Detrimental Impact of Comorbid Mental Disorders in Chronic Thromboembolic Pulmonary Hypertension　- A Retrospective Observational Study.

Background: The relationship between the prognosis of patients with both chronic thromboembolic pulmonary hypertension (CTEPH) and a mental disorder (MD) remains unclear. Methods and Results: The study group comprised 157 patients with CTEPH who underwent right heart catheterization and were subdivided into 2 groups according to the presence of MDs: MD and non-MD. The patients with MDs were defined as those who had visited a psychiatrist and were under psychotropic drug treatment. The primary outcome was a composite of all-cause death and worsening of PH. The median follow-up period was 1,164 days. The incidence of the primary composite outcome was higher in the MD group than in the non-MD group (24.0% vs. 6.8%), whereas the all-cause mortality rate was comparable between groups (12.0% vs. 6.1%). The mean pulmonary arterial pressure, cardiac index, and pulmonary vascular resistance at baseline were all similar between groups. The Cox proportional hazards model indicated that MD was an independent risk factor for the primary composite outcome (hazard ratio, 2.990; 95% confidence interval, 1.034-8.642). Conclusions: In the present study, concomitant CTEPH and MD was significantly associated with a poor prognosis and such patients should be carefully followed.

Prognostic efficacy of a post-discharge visiting program for patients with heart failure.

We aimed to investigate the impact of post-discharge scheduled hospital visits on readmission due to heart failure (HF). In this retrospective study, a total of 245 patients (N = 101 in the scheduled hospital visit group, N = 144 in the non-scheduled hospital visit group) who were alive with free from readmission due to HF for 90 days after discharge were enrolled. The patients had been hospitalized with acute decompensated HF between August 2018 and July 2019. Scheduled hospital visits were recommended 90 days after the patients had been discharged. After checking their self-care adherence, nurse-led self-care maintenance and monitoring were provided. To determine the effectiveness of the scheduled hospital visits, we conducted landmark analyses divided into two periods: Scheduled visits within 180 days, and after 180 days. The readmission rate due to HF within 180 days was lower in the scheduled visit group. In the landmark analysis, the 1-year incidence rate of readmission was significantly lower in patients with a scheduled hospital visit than in those without, in the period within 180 days (2.0% vs 9.0%, P = 0.029) but not after 180 days. After adjusting for age and estimated glomerular filtration rate as confounders, scheduled hospital visits tended to reduce readmission due to HF (P = 0.060); however, readmission was significantly reduced in the period within 180 days (P = 0.007). In conclusion, scheduled hospital visits at 90 days after discharge may be beneficial in delaying readmission due to HF by reducing risk of readmission during the early post-visit period.

Regional left atrial conduction velocity in the anterior wall is associated with clinical recurrence of atrial fibrillation after catheter ablation: efficacy in combination with the ipsilateral low voltage area.

BACKGROUND: Left atrial (LA) conduction velocity (CV) is an electrical remodeling parameter of atrial fibrillation (AF) substrate. However, the pathophysiological substrate of LA-CV and its impact on outcomes after catheter ablation for AF have not been well evaluated. METHODS: We retrospectively evaluated 119 patients with AF who underwent catheter ablation and electroanatomical mapping during sinus rhythm. To measure regional LA-CV, we took triplet sites (A, B, and C) on the activation map and calculated the magnitude of the matched orthogonal projection vector between vector-AB and vector-AC, indicating two-dimensional CV. The median of the LA-CVs from four triad sites in both the anterior and posterior walls was set as the 'model LA-CV'. We evaluated the impact of the model LA-CV on recurrence after ablation and relationship between the model LA-CV and LA-low voltage area (LVA) of < 0.5 mV. RESULTS: During the 12-month follow-up, 29 patients experienced recurrence. The LA-CV model was significantly correlated with ipsilateral LVA. The lower anterior model LA-CV was significantly associated with recurrence, with the cut-off value of 0.80 m/s having a sensitivity of 72% and specificity of 67%. Multivariable analysis revealed that the anterior model LA-CV (hazard ratio, 0.09; 95% confidence interval, 0.01-0.94; p = 0.043) and anterior LA-LVA (hazard ratio, 1.06; 95% confidence interval, 1.00-1.11; p = 0.033) were independently associated with AF recurrence. The anterior LA-LVA was mildly correlated with the anterior model LA-CV (r = -0.358; p < 0.001), and patients with both lower LA-CV and greater anterior LA-LVA based on each cut-off value had the worst prognosis. However, decreased LA-CV was more likely to be affected by the distribution pattern of the LVA rather than the total size of the LVA. CONCLUSION: Decreased anterior LA-CV was a significant predictor of AF recurrence and was a useful electrical parameter in addition to LA-LVA for estimating AF arrhythmogenicity.

