Association between anxiety and mortality in patients with congestive heart failure after implantation of cardiac electronic devices.

OBJECTIVE: Several studies suggest that psychological factors including anxiety are associated with negative outcomes and in particular higher mortality rates among heart failure (HF) patients. However, the impact of anxiety on mortality in patients with implanted cardiac devices has not been fully appreciated. The aim of this study was to assess the association between state (SA) and trait (TA) anxiety and all-cause mortality in patients with HF after cardiac electronic devices implantation. METHODS: The monocentric prospective study enrolled 265 patients (215 men and 50 women) aged 23 to 84 years (mean age 57.1 ± 10.0), who received cardiac resynchronization therapy or cardioverter-defibrillator implantation. Mean duration of prospective follow-up was 62.3 ± 36.6 months. State-Trait Anxiety Inventory (STAI) was used to measure anxiety symptoms. Cox proportional hazards multivariate regression model was used to calculate hazard ratio (HR) of all-cause mortality with 95% confidence interval (95% CI). RESULTS: During the prospective follow-up period, 45 (17.0%) patients died due to all causes. According to quantitative analysis, HR for death used for SA scale was 1.04 (95% CI 1.00-1.07, p = 0.07) and for the TA scale 1.02 (95% CI 0.99-1.05, p = 0.21). Analysis of categorical indicators found statistically significant higher HR of mortality in patients with severe SA (2.35, 95% CI 1.17-4.71, p = 0.02), and TA (2.02, 95% CI 1.04-3.94, p = 0.04). CONCLUSION: High levels of SA and TA was significantly and independently associated with a high risk of all-cause mortality in patients, who underwent implantation of cardiac electronic devices.

Social support for patients with coronary artery disease after percutaneous coronary intervention.

BACKGROUND: To assess how social support relates to parameters of patients with coronary artery disease (CAD) after percutaneous coronary intervention (PCI), and how social support affects patient's prognosis within 1 year after surgery. METHODS: The study included 739 male and 236 female patients (975) who underwent PCI. To determine level of social support, the Multidimensional Scale of Perceived Social Support was used. The mean duration of a prospective follow-up was 12.0 ±â€¯1.7 months. The Cox multivariate regression proportional hazard model was used to estimate the hazard ratio (HR) of death from all causes and cardiovascular disease (CVD). RESULTS: A low level of social support in 5.7% of patients was observed, while 30.5% had a moderate level and 63.8% had a high level. Patients with low and moderate levels of social support were older than those with high level. Among patients with high levels of social support, more were male compared to patients with moderate level. During observation, 24 patients died from all causes (2.5%), while 21 (2.2%) died from CVD. In the multivariate Cox regression model the HR of social support for all causes of death was 0.97 (95% confidence interval, [CI], 0.94-0.99, p = 0.007), while death from CVD was 0.97 (95% CI, 0.94-1.00, p = 0.048). For patients with low level of social support, the HR for death from all causes was 4.52 (95% CI, 1.37-14.95, p = 0.013), while death from CVD was 3.66 (95% CI, 0.94-14.25, p = 0.061). CONCLUSION: Social support level was associated with age and gender, and significantly and independently affected CAD patients' risk of death after PCI.

Type D personality in Russian patients with cardiovascular disease: validity of the Russian DS14 (DS14-RU).

BACKGROUND: Type D personality is associated with unfavorable outcomes in patients with cardiovascular diseases (CVD). However, there is no valid Type D Scale in Russian language. The purpose of the study was to examine the factor structure of a new Russian version of 14-item Type D Scale (DS14-RU), and to evaluate the reliability and construct validity of the DS14-RU in clinical research. METHODS: The study included 929 participants, 496 (53.4%) of which had coronary artery disease, 195 (21.0%) congestive heart failure, 84 (9.0%) arterial hypertension and 154 (16.6%) were relatively healthy volunteers. The mean age was 57.5 years, 565 (60.8%) participants were males. The respondents filled out an extended Russian version of the Type D scale and new DS14-RU, as well as the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Reeder Stress Inventory, and State-Trait Personality Inventory. RESULTS: The new Russian version of DS14-RU was internally consistent with Cronbach's α = .80 for both the negative affectivity and social inhibition subscales. The prevalence of Type D personality, as measured with the DS14-RU, was 21.4% among patients with CVD, and 20.0% among relatively healthy participants. The mean scores for anxiety, depression, psychosocial stress and anger were significantly higher in patients with Type D personality and they had significantly lower levels of social support and curiosity. CONCLUSIONS: The new DS14-RU is consistent with the original DS14 in terms of reliability, factor structure and construct validity. The DS14-RU can be used for the reliable assessment of Type D in Russian-speaking respondents.

