Statins use and recurrent venous thromboembolism in the direct oral anticoagulant era: insight from the COMMAND VTE Registry-2.

Statins were reported to have a potential effect of primary prevention of venous thromboembolism (VTE), although that of secondary prevention remains uncertain. To investigate the association between statins use and recurrent VTE in the current era. The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive VTE patients among 31 centers in Japan between January 2015 and August 2020. We divided the entire cohort into 2 groups according to statins use at the time of discharge; the statins (N = 865) and no statins groups (N = 4332). The statins group was older (72.9 vs. 66.7 years, P < 0.001), and less often had active cancer (22.0% vs. 30.4%, P < 0.001). The cumulative incidence of discontinuation of anticoagulation was significantly lower in the statins group (60.3% vs. 52.6%, Log-rank P < 0.001). The cumulative 5-year incidence of recurrent VTE was significantly lower in the statins group (6.8% vs. 10.1%, Log-rank P = 0.01). Even after adjusting for the confounders, the lower risk of the statins group relative to the no statins group remained significant for recurrent VTE (HR 0.65, 95% CI 0.45-0.91, P = 0.01). The cumulative 5-year incidence of major bleeding was significantly lower in the statins group (12.2% vs. 14.1%, Log-rank P = 0.04), although, after adjusting for the confounders, the risk of the statins group relative to the no statins group turned to be insignificant (HR 0.77, 95% CI 0.59-1.00, P = 0.054). In this large real-world VTE registry, statins use was significantly associated with a lower risk for the recurrent VTE in the current era.

Edoxaban for 12 Versus 3 Months in Cancer-associated Isolated Distal Deep Vein Thrombosis According to Different Doses: Insights from the ONCO DVT study.

BACKGROUND: The ONCO DVT study revealed the superiority of 12-month relative to 3-month edoxaban treatment for cancer-associated isolated distal deep vein thrombosis (DVT) regarding the thrombotic risk. METHODS: In this pre-specified subgroup analysis of the ONCO DVT study, we stratified the patients into those with a standard edoxaban dose (60 mg/day; N=151) and those with a reduced edoxaban dose (30 mg/day; N=450) and evaluated the clinical outcomes for the 12-month and 3-month treatments. RESULTS: The cumulative 12-month incidence of symptomatic recurrent venous thromboembolism was lower in the 12-month than 3-month group for both the 60 mg (1.3% vs. 11.6%, P=0.02; odds ratio [OR], 0.12; 95% CI, 0.01-0.97) and 30 mg (1.1% vs. 7.6%, P=0.002; OR, 0.14; 95% CI, 0.03-0.60) edoxaban subgroups, which was consistent across the edoxaban doses without a significant interaction (P =0.90). The 12-month cumulative incidence of major bleeding was higher in the 12-month group than 3-month group for the 60 mg edoxaban subgroup (14.3% vs. 4.4%, P=0.046; OR, 3.61; 95% CI, 0.97-13.52), whereas it did not significantly differ between the two groups for the 30 mg edoxaban subgroup (8.7% vs. 8.6%, P=0.89; OR, 0.97; 95% CI, 0.49-1.91), signaling there was a potential interaction (P=0.07). CONCLUSIONS: A 12-month edoxaban regimen for cancer-associated isolated distal DVT was consistently superior to a 3-month regimen, across the edoxaban doses for the thrombotic risk. However, caution was suggested for the standard dose of edoxaban due to the potential for an increased risk of bleeding with prolonged anticoagulation therapy.

Subclass phenotypes in patients with unprovoked venous thromboembolisms using a latent class analysis.