Safe and successful transition from oral selexipag to subcutaneous treprostinil in a patient with idiopathic pulmonary arterial hypertension treated with triple combination therapy.

Some patients with pulmonary arterial hypertension (PAH) might undergo transition to parenteral prostacyclin analogs due to inadequate response to oral combination therapy. However, there is no consensus on how transition from oral selexipag to subcutaneous treprostinil should be performed. Herein, we report a 56-year-old woman diagnosed with idiopathic PAH that was treated with initial combination therapy (10 mg of macitentan, 40 mg of tadalafil, and 3.2 mg of selexipag daily). Mean pulmonary arterial pressure (PAP) improved from 63 to 39 mm Hg. Transition to parenteral prostacyclin analog was required because cardiac index was below 2.5 L/min/m2. The selexipag was tapered off while subcutaneous treprostinil was titrated up to 30 ng/kg/min over 19 days. Hemodynamic parameters were slightly better than those before the transition. The mean PAP improved to 32 mm Hg by further gradual increases of subcutaneous treprostinil up to 60 ng/kg/min. Therefore, the patient having idiopathic PAH with inadequate response to oral triple combination therapy experienced successful transition from selexipag to subcutaneous treprostinil. Hemodynamic parameters were slightly more improved at a dose of 30 ng/kg/min of subcutaneous treprostinil than at a dose of 3200 µg daily of selexipag in the midst of disease progression. Learning objectives: There is limited evidence for transition of pulmonary vasodilators, especially from oral selexipag to subcutaneous treprostinil. Detailed change in hemodynamic parameters before and after transition and the way of performing transition in patients with idiopathic pulmonary arterial hypertension with exacerbations despite treatment with oral triple combination therapy may provide useful information for better management in the clinical setting.

Right ventricular pressure overload related to residual thrombotic burden in patients 1 year after acute pulmonary embolism: From the Nagoya PE study.

INTRODUCTION: Residual pulmonary thrombus is an important factor affecting long-term prognosis after acute pulmonary embolism (PE). In this sub-analysis of the Nagoya PE study, we aimed to evaluate the relationship between residual thrombi detected by our refined computed tomography (CT) imaging protocol and the results of a multifaceted assessment of patients 1 year after acute PE. MATERIALS AND METHODS: The Nagoya PE study was a prospective observational study of patients diagnosed with acute PE. At 1 year, patients were evaluated multifacetedly, including by enhanced CT using our refined protocol. RESULTS AND CONCLUSION: Forty-three patients completed full testing at 1 year. Patients were divided into three groups according to the modified CT obstruction index (mCTOI): no pulmonary thrombus, low mCTOI, and high mCTOI. At baseline, left ventricular end-diastolic dimension and tricuspid regurgitation (TR) pressure gradient differed significantly across the three groups. At 1 year, patients with TR velocity > 2.8 m/s were found only in the high mCTOI group (P = .022). No difference was observed in symptoms, exercise tolerance, and quality of life score. Multivariate regression analysis revealed that TR velocity > 2.8 m/s (P = .001) and change in oxygen saturation during a 6-min walking test (P = .043) at 1 year were significantly related to mCTOI at 1 year. High thrombotic burden might be detected in patients with right ventricular pressure overload at diagnosis of acute PE or after 1 year. These patients should be carefully and multifacetedly assessed for potential chronic thromboembolic pulmonary disease or chronic thromboembolic pulmonary hypertension.

Pulmonary tumor thrombotic microangiopathy with thrombus in pulmonary artery caused by diffuse sclerosing variant of thyroid papillary adenocarcinoma: A case report.

