Proarrhythmia

New arrhythmia or aggravation of pre-existing arrhythmia at a drug dose which is considered to be below the toxic level is considered to be proarrhythmia. It could be an acceleration of a tachycardia or causing of a clinically significant bradyarrhythmia.
Types of Proarrhythmia: Polymorphic tachycardia or torsades, monomorphic ventricular tachycardia, atrial flutter with 1:1 conduction, alteration of thresholds of devices inducing arrhythmia.
Genetic component is involved in most cases of proarrhythmia. Sometimes genetic factors may manifests only when one pathway is blocked by disease and another is affected genetically. This situation occurs in the setting of renal failure.
Pathophysiology of torsades – usually seen in a structurally normal heart. EAD (early afterdepolarization) and DAD (delayed afterdepolarization) are important mechanisms. EAD occurs in phases 2 or 3. DAD is due to early phase 4 re-entry. Basic reason for all these is prolongation of refractoriness.
EAD is seen in conditions like low pacing rates, hypokalemia. DAD is seen in conditions with intra cellular calcium overload – catecholamines, hypoxia and cardiac glycosides.
Goal of antiarrhythmic therapy is two fold: 1) conversion of unidirectional block is to bidirectional block. 2) prolongation of myocardial refractoriness. (1) is achieved by affecting the sodium channels and depolarisation while (2) is achieved by affecting the repolarisation.
When repolarisation is prolonged EADs can occur triggering a re-entrant tachycardia. This occurs in type IA drugs and does not occur in types IB and C.
Monomorphic re-entrant tachycardia can occur in the setting of myocardial infarction. Type IC drug can depress conduction to such an extent the recovery of some regions facilitate re-entry. This does not occur with type IA drugs. Type IC can cause incessant re-entrant monomorphic VT. For this reason, monomorphic VT occurs in the setting of a structurally abnormal heart while torsades occur in the setting of a structurally normal heart.

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