Categorization of disaster-related deaths in Minamisoma city after the Fukushima nuclear disaster using clustering analysis.

The medical situation during disasters often differs from that at usual times. Disasters can lead to significant mortality that can be difficult to monitor. The types of disaster-related deaths are largely unknown. In this study, we conducted a survey to categorize the disaster-related deaths caused by a radiation disaster. A total of 520 people living in Minamisoma City, Fukushima Prefecture, at the time of the Fukushima Daiichi Nuclear Power Plant accident, who were certified to have died due to disaster-related causes were surveyed. We divided the participants into those who were at home at the time of the earthquake and those who were in hospitals or facilities when the disaster struck and conducted a hierarchical cluster analysis of the two groups. Disaster-related deaths could be divided into seven groups for those who were at home at the time of the disaster and five groups for those who were in hospitals or facilities at the time of the disaster. Each group showed different characteristics, such as "the group with disabilities," "the group receiving care," and "the group with depression," and it became evident that not only uniform post-disaster support, but support tailored to the characteristics of each group is necessary.

Disaster-related deaths with alcohol-related diseases after the Fukushima Daiichi nuclear power plant accident: case series.

Introduction: The health of patients with mental disorders, such as alcohol-related diseases, often deteriorates after disasters. However, the causes of death among those with alcohol-related diseases during and after radiation disasters remain unclear. Methods: To minimize and prevent alcohol-related deaths in future radiation disasters, we analyzed and summarized six cases of alcohol-related deaths in Minamisoma City, a municipality near the Fukushima Daiichi nuclear power plant. Results: Patients were generally treated for alcohol-related diseases. In one case, the patient was forced to evacuate because of hospital closure, and his condition worsened as he was repeatedly admitted and discharged from the hospital. In another case, the patient's depression worsened after he returned home because of increased medication and drinking for insomnia and loss of appetite. Discussion: The overall findings revealed that, in many cases, evacuation caused diseases to deteriorate in the chronic phase, which eventually resulted in death sometime after the disaster. To mitigate loss of life, alcohol-related diseases must be addressed during the chronic phases of future large-scale disasters, including nuclear disasters.

Early therapeutic effects of adaptive servo-ventilation on cardiac sympathetic nervous function in patients with heart failure evaluated using a combination of 11C-HED PET and 123I-MIBG SPECT.

RATIONALE: Adaptive servo-ventilation (ASV), a novel respiratory support therapy for sleep disorders, may improve cardiac function in heart failure (HF). However, the reasons that ASV improves cardiac function have not been fully studied especially in sympathetic nervous function (SNF). The purpose of the present study was to investigate the effects of ASV therapy on cardiac SNF in patients with HF. METHODS: We evaluated ASV therapeutic effects before and 6 months after ASV therapy in 9 HF patients [57.3 ± 17.3 years old, left ventricular ejection fraction (LVEF) 36.1 ± 16.7%]. We performed echocardiography, polysomnography, biomarkers, 11C-hydroxyephedrine (HED) PET as a presynaptic function marker and planar 123I-metaiodobenzylguanidine (MIBG) to evaluate washout rate. RESULTS: ASV therapy reduced apnea-hypopnea index (AHI) and improved plasma brain natriuretic peptide (BNP) concentration. In 123I-MIBG imaging, the early heart/mediastinum (H/M) ratio increased after ASV therapy (2.19 ± 0.58 to 2.40 ± 0.67; P = 0.045). Washout rate did not change (23.8 ± 7.3% to 23.8 ± 8.8%; P = 0.122). Global 11C-HED retention index (RI) improved from 0.068 ± 0.033/s to 0.075 ± 0.034/s (P = 0.029). CONCLUSIONS: ASV reduced AHI and improved BNP. ASV might initially improve presynaptic cardiac sympathetic nervous function in HF patients after 6 months of treatment.

Amyloid Polyneuropathy and Myocardial Amyloidosis 10 Years after Domino Liver Transplantation from a Patient with a Transthyretin Ser50Arg Mutation.

