Mitral valve prolapse with symptoms of beta-adrenergic hypersensitivity. Beta 2-adrenergic receptor supercoupling with desensitization on isoproterenol exposure.

Autonomic nervous system dysfunction has recently been identified in a subset of patients with mitral valve prolapse. These autonomic nervous system abnormalities may correspond, in part, to biochemical alterations in beta-adrenergic receptors. Nine women with mitral valve prolapse and symptoms and signs of beta-adrenergic hypersensitivity and seven normal volunteer women were studied. Quiet standing (five minutes) increased both heart rate and plasma norepinephrine (p less than 0.05) in symptomatic patients with mitral valve prolapse compared with normal subjects. The dose of isoproterenol required either to increase heart rate 25 beats/minute (0.5 +/- 0.3 microgram versus 1.0 +/- 0.3 microgram) or to decrease mean arterial pressure 20 mm Hg (11.1 +/- 4.8 versus 78.2 +/- 25.2 micrograms) was significantly less in the patients with mitral valve prolapse than in the volunteers. Symptomatic patients with mitral valve prolapse were desensitized by a four-hour isoproterenol infusion, whereas sensitivity in normal control subjects did not change. In the patients with mitral valve prolapse, baseline beta-adrenergic receptor coupling was elevated compared with that in control subjects (220 +/- 7 versus 81 +/- 2; p less than 0.001). Isoproterenol infusion induced uncoupling in these patients (KL/KH = 35 +/- 3, p less than 0.05) but did not alter coupling in normal volunteers. This study demonstrates physiologic and pharmacologic beta-adrenergic hypersensitivity in vivo directly corresponding to biochemical supercoupling in a subset of patients with mitral valve prolapse.