TY - JOUR
AU - Krüger, Stefan
AB - This editorial describes the impact of the results of the SERVE-HF study for cardiac rehabilitation as heart failure and sleep apnoea in cardiac rehabilitation patients is very common. Sleep apnoea is an independent risk factor for cardiovascular diseases.1,2 The most prevalent type of sleep apnoea is obstructive sleep apnoea (OSA), contributing to 38,000 cardiovascular deaths every year.3 Myocardial damage is thought to occur secondary to increased sympathetic activity, heart rate variability, endothelial dysfunction, systemic inflammation, oxidative stress, platelet activation and/or metabolic abnormalities.4–6 OSA represents a significant, but modifiable, risk factor for cardiovascular disease.7 However, OSA appears to be under-diagnosed in patients with coronary artery disease.8,9 Data from the Reha-Sleep registry suggest that the prevalence of sleep apnoea in patients attending cardiac rehabilitation facilities could be as high as 33%, and that there are few differences between patients with and without sleep apnoea with respect to sleep quality and daytime sleepiness.10 The prevalence of heart failure in western countries is about 1–2% of the adult population, with significant increases with age. Recent guidelines differentiate between heart failure due to reduced systolic left ventricular ejection fraction (HF-REF) and heart failure with preserved ejection fraction (HF-PEF) and impaired diastolic function. HF-REF is the most widely investigated and best understood type of heart failure, with a high prevalence in men with ischaemic heart disease.3 In contrast, HF-PEF is more prevalent in women and often has a non-ischaemic aetiology. Epidemiological data suggest that HF-REF and HF-PEF have a similar prognostic impact. A number of comorbidities have been linked to the development and progression of heart failure. One that is gaining increasing recognition is sleep-disordered breathing (SDB) with predominant OSA or central sleep apnoea (CSA) with or without Cheyne–Stokes respiration (CSR). CSR occurs when arterial carbon dioxide partial pressures fall below the apnoeic threshold. The cycle length of alternating periods of hypocapnia induces apnoea and reflex hyperventilation. CSR is inversely proportional to cardiac output and thus directly related to the severity of heart failure.2 A reduced left ventricular function delays the circulation time between the lungs and the chemoreceptors and increases the sensitivity of chemoreceptors, especially to carbon dioxide. The degree of carbon dioxide hypersensitivity is a major determinant of CSR.11 Small studies published to date have reported that the prevalence of SDB was almost 70–80% in patients with HF-PEF and up to 76% in those with HF-REF based on a cut-off of an apnoea–hypopnoea index (apnoeas and hypopnoeas per hour; AHI) ≥5/hour while moderate to severe sleep apnoea with an AHI ≥15/hour was prevalent in about half of the patients.12,13 SDB in general, as well as OSA and, in particular, CSA have been shown to be independently associated with worse prognosis in patients with HF-REF.2 The Sleep Heart Health Study14 identified OSA as an independent risk factor for the development of heart failure, with more impact in men than in women. Patients with CSA have been shown to have a reduced quality of life and to be at increased risk of developing cardiac arrhythmias.15 In addition, the prevalence of CSA–CSR appears to increase as the severity of heart failure increases and cardiac function decreases.16 Management of HF-REF starts with an accurate diagnosis and requires a rational combination of drug therapy and non-pharmacological management (education, fluid control, weight monitoring and physical exercise training).17 The use of beta-blockers or cardiac resynchronisation therapy results in a reduction of CSR.18,19 However, even in these patients with optimal heart failure therapy, CSR or OSA can be still present and have a major impact on prognosis. Treatment of SDB in HF-REF is controversial. In the CANPAP-Trial Bradley et al. evaluated the outcome of nasal continuous positive airways pressure (CPAP) treatment in patients with HF-REF and CSR.20 Patients were randomly assigned to receive nasal CPAP or no CPAP. The trial was stopped prematurely and no beneficial effect of nasal CPAP was demonstrated on morbidity or mortality. A post hoc analysis suggested that mortality might be lower if the