Video polysomnographic analysis of elevated EMG activity and rapid eye movements before abnormal behaviors in REM sleep behavior disorder.

The pathogenesis of rapid eye movement (REM) sleep behavior disorder (RBD) is unclear. According to the cortical hypothesis, severe RBD episode (RBDE) occurs when spinal motoneurons are less inhibited and cortical and limbic systems are more active. We made this study to prove the hypothesis for the development of RBDE using video-polysomnography (VPSG). VPSG records of 35 patients with RBD were analyzed. According to severity, RBDEs were classified into three motor events (MEs): ME 1; small movements or jerks, ME 2; proximal movements including violent behavior, and ME 3; axial movements including bed falls. For each ME, we measured the number of MEs preceded or not preceded by both REM sleep without atonia (RWA) and REMs during the 10-s-period immediately before ME onset. In severe RBDE (ME 3), the number of MEs preceded by both RWA and REMs was significantly higher than that of MEs not preceded by both (0.8 vs. 0.2, P = 0.033). This was not the case for mild RBDE (ME 1) and moderate RBDE (ME 2). Our results suggest that both RWA and REMs are associated with the development of severe RBDE.

A rare genetic variant in the cleavage site of prepro-orexin is associated with idiopathic hypersomnia.

Idiopathic hypersomnia (IH) is a rare, heterogeneous sleep disorder characterized by excessive daytime sleepiness. In contrast to narcolepsy type 1, which is a well-defined type of central disorders of hypersomnolence, the etiology of IH is poorly understood. No susceptibility loci associated with IH have been clearly identified, despite the tendency for familial aggregation of IH. We performed a variation screening of the prepro-orexin/hypocretin and orexin receptors genes and an association study for IH in a Japanese population, with replication (598 patients and 9826 controls). We identified a rare missense variant (g.42184347T>C; p.Lys68Arg; rs537376938) in the cleavage site of prepro-orexin that was associated with IH (minor allele frequency of 1.67% in cases versus 0.32% in controls, P = 2.7 × 10-8, odds ratio = 5.36). Two forms of orexin (orexin-A and -B) are generated from cleavage of one precursor peptide, prepro-orexin. The difference in cleavage efficiency between wild-type (Gly-Lys-Arg; GKR) and mutant (Gly-Arg-Arg; GRR) peptides was examined by assays using proprotein convertase subtilisin/kexin (PCSK) type 1 and PCSK type 2. In both PCSK1 and PCSK2 assays, the cleavage efficiency of the mutant peptide was lower than that of the wild-type peptide. We also confirmed that the prepro-orexin peptides themselves transmitted less signaling through orexin receptors than mature orexin-A and orexin-B peptides. These results indicate that a subgroup of IH is associated with decreased orexin signaling, which is believed to be a hallmark of narcolepsy type 1.

A variant at 9q34.11 is associated with HLA-DQB1*06:02 negative essential hypersomnia.

Essential hypersomnia (EHS) is a lifelong disorder characterized by excessive daytime sleepiness without cataplexy. EHS is associated with human leukocyte antigen (HLA)-DQB1*06:02, similar to narcolepsy with cataplexy (narcolepsy). Previous studies suggest that DQB1*06:02-positive and -negative EHS are different in terms of their clinical features and follow different pathological pathways. DQB1*06:02-positive EHS and narcolepsy share the same susceptibility genes. In the present study, we report a genome-wide association study with replication for DQB1*06:02-negative EHS (408 patients and 2247 healthy controls, all Japanese). One single-nucleotide polymorphism, rs10988217, which is located 15-kb upstream of carnitine O-acetyltransferase (CRAT), was significantly associated with DQB1*06:02-negative EHS (P = 7.5 × 10-9, odds ratio = 2.63). The risk allele of the disease-associated SNP was correlated with higher expression levels of CRAT in various tissues and cell types, including brain tissue. In addition, the risk allele was associated with levels of succinylcarnitine (P = 1.4 × 10-18) in human blood. The leading SNP in this region was the same in associations with both DQB1*06:02-negative EHS and succinylcarnitine levels. The results suggest that DQB1*06:02-negative EHS may be associated with an underlying dysfunction in energy metabolic pathways.

