Background Previous studies suggest that vigorous myocardial contractions stimulate ventricular mechanoreceptors and lead to vasovagal syncope. We studied an endocardial index of myocardial contractility during the head-up tilt test in vasovagal patients and control patients, and we evaluated the effect of negative inotropic drugs on myocardial contractility and tilt test outcome. Methods and Results We investigated 19 patients with recurrent vasovagal syncope and positive tilt test (group 1) and 11 patients with no syncope and negative tilt test (group 2). Myocardial contractility was continuously measured during a tilt test (60°) through a microaccelerometer incorporated in the tip of a right ventricular electrode to sense left ventricular contractility. Patients in groups 1 and 2 were evaluated during an unmedicated tilt test, and patients in group 1 were reevaluated during a tilt test with infusion of esmolol (n = 10) or disopyramide (n = 9). During the unmedicated test, patients in group 1 exhibited a significant increase in myocardial contractility immediately on postural change (P <.05), unlike patients in group 2. Patients in group 1 also had a further increase in myocardial contractility before the end of tilt (P <.01). With drug administration, the changes in supine myocardial contractility were nonsignificant and were not related with the outcome of the tilt test (P <.05). Conclusions An increase in myocardial contractility is detected by the sensor during the tilt test. The changes induced by the drugs on supine myocardial contractility are minor and not related with the outcome of the head-up tilt test. (Am Heart J 2000;139:1022-30.)