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Previous research in cardiac patients suggested that type D personality, defined as a combination of negative affectivity (NA) and social inhibition (SI), was associated with adverse outcome.The objective of this prospective study was to examine the independent prognostic value of type D in patients with coronary artery disease (CAD).A total of 465 patients completed the Type D Scale (DS14) questionnaire before undergoing stent implantation and were followed up for 5 years.In a Cox regression model adjusted for selected confounders, we found a trend towards NA for the prediction of nonfatal major adverse cardiovascular event (MACE, hazard ratio (HR) = 1.07, 95 % confidence intervals (CIs) = 0.99-1.14, p = 0.074), while, in contrast, SI was a significant and independent predictor of better outcome (HR = 0.92, 95 % CI = 0.86-0.99, p = 0.027).In a cohort of CAD patients, the type D pattern was not linked to adverse outcome, whereas SI was negatively associated with MACE.

Angst und Depressivitat sind haufige Phanomene bei Herzpatienten, die je nach Fallgrenzwert, Krankheitssituation und Subgruppe bei 15–50% aller Patienten ein auffalliges Ausmas annehmen, in der Regel jedoch unzureichend diagnostiziert und behandelt werden. In ihrer Folge kommt es zu schlechtem korperlichen Befinden, reduzierter Leistungsfahigkeit und Lebensqualitat sowie zu ungunstigem Krankheitsverhalten. Depressivitat kann zumindest nach akutem Myokardinfarkt auch als Risikofaktor fur vermehrte somatische Krankheitskomplikationen angesehen werden. Hierfur sind vermutlich sowohl Verhaltens- als auch psychophysiologische Effekte verantwortlich.

Objective: To determine the independent effects of depressed mood and markers of medical disease severity on mortality in consecutive medical inpatients. Methods: Consecutive general medical inpatients were asked to complete the Hospital Anxiety and Depression Scale (HADS) at admission. Prognostic indicators were obtained from patients' records and physicians' ratings. The study endpoint was mortality from all causes at 1 year. Results: The baseline assessment was completed by 575 patients (87.7%). Survival data were available for 572 of these (86 deaths). HADS depression scores and several physical risk indicators predicted mortality. In multivariate analyses, physicians' rating of prognosis was the best predictor of mortality [adjusted odds ratio (OR) 3.6; 95% confidence interval (CI), 2.5–5.4]. Other independent predictors included a principal diagnosis of hemato-oncological disease, comorbidity scores, and HADS depression (adjusted OR 1.75; 95% CI, 1.10–2.79). Conclusion: Our data demonstrate an independent prognostic effect of depressed mood on mortality in general medical inpatients. Screening for depression may improve risk stratification in these patients over and above that obtained by routinely available physical parameters and physicians' clinical judgement.

BACKGROUND: To investigate the interaction of clinical characteristics with disease characterising parameters in heart failure with preserved ejection fraction (HFpEF). Methods and results In the multicenter, randomized, placebo-controlled, double-blinded, Aldo-DHF trial investigating the effects of spironolactone on exercise capacity (peakVO2) and diastolic function (E/e') n=422 patients with HFpEF (age 67 ± 8 years, 52% females, LVEF 67 ± 8%) were included. After multiple adjustment, higher age was significantly related to reduced peakVO2, and to increased E/e', NT-proBNP, LAVI as well as LVMI (all p

Despite suffering from poor prognosis, progressive exercise intolerance, and impaired quality of life (QoL), effective therapeutic strategies in heart failure with preserved ejection fraction (HFpEF) are sparse. Exercise training (ET) improves physical QoL in HFpEF, but the effects on other aspects of QoL are unknown.The multicentre, prospective, randomized, controlled Exercise training in Diastolic Heart Failure Pilot study included 64 HFpEF patients (65 ± 7 years, 56% female). They were randomized to supervised endurance/resistance training in addition to usual care (ET, n = 44) or usual care alone (UC, n = 20). At baseline and after 3 months, QoL was assessed (36-item Short-form Health Survey (SF-36), Minnesota Living With Heart Failure Questionnaire (MLWHFQ), and Patient Health Questionnaire (PHQ-9).Exercise improved the following SF-36 dimensions: physical functioning (p 0.001, p = 0.001 vs. UC), bodily pain (p = 0.046), general health perception (p 0.001, p = 0.016 vs. UC), general mental health (p = 0.002), vitality (p = 0.003), social functioning (p 0.001) physical (p 0.001, p = 0.001 vs. UC), and mental component score (p = 0.030). ET did not improve role limitations due to physical and emotional problems. The MLWHFQ total scale (p 0.001) and the MLWHFQ physical limitation scale (p 0.001, p = 0.04 vs. UC) also improved with ET. The MLWHFQ emotional limitation scale did not change with ET. With ET, also the PHQ-9 total score improved significantly (p = 0.004, p = 0.735 vs. UC).In patients with HFpEF, exercise training improved emotional status, physical and social dimensions of QoL as well as symptoms of depression from pre to post test. Physical dimensions of QoL and general health perception also improved significantly with exercise in comparison to usual care.

