Necessity of amoxicillin clavulanic acid in addition to prednisolone in mild-to-moderate COPD exacerbations

Background: The effectiveness of antibiotics in chronic obstructive pulmonary disease (COPD) exacerbations is still a matter of debate, especially in outpatients with an intermediate probability of bacterial infection. Methods: In this study, 35 COPD outpatients diagnosed by their chest physician with moderately severe COPD exacerbation, but without pneumonia, were randomised in a double blind, placebo-controlled study. Patients had one or two of the following characteristics: a positive Gram's stain of the sputum, 2 or more exacerbations in the previous year, a decrease in lung function of >200 mL and >12%. Patients received amoxicillin clavulanic acid (500/125 mg three times daily) or placebo for 7 days, always combined with a course of prednisolone (30 mg/day) for 7 days. Primary outcome was duration of the exacerbation. Additionally, we measured severity of the exacerbation, health-related quality of life, sputum parameters, number of relapses within 28 days and the number of re-exacerbations within 4 months after the study. Results: There was no difference observed in time to resolution of the exacerbation between the two groups (HR=1.12; (95% CI 0.5 to 2.3; p=0.77)), nor in any other treatment parameter. Conclusions: We detected no evidence for the effectiveness of addition of antibiotics to prednisolone for COPD exacerbations of moderate severity and with intermediate probability of bacterial infection in this underpowered study. More placebo-controlled studies are needed to properly define subgroups of COPD outpatients in which antibiotics are of additional value

‘Effects of a home-based bimodal lifestyle intervention in frail patients with end-stage liver disease awaiting orthotopic liver transplantation’:study protocol of a non-randomised clinical trial

Introduction Patients with end-stage liver disease awaiting orthotopic liver transplantation (OLT) are generally classified as frail due to disease-related malnutrition and a progressive decline in musculoskeletal and aerobic fitness, which is associated with poor pre-OLT, peri-OLT and post-OLT outcomes. However, frailty in these patients may be reversable with adequate exercise and nutritional interventions. Methods and analysis Non-randomised clinical trial evaluating the effect of a home-based bimodal lifestyle programme in unfit patients with a preoperative oxygen uptake (VO2) at the ventilatory anaerobic threshold ≤13 mL/ kg/min and/or VO2 at peak exercise ≤18 mL/kg/min listed for OLT at the University Medical Center Groningen (UMCG). The programme is patient tailored and comprises high-intensity interval and endurance training, and functional exercises three times per week, combined with nutritional support. Patients will go through two training periods, each lasting 6 weeks. The primary outcome of this study is the impact of the programme on patients’ aerobic fitness after the first study period. Secondary outcomes include aerobic capacity after the second study period, changes in sarcopenia, anthropometry, functional mobility, perceived quality of life and fatigue, incidence of hepatic encephalopathy and microbiome composition. Moreover, number and reasons of intercurrent hospitalisations during the study and postoperative outcomes up to 12 months post OLT will be recorded. Finally, feasibility of the programme will be assessed by monitoring the participation rate and reasons for non-participation, number and severity of adverse events, and dropout rate and reasons for dropout. Ethics and dissemination This study was approved by the Medical Research Ethics Committee of the UMCG (registration number NL83612.042.23, August 2023) and is registered in the Clinicaltrials.gov register (NCT05853484). Good Clinical Practice guidelines and the principles of the Declaration of Helsinki will be applied. Results of this study will be submitted for presentation at (inter)national congresses and publication in peer-reviewed journals.</p

TCT-47 Two-Year Clinical Outcome of the TWENTE Trial, a Randomized Controlled Trial Comparing Second-Generation Zotarolimus-Eluting Resolute Stents Versus Everolimus-Eluting Xience V Stents in Real-World Patients

