A Home Hospitalisation Strategy for Patients with an Acute Episode of Heart Failure Using a Digital Health-Supported Platform: A Multicentre Feasibility Study - A Rationale and Study Design.

BACKGROUND: Heart failure (HF) is a common cause of hospitalisation and mortality in elderly. The frequent rehospitalisations put a serious burden on patients, health-care budgets, and health-care capacity. Frequent hospital admissions are also associated with a substantial additional hazard for serious complications and reduced quality of life. The NWE-Chance project will explore the feasibility and scalability of providing home hospitalisation supported by a newly developed digital health-supported platform and daily visits of specialised nurses. METHODS/DESIGN: Hundred patients with chronic HF will be recruited over a 1-year period. The digital health-supported home hospitalisation strategy will be tested in 3 hospitals with different experience in delivering home hospitalisation: Isala Zwolle, Maastricht UMC+, both in The Netherlands, and Jessa Hospital, Hasselt in Belgium. The home hospitalisation intervention will have a maximal duration of 14 days. Feasibility will be measured with acceptability, satisfaction, and usability questionnaires for patients, nurses, and physicians. Furthermore, safety and costs will be assessed for 30 days after the start of the home hospitalisation intervention. DISCUSSION: The NWE-Chance project will be one of the first studies to examine the feasibility of a digital health-supported home hospitalisation platform for HF patients. It has the potential to augment current standard HF care and quality of life of HF patients and to innovate the standard HF care to potentially lower the hospitalisation-related complications, the burden of HF on health-care systems, and to potentially implement more patient-centred care strategies.

Clinical outcomes after cardiac rehabilitation in elderly patients with and without diabetes mellitus: The EU-CaRE multicenter cohort study.

BACKGROUND: The prevalence of patients with concomitant cardiovascular disease and diabetes mellitus (DM) is increasing rapidly. We aimed to compare the effectiveness of current cardiac rehabilitation (CR) programs across seven European countries between elderly cardiac patients with and without DM. METHODS: 1633 acute and chronic coronary artery disease (CAD) patients and patients after valve intervention with an age 65 or above who participated in comprehensive CR (3 weeks to 3 months, depending on centre) were included. Peak oxygen uptake (VO2 peak), body mass index, resting systolic blood pressure, low-density lipoprotein-cholesterol (LDL-C), and glycated haemoglobin (HbA1c) were assessed before start of CR, at termination of CR (variable time point), and 12 months after start of CR, with no intervention after CR. Baseline values and changes from baseline to 12-month follow-up were compared between patients with and without DM using mixed models, and mortality and hospitalisation rates using logistic regression. RESULTS: 430 (26.3%) patients had DM. Patients with DM had more body fat, lower educational level, more comorbidities, cardiovascular risk factors, and more advanced CAD. Both groups increased their VO2 peak over the study period but with a significantly lower improvement from baseline to follow-up in patients with DM. In the DM group, change in HbA1c was associated with weight change but not with change in absolute VO2 peak. 12-month cardiac mortality was higher in patients with DM. CONCLUSIONS: While immediate improvements in VO2 peak after CR in elderly patients with and without DM were similar, 12-month maintenance of this improvement was inferior in patients with DM, possibly related to disease progression. Glycemic control was less favourable in diabetic patients needing insulin in the short- and long-term. Since glycemic control was only related to weight loss but not to increase in exercise capacity, this highlights the importance of weight loss in obese DM patients during CR. Trial registration NTR5306 at trialregister.nl; trial registered 07/16/2015; https://www.trialregister.nl/trial/5166.

Usability of a digital health platform to support home hospitalization in heart failure patients: a multicentre feasibility study among healthcare professionals.

