Yoshinori Doi

Arrhythmia in hypertrophic cardiomyopathy. I: Influence on prognosis.

In order to examine the association between arrhythmia and subsequent prognosis, 72-hour ambulatory electrocardiographic monitoring was performed in 86 unselected patients with hypertrophic cardiomyopathy. During monitoring 23 patients experienced at least one episode of supraventricular tachycardia and 24 had ventricular tachycardia (of whom 10 had more than three episodes). The patients were then followed for a mean of 2.6 years (range one to four). Seven patients died suddenly. Of these, five had exhibited multiform and paired ventricular extrasystoles and ventricular tachycardia. These arrhythmias were significantly associated with sudden death whereas supraventricular arrhythmias were not. The patients who died suddenly were older and had experienced more symptoms than the survivors, and three had a family history of hypertrophic cardiomyopathy and sudden death. This experience provides the basis for the assessment of treatment in patients with hypertrophic cardiomyopathy and serious ventricular arrhythmia.

Prevalence of atrial fibrillation in the general population of Japan: An analysis based on periodic health examination

BACKGROUND The mortality and morbidity rates of various cardiovascular diseases differ between Western countries and Japan. The age- and gender-specific prevalence rate of atrial fibrillation (AF) in the general population of Japan was determined using the data from periodic health examinations in 2003. METHODS Data of 630,138 subjects aged 40 years or more (47% were men and 34% were employees of companies and local governments) were collected from northern to southern Japan. The prevalence of diagnosed AF in each 10-year age group of both men and women was determined. Based on these prevalence rates and the Registry of Residents, the number of people having AF in Japan was estimated. RESULTS The prevalence rate of AF increased as both male and female subjects aged, and it was 4.4% for men but only 2.2% for women aged 80 years or more (p<0.0001). As a whole, the AF prevalence of men was three times that of women (1.35 versus 0.43%, p<0.0001). There may be approximately 716,000 people (95% confidence interval (CI), 711,000-720,000) with AF in Japan, an overall prevalence of 0.56%. The number of people having AF was projected to be 1.034 (95% CI, 1.029-1.039) million, an overall prevalence of 1.09%, in 2050. CONCLUSIONS The prevalence of AF increased in Japan as the population aged, as in Western countries. The overall prevalence of AF in Japan is approximately two-thirds of that in the USA. The projected increase in the number of people having AF is modest in Japan in 2050.

Left ventricular diastolic function assessed using Doppler tissue imaging in patients with hypertrophic cardiomyopathy: relation to symptoms and exercise capacity

Background: Conventional Doppler indices of left ventricular diastolic function do not correlate with symptoms or exercise capacity in patients with hypertrophic cardiomyopathy, because of their dependence on loading conditions. Diastolic mitral annular velocity measured using Doppler tissue imaging has been reported to be a preload independent index of left ventricular diastolic function. Objective: To determine the relation between diastolic annular velocities combined with conventional Doppler indices and symptoms or exercise capacity in hypertrophic cardiomyopathy. Methods: 85 patients with hypertrophic cardiomyopathy and 60 normal controls were studied. Diastolic mitral annular velocities, transmitral left ventricular filling, and pulmonary venous velocities were measured. Results: Early diastolic velocities at lateral and septal annulus were lower in patients with hypertrophic cardiomyopathy than in controls (lateral Ea: 10 (3) v 18 (4) cm/s, p < 0.0001; septal Ea: 7 (2) v 12 (3) cm/s, p < 0.0001). Unlike conventional Doppler indices alone, transmitral early left ventricular filling velocity (E) to lateral Ea ratio correlated inversely with peak oxygen consumption (r = −0.42, p < 0.0001). Patients in New York Heart Association (NYHA) class III had a higher transmitral E to lateral Ea ratio (12.0 (4.6)) than those in NYHA class II (7.6 (3.1), p < 0.005) or class I (6.6 (2.6), p < 0.0001). Conclusions: Early diastolic mitral annular velocities are reduced in patients with hypertrophic cardiomyopathy. Unlike conventional Doppler indices alone, the transmitral E to lateral Ea ratio correlates with NYHA functional class and exercise capacity.

