ReviewPrognostic respiratory parameters in heart failure patients with and without exercise oscillatory ventilation — A systematic review and descriptive meta-analysis☆
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.
References (62)
- et al.
Prediction of severe cardiovascular events by VE/VCO2 slope versus peak VO2 in systolic heart failure: a meta-analysis of the published literature
Am. Heart J.
(12 2010) - et al.
Peak VO2 and VE/VCO2 slope in patients with heart failure: a prognostic comparison
Am. Heart J.
(Feb 2004) - et al.
Cardiopulmonary and noninvasive hemodynamic responses to exercise predict outcomes in heart failure
J. Card. Fail.
(2 2013) - et al.
End-tidal CO2 pressure decreases during exercise in cardiac patients: association with severity of heart failure and cardiac output reserve
J. Am. Coll. Cardiol.
(Jul 2000) - et al.
Prognostic value of timing and duration characteristics of exercise oscillatory ventilation in patients with heart failure
J. Heart Lung Transplant.
(Mar 2008) - et al.
Exercise oscillatory ventilation in heart failure
Trends Cardiovasc. Med.
(Oct 2012) - et al.
Metabolic exercise test data combined with cardiac and kidney indexes, the MECKI score: a multiparametric approach to heart failure prognosis
Int. J. Cardiol.
(Sep 10 2013) - et al.
Exercise oscillatory breathing and increased ventilation to carbon dioxide production slope in heart failure: an unfavorable combination with high prognostic value
Am. Heart J.
(May 2007) - et al.
Oscillatory ventilation during exercise in patients with chronic heart failure: clinical correlates and prognostic implications
Chest
(May 2002) - et al.
Oscillatory breathing and exercise gas exchange abnormalities prognosticate early mortality and morbidity in heart failure
J. Am. Coll. Cardiol.
(Apr 27 2010)
Oxygen uptake efficiency plateau best predicts early death in heart failure
Chest
Exertional periodic breathing potentiates erythrocyte rheological dysfunction by elevating pro-inflammatory status in patients with anemic heart failure
Int. J. Cardiol.
Relation between oscillatory ventilation at rest before cardiopulmonary exercise testing and prognosis in patients with left ventricular dysfunction
Chest
Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation
J. Am. Coll. Cardiol.
Exercise oscillatory ventilation: instability of breathing control associated with advanced heart failure
Chest
Mechanism of periodic breathing in patients with cardiovascular disease
Chest
Oscillatory hyperventilation in severe congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy
Am. J. Cardiol.
The partial pressure of resting end-tidal carbon dioxide predicts major cardiac events in patients with systolic heart failure
Am. Heart J.
Quantifying oscillatory ventilation during exercise in patients with heart failure
Respir. Physiol. Neurobiol.
Comparison of the ramp versus standard exercise protocols
J. Am. Coll. Cardiol.
Comparison of treadmill and bicycle exercise in patients with chronic heart failure
Chest
Prognostic value of end-tidal carbon dioxide during exercise testing in heart failure
Int. J. Cardiol.
A cardiopulmonary exercise testing score for predicting outcomes in patients with heart failure
Am. Heart J.
The minute ventilation/carbon dioxide production slope is prognostically superior to the oxygen uptake efficiency slope
J. Card. Fail.
Exercise oscillatory ventilation reflects diminished quality of life and perceived functional capacity in patients with heart failure
Int. J. Cardiol.
Prognostic implications of preoperative aerobic capacity and exercise oscillatory ventilation after liver transplantation
Am. J. Transplant.
Acetazolamide and inhaled carbon dioxide reduce periodic breathing during exercise in patients with chronic heart failure
J. Card. Fail.
Periodic breathing during exercise in severe heart failure. Reversal with milrinone or cardiac transplantation
Chest
Meta-analysis of aerobic interval training on exercise capacity and systolic function in patients with heart failure and reduced ejection fractions
Am. J. Cardiol.
The clinical and research applications of aerobic capacity and ventilatory efficiency in heart failure: an evidence-based review
Heart Fail. Rev.
ACC/AHA Guidelines for Exercise Testing. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Exercise Testing)
J. Am. Coll. Cardiol.
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Systematic review registration number: PROSPERO CRD42014010106.
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This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.