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In April 2021, destination therapy (DT) was finally approved in Japan. Since DT does not aim at heart transplantation (HT), our goal is to have a patient safely remain on an implantable ventricular assist device (VAD) for the rest of his/her life. To achieve this goal, similarly to bridge-to-transplant (BTT) patients, the authors believe the following six aspects are even more crucial in DT patients: (1) to appropriately assess risks before implantation, (2) to carefully determine the ability to manage the device by multidisciplinary discussions, (3) to prevent complications by improving the quality of care, (4) to expand the number of facilities that can take care of DT patients by improving collaboration among the facilities, (5) to reduce the burden of caregivers by utilizing social resources, and (6) to establish a home palliative care system based on advance care planning. In addition, for elderly DT patients to live happy and long lives, it is essential to help them to find a purpose of life and to keep activities of daily living, such as employment, schooling, and participation in social activities, just like the general elderly population. Our goals are not only to do our best for the patients just in front of us, but also to establish a system to follow up our DT cohort, same as BTT one, by all-Japan manner. In the present review, we discuss the current state of DT in Japan and what we need to focus on to maintain or improve its long-term performance., (© 2024. The Author(s).)

In pulmonary disease patients since oxygen desaturation during 6-min walk test (6MWT) affects walk distance (6MWD), some novel indices such as desaturation/distance ratio [DDR, oxygen desaturation area (DAO 2 )/6MWD] and distance-saturation product [DSP, 6MWD × minimum peripheral oxygen saturation (SpO 2 )] are evaluated. However, there has been no study examining these indices that consider exercise-induced desaturation (EID) in patients with cardiovascular disease. In 94 cardiovascular disease patients without pulmonary complications, 6MWT and echocardiography were performed at the entry of cardiac rehabilitation. SpO 2 was measured during 6MWT using a continuously monitorable pulse oximeter, and DSP and DDR were calculated using minimum SpO 2 and DAO 2 [sum of (100-SpO 2 ) per second during 6MWT], respectively. EID was defined as SpO 2 decrease of ≥ 4% or minimum SpO 2 of < 90% during 6MWT. DSP was slightly lower and DDR was markedly higher in patients with EID than in those without. When examining correlations of DSP and DDR with their components, DSP was correlated with 6MWD much closely than minimum SpO 2 , while DDR was correlated as closely with DAO 2 as 6MWD. Furthermore, DAO 2 , but not minimum SpO 2 , had a direct correlation with 6MWD. As for associations with cardiac function, DSP was correlated with several cardiac parameters, but DDR was not correlated with any of these parameters. Our findings suggest that oxygen desaturation during 6MWT affects walking distance in cardiovascular disease patients even without pulmonary complications and that DDR is more appropriate than DSP as an index of walking performance that takes EID into consideration, independently of cardiac function., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

Acute myocardial infarction (AMI) is associated with a decline in renal function. This study aimed to investigate the impact of engaging in moderate to vigorous intensity physical activity (MVPA) for more than 30 min per day on changes in renal function during the first 3 months after AMI onset. A prospective, observational study was conducted, enrolling 87 patients (75 men; average age, 65.2 ± 12.5 years) who had experienced AMI. The cystatin C-based estimated glomerular filtration rate (eGFRcys) was collected at and 3 months after discharge. Daily MVPA was measured using triaxial accelerometers at a threshold of 3.0 Metabolic equivalent of the task for 3 months. Generalized estimating equations (GEE) were applied to evaluate the longitudinal association between the number of days per week of MVPA for 30 min or more and within-patient changes in eGFRcys. The patients were categorized into three groups based on their MVPA engagement days: 0 days (n = 20), 1-2 days (n = 14), and 3-7 days (n = 53) groups. After adjusting for potential confounding variables, GEE analysis revealed that the eGFRcys slope over 3 months was significantly higher in the 3-7 days group than in 0 days group (B = 2.9, (95% confidence interval: 1.5-4.2), p < 0.001). Similar results were obtained when MVPA time thresholds were set to 40 and 60 min. These findings suggest a significant positive effect of engaging in MVPA for 30 min or more for 3-7 days per week in the improvement of renal function after AMI onset., (© 2024. Springer Nature Japan KK, part of Springer Nature.)

To evaluate the relationship of aortopulmonary collaterals and the development of central pulmonary arteries during staged palliation. A total of 287 patients, who underwent staged palliation with bidirectional cavopulmonary shunt and total cavopulmonary connection between 2008 and 2019, had available angiography. Pulmonary artery index was calculated using pulmonary angiography as described by Nakata and colleagues. Aortopulmonary collaterals were observed in 47 (16%) patients at stage II palliation, in 131 (46%) at total cavopulmonary connection, and afterwards in 49 (7%). The interventional closure of aortopulmonary collaterals was performed before stage II in 12 (4%) patients, before Fontan completion in 38 (13%), and afterwards in 39 (14%). Presence of aortopulmonary collaterals before stage II was not associated with the pulmonary artery index (129 vs. 150 mm 2 /m 2 , p = 0.176) at stage II. In contrast, aortopulmonary collaterals before the Fontan completion were associated with lower pulmonary artery index (154 vs. 172 mm 2 /m 2 , p = 0.005), and right pulmonary artery index (99 vs. 106 mm 2 /m 2 , p = 0.006). Patients who underwent interventional closure of aortopulmonary collaterals before total cavopulmonary connection had lower pulmonary artery index (141 vs. 169 mm 2 /m 2 , p < 0.001), lower right pulmonary artery index (93 vs. 106 mm 2 /m 2 , p = 0.007), and left pulmonary artery index (54 vs. 60 mm 2 /m 2 , p = 0.013) at Fontan completion. The presence of aortopulmonary collaterals did not influence pulmonary artery size by the time of stage II. However, presence of aortopulmonary collaterals was associated with under-developed pulmonary arteries at Fontan completion, especially in patients who needed interventional closure of aortopulmonary collaterals., (© 2024. The Author(s).)

Purpose: Bleeding complication is a critical risk factor for outcomes of acute heart failure patients requiring mechanical circulatory support (MCS), including percutaneous catheter-type heart pumps (Impella). The Japanese registry for Percutaneous Ventricular Assist Device (J-PVAD) is an ongoing, large-scale, real-world registry to characterize Japanese patients requiring Impella. Here we analyzed bleeding complication profiles in patients who received Impella., Methods: All consecutive Japanese patients who received Impella from October 2017 to January 2020 were enrolled. The 30-day survival and bleeding complications were analyzed., Results: A total of 1344 patients were included: 653 patients received Impella alone, 685 patients received a combination of veno-arterial extracorporeal membrane oxygenation and Impella (ECPELLA), and 6 patients had failed Impella delivery. Overall 30-day survival was 67.0%, with Impella alone at 81.9% and ECPELLA at 52.7%. Overall bleeding/hematoma adverse events with a relation or not-excluded relation to Impella was 6.92%. Among them, the rates of hematoma and bleeding from medical device access sites were 1.41% and 4.09%, respectively. There was no difference between etiologies for these events., Conclusion: This study represents the first 3-year survival and the safety profile focused on bleeding adverse events from the J-PVAD registry. The results show that the real-world frequency of bleeding adverse events for patients who received Impella was an expected range from previous reports, and future real-world studies should aim to expand this data set to improve outcomes and adverse events., (© 2024. The Japanese Society for Artificial Organs.)

