5-Aminolevulinic acid fermentation using engineered Saccharomyces cerevisiae.

BACKGROUND: 5'-Aminolevulinic acid (ALA) is widely used in the pharmaceutical industry, healthcare, and food production, and is a substrate for the biosynthesis of heme, which is required for respiration and photosynthesis. Enhancement of ALA biosynthesis has never been developed in Saccharomyces cerevisiae, which is a well-known model microorganism used for bioproduction of many value-added compounds. RESULTS: We demonstrated that metabolic engineering significantly improved ALA production in S. cerevisiae. First, we found that overexpression of HEM1, which encodes ALA synthetase, increased ALA production. Furthermore, addition of an optimal amount of glycine, a substrate for ALA biosynthesis, or levulinic acid, an inhibitor of ALA dehydrogenase, effectively increased ALA production. Next, we developed an assay for multiple metabolites including ALA and found that aconitase, encoded by ACO1 and ACO2, is the rate-limiting enzyme of ALA biosynthesis when sufficient glycine is supplied. Overexpression of ACO2 further enhanced ALA production in S. cerevisiae overexpressing HEM1. CONCLUSIONS: In this study, ALA production in S. cerevisiae was enhanced by metabolic engineering. This study also shows a strategy to identify the rate-limiting step of a target synthetic pathway by assay for multiple metabolites alongside the target product. This strategy can be applied to improve production of other valuable products in the well-studied and well-industrialized microorganism S. cerevisiae.

Reduction in Door-to-Balloon Time with Training for Effective and Efficient Action in Medical Service-Better Process (TEAMS-BP) at a Community Hospital in Japan.

ST-elevation myocardial infarction (STEMI) is a fatal condition. Prompt primary percutaneous coronary intervention is associated with lower mortality. However, community hospitals in Japan lack human and medical resources, and implementation of the same strategies as those used in the USA, such as an on-call cardiologist at the hospital, to achieve a door-to-balloon time of ≤ 90 min appears particularly challenging. Therefore, we used Training for Effective and Efficient Action in Medical Service-Better Process (TEAMS-BP) to develop a new process and assessed its effectiveness in reducing door-to-balloon time. TEAMS-BP can optimize the process by making the best use of available materials, machines, facilities and manpower. All processes conducted by physicians, nurses, electrocardiogram technicians, radiological technologists, and clerical staff in the emergency room were reviewed, documented, and standardized using the four steps of TEAMS-BP. The following processes were implemented: setting time goals, calling an electrocardiogram technician beforehand, minimizing tasks before calling a cardiologist, confirming the checklist, and providing data feedback. Forty-four STEMI patients who were treated after TEAMS-BP implementation were compared with 58 who were treated before implementation. Median door-to-balloon, door-to-electrocardiogram and door-to-laboratory times were significantly reduced after TEAMS-BP implementation, decreasing from 106 to 82 min, 14 to 6 min, and 67 to 45 min, respectively. In conclusion, implementation of TEAMS-BP improved the door-to-balloon time of STEMI cases without additional resources or costs incurred by the hospital. TEAMS-BP can be implemented by any hospital wishing to develop a new process that accommodates local working conditions.

Prognosis of myocardial infarction with left ventricular dysfunction in the coronary revascularization era.Subanalysis of the Japanese Coronary Artery Disease (JCAD) Study.

