Yoko Miyasaka

Obesity as a risk factor for the progression of paroxysmal to permanent atrial fibrillation: a longitudinal cohort study of 21 years

AIMS Obesity has been shown to be a risk factor for first atrial fibrillation (AF), but whether it is associated with progression from paroxysmal to permanent AF is unknown. METHODS AND RESULTS In this longitudinal cohort study, Olmsted County, MN residents confirmed to have developed paroxysmal AF during 1980-2000 were identified and followed passively to 2006. The interrelationships of body mass index (BMI), left atrial (LA) size, and progression to permanent AF were analysed. Of a total of 3248 patients (mean age 71 +/- 15 years; 54% men) diagnosed with paroxysmal AF, 557 (17%) progressed to permanent AF (unadjusted incidence, 36/1000 person-years) over a median follow-up period of 5.1 years (interquartile range 1.2-9.4). Adjusting for age and sex, BMI independently predicted the progression to permanent AF (hazard ratio, HR 1.04, CI 1.03-1.06; P < 0.0001). Compared with normal BMI (18.5-24.9 kg/m(2)), obesity (30-34.9 kg/m(2)) and severe obesity (>or=35 kg/m(2)) were associated with increased risk for progression [HR 1.54 (CI 1.2-2.0; P = 0.0004) and 1.87 (CI 1.4-2.5; P < 0.0001, respectively)]. BMI remained highly significant even after multiple adjustments. In the subgroup with echocardiographic assessment (n = 744), LA volume was incremental to BMI for independent prediction of progression after multiple adjustments, and did not weaken the association between BMI and progression to permanent AF (HR 1.04; CI 1.02-1.05; P < 0.0001). CONCLUSION There was a graded risk relationship between BMI and progression from paroxysmal to permanent AF. This relationship was not weakened by LA volume, which was independent of and incremental to BMI for the prediction of progression to permanent AF.

Changing Trends of Hospital Utilization in Patients After Their First Episode of Atrial Fibrillation

A marked increase in hospitalization for patients with atrial fibrillation (AF) has previously been noted. Whether this increase is related to a change in the prevalence of AF or a change in the pattern of practice with respect to the management of AF remains unclear. To determine the trends in hospital utilization after first AF in a community-based setting (Olmsted County, Minnesota), residents diagnosed with first AF from 1980 to 2000 were identified and followed until 2004. The primary outcome of interest was hospital admission for cardiovascular reasons. Of a total of 4,498 subjects (73 +/- 14 years old, 51% men), 2,503 (56%) were admitted to the hospital for cardiovascular causes >or=1 time during a mean follow-up of 5.5 +/- 5.0 years. Risk of first hospitalization was greatest during the first year of AF (cumulative incidence 31%, 95% confidence interval [CI] 30 to 32). First hospitalization was strongly related to age (p <0.0001) but not to sex (p = 0.38). From 1980 to 2000, the age-and sex-adjusted rate of first hospitalization increased, on average, by 2.5% a year (95% CI 1.8 to 3.2, p <0.0001), even after multivariable adjustment for co-morbidities. When we excluded all hospital admissions for the purposes of AF management, the increase in hospitalization was only 0.8% per year (95% CI 0.05 to 1.6, p = 0.04), which was no longer significant after multivariable adjustment for co-morbidities (p = 0.25). In conclusion, the marked increase in hospitalization after first AF diagnosis from 1980 to 2000 appeared to be largely driven by the changing practice pattern in AF management.

Effect of pioglitazone on arterial baroreflex sensitivity and sympathetic nerve activity in patients with acute myocardial infarction and type 2 diabetes mellitus.

