Abstract
Objective—To determine the benefit of midodrine, an α agonist, on symptom frequency and haemodynamic responses during head up tilt in patients with neurocardiogenic syncope. Setting—Cardiovascular investigation unit (a secondary and tertiary referral centre for the investigation and management of syncope). Patients—16 outpatients (mean (SD) age 56 (18) years; five men) with frequent hypotensive symptoms (more than two syncopal episodes and fewer than 20 symptom free days per month), and reproducible syncope with glyceryl trinitrate (GTN) during head up tilt. Design and intervention—Randomised double blind placebo controlled study. Patients were randomised to receive either placebo or midodrine for one month. Symptom events were recorded during each study month. At the end of each study month patients completed a quality of life scoring scale (Short Form 36) and a global assessment of therapeutic response. They received GTN with head up tilt for measurement of heart rate (electrocardiography), phasic blood pressure (digital photoplethysmography), and thoracic fluid index (transthoracic impedance plethysmography) during symptom provocation. Results—Patients administered midodrine had an average of 7.3 more symptom free days than those who received placebo (95% confidence interval (CI) 4.6 to 9; p < 0.0001). Eleven patients reported a positive therapeutic response with midodrine (p = 0.002). All domains of quality of life showed improvement with midodrine, in particular physical function (8.1; 95% CI 3.7 to 12.2), energy and vitality (14.6; 95% CI 7.3 to 22.1), and change in health status (22.2; 95% CI 11 to 33.4 ). Fourteen patients who were given placebo had tilt induced syncope compared with six given midodrine (p = 0.01). Baseline supine systolic blood pressure was higher and heart rate lower in patients who received midodrine than in those who were given placebo ( p < 0.05). A lower thoracic fluid index in patients administered midodrine indicates increased venous return when supine and during head up tilt. There were no serious adverse effects. Conclusions—Midodrine had a conspicuous beneficial effect on symptom frequency, symptoms during head up tilt, and quality of life. Midodrine is recommended for the treatment of neurocardiogenic syncope in patients with frequent symptoms. Keywords: midodrine; neurocardiogenic syncope; head up tilt test
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- Abi-Samra F., Maloney J. D., Fouad-Tarazi F. M., Castle L. W. The usefulness of head-up tilt testing and hemodynamic investigations in the workup of syncope of unknown origin. Pacing Clin Electrophysiol. 1988 Aug;11(8):1202–1214. doi: 10.1111/j.1540-8159.1988.tb03973.x. [DOI] [PubMed] [Google Scholar]
- Almquist A., Goldenberg I. F., Milstein S., Chen M. Y., Chen X. C., Hansen R., Gornick C. C., Benditt D. G. Provocation of bradycardia and hypotension by isoproterenol and upright posture in patients with unexplained syncope. N Engl J Med. 1989 Feb 9;320(6):346–351. doi: 10.1056/NEJM198902093200603. [DOI] [PubMed] [Google Scholar]
- Benditt D. G., Remole S., Bailin S., Dunnigan A., Asso A., Milstein S. Tilt table testing for evaluation of neurally-mediated (cardioneurogenic) syncope: rationale and proposed protocols. Pacing Clin Electrophysiol. 1991 Oct;14(10):1528–1537. doi: 10.1111/j.1540-8159.1991.tb04074.x. [DOI] [PubMed] [Google Scholar]