AIMS: Heart failure (HF) is a common cause of mortality and (re)hospitalizations. The NWE-Chance project explored the feasibility of providing hospitalizations at home (HH) supported by a newly developed digital health platform. The aim of this study was to explore the perceived usability by healthcare professionals (HCPs) of a digital platform in addition to HH for HF patients. METHODS AND RESULTS: A prospective, international, multicentre, single-arm interventional study was conducted. Sixty-three patients and 22 HCPs participated. The HH consisted of daily home visits by the nurse and use of the platform, consisting of a portable blood pressure device, weight scale, pulse oximeter, a wearable chest patch to measure vital signs (heart rate, respiratory rate, activity level, and posture), and an eCoach for the patient. Primary outcome was usability of the platform measured by the System Usability Scale halfway and at the end of the study. Overall usability was rated as sufficient (mean score 72.1 ± 8.9) and did not differ between the measurements moments (P = 0.690). The HCPs reported positive experiences (n = 7), negative experiences (n = 13), and recommendations (n = 6) for the future. Actual use of the platform was 79% of the HH days. CONCLUSION: A digital health platform to support HH was considered usable by HCPs, although actual use of the platform was limited. Therefore, several improvements in the integration of the digital platform into clinical workflows and in defining the precise role of the digital platform and its use are needed to add value before full implementation. REGISTRATION: clinicaltrials.gov NCT04084964.

Health-related quality of life in elderly cardiac patients undergoing cardiac rehabilitation and the association with exercise capacity: The EU-CaRE study.

AIMS: The ability to be physically active is pivotal to the quality of life in elderly patients. This study aims to describe the association between exercise capacity and health-related quality of life (HRQoL), anxiety, and depression following an exercise-based cardiac rehabilitation (CR) program in elderly cardiac patients. METHODS: Patients aged ≥65 years with acute and chronic coronary syndrome or heart valve surgery were consecutively included from 8 CR centers in 7 European countries. Exercise capacity (VO2peak(ml/kg/min)) was assessed with a cardiopulmonary exercise test (97%) or a six-minute walk test. Outcome variables included HRQoL (SF-36 physical and mental component scores (PCS and MCS)), anxiety (GAD-7), and depression (PHQ-9). Mixed models were used to address the association between baseline and the development in VO2peak, and outcome variables stratified on sex, and adjusted for baseline values, age, and CR center. RESULTS: A total of 1,633 patients were included (T0), 1,523 (93%) completed end-of-CR assessment (T1), and 1,457 (89%) 1-year follow-up (T2). Women had higher % of predicted VO2peak, but poorer scores in HRQoL, anxiety and depression at all time-points. All scores improved in both sexes at follow-up. We found significant associations between VO2peak at baseline as well as development in VO2peak and all outcome variables at T1 and T2 in men (all p < 0.001). In women, VO2peak was only associated with PCS scores (p < 0.001). CONCLUSIONS: Improvements in exercise capacity was strongly associated with improvements in HRQoL and mental health, however with stronger associations in men. The results highlight the importance of physical fitness for HRQol and mental health. The findings from this study might be useful to better target individual CR programs.

This study explores the association between exercise capacity and the well-being of elderly cardiac patients participating in a cardiac rehabilitation program, focusing on health-related quality of life (HRQoL), anxiety, and depression. Key Findings:Women, despite having higher percentages of predicted exercise capacity, consistently reported poorer HRQoL, anxiety, and depression scores compared to men at all assessed time points.Improvements in exercise capacity were strongly associated with positive changes in HRQoL and mental health, with these associations being more pronounced in men.

Bringing the hospital to home: Patient-reported outcome measures of a digital health-supported home hospitalisation platform to support hospital care at home for heart failure patients.

Background: Hospitalisations for heart failure are frequent and costly, linked with a lower quality of life, and lead to higher morbidity and mortality. Home hospitalisation interventions could be a substitute for in-hospital stays to reduce the burden on patients. The current study aims to investigate patient-reported satisfaction and usability in combination with the safety of a digital health-supported home hospitalisation intervention for heart failure patients. Methods: We conducted an international, multicentre, single-arm, interventional study to investigate the feasibility and safety of a digital health-supported home hospitalisation platform. Patients with acute decompensation of known and well-assessed chronic heart failure with an indication for hospital admission were included. The primary outcome was patient satisfaction. Secondary outcomes were usability, adherence, and safety. Results: A total number of 66 patients were included, of which the data of 65 patients (98.5%) was analysed. A total of 86.1% of patients reported being very satisfied or totally satisfied. No patients reported to be not satisfied with the home hospitalisation intervention. The patients reported a sufficient usability score (mean score: 75.8% of 100%) for the digital health-supported home hospitalisation platform. The adherence to the daily measurements of blood pressure and weight was very high, whereas the adherence to the daily interaction with the eCoach was lower (69.3%). In 7 patients (10.8%), a conversion from home hospitalisation to regular hospitalisation was needed. Furthermore, 6 patients (9.2%) had rehospitalisation within 30 days after the end of the home hospitalisation intervention. Conclusion: A digitally supported home hospitalisation intervention is feasible. This study demonstrates high patient satisfaction and sufficiently high usability scores. The safety outcomes are comparable with traditional heart failure hospitalisations. This indicates that digitally supported home hospitalisation could be an alternative to in-hospital care for all age groups, yet further research is needed to prove the (cost-) effectiveness.

