August 13, 2008
Oral Verapamil Effectively Suppressed Complex Ventricular Arrhythmias and Unmasked U Waves in a Patient With Andersen-Tawil Syndrome
By Erdogan, Okan Aksoy, Alper; Turgut, Nilda; Durusoy, Elcim; Samsa, Murat; Altun, Armagan
Abstract Andersen-Tawil syndrome (ATS) is a rare, heterogeneous, autosomal dominant, or sporadic disorder characterized by the clinical triad of periodic paralysis, dysmorphic features, and ventricular arrhythmias such as bidirectional ventricular tachycardia (BVT). We present a case of an elderly patient with ATS whose symptomatic ventricular arrhythmias including BVT were effectively suppressed by oral verapamil therapy. (c) 2008 Elsevier Inc. All rights reserved.Keywords: Andersen-Tawil; Verapamil; Bidirectional VT; U wave; Long QT; Therapy; Sudden death
Andersen-Tawil syndrome (ATS) is a rare, heterogeneous, autosomal dominant, or sporadic disorder characterized by the clinical triad of periodic paralysis, dysmorphic features, and ventricular arrhythmias.' One gene, KCNJ2, has been identified so far and more than 20 mutations have been reported. Reduced IKl resulting from KCNJ2 mutations alters late cardiac repolarization by increasing its duration and leads to both distinctive T-U wave morphology and an increased propensity to ventricular arrhythmias.2 Although the frequency and pattern of ventricular arrhythmias vary considerably among affected subjects, it is a common finding and includes frequent premature ventricular complexes (PVCs), bigeminy, polymorphic ventricular tachycardia (PVT), and bidirectional VT (BVT). Despite frequent VT burden, most ATS patients are remarkably asymptomatic, and sudden cardiac death is exceedingly rare.1-8 However, management of complex ventricular arrhythmias and prevention of cardiac arrest still remain elusive given the lack of large comparative clinical studies. We present here a case of an elderly lady who incidentally was diagnosed with ATS and successfully treated with oral verapamil for symptomatic complex ventricular arrhythmias including BVT.
A 65-year-old woman with a history of hypertension and abdominal surgery for hydatid cyst in the liver presented to the emergency department with presyncope, palpitation, and generalized muscle weakness associated with nausea and vomiting. Surface electrocardiogram (ECG) demonstrated that the rhythm was nonsustained VT (12 beats) consisting of polymorphic PVCs that originate late after T wave from prominent U waves and a short run of BVT preceded by sinus complex (Fig. 1). During previous admissions for symptomatic ventricular arrhythmias, both beta- blocker and propafenone as well as sotalol, whose first dose (40 mg) once elicited torsades de pointes according to past medical records, were ineffective for suppression of arrhythmias. Family history revealed that her brother suddenly died of unknown cause at a young age. Coronary angiography and transthoracic echocardiography performed during last admission showed normal findings. Her physical examination revealed short stature (height, 1 m 40 cm; weight, 40 kg), micrognathia, small hands and feet, and clinodactyly of fifth fingers in both hands. Her blood potassium level on admission was 3.5 mmol/L, although successive values on subsequent days showed slight variations (range, 3.84.7 mmol/L). Neurological evaluation revealed that she was having recurrent episodes of mild proximal muscle weakness beginning from childhood. She also referred difficulty releasing her hand grip. Her global cognitive status was impaired. Standardized mini-mental test (SMMT-E) score was calculated as 15 (normal, >24). Suggesting intracellular calcium overload and triggered activity as the probable mechanisms, we speculated that empiric therapy with verapamil might be effective in suppressing frequent BVT episodes. On the third day of oral verapamil (40 mg TID) therapy, BVTs were suppressed before the rhythm initially converted to bigeminy and then to sinus rhythm with interspersed PVCs every other third or fourth beat. We were then able to reliably measure the baseline ECG intervals (Fig. 2). The PR interval and QRS duration were normal. On precordial leads, there were prominent U waves maximally measured in amplitude as 0.3 mV, with a maximal duration of 200 milliseconds