Biomarkers in outpatient heart failure management; Are they correlated to and do they influence clinical judgment?

AIMS: Heart failure (HF) management is complicated by difficulties in clinical assessment. Biomarkers may help guide HF management, but the correspondence between clinical evaluation and biomarker serum levels has hardly been studied. We investigated the correlation between biomarkers and clinical signs and symptoms, the influence of patient characteristics and comorbidities on New York Heart Association (NYHA) classification and the effect of using biomarkers on clinical evaluation. METHODS AND RESULTS: This post-hoc analysis comprised 622 patients (77 ± 8 years, 76 % NYHA class ≥3, 80 % LVEF ≤45 %) participating in TIME-CHF, randomising patients to either NT-proBNP-guided or symptom-guided therapy. Biomarker measurements and clinical evaluation were performed at baseline and after 1, 3, 6, 12 and 18 months. NT-proBNP, GDF-15, hs-TnT and to a lesser extent hs-CRP and cystatin-C were weakly correlated to NYHA, oedema, jugular vein distension and orthopnoea (ρ-range: 0.12-0.33; p < 0.01). NT-proBNP correlated more strongly to NYHA class in the NT-proBNP-guided group compared with the symptom-guided group. NYHA class was significantly influenced by age, body mass index, anaemia, and the presence of two or more comorbidities. CONCLUSION: In HF, biomarkers correlate only weakly with clinical signs and symptoms. NYHA classification is influenced by several comorbidities and patient characteristics. Clinical judgement seems to be influenced by a clinician's awareness of NT-proBNP concentrations.

Prognostic impact of systemic inflammatory diseases in elderly patients with congestive heart failure.

BACKGROUND AND AIMS: Inflammation is part of the pathophysiology of congestive heart failure (CHF). However, little is known about the impact of the presence of systemic inflammatory disease (SID), defined as inflammatory syndrome with constitutional symptoms and involvement of at least two organs as co-morbidity on the clinical course and prognosis of patients with CHF. METHODS AND RESULTS: This is an analysis of all 622 patients included in TIME-CHF. After an 18 months follow-up, outcomes of patients with and without SID were compared. Primary endpoint was all-cause hospitalization free survival. Secondary endpoints were overall survival and CHF hospitalization free survival. At baseline, 38 patients had history of SID (6.1%). These patients had higher N-terminal pro brain natriuretic peptide and worse renal function than patients without SID. SID was a risk factor for adverse outcome [primary endpoint: hazard ratio (HR) = 1.73 (95% confidence interval: 1.18-2.55, P = 0.005); survival: HR = 2.60 (1.49-4.55, P = 0.001); CHF hospitalization free survival: HR = 2.3 (1.45-3.65, P < 0.001)]. In multivariate models, SID remained the strongest independent risk factor for survival and CHF hospitalization free survival. CONCLUSION: In elderly patients with CHF, SID is independently accompanied with adverse outcome. Given the increasing prevalence of SID in the elderly population, these findings are clinically important for both risk stratification and patient management.

Improved two-year outcomes after drug-eluting versus bare-metal stent implantation in women and men with large coronary arteries: importance of vessel size.

OBJECTIVES: To investigate the importance of vessel size on outcome differences by comparing the effects of drug-eluting stents (DES) versus bare-metal stents (BMS) in women and men with large coronary vessels. METHODS: All 2314 BASKET-PROVE patients randomized to DES versus BMS were followed for 2 years with a primary endpoint of major adverse cardiac events (MACE: cardiac death, non-fatal myocardial infarction, target-vessel revascularization). Cox proportional hazard models were used to evaluate the relative risk for women and men, respectively. All comparisons were adjusted for vessel size. RESULTS: Age, risk factors and complexity of coronary artery disease differed between women and men. DES reduced MACE rates at 2 years compared to BMS--in women: 4% vs. 15%, p<0.0001 with a hazard ratio (HR) of 0.27 (0.15-0.51), and men: 6% vs. 10%, p=0.003 (HR=0.60 (0.43-0.84)), respectively. The association persisted in both women (HR=0.25 (0.13-0.46)) and men (HR=0.60 (0.42-0.84)) following multivariable adjustments. A significant gender-treatment interaction was present (p=0.02). The reduced risk of MACE following DES vs. BMS implantation was present until 6 months in both women (HR=0.15 (0.06-0.36)) and men (HR=0.32 (0.17-0.59)) and remained significant until 2 years in women (HR=0.36 (0.15-0.87)), but not in men (HR=0.87 (0.49-1.55)). CONCLUSIONS: In women and men with similarly sized large coronary arteries, DES reduced 2-year MACE rates compared to BMS, but the significant gender-treatment interaction indicated a greater benefit of DES in women. Thus, factors other than vessel size seem to determine this gender difference.

