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Background: Congestive heart failure is associated with decreased stimulated myocardial adenylate cyclase activity, increased Gi-binding protein, attenuated parasympathetic tone, and increased modulation of beta-adrenergic inotropic left ventricular stimulation by parasympathetic agonists. Despite these abnormalities, changes in the density or affinity of ventricular muscarinic receptors have not been demonstrated in patients., Methods and Results: The density and affinity constants of myocardial muscarinic receptors were evaluated noninvasively by means of positron emission tomography with 11C-MQNB (methylquinuclidinyl benzilate), a specific hydrophilic antagonist, in 20 patients with congestive heart failure due to idiopathic dilated cardiomyopathy (mean left ventricular ejection fraction, 22+/-9%) and compared with values in 12 normal subjects. The mean receptor concentration was significantly higher in patients than in control subjects (B'max, 34.5+/-8.9 versus 25+/-7.7 pmol/mL, P<.005), with no changes in affinity constants. The change in heart rate after injection of 0.6 mg of cold MQNB was lower in patients than in control subjects (34+/-20% versus 55+/-36%, P<.05), and receptor density correlated negatively with maximal heart rate in the patients (r=.45, P<.05)., Conclusions: Congestive heart failure is associated with an upregulation of myocardial muscarinic receptors. This may be an adaptive mechanism to beta-agonist stimulation and should increase the number of potential targets for pharmacological intervention.