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Acquired long QT syndrome: Long-term electrocardiographic (Holter) recording of Torsades de Pointes ending in asystole: II
International Journal of Cardiology 116 (2007) 272 – 275 www.elsevier.com/locate/ijcard
Letter to the Editor
Acquired long QT syndrome: Long-term electrocardiographic (Holter) recording of Torsades de Pointes ending in asystole: II Tomas Raviña a,⁎, Javier Gutierrez a , Paula Raviña b a
Department of Internal Medicine, Section of Cardiology, Hospital de Cabueñes, 3394 Gijón, Spain b Department of Hospital Pharmacy, Hospital Universitario de Ourense, Ourense, Spain Received 20 April 2006; accepted 29 April 2006 Available online 21 July 2006
Abstract The Holter recording in an elderly female patient on Risperidone treatment who developed a longer than expected prolonged QT interval and associated Torsades de Pointes (TdP) at the onset of complete AV block is presented. The electrocardiographic manifestation of (likely) phase 2 early afterdepolarizations (EAD) as a trigger of TdP episodes; the TdP undulating or monomorphic morphologies as a counterpart of drifting or stationery scrolls, respectively, and the TdP final extinction leading to asystole and death are shown. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Torsades de Pointes; Spiral wave reentry; Holter recording
(1) Information provided by Holter electrocardiographic recordings in patients with Long QT Syndromes (LQTS) has important drawbacks, not being the less an unreliable QT/RR relation, given the hysteresis between heart rate and the subsequent change in QT interval; the limited number of leads available, the presence of noise in the recording, even the fact that normal ranges of QT interval may differ from those established in 12-lead conventional ECG tracings compound the limitation of Holter monitoring in patients with the LQTS [1]. However these drawbacks, we think worth reporting the Holter obtained in the old lady patient on Risperidone treatment who developed Torsades de Pointes (TdP) just at the onset of a complete AV block whose tracings were commented by large in [2]. The surface ECG presentation of (likely) phase 2 early afterdepolarizations (EAD), the TdP formation and extinction, and a final TdP episode which ended in asystole, are the main focus of this report. (2) The 21 h Holter monitoring data (from 1300 h to 0955 h next day) are as follow: the basic rhythm (common ⁎ Corresponding author. Fax: +34 985367169. E-mail address: [email protected] (T. Raviña). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.04.069
atrial flutter with complete AV block) remained stable throughout; an idioventricular escape rhythm paced the heart at a mean rate of 37 bpm. The QTa interval of escapes (measured when more than two were not interrupted) was 0.76 s; the automatic QT/RR ratio reading was beyond 526 ms; the density of beats arising in the ventricle was 58%, and many of them evoke a single response, as described in Fig. 1 [2]. Six bursts of Torsades de Pointes (TdP), lasting from 3 beats to 21 beats (the longest one, ending in asystole and death) were documented. At the time of recording (half of the time during sleep) the patient was stable; she was 4 days off Risperidone. (3) It is generally accepted that TdP in the LQTS is the result of triggered activity generated by phase 2 early afterdepolarization (EAD); subsequent re-entrant excitation in the form of rotating spiral waves (or scrolls, spiral waves in 3-D) follow this initial beat. The propagation and extinction of these scrolls have been studied in slices of sheep and dog epicardial muscle [3] and in the whole (healthy) rabbit heart [4] using high resolution video imaging in combination with a potentiometric dye, which allowed the construction of colour isochronal maps of activation. Using a
T. Raviña et al. / International Journal of Cardiology 116 (2007) 272–275
273
Fig. 1. Episodes of TdP triggered by (likely) phase 2 EAD. 3-lead Holter strips at different times during the 21 h monitoring. The basic rhythm is atrial flutter with complete AV block (best seen in panel D, middle lead); an escape idioventricular rhythm paces the heart. The TdP bursts are always preceded by a pause and are triggered by beats that seem to arise from the T wave (upward arrows). The TdP episodes comprise from 3 beats (marked by a bar in panel C) to 21 beats (panel A). Please note that, in panel A, the TdP burst in the middle and lower leads extinguish themselves, while full voltage is maintained in the upper lead. Undisturbed basic rhythm follows the TdP burst (downwards arrows); in all panels single ectopic ventricular beats are observed; specifically, and for that purpose, in panel D single (oblique arrowheads) or double (linked arrowheads) ectopic ventricular beats are shown and marked in the upper Holter lead; these beats (likely the result of phase 2 EAD) appear to merge from different levels of the 2nd part of the preceding T wave and, consequently, the beats configuration they inscribe is variable. See text. EAD: early afterdepolarization.
