Differential therapeutic responses of patients with isoproterenol-dependent and isoproterenol-independent vasodepressor syncope

Abstract

Orthostatic stress during tilt table testing (TTT) is used to examine patients who may have vasodepressor syncope. This response is thought to be mediated by activation of left ventricular mechanoreceptors. Isoproterenol, by increasing the rate of discharge of these mechanoreceptors, has been proposed to increase the sensitivity of TTT without decreasing its specificity. This mechanism is not, however, totally consistent with recent observations of vasodepressor responses after cardiac transplantation in patients with denervated hearts. These reports and data showing that not all sympathomimetic agents increase the sensitivity of TTT suggest that more than one mechanism may be responsible for a positive TTT result. Therefore we hypothesized that patients with positive TTT results tests not requiring isoproterenol (iso-independent) would have a different clinical and therapeutic response than patients who required isoproterenol (iso-dependent). One hundred sixty-one consecutive patients who underwent TTT for the evaluation of unexplained syncope were included in the study. TTT was performed without and during isoproterenol infusion. A positive TTT result was defined as syncope or presyncope with a sudden decrease in systolic blood pressure and reproduction of the patient's clinical symptoms. Patients with a positive TTT result underwent a second test after 1 to 2 weeks of therapy with an oral β-blocking agent; if the result remained positive, TTT was performed again with other agents until a satisfactory therapeutic response was obtained. Sixty-six (41%) of 161 patients had a positive result; 18 (27%) were iso-independent, and 48 (73%) were iso-dependent. There were no significant differences in age, gender, or presence of underlying heart disease between these two groups. Patients with iso-dependent and underlying heart disease between these two groups. Patients with iso-dependent and iso-independent syncope had similar hemodynamic responses to treatment with β-blockers. However, the response rate to β-blockers in the iso-dependent group was 100% versus 47% in the iso-independent group ( p < 0.0001). Patients with iso-dependent and iso-independent syncope during TTT have markedly different responses to treatment with β-blockers, a differential response that is not caused by differences in hemodynamics effects of treatment. This differential response cannot be attributed solely to differences in dosing or in pharmacologic effect of the drug, because both groups had a similar fall in heart rate and no substantial differences in blood pressure after initiation of therapy. These data, experimental data in animals, and the demonstration of a vasodepressor response in humans after cardiac transplantation suggest that the presently accepted left ventricular mechanoreceptor hypothesis of vasodepressor syncope may be incomplete and not applicable to all patients.