Whereas cytokine-induced tyrosine phosphorylation of STAT (signal transducer and activator of transcription) proteins by JAK kinases has been well studied, much less is known about STAT-specific serine kinases and their signal-dependent regulation. The paper by Joanna Bancerek and colleagues published recently in Immunity reports that upon interferon-γ (IFNγ) stimulation of cells the chromatin-associated cyclin-dependent kinase 8 (CDK8) phosphorylates the regulatory serine residue 727 in the transactivation domain of STAT1. The authors state that the CDK8 module of the Mediator complex is a key component in the STAT1 signal pathway, linking serine phosphorylation to gene-specific transcriptional events.

Most often it is assumed that the 'psychosomatic' concept originated from psychoanalysis. However, this term had already been introduced into medical literature about 80 years before Sigmund Freud - namely by Johann Christian August Heinroth, the first professor of psychiatry and psychotherapy in the western world. Widely through quotations from his works, the authors analyze Heinroth's understanding of the interrelations between the body and the soul. For Heinroth both formed a unified, indivisable whole, which interacted in many ways, including pathologically. According to him, a mental illness had its cause in the patient’s leading a 'wrong life'. This 'wrong life' deranged the soul from its normal functioning. In a second step, this derangement can have an impact on the body and produce the somatic symptoms that accompany a mental illness. Since both ‘components’ of the 'indivisible whole' were affected, it was clear for Heinroth that doctors needed to view their patients holistically and treat the whole person. Since in the end the somatic symptoms were caused by an underlying mental derangement, this needed to be treated in the first place - and the psyche could only be reached by direct psychological intervention. Hence what he called his ‘direct-psychische Methode’ ought to be the remedy of choice for mental illnesses. Through his clear understanding of the interactions of body and soul and by integrating somatic and psychological therapies into a holistic, unified treatment programm, Heinroth is of major importance for the history of psychosomatic medicine.

Importance Diastolic heart failure (ie, heart failure with preserved ejection fraction) is a common condition without established therapy, and aldosterone stimulation may contribute to its progression. Objective To assess the efficacy and safety of long-term aldosterone receptor blockade in heart failure with preserved ejection fraction. The primary objective was to determine whether spironolactone is superior to placebo in improving diastolic function and maximal exercise capacity in patients with heart failure with preserved ejection fraction. Design and Setting The Aldo-DHF trial, a multicenter, prospective, randomized, double-blind, placebo-controlled trial conducted between March 2007 and April 2012 at 10 sites in Germany and Austria that included 422 ambulatory patients (mean age, 67 [SD, 8] years; 52% female) with chronic New York Heart Association class II or III heart failure, preserved left ventricular ejection fraction of 50% or greater, and evidence of diastolic dysfunction. Intervention Patients were randomly assigned to receive 25 mg of spironolactone once daily (n=213) or matching placebo (n=209) with 12 months of follow-up. Main Outcome Measures The equally ranked co–primary end points were changes in diastolic function (E/e′) on echocardiography and maximal exercise capacity (peak VO 2 ) on cardiopulmonary exercise testing, both measured at 12 months. Results Diastolic function (E/e′) decreased from 12.7 (SD, 3.6) to 12.1 (SD, 3.7) with spironolactone and increased from 12.8 (SD, 4.4) to 13.6 (SD, 4.3) with placebo (adjusted mean difference, −1.5; 95% CI, −2.0 to −0.9; P 2 did not significantly change with spironolactone vs placebo (from 16.3 [SD, 3.6] mL/min/kg to 16.8 [SD, 4.6] mL/min/kg and from 16.4 [SD, 3.5] mL/min/kg to 16.9 [SD, 4.4] mL/min/kg, respectively; adjusted mean difference, +0.1 mL/min/kg; 95% CI, −0.6 to +0.8 mL/min/kg; P = .81). Spironolactone induced reverse remodeling (left ventricular mass index declined; difference, −6 g/m 2 ; 95% CI, −10 to−1 g/m 2 ; P = .009) and improved neuroendocrine activation (N-terminal pro–brain-type natriuretic peptide geometric mean ratio, 0.86; 95% CI, 0.75-0.99; P = .03) but did not improve heart failure symptoms or quality of life and slightly reduced 6-minute walking distance (–15 m; 95% CI, –27 to –2 m; P = .03). Spironolactone also modestly increased serum potassium levels (+0.2 mmol/L; 95% CI, +0.1 to +0.3; P 2 ; 95% CI, −8 to −3 mL/min/1.73 m 2 ; P Conclusions and Relevance In this randomized controlled trial, long-term aldosterone receptor blockade improved left ventricular diastolic function but did not affect maximal exercise capacity, patient symptoms, or quality of life in patients with heart failure with preserved ejection fraction. Whether the improved left ventricular function observed in the Aldo-DHF trial is of clinical significance requires further investigation in larger populations. Trial Registration clinicaltrials.gov Identifier: ISRCTN94726526; Eudra-CT No: 2006-002605-31