different animal model (a surrogate canine model of LQTS3), three-dimensional maps of ventricular activation could be also constructed from 256 bipolar electrograms, allowing detailed activation maps. It was found that the polymorphic ventricular tachycardia (PVT) (or TdP, name
that should be reserved for the PVT associated with a prolonged QT interval) in this animal model was the result either of single or paired (“figure-of-eight” = two counterrotating vortices) rotating scrolls. The TdP bursts ended when re-entrant excitation was terminated; the transition in
274
T. Raviña et al. / International Journal of Cardiology 116 (2007) 272–275
QRS axis reflected the bifurcation of a single scroll into two simultaneous scrolls (that involved right and left ventricles separately). Functional conduction block determines the dynamics of the bifurcation (initiation/termination) in this model [5]. In the structurally normal (rabbit) heart, in addition to figures-of-eight reentry as well observed, it was found that the PVT morphology recorded in the epicardium
correlated with the dynamics of drifting or meandering underlying scrolls: a twisting ECG pattern (continuous changes of voltage/electrical axis) coincides with a transient bifurcation of a predominantly rotating scroll which expands over a large portion of the ventricular surface; a monomorphic ECG pattern is associated with a stationery vortex (vortex anchored in one of the many heart heterogeneities,
Fig. 2. Drifting and stationery TdP configuration ending in asystole. Holter recording of the last episode of TdP (21 s) ending in asystolic death. Please note the twisting configuration of the torsades that, in the final seconds, adopts a (predominant) monomorphic appearance. This “double” morphology could be the counterpart of drifting or stationery spirals as observed in experimental conditions. All electrical activity stops when a beat with an intermediate (fusion) morphology and a coupling interval (520 ms) different from that of the TdP (360 ms) arises. This fusion beat likely reflects collision with other spiral wave in the vicinity. The panel C between bars is shown below at 25 mm/s paper speed. See text.
T. Raviña et al. / International Journal of Cardiology 116 (2007) 272–275
such a blood vessel, a scar, etc.). These experimental studies help in a better understanding of the TdP episodes shown in Figs. 1 and 2. When bradycardia, a prolonged QT interval and an augmented transmural dispersion of repolarization (TDR) are present the surge of phase 2 EAD and, eventually, reentry (reentry which conforms accordingly as spiral waves) are enhanced, as it happens in the case under consideration. The wave length in the spiral (distance from the wavefront to the waveback, that equals Conduction Velocity times APD) must have a minimum value below which the wave can no longer propagate regeneratively; if regeneration (restitution) is not possible it may drift away and dissipates at tissue borders or breaks and creates new areas (daughter spirals) where repolarization and depolarization meet. The diastolic interval between beats and the TDR are critical for the spiral wave formation and maintenance. In fact, the beats merging from the second part of the T wave (panels A to D in Fig. 1) trigger or do not TdP bursts depending on critical TDR, a major engine in wave formation, as exposed in [2]. The cycle length (rotating period) of the TdP (around 360 ms = 160 bpm) and the TDR determined (200 ms) [2] are so close that the diastolic interval left (160 ms) precludes the formation/extinction of spirals (sites in the ventricle, unpredictable behaviour, duration, at least as from a surface ECG can be predicted). In all panels in Fig. 1, but especially in panel A, the high voltage in the upper lead, coincident with wave fragmentation in the lower one, illustrates this assumption. The rate of the TdP, its waxing-and-waning modulation, its morphology and behaviour in experimental set-ups and in the surface, transmural ECG, makes a quasiperiodically meandering spiral wave the likely substrate of the arrhythmia [6]. Of particular interest is the extinction of the TdP episode; most times, TdP episodes extinguish when new developed rotating scrolls find functional conduction block ahead, leading to wavebreak; in the human heart this usually occurs between the anterior or posterior right ventricle free wall and the ventricular septum [5]. Thereafter, the basic rhythm
275