Abstract: Pioglitazone has been shown to reduce the occurrence of fatal and nonfatal myocardial infarction (MI) in type 2 diabetes mellitus (DM). However, the mechanisms of such favorable effects remain speculative. The aim of this study was to investigate the effect of pioglitazone on arterial baroreflex sensitivity (BRS) and muscle sympathetic nerve activity (MSNA) in 30 DM patients with recent MI. Patients were randomly assigned to those taking pioglitazone (n = 15) and those not taking pioglitazone (n = 15) at 4 weeks after the onset of MI. BRS, MSNA, calculated homeostasis model assessment of insulin resistance index (HOMA-IR), and plasma adiponectin were measured at baseline and after 12 weeks. Pioglitazone increased plasma adiponectin (from 6.9 ± 3.3 &mgr;g/dL to 12.2 ± 7.1 &mgr;g/dL) and reduced HOMA-IR (from 4.0 ± 2.2 to 2.1 ± 0.9). In the pioglitazone group, MSNA decreased significantly (from 37 ± 7 bursts/min to 25 ± 8 bursts/min) and BRS increased significantly (from 6.7 ± 3.0 to 9.9 ± 3.2 ms/mm Hg) after 12 weeks. Furthermore, a significant relationship was found between the change in MSNA and HOMA-IR (r = 0.6, P = 0.042). Thus, pioglitazone decreased the sympathetic nerve traffic through the improvement of insulin resistance in DM patients with recent MI, which indicate that the sympathoinhibitory effects of pioglitazone may, at least in part, have contributed to the beneficial effects of pioglitazone.

Obesity as an independent risk for left ventricular diastolic dysfunction in 692 Japanese patients

SUMMARY BACKGROUND Both obesity and left ventricular (LV) diastolic dysfunction are associated with an increased risk of cardiovascular morbidity and mortality. There is a paucity of data as to whether obesity is independently associated with LV diastolic dysfunction. METHODS Adult patients with sinus rhythm referred for a transthoracic echocardiography between July, 2007, and December, 2007, were prospectively included. Exclusion criteria were patient who had a history of congenital or valvular heart disease, treatment with pacemaker implantation or implantable cardioverter defibrillator, myocardial infarction, or impaired LV systolic function. Diastolic function was classified by an algorithm incorporating data from mitral and pulmonary venous flow indices, and Doppler tissue imaging. Body mass index (BMI) was evaluated as a categorical variable (normal weight <25.0 kg/m(2); overweight 25.0 to <30.0 kg/m(2); and obese ≥30 kg/m(2)). Logistic models were used to assess the risk of abnormal LV diastolic function associated with BMI categories. RESULTS Of a total number of 692 patients who met all study criteria (mean 59 ± 15 year-old; 50% women, 48% hypertension, 16% diabetes, 26% overweight, 8% obese), 538 (78%) had abnormal LV diastolic function. In multivariate analyses adjusting for age, sex, and cardiovascular risk factors, obesity was independently associated with LV diastolic dysfunction (odds ratio [OR]: 2.98, 95% confidence interval [CI]: 1.12-7.88; P = 0.03) compared to normal weight. LV mass did not weaken this association (OR: 2.88, 95% CI: 1.08-7.68; P = 0.04). Overweight was not independently associated with LV diastolic dysfunction. CONCLUSION Obesity was associated with LV diastolic dysfunction independent of cardiovascular risk factors and LV mass.

Real Time Three‐Dimensional Transesophageal Echocardiographic Images of Platypnea‐Orthodeoxia Due to Patent Foramen Ovale

