Review
Prognostic respiratory parameters in heart failure patients with and without exercise oscillatory ventilation — A systematic review and descriptive meta-analysis

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Highlights

  • We evaluate the presence of EOV on prognostic variables derived from CPET.

  • We include 19 citations totalling 3032 patients with heart failure.

  • We find that EOV significantly indicates aggravated prognostic markers.

  • We suggest the inclusion of the assessment of EOV in each CPET evaluation protocol.

Abstract

The purpose of this review was to describe the occurrence of prognostic variables as derived from cardiopulmonary exercise testing (CPET) in patients with heart failure (HF), presenting exercise oscillatory ventilation (EOV) compared to patients without EOV. The effect of EOV on peak oxygen consumption (VO2), minute ventilation/carbon dioxide production (VE/VCO2) slope, oxygen uptake efficiency slope (OUES), rest and peak pulmonary end-tidal carbon dioxide pressure (PETCO2) was meta-analysed. A systematic search strategy was performed in five databases (Pubmed, Cochrane Library, PEDro, Science Direct and Web of Science) assessing 252 articles for eligibility. Nineteen citations met the inclusion criteria totalling 3032 patients with HF (EOV = 1111; non-EOV = 1921). The risk of bias was assessed by two researchers. Extracted data were pooled using random or fixed effects meta-analysis, if appropriate. The level of significance was set at p  0.05. Overall, the presentation of EOV significantly indicated aggravated prognostic markers. Subgroup analysis revealed left ventricular ejection fraction (LVEF) and mode of CPET protocol as independent factors, whereas defining EOV significantly influenced the results. A meta-analysis of studies reporting hazard ratios for cardiovascular events demonstrated that HF patients with EOV run a fourfold risk for an adverse event compared to HF patients without EOV. In general, these findings suggest that the presence of EOV in patients with HF is associated with a deterioration of the prognostic CPET parameters. Furthermore, EOV can occur in HF patients with reduced as well as preserved ejection fraction. Further research on defining and assessing EOV in a more accurate and reproducible way is required.

Introduction

In clinical management and research of patients with heart failure (HF), the use of cardiopulmonary exercise testing (CPET) has become notable in providing information about aerobic capacity, ventilatory efficiency and diagnostic insights [1]. Accordingly, a wide range of CPET parameters demonstrated a considerable prognostic value in this population. Previously, researchers focussed mainly on the assessment of peak oxygen consumption (peak VO2), and therefore this value was stated to be the key CPET parameter in prognosis of HF [1], [2]. Nowadays, a shift arises towards the prognostic ability of the minute ventilation/carbon dioxide production (VE/VCO2) slope [3], [4], oxygen uptake efficiency slope (OUES) [5], [6], [7], pulmonary end-tidal carbon dioxide pressure (PETCO2) [7], [8] and exercise oscillatory ventilation (EOV) [9], [10]. These parameters have received more attention in research and proved their striking independently as well as complementary prognostic contribution [1], [3], [4], [7], [11]. Those novelties and multi-variable approaches caused researchers to develop and validate broader risk scores to obtain optimal prognosis in patients suffering this chronic disease [7], [10], [12], [13]. However, the clinical application of these tools seem to be difficult since there is an abundance of CPET-derived parameters [10], a wide range of applied CPET protocols [14] and a lack of general standardisation [10] mainly caused by the absence of gold standard definitions to describe the prognostic variables [11] and the diversity in proposed threshold values [7], [10], [15], [16]. Despite investigation and clarity regarding these major features is needed in every suggested prognostic parameter, this study will focus on EOV as primary parameter. A recent meta-analysis of Cahalin et al. [10] indicated EOV as very important variable in prognostic CPET assessment. This abnormal ventilatory pattern is currently manual determined by a researcher instead of automatically calculated by the software packages [10], [11]. Therefore EOV could be left unnoticed by the clinician in many cases. Furthermore, many significant differences were seen between an EOV presenting (EOV +) and a non-EOV presenting (EOV −) population. HF patients presenting EOV would have an aggravated prognosis since cardiac events significantly occurred more in patients presenting EOV [9]. Significant differences such as decreased peak VO2, increased VE/VCO2 slope and decreased peak PETCO2 were noted in this population [9], [17]. It was stated that patients with EOV had a decreased exercise capacity, yet in multivariate models, EOV occurred as the strongest independent predictor of events [15], [17], [18] and was therefore independent to other prognostic variables [19]. It was assumed that EOV presentation is a warning sign for aggravation of the symptoms and prognosis of the HF population [19]. However, the pathophysiological mechanisms that induce EOV are not yet clarified [19] since increased circulatory delay, increased chemosensitivity, pulmonary congestion or ergoreflex signalling is suggested as possible triggers [11]. The presentation of EOV could be an indication for adjusted medication prescription, individualised modified cardiac rehabilitation [20], intensive follow-up of the patient and even heart transplantation (HTX) [18]. Therefore it seems interesting to perform a systematic search strategy to overview the baseline characteristics of an EOV +, compared to an EOV − group. A meta-analysis of the available published literature was executed to investigate the effect of EOV on other key-variables and its prognostic value in patients with HF.

Section snippets

Methods

This systematic review and descriptive meta-analysis was registered in the PROSPERO database (registration number: CRD42014010106). The meta-analysis process was performed according to the Cochrane Collaboration recommendations [21]. Following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, a systematic search strategy was performed.

Systematically searched databases were Pubmed, the Cochrane Library, PEDro, Web of Science and Science

Results

After the initial search, 252 articles were assessed for eligibility. De-duplication resulted in 191 articles. After screening on title, abstract and full-text, 19 citations fulfilled the a priori set inclusion criteria (Fig. 1).

The risk of bias of 18 studies was assessed (Table 1). Since the group of Sun et al. reported on the same sample in two different studies [22], [23], description of the population was only mentioned once. The HR and OUES were the only supplementary values extracted from

Discussion

To our knowledge, this systematic review and descriptive meta-analysis is the first to investigate the differences in cardiorespiratory parameters based on the presence of EOV in patients with heart failure.

The key findings include in general worsened prognostic CPET parameters in the EOV population compared to a non-EOV population. Thus, in EOV presenting HF patients, a significant decrease in peak VO2, peak PETCO2, rest PETCO2 and OUES was apparent. A significant increase was visible in VE/VCO

Conclusions

In conclusion, prognostic CPET parameters such as peak VO2, peak PETCO2 and rest PETCO2 were aggravated in heart failure patients with EOV, where VE/VCO2 slope and OUES were significantly increased. Sub-study analysis revealed LVEF and CPET mode of protocol as independent factors, whereas the use of different EOV definitions significantly affected the results. A meta-analysis of studies reporting hazard ratios for cardiovascular events demonstrated that HF patients with EOV run a fourfold risk

Conflicts of interest

None.

Acknowledgement of grant support

None.

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    Systematic review registration number: PROSPERO CRD42014010106.

    1

    This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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