BACKGROUND: Indications of implantable cardioverter-defibrillator (ICD) for patients with an old myocardial infarction (OMI) and left ventricular dysfunction (LVD) were expanded in Western countries after the results of MADIT II. However, the prognosis of OMI patients with LVD and the merits of prophylactic implantation of ICD, based on evidence in Japan, have not yet been clarified. This subanalysis of the Japanese Coronary Artery Disease (JCAD) Study focused on MADIT II-compatible patients to clarify the prognosis of OMI patients with LVD in Japan. METHODS AND RESULTS: Consecutive 6,868 OMI patients were prospectively followed up for 3 years or until clinical events occurred. 291 patients had left ventricular ejection fraction (LVEF) ≤30%. Clinical events, congestive heart failure, cardiopulmonary arrest on arrival and vascular events were significantly more frequent in patients with LVEF ≤30% than in those with better LVEF. In the LVEF ≤30% group, cardiopulmonary arrest on arrival comprised 33% of all-cause deaths, and the survival curves at 2 years of the LVEF ≤30% group were almost compatible with those of the MADIT II ICD group. CONCLUSIONS: In this subanalysis, LVD was less frequent than in Western countries. The annual death rate in JCAD was better than for the MADIT II ICD group. The prophylactic use of ICD seemed to be less effective than in Western countries but still expected to be useful for OMI patients with LVD in Japan.

Appropriate duration of driving restrictions after inappropriate therapy from implantable cardiac shock devices-interim analysis of the Nippon Storm Study.

BACKGROUND: Little is known regarding the appropriate duration for driving restrictions after inappropriate implantable cardiac shock device (ICSD) therapy. METHODS AND RESULTS: We evaluated the Nippon Storm Study data, and found that inappropriate ICSD therapy occurred in 114 (7.6%) patients during a median follow-up of 464 days. Among those patients, 25 experienced further inappropriate ICSD therapy during a subsequent median follow-up of 380 days. Time-dependent recurrence of inappropriate ICSD therapy occurred in 19 (76%) patients within 180 days. CONCLUSIONS: The interval for driving restrictions after inappropriate ICSD therapy can be reduced.

Prediction of chronic renal insufficiency after coronary angiography by an early increase in oxidative stress and decrease in glomerular filtration rate.

BACKGROUND: Oxidative stress caused by contrast medium is thought to be one of the main mechanisms of contrast-induced acute kidney injury. A prospective study was conducted to evaluate the relationship between oxidative stress caused by contrast agent administration and long-term renal function. METHODS AND RESULTS: Thirty-six consecutive patients who underwent coronary angiography were enrolled. Urinary F2-isoprostane, a marker of oxidative stress, was measured at baseline and 24h after angiography, and serum creatinine was measured at baseline, 24h and 1 year after the procedure. The change in estimated glomerular filtration rate (eGFR) at 1 year after angiography correlated significantly with the change in eGFR at 24h after angiography (r=0.729, P<0.001). We also found a significant correlation between the increase in urinary F2-isoprostane at 24h and the decrease in eGFR at 1 year (r=0.439, P=0.022). In multivariate analysis, the decrease in eGFR at 1 year after coronary angiography correlated with the increase in F2-isoprostane at 24h after angiography as well as the decrease in eGFR at 24h after angiography (P=0.039 and P<0.001, respectively). CONCLUSIONS: Contrast-induced nephrotoxicity might be transient; however, an early decrease in eGFR and increase in oxidative stress are associated with chronic renal insufficiency. Careful long-term follow-up and adequate medical intervention are necessary for these patients.

Hybrid therapy of radiofrequency catheter ablation and percutaneous transvenous mitral commissurotomy in patients with atrial fibrillation and mitral stenosis.

BACKGROUND: The rhythm control of atrial fibrillation (AF) associated with mitral stenosis (MS) is often difficult using antiarrhythmic drugs (AADs), even after a percutaneous transvenous mitral commissurotomy (PTMC). Few studies have examined the efficacy and safety of simultaneously performing radiofrequency catheter ablation (RFCA) and a PTMC in patients with MS and AF. METHODS: Twenty consecutive patients with drug-resistant AF and rheumatic MS underwent RFCA combined with a PTMC (n = 10; persistent AF-8, long-lasting [>1 year] persistent AF-2; RFCA group) or transthoracic direct cardioversion (DC) following a PTMC (n = 10; persistent AF-7, long-lasting persistent AF-3; DC group). In all patients, the mitral valve morphology was amenable to a PTMC, and more than 2 AADs had been ineffective in maintaining sinus rhythm (SR). In the RFCA group, a segmental pulmonary vein isolation (PVI) was performed in the initial 5 patients, and an extensive PVI was performed in the remaining 5. RESULTS: During a mean follow-up period of 4.0 +/- 2.7 years, 8 patients (80%) in the RFCA group were maintained in SR, as compared to 1 (10%) in the DC group (hazard ratio, 0.16; 95% confidence interval, 0.03 to 0.75; P = 0.008 by the log-rank test). The prevalence of the concomitant use of class I and/or class III AADs was comparable between the 2 groups (P = 0.70). No complications occurred during the procedure or follow-up period in either group. CONCLUSIONS: The hybrid therapy using RFCA and a PTMC was safe and feasible, and significantly improved the AF free survival rate compared to DC following a PTMC.