[Clinical features of sleep disorders in older adults].

There are three major neurophysiological mechanisms underlying the sleep-waking cycle: the sleep system, the waking system, and the system that determines sleep-waking timing. Sleep dlisorders of older adults seem to be caused by functional or organic changes in one or more of the three systems, and are roughly classified into two categories: (i) normal age-related, and (ii) pathological. The former includes decreased amplitude and advanced phase of circadian rhythms (body temperature, melatonin secretion, and sleep-waking), as well as reduced sleep duration, sleep fragmentation, and a decrease of slow-wave sleep in sleep architecture. Pathological sleep disorders include medical and psychiatric diseases (e.g., lifestyle-related diseases, dementia, delirium, and depression) and primary age-related sleep disorders (e.g., REM sleep behavior disorder and periodic limb move- ment disorders). This mini-review delineates the clinical features of sleep disorders in older adults.

A polymorphism in CCR1/CCR3 is associated with narcolepsy.

Etiology of narcolepsy-cataplexy involves multiple genetic and environmental factors. While the human leukocyte antigen (HLA)-DRB1*15:01-DQB1*06:02 haplotype is strongly associated with narcolepsy, it is not sufficient for disease development. To identify additional, non-HLA susceptibility genes, we conducted a genome-wide association study (GWAS) using Japanese samples. An initial sample set comprising 409 cases and 1562 controls was used for the GWAS of 525,196 single nucleotide polymorphisms (SNPs) located outside the HLA region. An independent sample set comprising 240 cases and 869 controls was then genotyped at 37 SNPs identified in the GWAS. We found that narcolepsy was associated with a SNP in the promoter region of chemokine (C-C motif) receptor 1 (CCR1) (rs3181077, P=1.6×10(-5), odds ratio [OR]=1.86). This rs3181077 association was replicated with the independent sample set (P=0.032, OR=1.36). We measured mRNA levels of candidate genes in peripheral blood samples of 38 cases and 37 controls. CCR1 and CCR3 mRNA levels were significantly lower in patients than in healthy controls, and CCR1 mRNA levels were associated with rs3181077 genotypes. In vitro chemotaxis assays were also performed to measure monocyte migration. We observed that monocytes from carriers of the rs3181077 risk allele had lower migration indices with a CCR1 ligand. CCR1 and CCR3 are newly discovered susceptibility genes for narcolepsy. These results highlight the potential role of CCR genes in narcolepsy and support the hypothesis that patients with narcolepsy have impaired immune function.

An association analysis of HLA-DQB1 with narcolepsy without cataplexy and idiopathic hypersomnia with/without long sleep time in a Japanese population.

Narcolepsy without cataplexy (NA w/o CA) (narcolepsy type 2) is a lifelong disorder characterized by excessive daytime sleepiness and rapid eye movement (REM) sleep abnormalities, but no cataplexy. In the present study, we examined the human leukocyte antigen HLA-DQB1 in 160 Japanese patients with NA w/o CA and 1,418 control subjects. Frequencies of DQB1*06:02 were significantly higher in patients with NA w/o CA compared with controls (allele frequency: 16.6 vs. 7.8%, P=1.1×10(-7), odds ratio (OR)=2.36; carrier frequency: 31.3 vs. 14.7%, P=7.6×10(-8), OR=2.64). Distributions of HLA-DQB1 alleles other than DQB1*06:02 were compared between NA w/o CA and narcolepsy with cataplexy (NA-CA) to assess whether the genetic backgrounds of the two diseases have similarities. The distribution of the HLA-DQB1 alleles in DQB1*06:02-negative NA w/o CA was significantly different from that in NA-CA (P=5.8×10(-7)). On the other hand, the patterns of the HLA-DQB1 alleles were similar between DQB1*06:02-positive NA w/o CA and NA-CA. HLA-DQB1 analysis was also performed in 186 Japanese patients with idiopathic hypersomnia (IHS) with/without long sleep time, but no significant associations were observed.