usually re-initiates de novo, even though, eventually, may end in ventricular fibrillation and death. In the recording presented in Fig. 2, the beat that extinguish (the last and lasting) TdP episode in no way correspond to an externally applied force; collision with other self-sustaining spiral wave in the vicinity leading to extinction of all electrical activity, seems the most probable explanation. Therefore, collision between two wave fronts rather than self-extinction of a single or predominant wave underlies asystole in this particular example. Clinical and electrocardiographic observation, in addition to myocardial cell biology and organ physiology, may help in unraveling the mechanisms of the polymorphic ventricular tachycardia associated with a prolonged QT interval (TdP). References [1] Camm AJ, Malik M, Yap YG. Measurement of QT interval and repolarization assessment. In: Camm AJ, editor. Acquired long QT syndrome. Blacwell-Futura; 2004. p. 24–59. [2] Raviña T, Raviña P, Gutierrez J. Acquired Long QT Syndrome: Risperidone-facilitated triggered activity and Torsades de Pointes during complete AV block: I. Int J Cardiol [in press]. [3] Davidenko JM, Pertsov AV, Salomonsz R, Baxter W, Jalife J. Stationery and drifting spiral waves of excitation in isolated cardiac muscle. Nature 1992;355:349–51. [4] Gray RA, Jalife J, Penfilov A, et al. Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart. Circulation 1995;91:2454–69. [5] El-Sherif N, Chinushi M, Caref EB, Restivo M. Electrophysiological mechanism of the characteristic electrocardiograpic morphology of torsades de pointes tachyarrythmias in the long QT syndrome: detailed analysis of ventricular tridimensional activation patterns. Circulation 1997;96:4392–9. [6] Qu Z, Garfinkel A. Nonlinear dynamics of excitation and propagation in cardiac muscle. In: Zipes DP, Jalife J, editors. Cardiac electrophysiology: from cell to bedside. Philadelphia: Saunders; 2004. p. 327–35.
Letter to the Editor
Acquired long QT syndrome: Long-term electrocardiographic (Holter) recording of Torsades de Pointes ending in asystole: II Tomas Raviña a,⁎, Javier Gutierrez a , Paula Raviña b a
Department of Internal Medicine, Section of Cardiology, Hospital de Cabueñes, 3394 Gijón, Spain b Department of Hospital Pharmacy, Hospital Universitario de Ourense, Ourense, Spain Received 20 April 2006; accepted 29 April 2006 Available online 21 July 2006
Abstract The Holter recording in an elderly female patient on Risperidone treatment who developed a longer than expected prolonged QT interval and associated Torsades de Pointes (TdP) at the onset of complete AV block is presented. The electrocardiographic manifestation of (likely) phase 2 early afterdepolarizations (EAD) as a trigger of TdP episodes; the TdP undulating or monomorphic morphologies as a counterpart of drifting or stationery scrolls, respectively, and the TdP final extinction leading to asystole and death are shown. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Torsades de Pointes; Spiral wave reentry; Holter recording
(1) Information provided by Holter electrocardiographic recordings in patients with Long QT Syndromes (LQTS) has important drawbacks, not being the less an unreliable QT/RR relation, given the hysteresis between heart rate and the subsequent change in QT interval; the limited number of leads available, the presence of noise in the recording, even the fact that normal ranges of QT interval may differ from those established in 12-lead conventional ECG tracings compound the limitation of Holter monitoring in patients with the LQTS [1]. However these drawbacks, we think worth reporting the Holter obtained in the old lady patient on Risperidone treatment who developed Torsades de Pointes (TdP) just at the onset of a complete AV block whose tracings were commented by large in [2]. The surface ECG presentation of (likely) phase 2 early afterdepolarizations (EAD), the TdP formation and extinction, and a final TdP episode which ended in asystole, are the main focus of this report. (2) The 21 h Holter monitoring data (from 1300 h to 0955 h next day) are as follow: the basic rhythm (common ⁎ Corresponding author. Fax: +34 985367169. E-mail address: [email protected] (T. Raviña). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.04.069