Uranium oxide catalysts: environmental applications for treatment of chlorinated organic waste from nuclear industry.

Huge amounts of nuclear waste, including depleted uranium, significantly contribute to the adverse environmental situation throughout the world. An approach to the effective use of uranium oxides in catalysts for the deep oxidation of chlorine-containing hydrocarbons is suggested. Investigation of the catalytic activity of the synthesized supported uranium oxide catalysts doped with Cr, Mn and Co transition metals in the chlorobenzene oxidation showed that these catalysts are comparable with conventional commercial ones. Physicochemical properties of the catalysts were studied by X-ray diffraction, temperature-programmed reduction with hydrogen (H2-TPR), and Fourier transform infrared spectroscopy. The higher activity of Mn- and Co-containing uranium oxide catalysts in the H2-TPR and oxidation of chlorobenzene in comparison with non-uranium catalysts may be related to the formation of a new disperse phase represented by uranates. The study of chlorobenzene adsorption revealed that the surface oxygen is involved in the catalytic process.

Depression and all-cause mortality in patients with congestive heart failure and an implanted cardiac device.

OBJECTIVE: The purpose of this study was to assess the association between depression and all-cause mortality in patients with congestive heart failure (CHF) and an implanted cardiac device. METHODS: The study enrolled 260 patients (mean age 56.8±10.0 years; 83.1% male) with CHF and an implanted cardiac device (156 patients with a resynchronization therapy cardiac device, 104 patients with an implantable cardioverter defibrillator). The mean duration of follow-up was 48.6±32.2 months. The Beck Depression Inventory was used to measure depressive symptoms. Depression was considered absent for a score between 0 and 9, mild to moderate for a score between 10 and 18, and severe if the score was 19 or greater. The Cox proportional hazards regression model was used to estimate hazard ratios (HR) with a 95% confidence interval (CI) for the impact of depression on all-cause mortality. The HR was calculated after adjustment for the following confounders: age, gender, smoking status, hypertension, diabetes mellitus, body mass index, hypercholesterolemia, left ventricular ejection fraction, number of hemodynamically significant lesions of the coronary arteries, and the type of implanted cardiac device. RESULTS: During the follow-up period, 37 patients died (14.2%). The adjusted HR of depression for all-cause mortality was 1.05, with a 95% CI of 1.01-1.09. Patients without depression were accepted as a reference group with HR=1.0 for analysis of the categorical indicator. The HR was 1.32, with a 95% CI of 0.57-3.03, in patients with mild depressive symptoms, and the HR was 3.18 with a 95% CI of 1.31-7.73 in patients with severe depressive symptoms. CONCLUSION: Increased depressive symptoms were independently associated with all-cause mortality in patients with CHF and an implanted cardiac device.

Real-world geographic variations in the use of cardiac implantable electronic devices-The PANORAMA 2 observational cohort study.

BACKGROUND: Currently, several geographies around the world remain underrepresented in medical device trials. The PANORAMA 2 study was designed to assess contemporary region-specific differences in clinical practice patterns of patients with cardiac implantable electronic devices (CIEDs). METHODS: In this prospective, multicenter, observational, multinational study, baseline and implant data of 4,706 patients receiving Medtronic CIEDs (Medtronic plc, Minneapolis, MN, USA; either de novo device implants, replacements, or upgrades) were analyzed, consisting of: 54% implantable pulse generators (IPGs), 20.3% implantable cardiac defibrillators (ICDs), 15% cardiac resynchronization therapy -defibrillators, and 5.1% cardiac resynchronization therapy -pacemakers, from 117 hospitals in 23 countries across four geographical regions between 2012 and 2016. RESULTS: For all device types, in all regions, there were fewer females than males enrolled, and women were less likely to have ischemic cardiomyopathy. Implant procedure duration differed significantly across the geographies for all device types. Subjects from emerging countries, women, and older patients were less likely to receive a magnetic resonance imaging-compatible device. Defibrillation testing differed significantly between the regions. European patients had the highest rates of atrial fibrillation (AF), and the lowest number of implanted single-chamber IPGs. Evaluation of stroke history suggested that the general embolic risk is more strongly associated with stroke than AF. CONCLUSIONS: We provide comprehensive descriptive data on patients receiving Medtronic CIEDs from several geographies, some of which are understudied in randomized controlled trials. We found significant variations in patient characteristics. Several medical decisions appear to be affected by socioeconomic factors. Long-term follow-up data will help evaluate if these variations require adjustments to outcome expectations.

