adverse cardiovascular events (16.9% vs. 2.7%, P < 0.001) and major bleeding (6.5% vs. 1.6%, P < 0.001) were significantly higher in the heart failure admission group. Heart failure admission was associated with a higher risk of all-cause mortality, even after adjusting for potential confounders (adjusted hazard ratio: 2.41, 95% confidence interval: 1.33-4.39, P = 0.004). CONCLUSIONS: Utilizing real-world data of the contemporary percutaneous coronary intervention era from the Japan Acute Myocardial Infarction Registry database, this study demonstrates that the heart failure admission of AMI survivors was significantly associated with higher all-cause mortality rates.

Versatile extracellular vesicle-mediated information transfer: intercellular synchronization of differentiation and of cellular phenotypes, and future perspectives.

In recent years, extracellular vesicles (EVs) have attracted significant attention as carriers in intercellular communication. The vast array of information contained within EVs is critical for various cellular activities, such as proliferation and differentiation of multiple cell types. Moreover, EVs are being employed in disease diagnostics, implicated in disease etiology, and have shown promise in tissue repair. Recently, a phenomenon has been discovered in which cellular phenotypes, including the progression of differentiation, are synchronized among cells via EVs. This synchronization could be prevalent in widespread different situations in embryogenesis and tissue organization and maintenance. Given the increasing research on multi-cellular tissues and organoids, the role of EV-mediated intercellular communication has become increasingly crucial. This review begins with fundamental knowledge of EVs and then discusses recent findings, various modes of information transfer via EVs, and synchronization of cellular phenotypes.

Modeling mutation-specific arrhythmogenic phenotypes in isogenic human iPSC-derived cardiac tissues.

Disease modeling using human induced pluripotent stem cells (hiPSCs) from patients with genetic disease is a powerful approach for dissecting pathophysiology and drug discovery. Nevertheless, isogenic controls are required to precisely compare phenotypic outcomes from presumed causative mutations rather than differences in genetic backgrounds. Moreover, 2D cellular models often fail to exhibit authentic disease phenotypes resulting in poor validation in vitro. Here we show that a combination of precision gene editing and bioengineered 3D tissue models can establish advanced isogenic hiPSC-derived cardiac disease models, overcoming these drawbacks. To model inherited cardiac arrhythmias we selected representative N588D and N588K missense mutations affecting the same codon in the hERG potassium channel gene KCNH2, which are reported to cause long (LQTS) and short (SQTS) QT syndromes, respectively. We generated compound heterozygous variants in normal hiPSCs, and differentiated cardiomyocytes (CMs) and mesenchymal cells (MCs) to form 3D cardiac tissue sheets (CTSs). In hiPSC-derived CM monolayers and 3D CTSs, electrophysiological analysis with multielectrode arrays showed prolonged and shortened repolarization, respectively, compared to the isogenic controls. When pharmacologically inhibiting the hERG channels, mutant 3D CTSs were differentially susceptible to arrhythmic events than the isogenic controls. Thus, this strategy offers advanced disease models that can reproduce clinically relevant phenotypes and provide solid validation of gene mutations in vitro.

Inequalities in Resources for Preschool-Age Children by Parental Education: Evidence from Six Advanced Industrialized Countries.

This paper provides new evidence on inequalities in resources for children age 3-4 by parental education using harmonized data from six advanced industrialized countries-United States, United Kingdom, France, Germany, Netherlands, and Japan-that represent different social welfare regime types. We analyze inequalities in two types of resources for young children-family income, and center-based child care-applying two alternative measures of parental education-highest parental education, and maternal education. We hypothesize that inequalities in resources by parental education will be less pronounced in countries where social policies are designed to be more equalizing. The results provide partial support for this hypothesis: the influence of parental education on resources for children does vary by the social policy context, although not in all cases. We also find that the measurement of parental education matters: income disparities are smaller under a maternal-only definition whereas child care disparities are larger. Moreover, the degree of divergence between the two sets of estimates differs across countries. We provide some of the first systematic evidence about how resources for young children vary depending on parents' education and the extent to which such inequalities are buffered by social policies. We find that while early inequalities are a fact of life in all six countries, the extent of those inequalities varies considerably. Moreover, the results suggest that social policy plays a role in moderating the influence of parental education on resources for children.

