Levels of evidence in the European Society of Cardiology Guidelines: Gaps in knowledge?

Editorial on scientific evidence of current guideline

A multidisciplinary approach to prevention

Cardiovascular disease accounts for 17,500 deaths globally, representing nearly half of all non-communicable disease deaths. The World Health Organization has set nine lifestyle, risk factor and medicines targets to achieve by 2025 with the aim of reducing premature mortality from non-communicable diseases by 25%. In order to succeed in this, we need to equip our global health professional workforce with the skills to support patients and their families with making lifestyle changes and being in concordance with cardioprotective medication regimes at every opportunity. Success depends on collegiate working through effective interdisciplinary team-based care characterised by shared goals, clear roles, mutual trust, effective communication and measurable processes and outcomes, with the patient and family at the centre of care. Nurses are the largest sector of the health professional workforce and their role in prevention should be optimised. Nurse coordinated care is proven to be effective, especially where they work in an interdisciplinary way with other health professionals such as doctors, pharmacists and psychologists, who provide equally important expertise for supporting holistic care. Successful care models are those that comprehensively target all adverse lifestyles and risk factors that are responsible for the development of cardiovascular disease. These characteristics should be reflected in the standards and core components of prevention and rehabilitation programmes

Exercise training for chronic heart failure (ExTraMATCH II): individual participant data meta-analysis of randomised controlled trials

This is the author accepted manuscript. The final version is available from NIHR Journals Library via the DOI in this record.Background: Current national and international guidelines on the management of heart failure (HF) recommend exercise-based cardiac rehabilitation (ExCR), but do not differentiate this recommendation according to patient subgroups. Objective(s): (1) to obtain definitive estimates of the impact of ExCR interventions versus control (no exercise intervention) on mortality, hospitalisation, exercise capacity, and health-related quality of life (HRQoL) in HF patients; (2) to determine the differential (subgroup) effects of ExCR in HF patients according to their age, gender, ejection fraction, aetiology, New York Heart Association (NYHA) class, and baseline exercise capacity; (3) to assess whether the change in exercise capacity mediates for the impact of the ExCR on final outcomes (mortality, hospitalisation, and HRQoL) and is an acceptable surrogate endpoint. Design: Individual participant data (IPD) meta-analysis Setting: An international literature review Participants: HF patients in randomised controlled trials (RCTs) of ExCR Interventions: ExCR for at least 3 weeks compared with no exercise control with 6 months follow-up Main outcome measures: mortality (all cause and HF-specific), hospitalisation (all-cause & HF-specific), exercise capacity, and HRQoL Data sources: Individual participant data from eligible RCTs 3 Review methods: RCTs from ExTraMATCH IPD meta-analysis and 2014 Cochrane systematic review of ExCR Results: Out of the 23 eligible RCTs (4,398 patients), 19 RCTs (3,990 patients) contributed data to this IPD meta-analysis. There was a wide variation in exercise programme prescriptions across included studies. Compared with control, there was no statistically significant difference in pooled time to event estimates in favour of ExCR although confidence intervals were wide: all-cause mortality: hazard ratio (HR) 0.83 (95% confidence interval (CI): 0.67 to 1.04), HF-related mortality: HR 0.84 (95% CI: 0.49 to 1.46), all-cause hospitalisation: HR 0.90 (95% CI: 0.76 to 1.06), and HF-related hospitalisation: HR 0.98 (95% CI: 0.72 to 1.35). There was a statistically significant difference in favour of ExCR for exercise capacity and HRQoL. Compared to control, at 12-months follow-up, improvements were seen in the six-minute walk test (6MWT) (mean: 21.0 metres, 95% CI: 1.57 to 40.4, and Minnesota Living with HF Questionnaire score (mean: -5.94, 95% CI: -1.0 to -10.9, lower scores indicate improved HRQoL). No strong evidence for differential intervention effects across patient characteristics was found for any outcomes. Moderate to good levels of correlation (R2 trial>50% & ρ>0.50) between peak oxygen uptake (VO2peak) or 6MWT with mortality and HRQoL were seen. Estimated surrogate threshold effect (STE) was an increase of 1.6 to 4.6 ml/kg/min for VO2peak. Limitations: Lack consistency in how included RCTs defined and collected the outcomes; we were unable to obtain IPD from all includable trials for all outcomes; and we did not seek patient level on exercise adherence. . Conclusions: In comparison to no exercise control, participation in ExCR improves the exercise and HRQoL in HF patients but appears to have no effect on their mortality or hospitalisation. No strong evidence was found of differential intervention effects of ExCR across patient characteristics. VO2peak and 6MWT may be suitable surrogate endpoints for the treatment effect of ExCR on mortality and HRQoL in HF.NIHR Health Technology Assessment programm

