Learning-dependent structural plasticity of intracortical and sensory connections to functional domains of the olfactory tubercle.

The olfactory tubercle (OT), which is a component of the olfactory cortex and ventral striatum, has functional domains that play a role in odor-guided motivated behaviors. Learning odor-guided attractive and aversive behavior activates the anteromedial (am) and lateral (l) domains of the OT, respectively. However, the mechanism driving learning-dependent activation of specific OT domains remains unknown. We hypothesized that the neuronal connectivity of OT domains is plastically altered through olfactory experience. To examine the plastic potential of synaptic connections to OT domains, we optogenetically stimulated intracortical inputs from the piriform cortex or sensory inputs from the olfactory bulb to the OT in mice in association with a food reward for attractive learning and electrical foot shock for aversive learning. For both intracortical and sensory connections, axon boutons that terminated in the OT domains were larger in the amOT than in the lOT for mice exhibiting attractive learning and larger in the lOT than in the amOT for mice exhibiting aversive learning. These results indicate that both intracortical and sensory connections to the OT domains have learning-dependent plastic potential, suggesting that this plasticity underlies learning-dependent activation of specific OT domains and the acquisition of appropriate motivated behaviors.

Expression of feeding-related neuromodulatory signalling molecules in the mouse central olfactory system.

Various neural systems cooperate in feeding behaviour, and olfaction plays crucial roles in detecting and evaluating food objects. While odour-mediated feeding behaviour is highly adaptive and influenced by metabolic state, hedonic cues and learning processes, the underlying mechanism is not well understood. Feeding behaviour is regulated by orexigenic and anorexigenic neuromodulatory molecules. However, knowledge of their roles especially in higher olfactory areas is limited. Given the potentiation of feeding behaviour in hunger state, we systemically examined the expression of feeding-related neuromodulatory molecules in food-restricted mice through quantitative PCR, in the olfactory bulb (OB), olfactory tubercle (OT), and remaining olfactory cortical area (OC). The OT was further divided into attraction-related anteromedial, aversion-related lateral and remaining central regions. Examination of 23 molecules including neuropeptides, opioids, cannabinoids, and their receptors as well as signalling molecules showed that they had different expression patterns, with many showing elevated expression in the OT, especially in the anteromedial and central OT. Further, in mice trained with odour-food association, the expression was significantly altered and the increase or decrease of a given molecule varied among areas. These results suggest that different olfactory areas are regulated separately by feeding-related molecules, which contributes to the adaptive regulation of feeding behaviour.

Olfactory Stimulation with Japanese Soy Sauce Improves Upper Limb Performance.

BACKGROUND: We have observed changes in body reactions during cooking, which is one of the treatment modalities used in occupational therapy. The perception of food-related odors during cooking may have behavioral effects on human activities through the activation of appetitive motivation. OBJECTIVES: We investigated whether odor components contained in seasonings could facilitate the human motor system and the specificity of this effect. METHODS: The subjects were 72 healthy adults, randomly assigned to a water exposure group, a phenylethyl alcohol (PEA, pleasant rose-like odor) exposure group, and a Japanese soy sauce (Koikuchi Shoyu) exposure group (n = 24 each). The subjects' olfactory sense was stimulated by their sniffing of three different test tubes containing 5 ml of water, PEA, or Japanese soy sauce for 20 sec while they were seated. The modified Functional Reach Test (mFRT), which mimics a functional activity that is required in daily living and assesses a reliable measure of sitting balance, was performed prior to and immediately after the sniffing. RESULTS: Sniffing the soy sauce increased the subjects' mFRT scores. This facilitation effect was odorant-specific and was absent when the subjects were presented with water or PEA. CONCLUSIONS: Cooking interventions are aimed at improving tool-handling skills such as using knives and chopsticks. The results indicate that treatment interventions using odors of seasonings would be effective for improving subjects' physical functions.

