Weight-loss Endoscopy Trial (WET): a multi-center, randomized, controlled trial comparing weight loss in endoscopically implanted duodenal-jejunal bypass liners vs. intragastric balloons vs. a sham procedure.

INTRODUCTION: Obesity is associated with reduced life expectancy and various comorbidities. Surgical interventions are effective but accompanied by risk of serious complications. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). A randomized, sham-controlled study comparing both procedures has not been undertaken so far. METHODS: We performed a randomized, patient- and assessor-blinded, controlled trial comparing weight loss in IB vs. DJBL vs. a sham procedure (2:2:1 ratio). Patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities were included. The IB was removed after 6 months and the DJBL after 12 months. Main objective was successful weight loss (>10% from baseline) 12 months after explantation of the devices. Secondary outcomes were changes in comorbidities, quality of life and complications. RESULTS: 33 patients were randomized. Recruitment has to be stopped suddenly in after the DJBL device lost its CE mark in Europe. 11 patients received DJBL, 15 IB and 7 were allocated to sham group. Blinding was feasible in all patients. Weight decreased from baseline until explantation (DJBL: 129.4±28.3kg to 107.4±16.7kg; IB: 118.3±22.8kg to 107.4±25.7kg; sham: 134.6±18.0kg to 131.2±14.3kg) but patients regained weight almost to baseline level 12 months after explantation. Only one patient in IB group reached the primary endpoint. Severe device-related complications were very rare. CONCLUSION: Endoscopic bariatric procedures failed to achieve effective weight loss 12 months after explantation of the devices. The results of this trial need to be interpreted with caution due to its early termination.

Near-infrared spectroscopy and electroencephalography neurofeedback for binge-eating disorder: an exploratory randomized trial.

BACKGROUND: Binge-eating disorder (BED) co-occurs with neurobehavioral alterations in the processing of disorder-relevant content such as visual food stimuli. Whether neurofeedback (NF) directly targeting them is suited for treatment remains unclear. This study sought to determine feasibility and estimate effects of individualized, functional near-infrared spectroscopy-based real-time NF (rtfNIRS-NF) and high-beta electroencephalography-based NF (EEG-NF), assuming superiority over waitlist (WL). METHODS: Single-center, assessor-blinded feasibility study with randomization to rtfNIRS-NF, EEG-NF, or WL and assessments at baseline (t0), postassessment (t1), and 6-month follow-up (t2). NF comprised 12 60-min food-specific rtfNIRS-NF or EEG-NF sessions over 8 weeks. Primary outcome was the binge-eating frequency at t1 assessed interview-based. Secondary outcomes included feasibility, eating disorder symptoms, mental and physical health, weight management-related behavior, executive functions, and brain activity at t1 and t2. RESULTS: In 72 patients (intent-to-treat), the results showed feasibility of NF regarding recruitment, attrition, adherence, compliance, acceptance, and assessment completion. Binge eating improved at t1 by -8.0 episodes, without superiority of NF v. WL (-0.8 episodes, 95% CI -2.4 to 4.0), but with improved estimates in NF at t2 relative to t1. NF was better than WL for food craving, anxiety symptoms, and body mass index, but overall effects were mostly small. Brain activity changes were near zero. CONCLUSIONS: The results show feasibility of food-specific rtfNIRS-NF and EEG-NF in BED, and no posttreatment differences v. WL, but possible continued improvement of binge eating. Confirmatory and mechanistic evidence is warranted in a double-blind randomized design with long-term follow-up, considering dose-response relationships and modes of delivery.

Intensive heart rhythm monitoring to decrease ischemic stroke and systemic embolism-the Find-AF 2 study-rationale and design.