Background: In the prospective, randomized TWENTE trial, the zotarolimus-eluting Resolute stent was at 1 year follow-up non-inferior to the everolimus-eluting Xience V stent for the primary endpoint target vessel failure. This composite endpoint consisted of cardiac death, clinically indicated target vessel revascularization, or target vessel-related myocardial infarction (MI). So far, few long-term data of prospective head-to-head comparisons between both DES have been reported. Methods: Patients requiring percutaneous coronary interventions (PCI) with DES implantation at Thoraxcentrum Twente in Enschede were randomization between Resolute (Medtronic Vascular, Santa Rosa, CA, USA) and Xience V (Abbott Vascular, Santa Clara, CA, USA) in a 1:1 fashion. Inclusion of all coronary or bypass graft lesions and all clinical settings was permitted except for primary PCI (i.e. acute ST-elevation myocardial infarction (STEMI) was an exclusion criterion). Both external monitoring and clinical event adjudication were performed by an independent external contract research organization (Cardialysis, Rotterdam, the Netherlands). Two year clinical follow-up was performed as indicated in the study protocol. Results: A total of 1,391 patients were enrolled in the TWENTE trial between June 2008 and August 2010. The study population comprised 21.6% diabetics with a vast majority of complex lesions and “off-label” indications for drug-eluting stents (77.4%). Patients presented with either stable angina (48.5%) or unstable angina/Non-STEMI (51.5%). Demographics, baseline angiographic and procedural data, and 2-year clinical follow-up data will be presented. This includes the primary endpoint of the study: Target vessel failure (TVF) at 2 year follow-up. Secondary endpoints include the individual components of the primary endpoint and the incidence of very late stent thrombosis. In addition, results of subgroup analyses will be reported. Conclusions: Results of pre-specified analyses of 2-year clinical outcome of the TWENTE trial will be presented at TCT 2012

A Randomized Controlled Trial in Second-Generation Zotarolimus-Eluting Resolute Stents Versus Everolimus-Eluting Xience V Stents in Real-World Patients : The TWENTE Trial

ObjectivesThe aim of this study was to compare the safety and efficacy of Resolute zotarolimus-eluting stents (ZES) (Medtronic Cardiovascular, Santa Rosa, California) with Xience V everolimus-eluting stents (EES) (Abbott Vascular Devices, Santa Clara, California) at 1-year follow-up.BackgroundOnly 1 randomized trial previously compared these stents.MethodsThis investigator-initiated, patient-blinded, randomized noninferiority study had limited exclusion criteria (acute ST-segment elevation myocardial infarctions not eligible). Patients (n = 1,391; 81.4% of eligible population) were randomly assigned to ZES (n = 697) or EES (n = 694). Liberal use of stent post-dilation was encouraged. Cardiac biomarkers were systematically assessed. The primary endpoint was target vessel failure (TVF), a composite of cardiac death, myocardial infarction not clearly attributable to non-target vessels, and clinically indicated target-vessel revascularization. An external independent research organization performed clinical event adjudication (100% follow-up data available). Analysis was by intention-to-treat.ResultsAcute coronary syndromes were present in 52% and “off-label” feature in 77% of patients. Of the lesions, 70% were type B2/C; the post-dilation rate was very high (82%). In ZES and EES, TVF occurred in 8.2% and 8.1%, respectively (absolute risk-difference 0.1%; 95% confidence interval: −2.8% to 3.0%, pnoninferiority = 0.001). There was no significant between-group difference in TVF components. The definite-or-probable stent thrombosis rates were relatively low and similar for ZES and EES (0.9% and 1.2%, respectively, p = 0.59). Definite stent thrombosis rates were also low (0.58% and 0%, respectively, p = 0.12). In EES, probable stent thrombosis beyond day 8 was observed only in patients not adhering to dual antiplatelet therapy.ConclusionsResolute ZES were noninferior to Xience V EES in treating “real-world” patients with a vast majority of complex lesions and “off-label” indications for drug-eluting stents, which were implanted with liberal use of post-dilation. (The Real-World Endeavor Resolute Versus XIENCE V Drug-Eluting SteNt Study: Head-to-head Comparison of Clinical Outcome After Implantation of Second Generation Drug-eluting Stents in a Real World Scenario; NCT01066650

Clinical Outcome Following Stringent Discontinuation of Dual Antiplatelet Therapy After 12 Months in Real-World Patients Treated With Second-Generation Zotarolimus-Eluting Resolute and Everolimus-Eluting Xience V Stents : 2-Year Follow-Up of the Randomized TWENTE Trial

Objectives The aim of this study was to assess the safety and efficacy of the implantation of Resolute zotarolimus-eluting stents (ZES) (Medtronic Inc., Santa Rosa, California) and Xience V everolimus-eluting stents (EES) (Abbott Vascular, Santa Clara, California) following strict discontinuation of dual antiplatelet therapy (DAPT) after 12 months. Background Only limited long-term follow-up data are available from head-to-head comparisons of second-generation drug-eluting stents. Methods The randomized TWENTE (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twente) trial is an investigator-initiated study performed in a population with many complex patients and lesions and only limited exclusion criteria. Patients were randomly assigned 1:1 to ZES (n = 697) or EES (n = 694). Results Two-year follow-up information was available on all patients. The rate of continuation of DAPT beyond 12 months was very low (5.4%). The primary endpoint of target vessel failure, a composite of cardiac death, target vessel–related myocardial infarction, and target vessel revascularization, did not differ between ZES and EES (10.8% vs. 11.6, p = 0.65), despite fewer target lesion revascularizations in patients with EES (2.6% vs. 4.9%, p = 0.03). The patient-oriented composite endpoint was similar (16.4% vs. 17.1%, p = 0.75). Two-year rates of definite or probable stent thrombosis were 1.2% and 1.4%, respectively (p = 0.63). Very late definite or probable stent thrombosis occurred only in 2 patients in each study arm (0.3% vs. 0.3%, p = 1.00). Conclusions After 2 years of follow-up and stringent discontinuation of DAPT beyond 12 months, Resolute ZES and Xience V EES showed similar results in terms of safety and efficacy for treating patients with a majority of complex lesions and off-label indications for drug-eluting stents. (The Real-World Endeavor Resolute Versus Xience V Drug-Eluting Stent Study in Twent