Breathing pattern and pulmonary gas exchange in elderly patients with and without left ventricular dysfunction-modification with exercise-based cardiac rehabilitation and prognostic value.

Background: Inefficient ventilation is an established prognostic marker in patients with heart failure. It is not known whether inefficient ventilation is also linked to poor prognosis in patients with left ventricular dysfunction (LVD) but without overt heart failure. Objectives: To investigate whether inefficient ventilation in elderly patients with LVD is more common than in patients without LVD, whether it improves with exercise-based cardiac rehabilitation (exCR), and whether it is associated with major adverse cardiovascular events (MACE). Methods: In this large multicentre observational longitudinal study, patients aged ≥65 years with acute or chronic coronary syndromes (ACS, CCS) without cardiac surgery who participated in a study on the effectiveness of exCR in seven European countries were included. Cardiopulmonary exercise testing (CPET) was performed before, at the termination of exCR, and at 12 months follow-up. Ventilation (VE), breathing frequency (BF), tidal volume (VT), and end-expiratory carbon dioxide pressure (PETCO2) were measured at rest, at the first ventilatory threshold, and at peak exercise. Ventilatory parameters were compared between patients with and without LVD (based on cardio-echography) and related to MACE at 12 month follow-up. Results: In 818 patients, age was 72.5 ± 5.4 years, 21.9% were women, 79.8% had ACS, and 151 (18%) had LVD. Compared to noLVD, in LVD resting VE was increased by 8%, resting BF by 6%, peak VE, peak VT, and peak PETCO2 reduced by 6%, 8%, and 5%, respectively, and VE/VCO2 slope increased by 11%. From before to after exCR, resting VE decreased and peak PETCO2 increased significantly more in patients with compared to without LVD. In LVD, higher resting BF, higher nadir VE/VCO2, and lower peak PETCO2 at baseline were associated with MACE. Conclusions: Similarly to patients with HF, in elderly patients with ischemic LVD, inefficient resting and exercise ventilation was associated with worse outcomes, and ExCR alleviated abnormal breathing patterns and gas exchange parameters.

Transintestinal cholesterol efflux.

PURPOSE OF REVIEW: Regulation of cholesterol homeostasis is a complex interplay of a multitude of metabolic pathways situated in different organs. The liver plays a central role and has received most attention of the research community. In this review, we discuss recent progress in the understanding of the emerging role of the intestine in cholesterol transport. RECENT FINDINGS: In recent years, insight in the transport systems that mediate intestinal cholesterol excretion has deepened considerably. Evidence is emerging that the proximal part of the small intestine is able to secrete cholesterol actively, a pathway called transintestinal cholesterol efflux (TICE). In mice, TICE accounts for up to 70% of fecal neutral sterol excretion. SUMMARY: The small intestine plays a significant role in the regulation of body cholesterol homeostasis. Active processes control both absorption and excretion of the sterol and the pathways involved are being elucidated. TICE might provide an attractive target for therapy aiming at reduction of atherosclerosis.

Changes and prognostic value of cardiopulmonary exercise testing parameters in elderly patients undergoing cardiac rehabilitation: The EU-CaRE observational study.