Pulmonary tumor thrombotic microangiopathy (PTTM) is a fatal disease associated with malignant tumors that progresses to pulmonary hypertension. Gastric cancer is the most common cause, followed by breast cancer and lung cancer, whereas PTTM due to thyroid cancer has not been reported. In addition to pulmonary obstruction by tumor embolism, tumor cells stimulate endothelial cells to release angiogenetic factors, which induce remodeling of pulmonary arteries and veins and lead to lymphatic obstruction. There is limited information on the relationship between thrombus and PTTM. We herein report an autopsy case with PTTM which was caused by diffuse sclerosing variant of thyroid papillary adenocarcinoma, in which differential diagnosis included the acute phase of chronic thromboembolic pulmonary hypertension.

Inhaled iloprost induces long-term beneficial hemodynamic changes in patients with pulmonary arterial hypertension receiving combination therapy.

Inhaled iloprost is an established treatment for pulmonary arterial hypertension (PAH). However, the long-term hemodynamic changes that inhaled iloprost induces are unclear. Here, we retrospectively enrolled 18 patients with PAH who received inhaled iloprost as add-on to oral combination therapy from December 2016 to January 2021 at our institute in Japan. We then examined the changes in hemodynamic parameters induced by iloprost in these patients during right heart catheterization (RHC). To examine the long-term effects of iloprost, we repeated the RHC examination at follow-up (median time to follow-up, 8.5 months). During both catheterization procedures, iloprost was administered by using an I-neb AAD system (Philips NV). In a comparison of pre-inhalation values at the first and follow-up RHCs, inhaled iloprost significantly improved mean pulmonary artery pressure (mPAP; 39.9 ± 7.8 to 32.5 ± 7.2 mmHg, p = 0.016) and pulmonary vascular resistance (PVR; 588.5 ± 191.7 to 464.4 ± 188.5 dyn s cm-5, p = 0.047). During the follow-up RHC, in a comparison of the pre-inhalation and best recorded values out to 30 min after the end of iloprost inhalation, iloprost significantly decreased mPAP (32.5 ± 7.2 to 30.0 ± 6.6 mmHg, p = 0.007) and PVR (457.8 ± 181.4 to 386.2 ± 142.8 dyn s cm-5, p = 0.025) and significantly increased cardiac output (4.19 ± 0.91 to 4.64 ± 1.01 L/min, p = 0.035). Iloprost may have not only acute vasodilation effects but also long-term hemodynamic benefits in PAH patients receiving combination therapy.

Usefulness of a refined computed tomography imaging method to assess the prevalence of residual pulmonary thrombi in patients 1 year after acute pulmonary embolism: The Nagoya PE study.

BACKGROUND: Post-pulmonary embolism (PE) syndrome is an important clinical condition that can affect the long-term prognosis after acute PE. OBJECTIVE: We aimed to evaluate the prevalence of residual pulmonary thrombi and the thrombotic burden 1 year after acute PE, by using our refined computed tomography (CT) imaging method. PATIENTS/METHODS: In this prospective study, patients diagnosed with acute PE were recruited and examinations were conducted at 1 month, 6 months, and 1 year. Especially at 1 year, patients were evaluated multifacetedly, including by laboratory tests, quality-of-life, 6-min walking test, and enhanced CT. RESULTS: Fifty-two patients were enrolled. Two patients (3.8%) developed chronic thromboembolic pulmonary hypertension. A total of 43 patients completed evaluation at 1 year, among whom (74%) had residual thrombi, with a median modified CT obstruction index (mCTOI) of 10.7%. In multivariate analysis, residual thrombi at 1 month was the only factor significantly related to residual thrombi at 1 year (odds ratio, 103.4; 95% confidence interval, 4.2-2542.1). The tricuspid regurgitation pressure gradient ≥60 mmHg and left ventricular end-diastolic dimension at diagnosis were significantly related to mCTOI at 1 year (ß = 0.367, P = .003; and ß = -0.435, P = .001, respectively). CONCLUSIONS: Using our improved CT imaging protocol, we found a high prevalence of residual thrombi 1 year after acute PE. Furthermore, right ventricular overload was related to the thrombotic burden. The long-term treatment strategy of acute PE could be modified to include precise CT imaging.