[Consensus for the identification of geriatric patients in the emergency care setting in Germany]. / Positionspapier zur Identifizierung geriatrischer Patienten in Notaufnahmen in Deutschland: consensus for the identification of geriatric patients in the emergency care setting in Germany.

For the treatment of geriatric inpatients, the efficacy of a multimodal geriatric intervention based on findings of a comprehensive geriatric assessment has well been established. Therefore, the focus of elderly inpatient care switched to the identification of geriatric patients who have unintended or unscheduled contact to an accident and emergency department. In Germany, a uniform standard on how to correctly identify geriatric patients in such settings has yet to be established.Three medical societies, the Federal Association of Geriatrics ("Bundesverband Geriatrie", BVG), the German Society for Gerontology and Geriatrics ("Deutsche Gesellschaft für Gerontologie und Geriatrie", DGGG) and the German Geriatrics Society ("Deutsche Gesellschaft für Geriatrie", DGG) have reached a consensus on tools and instruments for the identification of geriatric patients in the emergency care setting. Basis of the consensus were the existing scientific evidence and further considerations, especially the applicability of international findings in Germany and feasibility.Three recommendations are made: (1) The use of prognostic indices is not recommended, as prognostic indices appear to be inappropriate to disclose the complex needs of geriatric patients. (2) Comprehensive geriatric assessment is established and effective, but too complex for use in the emergency setting. It is recommended for cases in which information from screening instruments or other sources does not allow a clear decision. (3) Among screening instruments, the Identification of Seniors At Risk (ISAR) screening tool seems to be well established and suitable for screening purposes in Germany. A German adaption is recommended as well as the implementation in settings where no other tools or geriatric expertise are available.

[Palliative care for patients with dementia]. / Palliativversorgung von Menschen mit Demenz.

Patients with dementia are an important target group for palliative care since particularly in advanced stages and at the end of life they often have complex health care and psychosocial needs. However, people with dementia have inappropriate access to palliative care. So far, palliative care focuses on cancer patients. Among other reasons, this is due to the different illness trajectories: while in cancer a relatively clear terminal phase is typical, in dementia functional decline is gradual without a clear terminal phase, making advanced care planning more difficult. Good communication among health care providers and with the patient and his/her family is essential to avoid unnecessary or even harmful interventions at the end of life (e.g., inserting a percutaneous endoscopic gastrostomy, PEG). To maintain the patient's autonomy and to deliver health care according to the individual preferences, it is important to appropriately inform the patient and the family at an early stage about the disease and problems that may occur. In this context, advanced directives can be helpful.

Combined clopidogrel and proton pump inhibitor therapy is associated with higher cardiovascular event rates after percutaneous coronary intervention: a report from the BASKET trial.

