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Nitrate-stimulated tilt test To the Editor: We read with interest the article by Del Rosso et all in the April 1998 issue and wish to make some comment'). The statement that cardioinhibition Is specific for patents with vasovagal syncope is contradicted by our own experience and data from other researchers. Using a slightly different nitrate-stimulated tilt test (Hun, we found an asystole of more than 6 seconds in a normal volunteerr' Dhala et al 3 provoked an asystole in 4% of controls with an unstimulated HUT, and Karp et al 4 induced bradycardia and asystole in 33% of normal volunteers. We therefore assume that the cardioinhibi- tion is not specific for patients with vasovagal syncope and may be more related to the HUT protocol. We found a relatively high percentage of asystole with a motorized tilt table (in the patient group and the con- trols) with a descent time of approximately 20 second'). Another group of investigators that used a manual table with a descent time of 1 or 2 seconds found no asystole at all. Therefore the assumption that HUT induced cardioinhibition might guide the initial therapeutic approach remains debatable, knowing that the presence of asystole during HUT does not predict the clinical outcome. 5 The important shortening of the HUT with nitrates and the increase in sensitivity make it an interesting alternative to the classic test. Reproducibility of the test in our experience is excellent; with a sublingual stimu- lation of 5 mg isosorbide dinitrate after 30 minutes of passive tilt, a positive test was reproducible in IOOOA! and a negative test in 94% of cases," We further exam- ined the importance of the duration of the preceding unstimulated test when using nitrate stimulation: 45 minutes, 30 minutes, and no preceding passive tilt were compared. The accuracy of the 3 protocol" was similar, with a slightly higher sensitivity for the longest test.'·1:! We therefore believe that the HUT can be further short- ened by dropping the unstimulated phase and directly proceeding to the nitrate stimulation, In this way, a I5-minute test duration would make HUT attractive even in a busy cardiology practice. This ultrashort nitrate-stimulated HUT protocol should of course be tested in different populations to determine the reproducibility and the predictive accuracy, References 1. Del Rosso A, Bartoli P, Bartolelti A, A, Bonechi F, Maioli M, et al. Shortened head-up tilttesting potentiated with sublingual nitroglycerin in patients with unexplained syncope. Am HeartJ 1998;135:564-70. 2. OhalaA, Natale A, SraJ, Deshpande S, Blanck Z,Jazayeri MR, et al. Relevance of asystole dUring head-up tilt testing. Am J Cardiol 1995;75:251-4. 3. Aerts A, Dendale P, Strobel G, Block P. Sublingual nitrates during head-up tilttesting for the diagnosis of vasovagal syncope. Am HeartJ 1997;133:504-7. 4. Karp HR, Weissler AM, Heyman A. Vasodepressor syncope: EEG and circulatory changes. Arch Neurol 1961;5:106-13. 5. Sheldon R, Rose S, Koshman L Comparison of patients with syncope of unknown cause having negativeor positive tilt table tests. Am J CardioI1997;581-5. 6. AertsA, Oendale P, Block P. ReprodUcibility of sublingualnitrate stimulated head-up tilt testin patients withvasovagal syncopeand healthy volunteers [abstract]. Eur HeartJ 1997;18:197. 7. Aerts A, Oendale P, Block P. Influence of tilt duration on diagnostic value in sublingual nitrate stimulated head up tilt testing[abstract]. ActaCardiologica 1997;51:586. 8. Dendale P, AertsA, Melis P, Block P. Influence of tiltduration on specificity in sublingual nitrate stimulated tilttesting [abstract]. Eur HeartJ 1996; 17:581. Arnaud], J. Aerts, MD Department of Cardiology Atrium Medtsch Centrum Heerlen Henri Dunantstraat5 6401 CXHeeden The Netherlands Paul Dendale, PhD Department of Cardiology virgafesse Hospital Stadskanaal11 Hasselt, Belgium 4/8/92777 Reply To the Editor: In our study, 1 as in the previous study from Raviele et al,2 no subject in the control group had a positive car- dioinhibitory response to head-up tilt test (Hun. On the other hand, in both studies a positive response to HUT was observed in only 2 of the control subjects. The absence of a cardioinhibitory response in the con- trol groups could be linked to the small number of pos- itive responses. Therefore the observation that cardioin- hibition is specific for patient') with vasovagal syncope would need to be confirmed in larger samples. Rather, the letter from Aerts and Dendale raises seri- ous concerns about the classification of the positive HUT responses, in patient') and control subject'), inde- pendently from the BeT protocol. Indeed, when we