BACKGROUND: Patients with unprovoked venous thromboembolisms (VTEs) can be sub-classified based on the different phenotypes using a latent class analysis (LCA), which might be useful for selecting individual management strategies. METHODS: In the COMMAND VTE Registry-2 database enrolling 5197 VTE patients, the current derivation cohort consisted of 1556 patients with unprovoked VTEs. We conducted clustering with an LCA, and the patients were classified into subgroups with the highest probability. We compared the clinical characteristics and outcomes among the developed subgroups. RESULTS: This LCA model proposed 3 subgroups based on 8 clinically relevant variables, and classified 592, 813, and 151 patients as Class I, II, and III, respectively. Based on the clinical features, we named Class I the younger, Class II the older with a few comorbidities, and Class III the older with many comorbidities. The cumulative 3-year anticoagulation discontinuation rate was highest in the older with many comorbidities (Class III) (39.9 %, 36.1 %, and 48.4 %, P = 0.02). There was no significant difference in the cumulative 5-year incidence of recurrent VTEs among the 3 classes (12.8 %, 11.1 %, and 4.0 % P = 0.20), whereas the cumulative 5-year incidence of major bleeding was significantly higher in the older with many comorbidities (Class III) (7.8 %, 12.7 %, and 17.8 %, P = 0.04). CONCLUSION: The current LCA revealed that patients with unprovoked VTEs could be sub-classified into further phenotypes depending on the patient characteristics. Each subclass phenotype could have different clinical outcomes risks especially a bleeding risk, which could have a potential benefit when considering the individual anticoagulation strategies. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm COMMAND VTE Registry-2: Unique identifier, UMIN000044816 COMMAND VTE Registry: Unique identifier, UMIN000021132.

Fragility and long-term clinical outcomes in patients with venous thromboembolism receiving direct oral anticoagulants: From the COMMAND VTE REGISTRY-2.

INTRODUCTION: There is limited data on the safety of direct oral anticoagulants (DOACs) in fragile patients with venous thromboembolism (VTE). MATERIALS AND METHODS: We used the COMMAND VTE Registry-2 enrolling patients with acute symptomatic VTE. The study population consisted of 3928 patients receiving DOACs, who were divided into fragile (2136 patients) and non-fragile groups (1792 patients). Fragility was defined as patients of age ≥ 75 years, creatinine clearance level ≤ 50 ml/min, and/or body weight ≤ 50 kg. RESULTS: The fragile group significantly more often received reduced doses of DOACs compared to the non-fragile group (51 % and 19 %, P < 0.001). The cumulative 5-year incidence of major bleeding was numerically higher in the fragile group than the non-fragile group (15.0 % and 11.1 %, P = 0.052), even with no significant excess risk after adjusting for confounders (HR 1.03, 95%CI 0.81-1.31, P = 0.78). The cumulative 5-year incidence of clinically relevant bleeding was significantly higher in the fragile group than the non-fragile group (28.6 % and 19.6 %, P < 0.001), even after adjusting for confounders (HR 1.28, 95%CI 1.08-1.53, P = 0.005). There was no significant difference in cumulative 5-year incidence of recurrent VTE between the groups (9.6 % and 8.9 %, P = 0.68), which was consistent after adjusting for confounders (HR 1.13, 95%CI 0.84-1.51, P = 0.41). CONCLUSIONS: Among VTE patients receiving DOACs, fragile patients were associated with a numerically higher rate of major bleeding and a significantly increased risk of clinically relevant bleeding, but not an increased risk of recurrent VTE.

Home Treatment for Active Cancer Patients With Low-Risk Pulmonary Embolism　- A Predetermined Companion Report From the ONCO PE Trial.

BACKGROUND: Patients with appropriately selected low-risk pulmonary embolism (PE) can be treated at home, although it has been controversial whether applies to patients with cancer, who are considered not to be at low risk.Methods and Results: The current predetermined companion report from the ONCO PE trial evaluated the 3-month clinical outcomes of patients with home treatment and those with in-hospital treatment. The ONCO PE trial was a multicenter, randomized clinical trial among 32 institutions in Japan investigating the optimal duration of rivaroxaban treatment in cancer-associated PE patients with a score of 1 using the simplified version of the Pulmonary Embolism Severity Index (sPESI). Among 178 study patients, there were 66 (37%) in the home treatment group and 112 (63%) in the in-hospital treatment group. The primary endpoint of a composite of PE-related death, recurrent venous thromboembolism (VTE) and major bleeding occurred in 3 patients (4.6% [0.0-9.6%]) in the home treatment group and in 2 patients (1.8% [0.0-4.3%]) in the in-hospital treatment group. In the home treatment group, there were no cases of PE-related death or recurrent VTE, but major bleeding occurred in 3 patients (4.6% [0.0-9.6%]), and 2 patients (3.0% [0.0-7.2%]) required hospitalization due to bleeding events. CONCLUSIONS: Active cancer patients with PE of sPESI score=1 could be potential candidates for home treatment.