New susceptibility variants to narcolepsy identified in HLA class II region.

Narcolepsy, a sleep disorder characterized by excessive daytime sleepiness, cataplexy and rapid eye movement sleep abnormalities, is tightly associated with human leukocyte antigen HLA-DQB1*06:02. DQB1*06:02 is common in the general population (10-30%); therefore, additional genetic factors are needed for the development of narcolepsy. In the present study, HLA-DQB1 in 664 Japanese narcoleptic subjects and 3131 Japanese control subjects was examined to determine whether HLA-DQB1 alleles located in trans of DQB1*06:02 are associated with narcolepsy. The strongest association was with DQB1*06:01 (P = 1.4 × 10(-10), odds ratio, OR = 0.39), as reported in previous studies. Additional predisposing effects of DQB1*03:02 were also found (P = 2.5 × 10(-9), OR = 1.97). A comparison between DQB1*06:02 heterozygous cases and controls revealed dominant protective effects of DQB1*06:01 and DQB1*05:01. In addition, a single-nucleotide polymorphism-based conditional analysis controlling for the effect of HLA-DQB1 was performed to determine whether there were other independent HLA associations outside of HLA-DQB1. This analysis revealed associations at HLA-DPB1 in the HLA class II region (rs3117242, P = 4.1 × 10(-5), OR = 2.45; DPB1*05:01, P = 8.1 × 10(-3), OR = 1.39). These results indicate that complex HLA class II associations contribute to the genetic predisposition to narcolepsy.

[Effects of ramelteon on a patient with circadian rhythm sleep disorder and mood disorder].

Ramelteon is a novel hypnotic characterized by its action as a melatonin receptor (MT1/MT2) agonist. It has been reported that ramelteon can alter the phase of the sleep period. We report a patient with circadian rhythm sleep disorder and mood disorder who improved with ramelteon. A 25-year-old man had a 5-year history of emotional instability, excessive daytime sleepiness, and difficulty awakening. He had been diagnosed with mood disorder and narcolepsy by a psychiatrist. Sertraline, milnacipran, valproate, and methylphenidate were ineffective, and so he presented to our hospital. Interview data and a sleep log demonstrated a delayed sleep phase. As other examinations such as actigraphy and video-polysomnography indicated no other diseases, the patient was diagnosed with circadian rhythm sleep disorder, delayed sleep phase type (ICSD-2). In addition, his mental symptoms were consistent with the criteria for cyclothymia (ICD-10). After the administration of ramelteon, the phase of his sleep period gradually advanced and his emotional instability improved. Because of the high rate of comorbidity between these two diseases, we should be aware of circadian rhythm sleep disorders that are masked by mood disorders.

A novel Doppler echocardiographic score reflecting cardiac functional status can predict adverse outcome in acute myocardial infarction.

BACKGROUND: E/e' and s' are thought to reflect left ventricular diastolic and systolic function, respectively. However, there are no reports on the combined use of E/e' and s' in predicting the outcome in acute myocardial infarction (AMI). METHODS: For 20 months beginning in October 2006, we enrolled 65 AMI patients who had undergone Swan-Ganz (SG) catheterization and echocardiography just after reperfusion therapy. We measured the cardiac index (CI) and the pulmonary capillary wedge pressure (PCWP) via an SG catheter and determined routine echocardiographic indices, including transmitral flow velocity (E), mitral annulus velocities at systole (s') and early diastole (e'), and E/e'. In addition, we rounded off the values of s' (cm/s) and E/e' (ratio of cm/s to cm/s) to the nearest integer, and designated them the s'-score and E/e'-score, respectively. We also defined the cardiac status score as the s'-score subtracted from the E/e'-score. In Study 1, we investigated the relationships between hemodynamic parameters (CI and PCWP) and echocardiographic indices, including the cardiac status score. In Study 2, we excluded patients with Killip class ≥II, yielding a final study population of 55 patients in whom we investigated whether the cardiac status score could predict adverse cardiac events. RESULTS: Only the cardiac status score significantly correlated with both the PCWP and the CI. In the Cox proportional hazards model, significant predictors were the left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), and cardiac score ≥3.0. CONCLUSIONS: The novel score achieved in this study by subtracting the s'-score from the E/e'-score could be highly useful for predicting outcomes in AMI with Killip class I.

