Determinants and consequences of heart rate and stroke volume response to exercise in patients with heart failure and preserved ejection fraction

E Wolsk, DM Kaye, J Komtebedde, SJ Shah, BA Borlaug, D Burkhoff, DW Kitzman, JG Cleland, G Hasenfuß, C Hassager, JE Møller and F Gustafsson
Eur J Heart Fail 2021

AIMS: A hallmark of heart failure with preserved ejection fraction (HFpEF) is impaired exercise capacity of varying severity. The main determinant of exercise capacity is cardiac output (CO), however little information is available about the relation between the constituents of CO – heart rate and stroke volume and exercise capacity in HFpEF. We sought to determine if a heterogeneity in heart rate and stroke volume response to exercise exists in patients with HFpEF and describe possible clinical phenotypes associated with differences in these responses.

METHODS AND RESULTS: Data from two prospective trials of HFpEF (n=108) and a study of healthy participants (n=42) with invasive hemodynamic measurements during exercise were utilized. Differences in central hemodynamic responses were analyzed with regression models. Chronotropic incompetence was present in 39-56% of patients with HFpEF and 3-56% of healthy participants depending on the definition used, but some (n=47, 44%) had an increase in heart rate similar to that of healthy controls. Patients with HFpEF had a smaller increase in their stroke volume index (SVI) [HFpEF: +4±10 ml/m(2) , healthy participants: +24±12 ml/m(2) , p<0.0001], indeed, SVI fell in 28% of patients at peak exercise. Higher BMI and lower SVI at rest were associated with smaller increases in heart rate during exercise, whereas higher resting heart rate, and ACE-inhibitor/angiotensin II receptor blocker use were associated with a greater increase in SVI in patients with HFpEF.

CONCLUSION: The hemodynamic response to exercise was very heterogenous among patients with HFpEF, with chronotropic incompetence observed in up to 56% and 28% had impaired increase in SVI. This suggests that hemodynamic exercise testing may be useful to identify which HFpEF patients may benefit from interventions targeting stroke volume and chronotropic response. CLINICAL TRIAL REGISTRATION: (NCT01913613, NCT02600234, NCT01974557).

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