The impact of renal function on clinical outcomes of patients with cancer-associated isolated distal deep vein thrombosis: Insights from the ONCO DVT study.

BACKGROUND: The multicenter, open-label, randomized clinical trial ONCO DVT compared 3-month and 12-month edoxaban treatment regimens for isolated distal deep vein thrombosis (DVT) and suggested potential benefits of prolonged edoxaban treatment in terms of thrombotic risk. However, the risk-benefit balance of prolonged edoxaban treatment in patients with renal function remains unclear. OBJECTIVES: To compare the safety and efficacy of 3-month and 12-month edoxaban treatment regimens in patients with cancer-associated isolated distal DVT and different renal functions. METHODS: This pre-specified subgroup analysis of the ONCO DVT study included 601 patients divided into subgroups according to renal function using a 50 mL/min creatinine clearance (Ccr) cutoff. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) and VTE-related death at 12 months and the major secondary endpoint was major bleeding at 12 months. RESULTS: Among the 601 patients, 131 (21.8 %) comprised the renal dysfunction subgroup. The primary endpoint occurred in 6 (9.7 %) and 1 (1.4 %) patients in the 3-month and 12-month edoxaban groups in the renal dysfunction subgroup, respectively, and in 16 (6.6 %) and 2 (0.9 %) patients in the no renal dysfunction subgroup, respectively. The major secondary endpoint occurred in 9 (14.5 %) and 7 (10.1 %) patients in the 12-month and 3-month edoxaban groups in the renal dysfunction subgroup, and in 13 (5.3 %) and 21 (9.3 %) patients in the no renal dysfunction subgroup, respectively. CONCLUSIONS: A 12-month edoxaban regiment was superior to a 3-month treatment in terms of thrombotic risk irrespective of renal function. A higher bleeding risk was not identified in patients with renal dysfunction who received prolonged edoxaban treatment.

Cancer-associated venous thromboembolism in the direct oral anticoagulants era: Insight from the COMMAND VTE Registry-2.

BACKGROUND: There is a paucity of data on real-world management strategies and clinical outcomes of cancer-associated venous thromboembolism (VTE) in the direct oral anticoagulants (DOACs) era. OBJECTIVES: To investigate the status of cancer-associated VTE in the DOAC era. METHODS: This multicenter, retrospective cohort study among 31 centers in Japan between 2015 and 2020 enrolled 5197 consecutive patients with acute symptomatic VTE, who were divided into 1507 patients (29 %) with active cancer and 3690 patients (71 %) without. RESULTS: The cumulative 3-year rate of anticoagulation discontinuation was significantly higher in patients with active cancer than in those without (62.7 % vs. 59.1 %, P < 0.001). The cumulative 5-year incidence of recurrent VTE was higher in patients with active cancer than in those without (10.1 % vs. 9.1 %, P = 0.01), however, after adjusting for the confounders and competing risk of mortality, the excess risk of the active cancer group relative to the no active cancer group was no longer significant (HR: 0.95, 95 % CI: 0.73-1.24). The cumulative 5-year incidence of major bleeding was much higher in the active cancer group (20.4 % vs. 11.6 %, P < 0.001). Even after adjusting for the confounders and competing risk of mortality, the risk of the active cancer group relative to the no active cancer group remained significant (HR: 1.36, 95 % CI: 1.11-1.66). CONCLUSIONS: The current large real-world registry revealed that the risk of major bleeding was still higher in patients with active cancer than in those without, leading to the frequent anticoagulation discontinuation, which has been still a huge challenge to overcome in the DOAC era.

Left Ventricular End-Systolic Diameter May Predict Persistent Heart Failure with Reduced Ejection Fraction.