Adult-onset idiopathic peripheral pulmonary artery stenosis.

BACKGROUND: Peripheral pulmonary artery stenosis (PPS) refers to stenosis of the pulmonary artery from the trunk to the peripheral arteries. Although paediatric PPS is well described, the clinical characteristics of adult-onset idiopathic PPS have not been established. Our objectives in this study were to characterise the disease profile of adult-onset PPS. METHODS: We collected data in Japanese centres. This cohort included patients who underwent pulmonary angiography (PAG) and excluded patients with chronic thromboembolic pulmonary hypertension or Takayasu arteritis. Patient backgrounds, right heart catheterisation (RHC) findings, imaging findings and treatment profiles were collected. RESULTS: 44 patients (median (interquartile range) age 39 (29-57) years; 29 females (65.9%)) with PPS were enrolled from 20 centres. In PAG, stenosis of segmental and peripheral pulmonary arteries was observed in 41 (93.2%) and 36 patients (81.8%), respectively. 35 patients (79.5%) received medications approved for pulmonary arterial hypertension (PAH) and 22 patients (50.0%) received combination therapy. 25 patients (56.8%) underwent transcatheter pulmonary angioplasty. RHC data showed improvements in both mean pulmonary arterial pressure (44 versus 40 mmHg; p<0.001) and pulmonary vascular resistance (760 versus 514 dyn·s·cm-5; p<0.001) from baseline to final follow-up. The 3-, 5- and 10-year survival rates of patients with PPS were 97.5% (95% CI 83.5-99.6%), 89.0% (95% CI 68.9-96.4%) and 67.0% (95% CI 41.4-83.3%), respectively. CONCLUSIONS: In this study, patients with adult-onset idiopathic PPS presented with segmental and peripheral pulmonary artery stenosis. Although patients had severe pulmonary hypertension at baseline, they showed a favourable treatment response to PAH drugs combined with transcatheter pulmonary angioplasty.

Prevalence and Impact of Polyvascular Disease in Patients With Acute Myocardial Infarction in the Contemporary Era of Percutaneous Coronary Intervention　- Insights From the Japan Acute Myocardial Infarction Registry (JAMIR).

BACKGROUND: This post hoc subanalysis aimed to investigate the impact of polyvascular disease (PolyVD) in patients with acute myocardial infarction (AMI) in the contemporary era of percutaneous coronary intervention (PCI).Methods and Results: The Japan Acute Myocardial Infarction Registry (JAMIR), a multicenter prospective registry, enrolled 3,411 patients with AMI between December 2015 and May 2017. Patients were classified according to complications of a prior stroke and/or peripheral artery disease into an AMI-only group (involvement of 1 vascular bed [1-bed group]; n=2,980), PolyVD with one of the complications (2-bed group; n=383), and PolyVD with both complications (3-bed group; n=48). The primary endpoint was all-cause death. Secondary endpoints were major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and major bleeding. In the 1-, 2-, and 3-bed groups, the cumulative incidence of all-cause death was 6.8%, 17.5%, and 23.7%, respectively (P<0.001); that of MACE was 7.4%, 16.4%, and 33.8% (P<0.001), respectively; and that of major bleeding was 4.8%, 10.0%, and 13.9% (P<0.001), respectively. PolyVD was independently associated with all-cause death (hazard ratio [HR] 2.21; 95% confidence interval [CI], 1.48-3.29), MACE (HR 2.07; 95% CI 1.40-3.07), and major bleeding (HR 1.68; 95% CI 1.04-2.71). CONCLUSIONS: PolyVD was significantly associated with worse outcomes, including thrombotic and bleeding events, in the contemporary era of PCI in AMI patients.

Therapeutic potential of human induced pluripotent stem cell-derived cardiac tissue in an ischemic model with unloaded condition mimicking left ventricular assist device.