A 54-year-old man with polycystic liver disease received a domino liver transplantation (DLT) from a patient of hereditary ATTR amyloidosis with the transthyretin Ser50Arg mutation. Ten years after transplantation, he felt a slight numbness in his toes, and cardiac amyloidosis was simultaneously suspected upon a heart function evaluation. Biopsy specimens from the myocardium revealed transthyretin amyloidosis with the Ser50Arg mutation. Oral tafamidis therapy has inhibited the progression of neurological and cardiovascular symptoms this far. We herein report this first case of amyloid polyneuropathy and myocardial amyloidosis after DLT from hereditary ATTR amyloidosis with a transthyretin Ser50Arg mutation and discuss similar cases of other mutations.

Immunohistochemical identification of Propionibacterium acnes in granuloma and inflammatory cells of myocardial tissues obtained from cardiac sarcoidosis patients.

BACKGROUND: Although rare, cardiac sarcoidosis (CS) is potentially fatal. Early diagnosis and intervention are essential, but histopathologic diagnosis is limited. We aimed to detect Propionibacterium acnes, a commonly implicated etiologic agent of sarcoidosis, in myocardial tissues obtained from CS patients. METHODS AND RESULTS: We examined formalin-fixed paraffin-embedded myocardial tissues obtained by surgery or autopsy and endomyocardial biopsy from patients with CS (n = 26; CS-group), myocarditis (n = 15; M-group), or other cardiomyopathies (n = 39; CM-group) using immunohistochemistry (IHC) with a P. acnes-specific monoclonal antibody. We found granulomas in 16 (62%) CS-group samples. Massive (≥14 inflammatory cells) and minimal (<14 inflammatory cells) inflammatory foci, respectively, were detected in 16 (62%) and 11 (42%) of the CS-group samples, 10 (67%) and 10 (67%) of the M-group samples, and 1 (3%) and 18 (46%) of the CM-group samples. P. acnes-positive reactivity in granulomas, massive inflammatory foci, and minimal inflammatory foci were detected in 10 (63%), 10 (63%), and 8 (73%) of the CS-group samples, respectively, and in none of the M-group and CM-group samples. CONCLUSIONS: Frequent identification of P. acnes in sarcoid granulomas of originally aseptic myocardial tissues suggests that this indigenous bacterium causes granuloma in many CS patients. IHC detection of P. acnes in massive or minimal inflammatory foci of myocardial biopsy samples without granulomas may be useful for differentiating sarcoidosis from myocarditis or other cardiomyopathies.

Usefulness of the Continuous-Wave Doppler-Derived Pulmonary Arterial-Right Ventricular Pressure Gradient Just before Atrial Contraction for the Estimation of Pulmonary Arterial Diastolic and Wedge Pressures.

In our new echocardiographic method, pulmonary regurgitant velocity immediately before right atrial (RA) contraction is used to estimate pulmonary artery diastolic pressure (PADP) and mean PA wedge pressure (MPAWP). Our aim here was to compare the usefulness of this new method with that of the conventional method, which uses pulmonary regurgitant velocity at end diastole. We studied 55 consecutive patients who underwent echocardiography and right-sided heart catheterization. The pulmonary regurgitant velocities just before RA contraction and at end diastole were measured to obtain echocardiographic estimates of PADP (EPADPpreA and EPADPED, respectively) by adding the pressure gradients to the echocardiographically estimated RA pressure. Compared with EPADPED, EPADPpreA correlated better with PADP (r = 0.87) and MPAWP (r = 0.80), and direct fixed biases were detected for EPADPED but not for EPADPpreA. The area under the receiver operating characteristic curve distinguishing patients with MPAWP ≥18 mm Hg was greater for EPADPpreA (0.97) than for E/e' (0.94) and E/A (0.83). EPADPpreA is thus useful in estimating PADP and MPAWP in patients with heart disease.

Overestimation by echocardiography of the peak systolic pressure gradient between the right ventricle and right atrium due to tricuspid regurgitation and the usefulness of the early diastolic transpulmonary valve pressure gradient for estimating pulmonary artery pressure.