Patients with persistent heart failure (HF) with reduced ejection fraction (HFrEF) have a poorer prognosis than those with HF with improved ejection fraction (HFimpEF). However, data on the predictive value of echocardiographic parameters for persistent HFrEF are lacking. We retrospectively studied 443 patients who were diagnosed with HFrEF (EF ≤ 40%) during hospitalization and underwent echocardiography at the 1-year follow-up. We divided them into the 2 groups: HFimpEF (EF > 40%) and persistent HFrEF group at 1-year follow-up, and assessed the predictive value of echocardiographic parameters at discharge for persistent HFrEF. In total, 301/443 patients (68%) were diagnosed with persistent HFrEF and 142/443 (32%) with HFimpEF at the 1-year follow-up. Kaplan-Meier analysis revealed that the persistent HFrEF group had a poorer prognosis than the HFimpEF group (log-rank, P < 0.001). Receiver operating characteristic curve analysis revealed that left ventricular end-systolic diameter (LVESD) had the highest area under the curve (AUC) (0.70; 95% confidence interval [CI]: 0.64-0.75; cutoff value: 55 mm) among various echocardiographic parameters. LVESD was an independent predictor of persistent HFrEF at the 1-year follow-up (odds ratio: 1.07, 95%CI: 1.02-1.12) upon multivariable logistic regression analysis. The incidence of persistent HFrEF was higher in patients with an LVESD ≥ 55 mm than in those with an LVESD < 55 mm (81% versus 55%, Fisher's exact test, P < 0.001). In conclusion, an LVESD (≥ 55 mm) was associated with persistent HFrEF. Focusing on LVESD in daily practice may help clinicians with risk stratification for decision-making regarding management in patients with advanced HF refractory to guideline-directed medical therapy.

Anticoagulation strategies and long-term recurrence in patients with venous thromboembolism in the era of direct oral anticoagulants.

BACKGROUND: There has been limited data on anticoagulation strategies and long-term recurrence in patients with venous thromboembolism (VTE) in the era of direct oral anticoagulant (DOAC). METHODS: The COMMAND VTE Registry-2 is a multicenter retrospective cohort study enrolling 5197 consecutive patients with acute symptomatic VTE between January 2015 and August 2020 among 31 centers in Japan. In this primary report, the entire cohort was divided into 5 groups; major transient risk factors (N = 475, 9.1%), minor transient risk factors (N = 788, 15%), unprovoked (N = 1913, 37%), non-malignant persistent risk factors (N = 514, 9.9%), and active cancer (N = 1507, 29%) groups. RESULTS: DOACs were administered in 79% of patients who received oral anticoagulants. Discontinuation of anticoagulant at 1 year was most frequent in the major transient risk factors group (57.2%, 46.3%, 29.1%, 32.0%, and 45.6%). The cumulative 5-year incidence of recurrent VTE was lowest in the major transient risk factors group (2.6%, 6.4%, 11.0%, 12.1%, and 10.1%, P < 0.001). The cumulative 5-year incidence of major bleeding was highest in the active cancer group (9.8%, 11.4%, 11.0%, 15.5%, and 20.4%, P < 0.001). After discontinuation of anticoagulation therapy, the cumulative 5-year incidence of recurrent VTE was highest in the unprovoked group (3.3%, 11.0%, 24.9%, 17.5%, and 11.8%, P < 0.001). CONCLUSIONS: In this large real-world VTE registry, anticoagulation strategies and long-term recurrence widely differed depending on the baseline characteristics. Detailed risk stratifications of recurrent VTE could be useful for decision-making of anticoagulation strategies, whereas the bleeding-risk assessment might be especially important in the era of DOAC. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.

