Effect of organic and inorganic nitrates on cerebrovascular pulsatile power transmission in patients with heart failure and preserved ejection fraction

Londono-Hoyos, Francisco; Zamani, Payman; Beraun, Melissa; Vasim, Izzah; Segers, Patrick; Chirinos, Julio A.

doi:10.1088/1361-6579/aab2ef

Cited by 11 publications

(13 citation statements)

References 27 publications

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“…What we found is consistent with a recently published multicenter trial by Borlaug et al (28), which demonstrated that inhaled sodium nitrite did not improved the clinical status of patients with chronic HFpEF. Our results are also in agreement with several previous studies showing that a dietary nitrate intake in the form of BRJ did not improve exercise intolerance or hemodynamics indicators such as mean arterial pressure, heart rate, or cardiac output in HFpEF patients, although the concentration and duration of BRJ intervention in these studies varied (29,31,32). The reasons for the discrepancies between the rationale that nitric oxide possesses the ability of improving microcirculation and cardiac function in patients with HFpEF and the absence of clinical benefit are not clear.…”

Section: Discussionsupporting

confidence: 93%

“…Through a literature searching, we identified 421 studies, of which eight RCTs with 335 patients were eventually included in the current meta-analysis (Figure 1). The eight RCTs were all published after 2014, comparing the effect of inorganic nitrate/nitrite on HFpEF with that of placebo (21,25,26,(28)(29)(30)(31)(32). Four trials were parallel-group design with baseline characteristics well matched in two arms (25,26,30,32).…”

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

“…This suggests that nitrate/nitrite might better target hemodynamic derangements developed during exercise in people with HFpEF (24)(25)(26)(27). Moreover, compared to organic nitrates such as isosorbide mononitrate and dinitrate, inorganic nitrate/nitrite is less likely to cause hypotension/ headache and rarely develops tolerance (28,29), which provides a considerable promise for the use of inorganic nitrate/nitrite in the treatment of HFpEF.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of inorganic nitrate/nitrite supplementary therapy in heart failure with preserved ejection fraction

Zhang²,

Yuan³

2023

Front. Cardiovasc. Med.

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BackgroundApproximately half of patients with heart failure have a preserved ejection fraction (HFpEF). To date, only SGLT-2i, ARNi, and MRAs treatments have been shown to be effective for HFpEF. Exercise intolerance is the primary clinical feature of HFpEF. The aim of this meta-analysis was to explore the effect of inorganic nitrate/nitrite supplementary therapy on the exercise capacity of HFpEF patients.MethodsWe searched PubMed, Embase, Cochrane Library, OVID, and Web of Science for eligible studies for this meta-analysis. The primary outcomes were peak oxygen consumption (peak VO2), exercise time, and respiratory exchange ratio (RER) during exercise. The secondary outcomes were cardiac output, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and systemic vascular resistance during rest and exercise, respectively.ResultsA total of eight randomized-controlled trials were enrolled for this meta-analysis. We found no benefit of inorganic nitrate/nitrite on exercise capacity in patients with HFpEF. Inorganic nitrate/nitrite compared to placebo, did not significantly increased peak VO2 (MD = 0.361, 95% CI = −0.17 to 0.89, p = 0.183), exercise time (MD = 9.74, 95% CI = −46.47 to 65.95, p = 0.734), and respiratory exchange ratio during exercise (MD = −0.003, 95% CI = −0.036 to 0.029, p = 0.834). Among the six diameters reflecting cardiac and artery hemodynamics, inorganic nitrate/nitrite can lower rest SBP, rest/exercise DBP, rest/exercise MAP, and exercise SVR, but has no effect in cardiac output and heart rate for HFpEF patients.ConclusionOur meta-analysis suggested that inorganic nitrate/nitrite supplementary therapy has no benefit in improving the exercise capacity of patients with HFpEF, but can yield a blood pressure lowering effect, especially during exercise.

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Section: Discussionsupporting

confidence: 93%

Section: Search Results and Study Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Efficacy and safety of inorganic nitrate/nitrite supplementary therapy in heart failure with preserved ejection fraction

Zhang²,

Yuan³

2023

Front. Cardiovasc. Med.

