Insights Into the Metabolic Aspects of Aortic Stenosis With the Use of Magnetic Resonance Imaging

Figures

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  Figure 1. Schematic Representation of Metabolic Remodeling and the Development of Heart Failure in Aortic Stenosis Pathologic hypertrophy in response to mechanical overload, as in aortic stenosis, is accompanied by metabolic remodeling characterized by decreases in fatty acid oxidation (FAO) and increases in glycolysis. This fetal-like metabolic profile decreases the capacity for adenosine triphosphate synthesis, which is consistent with the energy starvation model. Persistent metabolic derangements elicit decreased oxidative metabolism, increased oxidative stress, lipid accumulation, and energy deprivation, all contributing to the progression of heart failure.

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  Central Illustration. Role of Cardiac Magnetic Resonance Metabolic Imaging in Aortic Stenosis An overview of the various cardiac magnetic resonance metabolic imaging techniques and their ability to study specific aspects of cardiac metabolism in aortic stenosis. 1H = proton; 13C = carbon; 31P = phosphorous; ATP = adenosine triphosphate; DPG = diphosphoglycerol; LV = left ventricular; MRS = magnetic resonance spectroscopy; PCr = phosphocreatine.

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  Figure 2. Normal Cardiac Metabolism, Illustrating 3 Main Steps in Energy Production (A) Substrate utilization. (B) Oxidative phosphorylation. (C) Adenosine triphosphate (ATP) transfer and utilization. Myocardial triglyceride content (TG) and total creatine (Cr) can be measured with the use of 1H magnetic resonance spectroscopy (MRS). Phosphocreatine (PCr) and ATP can be assessed with the use of 31P-MRS. Acetyl-CoA = acetyl coenzyme A; ADP = adenosine diphosphate; CKmito = mitochondrial creatine kinase; CKmyo = myofibrill creatine kinase; FAT = fatty acid transporter; GLUT = glucose transporter; NAD+ = nicotinamide adenine dinucleotide; NADH = reduced nicotinamide adenine dinucleotide. From Masliza Mahmod, DPhil thesis 2013.

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  Figure 3. The Energy-Yielding Substrates (Fatty Acids, Glucose, Ketones, and Amino Acids), via Specific Catabolic Pathways, Converge on Acetyl-CoA Production With Subsequent Entry Into the TCA Cycle The final step of energy transfer is accomplished through oxidative phosphorylation (Ox Phos), supplying >95% of ATP consumed by the heart. The boxes above each metabolic pathway indicate the pathologic and physiologic condition in which the specific substrate becomes a predominant contributor to metabolism. ATGL = adipose triglyceride lipase; DGAT = diacylglycerol acyltransferase; mCPT1 = muscle form of carnitine-palmitoyl transferase 1; PDH = pyruvate dehydrogenase; TAG = triacylglycerol; TCA = tricarboxylic acid; other abbreviations as in Figure 2.

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  Figure 4. Myocardial Lipid Content 1H Spectrum of the Heart (A) Images on the left show the typical position of voxel in the interventricular septum. Spectra with and without water suppression are acquired as shown on the right. Myocardial triglyceride (MTG) is then calculated as the sum of detected lipid signal amplitudes (=CH-CH2-CH= @ 2.2 ppm, -CH2- @ 1.3 ppm, -CH3 @ 0.9 ppm)/water signal amplitude × 100. (B) Graph on the left compares the myocardial lipid content in symptomatic severe aortic stenosis (AS), asymptomatic severe AS, and healthy control subjects. Graph on the right depicts relationship between myocardial steatosis (as measured by 1H-MRS) and left ventricular strain in asymptomatic and symptomatic AS patients. Figure 4B reproduced with permission from Mahmod et al.28

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  Figure 6. 31P Spectra of the Heart From a Patient With Aortic Stenosis Image on the top left shows the position of the voxel in the interventricular septum (short-axis view). Overlaid with spectra showing 2,3-diphosphoglycerol (DPG), phosphocreatine (PCr), and adenosine triphosphate (ATP) peaks derived from postprocessing of phosphorous (31P) magnetic resonance spectroscopy data in healthy volunteers and asymptomatic and symptomatic aortic stenosis (AS).

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  Figure 5. Pyruvate Metabolism Hyperpolarization imaging helps in investigating the metabolic fate of the first carbon atom (blue) when pyruvate is metabolized to alanine via alanine transaminase (ALT), to lactate via lactate dehydrogenase (LDH), and to bicarbonate via pyruvate dehydrogenase (PDH). The second and third carbon atoms (red, green) enter the tricarboxylic acid cycle (TCA) when incorporated into acetyl coenzyme A (acetyl-CoA).