Combined prognostic value of malnutrition using GLIM criteria and renal insufficiency in elderly heart failure.

AIMS: We aimed to investigate the prognostic impact of malnutrition, defined by the Global Leadership Initiative on Malnutrition (GLIM) criteria, stratified by renal function in hospitalized patients with acute decompensated heart failure (HF). METHODS AND RESULTS: In this retrospective study, 314 patients who were hospitalized for acute decompensated HF from August 2019 to October 2020 were enrolled. We evaluated malnutrition using the GLIM criteria during the time of admission. The primary outcome was 90-day all-cause mortality. The median patient age was 82 years, and 90-day mortality was 14.0%. In total, 76 (24.2%) patients were malnourished according to the GLIM criteria. Malnutrition defined by the GLIM criteria [adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.02-1.91, P = 0.036] and renal insufficiency [adjusted HR 2.59, 95% CI 1.07-6.28, P = 0.035 for estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 vs. ≥60 mL/min/1.73 m2 ] were identified as independent predictors of 90-day mortality after adjustment for age, systolic blood pressure, and serum sodium level. In the combined setting of both variables, patients with malnutrition and eGFR < 30 mL/min/1.73 m2 had a markedly higher risk of 90-day mortality compared with those without malnutrition and eGFR ≥ 60 mL/min/1.73 m2 (adjusted HR 3.92, 95% CI 1.10-13.9, P = 0.035). Adding both eGFR and malnutrition, defined by the GLIM criteria, to the baseline model with established risk factors improved both net reclassification and integrated discrimination greater than that of the baseline model (0.606, P < 0.001 and 0.050, P = 0.002, respectively), even when compared with the model with malnutrition by the GLIM alone (0.463, P = 0.002 and 0.034, P < 0.001, respectively). CONCLUSIONS: Nutrition screening using the GLIM criteria stratified by renal function could clearly predict 90-day mortality in hospitalized patients with acute decompensated HF.

Long P-wave duration immediately after pulmonary vein isolation on radiofrequency catheter ablation for atrial fibrillation predicts clinical recurrence: correlation with atrial remodeling in persistent atrial fibrillation.

P-wave morphology reflects atrial remodeling and indicates prognosis after radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF). The impact of p-wave morphology after excluding the effect of pulmonary vein (PV) substrate on outcomes is unknown. We evaluated the p-wave morphology on electrocardiography immediately after PV isolation for clinical outcomes. Eighty-four consecutive patients (47 with paroxysmal AF and 37 with persistent AF) who underwent RFCA were included. P-wave duration (PWD) and amplitude in all leads were examined during sinus rhythm immediately after PV isolation. We evaluated the relationship between electrocardiogram parameters and AF recurrence, according to the type of AF and following ablation, and the correlation with left atrial (LA) volume, low voltage ratio, and fixed conduction time. During 12 months of follow-up, 20 patients experienced recurrence. The cut-off value of PWD > 120 ms in lead I showed a sensitivity of 75% and specificity of 69% for predicting recurrence. PWD was significantly correlated with LA volume, low voltage, and conduction velocity. Significantly higher recurrence rates were observed in patients with PWD > 120 ms than in those with PWD ≤ 120 ms (p < 0.001), and the difference was more pronounced in patients with persistent AF. Multivariate analysis demonstrated that PWD > 120 ms was independently associated with recurrence in the total population (hazard ratio 2.00; 95% confidence interval 1.27-3.22; p = 0.003) and in patients with persistent AF. In conclusion, long PWD after PV isolation predicts AF recurrence, which might be associated with the extent of the LA substrate in persistent AF.

Efficacy of Rapid Decongestion Strategy in Patients Hospitalized for Acute Heart Failure.