atrial flutter with complete AV block) remained stable throughout; an idioventricular escape rhythm paced the heart at a mean rate of 37 bpm. The QTa interval of escapes (measured when more than two were not interrupted) was 0.76 s; the automatic QT/RR ratio reading was beyond 526 ms; the density of beats arising in the ventricle was 58%, and many of them evoke a single response, as described in Fig. 1 [2]. Six bursts of Torsades de Pointes (TdP), lasting from 3 beats to 21 beats (the longest one, ending in asystole and death) were documented. At the time of recording (half of the time during sleep) the patient was stable; she was 4 days off Risperidone. (3) It is generally accepted that TdP in the LQTS is the result of triggered activity generated by phase 2 early afterdepolarization (EAD); subsequent re-entrant excitation in the form of rotating spiral waves (or scrolls, spiral waves in 3-D) follow this initial beat. The propagation and extinction of these scrolls have been studied in slices of sheep and dog epicardial muscle [3] and in the whole (healthy) rabbit heart [4] using high resolution video imaging in combination with a potentiometric dye, which allowed the construction of colour isochronal maps of activation. Using a
T. Raviña et al. / International Journal of Cardiology 116 (2007) 272–275
273
Fig. 1. Episodes of TdP triggered by (likely) phase 2 EAD. 3-lead Holter strips at different times during the 21 h monitoring. The basic rhythm is atrial flutter with complete AV block (best seen in panel D, middle lead); an escape idioventricular rhythm paces the heart. The TdP bursts are always preceded by a pause and are triggered by beats that seem to arise from the T wave (upward arrows). The TdP episodes comprise from 3 beats (marked by a bar in panel C) to 21 beats (panel A). Please note that, in panel A, the TdP burst in the middle and lower leads extinguish themselves, while full voltage is maintained in the upper lead. Undisturbed basic rhythm follows the TdP burst (downwards arrows); in all panels single ectopic ventricular beats are observed; specifically, and for that purpose, in panel D single (oblique arrowheads) or double (linked arrowheads) ectopic ventricular beats are shown and marked in the upper Holter lead; these beats (likely the result of phase 2 EAD) appear to merge from different levels of the 2nd part of the preceding T wave and, consequently, the beats configuration they inscribe is variable. See text. EAD: early afterdepolarization.
different animal model (a surrogate canine model of LQTS3), three-dimensional maps of ventricular activation could be also constructed from 256 bipolar electrograms, allowing detailed activation maps. It was found that the polymorphic ventricular tachycardia (PVT) (or TdP, name
that should be reserved for the PVT associated with a prolonged QT interval) in this animal model was the result either of single or paired (“figure-of-eight” = two counterrotating vortices) rotating scrolls. The TdP bursts ended when re-entrant excitation was terminated; the transition in
274
T. Raviña et al. / International Journal of Cardiology 116 (2007) 272–275
QRS axis reflected the bifurcation of a single scroll into two simultaneous scrolls (that involved right and left ventricles separately). Functional conduction block determines the dynamics of the bifurcation (initiation/termination) in this model [5]. In the structurally normal (rabbit) heart, in addition to figures-of-eight reentry as well observed, it was found that the PVT morphology recorded in the epicardium
correlated with the dynamics of drifting or meandering underlying scrolls: a twisting ECG pattern (continuous changes of voltage/electrical axis) coincides with a transient bifurcation of a predominantly rotating scroll which expands over a large portion of the ventricular surface; a monomorphic ECG pattern is associated with a stationery vortex (vortex anchored in one of the many heart heterogeneities,
Fig. 2. Drifting and stationery TdP configuration ending in asystole. Holter recording of the last episode of TdP (21 s) ending in asystolic death. Please note the twisting configuration of the torsades that, in the final seconds, adopts a (predominant) monomorphic appearance. This “double” morphology could be the counterpart of drifting or stationery spirals as observed in experimental conditions. All electrical activity stops when a beat with an intermediate (fusion) morphology and a coupling interval (520 ms) different from that of the TdP (360 ms) arises. This fusion beat likely reflects collision with other spiral wave in the vicinity. The panel C between bars is shown below at 25 mm/s paper speed. See text.
