In and Out of the Rhythm – A Dance with Sudden Cardiac Death
CASE
A 60-year-old female presents with generalized abdominal pain, chills, and innumerable episodes of non-bloody vomit x1 day.
PMH notable for HTN, HLD, CAD, and COPD. FH notable for father with MI at age 40.
Initial vitals: BP 101/63 HR 75 RR 18 Temp 36.8C SpO2 100% on room air
While collecting the HPI, the patient becomes unresponsive with pulselessness for 10 seconds and subsequent ROSC as well as eye deviation, jaw clenching, and full body stiffening for 1 minute that spontaneously resolves. Afterward, she immediately returns to baseline mentation complaining of nausea and warmth. She denies any history of seizures. Intake EKG showed NSR and QTc 461 ms. She is placed on the monitor, and a few minutes later she experiences a repeat episode for which the rhythm strip showed torsade de points (Fig. 1). IV magnesium and amiodarone were initiated and repeat EKG showed evidence of marked QTc prolongation (Fig. 2). Notable lab results included Mg 1.3 mg/dL, K 3.3 meq/L, lactate 2.2 mmol/L, and troponin 0.23 ng/mL. The patient was transferred to the CCU where she was placed on an isoproterenol drip. Subsequent coronary angiography revealed no myocardial injury. Aggressive electrolyte repletion did not improve QT prolongation after >24 hrs and ICD was eventually placed for presumed channelopathy.
Clinical Question: What is the presentation and acute management of torsade de points (TdP)?
Summary of the Evidence: TdP is a polymorphic ventricular tachycardia with a prolonged QT interval. Typically, TdP presents as recurrent self-terminating bursts commonly caused by acquired QT prolongation.[i] Clinically, this may manifest in syncope/pre-syncope, seizure-like episodes, or cardiac arrest. More rarely, TdP may be caused by congenital long QT syndrome or other structural causes. The dreaded outcome is when TdP does not spontaneously resolve resulting in severe hypotension or prolonged cardiac arrest.[ii] QTc >500 ms dramatically increases risk of TdP.[iii]
QT prolongation can be caused iatrogenically (full list of QT prolonging medications can be found at crediblemeds.org), by electrolyte imbalances such as low magnesium, or by structural alterations in the heart such as after an MI. Due to the hyperacute and high-risk nature of TdP, there have been no RCTs done in humans for management of recurrent TdP. Current practice is guided primarily by animal research and anecdotal evidence. To prevent recurrence of TdP, the following options are commonly considered.
Magnesium is the currently recommended first-line treatment which is thought to act by delaying ventricular repolarization through inhibition of late calcium influx into cardiac myocytes.[iv] Although no RCTs exist evaluating its efficacy, a case series in 12 adults showed that a dose of 2g of IV magnesium sulfate resolved acute episodes of TdP in 100% of patients within 2 administrations.[v] Other case series internationally have shown similar effectiveness in acutely terminating and suppressing TdP in both adult (n=6 with 60% effectiveness)[vi] and pediatric (n=6 with 80% effectiveness)[vii] populations.
Increasing HR is thought to prevent TdP recurrence in the acute care setting by shortening the QT interval and the effective refractory period. Transvenous pacing, to increase HR and prevent pauses, has been studied in an animal model[viii] and case series in humans[ix] showing effectiveness at suppressing certain medication-induced torsades. Evidence suggests that rates of at least 70 bpm and up to 140 bpm are required.[x] Case studies have also shown some usefulness of isoproterenol which can increase HR by non-selective β1/β2 adrenoceptor agonist action in prevention of TdP recurrence.[xi] Although atropine also increases HR and has been used to suppress TdP, it can also induce paradoxical bradycardia which can worsen TdP.[xii]
Anti-arrhythmic medications are contraindicated as class 1A and III agents can prolong the QT interval. This includes amiodarone, which although regarded as low risk for precipitating TdP, was administered to the patient after her first episode and may have contributed to QT prolongation.[xiii] There exists some evidence of class 1b anti-arrhythmics for suppressing TdP including case reports for the use of lidocaine[xiv] and phenytoin.x
Definitive management for recurrent TdP depends on etiology. The above-described temporizing measures can be useful for short-acting medication-induced or easily correctable electrolyte-induced TdP. For TdP triggered by suspected congenital Long QT-syndrome (LQTS) or other difficult-to-reverse/structural cause (cardiac hypertrophy, high-grade AV block, CHF, or myocardial fibrosis), coronary catheterization, ablation, or ICD placement may be considered.[xv]
RECOMMENDATIONS
Start 2g of IV magnesium promptly in adults as first-line therapy to abort and suppress TdP.