Background International disease management guidelines recommend the regular assessment of depression and anxiety in heart failure patients. Currently there is little data on the effect of screening for depression and anxiety on the quality of life and the prognosis of heart failure (HF). We will investigate the association between the recognition of current depression/anxiety by the general practitioner (GP) and the quality of life and the patients’ prognosis. Methods/Design In this multicenter, prospective, observational study 3,950 patients with HF are recruited by general practices in Germany. The patients fill out questionnaires at baseline and 12-month follow-up. At baseline the GPs are interviewed regarding the somatic and psychological comorbidities of their patients. During the follow-up assessment, data on hospitalization and mortality are provided by the general practice. Based on baseline data, the patients are allocated into three observation groups: HF patients with depression and/or anxiety recognized by their GP (P+/+), those with depression and/or anxiety not recognized (P+/−) and patients without depression and/or anxiety (P−/−). We will perform multivariate regression models to investigate the influence of the recognition of depression and/or anxiety on quality of life at 12 month follow-up, as well as its influences on the prognosis (hospital admission, mortality). Discussion We will display the frequency of GP-acknowledged depression and anxiety and the frequency of installed therapeutic strategies. We will also describe the frequency of depression and anxiety missed by the GP and the resulting treatment gap. Effects of correctly acknowledged and missed depression/anxiety on outcome, also in comparison to the outcome of subjects without depression/anxiety will be addressed. In case results suggest a treatment gap of depression/anxiety in patients with HF, the results of this study will provide methodological advice for the efficient planning of further interventional research. peerReviewed

Sequence-specific binding of STAT1 (signal transducer and activator of transcription 1) transcription factor to palindromic promoter elements, termed γ-activated sites (GAS), and an extended spatial reorientation between two dimer configurations are key events in the interferon signaling pathway. Although the DNA-binding domain of STAT1 is engaged in both processes, how the conformational change from a parallel to an antiparallel dimer configuration affects cytokine-induced target gene activation is unknown. In order to study the impact of the conformational shift on gene expression, we generated a STAT1 point mutant with a structurally altered architecture of the DNA-binding domain and characterized the resulting mutant (F364A) in cells stimulated with interferon-γ. Here, we report that substituting alanine for phenylalanine at position 364 resulted in reduced affinity to GAS sites and, additionally, a decreased dephosphorylation rate by the inactivating Tc45 phosphatase. The mutant had no defect in cooperative DNA binding and displayed normal kinetics of interferon-γ-induced nuclear accumulation, despite its elevated level of tyrosine phosphorylation. By assessing the transcriptional activity of the mutant, we found a strikingly robust expression of known interferon-γ-driven target genes, indicating that an impaired stability of the antiparallel dimer configuration can compensate for a reduced affinity to GAS sites. However, the mutant followed changes in ligand-induced receptor activation more slowly than the wild-type molecule, as demonstrated by its elevated phospho-STAT1 concentration following addition of the kinase inhibitor staurosporine to interferon-pretreated cells. This finding showed that the DNA-binding mutant F364A had partially lost its ability to terminate signal transmission rapidly. Thus, the coupling of high-affinity GAS binding to a rapid exchange from a parallel to an antiparallel dimer conformation is not necessarily required for optimal signal amplification, but rather allows for a dynamic signal response and ensures high adaptability to changes in signal input.

The body-mind dualism of somatic medicine is resolved through the concept of psychosomatic medicine. More unspecific descriptions such as "integrative medicine" (which does not clarify what should be integrated) or the "holistic approach" (which comes close to esoterics) suggest the unity of mind, body and soul, although the term "psycho-somatic" still reflects dualistic thinking.The American Psychosomatic Society has been considering a name change for years, partially to rid itself of the dualistic label, but so far these efforts have not resulted in a viable alternative. Engel's concept of biopsychosocial medicine supposes a triangular array of the body, mind, and social environment, setting body and mind into a relationship with each other and with a third party. Based on the physician-patient relationship (Balint), psychosomatic medicine can be understood in a broader sense as "relationship medicine," covering not only the use of the interpersonal relationship as a medical agent, but also a science of medicine that puts mind, body, and social environment into a theoretical framework of interrelations, with the perspective of integrating the different system levels. The translation processes among the system levels are, for example, addressed by biosemiotics (v. Uexküll).Both clinical medicine and medical research, if they intend to be psychosomatic, need to take these theoretical concepts into account and utilize them practically for (team)work with patients. Together with a clear differentiation from other cultures of (para)medicine, this can serve to develop a "psychosomatic identity."

Health-related quality of life (QoL) in breast cancer patients strongly depends on emotional well-being. QoL (EORTC-QLQ-C30), psychological distress (HADS), and patient's request for psycho-oncological care were assessed in 103 breast cancer patients during initial hospitalization. Clinical diagnoses according to ICD-10-F were made by clinical interview. As expected, both positive HADS screens (13) and clinical diagnoses of mental disorders were inversely related to QoL. However, in multivariate analysis of variance only positive HADS scores but not clinical diagnoses of mental disorders significantly predicted QoL. The performance of psychological screening instruments should therefore not only be judged by their ability to detect clinical diagnoses but also by their relevance for reflecting patients' QoL.

It has been suggested that patients with chronic HF and atrial fibrillation (AF) may respond differently to beta-blockers than those in sinus rhythm (SR).In this predefined analysis of the CIBIS-ELD trial, a total of 876 chronic HF patients (164 patients with AF) were randomized to bisoprolol or carvedilol. During the 12-week-treatment phase, beta-blockers were doubled fortnightly up to the target dose or maximally tolerated dose, which was maintained for 4 weeks.Patients with AF had lower left ventricular ejection fraction (LVEF), exercise capacity, self-rated health, quality of life (QoL) scores for both SF36 physical and psychosocial component, and higher NYHA class than those in SR. Beta-blocker titration was associated with clinical improvement in both AF and SR patients: LVEF, 6-minute walk distance, physical and psychosocial components of QoL scores, self-rated health and NYHA class (p0.05, for all). The extent of improvement did not differ between patients with AF and in SR and did not differ between bisoprolol and carvedilol. Heart rate (HR) at baseline was higher in the AF group, and remained higher until the end of the trial. Patients with higher baseline HR had larger reductions in HR, regardless of rhythm. AF patients more frequently reached target beta-blocker dose compared to those in SR (p0.005).Elderly patients with chronic HF and AF derive comparable clinical benefits from beta-blocker titration as those in SR. Patients with AF tolerate higher beta-blocker doses than those in SR, which appears to be related to higher baseline HR.