We investigated the influence of tricuspid regurgitation (TR) severity on the echocardiographic peak systolic transtricuspid pressure gradient (TRPG) and evaluated the usefulness of the peak early diastolic transpulmonary valve pressure gradient (PRPG) for estimating pulmonary artery (PA) pressure. In 55 consecutive right heart-catheterized patients, we measured the peak systolic right ventricular (RV)-right atrial (RA) pressure gradient (RV-RACATH), peak early diastolic PA-RV pressure gradient (PA-RVCATH), and mean PA pressure (MPAPCATH). Using echocardiography, we obtained the TRPG, PRPG, and an estimate of the mean PA pressure (EMPAP) as the sum of PRPG and the estimated RA pressure, and measured the vena contracta width of TR (VCTR). The difference between the TRPG and RV-RACATH was significantly greater in the very severe TR group (VCTR > 11 mm) than in the mild, moderate, and severe TR groups, and significantly greater in the severe TR group (7 < VCTR ≤ 11 mm) than in the mild TR group. The overestimation of the pressure gradient >10 mmHg by TRPG was not seen in the mild or moderate TR groups, but was observed in the severe and very severe TR groups (22 and 83%, respectively). In the ROC analysis, EMPAP could distinguish patients with MPAPCATH ≥ 25 mmHg with the area under the curve of 0.93, 100% sensitivity, and 87% specificity. In conclusion, TRPG frequently overestimated RV-RACATH when VCTR was >11 mm and sometimes did when VCTR was >7 mm, where EMPAP using PRPG was useful for estimating PA pressure.

A new method to estimate pulmonary vascular resistance using diastolic pulmonary artery-right ventricular pressure gradients derived from continuous-wave Doppler velocity measurements of pulmonary regurgitation.

Pulmonary vascular resistance (PVR) is an important hemodynamic parameter in patients with heart failure, especially when the pulmonary arterial pressure is lower due to reduced stroke volume. Several echocardiographic methods to estimate PVR have been proposed, but their applications in patients with organic left-sided heart diseases have been limited. The aim of the present study was to examine the usefulness of our new method to estimate PVR (PVRPR) based on the continuous-wave Doppler velocity measurements of pulmonary regurgitation in these patients. In 43 patients who underwent right heart catheterization, PVRPR was calculated as the difference between the Doppler-derived early- and end-diastolic pulmonary artery (PA)-right ventricular (RV) pressure gradients divided by the cardiac output measured in the left ventricular outflow tract by echocardiography. The PVRPR correlated well with invasive PVR (PVRCATH) (r = 0.81, p < 0.001) without any fixed bias in Bland-Altman analysis. The conventional echocardiographic PVRs showed inadequate correlations with PVRCATH, or a obvious overestimation of PVRCATH. In the receiver operating characteristic analyses to determine the patients with abnormal elevation of PVRCATH (>3 Wood units, WU), the area under the curve was the greatest for PVRPR (0.964) compared to the conventional PVRs (0.649-0.839). PVRPR had 83 % sensitivity and 100 % specificity at the optimal cut-off value of 3.10 WU in identifying patients with PVRCATH >3 WU. Our simple and theoretical PVRPR is useful for the noninvasive estimation of PVR.

Association of contrast-induced nephropathy with risk of adverse clinical outcomes in patients with cardiac catheterization: From the CINC-J study.

