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Myocardial viability testing can identify patients with ischaemic heart disease and left ventricular dysfunction who can potentially benefit from both improved cardiac function and prognosis after revascularisation. Evaluation of myocardial glucose metabolism by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is considered the most sensitive tool to detect viability, and it predicts functional recovery as well as improved prognosis upon revascularisation. In parallel with the improved availability of PET, scanners have been changed into hybrid devices consisting of both multidetector computed tomography (CT) and PET (PET-CT). The immediate benefit for viability imaging is the ability to merge the coronary CT angiography images with FDG PET viability data. In addition, the possibility to utilise CT for myocardial viability imaging, such as delayed-enhancement imaging of myocardial infarction with acceptable radiation dose has been intensely investigated. This review will describe the principles of viability assessment by PET, and discuss the possibilities provided by hybrid PET-CT in this setting.

Purpose: Right ventricular (RV) apical pacing induces dyssynchrony by a left bundle branch block type electrical activation sequence in the heart and may impair left ventricular (LV) function. Whether these functional changes are accompanied by changes in myocardial perfusion, oxidative metabolism and efficiency, and the relation with the induction of LV dyssynchrony are unknown. Our study was designed to investigate the acute effects of RV pacing on these parameters., Methods: Ten patients with normal LV ejection fraction and VVI/DDD pacemaker were studied during AAI pacing/sinus rhythm without RV pacing (pacing-OFF) and with RV pacing (pacing-ON) at the same heart rate. Dynamic [15O]water and [11C]acetate positron emission tomography was used to measure perfusion and oxidative metabolism (kmono) of the LV. An echocardiographic examination was used to assess LV stroke volume (SV) and LV dyssynchrony. Myocardial efficiency of forward work was calculated as systolic blood pressure × cardiac output/LV mass/kmono., Results: RV pacing decreased SV in all subjects (mean decrease 13%, from 76 ± 7 to 66 ± 7 ml, p = 0.004), but global perfusion and kmono were unchanged. The efficiency tended to be lower with pacing-ON (70 ± 20 vs 81 ± 21 mmHg l/g, p = 0.066). In patients with dyssynchrony during pacing (n = 6) efficiency decreased by 23% (from 78 ± 25 to 60 ± 14 mmHg l/g, p = 0.02), but in patients without dyssynchrony no change in efficiency was detected. Accordingly, heterogeneity in myocardial perfusion and oxidative metabolism was detected during pacing in patients with dyssynchrony but not in those without dyssynchrony., Conclusion: RV pacing resulted in a significant decrease in SV. However, deleterious effects on LV oxidative metabolism and efficiency were observed only in patients with dyssynchrony during RV pacing.

It is well established that cardiac metabolism is abnormal in heart failure (HF). Experimental studies suggest that in severe HF, cardiac metabolism reverts to a more fetal-like substrate use characterized by enhanced glucose and downregulated free fatty acid (FFA) metabolism. Correspondingly, in humans, when FFA levels are similar, myocardial glucose metabolism is increased, and FFA metabolism is decreased. However, depression of left ventricular function and insulin resistance induces a shift back to greater FFA uptake and oxidation by increasing circulating FFA availability. Myocardial insulin resistance may further impair myocardial glucose uptake and lead to an energy depletion state. Experimental and preliminary clinical studies suggest that metabolic modulators enhancing myocardial glucose oxidation may improve cardiac function in patients with chronic HF. However, it has been found that acute FFA deprivation is harmful to the cardiac performance. Optimizing myocardial energy metabolism may serve as an additional approach for managing HF, but further studies are warranted.

Background: Metabolic modulators that enhance myocardial glucose metabolism by inhibiting free fatty acid (FFA) metabolism may improve cardiac function in heart failure patients. We studied the effect of acute FFA withdrawal on cardiac function in patients with heart failure caused by idiopathic dilated cardiomyopathy (IDCM)., Methods and Results: Eighteen fasting nondiabetic patients with IDCM (14 men, 4 women, aged 58.8+/-8.0 years, ejection fraction 33+/-8.8%) and 8 matched healthy controls underwent examination of myocardial perfusion and oxidative and FFA metabolism, before and after acute reduction of serum FFA concentrations by acipimox, an inhibitor of lipolysis. Metabolism was monitored by positron emission tomography and [15O]H2O, [11C]acetate, and [11C]palmitate. Left ventricular function and myocardial work were echocardiographically measured, and efficiency of forward work was calculated. Acipimox decreased myocardial FFA uptake by >80% in both groups. Rate-pressure product and myocardial perfusion remained unchanged, whereas stroke volume decreased similarly in both groups. In the healthy controls, reduced cardiac work was accompanied by decreased oxidative metabolism (from 0.071+/-0.019 to 0.055+/-0.016 min(-1), P<0.01). In IDCM patients, cardiac work fell, whereas oxidative metabolism remained unchanged and efficiency fell (from 35.4+/-12.6 to 31.6+/-13.3 mm Hg x L x g(-1), P<0.05)., Conclusions: Acutely decreased serum FFA depresses cardiac work. In healthy hearts, this is accompanied by parallel decrease in oxidative metabolism, and myocardial efficiency is preserved. In failing hearts, FFA depletion did not downregulate oxidative metabolism, and myocardial efficiency deteriorated. Thus, failing hearts are unexpectedly more dependent than healthy hearts on FFA availability. We propose that both glucose and fatty acid oxidation are required for optimal function of the failing heart.

