A specific combination of P wave duration and morphology accurately predicts the presence of left atrial low voltage area in patients with atrial fibrillation.

BACKGROUND: Since low voltage area (LVA) impairs not only intra atrial conduction velocity but also intra atrial propagate direction, these alternates may reflect the P wave duration (PWD) and morphology. We examined the relationship between the PWD, morphology and LVA. METHODS: Consecutive 127 AF patients were divided into 2 groups depending on the presence of LVA (35 subjects LVA positive group, 92 subjects LVA negative group). P wave morphologies were divided into 3 categories, normal: P-wave duration<120 ms, partial interatrial block (IAB): P wave duration≥120 ms, advanced IAB: PWD ≥ 120 ms with biphasic P waves in inferior leads. LVA was defined as a voltage amplitude<0.5 mV, and qualitatively assessed to be categorized into three grades (mild<10%, 10% ≤ moderate<30%, 30% ≤ extensive). RESULTS: LVA was significantly highly detected in patients of advanced age, female, comorbidities of hypertension, prior brain infarction, LA enlargement. PWD was correlated with LA volume in the LVA negative group, but not in the LVA positive group. Advanced IAB was significantly accumulated in the LVA positive group while partial IAB was found in both LVA positive and negative groups. Receiver-operating characteristics curve revealed that a combination of IAB and biphasic P wave in any inferior lead identified the presence of LVA with 83% sensitivity and 98% specificity. PWD and the presence of advanced IAB were independent predictors of LVA as determined by multivariate logistic regression analysis. CONCLUSION: Advanced IAB is a favorable parameter for the presence of LVA.

Comparison Between Contact Force Monitoring and Unipolar Signal Modification as a Guide for Catheter Ablation of Atrial Fibrillation: Prospective Multi-Center Randomized Study.

BACKGROUND: Both contact force monitoring (CFM) and unipolar signal modification (USM) are guides for ablation, which improve the efficacy of pulmonary vein isolation of atrial fibrillation. We sought to compare the outcomes of atrial fibrillation ablation guided by CFM or USM. METHODS: A total of 136 patients with paroxysmal atrial fibrillation underwent a circumferential pulmonary vein isolation using CF sensing ablation catheters and were randomly assigned to undergo catheter ablation guided by either CFM (CFM-guided group: n=70) or USM (USM-guided group: n=66). In the USM-guided group, each radiofrequency application lasted until the development of completely positive unipolar electrograms. In the CFM-guided group, a CF of 20 g (range, 10-30 g) and minimum force-time integral of 400 g were the targets for each radiofrequency application. The primary end point was freedom from any atrial tachyarrhythmia recurrence without antiarrhythmic drugs at 12-months of follow-up. RESULTS: The cumulative freedom from recurrences at 12-months was 85% in the USM-guided group and 70% in the CFM-guided group (P=0.031). The incidence of time-dependent and ATP-provoked early electrical reconnections between the left atrium and PVs, procedural time, fluoroscopic time, and average force-time integral, did not significantly differ between the 2 groups. The radiofrequency time for the pulmonary vein isolation was shorter in the USM-guided group than CFM-guided group but was not statistically significant (P=0.077). CONCLUSIONS: USM was superior to CFM as an end point for radiofrequency energy deliveries during the pulmonary vein isolation in patients with paroxysmal atrial fibrillation in terms of the 12-month recurrence-free rate. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000021127.

Catheter ablation of atrial fibrillation in patients with severely impaired left ventricular systolic function.

Little is known about the outcome of catheter ablation of atrial fibrillation (AF) in patients with heart failure (HF) and a severely reduced left ventricular ejection fraction (LVEF). We aimed to clarify the effectiveness of catheter ablation of AF in patients with a severely low LVEF. This retrospective study included 18 consecutive patients with HF and an LVEF of ≤ 35 % who underwent catheter ablation of AF. We investigated the clinical parameters, echocardiographic parameters and the incidence of hospitalizations for HF. During a median follow-up of 21 months (IQR, 13-40) after the final procedure (9 with repeat procedures), 11 patients (61 %) maintained sinus rhythm (SR) (6 with amiodarone). The LVEF and NYHA class significantly improved at 6 months after the CA in 12 patients (67 %) who were in SR or had recurrent paroxysmal AF (from 25.8 ± 6.3 to 37.0 ± 11.7 %, P = 0.02, and from 2.3 ± 0.5 to 1.5 ± 0.7, P < 0.01, respectively) but not in patients who experienced recurrent persistent AF. The patients with SR or recurrent paroxysmal AF had significantly fewer hospitalizations for HF than those with recurrent persistent AF after the AF ablation (log-rank test; P < 0.01). Catheter ablation of AF improved the clinical status in patients with an LVEF of ≤ 35 %. A repeat ablation procedure and amiodarone were often necessary to obtain a favorable outcome.