BACKGROUND: Atrial fibrillation (AF) is one of the most frequent causes of stroke. Several randomized trials have shown that prolonged monitoring increases the detection of AF, but the effect on reducing recurrent cardioembolism, ie, ischemic stroke and systemic embolism, remains unknown. We aim to evaluate whether a risk-adapted, intensified heart rhythm monitoring with consequent guideline conform treatment, which implies initiation of oral anticoagulation (OAC), leads to a reduction of recurrent cardioembolism. METHODS: Find-AF 2 is a randomized, controlled, open-label parallel multicenter trial with blinded endpoint assessment. 5,200 patients ≥ 60 years of age with symptomatic ischemic stroke within the last 30 days and without known AF will be included at 52 study centers with a specialized stroke unit in Germany. Patients without AF in an additional 24-hour Holter ECG after the qualifying event will be randomized in a 1:1 fashion to either enhanced, prolonged and intensified ECG-monitoring (intervention arm) or standard of care monitoring (control arm). In the intervention arm, patients with a high risk of underlying AF will receive continuous rhythm monitoring using an implantable cardiac monitor (ICM) whereas those without high risk of underlying AF will receive repeated 7-day Holter ECGs. The duration of rhythm monitoring within the control arm is up to the discretion of the participating centers and is allowed for up to 7 days. Patients will be followed for at least 24 months. The primary efficacy endpoint is the time until recurrent ischemic stroke or systemic embolism occur. CONCLUSIONS: The Find-AF 2 trial aims to demonstrate that enhanced, prolonged and intensified rhythm monitoring results in a more effective prevention of recurrent ischemic stroke and systemic embolism compared to usual care.

Smartphone-supported behavioural weight loss treatment in adults with severe obesity: study protocol for an exploratory randomised controlled trial (SmartBWL).

INTRODUCTION: Behavioural weight loss (BWL) treatment is the standard evidence-based treatment for severe obesity (SO; body mass index ≥40.0 kg/m2 or ≥35.0 kg/m2 with obesity-related comorbidity), leading to moderate weight loss which often cannot be maintained in the long term. Because weight loss depends on patients' use of weight management skills, it is important to support them in daily life. In an ecological momentary intervention design, this clinical trial aims to adapt, refine and evaluate a personalised cognitive-behavioural smartphone application (app) in BWL treatment to foster patients' weight management skills use in everyday life. It is hypothesised that using the app is feasible and acceptable, improves weight loss and increases skills use and well-being. METHODS AND ANALYSIS: In the pilot phase, the app will be adapted, piloted and optimised for BWL treatment following a participatory patient-oriented approach. In the subsequent single-centre, assessor-blind, exploratory randomised controlled trial, 90 adults with SO will be randomised to BWL treatment over 6 months with versus without adjunctive app. Primary outcome is the amount of weight loss (kg) at post-treatment (6 months), compared with pretreatment, derived from measured body weight. Secondary outcomes encompass feasibility, acceptance, weight management skills use, well-being and anthropometrics assessed at pretreatment, midtreatment (3 months), post-treatment (6 months) and 6-month follow-up (12 months). An intent-to-treat linear model with randomisation arm, pretreatment weight and stratification variables as covariates will serve to compare arms regarding weight at post-treatment. Secondary analyses will include linear mixed models, generalised linear models and regression and mediation analyses. For safety analysis (serious) adverse events will be analysed descriptively. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of the University of Leipzig (DE-21-00013674) and notified to the Federal Institute for Drugs and Medical Devices. Study results will be disseminated through peer-reviewed publications. REGISTRATION: This study was registered at the German Clinical Trials Register (DRKS00026018), www.drks.de. TRIAL REGISTRATION NUMBER: DRKS00026018.

Prevalence and prognostic impact of chronic kidney disease and anaemia across ACC/AHA precursor and symptomatic heart failure stages.