Combined assessment of carotid vulnerable plaque, renal insufficiency, eosinophilia, and hs-CRP for predicting risky aortic plaque of cholesterol crystal embolism.

BACKGROUND: Cholesterol crystal embolism (CCE) is a serious complication of vascular procedures and based on the clinical features of patients with CCE, the aim of the present study was to establish screening criteria for aortic complex plaques (ACP) at high-risk of CCE. METHODS AND RESULTS: For the first study, 10 patients diagnosed as having CCE were recruited. They had prior multiple atherosclerotic disease and a high proportion of complex plaques of the carotid artery and aorta. Elevated levels of high-sensitivity C-reactive protein (hs-CRP), eosinophilia, and renal insufficiency were already recognized before CCE diagnosis. The second study prospectively enrolled 102 patients. ACP is related to CCE and predictive criteria of ACP were established. Among 19 patients with ACP, 2 presented with CCE. Multivariate analysis revealed carotid complex plaque, eosinophilia and multiple atherosclerotic risk factors as independent predictors of ACP. The criteria including these factors (multiple atherosclerotic risk factors, carotid complex plaque, hs-CRP > or =0.2 mg/dl, eGFR < or =60 ml . min(-1) . 1.73 m(-2), eosinophil count > or =400 /microl) could detect patients with ACP with 95% sensitivity, 94% specificity, and 79% positive predictive value. CONCLUSIONS: Multiple atherosclerotic risk factors, elevated hs-CRP, renal insufficiency, eosinophilia before CCE diagnosis and carotid complex plaques were features of patients with CCE. Diagnostic criteria including these characteristics effectively predict ACP patients at high-risk of CCE. (Circ J 2010; 74: 51 - 58).

Subtraction magnetocardiogram for detecting coronary heart disease.

BACKGROUND: A large-scale magnetocardiogram (MCG) database was produced, and standard MCG waveforms of healthy patients were calculated by using this database. It was clarified that the standard MCG waveforms are formed with the same shape and current distribution in healthy patients. A new subtraction method for detecting abnormal ST-T waveforms in coronary heart disease (CHD) patients by using the standard MCG waveform was developed. METHODS: We used MCGs of 56 CHD patients (63 ± 3 years old) and 101 age-matched normal control patients (65 ± 5 years old). To construct a subtracted ST-T waveform, we used standard MCG waveforms produced from 464 normal MCGs (male: 268, female: 196). The standard MCG waveforms were subtracted from each subject's measured MCGs, which were shortened or lengthened and normalized to adjust to the data length and magnitude of the standard waveform. We evaluated the maximum amplitude and maximum current-arrow magnitude of the subtracted ST-T waveform. RESULTS: The maximum magnetic field, maximum magnitude of current arrows, and maximum magnitude of total current vector increased according to the number of coronary artery lesions. The sensitivity and specificity of detecting CHD and normal control patients were 74.6% and 84.1%, respectively. CONCLUSIONS: The subtraction MCG method can be used to detect CHD with high accuracy, namely, sensitivity of 74.6% and specificity of 84.1% (in the case of maximum amplitude of total current vector). Furthermore, the subtraction MCG magnitude and its current distribution can reflect the expanse of the ischemic lesion area and the progress from ischemia to myocardial infarction.

Repolarization spatial-time current abnormalities in patients with coronary heart disease.