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Nitrate-stimulated tilt test
To the Editor:We read with interest the article by Del Rosso et all in
the April 1998 issue and wish to make some comment').The statement that cardioinhibition Is specific for patentswith vasovagal syncope is contradicted by our ownexperience and data from other researchers. Using aslightly different nitrate-stimulated tilt test (Hun, wefound an asystole of more than 6 seconds in a normalvolunteerr' Dhala et al3 provoked an asystole in 4% ofcontrols with an unstimulated HUT, and Karp et al4
induced bradycardia and asystole in 33% of normalvolunteers. We therefore assume that the cardioinhibition is not specific for patients with vasovagal syncopeand may be more related to the HUT protocol. Wefound a relatively high percentage of asystole with amotorized tilt table (in the patient group and the controls) with a descent time of approximately 20 second').Another group of investigators that used a manual tablewith a descent time of 1 or 2 seconds found no asystoleat all. Therefore the assumption that HUT inducedcardioinhibition might guide the initial therapeuticapproach remains debatable, knowing that the presenceof asystole during HUT does not predict the clinical
outcome.5
The important shortening of the HUT with nitratesand the increase in sensitivity make it an interestingalternative to the classic test. Reproducibility of the testin our experience is excellent; with a sublingual stimulation of 5 mg isosorbide dinitrate after 30 minutes ofpassive tilt, a positive test was reproducible in IOOOA!and a negative test in 94% of cases," We further examined the importance of the duration of the precedingunstimulated test when using nitrate stimulation: 45minutes, 30 minutes, and no preceding passive tilt werecompared. The accuracy of the 3 protocol" was similar,with a slightly higher sensitivity for the longest test.'·1:!We therefore believe that the HUT can be further shortened by dropping the unstimulated phase and directlyproceeding to the nitrate stimulation, In this way, aI5-minute test duration would make HUT attractiveeven in a busy cardiology practice. This ultrashortnitrate-stimulated HUT protocol should of course betested in different populations to determine thereproducibility and the predictive accuracy,
References1. DelRosso A, Bartoli P, Bartolelti A, Brandinell~Geri A, Bonechi F,
Maioli M, et al. Shortened head-up tilttesting potentiated with
sublingual nitroglycerin in patients with unexplained syncope. AmHeartJ 1998;135:564-70.
2. OhalaA, Natale A,SraJ, Deshpande S, Blanck Z,Jazayeri MR, etal. Relevance of asystole dUring head-up tilt testing. Am J Cardiol1995;75:251-4.
3. Aerts A, Dendale P, Strobel G, Block P. Sublingual nitrates duringhead-up tilttesting for the diagnosis of vasovagal syncope. AmHeartJ 1997;133:504-7.
4. Karp HR, Weissler AM,Heyman A.Vasodepressor syncope:EEGand circulatory changes. Arch Neurol 1961;5:106-13.
5. Sheldon R, Rose S, Koshman L Comparison of patients with syncopeof unknown cause having negativeor positive tilt table tests. Am JCardioI1997;581-5.
6. AertsA, Oendale P, Block P. ReprodUcibility of sublingualnitratestimulated head-uptilt testin patients withvasovagal syncopeandhealthy volunteers [abstract]. Eur HeartJ 1997;18:197.
7. Aerts A, Oendale P, Block P. Influence of tilt duration on diagnosticvalue insublingual nitrate stimulated head up tilt testing[abstract].ActaCardiologica 1997;51:586.
8. Dendale P, AertsA, Melis P, Block P. Influence of tiltduration onspecificity in sublingualnitrate stimulated tilttesting [abstract].Eur HeartJ 1996; 17:581.
Arnaud],J. Aerts, MDDepartment ofCardiology
Atrium Medtsch Centrum HeerlenHenri Dunantstraat 5
6401 CXHeedenThe Netherlands
Paul Dendale, PhDDepartment ofCardiology
virgafesseHospitalStadskanaal11
Hasselt, Belgium
4/8/92777
ReplyTo the Editor:In our study,1 as in the previous study from Raviele et
al,2 no subject in the control group had a positive car
dioinhibitory response to head-up tilt test (Hun. Onthe other hand, in both studies a positive response toHUT was observed in only 2 of the control subjects.The absence of a cardioinhibitory response in the control groups could be linked to the small number of positive responses. Therefore the observation that cardioinhibition is specific for patient') with vasovagal syncopewould need to be confirmed in larger samples.
