Background: Myocardial utilization of 3-hydroxybutyrate (3-OHB) is increased in patients with heart failure and reduced ejection fraction (HFrEF). However, the cardiovascular effects of increased circulating plasma-3-OHB levels in these patients are unknown. Consequently, the authors' aim was to modulate circulating 3-OHB levels in HFrEF patients and evaluate: (1) changes in cardiac output (CO); (2) a potential dose-response relationship between 3-OHB levels and CO; (3) the impact on myocardial external energy efficiency (MEE) and oxygen consumption (MVO); and (4) whether the cardiovascular response differed between HFrEF patients and age-matched volunteers.
Methods: Study 1: 16 chronic HFrEF patients (left ventricular ejection fraction: 37±3%) were randomized in a crossover design to 3-hour of 3-OHB or placebo infusion. Patients were monitored invasively with a Swan-Ganz catheter and with echocardiography. Study 2: In a dose-response study, 8 HFrEF patients were examined at increasing 3-OHB infusion rates. Study 3 to 4: 10 HFrEF patients and 10 age-matched volunteers were randomized in a crossover design to 3-hour 3-OHB or placebo infusion. MEE and MVO were evaluated using 11C-acetate positron emission tomography.
Results: 3-OHB infusion increased circulating levels of plasma 3-OHB from 0.4±0.3 to 3.3±0.4 mM ( P<0.001). CO rose by 2.0±0.2 L/min ( P<0.001) because of an increase in stroke volume of 20±2 mL ( P<0.001) and heart rate of 7±2 beats per minute (bpm) ( P<0.001). Left ventricular ejection fraction increased 8±1% ( P<0.001) numerically. There was a dose-response relationship with a significant CO increase of 0.3 L/min already at plasma-3-OHB levels of 0.7 mM ( P<0.001). 3-OHB increased MVO without altering MEE. The response to 3-OHB infusion in terms of MEE and CO did not differ between HFrEF patents and age-matched volunteers.
Conclusions: 3-OHB has beneficial hemodynamic effects in HFrEF patients without impairing MEE. These beneficial effects are detectable in the physiological concentration range of circulating 3-OHB levels. The hemodynamic effects of 3-OHB were observed in both HFrEF patients and age-matched volunteers. 3-OHB may potentially constitute a novel treatment principle in HFrEF patients.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.118.036459 | DOI Listing |
Front Cardiovasc Med
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Department of Cardiology, University of Medicine and Pharmacy of Craiova, Craiova, Romania.
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View Article and Find Full Text PDFHeart Rhythm
December 2024
Christian-Albrechts-University, Medical Faculty, Christian-Albrechts-Platz 4, 24118 Kiel, Germany; University of Applied Science, Life Sciences, An der Karlstadt 8, 27568 Bremerhaven, Germany. Electronic address:
Left bundle branch block (LBBB) causes immediate electrical and mechanical dys-synchrony of the left ventricle (LV) and gradual structural damages in the Purkinje cells and myocardium. Mechanical dys-synchrony reduces the LV ejection fraction (EF) instantly, but only to ≈55% in an otherwise normal heart. Because of the heart's in-built functional redundancy, a patient with LBBB does not always notice the heart's reduced efficiency straight away.
View Article and Find Full Text PDFCardiovasc Ther
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Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
The left ventricular pressure-strain loop (PSL) is a new technique based on ultrasound for noninvasive quantitative evaluation of global and local myocardial work (MW). This study is aimed at evaluating improvement factors of patients with heart failure (HF) reduced ejection fraction (HFrEF) using the PSL technique. A total of 88 patients with HF were enrolled in this study, which had ≤ 40% left ventricular ejection fraction (LVEF).
View Article and Find Full Text PDFJ Cardiovasc Pharmacol
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Istanbul Medipol University, Medipol Mega University Hospital, Dept. of Cardiology, Istanbul, Turkey.
Although sodium-glucose cotransporter-2 inhibitors (SGLT2i) are known to reduce the incidence of atrial fibrillation (AF) and AF-related adverse events, evidence on their prognostic effect in patients undergoing catheter ablation (CA) for AF is limited. In a single-center, 614 patients (mean age 58.1±9.
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