BACKGROUND: Clinical congestion is the most dominant feature in patients with acute decompensated heart failure (HF). However, uncertainty exists due to the permutations and combinations of congestion status and decongestion strategies. This study investigated the effect of congestion status and its improvement on 1-year mortality.Methods and Results:In all, 453 consecutive patients hospitalized for acute decompensated HF between July 2015 and March 2017 were prospectively included in the study. Congestion was evaluated using the congestion score. The 1-year mortality rate was 22.7%. The mean (±SD) congestion scores at admission, on Day 3, and at discharge were 10.7±3.9, 3.4±3.5, and 0.3±0.8, respectively. The improvement rate in congestion scores during the first 3 days was 78%; 46.6% of patients had residual congestion. The Day 3 congestion score and the improvement rate during the first 3 days were related to 1-year all-cause mortality and cardiovascular mortality. Combined predictive values were examined by calculating multivariable-adjusted hazard ratios for associations of residual congestion and improvement rate during the first 3 days, and prognostic variables identified by the Cox regression model. Residual congestion and lesser improvement (<64%) were associated with higher relative risk of 1-year all-cause mortality and cardiovascular mortality than residual congestion and higher improvement (≥64%) or resolved congestion. CONCLUSIONS: Rapid decongestion could be a prerequisite regardless of residual congestion in hospitalized acute decompensated HF patients.

A Patient with Heart Failure and Sleep-disordered Breathing Who Presented with Marked Reverse Remodeling by Continuous Positive Airway Pressure Therapy.

A 49-year-old Japanese man with worsening dyspnea was admitted with the diagnosis of new-onset heart failure (HF). His HF symptoms improved with standard treatment, but his left ventricular ejection fraction (LVEF) 21% remained unchanged. After he was discharged, he was diagnosed with severe sleep-disordered breathing (SDB). Continuous positive airway pressure (CPAP) therapy was introduced. Seven months later, his cardiac function had greatly improved (LVEF 50%). We report this case of a HF patient with SDB whose cardiac function greatly improved by CPAP therapy, and we discuss the pathophysiologic mechanisms of successful cardiac "reverse remodeling" in this case.

Analysis of plutonium isotope ratios including 238Pu/239Pu in individual U-Pu mixed oxide particles by means of a combination of alpha spectrometry and ICP-MS.

Isotope ratio analysis of individual uranium-plutonium (U-Pu) mixed oxide particles contained within environmental samples taken from nuclear facilities is proving to be increasingly important in the field of nuclear safeguards. However, isobaric interferences, such as 238U with 238Pu and 241Am with 241Pu, make it difficult to determine plutonium isotope ratios in mass spectrometric measurements. In the present study, the isotope ratios of 238Pu/239Pu, 240Pu/239Pu, 241Pu/239Pu, and 242Pu/239Pu were measured for individual Pu and U-Pu mixed oxide particles by a combination of alpha spectrometry and inductively coupled plasma mass spectrometry (ICP-MS). As a consequence, we were able to determine the 240Pu/239Pu, 241Pu/239Pu, and 242Pu/239Pu isotope ratios with ICP-MS after particle dissolution and chemical separation of plutonium with UTEVA resins. Furthermore, 238Pu/239Pu isotope ratios were able to be calculated by using both the 238Pu/(239Pu+240Pu) activity ratios that had been measured through alpha spectrometry and the 240Pu/239Pu isotope ratios determined through ICP-MS. Therefore, the combined use of alpha spectrometry and ICP-MS is useful in determining plutonium isotope ratios, including 238Pu/239Pu, in individual U-Pu mixed oxide particles.

Clinical characteristics of patients hospitalized for acute heart failure according to hospital arrival timing.

BACKGROUND: Whether clinical characteristics and outcomes in patients suffering acute heart failure (AHF) vary according to the timing of hospital arrival is unclear. We aimed to evaluate differences between subjects presenting in the daytime and nighttime. METHODS: A total of 679 patients with AHF were examined, classified into the two groups from the viewpoint of hospital arrival period into daytime (n=370; 8am-6pm) and nighttime (n=309; 6pm-8am). RESULTS: The prevalence of malnutrition and longer pre-hospital delay (≥48h) were greater, whereas a previous history of myocardial infarction, proportion of arrival by ambulance, and the frequency of New York Heart Association class IV symptoms, as well as systolic and diastolic blood pressure, and heart rate were lower in subjects presenting in the daytime. Patients with malnutrition defined as 5≥of the Controlling Nutrition Status scores demonstrate a longer pre-hospital delay compared to those without (34.2% vs. 19.9%, p<0.05). There was no significant difference in the 30-day outcomes but length of stay was significantly longer in subjects presenting in the daytime than in the nighttime. Multivariable logistic regression analysis revealed that systolic blood pressure, malnutrition, and chronic kidney disease were significantly related to prolonged length of stay. CONCLUSIONS: Our present results suggest that patients with AHF who present in the daytime may have higher rate of malnutrition status and lower systolic blood pressure compared to those presenting in the nighttime.