Comparison of autonomic J-wave modulation in patients with idiopathic ventricular fibrillation and control subjects.

BACKGROUND: Although J-waves are seen in both patients with idiopathic ventricular fibrillation (IVF) and the general population, their genesis remains unclear. To assess the relationship between J-waves and autonomic tone we investigated the circadian variation of J-waves in individuals with and without IVF. METHODS AND RESULTS: In study 1, we obtained resting 12-lead ECG and Holter ECG recordings in 258 individuals undergoing screening for heart disease. In 60 of these subjects (23.3%), we detected J-waves on Holter ECGs; 40 of them (66.7%) had shown no J-waves on 12-lead ECGs. In study 2, we measured the J-wave amplitude, heart rate (HR), and HR variability [high frequency (HF) and the ratio of low- to high-frequency (LF/HF)] on Holter ECGs recorded in 5 patients with IVF and 20 control subjects who had manifested J-waves. The J-wave amplitude increased at night and decreased during the day in both groups; it was significantly higher in the IVF patients (P<0.0001). In both groups, the J-wave amplitude showed a significant negative correlation with HR and LF/HF and a significant positive correlation with HF. The slope of the J/HR and J/(LF/HF) relationship was significantly steeper in the IVF patients. CONCLUSIONS: The J-wave amplitude was more significantly influenced by the autonomic balance in IVF patients than in the controls. Autonomic J-wave modulation may yield important information on the genesis of J-waves.

Localized reentrant tachycardia in the aorta contiguity region mimicking perimitral atrial flutter in the context of atrial fibrillation ablation.

We describe a case with a focal atrial tachycardia (AT) masquerading as perimitral atrial flutter revealed after circumferential pulmonary vein antral isolation for atrial fibrillation. It was successfully terminated and became noninducible by a point ablation on the left atrial anterior wall (LAAW) near the mitral annulus in contact with the aortic root and on the left superior pulmonary vein-left atrial appendage ridge, without any linear ablation, using electroanatomical mapping and conventional precise mapping with a maximum amplified gain within the low-voltage area. The AT revealed in our case was an LAAW-aorta contiguity area-related AT.

Novel strategy to prevent atrial fibrosis and fibrillation.

To explore a novel strategy of preventing atrial fibrosis and atrial fibrillation (AF), we have established 3 appropriate experimental models of AF. Firstly, atrial fibrosis was induced by pressure overload by abdominal aortic constriction (AAC). AAC enhanced left atrial (LA) expression of monocyte chemoattractant protein-1. Scanning electron microscopy revealed that LA endothelial cells were irregularly hypertrophied, with disarrangement of lines of cells. Possible "arrested" leukocyte-derived cells were observed on the surface of LA endothelial cells. Treatment with pioglitazone, a peroxisome proliferator-activated receptor-γ agonist, resulted in attenuation of pressure overload-induced LA fibrosis. Secondly, LA fibrosis was induced by continuous infusion of angiotensin II (AII). Repeated whole-body hyperthermia led to the induction of heat shock protein (HSP) 72, which resulted in attenuation of AII-induced LA fibrosis. Thirdly, atrial fibrosis was induced by 5/6 nephrectomy as a model of AF associated with chronic kidney disease. Because the amount of nicotinamide adenine dinucleotide phosphate oxidase was increased and the potent antioxidant agent was effective, oxidative stress may be involved in the pathogenesis of LA fibrosis and enhanced AF vulnerability in this model. These observations suggest that inflammatory profibrotic processes are essential for the development of atrial fibrosis in these 3 models. Pioglitazone, induction of HSPs and antioxidant agent could be novel therapeutic approaches to preventing atrial fibrosis and AF.

Electrocardiographic characteristics of patients with false tendon: possible association of false tendon with J waves.

