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

ObjectiveThe time needed to increase oxygen utilisation to meet metabolic demand (V̇O2 kinetics) is impaired in heart failure (HF) with reduced ejection fraction and is an independent risk factor for HF mortality. It is not known if V̇O2 kinetics are slowed in HF with preserved ejection fraction (HFpEF). We tested the hypothesis that V̇O2 kinetics are slowed during submaximal exercise in HFpEF and that slower V̇O2 kinetics are related to impaired peripheral oxygen extraction.MethodsEighteen HFpEF patients (68±7 years, 10 women) and 18 healthy controls (69±6 years, 10 women) completed submaximal and peak exercise testing. Cardiac output (acetylene rebreathing, Q̇c), ventilatory oxygen uptake (V̇O2, Douglas bags) and arterial-venous O2 difference (a-vO2 difference) derived from Q̇c and V̇O2 were assessed during exercise. Breath-by-breath O2 uptake was measured continuously throughout submaximal exercise, and V̇O2 kinetics was quantified as mean response time (MRT).ResultsHFpEF patients had markedly slowed V̇O2 kinetics during submaximal exercise (MRT: control: 40.1±14.2, HFpEF: 65.4±27.7 s; p<0.002), despite no relative impairment in submaximal cardiac output (Q̇c: control: 8.6±1.7, HFpEF: 9.7±2.2 L/min; p=0.79). When stratified by MRT, HFpEF with an MRT ≥60 s demonstrated elevated Q̇c, and impaired peripheral oxygen extraction that was apparent during submaximal exercise compared with HFpEF with a MRT <60 s (submaximal a-vO2 difference: MRT <60 s: 9.7±2.1, MRT ≥60 s: 7.9±1.1 mL/100 mL; p=0.03).ConclusionHFpEF patients have slowed V̇O2 kinetics that are related to impaired peripheral oxygen utilisation. MRT can identify HFpEF patients with peripheral limitations to submaximal exercise capacity and may be a target for therapeutic intervention.

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Ejection fraction in patients with heart failure and preserved ejection fraction is greater than that in controls – A mechanism facilitating left ventricular filling and maximizing cardiac output

Medical Hypotheses ◽

10.1016/j.mehy.2012.06.001 ◽

2012 ◽

Vol 79 (3) ◽

pp. 384-387 ◽

Cited By ~ 6

Author(s):

Guy Dori ◽

Michael Rudman ◽

Oscar Lichtenstein ◽

Jorge E. Schliamser

Keyword(s):

Heart Failure ◽

Cardiac Output ◽

Ejection Fraction ◽

Left Ventricular ◽

Left Ventricular Filling ◽

Preserved Ejection Fraction ◽

Patients With Heart Failure ◽

Ventricular Filling

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Pulmonary Vascular Pressures and Gas Exchange Response to Exercise in Heart Failure With Preserved Ejection Fraction

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2020.07.009 ◽

2020 ◽

Vol 26 (11) ◽

pp. 1011-1015

Author(s):

Caitlin C. Fermoyle ◽

Glenn M. Stewart ◽

Barry A. Borlaug ◽

Bruce D. Johnson

Keyword(s):

Heart Failure ◽

Gas Exchange ◽

Ejection Fraction ◽

Preserved Ejection Fraction ◽

Response To Exercise

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Comparison of cardiac output estimates by echocardiography and bioreactance at rest and peak dobutamine stress test in heart failure patients with preserved ejection fraction

Echocardiography ◽

10.1111/echo.14836 ◽

2020 ◽

Vol 37 (10) ◽

pp. 1603-1609

Author(s):

Shantanu P. Sengupta ◽

Kunda Mungulmare ◽

Nduka C. Okwose ◽

Guy A. MacGowan ◽

Djordje G. Jakovljevic

Keyword(s):

Heart Failure ◽

Cardiac Output ◽

Ejection Fraction ◽

Stress Test ◽

Dobutamine Stress ◽

Preserved Ejection Fraction ◽

Heart Failure Patients ◽

Dobutamine Stress Test

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The neurohormonal basis of pulmonary hypertension in heart failure with preserved ejection fraction

European Heart Journal ◽

10.1093/eurheartj/ehz626 ◽

2019 ◽

Vol 40 (45) ◽

pp. 3707-3717 ◽

Cited By ~ 12

Author(s):

Masaru Obokata ◽

Garvan C Kane ◽

Yogesh N V Reddy ◽

Vojtech Melenovsky ◽

Thomas P Olson ◽

...