Validation of Exercise Capacity as a Surrogate Endpoint in Exercise-Based Rehabilitation for Heart Failure: A Meta-Analysis of Randomized Controlled Trials

This is the final version. Available on open access from Elsevier via the DOI in this recordObjectives: This study sought to validate exercise capacity (EC) as a surrogate for mortality, hospitalization, and health-related quality of life (HRQOL). Background: EC is often used as a primary outcome in exercise-based cardiac rehabilitation (CR) trials of heart failure (HF) via direct cardiorespiratory assessment of maximum oxygen uptake (VO2peak) or through submaximal tests, such as the 6-min walk test (6MWT). Methods: After a systematic review, 31 randomized trials of exercise-based CR compared with no exercise control (4,784 HF patients) were included. Outcomes were pooled using random effects meta-analyses, and inverse variance weighted linear regression equations were fitted to estimate the relationship between the CR on EC and all-cause mortality, hospitalization, and HRQOL. Spearman correlation coefficient (ρ), R2 at trial level, and surrogate threshold effect (STE) were calculated. STE represents the intercept of the prediction band of the regression line with null effect on the final outcome. Results: Exercise-based CR is associated with positive effects on EC measured through VO2peak (+3.10 ml/kg/min; 95% confidence interval [CI]: 2.01 to 4.20) or 6MWT (+41.15 m; 95% CI: 16.68 to 65.63) compared to control. The analyses showed a low level of association between improvements in EC (VO2peak or 6MWT) and mortality and hospitalization. Moderate levels of correlation between EC with HRQOL were seen (e.g., R2 <52%; |ρ| < 0.72). Estimated STE was an increase of 5 ml/kg/min for VO2peak and 80 m for 6MWT to predict a significant improvement in HRQOL. Conclusions: The study results indicate that EC is a poor surrogate endpoint for mortality and hospitalization but has moderate validity as a surrogate for HRQOL. Further research is needed to confirm these findings across other HF interventions.National Institute for Health Research (NIHR)University of Exete

Contribution of the lung to the genesis of cheyne-stokes respiration in heart failure: Plant gain beyond chemoreflex gain and circulation time

Background-The contribution of the lung or the plant gain (PG; ie, change in blood gases per unit change in ventilation) to Cheyne-Stokes respiration (CSR) in heart failure has only been hypothesized by mathematical models, but never been directly evaluated.Methods and Results-Twenty patients with systolic heart failure (age, 72.4 +/- 6.4 years; left ventricular ejection fraction, 31.5 +/- 5.8%), 10 with relevant CSR (24-hour apnea-hypopnea index [AHI] &gt;= 10 events/h) and 10 without (AHI &lt;10 events/h) at 24-hour cardiorespiratory monitoring underwent evaluation of chemoreflex gain (CG) to hypoxia (CG(O2)) and hypercapnia (CG(CO2)) by rebreathing technique, lung-to-finger circulation time, and PG assessment through a visual system. PG test was feasible and reproducible (intraclass correlation coefficient, 0.98; 95% CI, 0.91-0.99); the best-fitting curve to express the PG was a hyperbola (R-2 &gt;= 0.98). Patients with CSR showed increased PG, CG(CO2) (but not CG(O2)), and lung-to-finger circulation time, compared with patients without CSR (all P&lt;0.05). PG was the only predictor of the daytime AHI (R=0.56, P=0.01) and together with the CG(CO2) also predicted the nighttime AHI (R=0.81, P=0.0003) and the 24-hour AHI (R=0.71, P=0.001). Lung-to-finger circulation time was the only predictor of CSR cycle length (R=0.82, P=0.00006).Conclusions-PG is a powerful contributor of CSR and should be evaluated together with the CG and circulation time to individualize treatments aimed at stabilizing breathing in heart failure

Factors associated with lack of improvement in submaximal exercise capacity of patients with heart failure