A 74-year-old man with a patent foramen ovale was admitted with dyspnea and cyanosis that had become progressively worse along with dehydration. Transthoracic echocardiography (iE33, Philips Medical Systems, Andover, MA, USA) revealed a normal ventricular size and function and no evidence of intracardiac shunting by Doppler color interrogation. Neither chest x-ray nor chest computed tomography (Aquilion 64, Toshiba Medical Systems, Otawara, Japan) revealed any apparent pulmonary disease that could cause his dyspnea. A right and left heart catheterization demonstrated normal coronaries with a mean right atrial pressure of 3 mmHg and a normal mean pulmonary artery pressure of 13 mmHg. Careful history taking revealed that he developed dyspnea in a sitting position, whereas the symptoms were relieved in a supine position. The transesophageal echocardiographic images taken in the supine position showed the foramen ovale was closed (Fig. 1 right), and no apparent right-to-left shunt by Doppler color flow (Fig. 1 left). The images taken in the sitting position showed the foramen ovale was wide open (Fig. 2 right, Fig. 3), with a massive rightto-left shunt across the patent foramen ovale by Doppler color flow (Fig. 2 left), caused hypoxemia and dyspnea. The patient was given the diagnosis of platypnea-orthodeoxia syndrome. Platypnea-orthodeoxia, a syndrome character-

Lower mortality in patients with the DD genotype of the angiotensin-converting enzyme gene after acute myocardial infarction.

Objective — The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with different serum ACE concentrations and cardiac ACE activity.We assessed whether the ACE gene I/D polymorphism influenced cardiac mortality in Japanese patients with acute myocardial infarction. Methods and results — The ACE gene I/D polymorphism was determined in 441 consecutive patients with a first myocardial infarction.There were 69 patients (16%) with the DD genotype, 194 patients (44%) with the ID genotype, and 178 patients (40%) with the II genotype. During a mean follow-up of 9.4 months, there were 49 cardiac deaths (DD, n = 4; ID, n = 26; II, n = 19).The DD genotype was significantly associated with a lower mortality than the other genotypes (p = 0.0363) by Cox regression analysis adjusted for age, sex, site of myocardial infarction, Killip functional class, reperfusion therapy during acute phase, ACE inhibitor use, and beta-blocker use. Conclusions — In a selected cohort of Japanese patients, the DD genotype was associated with a significantly lower cardiac mortality after a first myocardial infarction.

Effect of eicosapentaenoic acid on regional arterial stiffness: Assessment by tissue Doppler imaging

AIM To evaluate the effects of eicosapentaenoic acid (EPA) on regional arterial stiffness assessed by strain rate using tissue Doppler imaging. METHODS Nineteen eligible patients were prospectively studied (mean age 62 ± 8 years, 68% men). Subjects with large vessel complications and/or diabetes mellitus were excluded. The strain rate of the ascending aorta was measured by tissue Doppler imaging as an index of regional arterial stiffness, and brachial-ankle pulse wave velocity (baPWV) was measured as an index of degree of systemic arteriosclerosis. These indices were compared before and after administration of EPA at 1800 mg/d for one year. RESULTS The plasma concentration of EPA increased significantly after EPA administration (3.0% ± 1.1% to 8.5% ± 2.9%, P < 0.001). There were no significant changes in baPWV (1765 ± 335 cm/s to 1745 ± 374 cm/s), low-density lipoprotein cholesterol levels (114 ± 29 mg/dL to 108 ± 28 mg/dL), or systolic blood pressure (131 ± 16 mmHg to 130 ± 13 mmHg) before and after EPA administration. In contrast, the strain rate was significantly increased by administration of EPA (19.2 ± 5.6 s(-1), 23.0 ± 6.6 s(-1), P < 0.05). CONCLUSION One year of administration of EPA resulted in an improvement in regional arterial stiffness which was independent of blood pressure or serum cholesterol levels.

New index of regional arterial stiffness assessed by tissue Doppler imaging.