[Association of Japanese doctors' sleep habits with working environments and lifestyle].

To clarify the association of Japanese doctors' sleep habits with working environments and lifestyle, a survey was performed using a self-administered questionnaire in February 2002, targeting a population of 2,455 Asahikawa Medical University alumni. A total of 881 subjects completed questionnaires, yielding a response rate of 35.9%. The mean+/-SD sleep duration on workdays was 410.4+/-60.5 minutes, approximately 30 minutes shorter than that of the general Japanese population. The prevalence of subjective insufficient sleep (SIS) on workdays was 64.5%, significantly higher than that in the general Japanese population. The estimated overall prevalences of various sleep problems are as follows: difficulty initiating sleep, 14.7%; difficulty maintaining sleep, 15.3%; poor perceived quality of sleep, 15.6%; waking without feeling refreshed (WWFR), 30.0%; and excessive daytime sleepiness (EDS), 30.8%. SIS had a significant positive association with WWFR and EDS. Doctors' sleeplessness differed depending on their working style. The prevalence of SIS among doctors working at hospitals and clinics with inpatient wards was significantly higher than that among those working in environments without inpatient wards. The prevalence of SIS was significantly associated with the number of working hours, fatigue, and an irregular lifestyle. Habitual exercise did not appear to affect SIS. A multiple logistic regression model revealed that working in hospitals, long working hours (more than 9 hours a day), fatigue, and an irregular lifestyle were independently associated with SIS [OR=2.19 (95% CI=1.29-3.70); OR=1.95 (95% CI=1.37-2.77); OR=1.93 (95% CI=1.38-2.69); OR=3.27 (95% CI=2.21-4.84)]. Sleep duration on holidays was approximately 60 minutes longer than that on workdays, and the prevalence of SIS decreased to 32.3%. These results demonstrate that the prevalence of SIS is higher among doctors working at hospitals and clinics with inpatient wards, who tend to have long working hours and irregular lifestyles.

Preventive effect of renin-angiotensin system inhibitor on left atrial remodelling in patients with chronic atrial fibrillation: long-term echocardiographic study.

AIMS: Left atrium (LA) gradually enlarges with the time course of atrial fibrillation (AF). The aim of this study was to examine whether the renin-angiotensin system (RAS) inhibitor could prevent LA remodelling in patients with chronic AF. METHODS AND RESULTS: Forty-one patients with chronic non-valvular AF were enrolled and divided into the following two groups: the RAS group taking an RAS inhibitor and the non-RAS group not taking it. We compared echocardiographic parameters including LA volume at the beginning and the end of follow-up. Percent change of these parameters was calculated from the value at the end of follow-up divided by the value at the beginning of follow-up. An enlargement of LA volume index and a decrease in LA expansion fraction was significantly prevented in the RAS group. Administration of RAS inhibitors was significantly associated with the prevention of increasing LA volume in multivariate analysis. CONCLUSION: RAS inhibitors may prevent structural and functional degradation of LA in chronic non-valvular AF.

Emphysematous cystitis with diabetic neurogenic bladder.