- Brignole M., Menozzi C., Gianfranchi L., Lolli G., Bottoni N., Oddone D. A controlled trial of acute and long-term medical therapy in tilt-induced neurally mediated syncope. Am J Cardiol. 1992 Aug 1;70(3):339–342. doi: 10.1016/0002-9149(92)90615-6. [DOI] [PubMed] [Google Scholar]
- Come P. C., Pitt B. Nitroglycerin-induced severe hypotension and bradycardia in patients with acute myocardial infarction. Circulation. 1976 Oct;54(4):624–628. doi: 10.1161/01.cir.54.4.624. [DOI] [PubMed] [Google Scholar]
- Ferguson D. W., Thames M. D., Mark A. L. Effects of propranolol on reflex vascular responses to orthostatic stress in humans. Role of ventricular baroreceptors. Circulation. 1983 Apr;67(4):802–807. doi: 10.1161/01.cir.67.4.802. [DOI] [PubMed] [Google Scholar]
- Fitzpatrick A., Sutton R. Tilting towards a diagnosis in recurrent unexplained syncope. Lancet. 1989 Mar 25;1(8639):658–660. doi: 10.1016/s0140-6736(89)92155-7. [DOI] [PubMed] [Google Scholar]
- Goldstein D. S., Spanarkel M., Pitterman A., Toltzis R., Gratz E., Epstein S., Keiser H. R. Circulatory control mechanisms in vasodepressor syncope. Am Heart J. 1982 Nov;104(5 Pt 1):1071–1075. doi: 10.1016/0002-8703(82)90442-2. [DOI] [PubMed] [Google Scholar]
- Grubb B. P., Kosinski D. Current trends in etiology, diagnosis, and management of neurocardiogenic syncope. Curr Opin Cardiol. 1996 Jan;11(1):32–41. doi: 10.1097/00001573-199601000-00006. [DOI] [PubMed] [Google Scholar]
- Grubb B. P., Temesy-Armos P., Moore J., Wolfe D., Hahn H., Elliot L. Head-upright tilt-table testing in evaluation and management of the malignant vasovagal syndrome. Am J Cardiol. 1992 Apr 1;69(9):904–908. doi: 10.1016/0002-9149(92)90790-6. [DOI] [PubMed] [Google Scholar]
- Hainsworth R., Al-Shamma Y. M. Cardiovascular responses to upright tilting in healthy subjects. Clin Sci (Lond) 1988 Jan;74(1):17–22. doi: 10.1042/cs0740017. [DOI] [PubMed] [Google Scholar]
- Hargreaves A. D., Muir A. L. Lack of variation in venous tone potentiates vasovagal syncope. Br Heart J. 1992 Jun;67(6):486–490. doi: 10.1136/hrt.67.6.486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hargreaves A. D., el Hag O., Boon N. A. Head-up tilt testing. The balance of evidence. Br Heart J. 1994 Sep;72(3):216–217. doi: 10.1136/hrt.72.3.216. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Imholz B. P., Settels J. J., van der Meiracker A. H., Wesseling K. H., Wieling W. Non-invasive continuous finger blood pressure measurement during orthostatic stress compared to intra-arterial pressure. Cardiovasc Res. 1990 Mar;24(3):214–221. doi: 10.1093/cvr/24.3.214. [DOI] [PubMed] [Google Scholar]
- Jankovic J., Gilden J. L., Hiner B. C., Kaufmann H., Brown D. C., Coghlan C. H., Rubin M., Fouad-Tarazi F. M. Neurogenic orthostatic hypotension: a double-blind, placebo-controlled study with midodrine. Am J Med. 1993 Jul;95(1):38–48. doi: 10.1016/0002-9343(93)90230-m. [DOI] [PubMed] [Google Scholar]
- Kapoor W. N., Smith M. A., Miller N. L. Upright tilt testing in evaluating syncope: a comprehensive literature review. Am J Med. 1994 Jul;97(1):78–88. doi: 10.1016/0002-9343(94)90051-5. [DOI] [PubMed] [Google Scholar]
- Kaufmann H., Brannan T., Krakoff L., Yahr M. D., Mandeli J. Treatment of orthostatic hypotension due to autonomic failure with a peripheral alpha-adrenergic agonist (midodrine). Neurology. 1988 Jun;38(6):951–956. doi: 10.1212/wnl.38.6.951. [DOI] [PubMed] [Google Scholar]
- Kenny R. A., Ingram A., Bayliss J., Sutton R. Head-up tilt: a useful test for investigating unexplained syncope. Lancet. 1986 Jun 14;1(8494):1352–1355. doi: 10.1016/s0140-6736(86)91665-x. [DOI] [PubMed] [Google Scholar]