Edoxaban for 12 Months Versus 3 Months in Patients With Cancer With Isolated Distal Deep Vein Thrombosis (ONCO DVT Study): An Open-Label, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of anticoagulation therapy for isolated distal deep vein thrombosis in patients with cancer is clinically relevant, but the evidence is lacking. The prolonged anticoagulation therapy could have a potential benefit for prevention of thrombotic events; however, it could also increase the risk of bleeding. METHODS: In a multicenter, open-label, adjudicator-blinded, randomized clinical trial at 60 institutions in Japan, we randomly assigned patients with cancer with isolated distal deep vein thrombosis, in a 1-to-1 ratio, to receive either a 12-month or 3-month edoxaban treatment. The primary end point was a composite of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death at 12 months. The major secondary end point was major bleeding at 12 months, according to the criteria of the International Society on Thrombosis and Haemostasis. The primary hypothesis was that a 12-month edoxaban treatment was superior to a 3-month edoxaban treatment with respect to the primary end point. RESULTS: From April 2019 through June 2022, 604 patients were randomized, and after excluding 3 patients who withdrew consent, 601 patients were included in the intention-to-treat population: 296 patients in the 12-month edoxaban group and 305 patients in the 3-month edoxaban group. The mean age was 70.8 years, 28% of the patients were men, and 20% of the patients had symptoms of deep vein thrombosis at baseline. The primary end point of a symptomatic recurrent VTE event or VTE-related death occurred in 3 of the 296 patients (1.0%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 0.13; 95% CI, 0.03-0.44). The major secondary end point of major bleeding occurred in 28 of the 296 patients (9.5%) in the 12-month edoxaban group and in 22 of the 305 patients (7.2%) in the 3-month edoxaban group (odds ratio, 1.34; 95% CI, 0.75-2.41). The prespecified subgroups did not affect the estimates on the primary end point. CONCLUSIONS: In patients with cancer with isolated distal deep vein thrombosis, 12 months was superior to 3 months for an edoxaban treatment with respect to the composite outcome of a symptomatic recurrent VTE or VTE-related death. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03895502.

Prognostic impact of guideline-directed medical therapy in patients with heart failure on regular hemodialysis.

BACKGROUND: Renin-angiotensin system inhibitor (RASi) and ß-blocker provide prognostic benefits as guideline-directed medical therapy (GDMT) in patients with heart failure and reduced ejection fraction (HFrEF). However, there is limited data for the favorable effects in such patients receiving regular hemodialysis. We aimed to evaluate the prognostic impact of RASi and ß-blocker in patients with HFrEF who receive regular hemodialysis. METHODS: In this retrospective, single-center, observational study, from 2110 consecutive patients hospitalized for HF and who survived to discharge, 97 with HFrEF who received regular hemodialysis were included for analysis. They were classified into three groups according to prescribed medication at discharge following index hospitalization: both RASi and ß-blocker (Dual-GDMT group: n = 55), either RASi or ß-blocker (Mono-GDMT group: n = 34), and neither RASi nor ß-blocker (No-GDMT group: n = 8). The primary endpoint was a composite of all-cause death and rehospitalization for heart failure. RESULTS: The mean age was 66 years and 79% of the patients were men. During the median follow-up of 501 days, the primary endpoint occurred in 43 patients (44%). Kaplan-Meier analysis revealed that the Dual-GDMT group had the lowest rates of the primary endpoint (log-rank test for trend: p < 0.001). Even after adjustment for diverse covariates (multivariate Cox regression), the Dual-GDMT (hazard ratio [HR]: 0.04, 95% confidence interval (CI): 0.005-0.32) and Mono-GDMT (HR: 0.08, 95% CI: 0.01-0.50) groups had better prognoses than the No-GDMT group. CONCLUSIONS: The prescription of RASi and/or ß-blocker was associated with a lower adverse-event rate after discharge in patients with HFrEF who were on regular hemodialysis.

Renin-angiotensin system inhibitor exerts prognostic effects in HFpEF patients with low baseline chloride level.