The etiology of TdP is important for management of recurrence. Magnesium levels should be obtained and repleted if low. Stop all QT prolonging medications. EKGs and troponins should be obtained to assess for ACS as a potential cause.
For iatrogenic causes, transvenous pacing titrating up from 70 bpm can be an effective option to suppress episodes until the effects of QT-prolonging medications (which can have long half-lives) wear off.
For suspected structural or ischemic causes, isoproterenol or transvenous pacing can be used to suppress episodes until more definitive management can be implemented. Cardiology should be involved early to consider intervention for undetermined, structural, and congenital causes of TdP.
REFERENCES
[i] Thomas, S. H. L., and Behr, E. R. (2016) Pharmacological treatment of acquired QT prolongation and torsade de pointes. Br J Clin Pharmacol, 81: 420– 427. doi: 10.1111/bcp.12726.
[ii] Farkas, J. Torsade de pointes. The Internet Book of Critical Care. 2021 <https://emcrit.org/ibcc/tdp/>
[iii] R.R Makkar, B.S Fromm, R.T Steinman, M.D Meissner, M.H Lehmann. Female gender as a risk factor for torsade de pointes associated with cardiovascular drugs. JAMA, 270 (1993), pp. 2590-2597
[iv] Kaye P, O'Sullivan I. The role of magnesium in the emergency department. Emerg Med J 2002; 19: 288–91.
[v] Tzivoni D, Banai S, Schuger C, Benhorin J, Keren A, Gottlieb S, Stern S. Treatment of torsade de pointes with magnesium sulfate. Circulation 1988; 77: 392–7.
[vi] Etienne Y, Blanc JJ, Songy B, Boschat J, Guiserix J, Etienne E, Egreteau JP, Penther P. Antiarrhythmic effects of intravenous magnesium sulfate in torsade de pointes. Apropos of 6 cases. Arch Mal Coeur Vaiss 1986; 79: 362–7.
[vii] Hoshino K, Ogawa K, Hishitani T, Isobe T, Eto Y. Optimal administration dosage of magnesium sulfate for torsade de pointes in children with long QT syndrome. J Am Coll Nutr 2004; 23: 497S–500.
[viii] Oosterhoff P, Thomsen MB, Maas JN, Atteveld NJ, Beekman JD, Van Rijen HV, Van Der Heyden MA, Vos MA. High-rate pacing reduces variability of repolarization and prevents repolarization-dependent arrhythmias in dogs with chronic AV block. J Cardiovasc Electrophysiol 2010; 21: 1384–91.
[ix] Charlton NP, Lawrence DT, Brady WJ, Kirk MA, Holstege CP. Termination of drug-induced torsade de pointes with overdrive pacing. Am J Emerg Med 2010; 28: 95–102.
[x] Pinski SL, Eguia LE, Trohman RG. What is the minimal pacing rate that prevents torsade de pointes? Insights from patients with permanent pacemakers. Pace 2002; 25: 1612–5.
[xi] Omar HR, Sprenker C, Karlnoski R, Mangar D, Camporesi EM. The use of isoproterenol and phenytoin to reverse torsade de pointes. Am J Emerg Med 2014; 32: 683 e5–7.
[xii] Banai S, Tzivoni D. Drug therapy for torsade de pointes. J Cardiovasc Electrophysiol 1993; 4: 206–10.
[xiii] Lazzara R. Amiodarone and torsade de pointes. Ann Intern Med. 1989; 111: 549–551.
[xiv] Takahashi N, Ito M, Inoue T, Koumatsu K, Takeshita Y, Tsumabuki S, Tamura M, Inoue K, Maeda T, Saikawa T. Torsade de pointes associated with acquired long QT syndrome: observation of 7 cases. J Cardiol 1993; 23: 99–106.
[xv] Sauer AJ, Newton-Cheh C. Clinical and genetic determinants of torsade de pointes risk. Circulation. 2012 Apr 3;125(13):1684-94. doi: 10.1161/CIRCULATIONAHA.111.080887. PMID: 22474311; PMCID: PMC3347483.