AIMS: Various beta-blockers with distinct pharmacological profiles are approved in heart failure, yet they remain underused and underdosed. Although potentially of major public health importance, whether one agent is superior in terms of tolerability and optimal dosing has not been investigated. The aim of this study was therefore to compare the tolerability and clinical effects of two proven beta-blockers in elderly patients with heart failure. METHODS AND RESULTS: We performed a double-blind superiority trial of bisoprolol vs. carvedilol in 883 elderly heart failure patients with reduced or preserved left ventricular ejection fraction in 41 European centres. The primary endpoint was tolerability, defined as reaching and maintaining guideline-recommended target doses after 12 weeks treatment. Adverse events and clinical parameters of patient status were secondary endpoints. None of the beta-blockers was superior with regards to tolerability: 24% [95% confidence interval (CI) 20-28] of patients in the bisoprolol arm and 25% (95% CI 21-29) of patients in the carvedilol arm achieved the primary endpoint (P= 0.64). The use of bisoprolol resulted in greater reduction of heart rate (adjusted mean difference 2.1 b.p.m., 95% CI 0.5-3.6, P= 0.008) and more, dose-limiting, bradycardic adverse events (16 vs. 11%; P= 0.02). The use of carvedilol led to a reduction of forced expiratory volume (adjusted mean difference 50 mL, 95% CI 4-95, P= 0.03) and more, non-dose-limiting, pulmonary adverse events (10 vs. 4%; P < 0.001). CONCLUSION: Overall tolerability to target doses was comparable. The pattern of intolerance, however, was different: bradycardia occurred more often in the bisoprolol group, whereas pulmonary adverse events occurred more often in the carvedilol group. This study is registered with controlled-trials.com, number ISRCTN34827306.

We sought to determine whether structured exercise training (ET) improves maximal exercise capacity, left ventricular diastolic function, and quality of life (QoL) in patients with heart failure with preserved ejection fraction (HFpEF).Nearly one-half of patients with heart failure experience HFpEF, but effective therapeutic strategies are sparse.A total of 64 patients (age 65 ± 7 years, 56% female) with HFpEF were prospectively randomized (2:1) to supervised endurance/resistance training in addition to usual care (ET, n = 44) or to usual care alone (UC) (n = 20). The primary endpoint was the change in peak Vo(2) after 3 months. Secondary endpoints included effects on cardiac structure, diastolic function, and QoL.Peak Vo(2) increased (16.1 ± 4.9 ml/min/kg to 18.7 ± 5.4 ml/min/kg; p0.001) with ET and remained unchanged (16.7 ± 4.7 ml/min/kg to 16.0 ± 6.0 ml/min/kg; p = NS) with UC. The mean benefit of ET was 3.3 ml/min/kg (95% confidence interval [CI]: 1.8 to 4.8, p0.001). E/e' (mean difference of changes: -3.2, 95% CI: -4.3 to -2.1, p0.001) and left atrial volume index (milliliters per square meter) decreased with ET and remained unchanged with UC (-4.0, 95% CI: -5.9 to -2.2, p0.001). The physical functioning score (36-Item Short-Form Health Survey) improved with ET and remained unchanged with UC (15, 95% CI: 7 to 24, p0.001). The ET-induced decrease of E/e' was associated with 38% gain in peak Vo(2) and 50% of the improvement in physical functioning score.Exercise training improves exercise capacity and physical dimensions of QoL in HFpEF. This benefit is associated with atrial reverse remodeling and improved left ventricular diastolic function. (Exercise Training in Diastolic Heart Failure-Pilot Study: A Prospective, Randomised, Controlled Study to Determine the Effects of Physical Training on Exercise Capacity and Quality of Life [Ex-DHF-P]; ISRCTN42524037).

Quality of life (QoL) is impaired in diastolic heart failure. Little is known about QoL in diastolic dysfunction (DD) without heart failure.In the DIAST-CHF observational study, outpatients with risk factors for or a history of heart failure were included. In a cross-sectional analysis, we classified patients with preserved systolic function as having normal diastolic function (N, n = 264) or DD without (DD-, n = 957) or with (DD+, n = 321) elevated filling pressures according to echocardiography. Quality of life was evaluated by the Short Form 36 (SF-36) questionnaire.Short Form 36 physical function (SF-36-PF) was worse in DD+ (mean ± SD 67.2 ± 25.6) than in DD- (76.2 ± 22.7, P.05) than in N (mean ± SD 81.1 ± 23.5, P.01). Other physical dimensions and the physical component score were also lower in DD, whereas the mental component score did not differ. The SF-36-PF correlated weakly with echocardiographic indicators of diastolic function. In multivariate linear regression controlling for age, sex, body mass index, depressiveness as assessed by Patient Health Questionnaire 9, N-terminal probrain-type natriuretic peptide, and midregional proadrenomedullin (MR-proADM), individual echocardiographic parameters or grade of DD was not independently associated with SF-36-PF, whereas the presence of DD+ was. Both N-terminal probrain-type natriuretic peptide and MR-proADM were independently associated with SF-36-PF, with MR-proADM showing the stronger association.Physical dimensions of QoL are reduced in DD. Impaired SF-36-PF is only weakly associated with DD per se but rather seems to be contingent on the presence of elevated filling pressures. Biomarkers are more strongly and independently associated with SF-36-PF and may be more adequate surrogate markers of QoL in DD than echocardiographic measurements.