Gender in cardiac resynchronisation therapy.

Introduction: Gender differences in cardiac resynchronisation therapy (CRT) response are not clear enough. This study aimed to assess gender influence on systemic inflammation, neurohormonal activation, fibrosis in patients with congestive heart failure (CHF) and CRT. Methods: We compared group I (61 men) and group II (16 women) of patients undergoing CRT. Plasma levels of Nt-proBNP, interleukin (IL)-1ß, IL-6, IL-10, tumor necrosis factor alpha (TNF-α), C-reactive protein, galectin-3 (Gal-3), metalloproteinase-9 (MMP-9), tissue inhibitors of metalloproteinase 1 and 4 (TIMP-1, TIMP-4), ratio MMP-9/TIMP-1, MMP-9/TIMP-4 were measured. According to dynamics of left ventricular end-systolic volume patients were classified into non-responders, responders, super-responders. Results: Women more likely had left bundle branch block (81.3 vs 47.5%, P = 0.016), were more super-responders (66.7 vs 30.5%). Both groups showed decrease of IL-6 (P < 0.05), TNF-α (P < 0.001; P < 0.05), NT-proBNP (P = 0.001; P < 0.05), Gal-3 (P < 0.05). In women there was decrease of IL-6 by 44.4 vs 23.5% in men (PP = 0.029), TNF-α by 41.4 vs 30.9%, NT-proBNP by 73.3 vs 46% (P = 0.002), Gal-3 by 82.3 vs 64.9% (P < 0.05). Group I also showed decrease of IL-10 by 34.2% (P < 0.05). Group dynamics of TIMP-1 was opposite: men showed tendency to reduction of TIMP-1 (P = 0.054), women showed increase of TIMP-1 (P < 0.05). Besides, men showed decrease of MMP-9 (P < 0.05) and ratio MMP-9/TIMP-4 (P < 0.05). Conclusion: The best response to CRT is associated with female gender explained by greater decrease of neurohormonal activation, systemic inflammation and fibrosis. The revealed opposite dynamics of TIMP-1 in the groups can demonstrate the existence of gender features of matrix metalloproteinase system activity and their tissue inhibitors.

Comparison of squatting stress echocardiography and dobutamine stress echocardiography for the diagnosis of coronary artery disease.

BACKGROUND: Dobutamine stress echocardiography (DSE) is commonly used for the diagnosis for coronary artery disease (CAD). We previously demonstrated that squatting induces wall motion abnormalities (WMA) in areas subtended by stenotic coronary arteries. OBJECTIVE: This study was designed to test the hypothesis that dobutamine and squatting stress echocardiography are equally useful for the diagnosis of CAD. METHODS: We studied 39 patients who were scheduled to have coronary angiography for the evaluation of chest pain. Each patient had squatting stress echocardiography followed by DSE. For squatting stress echocardiography the echocardiogram in standard views was recorded in the standing position. The procedure was repeated during squatting for 2 minutes. Dobutamine echocardiography was performed using standard protocol. The squatting and dobutamine stress echocardiograms were interpreted by an observer blinded to the results of coronary angiography. RESULTS: During squatting, new or worsening WMA developed in 20 patients. Six patients developed WMA in the left anterior descending artery territory, three in circumflex territory, three in the right coronary artery territory, and eight in multiple coronary territories. The sensitivity, specificity, and accuracy of squatting echocardiography for diagnosis of CAD were 95%, 94%, and 94%, respectively. For DSE, the sensitivity, specificity, and accuracy for the diagnosis of CAD were 85%, 94%, and 90%, respectively. There was no significant difference between squatting and dobutamine stress echocardiography for the diagnosis of CAD (P = 0.702). CONCLUSION: These data indicate that squatting and dobutamine echocardiography are equally useful in the diagnosis of CAD. In selected patients, squatting echocardiography may be used in place of dobutamine echocardiography for the diagnosis of CAD.

Clinical manifestations and risk factors of coronary artery disease in patients with diabetes mellitus in western Siberia.