BACKGROUND: The importance of chronic kidney disease (CKD) and anaemia has not been comprehensively studied in asymptomatic patients at risk for heart failure (HF) versus those with symptomatic HF. We analysed the prevalence, characteristics and prognostic impact of both conditions across American College of Cardiology/American Heart Association (ACC/AHA) precursor and HF stages A-D. METHODS AND RESULTS: 2496 participants from three non-pharmacological German Competence Network HF studies were categorized by ACC/AHA stage; stage C patients were subdivided into C1 and C2 (corresponding to NYHA classes I/II and III, respectively). Overall, patient distribution was 8.1%/35.3%/32.9% and 23.7% in ACC/AHA stages A/B/C1 and C2/D, respectively. These subgroups were stratified by the absence ( - ) or presence ( +) of CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2) and anaemia (haemoglobin in women/men < 12/ < 13 g/dL). The primary outcome was all-cause mortality at 5-year follow-up. Prevalence increased across stages A/B/C1 and C2/D (CKD: 22.3%/23.6%/31.6%/54.7%; anaemia: 3.0%/7.9%/21.7%/33.2%, respectively), with concordant decreases in median eGFR and haemoglobin (all p < 0.001). Across all stages, hazard ratios [95% confidence intervals] for all-cause mortality were 2.1 [1.8-2.6] for CKD + , 1.7 [1.4-2.0] for anaemia, and 3.6 [2.9-4.6] for CKD + /anaemia + (all p < 0.001). Population attributable fractions (PAFs) for 5-year mortality related to CKD and/or anaemia were similar across stages A/B, C1 and C2/D (up to 33.4%, 30.8% and 34.7%, respectively). CONCLUSIONS: Prevalence and severity of CKD and anaemia increased across ACC/AHA stages. Both conditions were individually and additively associated with increased 5-year mortality risk, with similar PAFs in asymptomatic patients and those with symptomatic HF.

Design of the Weight-loss Endoscopy Trial (WET): a multi-center, randomized, controlled trial comparing weight loss in endoscopically implanted duodenal-jejunal bypass liners vs. intragastric balloons vs. a sham procedure.

BACKGROUND: Obesity is a global problem leading to reduced life expectancy, cardiovascular diseases, diabetes and many types of cancer. Even people willing to accept treatment only achieve a mean weight loss of about 5 kg using commercial weight loss programs. Surgical interventions, e.g. sleeve gastrectomy or gastric bypass are effective but accompanied by risk of serious complications and side effects. Less invasive endoscopic procedures mainly comprise the intragastric balloon (IB) and the duodenal-jejunal bypass liner (DJBL). To date, a randomized comparison between these devices has not been undertaken or shown to be superior to a sham procedure. METHODS: We designed a multi-center, randomized, patient and assessor-blinded, controlled trial comparing weight loss in endoscopically implanted IB vs. DJBL vs. a sham procedure. A total of 150 patients with a BMI > 35 kg/m2 or > 30 with obesity-related comorbidities and indication for proton pump inhibitors are randomized to receive either IB, DJBL or a sham gastroscopy (2:2:1 ratio). All participants undergo regular dietary consultation. The IB will be removed after 6 months, whereas the DJBL will be explanted after 12 months. All patients will receive gastroscopies at implantation and explantation of the devices or sedation without gastroscopy to maintain blinding. Main exclusion criteria are malignant diseases, peptic ulcer or previous bariatric intervention. Weight loss 12 months after explantation of the devices, changes in comorbidities, quality of life, complication rates and safety will be evaluated. DISCUSSION: This trial could help to identify the most effective and safest endoscopic device, thus determining the new standard procedure for endoscopic bariatric treatment. TRIAL REGISTRATION: 16th January 2017. DRKS00011036. Funded by the German Research Foundation (DFG).

Point-of-care B-type natriuretic peptide and portable echocardiography for assessment of patients with suspected heart failure in primary care: rationale and design of the three-part Handheld-BNP program and results of the training study.

