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

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.

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

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000677448.10880.cc ◽

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

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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 ◽

10.3390/nu12072132 ◽

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00263.2016 ◽

2017 ◽

Vol 312 (1) ◽

pp. R13-R22 ◽

Cited By ~ 40

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.

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Regional muscle-adipose distribution is different in patients with heart failure with preserved or reduced ejection fraction

European Heart Journal ◽

10.1093/ehjci/ehaa946.1075 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

H Ishikawa ◽

Y Izumiya ◽

A Shibata ◽

T Yoshida ◽

H Hayashi ◽

...

Keyword(s):

Heart Failure ◽

Body Mass Index ◽

Adipose Tissue ◽

Ejection Fraction ◽

Exercise Capacity ◽

Exercise Tolerance ◽

The Other ◽

Reduced Ejection Fraction ◽

Significant Difference ◽

Regional Muscle

Abstract Background Epicardial adipose tissue (EAT) has been recognized to contribute inflammatory activity and atherosclerosis. On the other hand, it has been reported that the volume of EAT is lower in non-ischemic heart failure (HF) patients than healthy individuals. However, the difference in regional muscle-adipose distribution including EAT between HF with preserved ejection fraction (HFpEF) and HF reduced ejection fraction (HFrEF) has not been investigated. In addition, we investigated whether distribution of body composition contributed to exercise capacity. Methods The study included 105 non-ischemic HF patients diagnosed by cardiac catheterization between September 2017 and November 2019. Epicardial, abdominal and thigh muscle and adipose tissue volume were measured by computed tomography (CT), and exercise tolerance was evaluated by symptom-limited cardiopulmonary exercise test. Results Patients were divided into 2 groups according to the left ventricular ejection fraction, ≥40% as HFpEF (n=28) or <40% as HFrEF (n=77). There was no significant difference comorbidity, including hypertension, dyslipidemia, chronic kidney disease, and body mass index. Plasma B-type natriuretic peptide level was significantly higher in HFrEF than HFpEF group (146.2 vs 393.2 pg/ml, p<0.01), whereas, high-sensitive troponin T level was not different between two groups. Although there was no significant difference in BMI between two groups, the volume of EAT was significantly higher in HFpEF than HFrEF group (81.8 vs 136.4 ml, p=0.01). On the other hand, HFpEF had more thigh adipose tissue compared with HFrEF group (54.6 vs 42.1 ml, p=0.03). There were negative correlations between EAT volume and parameters of exercise capacity such as anaerobic threshold (r=−0.42, p<0.01) and peak VO2 (r=−0.32, p<0.01). Muscle volume itself does not corelate with these parameters. Conclusion In patient with nonischemic HF, the pattern of regional adipose distribution may have important role in pathologically. HFpEF and HFrEF has different pattern despite similar body mass index. These differences may be related to impaired exercise tolerance in these 2 different types of HF. Correlation between EAT and AT, peak VO2 Funding Acknowledgement Type of funding source: None

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

10.2196/preprints.8865 ◽

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)

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P2768Post-PE impairment is mostly related to newly diagnosed heart failure with preserved ejection fraction

European Heart Journal ◽

10.1093/eurheartj/ehz748.1085 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

O Dzikowska-Diduch ◽

M Kostrubiec ◽

K Brodka ◽

A Wyzgal-Chojecka ◽

S Pacho ◽

...

Keyword(s):

Heart Failure ◽

Ejection Fraction ◽

Pulmonary Disease ◽

Exercise Tolerance ◽

Functional Limitation ◽

Left Ventricular Diastolic Dysfunction ◽

Left Ventricular ◽

Diagnostic Workup ◽

Reduced Ejection Fraction ◽

Ventricular Diastolic Dysfunction

Abstract Introduction Recently, the concept of post-PE impairment (PPEI) was proposed which includes various combinations of functional, haemodynamic or imaging abnormalities in patients after acute pulmonary embolism (PE). Chronic residual obstruction of pulmonary vascular bed, despite adequate anticoagulation, is suggested to be a major cause of PPEI. Material and methods We report data of consecutive 700 PE survivors (390 F, aged 62±18 yrs). In all patients PE was diagnosed and treated according to ESC recommendations. Patients were anticoagulated and followed for at least 6 months in outpatient clinic (median 6, 6–18 months). All symptomatic subjects underwent detailed diagnostic workup which included standardized echocardiography, lung scintigraphy, pulmonary functional tests, and chest CT, RHC and coronary angiography when appropriate. Results 207/700 (29,6%) of PE survivors completely recovered functionally. However, when compared to prePEperiod 493/700 (70,4%) patients reported functional limitation compatible with PPEI. Exertional dyspnoea was present in 36,5% of symptomatic patients, then 25,5% others presented effort angina with or without dyspnoea, 11% of symptomatic patients reported palpitations and 27% complained of reduced exercise tolerance. After diagnostic workup, CTEPH was diagnosed in 38 of 493 (7,7%) symptomatic subjects (5,4% of all survivors) and chronic thromboembolic pulmonary disease (CTED) in 12/493 (2,4%) of them. 52,9% pts have chronic heart failure with reduced ejection fraction (EF) 4,2% and 37,2% with preserved EF; valve heart disease was detected in 8,9% and significant arrhythmia, mostly atrial fibrillation, in 2,6%. Breathlessness and reduce exercise tolerance in the others were caused by coronary artery diseases or non-cardiovascular pathologies (e.g. anaemia, pulmonary disease). Conclusions Follow-up demonstrated that after an episode of PE, approximately 70% of patients report functional impairment. Although persistent pulmonary artery thromboemobli resulting in CTEPH or CTED were detected in 7,1% of PE survivors and 10% of symptomatic patients. Left ventricular diastolic dysfunction is the most common cause of PPEI.

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

Clinical Medicine Insights Cardiology ◽

10.4137/cmc.s21372 ◽

2015 ◽

Vol 9 ◽

pp. CMC.S21372 ◽

Cited By ~ 9

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.

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