Implantation of continuous-flow left ventricular assist device in a narrow lumen is technically challenging to secure an optimal support. We experienced a patient with the transposition of the great arteries after the Senning procedure who was initially implanted with Jarvik 2000®. She presented with worsening heart failure symptoms 2 years after implanting Jarvik 2000®. We assumed that the inflow cannula was stuck in the highly developed trabeculae on the interventricular septum, which disturbed the VAD to maintain an expected support. After converting to the EVAHEART® 2, we successfully obtained an adequate inflow. We consider that the tipless cannula of EVAHEART® 2 is the most suitable when there is no sufficient room to place a conventional inflow cannula in the systemic ventricle., (© 2023. The Japanese Society for Artificial Organs.)

Decision-making is an important component in the perception-action coupling required for athletes to achieve fine performance. Signal detection theory (SDT) provides a means of quantifying athletes' decision-making processes, based on their ability to discriminate between different types of stimuli (sensitivity) and the locations of their response criteria along a decision axis in a given situation. Studies have shown differences in these two indices between athletes and less-experienced counterparts, although these studies were limited to unidimensional decision-making problems. In the present study, SDT analysis was applied to two-dimensional decision-making by volleyball players regarding their opponents' attacks, using a four-alternative forced-choice task combining judgments of the type (spike or tip) and direction (cross-court or down-the-line) of attacks. Furthermore, a temporal occlusion task was used to reveal the timecourses of changes in sensitivity and the location of response criteria relating to judgments of attack type and direction. There were three groups of participants, eight top-league players, ten collegiate players, and ten novices. The results showed clear effects of expertise and distinct timecourses for the two types of judgment. For the attack type judgments, the sensitivities of the top-league players were relatively low at the early occlusion points, and their response criteria were biased toward judging attacking actions as spikes. At the late occlusion points, their sensitivity peaked, and there was no bias in their response criteria. For the directional judgments, the sensitivity of the three groups improved as the occlusion point advanced, while their response criteria tended to become more similar, which was not the case for the attack type judgments. These results are discussed together with previous studies of volleyball players' decision-making and judgments regarding deceptive actions in sports., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Trans-catheter aortic valve replacement (TAVR) is an excellent alternative intervention for surgical aortic valve replacement. Cardiac sympathetic nervous (CSN) function and left atrial (LA) volume are both important prognostic factors in patients with aortic stenosis (AS) after TAVR. The relationship between the two clinical factors is unknown, however. This retrospective observational study aimed to assess the correlation between CSN function and LA volume in 48 symptomatic patients with severe AS (median age: 85 years, IQR 82-88 years; 81% female) before and after TAVR. CSN function was assessed by performing 123 I-metaiodobenzylguanidine (MIBG) scintigraphy before and 6 months after TAVR, and the delayed heart-to-mediastinum ratio (dHMR) and washout rate (WR) were calculated. We also performed transthoracic echocardiography near the same time. TAVR improved the dHMR, WR, and LA volume index (LAVI) (dHMR: median 2.89 [IQR 2.62-3.23] vs. 2.98 [2.49-3.25], p = 0.0182; WR: 28% [24-38] vs. 23% [16-32], p < 0.0001; LAVI: 47.7 mL/m 2 [37.8-56.3] vs. 41.2 mL/m 2 [33.7-56.1], p = 0.0024). In multiple linear regression analysis, the percentage change in LAVI from baseline to post-TAVR (∆LAVI%) was an independent predictor of change in dHMR from baseline to post-TAVR (β =  - 0.35, p = 0.0110). In conclusion, LA volume reduction reflected CSN functional improvement after TAVR. In patients with TAVR, ∆LAVI% might be a valuable parameter for evaluating CSN functional recovery., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

This single-centre prospective feasibility study (UMIN000030232) evaluated whether zinc supplementation was safe and effective for improving outcomes among patients with acute myocardial infarction (AMI). Within 24 h after successful primary percutaneous coronary intervention, consenting patients with AMI were randomly assigned 1:1 to receive conventional treatment (conventional treatment group) or conventional treatment plus zinc acetate supplementation (zinc supplementation group). The two groups were compared in terms of major adverse cardiovascular events (MACE), and scar size, which was evaluated using cardiac magnetic resonance imaging (CMR) at 4 weeks after discharge. A total of 56 patients underwent randomization (with 26 assigned to the zinc supplementation group and 27 to the conventional treatment group). The two groups had generally similar laboratory findings and clinical characteristics. The two groups also had similar lengths of hospital stay and rates of MACE. Forty of the 53 patients underwent CMR and it revealed that % core zone was numerically lower in the zinc supplementation group than in the conventional treatment group (9.3 ± 6.9% vs. 14.2 ± 9.1%, P = 0.07). This small single-centre study failed to detect a significant reduction in mid-term MACE after AMI among patients who received zinc supplementation., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Catheter-based micro-axial ventricular assist device Impella® (Abiomed, Danvers, MA) has been used in Japanese patients with drug-refractory acute heart failure (AHF) since 2017. This is the first interim analysis of the ongoing Japan Registry for Percutaneous Ventricular Assist Device (J-PVAD) to investigate the safety and efficacy of Impella support. Between October 2017 and January 2020, 823 Japanese patients, who were treated with the Impella 2.5, CP, or 5.0 pump, were enrolled. The primary endpoints were safety profiles and cumulative 30-day survival. Among them, 44.8% of patients were acute myocardial infarction with cardiogenic shock. The Impella pumps were unable to implant in 4 patients. The Impella 2.5, CP, and 5.0 pumps were used in 72.4%, 6.2%, and 16.6%, respectively, and mean support duration was 8.1 ± 10.2 days. Combination use of Impella and venoarterial extracorporeal membrane oxygenation (VA-ECMO) was applied for 387 patients (47.3%). Pump stop occurred 22 patients (2.7%). Major adverse events included hemolysis (11.2%), hemorrhage/hematoma (6.1%), peripheral ischemia (1.6%), and stroke (1.6%). The overall 30-day survival was 62.2%. Survival of patients with single Impella support was significantly higher than patients with Impella combined with VA-ECMO support (81.1% vs 49.6%; p < 0.01), who had lower blood pressure, lower left ventricular ejection fraction, and higher degree of inotropic support. Results suggest that short-term outcome of Impella support for Japanese patients was favorable with acceptable safety profiles., (© 2022. The Japanese Society for Artificial Organs.)

This study aimed to determine the optimal cut-off value of the early drop in systolic blood pressure (SBP) for worsening renal function (WRF) in hospitalized patients with heart failure (HF) and analyze predictors of WRF and the early drop in SBP at that threshold. We retrospectively enrolled 396 patients with acute decompensated HF. The early drop in SBP was defined as the difference between baseline and SBP measured 24 h after hospitalization. We performed receiver operating characteristic (ROC) analysis to determine the optimal cut-off value of the early drop in SBP for WRF and evaluated the effect of the early drop in SBP on in-hospital mortality by multivariate logistic regression analyses. The mean age of the patients was 73.4 ± 14.7 years, and 61.2% were men. A 14.0% drop in SBP was identified as the optimal cut-off value for WRF from the ROC curve analysis. An early drop in SBP ≥ 14.0% was associated with WRF in multivariate logistic regression analysis (odds ratio 7.84; 95% confidence interval 4.06-15.14; P < 0.0001). The dose of intravenous furosemide within 24 h of admission was one of the predictors of the early drop in SBP ≥ 14.0%, while no early drop in SBP was a predictor of in-hospital mortality in multivariate logistic regression models. In conclusion, the optimal cut-off value for WRF in patients with HF was a 14.0% drop in SBP within 24 h of admission. The early drop in SBP ≥ 14.0% was one of the predictors of WRF in patients with HF. However, no early drop in SBP was associated with in-hospital mortality. This study was registered with the University Hospital Medical Information Network in Japan (UMIN000035989)., (© 2022. Springer Japan KK, part of Springer Nature.)