OBJECTIVE: We aimed 1) to test the applicability of the previously suggested prognostic value of CPET to elderly cardiac rehabilitation patients and 2) to explore the underlying mechanism of the greater improvement in exercise capacity (peak oxygen consumption, VO2) after CR in surgical compared to non-surgical cardiac patients. METHODS: Elderly patients (≥65 years) commencing CR after coronary artery bypass grafting, surgical valve replacement (surgery-group), percutaneous coronary intervention, percutaneous valve replacement or without revascularisation (non-surgery group) were included in the prospective multi-center EU-CaRE study. CPETs were performed at start of CR, end of CR and 1-year-follow-up. Logistic models and receiver operating characteristics were used to determine prognostic values of CPET parameters for major adverse cardiac events (MACE). Linear models were performed for change in peak VO2 (start to follow-up) and parameters accounting for the difference between surgery and non-surgery patients were sought. RESULTS: 1421 out of 1633 EU-CaRE patients performed a valid CPET at start of CR (age 73±5.4, 81% male). No CPET parameter further improved the receiver operation characteristics significantly beyond the model with only clinical parameters. The higher improvement in peak VO2 (25% vs. 7%) in the surgical group disappeared when adjusted for changes in peak tidal volume and haemoglobin. CONCLUSION: CPET did not improve the prediction of MACE in elderly CR patients. The higher improvement of exercise capacity in surgery patients was mainly driven by restoration of haemoglobin levels and improvement in respiratory function after sternotomy. TRIAL REGISTRATION: Netherlands Trial Register, Trial NL5166.

Predictors for one-year outcomes of cardiorespiratory fitness and cardiovascular risk factor control after cardiac rehabilitation in elderly patients: The EU-CaRE study.

INTRODUCTION: Studies on effectiveness of cardiac rehabilitation (CR) in elderly cardiovascular disease patients are rare, and it is unknown, which patients benefit most. We aimed to identify predictors for 1-year outcomes of cardiorespiratory fitness and CV risk factor (CVRF) control in patients after completing CR programs offered across seven European countries. METHODS: Cardiovascular disease patients with minimal age 65 years who participated in comprehensive CR were included in this observational study. Peak oxygen uptake (VO2), body mass index (BMI), resting systolic blood pressure (BPsys), and low-density lipoprotein-cholesterol (LDL-C) were assessed before CR (T0), at termination of CR (T1), and 12 months after start of CR (T2). Predictors for changes were identified by multivariate regression models. RESULTS: Data was available from 1241 out of 1633 EU-CaRE patients. The strongest predictor for improvement in peak VO2 was open chest surgery, with a nearly four-fold increase in surgery compared to non-surgery patients. In patients after surgery, age, female sex, physical inactivity and time from index event to T0 were negative predictors for improvement in peak VO2. In patients without surgery, previous acute coronary syndrome and higher exercise capacity at T0 were the only negative predictors. Neither number of attended training sessions nor duration of CR were significantly associated with change in peak VO2. Non-surgery patients were more likely to achieve risk factor targets (BPsys, LDL-C, BMI) than surgery patients. CONCLUSIONS: In a previously understudied population of elderly CR patients, time between index event and start of CR in surgery and disease severity in non-surgery patients were the most important predictors for long-term improvement of peak VO2. Non-surgery patients had better CVRF control.

Greater burden of risk factors and less effect of cardiac rehabilitation in elderly with low educational attainment: The Eu-CaRE study.

AIMS: Socioeconomic status is a strong predictor of cardiovascular health. The aim of this study was to describe the immediate and long-term effects of cardiac rehabilitation (CR) across socioeconomic strata in elderly cardiac patients in Europe. METHODS AND RESULTS: The observational EU-CaRE study is a prospective study with eight CR sites in seven European countries. Patients ≥65 years with coronary heart disease or heart valve surgery participating in CR were consecutively included. Data were obtained at baseline, end of CR and at one-year follow up. Educational level as a marker for socioeconomic status was divided into basic, intermediate and high. The primary endpoint was exercise capacity (peak oxygen consumption (VO2peak)). Secondary endpoints were cardiovascular risk factors, medical treatment and scores for depression, anxiety and quality of life (QoL). A total of 1626 patients were included; 28% had basic, 48% intermediate and 24% high education. A total of 1515 and 1448 patients were available for follow-up analyses at end of CR and one-year, respectively. Patients with basic education were older and more often female. At baseline we found a socioeconomic gradient in VO2peak, lifestyle-related cardiovascular risk factors, anxiety, depression and QoL. The socioeconomic gap in VO2peak increased following CR (p for interaction <0.001). The socioeconomic gap in secondary outcomes was unaffected by CR. The use of evidence-based medication was good in all socioeconomic groups. CONCLUSIONS: We found a strong socioeconomic gradient in VO2peak and cardiovascular risk factors that was unaffected or worsened after CR. To address inequity in cardiovascular health, the individual adaption of CR according to socioeconomic needs should be considered.

