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.

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.

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).

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).

Proteinuria and Reduced Estimated Glomerular Filtration Rate Are Independent Risk Factors for Contrast-Induced Nephropathy After Cardiac Catheterization.

BACKGROUND: The aim of this study was to investigate the incidence of contrast-induced nephropathy (CIN) according to renal function in patients with or without proteinuria after cardiac catheterization in Japan. METHODS AND RESULTS: We conducted a multicenter prospective observational study involving 27 hospitals from all over Japan, which enrolled 906 patients with cardiac catheterization. CIN was defined as increase in serum creatinine ≥0.5 mg/dl or ≥25% from baseline between 48 and 72 h after exposure to contrast. The incidence of CIN in patients with estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m2was significantly higher than that in patients with eGFR ≥60 ml/min/1.73 m2. In patients without proteinuria, the incidence of CIN did not increase as eGFR decreased, but such a trend was observed in patients with proteinuria. Proteinuria was highly significantly associated with CIN in patients with eGFR 30-44 ml/min/1.73 m2(OR, 12.1; 95% CI: 2.81-82.8; P=0.0006) and eGFR <30 ml/min/1.73 m2(OR, 17.4; 95% CI: 3.32-321; P=0.0001). On multivariate logistic regression analysis, proteinuria (OR, 4.09; 95% CI: 1.66-10.0), eGFR (OR, 1.02; 95% CI: 1.00-1.04), contrast volume/eGFR (OR, 1.31; 95% CI: 1.04-1.65), and Ca antagonist use (OR, 3.79; 95% CI: 1.52-10.8) were significant predictors of CIN. CONCLUSIONS: Proteinuria and reduced eGFR are independent risk factors for CIN after cardiac catheterization.

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.

Cardiac magnetic resonance performs better in the detection of functionally significant coronary artery stenosis compared to single-photon emission computed tomography and dobutamine stress echocardiography.

BACKGROUND: Fractional flow reserve (FFR) measured on catheterization is now widely used for the diagnosis of functional myocardial ischemia in patients with coronary artery disease (CAD). FFR, however, is invasive and carries potential procedural complications. Therefore, the aim of this study was to compare the diagnostic capability in functionally significant stenosis identified on FFR, between cardiac magnetic resonance myocardial perfusion imaging (CMR-MPI), single-photon emission computed tomography MPI (SPECT-MPI), and dobutamine stress echocardiography (DSE) in patients with CAD. METHODS AND RESULTS: A total of 25 patients who had at least 1 angiographic stenosis ≥50% on coronary angiography was studied. CMR-MPI, SPECT-MPI and DSE were done before FFR measurement. FFR was measured in all 3 major epicardial coronary arteries. Out of 71 vascular territories excluding 4 territories due to inadequate imaging, 29 (41%) had FFR <0.80. The sensitivity of CMR-MPI was significantly higher than that of SPECT-MPI and DSE (P=0.02 and P=0.001, respectively). The area under the receiver operating characteristic curve (AUC) for CMR-MPI (AUC, 0.92) was significantly greater than for SPECT-MPI (AUC, 0.73; P=0.006) and DSE (AUC, 0.69; P<0.001). CONCLUSIONS: CMR-MPI performed well in the detection of functionally significant stenosis defined according to FFR, and had the highest diagnostic sensitivity among the 3 modalities tested in patients with CAD.

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.

Acute hemodynamic effects of adaptive servo-ventilation in patients with heart failure.

BACKGROUND: Adaptive servo-ventilation (ASV) improves cardiac function in patients with heart failure (HF). We compared the hemodynamics of control and HF patients, and identified the predictors for acute effects of ASV in HF. METHODS AND RESULTS: We performed baseline echocardiographic measurements and hemodynamic measurements at baseline and after 15 min of ASV during cardiac catheterization in 11 control and 34 HF patients. Heart rate and blood pressure did not change after ASV in either the control or HF group. Stroke volume index (SVI) decreased from 49.3±7.6 to 41.3±7.6 ml/m2 in controls (P<0.0001) but did not change in the HF patients (from 34.8±11.5 to 32.8±8.9 ml/m2, P=0.148). In the univariate analysis, pulmonary capillary wedge pressure (PCWP), mitral regurgitation (MR)/left atrial (LA) area, E/A, E/e', and the sphericity index defined by the ratio between the short-axis and long-axis dimensions of the left ventricle significantly correlated with % change of SVI from baseline during ASV. PCWP and MR/LA area were independent predictors by multivariate analysis. Moreover, responders (15 of 34 HF patients; 44%) categorized by an increase in SVI showed significantly higher PCWP, MR, and sphericity index. CONCLUSIONS: Left ventricular structure and MR, as well as PCWP, could predict acute favorable effects on hemodynamics by ASV therapy in HF patients.