Keyword(s):

Heart Failure ◽

Pulmonary Hypertension ◽

Cardiac Output ◽

Ejection Fraction ◽

Plasma Levels ◽

Preserved Ejection Fraction ◽

Clinical Trial Registration ◽

Endothelin 1 ◽

Mechanistic Basis ◽

Highly Correlated

Abstract Aims Pulmonary hypertension (PH) represents an important phenotype among the broader spectrum of patients with heart failure with preserved ejection fraction (HFpEF), but its mechanistic basis remains unclear. We hypothesized that activation of endothelin and adrenomedullin, two counterregulatory pathways important in the pathophysiology of PH, would be greater in HFpEF patients with worsening PH, and would correlate with the severity of haemodynamic derangements and limitations in aerobic capacity and cardiopulmonary reserve. Methods and results Plasma levels of C-terminal pro-endothelin-1 (CT-proET-1) and mid-regional pro-adrenomedullin (MR-proADM), central haemodynamics, echocardiography, and oxygen consumption (VO2) were measured at rest and during exercise in subjects with invasively-verified HFpEF (n = 38) and controls free of HF (n = 20) as part of a prospective study. Plasma levels of CT-proET-1 and MR-proADM were highly correlated with one another (r = 0.89, P < 0.0001), and compared to controls, subjects with HFpEF displayed higher levels of each neurohormone at rest and during exercise. C-terminal pro-endothelin-1 and MR-proADM levels were strongly correlated with mean pulmonary artery (PA) pressure (r = 0.73 and 0.65, both P < 0.0001) and pulmonary capillary wedge pressure (r = 0.67 and r = 0.62, both P < 0.0001) and inversely correlated with PA compliance (r = −0.52 and −0.43, both P < 0.001). As compared to controls, subjects with HFpEF displayed right ventricular (RV) reserve limitation, evidenced by less increases in RV s′ and e′ tissue velocities, during exercise. Baseline CT-proET-1 and MR-proADM levels were correlated with worse RV diastolic reserve (ΔRV e′, r = −0.59 and −0.67, both P < 0.001), reduced cardiac output responses to exercise (r = −0.59 and −0.61, both P < 0.0001), and more severely impaired peak VO2 (r = −0.60 and −0.67, both P < 0.0001). Conclusion Subjects with HFpEF display activation of the endothelin and adrenomedullin neurohormonal pathways, the magnitude of which is associated with pulmonary haemodynamic derangements, limitations in RV functional reserve, reduced cardiac output, and more profoundly impaired exercise capacity in HFpEF. Further study is required to evaluate for causal relationships and determine if therapies targeting these counterregulatory pathways can improve outcomes in patients with the HFpEF-PH phenotype. Clinical trial registration NCT01418248; https://clinicaltrials.gov/ct2/results? term=NCT01418248&Search=Search

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Quantification of the Impaired Cardiac Output Response to Exercise in Heart Failure: Application of a Non-Invasive Device

Journal of Cardiac Failure ◽

10.1016/j.cardfail.2008.06.073 ◽

2008 ◽

Vol 14 (6) ◽

pp. S21

Author(s):

Jonathan Myers ◽

Pradeep Gujja ◽

Suresh Neelagaru ◽

Leon Hsu ◽

Daniel Burkhoff

Keyword(s):

Heart Failure ◽

Cardiac Output ◽

Output Response ◽

Non Invasive ◽

Invasive Device ◽

Response To Exercise

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Clinical performance and exercise hemodynamics in patients with severe secondary tricuspid regurgitation and chronic atrial fibrillation

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-02094-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Jesper K. Jensen ◽

Tor S. Clemmensen ◽

Christian A. Frederiksen ◽

Joachim Schofer ◽

Mads J. Andersen ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Cardiac Output ◽

Ejection Fraction ◽

Exercise Capacity ◽

Tricuspid Regurgitation ◽

Clinical Performance ◽

Chronic Atrial Fibrillation ◽

Peak Exercise ◽

Preserved Ejection Fraction

Abstract Objective The study aimed to investigate the functional capacity and hemodynamics at rest and during exercise in patients with chronic atrial fibrillation and severe functional symptomatic tricuspid regurgitation (AF-FTR). Background Symptoms and clinical performance of severe AF-FTR mimic the population of patients with heart failure with preserved ejection fraction (HFpEF). Severe AF-FTR is known to be associated with an adverse prognosis whereas less is reported about the clinical performance including exercise capacity and hemodynamics in patients symptomatic AF-FTR. Methods Right heart catheterization (RHC) at rest and during exercise was conducted in a group of patients with stable chronic AF-TR and compared with a group of patients with HFpEF diagnosed with cardiac amyloid cardiomyopathy (CA). All patients had preserved ejection fraction and no significant left-sided disease. Results Patients with AF-FTR demonstrated a low exercise capacity that was comparable to CA patients (TR 4.9 ± 1.2 METS vs. CA 4. 7 ± 1.5 METS; P = 0.78) with an average peak maximal oxygen consumption of 15 mL/min/kg. Right atrium pressure increased significantly more in the AF-FTR patients as compared to CA patients at peak exercise (25 ± 8 vs 19 ± 9, p < 0.01) whereas PCWP increased significantly to a similar extent in both groups (31 ± 4 vs 31 ± 8 mmHg, p = 0.88). Cardiac output (CO) was significantly lower among AF-FTR at rest as compared to CA patients (3.6 ± 0.9 vs 4.4 ± 1.3 l/min; p < 0.05) whereas both groups demonstrated a poor but comparable CO reserve at peak exercise (7.3 ± 2.9 vs 7.9 ± 3.8 l/min, p = 0.59). Conclusions AF-FTR contributes to the development of advanced heart failure symptoms and poor exercise capacity reflected in increased atrial filling pressures, reduced cardiac output at rest and during exercise sharing common features seen in HFpEF patients with other etiologies.