BACKGROUND: Patients with suspected heart failure (HF) often present first to general practitioners (GPs). Timely and accurate HF diagnosis and reliable prognostic information have remained unmet goals in primary care, where patient evaluation often relies on clinical assessment only. The Handheld-BNP program investigates whether additional use of portable echocardiography (ECHO) and point-of-care determination of B-type natriuretic peptide (BNP) improves the accuracy of HF diagnosis and aids risk prediction in primary care. METHODS AND RESULTS: A research network was established between 2 academic centers, 2 × 6 cardiologists, and 2 × 24 GPs inexperienced with ECHO and BNP. The Training Study investigates the feasibility of implementing GP use and interpretation of ECHO and BNP. After training, competence is assessed using multiple-choice testing (pass mark: > 80% correct diagnoses). In the cluster-randomized four-arm Screening Study, each GP passes in random order through four study arms: clinical assessment (CA), CA + BNP, CA + ECHO, and CA + ECHO + BNP. Cardiologists' diagnoses serve as reference. Primary endpoint is the rate of correct GP diagnoses per study arm. In the Prognostic Follow-Up Study, patients are followed up centrally for 72 months. Forty-four GPs were successfully trained. With 225 ± 34 (75 ± 3) and 233 ± 28 (81 ± 7) min, respectively, total ECHO (BNP) training times were similar between centers I and II. Furthermore, training results did not differ between centers. CONCLUSIONS: Standardized training of limited duration enabled GPs to use ECHO and BNP for HF diagnosis. The Handheld-BNP program will provide robust evaluation of the diagnostic effectiveness and prognostic value of these tools in primary care. TRIAL REGISTRATION: http://www.controlled-trials.com (ISRCTN23325295).

Exercise training in Diastolic Heart Failure (Ex-DHF): rationale and design of a multicentre, prospective, randomized, controlled, parallel group trial.

Heart failure with preserved ejection fraction (HFpEF) is a common disease with high incidence and increasing prevalence. Patients suffer from functional limitation, poor health-related quality of life, and reduced prognosis. A pilot study in a smaller group of HFpEF patients showed that structured, supervised exercise training (ET) improves maximal exercise capacity, diastolic function, and physical quality of life. However, the long-term effects of ET on patient-related outcomes remain unclear in HFpEF. The primary objective of the Exercise training in Diastolic Heart Failure (Ex-DHF) trial is to investigate whether a 12 month supervised ET can improve a clinically meaningful composite outcome score in HFpEF patients. Components of the outcome score are all-cause mortality, hospitalizations, NYHA functional class, global self-rated health, maximal exercise capacity, and diastolic function. After undergoing baseline assessments to determine whether ET can be performed safely, 320 patients at 11 trial sites with stable HFpEF are randomized 1:1 to supervised ET in addition to usual care or to usual care alone. Patients randomized to ET perform supervised endurance/resistance ET (3 times/week at a certified training centre) for 12 months. At baseline and during follow-up, anthropometry, echocardiography, cardiopulmonary exercise testing, and health-related quality of life evaluation are performed. Blood samples are collected to examine various biomarkers. Overall physical activity, training sessions, and adherence are monitored and documented throughout the study using patient diaries, heart rate monitors, and accelerometers. The Ex-DHF trial is the first multicentre trial to assess the long-term effects of a supervised ET programme on different outcome measures in patients with HFpEF.

Effect of Escitalopram on All-Cause Mortality and Hospitalization in Patients With Heart Failure and Depression: The MOOD-HF Randomized Clinical Trial.