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.

Quantification of regional myocardial blood flow estimation with three-dimensional dynamic rubidium-82 PET and modified spillover correction model.

PURPOSE: Myocardial blood flow (MBF) estimation with (82)Rubidium ((82)Rb) positron emission tomography (PET) is technically difficult because of the high spillover between regions of interest, especially due to the long positron range. We sought to develop a new algorithm to reduce the spillover in image-derived blood activity curves, using non-uniform weighted least-squares fitting. METHODS: Fourteen volunteers underwent imaging with both 3-dimensional (3D) (82)Rb and (15)O-water PET at rest and during pharmacological stress. Whole left ventricular (LV) (82)Rb MBF was estimated using a one-compartment model, including a myocardium-to-blood spillover correction to estimate the corresponding blood input function Ca(t)(whole). Regional K1 values were calculated using this uniform global input function, which simplifies equations and enables robust estimation of MBF. To assess the robustness of the modified algorithm, inter-operator repeatability of 3D (82)Rb MBF was compared with a previously established method. RESULTS: Whole LV correlation of (82)Rb MBF with (15)O-water MBF was better (P < .01) with the modified spillover correction method (r = 0.92 vs r = 0.60). The modified method also yielded significantly improved inter-operator repeatability of regional MBF quantification (r = 0.89) versus the established method (r = 0.82) (P < .01). CONCLUSION: A uniform global input function can suppress LV spillover into the image-derived blood input function, resulting in improved precision for MBF quantification with 3D (82)Rb PET.

Sleep-disordered breathing is an independent risk factor of aborted sudden cardiac arrest in patients with coronary artery spasm.

BACKGROUND: Sleep-disordered breathing (SDB) is often associated with sudden cardiac arrest (SCA) during sleep. Coronary artery spasm (CS) also occurs during sleep and is rarely associated with SCA, but the role of SDB in the risk of SCA is unknown in CS patients. This study evaluated the breathing patterns during sleep in CS patients with a prior history of aborted SCA. METHODS AND RESULTS: This study enrolled 24 patients (age 61.6 ± 11.0 years, male/female 19/5) with CS proven by an acetylcholine provocation test. They were divided into 2 groups: prior history of aborted SCA due to fatal arrhythmia (SCA group; n=9) and no such history (no-SCA group; n=15). Patients underwent overnight polysomnography with ambulatory electrocardiography. The overall prevalence of SDB (apnea hypopnea index ≥15) was 45.8% in this cohort. SDB was more frequent in the SCA group than in the no-SCA group (88.9% vs. 20.0% P=0.001) and identified as a pivotal risk factor of aborted SCA (odds ratio: 38.9, 95% CI: 2.80-1,498.2, P=0.01). Very-low-frequency was significantly correlated with the apnea hypopnea index in patients with SCA (P=0.01, r=0.78) during sleep. CONCLUSIONS: SDB is a significant risk factor for SCA in CS patients and autonomic instability during sleep might be involved in this association.

Incremental diagnostic value of regional myocardial blood flow quantification over relative perfusion imaging with generator-produced rubidium-82 PET.

BACKGROUND: Myocardial blood flow (MBF) can be measured with positron emission tomography (PET) and its quantification should provide diagnostic information beyond that obtained through standard visual analysis. However, this possibility has not been fully studied with PET and generator-produced rubidium-82 (8²Rb). We evaluated regional MBF in segments with and without ischemia using 8²Rb PET in patients with coronary artery disease (CAD). METHODS AND RESULTS: Rest and stress 8²Rb PET and coronary angiography were performed for 12 patients with CAD. Based on angiography and relative 8²Rb perfusion images, segments were classified into 4 groups (Group A: myocardial ischemia with >70% diameter stenosis; Group B: no ischemia with stenosis; Group C: no ischemia without stenosis; Group D: ischemia without stenosis). Rest MBF was similar among the 4 groups. Groups A and B showed reduced hyperemic MBF compared with Group C (P < 0.05 vs. Group C) [Group A (n=16) 1.28 ± 0.58 ml·min⁻¹·g⁻¹; Group B (n=11) 1.72 ± 0.64 ml·min⁻¹·g⁻¹; Group C (n=9) 2.60 ± 1.09 ml·min⁻¹·g⁻¹; Group D (n=2) 2.33 ml·min⁻¹·g⁻¹]. Coronary flow reserves were inversely correlated with percent diameter stenosis (r=0.76, P < 0.0001). CONCLUSIONS: Segments with ischemia and coronary stenosis had reduced hyperemic MBF. Segments with coronary stenosis without ischemia also had reduced hyperemic MBF compared with non-stenotic segments. MBF quantification using 8²Rb PET may provide additional diagnostic information.

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.