BACKGROUND: Few interventions have shown improved prognosis in patients with heart failure and preserved ejection fraction (HFpEF). Serum chloride levels, which are affected by serum renin secretion, are associated with the prognosis of HFpEF patients. However, the relationship between serum chloride levels and the effects of renin-angiotensin system inhibitors (RASi) in HFpEF patients remains unclear. We investigated whether the prognostic benefit of RASi depends on baseline serum chloride levels in HFpEF patients. METHODS: This observational study included 506 hospitalized patients with HFpEF (ejection fraction ≥50%) who were discharged. They were divided into two categories based on serum chloride levels at admission (cutoff level: 101 mEq/L) according to previous reports. In each chloride category, all-cause mortality, the primary endpoint, was compared between patients who received RASi and those who did not. RESULTS: Patients who received RASi had a significantly lower mortality rate after discharge than those who did not, but only in the lower chloride category (log-rank, P = 0.001). Multivariable Cox regression analysis confirmed the effect of risk reduction by RASi on all-cause mortality in the lower chloride category (adjusted hazard ratio: 0.31, 95% confidence interval: 0.11-0.84). The prognostic advantages of RASi were evident in the lower chloride category, but not in the higher chloride category, at admission (P for interaction = 0.027). CONCLUSION: RASi administration was associated with an improved prognosis only in HFpEF patients with a low baseline serum chloride level. Clinicians should consider RASi administration if patients' serum chloride levels are low, to improve the long-term prognosis of HFpEF patients.

Prognosis and diastolic dysfunction predictors in patients with heart failure and recovered ejection fraction.

There is limited data on whether diastolic dysfunction in patients with heart failure (HF) and recovered ejection fraction (HFrecEF) is associated with worse prognosis. We retrospectively assessed 96 patients diagnosed with HFrecEF and created ROC curve of their diastolic function at the 1-year follow-up for the composite endpoint of cardiovascular death and HF readmission after the follow-up. Eligible patients were divided into two groups according to the cutoff value of E/e' ratio (12.1) with the highest AUC (0.70). Kaplan-Meier analysis showed that HFrecEF with high E/e' group had a significantly poorer prognosis than the low E/e' group (log-rank, p = 0.01). Multivariate Cox regression analysis revealed that the high E/e' group was significantly related to the composite endpoint (hazard ratio 5.45, 95% confidence interval [CI] 1.23-24.1). The independent predictors at discharge for high E/e' ratio at the 1-year follow-up were older age and female sex after adjustment for covariates (odds ratio [OR] 1.07, 95% CI 1.01-1.13 and OR 4.70, 95% CI 1.08-20.5). In conclusion, HFrecEF with high E/e' ratio might be associated with a poor prognosis. Older age and female sex were independent predictors for a sustained high E/e' ratio in patients with HFrecEF.

Functional Evaluation of Human Bioengineered Cardiac Tissue Using iPS Cells Derived from a Patient with Lamin Variant Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is caused by various gene variants and characterized by systolic dysfunction. Lamin variants have been reported to have a poor prognosis. Medical and device therapies are not sufficient to improve the prognosis of DCM with the lamin variants. Recently, induced pluripotent stem (iPS) cells have been used for research on genetic disorders. However, few studies have evaluated the contractile function of cardiac tissue with lamin variants. The aim of this study was to elucidate the function of cardiac cell sheet tissue derived from patients with lamin variant DCM. iPS cells were generated from a patient with lamin A/C (LMNA) -mutant DCM (LMNA p.R225X mutation). After cardiac differentiation and purification, cardiac cell sheets that were fabricated through cultivation on a temperature-responsive culture dish were transferred to the surface of the fibrin gel, and the contractile force was measured. The contractile force and maximum contraction velocity, but not the maximum relaxation velocity, were significantly decreased in cardiac cell sheet tissue with the lamin variant. A qRT-PCR analysis revealed that mRNA expression of some contractile proteins, cardiac transcription factors, Ca2+-handling genes, and ion channels were downregulated in cardiac tissue with the lamin variant.Human iPS-derived bioengineered cardiac tissue with the LMNA p.R225X mutation has the functional properties of systolic dysfunction and may be a promising tissue model for understanding the underlying mechanisms of DCM.

Aligned human induced pluripotent stem cell-derived cardiac tissue improves contractile properties through promoting unidirectional and synchronous cardiomyocyte contraction.