To test the possibility of predicting psychotherapy outcome by measures of cardiovascular adaptability to stress at the beginning of treatment we used a prospective, within-subject design with experimental induction of short-term stress. Cardiovascular data during induced stress (mental arithmetic, anger recall) and relaxation were assessed in 21 patients with a main diagnosis of depression at the beginning of their 12-week inpatient psychotherapy treatment. Lower change scores in blood pressure during induced stress at the beginning of therapy were significantly related to better treatment outcome, accounting for 41% of variance, even after controlling for several covariates. Furthermore, there was evidence for the impact of negative affect. Using cardiovascular stress testing as an additional area of information seems a feasible method of incorporating biological parameters in psychotherapy evaluation.

Aims Heart failure with normal ejection fraction (HFnEF) is an important clinical entity that remains incompletely understood. The novel biomarker growth differentiation factor 15 (GDF-15) is elevated in systolic heart failure (HFrEF) and is predictive of an adverse outcome. We investigated the clinical relevance of GDF-15 plasma levels in HFnEF. Methods and results A subgroup of patients from the ongoing DIAST-CHF observational trial, with a history of chronic heart failure (CHF) or positive Framingham criteria at presentation, was selected. Patients were classified as having either HFrEF (n = 86) or HFnEF (n = 142) and compared with healthy elderly controls (n = 188) from the same cohort. Growth differentiation factor 15 levels in HFnEF were significantly higher than in controls and similar to those in HFrEF. In multivariate analysis, factors significantly associated with GDF-15 levels were age, sex, estimated glomerular filtration rate (eGFR), presence of HFrEF and HFnEF. Growth differentiation factor 15 correlated with multiple echocardiographic markers of diastolic function and was associated with 6 min walk test performance and SF-36 physical score on multivariate analysis in all patients. When using a classification for HFnEF that did not employ N-terminal pro brain natriuretic peptide (NT-proBNP) as a diagnostic criterion, the diagnostic properties of GDF-15 for detecting HFnEF tended to be superior to those of NT-proBNP, and a combination significantly improved diagnostic accuracy. Conclusion Growth differentiation factor 15 is elevated in HFnEF to a similar degree as in HFrEF. It is independently associated with impairment in exercise capacity and in physical components of quality of life. Diagnostic precision of GDF-15 is at least as good as that of NT-proBNP and combining both markers improves diagnostic accuracy.

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.The purpose of this study was to investigate the relationship between vital exhaustion and cytokine levels in patients with cardiovascular risk factors.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.We found that elevated serum concentrations of IL-6, TNFα, and IL-10, but not IL-1β 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].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.

Objectives. Despite its clinical importance and relevance for health care policy, the pathways between depression and stress regulation remain poorly understood. The objective of our study was to compare cardiovascular and autonomic responses to brief psychosocial stress in a group of severely depressed subjects without heart disease and a non-depressed controlgroup. Methods.We recorded cardiovascular and autonomic reactions to two different stress tasks including anger recall and mental arithmetic in a sample of 25 severely depressed and 25 non-depressed subjects. Aggregated data were compared with repeated-measures MANOVA. We used contrasts to evaluate different response patterns concerning cardiovascular and autonomic reactivity vs. recovery. Results. Depressed subjects showed overall reduced high-frequency heart rate variability and an altered cardiovascular adaptability concerning heart rate, blood pressure, cardiac output, and, on a trend level, peripheral resistance. With few exceptions, we found no differences between reactivity vs. recovery response patterns. Conclusions. Our results provide further evidence for altered cardiovascular reactivity and impaired cardiac autonomic functioning in depression. Further research is needed on psychophysiological response to either more disease-oriented or more personality-oriented stressors.

Aims/hypothesis Hyperglycaemia and insulin resistance have been linked to diastolic dysfunction experimentally. We investigated the association between glucose metabolism and diastolic function along the whole spectrum of glucose metabolism states. Methods In the observational Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Diastolic Heart Failure (DIAST-CHF) study, patients with risk factors for heart failure were included. We analysed data including comprehensive echocardiography from a subgroup of patients classified by OGTT and history as normal (n = 343), prediabetic (n = 229) and non-insulin treated (n = 335) or insulin-treated (n = 178) type 2 diabetic. Results While ejection fraction did not differ, markers of diastolic function significantly worsened across groups. Prediabetes represented an intermediate between normal glucose metabolism and diabetes with regard to echocardiography changes. Prevalence and severity of diastolic dysfunction increased significantly (p

