Determinants of exercise ventilatory inefficiency in heart failure with reduced or preserved ejection fraction: Application of classical and emerging integrative physiology concepts

While it is well-recognized that ventilatory inefficiency during exercise signals worsened prognosis in patients with heart failure (HF), the underlying pathophysiological mechanisms of this relationship have yet to be well defined. Further complicating this question is the evolving body of evidence suggesting the etiology of HF with reduced versus preserved ejection fraction is discernably different. Therefore, to advance this field of study, while simultaneously strengthening the clinical utility of quantifying exercise ventilatory inefficiency in HF, it is critical that this field as an entirety demonstrates a commitment toward conducting patient-based studies that foremost consider the integrative physiological nature of human ventilation. Thus, by merging discussions between multiple independent lines of study focusing on ventilatory responses to exercise in HF, this chapter narrows the scope of this topic to demonstrate that there are indeed integrative associations across anatomical, physiological, and biochemical factors that synergize to provoke ventilatory inefficiency and exercise intolerance in HF.