- Email: [email protected]
Polymorphous ventricular tachycardia due to alpha-blockade
125
IJC 0494B
Polymorphous ventricular tachycardia due to alpha-blockade M.A. James, W. Culling, J. Vann Jones Department
of Curdtolo,~.
(Received
Brrstol Rqwl
Infmun.
18 July 1986; accepted
Brrstol,
U.K.
28 July 1986)
We report a case of polymorphous ventricular tachycardia caused by treatment with the post-synaptic alpha-blocking agent indoramin. This has not been reported with indoramin previously, nor to our knowledge with any other alpha-blocker. This pro-arrhythmic effect appears to be related to its class 3 anti-arrhythmic properties (QT interval prolongation) which is dose dependent, occurring only at large doses.
(Key words: Polymorphous
ventricular
tachycardia;
a-Blockade:
Pro-arrhythmic)
Introduction Many laboratory studies have suggested that alpha-receptor blockade is anti-arrhythmic. One recent study has suggested that the mechanism for this anti-arrhythmic effect may be due to QT prolongation [l]. We have recently confirmed that the alpha-blocker indoramin is anti-arrhythmic in man, and furthermore there was some evidence to suggest that the anti-arrhythmic effect was dependent upon QT prolongation [2]. Anti-arrhythmic drugs that cause QT prolongation can be associated with pro-arrhythmic effects [3]. We report a case of polymorphous ventricular tachycardia with syncope, which occurred in a patient whilst being treated with indoramin. Case Report A 63-year-old man was first investigated for hypertension, dizzy spells and palpitation in 1983. Numerous 24-hour electrocardiograms had shown frequent ventricular ectopics and occasional episodes of paroxysmal atrial fibrillation. However, no serious cardiac arrhythmia could be identified, and dizzy spells did not correlate with any change in cardiac rhythm. The dizzy spells were diagnosed as due to vertebro-basilar insufficiency and treated with a cervical collar with good effect. His other treatment consisted of digoxin 0.25 mg daily, hydroflumethiazide 100 mg daily and spironolactone 75 mg daily. In 1986 he agreed to take part in an anti-arrhythmic study in order to try and obtain better control of his palpitation. He started indoramin at a dose of 25 mg three times a day, during which there were no problems.
(~orresponkwe
to: M.A. James, Dept. of Cardiology,
Int.w~utronul Journal 01 Curdiologv+ 14 (1987) 225-227 ‘C Elsevier Science Publishers B.V. (Biomedical Division)
Bristol Royal Infirmarv.
Bristol BS2 XHW. U K.
Fig. 1, Electrocardiogram showing interval ( > 0.68 set), precipitating
an R-on-T ventricular ectopic occurring on a markedly a burst of polymorphous ventricular tachycardia.
prolonged
QT
He then proceeded to a dose of 50 mg three times a day. During this treatment he experienced a blackout which was not similar to his previous dizzy spells and during which he completely lost consciousness for several minutes. Subsequent 24-hour electrocardiographic monitoring showed that he was experiencing recurrent short bursts of polymorphous ventricular tachycardia and his electrocardiogram showed that he had developed marked QT prolongation, up to 0.7 seconds (uncorrected) on occasions. (QT intervals were variable due to interference from ventricular ectopics, indeed most episodes of polymorphous ventricular tachycardia were initiated by an R-on-T ectopic occurring on the longer QT intervals induced by post-ectopic pauses - see Fig. 1). This sort of rhythm disturbance had never been observed before in his many previous 24-hour recordings. His indoramin therapy was stopped immediately; the following day his electrocardiogram showed that his QT intervals had returned substantially toward normal (max 0.48 set) and he has not experienced a further blackout. All electrolytes that have been associated with this syndrome were checked and were normal (potassium 3.8, calcium 2.36 and magnesium 0.77 mmol/litre): the digoxin concentration was also well below the toxic level (0.6 pg/litre). The plasma bicarbonate and protein levels were normal suggesting that the potassium and calcium measurements were a reasonably accurate reflection of the true electrolyte status. Discussion Neither polymorphous ventricular tachycardia nor torsades de pointes has been reported in association with alpha-blocker therapy previously. However, it is a syndrome that is well known to be associated with QT prolongation [3] and as such might be anticipated to occur at some time with any anti-arrhythmic treatment that is dependent upon QT prolongation, indeed it is well known to occur on occasions during treatment with amiodarone. disopyramide and quinidine [4], all of which prolong’ QT intervals. The QT prolonging effect of indoramin is dose-dependent but only becomes apparent at relatively large doses [5]. This we believe explains why the antiarrhythmic effect of indoramin is only seen at large doses (> 50 mg three times a day) and would also explain why this pro-arrhythmic effect has not been
‘21
seen times even have
during treatment of hypertension which usually only requires doses up to 25 mg three a day. Nonetheless this pro-arrhythmic effect appears to remain relatively uncommon at the larger dosage as this is the first case we have experienced amongst 56 patients who received doses of indoramin of 50 mg or more three times a day.