BACKGROUND: The association between the incidence of contrast-induced nephropathy (CIN) and subsequent clinical outcomes is unclear in Japan. We evaluated the association between CIN and cardiovascular and renal events after cardiac catheterization. METHODS: The CINC-J multicenter prospective cohort study examined 853 patients undergoing cardiac catheterization from 27 hospitals. CIN was defined as increase in serum creatinine (SCr)≥0.5mg/dL or ≥25% from baseline between 48 and 72h after exposure to contrast. Major adverse cardiovascular and cerebrovascular events (MACCE) included all-cause deaths, non-fatal myocardial infarction, acute decompensated heart failure (ADHF), and stroke. Renal events included newly-required hemodialysis and increase of SCr≥2× from baseline. RESULTS: During follow-up periods (477±214days), CIN, MACCE, and renal events occurred in 44 (5.2%), 71 (8.3%), and 26 (3.0%) patients, respectively. Kaplan-Meier analysis showed that CIN yielded increasing risk for MACCE, ADHF, newly-required hemodialysis, and renal events. In multivariable Cox proportional hazards analysis, age (HR: 1.03; 95% CI, 1.00-1.07; P=0.0425), anemia (HR: 1.94; 95% CI, 1.08-3.61; P=0.0264), and diabetes mellitus (HR: 1.86; 95% CI, 1.10-3.21; P=0.0119) were independent predictors of MACCE, whereas CIN (HR: 7.78; 95% CI, 3.23-17.9; P=0.0005) and SCr (HR: 2.09; 95% CI, 1.56-2.73; P=0.0006) were independent predictors of renal events. Compared to subjects without both anemia and CIN as the reference, those with both were high risk for MACCE (HR: 3.97; 95% CI, 1.25-10.6; P=0.0218). CONCLUSION: CIN was a significant predictor of subsequent renal events after cardiac catheterization. CIN and anemia were associated with increased risk for worse long-term clinical outcome, especially when both were present.

Myocardial Immunocompetent Cells and Macrophage Phenotypes as Histopathological Surrogates for Diagnosis of Cardiac Sarcoidosis in Japanese.

BACKGROUND: The histological diagnosis of cardiac sarcoidosis (CS) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells (DC) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis. METHODS AND RESULTS: The numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls. All patients underwent endomyocardial biopsy, and immunohistochemical staining was performed on all samples. We examined these immunocompetent cells in nongranuloma sections in CS patients diagnosed by the presence of myocardial granulomas (n=26) and in CS patients without myocardial granulomas diagnosed by the Japanese Ministry of Health Welfare 2007 criteria (n=65) or the Heart Rhythm Society 2014 criteria (n=26). In CS patients with and without myocardial granulomas, CD209+ DC and CD68+ macrophages were more frequently observed (P<0.01) and CD163+M2 macrophages were less frequently observed (P<0.01) in nongranuloma sections compared to controls. Furthermore, the combination of decreased CD163+M2/CD68+ macrophage ratio and increased number of CD209+ DC in nongranuloma sections of CS patients demonstrated high specificity (100%, 95% CI 92.7-100) for CS diagnosis with each diagnostic criteria and the presence of myocardial granulomas. CONCLUSIONS: Increased number of DC and decreased M2 among all macrophages in nongranuloma sections of myocardium showed high specificity for CS diagnosis, suggesting DC and macrophage phenotypes as histopathological surrogates for the diagnosis of CS.

Higher Hemoglobin A1c After Discharge Is an Independent Predictor of Adverse Outcomes in Patients With Acute Coronary Syndrome　- Findings From the PACIFIC Registry.

BACKGROUND: Optimal medical therapy (OMT) and the management of coronary risk factors are necessary for secondary prevention of major adverse cardiac and cerebrovascular events (MACCE) in post-acute coronary syndrome (ACS) patients. However, the effect of post-discharge patient adherence has not been investigated in Japanese patients. METHODS AND RESULTS: The Prevention of AtherothrombotiC Incidents Following Ischemic Coronary Attack (PACIFIC) registry was a multicenter, prospective observational study of 3,597 patients with ACS. Death or MACCE occurred in 229 patients between hospitalization and up to 1 year after discharge. Among 2,587 patients, the association between OMT adherence and risk factor control at 1 year and MACCE occurring between 1 and 2 years after discharge was assessed. OMT was defined as the use of antiplatelet agents, angiotensin-converting enzyme inhibitors, ß-blockers, and statins. Risk factor targets were: low-density lipoprotein-cholesterol <100 mg/dl, HbA1c <7.0%, non-smoking status, blood pressure <130/80 mmHg, and 18.5≤body mass index≤24.9 kg/m(2). The incidence of MACCE was 1.8% and associated with female sex (P=0.020), age ≥75 years (P=0.004), HbA1c ≥7.0% (P=0.004), LV ejection fraction <35% (P<0.001), estimated glomerular filtration rate <60 ml/min (P=0.008), and history of cerebral infarction (P=0.003). In multivariate analysis, lower post-discharge HbA1c was strongly associated with a lower risk of MACCE after ACS (P=0.004). CONCLUSIONS: Hyperglycemia after discharge is a crucial target for the prevention of MACCE in post-ACS patients. (Circ J 2016; 80: 1607-1614).

