Some heart failure (HF) patients develop ventilatory oscillation which is composed of exercise periodic breathing (EPB) and sleep apnea. The ventilatory oscillation is associated with exercise intolerance. This study employed an integrated monitoring system to elucidate the way of central and peripheral hemodynamic adaption responding to exercise. This study recruited 157 HF patients to perform exercise testing using a bicycle ergometer. A noninvasive bio-reactance device was adopted to measure cardiac hemodynamics, whereas a near-infrared spectroscopy (NIRS) was used to assess perfusion and O₂ extraction in the frontal cerebral lobe (FC) and vastus lateralis muscle (VL) during exercise respectively. Furthermore, quality of life (QoL) was measured with the Short Form-36 (SF-36) and the Minnesota Living with Heart Failure questionnaires (MLHFQ). The patients were divided into an EPB group (n = 65) and a non-EPB group (n = 92) according to their ventilation patterns during testing. Compared to their non-EPB counterparts, the patients with EPB exhibited 1) impaired aerobic capacity with a smaller peak oxygen consumption (VO_2peak) and oxygen uptake efficiency slopes; 2) impaired circulatory and ventilatory efficiency with relatively high cardiac output and ventilation per unit workload; 3) impaired ventilatory/hemodynamic adaptation in response to exercise with elevated deoxyhemoglobin levels in the FC region; and 4) impaired QoL with lower physical component scores on the SF-36 and higher scores on the MLHFQ. In conclusion, EPB may reduce circulatory-ventilatory-hemodynamic efficiency during exercise, thereby impairing functional capacity in patients with HF.