Root infection or dissection involving coronary artery frequently necessitates an emergent Bentall procedure, with low left ventricular ejection fraction (LVEF). In contrast, concerning an elective Bentall for aneurysm, surgeons should balance the risk and benefit of surgery, especially in low LVEF cases. We investigated the association between preoperative LVEF and outcomes after Bentall. We analyzed 98 patients undergoing Bentall between April 2000 and March 2020. The patients were stratified into three groups: (a) 65 with LVEF ≥ 60%, (b) 21 with LVEF 45 to < 60%, and (c) 12 with LVEF < 45%. Baseline characteristics, survivals, and major adverse cardiovascular events (MACE) were compared. To assess potential non-linear relationship between LVEF and mortality, cubic spline analysis was conducted. Median age was similar (a vs b vs c, 52 vs 50 vs 44). In all groups, elective root aneurysm was 50-60%, indicating the rest were complicated and sick. Operative mortality was the highest in group c (4.6% vs 9.5% vs 16.7%, p = 0.294). Survival and MACE-free rate were the worst in group c, though their 10-year survival was 40%. LVEF was an independent risk for mortality, and cubic spline analysis showed potential non-linear association between LVEF and mortality. Although LVEF is an independent predictor of mortality after Bentall, long-term survival was occasionally achieved in low LVEF cases. While surgeons should carefully balance the risk of low LVEF and the benefit of surgery in elective cases, we should perform a non-elective procedure as needed, even if LVEF is low., (© 2022. Springer Japan KK, part of Springer Nature.)

Although the influence of continuous-flow left ventricular assist device (CF-LVAD) support on peripheral circulation has been widely discussed, its monitoring modalities are limited. The aim of this study was to assess the peripheral circulation using the laser speckle flowgraph (LSFG) which can quantitatively measure the ocular blood flow. We implanted a centrifugal CF-LVAD (EVAHEART ® ; Sun Medical Technology Research Corporation, Nagano, Japan) in five adult goats (body weight 44.5 ± 2.9 kg) under general anesthesia. The waveform of the central retinal artery using the mean blur rate (MBR) for ocular blood velocity and fluctuations as a parameter of pulsatility were obtained before LVAD implantation and after LVAD full-bypass support. The MBR waveform and LSFG fluctuation data were compared with the waveform and pulsatility index of the external carotid artery using an ultrasonic flow meter to evaluate circulatory patterns at different levels. The MBR waveform pattern of the central retinal artery was pulsatile before LVAD implantation and less pulsatile under LVAD full bypass. The fluctuation was 14.7 ± 1.86 before LVAD implantation and 3.85 ± 0.61 under LVAD full bypass (p < 0.01), respectively. The fluctuations of LSFG showed a strong correlation with the pulsatility index of the external carotid artery meaning that similar changes in circulatory pattern were observed at two different levels. Measuring the ocular blood flow using LSFG has potential utility for the assessment of the status of the peripheral circulation and its pulsatility during CF-LVAD., (© 2021. The Japanese Society for Artificial Organs.)

Recording the electrical potentials of bioengineered cardiac tissue after transplantation would help to monitor the maturation of the tissue and detect adverse events such as arrhythmia. However, a few studies have reported the measurement of myocardial tissue potentials in vivo under physiological conditions. In this study, human-induced pluripotent stem cell-derived cardiomyocyte (hiPSCM) sheets were stacked and ectopically transplanted into the subcutaneous tissue of rats for culture in vivo. Three months after transplantation, a flexible nanomesh sensor was implanted onto the hiPSCM tissue to record its surface electrical potentials under physiological conditions, i.e., without the need for anesthetic agents that might adversely affect cardiomyocyte function. The nanomesh sensor was able to record electrical potentials in non-sedated, ambulating animals for up to 48 h. When compared with recordings made with conventional needle electrodes in anesthetized animals, the waveforms obtained with the nanomesh sensor showed less dispersion of waveform interval and waveform duration. However, waveform amplitude tended to show greater dispersion for the nanomesh sensor than for the needle electrodes, possibly due to motion artifacts produced by movements of the animal or local tissue changes in response to surgical implantation of the sensor. The implantable nanomesh sensor utilized in this study potentially could be used for long-term monitoring of bioengineered myocardial tissue in vivo under physiological conditions.

Aortic insufficiency (AI) is known to associate with a persistently closed aortic valve during continuous-flow ventricular assist device support. Some devices carry an intermittent low-speed (ILS) function, which facilitates aortic valve opening, but whether this function prevents AI is unknown. In this study, the Jarvik 2000 device, which is programmed to reduce the pump speed each minute for 8 s, was chosen to examine this potential effect. Prospectively collected data of 85 heart transplant-eligible Jarvik 2000 recipients who met the study criteria (no pre-existing AI and aortic valve surgery) were retrospectively analyzed for the incidence, correlating factors, and clinical outcomes of de novo AI. All data were provided by the Japanese Registry for Mechanically Assisted Circulatory Support. De novo AI occurred in 58 patients, 23 of whom developed at least moderate AI during a median support duration of 23.5 months. Freedom from moderate or greater AI was 84.4%, 66.1% and 60.2% at 1, 2 and 3 years, respectively. Multivariate analyses revealed that progressive AI was correlated with decreased pulse pressure after implantation (hazard ratio 1.060, 95% confidence interval 1.001-1.127, p = 0.045). No correlation was found for mortality or other adverse events, including stroke, bleeding, infection, pump failure, hemolysis, and readmission. The benefit of the Jarvik 2000's current ILS mode against AI appears to be minimal. However, in this limited cohort where all recipients underwent implantation as a bridge to transplantation, the impact of de novo progressive AI on other clinical adversities was also minimal.

The aim of the study was to investigate the incidence of and risk factors for de novo malignancy after heart transplantation (HTx) in a single center. We assessed 102 consecutive patients who received HTx and were followed-up in our center regularly for > 1 year from June 2006 to May 2018. We investigated the incidence of and risk factors for de novo malignancy. The cumulative incidence of each malignancy type during the follow-up period was one (0.98%) for skin cancer, four (3.92%) for nonskin solid organ cancer, and six (5.88%) for posttransplant lymphoproliferative disorder (PTLD). The percentage of patients with more than one infectious event ≤ 1 year after HTx was higher in the malignancy group than in the non-malignancy group. Furthermore, Kaplan-Meier analysis revealed that the incidence rate of infectious events was higher in patients with malignancies than in those without (log-rank P < 0.001). After dividing malignancies into a PTLD group and a solid organ malignancy group, we found that negative Epstein-Barr virus serostatus, cytomegalovirus-positive antigenemia, and the occurrence of any viral or gastrointestinal infectious event at ≤ 1 year were more frequent in patients with PTLD than in patients without it. The survival rate was significantly lower for patients with solid organ malignancy than for patients without malignancy. In conclusion, there was a correlation between infectious events and de novo malignancy, particularly in patients with PTLD. We should confirm this finding by conducting a larger cohort study.