Offering, participation and adherence to cardiac rehabilitation programmes in the elderly: a European comparison based on the EU-CaRE multicentre observational study.

AIMS: Cardiac rehabilitation (CR) is strongly recommended but participation of elderly patients has not been well characterized. This study aims to analyse current rates and determinants of CR referral, participation, adherence, and compliance in a contemporary European cohort of elderly patients. METHODS AND RESULTS: The EU-CaRE observational study included data from consecutive patients aged ≥ 65 with acute coronary syndrome, revascularization, stable coronary artery disease, or heart valve replacement, recruited in eight European centres. Rates and factors determining offering, participation, and adherence to CR programmes and compliance with training sessions were studied across centres, under consideration of extensive-outpatient vs. intensive-inpatient programmes. Three thousand, four hundred, and seventy-one patients were included in the offering and participation analysis. Cardiac rehabilitation was offered to 80.8% of eligible patients, formal contraindications being the main reason for not offering CR. Mean participation was 68.0%, with perceived lack of usefulness and transport issues being principal barriers. Mean adherence to CR programmes of participants in the EU-CaRE study (n = 1663) was 90.3%, with hospitalization/physical impairment as principal causes of dropout. Mean compliance with training sessions was 86.1%. Older age was related to lower offering and participation, and comorbidity was associated with lower offering, participation, adherence, and compliance. Intensive-inpatient programmes displayed higher adherence (97.1% vs. 85.9%, P < 0.001) and compliance (full compliance: 66.0% vs. 38.8%, P < 0.001) than extensive-outpatient programmes. CONCLUSION: In this European cohort of elderly patients, older age and comorbidity tackled patients' referral and uptake of CR programmes. Intensive-inpatient CR programmes showed higher completion than extensive-outpatient CR programmes, suggesting this formula could suit some elderly patients.

Effectiveness of Home-Based Mobile Guided Cardiac Rehabilitation as Alternative Strategy for Nonparticipation in Clinic-Based Cardiac Rehabilitation Among Elderly Patients in Europe: A Randomized Clinical Trial.

Importance: Although nonparticipation in cardiac rehabilitation is known to increase cardiovascular mortality and hospital readmissions, more than half of patients with coronary artery disease in Europe are not participating in cardiac rehabilitation. Objective: To assess whether a 6-month guided mobile cardiac rehabilitation (MCR) program is an effective therapy for elderly patients who decline participation in cardiac rehabilitation. Design, Setting, and Participants: Patients were enrolled in this parallel multicenter randomized clinical trial from November 11, 2015, to January 3, 2018, and follow-up was completed on January 17, 2019, in a secondary care system with 6 cardiac institutions across 5 European countries. Researchers assessing primary outcome were masked for group assignment. A total of 4236 patients were identified with a recent diagnosis of acute coronary syndrome, coronary revascularization, or surgical or percutaneous treatment for valvular disease, or documented coronary artery disease, of whom 996 declined to start cardiac rehabilitation. Subsequently, 179 patients who met the inclusion and exclusion criteria consented to participate in the European Study on Effectiveness and Sustainability of Current Cardiac Rehabilitation Programmes in the Elderly trial. Data were analyzed from January 21 to October 11, 2019. Interventions: Six months of home-based cardiac rehabilitation with telemonitoring and coaching based on motivational interviewing was used to stimulate patients to reach exercise goals. Control patients did not receive any form of cardiac rehabilitation throughout the study period. Main Outcomes and Measures: The primary outcome parameter was peak oxygen uptake (Vo2peak) after 6 months. Results: Among 179 patients randomized (145 male [81%]; median age, 72 [range, 65-87] years), 159 (89%) were eligible for primary end point analysis. Follow-up at 1 year was completed for 151 patients (84%). Peak oxygen uptake improved in the MCR group (n = 89) at 6 and 12 months (1.6 [95% CI, 0.9-2.4] mL/kg-1/min-1 and 1.2 [95% CI, 0.4-2.0] mL/kg-1/min-1, respectively), whereas there was no improvement in the control group (n = 90) (+0.2 [95% CI, -0.4 to 0.8] mL/kg-1/min-1 and +0.1 [95% CI, -0.5 to 0.7] mL/kg-1/min-1, respectively). Changes in Vo2peak were greater in the MCR vs control groups at 6 months (+1.2 [95% CI, 0.2 to 2.1] mL/kg-1/min-1) and 12 months (+0.9 [95% CI, 0.05 to 1.8] mL/kg-1/min-1). The incidence of adverse events was low and did not differ between the MCR and control groups. Conclusions and Relevance: These results suggest that a 6-month home-based MCR program for patients 65 years or older with coronary artery disease or a valvular intervention was safe and beneficial in improving Vo2peak when compared with no cardiac rehabilitation. Trial Registration: trialregister.nl Identifier: NL5168.