A 62-year-old diabetic woman suffering from high fever was admitted to our hospital. She had a lower abdominal phantom tumor and hyperglycemia. The results of urine analysis showed hematuria and bacteriuria. X-ray and computed tomography revealed gas accumulation in the wall of the bladder. Escherichia coli was identified in urine culture. On the basis of the lack of urine output and the identification of residual urine on catheterization, a diagnosis of emphysematous cystitis with diabetic neurogenic bladder was established. The patient recovered after discontinuation of urinary drainage, intensive insulin therapy, and antibiotic therapy.

Relation of gender and interatrial dyssynchrony on tissue Doppler imaging to the prediction of the progression to chronic atrial fibrillation in patients with nonvalvular paroxysmal atrial fibrillation.

This prospective study aimed to identify the relation of gender and interatrial dyssynchrony on tissue Doppler imaging (TDI) to the prediction of the progression to chronic atrial fibrillation (CAF) in nonvalvular paroxysmal AF (PAF) patients. Nineteen consecutive men and 19 women with nonvalvular PAF were prospectively followed after echocardiography. We measured the interval of time from initiation of the P wave on the electrocardiogram until the beginning of the late diastolic TDI signal at the lateral border of the mitral (P-A'(M)) and the tricuspid annulus (P-A'(T)). Interatrial dyssynchrony was defined as the difference between the P-A'(M) and P-A'(T) intervals (A'(M)-A'(T)). The study endpoint was the onset of CAF (>6 months). Six men developed CAF during a follow-up of 32 +/- 26 months, and 3 women developed CAF during a follow-up of 25 +/- 19 months. Compared to those without CAF, the patients with CAF had significantly longer A'(M)- A'(T) intervals (men: 41 +/- 10 vs 27 +/- 12 ms, women: 64 +/- 4 vs 23 +/- 9 ms; P < 0.01) in both genders. Kaplan-Meier analysis, using cutoff values determined by analysis of receiver-operating characteristics curves, revealed that the progression to CAF was significantly observed more often when A'(M)-A'(T) interval was >34 ms in men and >43 ms in women. This prospective study suggests that nonvalvular PAF men and women with a high risk of developing CAF have "interatrial dyssynchrony" on atrial TDI, whose cutoff values are shorter and may affect the vulnerability of AF in men.

Antioxidant activity of fish sauces including puffer (Lagocephalus wheeleri) fish sauce measured by the oxygen radical absorbance capacity method.

Fish sauces are fermented seasonings traditionally used throughout Asia, including Japan. Here, we report on the antioxidant activity of 30 fish sauces, among them a puffer fish sauce developed specifically for this study. To determine the antioxidant activity (i.e., the peroxyl radical elimination capacity) of the fish sauces, the oxygen radical absorbance capacity (ORAC) was measured. ORAC values ranged between 104 µmol (flatfish sauce 1) and 103 µmol (sandfish sauce) trolox equivalent (TE)/100 ml of fish sauce. Hydroxyl radical scavenging activity (IC50) was measured using electron spin resonance. IC50 values ranged between 0.081% (puffer fish sauce) and 0.653% (sardine fish sauce 7). Puffer fish sauce had a high ORAC value (8,365 µmol TE/100 ml) and the highest hydroxyl radical scavenging activity (0.081). The relationship between the ORAC and IC50 values of the 30 fish sauces was determined to be intermediate (r =-0.521, p=0.01).

Effects of levetiracetam on hippocampal kindling in Noda epileptic rats.

