Prospective Evaluation of a Two‐Step Therapeutic Strategy in Neurocardiogenic Syncope: Midodrine as Second Line Treatment in Patients Refractory to β‐Blockers

Abstract

Pharmacological therapy of neurocardiogenic syncope is often limited by the relatively low response rate to such treatment. In particular, response to beta-blocker treatment has been reported to average 50%. Therefore, a two-step protocol, with metoprolol being the drug of first choice, was developed and prospectively evaluated in consecutive patients with a history of repeated syncopal attacks and a positive tilt table test indicative of neurocardiogenic syncope. Patients not responding to the beta-blocker were switched to the alpha-adrenoceptoragonist midodrine. Acute drug efficacy was assessed by repeated tilt table testing. The incidence of syncope recurrence rate was determined during a 7-month follow-up. In 16 of 30 (53%) patients, metoprolol was primarily effective; this was also the case in 7 of 11 patients receiving midodrine. Thus, the overall efficacy rate could be increased to 77% by the treatment protocol (P = 0.009, as compared to beta-blocker treatment alone). During follow-up, only 1 of 27 patients (4%) had a syncopal event. Thus, the two-step treatment protocol presented in this study proved to be safe and to improve significantly patients clinical symptoms, as well as results of repeated tilt table testing as compared to beta-blocker treatment alone.

Autonome Dysfunktion und orthostatische Intoleranz

“…Alternativ haben sich vasokonstriktiv wirksame Pharmaka als sehr effektiv erwiesen. Hier hat sich in jüngerer Zeit die Behandlung mit Midodrin, einem α-Rezeptoragonisten der überwiegend peripher wirksam ist, durchgesetzt [18,20].…”

“…In mehreren Studien haben sich β-Blocker als effektiv erwiesen [20,21,26,34]. Diese Substanzen vermindern die ventrikuläre Hyperkontraktilität durch ihre negativ-inotrope Wirkung, was zu einer verminderten Stimulation vagaler Afferenzen durch ventrikuläre Mechanorezeptoren führt.…”

“…Diese Substanzen vermindern die ventrikuläre Hyperkontraktilität durch ihre negativ-inotrope Wirkung, was zu einer verminderten Stimulation vagaler Afferenzen durch ventrikuläre Mechanorezeptoren führt. Dennoch sprechen nur etwa 50% der behandelten Patienten auf β-Blocker an [20,26]. Besonders scheinen diejenigen zu profitieren, bei denen es zu einem deutlichen Herzfrequenzanstieg während der Kipptischuntersuchung -begleitet von einem signifikanten Anstieg der Noradrenalinspiegel im Serum -kommt [21].…”

“…In einer eigenen Untersuchung [20] bei 30 Patienten mit NCS wurde diese Substanz denjenigen Patienten (47%) gegeben, bei denen eine primäre β-Blockertherapie in- effektiv war. Von diesen sprachen etwa 60% auf die Therapie an, sodass die Gesamtresponderrate dieses 2-Stufen-Konzepts bei 77% lag.…”

Recurrent Postural Vasovagal Syncope

“…Drinking more fluids, increasing dietary salt intake, and physical counterpressure maneuvers 1 should still be universally applied, with administration where indicated of medication, such as fludrocortisone, to expand plasma volume 27 and pressor agents such as midodrine. 28 However, more specific, targeted drug treatment, directed at elucidated mechanisms of syncope, should now follow.…”