scholarly journals Dietary nitrate supplementation and exercise tolerance in patients with heart failure with reduced ejection fraction

2017 ◽  
Vol 312 (1) ◽  
pp. R13-R22 ◽  
Author(s):  
Daniel M. Hirai ◽  
Joel T. Zelt ◽  
Joshua H. Jones ◽  
Luiza G. Castanhas ◽  
Robert F. Bentley ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Exercise Tolerance ◽  
Lactate Concentration ◽  
Blood Lactate Concentration ◽  
Pulmonary Oxygen Uptake ◽  
Reduced Ejection Fraction ◽  
Arterial Blood ◽  
Inorganic Nitrate ◽  
Patients With Heart Failure ◽  
Nitrate Supplementation

Endothelial dysfunction and reduced nitric oxide (NO) signaling are key abnormalities leading to skeletal muscle oxygen delivery-utilization mismatch and poor physical capacity in patients with heart failure with reduced ejection fraction (HFrEF). Oral inorganic nitrate supplementation provides an exogenous source of NO that may enhance locomotor muscle function and oxygenation with consequent improvement in exercise tolerance in HFrEF. Thirteen patients (left ventricular ejection fraction ≤40%) were enrolled in a double-blind, randomized crossover study to receive concentrated nitrate-rich (nitrate) or nitrate-depleted (placebo) beetroot juice for 9 days. Low- and high-intensity constant-load cardiopulmonary exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary oxygen uptake, quadriceps muscle oxygenation (near-infrared spectroscopy), and blood lactate concentration. Ten patients completed the study with no adverse clinical effects. Nitrate-rich supplementation resulted in significantly higher plasma nitrite concentration compared with placebo (240 ± 48 vs. 56 ± 8 nM, respectively; P < 0.05). There was no significant difference in the primary outcome of time to exercise intolerance between nitrate and placebo (495 ± 53 vs. 489 ± 58 s, respectively; P > 0.05). Similarly, there were no significant differences in central hemodynamics, arterial blood pressure, pulmonary oxygen uptake kinetics, skeletal muscle oxygenation, or blood lactate concentration from rest to low- or high-intensity exercise between conditions. Oral inorganic nitrate supplementation with concentrated beetroot juice did not present with beneficial effects on central or peripheral components of the oxygen transport pathway thereby failing to improve exercise tolerance in patients with moderate HFrEF.

scholarly journals Effect of inorganic nitrate on exercise capacity, mitochondria respiration, and vascular function in heart failure with reduced ejection fraction

2020 ◽  
Vol 128 (5) ◽  
pp. 1355-1364 ◽  
Author(s):  
Mary N. Woessner ◽  
Christopher Neil ◽  
Nicholas J. Saner ◽  
Craig A. Goodman ◽  
Luke C. McIlvenna ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Exercise Capacity ◽  
Mitochondrial Respiration ◽  
Vascular Function ◽  
Reduced Ejection Fraction ◽  
Inorganic Nitrate ◽  
Patients With Heart Failure ◽  
Nitrate Supplementation ◽  
Plasma Nitrite

This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure with reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration. Although daily supplementation increased plasma nitrite, our data indicate that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.

scholarly journals Dietary Inorganic Nitrate Supplementation And Exercise Tolerance In Patients With Reduced Ejection Fraction Heart Failure

2020 ◽  
Vol 52 (7S) ◽  
pp. 341-341
Author(s):  
Jason D. Allen ◽  
Christopher Neil ◽  
Luke C. McIlvenna ◽  
Joaquin Ortiz de Zevallos ◽  
Itamar Levinger ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Exercise Tolerance ◽  
Reduced Ejection Fraction ◽  
Inorganic Nitrate ◽  
Nitrate Supplementation

scholarly journals Effects of Dietary Inorganic Nitrate Supplementation on Exercise Performance in Patients With Heart Failure: Protocol for a Randomized, Placebo-Controlled, Cross-Over Trial (Preprint)

2017 ◽  
Author(s):  
Mary N. Woessner ◽  
Itamar Levinger ◽  
Christopher Neil ◽  
Cassandra Smith ◽  
Jason D Allen
Keyword(s):  
Heart Failure ◽  
Chronic Heart Failure ◽  
Exercise Test ◽  
Exercise Tolerance ◽  
Cardiopulmonary Exercise Test ◽  
Cardiopulmonary Exercise ◽  
Inorganic Nitrate ◽  
Patients With Heart Failure ◽  
Nitrate Supplementation ◽  
Nitric Oxide Bioavailability