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Clinical Performance and Exercise Hemodynamics in Patients with Severe Secondary Tricuspid Regurgitation and Chronic Atrial Fibrillation

10.21203/rs.3.rs-240366/v1 ◽

2021 ◽

Author(s):

Jesper Jensen ◽

Tor Clemmensen ◽

Christian Frederiksen ◽

Joachim Schofer ◽

Mads Andersen ◽

...

Keyword(s):

Heart Failure ◽

Atrial Fibrillation ◽

Cardiac Output ◽

Ejection Fraction ◽

Exercise Capacity ◽

Tricuspid Regurgitation ◽

Clinical Performance ◽

Chronic Atrial Fibrillation ◽

Peak Exercise ◽

Preserved Ejection Fraction

Abstract ObjectiveThe study aimed to investigate the functional capacity and hemodynamics at rest and during exercise in patients with chronic atrial fibrillation and severe functional symptomatic tricuspid regurgitation (AF-FTR).BackgroundSymptoms and clinical performance of severe AF-FTR mimic the population of patients with heart failure with preserved ejection fraction (HFpEF). Severe AF-FTR is known to be associated with an adverse prognosis whereas less is reported about the clinical performance including exercise capacity and hemodynamics in patients symptomatic AF-FTR. MethodsRight heart catheterization (RHC) at rest and during exercise was conducted in a group of patients with stable chronic AF-TR and compared with a group of patients with HFpEF diagnosed with cardiac amyloid cardiomyopathy (CA). All patients had preserved ejection fraction and no significant left-sided disease. ResultsPatients with AF-FTR demonstrated a low exercise capacity that was comparable to CA patients (TR 4.9 ± 1.2 METS vs. CA 4. 7 ± 1.5 METS; P = 0.78) with an average peak maximal oxygen consumption of 15 mL/min/kg. Right atrium pressure increased significantly more in the AF-FTR patients as compared to CA patients at peak exercise (25 ± 8 vs 19 ± 9, p<0.01) whereas PCWP increased significantly to a similar extent in both groups (31 ± 4 vs 31 ± 8 mmHg, p=0.88). Cardiac output (CO) was significantly lower among AF-FTR at rest as compared to CA patients (3.6 ± 0.9 vs 4.4 ± 1.3 l/min; p<0.05) whereas both groups demonstrated a poor but comparable CO reserve at peak exercise (7.3 ± 2.9 vs 7.9 ± 3.8 l/min, p=0.59). ConclusionsAF-FTR contributes to the development of advanced heart failure symptoms and poor exercise capacity reflected in increased atrial filling pressures, reduced cardiac output at rest and during exercise sharing common features seen in HFpEF patients with other etiologies.

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Definition, epidemiology, and burden of disease: HFrEF

ESC CardioMed ◽

10.1093/med/9780198784906.003.0402_update_001 ◽

2018 ◽

pp. 1745-1748

Author(s):

Aldo Pietro Maggioni ◽

Ovidiu Chioncel

Keyword(s):

Heart Failure ◽

Cardiac Output ◽

Ejection Fraction ◽

Burden Of Disease ◽

Clinical Profile ◽

Preserved Ejection Fraction ◽

Economic Costs ◽

Reduced Ejection Fraction ◽

Cardiac Abnormalities ◽

Patients With Heart Failure

Heart failure is the final common stage of many diseases of the heart, caused by structural and/or functional cardiac abnormalities, resulting in a reduced cardiac output. The clinical profile of patients with heart failure with reduced ejection fraction (HFrEF) is generally more severe than that of patients with heart failure and preserved ejection fraction. HFrEF remains a relevant problem, despite the improvements in its management achieved in the last decades, leading to large economic costs, frequent hospitalization, and high levels of mortality.

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Definition, epidemiology, and burden of disease: HFrEF

ESC CardioMed ◽

10.1093/med/9780198784906.003.0402 ◽

2018 ◽

pp. 1745-1748

Author(s):

Aldo Pietro Maggioni ◽

Ovidiu Chioncel

Keyword(s):

Heart Failure ◽

Cardiac Output ◽

Ejection Fraction ◽

Burden Of Disease ◽

Clinical Profile ◽

Preserved Ejection Fraction ◽

Economic Costs ◽

Reduced Ejection Fraction ◽

Cardiac Abnormalities ◽

Patients With Heart Failure

Heart failure is the final common stage of many diseases of the heart, caused by structural and/or functional cardiac abnormalities, resulting in a reduced cardiac output. The clinical profile of patients with heart failure with reduced ejection fraction (HFrEF) is generally more severe than that of patients with heart failure and preserved ejection fraction. HFrEF remains a relevant problem, despite the improvements in its management achieved in the last decades, leading to large economic costs, frequent hospitalization, and high levels of mortality.

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