Alignment, as seen in the native myocardium, is crucial for the fabrication of functional cardiac tissue. However, it remains unclear whether the control of cardiomyocyte alignment influences cardiac function and the underlying mechanisms. We fabricated aligned human cardiac tissue using a micro-processed fibrin gel with inverted V-shaped ridges (MFG) and elucidated the effect of alignment control on contractile properties. When human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were seeded on MFG, hiPSC-CMs were aligned more uniformly than the control, and we succeeded in fabricating the aligned cardiac tissue. Assessing the contractile properties with the direct contractile measurement system, the contractile force, maximum contractile velocity, and relaxation velocity were significantly increased in aligned cardiac tissue compared with non-aligned cardiac tissue. However, gene expression profiles were not different between the two groups, suggesting that functional improvement of cardiac tissue through alignment control might not be dependent on cardiomyocyte maturation. Motion capture analysis revealed that the cardiomyocytes in the aligned cardiac tissues showed more unidirectional and synchronous contraction than the non-aligned cardiac tissues, indicating that cardiac tissue maturation involves electrical integration of cardiomyocytes. Herein, cardiomyocyte alignment control might improve the contractile properties of cardiac tissue through promoting unidirectional and synchronous cardiomyocyte contraction.

Impact of anatomical position of the inflow cannula on stroke in patients with left ventricular assist devices.

OBJECTIVES: Stroke is a substantial complication of left ventricular assist device (LVAD) implantation. The relationship between stroke and the anatomical position of the inflow cannula of patients who underwent LVAD implantation was investigated. METHODS: We enrolled 15 patients with advanced-stage heart failure who underwent implantation of continuous-flow-LVAD. Data of patients who suffered a stroke within 6 months after LVAD implantation were retrospectively compared to those who remained free of stroke. The distance between the inflow duct and left ventricular (LV) septum (duct-sep distance) and its ratio to LV diastolic diameter (LVDd) were measured from echocardiography at 1 month after LVAD implantation. Receiver operating characteristic curves for the endpoint of stroke using the duct-sep distance to LVDd ratio was created and the cut-off value was calculated. The incidence of stroke during the 6 months after LVAD implantation according to this ratio was estimated using the Kaplan-Meier method. RESULTS: At 1 month after LVAD implantation, there were no significant differences in baseline characteristics and echocardiography parameters between the stroke and stroke-free groups. Receiver operating characteristic curve analysis for the endpoint of stroke using the duct-sep distance to LVDd ratio revealed 0.217 as a cut-off value (sensitivity: 80%, specificity: 80%, area under the curve: 0.72). Stroke was more frequent in patients with a duct-sep distance to LVDd ratio ⩾0.217 at 1 month than in those with a lower ratio. CONCLUSION: The duct-sep distance to LVDd ratio was associated with the occurrence of stroke, suggesting that inflow cannula position influences the incidence of stroke.

Nutritional status during hospitalization is associated with the long-term prognosis of patients with heart failure.

AIMS: The CONtrolling NUTritional status (CONUT) score represents the nutritional status of patients with heart failure (HF). Although high CONUT scores on admission are associated with increased risks of cardiovascular (CV) events in patients with HF, the impact of CONUT changes during hospitalization on their long-term prognosis is unclear. This study aimed to investigate the impact of CONUT score changes on the clinical outcomes of patients with HF after discharge. METHODS AND RESULTS: This observational study included 1705 patients hospitalized with HF who were discharged alive. The patients were categorized depending on their CONUT scores at admission and discharge into persistently high, high at admission and normal at discharge, normal at admission and high at discharge, and persistently normal CONUT groups. The primary endpoint was a composite of CV death and readmission for HF after discharge. The primary endpoint occurred in 652 patients (38%) during the median 525 day follow-up period. Patients with persistently high CONUT scores had the highest composite endpoint rate (log-rank trend test: P < 0.001). After adjusting for covariates, the hazard ratio for the composite outcome was significantly lower for the patients with high CONUT scores at admission and normal CONUT scores at discharge than that for those with persistently high CONUT scores (hazard ratio: 0.69; 95% confidence interval: 0.49-0.98). CONCLUSIONS: Nutritional status changes in patients with HF that occurred during hospitalization were associated with CV events after discharge. Improving the nutritional status of patients may improve their clinical outcomes.

Heart transplant candidate with medical complexity in the era of prolonged left ventricular assist device support - A case report.

