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BACKGROUND Previous studies suggested the presence of myocardial ischemia in symptomatic patients with hypertrophic cardiomyopathy. Positron emission tomography, a technique that can identify metabolic consequences of ischemia in coronary artery disease, permits the noninvasive measurements of regional myocardial blood flow and glucose metabolism. This new quantitative imaging approach should therefore be suitable for detecting a possible enhancement of glucose utilization in myocardium of patients with hypertrophic cardiomyopathy and thus may help to elucidate the pathomechanism of ischemia in this disease. METHODS AND RESULTS In 13 symptomatic patients with hypertrophic cardiomyopathy, myocardial blood flow and glucose utilization were measured with intravenous N-13-ammonia and F-18 deoxyglucose at rest and, in four patients, again during supine bicycle exercise. At rest, blood flow was significantly lower in hypertrophied than in normal myocardium (0.78 +/- 0.19 versus 0.99 +/- 0.13 mL.min-1.g-1, p < 0.025), whereas rates of glucose utilization were similar (0.88 +/- 0.31 versus 0.87 +/- 0.35 mumol.min-1.g-1). With exercise, blood flow and glucose utilization failed to increase in hypertrophic and normal segments but became more heterogeneously distributed throughout the left ventricular myocardium. Blood flow-metabolism mismatches indicative of myocardial ischemia were noted in three patients at rest and in three of the four patients during exercise and were due to reduced flow in the presence of maintained glucose uptake. The discordance between flow and glucose metabolism in hypertrophied myocardium was significantly more prominent in younger than in older patients. CONCLUSIONS Normal or even elevated rates of glucose utilization and the presence of diminished blood flow in hypertrophied relative to normal myocardium suggest the presence of myocardial ischemia in symptomatic hypertrophic cardiomyopathy. The age dependence of blood flow metabolism disparity suggests differences in the underlying pathophysiology or severity of disease.

Background Studies of patients with coronary artery disease and left ventricular dysfunction have shown that preoperative quantification of myocardial viability may be clinically useful to identify those patients who will benefit most from revascularization both functionally and prognostically. However, the relation between preoperative extent of viability and change in heart failure symptoms has not been documented carefully. We assessed the relation between the magnitude of improvement in heart failure symptoms after coronary artery bypass surgery (CABG) and the extent of myocardial viability as assessed by use of quantitative analysis of preoperative positron emission tomography (PET) images. Methods and Results We studied 36 patients with ischemic cardiomyopathy (mean left ventricular ejection fraction, 28±6%) undergoing CABG. Preoperative extent and severity of perfusion abnormalities and myocardial viability (flow-metabolism mismatch) were assessed by use of quantitative analysis of PET images with 13 N ammonia and fluorine-18-deoxyglucose. Each patient’s functional status was determined before and after CABG by use of a Specific Activity Scale. Mean perfusion defect size and severity were 63±13% and 33±12%, respectively. Total extent of a PET mismatch correlated linearly and significantly with percent improvement in functional status after CABG ( r =.87, P P =.009). This resulted in an improvement of 107% in patients with large mismatches compared with only 34% in patients with minimal or no PET mismatch. Conclusions In patients with ischemic cardiomyopathy, the magnitude of improvement in heart failure symptoms after CABG is related to the preoperative extent and magnitude of myocardial viability as assessed by use of PET imaging. Patients with large perfusion-metabolism mismatches exhibit the greatest clinical benefit after CABG.

