Torsades occurs as both an inherited and as an acquired form caused most often by drugs and/or electrolyte disorders that cause excessive lengthening of the QT interval. Common causes for torsades de pointes include drug-induced QT prolongation and less often diarrhea, low serum magnesium, and low serum potassium or congenital long QT syndrome. It can be seen in malnourished individuals and chronic alcoholics, due to a deficiency in potassium and/or magnesium. Certain drugs and combinations of drugs resulting in drug interactions are common contributors to torsades de pointes risk. QT-prolonging medications such as clarithromycin, levofloxacin, or haloperidol, when taken concurrently with cytochrome P450 inhibitors, such as fluoxetine, cimetidine, or particular foods including grapefruit, can result in higher-than-normal levels of medications that prolong the QT interval in the bloodstream and therefore increase a person's risk of developing torsades de pointes. At least one mention of the common over-the-counter medication loperamide causing TdP has been made in the literature, although the dose preceding this particular cardiac event was well beyond the therapeutic range of the medication. In addition, patients with inherited long QT syndrome have a very high risk of episodes of TdP and that risk can be further increased by drugs and electrolyte disorders that further prolong QT.
Knowledge that TdP may occur in patients taking certain prescription drugs has been both a major liability and reason for removal of 14 medications from the marketplace. Forty nine drugs known to cause TdP and another 170 that are known to prolong QTc remain on the market because the drugs provide medical benefit and the risk of TdP can be managed and mitigated by instructions in the drug label. Examples of compounds linked to clinical observations of TdP include amiodarone, most fluoroquinolones, methadone, lithium, chloroquine, erythromycin, azithromycin, pimozide, and phenothiazines. The anti-emetic agent ondansetron may also increase the risk of developing TdP. It has also been shown as a side effect of certain anti-arrhythmic medications, such as sotalol, procainamide, quinidine, ibutilide, and dofetilide In one example, the gastrokinetic drug cisapride was withdrawn from the US market in 2000 after it was linked to deaths caused by long QT syndrome-induced torsades de pointes. This effect can be directly linked to QT prolongation mediated predominantly by inhibition of the hERG channel and, in some cases, augmentation of the late sodium channel.
Risk factors
The following is a partial list of factors associated with an increased tendency towards developing torsades de pointes:
Action potential of cardiac muscles can be broken down into five phases:
Phase 0: Sodium channels open, resulting in the entrance of Na+ into the cells; this results in the depolarization of the cardiac muscles.
Phase 1: Sodium channels close; this stops depolarization. Potassium channels open, leading to an outward current of K+ out of the cells.
Phase 2: Potassium channels remain open, and calcium channels now also open, resulting in a plateau state.
Phase 3: Calcium channels close, but potassium channels are still open ; this persists until the cells gain back normal polarization. Please note that phase 0 leads to a net gain of Na+, while phases 1-3 lead to a net loss of K+. This imbalance is corrected by the Na+/K+-ATPase channel that pumps K+ into the cell and sodium out of the cell; this does not change polarization of the cells, but does restore ionic content to its initial state.
Phase 4: Exciting triggers will cause minor depolarization in the cells; this will result in increasing permeability of sodium channels, which trigger the opening of sodium channels.
Repolarization of the cardiomyocytes occurs in phases 1-3, and is caused predominantly by the outward movement of potassium ions. In Torsades de pointes, however, the repolarization is prolonged; this can be due to electrolyte disturbances, bradycardia, certain drugs and/or congenital syndromes. The prolongation of repolarisation may result in subsequent activation of an inward depolarisation current, known as an early after-depolarisation, which may promote triggered activity. Re-entry, due to a dispersion of refractory periods, is also possible; this is because M Cells show a more prolonged repolarization phase in response to potassium blockage than other cells. In turn, this produces a zone of functional refractoriness in the mid myocardial layer. When new action potential is generated, the mid myocardial layer will remain in a refractory period, but the surrounding tissue will depolarize. As soon as the mid myocardial layer is no longer in a refractory period, excitation from nearby tissue will cause a retrograde current and a reentry circuit that will result in a positive chronotropic cycle, leading to tachycardia.
Diagnosis
The ECG tracing in torsades demonstrates a polymorphic ventricular tachycardia with a characteristic illusion of a twisting of the QRS complex around the isoelectric baseline. It is hemodynamically unstable and causes a sudden drop in arterial blood pressure, leading to dizziness and fainting. Depending on their cause, most individual episodes of torsades de pointes revert to normal sinus rhythm within a few seconds; however, episodes may also persist and possibly degenerate into ventricular fibrillation, leading to sudden death in the absence of prompt medical intervention. Torsades de pointes is associated with long QT syndrome, a condition whereby prolonged QT intervals are visible on an ECG. Long QT intervals predispose the patient to an, wherein the R-wave, representing ventricular depolarization, occurs during the relative refractory period at the end of repolarization. An R-on-T can initiate torsades. Sometimes, pathologic T-U waves may be seen in the ECG before the initiation of torsades. A "short-coupled variant of torsade de pointes", which presents without long QT syndrome, was also described in 1994 as having the following characteristics:
Drastic rotation of the heart's electrical axis
Prolonged QT interval - may not be present in the short-coupled variant of torsade de pointes
Preceded by long and short RR-intervals - not present in the short-coupled variant of torsade de pointes
The treatment of torsades de pointes aims to restore a normal rhythm and to prevent the arrhythmia recurring. While torsades may spontaneously revert to a normal sinus rhythm, sustained torsades requires emergency treatment to prevent cardiac arrest. The most effective treatment to terminate torsades is an electrical cardioversion - a procedure in which an electrical current is applied across the heart to temporarily stop and then resynchronise the heart's cells. Treatment to prevent recurrent torsades includes infusion of magnesium sulphate, correction of electrolyte imbalances such as low blood potassium levels, and withdrawal of any medications that prolong the QT interval. Treatments used to prevent torsades in specific circumstances include beta blockers or mexiletine in long QT syndrome. Occasionally a pacemaker may be used to accelerate the heart's own sinus rhythm, and those at risk of further torsades may be offered an implantable defibrillator to automatically detect and defibrillate further episodes of the arrhythmia.
History
The phenomenon was originally described in a French medical journal by Dessertenne in 1966, when he observed this cardiac rhythm disorder in an 80-year-old female patient with complete intermittent atrioventricular block. In coining the term, he referred his colleagues to the "Dictionnaire Le Robert", a bilingual French English dictionary, of which his wife had just given him a copy. Here, "torsade" is defined as:
a bundle of threads, twisted in a helix or spiral, for ornamental purposes ;
an ornamental motif, as seen on architectural columns.
Terminology
The singular and plural forms have both often been used. The question of whether either one is grammatically "correct" and the other "incorrect" has repeatedly arisen. This is seen among major medical dictionaries, where one enters only the plural form, another enters the plural form as the headword but lists the singular as a variant, and yet another enters the singular form as the headword and gives a usage comment saying that the plural is not preferred. One group of physicians has suggested that it would make the most sense to use the singular form to refer to the arrhythmia entity, and that one might best reserve the plural form for describing repeated twisting during a single episode. Regarding the natural language variation, they concluded, in good nature, "Wasn't it the French who coined the term vive la difference?"