BACKGROUND: Magnetocardiography (MCG) is a new technique for visualizing a current distribution in the myocardium. In recent years, current distribution parameters (CDPs) have been developed based on the distribution. The CDPs reflect spatial-time current abnormalities in patients with coronary heart disease (CHD). However, the criteria and scoring method of the abnormalities using CDPs are still controversial. METHOD: We measured MCG signals for 101 normal controls and 56 CHD patients (single-, double-, and triple-vessel diseases) using a MCG system. The CDPs (maximum current vector [MCV], total current vector [TCV], current integral map, and current rotation) during ventricular repolarization were analyzed. To evaluate the CDPs that are effective in distinguishing between normal controls and CHD patients, the areas under the receiver operating characteristic curve (A(z)) are calculated. Furthermore, the total scores ("0" to "4") of four CDPs with high A(z) values are also calculated. RESULTS: MCV and TCV angles at the T-wave peak had the highest A(z) value. Furthermore, TCV angular differences between the ST-T segment also had high A(z) values. Using the four CDPs, the averaged total score for patients with triple-vessel disease was the highest ("2.67") compared to the other groups (normal controls: 0.53). Furthermore, based on the assumption that subjects with a total score over "1" were suspected of having CHD, sensitivity and specificity were 85.7% and 74.3%, respectively. CONCLUSION: We concluded that the score and criteria using MCV and TCV during repolarization in CHD patients can reflect lesion areas and time changes of electrical activation dispersion due to ischemia.

Electrical storm 11 days after acute myocardial infarction: a case report.

BACKGROUND: The definition of electrical storm is still debated. For example, an electrical storm is defined as a clustering of three or more separate episodes of ventricular tachycardia/ventricular fibrillation within 24 hours or one or more episodes occurring within 5 minutes of termination of the previous episode of ventricular tachycardia/ventricular fibrillation. When it is refractory to medications, prompt assessments by coronary angiography, sedation, and overdrive pacing should be performed. An electrical storm may occur anytime, including at night or after the patient leaves an intensive care unit. CASE PRESENTATION: A 70-year-old Japanese man with type 2 diabetes mellitus was diagnosed as having ST-elevation myocardial infarction. His clinical course after an urgent percutaneous coronary intervention was uneventful, but he developed electrical storm that was refractory to antiarrhythmic medications on day 11 of hospitalization. We used sedative medications and performed ventricular overdrive pacing and transferred him to a university hospital for further treatment, which included electrical ablation and cardioverter-defibrillator implantation. CONCLUSION: An electrical storm is a relatively rare and fatal complication of acute myocardial infarction. It is important that the treatment choices for this condition are known by non-cardiologist physicians who might encounter this rare condition.

Clinical significance of reversed R wave progression in right precordial leads.

Objective: Poor R wave progression in right precordial leads is a relatively common electrocardiogram (ECG) finding that indicates possible prior anterior myocardial infarction (MI); however, it is observed frequently in apparently normal individuals. In contrast, reversed R wave progression (RRWP) may be more specific to cardiac disorders; however, the significance of RRWP in daily clinical practice is unknown. The purpose of this study was to clarify the significance of RRWP in clinical practice. Materials and Methods: We analyzed consecutive ECGs obtained from 12,139 patients aged ≥20 years at Mito Kyodo General Hospital in Ibaraki between November 2009 and August 2012. Our setting is a secondary emergency hospital in the community, and the study participants were inpatients or patients who visited the general or emergency outpatient departments. RRWP was defined as RV2 < RV1, RV3 < RV2, or RV4 < RV3. Regarding ECGs considered to show RRWP, we confirmed the presence or absence of an abnormal Q wave and whether ultrasound cardiography, contrast-enhanced computed tomography, coronary angiography, and/or left ventriculography were performed to obtain detailed information. Results: RRWP was identified in 34 patients (0.3%). Among these patients, 29 (85%) had undergone cardiac evaluation. The final diagnosis was previous anterior MI in 12 patients (41%) and ischemic heart disease (IHD) without MI in 5 patients (17%). All 17 patients with IHD had left anterior descending (LAD) artery stenosis. The other patients were diagnosed with dilated (two patients, 7%) and hypertrophic (one patient, 3%) cardiomyopathy, left ventricular hypertrophy (one patient, 3%), or pulmonary embolism (one patient, 3%). Only seven patients (24%) were normal. Conclusions: RRWP is rare in daily clinical practice; however, it is a highly indicative marker for cardiac disease, particularly IHD with LAD artery stenosis.

