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Review
. 2007 Aug;23 Suppl A(Suppl A):16A-22A.
doi: 10.1016/s0828-282x(07)71001-2.

Electrical heart disease: Genetic and molecular basis of cardiac arrhythmias in normal structural hearts

David Farwell  1 , Michael H Gollob
Affiliations
Review

Electrical heart disease: Genetic and molecular basis of cardiac arrhythmias in normal structural hearts

David Farwell et al. Can J Cardiol. 2007 Aug.

Abstract
in English, French

Purely electrical heart diseases, defined by the absence of any structural cardiac defects, are responsible for a large number of sudden, unexpected deaths in otherwise healthy, young individuals. These conditions include the long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia and the short QT syndrome. Collectively, these conditions have been referred to as channelopathies. Ion channels provide the molecular basis for cardiac electrical activity. These channels have specific ion selectivity and are responsible for the precise and timely regulation of the passage of charged ions across the cell membrane in myocytes, and the summation of their activity in cardiac muscle defines the surface electrocardiogram. Impairment in the flow of these ions in heart cells may mean the difference between a normal, prosperous life and the tragedy of a sudden, unexpected death due to ventricular arrhythmia. The present paper reviews the current clinical and molecular understanding of the electrical diseases of the heart associated with sudden cardiac death.

Les troubles purement électriques, définis comme l’absence de lésions cardiaques structurales, entraînent la mort subite d’un grand nombre de jeunes, par ailleurs en bonne santé. Ces troubles comprennent notamment le syndrome de l’allongement de l’intervalle QT, le syndrome de Brugada, la tachycardie ventriculaire polymorphe catécholaminergique et le syndrome du raccourcissement de l’intervalle QT. Ce type d’arythmie est désigné par le terme de maladie des canaux ioniques. Ceux-ci constituent la base moléculaire de l’activité électrique du cœur; ils ont une sélectivité ionique spécifique et ils sont responsables du passage régulier des ions chargés par la membrane cellulaire dans les myocytes, et l’ensemble de leur activité dans le muscle cardiaque est rendu visible par l’électrocardiogramme de surface. Ainsi, les troubles de la circulation des ions dans les cellules du cœur peuvent faire toute la différence entre une vie normale, heureuse et une mort subite, tragique, causée par l’arythmie ventriculaire. Le présent article fait le point sur les facteurs cliniques et moléculaires des troubles de la conduction électrique, liés à la mort cardiaque subite.

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Figures

Figure 1)
Figure 1)
Long QT syndrome genes and their currents comprising the normal cardiac action potential. Prolongation of the cardiac action potential may occur by impaired flow of potassium ions out of the cell during phase 3 of the action potential, or due to an increased inward sodium or calcium current during the plateau phase. Action potential phases: 0 = depolarization, 1 = fast repolarization, 2 = plateau, 3 = repolarization and 4 = resting potential. ICa Inward calcium current; IK1 Inward rectifier potassium current; IKr Rapidly activating potassium current; IKs Slowly activating potassium current; INa Inward sodium current
Figure 2)
Figure 2)
Genotype-phenotype electrocardiogram (ECG) characteristics in the three most common forms of inherited long QT syndrome (LQTS). Typical T wave morphological abnormalities in LQTS are best seen in the precordial ECG leads. LQTS type 1 (LQT1) commonly shows a broad-based T wave pattern, LQTS type 2 (LQT2) shows notched or bifurcated T waves, and LQTS type 3 (LQT3) shows a late-appearing T wave with a prolonged ST segment
Figure 3)
Figure 3)
The two predominant electrocardiogram (ECG) repolarization abnormalities observed in the Brugada syndrome. Brugada syndrome ECG pattern abnormalities are observed in the anterior precordial leads (V1 and/or V2). ECG abnormalities may be dynamic, and alternate between normal or abnormal ECG patterns. The coved-shaped pattern is suggested to be associated with an increased risk of cardiac events
Figure 4)
Figure 4)
Simplified schemata of relevant proteins involved in intracellular calcium (iCa) regulation. Coupling of myocyte excitation-contraction is mediated through calcium (Ca), initiated by the inward L-type Ca channel. This current leads to sarcoplasmic reticulum (SR) release of Ca via the ryanodine receptor type 2 (RyR2) and the subsequent contractile process. βAR Beta-adrenergic receptor; cAMP Cyclic AMP; Na Sodium; PKA Protein kinase A; SERCA2a Sarcoplasmic reticulum calcium ATPase-2a
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