IMPORTANCE: Depression is frequent in patients with heart failure and is associated with adverse clinical outcomes. Long-term efficacy and safety of selective serotonin reuptake inhibitors in these patients are unknown. OBJECTIVE: To determine whether 24 months of treatment with escitalopram improves mortality, morbidity, and mood in patients with chronic systolic heart failure and depression. DESIGN, SETTING, AND PARTICIPANTS: The Effects of Selective Serotonin Re-Uptake Inhibition on Morbidity, Mortality, and Mood in Depressed Heart Failure Patients (MOOD-HF) study was a double-blind, placebo-controlled randomized clinical trial conducted at 16 tertiary medical centers in Germany. Between March 2009 and February 2014, patients at outpatient clinics with New York Heart Association class II-IV heart failure and reduced left ventricular ejection fraction (<45%) were screened for depression using the 9-item Patient Health Questionnaire. Patients with suspected depression were then invited to undergo a Structured Clinical Interview based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) to establish the diagnosis. INTERVENTIONS: Patients were randomized 1:1 to receive escitalopram (10-20 mg) or matching placebo in addition to optimal heart failure therapy. Study duration was 24 months. MAIN OUTCOMES AND MEASURES: The composite primary outcome was time to all-cause death or hospitalization. Prespecified secondary outcomes included safety and depression severity at 12 weeks of treatment (including the titration period), which were determined using the 10-item Montgomery-Åsberg Depression Rating Scale (total possible score, 0 to 60; higher scores indicate more severe depression). RESULTS: A total of 372 patients (mean age, 62 years; 24% female) were randomized and had taken at least 1 dose of study medication when the data and safety monitoring committee recommended the trial be stopped early. During a median participation time of 18.4 months (n = 185) for the escitalopram group and 18.7 months (n = 187) for the placebo group, the primary outcome of death or hospitalization occurred in 116 (63%) patients and 119 (64%) patients, respectively (hazard ratio, 0.99 [95% CI, 0.76 to 1.27]; P = .92). The mean Montgomery-Åsberg Depression Rating Scale sum score changed from 20.2 at baseline to 11.2 at 12 weeks in the escitalopram group and from 21.4 to 12.5 in the placebo group (between-group difference, -0.9 [95% CI,-2.6 to 0.7]; P = .26). Safety parameters were comparable between groups. CONCLUSIONS AND RELEVANCE: In patients with chronic heart failure with reduced ejection fraction and depression, 18 months of treatment with escitalopram compared with placebo did not significantly reduce all-cause mortality or hospitalization, and there was no significant improvement in depression. These findings do not support the use of escitalopram in patients with chronic systolic heart failure and depression. TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN33128015.

Evaluation of Transient Elastography, Acoustic Radiation Force Impulse Imaging (ARFI), and Enhanced Liver Function (ELF) Score for Detection of Fibrosis in Morbidly Obese Patients.

BACKGROUND: Liver fibrosis induced by non-alcoholic fatty liver disease causes peri-interventional complications in morbidly obese patients. We determined the performance of transient elastography (TE), acoustic radiation force impulse (ARFI) imaging, and enhanced liver fibrosis (ELF) score for fibrosis detection in bariatric patients. PATIENTS AND METHODS: 41 patients (median BMI 47 kg/m2) underwent 14-day low-energy diets to improve conditions prior to bariatric surgery (day 0). TE (M and XL probe), ARFI, and ELF score were performed on days -15 and -1 and compared with intraoperative liver biopsies (NAS staging). RESULTS: Valid TE and ARFI results at day -15 and -1 were obtained in 49%/88% and 51%/90% of cases, respectively. High skin-to-liver-capsule distances correlated with invalid TE measurements. Fibrosis of liver biopsies was staged as F1 and F3 in n = 40 and n = 1 individuals. However, variations (median/range at d-15/-1) of TE (4.6/2.6-75 and 6.7/2.9-21.3 kPa) and ARFI (2.1/0.7-3.7 and 2.0/0.7-3.8 m/s) were high and associated with overestimation of fibrosis. The ELF score correctly classified 87.5% of patients. CONCLUSION: In bariatric patients, performance of TE and ARFI was poor and did not improve after weight loss. The ELF score correctly classified the majority of cases and should be further evaluated.

Effects of structured heart failure disease management on mortality and morbidity depend on patients' mood: results from the Interdisciplinary Network for Heart Failure Study.