ECG Quantification of Myocardial Scar Does Not Differ between Primary and Secondary Prevention ICD Recipients with Ischemic Heart Disease

Background: Myocardial scar is an anatomic substrate for potentially lethal arrhythmias. Recent study showed that higher QRS-estimated scar size using the Selvester QRS score was associated with increased arrhythmogenesis during electrophysiologic testing. Therefore, QRS scoring might play a potential role in risk stratification before implantable cardioverter defibrillator (ICD) implantation. In this study, we tested the hypothesis that QRS scores among ICD recipients for secondary prevention are higher than QRS scores in primary prevention patients. Methods and Results: From the hospital database, 100 consecutive patients with ischemic heart disease and prior ICD implantation were selected. Twelve-lead electrocardiograms (ECGs) had been obtained before implantation. ECGs were scored following the 32-points Selvester QRS scoring system and corrected for underlying conduction defects and/or hypertrophy. Ninety-three ECGs were suitable for scoring; seven ECGs were rejected because of noise, missing leads, excessive ventricular extrasystoles, or ventricular pacing. No statistically significant difference in QRS score was found between the primary [6.90 (standard deviation [SD] 3.94), n = 63] and secondary prevention group [6.17 (SD 4.50) (P = 0.260), n = 30]. Left ventricular ejection fraction (LVEF) was significantly higher in the secondary prevention group [31% (SD 13.5) vs 24% (SD 11.7) (P = 0.015)]. When patients with LVEF ≥35% were excluded, QRS scores were still comparable, namely 7.02 (SD 4.04) in the primary prevention group (n = 52) and 6.28 (SD 4.24) in the secondary (P = 0.510) (n = 18). Conclusion: We found no significant difference in QRS score between the ischemic primary and secondary prevention groups. Therefore, a role of the Selvester QRS score as a risk stratifier remains unlikely. (PACE 2010; 33:192–197

A community-based exercise programme in COPD self-management: Two years follow-up of the COPE-II study

Introduction It is still unknown how best to maintain effects of exercise programmes in COPD in the long-term. We present the long-term effects of a community-based exercise programme incorporated in a self-management programme, compared to a self-management programme only in patients with COPD. Methods All included patients participated in four self-management sessions. Additionally, patients in the intervention group participated in an 11-month community-based exercise programme led by physiotherapists. Patients trained three times/week for six months and two times/week during the subsequent five months. To encourage a behavioural change towards exercise, one of these weekly training sessions was home-based (unsupervised). No formal exercise training was offered to intervention patients in the second year. Results The intervention was assigned to 80 patients, and the control condition to 79 patients. 82.5% and 78.5% of the intervention and control group, respectively, completed 24 months follow-up. Modified intention-to-treat analyses were performed. Although statistically significant after 12 months (35.1 m (95%CI: 8.4–61.8)), the between-group difference on maximal exercise capacity was not statistically significant after 24 months (12.2 m (95%CI: −16.6 to 41.0). Nevertheless, the between-group difference in daily physical activity was maintained after 24 months (1193 steps/day (95%CI: 203–2182)). A beneficial effect was also found on CRQ dyspnoea score but not on other CRQ domains, CCQ and HADS. Conclusions Our intervention was effective in achieving a behavioural change reflected by a sustained increase in daily physical activity, not accompanied by a sustained increase in maximal exercise capacity after two years of follow-up (ISRCTN81447311)