OBJECTIVE: To investigate whether there is an increased risk of cardiac events with a combined therapy of clopidogrel and proton pump inhibitors (PPIs) after percutaneous coronary intervention (PCI). DESIGN: In the BAsel Stent Kosten Effektivitäts Trial (BASKET), all patients undergoing PCI received 6 months of clopidogrel and were analysed for the use of PPI therapy. Endpoints were major adverse cardiac events (MACE), myocardial infarction (MI), death and target vessel revascularization (TVR) after 36 months. RESULTS: Of 801 patients with available discharge medication data, 109 (14%) received PPIs. Patients who received PPIs were older (66.5 ± 10.5 vs. 63.3 ± 11.3 years, P = 0.006), more likely to be woman (80% vs. 69%, P = 0.009) and have a history of diabetes (29.6% vs. 17.3%, P = 0.002) or gastrointestinal ulcer disease (8.3% vs. 3.3%, P = 0.015) and more often received nonsteroidal anti-inflammatory drugs (7.3% vs. 2.2%, P = 0.003) and corticosteroids (11% vs. 3.6%, P = 0.001) but not aspirin (91.7% vs. 97%, P = 0.008) compared with those who did not receive PPIs. Patients who received PPI therapy had higher rates of MACE (30.3% vs. 20.8%, P = 0.027) and MI (14.7% vs. 7.4%, P = 0.01) but similar rates of death (9.2% vs. 7.4%, P = 0.51) and TVR (20.2% vs. 15.3%, P = 0.2) compared with those who did not. By multivariate analysis, diabetes (hazard ratio 1.83, 95% confidence interval 1.07-3.15) and PPI use (hazard ratio 1.88, 95% confidence interval 1.05-3.37) were the only independent risk factors for MI. CONCLUSION: In a real-world PCI population, the combination of PPIs and clopidogrel was associated with a doubling of MI rates after 3 years. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of outcome emphasizing the clinical importance of this drug-drug interaction.

Primary PCI in STEMI--dilemmas and controversies: multivessel disease in STEMI patients. Complete versus Culprit Vessel revascularization in acute ST--elevation myocardial infarction.

The best strategy regarding percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) in multivessel disease is an unresolved issue. Although current guidelines recommend that PCI in non-culprit arteries should not be attempted unless the patient is hemodynamically unstable, it is unclear whether PCI of the infarct-related artery only or a strategy of complete revascularization, either in a simultaneous or staged multivessel PCI approach, will improve outcome. Based on available data, PCI of the culprit lesion has the advantages of shorter procedure duration, a smaller amount of dye used, and a lower rate of periprocedural myocardial infarctions, while complete revascularization has lower rates of recurrent angina and a better left ventricular ejection fraction. Although data available give controversial results for the right strategy to choose, the only adequately powered randomized controlled trial shows that a strategy of multivessel PCI should be pursued notwithstanding the timing of complete revascularization. However, to avoid the potential risks of simultaneous multivessel PCI, a strategy of staged complete revascularization appears to be the best choice. It should be considered whether current guidelines should be changed to account for these considerations, and other adequately powered randomized controlled trials should be performed to endorse current knowledge.

Palliative care for the geriatric patient in Europe. Survey describing the services, policies, legislation, and associations.

BACKGROUND: Knowledge about the quality of end-of-life care in the elderly patient in Europe is fragmented. The European Union Geriatric Medicine Society (EUGMS) Geriatric Palliative Medicine (GPM) Interest Group set as one of its goals to better characterize geriatric palliative care in Europe. OBJECTIVE: The goal of the current study was to map the existing palliative care structures for geriatric patients, the available policies, legislation, and associations in geriatric palliative medicine in different countries of Europe. METHODS: A questionnaire was sent to Geriatric and Palliative Medicine Societies of European countries through contact persons. The areas of interest were (1) availability of services for the management of geriatric patients by using vignette patients (advanced cancer, severe cardiac disease, and severe dementia), (2) policies, legislation of palliative care, and (3) associations involved in geriatric palliative medicine. RESULTS: Out of 21 countries contacted, 19 participated. Palliative care units and home care palliative consultation teams are available in most countries. In contrast, palliative care in long-term care facilities and in geriatric wards is less developed. A disparity was found between the available services and those most appropriate to take care of the three cases described in the vignettes, especially for the patient dying from non-malignant diseases. The survey also demonstrated that caregivers are not well prepared to care for the elderly palliative patient at home or in nursing homes. CONCLUSION: One of the challenges for the years to come will be to develop palliative care structures adapted to the needs of the elderly in Europe, but also to improve the education of health professionals in this field.

