Idiopathic long QT syndrome exacerbated by beta-adrenergic blockade and responsive to left cardiac sympathetic denervation: Implications regarding electrophysiologic substrate and adrenergic modulation

G. Malfatto, M. R. Rosen, A. Foresti, P. J. Schwartz

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Introduction: The mechanisms of T wave abnormalities and arrhythmias in patients affected by the long QT syndrome (LQTS) are unclear, as are the reasons why a high-risk subgroup (20%) continues to have syncope during therapy with beta blockers but is protected after left cardiac sympathetic denervation (LCSD). Afterdepolarizations, both early (EAD) or delayed (DAD), have been implicated as likely electrophysiologic substrates for the ECG abnormalities and arrhythmias in LQTS. To test this hypothesis, we analyzed nine Holter recordings of a LQTS patient typical of the high-risk subgroup. Methods and Results: We applied to the ECG rules derived from previous in vitro and in vivo studies, which relate the coupling intervals of the dysrhythmic beats to the preceding cycle lengths, to discriminate among arrhythmia mechanisms. In the absence of therapy, the patient's ECG showed peaked T waves, with a notched second component accentuated by sinus pauses. The amplitude of the notches increased directly with the preceding RR interval (r = 0.58, P <0.05), as it is observed with EAD. Therapy with the beta blocker propranolol did not modify the notches, which maintained their amplitude and their relationship with the preceding RR (r = 0.62, P <0.05). Moreover, during beta-blocker therapy, ventricular premature beats, couplets, and runs of ventricular tachycardia (VT) occurred. The coupling intervals of ventricular premature beats and couplets were not influenced by the preceding RR intervals. By contrast, the coupling interval of the first beat of VT decreased as the preceding RR shortened, as it occurs with DAD-induced triggered activity. After LCSD, T wave notch amplitude was reduced (P <0.05) and was no longer influenced by the preceding RR (r = 0.31, P = 0.22). The same was true when the calcium entry blocker verapamil was administered. Conclusion: In this patient, T wave abnormalities and some ventricular arrhythmias had the behavior observed in vitro for EAD and the consequent triggered activity. However, the cycle length dependence of VT manifested the behavior observed in vitro for DAD and the related triggered activity. The fact that these phenomena were accentuated by beta blockade and disappeared after LCSD suggests that the alpha-adrenergic receptor-effector system may be a modulator of T wave abnormalities and arrhythmias in some patients unresponsive to beta blockade and protected by LCSD.

Original languageEnglish
Pages (from-to)295-305
Number of pages11
JournalJournal of Cardiovascular Electrophysiology
Volume3
Issue number4
Publication statusPublished - 1992

Fingerprint

Long QT Syndrome
Sympathectomy
Adrenergic Agents
Cardiac Arrhythmias
Ventricular Tachycardia
Electrocardiography
Ventricular Premature Complexes
Receptors, Adrenergic, alpha
Syncope
Therapeutics
Verapamil
Propranolol
Calcium
In Vitro Techniques

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

@article{bda73190284143d08bc5fce8460812f8,
title = "Idiopathic long QT syndrome exacerbated by beta-adrenergic blockade and responsive to left cardiac sympathetic denervation: Implications regarding electrophysiologic substrate and adrenergic modulation",
abstract = "Introduction: The mechanisms of T wave abnormalities and arrhythmias in patients affected by the long QT syndrome (LQTS) are unclear, as are the reasons why a high-risk subgroup (20{\%}) continues to have syncope during therapy with beta blockers but is protected after left cardiac sympathetic denervation (LCSD). Afterdepolarizations, both early (EAD) or delayed (DAD), have been implicated as likely electrophysiologic substrates for the ECG abnormalities and arrhythmias in LQTS. To test this hypothesis, we analyzed nine Holter recordings of a LQTS patient typical of the high-risk subgroup. Methods and Results: We applied to the ECG rules derived from previous in vitro and in vivo studies, which relate the coupling intervals of the dysrhythmic beats to the preceding cycle lengths, to discriminate among arrhythmia mechanisms. In the absence of therapy, the patient's ECG showed peaked T waves, with a notched second component accentuated by sinus pauses. The amplitude of the notches increased directly with the preceding RR interval (r = 0.58, P <0.05), as it is observed with EAD. Therapy with the beta blocker propranolol did not modify the notches, which maintained their amplitude and their relationship with the preceding RR (r = 0.62, P <0.05). Moreover, during beta-blocker therapy, ventricular premature beats, couplets, and runs of ventricular tachycardia (VT) occurred. The coupling intervals of ventricular premature beats and couplets were not influenced by the preceding RR intervals. By contrast, the coupling interval of the first beat of VT decreased as the preceding RR shortened, as it occurs with DAD-induced triggered activity. After LCSD, T wave notch amplitude was reduced (P <0.05) and was no longer influenced by the preceding RR (r = 0.31, P = 0.22). The same was true when the calcium entry blocker verapamil was administered. Conclusion: In this patient, T wave abnormalities and some ventricular arrhythmias had the behavior observed in vitro for EAD and the consequent triggered activity. However, the cycle length dependence of VT manifested the behavior observed in vitro for DAD and the related triggered activity. The fact that these phenomena were accentuated by beta blockade and disappeared after LCSD suggests that the alpha-adrenergic receptor-effector system may be a modulator of T wave abnormalities and arrhythmias in some patients unresponsive to beta blockade and protected by LCSD.",
author = "G. Malfatto and Rosen, {M. R.} and A. Foresti and Schwartz, {P. J.}",
year = "1992",
language = "English",
volume = "3",
pages = "295--305",
journal = "Journal of Cardiovascular Electrophysiology",
issn = "1045-3873",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Idiopathic long QT syndrome exacerbated by beta-adrenergic blockade and responsive to left cardiac sympathetic denervation

T2 - Implications regarding electrophysiologic substrate and adrenergic modulation

AU - Malfatto, G.