Bilateral superior vena cava (SVC), which occurs following bilateral bidirectional cavopulmonary shunt (BCPS), is an anomaly marked by unique hemodynamics. This study aimed to determine its effects on outcomes after Fontan completion. Among 405 patients who underwent BCPS and total cavopulmonary connection (TCPC) between 1997 and 2017, 40 required a bilateral-BCPS. The dominant SVC prior to TCPC was identified according to the direction of blood flow in the central pulmonary artery, and its relationship to the inferior vena cava (IVC) was classified as a concordant or discordant relationship. Preoperative factors were analyzed to identify the risk factors for specific adverse outcomes. The length of intensive care unit (ICU) stay after TCPC was longer in the 40 patients who underwent bilateral-BCPS than in those who underwent unilateral BCPS (p = 0.024), and the survival rate was lower in the former group than in the latter group (p = 0.004). In the patients who underwent bilateral-BCPS, the dominant SVC was concordant with the IVC in 30 patients and discordant in 10 patients. With regard to whether certain morphological, hemodynamic, and flow dynamics-related variables were risk factors for adverse outcomes following TCPC, a discordant relationship between dominant SVC and IVC was identified as an independent risk factor for both a longer ICU stay (p = 0.037, HR 2.370) and worse survival (p = 0.019, HR 13.880). Therefore, in patients with a bilateral SVC who have previously undergone bilateral-BCPS, a discordant relationship between dominant SVC and IVC might contribute to worse outcomes following TCPC.

The precise physiological changes associated with the use of left ventricular assist device (LVAD) are not well characterized. We examined the impact of changes in hemodynamic state using LVAD on endothelial function. We measured flow-mediated vasodilation (FMD) to evaluate endothelial vasodilator function of the brachial artery in 53 patients (dilated cardiomyopathy: 39, ischemic cardiomyopathy: 4, and others: 10) with an implanted LVAD (DuraHeart, EVAHEART, or HeartMate II). We found that FMD value in the HeartMateII LVAD group (9.3% ± 2.9%) was significantly higher than those in the other two groups (EVAHEART: 6.7% ± 2.8% and DuraHeart: 6.2% ± 4.0%). Other factors that affected the FMD value were age (r =  - 0.31, p = 0.026), Brinkman index (r =  - 0.30, p = 0.029); however, aortic opening, aortic regurgitation, and other hemodynamic parameters such as cardiac index or pulmonary capillary wedge pressure did not correlate with FMD. Multivariate analyses revealed that the difference among the LVAD models most significantly affected the FMD values after adjusting for age and smoking status (t = 2.6, p = 0.014). Event free survival rate of death and cerebral infarction was not significantly different according to the value of FMD. The difference among the LVAD groups most significantly affected the state of endothelial function and it had more impact than other clinical factors.

Under continuous-flow left ventricular assist device (CF-LVAD) support, the ventricular volume change and cardiac cycle between the left ventricle (LV) and right ventricle (RV) become dyssynchronous due to the shortening of the LV systole. The purpose of this study was to quantify interventricular dyssynchrony based on different CF-LVAD support conditions and assess its relationship with LV unloading. In this study, we evaluated seven goats (body weight 44.5 ± 6.5 kg) with normal hearts. A centrifugal LVAD was implanted under general anesthesia. We inserted the conductance catheters into the left ventricle (LV) and right ventricle (RV) to assess the volume signal simultaneously. We defined the interventricular dyssynchrony as a signal (increase or decrease) of LV volume (LVV) change opposite to that of RV volume (RVV) (i.e., (dLVV/dt) × (dRVV/dt) < 0). The duration of interventricular dyssynchrony (DYS) was reported as the percentage of time that a heart was in a dyssynchronous state within a cardiac cycle. The mean DYS of normal hearts, hearts with LVAD clamp and hearts supported by LVADs with a bypass rate of 50%, 75% and 100% were 5.6 ± 1.6%, 8.7 ± 2.4%, 8.6 ± 2.8%, 15.1 ± 5.1%, and 25.6 ± 8.0%, respectively. Furthermore, the DYS was found to be associated with the degree of LV stroke volume reduction caused by LV unloading. These findings may be useful for understanding interventricular interactions and physiology during CF-LVAD support. Influences on the right ventricular function and heart failure models warrant further study.

The purpose of this study was to observe and clarify the interventricular dysscynchrony caused by continuous-flow left ventricular assist device (CF-LVAD) support using the conductance method. During CF-LVAD support, the systolic phase of the left ventricle (LV) becomes shorter than that of the right ventricle (RV). Accordingly, timing of the systole and diastole during the cardiac cycle is not synchronous between the LV and RV. In this study, we evaluated this phenomenon in a normal heart model using the adult goat (n = 5, body weight 44.5 ± 2.9 kg). A centrifugal LVAD was implanted under general anesthesia. We inserted the conductance catheter into the RV and LV to obtain the pressure-volume relationship of the two ventricles simultaneously. We defined the dyssynchronous status as the sign (plus or minus) of the LV volume-change opposite to that of RV volume-change. Dyssynchronous phase of the cardiac cycle was observed in 5.6 ± 0.65% of hearts under LVAD pump-off and 25.3 ± 3.3% under LVAD full bypass, respectively (p < 0.05). To the best of our knowledge, this is the first experimental report clarifying interventricular dyssynchrony during CF-LVAD support using the conductance method. Quantification of this phenomenon under various support conditions and assessment of influences on the right ventricular function will be studied in future studies.

The optimal timing of stage-2-palliation (S2P) in single left ventricle is not clear. The aim of this study was to identify S2P related factors associated with outcomes after total cavopulmonary connection (TCPC), particularly relative to the dominant systemic ventricle. A total of 405 patients who underwent both S2P and TCPC at our institute between 1997 and 2017 was included. Patients were divided into two groups, dominant right ventricle (RV type, n = 235) and dominant left ventricle (LV type, n = 170). S2P related factors associated with mortality, postoperative ventricular function, and late exercise capacity following TCPC, were analyzed. The median age at S2P was 4 [3-7] and 6 [3-11] months in RV and LV type patients, respectively (p = 0.092). Survival after TCPC was similar in RV and LV type patients (p = 0.280). In those with RV type, risk factors for mortality following TCPC were older age (p < 0.001), heavier weight (p = 0.001), higher PAP (p < 0.001), higher TPG (p = 0.010), and lower SO2 (p = 0.008) at S2P. In those with LV type, no risk factor was identified. Risk factors for postoperative impaired ventricular function were older age and higher weight at S2P in both RV and LV type patients. Older age at S2P was also identified as a risk for inferior peak oxygen uptake (VO2) years after TCPC both in RV and LV type patients. Older age at S2P was associated with higher mortality after Fontan completion only in RV type patients. However, it was associated with postoperative ventricular dysfunction and lower exercise capacity after TCPC in both RV and LV type patients.

We recently experienced a 70-year-old woman with left main trunk-acute coronary syndrome who was initially supported by Impella 5.0 which converted to paracorporeal left ventricular assist device (LVAD) implantation as a bridge to recovery. Optimized guideline-directed medical therapy with cardiac rehabilitation resulted in successful explantation of LVAD and she discharged on foot.

Currently, we use the Nipro paracorporeal VAD (p-VAD) for initial short-term ventricular support, as a bridge to decision (BTD) or a bridge to candidacy (BTC) treatment, in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels 1 and 2 patients. However, it is possible that compared to patients with primary implantable-VADs (P-iVAD), the bridge-to-bridge (BTB) patients are more likely to develop complications. This retrospective study used data from 24 consecutive BTB patients who were initially implanted with Nipro p-VAD as BTD or BTC treatments between April 2011 and March 2016, and subsequently underwent conversion to an i-VAD. The data from 72 patients who underwent a primary i-VAD (P-iVAD) procedure were used for comparison. Between the two groups, there was no significant difference in the incidence of infectious events (p = 0.72) or stroke (p = 0.44). Orthotropic heart transplantation was performed in 6 of the 24 patients in the BTB group and in 21 of the 72 patients in the P-iVAD group. The 1- and 2-year survival rates were 95.8% and 95.8% in the BTB group and 91% and 85.8% in the P-iVAD group; these values were not significantly different between groups (p = 0.91). Based on these results we conclude that BTB using Nipro p-VAD is a reasonable strategy for treating patients with severe decompensated end-stage heart failure.