Value of Virtual Touch Quantification Elastography for Assessing Liver Congestion in Patients With Heart Failure.

BACKGROUND: Heart failure (HF) causes organ congestion, which is thought to increase organ stiffness. The virtual touch quantification (VTQ) method can be used to assess liver stiffness in patients with chronic liver diseases. This study aimed to measure liver and kidney stiffness using VTQ and to determine its value for assessing organ congestion in patients with HF. METHODS AND RESULTS: This study included 10 normal subjects and 38 HF patients (age 52.3±16.7 years, left ventricular ejection fraction 27.0±9.4%, plasma B-type natriuretic peptide [BNP] 1,297.3±1,155.1 pg/ml). We investigated the relationships between clinical characteristics and hemodynamics and liver and kidney stiffness, and assessed the effects of medical treatment on these measurements. Liver stiffness was significantly higher in HF patients (1.17±0.13 m/s vs. 2.03±0.91 m/s, P=0.004) compared with normal subjects, but kidney stiffness was similar in both groups. Central venous pressure (CVP) (P=0.021) and BNP (P=0.025) were independent predictive factors for increased liver stiffness in HF patients. Liver stiffness decreased significantly from 2.37±1.09 to 1.27±0.33 m/s (P<0.001) after treatment. Changes in liver stiffness in HF patients significantly correlated with changes in CVP (R=0.636, P=0.014) and cardiac index (R=-0.557, P=0.039) according to univariate analysis, and with changes in CVP in multivariate analysis. CONCLUSIONS: Liver stiffness measured by noninvasive VTQ methods can be used to assess liver congestion and therapeutic effects in patients with HF. (Circ J 2016; 80: 1187-1195).

Left Ventricular Global Strain for Estimating Relaxation and Filling Pressure　- A Multicenter Study.

BACKGROUND: Speckle-tracking echocardiography (STE)-derived parameters may have better correlation with left ventricular (LV) relaxation and filling pressure than tissue Doppler-derived parameters. However, it has not been elucidated which parameter - strain or strain rate - and which direction of myocardial deformation - longitudinal or circumferential - is the most useful marker of LV relaxation and filling pressure. METHODS AND RESULTS: We conducted a prospective multicenter study and compared the correlation of tissue Doppler- and STE-derived parameters with the time constant of LV pressure decay (τ) and LV mean diastolic pressure (MDP) in 77 patients. The correlation of early-diastolic mitral annular velocity (e´) with τ was weak (r=-0.32, P<0.01), and that of peak longitudinal strain (LS) was the strongest (r=-0.45, P<0.001) among the STE-derived parameters. There was a modest correlation between LVMDP and the ratio of early-diastolic inflow velocity (E) to e´ (E/e´) (r=0.50, P<0.001). In contrast, the ratio of E to LS (E/LS) correlated strongly with LVMDP (r=0.70, P<0.001). The correlation of E/LS with LVMDP was significantly better than that for E/e´ (P<0.01). Receiver-operating characteristic analysis showed that E/LS had the largest area under the curve for distinguishing elevated LVMDP (E/LS 0.86, E/e´ 0.74, E/A 0.67). CONCLUSIONS: STE-derived longitudinal parameters correlated well with LV relaxation and filling pressure. In particular, E/LS could be more accurate than E/e´ for estimating LV filling pressure. (Circ J 2016; 80: 1163-1170).

Prediction of contrast-induced nephropathy by the serum creatinine level on the day following cardiac catheterization.

