Torsade de Pointes

Etiology

Torsades de pointes is the result of QTc prolongation which can either be congenital or acquired. Acquired QTc prolongation is most often drug-related. There is an extensive list of medications that can predispose a person to torsades. The list includes but is not limited to: antiarrhythmics, antipsychotics, antiemetics, antifungals, and antimicrobials. Substances that slow the hepatic metabolism of these medications can potentiate QTc prolongation leading to an increased likelihood of torsades de pointes. Congenital prolonged QT has two genetic variants: Jervell and Lange-Nielsen and Romano-Ward syndrome. The former is associated with congenital deafness. Prolonged QTc and Torsades are also associated with certain risk factors that include: older age (older than 65), female gender, hypokalemia, hypocalcemia, hypomagnesemia, bradycardia, heart disease, and diuretic use.[4][5]

Two rare congenital long QT syndromes include Romano-Ward syndrome and Jervell and Lange Nielsen syndrome.

Epidemiology

The prevalence of congenital prolonged QT is largely unknown. Figures estimate between 1:2000 and 1:20,000 have the genetic mutation for QT prolongation. Clinically more males than females exhibit the trait. Little is also known about the prevalence or incidence of drug-induced torsades de pointes. This is mainly because the arrhythmia is often transient, and an accurate diagnosis requires an ECG to be recorded during the event. Several European centers estimate that the annual reporting rate of drug-induced Torsades de Pointes is between 0.8 and 1.2 per million person-years. The incidence of drug-induced Torsades de Pointes also varies based on the drug in question and the population being studied.[6][7][8]

Pathophysiology

The proposed mechanism for Torsades de Pointes involves inhibition of the delayed rectifier potassium current. This leads to an excess of positive ions within the cellular membrane causing a prolonged repolarization phase. If an ectopic beat is generated during this prolonged repolarization phase, known as an R on T phenomenon, this can result in Torsades de Pointes. Both congenital and drug-induced QT prolongation affect the cellular membrane in similar fashions by blocking the potassium channel. Torsades de Pointes is slightly different from ventricular fibrillation in that it can spontaneously resolve. However, Torsades de Pointes can ultimately progress into venticular fibrillation if left untreated.[9]

History and Physical

Around 50% of patients with Torsades de Pointes are asymptomatic. The most common symptoms reported are syncope, palpitations, and dizziness. However, cardiac death is the presenting symptom in up to 10% of patients.

Patients with Jervell and Lange Nielsen syndrome may have a history of deafness.

Today one needs to be aware that drug-induced long QT syndrome is common and hence, a thorough medication history must be obtained.

Patients with torsade may be hypotensive, have a rapid pulse and have loss of consciousness.

Evaluation

An electrocardiogram is paramount in the diagnosis of Torsades de Pointes. The characteristic finding is a twisting of the QRS complexes around an isoelectric line. Torsades de Pointes is triggered by a PVC occurring on a preceding T wave. The onset of Torsades de Pointes is often preceded by a run of short-long-short R-R intervals. A QT nomogram can provide a sensitive and specific assessment of the risk of Torsades de Pointes in drug-induced QTc prolongation. Any value plotted above the line on the nomogram puts the patient at risk of Torsades de Pointes.[10][11]

Treatment / Management

The first step in managing Torsades de Pointes is preventing its onset by targeting modifiable risk factors. This includes discontinuing any QT prolonging drugs and optimizing a patient’s electrolyte profile. Correcting hypokalemia, hypomagnesemia, and hypocalcemia can all help to prevent the onset of torsades. There are a small number of studies that show a possible prophylactic benefit of oral or IV magnesium for those patients with drug-induced prolonged QT. However, the overall benefit is not well established, and there is little evidence that magnesium has any effect on the actual QT interval. The management of Torsades de Pointes begins with assessing if the patient is hemodynamically stable. Most episodes of torsades are self-limiting. However, the danger lies in those patients who go on to develop ventricular fibrillation. For those patients with hypotension or in cardiac arrest from Torsades de Pointes, electrical cardioversion should be performed. Synchronized cardioversion should be performed on a hemodynamically unstable patient in torsades who has a pulse, (100J monophasic, 50J Biphasic). Pulseless torsades should be defibrillated. Intravenous magnesium is the first-line pharmacologic therapy in Torsades de Pointes. Magnesium has been shown to stabilize the cardiac membrane, though the exact mechanism is unknown. The recommended initial dose of magnesium is a slow 2 g IV push. An infusion of 1 gm to 4 gm/hr should be started to keep the magnesium levels greater than 2 mmol/L. Once the magnesium level is greater than 3 mmol/L, the infusion can be stopped. Severe magnesium toxicity is seen with levels greater than 3.5 mmol/L and can present as confusion, respiratory depression, coma, and cardiac arrest. It is important to remember to correct any hypokalemia as well. Serum potassium should be maintained between 4.5 mmol/L and 5 mmol/L when treating Torsades de Pointes.

For a patient that continues to have intermittent runs of Torsades de Pointes, despite treatment with magnesium, increasing the heart rate may also help. This can be done pharmacologically with medications such as isoproterenol. Isoproterenol has been shown to help prevent Torsades de Pointes in patients with prolonged QT that is refractory to magnesium. It is a non-selective beta agonist, which increases the heart rate and shortens the QT interval. This lowers the likelihood of an R-on-T phenomenon that can lead to TdP. Isoproterenol can be given as an IV push of 10 mcg to 20mcg or an infusion titrated to maintain a heart rate of 100 bpm. Isoproterenol is, however, contraindicated in patients with congenital prolonged QT, because it can paradoxically lengthen the QT interval. A final option for terminating torsades is overdrive pacing. There are limited studies on the success of pacing for treatment of Torsades de Pointes; however, there are numerous case reports that show it is a viable option. Overdrive pacing can be used in the setting of both frequent runs of torsades and Torsades de Pointes that is refractory to magnesium. The rate must be set to overcome the patient’s intrinsic rate of ectopy. Ventricular rates of 90 bpm to 110 bpm are usually sufficient to overcome the arrhythmia, however occasionally rates up to 140 bpm have been required for some patients. Overdrive pacing is recommended for both drug and chemical induced Torsades de Pointes.[12][7][13](A1)

Differential Diagnosis

• Ventricular tachycardia/fibrillation
• Dialysis-related complications
• Syncope
• Drug toxicity- antihistamines, antiarrhythmics

Complications

• Ventricular fibrillation
• Sudden cardiac death