AIMS: Depression is common in heart failure (HF) and associated with adverse outcomes. Randomized comparisons of the effectiveness of HF care strategies by patients' mood are scarce. We therefore investigated in a randomized trial a structured collaborative disease management programme (HeartNetCare-HF™; HNC) recording mortality, morbidity, and symptoms in patients enrolled after hospitalization for decompensated systolic HF according to their responses to the 9-item Patient Health Questionnaire (PHQ-9) during an observation period of 180 days. METHODS AND RESULTS: Subjects scoring <12/≥12 were categorized as non-depressed/depressed, and those ignoring the questionnaire as PHQ-deniers. Amongst 715 participants (69 ± 12 years, 29% female), 141 (20%) were depressed, 466 (65%) non-depressed, and 108 (15%) PHQ-deniers. The composite endpoint of mortality and re-hospitalization was neutral overall and in all subgroups. However, HNC reduced mortality risk in both depressed and non-depressed patients [adjusted hazard ratios (HRs) 0.12, 95% confidence interval (CI) 0.03-0.56, P = 0.006, and 0.49, 95% CI 0.25-0.93, P = 0.03, respectively], but not in PHQ-deniers (HR 1.74, 95% CI 0.77-3.96, P = 0.19; P = 0.006 for homogeneity of HRs). Average frequencies of patient contacts in the HNC arm were 12.8 ± 7.9 in non-depressed patients, 12.4 ± 7.1 in depressed patients, and 5.5 ± 7.2 in PHQ-deniers (P < 0.001). CONCLUSIONS: Early after decompensation, HNC reduced mortality risk in non-depressed and even more in depressed subjects, but not in PHQ-deniers. This suggests that differential acceptability and chance of success of care strategies such as HNC might be predicted by appropriate assessment of patients' baseline characteristics including psychological disposition. These post-hoc results should be reassessed by prospective evaluation of HNC in larger HF populations.

Differential interaction of clinical characteristics with key functional parameters in heart failure with preserved ejection fraction--results of the Aldo-DHF trial.

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<0.05). Female gender (p<0.001), CAD (p=0.002), BMI (p<0.001), sleep apnoea (p=0.02), and chronotropic incompetence (CI, p=0.002) were related to lower peakVO2 values. Higher pulse pressure (p=0.04), lower heart rates (p=0.03), CI (p=0.03) and beta-blocker treatment (p=0.001) were associated with higher E/e'. BMI correlated inversely (p=0.03), whereas atrial fibrillation (p<0.001), lower haemoglobin levels (p<0.001), CI (p=0.02), and beta-blocker treatment (p<0.001) were associated with higher NT-proBNP. After multiple adjustment for demographic and clinical variables peakVO2 was not significantly associated with E/e' (r=+0.01, p=0.87), logNT-proBNP (r=0.09, p=0.08), LAVI (r=+0.03, p=0.55), and LVMI (r=+0.05, p=0.37). The associations of E/e' with logNT-proBNP (r=0.21, p<0.001), LAVI (r=+0.29, p<0.001) and LVMI (r=0.09, p=0.06) were detectable also after multiple adjustment. CONCLUSIONS: Demographic and clinical characteristics differentially interact with exercise capacity, resting left ventricular filling index, neurohumoral activation, and left atrial and ventricular remodelling in HFpEF. Exercise intolerance in HFpEF is multi-factorial and therapeutic approaches addressing exercise capacity should therefore not only aim to improve single pathological mechanisms. REGISTRATION: ISRCTN94726526 (http://www.controlled-trials.com), Eudra-CT-number 2006-002605-31.

Use of Floseal and effects on wound healing and pain in adults undergoing tonsillectomy: randomised comparison versus electrocautery.

