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The main purpose of this study is to determine whether dietary nitrate supplementation via concentrated beetroot juice improves central and peripheral cardiovascular control and physical capacity in patients with systolic heart failure.
Chronic heart failure (CHF) is a leading cause of morbidity and mortality worldwide. Although affecting the heart at first, it is now recognized that disability is largely due to impaired cerebral and skeletal muscle blood flow and consequently microvascular oxygenation. Reduced muscle oxygenation compromises oxidative metabolism and thus contractile performance. Impaired cerebral oxygenation not only reduces motor output (thus exacerbating muscle fatigue) but also constitutes a predictor of cerebral ischemic events and an independent prognostic risk factor.
Reduced levels of the vasodilator nitric oxide (NO) contribute to impaired blood flow and oxygenation in CHF. Development of new effective therapeutic strategies is therefore crucial given that current pharmacological treatment has failed to abrogate oxygenation deficits in CHF patients. Emerging evidence shows that nitrate serves as an alternative source for NO and improves muscle blood flow and oxygenation in health. Another striking feature of nitrate is that it can improve muscle work efficiency, a tenet of physiology that was once considered immutable.
Objective: To investigate systematically the role of dietary nitrate supplementation on central and peripheral cardiovascular function in CHF patients.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Nitrate supplementation | Active Comparator | Concentrated nitrate-rich beetroot juice |
|
| Placebo | Placebo Comparator | Nitrate-depleted beetroot juice |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nitrate supplementation | Dietary Supplement | Nitrate supplementation: concentrated nitrate-rich beetroot juice (2 x 70 ml/day; approximately 10 mmol nitrate/day; Beet It, James White Drinks, Ipswich, UK) for 8 consecutive days. |
| Measure | Description | Time Frame |
|---|---|---|
| Exercise tolerance | Cycle ergometer exercise test to the limit of tolerance | 8 days |
| Measure | Description | Time Frame |
|---|---|---|
| Plasma nitrate and nitrite concentrations | Assessed by chemiluminescence | 8 days |
| Central and peripheral fatigue | Assessed by transcutaneous femoral nerve magnetic stimulation |
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Inclusion Criteria:
- previous diagnosis of systolic heart failure (left ventricular ejection fraction <40%) under optimized clinical treatment as judged by the accompanying physician.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| J. Alberto Neder, MD, PhD | Queen's University | Principal Investigator |
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| ID | Term |
|---|---|
| D054143 | Heart Failure, Systolic |
| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| Placebo | Dietary Supplement | Placebo: nitrate-depleted beetroot juice (2 x 70 ml/day; approximately 0.01 mmol nitrate/day; Beet It, James White Drinks, Ipswich, UK) for 8 consecutive days. The placebo juice is similar to the concentrated beetroot juice in appearance, texture, smell and taste and is obtained by removing nitrate ions from the latter. |
|
|
| 8 days |
| Skeletal muscle and cerebral blood flow and oxygenation | Assessed by near-infrared spectroscopy and the rate of appearance of the optically-dense indocyanine green dye | 8 days |
| Neuromuscular activity | Assessed by electromyography | 8 days |
| Dyspnea and leg effort scores | Evaluated via a 10-point Borg scale | 8 days |
| Cognitive performance | Assessed by computer-based tests | 8 days |
| Cardiorespiratory responses to exercise | Non-invasive evaluation of cardiac (mean arterial pressure, cardiac output, stroke volume and heart rate) and pulmonary gas exchange (e.g., minute ventilation and oxygen uptake) responses during the transition from rest to exercise | 8 days |