AHI was successfully reduced to <15/hour by nasal CPAP.21 Adaptive servoventilation (ASV) is another alternative for ventilatory support in CSR, with effective alleviation of central apnoea by delivering servo-controlled inspiratory pressure support on top of expiratory positive airway pressure.22 Small studies revealed a positive effect on daytime sleepiness, reduction of the AHI, effects on impaired ejection fraction, quality of life, plasma brain natriuretic peptide and catecholamine urinary excretion as biomarkers of HF-REF prognosis. The SERVE-HF trial, the largest study on SDB in heart failure ever performed, is an international, multicentre randomised parallel-group study to evaluate the effects of ASV in patients with CSA and HF-REF.23,24 A total of 1325 patients was included (inclusion criteria: ejection fraction <45%, AHI >15/hour) and were randomly assigned to optimal medical treatment with additional ASV or medical treatment only. After 12 months follow-up, the mean AHI was 6.6/hour in the ASV group, showing an effective treatment of CSA. Unfortunately, in ASV treated patients compared to optimal medical therapy alone all-cause mortality (hazard ratio 1.28; 95% confidence interval 1.06–1.55; P = 0.01) and cardiovascular mortality (hazard ratio 1.34; 95% confidence interval 1.09–1.65; P = 0.006) were significantly higher. Furthermore, there was no beneficial effect of ASV on functional measures such as quality of life measures or 6 minute walk distance or symptoms. What does this surprising result of the SERVE-HF study mean for cardiac rehabilitation? HF-REF is common in cardiac rehabilitation facilities and the presence of CSA is high. In a small study we were able to determine CSA in about 60% of patients with stabilised HF-REF during cardiac rehabilitation.25 Based on current guidelines, an optimal heart failure medication with use of beta-blockers is necessary, followed by discussion about the implantation of a CRT device. If OSA is present, treatment with nasal CPAP is needed.26 If CSA is the main SDB, oxygen therapy can be considered.27 According to the results of the CANPAP study and the SERVE-HF study the use of nasal CPAP or ASV treatment does not seem to be helpful; in the case of ASV it turned out to be even harmful. The treatment of CSA in HF-REF by phrenic nerve stimulation with a pacemaker is under investigation.28–30 With respect to the results of the SERVE-HF study there are reasonable doubts that this intervention might be beneficial for the therapy of HF-REF. More trials are needed to evaluate the effect of aerobic training on CSA. As training in HF-REF exhibits an improvement on peak oxygen consumption and in one study also on CSA,31 more data are needed.32 In summary, the SERVE-HF study showed that ASV therapy did not have a positive effect on the composite endpoint of death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalisation for worsening heart failure. In contrast, all-cause mortality and cardiovascular mortality were higher under ASV treatment in HF-REF patients. The early and sustained increase in cardiovascular mortality in this trial was very surprising and unexpected. The pathophysiological reasons of this effect are not definitely clear and remain to be elucidated by further studies. Funding The authors received no financial support for the research, authorship, and/or publication of this article. Declaration of conflicting interests The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: ECS received grants and personal fees from ResMed for lectures during the Reha-Sleep study, SK reported grants from ResMed during the study period of the Reha-Sleep study. References 1 Jean-Louis G , Brown CD, Zizi Fet al. . Cardiovascular disease risk reduction with sleep apnea treatment . Expert Rev Cardiovasc Ther 2010 ; 8 ( 7 ): 995 – 1005 . Google Scholar Crossref Search ADS PubMed WorldCat 2 Lanfranchi PA , Braghiroli A, Bosimini Eet al. . Prognostic value of nocturnal Cheyne–Stokes respiration in chronic heart failure . Circulation 1999 ; 99 ( 11 ): 1435 – 1440 . 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TI - SERVE-HF: What does it mean for cardiac rehabilitation?
JF - European Journal of Preventive Cardiology
DO - 10.1177/2047487315619769
DA - 2016-01-01
UR - https://www.deepdyve.com/lp/oxford-university-press/serve-hf-what-does-it-mean-for-cardiac-rehabilitation-rOZBty4RQJ
SP - 125
EP - 128
VL - 23
IS - 2
DP - DeepDyve
ER -