[Palliative geriatrics. What are the differences between oncologic and non-oncologic palliative geriatric inpatients?]. / Palliative Geriatrie. Wie unterscheiden sich onkologische von nichtonkologischen geriatrischen Palliativpatienten im Krankenhaus?

AIM OF THE STUDY: Analysis of differences between oncologic and non-oncologic patients in the first German hospital-based special care unit for palliative geriatrics. METHODS: Systematic analysis of patients' records according to a standardized protocol. RESULTS: A total of 217 patients from a hospital-based special care unit for palliative geriatrics (56.7% women, 43.4% men) were included over a retrospective period of 1.5 years. Patients were categorized as non-oncologic (53.4%, n=116) or oncologic (46.5%, n=101). Non-oncologic patients were older than oncologic patients (84.0 vs. 76.8 years, p=0.02), and showed a higher degree of functional dependence (p<0.001) and mortality (87.1% vs. 53.3%, p<0.001). The two most common non-oncologic categories of primary diagnoses were pulmonary and neurologic diseases: 19% each. Certain secondary diagnoses had a higher incidence with non-oncologic than oncologic patients, such as pulmonary disease (39% vs. 24%, p=0.02) and dementia (38% vs. 8%, p<0.001). The Charlson comorbidity index was found to be higher for oncologic patients than for non-oncologic patients (6.6 vs. 4.1, p=0.001). Non-oncologic patients also experienced more dysphagia (57% vs. 17%, p<0.001), NPO (43% vs. 12%, p<0.001), and tube or parenteral feeding (31% vs. 9%, p=0.001). Oncologic patients experienced more often symptoms of pain, constipation, agitation, diarrhea, vomiting, and nausea. CONCLUSION: There are clinically relevant differences between oncologic and non-oncologic palliative geriatric inpatients regarding the constellation of symptoms, care, mortality, and the prevalence of concerns about hydration and feeding. These differences ought to be taken into account for further education, as well as further improvement of the healthcare system, to enable an appropriate standard of palliative care for geriatric patients.

Benefit of angiographic spontaneous reperfusion in STEMI: does it extend to diabetic patients?

BACKGROUND: Spontaneous reperfusion (SR) in ST elevation myocardial infarction (STEMI) improves clinical outcome, yet its incidence and impact among diabetic patients is unclear. OBJECTIVE: To carry out a systematic analysis of SR in the diabetic cohort of a large primary percutaneous coronary intervention (PCI)-treated population with STEMI. METHODS AND RESULTS: 4944 patients (15.5% diabetic) undergoing primary PCI in the APEX AMI study were evaluated. SR defined as pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow occurred in 11.5% of patients; it was more common in non-diabetic (11.9%) than in diabetic patients (9.2%) (p = 0.028). Patients with SR versus no SR had improved post-PCI TIMI 3 flow: in non-diabetic patients (99.8% vs 90.3%, p<0.001) and in diabetic patients (98.6% vs 84.9%, p<0.001). Non-diabetic patients with SR showed a significant improvement in 90-day death/shock/congestive heart failure (CHF) compared with those without SR: 4.4% versus 8.9% (p = 0.001), respectively. The composite outcome in diabetic patients with versus without SR was 10.0% versus 14.9% (p = 0.270), respectively. When outcomes were examined according to tertiles of baseline blood glucose, both non-diabetic and diabetic patients with normoglycaemia showed higher SR rates (15.5%, 10.3%, 7.3% for non-diabetic patients, p<0.001; 17.4%, 7.2%, 9.1% for diabetic patients, p = 0.132), greater ST resolution (55.4%, 52.6%, 49.7% for non-diabetic patients, p = 0.030; 50%, 46.4%, 39.1% for diabetic patients, p = 0.179), and improved 90-day death/shock/CHF (5.2%, 8.3%, 14% for non-diabetic patients p<0.001; 8.7%, 4.2%, 15.8% for diabetic patients, p = 0.006). CONCLUSIONS: These data indicate that SR is less common in diabetic patients with STEMI. Diabetic patients without SR have worse post-PCI epicardial patency, which contributes to adverse outcomes. Diabetic patients with normal baseline blood glucose and SR have enhanced epicardial flow after PCI and improved prognosis.