Rather, the letter from Aerts and Dendale raises serious concerns about the classification of the positiveHUT responses, in patient') and control subject'), independently from the BeT protocol. Indeed, when we
576 Aerts and Dendale
classify the positive responses to HUT as cardioinhibitory. we refer to bradycardia or asystolic pauses observedimmediately before or at the moment of the loss of consciousness--not to the response observed after the syncope occurrence while the patient is returning to thesupine position. In the latter phase a bradycardia is alsofrequently observed when the mechanism of syncope isdominant vasodepressor, particularly if the descent timeof the tilt table is relatively long. Obviously the latterresponse is not considered significant for the mechanism of the loss of consciousness.
The clinical outcome of patients with asystole duringHUT appears similar to that of patients who are syncopal but not asystolic.3
Nevertheless, in selected cases, the response to HUTmay be used to guide the therapeutic approach. Indeed,the preliminary data of North American VasovagalPacemaker Study! showed dual-ehamber cardiac pacingwith rate-drop sensing as able to reduce the syncoperecurrence in selected highly symptomatic patients.
In our recent randomized study, we found the shortened HUT potentiated with oral nitroglycerin to have apositive rate similar to the conventional one.? On theother hand, the further reduction of the basal phase to 5minutes has been shown to reduce the positive rate ofthe test," Thus we do not agree with Aerts and Dendalewhen they propose the complete suppression of thebasal phase of HUT.
Furthermore, the specificity of the Dendale's protocolwas 88%7 in a population aged 26 ± 5 years, but dataregarding older subjects are still lacking.
Finally, an observation of at least 3 minutes is mandatory to exclude orthostatic hypotension as a cause ofsyncope's indeed, the immediate administration of nitroglycerin would not allow differentiation between vasovagal and orthostatic mechanism as a cause of syncope.
American HeartJournalMarch 1999
Therefore, at the present, when performing HUT potentiated with oral nitroglycerin, the shortened protocolwith a basal phase of 20 minutes should be preferred.
References1. Del Rosso A, Bartoli P, Bartoletti A, Bonechi F, Brandinelli-Geri A,
Maioli M, et al. Shortened head-uptilt testing potentiatedwithsublingual nitroglycerin in patientswith unexplained syncope.Am HeartJ 1998;135:564-70.
2. Raviele A, Menozzi C, Brignole M, GaspariniG, Alboni P, MussoG, et al. Valueof head-up tilt testing potentiated withsublingualnitroglycerin to assess the origin of unexplainedsyncope. Am JCardiol 1995;76:267-72.
3. Brignole M, MenozziC, Gianfranchi l, BoltoniN, Lolli G. Theclinicaland prognosticsignificanceof the asystolicresponse during thehead-uptilltest. EurJ Card Pacing ElectrophysI992;2:109.13.
4. Sheldon R. The NorthAmerican experience: the VPS study. CardiacArrhythmias-Fifth International Workshop, Venice, October7-10, 1997.
5. Bartoletti A, Del Rosso A, BortoliP, Bonechi F, Maioli M, Mazza F, etal. Head-uptilt testing potentiated with sublingualnitroglycerin inpatients with unexplained syncope: shortvs long duration protocol[abstract).J Cardiovasc Diag Proc 1997;14:125.
6. Bartoletti A, Gaggioli G, Menozzi C, Del Rosso A, Mureddu R,Foglia-Manzillo G, et al. Randomized trial of contribution of drugfree phaseand nitroglycerin in the diagnosisof neurallymediatedsyncope [abstract]. Pace 1998;21:968.
7. Dendale P, AertsA, Melis P, Block P. Influenceof tilt duration onspecificity in sublingualnitratestimulated head up tilt testing[abstract). EurHeartJ 1996;17:581.
8. The Consensus Committee of theAmerican Autonomic SocietyandtheAmericanAcademyof Neurology: consensus statement on thedefinitionof orthostatic hypotension, pureautonomic failureandmultiple system. Neurology 1996;46: 1470.
Atttlio Del Rosso, MD
Angelo Bartoletti, MDDepartment ofCardiology
Ospedale S. Pietro Igneo
P.za Lavagnini 1Fuceccbio, Italy
4/8/92778
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