Association of sleep-disordered breathing and ventricular arrhythmias in patients without heart failure.

The prevalence and characteristics of sleep-disordered breathing (SDB) in patients with ventricular arrhythmias, such as premature ventricular complexes and ventricular tachycardia, are unknown. Therefore, this study was conducted to evaluate the prevalence of SDB in patients with severe ventricular arrhythmias and normal left ventricular (LV) function. Thirty-five patients (63% men, mean age 57.4 +/- 13.8 years) underwent a sleep study. All patients had ventricular tachycardia or frequent premature ventricular complexes (>or=300/hour) and had been referred to the cardiology department for medication, catheter ablation therapy, or the implantation of a cardioverter-defibrillator. Patients with heart failure with LV ejection fractions <50% were excluded; in the remaining patients, the mean LV ejection fraction was 63.9 +/- 8.0%. Twenty-one patients (60%) had SDB with apnea-hypopnea indexes >or=5/hour, and the average apnea-hypopnea index was 22.7 +/- 17.9/hour. Twelve patients (34%) had moderate to severe SDB, with an average apnea-hypopnea index of 33.6 +/- 16.6/hour. Central dominant sleep apnea was evident in 3 patients with SDB. The average age and body mass index were significantly higher in patients with SDB than in those without SDB (age 62.0 +/- 12.8 vs 50.6 +/- 12.7 years, body mass index 26.3 +/- 4.0 vs 21.2 +/- 2.0 kg/m2). In conclusion, this study found a high prevalence of SDB in patients with ventricular arrhythmias and normal LV function.

Stratification of impaired relaxation filling patterns by passive leg lifting in patients with preserved left ventricular ejection fraction.

METHODS: We evaluated diastolic functional reserve in 108 patients with normal left ventricular ejection fraction (LVEF)> or =50% but abnormal relaxation (ratio of transmitral peak velocity of early and late diastolic flow (E/A)<1) using passive leg lifting. We calculated the pulmonary venous systolic to diastolic flow ratio (S/D) as a marker of left atrial reservoir function, and the time difference between the duration of pulmonary venous retrograde flow (PVAd) and the duration of the mitral A wave (PVAd-Ad) as a marker of left ventricular end-diastolic pressure (LVEDP). RESULTS: During leg lifting, the E/A was > or =1 in 39 patients (the inverted group); the remaining 69 patients comprised the stable group. Comparing the inverted group with the stable group at baseline, S/D was smaller (1.5+/-0.4 vs. 1.8+/-0.5, P=0.002) and PVAd-Ad greater (11+/-23 ms vs. -23+/-28 ms, P<0.001). Multiple logistic regression analysis revealed that PVAd-Ad and S/D predicted E/A inversion with leg lifting after adjustment for age, LV wall thickness, LV dimension, LVEF, deceleration time of E, and E/E'. CONCLUSION: In patients with preserved LVEF but early diastolic dysfunction, passive leg lifting may identify patients having a less compliant left ventricle and impaired left atrial reservoir function.

Standard template of adult magnetocardiogram.