Training intensity and improvements in exercise capacity in elderly patients undergoing European cardiac rehabilitation - the EU-CaRE multicenter cohort study.

OBJECTIVES: Guidelines for exercise intensity prescription in Cardiac Rehabilitation (CR) are inconsistent and have recently been discussed controversially. We aimed (1) to compare training intensities between European CR centres and (2) to assess associations between training intensity and improvement in peak oxygen consumption ([Formula: see text]O2) in elderly CR patients. METHODS: Peak [Formula: see text]O2, heart rate and work rate (WR) at the first and second ventilatory thresholds were measured at start of CR. Training heart rate was measured during three sessions spread over the CR. Multivariate models were used to compare training characteristics between centres and to assess the effect of training intensity on change in peak [Formula: see text]O2. RESULTS: Training intensity was measured in 1011 out of 1633 EU-CaRE patients in 7 of 8 centers and the first and secondary ventilatory threshold were identified in 1166 and 817 patients, respectively. The first and second ventilatory threshold were found at 44% (SD 16%) and 78% (SD 9%) of peak WR and 78% (SD 9%) and 89% (SD 5%) of peak heart rate, respectively. Training intensity and session duration varied significantly between centres but change in peak [Formula: see text]O2 over CR did not. Training above the first individual threshold (ß 0.62, 95% confidence interval [0.25-1.02]) and increase in training volume per hour (ß 0.06, 95%CI [0.01-0.12]) were associated with a higher change in peak [Formula: see text]O2. CONCLUSION: While training intensity and volume varied greatly amongst current European CR programs, changes in peak [Formula: see text]O2 were similar and the effect of training characteristics on these changes were small.

Cardiac rehabilitation of elderly patients in eight rehabilitation units in western Europe: Outcome data from the EU-CaRE multi-centre observational study.

AIMS: The European Cardiac Rehabilitation in the Elderly (EU-CaRE) HORIZON 2020 project compares the sustainable effects of cardiac rehabilitation (CR) in elderly patients. METHODS AND RESULTS: A total of 1633 patients with coronary artery disease (CAD) or heart valve replacement (HVR), with or without revascularization, aged 65 or above, who participated in CR were included. Peak oxygen uptake (VO2peak), smoking, body mass index, diet, physical activity, serum lipids, psychological distress and medication were assessed before and after CR (T0 and T1) and after 12 months (T2). Patients undergoing coronary artery bypass surgery or surgical HVR had lower VO2peak at T0 and a greater increase to T1 and T2 (2.8 and 4.4 ml/kg/min, respectively) than CAD patients undergoing percutaneous or no revascularization (1.6 and 1.4 ml/kg/min, respectively). After multivariable adjustment, earlier CR uptake was associated with greater improvements in VO2peak. The proportion of CAD patients with three or more uncontrolled risk factors declined from 58.4% at T0 to 40.1% at T2 (p < 0.0001). Psychological distress scores all improved and adherence to medication was overall good at all sites. There were significant differences in risk factor burden across sites, but no CR program was superior to others. CONCLUSIONS: The outcomes of VO2peak in CR programs across Europe seemed mainly determined by timing of uptake and were maintained or even further improved at 1-year follow-up. Despite significant improvements, 40.1% of CAD patients still had three or more risk factors not at target after 1 year. Differences across sites could not be ascribed to characteristics of the CR programs offered.

Predictors of pre-rehabilitation exercise capacity in elderly European cardiac patients - The EU-CaRE study.