BACKGROUND: The false tendons (FTs) are fibromuscular bands that transverse the left ventricular cavity and often contain conduction tissue, suggesting that FTs may contribute to the occurrence of ventricular arrhythmias. The presence of J waves is associated with vulnerability to ventricular arrhythmias; however, the mechanisms underlying the manifestation of J waves remain to be elucidated. OBJECTIVE: To investigate the electrocardiographic characteristics, including the presence of J waves, in patients with FTs. METHODS: We studied 44 patients with distinct FTs detected by echocardiography (FT group) and 88 age- and sex-matched healthy subjects without FTs (control group). The PQ, QRS, JT, QT, corrected JT, and corrected QT intervals were automatically measured on surface 12-lead electrocardiograms, and the presence or absence of J waves was also determined. J waves were defined as terminal QRS notching or slurring. FTs were classified according to their points of attachment as type 1 (longitudinal, 52%), type 2 (diagonal, 25%), type 3 (transverse, 16%), and type 4 (weblike, 7%). RESULTS: QRS and corrected QT intervals were significantly longer in the FT group than in the control group (P <.005 and P <.05, respectively). The incidence of J waves was significantly higher in the FT group (64%) than in the control group (19%) (P <.0001). J waves were more prevalent in type 1 (78%) and type 2 (73%) than in type 3 (14%) and 4 FTs (33%) (P <0.05) and in patients with thick FTs (≥ 2 mm) than with thinner FTs (<2 mm) (71% vs 33%; P <.05). The J-wave location differed according to the FT type. CONCLUSIONS: Our results suggest that FTs may carry a certain role to the genesis of J waves.

Candesartan restored cardiac Hsp72 expression and tolerance against reperfusion injury in hereditary insulin-resistant rats.

AIMS: We tested the hypothesis that candesartan, an angiotensin II (AII) type 1 receptor antagonist, would restore the depressed phosphatidylinositol 3 (PI3) kinase-dependent Akt phosphorylation, an essential signal to induce heat-shock protein 72 (Hsp72) in response to hyperthermia, in Otsuka Long-Evans Tokushima fatty (OLETF) rats. METHODS AND RESULTS: At 14 weeks of age, male OLETF rats and Long-Evans Tokushima Otsuka (LETO) rats were treated with candesartan (0.25 mg/kg/day) for 2 weeks. Thereafter, hyperthermia (43°C for 20 min) was applied. We observed the following: (i) Candesartan did not improve insulin sensitivity in OLETF rats. (ii) Candesartan restored depressed PI3 kinase-dependent Akt phosphorylation and Hsp72 expression in OLETF rat hearts. (iii) Cardiac ventricular tissue contents of AII were greater in OLETF rats, which were suppressed by candesartan. (iv) Cardiac levels of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) phosphorylation were greater in OLETF rats, which were suppressed by candesartan. In cultured cardiomyocytes, application of AII induced PTEN phosphorylation, which was suppressed by candesartan. (v) In high-fat diet insulin-resistant rats, similar results were observed with respect to Hsp72 expression, Akt phosphorylation and PTEN phosphorylation. (vi) In isolated, perfused heart experiments, reperfusion-induced cardiac functional recovery was suppressed in OLETF rat hearts, which was improved by candesartan. CONCLUSION: Our results suggest that the depression of PI3 kinase-dependent Akt activation in response to hyperthermia in OLETF rats can be restored by candesartan. Substantial activation of the renin-angiotensin system, represented by increased myocardial AII content and subsequent PTEN phosphorylation, may underlie the pathogenesis which is ameliorated by candesartan.

Effect of cardiac resynchronization therapy on cardiac sympathetic nervous dysfunction and serum C-reactive protein level.