BACKGROUND: We need to know the magnetocardiogram (MCG) features regarding waveform and two-dimensional current distribution in normal subjects in order to classify the abnormal waveform in patients with heart disease. However, a standard MCG waveform has not been produced yet, therefore, we have first made the standard template MCG waveform. METHODS AND RESULTS: We used data from 464 normal control subjects' 64-channel MCGs (268 males, 196 females) to produce a template MCG waveform. The measured data were averaged after shortening or lengthening and normalization. The time interval and amplitude of the averaged data were adjusted to mean values obtained from a database. Furthermore, the current distributions (current arrow maps [CAMs]) were calculated from the produced templates to determine the current distribution pattern. The produced template of the QRS complex had a typical shape in six regions that we defined (M1, M2, M3, M4, M5, and M6). In the P wave, the main current arrow in CAMs pointing in a lower-left direction appeared in M1. In the QRS complex, the typical wave appeared in each region, and there were two main current arrows in M2 and M5. There were negative T waves in M1, M4, and M5, and positive T waves in M3 and M6, and the main current arrow pointing in a lower-left direction appeared in M2. CONCLUSION: Template MCG waveforms were produced. These morphologic features were classified into six regions, and the current distribution was characterized in each region. Consequently, the templates and classifications enable understanding MCG features and writing clinical reports.

Macrophage metalloelastase accelerates the progression of atherosclerosis in transgenic rabbits.

BACKGROUND: Macrophage metalloelastase (matrix metalloproteinase [MMP]-12) is upregulated in atherosclerotic lesions and aneurysm; thus, increased MMP-12 activity may play an important role in the pathogenesis of atherosclerosis. However, the pathological roles of MMP-12 in the initiation and progression of atherosclerosis have not been defined. METHODS AND RESULTS: We compared the susceptibility of MMP-12 transgenic (Tg) rabbits to cholesterol-rich diet-induced atherosclerosis with that of non-Tg littermate rabbits. The rabbits were maintained at either relatively lower levels of hypercholesterolemia for shorter periods or higher levels of hypercholesterolemia for longer periods through a diet containing different amounts of cholesterol. We found no significant difference in the aortic atherosclerotic lesion size or quality between Tg and non-Tg rabbits at lower hypercholesterolemia. At higher hypercholesterolemia for longer periods, however, Tg rabbits developed more extensive atherosclerosis in the aortas and coronary arteries than did non-Tg rabbits. Histological examinations revealed that atherosclerotic lesions of Tg rabbits contained prominent macrophage infiltration associated with marked disruption of the elastic lamina in the tunica media with occasional formation of aneurysm-like lesions. Furthermore, increased expression of MMP-12 derived from macrophages was associated with elevated expression of MMP-3, suggesting that MMP-12 may play a pivotal role in the cascade activation of other MMPs, thereby exacerbating extracellular matrix degradation during the progression of atherosclerosis. CONCLUSIONS: Overexpression of MMP-12 causes accelerated atherosclerosis in Tg rabbits. These results suggest that macrophage-derived MMP-12 participates in the progression of atherosclerosis.

Driving restrictions in patients with implantable cardioverter defibrillators and pacemakers.

Implantable cardioverter-defibrillators (ICDs) improve the survival in patients at risk of sudden cardiac death. However, these patients have an ongoing risk of sudden incapacitation that may cause harm to individuals and others when driving. Considerable disagreement exists about whether and when these patients should be allowed to resume driving after ICD therapies. This information is critical for the management decisions to avoid future potentially lethal incidents and unnecessary restrictions for ICD patients. The cardiac implantable device committee of the Japanese Heart Rhythm Society reassessed the risk of driving for ICD patients based on the literature and domestic data. We reviewed the driving restrictions of ICD patients in various regions and here present updated Japanese driving restrictions.

Inappropriate implantable cardioverter defibrillator shocks-incidence, effect, and implications for driver licensing.