AIMS: Functional capacity is an important endpoint for therapies oriented to older adults with cardiovascular diseases. The literature on predictors of exercise capacity is sparse in the elderly population. In a longitudinal European study on effectiveness of cardiac rehabilitation of seven European countries in elderly (>65 years) coronary artery disease or valvular heart disease patients, predictors for baseline exercise capacity were determined, and reference ranges for elderly cardiac patients provided. METHODS: Mixed models were performed in 1282 patients (mean age 72.9 ± 5.4 years, 79% male) for peak oxygen consumption relative to weight (peak VO2; ml/kg per min) with centre as random factor and patient anthropometric, demographic, social, psychological and nutritional parameters, as well as disease aetiology, procedure, comorbidities and cardiovascular risk factors as fixed factors. RESULTS: The most important predictors for low peak VO2 were coronary artery bypass grafting or valve surgery, low resting forced expiratory volume, reduced left ventricular ejection fraction, nephropathy and peripheral arterial disease. Each cumulative comorbidity or cardiovascular risk factors reduced exercise capacity by 1.7 ml/kg per min and 1.1 ml/kg per min, respectively. Males had a higher peak VO2 per body mass but not per lean mass. Haemoglobin was significantly linked to peak VO2 in both surgery and non-surgery patients. CONCLUSIONS: Surgical procedures, cumulative comorbidities and cardiovascular risk factors were the factors with the strongest relation to reduced exercise capacity in the elderly. Expression of peak VO2 per lean mass rather than body mass allows a more appropriate comparison between sexes. Haemoglobin is strongly related to peak VO2 and should be considered in studies assessing exercise capacity, especially in studies on patients after cardiac surgery.

Peroxisome proliferator-activated receptor delta activation leads to increased transintestinal cholesterol efflux.

Peroxisome proliferator-activated receptor delta (PPARdelta) is involved in regulation of energy homeostasis. Activation of PPARdelta markedly increases fecal neutral sterol secretion, the last step in reverse cholesterol transport. This phenomenon can neither be explained by increased hepatobiliary cholesterol secretion, nor by reduced cholesterol absorption. To test the hypothesis that PPARdelta activation leads to stimulation of transintestinal cholesterol efflux (TICE), we quantified it by intestine perfusions in FVB mice treated with PPARdelta agonist GW610742. To exclude the effects on cholesterol absorption, mice were also treated with cholesterol absorption inhibitor ezetimibe or ezetimibe/GW610742. GW601742 treatment had little effect on plasma lipid levels but stimulated both fecal neutral sterol excretion ( approximately 200%) and TICE ( approximately 100%). GW610742 decreased intestinal Npc1l1 expression but had no effect on Abcg5/Abcg8. Interestingly, expression of Rab9 and LIMPII, encoding proteins involved in intracellular cholesterol trafficking, was increased upon PPARdelta activation. Although treatment with ezetimibe alone had no effect on TICE, it reduced the effect of GW610742 on TICE. These data show that activation of PPARdelta stimulates fecal cholesterol excretion in mice, primarily by the two-fold increase in TICE, indicating that this pathway provides an interesting target for the development of drugs aiming at the prevention of atherosclerosis.

Cardiac rehabilitation in the elderly patient in eight rehabilitation units in Western Europe: Baseline data from the EU-CaRE multicentre observational study.

BACKGROUND: Due to the progressive deconditioning, comorbidities and higher complication rates, elderly patients are in particular need of cardiac rehabilitation. We compared elderly patients (65+ years old) participating in cardiac rehabilitation, focusing on baseline characteristics, risk factor control and functional assessment. METHODS: The EU-CaRE study is a prospective study comparing cardiac rehabilitation in eight centres across Western Europe. Consecutive patients with acute coronary syndrome, stable coronary artery disease and heart valve replacement undergoing cardiac rehabilitation were included. RESULTS: Of 1633 patients (median age 72 years) participating, 54% had acute coronary syndrome, 33% had stable coronary artery disease and 13% followed valve replacement. Fifty-five per cent had undergone percutaneous coronary intervention and 29% coronary artery bypass grafting. Characteristics varied across centres: 23% (17-27%) were women, 4% (0-12%) were of non-European origin and 16% (4-32%) were living alone. Median time from index event to start of cardiac rehabilitation varied from 11 to 49 days (p < 0.001). Mean VO2peak was relatively low (16 mL/kg per min) and varied significantly between the participating centres, largely unaffected by multivariable adjustment. Overall patients received guideline recommended treatment: 93% (87-97%) were on a statin and 70% (55-85%) an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. However, risk factor control was inadequate: 58% had three or more risk factors not controlled. CONCLUSION: EU-CaRE provides a snapshot of the elderly population with heart disease participating in cardiac rehabilitation across countries in Western Europe. Risk factors and exercise capacity indicate the continued need for cardiac rehabilitation in these patients. Of concern, the lag-time to start of cardiac rehabilitation needs improvement in many centres.