Correction: Sequential separation of ultra-trace U, Th, Pb, and lanthanides using a simple automatic system.

Correction for 'Sequential separation of ultra-trace U, Th, Pb, and lanthanides using a simple automatic system' by Yutaka Miyamoto, et al., Analyst, 2015, DOI: 10.1039/c5an00027k.

Sequential separation of ultra-trace U, Th, Pb, and lanthanides using a simple automatic system.

Uranium, thorium, lead, and the lanthanides were automatically and sequentially separated with a single anion-exchange column. This separation was achieved using eluents consisting of a simple and highly pure acid mixture of HCl, HNO3, acetic acid, and HF. The elements of interest were separated from the major constituents, which included alkaline metal elements, alkaline earth metal elements, and iron. This simple and automatic system is driven with pressurized nitrogen gas and controlled using a computer program. An optimized separation was accomplished under the following conditions: a 50 mm long and 2 mm diameter column, 11 µm diameter anion-exchange resin, and a 35 µL min(-1) flow rate. Using this system, 50 ng of varied elements in a 100 µL feed solution were perfectly separated within 5 h with >400 decontamination factors and >95% yield. In order to evaluate the performance of this system, a reference powdered rock sample was separated using this system. Abundances of objective elements, including 0.23 ng of lutetium, were accurately determined without corrections of chemical recovery yield or subtraction of the process blank. This separation technique saves time and effort for chemical processing, and is useful for ultra-trace quantitative and isotopic analyses of elements in small environmental samples.

Size distribution of radioactive particles collected at Tokai, Japan 6 days after the nuclear accident.

Airborne radioactive particles released by the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident in 2011 were collected with a cascade low-pressure impactor at the Japan Atomic Energy Agency (JAEA) in Tokai, Japan, 114 km south of the FDNPP. Size-fractionated samples were collected twice, in the periods of March 17-April 1, 2011, and May 9-13, 2011. These size-fractionated samplings were carried out in the earliest days at a short distance from the FDNPP. Radioactivity of short-lived nuclides (several ten days of half-life) was determined as well as (134)Cs and (137)Cs. The elemental composition of size-fractionated samples was also measured. In the first collection, the activity median aerodynamic diameter (AMAD) of (129m)Te, (140)Ba, (134)Cs, (136)Cs and (137)Cs was 1.5-1.6 µm, while the diameter of (131)I was 0.45 µm. The diameters of (134)Cs and (137)Cs in the second collection were expressed as three peaks at <0.5 µm, 0.94 µm, and 7.8 µm. The (134)Cs/(137)Cs ratio of the first collection was 1.02 in total, but the ratio in the fine fractions was 0.91. A distribution map of (134)Cs/(137)Cs - (136)Cs/(137)Cs ratios was helpful in understanding the change of radioactive Cs composition. The Cs composition of size fractions <0.43 µm and the composition in the 1.1-2.1 µm range (including the AMAD of 1.5-1.6 µm) were similar to the calculated compositions of fuels in the reactors No. 1 and No. 3 at the FDNPP using the ORIGEN-II code. The Cs composition collected in May, 2011 was similar to the calculation results of reactor No. 2 fuel composition. The change of Cs composition implies that the radioactive Cs was released from the three reactors at the FDNPP via different processes.

Fluoride complexation of element 104, rutherfordium.

Fluoride complexation of element 104, rutherfordium (Rf), produced in the 248Cm(18O,5n)261Rf reaction has been studied by anion-exchange chromatography on an atom-at-a-time scale. The anion-exchange chromatographic behavior of Rf was investigated in 1.9-13.9 M hydrofluoric acid together with those of the group-4 elements Zr and Hf produced in the 18O-induced reactions on Ge and Gd targets, respectively. It was found that the adsorption behavior of Rf on anion-exchange resin is quite different from those of Zr and Hf, suggesting the influence of relativistic effects on the fluoride complexation of Rf.