OBJECTIVE: This study aimed to explore the therapeutic potential of human induced pluripotent stem cell (hiPSC)-derived cardiac tissues (HiCTs) in the emerging approach of bridge to recovery for severe heart failure with ventricular assist devices. We used a rat model of heterotopic heart transplantation (HTx) to mimic ventricular assist device support and heart unloading. METHODS: HiCTs were created by inserting gelatin hydrogel microspheres between cell sheets made from hiPSC-derived cardiovascular cells. Male athymic nude rats underwent myocardial infarction (MI) and were divided into the following groups: MI (loaded, untreated control), MI + HTx (unloaded, untreated control), MI + HTx + HiCT (unloaded, treated), and MI + HiCT (loaded, treated). HiCTs were placed on the epicardium of the heart in treated groups. We evaluated HiCT engraftment, fibrosis, and neovascularization using histologic analysis. RESULTS: After 4 weeks, HiCTs successfully engrafted in 5 of 6 rats in the MI + HTx + HiCT group (83.3%). The engrafted HiCT area was greater under unloaded conditions (MI + HTx + HiCT) than loaded conditions (MI + HiCT) (P < .05). MI + HTx + HiCT had a significantly smaller infarct area compared with MI and MI + HTx. The MI + HTx + MiCT group exhibited greater vascular density in the border zone than MI and MI + HTx. HiCT treatment suppressed cardiomyocyte atrophy due to left ventricular unloading (P = .001). The protein level of muscle-specific RING finger 1, an atrophy-related ubiquitin ligase, was lower in the MI + HTx + HiCT group than in MI + HTx (P = .036). CONCLUSIONS: Transplanting HiCTs into ischemic hearts under unloaded conditions promoted engraftment, neovascularization, attenuated infarct remodeling, and suppressed myocyte atrophy. These results suggest that HiCT treatment could contribute to future advancements in bridge to recovery.

Diagnosis and Prognostic Value of the Underlying Cause of Acute Coronary Syndrome in Optical Coherence Tomography-Guided Emergency Percutaneous Coronary Intervention.

Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.

Prognostic Values of Fractional Flow Reserve Based on Clinical Outcomes in Patients on Chronic Hemodialysis.

The fractional flow reserve (FFR) cut-off values of 0.75 or 0.8 have been widely used; however, whether they apply to patients on hemodialysis remains unknown. We aimed to investigate the cut-off value of FFR associated with clinical outcomes in patients on hemodialysis. Using the Japanese multicenter registry, we analyzed data of patients on hemodialysis with measured FFR between January 2010 and December 2016. Survival classification and regression tree analysis for the composite primary outcome of cardiovascular mortality, myocardial infarction, and target vessel revascularization revealed a threshold FFR of 0.83. Multivariate Cox regression analyses were performed for the clinical outcomes. Additionally, the primary outcome was analyzed using propensity score matching by dividing the patients into complete and incomplete revascularization groups according to the presence of residual lesions with an FFR of ≤0.83 after the intervention. Of the 212 included patients, 112 (52.8%) had lesions with an FFR of ≤0.83. After adjusting for confounders, an FFR of ≤0.83 was associated with a higher risk for the primary outcome (adjusted hazard ratio 2.01, 95% confidence interval 1.11 to 3.66, p = 0.021). Propensity score matching showed that complete revascularization for lesions with an FFR of ≤0.83 was associated with a reduced risk for the primary outcome compared with incomplete revascularization (hazard ratio 0.38, 95% confidence interval 0.20 to 0.71, log-rank p = 0.0016). In conclusion, an FFR of ≤0.83 was an independent predictor of clinical events in patients on hemodialysis. Furthermore, complete revascularization was associated with better clinical outcomes. Thus, this population may require a distinct FFR cut-off value.

Extracellular vesicles and microRNAs in the regulation of cardiomyocyte differentiation and proliferation.

Cardiomyocyte differentiation and proliferation are essential processes for the regeneration of an injured heart. In recent years, there have been several reports highlighting the involvement of extracellular vesicles (EVs) in cardiomyocyte differentiation and proliferation. These EVs originate from mesenchymal stem cells, pluripotent stem cells, and heart constituting cells (cardiomyocytes, cardiac fibroblasts, cardiac progenitor cells, epicardium). Numerous reports also indicate the involvement of microRNAs (miRNAs) in cardiomyocyte differentiation and proliferation. Among them, miRNA-1, miRNA-133, and miRNA-499, recently demonstrated to promote cardiomyocyte differentiation, and miRNA-199, shown to promote cardiomyocyte proliferation, were found effective in various studies. MiRNA-132 and miRNA-133 have been identified as cargo in EVs and are reported to induce cardiomyocyte differentiation. Similarly, miRNA-30a, miRNA-100, miRNA-27a, miRNA-30e, miRNA-294 and miRNA-590 have also been identified as cargo in EVs and are shown to have a role in the promotion of cardiomyocyte proliferation. Regeneration of the heart by EVs or artificial nanoparticles containing functional miRNAs is expected in the future. In this review, we outline recent advancements in understanding the roles of EVs and miRNAs in cardiomyocyte differentiation and proliferation. Additionally, we explore the related challenges when utilizing EVs and miRNAs as a less risky approach to cardiac regeneration compared to cell transplantation.

