Macrovascular and microvascular function after implantation of left ventricular assist devices in end-stage heart failure: Role of microparticles.

BACKGROUND: The hemodynamic vascular consequences of implanting left ventricular assist devices (LVADs) have not been studied in detail. We investigated the effect of LVAD implantation compared with heart transplant (HTx) on microvascular and macrovascular function in patients with end-stage heart failure and evaluated whether microparticles may play a role in LVAD-related endothelial dysfunction. METHODS: Vascular function was assessed in patients with end-stage heart failure awaiting HTx, patients who had undergone implantation of a continuous-flow centrifugal LVAD, and patients who had already received a HTx. Macrovascular function was measured by flow-mediated vasodilation (FMD) using high-resolution ultrasound of the brachial artery. Microvascular function was assessed in the forearm during reactive hyperemia using laser Doppler perfusion imaging and pulsed wave Doppler. Age-matched patients without heart failure and without coronary artery disease (CAD) (healthy control subjects) and patients with stable CAD served as control subjects. Circulating red blood cell (CD253(+)), leukocyte (CD45(+)), platelet (CD31(+)/CD41(+)), and endothelial cell (CD31(+)/CD41(-), CD62e(+), CD144(+)) microparticles were determined by flow cytometry and free hemoglobin by enzyme-linked immunosorbent assay. RESULTS: FMD and microvascular function were significantly impaired in patients with end-stage heart failure compared with healthy control subjects and patients with stable CAD. LVAD implantation led to recovery of microvascular function, but not FMD. In parallel, increased free hemoglobin was observed along with red and white cell microparticles and endothelial and platelet microparticles. This finding indicates destruction of blood cells with release of hemoglobin and activation of endothelial cells. HTx and LVAD implantation led to similar improvements in microvascular function. FMD increased and microparticle levels decreased in patients with HTx, whereas shear stress during reactive hyperemia was similar in patients with LVADs and patients with HTx. CONCLUSIONS: Our data suggest that LVAD support leads to significant improvements in microvascular perfusion and hemodynamics. However, destruction of blood cells may contribute to residual endothelial dysfunction potentially by increasing nitric oxide scavenging capacity.

Serum levels of interleukin-6 and interleukin-10 in relation to depression scores in patients with cardiovascular risk factors.

It is currently unknown whether elevated cytokine levels in depression are confined to any specific subgroup of depressive patients. In this study, medical out-patients presenting with cardiovascular risk factors (N = 356) were assessed for both cognitive-affective and physical symptoms of depression using the Hospital Anxiety and Depression Scale (HADS) and the Maastricht questionnaire (MQ), respectively. In study participants assigned to the highest (≥21) and lowest (≤5) quartile for the MQ score, serum levels of cytokines were measured. We found highly significant associations between cognitive-affective symptoms of depression and elevated serum levels of interleukin-6 (IL-6; ρ = .231; p = .002) and interleukin-10 (IL-10; ρ = .370; p < .001), respectively. In multiple regression models elevated IL-10 serum concentration was independently related to cognitive-affective symptoms of depression (ρ = .165; p = .002). When all cytokines were included in one model, elevated IL-10 serum concentrations remained a significant predictor for depressive mood (ρ = .157; p = .009). In patients with cardiovascular risk factors and extreme scores for vital exhaustion, elevated serum IL-6 and even more IL-10 concentrations are linked to the presence of depressive mood. Future studies will have to test whether the so far unreported association of IL-10 with depressive mood represents a causal pathway involved in the pathogenesis or in the prognostic effect of depressive mood in cardiac patients.

Elevated serum levels of interleukin-10 and tumor necrosis factor α [corrected] are both associated with vital exhaustion in patients with cardiovascular risk factors.

BACKGROUND: Vital exhaustion, a psychological state characterized by unusual fatigue, irritability, and feelings of demoralization, has been identified as a risk factor for cardiovascular diseases and linked to elevated levels of pro-inflammatory cytokines. OBJECTIVE: The purpose of this study was to investigate the relationship between vital exhaustion and cytokine levels in patients with cardiovascular risk factors. METHOD: The entire cohort consisted of 356 primary-care patients with cardiovascular risk factors who participated in a study of early recognition of heart failure. All participants completed the Maastricht questionnaire (MQ) for assessing vital exhaustion. Cytokine serum levels were measured in all those subjects (N=178) who were assigned to the highest and lowest quartiles of the MQ, respectively. RESULTS: We found that elevated serum concentrations of IL-6, TNFα, and IL-10, but not IL-1ß or natriuretic peptides were associated with high MQ scores indicative of vital exhaustion. Using logistic regression analyses controlling for clinical variables and Type D personality, both TNFα (multivariate odds ratio [OR] =1.86; 95%-confidence interval [CI] =1.30-2.68; p=0.001) and IL-10(OR=1.62; 95%-CI=1.15-2.28; p=0.006), but not other cytokines significantly predicted vital exhaustion independently of other clinical and laboratory parameters examined [corrected]. CONCLUSION: The subjective state of vital exhaustion is linked to a substantial alteration in the pattern of secreted cytokines. Data suggest that a disturbance in the levels of both pro-inflammatory and anti-inflammatory mediators, rather than isolated stimulation by pro-inflammatory cytokines, is associated with the mental and physical changes of vital exhaustion.