Aims Improvement in exercise capacity is the primary goal of physical activity programmes for patients with heart failure (HF). Although activity programmes are effective for some patients, others do not benefit. Identifying factors related to a lack of improvement in submaximal exercise capacity may help us interpret findings and design new interventions. The aim of this study is to identify factors contributing to a lack of improvement in submaximal exercise capacity 3 months after physical activity advice or an exergame intervention in patients with HF. Additionally, we aimed to assess differences in lack of improvement in submaximal exercise capacity of patients whose baseline exercise capacity predicted a worse compared with better prognosis of HF.Methods and results This secondary analysis of the HF-Wii study analysed baseline and 3 month data of the 6 min walk test (6MWT) from 480 patients (mean age 67 years, 72% male). Data were analysed separately in patients with a pre-defined 6 min walking distance at baseline of &lt;300 m (n = 79) and &gt;= 300 m (n = 401). Among patients with a baseline 6MWT of &gt;= 300 m, 18% had deteriorated submaximal exercise capacity. In the multiple logistic regression analysis, lower baseline levels of self-reported physical activity [odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.60-0.97], lower baseline levels of cognitive function (OR = 0.87, 95%CI = 0.79-0.96) were significantly associated with lack of improvement in exercise capacity at 3 months. Not randomized to exergaming (OR = 0.63, 95%CI = 0.37-1.09) was likely (P = 0.097) to be associated with lack of improvement in exercise capacity at 3 months. Among the 79 patients with baseline 6MWT of &lt;300 m, 41% (n = 32) did not improve 6MWT distance at 3 months. Independent predictors for the lack of improvement for 6MWT were New York Heart Association class III/IV (OR = 4.68, 95%CI = 1.08-20.35), higher levels of serum creatinine (OR = 1.02, 95%CI = 1.003-1.03), lower cognitive function (OR = 0.86, 95%CI = 0.75-0.99), and fewer anxiety symptoms (OR = 0.84, 95%CI = 0.72-0.98).Conclusions Lower self-reported physical activity and cognitive impairment predict lack of improvement in submaximal exercise capacity in HF patients. Patients who have a worse prognosis (score &lt;300 m at the 6MWT) are often frail and gain less in exercise capacity. These patients may need a more comprehensive approach to have an effect on exercise capacity, including an individually tailored exercise programme with aerobic exercise (if tolerated) and strength exercises

Effects of exergaming on exercise capacity in patients with heart failure: results of an international multicentre randomized controlled trial

Aims Exergaming is a new tool to increase physical activity. This study aimed to determine the effects of access to a home-based exergame (Nintendo Wii) in patients with heart failure (HF) on exercise capacity, self-reported physical activity and patient-reported outcome measures.Methods and results We enrolled 605 HF patients in New York Heart Association functional class I-IV, independent of ejection fraction, in an international multicentre randomized controlled trial. Patients were randomized to exergame (intervention) or motivational support (control). The primary endpoint was change in submaximal aerobic exercise capacity as measured by the distance walked in 6 min (6MWT) between baseline and 3 months. Secondary endpoints included long-term submaximal aerobic exercise capacity, muscle function, self-reported physical activity, exercise motivation, exercise self-efficacy at 3, 6 and 12months. At baseline, patients on average walked 403142m on the 6MWT. Patients in the exergame group walked further compared to controls at 3 months (454123 vs. 420 +/- 127m, P = 0.005), at 6 months (452 +/- 123 vs. 426 +/- 133m, P = 0.015) and 12months (456 +/- 122 vs. 420 +/- 135m, P = 0.004). However, correcting for baseline 6MWT values by means of a linear mixed-effects model revealed no main effect for the intervention on 6MWT. Small significant effects on muscle function were found. Statistically significant treatment effects were found for muscle function but after correction for baseline and confounders, only the treatment effect for the heel-rise left at 6 months was significant (P&lt;0.05). No treatment effect was found for exercise motivation, exercise self-efficacy, or self-reported physical activity.ConclusionExergaming was safe and feasible in patients with HF with different profiles in different health care systems, cultures and climates. However, it was not effective in improving outcomes on submaximal aerobic exercise capacity. Subgroup analysis did not identify specific subgroups benefiting from the intervention.Clinical Trial Registration: Identifier: NCT01785121