Percutaneous coronary intervention for ST-elevation myocardial infarction complicated by cardiogenic shock in a super-aging society.

AIMS: ST-segment elevation myocardial infarction complicated by cardiogenic shock (STEMICS) is associated with substantial mortality. As life expectancy increases, percutaneous coronary intervention (PCI) is being performed more frequently, even in elderly patients with acute myocardial infarction (AMI). This study sought to investigate the characteristics and impact of PCI on in-hospital mortality in patients with STEMICS. METHODS AND RESULTS: The Japan AMI Registry (JAMIR) is a retrospective, nationwide, real-world database. Among 46 242 patients with AMI hospitalized in 2011-2016, 2760 patients with STEMICS (median age, 72 years) were studied. We compared 2396 (86.8%) patients who underwent PCI with 364 (13.2%) patients who did not. The percentage of mechanical circulatory support use in patients with STEMICS was 69.3% and in-hospital mortality was 34.6%. Compared with patients who did not undergo PCI, patients undergoing PCI were younger and had a higher rate of intra-aortic balloon pump use. A higher proportion was male or current smokers. In-hospital mortality was significantly lower in the PCI group than in the no-PCI group (31.3% vs. 56.0%, P < 0.001). Percutaneous coronary intervention was independently associated with lower in-hospital mortality [adjusted odds ratio (OR), 0.508; 95% confidence interval (CI), 0.347-0.744]. In 789 (28.6%) patients aged ≥80 years, PCI was associated with fewer in-hospital cardiac deaths (adjusted OR, 0.524; 95% CI, 0.281-0.975), but was not associated with in-hospital mortality (adjusted OR, 0.564; 95% CI, 0.300-1.050). CONCLUSION: In Japan, PCI was effective in reducing in-hospital cardiac death in elderly patients with STEMICS. Age alone should not preclude potentially beneficial invasive therapy.

Preoperative planning for transaortic septal myectomy using cardiac computed tomography in patients with subaortic septal hypertrophy associated with aortic stenosis: case series.

Background: Electrocardiogram-gated cardiac computed tomography (CT) imaging enables a more accurate understanding of the patient's cardiac anatomy. Preoperative planning for transaortic septal myectomy (TASM), based on cardiac CT, may be useful in patients with subaortic septal hypertrophy associated with severe aortic stenosis (AS). Case summary: Two elderly patients (age >80 years) with subaortic septal hypertrophy associated with AS underwent surgical aortic valve replacement (SAVR) and concomitant TASM after preoperative planning based on cardiac CT. Both patients showed subaortic septal hypertrophy with blood flow acceleration, left ventricular (LV) hypercontractility, and a short distance from the coaptation point of the mitral valve to the septum, resulting in possible dynamic LV outflow tract (LVOT) obstruction after resolution of AS. Optimal mid-diastolic images, selected from the 70-80% phase, were used for preoperative TASM planning. Planned sizes for myectomy based on multi-planar reconstruction were 10 × 26 × 9 mm (width × length × depth) and 10 × 25 × 9 mm for patient 1 and 2, respectively, while resected tissue size was 10 × 24 × 8 mm and 9 × 24 × 8 mm in patient 1 and 2, respectively. After TASM procedure, SAVR was performed with bioprosthetic valve. Postoperative course of both patients was uneventful with no evidence of complete atrioventricular block, septal perforation, or blood flow acceleration at the LVOT. Discussion: Preoperative planning based on cardiac CT images is safe and useful for guiding adequate myectomy and preventing associated complications in patients with subaortic septal hypertrophy associated with AS.

eSPRESSO: topological clustering of single-cell transcriptomics data to reveal informative genes for spatio-temporal architectures of cells.

