Comment on Minamimoto: incidental focal FDG uptake in heart is a lighthouse for considering cardiac screening

Abstract

Dear Sir,An interesting article has recently been published [1] on theclinical significance of focal cardiac FDG uptake inpatients with unknown cardiac disease studied for unre-lated purposes. The topic is of great interest because thepossibility to identify unexpected cardiac disease duringPET studies could allow an early diagnosis and reduceunfavorable events. The paper suggests a correlationbetween focal cardiac FDG uptake and the likelihood ofcoronary artery disease (CAD) in patients without cardiacsymptoms and unknown cardiac disease. Apart from theinteresting analysis and the effort to identify the clinicalsignificance of focal uptakes, we agree and highlight theremarks and concerns reported by the authors in the paper.The myocardium derives energy from many sources suchas free fatty acid (FFAs), glucose, pyruvate, ketone bodies,lactate, and amino acids [2–4]. In fasting and resting con-dition, heart metabolism is mainly based on FFAs oxida-tion, the myocardial FDG uptake should be negligible,glycolysis contributes only about 30 % of substrate butdietary and hormonal conditions can modify this situation[5]. In the fasting state, the rate of myocardial FFAs oxi-dation is high, inhibiting glycolysis and glucose oxidationwith consequently low levels of glucose and insulin, while,after glucose load or during hyperglycemic condition,plasma concentrations of glucose and insulin rise reducingperipheral lipolysis, lowering plasma concentrations ofFFAs and hence reducing their availability to the myo-cardium. Glucose then becomes the dominant substrate formyocardial energy production [5, 6]. However, the myo-cardial FDG uptake in the fasting healthy subjects variesunder the clinical fasting conditions [7, 8] and increasedFDG uptake in the myocardium does not significantlycorrelate with the blood glucose level, age, or duration offasting in non-diabetic patients [7, 9]. Only in the uncon-trolled diabetic patients with high levels of blood glucosethere is absent or faint myocardial FDG uptake. Myocardialischemia strikingly alters myocardial substrate metabolism[5]. As blood flow and oxygen supply decline, oxidativemetabolism decreases but still remains the dominant sourceof residual ATP production accounting for more than 90 %[10]. Ischemia is also associated with increased glycolysisbut becomes uncoupled from glucose oxidation with excessproduction of pyruvate and lactate which impair glycolysis[4, 11]. In the normal myocardium FDG distribution pat-terns could be classified into three types (absent to faintuptake; regional uptake; diffuse uptake), but they couldhave no specific meaning [7]. Moreover, even in the sameindividual and under similar fasting conditions, the myo-cardial FDG uptake is neither stable nor reproducible andthe transition from the intense FDG uptake of a dominantlyglycolytic myocardial metabolism to the absent FDGuptake of a dominantly FFAs metabolism is not entirelyuniform either temporally or regionally [6]. In daily clini-cal practise, despite adequate fasting period, the pattern ofmyocardial FDG heart uptake varies a lot, making difficultthe differential diagnosis between physiological and path-ological uptakes. For these reasons the results of