Repressive coping in geriatric patients' reports - impact on fear of falling.

We investigated the influence of repressive coping, depression, cognition, education and age on geriatric patients' reports on health-related status in 80 geriatric patients with a history of injurious falls. For patient reports, subjective statements on activity avoidance, perception of terminal decline, falls, and fear of falling were assessed. Co-morbidity and number of medications were documented based on patient charts. Repressive coping was significantly associated with underreporting in geriatric patients in all items documented and predicted most variables of patients' reports. Because of underreporting significant health problems geriatric patients with repressive coping may therefore be at risk for inadequate medical treatment.

[Situation of nursing home residents with continence problems: a study in two German nursing homes]. / Die Situation von PflegeheimbewohnerInnen mit Kontinenzproblemen: eine Studie in 2 deutschen Pflegeheimen.

AIM OF THE STUDY: To describe the situation of residents with continence problems (CP) in two German nursing homes. METHODS: Medical and nursing records of all residents were reviewed and categorised according to a standardised protocol. Structured interviews were performed with the responsible nursing staff of each resident. Qualitative methods like focus groups and participating observations were used to collect further information. RESULTS: In the investigated nursing homes 177 residents with and 70 without CP were identified (81.5% women; mean age 83.7 years). For these 247 residents 57 physicians and 116 nurses or nurses-aides were in charge. 71% of female and 76% of male residents had at least one CP. The three most common CP among residents were combined urinary and faecal incontinence (32%), urinary incontinence (21%), and urinary catheters (17%). Residents with CP were significantly more dependent in functional abilities like toileting, dressing or cognitive function than those without CP (P<0.01). In a high proportion of residents with CP physicians (64%) were not consulted nor were relatives (86%) involved in continence related activities. CONCLUSION: Nursing home residents are commonly affected by continence problems which are associated with functional dependency and relevant co-morbidity. The public and expert debate on continence problems of nursing home residents has to be promoted to achieve long-term changes.

Improvements in physical and mental domains of quality of life by anti-ischaemic drug and revascularisation treatment in elderly men and women with chronic angina.

BACKGROUND: The severity of angina is related to a reduction in global quality of life (QoL), which may be improved by anti-ischaemic treatment. It is not known, however, whether improvements relate only to physical or also to mental and social domains of QoL and whether women benefit in a similar way to men. OBJECTIVES: To relate improvements in angina severity through anti-ischaemic treatment to physical and mental domains of QoL in elderly men and women and to assess differences in this relation between the sexes. METHODS: Angina severity and full assessment of QoL by structured, self-administered and validated questionnaires were measured prospectively at baseline and after 6 months' optimal drug or revascularisation treatment in all 301 patients of the Trial of Invasive versus Medical therapy in Elderly (TIME) patients with chronic angina. RESULTS: At baseline, angina severity correlated significantly with physical domains of QoL (trend test at least p<0.02) and daily activities (p = 0.05). At similar angina levels, women had significantly lower QoL scores than men. With anti-ischaemic treatment, physical as well as mental and social QoL domains and daily activities improved, together with a relief in angina (trend tests at least p<0.02). This was true for women and men and was more pronounced after revascularisation than with medical treatment. CONCLUSIONS: These findings confirm the relation between angina severity and physical limitation. In addition, they show that anti-ischaemic treatment not only relieves angina and improves physical components of QoL but also improves mental and social domains. This is true for women as well as for men despite the lower overall scores for women.

Impact of contemporary emergency percutaneous coronary angioplasty for acute myocardial infarction on length of hospital stay.