In order to clarify the seizure susceptibility of Noda epileptic rat (NER) and the antiepileptic effects of levetiracetam (LEV), we performed electrical hippocampal kindling in NERs compared with Wistar rats (experiment 1), and hippocampal kindling in NERs with LEV administration (experiment 2). In experiment 1, electrical stimulation was administered to the right dorsal hippocampus of NERs and Wistar rats once per day. In experiment 2, NERs were randomly assigned to group L (LEV administration) and C (saline administration). Following daily administration of LEV (240 mg/kg, i.p.) to group L and saline to group C, hippocampal kindling was performed from the 5th day of consecutive LEV or saline administration. As a result of experiment 1, all NERs exhibited stage 5 (falling) or stage 6 seizure (running/jumping, subsequent seizure) from the first electrical stimulation. In experiment 2, LEV suppressed development of hippocampal kindling, increased the afterdischarge threshold of the hippocampus and inhibited stage 6 seizures in NER. Although LEV prolonged the afterdischarge duration at the first stage 5 seizure significantly, there was a tendency to prolong the latency to generalization by LEV. These findings indicate that NER is susceptible not only to limbic seizures but also to brainstem seizures. Furthermore, LEV may have inhibitory effects not only on the hippocampus but also on other neuronal pathways to secondary generalization in this rat model.

Diastolic flow velocity pattern of the left anterior descending coronary artery in hypertrophied heart, with special reference to the difference between hypertrophic cardiomyopathy and hypertensive left ventricular hypertrophy.

BACKGROUND: This study aimed to clarify the characteristics of diastolic flow velocity pattern of the left anterior descending coronary artery (LAD) in patients with left ventricular hypertrophy (LVH), and the difference in diastolic LAD flow velocity pattern between hypertensive LVH and hypertrophic cardiomyopathy (HCM). METHODS: The flow velocity pattern was recorded at the mid-portion of the LAD by high-frequency transthoracic Doppler echocardiography in 22 patients with HCM, 10 hypertensive patients with LVH [LVH(+)HT], and 9 hypertensive patients without LVH [LVH(-)HT]. The diastolic flow pattern was analyzed. Standard two-dimensional echocardiogram and apexcardiogram (ACG) were also recorded. RESULTS: The interventricular septal thickness (IVST) and the sum of the IVST and LV posterior wall thickness (PWT) (IVST + PWT) were greater in HCM than in HT (p < 0.01) patients. Early diastolic upstroke time (D-UT) of the LAD flow velocity wave was longest in HCM, and was longer in LVH(+)HT than in LVH(-)HT (p < 0.01) patients. Direct correlation was found between D-UT and IVST, IVST + PWT in patients with LVH(+)HT and LVH(-)HT (r = 0.80, 0.79, respectively; p < 0.01), but no correlation was found between these parameters in HCM. Late-diastolic step (LDS) formation of the LAD flow velocity wave was observed in 68% of HCM, 20% of LVH(+)HT, but none of the LVH(-)HT patients. The A wave ratio of ACG was higher in patients with LDS than in those without (p < 0.01). The LDS occurred coincidently with the A wave of ACG. CONCLUSIONS: The diastolic LAD flow velocity pattern in hypertrophied heart is characterized by slow acceleration and LDS formation, reflecting impaired relaxation and increased stiffness of the LV, respectively. These abnormalities correlate with the degree of hypertrophy in hypertensive heart, but do not correlate with that in HCM.

Prediction of transition to chronic atrial fibrillation in elderly patients with nonvalvular paroxysmal atrial fibrillation by transthoracic Doppler echocardiography.

BACKGROUND: It is well known that paroxysmal atrial fibrillation (PAF) often precedes the development of chronic atrial fibrillation (CAF). HYPOTHESIS: The purpose of this study was to determine prospectively whether transthoracic echocardiography is useful for the prediction of the transition to CAF in elderly patients with nonvalvular PAF. METHODS: Forty-two consecutive elderly patients (> or =65 years) with nonvalvular PAF were prospectively evaluated after undergoing transthoracic echocardiography. The study endpoint was the transition to CAF (AF; > or = 6 mo). RESULTS: During a follow-up period of 32 +/- 24 mo, 12 patients developed CAF. Patients with CAF had a significantly lower peak A velocity (A) and a higher E/A ratio of the transmitral inflow (TMF) such as a pseudonormalization pattern, and a lower peak atrial reversal wave velocity, higher peak diastolic wave velocity (D), and lower peak systolic/diastolic wave velocity ratio (S/D ratio) of the pulmonary venous flow (PVF). Kaplan-Meier analysis revealed that the transition to CAF was observed more often when A was < or = 70 cm/sec and E/A ratio was > or = 1.07 of TMF, and D was > or = 44 cm/sec and the S/D ratio was < or = 1.34 of PVF. All patients developed CAF when the E/A ratio was > or = 1.15 or the S/D ratio was < or = 0.75. CONCLUSIONS: This prospective study suggests that elderly patients at high risk for transition to CAF have a pseudonormalization pattern of TMF and a diastolic dominant pattern of PVF, and that transthoracic Doppler estimation of TMF and PVF may be useful in identifying elderly patients at high risk for the transition from nonvalvular PAF to CAF.