References Penny WJ. Culling W, Lewis MJ. Sheridan DJ. Anti-arrhythmic and electrophysiological effects of alpha adrenoceptor blockade during myocardial ischaemia and reperfusion. J Mall Cell Cardiol 1985;17:399-409, James MA. Vann Jones J. The anti-arrhythmic properties of alpha receptor blockade. Clin Sci 1986;7O(suppl 13):86p-87~. Sclarovsky S, Strasberg B. Lewin RF, Agmon J. Polymorphous ventricular tachycardia. clinical features and treatment. Am J Cardiol 1979;44:339-344. Roden DM, Woosley RL. QT prolongation and arrhythmia suppression. Am Heart J 19X5: IO9:41 I-41 5. Manz M. Wagner WL. Grube E, Luderitz B. Current concepts in the treatment of cardiac arrhythmias. J Cardiovasc Pharmacol 1986:8(suppl 2):S124-S130.
IJC 0494C
Absent right atrioventricular connexion with a straddling left atrioventricular valve connecting the left atrium to a ventricular mass with a dominant left ventricle Lydia H. Rodriguez ’ Depmtment
‘, M. Consuelo
R. Calleja ’
of Puediutric Cardiology. Centro Midico iu Raza, Mexico; Institute Nacionol de Cordtologia. Mexico (Received
and accepted
’ Deportment
of Puthologv.
2X July 1986)
We present clinical and postmortem examination of a child who presented in life with severe obstruction to the left ventricular outflow tract. The heart was right-sided with usual atrial arrangement. The right atrioventrfcular connexion was absent. There was straddling of the left atrioventticular valve which had a double orifice; Each orifice was connected to a well-differentiated ventricle, the left ventricle being dominant and right-sided (left-hand topology). An inlet ventricular septal defect was restricted by the leaflet tissue of the straddling valve. words: Morphological left ventricle; Morphological atrium: Morphological left atrial appendage)
(Key
Correspondence 06850, Mexico.
to: Lydia
H. Rodriguez
M.D.,
Marcos
Intenzotionul Journal of Curdiologv, 14 (1987) 227-231 a Elsevier Science Publishers B.V. (Biomedical Division)
right ventricle;
Carrillo
Morphological
219 Col. Asturias.
Mexico
right
8 D.F.
IJC 0494B
Polymorphous ventricular tachycardia due to alpha-blockade M.A. James, W. Culling, J. Vann Jones Department
of Curdtolo,~.
(Received
Brrstol Rqwl
Infmun.
18 July 1986; accepted
Brrstol,
U.K.
28 July 1986)
We report a case of polymorphous ventricular tachycardia caused by treatment with the post-synaptic alpha-blocking agent indoramin. This has not been reported with indoramin previously, nor to our knowledge with any other alpha-blocker. This pro-arrhythmic effect appears to be related to its class 3 anti-arrhythmic properties (QT interval prolongation) which is dose dependent, occurring only at large doses.
(Key words: Polymorphous
ventricular
tachycardia;
a-Blockade:
Pro-arrhythmic)
Introduction Many laboratory studies have suggested that alpha-receptor blockade is anti-arrhythmic. One recent study has suggested that the mechanism for this anti-arrhythmic effect may be due to QT prolongation [l]. We have recently confirmed that the alpha-blocker indoramin is anti-arrhythmic in man, and furthermore there was some evidence to suggest that the anti-arrhythmic effect was dependent upon QT prolongation [2]. Anti-arrhythmic drugs that cause QT prolongation can be associated with pro-arrhythmic effects [3]. We report a case of polymorphous ventricular tachycardia with syncope, which occurred in a patient whilst being treated with indoramin. Case Report A 63-year-old man was first investigated for hypertension, dizzy spells and palpitation in 1983. Numerous 24-hour electrocardiograms had shown frequent ventricular ectopics and occasional episodes of paroxysmal atrial fibrillation. However, no serious cardiac arrhythmia could be identified, and dizzy spells did not correlate with any change in cardiac rhythm. The dizzy spells were diagnosed as due to vertebro-basilar insufficiency and treated with a cervical collar with good effect. His other treatment consisted of digoxin 0.25 mg daily, hydroflumethiazide 100 mg daily and spironolactone 75 mg daily. In 1986 he agreed to take part in an anti-arrhythmic study in order to try and obtain better control of his palpitation. He started indoramin at a dose of 25 mg three times a day, during which there were no problems.
(~orresponkwe
to: M.A. James, Dept. of Cardiology,
Int.w~utronul Journal 01 Curdiologv+ 14 (1987) 225-227 ‘C Elsevier Science Publishers B.V. (Biomedical Division)
Bristol Royal Infirmarv.