AF : Atrial fibrillation ATP : Antitachycardia pacing CRT : Cardiac resynchronization therapy EHRA : European Heart Rhythm Association ES : Electrical storm HRS : Heart Rhythm Society ICD : Implantable cardiac defibrillator SCD : Sudden cardiac death SSRI : Selective serotonin receptor inhibitor VF : Ventricular fibrillation VT : Ventricular tachycardia This expert consensus aims to provide guidance for the management of patients receiving one or multiple shocks from an ICD. The document expresses the view of a multidisciplinary group of experts in the fields of general adult cardiology, ICD treatment, invasive electrophysiology, and psychosomatic medicine. A variety of clinical settings, including emergency medicine, general cardiology, and interventional electrophysiology, are addressed as well as the different groups of clinicians involved in the care of these patients. To cover different levels of expertise in ICD treatment, it is intended to provide comprehensive information ranging from a basic explanation of how an ICD works to specialist advice for device programming. Almost 30 years after the first human implants, ICD therapy has become the treatment of choice in patients at risk of developing malignant ventricular arrhythmias.1,2 Accordingly, the number of patients implanted with an ICD has increased substantially over the past decade,3 mainly as a consequence of the expansion of ICD indications into the field of primary prevention of SCD in patients with decreased left ventricular function. In 2008, ∼120 000 patients received an ICD worldwide.3 As a result of the growing number of ICD patients, ICD-related problems are increasingly encountered and patients with one or multiple shocks are to day frequently seen at emergency departments, hospital wards, or ICD clinics. Therefore, personnel working in these environments should have specific knowledge concerning the management of ICD-related problems. Table 1 summarizes the most common causes of ICD shocks. Trials reported appropriate therapies in 17–64% of patients, whereas inappropriate shocks, most often caused by supraventricular tachycardia, occurred in 10–24%.4 Among patients enrolled in primary prevention ICD trials, women experienced less appropriate ICD interventions than men.5 Modern device algorithms facilitate effective termination of VT without shock delivery by ATP, discrimination …

The Neck Pain and Disability Scale (NPAD) is a 20-item instrument to measure neck pain and related disability. The aim of this study was to assess sensitivity to change of the NPAD. A total of 411 participants from 15 general practices in the middle of Germany completed a multidimensional questionnaire including the German version of the NPAD and self-reported demographic and clinical information. Sensitivity to change was analysed by linear regression analysis of the NPAD at follow-up and educational level, age class, depression, anxiety, and deficits in social support, respectively, and by Pearson’s correlation analyses between mean change in NPAD at follow-up and mean change in prognostic markers. Those having more than basic education (regression coefficient −7.2, p

Depressive Heart Patients. How to Identify? How to Treat? Depressive symptoms or disorders are frequent comorbidities in patients with heart disease. They interact with heart disease via psychophysiological and behavioural pathways. Their impact on subjective and objective disease outcomes includes, among others, increased health care costs, early retirement and premature death from heart disease. For the detection of depression, a stepwise approach consisting of screening and, if positive, diagnostic interviews has been recommended. Both specific questions asked during history taking and self-rating questionnaires have been found useful as screening tools. Specific treatment options for depression include psychotherapy and – in severe or recurrent cases – antidepressant medication peerReviewed

Aims The diagnostic value of natriuretic peptides in asymptomatic patients at risk for diastolic or systolic HF is controversial. We tested (1) the prevalence of preclinical LV dysfunction in an at-risk cohort; (2) the diagnostic accuracy of natriuretic peptides alone or in combination with clinical parameters for predicting asymptomatic left ventricular systolic or diastolic dysfunction. Methods 542 primary care patients (mean age 63 ± 11 years, 42% female) without prediagnosed HF, but with risk factors for left ventricular dysfunction, underwent thorough cardiological workup, including echocardiography and analysis of natriuretic peptides. Results 23 patients (4%) showed reduced systolic function (EF

Objective: Psychosocial symptoms are common in patients with heart failure. Little research, however, has been done to determine which psychosocial factors influence primary care patients’ consultation frequency in the case of heart failure. Methods: We recruited 310 primary care patients with heart failure by analysing electronic patient records. At baseline, psychological distress (anxiety and depression; HADS), disease coping (FKV), negative affectivity and social inhibition (DS-14), disease-specific quality of life (MLHFQ) and social support (F-SozU) were measured by validated questionnaires. Severity of heart failure (according to NYHA-classification and Goldman’s Specific Activity Scale) and sociodemographic characteristics were documented by self-report instruments. Nine month later, patients were contacted by telephone in order to assess GP consultation frequency. Logistic regression was done to determine whether these psychological, medical and sociodemographic factors were associated with primary care utilisation. Results: On average, patients consulted their general practitioner (GP) 8.2 times during nine months. Female subjects and patients with higher levels of perceived heart failure severity, physical problems and anxiety or depression as well as those living alone visited their GP significantly more often. In multivariate analysis, frequent attendance in general practices was predicted by physical problems and living alone. These factors explained 11.6% of the variance of frequent attendance in general practices. Conclusion: Psychosocial factors of help-seeking behaviour in heart failure patients focus on mental and physical discomfort and a lonely home situation. These factors might need to be compensated by GP consultation. GPs should address the rearrangement of physical, mental, and social resources to strengthen self-reliance of patients with heart failure.