α2-Adrenergic receptor activation promotes long-term potentiation at excitatory synapses in the mouse accessory olfactory bulb.

The formation of mate recognition memory in mice is associated with neural changes at the reciprocal dendrodendritic synapses between glutamatergic mitral cell (MC) projection neurons and GABAergic granule cell (GC) interneurons in the accessory olfactory bulb (AOB). Although noradrenaline (NA) plays a critical role in the formation of the memory, the mechanism by which it exerts this effect remains unclear. Here we used extracellular field potential and whole-cell patch-clamp recordings to assess the actions of bath-applied NA (10 µM) on the glutamatergic transmission and its plasticity at the MC-to-GC synapse in the AOB. Stimulation (400 stimuli) of MC axons at 10 Hz but not at 100 Hz effectively induced N-methyl-d-aspartate (NMDA) receptor-dependent long-term potentiation (LTP), which exhibited reversibility. NA paired with subthreshold 10-Hz stimulation (200 stimuli) facilitated the induction of NMDA receptor-dependent LTP via the activation of α2-adrenergic receptors (ARs). We next examined how NA, acting at α2-ARs, facilitates LTP induction. In terms of acute actions, NA suppressed GC excitatory postsynaptic current (EPSC) responses to single pulse stimulation of MC axons by reducing glutamate release from MCs via G-protein coupled inhibition of calcium channels. Consequently, NA reduced recurrent inhibition of MCs, resulting in the enhancement of evoked EPSCs and spike fidelity in GCs during the 10-Hz stimulation used to induce LTP. These results suggest that NA, acting at α2-ARs, facilitates the induction of NMDA receptor-dependent LTP at the MC-to-GC synapse by shifting its threshold through disinhibition of MCs.

Tunicamycin impairs olfactory learning and synaptic plasticity in the olfactory bulb.

Tunicamycin (TM) induces endoplasmic reticulum (ER) stress and inhibits N-glycosylation in cells. ER stress is associated with neuronal death in neurodegenerative disorders, such as Parkinson's disease and Alzheimer's disease, and most patients complain of the impairment of olfactory recognition. Here we examined the effects of TM on aversive olfactory learning and the underlying synaptic plasticity in the main olfactory bulb (MOB). Behavioral experiments demonstrated that the intrabulbar infusion of TM disabled aversive olfactory learning without affecting short-term memory. Histological analyses revealed that TM infusion upregulated C/EBP homologous protein (CHOP), a marker of ER stress, in the mitral and granule cell layers of MOB. Electrophysiological data indicated that TM inhibited tetanus-induced long-term potentiation (LTP) at the dendrodendritic excitatory synapse from mitral to granule cells. A low dose of TM (250nM) abolished the late phase of LTP, and a high dose (1µM) inhibited the early and late phases of LTP. Further, high-dose, but not low-dose, TM reduced the paired-pulse facilitation ratio, suggesting that the inhibitory effects of TM on LTP are partially mediated through the presynaptic machinery. Thus, our results support the hypothesis that TM-induced ER stress impairs olfactory learning by inhibiting synaptic plasticity via presynaptic and postsynaptic mechanisms in MOB.

Donor-Transmitted Atherosclerosis Associated With Worsening Cardiac Allograft Vasculopathy After Heart Transplantation: Serial Volumetric Intravascular Ultrasound Analysis.