- Kubicek W. G., Karnegis J. N., Patterson R. P., Witsoe D. A., Mattson R. H. Development and evaluation of an impedance cardiac output system. Aerosp Med. 1966 Dec;37(12):1208–1212. [PubMed] [Google Scholar]
- Linzer M., Pontinen M., Gold D. T., Divine G. W., Felder A., Brooks W. B. Impairment of physical and psychosocial function in recurrent syncope. J Clin Epidemiol. 1991;44(10):1037–1043. doi: 10.1016/0895-4356(91)90005-t. [DOI] [PubMed] [Google Scholar]
- McHorney C. A., Ware J. E., Jr, Raczek A. E. The MOS 36-Item Short-Form Health Survey (SF-36): II. Psychometric and clinical tests of validity in measuring physical and mental health constructs. Med Care. 1993 Mar;31(3):247–263. doi: 10.1097/00005650-199303000-00006. [DOI] [PubMed] [Google Scholar]
- Milstein S., Buetikofer J., Dunnigan A., Benditt D. G., Gornick C., Reyes W. J. Usefulness of disopyramide for prevention of upright tilt-induced hypotension-bradycardia. Am J Cardiol. 1990 Jun 1;65(20):1339–1344. doi: 10.1016/0002-9149(90)91324-y. [DOI] [PubMed] [Google Scholar]
- Morillo C. A., Leitch J. W., Yee R., Klein G. J. A placebo-controlled trial of intravenous and oral disopyramide for prevention of neurally mediated syncope induced by head-up tilt. J Am Coll Cardiol. 1993 Dec;22(7):1843–1848. doi: 10.1016/0735-1097(93)90767-u. [DOI] [PubMed] [Google Scholar]
- Moya A., Permanyer-Miralda G., Sagrista-Sauleda J., Carne X., Rius T., Mont L., Soler-Soler J. Limitations of head-up tilt test for evaluating the efficacy of therapeutic interventions in patients with vasovagal syncope: results of a controlled study of etilefrine versus placebo. J Am Coll Cardiol. 1995 Jan;25(1):65–69. doi: 10.1016/0735-1097(94)00336-o. [DOI] [PubMed] [Google Scholar]
- Natale A., Sra J., Dhala A., Wase A., Jazayeri M., Deshpande S., Blanck Z., Akhtar M. Efficacy of different treatment strategies for neurocardiogenic syncope. Pacing Clin Electrophysiol. 1995 Apr;18(4 Pt 1):655–662. doi: 10.1111/j.1540-8159.1995.tb04660.x. [DOI] [PubMed] [Google Scholar]
- Piwinski S. E., Jankovic J., McElligott M. A. A comparison of postspace-flight orthostatic intolerance to vasovagal syncope and autonomic failure and the potential use of the alpha agonist midodrine for these conditions. J Clin Pharmacol. 1994 May;34(5):466–471. doi: 10.1002/j.1552-4604.1994.tb04988.x. [DOI] [PubMed] [Google Scholar]
- Raviele A., Menozzi C., Brignole M., Gasparini G., Alboni P., Musso G., Lolli G., Oddone D., Dinelli M., Mureddu R. Value of head-up tilt testing potentiated with sublingual nitroglycerin to assess the origin of unexplained syncope. Am J Cardiol. 1995 Aug 1;76(4):267–272. doi: 10.1016/s0002-9149(99)80079-4. [DOI] [PubMed] [Google Scholar]
- Sra J. S., Anderson A. J., Sheikh S. H., Avitall B., Tchou P. J., Troup P. J., Gilbert C. J., Akhtar M., Jazayeri M. R. Unexplained syncope evaluated by electrophysiologic studies and head-up tilt testing. Ann Intern Med. 1991 Jun 15;114(12):1013–1019. doi: 10.7326/0003-4819-114-12-1013. [DOI] [PubMed] [Google Scholar]
- Ward C., Kenny R. A. Observations on midodrine in a case of vasodepressor neurogenic syncope. Clin Auton Res. 1995 Oct;5(5):257–260. doi: 10.1007/BF01818889. [DOI] [PubMed] [Google Scholar]
- van Lieshout J. J., Wieling W., Karemaker J. M., Eckberg D. L. The vasovagal response. Clin Sci (Lond) 1991 Nov;81(5):575–586. doi: 10.1042/cs0810575. [DOI] [PubMed] [Google Scholar]