Background: Results on myocardial substrate metabolism in the failing heart have been contradictory. Insulin resistance, a common comorbidity in heart failure patients, and medical therapy may modify myocardial metabolism in complex fashions. Therefore, we characterized myocardial oxidative and free fatty acid (FFA) metabolism in patients with idiopathic dilated cardiomyopathy (IDCM) and investigated the contributions of insulin resistance and beta-blocker therapy., Methods and Results: Nineteen patients with IDCM (age 58 +/- 8 years, ejection fraction 33 +/- 8.8%) and 15 healthy controls underwent examination of myocardial blood perfusion, oxidative and FFA metabolism using positron emission tomography and [(15)O]H(2)O, [(11)C]acetate and [(11)C]palmitate, respectively. Echocardiography was used to assess myocardial function, work, and efficiency of forward work. Insulin resistance was calculated using the homeostasis model assessment index (HOMA index) and the degree of beta-blockade was estimated with a beta-adrenoceptor occupancy test. IDCM patients were characterized by decreased cardiac efficiency (35 +/- 2 versus 57 +/- 12 mm Hg.L.g(-1), P < .0001) and reduced myocardial FFA uptake (5.5 +/- 2.0 versus 6.4 +/- 1.2 mumol.100 g(-1).min(-1), P < .05), but the FFA beta-oxidation rate constant was not changed. In the patients, myocardial FFA uptake was inversely associated with left ventricular (LV) ejection fraction (r = -0.63, P < .01), indicating that further depression of LV function induces an opposite switch to greater FFA uptake. The FFA beta-oxidation rate constant correlated positively with the HOMA index (r = 0.53, P < .05). In patients on beta-1 selective beta-blockers, beta-1 adrenoceptor occupancy correlated inversely with LV work, oxidative metabolism, and FFA uptake; similar relationships were not found in patients on nonselective beta-blocker., Conclusions: Myocardial FFA metabolism is reduced in patients with IDCM. However, when LV function is further depressed and insulin resistance manifested, myocardial FFA uptake and oxidation are, in turn, upregulated. These findings may partly explain the discrepancies between previous studies about cardiac metabolism in heart failure.

Abnormalities of the autonomic nervous system are known to be of prognostic significance in chronic heart failure (CHF). The prognostic value of positron emission tomography (PET) imaging of cardiac autonomic innervation in CHF has not been explored previously. We retrospectively studied the survival data of 46 NYHA class II-III CHF patients (mean LVEF 35% +/- 8%) who had undergone carbon-11 hydroxyephedrine (11C-HED) studies at the Turku PET Centre between August 1992 and March 1996. The origin of CHF was dilated cardiomyopathy in 13 of the 46 patients and coronary artery disease with at least one prior myocardial infarction in the remaining 33. Data on causes of death and heart transplantation were collected, and the statistically significant predictors of prognosis were analysed using Cox's proportional hazards regression. During the mean follow-up period of 55 +/- 19 months, 11 deaths occurred and two patients underwent heart transplantation successfully. Eleven end-points were classified as cardiac (nine sudden cardiac deaths and two deaths due to progressive heart failure) and two as non-cardiac. When divided into two groups based on the median of 11C-HED retention (mean 0.184 +/- 0.061, median 0.183), eight end-points (death or cardiac transplantation) were reached in the group with 11C-HED retention below the median and three in the group with 11C-HED retention above the median (P < 0.02). In proportional hazards regression analysis, only peak oxygen uptake (peak VO2), left ventricular end-diastolic volume and HED retention were found to be statistically significant. It is concluded that 11C-HED PET provides independent prognostic information in patients with CHF.

Carbon-11 acetate positron emission tomography (PET) has been widely used to assess regional oxidative metabolism of the heart. However, the accuracy of [11C]acetate PET in assessing oxidative metabolism in infarcted myocardium remains controversial. Thirteen patients with stable coronary artery disease and old myocardial infarction were studied. The 15O-based PET studies yielded regional blood flow (rMBF, ml/min/g) and oxygen consumption (rMMRO2, ml/min/g), which was compared with the myocardial clearance rate constant (kmono) of [11C]acetate in segments with rMBF > or = 75% (group A), 50%-74% (group B) or < 50% (group C) of the normal reference segment. Mean MBF was 0.96 +/- 0.08 ml/g/min in group A, 0.67 +/- 0.06 ml/g/min in group B and 0.42 +/- 0.07 ml/g/min in group C segments. The segmental rMMRO2 correlated linearly with kmono (r = 0.89, P < 0.001, y = 0.61x + 0.026). The kmono/rMMRO2 ratio was comparable in the group A and B segments (0.99 +/- 0.19 vs 1.07 +/- 0.21, P = NS). However, the ratio was significantly higher in the group C segments (1.28 +/- 0.35, P = 0.037). It is concluded that kmono of [11C]acetate correlates linearly with rMMRO2 determined by [15O]O2 inhalation. However, kmono appears to yield higher rMMRO2 estimates than the [15O]O2 method in low-flow areas.

Dynamic positron emission tomography (PET) with [11C]acetate allows noninvasive assessment of myocardial oxygen consumption. In combination with echocardiography, PET enables determination of cardiac efficiency (defined as useful cardiac work per unit of oxygen consumption). We used this approach to compare the effects of levosimendan, a Ca(2+)-dependent calcium sensitizer, with dobutamine and sodium nitroprusside in healthy male volunteers. The effects of levosimendan on k(mono), an index of oxygen consumption, and cardiac efficiency were neutral, whereas the hemodynamic profile was consistent with balanced inotropism and vasodilatation. Dobutamine enhanced cardiac efficiency at the expense of increased oxygen requirement, but the effects of nitroprusside on k(mono) and cardiac efficiency were neutral. This study shows the feasibility of PET in phase 1 pharmacodynamic studies and suggests potential energetical advantages of calcium sensitization with levosimendan.