QUESTIONS UNDER STUDY: Compared to thrombolysis, acute percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) allows both immediate revascularisation and identification of additional relevant stenosis, so that subsequently no further risk stratification should be necessary and hospital stay shortened. Our aim was to evaluate the impact of PCI on outcome and length of hospital stay after MI compared to that in the thrombolysis era. METHODS: Retrospective evaluation in a Swiss tertiary referral centre of 105 patients with AMI undergoing emergency PCI, who initially were neither in cardiogenic shock nor transferred to another primary or secondary care hospital for further treatment. Main outcome measurement was length of overall hospital stay. Additional measurements included mortality, left ventricular function, and time point of the last major adverse cardiac event (MACE). RESULTS: Overall hospitalisation time was 11.1 +/- 6.8 days, thus being only 1.5 days shorter than in the thrombolysis era. Age above 70 or type of infarction did not influence hospitalisation time, but age below 60 years did. In-hospital mortality was 1%. Left-ventricular function was considerably impaired (<35%) in 6 patients. After the sixth hospital day, 97% of MACE had occurred. According to a validated risk score, 92% of patients belonged to a low risk group with a 30-day mortality risk of 1.4% or less and could have been discharged not later than day 6. CONCLUSIONS: Our data suggest that an early discharge strategy, although safe in low risk patients is not followed at the present time. This approach could further reduce costs without jeopardizing outcome.

["HAART-attack" in young female HIV-patient]. / "HAART-Attack" bei junger HIV-Patientin.

Since the implementation of highly active antiretroviral therapy (HAART) there is a dramatic decline in morbidity and mortality due to reduction of opportunistic infections in HIV-infected patients resulting in improved prognosis. Unfortunately, patients receiving HAART are at risk for metabolic complications, which may induce the development of coronary artery and cerebrovascular disease, particularly in young patients and in the presence of additional cardiovascular risk factors. A 30-years old female HIV-infected patient who developed an acute myocardial infarction is described.

Rationale and design of ACTIVE: the atrial fibrillation clopidogrel trial with irbesartan for prevention of vascular events.

BACKGROUND: Atrial fibrillation (AF) is the most frequently occurring cardiac arrhythmia with often serious clinical consequences. Many patients have contraindications to anticoagulation, and it is often underused in clinical practice. The addition of clopidogrel to aspirin (ASA) has been shown to reduce vascular events in a number of high-risk populations. Irbesartan is an angiotensin receptor-blocking agent that reduces blood pressure and has other vascular protective effects. METHODS AND RESULTS: ACTIVE W is a noninferiority trial of clopidogrel plus ASA versus oral anticoagulation in patients with AF and at least 1 risk factor for stroke. ACTIVE A is a double-blind, placebo-controlled trial of clopidogrel in patients with AF and with at least 1 risk factor for stroke who receive ASA because they have a contraindication for oral anticoagulation or because they are unwilling to take an oral anticoagulant. ACTIVE I is a partial factorial, double-blind, placebo-controlled trial of irbesartan in patients participating in ACTIVE A or ACTIVE W. The primary outcomes of these studies are composites of vascular events. A total of 14000 patients will be enrolled in these trials. CONCLUSIONS: ACTIVE is the largest trial yet conducted in AF. Its results will lead to a new understanding of the role of combined antiplatelet therapy and the role of blood pressure lowering with an angiotensin II receptor blocker in patients with AF.

[Pain killers--killing the pain or the patient?]. / Nichtsteroidale Antirheumatika und Coxibe--die sanften Herzensbrecher?

Over the last years, the coxibes were widely used as potent and well tolerated pain killers. This was in part due to the better gastrointestinal tolerability of the coxibes. On the other hand the higher cox-2 selectivity is consistent with a higher cardio-vascular event rate in patients with coxibe therapy which has been demonstrated by several studies. Side effects are probably caused by the interaction of the following factors: impact on thrombocytes, coagulation, blood vessel physiology, and blood pressure. Of note, the reported cardio-vascular adverse event rates in trials evaluating coxibes and older non-steroidal anti-inflammatory drugs was very low. Furthermore, there were no difference in fatal event rates. This underscores the need to carefully deliberate about the beneficial and potentially harmful use of these drugs. In daily practice it therefore might be suitable to still use these drugs to alleviate pain in selected patients.