La terapia con teofillina nelle sincopi adenosino-sensibili

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1 La terapia con teofillina nelle sincopi adenosino-sensibili Matteo Iori Aritmologia Interventistica Az. Ospedaliera - IRCCS S. Maria Nuova Reggio Emilia

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4 The median baseline APL of these patients was significantly lower than that found in age- and sexmatched population of 81 healthy subjects: 0,33 microm versus 0,49 microm (p=0.017). The median APL value of these patients was also 4-fold lower than that found in 9 control patients with syncope due to reflex sinus arrest (1,2 microm; p=0.001). Common features 1. Long history of recurrent syncope due to idiopatic paroxysmal AV block. 2. Absence of cardiac and ECG abnormalities. 3. Absence of progression to persistent form of AV block. 4. Low baseline APL values and increased susceptibility to exogenous adenosine. 5. Permanent pacing was completely successful in preventing syncope recurrences. SINCOPE

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6 On receiver-operating characteristic curve analysis the adenosine plasmatic level of <0.36 best discriminated between groups displaying 73% sensitivity and 93% specificity Common clinical features and low-apl define a distinct form of syncope distinguish it from VVS and suggest a causal role of the adenosine pathway SINCOPE

7 In the heart, in addition to cause coronary vasodilatation, adenosine depresses SA node activity, AV nodal conduction, atrial contractility and ventricular automaticity. Stimulation by adenosine of Ik in supraventricular tissue expalins: shortening of the action potential in atrial cells, sinus slowing and hyperpolarization of SA nodal cells and depression of the action potential in AV nodal cells. SINCOPE

8 Sinus node: bolus doses of adenosine have a biphasic effect, an initial period of sinus bradycardia is followed by sinus tachycardia AV node: adenosine slow conduction within the AV node which can result in transient AV block; heart block is preceded by prolongation of the A-H interval His-Purkinje system: adenosine has little if any on the His-Purkinje system; H-V interval is unalterated by adenosine SINCOPE

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10 A2AR expression was higher in patients than controls The function of A2AR was preserved In some cases may exist receptors of reserve (spare receptors): the maximal biological effects occurs while not all the receptors are occupied by the agonist SINCOPE

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14 To summarize, in 5 patients, symptoms disappeared and the number of prolonged asystolic pause detected by the ILR decrease impressively from a median of 1.11 per month during 13 months of no treatment to 0 per month during 20 months of teophylline treatment SINCOPE

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18 At present it is unknown how many patients with unexplained syncope are actually patients with low adenosine syncope who could benefit from theophylline treatment. In pooled ISSUE 2 and ISSUE 3 studies an idiopatic-like AV block was observed in 13% (35\264) of patients who had an ILR documentation of syncope and accounted for 22% of those 146 who had an asystolic event. It is possible that some of these patients were patients with low adenosine syncope. This study provides the rationale for planning a randomized controlled trial aimed at confirming or refusing these results. SINCOPE

19 Take home massage 1. Common clinical features and low adenosine plasmatic level define a distinct form of syncope distinguish it from VVS a suggest a causal role of adenosine patway. 2. Theophylline may prevent syncopal recurrences and asystolic events in patients with low adenosine syncope and may be considered an alternative to permanent pacing theraphy in such patients. SINCOPE