BACKGROUND: Cardiac autonomic dysfunction is associated with a poor prognosis in patients with heart failure (HF). Systemic inflammation is elevated in patients with HF. We hypothesized that cardiac resynchronization therapy (CRT) improves cardiac sympathetic nervous dysfunction and systemic inflammation. To test our hypothesis, we evaluated cardiac sympathetic activity and serum levels of high sensitive C-reactive protein (hs-CRP) before and after CRT. METHODS: Twenty-seven patients with chronic HF (19 men, eight women; mean age 67 ± 10 years) with nonischemic cardiomyopathy who underwent CRT were evaluated. Each patient was evaluated before and 6 months after CRT. Responders were defined as patients showing ≥15% absolute decrease in left ventricular end-systolic volume. Cardiac sympathetic activity was estimated with cardiac (123) I-metaiodobenzylguanidine (MIBG) scintigrams. RESULTS: Patients were categorized as responders (n = 19) and nonresponders (n = 8) according to echocardiographic findings. In responders, the mean heart-to-mediastinum (H/M) ratio at the delayed phase in cardiac (123) I-MIBG scintigraphic findings was significantly increased (P<0.05) and serum levels of hs-CRP were decreased (P <0.01). Such improvements were not observed in nonresponders. Stepwise multiple regression analysis showed that the reduction in hs-CRP level was independently associated with the increase in the H/M ratio at delayed phase. CONCLUSIONS: Our results demonstrated that cardiac sympathetic nervous dysfunction and systemic inflammation were improved in responder HF patients to CRT. Furthermore, the reduction in systemic inflammation was associated with the improvement in cardiac sympathetic nervous dysfunction.

Gender difference in baroreflex sensitivity to predict cardiac and cerebrovascular events in type 2 diabetic patients.

BACKGROUND: Cardiovascular autonomic neuropathy is a major complication in patients with diabetes mellitus (DM), and baroreflex sensitivity (BRS) reportedly can predict cardiovascular prognosis in type 2 DM patients. The hypothesis that cardiovascular events are associated with gender differences in BRS was tested in the present study. METHODS AND RESULTS: From 1998, we have evaluated BRS by phenylephrine methods in 185 consecutive type 2 DM patients. The long-term prognostic value of BRS was compared between 91 female (5812 years) and 94 male patients (5811 years). There was no significant difference in age or severity and duration of DM between the 2 groups. When compared to male, the BRS value in female patients was significantly lower (9.266.0 vs. 5.975.0 ms/mmHg, P < 0.0001). During a mean of 62.7 months of follow-up, 16 female patients developed cardiovascular events (17.6%) including stroke, acute myocardial infarction, angina pectoris requiring percutaneous coronary intervention or coronary artery bypass grafting and congestive heart failure requiring admission, while only 4 male patients developed events (4.3%, P < 0.005). In females, the Kaplan-Meier curves revealed that those with depressed BRS (< 6 ms/mmHg) had a higher incidence of cardiovascular events than those with preserved BRS (P < 0.05), but this relationship was not observed in male patients. CONCLUSIONS: Although the reason why females had a more depressed BRS remains unclear, our findings demonstrated that a depressed BRS value can accurately predict cardiovascular events, especially in female patients with type 2 DM.

Pioglitazone attenuates inflammatory atrial fibrosis and vulnerability to atrial fibrillation induced by pressure overload in rats.

BACKGROUND: Inflammatory processes are involved in the pathogenesis of atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to test the hypothesis that atrial fibrosis and enhanced vulnerability to AF evoked by pressure overload can be attenuated by pioglitazone, a peroxisome proliferator-activated receptor-γ agonist, via suppression of inflammatory profibrotic signals. METHODS: Male Sprague-Dawley rats were subjected to abdominal aortic constriction (AAC). Pioglitazone 3 mg/kg/day or vehicle was orally administered for 4 weeks. RESULTS: Western blot analysis revealed that AAC enhanced expression of monocyte chemoattractant protein (MCP)-1, transforming growth factor-ß1 and α-smooth muscle actin in the left atrium (LA), which was suppressed by pioglitazone. Messenger RNA expression of collagen type 1 and atrial natriuretic peptide in the LA was increased by AAC, which was suppressed by pioglitazone. Gelatin zymography demonstrated that activity of matrix metalloproteinase-9 was increased by AAC, which was suppressed by pioglitazone. Pioglitazone attenuated AAC-induced LA fibrosis. In isolated-perfused heart experiments, AAC did not alter the refractory period of the LA or the right atrium (RA), but it did prolong the interatrial conduction time. Programmed extrastimuli from the RA induced AF in all of the AAC-treated rats (8/8 [100%]). This was suppressed by pioglitazone (2/8 [25%], P <.05) with normalization to interatrial conduction time. CONCLUSION: The results of this study suggest that inflammatory profibrotic mechanisms are involved in this pressure-overloaded AF model. The results also suggest that pioglitazone is effective at attenuating atrial fibrosis, possibly via suppression of MCP-1-mediated inflammatory profibrotic processes.