Although the outcomes of patients with end-stage heart failure treated with implantable left ventricular assist devices have improved, extracorporeal left ventricular assist devices continue to play an important role, especially in pediatric patients. The present study aimed to examine the long-term biocompatibility of a small-sized extracorporeal pneumatic left ventricular assist device (NIPRO-LVAD) used in a 30- to 90-day animal experiment. The NIPRO-LVAD was designed for pediatric patients or small-sized adults. The left ventricular assist device system was installed in four adult Shiba goats weighing 25.7 ± 4.78 kg via a left thoracotomy. The outflow graft was sewn to the descending aorta and the inflow cannula was placed in the left ventricle through the left ventricular apex. Oral antiplatelet (aspirin) and oral anticoagulation therapies (warfarin) were also administered. Three out of four animals survived for a 30-day period and two goats survived for 90 days. One animal was killed early because of low pump flow due to obstruction of the inflow cannula by a left ventricular endocardial vegetation. The blood pump exhibited sufficient hydrodynamic performance with blood flows of 1.5-2.0 L/min. The animals' laboratory values were within normal limits by postoperative day 7. There was no significant thrombus formation on the housing, diaphragm, or valves of the explanted pumps. Based on the biocompatibility demonstrated in this animal study, the explanted small-sized pump may be suitable for use in left ventricular assist device systems for pediatric patients.

The optimal timing for pulmonary valve replacement after Tetralogy of Fallot (TOF) repair remains controversial. In this study, we estimated the feasibility of using flow energy loss (FEL) to predict right ventricular (RV) deterioration due to pulmonary regurgitation after TOF repair. We examined RV outflow tract (RVOT) flow in nine patients who underwent TOF or double-outlet right ventricle repair in the intervention group (Group I) and compared them with three healthy children in the control group (Group C). We evaluated flow across the RVOT and pulmonary valve by vector flow mapping (VFM) on echocardiography and by phase contrast-magnetic resonance imaging (PC-MRI). Next, we calculated FEL and analyzed the relationship between FEL and clinical parameters of RV function. The mean FEL was significantly greater in Group I than in Group C (p = 0.002). Flow pattern and FEL were comparable by VFM and PC-MRI at the same phase 14.6 years after TOF repair. There was a significant positive correlation for the cardiothoracic ratio with both the mean FEL [correlation coefficient (r) = 0.78; p = 0.012] and the diastolic peak FEL (r = 0.75; p = 0.021) in Group I. There was also a significant positive correlation between the serial change in QRS duration with both the mean FEL (r = 0.82; p = 0.014) and the diastolic FEL (r = 0.70; p = 0.052) in Group I. FEL by VFM is an effective tool for evaluating ventricular deterioration caused by RV workload.

Continuous flow left ventricular assist device (CF-LVAD) therapy has improved the survival of patients with advanced heart failure. However, the readmission rate of CF-LVAD patients is still relatively high. A total of 90 patients who received CF-LVADs between April 2011 and March 2016 at our institute and were discharged home were analyzed retrospectively. They were followed up through March 2017. Clinical data, including frequency, length and etiology of readmission, were obtained from medical records. The mean observation period after initial discharge was 713 ± 322 days. In total, 73 patients (81%) had 236 readmissions, 214 unplanned and 22 planned. The overall and unplanned readmission rates were 1.34 and 1.22 per patient-year, respectively. The rate of freedom from unplanned first readmission at 1 year after initial discharge was 39%. The median interval between the previous hospital discharge and first and second readmissions was 311 and 213 days, respectively (log-rank test, p = 0.117). The rate of readmission after more than three readmissions was significantly higher than that of first or second readmission (log-rank test, p < 0.001). The most common etiology of readmission was driveline infection (DLI) (36%), followed by stroke (9%). The median length of hospital stay due to DLI was 23 days. The patients with repeated unplanned readmissions had significantly lower EuroQol 5 dimensions questionnaire utility score than those with no or just one readmission. Readmission was common in CF-LVAD patients, and the most common etiology of readmissions was DLI. The interval to the next readmission seemed shorter for patients with repeated readmissions.

To explore the role of the volatiles emitted from male labial gland (LG) of the bumblebee Bombus ardens ardens, we investigated the responses of virgin queens and males to volatiles using a gas chromatography-electroantennographic detector (GC-EAD) system and Y-tube olfactometer. GC-EAD analysis revealed that citronellol, the main compound detected in the male LG, caused clear electrophysiological responses in the antennae of B. a. ardens virgin queens and males although two minor compounds elicited antennal responses when applied in a high concentration. Behavioral tests using a Y-tube olfactometer showed that queens and males were significantly attracted to both LG extracts and citronellol more than to the solvent alone. This is the first study to demonstrate that citronellol as a major compound of male scent-marking pheromone in B. a. ardens functions as a sex attractant for queens. The results also suggest that this compound has another function as a trail marker used by males.

Patients with mechanical aortic valves are generally contraindicated for left ventricular assist device (LVAD) insertion because the prosthetic valve often becomes fixed in closed position. A 41-year-old woman with mechanical aortic valve prosthesis experienced sudden chest pain and developed cardiogenic shock. A paracorporeal pulsatile LVAD and a monopivot centrifugal pump as a right VAD (RVAD) were implanted. The mechanical aortic valve was intentionally left in place. Soon after the operation, LVAD support was discontinued daily for few seconds to allow the mechanical aortic valve to open and to avoid thrombus formation. The patient was successfully weaned off RVAD and received anticoagulation therapy with warfarin. On postoperative day 141, she was transferred to a university hospital where a HeartMate II LVAD was implanted, and the aortic valve was successfully replaced with a bioprosthetic valve. The patient is currently awaiting heart transplantation.

Current studies on the incidence of arrhythmias after the intra-atrial lateral tunnel (ILT) Fontan operation and the extra-cardiac conduit (ECC) Fontan operation are limited, with controversial results. This systematic review aimed to compare the prevalence of arrhythmias in patients who underwent ECC or ILT Fontan. Relevant studies comparing the incidence of arrhythmias and pacemaker implantation in ILT with ECC were identified through a literature search using MEDLINE, EMBASE, and the cochrane central register of controlled trials. The outcome measures included baseline characteristics, early (≤30 days) and late (>30 days) arrhythmias and pacemaker implantation. 16 publications involving 3499 patients were included. In the meta-analysis, although the overall risk of early arrhythmias was lower for the ILT group, statistically, no significant difference was observed (odds ratio [OR] 0.78; 95% confidence interval [CI] 0.61-1.01; p = 0.06). Similarly, there was no significant difference between the two cohorts in the incidence of postoperative permanent pacemaker therapy (OR 1.36; 95% CI 0.86-2.14; p = 0.19). However, we found significantly increased incidence of late arrhythmias in ILT group compared with ECC group (OR 1.96; 95% CI 1.64-2.35; p < 0.01). Although our systematic review and meta-analysis suggested that there was no significant difference in early arrhythmias and in pacemaker implantation between the ILT and ECC groups, ECC procedure could significantly lower the risk of late arrhythmias after Fontan surgery. Given that some limitations cannot be overcome, well-designed randomized controlled trials are needed to confirm our findings.