BACKGROUND: The influence of preexisting donor-transmitted atherosclerosis (DA) on cardiac allograft vasculopathy (CAV) development remains unclear. METHODS: We performed 3-dimensional intravascular ultrasound (3D-IVUS) analysis in 42 heart transplantation (HTx) recipients at 2.1 ± 0.9 months (baseline) and 12.2 ± 0.4 months post-HTx, as well as consecutive 3D-IVUS analyses up to 3 years post-HTx in 35 of the 42 recipients. Donor-transmitted atherosclerosis was defined as a maximal intimal thickness of 0.5 mm or greater at baseline. Changes in volumetric IVUS parameters were compared in recipients with (DA group) and without DA (DA-free group) at baseline, 1 year, and 3 years post-HTx. RESULTS: Donor-transmitted atherosclerosis was observed in 57.1% of 42 recipients. The DA group exhibited a significantly greater increase in plaque volume at 1 year post-HTx (P < 0.001), leading to increased percent plaque volume (plaque volume/vessel volume, [%]) (P < 0.001) and decreased luminal volume (P = 0.021). Donor-transmitted atherosclerosis was independently associated with a greater increase in percent plaque volume during the first post-HTx year (P = 0.011). From 1 to 3 years post-HTx, the DA group underwent continuous reduction in luminal volume (P = 0.022). These changes resulted in a higher incidence of angiographic CAV at 3 years post-HTx in the DA group (58.8% vs 5.6%, P = 0.002). CONCLUSIONS: This volumetric IVUS study suggests that DA correlates with the worsening change in CAV several years post-HTx. Donor-transmitted atherosclerosis recipients may require more aggressive treatment to prevent subsequent CAV progression.

Activation of arginine vasopressin receptor 1a facilitates the induction of long-term potentiation in the accessory olfactory bulb of male mice.

Olfaction plays an important role in social recognition in most mammals. Central arginine vasopressin (AVP) plays a role in this olfaction-based recognition. The high level of expression of AVP receptors in the accessory olfactory bulb (AOB) at the first relay of the vomeronasal system highlights the importance of AVP signaling at this stage. We therefore analyzed the effects of AVP on the synaptic plasticity of glutamatergic transmission from mitral cells to granule cells in AOB slices from male mice. To monitor the strength of the glutamatergic transmission, we measured the maximal initial slope of the lateral olfactory tract-evoked field potential, which represents the granule cell response to mitral cell activation. AVP paired with 100-Hz stimulation that only produced short-term potentiation enhanced the induction of long-term potentiation (LTP) in a dose-dependent manner. AVP-paired LTP was blocked by the selective AVP receptor 1a (AVPR1a) antagonist, d(CH2)5[Tyr(Me)2]AVP (Manning compound), but not by the AVPR1b antagonist SSR149415, and it was mimicked by the selective AVPR1a agonist [Phe2, Ile3, Orn8]-vasopressin. We further examined the effect of AVP on the reciprocal transmission between mitral and granule cells by stimulating a mitral cell and recording the evoked inhibitory postsynaptic currents (IPSCs) from the same cell using conventional whole-cell patch-clamp techniques. AVP reduced the reciprocal IPSCs triggered by endogenous glutamate release from the excited mitral cell. These results suggest that AVP promotes the induction of LTP at the mitral-to-granule cell synapse via the activation of AVPR1a through an as-yet-to-be-determined mechanism in the AOB of male mice.

Suppressive effects of conversion from mycophenolate mofetil to everolimus for the development of cardiac allograft vasculopathy in maintenance of heart transplant recipients.

BACKGROUND: Whether converting to everolimus (EVL) from mycophenolate mofetil (MMF) during the maintenance period after heart transplantation (HTx) reduces cardiac allograft vasculopathy (CAV) progression remains unclear. We sought to determine the effect of converting from MMF with standard-dose calcineurin inhibitors (CNIs) to EVL with low-dose CNIs on CAV progression. METHODS: We retrospectively reviewed the medical records of 63 HTx recipients who survived at least at 1 year after HTx. Twenty-four recipients were converted from MMF to EVL (EVL group, 2.2 ± 2.3 years after HTx), while 39 recipients were maintained on MMF (MMF group, 2.4 ± 2.2 years after HTx). The EVL group underwent three-dimensional intravascular ultrasound (3D-IVUS) analysis before and 1 year after conversion to EVL, and these data were compared with data from 2 consecutive IVUS in the MMF group. RESULTS: IVUS indices in the EVL group at 1 year after conversion did not show increased CAV development, whereas a significant increase in %plaque volume (p=0.006) and decrease in lumen volume (p<0.001) were observed in the MMF group. EVL conversion was significantly associated with smaller increases in %plaque volume (p=0.004) and smaller decreases in lumen volume (p=0.017). IVUS indices in the late EVL conversion group (≥ 2 years) also did not exhibit increased CAV development, while those in the MMF group did. CONCLUSIONS: Conversion to EVL from MMF in maintenance periods after HTx may decrease the rate of CAV progression based on IVUS indices.