Postural Dysregulation in Systolic Blood Pressure Is Associated With Worsened Scoring on Neurobehavioral Function Tests and Leukoaraiosis in the Older Elderly Living in a Community

BACKGROUND AND PURPOSE Postural hypotension, which occurs frequently in community-living, apparently healthy elderly adults, is usually asymptomatic. However, the relation between postural changes in blood pressure and quantitative higher cerebral function or silent brain lesions remains unclear. We examined the association of exaggerated postural changes in systolic blood pressure with cognitive and quantitative neurobehavioral functions and with brain lesions on MRI in the community-dwelling older elderly. METHODS The study population consisted of 334 community-dwelling elderly adults, aged 75 years or older (mean age, 80 years). Postural changes in systolic blood pressure (SBP) were assessed using an autosphygmomanometer (BP-203 I). By the difference between the mean of two measurements of SBP at standing and at supine position (dSBP = SBP at upright-SBP at supine position), we divided the subjects into three groups: (1) 20 subjects with postural hypotension (d-SBP < or = -20 mm Hg), (2) 29 subjects with postural hypertension (dSBP > or = 20 mm Hg), and (3) 285 subjects with postural normotension (20 < dSBP < 20 mm Hg). We defined the former two groups as the postural dysregulation group. Scores in four neurobehavioral function tests (Mini-Mental State Exam. Hasegawa Dementia Scale Revised, computer-assisted visuospatial cognitive performance score, and the Up and Go Test) and activities of daily living were compared among the three groups. Brain lesions on MRI, including number of lacunes and periventricular hyperintense lesions, were compared among 15 age- and sex-matched control subjects with postural hypotension, 15 with postural hypertension, and 30 with postural normotension. RESULTS Twenty subjects (6.0%) exhibited postural hypotension and 29 (8.7%) postural hypertension. Scores in neurobehavioral functions and activities of daily living were significantly lower in the postural dysregulation group (both postural hypotension and hypertension groups) than in the postural normotension group. The postural dysregulation group exhibited significantly more advanced periventricular hyperintensities than the normotension group. CONCLUSIONS Asymptomatic community dwelling elderly individuals with postural hypotension as well as those with postural hypertension had poorer scores on neurobehavioral function tests and more advanced leukoaraiosis demonstrated on MRI than those without exaggerated postural changes in SBP.

Cardiac Ankyrin Repeat Protein Gene (ANKRD1) Mutations in Hypertrophic Cardiomyopathy

OBJECTIVES The purpose of this study was to explore a novel disease gene for hypertrophic cardiomyopathy (HCM) and to evaluate functional alterations caused by mutations. BACKGROUND Mutations in genes encoding myofilaments or Z-disc proteins of the cardiac sarcomere cause HCM, but the disease-causing mutations can be found in one-half of the patients, indicating that novel HCM-susceptibility genes await discovery. We studied a candidate gene, ankyrin repeat domain 1 (ANKRD1), encoding for the cardiac ankyrin repeat protein (CARP) that is a Z-disc component interacting with N2A domain of titin/connectin and N-terminal domain of myopalladin. METHODS We analyzed 384 HCM patients for mutations in ANKRD1 and in the N2A domain of titin/connectin gene (TTN). Interaction of CARP with titin/connectin or myopalladin was investigated using coimmunoprecipitation assay to demonstrate the functional alteration caused by ANKRD1 or TTN mutations. Functional abnormalities caused by the ANKRD1 mutations were also examined at the cellular level in neonatal rat cardiomyocytes. RESULTS Three ANKRD1 missense mutations, Pro52Ala, Thr123Met, and Ile280Val, were found in 3 patients. All mutations increased binding of CARP to both titin/connectin and myopalladin. In addition, TTN mutations, Arg8500His, and Arg8604Gln in the N2A domain were found in 2 patients, and these mutations increased binding of titin/connectin to CARP. Myc-tagged CARP showed that the mutations resulted in abnormal localization of CARP in cardiomyocytes. CONCLUSIONS CARP abnormalities may be involved in the pathogenesis of HCM.

Effects of Exercise on Neurobehavioral Function in Community‐Dwelling Older People More Than 75 Years of Age

OBJECTIVE: We evaluated the effects of exercise on neurobehavioral function in healthy older people more than 75 years of age.

