Cardiovascular 15: Long QT Syndrome Portal

The long QT syndrome (LQTS) represents a diverse group of disorders that may be inherited (the genetic form) or acquired. The inherited cases are caused either by the more common autosomal dominant Romano-Ward type or the rare autosomal recessive Jervell and Lange Nielsen type that is associated with congenital deafness. These genetic mutations encode for abnormal cardiac ion channels. The acquired forms are caused by a large number of stimuli. The most common causative agents are the Class I and Class III antiarrhythmic agents, but many other drugs and conditions are known to increase the risk of prolonging the QT interval. One important distinction between the inherited and the acquired forms of long QT syndrome is that correcting the underlying disorder or discontinuing the offending drug can often reverse the acquired form. All patients with the long QT syndrome share a prolongation of the QT interval. This is associated with an increased risk of developing a specific type of polymorphic ventricular tachycardia called torsades de pointes or “twisting of points.”

Causes of Acquired Long QT Syndrome¹:

Metabolic Disorders: hypokalemia, hypomagnesemia, starvation, anorexia nervosa, liquid protein diets, hypocalcemia.
Bradyarrhythmias: second- or third-degree AV block, sinus node dysfunction
Class I (eg, procainamide, quinidine, disopyramide) and Class III (eg, sotalol, ibutilide, amiodarone) antiarrhythmic drugs
Psychotropic drugs: phenothiazines, tricyclic antidepressants, halperidol, SSRIs
Antimicrobial drugs: erythromycin, ketoconazole, itraconazole, ampicillin, azithromycin, and others
Antihistamines: Terfenadine, astemizole
Other drugs: thiazide, furosemide, cocaine
Others: HIV disease, mitral valve prolapse, intracranial disease

Risk factors that increase the risk of development of drug-induced torsades de pointes^2,3:

Hypokalemia, hypomagnesemia
Bradycardia
Diuretic use
Female gender
Congestive heart failure or cardiac hypertrophy
Baseline ECG showing prolonged QT or lability of T-wave
ECG during drug therapy showing markedly prolonged QT or T-wave lability
Congenital long QT syndrome

Measurement of the QT interval⁴:
The QT interval is measured from the very beginning of the QRS complex to the latest point at which the T wave crosses the baseline. U waves are not measured as part of the QT interval. The QT interval is measured in all twelve leads, but lead II is particularly useful.

Determination of the corrected QT interval (QTc) based on heart rate:
The normal QT interval varies according to the heart rate of the patient. Several formulas have been developed to adjust the QT interval (corrected QT interval or QTc) for the heart rate. The most commonly used formula to calculate the QTc was postulated by Bazett in 1920. The Bazett formula states that the QTc = QT interval/ square root of the RR interval. The QT intervals and the preceding RR intervals should be measured for at least three consecutive cycles and averaged.

Calculation of QTc (Corrected QT Interval)

QTc calculated by Bazett's formula where 16_cv_15_B

Example of calculation of the corrected QT interval (QTc) by Bazett’s formula:

The corrected QT interval (QTc) is calculated by dividing the QT interval (0.60 seconds) by the square root of the RR interval (0.84 seconds). In this case above, the QTc is 0.65 seconds.

While the Bazett formula is frequently used to calculate the QTc, in a study by Karjalainen,⁵ a nomogram method (see Table 1 below) was found to be more accurate over the whole range of heart rates.

Table 1. Nomogram for Measured QT-intervals in msec to obtain a heart rate-adjusted QT value (QTc). (Note: The QT interval correction indicated below is subtracted or added to the measured QT interval to determine the QTc.)⁵

Heart Rate (bpm)	QT-interval correction	Heart Rate (bpm)	QT-interval correction	Heart Rate (bpm)	QT-interval correction
40	-59	67	16	94	56
41	-55	68	18	95	57
42	-50	69	20	96	59
43	-47	70	23	97	60
44	-44	71	25	98	61
45	-40	72	27	99	63
46	-36	73	29	100	65
47	-32	74	31	101	67
48	-29	75	32	102	69
49	-26	76	34	103	71
50	-23	77	35	104	73
51	-21	78	37	105	75
52	-18	79	38	106	77
53	-16	80	40	107	79
54	-13	81	41	108	81
55	-11	82	42	109	83
56	-9	83	43	110	85
57	-6	84	44	111	87
58	-4	85	45	112	89
59	-2	86	46	113	91
60	0	87	47	114	93
61	2	88	48	115	95
62	5	89	50	116	97
63	7	90	51	117	99
64	9	91	52	118	101
65	11	92	53	119	103
66	14	93	55	120	105

Age and gender differences of normal corrected QT valves (QTc):

QT intervals are similar in males and females from birth until late adolescence. In adulthood, the QT interval in females is slightly longer than in males.