Aortic insufficiency (AI) is a significant complication of long-term support of continuous flow left ventricular assist device (CF-LVAD) for patients with end-stage heart failure. A 26-year-old female with osteogenesis imperfecta (OI) was diagnosed with dilated phase hypertrophic cardiomyopathy (d-HCM)) and was implanted with Jarvik 2000, for bridge to transplantation. AI gradually developed and surgical intervention was indicated. We performed central aortic valve closure (CAVC) instead of valve replacement 20 months after CF-LVAD implantation. Patient's symptoms dramatically improved postoperatively. This is the first report of CAVC for a patient supported with Jarvik 2000.

Continuous-flow left ventricular assist devices (LVADs) have improved the prognosis of end-stage heart failure. However, continuous-flow LVADs diminish pulsatility, which possibly result in bleeding, aortic insufficiency, and other adverse effects. We previously developed a novel control system for a continuous-flow LVAD (EVAHEART ® ; Sun Medical), and demonstrated that we could create sufficient pulsatility by increasing its rotational speed (RS) in the systolic phase (Pulsatile Mode) in the normal heart model. Here, we aimed to evaluate differences between systolic assist with advanced and delayed loads by shifting the timing of increased RS. We implanted EVAHEART in six goats (55.3 ± 4.3 kg) with normal hearts. We reduced their heart rates to <60 bpm using propranolol and controlled the heart rates at 80 and 120 bpm using ventricular pacing. We shifted the timing of increasing RS from -60 to +60 ms in the systolic phase. We found significant increases in all the following parameters when assessments of delayed timing (+60 ms) were compared with assessments of advanced timing (-60 ms): pulse pressure, mean dP/dt max of aortic pressure, and energy-equivalent pulse pressure. During continuous-flow LVAD support, pulsatility can be controlled using a rotary pump. In particular, pulsatility can be shifted by delaying increased RS.

Although the survival rate for left ventricular assist device (LVAD) therapy has improved, device-related complications are an unpredictable threat to the patient's quality of life. We focused on driveline infection, and aimed to determine whether specific features of drivelines affect the frequency of infection. We enrolled patients who underwent LVAD implantation and were followed-up at our institute between 2007 and 2015. We counted the occurrences of driveline infection requiring any antibiotic therapy over a 2-year study period. Furthermore, we experimentally measured and compared the outer diameters and stiffness of three devices. Of all, 72 patients received an LVAD during the enrollment period. LVADs were HeartMate II (n = 32), EVAHEART (n = 22), and DuraHeart (n = 18). The outer diameters and stiffness were measured in five of each device. HeartMate II group had the highest driveline infection-free rate among all three devices during the study period (p = 0.042). The driveline of the HeartMate II LVAD had a significantly smaller outer diameter and lower stiffness than that of the other two devices (p < 0.05 for both). In conclusion, device-specific driveline features may affect the development of driveline infection during LVAD therapy.

Nipro-Toyobo-paracorporeal pulsatile flow VAD (Nipro VAD; Nipro, Osaka, Japan) has been used most commonly as a paracorporeal VAD (p-VAD) in Japan. There are few reports describing clinical course of post LVAD explantation and its complication. We herein present two cases of apical abscess after the explantation of the device. SSI is a main risk factor of formation of the apical abscess at the time of LVAD explantation. It is mandatory to perform sufficient debridement and closure of the layers including abdominal muscle and anterior abdominal fascia at exit sites in the explantation surgery. Omentopexy is also helpful for prevention from infection. Routine removal of apical cuff and outflow graft could be considered as one of the options when LVAD is explanted as bridge to recovery.

Cardiac replacement therapy, consisting of left ventricular assist device (LVAD) implant surgery and heart transplantation, has considerably reduced the mortality and morbidity of patients with stage D heart failure. However, its impact on pulmonary function remains unclear. We retrospectively evaluated 22 consecutive patients (16 men; 42 ± 13 years old) who had undergone pulmonary function tests during the heart failure, LVAD, and heart transplantation periods. The LVAD therapy lasted an average of 871 ± 267 days. The % vital capacity and forced expiratory volume in 1 s decreased significantly after LVAD implantation and returned to baseline levels after heart transplantation. Correlation analysis indicated that a shorter duration of LVAD support was associated with a more significant improvement in % vital capacity in heart transplantation recipients, compared to the pre-LVAD period and the LVAD period. In conclusion, we provide evidence that a decrease in pulmonary function occurs during LVAD support but it may be reversible. Limited LVAD duration may be a key for the recovery of pulmonary dysfunction.

We successfully managed a splenic injury and delayed splenic rupture in a patient with an implantable left ventricular assist device (iLVAD). A 42-year-old man with an iLVAD for idiopathic dilated cardiomyopathy was admitted to our department complaining of dizziness. Laboratory data showed severe anemia, and computed tomography demonstrated a traumatic splenic injury. Following conservative treatment, partial splenic embolization was performed. Fifteen days after the intervention, the patient went into hemorrhagic shock due to delayed splenic rupture. Emergency total splenic embolization was performed, and total splenectomy was conducted later to prevent re-bleeding or abscess formation. His postoperative course was uneventful, and he was discharged on postoperative day 22. Finally, he underwent orthotropic heart transplantation without post-splenectomy sepsis or thrombotic complications 472 days after splenectomy. Splenic injury should be considered as a possible complication of iLVAD. In addition, careful follow-up after transcatheter arterial embolization for splenic injury is essential for managing delayed splenic rupture.

The acetylcholine (ACh) provocation test (ACh-test) is used for the diagnosis of vasospastic angina (VSA). However, subjects often show a moderate spasm (MS) response for which diagnosis of VSA is not definitive, and the clinical significance of this response is unknown. We assessed moderate coronary vasomotor response to the ACh test as an indicator of long-term prognosis. A total of 298 consecutive patients who underwent the ACh test for suspected VSA were retrospectively investigated. Coronary spasm severity after intracoronary administration of isosorbide dinitrate was evaluated by measuring epicardial coronary artery diameter reduction after ACh injection. Patients were divided into three groups according to the diameter reduction during the ACh test: severe spasm (SS) showing ≥75 % diameter reduction, MS showing ≥50 % diameter reduction, and others (N). In Kaplan-Meier analysis, the major adverse cardiac event (MACE) rates with a median follow-up of 4.6 years were significantly worse in SS (11.1 %) and MS (8.5 %) than N (1.9 %), (SS vs N; P = 0.009, MS vs N; P = 0.029). Significant difference in MACE rates was not observed between SS and MS (P = 0.534). Cox regression analysis revealed that MS remained an independent predictor of MACE after adjustment for other confounders (HR: 7.18, 95 % CI 1.42-36.4, P = 0.017). Patients with MS by ACh test had a cardiac event rate comparable with that of patients with SS and significantly worse than that of patients with normal vasomotor responses.