Previous evaluations of the 20-item Neck Pain and Disability Scale (NPAD) were indicative of excessive redundancy of the measure. The aim of this study was to develop a shortened version of the NPAD (sf-NPAD) based on results of item-to-total-score correlations and factor analysis as published by the developers of the original NPAD. Two items with the highest item-to-total score correlation were selected per factor subscale with the exception of one factor consisting of only one item. This resulted in the selection of 9 items for the sf-NPAD. The sf-NPAD was validated in a separate sample of 448 neck pain patients from 15 general practices in the area of Gottingen/Germany. Participants completed the 20-item NPAD German version and gave additional sociodemographic and clinical information. Psychometric properties of the sf-NPAD were evaluated using Cronbach's alpha, item-to-total-score correlation, and unrestricted principal factor analysis. Construct validity was evaluated by Pearson's r with clinical characteristics. Discriminative validity was examined by comparing differences between subgroups stratified by psychosocial characteristics using t-tests for mean scores. Cronbach's alpha of the sf-NPAD was 0.88. Item-to-total-scale correlations ranged between 0.628 and 0.815, and sf-NPAD items homogeneously loaded on a single factor. Correlation analysis showed high correlations with criterion variables. The sf-NPAD scores of patient subgroups were significantly different showing good discriminative validity. In conclusion, the sf-NPAD demonstrated good validity and internal consistency in this general practice setting. The abbreviated version may facilitate applicability of the scale in clinical and research settings.

Quality of life is an important patient-centered outcome and predictor of mortality in heart failure, but little is known about the role of personality as a determinant of quality of life in this patient group. We examined the influence of Type D personality (i.e., increased negative emotions paired with emotional non-expression) on quality of life in primary care heart failure patients, using a prospective study design. Heart failure patients (n = 251) recruited from 44 primary care practices in Germany completed standardized questionnaires at baseline and 9 months. The prevalence of Type D was 31.9%. Type D patients experienced poorer emotional (P < .001) and physical quality of life (P = .01) at baseline and 9 months compared to non-Type D patients. There was no significant change in emotional (P = .78) nor physical quality of life (P = .74) over time; neither the interaction for time by Type D for emotional (P = .31) nor physical quality of life (P = .91) was significant, indicating that Type D exerted a stable effect on quality of life over time. Adjusting for demographics, New York Heart Association functional class, and depressive symptoms, Type D remained an independent determinant of emotional (P = .03) but not physical quality of life (P = .29). Primary care heart failure patients with a Type D personality experienced poorer emotional but not physical quality of life compared to non-Type D patients. Patients with this personality profile should be identified in primary care to see if their treatment is optimal, as both Type D and poor quality of life have been associated with increased morbidity and mortality. peerReviewed

The aim of this health service research study was to investigate the change in the psychological distress of cancer in-patients. According to the structured psychooncological care program Case Management Psychoonkologie (CMP) the patients received psychological treatment during the acute cancer therapy. The CMP was implemented in routine healthcare practice of 6 hospitals. The improvement in the patient's symptoms of anxiety and depression was analyzed as an indication for the effectiveness of the CMP. In order to assess the psychological distress, quality of life, and the functional status the German version of the Hospital Anxiety and Depression Scale (HADS) and a checklist of single-item-scales were administered at hospital admission (t1), 120 days later (t2) and one year after the hospital admission (t3). According to the HADS, the pre-post effect sizes of the psychooncological care program for 258 patients were 0.35 at t2 and 0.46 at t3. The effect sizes of 1.05 at t2 and 1.38 at t3 were calculated for the sub-group of patients with high psychological distress at t1. In 34.4 % of these patients clinical significant improvements in symptoms of anxiety and depression could be identified at t2 and in 45.3 % of the cases at t3. Symptom changes were significantly influenced by the patient's age and the intensity of psychooncological interventions. Symptom improvement was most evident for patients with a high use of psychooncological care. The correlation between HADS and single Item scales is in the moderate to high range. This is an indication of improvement not only in the psychological domain but also in the quality of life and functional status one year after the beginning of cancer treatment. These findings implicate that this study is one of the first to demonstrate the potential effectiveness of structured psychooncological care interventions in routine hospital care.

Die chronische Herzinsuffizienz ist eine typische somatopsychisch-psychosomatische Erkrankung, in der die korperliche Funktionsstorung auf dem Wege ihrer psychischen (Fehl-)Verarbeitung ihre subjektive Bedeutung erhalt. Beispielsweise ist die Lebensqualitat von Patienten mit Herzinsuffizienz durchschnittlich erheblich eingeschrankt; einen wesentlichen Anteil an dieser Einschrankung hat dabei eine komorbide psychische Problematik. Auch fur die Prognose spielen psychische bzw. psychosoziale Faktoren eine wichtige Rolle. So ist wie bei KHK-Patienten auch fur herzinsuffiziente Patienten eine erhohte Mortalitat beim gleichzeitigen Vorliegen erhohter Depressivitat bzw. schlechter subjektiver Lebensqualitat wiederholt beschrieben worden. Auch Verhaltensfaktoren spielen eine wichtige prognostische Rolle (s. u.).