Telmisartan effectively improves insulin sensitivity in hypertensive patients with insulin resistance.

OBJECTIVE: The angiotensin II receptor blocker (ARB) telmisartan has been shown to activate peroxisome proliferator-activated receptor γ and increase adiponectin protein content in adipocytes. We tested the hypothesis that telmisartan can increase the serum level of adiponectin and improve insulin resistance. METHODS: The study participants were 25 consecutive hypertensive patients (8 females, 17 males; 65 ± 10 years). Insulin resistance was defined as a patient showing ≥2.5 in the homeostasis model assessment (HOMA) index. We divided subjects into non-insulin resistance (n = 10) and insulin resistance groups (n = 15) based on the HOMA index. Telmisartan was administered (40 mg/day) was administered for 24 weeks. RESULTS: In the insulin resistance group, telmisartan treatment resulted in a significant decrease in the HOMA index and serum level of C-reactive protein, and it increased the serum level of adiponectin (P < 0.05, respectively). Such improvements were not observed in the non-insulin resistance group. Stepwise multiple regression analysis showed that the increase in the serum level of adiponectin was independently associated with reduction in the HOMA index. CONCLUSIONS: Our findings suggest that telmisartan improves insulin resistance that parallels an increase in the serum level of adiponectin in hypertensive patients with insulin resistance. It may therefore have advantages in treating such populations.

Baroreflex sensitivity predicts cardiovascular events in patients with type 2 diabetes mellitus without structural heart disease.

BACKGROUND: Cardiovascular autonomic neuropathy is a major complication in patients with diabetes mellitus (DM). However, the relationship between cardiovascular autonomic neuropathy and the incidence of cardiovascular events has been poorly investigated in type 2 DM. The present study aimed to assess the long-term cardiovascular predictive value of baroreflex sensitivity (BRS) in Japanese patients with type 2 DM without structural heart disease. METHODS AND RESULTS: BRS was evaluated using the phenylephrine method in 210 patients with type 2 DM who did not have structural heart disease or other severe complications. BRS was considered depressed if <6 ms/mmHg. Accurate follow-up information for 3-10 years (mean 4.7 years) was obtained in 184 patients (90 females, 94 males; mean age 58+/-12 years). The initial onset of a major adverse cardiovascular event (MACE) was investigated. During follow-up, 19 patients presented with a MACE (4 cardiovascular deaths, 3 nonfatal myocardial infarctions, 4 coronary revascularizations, 5 strokes, 2 congestive heart failures). Cox proportional hazards regression analysis revealed that depressed BRS was independently associated with the incidence of MACE (hazard ratio 1.93, 95% confidence interval 1.09-3.82, P=0.0236). CONCLUSIONS: Depressed BRS at baseline has long-term cardiovascular predictive value in Japanese patients with type 2 DM without structural heart disease.

Hyperthermia treatment prevents angiotensin II-mediated atrial fibrosis and fibrillation via induction of heat-shock protein 72.

We tested the hypothesis that atrial fibrosis and atrial fibrillation (AF) evoked by angiotensin II (AII) could be prevented by the induction of heat-shock protein 72 (HSP72) by hyperthermia (HT). In cultured atrial fibroblasts isolated from male Sprague-Dawley rats, HT (42 degrees C) was applied for 30 min. AII (100 nmol/L) was added to the medium 8 h later. HT induced the expression of HSP72, which was associated with the attenuation of AII-induced extracellular signal-regulated kinase (ERK1/ERK2) phosphorylation, alpha-smooth muscle actin (alpha-SMA) expression, transforming growth factor-beta(1) secretion, collagen synthesis, and expression of collagen type I and tissue inhibitor of metalloproteinases-1. A small interfering RNA targeting HSP72 abolished these anti-fibrotic effects of HT. In male Sprague-Dawley rats in vivo, an osmotic mini-pump was subcutaneously implanted for continuous infusion of AII (400 ng/kg/min). Whole-body HT (43 degrees C, 20 min) was applied 24 h before and 7, 14, and 21 days after the start of the AII infusion. Repeated HT led to the induction of HSP72 expression, which resulted in an attenuation of AII-induced left atrial fibrosis. In an electrophysiological study using isolated perfused heart, continuous AII caused slowing of interatrial conduction without affecting atrial refractoriness. In AII-treated hearts, extrastimuli from the right atrial appendage resulted in a high incidence of repetitive atrial responses, which were suppressed by treatment with HT. Our results suggest that HT treatment is effective in suppressing AII-mediated atrial fibrosis and AF via induction of HSP72 at least in parts, and is thus expected to be a novel strategy for prevention of AF.