We have previously developed a native heart load control system for a continuous-flow left ventricular assist device (LVAD) ((EVAHEART ® ; Sun Medical) and demonstrated that the rotational speed (RS) in synchronization with the cardiac cycle can alter pulsatility and left ventricular (LV) load under general anesthesia. In this study, we assessed the effects of different levels of increase in RS on pulsatility and LV load in the chronic awake phase. We implanted the EVAHEART via left thoracotomy in 7 normal goats (59.3 ± 4.6 kg). Two weeks after implantation, we examined the effects of co-pulse mode (increased RS in the systolic phase) and counter-pulse mode (increased RS in the diastolic phase), as well as shifting the change in RS from 250 to 500 rpm, and 750 rpm in both modes on pulsatility and LV load. Pulsatility was assessed using pulse pressure and mean dP/dt max of aortic pressure. LV load was assessed using stroke work and left ventricle end-diastolic volume determined from LV pressure-volume loops. In the co-pulse mode, pulsatility values increased as the change in RS increased. By contrast, in the counter-pulse mode, these values decreased as the change in RS increased. LV load increased significantly in the co-pulse mode compared with the counter-pulse mode, but there were no significant differences among the three levels of RS increase in either mode. Increasing RS to varying degrees with our newly developed system could contribute to pulsatility. However, it appeared to have little effect on LV load in normal hearts.

We successfully controlled infection of a left ventricular assist device by performing pump exchange. A 53-year-old man was implanted with DuraHeart for ischemic cardiomyopathy as a bridge to transplantation. Two years later, he was hospitalized with the diagnosis of driveline infection. The blood cultures detected Pseudomonas aeruginosa. During the admission, he developed brain hemorrhage perhaps due to septic emboli. The chest computed tomography scan revealed a small defect inside the outflow graft of the DuraHeart, which was highly suspected of vegetation. He underwent pump exchange, from DuraHeart to Jarvik 2000 with concomitant omentopexy. His postoperative course was uneventful, and he was discharged with no sequela of the brain hemorrhage. Four months after the pump exchange, he successfully underwent heart transplantation. No infectious tissue was observed in the pericardial space at the time of heart transplantation. Pump exchange is an effective way to manage refractory left ventricular assist device infection, and the timing of surgical intervention is of great importance.

Cardiopulmonary exercise testing (CPXT) is a promising tool for predicting 2-year cardiac death or ventricular assist device (VAD) implantation in patients assigned to INTERMACS profile 4-7. However, CPXT is not available in all hospitals. We evaluated 130 patients <65 years old with advanced heart failure assigned to INTERMACS profile 4-7 who underwent CPXT. CPXT scores (0-8 points), which we created recently, and the Seattle HF Model (SHFM) scores were both significant predictors of 2-year cardiac death or VAD implantation (14 events) by Cox-regression analysis (P < 0.05 for both) and had comparable areas under the curve (AUCs) in receiver operating characteristic analyses (0.811 vs. 0.737, P > 0.05). The combination score: age <46 years and serum sodium concentration <137 mEq/L, both of which were significant predictors of cardiac death or VAD implantation by uni/multivariate Cox-regression analyses, had a significantly higher AUC than did CPXT scores (0.909, P < 0.05). In a validation study, the AUC of the combination score was comparable with that of SHFM among 52 patients <65 years old receiving adaptive servo-ventilator treatment (0.753 vs. 0.794, P > 0.05). In conclusion, VAD indication may be discussed without CPXT in patients <65 years old with INTERMACS profile 4-7 at least in the current Japanese situation.

For the continued development of improved mechanical circulatory systems, longer term evaluation of new devices in animal model experiments may be critical. The effects of anticoagulants in adult goats have not been well studied. We assessed the effects of oral warfarin in three adult goats during fasting or after feeding. The goats [weighing 57.8 ± 8.1 kg (53.0-67.2 kg)] were administered warfarin orally beginning at a dose of 5 mg/day and then increasing to 10, 20, 40, and 60 mg every 2 weeks. One goat (receiving 10 mg/day warfarin) was killed on day 27 because of the inability to stand. After administration of 60 mg warfarin, the remaining goat received no warfarin for 4 days to return to coagulated state. The goats were then fasted and treated with 40 mg warfarin. During warfarin administration, both goats required a dose of 60 mg/day to achieve International Normalized Ratios (INRs) of approximately 2.5; however, when, the animals were in the fasted condition, precipitous extension of INR was observed in 5 days. After resuming feeding, the INR was reduced to the proper range. We showed the tendency that warfarin therapy in goats required higher doses than the doses administered to human patients and that the effects of therapy were related to the feeding state. The results of this study provide important information for development of anticoagulation protocols to assess mechanical circulatory support devices for long-term use in preclinical examination.

We present a case of paracorporeal left ventricular assist device (p-LVAD)-related infection, caused by multi-drug resistant Pseudomonas aeruginosae (MDRP), and successfully treated by p-LVAD re-implantation with omental covering. A 59-year-old man underwent p-LVAD implantation and coronary artery bypass grafting after percutaneous cardiopulmonary support and intra-aortic balloon pumping for cardiogenic shock due to acute myocardial infarction. Then, he was registered for heart transplantation. He suffered from blood stream infection causative organism of Pseudomonas aeruginosa, 2 months after that operation. He underwent re-median sternotomy and open drainage, 15 months after the p-LVAD implantation. However, he suffered from septic shock due to MDRP. He underwent p-LVAD re-implantation under hypothermic circulatory arrest and iodine gauze packing, followed by omental covering of the all artificial materials in his body 10 days after that operation. Soon after that, the infection was well controlled and the intravenous antibiotics could be discontinued 2 months after that operation. He successfully underwent heart transplantation, 17 months after that procedure. We concluded that p-LVAD re-implantation with omental covering is seemed to be useful in the treatment of massive device infection. This procedure might be a novel treatment for severe VAD-related infection until heart transplantation.

For coronary artery bypass grafting (CABG), free grafts such as a saphenous vein or radial artery are often used for grafts to the lateral and posterior walls. However, the relationship between top-end anastomosis design and long-term patency remains unknown. Because coronary artery blood flow is dominant during diastole, top-end anastomosis may work better if the graft is directed towards the apex, whereas the shortest graft pathway appears to be most efficient. Using computational fluid dynamic models, we evaluated the hemodynamic variables that were affected by the angle of the top-end anastomosis. We created three-dimensional geometries of the aortic root with coronary arteries that involved 75 % stenosis in the obtuse marginal and postero-lateral branches. Two bypass models under vasodilator administration were created: in a"Model A", the top-end anastomosis is parallel to the long axis of the ascending aorta and the graft passed over the conus directed towards the apex; in a "Model B", the top-end anastomosis is directed toward the shortest pathway, and form near the right angles to the long axis of the ascending aorta. Wall shear stress (WSS) and its fluctuation, an oscillatory shear index (OSI) were evaluated to predict fibrosis progression at the anastomosis site and graft flow. Graft flow was 197.3 ml/min and 207.3 ml/min in the "Model A" and "Model B", respectively. The minimal WSS value inside the graft with the "Model A" and "Model B" was 0.53 Pa and 4.09 Pa, respectively, and the OSI value was 0.46 and 0.04, respectively. The top-end anastomosis of a free graft should be directed vertically towards the aorta to achieve the shortest graft pathway to maintain a high graft flow rate and to avoid the risks of endothelial fibrosis and plaque progression over the long-term after CABG.

Gynandromorphy that has both male and female features is known in many insect orders, including Hymenoptera. In most cases, however, only external morphology and behavioral aspects have been studied. We found a gynandromorph of bumblebee, Bombus ignitus, that showed almost bilateral distribution of external sexual traits, with male characters observed on the left side and female characters on the right side. This individual never exhibited sexual behavior toward new queens. The dissection of the head part showed that it had bilaterally dimorphic labial glands, only the left of which was well developed and synthesized male-specific pheromone components. In contrast, the gynandromorph possessed an ovipositor and a pair of ovaries in the abdominal part, suggesting that it had a uniformly female reproductive system. Furthermore, we characterized several internal organs of the gynandromorph by a molecular biological approach. The expression analyses of a sex determination gene, doublesex, in the brain, the fat bodies, the hindgut, and the ovaries of the gynandromorph revealed a male-type expression pattern exclusively in the left brain hemisphere and consistent female-type expression in other tissues. These findings clearly indicate the sexual discordance between external traits and internal organs in the gynandromorph. The results of genetic analyses using microsatellite markers suggested that this individual consisted of both genetically male- and female-type tissues.

