Exercise and Metabolic Demand in HF With Preserved EF
Exercise and Metabolic Demand in HF With Preserved EF
Aims Exercise 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 results Patients with HFpEF (n = 109) and controls (n = 73) exercised to volitional fatigue with simultaneous invasive (n = 96) or non-invasive (n = 86) haemodynamic assessment and expired gas analysis to determine oxygen consumption (VO2) 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 VO2 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 VO2 in HFpEF patients was predominantly attributable to CO limitation, as the slope of the increase in CO relative to VO2 was 20% lower in HFpEF patients (5.9 ± 2.5 vs. 7.4 ± 2.6 L blood/L O2, P = 0.0005). While absolute increases in arterial–venous O2 difference with exercise were similar in HFpEF patients and controls, augmentation in arterial–venous O2 difference relative to VO2 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.
Conclusion While 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.
Heart failure (HF) has been defined as an inability of the heart to provide cardiac output (CO) to the body at a rate commensurate with its needs, or to do so only at the cost of elevated filling pressures. Resting CO is generally preserved until the most advanced stages of disease, but CO reserve with exercise is impaired at earlier stages in HF with reduced ejection fraction (HFrEF). In practice, CO reserve is estimated indirectly by measuring the peak oxygen consumption (peak VO2) attained during exercise. However, because increases in CO are tightly coupled to changes in VO2, simultaneous measurement of CO and VO2 allows for more robust assessment of the adequacy of cardiac oxygen delivery relative to metabolic needs. This relationship (ΔCO/ΔVO2 slope) is characteristically depressed in HFrEF.
Half of patients with HF have preserved EF (HFpEF). Peak VO2 is similarly depressed in HFpEF and HFrEF, yet the nature of VO2 impairment with exercise in HFpEF remains controversial. Potential mechanisms include CO limitation, subjective dyspnoea, impaired vasodilation, skeletal muscle dysfunction, deranged pulmonary gas exchange or mechanics, patient motivation, fitness level, body habitus, and medical co-morbidities. It has recently been reported that exertional capacity in HFpEF is constrained predominantly by abnormalities in cardiac filling or peripheral O2 extraction, rather than CO impairment. Distinguishing these possibilities is of fundamental importance when contemplating novel treatments for HFpEF, a disease with no proven therapy.
The current study aimed to characterize the relationships between ventricular filling and ejection relative to metabolic demand, oxygen delivery, and extraction during exercise in patients with HFpEF. Because haemodynamics differ in the upright and supine positions, and because of potential for referral bias when exclusively studying a catheterization population, we include subjects studied using both invasive and non-invasive methods to measure CO in both the supine and upright positions. We hypothesized that CO reserve relative to VO2 would be impaired in HFpEF patients compared with controls.
Abstract and Introduction
Abstract
Aims Exercise 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 results Patients with HFpEF (n = 109) and controls (n = 73) exercised to volitional fatigue with simultaneous invasive (n = 96) or non-invasive (n = 86) haemodynamic assessment and expired gas analysis to determine oxygen consumption (VO2) 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 VO2 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 VO2 in HFpEF patients was predominantly attributable to CO limitation, as the slope of the increase in CO relative to VO2 was 20% lower in HFpEF patients (5.9 ± 2.5 vs. 7.4 ± 2.6 L blood/L O2, P = 0.0005). While absolute increases in arterial–venous O2 difference with exercise were similar in HFpEF patients and controls, augmentation in arterial–venous O2 difference relative to VO2 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.
Conclusion While 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.
Introduction
Heart failure (HF) has been defined as an inability of the heart to provide cardiac output (CO) to the body at a rate commensurate with its needs, or to do so only at the cost of elevated filling pressures. Resting CO is generally preserved until the most advanced stages of disease, but CO reserve with exercise is impaired at earlier stages in HF with reduced ejection fraction (HFrEF). In practice, CO reserve is estimated indirectly by measuring the peak oxygen consumption (peak VO2) attained during exercise. However, because increases in CO are tightly coupled to changes in VO2, simultaneous measurement of CO and VO2 allows for more robust assessment of the adequacy of cardiac oxygen delivery relative to metabolic needs. This relationship (ΔCO/ΔVO2 slope) is characteristically depressed in HFrEF.
Half of patients with HF have preserved EF (HFpEF). Peak VO2 is similarly depressed in HFpEF and HFrEF, yet the nature of VO2 impairment with exercise in HFpEF remains controversial. Potential mechanisms include CO limitation, subjective dyspnoea, impaired vasodilation, skeletal muscle dysfunction, deranged pulmonary gas exchange or mechanics, patient motivation, fitness level, body habitus, and medical co-morbidities. It has recently been reported that exertional capacity in HFpEF is constrained predominantly by abnormalities in cardiac filling or peripheral O2 extraction, rather than CO impairment. Distinguishing these possibilities is of fundamental importance when contemplating novel treatments for HFpEF, a disease with no proven therapy.
The current study aimed to characterize the relationships between ventricular filling and ejection relative to metabolic demand, oxygen delivery, and extraction during exercise in patients with HFpEF. Because haemodynamics differ in the upright and supine positions, and because of potential for referral bias when exclusively studying a catheterization population, we include subjects studied using both invasive and non-invasive methods to measure CO in both the supine and upright positions. We hypothesized that CO reserve relative to VO2 would be impaired in HFpEF patients compared with controls.
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