BACKGROUND: The majority of patients who undergo coronary arteriography are discharged from the hospital on the day of the procedure or on the following day. The aim of this study is to investigate whether the change in serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) on the day following cardiac catheterization can predict the development of contrast-induced nephropathy (CIN). METHODS: This is a multicenter prospective observational study, which consists of 860 patients who underwent cardiac catheterization. We measured SCr and eGFR before cardiac catheterization, on the following day, and 48-72h post-procedure. Definition of CIN is changes in SCr ≥0.5mg/dL or ≥25% from baseline 48-72h after contrast exposure. RESULTS: CIN occurred in 40 patients. SCr levels significantly increased from a baseline of 1.55±1.08mg/dL to 1.79±1.26mg/dL on the following day in patients with CIN (p<0.0001), but significantly decreased from a baseline of 1.21±0.65mg/dL to 1.18±0.61mg/dL on the following day in those without CIN (p<0.0001). eGFR significantly decreased from a baseline of 47.3±28.3mL/min/1.73m2 to 40.6±26.7mL/min/1.73m2 on the following day in patients with CIN (p<0.0001), but significantly increased from a baseline of 53.1±22.0mg/dL to 53.6±21.2mg/dL on the following day in those without CIN (p=0.0236). Receiver operating characteristic curve analysis indicated that SCr change ≥0.1mg/dL [area under the curve (AUC)=0.852, sensitivity 72.5%, specificity 86.1%] and eGFR change ≤-1.1mL/min/1.73m2 (AUC=0.789, sensitivity 85.0%, specificity 64.9%) were the best cut-off values for predicting CIN. Multivariate logistic regression showed that a change in SCr ≥0.1mg/dL [odds ratio (OR), 29.3; 95% confidence interval (CI), 10.8-96.2] and change in eGFR ≤-1.1mL/min/1.73m2 (OR, 69.7; 95% CI, 13.3-952) were powerful independent predictors of CIN. CONCLUSIONS: Changes in SCr and eGFR on the day following cardiac catheterization predict the development of CIN.

Adaptive Servo-Ventilation Has More Favorable Acute Effects on Hemodynamics Than Continuous Positive Airway Pressure in Patients With Heart Failure.

Adaptive servo-ventilation (ASV) has been attracting attention as a novel respiratory support therapy for heart failure (HF). However, the acute hemodynamic effects have not been compared between ASV and continuous positive airway pressure (CPAP) in HF patients.We studied 12 consecutive patients with stable chronic HF. Hemodynamic measurement was performed by right heart catheterization before and after CPAP 5 cmH2O, CPAP 10 cmH2O, and ASV for 15 minutes each.Heart rate, blood pressure, pulmonary capillary wedge pressure (PCWP), and stroke volume index (SVI) were not changed by any intervention. Right atrial pressure significantly increased after CPAP 10 cmH2O (3.6 ± 3.3 to 6.7 ± 1.6 mmHg, P = 0.005) and ASV (4.1 ± 2.6 to 6.8 ± 1.5 mmHg, P = 0.026). Cardiac index was significantly decreased by CPAP 10 cmH2O (2.3 ± 0.4 to 1.9 ± 0.3 L/minute/m(2), P = 0.048), but was not changed by ASV (2.3 ± 0.4 to 2.0 ± 0.3 L/ minute/m(2), P = 0.299). There was a significant positive correlation between baseline PCWP and % of baseline SVI by CPAP 10 cmH2O (r = 0.705, P < 0.001) and ASV (r = 0.750, P < 0.001). ASV and CPAP 10 cmH2O had significantly greater slopes of this correlation than CPAP 5 cmH2O, suggesting that patients with higher PCWP had a greater increase in SVI by ASV and CPAP 10 cmH2O. The relationship between baseline PCWP and % of baseline SVI by ASV was shifted upwards compared to CPAP 10 cmH2O. Furthermore, based on the results of a questionnaire, patients accepted CPAP 5 cmH2O and ASV more favorably compared to CPAP 10 cmH2O.ASV had more beneficial effects on acute hemodynamics and acceptance than CPAP in HF patients.