THE TIMED “UP & GO” TEST IS A USEFUL PREDICTOR OF FALLS IN COMMUNITY-DWELLING OLDER PEOPLE

ratio.3 Fihn et al. concluded that “age did not appear to be an important determinant of risk for bleeding in patients receiving warfarin, with the possible exception of age 80 years or older.” These investigators reported that life-threatening or fatal bleeding complications occurred more often among the oldest patients; the incidence of these events was 0.75 per 100 patient-years in patients younger than SO years of age and 3.38 in patients 80 years of age and older (relative risk 4.50; 95% confidence interval, 1.315.6).4 We agree with Dr. Portnoi that the decision-making process regarding the use of warfarin therapy in the management of older patients with atrial fibrillation should engage patients and, when appropriate, their families. In addition, therapeutic management with regard to warfarin therapy does not end with the initiation of treatment. Continued reevaluation of treatment appropriateness, adequate patient surveillance, and maintenance of the patient in the appropriate therapeutic range are essential. In our study, more than one-quarter of the physicians surveyed responded that they preferred a target therapeutic range with a lower INR limit less than 2 for their older patients with atrial fibrillation who are residents in nursing homes.’ More widespread use of specialized clinics to manage warfarin therapy in the long-term care setting may provide a mechanism to address some of these important issues.

Trunk deformity is associated with a reduction in outdoor activities of daily living and life satisfaction in community-dwelling older people

We have evaluated the association between trunk deformities of the sagittal plane and functional impairment of daily living in community-dwelling elderly subjects. The analysis involved a detailed assessment of indoor and outdoor activities of daily living, satisfaction with life, and mental status. The participants in this study were 236 community-dwelling older adults, aged 65 years and older, living in Kahoku district of Kochi in Japan. The participants were classified based on their posture, which was assessed using photographs of the subjects, and interviewed to assess their basic activities of daily living (BADL), instrumental ADL (IADL), and cognitive well-being in the cross-sectional study. The statistical analysis was performed using the Mann-Whitney U-test. The lumbar kyphosis group received significantly lower BADL and IADL scores than the normal group. The trunk deformity group which were defined as kyphosis, flat back, and lumbar lordosis groups exhibited decreases in activities that included going out, shopping, depositing and withdrawing money, and visiting friends in the hospital. These activities require going outdoors; thus, this study showed that the trunk deformity group had limitations in outdoor activities. There was no significant difference between the geriatric depression score (GDS) and the pattern of posture. The abnormal trunk deformity groups tended to score lower than the normal group with regard to subjective healthiness and life satisfaction measures, including subjective health condition, everyday feeling, satisfaction with human relationships, satisfaction with economic condition, and satisfaction with present life.

A U-shaped association between home systolic blood pressure and four-year mortality in community-dwelling older men.

BACKGROUND: Several studies in older people have found a U‐shaped or J‐shaped association of blood pressure with mortality. The increased mortality associated with the lowest levels of blood pressure in older people have been explained by concurrent illnesses and frailty, but previous studies used blood pressure measured on a single occasion. Such a casual value is different from the long‐term average of blood pressure. We investigated the relation between the average level of 5‐day consecutive home blood pressure and mortality in older people while adjusting for potential confounding factors including morbidity and frailty at baseline.

Quality of life of old people living in the community

Vol 350 • November 22, 1997 1521 reported to be expressed specifically in the brain based on northern studies, our ability to detect necdin transcripts in the liver suggests a lower, but detectable level of expression in peripheral tissues. We further examined necdin imprinting by testing expression by RT-PCR with RNA from cultured fibroblasts derived from a normal control and three patients with PWS and three with Angelman syndrome (AS), each with a documented 15q11-q13 deletion (figure B). This analysis likewise revealed imprinted expression, with necdin mRNA detectable in normal and AS samples, but not in PWS samples. The overall level of expression in cultured fibroblast cells may be quite low, given a less robust PCR product than that seen in the liver. These results show that necdin is imprinted with paternal-specific transcription in multiple tissues, including brain, which is the predominant site of its expression, and are consistent with another report indicating imprinted expression of necdin in newborn mouse brain and human fibroblasts. Necdin was initially identified as a mRNA specific to postmitotic, differentiated neuron from embryonal carcinoma cells, and found in the mouse to be expressed only in the central nervous system by northern analysis. In mouse development, necdin is expressed abundantly during periods of neural generation and differentiation, and expression is detected throughout the brain of the adult mouse, with the highest expression in the hypothalamus and midbrain. This Imprinting analysis of the human necdin gene RT-PCR on RNA from brain and liver controls and a PWS patient with a 15q11-q13 deletion (A), and RNA from cultured fibroblast cell lines from a control, three deletion PWS patients and three deletion AS patients (B). Expression of a second gene not on chromosome 15 (LDL receptor) was used as a control for RNA quality, and –RT controls are shown for necdin, whose product is colinear with genomic DNA. Details of RNA preparation and RT-PCR can be obtained from the author. Quality of life of old people living in the community