Bristol BS2 XHW. U K.
Fig. 1, Electrocardiogram showing interval ( > 0.68 set), precipitating
an R-on-T ventricular ectopic occurring on a markedly a burst of polymorphous ventricular tachycardia.
prolonged
QT
He then proceeded to a dose of 50 mg three times a day. During this treatment he experienced a blackout which was not similar to his previous dizzy spells and during which he completely lost consciousness for several minutes. Subsequent 24-hour electrocardiographic monitoring showed that he was experiencing recurrent short bursts of polymorphous ventricular tachycardia and his electrocardiogram showed that he had developed marked QT prolongation, up to 0.7 seconds (uncorrected) on occasions. (QT intervals were variable due to interference from ventricular ectopics, indeed most episodes of polymorphous ventricular tachycardia were initiated by an R-on-T ectopic occurring on the longer QT intervals induced by post-ectopic pauses - see Fig. 1). This sort of rhythm disturbance had never been observed before in his many previous 24-hour recordings. His indoramin therapy was stopped immediately; the following day his electrocardiogram showed that his QT intervals had returned substantially toward normal (max 0.48 set) and he has not experienced a further blackout. All electrolytes that have been associated with this syndrome were checked and were normal (potassium 3.8, calcium 2.36 and magnesium 0.77 mmol/litre): the digoxin concentration was also well below the toxic level (0.6 pg/litre). The plasma bicarbonate and protein levels were normal suggesting that the potassium and calcium measurements were a reasonably accurate reflection of the true electrolyte status. Discussion Neither polymorphous ventricular tachycardia nor torsades de pointes has been reported in association with alpha-blocker therapy previously. However, it is a syndrome that is well known to be associated with QT prolongation [3] and as such might be anticipated to occur at some time with any anti-arrhythmic treatment that is dependent upon QT prolongation, indeed it is well known to occur on occasions during treatment with amiodarone. disopyramide and quinidine [4], all of which prolong’ QT intervals. The QT prolonging effect of indoramin is dose-dependent but only becomes apparent at relatively large doses [5]. This we believe explains why the antiarrhythmic effect of indoramin is only seen at large doses (> 50 mg three times a day) and would also explain why this pro-arrhythmic effect has not been
‘21
seen times even have
during treatment of hypertension which usually only requires doses up to 25 mg three a day. Nonetheless this pro-arrhythmic effect appears to remain relatively uncommon at the larger dosage as this is the first case we have experienced amongst 56 patients who received doses of indoramin of 50 mg or more three times a day.
References Penny WJ. Culling W, Lewis MJ. Sheridan DJ. Anti-arrhythmic and electrophysiological effects of alpha adrenoceptor blockade during myocardial ischaemia and reperfusion. J Mall Cell Cardiol 1985;17:399-409, James MA. Vann Jones J. The anti-arrhythmic properties of alpha receptor blockade. Clin Sci 1986;7O(suppl 13):86p-87~. Sclarovsky S, Strasberg B. Lewin RF, Agmon J. Polymorphous ventricular tachycardia. clinical features and treatment. Am J Cardiol 1979;44:339-344. Roden DM, Woosley RL. QT prolongation and arrhythmia suppression. Am Heart J 19X5: IO9:41 I-41 5. Manz M. Wagner WL. Grube E, Luderitz B. Current concepts in the treatment of cardiac arrhythmias. J Cardiovasc Pharmacol 1986:8(suppl 2):S124-S130.
IJC 0494C
Absent right atrioventricular connexion with a straddling left atrioventricular valve connecting the left atrium to a ventricular mass with a dominant left ventricle Lydia H. Rodriguez ’ Depmtment
‘, M. Consuelo
R. Calleja ’
of Puediutric Cardiology. Centro Midico iu Raza, Mexico; Institute Nacionol de Cordtologia. Mexico (Received
and accepted
’ Deportment
of Puthologv.
2X July 1986)
We present clinical and postmortem examination of a child who presented in life with severe obstruction to the left ventricular outflow tract. The heart was right-sided with usual atrial arrangement. The right atrioventrfcular connexion was absent. There was straddling of the left atrioventticular valve which had a double orifice; Each orifice was connected to a well-differentiated ventricle, the left ventricle being dominant and right-sided (left-hand topology). An inlet ventricular septal defect was restricted by the leaflet tissue of the straddling valve. words: Morphological left ventricle; Morphological atrium: Morphological left atrial appendage)
(Key
Correspondence 06850, Mexico.
to: Lydia
H. Rodriguez
M.D.,
Marcos
Intenzotionul Journal of Curdiologv, 14 (1987) 227-231 a Elsevier Science Publishers B.V. (Biomedical Division)
right ventricle;
Carrillo
Morphological
219 Col. Asturias.
Mexico
right
8 D.F.