Incidence, etiology, and outcome of primary graft dysfunction in adult heart transplant recipients: a single-center experience in Japan.

Donor and recipient characteristics, as well as donor-recipient matching, affect clinical outcomes after heart transplantation (HTx). This study aimed to clarify how donor and recipient characteristics affect the clinical course after HTx. The medical records of all the patients who underwent HTx at the National Cerebral and Cardiovascular Center from 1999 to 2014 were retrospectively reviewed. Sixty-one patients (48 males) underwent HTx. Six recipients (9.8 %) developed primary graft dysfunction (PGD) determined by criteria recently established at a consensus conference. Development of PGD was associated with high-dose inotropic support for the donor heart and a history of stroke in the recipient (p = 0.04 and p = 0.002, respectively). Recipients with PGD had higher right atrial pressure (RAP) and lower cardiac output (CO) compared with those without PGD at 6 months after HTx (RAP, 6.8 ± 3.6 vs. 2.8 ± 2.2 mmHg, p < 0.001; CO, 4.6 ± 0.8 l vs. 5.8 ± 1.2 l/min, p = 0.02). With respect to survival, patients with PGD had a 5-year survival rate equivalent to those without PGD (83.3 vs. 93.3 %, p = 0.23). High-dose inotropic support for the donor heart and a history of stroke in the recipient are significant predictive factors for the development of PGD. However, recipients with PGD demonstrate mid-term survival comparable to those without PGD.

Serum Brain Natriuretic Peptide Concentration 60 Days After Surgery as a Predictor of Long-Term Prognosis in Patients Implanted With a Left Ventricular Assist Device.

Mechanical circulatory support by a left ventricular assist device (LVAD) is used to bridge patients with advanced heart failure to transplant or as a definitive treatment. We retrospectively sought predictors of long-term outcome in a cohort of 83 patients who had undergone LVAD treatment. We subjected perioperative clinical data of patients to statistical analysis to establish parameters associated with all-cause mortality, and the cutoff values, sensitivity, and specificity of those that had a statistically significant relation with survival. Mean follow-up was 717 days (standard deviation, 334 days; range, 17-1,592 days). Fourteen patients (16.8%) died, but nine (10.8%) were weaned from support. Serum brain natriuretic peptide (BNP) concentration measured 60 days after implantation was significantly associated with all-cause mortality. The optimal BNP cutoff value to predict death during LVAD support was 322 pg/ml, with a sensitivity of 71.4% and specificity of 79.8%. Two-year survival was 92.0% in those with 60 days serum BNP concentration <322 pg/ml compared with 70.5% in those in whom it was ≥322 pg/ml (p = 0.003). The relation between BNP and survival likely reflects recovery of native myocardial function and improvements in global health and should assist clinicians in the on-going management of long-term LVAD therapy.

Restrictive myocardium with an unusual pattern of apical hypertrophic cardiomyopathy.