PURPOSE: Patients with implantable cardioverter defibrillators (ICDs) have an ongoing risk of sudden incapacitation that may cause traffic accidents. However, there are limited data on the magnitude of this risk after inappropriate ICD therapies. We studied the rate of syncope associated with inappropriate ICD therapies to provide a scientific basis for formulating driving restrictions. METHODS: Inappropriate ICD therapy event data between 1997 and 2014 from 50 Japanese institutions were analyzed retrospectively. The annual risk of harm (RH) to others posed by a driver with an ICD was calculated for private driving habits. We used a commonly employed annual RH to others of 5 in 100,000 (0.005%) as an acceptable risk threshold. RESULTS: Of the 4089 patients, 772 inappropriate ICD therapies occurred in 417 patients (age 61 ± 15 years, 74% male, and 65% secondary prevention). Patients experiencing inappropriate therapies had a mean number of 1.8 ± 1.5 therapy episodes during a median follow-up period of 3.9 years. No significant differences were found in the age, sex, or number of inappropriate therapies between patients receiving ICDs for primary or secondary prevention. Only three patients (0.7%) experienced syncope associated with inappropriate therapies. The maximum annual RH to others after the first therapy in primary and secondary prevention patients was calculated to be 0.11 in 100,000 and 0.12 in 100,000, respectively. CONCLUSIONS: We found that the annual RH from driving was far below the commonly cited acceptable risk threshold. Our data provide useful information to supplement current recommendations on driving restrictions in ICD patients with private driving habits.

[Magnetocardiographic diagnosis for myocardial ischemia and arrhythmias].

Magnetocardiography (MCG) is a non-invasive and non-contact mapping technique to analyze cardiac electromagnetic activities. The SQUID (superconducting quantum interference device) system has made it possible to detect very weak cardiac magnetic signals noninvasively. In electrocardiography (ECG), the conductivity of electric current varies according to body composition, while in MCG, conductivity of magnetic field is constant regardless of body composition. Moreover, as the magnetic field detected in MCG originates not from the cardiac 'volume current' as in ECG, but from the cardiac 'primary current', the cardiac electromagnetic information of the MCG is minimally distorted. Furthermore, ECG is a record of a potential difference, so it gives only a relative value, while magnetic field strength is an absolute value. Therefore, MCG is expected to be more sensitive to minute electromagnetic abnormalities of heart disease than ECG. In this article, we discuss the usefulness of MCG in diagnosing ischemic heart diseases and arrhythmias.

A slight increase of fasting plasma glucose after 2 years was associated with electrocardiogram changes suggestive of coronary heart disease in normal subjects.

BACKGROUND: Much attention has been focused on the primary prevention of ischemic heart disease (IHD), but the prevalence and prognostic indicators of IHD remain unclear in healthy Japanese subjects. HYPOTHESIS: The purpose of this study was to determine the predictors for the transition of IHD in healthy adult subjects using data from annual medical examinations. METHODS: We analyzed clinical data on 2710 healthy subjects (1836 men and 874 women aged 26-76 years in 2000) who underwent medical examinations in both 2000 and 2002. Ischemic changes in the electrocardiogram (ECG) suggestive of IHD were defined as the existence of abnormal Q-wave and/or ST-T abnormalities without left ventricular high voltage. We assigned the subjects to two groups: the ischemic heart group (Group I), including subjects with normal ECG findings in 2000, followed by suspicious ischemic changes in the ECGs in 2002; and the normal group (Group N), including subjects with normal ECGs in both 2000 and 2002. RESULTS: Fifty-nine subjects (2%, 20 women) were assigned to Group I and 2,538 subjects (96%, 810 women) were assigned to Group N. There were significant differences between the two groups in baseline age (Group I vs. Group N: 53 vs. 47 years, p < 0.001), body mass index (24 vs. 23 kg/m2, p = 0.036), systolic blood pressure (132 vs. 122 mmHg, p < 0.001), diastolic blood pressure (83 vs. 76 mmHg, p < 0.001), and fasting plasma glucose (109 vs. 96 mg/dl, p < 0.001). Fasting plasma glucose significantly increased in Group I (from 109 to 113 mg/dl, p = 0.034) during the study. Multivariate analysis showed significant differences in age (p < 0.001) and fasting plasma glucose (p = 0.0053). CONCLUSION: Advanced age and relatively elevated fasting plasma glucose appeared to be significant predictors of ECG findings suggestive of IHD in normal subjects in the short period of 2 years.