Background — Although brachial-ankle pulse wave velocity is a widely used index of arterial stiffness, there are several limitations of this method. The actual length of an artery used for measuring pulse wave velocity is estimated based on an anatomical correction value, and brachial-ankle pulse wave velocity is directly affected by systemic blood pressure or vascular occlusion. Thus, the aim of this study was to determine whether aortic wall strain rate as measured by tissue Doppler imaging is a more useful modality for evaluating regional arterial stiffness than brachial-ankle pulse wave velocity. Methods — Seventy-two patients (18 to 78 years) with normal cardiac function and without large vessel complications were enrolled in this study. Results — A significant positive correlation was found between brachial-ankle pulse wave velocity and age, and brachial-ankle pulse wave velocity increased with age (r = 0.64, P< 0.0001).A significant negative correlation was found between strain rate and age, and strain rate decreased with age (r = –0.44, P < 0.05). A significant correlation was also found between brachial-ankle pulse wave velocity and systolic blood pressure (r = 0.45, P < 0.02), but not between strain rate and systolic blood pressure. There was no significant difference in brachial-ankle pulse wave velocity between hyperlipidaemic and normolipidaemic subjects. However, strain rate was lower in hyperlipidaemic than in normolipidaemic subjects (P < 0.05). Conclusion — Strain rate on the ascending aortic wall is a novel and more accurate index of regional arterial stiffness than brachial-ankle pulse wave velocity.

Pseudoaneurysm with left-to-right shunt in a patient with myocardial infarction: evaluation by three-dimensional echocardiography

It is often difficult to noninvasively differentiate a post-infarction left ventricular (LV) pseudoaneurysm from a post-infarction true aneurysm. A 66-year-old woman with a past history of inferior acute myocardial infarction was admitted to our hospital because of acute decompensated heart failure. Two-dimensional transthoracic echocardiography showed an aneurysm with a narrow orifice in the inferoposterior basal area. The pulmonary to systemic flow ratio (Qp/Qs) was 2.2:1, which corresponded to moderate left–right shunting. Three-dimensional transesophageal echocardiography (3D-TEE) showed the orifice in the perforated right ventricular basal area with a color jet through the orifice from the LV to the right ventricle. Collectively, based on the 3D-TEE findings, we diagnosed the case as inferoposterior pseudoaneurysm with a left-to-right shunt caused by myocardial infarction.

Takotsubo cardiomyopathy associated with serotonin syndrome: A disease that we should be aware of

Takotsubo cardiomyopathy was first described in 1990 in Japan 1], and is characterized by: (1) transient left ventricular wall otion abnormalities in the left ventricular mid segments with or ithout apical involvement; (2) the absence of obstructive coroary disease or angiographic evidence of acute plaque rupture; (3) lectrocardiographic changes that mimic acute myocardial infarcion in spite of minimal release of myocardial enzymes; and (4) he absence of pheochromocytoma and myocarditis [2]. Given the ransient nature of this syndrome and its complete resolution, the rognosis of patients with takotsubo cardiomyopathy is generally avorable [3–5]. However, it is important to pay attention to the emodynamics of patients with takotsubo cardiomyopathy in the cute phase, because heart failure is the most common clinical comlication and some fatal complications such as left ventricular free all rupture were also reported [3]. The precise etiology and pathohysiology of this syndrome remain unknown, and the treatment f this syndrome is usually empirical and individualized according o the patient’s characteristics at the time of presentation. Because the onset of takotsubo cardiomyopathy is often preeded by emotional or physical stress, abnormal catecholamine ynamics related to emotional distress seem to play a major role in he pathogenesis of takotsubo cardiomyopathy, and several mechnisms have been proposed to explain the unusual features of his syndrome, such as catecholamine-mediated multivessel epiardial spasm [6], microvascular coronary spasm [7], or direct atecholamine-mediated myocyte injury [8]. In addition, it was eported that drugs with sympathetic effects could also precipitate akotsubo cardiomyopathy [9], and drug-induced takotsubo cariomyopathy needs be considered in patients suffering from this isease without any apparent emotional or stress trigger. A case report by Sasaki et al. [10] in this issue of Journal of ardiology Cases describes a case of a 65-year-old woman who uffered from takotsubo cardiomyopathy and concomitant seroonin syndrome due to interaction of an anti-depressant agent maprotiline) and an antitussive agent (dextromethorphan). After