Loeffler endocarditis is a fibrous restrictive cardiomyopathy thought to be caused by persistent eosinophilia. It is difficult to diagnose, and the prognosis is often poor if the underlying eosinophilia is not promptly recognized and treated. We describe the case of a middle-aged woman treated for hypertrophic cardiomyopathy first detected during a routine check-up at age 35years but whose symptoms gradually progressed over the next 14years. Right ventricular biopsy showed extensive fibrosis of the endocardial tissue, and right heart catheterization revealed right heart failure and a low cardiac output state. Ultimately, she became reliant on inotropic and mechanical cardiovascular support, but we were not able to bridge her to transplant. Autopsy findings were typical of endocardial fibroelastosis, but she had not suffered from any tropical disease or traveled to high-risk areas. The presence of abnormal capillary proliferation suggested a diagnosis of Loeffler endocarditis. Nonetheless, apart from a 6-month period of eosinophilia 7years before her death, a history of well-controlled asthma and several drug sensitivities, we were unable to definitively identify the disease trigger. It is critical to diagnose and treat the underlying eosinophilia of Loeffler endocarditis to avoid a poor prognosis. This case highlights the importance of considering the diagnosis of eosinophilic endomyocarditis in patients with an unusual pattern of apical hypertrophic cardiomyopathy (or myocardial fibrosis of unknown etiology), even when there is no apparent history of eosinophilia.

Effects of enriched environment on hippocampal neuronal cell death and neurogenesis in rat global ischemia.

Enriched environments reportedly show neuroprotective effects. Here, we evaluated the effect of an enriched environment prior to cerebral ischemia on neuronal cell death and neurogenesis in rats. Male SD rats were housed under standard conditions (SC) or in an enriched environment (EE), then subjected to global ischemia. The Y-maze test and novel object cognition test were used to evaluate cognitive function before and after ischemia. At 7 days post-ischemia, we evaluated hippocampal neuronal cell death with Fluoro-Jade B staining and neurogenesis with BrdU staining. Phosphorylated cAMP response element-binding protein (phospho-CREB) was also evaluated immunohistochemically. The EE + ischemia group showed a significant decrease of cell death post-ischemia compared with the SC + ischemia group. There was no difference in neurogenesis post-ischemia between SC + ischemia and EE + ischemia. The EE + ischemia group showed a significant increase of performance before and after ischemia compared with the SC + ischemia group. Phospho-CREB-positive cells were significantly increased post-ischemia in EE + ischemia compared with SC + ischemia. EE suppressed hippocampal cell death due to global ischemia. Additionally, enhancement of cognitive function before and after ischemia and prevention of cognitive impairment associated with ischemia were observed compared with the controls (rats housed in SC without ischemia). The CREB pathway may play an important role in protection of cognitive ability.

Right heart failure and benefits of adjuvant tricuspid valve repair in patients undergoing left ventricular assist device implantation.

OBJECTIVES: Although right heart failure (RVF) is an important issue in the management of patients with left ventricular assist devices (LVADs), the benefits of performing tricuspid valve repair in conjunction with LVAD implantation have not been demonstrated. METHODS: We retrospectively reviewed the records of 141 patients who received LVAD implantation as a bridge to transplant from May 1999 to January 2013. We assessed short- and long-term right heart function in 69 of these patients who underwent tricuspid valve repair because of moderate-to-severe tricuspid regurgitation (TR) or severe dilatation of the tricuspid annulus. RVF was defined as the need for a right ventricular assist device or >30 days of intravenous inotropic support. TR was graded from 0 to 4, while fibrosis in myocardial biopsy samples was graded pathologically from 0 to 3. RESULTS: The average duration of LVAD support was 595 days. Twenty-seven patients developed RVF and their survival rate was significantly worse than that of patients who did not develop RVF (65 vs 91% at 1 year). RVF was significantly related to high preoperative ratio of central venous pressure (CVP) to pulmonary capillary wedge pressure, high total bilirubin, high fibrosis score and high TR grade. In patients who underwent tricuspid valve repair, the TR grade was significantly reduced from 2.6 to 1.0, and this decrease was maintained for 2 years. Although patients who underwent tricuspid valve repair had significantly higher TR grades, ratios of CVP to pulmonary capillary wedge pressure and fibrosis scores preoperatively, no survival impairment was seen. CONCLUSIONS: Tricuspid valve repair is a useful and durable adjuvant procedure for restoring deteriorated right ventricular function in patients requiring LVAD implantation.