Can student tutors act as examiners in an objective structured clinical examination?

CONTEXT: The dissemination of objective structured clinical examinations (OSCEs) is hampered by requirements for high levels of staffing and a significantly higher workload compared with multiple-choice examinations. Senior medical students may be able to support faculty staff to assess their peers. The aim of this study is to assess the reliability of student tutors as OSCE examiners and their acceptance by their peers. METHODS: Using a checklist and a global rating, teaching doctors (TDs) and student tutors (STs) simultaneously assessed students in basic clinical skills at 4 OSCE stations. The inter-rater agreement between TDs and STs was calculated by kappa values and paired t-tests. Students then completed a questionnaire to assess their acceptance of student peer examiners. RESULTS: All 214 Year 3 students at the University of Göttingen Medical School were evaluated in spring 2005. Student tutors gave slightly better average grades than TDs (differences of 0.02-0.20 on a 5-point Likert scale). Inter-rater agreement at the stations ranged from 0.41 to 0.64 for checklist assessment and global ratings; overall inter-rater agreement on the final grade was 0.66. Most students felt that assessment by STs would result in the same grades as assessment by TDs (64%) and that it would be similarly objective (69%). Nearly all students (95%) felt confident that they could evaluate their peers themselves in an OSCE. CONCLUSIONS: On the basis of our results, STs can act as examiners in summative OSCEs to assess basic medical skills. The slightly better grades observed are of no practical concern. Students accepted assessment performed by STs.

Psychological distress in primary care patients with heart failure: a longitudinal study.

BACKGROUND: Psychological distress is a common phenomenon in patients with heart failure. Depressive symptoms are often under-diagnosed or inadequately treated in primary care. AIM: To analyse anxiety and/or depression in primary care patients with heart failure according to psychosocial factors, and to identify protective factors for the resolution of psychological distress. DESIGN OF STUDY: Longitudinal observation study. SETTING: Primary care practices in lower Saxony, Germany. METHOD: In 291 primary care patients with heart failure the following factors were measured using validated questionnaires at baseline and 9 months later: anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), quality of life (Minnesota Living with Heart Failure Questionnaire), coping with illness (Freiburg questionnaire for coping with illness), and social support (social support questionnaire). Severity of heart failure (New York Heart Association [NYHA] classification and Goldman's Specific Activity Scale), and sociodemographic characteristics were documented using self-report instruments. RESULTS: Twenty-six (32.5%) of the 80 patients who were distressed at baseline had normal HADS scores 9 months later, while the remainder stayed distressed. In logistic regression, baseline distress (odds ratios [OR] 5.51; 95% confidence intervals [CI] = 2.56 to 11.62), emotional problems (OR = 1.08; 95% CI = 1.00 to 1.17), social support (OR = 0.54; 95% CI = 0.35 to 0.83), and NYHA classification (OR = 1.70; 95% CI = 1.05 to 2.77) independently predicted distress at follow up. High social support contributed to a resolution of anxiety or depression, while partnership and low levels of emotional problems protected patients who began the study in a good emotional state from psychological distress. CONCLUSION: In everyday practice it is important to consider that a high NYHA classification and emotional problems may contribute to anxiety or depression, while high social support and living in a relationship may positively influence the psychological health of patients with heart failure.

[Disease-specific quality of life in primary care patients with heart failure]. / Die krankheitsspezifische Lebensqualität von hausärztlichen Patienten mit Herzinsuffizienz.

BACKGROUND: Quality of Life (QoL) is an important predictor of mortality and re-admission in patients with heart failure (HF). Our aim was to analyze disease-specific quality of life and its relationship to psycho-social factors and HF severity. METHODS: In primary care patients with HF, quality of life (MLHFQ), anxiety, depression (HADS) and negative affectivity (DS-14), disease coping (FKV) and social support (F-SozU) were measured by validated questionnaires. Severity of HF (according to NYHA classification and Goldman's Specific Activity Scale) and sociodemographic characteristics were documented by self-report instruments. RESULTS: 363 patients from 44 general practices participated in the study (191 [52.6%] female). Women had more physical but not more emotional problems than men. Increased emotional and physical problems and global disease-related impairment in QoL (F = 63.29; p < 0.001) correlated with higher HF classes. Using regression analysis, more than 50% of the QoL values were predicted by psychological variables and perceived severity (significant for depression [HADS; p < 0.001], coping by dissimulation and wishful thinking [FKV; p = 0.027], HF severity [NYHA, Goldman; CONCLUSION: Psychosocial distress is a strong predictor of QoL impairment in primary care patients with HF. Because of its impact on both long-term prognosis and disease-specific QoL, psychosocial symptoms should be considered essential for the diagnosis and therapy in the routine care of patients with HF.