The objective of this study was to evaluate the effect of FloSeal(®) (FS, Baxter Healthcare, Deerfield, IL, USA) as a haemostatic matrix in comparison to bipolar electrocautery (EC) after tonsillectomy. Eligible patients were adults undergoing cold-knife tonsillectomy because of recurrent tonsillitis, tonsillar hypertrophy, or peritonsillar abscess (more than 3 months previously). Patients were randomly allocated, on a single-blind basis, to either FS or EC for haemostasis during tonsillectomy. Five experienced surgeons judged the handling of FS application using a five-point scale (very good, good, fair, poor, very poor). Postoperative pain scores were evaluated with a visual analogue scale for 20 days, and the duration under pain medication together with the consumption of pain medication was compared. Wound healing was documented on Days 1-5, 10, and 20. A total of 176 patients were enrolled. Overall, 76/77 (98.7%) of surgeon evaluations of FS handling were judged at least "good". FS-treated patients showed significantly improved wound healing (less thickness of wound plaques) throughout the postoperative observation period, a trend for less postoperative pain (cumulative pain intensity score; P = 0.074), and a significantly shorter duration of pain-medication use (9.5 vs. 11.6 days; P = 0.014) as well as reduced pain-medication consumption/demand (P = 0.032). No difference in the rate of postoperative haemorrhage was observed between the two treatment groups (4.9% for FS patients, 6.0% for EC patients, P = 0.76). In conclusion, this study demonstrates the easy handling of FS application in tonsillectomy. Its use instead of EC after cold-steel tonsillectomy shows beneficial effects on mucosal recovery, as assessed by a decrease in the thickness of wound coating. Furthermore, FS is associated with a significantly shortened duration of pain-medication use and overall reduction in consumption/demand.

Titration to target dose of bisoprolol vs. carvedilol in elderly patients with heart failure: the CIBIS-ELD trial.

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.

Prevalence and natural history of heart failure in outpatient HIV-infected subjects: rationale and design of the HIV-HEART study.

BACKGROUND: HIV infection is a global public health issue that is frequently associated with cardiac involvement. However, myocardial dysfunction and heart failure are often clinically occult or attributed incorrectly to other non-cardiac disease processes even a heightened awareness and knowledge for these cardiac diseases in HIV-infected patients may lead to earlier detection and a reduction in morbidity and mortality. The present study evaluates the frequency and clinical course of myocardial dysfunction and heart failure in a HIV-infected population. METHODS: The HIV-HEART (HIV-infection and HEART disease) study is a prospective, long-term cohort study. The study is designed and powered to define prevalence and natural history of chronic heart failure. Following a pilot-study of 105 HIV-infected subjects the HIV-HEART trial will contain 802 HIV-infected males and females with and without antiretroviral therapy in an urban population. HIV-HEART is performed by using non-invasive techniques for the quantification of exercise intolerance and ventricular dysfunction, including concentration of B-type natriretic peptide (BNP), transthoracal echocardiography and endurance testing. Patients with BNP >100 pg/ml achieve a magnetic resonance tomography of the heart for characterization of myocardial dysfunction and type of cardiomyopathy. To determine incidence and natural history of myocardial dysfunction and heart failure, a 2 year follow-up started in September 2006. CONCLUSIONS: The HIV-HEART study will define the significance of myocardial dysfunction and heart failure in a HIV-infected urban population and classify appropriate methods for identifying high-risk patients, the basis for risk stratification and therapy.

Intentional single-stage revascularization of two different vascular beds in patients with vascular multimorbidity; a feasibility study.

AIMS: The aim of this retrospective study was to assess the feasibility of catheter-based interventions in two different vascular beds performed in a single stage in patients with vascular multimorbidity. METHODS AND RESULTS: Fifty patients, 28 males, mean age 68.6 (+/- 9.2) years and 22 females, mean ages 72.2 (+/- 6.4) years were studied. At least one major cardiovascular risk factor was present in 48 (94%) of all patients. The most frequent combination of interventions was coronary artery disease (CAD) and renovascular disease (RVD) (20 patients, 40%) followed by CAD and peripheral artery disease (PAD) (17 patients, 34%). In all patients technical success, defined as residual stenosis < or = 30% diameter, and procedural success, defined as lack of major adverse cardiac and cerebrovascular events (MACCE) during the in-hospital period, were achieved. In two patients surgical revision of the access site was required and in two additional patients minor local bleeding was observed. CONCLUSIONS: Sequential vascular interventions in different vascular beds may be performed in a single stage with high success rates, however, compared to historical controls possibly at a higher rate of access site complications. A larger study using controls is needed to assess the medical benefits and cost efficacy of a single stage approach in patients with clinically relevant vascular multimorbidity.