Shifting gears: liver SR-BI drives reverse cholesterol transport in macrophages.

Cholesterol efflux from macrophages, the first step in reverse cholesterol transport (RCT), is assumed to play a critical role in the pathogenesis of atherosclerosis. However, in vivo proof supporting this hypothesis is lacking, due to difficulties in determining the activity of this first step in RCT. In this issue of the JCI, Zhang et al. apply their recently developed method for measuring RCT in vivo to estimate RCT in mouse models with varying levels of HDL turnover. A surprisingly efficient clearance of cholesterol to feces is observed in mice overexpressing hepatic scavenger receptor class B type I (SR-BI), whereas in SR-BI-knockout mice, cholesterol clearance is diminished. The study demonstrates that hepatic SR-BI is a positive regulator of macrophage RCT in vivo.

ABCA1-dependent but apoA-I-independent cholesterol efflux mediated by fatty acid-bile acid conjugates (FABACs).

FABACs (fatty acid-bile acid conjugates) are synthetic molecules that are designed to treat a range of lipid disorders. The compounds prevent cholesterol gallstone formation and diet-induced fatty liver, and increase reverse cholesterol transport in rodents. The aim of the present study was to investigate the effect of FABACs on cholesterol efflux in human cells. Aramchol (3beta-arachidylamido-7alpha,12alpha,5beta-cholan-24-oic acid) increased cholesterol efflux from human skin fibroblasts in a dose-dependent manner in the absence of known efflux mediators such as apoA-I (apolipoprotein A-I), but had little effect on phospholipid efflux. An LXR (liver X receptor) agonist strongly increased Aramchol-induced cholesterol efflux; however, in ABCA1 (ATP-binding cassette transporter A1)-deficient cells from Tangier disease patients, the Aramchol effect was absent, indicating that activity of ABCA1 was required. Aramchol did not affect ABCA1 expression, but plasma membrane levels of the transporter increased 2-fold. Aramchol is the first small molecule that induces ABCA1-dependent cholesterol efflux without affecting transcriptional control. These findings may explain the beneficial effect of the compound on atherosclerosis.

A EUropean study on effectiveness and sustainability of current Cardiac Rehabilitation programmes in the Elderly: Design of the EU-CaRE randomised controlled trial.

BACKGROUND: Cardiac rehabilitation (CR) is an evidence-based intervention to increase survival and quality of life. Yet studies consistently show that elderly patients are less frequently referred to CR, show less uptake and more often drop out of CR programmes. DESIGN: The European study on effectiveness and sustainability of current cardiac rehabilitation programmes in the elderly (EU-CaRE) project consists of an observational study and an open prospective, investigator-initiated multicentre randomised controlled trial (RCT) involving mobile telemonitoring guided CR (mCR). OBJECTIVE: The aim of EU-CaRE is to map the efficiency of current CR of the elderly in Europe, and to investigate whether mCR is an effective alternative in terms of efficacy, adherence and sustainability. METHODS AND RESULTS: The EU-CaRE study includes patients aged 65 years or older with ischaemic heart disease or who have undergone heart valve surgery. A total of 1760 patients participating in existing CR programmes in eight regions of Europe will be included. Of patients declining regular CR, 238 will be included in the RCT and randomised in two study arms. The experimental group (mCR) will receive a personalised home-based programme while the control group will receive no advice or coaching throughout the study period. Outcomes will be assessed after the end of CR and at 12 months follow-up. The primary outcome is VO2peak and secondary outcomes include variables describing CR uptake, adherence, efficacy and sustainability. CONCLUSION: The study will provide important information to improve CR in the elderly. The EU-CaRE RCT is the first European multicentre study of mCR as an alternative for elderly patients not attending usual CR.