Left coronary artery occlusion caused by a large thrombus on the left coronary cusp in a patient with a continuous-flow ventricular assist device.

Despite continual improvements in ventricular assist device (VAD) therapy, various clinical issues are emerging. Importantly, various types of thromboembolic complications have been reported to date. Recently, we encountered a rare continuous-flow VAD-related thromboembolic event that resulted in acute myocardial infarction. A 26-year-old female who just underwent HeartMate II(®) VAD implantation suddenly developed widespread anterolateral myocardial infarction on postoperative day 16. Echocardiography and aortography revealed a large thrombus on the left coronary cusp of the aortic valve that almost completely occluded the left coronary ostium. After VAD implantation, her aortic valve did not open, even at relatively low pump speeds; this was thought to be one of the causes for thrombus formation. Continuous suction of blood from the left ventricle and non-pulsatile flow into the ascending aorta resulted in a continuously closed aortic valve and stagnation of blood in the coronary cusp. Furthermore, both small body size (body surface area <1.3 m(2)) and postoperative right ventricular failure may have exacerbated blood stagnation and thrombus formation in this patient. We should have adjusted the anticoagulation and antiplatelet therapy protocols based on the patient's condition. She underwent off-pump coronary artery bypass surgery and remained in clinically stable condition afterwards.

Paracorporeal ventricular assist device as a bridge to transplant candidacy in the era of implantable continuous-flow ventricular assist device.

Ventricular assist devices (VADs) have long been used as bridge to transplant therapy (BTT). Nipro-Toyobo paracorporeal pulsatile-flow VAD (nt-VAD) was the only device available until April 2011, when implantable continuous-flow VADs (cf-VADs) became available. Although cf-VADs are central to BTT, nt-VAD remains a necessary option. We aimed to clarify the role of nt-VAD in an era of increasing cf-VAD use. We retrospectively reviewed patients who underwent VAD implantation at the National Cerebral and Cardiovascular Center from May 2011 to March 2013. Characteristics were compared between the nt-VAD and cf-VAD groups. Twenty-nine patients (mean age 37.7 ± 11.1 years, 23 males) underwent VAD implantation. Fifteen patients initially received nt-VADs, although 4 were converted to cf-VADs. Of these 15 patients, 3 were too small for cf-VADs and 2 needed bilateral ventricular support. The remaining 10 patients received nt-VADs (7 patients at INTERMACS level 1 and 3 at level 2). The nt-VAD group patients had significantly more preoperative mechanical circulatory support and were in a more critical condition before VAD implantation than the cf-VAD group. The 2-year survival rate was not significantly different. Despite the critical conditions of nt-VAD patients, their overall survival is not statistically inferior to that of cf-VAD patients. nt-VAD is a good option as a BTC for the patient with urgent and critical condition.

Off-pump coronary artery bypass grafting for a left main lesion due to cardiac allograft vasculopathy in Japan: first report of a case.

Cardiac allograft vasculopathy (CAV) is a major cause of mortality after transplantation. We treated a 44-year-old female with off-pump coronary artery bypass grafting (OPCAB) 4 years after heart transplantation. Annual examinations, including coronary angiography and intravenous ultrasound (IVUS), revealed a severe lesion in the left main trunk. The left internal mammary artery was successfully anastomosed to the left anterior descending artery in an off-pump manner. To ensure that patients have a good long-term outcome after heart transplantation, routine examinations, including IVUS, are crucial, because of the nature of CAV. OPCAB is a good option for a left main trunk lesion due to CAV.

[Heart transplantation and ventricular assit systems].