Mitochondria are targets for geranylgeranylacetone-induced cardioprotection against ischemia-reperfusion in the rat heart.

It has been shown that orally administered geranylgeranylacetone (GGA), an anti-ulcer drug, induces expression of heat shock protein 72 (HSP72) and provides protection against ischemia-reperfusion in rat hearts. The underlying protective mechanisms, however, remain unknown. Mitochondria have been shown to be a selective target for heat stress-induced cardioprotection. Therefore, we hypothesized that preservation of mitochondrial function, owing to an opening of a putative channel in the inner mitochondrial membrane, the mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel, could be involved in GGA- or heat stress-induced cardioprotection against ischemia-reperfusion. Rats were treated with oral GGA or vehicle. Twenty-four hours later, each heart was isolated and perfused with a Langendorff apparatus. GGA-treated hearts showed better functional recovery, and less creatine kinase was released during a 30-min reperfusion period, after 20 min of no-flow ischemia. Concomitant perfusion with 5-hydroxydecanoate (5-HD, 100 microM) or glibenclamide (10 microM) abolished the GGA-induced cardioprotective effect. GGA also showed preserved mitochondrial respiratory function, isolated at the end of the reperfusion period, which was abolished with 5-HD treatment. GGA prevented destruction of the mitochondrial structure by ischemia-reperfusion, as shown by electron microscopy. In cultured cardiomyocytes, GGA induced HSP72 expression and resulted in less damage to cells, including less apoptosis in response to hypoxia-reoxygenation. Treatment with 5-HD abolished the GGA-induced cardioprotective effects but did not affect HSP72 expression. Our results indicate that preserved mitochondrial respiratory function, owing to GGA-induced HSP72 expression, may, at least in part, have a role in cardioprotection against ischemia-reperfusion. These processes may involve opening of the mitoK(ATP) channel.

Effects of insulin resistance on geranylgeranylacetone-induced expression of heat shock protein 72 and cardioprotection in high-fat diet rats.

We investigated the effects of insulin resistance on the expression of heat-shock proteins (HSPs) and myocardial protection against ischemia/reperfusion injury. Male Sprague-Dawley rats received normal chow (CNT) or high-fat (HiF) diet. HiF diet for 6 weeks resulted in the development of insulin resistance, which was evaluated by oral glucose test and insulin tolerance test. Twenty-four hour after oral administration of geranylgeranylacetone (GGA) (200 mg/kg), the heart was isolated and perfused retrogradely with two different doses of insulin (0.1 or 1 mU/ml). Myocardial expression of HSP72 was examined using Western blot analysis. In the HiF group, the expression of HSP72 in response to GGA was decreased. The recovery of left ventricular developed pressure (LVDP) 30 min after reperfusion was tended to be lower in HiF group than in CNT group. Although GGA improved the recovery of LVDP in both CNT and HiF rats, LVDP during reperfusion period was significantly lower in HiF group than in CNT group. High-dose insulin perfusion caused deterioration of post-ischemic functional recovery and LVDP was not different between the two groups, but GGA-induced cardioprotection was preserved irrespective of the dose of insulin both in the CNT and HiF rats. This is the first demonstration that expression of HSP72 was depressed in the heart and that reduced HSP72 was related with less cardioprotection against ischemic insult in high-fat diet-induced insulin resistance rats.

Selenium deficiency in a patient with Crohn's disease receiving long-term total parenteral nutrition.

We report a case of selenium deficiency in a patient with Crohn's disease on long-term total parenteral nutrition (TPN). She manifested lassitude of the legs, discoloration of the nail beds, and macrocytosis. Since her plasma selenium level was found to be below the measurable level, we diagnosed this case as selenium deficiency. After intravenous administration of sodium selenite, her symptoms were reversed. Careful attention should be paid to selenium deficiency when a patient receives long-term TPN; supplementary administration of selenium via TPN may be required because selenium is often not routinely added to TPN formulations.