Cardiac output response to exercise in relation to metabolic demand in heart failure with preserved ejection fraction

Abstract

AimsExercise intolerance is a hallmark of heart failure with preserved ejection fraction (HFpEF), yet its mechanisms remain unclear. The current study sought to determine whether increases in cardiac output (CO) during exercise are appropriately matched to metabolic demands in HFpEF. Methods and resultsPatients with HFpEF (n ¼ 109) and controls (n ¼ 73) exercised to volitional fatigue with simultaneous invasive (n ¼ 96) or non-invasive (n ¼ 86) haemodynamic assessment and expired gas analysis to determine oxygen consumption (VO 2 ) during upright or supine exercise. At rest, HFpEF patients had higher LV filling pressures but similar heart rate, stroke volume, EF, and CO. During supine and upright exercise, HFpEF patients displayed lower peak VO 2 coupled with blunted increases in heart rate, stroke volume, EF, and CO compared with controls. LV filling pressures increased dramatically in HFpEF patients, with secondary elevation in pulmonary artery pressures. Reduced peak VO 2 in HFpEF patients was predominantly attributable to CO limitation, as the slope of the increase in CO relative to VO 2 was 20% lower in HFpEF patients (5.9 + 2.5 vs. 7.4 + 2.6 L blood/L O 2 , P ¼ 0.0005). While absolute increases in arterial -venous O 2 difference with exercise were similar in HFpEF patients and controls, augmentation in arterial-venous O 2 difference relative to VO 2 was greater in HFpEF patients (8.9 + 3.4 vs. 5.5 + 2.0 min/dL, P , 0.0001). These differences were observed in the total cohort and when upright and supine exercise modalities were examined individually. ConclusionWhile diastolic dysfunction promotes congestion and pulmonary hypertension with stress in HFpEF, reduction in exercise capacity is predominantly related to inadequate CO relative to metabolic needs.--

Mechanisms of Exercise Intolerance in Heart Failure With Preserved Ejection Fraction

“…In summary, numerous recent studies have changed the way we conceptualize the pathophysiology of HFpEF: away from being simply a disorder of diastolic dysfunction to more of a global impairment in the multiple components of cardiovascular 15, 23 and peripheral 18,20 reserves, which limits the ability to cope with physiologic stresses such as exercise. Further research is required to refine our understanding, enabling more optimal treatment for patients with HFpEF.…”

“…45 In a separate study, Abudiab et al noted that for any increase in LVEDP, the increase in cardiac output was markedly attenuated in patients with HFpEF compared to controls. 23 Clinically, this failure of the Frank-Starling reserve is most clearly manifest as an elevation in LVFP, and recent studies have provided insight into the pathogenesis of this process. Westermann et al performed conductance catheter analysis in 70 HFpEF patients and 20 controls, and observed both prolonged relaxation and increased diastolic elastance.…”

“…Heart rate acceleration during the onset of exercise (C) and deceleration during early recovery (D) were abnormal in HFpEF compared to controls. (Data taken from Borlaug et al 15 and Abudiab et al 23 ) Exercise Intolerance in HFpEF minants of exercise capacity. 76 Intriguingly, the presence of AF in HFpEF was found to be an independent predictor of RV dysfunction, which may additionally explain the adverse outcome and greater impairment in exercise capacity in subjects with AF.…”

“…The authors speculated that this represents a chronic adaptation to inadequate QC, citing the fact that with a lower QC, there is greater time available for gas exchange in the capillaries, which may serve to counterbalance any potential abnormalities in convective and diffusive O2 transfer. 23 In that …”

Exercise Intolerance in Heart Failure with Preserved Ejection Fraction

“…Santos et al 11 and Abudiab et al 12 suggested that the major contributor to exercise inability in HFpEF patients is the reduced cardiac output relative to metabolic needs, indicating a cardiac cause. Extensive fibrosis and titin hypophosphorylation 7 is thought to create stiffness in the LV of patients with HFpEF, contributing to the cardiac limitations in exercise capacity.…”