OBJECTIVE: To compare the prevalence of cardiovascular risk factors and clinical manifestations of coronary artery disease (CAD) between patients with type 2 diabetes mellitus (DM) and CAD who lived at northern latitudes vs. those who resided at southern latitudes in the Tyumen region, western Siberia. STUDY DESIGN: This retrospective study involved 382 patients with type 2 DM selected from 8,573 patients with angiographic CAD (>50% stenosis). Out of the total, 243 patients were permanent residents at the high latitudes of the Tyumen region ("northern patients"), and 139 patients were permanent residents in areas south of the Tyumen region ("southern patients"). RESULTS: On average, northern patients were younger than southern patients (53 vs. 57 years, respectively). The odds ratio (OR) for living in the north was 2.1 (95% CI 0.99-4.53) for obesity (BMI>or=30 kg/m2), 1.87 (95% CI 1.05-3.31) for smoking, 0.93 (95% CI 0.89-0.96) per 1 year increase in age, 0.84 (95% CI 0.76-0.94) per 1 mmol/L increase of fasting plasma glucose, and 1.15 (95% CI 1.04-1.28) per 1 mm increase of right ventricular end-diastolic diameter. The proportion of patients with 3 or more CAD risk factors was higher in the north. Most patients in both groups had a history of myocardial infarction, severe angina in class III/IV as defined by the Canadian Cardiovascular System (CCS), heart failure in class II/IV as defined by the New York Heart Association (NYHA) and hypertension. CONCLUSIONS: A north-south gradient was observed in cardiovascular risk factors among patients with DM and CAD in the Tyumen region. The clinical manifestations of CAD in DM patients at high latitudes were comparable with those of patients who reside south of the Tyumen region of western Siberia, despite the younger age of northern patients.

Asymmetric septal hypertrophy in patients with coronary artery disease.

AIMS: To assess the relationship between asymmetric septal hypertrophy (ASH) and manifestations of coronary artery disease (CAD). METHODS AND RESULTS: A total of 5128 consecutive patients with proven diagnosis of CAD were examined. There were 2469 patients with left ventricular (LV) hypertrophy (LVH) (48.2%), among whom 297 (5.8%) had ASH (echocardiographic ventricular septum thickness to LV posterior wall thickness ratio > or =1.3). There were more male patients with ASH than patients with symmetric LVH (SLVH). ASH patients were significantly older and more obese, more of them were in NYHA class III/IV compared with SLVH patients. The prevalence of prior myocardial infarction (MI), systemic hypertension, heart rhythm disorders were higher in patients with ASH compared with SLVH patients. The groups differed significantly in echocardiographic parameters: LV and right ventricular (RV) end-diastolic dimensions, LV ejection fraction, left atrial dimension, extent of LV wall motion abnormalities, wall motion score index, LV mass/body surface area, signs of prior MI, and frequency of moderate mitral regurgitation. The frequency of stenosis and more severe (>90% stenosis) lesion of right coronary artery (RCA) and left circumflex artery (LCA) were higher in patients with ASH. Multivariate analysis identified that heart rhythm disorder, LV and RV end-diastolic dimensions, aortic root diameter, impaired LV ejection fraction, echocardiographic signs of previous MI, LV mass, and severe lesions of RCA were independently associated with ASH. CONCLUSION: In patients with CAD, ASH is associated with significant atherosclerosis of RCA and LCA, and more severe clinical manifestations of CAD and impaired LV function.

Putidaredoxin-to-cytochrome P450cam electron transfer: differences between the two reductive steps required for catalysis.

Cytochrome P450cam (P450cam) is the terminal monooxygenase in a three-component camphor-hydroxylating system from Pseudomonas putida. The reaction cycle requires two distinct electron transfer (ET) processes from the [2Fe-2S] containing putidaredoxin (Pdx) to P450cam. Even though the mechanism of interaction and ET between the two proteins has been under investigation for over 30 years, the second reductive step and the effector role of Pdx are not fully understood. We utilized mutagenesis, kinetic, and computer modeling approaches to better understand differences between the two Pdx-to-P450cam ET events. Our results indicate that interacting residues and the ET pathways in the complexes formed between reduced Pdx (Pdx(r)) and the ferric and ferrous dioxygen-bound forms of P450cam (oxy-P450cam) are different. Pdx Asp38 and Trp106 were found to be key players in both reductive steps. Compared to the wild-type Pdx, the D38A, W106A, and delta106 mutants exhibited considerably higher Kd values for ferric P450cam and retained ca. 20% of the first electron transferring ability. In contrast, the binding affinity of the mutants for oxy-P450cam was not substantially altered while the second ET rates were <1%. On the basis of the kinetic and modeling data we conclude that (i) P450cam-Pdx interaction is highly specific in part because it is guided/controlled by the redox state of both partners; (ii) there are alternative ET routes from Pdx(r) to ferric P450cam and a unique pathway to oxy-P450cam involving Asp38; (iii) Pdx Trp106 is a key structural element that couples the second ET event to product formation possibly via its "push" effect on the heme-binding loop.