Positron-emission tomography with 13N-ammonia and 18F-2-deoxyglucose was used to assess regional perfusion and glucose utilization in 31 chronic electrocardiographic Q wave regions in 20 patients. With previously published criteria, regions of infarction were identified by a concordant reduction in regional perfusion and glucose utilization, and regions of ischemia were identified by preservation of glucose utilization in regions of diminished perfusion. Only 10 of the 31 regions (32%) exhibited myocardial infarction tomographically. In contrast, positron tomography revealed ischemia in six regions (20%) and was normal in 15 regions (48%). Even when Q wave regions were reassigned and consolidated to enhance the specificity of the electrocardiogram, uptake of 18F-2-deoxyglucose was noted in the majority (54%) of the regions. Neither electrocardiographic ST-T changes nor severity of associated wall motion abnormality reliably distinguished tomographically identified regions of ischemia from infarction. Thus positron tomography reveals evidence of persistent tissue metabolism in a high proportion of chronic electrocardiographic Q wave regions, and commonly used clinical tests do not reliably distinguish hypoperfused but viable regions from tomographically defined regions of myocardial infarction.

We investigated myocardial 11C-palmitate clearance kinetics at a resting heart rate (control) and during pacing using positron-emission tomography in 10 patients with significant coronary artery stenosis (greater than 70%) and evidence of exercise-induced ischemia. Serial 11C-palmitate images acquired at control and during pacing revealed biexponential myocardial 11C clearance both in myocardium supplied by a stenotic coronary artery (myocardium "at risk") and in myocardium supplied by a normal coronary artery (normal myocardium). At control, the average rate of myocardial 11C clearance from the early rapid curve component (the clearance half-time) was similar in normal myocardium and in that at risk (22.2 +/- 5.2 vs 21.0 +/- 5.4 min, NS), as was the amount of myocardial 11C activity at the end of the early rapid phase (residual fraction 56.3 +/- 7.2% vs 54.7 +/- 7.3%, NS). Thus, myocardial clearance was homogeneous at control, suggesting a similar rate and amount of 11C-palmitate oxidation in normal myocardium and in that at risk. Pacing shortened clearance half-times and decreased residual fraction in both normal myocardium and that at risk compared with control. However, clearance half-times were 17% longer and residual fractions 14% higher in myocardium at risk compared with normal myocardium (p less than .005 and p less than .01, respectively). Therefore, during pacing myocardial 11C clearance became heterogeneous, suggesting impaired 11C-palmitate oxidation in myocardium at risk compared with normal myocardium. Increased substrate utilization in response to increased workload can be thought of as a measure of metabolic reserve. Our data suggest metabolic reserve for free fatty acid oxidation is impaired in myocardium supplied by a significantly stenosed coronary artery and that this impairment can be detected by analysis of myocardial 11C-palmitate clearance.

SUMMARY We have characterized N-13 ammonia as a myocardial blood flow imaging agent suitable for positron-emission computed tomography. However, the mechanisms of uptake and retention of this agent in myocardium are not known, and effects of altered metabolism were not considered. Therefore, we studied the uptake and retention of N-13 ammonia in myocardium under various hemodynamic and metabolic conditions in open-chest dogs. N-13 ammonia was extracted nearly 100% during its initial capillary transit, followed by metabolic trapping that competed with flow-dependent back diffusion. At control flows, the first capillary transit extraction fraction (E) of N-13 ammonia averaged 0.82 ± 0.06. It fell with higher flows by E = 1 − 0.607 exp − 125/F. Myocardial N-13 tissue clearance half-times were similarly inversely related to blood flow, and ranged from 110–642 minutes. Cardiac work and changes in the myocardial inotropic state induced by isoproterenol and propranolol did not affect E or the tissue clearance half-times. Low plasma pH reduced E by an average of 20%, while elevated plasma pH had no effect. Decreases in flow below control also were associated with a fall in E. Inhibition of glutamine synthetase with L-methionine sulfoximine impaired metabolic trapping of N-13 ammonia and implicates the glutamic acid-glutamine reaction as the primary mechanism for ammonia fixation. The product of E times flow predicts the myocardial N-13 tissue concentrations, which increased by 70% when flow was doubled. Thus, blood flow and metabolic trapping are the primary determinants of myocardial uptake and retention of N-13 ammonia. The relative constancy of metabolic trapping over a wide range of hemodynamic and metabolic conditions demonstrates the value of N-13 ammonia as a myocardial blood flow imaging agent.