Current Respiratory Medicine Reviews, 2007, 3, 000-000 1 1573-398X/07 $50.00+.00 © 2007 Bentham Science Publishers Ltd. Ventilatory Abnormalities During Exercise in Heart Failure: A Mini Review Ross Arena *,1 , Marco Guazzi 2 and Jonathan Myers 3 1 Department of Physical Therapy, Virginia Commonwealth University, Health Sciences Campus, Richmond, Virginia, USA 2 University of Milano, San Paolo Hospital, Cardiopulmonary Laboratory, Cardiology Division, University of Milano, San Paolo Hospital, Milano, Italy 3 VA Palo Alto Health Care System, Cardiology Division, Stanford University, Palo Alto, CA, USA Abstract: Heart Failure (HF) is a significant health care concern with in both the United States and Europe. While there are a number of mechanisms that lead to HF, a decline in the response to exercise is common amongst the various etiolo- gies. Cardiopulmonary exercise testing (CPET) is a well established diagnostic and prognostic tool in the HF population. This exercise testing technique allows for the measurement of oxygen consumption (VO 2 ), carbon dioxide production (VCO 2 ) and minute ventilation (VE) across time. Cardiovascular and skeletal muscle dysfunction is considered central to the often abnormal exercise response observed in the HF population. As such, VO 2 at peak exercise is the most recognized CPET variable in patients with HF. In recent years however, the importance of assessing VE during exercise, either alone or in combination with expired gases, has been highlighted in a number of investigations. The VE-VCO 2 relationship, ex- ercise periodic breathing (EPB) and the oxygen uptake efficiency slope (OUES) are, to this point, the most studied CPET measurements incorporating VE in the HF population. Of these, the VE-VCO 2 relationship has received the greatest amount of attention. This review will address the clinical significance of these CPET measurements in the HF population. INTRODUCTION Heart Failure (HF) is a significant health care concern with approximately five and ten million individuals diag- nosed with this condition in the United States and Europe, respectively [1,2]. While there are a number of mechanisms that lead to HF, an impairment in the response to exercise is common amongst the various etiologies. Cardiopulmonary exercise testing (CPET) is a well established diagnostic and prognostic tool in the HF population and well respected American and European organizations have both put forth consensus statements supporting its use [3,4]. This exercise testing technique allows for the measurement of oxygen con- sumption (VO 2 ), carbon dioxide production (VCO 2 ) and minute ventilation (VE) across time. Cardiovascular and skeletal muscle dysfunction is considered central to the often abnormal exercise response observed in the HF population. As such, VO 2 at peak exercise (the product of cardiac output and the difference in oxygen content between the arterial and venous blood) is the most recognized CPET variable in pa- tients with HF. In recent years, however, the importance of assessing VE during exercise, either alone or in combination with expired gases, has been highlighted in a number of in- vestigations. The VE-VCO 2 relationship, exercise periodic breathing (EPB) and the oxygen uptake efficiency slope (OUES) are, to this point, the most studied CPET measure- ments incorporating VE in the HF population, of which, the VE-VCO 2 relationship has received the greatest amount of *Address correspondence to this author at the Department of Physical Ther- apy, P.O. Box 980224, Virginia Commonwealth University, Health Sci- ences Campus, Richmond, VA 23298-0224, USA; Tel: 804-828-0234; Fax: 804-828-8111; E-mail: raarena@.vcu.edu attention. This review will address the clinical significance of these CPET measurements in the HF population. The VE-VCO 2 Relationship The rise in VE and VCO 2 with aerobic exercise is tightly coupled as increasing carbon dioxide levels as a consequence of increased metabolism and, at higher exercise intensities, lactic acid buffering drive the ventilatory response. This rela- tionship is most commonly expressed as the VE/VCO 2 slope, although the ratio between VE and VCO 2 at maximal exer- cise has also been shown to provide prognostic value [5,6]. Furthermore, a change in VE/VCO 2 from rest to anaerobic threshold of less then 10% has been shown to effectively identify HF patients with a diminished aerobic capacity (<14 mlO 2 •kg -1 •min -1 , 96% positive predictive value and 88% negative predictive value) although the prognostic signifi- cance of this submaximal calculation has not been investi- gated [7]. The VE/VCO 2 slope is, however, the preferred expression since a greater amount of the exercise data is used for its calculation, thereby reducing the potential variability secondary to measurement error. During an incremental ex- ercise test to maximal exertion, the VE/VCO 2 slope is gener- ally linear although there is a notable and widely variable non-linear break point beyond the anaerobic threshold. The resultant second slope from the anaerobic threshold to maximal exertion has been shown to increase a mean of 2. 6 ±4. 1 units compared to the VE/VCO 2 slope measured from the onset of exercise to the point of anaerobic threshold, with a greater difference indicating worse prognosis [8]. Although submaximal VE/VCO 2 slope calculations provide valuable information, several investigations have demonstrated a VE/VCO 2 slope calculation incorporating all exercise data (onset of exercise to maximal exertion) produces clinically optimal information compared to submaximal calculations