Since the organ transplantation law was passed, we performed 50 heart transplantation at National Cerebral and Cardiovascular Center. Of those, 2 patients have been doing well over 13 years and 10 years survival rate was 93.4%.During those years, we performed 139 applications of left ventricular assist systems( LVAS). Initially, extracorporeal LVASs had been used. Now, 2 implantable LVAS were approved by medical insurance as bridge to transplant in 2011. Now, our 1st option as bridge to transplantation(BTT) is implantable LVAS.

Monitoring of hemodynamic change in patients with carotid artery stenosis during the tilt test using wearable near-infrared spectroscopy.

Transient ischemic attack (TIA) is a major complication in patients with carotid artery stenosis. Patients with severe stenosis sometimes complain of orthostatic dizziness, such as syncope. The purpose of this study was to examine the usefulness of near-infrared spectroscopy (NIRS) for evaluating cerebral circulation in patients with carotid artery stenosis during head-up tilt test (HUTT). Fourteen patients with carotid artery stenosis and nine normal control subjects participated. In addition to blood pressure monitoring, hemoglobin (Hb) values (oxy-Hb, deoxy-Hb, and total Hb) were recorded by a wearable NIRS instrument with a high time resolution during HUTT. Oxy-Hb, which decreased initially when the test table was elevated, subsequently increased in normal volunteers and patients with carotid artery stenosis and did not differ significantly between the two groups. However, the oxy-Hb reduction in the carotid artery stenosis group (-0.02 ± 0.03 a.u.) at 30 s after elevation of the table was significantly larger than in the normal group (0.02 ± 0.02 a.u., P < 0.01). Our results indicate that oxy-Hb reduction in patients with carotid artery stenosis may be related to orthostatic dizziness. We concluded that NIRS monitoring is useful for evaluating cerebral autoregulation in patients with severe carotid artery stenosis.

Impact of pump replacement on outcome in advanced heart failure patients with left ventricular assist system.

Pump thrombosis is one of the major adverse events associated with the use of a left ventricular assist system (LVAS) in patients with advanced heart failure. We investigated the clinical implication of pump replacement because of thrombus formation. This study included 87 patients who underwent implantation of a Nipro (Toyobo) pulsatile extracorporeal LVAS intended as a bridge to transplantation and were alive more than 3 months after implantation. The pump of this device is translucent, and daily evaluation for signs of thrombus formation was performed. Pump replacement was performed for significant thrombus formation that became visible. Data collection including demographics as well as hematologic values were performed 1 day before (baseline) and 3 months after implantation, and all patients were followed for 2 years or until death. At 3 months after LVAS implantation, 41 patients (47.1%) had undergone pump replacement because of pump thrombus. Baseline body surface area <1.63 m(2) was a significant predictor of pump replacement (hazard ratio [HR] 2.15, P = 0.04). At 3 months after implantation, there was a significantly higher incidence of stroke (P < 0.05) as well as a significantly greater decrease in body weight (F = 4.92, P = 0.03) in patients who underwent pump replacement as compared to those without. The 2-year mortality after implantation was 26.4%. Multivariate Cox regression analysis showed that pump replacement within 3 months after implantation was an independent predictor of mortality (HR 2.50, P = 0.03). In conclusion, pump replacement for thrombus formation may have a strong association with worse outcome. Our results reconfirm the clinical importance of device thrombus in the management of LVAS.

Bone-destroying candida infection following left ventricular assist device explant.

Infections associated with left ventricular assist devices (LVADs) constitute an important clinical issue because they are difficult to completely eradicate without removal of the LVAD itself and can sometimes be fatal. We encountered a case of extracorporeal LVAD-related candida infection in a patient who was successfully weaned from LVAD support. Although the patient appeared to have recovered from the infection, the patient was readmitted to our institute due to a relapse of candida infection 9 months after LVAD removal. Although the patient did not demonstrate any systemic sign of infection on admission, computed tomography images clearly showed that the residual apical cuff of the LVAD inflow cannula, which was infected with Candida albicans during the initial admission, resulted in re-infection that involved the chest wall with destruction of the adjacent rib.