Consequences of group III/IV afferent feedback and respiratory muscle work on exercise tolerance in heart failure with reduced ejection fraction

Abstract

Exercise intolerance and exertional dyspnoea are the cardinal symptoms of heart failure with reduced ejection fraction (HFrEF). In HFrEF, abnormal autonomic and cardiopulmonary responses arising from locomotor muscle group III/IV afferent feedback is one of the primary mechanisms contributing to exercise intolerance. HFrEF patients also have pulmonary system and respiratory muscle abnormalities that impair exercise tolerance. Thus, the primary impetus for this review was to describe the mechanistic consequences of locomotor muscle group III/IV afferent feedback and respiratory muscle work in HFrEF. To address this, we first discuss the abnormal autonomic and cardiopulmonary responses mediated by locomotor muscle afferent feedback in HFrEF. Next, we outline how respiratory muscle work impairs exercise tolerance in HFrEF through its effects on locomotor muscle O2 delivery. We then discuss the direct and indirect evidence supporting an interaction between locomotor muscle group III/IV afferent feedback and respiratory muscle work during exercise in HFrEF. Last, we outline future research directions related to locomotor and respiratory muscle abnormalities to progress the field forward in understanding the pathophysiology of exercise intolerance in HFrEF.New Findings What is the topic of this review? This review is focused on understanding the role that locomotor muscle group III/IV afferent feedback and respiratory muscle work play in the pathophysiology of exercise intolerance in patients with heart failure. What advances does it highlight? This review proposes that the concomitant effects of locomotor muscle afferent feedback and respiratory muscle work worsen exercise tolerance and exacerbate exertional dyspnoea in patients with heart failure.

Exaggerated Inspiratory Muscle Metaboreflex in Arterial Hypertension

“…These findings have important implications for older patients with hypertension as exaggerated cardiovascular responses to inspiratory muscle metaboreflex activation are important contributors to exercise intolerance and exertional symptoms for patients with CVD. 3 Further, the present findings are directionally consistent with those recently reported in heart failure with preserved ejection fraction 4 ; a population with a high prevalence of hypertension. In this context, our findings suggest that these inspiratory muscle pathophysiologic mechanisms may present earlier in the CVD progression than previously recognized.…”

“… 2 Heart failure is also associated with pulmonary system abnormalities that directly relate to exercise intolerance and exertional symptoms including inspiratory muscle weakness and reduced inspiratory muscle endurance. 3 We found that inspiratory muscle metaboreflex activation via high inspiratory muscle work results in exaggerated increases in mean arterial pressure (MAP) and leg vasoconstriction, resulting in reduced leg blood flow in patients with heart failure compared with controls. 4 However, it is unclear whether these inspiratory muscle abnormalities are present earlier in the progression of CVD.…”

“…Recent evidence supports that older patients with hypertension without overt CVD may exhibit pulmonary system abnormalities that are often associated with overt heart failure, exertional symptoms, and mortality. 2 , 3 Specifically, older patients with hypertension have higher ventilatory to carbon dioxide slopes during exercise than older adults with normotension, with >70% of these slopes being abnormal in patients with hypertension. 2 Heart failure is also associated with pulmonary system abnormalities that directly relate to exercise intolerance and exertional symptoms including inspiratory muscle weakness and reduced inspiratory muscle endurance.…”