BACKGROUND Chronic heart failure is characterized by an inability of the heart to pump enough blood to meet the demands of the body, resulting in the hallmark symptom of exercise intolerance. Chronic underperfusion of the peripheral tissues and impaired nitric oxide bioavailability have been implicated as contributors to the decrease in exercise capacity in these patients. nitric oxide bioavailability has been identified as an important mediator of exercise tolerance in healthy individuals, but there are limited studies examining the effects in patients with chronic heart failure. OBJECTIVE The proposed trial is designed to determine the effects of chronic inorganic nitrate supplementation on exercise tolerance in both patients with heart failure preserved ejection fraction (HFpEF) and heart failure reduced ejection fraction (HFrEF) and to determine whether there are any differential responses between the 2 cohorts. A secondary objective is to provide mechanistic insights into the 2 heart failure groups’ exercise responses to the nitrate supplementation. METHODS Patients with chronic heart failure (15=HFpEF and 15=HFrEF) aged 40 to 85 years will be recruited. Following an initial screen cardiopulmonary exercise test, participants will be randomly allocated in a double-blind fashion to consume either a nitrate-rich beetroot juice (16 mmol nitrate/day) or a nitrate-depleted placebo (for 5 days). Participants will continue daily dosing until the completion of the 4 testing visits (maximal cardiopulmonary exercise test, submaximal exercise test with echocardiography, vascular function assessment, and vastus lateralis muscle biopsy). There will then be a 2-week washout period after which the participants will cross over to the other treatment and complete the same 4 testing visits. RESULTS This study is funded by National Heart Foundation of Australia and Victoria University. Enrolment has commenced and the data collection is expected to be completed in mid 2018. The initial results are expected to be submitted for publication by the end of 2018. CONCLUSIONS If inorganic nitrate supplementation can improve exercise tolerance in patients with chronic heart failure, it has the potential to aid in further refining the treatment of patients in this population. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12615000906550; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368912 (Archived by WebCite at http://www.webcitation.org/6xymLMiFK)

scholarly journals Clinical Utility of Exercise Training in Heart Failure with Reduced and Preserved Ejection Fraction

2015 ◽  
Vol 9 ◽  
pp. CMC.S21372 ◽  
Author(s):  
Muhammad Asrar Ul Haq ◽  
Cheng Yee Goh ◽  
Itamar Levinger ◽  
Chiew Wong ◽  
David L. Hare
Keyword(s):  
Heart Failure ◽  
Exercise Training ◽  
Ejection Fraction ◽  
Exercise Tolerance ◽  
Exercise Intolerance ◽  
Sufficient Evidence ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Patients With Heart Failure

Reduced exercise tolerance is an independent predictor of hospital readmission and mortality in patients with heart failure (HF). Exercise training for HF patients is well established as an adjunct therapy, and there is sufficient evidence to support the favorable role of exercise training programs for HF patients over and above the optimal medical therapy. Some of the documented benefits include improved functional capacity, quality of life (QoL), fatigue, and dyspnea. Major trials to assess exercise training in HF have, however, focused on heart failure with reduced ejection fraction (HFREF). At least half of the patients presenting with HF have heart failure with preserved ejection fraction (HFPEF) and experience similar symptoms of exercise intolerance, dyspnea, and early fatigue, and similar mortality risk and rehospitalization rates. The role of exercise training in the management of HFPEF remains less clear. This article provides a brief overview of pathophysiology of reduced exercise tolerance in HFREF and heart failure with preserved ejection fraction (HFPEF), and summarizes the evidence and mechanisms by which exercise training can improve symptoms and HF. Clinical and practical aspects of exercise training prescription are also discussed.

scholarly journals Dietary Inorganic Nitrate Supplementation And Ventilatory Threshold In Patients With Reduced Ejection Fraction Heart Failure

2020 ◽  
Vol 52 (7S) ◽  
pp. 340-340
Author(s):  
Joaquin Ortiz de Zevallos ◽  
Christopher Neil ◽  
Luke C. McIlvenna ◽  
Itamar Levinger ◽  
Jason D. Allen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Ventilatory Threshold ◽  
Reduced Ejection Fraction ◽  
Inorganic Nitrate ◽  
Nitrate Supplementation

scholarly journals The Effect of Dietary Inorganic Nitrate Supplementation on Cardiac Function during Submaximal Exercise in Men with Heart Failure with Reduced Ejection Fraction (HFrEF): A Pilot Study

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2132
Author(s):  
Mary N. Woessner ◽  
Itamar Levinger ◽  
Jason D. Allen ◽  
Luke C. McIlvenna ◽  
Christopher Neil
Keyword(s):  
Heart Failure ◽  
Cardiac Output ◽  
Pilot Study ◽  
Ejection Fraction ◽  
Cardiac Function ◽  
Submaximal Exercise ◽  
Exercise Intolerance ◽  
Reduced Ejection Fraction ◽  
Inorganic Nitrate ◽  
Nitrate Supplementation

Heart failure with reduced ejection fraction (HFrEF) is a common end point for patients with coronary artery disease and it is characterized by exercise intolerance due, in part, to a reduction in cardiac output. Nitric oxide (NO) plays a vital role in cardiac function and patients with HFrEF have been identified as having reduced vascular NO. This pilot study aimed to investigate if nitrate supplementation could improve cardiac measures during acute, submaximal exercise. Five male participants (61 ± 3 years) with HFrEF (EF 32 ± 2.2%) completed this pilot study. All participants supplemented with inorganic nitrate (beetroot juice) or a nitrate-depleted placebo for ~13 days prior to testing. Participants completed a three-stage submaximal exercise protocol on a recumbent cycle ergometer with simultaneous echocardiography for calculation of cardiac output (Q), stroke volume (SV), and total peripheral resistance (TPR). Heart rate and blood pressure were measured at rest and during each stage. Both plasma nitrate (mean = ~1028%, p = 0.004) and nitrite (mean = ~109%, p = 0.01) increased following supplementation. There were no differences between interventions at rest, but the percent change in SV and Q from rest to stage two and stage three of exercise was higher following nitrate supplementation (all p > 0.05, ES > 0.8). Both interventions showed decreases in TPR during exercise, but the percent reduction TPR in stages two and three was greater following nitrate supplementation (p = 0.09, ES = 0.98 and p = 0.14, ES = 0.82, respectively). There were clinically relevant increases in cardiac function during exercise following supplementation with nitrate. The findings from this pilot study warrant further investigation in larger clinical trials.

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