Abstract 9649: Challenging The Dogma: Increasing Cardiac Fatty Acid Rather Than Glucose Utilisation Improves Cardiac Function in Severe Non-Ischaemic Heart Failure With Reduced Ejection Fraction (HFrEF)
| Autor: | William Watson, Peregrine Green, Andrew J Lewis, Stefan Neubauer, Giovanni Luigi De Maria, Neil Herring, Oliver J Rider |
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| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Circulation. 144 |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | Introduction: Based on the premise that in HFrEF the heart is metabolically inflexible and oxygen limited, current metabolic therapies aim to increase glucose oxidation. However, if the human failing heart is neither inflexible nor oxygen limited, this approach is called into question. Methods: During either insulin-glucose (GI) or Intralipid infusion (IL) (random order), 20 non-ischaemic HFrEF patients underwent cardiac magnetic resonance imaging and 31 P-spectroscopy at rest and during dobutamine infusion (mean 100 bpm). 10 patients underwent invasive arteriovenous blood sampling (left main–coronary sinus), coronary flow and left ventricular (LV) pressure-volume loop measurements, during GI and IL infusion, at rest and during rapid atrial pacing (100 bpm). Results: At rest, during IL fatty acid (FA) uptake was higher (61±53 vs 5±13 μmol/min, p=0.03) and during GI, glucose uptake was higher (97±53 vs 45±36 μmol/min, p=0.04). Compared to fasting conditions, LV ejection fraction was higher during IL (40±9 vs 35±9%, p2 20±9 vs 15±9 ml/min, p=0.05) and phosphocreatine/ATP ratio (PCr/ATP 2.01±0.33 vs 1.86±0.25, p=0.02) were higher and lactate was consumed. Stress cardiac work was again higher during IL (by 62mmHg.L/min, p=0.009). Despite higher cardiac work and MVO 2 during IL at stress, PCr/ATP was again unchanged and lactate consumed. During GI, with atrial pacing (100 bpm) FA uptake was increased >4 fold (5±14 vs 24±32 μmol/min, p=0.04), suggesting selective FA preference. Conclusions: In severe HFrEF cardiac metabolic flexibility is retained changing substrate use to match arterial supply and workload. At rest and stress, increased FA uptake, but not glucose is associated with increased contractility. Cardiac preference to FA was observed during stress. Despite increased MVO 2 , the phosphocreatine pool remains stable and lactate is consumed, showing that mitochondrial oxygen supply was not fixed or limited. This challenges existing dogma, suggesting increasing FA oxidation and not glucose should be the therapeutic target in HFrEF. |
| Databáze: | OpenAIRE |
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