[Actigraphy in sleep medicine and sleep research].

Actigraphy is a method that utilizes a miniaturized computerized wristwatch-like device to monitor and collect data generated by body movements over extended periods of time. It allows estimation of sleep and wakefulness based on motor activity. It provides a noninvasive, objective, and longitudinal method for the diagnostic and post-treatment evaluation of patients with sleep disorders in the ambulatory setting. It has been used for researchers to study sleep disturbances in a variety of populations, most frequently for the evaluation of insomnia, paradoxical insomnia, and circadian rhythm sleep disorders. In addition, it is particularly useful in populations where polysomnography would be difficult to record, such as in patients with dementia and delirium. Actigraphy should be extensively carried out in sleep medicine as well as sleep research.

Transthoracic echocardiography during sinus rhythm identifies elderly patients with nonvalvular paroxysmal atrial fibrillation at high risk of cerebral infarction.

We performed transthoracic echocardiography during sinus rhythm in elderly nonvalvular paroxysmal atrial fibrillation (NV-PAF) patients (> or =65 years) with cerebral infarction and in patients without cerebral infarction. This study suggests that elderly NV-PAF patients at high risk for cerebral infarction seem to have a pseudonormalization pattern of transmitral inflow, and decreased atrial reversal flow of pulmonary venous flow, and increased left atrial volume.

Clinical significance of anterior mitral leaflet fibrillation in patients with nonvalvular atrial fibrillation: comparison with blood flow and wall motion of the left atrial appendage.

BACKGROUND AND PURPOSE: Diastolic fibrillation of the anterior mitral leaflet (AML) is seen in patients with atrial fibrillation (AF). However, its clinical significance has been unclear. On the other hand, reduced blood flow velocity in the left atrial appendage (LAA) may be associated with LA thrombus formation. In this study, we investigate the relationship between the flow velocity and the wall motion velocity of the LAA and diastolic fibrillation of the AML in patients with nonvalvular AF. METHODS: We performed transthoracic echocardiography (TTE) in 45 consecutive patients with chronic nonvalvular AF. The LAA flow velocity was measured by pulsed Doppler echocardiography with the sample volume positioned at the center of the LAA. The LAA wall motion velocity was measured by pulsed Doppler tissue imaging (DTI) with the sample volume at the medial wall of the LAA. The AML fibrillation velocity was measured by pulsed DTI with the sample volume at the AML tip. RESULTS: The AML fibrillation velocity could be measured in 44 patients (97.8%), and the LAA flow and wall motion velocities were measurable in 35 (77.8%) and 42 (93.3%) patients, respectively. The AML fibrillation velocity had a range from 4 to 21 cm/s and showed significant positive correlation with the LAA flow velocity (r = 0.82, P < 0.001) and the wall motion velocity (r = 0.80, P < 0.001) of the LAA. An AML fibrillation velocity of ≤7 cm/s predicted patients having a tendency to LA thrombus formation (LAA flow velocity ≤20 cm/s) with high sensitivity (87.5%) and specificity (88.9%). CONCLUSION: The AML fibrillation velocity seems to be a viable substitute for the LAA flow velocity in the detection of flow stagnation in the LA.