Cardiovascular response to exercise is primarily aimed at increasing oxygen (O 2 ) delivery to the working muscle. Most cardiovascular diseases impair the physiology of O 2 uptake during exercise because of a reduction in O 2 delivery and an impaired extraction. Expired gas analysis during exercise assesses the overall functional capacity and provides a series of information beyond maximal O 2 consumption (VO 2 max). Specifically, the rate of VO 2 increase as related to work rate (ΔVO 2 /ΔWR slope) is commonly viewed as an indicator of cardiovascular efficiency and reflects the aerobic generated ATP. Under physiological conditions, the ΔVO 2 /ΔWR slope increases linearly with reduced variability because of the functional state. In the presence of a normal delivery and extraction, the ΔVO 2 /ΔWR slope mirrors the cardiac output (CO) increase during exercise. An abrupt change of ΔVO 2 /ΔWR slope (or flattening) during incremental workload, before reaching the maximum O 2 , is commonly interpreted as the inability of the heart to adequately increase CO. This pattern has been primarily observed in heart failure (HF) and myocardial ischemia but can also be observed in severe restrictive lung disease. A reduced contractile reserve, resulting from myocardium loss and transient ischemia, limits the stroke volume (SV) increase, as well as a complete β-receptors blockade reduces heart rate (HR) reserve, both leading to blunted CO response.