Normal Corrected QT Values (QTc)

	1 to 15 yrs	Female	Male
Normal	<0.44 sec	<0.45 sec	<0.43 sec
Borderline	0.44 - 0.46 sec	0.45 - 0.47 sec	0.43 - 0.45 sec
Prolonged	>0.46 sec	>0.47 sec	>0.45 sec

Symptoms related to Long QT Syndrome:

Many people with a long QT syndrome live for many years without any symptoms from their long QT syndrome, but when symptoms do appear they are often very serious. The most common symptoms are syncope or sudden death typically occurring during physical activity or emotional upset. The most common age to see the symptoms is in the preteen to teenage years, but the symptoms may first appear from a few days of age to middle age. Sudden and unexplained loss of consciousness or cardiac arrest in a child or teenager or a family history of unexplained syncope or sudden death in young people should raise the suspicion of long QT syndrome.

Treatment of patients with Long QT Syndrome:

The treatment of patients with acquired and congenital long QT syndrome differ to some extent due to the pathophysiologic differences between the two forms.

Treatment of Acquired Long QT Syndrome:

The primary focus in the management of patients with the acquired long QT syndrome is to discontinue any precipitating drugs, such as quinidine, and to correct any metabolic abnormality, such as hypokalemia. If serious arrhythmias necessitate more immediate treatment, consider the following therapies:

Magnesium sulfate IV is indicated for long QT related torsades de pointes or ventricular ectopic beats. Give 50% magnesium sulfate 1 to 2 g by IV bolus over 1 to 2 minutes. This dose may be repeated if needed in 15 minutes.⁶
Atrial or ventricular pacing at rates above 70 to 80 bpm is useful in treating torsades de pointes. Pacing helps to decrease QT dispersion and shorten the surface QT interval especially if there is an associated bradycardia.
Isoproterenol may be helpful to increase the sinus rate and decrease the QT interval and thus be useful in torsades de pointes.
Class Ib agents, such as lidocaine or phenytoin, are useful in the acute management of torsades de pointes and ventricular fibrillation due to their ability to shorten the action potential.
When torsades de pointes is due to quinidine, alkalinization of the plasma with IV sodium bicarbonate is useful. Alkalinization significantly increases the protein binding of quinidine and therefore quickly lowers the free quinidine concentration and results in the shortening of the QT interval.
Potassium by IV infusion is not only helpful in patients who are hypokalemic but also may be beneficial in patients with a normal serum potassium who have a prolonged QT interval due to CHF or quinidine.⁷ Giving 0.5 mEq/kg IV potassium (maximum of 40 mEq) raises the plasma potassium level by 0.7/L and helps to reduce the QT interval.⁷ Potassium IV may not reverse torsades de pointes.

Treatment of Congenital Long QT Syndrome: The primary treatment approach to the congenital form of long QT syndrome consists of the interruption of the sympathetic input to the myocardium either with beta blockade or by surgical cervicothoracic sympathectomy.

Beta blockers interrupt the trigger for torsades de pointes and help to shorten the QT interval by decreasing activation from the left stellate ganglion. In so doing, beta blockers have been shown to decrease syncope and sudden cardiac death in patients with congenital long QT syndrome. Other treatments include cardiac pacing and the insertion of an implantable cardioverter defibrillator (ICD). ICDs often are used in patients who have recurrent symptoms in spite of other therapies, such as the use of beta blockers.⁸

References

Haverkamp W, et al. The potential for QT prolongation and proarrhythmia by non-antiarrhythmic drugs: clinical and regulatory implications. Report on a Policy Conference of the European Society of Cardiology. Eur Heart J. 2000;21:1216.
Roden, DM. Taking the “idio” out of “idiosyncratic”: Predicting torsades de pointes. Pacing Clin Electrophysiol. 1998;21:1029.
Makkar R, et al. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA. 1993;270:2590.
Moss A. Measurement of the QT interval and the risk associated with QTc interval prolongation: A review. Am J Cardiol. 1993;72:23B.
Karjalainen, et al. Relation Between QT Intervals and Heart Rates from 40 to 129 Beats/min in Rest Electrocardiograms of Men and a simple Method to adjust QT Interval Values. JACC.1994;23:1547-53.
Tzivoni D, et al. Treatment of torsades de pointes with magnesium sulfate. Circulation. 1988;77:392.
Choy AM, et al. Normalization of acquired QT prolongation in humans by intravenous potassium. Circulation. 1997;96:2149.
Priori SG, et al. Task force on sudden cardiac death of the European Society of Cardiology. Eur Heart J. 2001;22:1374.

Cardiovascular 15: Long QT Syndrome Portal

References

Editiion 13-October 2011