BACKGROUND: Bioinformatics capability to analyze spatio-temporal dynamics of gene expression is essential in understanding animal development. Animal cells are spatially organized as functional tissues where cellular gene expression data contain information that governs morphogenesis during the developmental process. Although several computational tissue reconstruction methods using transcriptomics data have been proposed, those methods have been ineffective in arranging cells in their correct positions in tissues or organs unless spatial information is explicitly provided. RESULTS: This study demonstrates stochastic self-organizing map clustering with Markov chain Monte Carlo calculations for optimizing informative genes effectively reconstruct any spatio-temporal topology of cells from their transcriptome profiles with only a coarse topological guideline. The method, eSPRESSO (enhanced SPatial REconstruction by Stochastic Self-Organizing Map), provides a powerful in silico spatio-temporal tissue reconstruction capability, as confirmed by using human embryonic heart and mouse embryo, brain, embryonic heart, and liver lobule with generally high reproducibility (average max. accuracy = 92.0%), while revealing topologically informative genes, or spatial discriminator genes. Furthermore, eSPRESSO was used for temporal analysis of human pancreatic organoids to infer rational developmental trajectories with several candidate 'temporal' discriminator genes responsible for various cell type differentiations. CONCLUSIONS: eSPRESSO provides a novel strategy for analyzing mechanisms underlying the spatio-temporal formation of cellular organizations.

Predictors of procedural complications in balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension.

BACKGROUND: Balloon pulmonary angioplasty (BPA) is an effective treatment for inoperable chronic thromboembolic pulmonary hypertension, with good results reported for residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). However, BPA is associated with complications, such as pulmonary artery perforation and vascular injury, which can lead to critical pulmonary hemorrhage requiring embolization and mechanical ventilation. Furthermore, the risk factors for occurrence of complications in BPA are unclear; therefore, this study aimed to evaluate predictors of procedural complications in BPA. METHODS: In this retrospective study, we collected clinical data (patient characteristics, details of medical therapy, hemodynamic parameters, and details of the BPA procedure) from 321 consecutive sessions involving 81 patients who underwent BPA. Procedural complications were evaluated as endpoints. RESULTS: BPA for residual PH after PEA was performed in 141 sessions (43.9 %), which involved 37 patients. Procedural complications were observed in 79 sessions (24.6 %), including severe pulmonary hemorrhage requiring embolization in 29 sessions (9.0 % of all sessions). No patients experienced severe complications requiring intubation with mechanical ventilation or extracorporeal membrane oxygenation. Age ≥ 75 years and mean pulmonary artery pressure ≥ 30 mmHg were independent predictors of procedural complications. Residual PH after PEA was a significant predictor of severe pulmonary hemorrhage requiring embolization (adjusted odds ratio, 3.048; 95 % confidence interval, 1.042-8.914, p = 0.042). CONCLUSIONS: Older age, high pulmonary artery pressure, and residual PH after PEA increase the risk of severe pulmonary hemorrhage requiring embolization in BPA.

Long-term outcome of chronic thromboembolic pulmonary hypertension using direct oral anticoagulants and warfarin: a Japanese prospective cohort study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) requires lifelong anticoagulation. Long-term outcomes of CTEPH under current anticoagulants are unclear. OBJECTIVES: The CTEPH AC registry is a prospective, nationwide cohort study comparing the safety and effectiveness of direct oral anticoagulants (DOACs) and warfarin for CTEPH. PATIENTS/METHODS: Patients with CTEPH, both tre atment-naïve and on treatment, were eligible for the registry. Inclusion criteria were patients aged ≥20 years and those who were diagnosed with CTEPH according to standard guidelines. Exclusion criteria were not specified. The primary efficacy outcome was a composite morbidity, and mortality outcome comprised all-cause death, rescue reperfusion therapy, initiation of parenteral pulmonary vasodilators, and worsened 6-minute walk distance and WHO functional class. The safety outcome was clinically relevant bleeding, including major bleeding. RESULTS: Nine hundred twenty-seven patients on oral anticoagulants at baseline were analyzed: 481 (52%) used DOACs and 446 (48%) used warfarin. The 1-, 2-, and 3-year rates of composite morbidity and mortality outcome were comparable between the DOAC and warfarin groups (2.6%, 3.1%, and 4.2% vs 3.0%, 4.8%, and 5.9%, respectively; P = .52). The 1-, 2-, and 3-year rates of clinically relevant bleeding were significantly lower in DOACs than in the warfarin group (0.8%, 2.4%, and 2.4% vs 2.5%, 4.8%, and 6.4%, respectively; P = 0.036). Multivariable Cox proportional-hazards regression models revealed lower risk of clinically relevant bleeding in the DOAC group than the warfarin group (hazard ratio: 0.35; 95% CI: 0.13-0.91; P = .032). CONCLUSION: This registry demonstrated that under current standard of care, morbidity and mortality events were effectively prevented regardless of anticoagulants, while the clinically relevant bleeding rate was lower when using DOACs compared with warfarin.