Background Screening of primary care patients at risk for left ventricular systolic dysfunction by a simple blood-test might reduce referral rates for echocardiography. Whether or not natriuretic peptide testing is a useful and cost-effective diagnostic instrument in primary care settings, however, is still a matter of debate. Methods N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, clinical information, and echocardiographic data of left ventricular systolic function were collected in 542 family practice patients with at least one cardiovascular risk factor. We determined the diagnostic power of the NT-proBNP assessment in ruling out left ventricular systolic dysfunction and compared it to a risk score derived from a logistic regression model of easily acquired clinical information. Results 23 of 542 patients showed left ventricular systolic dysfunction. Both NT-proBNP and the clinical risk score consisting of dyspnea at exertion and ankle swelling, coronary artery disease and diuretic treatment showed excellent diagnostic power for ruling out left ventricular systolic dysfunction. AUC of NT-proBNP was 0.83 (95% CI, 0.75 to 0.92) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.46 (95% CI, 0.41 to 0.50). AUC of the clinical risk score was 0.85 (95% CI, 0.79 to 0.91) with a sensitivity of 0.91 (95% CI, 0.71 to 0.98) and a specificity of 0.64 (95% CI, 0.59 to 0.67). 148 misclassifications using NT-proBNP and 55 using the clinical risk score revealed a significant difference (McNemar test; p < 0.001) that was based on the higher specificity of the clinical risk score. Conclusion The evaluation of clinical information is at least as effective as NT-proBNP testing in ruling out left ventricular systolic dysfunction in family practice patients at risk. If these results are confirmed in larger cohorts and in different samples, family physicians should be encouraged to rely on the diagnostic power of the clinical information from their patients.

Psychological distress is a common phenomenon in patients with heart failure. Depressive symptoms are often under-diagnosed or inadequately treated in primary care.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.Longitudinal observation study.Primary care practices in lower Saxony, Germany.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.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.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.

Guidelines and Expert Consensus Documents summarize and evaluate all currently available evidence on a particular issue with the aim to assist physicians in selecting the best management strategies for a typical patient, suffering from a given condition, taking into account the impact on outcome, as well as the risk–benefit ratio of particular diagnostic or therapeutic means. Guidelines are not substitutes for textbooks. The legal implications of medical guidelines have been discussed previously. A great number of Guidelines and Expert Consensus Documents have been issued in recent years by the European Society of Cardiology (ESC) as well as by other societies and organizations. Because of the impact on clinical practice, quality criteria for development of guidelines have been established in order to make all decisions transparent to the user. The recommendations for formulating and issuing ESC Guidelines and Expert Consensus Documents can be found on the ESC web site (http://www.escardio.org/knowledge/guidelines/rules). In brief, experts in the field are selected and undertake a comprehensive review of the published evidence for management and/or prevention of a given condition. A critical evaluation of diagnostic and therapeutic procedures is performed, including assessment of the risk–benefit ratio. Estimates of expected health outcomes for larger societies are included, where data exist. The level of evidence and the strength of recommendation of particular treatment options are weighed and graded according to predefined scales, as outlined in the tables below. The experts of the writing panels have provided disclosure statements of all relationships they may have which might be perceived as real or potential sources of conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. Any changes in conflict of interest that arise during the writing period must be notified to the ESC. The Task Force report was entirely …

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.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.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; p0.001) 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; p0.001], coping by dissimulation and wishful thinking [FKV; p = 0.027], HF severity [NYHA, Goldman;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.

Objective The implantable cardioverter defibrillator (ICD) has been proven to prolong the lives of patients with life-threatening ventricular arrhythmia. However, implant recipients must cope with numerous challenges. We studied the effects of specific coping strategies and the adaptability of coping in ICD implant recipients. Method This prospective study investigated the subjective well-being and objective disease course in 180 patients with life-threatening cardiac arrhythmias, who were recruited while awaiting implantation of a cardioverter defibrillator. Patients completed well-validated self-assessment questionnaires before implantation (T0), as well as 3 months (T1) and 1 year (T2) after implantation. In addition, cardiological findings were documented. Results Depressive coping (range Beta, −0.36 to −0.58) was found to be a stable highly-significant predictor for low emotional well-being and quality of life. Active problem-oriented coping showed small positive influence (range Beta, 0.10 to 0.19). Employing a broad range of coping strategies was predictive of less emotional distress and better quality of life. Conclusions Depressive coping is a risk factor for emotional distress and poor quality of life after ICD implantation. Patients with this tendency should be identified early and offered supportive psychotherapy.

Recently, it has been shown that substitution of alanine for phenylalanine 77 in the N-domain of STAT1 (signal transducer and activator of transcription (1) prevents cooperative binding of tetramers on DNA and severely impairs transcriptional responses upon stimulation of cells with interferon-gamma (IFN-gamma). Cooperative DNA binding is the basis of efficient switching between non-occupied and occupied promoter states. In this study, we generated N-terminal mutants of STAT1 which showed improved tetramer stability on DNA. We identified two negatively charged N-terminal residues in each protomer of dimeric STAT1 which are required for the dissociation of higher-order oligomers on DNA. Similarly to the STAT1 mutant with impaired tetramerization, these N-terminal mutants showed elevated tyrosine-phosphorylation levels and prolonged nuclear accumulation upon stimulation of cells with IFN-gamma. Unlike the global impairment of IFN-gamma signalling in the tetramerization-deficient mutant, improved tetramer stability of the N-terminal mutants affected transcription in a promoter-specific manner and resulted in a distinct gene expression pattern. In summary, using these mutants we have gained a new mechanistic insight into how protein-DNA interactions regulate STAT1-mediated target gene recognition. While one side of the N-terminal dimer is crucial for the formation of tetrameric complexes on IFN-gamma-regulated promoters, the other side localized in close contact to the longitudinal axis of DNA has a rather inhibitory effect on the formation of higher-order oligomers, simply by disrupting cooperative DNA binding.