The putidaredoxin reductase-putidaredoxin electron transfer complex: theoretical and experimental studies.

Interaction and electron transfer between putidaredoxin reductase (Pdr) and putidaredoxin (Pdx) from Pseudomonas putida was studied by molecular modeling, mutagenesis, and stopped flow techniques. Based on the crystal structures of Pdr and Pdx, a complex between the proteins was generated using computer graphics methods. In the model, Pdx is docked above the isoalloxazine ring of FAD of Pdr with the distance between the flavin and [2Fe-2S] of 14.6 A. This mode of interaction allows Pdx to easily adjust and optimize orientation of its cofactor relative to Pdr. The key residues of Pdx located at the center, Asp(38) and Trp(106), and at the edge of the protein-protein interface, Tyr(33) and Arg(66), were mutated to test the Pdr-Pdx computer model. The Y33F, Y33A, D38N, D38A, R66A, R66E, W106F, W106A, and Delta106 mutations did not affect assembly of the [2Fe-2S] cluster and resulted in a marginal change in the redox potential of Pdx. The electron-accepting ability of Delta106 Pdx was similar to that of the wild-type protein, whereas electron transfer rates from Pdr to other mutants were diminished to various degrees with the smallest and largest effects on the kinetic parameters of the Pdr-to-Pdx electron transfer reaction caused by the Trp(106) and Tyr(33)/Arg(66) substitutions, respectively. Compared with wild-type Pdx, the binding affinity of all studied mutants to Pdr was significantly higher. Experimental results were in agreement with theoretical predictions and suggest that: (i) Pdr-Pdx complex formation is mainly driven by steric complementarity, (ii) bulky side chains of Tyr(33), Arg(66), and Trp(106) prevent tight binding of oxidized Pdx and facilitate dissociation of the reduced iron-sulfur protein from Pdr, and (iii) transfer of an electron from FAD to [2Fe-2S] can occur with various orientations between the cofactors through multiple electron transfer pathways that do not involve Trp(106) but are likely to include Asp(38) and Cys(39).

Atomic force microscopy revelation of molecular complexes in the multiprotein cytochrome P450 2B4-containing system.

The application of atomic force microscopy (AFM) to the identification and visualization of individual molecules and their complexes in a reconstituted monooxygenase P450 2B4 system without the phospholipid was demonstrated. The method employed in this study distinguishes the monomeric proteins from their binary complexes and, also, the binary from the ternary complexes. The AFM images of the full-length P450 2B4 system's constituent components - cytochrome P450 2B4 (2B4), NADPH-cytochrome P450 reductase and cytochrome b5 (b5), were obtained on highly-oriented pyrolitic graphite. The typical heights of the d-2B4, d-flavoprotein (Fp) and d-b5 molecules were measured and found to be 2.2 +/- 0.2, 2.3 +/- 0.2 and 1.8 +/- 0.1 nm, respectively. The measured heights of the binary d-Fp/d-2B4 and d-2B4/d-b5 complexes were estimated to be 3.4 +/- 0.2 and 2.8 +/- 0.2 nm, respectively. No formation of d-Fp/d-b5 complexes was registered. The ternary d-Fp/d-2B4/d-b5 complexes were visualized and their heights were found to be roughly equal to 4.3 +/- 0.3 nm and 6.2 +/- 0.3 nm.

Atomic force microscopy detection of molecular complexes in multiprotein P450cam containing monooxygenase system.

The application of atomic force microscopy (AFM) technique in proteomic research, identification and visualization of individual molecules and molecular complexes within the P450cam containing monooxygenase system was demonstrated. The method distinguishes between the binary protein complexes and appropriate monomeric proteins and, also, between the binary and ternary complexes. The AFM images of the components of a cytochrome P450cam containing monooxygenase system - cytochrome P450cam (P450cam), putidaredoxin (Pd) and putidaredoxin reductase (PdR) - were obtained on a mica support. The molecules of P450cam, Pd and PdR were found to have typical heights of 2.6 +/- 0.3 nm, 2.0 +/- 0.3 and 2.8 +/- 0.3 nm, respectively. The measured heights of the binary Pd/PdR and P450cam/PdR complexes were 4.9 +/- 0.3 nm and 5.1 +/- 0.3 nm, respectively. The binary P450cam/Pd complexes were found to have a typical height of about (3.9 / 5.7 nm) and the ternary PdR/Pd/P450cam complexes, a typical height of about 9.1 +/- 0.3 nm.