Balloon pulmonary angioplasty followed by pulmonary endarterectomy: Combination treatment for high-surgical-risk patients with chronic thromboembolic pulmonary hypertension.

OBJECTIVES: Our goal was to evaluate the combined effects of balloon pulmonary angioplasty (BPA) followed by pulmonary endarterectomy (PEA) to treat high-surgical-risk patients with chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: This study included 58 patients with CTEPH who had pulmonary vascular resistance of ≥1000 dyn·s/cm5, mean pulmonary arterial pressure (mPAP) of ≥45 mmHg or mPAP of 38-44 mmHg with comorbidities. Of these, 21 patients underwent the combined therapy of BPA followed by PEA (BPA group) and 37 underwent direct PEA (non-BPA group). Preoperative and postoperative results were compared between the 2 groups. An early postoperative composite event comprised the postoperative use of extracorporeal membrane oxygenation or intra-aortic balloon pump, in-hospital death, rescue BPA, prolonged ventilation, tracheostomy, prolonged stay in the intensive care unit, deep sternal wound infection and cerebral infarction. RESULTS: Before the first intervention (before BPA or direct PEA), patients in the BPA group had a higher mPAP than those in the non-BPA group. After undergoing BPA before PEA, the BPA group demonstrated significantly decreased mPAP and pulmonary vascular resistance (43 vs 52 mmHg, P < 0.001; 636 vs 965 dyn·s/cm5, P = 0.003, respectively) and significantly increased cardiac output (4.1 vs 3.5 l/min, P = 0.041). Notably, the number of patients with the early postoperative composite event was significantly lower in the BPA group than in the non-BPA group (4.8% vs 35.1%, P = 0.011). CONCLUSIONS: Compared with direct PEA, the combination therapy of BPA followed by PEA can be a feasible and effective risk-reduction strategy for high-surgical-risk patients with CTEPH.

Clinical features and predictors of non-cardiac death in patients hospitalised for acute myocardial infarction: Insights from the Tokyo CCU network multicentre registry.

BACKGROUND: Patients with acute myocardial infarction (AMI) commonly have multiple comorbidities, and some die in hospitals due to causes other than cardiac complications. However, limited information is available on noncardiac death in patients hospitalised for AMI. Therefore, the present study was performed to determine the incidence, annual trend, clinical characteristics, and predictors of in-hospital non-cardiac death in patients with AMI using the Tokyo Cardiovascular Care Unit (CCU) network registry. METHODS: The registry included 38,589 consecutive patients with AMI who were admitted to the CCU between 2010 and 2019. The primary endpoint was in-hospital noncardiac death. Further, predictors of cardiac and non-cardiac death were identified. RESULTS: The incidence of all-cause in-hospital mortality was 7.0% (n = 2700), and the proportion of mortality was 15.6% (n = 420) and 84.4% (n = 2280) for noncardiac and cardiac causes, respectively. The proportion of noncardiac deaths did not change annually over the last decade (p = 0.66). After adjusting for all variables, age, Killip classification grade, peak creatine kinase, hemoglobin, serum creatinine, and C-reactive protein were common predictors of cardiac and non-cardiac deaths. Indicators of malnutrition, such as lower body mass index (kg/m2) [odds 0.94, 95%CI (0.90-0.97), p < 0.001] and serum low-density lipoprotein cholesterol level (per 10 mg/dl) [odds 0.92, 95%CI (0.89-0.96), p < 0.001] were the specific predictors for non-cardiac deaths. CONCLUSIONS: The incidence of in-hospital noncardiac death was significant in patients with AMI, accounting for 15.6% of all in-hospital mortalities. Thus, prevention and management of non-cardiac complications are vital to improve acute-phase outcomes, especially those with predictors of non-cardiac death.