Although the right ventricular stroke work index (RVSWI) is a good index for RV function, a low RVSWI is not necessarily an indicator for the need for a right ventricular assist device at the time of left VAD implantation. We here aimed to determine a more precise indicator for the need for a biventricular assist device (BiVAD). In total, 116 patients (mean age, 38 ± 14 years), who underwent hemodynamic assessments preoperatively including 12 BiVAD patients, and had been followed at our institute from 2003 to 2015, were included. Multivariate logistic regression analysis indicated that RVSWI and pulmonary vascular resistance (PVR) were independent predictors of BiVAD requirement (P < 0.05 for both). In addition, all patients were classified into 4 groups: (1) normal (RVSWI > 5 g/m, PVR < 3.7 WU), (2) pulmonary hypertension (RVSWI > 5, PVR > 3.7), (3) RV failure (RVSWI < 5, PVR < 3.7), and (4) both pulmonary hypertension and RV failure (RVSWI < 5, PVR > 3.7), and examined. Most of the patients in Group 4 (75 %), with acutely depressed hemodynamics and inflammatory responses in the myocardium, required BiVAD. Overall, patients with BiVAD had a worse survival rate as compared with those with LVAD alone. In conclusion, high PVR in addition to low RVSWI effectively predicts BiVAD requirement.

We recently reported a multi-center, single-arm, phase II study that evaluated the efficacy and safety of autologous skeletal myoblast sheet (TCD-51073) transplantation. The advantage of this procedure over a control group has not yet been analyzed. Seven patients with advanced heart failure due to ischemic etiology (TCD-51073 group, New York Heart Association (NYHA) class III; left ventricular ejection fraction (LVEF) <35 %) refractory to optimal medical and coronary revascularization therapy, received TCD-51073 at 3 study centers between 2012 and 2013 with a 2-year follow-up period. As previously reported, 112 patients received cardiac resynchronization therapy (CRT) with follow-up at the University of Tokyo Hospital between 2007 and 2014. Of them, 21 patients were selected for the control group by propensity score matching. No significant difference in baseline variables between the groups was observed. LVEF and NYHA class improved significantly in the TCD-51073 group during the 6-month study period (p < 0.05). During the 2-year follow-up, 7 patients (33 %) in the CRT group and no patient in the TCD-51073 group died due to cardiac disease or received VAD implantation (p = 0.128 by the log-rank test). In conclusion, transplantation of TCD-51073 is clinically advantageous in facilitating LV reverse remodeling, improving HF symptoms, and preventing cardiac death in patients with ischemic etiology when compared to background-matched patients receiving CRT.

Although left ventricular reverse remodeling (LVRR) is accompanied with an improved clinical course during LV assist device (LVAD) treatment, its preoperative prediction remains uncertain. Twenty-seven heart failure patients with dilated cardiomyopathy were enrolled in this study. Patients underwent (123)I-meta-iodobenzylguanidine (MIBG) scintigraphy before LVAD implantation, and were monitored at our institute from 2010 to 2014. This study investigated the prognostic value of preoperative (123)I-MIBG parameters for predicting postoperative LVRR. Of the preoperative variables studied, including (123)I-MIBG data, washout rate (WR) ≤ 39 % was the only significant, independent predictor of LVRR (defined as LV ejection fraction ≥35 % at 6 months post-LVAD implant using univariate and multivariate logistic regression analyses) (p = 0.036, odds ratio [OR]:14.45). Improved exercise capacity and more frequent opening of the native aortic valve, as well as lower B-type natriuretic peptide plasma levels, were observed in LVRR patients (p < 0.05 for all), although β-blocker doses were comparable with those of non-LVRR patients throughout the 6-month LVAD support period. In conclusion, preoperative (123)I-MIBG is a novel predictive tool of LVRR during LVAD support.

The aim of the present study was to perform a cost-effectiveness analysis (CEA) of ventricular assist devices (VAD) implantation surgery in the Japanese medical reimbursement system. The study group consisted of thirty-seven patients who had undergone VAD implantation surgery for dilated cardiomyopathy (n = 25; 67.6 %) or hypertrophic cardiomyopathy (n = 4; 10.8 %), and others (n = 8; 21.6 %). Quality-adjusted life years (QALYs) were calculated using the utility score and years of life. Medical reimbursement bills were chosen as cost indices. The observation period was the 12-month period after surgery. Then, the incremental cost-effectiveness ratio was calculated according to the VAD type. In addition, the prognosis after 36 months was estimated on the basis of the results obtained using the Markov chain model. The mean preoperative INTERMACS profile score was 2.35 ± 0.77. Our results showed that the utility score, which indicates the effectiveness of VAD implantation surgery, improved by 0.279 ± 0.188 (ΔQALY, p < 0.05). The cost of VAD implantation surgery was 313,282 ± 25,275 (ΔUS$/year) on the basis of medical reimbursement bills associated with therapeutic interventions. The calculated result of CEA was 364,501 ± 190,599 (ΔUS$/QALY). The improvement in the utility score was greater for implantable versus extracorporeal VADs (0.233 ± 0.534 vs. 0.371 ± 0.238) and ICER was 303,104 (ΔUS$/ΔQALY). Furthermore, when we estimated CEA for 36 months, the expected baseline value was 102,712 (US$/QALY). Therefore, VAD implantation surgery was cost effective considering the disease specificities.

Background: Negative pressure wound therapy (NPWT) is commonly used to accelerate wound healing, especially following thoracic surgery; however, the mechanism remains elusive. Given the important role of vasculogenesis in wound healing, we evaluated whether NPWT might accelerate vasculogenesis in the wound area. Toward this end, we investigated the temporal expression of vascular endothelial growth factor receptors (VEGFRs) in an NPWT-wound healing rabbit model., Methods: Rabbits were divided into an NPWT group and a non-NPWT control group, and tissue samples were collected around wounds made in the skin of each rabbit at five time points: 0, 7, 14, 21, and 28 days after wound creation. Cryopreserved samples were then immunostained and subject to image analysis to evaluate the temporal changes in VEGFR1, VEGFR2, and VEGFR3 expression in the wound-healing process., Results: Results of histological analysis of the temporal changes in VEGFR expression throughout the healing process showed that compared to the control group, VEGFR2 and VEGFR3 were abundantly and rapidly expressed in the NPWT group, and were expressed earlier than VEGFR1., Conclusions: NPWT promotes the expression of VEGFR2 and VEGFR3, which provides insight into the mechanism by which NPWT accelerates wound healing. Level of Evidence: Not ratable.

How to manage preoperative right ventricular dysfunction (RVD) in heart failure patients without cardiogenic shock remains as a matter to be debated because implantable biventricular assist device treatment has not been established thus far. We here presented a patient with significant RVD indicated by low RV stroke work index (0.3 g/m) and RV dilatation as well as low pulmonary vascular resistance (PVR, 0.8 Wood Unit), who was managed by the introduction of pimobendan and sildenafil after the implantation of DuraHeart and tricuspid annuloplasty without right VAD, although his New York Heart Association symptom remained class III. Preoperative low PVR may be a key for successful LVAD treatment alone without right VAD in patients with INTERMACS profile 3 suffering RVD.