[Psychosomatic medicine and psychotherapy--a female subject?]. / Psychosomatische Medizin und Psychotherapie - ein weibliches Fachgebiet?

OBJECTIVES: In the areas of psychosomatic medicine and psychotherapy, the relative proportion of female physicians is above average compared with other medical specialty areas. Is there a gender-specific affinity for the subject even among medical students and if so, how does it affect the students' choice of their subsequent specialty and their further professional career? METHODS: Gender proportions were studied in a) students of elective courses in psychosomatics and psychotherapy at the University of Goettingen, b) graduate students of German medical faculties between 1993 and 2004 and c) advanced ranks of medical career. RESULTS: Female preponderance in psychosomatics and psychotherapy is already to be found among students and extends to the rank of specialists. However--as in other medical specialties--women are not adequately represented in managerial positions. CONCLUSIONS: The relatively high proportion of female physicians might be the result of women's special disposition for the field. While an adequate representation of both sexes among medical psychotherapists is desirable for clinical practice, an increase of female physicians in management and research positions would be expedient in order to direct more attention to gender-specific questions in psychosomatics and psychotherapy.

[Psychosocial co-symptoms in primary care patients with heart failure]. / Psychische Kosymptomatik von hausärztlichen Patienten mit Herzinsuffizienz.

BACKGROUND AND PURPOSE: Psychosocial distress is a common phenomenon in patients with heart failure (HF). The aim of this study was to analyze psychosocial co-symptoms and their relationship with clinical and sociodemographic factors. METHODS: In 363 primary care patients with HF, anxiety, depression and negative affectivity (HADS, DS-14), disease coping (FKV) and social support (F-SozU) were measured by validated questionnaires. Severity of HF (according to NYHA classification and Goldman's Specific Activity Scale) and sociodemographic characteristics were documented by self-report instruments. RESULTS: Increased anxiety and/or depression was found in 29.2% of patients. Anxiety and depression scores were significantly higher than in the German general population (p < 0.005). They were furthermore associated with NYHA and Goldman class (anxiety: p = 0.001; depression: p = 0.001). One third of the sample showed the type D personality pattern, which has been associated with increased mortality in cardiac patients. While HF severity correlated positively with psychological distress, patients living together with other persons had lower HF class than those living alone. Using regression analysis, sociodemographic and psychological variables predicted perceived severity of HF in 20.3% if measured by Goldman's scale (significant for sex, age, depressive symptoms and disease coping), and in 18.6% if measured by NYHA (significant for anxiety). DISCUSSION: Severity of HF symptoms and psychosocial factors are interrelated. Self-reported severity of HF is substantially influenced by demographic and psychological variables. In this, it is not relevant if severity is measured by a nonvalidated (NYHA) or a validated instrument (Goldman). CONCLUSION: In primary care patients with HF, psychosocial co-symptoms are frequent and interfere with perceived severity of disease. Psychological distress should be considered important in diagnostics and treatment, especially in patients living alone.

[Stress and heart disease in women]. / Stress und Herzkrankheit bei Frauen Geschlechtsspezifische Risiken, Bewältigungsprobleme und Behandlungsansätze.

Psychosocial aspects of heart diseases have usually been studied in predominantly male patients. Growing evidence shows that the results of these studies cannot simply be generalized to women. The research on associations between psychosocial factors and heart disease, especially coronary heart disease, in women is therefore summarized in a literature review. The literature shows that women are subject to adverse cardiac effects of stress and chronic negative affects in a similar way as men. However, in women the relevant sources of distress are often found in other areas, i.e., in the family and household environment, and less often at the workplace. Especially for working mothers, the combination of professional and household work constitutes a considerable stressor.Stress is also perceived differently in men and women, and it leads to different physiological reactions. One striking example is the recently described "stress cardiomyopathy", an acute, life-threatening illness, which is often triggered by sudden emotional distress and can mainly be found in women. Women with heart disease report more psychological distress in response to their illness than men. As in men, depressive symptoms may negatively impact prognosis. Nevertheless, women receive less rehabilitation treatment than men and also benefit less from common psychological offerings. There is some evidence that women need specially developed psychosocial interventions and should not simply be treated in predominantly male stress-management groups. In clinical practice, gender-specific stressors and accompanying psychological symptoms should be discussed with the female heart patient. If needed, she should receive individualized psychosomatic treatment.