Scar tissue and microvolt T-wave alternans

Microvolt T-wave alternans (MTWA) is an electrocardiographic marker for predicting sudden cardiac death. In this study, we aimed to study the relation between MTWA and scar assessed with cardiac magnetic resonance imaging (CMR) in patients with ischemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM). Sixty-eight patients with positive or negative MTWA and analysable CMR examination were included. Using CMR and the delayed enhancement technique, left ventricular ejection fraction (LVEF), volumes, wall motion and scar characteristics were assessed. Overall, positive MTWA (n = 40) was related to male gender (p = 0.04), lower LVEF (p = 0.04) and increased left ventricular end-diastolic volume (LVEDV) (p < 0.01). After multivariate analysis, male gender (p = 0.01) and lower LVEF remained significant (p = 0.02). Scar characteristics (presence, transmurality, and scar score) were not related to MTWA (all p > 0.5). In the patients with ICM (n = 40) scar was detected in 38. Positive MTWA (n = 18) was related to higher LVEDV (p = 0.05). In patients with DCM (n = 28), scar was detected in 11. Trends were found between positive MTWA (n = 15) and male gender (p = 0.10), lower LVEF (p = 0.10), and higher LVEDV (p = 0.09). In both subgroups, the presence, transmurality or extent of scar was not related to MTWA (all p > 0.45). In this small study, neither in patients with ICM or DCM a relation was found between the occurrence of MTWA and the presence, transmurality or extent of myocardial scar. Overall there was a significant relation between heart failure remodeling parameters and positive MTWA

Stable-State Midrange-Proadrenomedullin Level Is a Strong Predictor of Mortality in Patients With COPD

Background: Midrange-proadrenomedullin (MR-proADM) has been shown to be elevated in patients hospitalized for an acute exacerbation of COPD (AECOPD) and in patients with community-acquired pneumonia. When measured during AECOPDs, MR-proADM has also been shown to be a predictor of mortality. We hypothesized that MR-proADM levels measured in a stable state could also predict mortality. Methods: We included 181 patients in whom we had paired plasma samples for MR-proADM determinations during a stable state and at hospitalization for an AECOPD when they also produced sputum. Time to death or censoring was compared between patients with MR-proADM above or below the median of 0.71 nmol/L. The predictive value of MR-proADM for survival was determined by calculating the C statistic. Results: Patients with COPD and MR-proADM levels > 0.71 nmol/L in the stable state had a threefold-higher risk of dying than did patients with MR-proADM levels < 0.71 nmol/L (hazard ratio, 2.98 [95% CI, 1.51-5.90]; C statistic, 0.76). The corrected OR for 1-year mortality was 8.90 (95% CI, 1.94-44.6) in patients with high MR-proADM levels measured in the stable state, compared with patients with low levels measured in the stable state. Conclusions: MR-proADM measured in the stable state appeared to be a strong predictor of mortality in patients with COPD. MR-proADM is far easier to measure than other predictors of mortality in COPD, such as BMI, airflow obstruction, dyspnea, and exercise capacity score

Quality of life after diet or exercise-induced weight loss in overweight to obese postmenopausal women: The SHAPE-2 randomised controlled trial

Introduction This study investigates the effect of a modest weight loss either by a calorie restricted diet or mainly by increased physical exercise on health related quality of life (HRQoL) in overweight-to-obese and inactive postmenopausal women. We hypothesize that HRQoL improves with weight loss, and that exercise-induced weight loss is more effective for this than diet-induced weight loss. Methods The SHAPE-2 trial was primarily designed to evaluate any additional effect of weight loss by exercise compared with a comparable amount of weight loss by diet on biomarkers relevant for breast cancer risk. In the present analysis we focus on HRQoL. We randomly assigned 243 eligible women to a diet (n = 97), exercise (n = 98), or control group (n = 48). Both interventions aimed for 5–6 kg weight loss. HRQoL was measured at baseline and after 16 weeks by the SF-36 questionnaire. Results Data of 214 women were available for analysis. Weight loss was 4.9 kg (6.1%) and 5.5 kg (6.9%) with diet and exercise, respectively. Scores of the SF-36 domain ‘health change’ increased significantly by 8.8 points (95% CI 1.6;16.1) with diet, and by 20.5 points (95% CI 13.2;27.7) with exercise when compared with control. Direct comparison of diet and exercise showed a statistically significantly stronger improvement with exercise. Both intervention groups showed a tendency towards improvements in most other domains, which were more pronounced in the exercise group, but not statistically different from control or each other. Conclusion In a randomized trial in overweight-to-obese and inactive postmenopausal women a comparable 6%-7% weight loss was achieved by diet-only or mainly by exercise and showed improvements in physical and mental HRQoL domains, but results were not statistically significant in either the diet or exercise group. However, a modest weight loss does lead to a positive change in self-perceived health status. This effect was significantly larger with exercise-induced weight loss than with comparable diet-induced weight loss