AU - Rosen, M. R.

AU - Foresti, A.

AU - Schwartz, P. J.

PY - 1992

Y1 - 1992

N2 - Introduction: The mechanisms of T wave abnormalities and arrhythmias in patients affected by the long QT syndrome (LQTS) are unclear, as are the reasons why a high-risk subgroup (20%) continues to have syncope during therapy with beta blockers but is protected after left cardiac sympathetic denervation (LCSD). Afterdepolarizations, both early (EAD) or delayed (DAD), have been implicated as likely electrophysiologic substrates for the ECG abnormalities and arrhythmias in LQTS. To test this hypothesis, we analyzed nine Holter recordings of a LQTS patient typical of the high-risk subgroup. Methods and Results: We applied to the ECG rules derived from previous in vitro and in vivo studies, which relate the coupling intervals of the dysrhythmic beats to the preceding cycle lengths, to discriminate among arrhythmia mechanisms. In the absence of therapy, the patient's ECG showed peaked T waves, with a notched second component accentuated by sinus pauses. The amplitude of the notches increased directly with the preceding RR interval (r = 0.58, P <0.05), as it is observed with EAD. Therapy with the beta blocker propranolol did not modify the notches, which maintained their amplitude and their relationship with the preceding RR (r = 0.62, P <0.05). Moreover, during beta-blocker therapy, ventricular premature beats, couplets, and runs of ventricular tachycardia (VT) occurred. The coupling intervals of ventricular premature beats and couplets were not influenced by the preceding RR intervals. By contrast, the coupling interval of the first beat of VT decreased as the preceding RR shortened, as it occurs with DAD-induced triggered activity. After LCSD, T wave notch amplitude was reduced (P <0.05) and was no longer influenced by the preceding RR (r = 0.31, P = 0.22). The same was true when the calcium entry blocker verapamil was administered. Conclusion: In this patient, T wave abnormalities and some ventricular arrhythmias had the behavior observed in vitro for EAD and the consequent triggered activity. However, the cycle length dependence of VT manifested the behavior observed in vitro for DAD and the related triggered activity. The fact that these phenomena were accentuated by beta blockade and disappeared after LCSD suggests that the alpha-adrenergic receptor-effector system may be a modulator of T wave abnormalities and arrhythmias in some patients unresponsive to beta blockade and protected by LCSD.

AB - Introduction: The mechanisms of T wave abnormalities and arrhythmias in patients affected by the long QT syndrome (LQTS) are unclear, as are the reasons why a high-risk subgroup (20%) continues to have syncope during therapy with beta blockers but is protected after left cardiac sympathetic denervation (LCSD). Afterdepolarizations, both early (EAD) or delayed (DAD), have been implicated as likely electrophysiologic substrates for the ECG abnormalities and arrhythmias in LQTS. To test this hypothesis, we analyzed nine Holter recordings of a LQTS patient typical of the high-risk subgroup. Methods and Results: We applied to the ECG rules derived from previous in vitro and in vivo studies, which relate the coupling intervals of the dysrhythmic beats to the preceding cycle lengths, to discriminate among arrhythmia mechanisms. In the absence of therapy, the patient's ECG showed peaked T waves, with a notched second component accentuated by sinus pauses. The amplitude of the notches increased directly with the preceding RR interval (r = 0.58, P <0.05), as it is observed with EAD. Therapy with the beta blocker propranolol did not modify the notches, which maintained their amplitude and their relationship with the preceding RR (r = 0.62, P <0.05). Moreover, during beta-blocker therapy, ventricular premature beats, couplets, and runs of ventricular tachycardia (VT) occurred. The coupling intervals of ventricular premature beats and couplets were not influenced by the preceding RR intervals. By contrast, the coupling interval of the first beat of VT decreased as the preceding RR shortened, as it occurs with DAD-induced triggered activity. After LCSD, T wave notch amplitude was reduced (P <0.05) and was no longer influenced by the preceding RR (r = 0.31, P = 0.22). The same was true when the calcium entry blocker verapamil was administered. Conclusion: In this patient, T wave abnormalities and some ventricular arrhythmias had the behavior observed in vitro for EAD and the consequent triggered activity. However, the cycle length dependence of VT manifested the behavior observed in vitro for DAD and the related triggered activity. The fact that these phenomena were accentuated by beta blockade and disappeared after LCSD suggests that the alpha-adrenergic receptor-effector system may be a modulator of T wave abnormalities and arrhythmias in some patients unresponsive to beta blockade and protected by LCSD.

UR - http://www.scopus.com/inward/record.url?scp=0026639744&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026639744&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0026639744

VL - 3

SP - 295

EP - 305

JO - Journal of Cardiovascular Electrophysiology

JF - Journal of Cardiovascular Electrophysiology

SN - 1045-3873

IS - 4

ER -