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“… 135) Unlike organic nitrates, these effects were achieved without significantly reducing MAP or cerebrovascular resistance and without increasing pulsatile power penetration into the cerebrovascular circulation. 133) 136) Inhaled sodium nitrite, on the other hand, has a very short half (<40 minutes) and its intermittent administration results in pronounced circulating nitrite level fluctuations, which are unlikely to exert sustained therapeutic effects throughout the day. Accordingly, inhaled inorganic nitrite was not effective in improving exercise capacity in patients with HFpEF.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

The Role of Arterial Stiffness and Central Hemodynamics in Heart Failure

Weber

2020

Int J Heart Fail

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Whereas traditional understanding of left ventricular afterload was focused on a steady-state circulation model with continuous pressures and flow, a more realistic concept is emerging, taking the pulsatile nature of the heart and the arterial system into account. The most simple measure of pulsatility is brachial pulse pressure, representing the pulsatility fluctuating around the mean blood pressure level. Brachial pulse pressure is widely available, fundamentally associated with the development and treatment of heart failure (HF), but its analysis is often confounded in patients with established HF. The next step of analysis consists of arterial stiffness, central (rather than brachial) pressures, and of wave reflections. The latter are closely related to left ventricular late systolic afterload, ventricular remodeling, diastolic dysfunction, exercise capacity, and, in the long term, the risk of new-onset HF. Wave reflection may also evolve as a suitable therapeutic target for HF with preserved and reduced ejection fraction. A full understanding of ventricular-arterial coupling, however, requires dedicated analysis of time-resolved pressure and flow signals. This review provides a summary of current understanding of pulsatile hemodynamics in HF.

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“…Third, wave power is conserved at junctions and therefore the distribution of wave power to different vessel branches can be quantified. For example, unlike wave intensity which is not conserved, it has been possible to meaningfully quantify the percentage of ascending aortic wave power that passes into the carotid artery and how this changes with pharmacological intervention ( Londono-Hoyos et al, 2018 ). Finally, wave power is linked to the hydraulic pressure power of flowing blood (Π P = PQ ), which determines total ventricular workload ( Laskey et al, 1985 ).…”

Section: Wave Intensitymentioning

confidence: 99%

Measurement, Analysis and Interpretation of Pressure/Flow Waves in Blood Vessels

et al. 2020

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The optimal performance of the cardiovascular system, as well as the breakdown of this performance with disease, both involve complex biomechanical interactions between the heart, conduit vascular networks and microvascular beds. 'Wave analysis' refers to a group of techniques that provide valuable insight into these interactions by scrutinizing the shape of blood pressure and flow/velocity waveforms. The aim of this review paper is to provide a comprehensive introduction to wave analysis, with a focus on key concepts and practical application rather than mathematical derivations. We begin with an overview of invasive and non-invasive measurement techniques that can be used to obtain the signals required for wave analysis. We then review the most widely used wave analysis techniques-pulse wave analysis, wave separation and wave intensity analysis-and associated methods for estimating local wave speed or characteristic impedance that are required for decomposing waveforms into forward and backward wave components. This is followed by a discussion of the biomechanical phenomena that generate waves and the processes that modulate wave amplitude, both of which are critical for interpreting measured wave patterns. Finally, we provide a brief update on several emerging techniques/concepts in the wave analysis field, namely wave potential and the reservoir-excess pressure approach.

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Effect of organic and inorganic nitrates on cerebrovascular pulsatile power transmission in patients with heart failure and preserved ejection fraction

Cited by 11 publications

References 27 publications

Efficacy and safety of inorganic nitrate/nitrite supplementary therapy in heart failure with preserved ejection fraction

Efficacy and safety of inorganic nitrate/nitrite supplementary therapy in heart failure with preserved ejection fraction

The Role of Arterial Stiffness and Central Hemodynamics in Heart Failure

Measurement, Analysis and Interpretation of Pressure/Flow Waves in Blood Vessels

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