T. Raviña et al. / International Journal of Cardiology 116 (2007) 272–275
such a blood vessel, a scar, etc.). These experimental studies help in a better understanding of the TdP episodes shown in Figs. 1 and 2. When bradycardia, a prolonged QT interval and an augmented transmural dispersion of repolarization (TDR) are present the surge of phase 2 EAD and, eventually, reentry (reentry which conforms accordingly as spiral waves) are enhanced, as it happens in the case under consideration. The wave length in the spiral (distance from the wavefront to the waveback, that equals Conduction Velocity times APD) must have a minimum value below which the wave can no longer propagate regeneratively; if regeneration (restitution) is not possible it may drift away and dissipates at tissue borders or breaks and creates new areas (daughter spirals) where repolarization and depolarization meet. The diastolic interval between beats and the TDR are critical for the spiral wave formation and maintenance. In fact, the beats merging from the second part of the T wave (panels A to D in Fig. 1) trigger or do not TdP bursts depending on critical TDR, a major engine in wave formation, as exposed in [2]. The cycle length (rotating period) of the TdP (around 360 ms = 160 bpm) and the TDR determined (200 ms) [2] are so close that the diastolic interval left (160 ms) precludes the formation/extinction of spirals (sites in the ventricle, unpredictable behaviour, duration, at least as from a surface ECG can be predicted). In all panels in Fig. 1, but especially in panel A, the high voltage in the upper lead, coincident with wave fragmentation in the lower one, illustrates this assumption. The rate of the TdP, its waxing-and-waning modulation, its morphology and behaviour in experimental set-ups and in the surface, transmural ECG, makes a quasiperiodically meandering spiral wave the likely substrate of the arrhythmia [6]. Of particular interest is the extinction of the TdP episode; most times, TdP episodes extinguish when new developed rotating scrolls find functional conduction block ahead, leading to wavebreak; in the human heart this usually occurs between the anterior or posterior right ventricle free wall and the ventricular septum [5]. Thereafter, the basic rhythm
275
usually re-initiates de novo, even though, eventually, may end in ventricular fibrillation and death. In the recording presented in Fig. 2, the beat that extinguish (the last and lasting) TdP episode in no way correspond to an externally applied force; collision with other self-sustaining spiral wave in the vicinity leading to extinction of all electrical activity, seems the most probable explanation. Therefore, collision between two wave fronts rather than self-extinction of a single or predominant wave underlies asystole in this particular example. Clinical and electrocardiographic observation, in addition to myocardial cell biology and organ physiology, may help in unraveling the mechanisms of the polymorphic ventricular tachycardia associated with a prolonged QT interval (TdP). References [1] Camm AJ, Malik M, Yap YG. Measurement of QT interval and repolarization assessment. In: Camm AJ, editor. Acquired long QT syndrome. Blacwell-Futura; 2004. p. 24–59. [2] Raviña T, Raviña P, Gutierrez J. Acquired Long QT Syndrome: Risperidone-facilitated triggered activity and Torsades de Pointes during complete AV block: I. Int J Cardiol [in press]. [3] Davidenko JM, Pertsov AV, Salomonsz R, Baxter W, Jalife J. Stationery and drifting spiral waves of excitation in isolated cardiac muscle. Nature 1992;355:349–51. [4] Gray RA, Jalife J, Penfilov A, et al. Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart. Circulation 1995;91:2454–69. [5] El-Sherif N, Chinushi M, Caref EB, Restivo M. Electrophysiological mechanism of the characteristic electrocardiograpic morphology of torsades de pointes tachyarrythmias in the long QT syndrome: detailed analysis of ventricular tridimensional activation patterns. Circulation 1997;96:4392–9. [6] Qu Z, Garfinkel A. Nonlinear dynamics of excitation and propagation in cardiac muscle. In: Zipes DP, Jalife J, editors. Cardiac electrophysiology: from cell to bedside. Philadelphia: Saunders; 2004. p. 327–35.