Heart transplantation improves quality of life and survival in patients with advanced heart failure. However, the shortage of available heart donors and technological advances for left ventricular assist devices (LVAD) have led to longer waiting times for transplantation, and long-term use of LVAD may increase the medical complexity of subsequent transplantation. We present the case of a 35-year-old man who underwent heart transplantation after being supported by an LVAD for 1490 days (∼4 years). He was sensitized with kidney dysfunction and recurrent infections, including candidemia, at the time of transplantation. He underwent a successful heart transplantation with pretransplant plasma exchange, intravenous immunoglobulin administration, early initiation of everolimus, and prompt management of infections. .

Predictors of neo-aortic valve regurgitation in the long term after arterial switch operation.

Although arterial switch operations (ASOs) have been performed globally to repair d-transposition of the great arteries (d-TGA) in neonates and infants, few studies have been reported regarding the influence of the hemodynamics of patients with d-TGA who have undergone ASO on the development of neo-aortic valve regurgitation (AR). We aimed to investigate the relationship between the hemodynamics and development of AR after ASO in patients with d-TGA by catheter evaluation. This observational study screened 114 consecutive patients who underwent ASO for d-TGA or Taussig-Bing anomaly and who subsequently underwent catheter evaluations in our institution. We reviewed their records for the past 20 years and collected their first catheterization data post-ASO in early childhood. Thirty-six post-ASO patients who underwent catheter evaluations in both the early surgical and long-term phases were finally analyzed. Patients were divided into the following groups according to the presence of significant AR in the long-term phase: the AR group (n = 9 with AR ≥ grade II by the Sellers classification) and the non-AR group (n = 27 with AR < grade II). In the long-term phase, the diastolic blood pressure was significantly lower and the ascending aortic diameter was significantly larger in the AR group than in the non-AR group (p = 0.004 and p = 0.006, respectively). The systolic blood pressure (SBP) and pulse pressure (PP) were similar in both groups. Meanwhile, in the early surgical phase, SBP and PP were significantly higher in the AR group than in the non-AR group (p = 0.029 and p = 0.002, respectively). The receiver operating characteristic curve for late AR showed that the area under the curve for SBP and PP in the early surgical phase were 0.746 and 0.853, respectively. Even though sensitivity analysis was performed, SBP or PP greater than the cutoff value in the early surgical phase was identified as predictors for late AR. Our results suggested that high SBP or PP in the early surgical phase could influence the development of AR in the long term after ASO.

Recurrent takotsubo syndrome with worsening of left ventricular outflow obstruction during haemodialysis: a case report.

BACKGROUND: The recurrence rate of takotsubo syndrome (TS) has been reported as 1.8% per patient-year while left ventricular outflow tract (LVOT) obstruction is comorbid in 10-25% of all instances of TS. The clinical course of recurrent TS with associated LVOT while on haemodialysis has rarely been reported. CASE SUMMARY: This case report involves a 60-year-old female patient receiving regular haemodialysis who was admitted for chest pain during ballroom dancing. Four years prior, she had suffered TS, and fully recovered after the hospitalization. An emergent coronary angiogram done during the second hospitalization showed no significant stenosis, and left ventriculography demonstrated mid-apical akinesia and basal hyperkinesia. Based on these findings, we diagnosed the recurrence of TS. Later in the admission, chest pain reappeared with the start of haemodialysis. A transthoracic echocardiogram demonstrated mean pressure gradient (PG) of LVOT was 58 mmHg, with systolic anterior motion of the mitral valve and basal-wall hyperkinesia. The main aetiology for her symptoms was considered as an exacerbation of LVOT obstruction due to removing intravascular volume by haemodialysis. After starting landiolol at 3 µg/kg/min, PG of LVOT and symptoms gradually improved with uptitration of landiolol. Finally, her chest pain resolved when mean PG of LVOT was down to 38 mmHg using 10 µg/kg/min of landiolol. DISCUSSION: To our knowledge, this is the first report of a recurrent TS case comorbid with LVOT obstruction while on regular haemodialysis. Landiolol, the ultrashort-acting beta-blocker, may be a promising therapeutic option for rapid recovery of increased PG due to LVOT obstruction.