in lead V5. The interval between T peak and U peak was significantly prolonged and measured 240 milliseconds. Both QU and QUc intervals were prolonged and maximally measured 720 milliseconds, whereas QT and QTc intervals remained normal and were measured as 440 milliseconds at a heart rate of 60 beats per minute, respectively. T-wave amplitude and duration were 0.15 mV and 120 milliseconds, respectively. The QU dispersion measured in all leads including limb leads was calculated to be 60 milliseconds, which was mainly related to prolongation of QU intervals between right and left precordial leads. Prolonged repolarization times including prominent U waves, high ventricular arrhythmia burden associated with typical BVT episodes, and symptoms suggestive of periodic muscle paralysis and typical dysmorphic features mentioned previously suggested a high clinical probability of ATS. Treadmill exercise test performed during verapamil therapy induced bigeminy, which gradually subsided during recovery phase (Fig. 3, A and B). The QT and QU intervals during and after exercise were not significantly changed. Holter ECG recorded on the 12th day after oral verapamil therapy revealed that the high burden of complex ventricular arrhythmias such as BVT, couplets and triplets, were completely suppressed. There were no significant changes in U- wave amplitude and duration after verapamil therapy. At follow-up 7 months later, while the patient was still on verapamil therapy, Holter ECG revealed absence of BVT and nonsustained VT with frequent episodes of bigeminy, which however could not be effectively suppressed by oral verapamil. In addition, symptoms related to arrhythmias disappeared, and the patient's quality of life significantly improved during follow-up.
Fig. 1. Nonsustained VT episode (12 beats) consisting of polymorphic PVCs and a short run of BVT preceded by sinus complex.
Fig. 2. Surface ECG was recorded after verapamil therapy was started, and complex ventricular arrhythmias were suppressed.
Fig. 3. Recovery phase of treadmill exercise test during oral verapamil therapy. A, Bigeminy induced with exercise gradually subsided during recovery. B, Note prominent U waves on precordial leads.
Andersen-Tawil syndrome is a rare autosomal dominantly inherited disorder that demonstrates high clinical variability and nonpenetrance. Specific ventricular arrhythmias such as BVT, although rare, have been described extensively in association with ATS.1 In the absence of other causes such as digitalis toxicity and catecholaminergic PVT, occurrence of BVT should prompt a thorough search for other features of ATS in a given individual. It is associated with intracellular calcium overload and sodium/calcium- mediated triggered activity in ATS.3 Verapamil given intravenously at a dose of 2.5 mg effectively terminated BVT and suppressed further episodes of BVT in a young patient with ATS.7 Similar to that reported case, oral verapamil effectively suppressed BVT and decreased the frequency of polymorphic PVCs in our patient. It also unmasked underlying prominent U waves that are now considered as markers of delayed afterdepolarizations and promoters of BVT/ polymorphic VT by triggering delayed afterdepolarizations at multiple shifting sites.3 Amiodarone, beta blockers, and other class 1 antiarrhythmic drugs including mexiletine and propafenone have been described ineffective in select patients.8 A recent study demonstrated genotype-specific T-U-wave patterns that included prolonged terminal T-wave downslope, a wide T-U junction, and biphasic enlarged U waves. These T-U-wave patterns were not seen in the ATS non-KCNJ2 patients or normal subjects and could therefore be used to distinguish carriers of KCNJ2 mutations from normal subjects or ATS patients without KCNJ2 mutations and long QT syndrome, with excellent sensitivity and specificity.2 Our patient interestingly demonstrated similar ECG features observed in patients with KCNJ2 mutation and accordingly could be inferred to be an ATS1 genotype- positive individual. In conclusion, verapamil seems to be an effective agent for treating BVT and suppressing VT episodes in patients with ATS.
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Okan Erdogan, MD,a,* Alper Aksoy, MD,b Nilda Turgut, MD,b Elcim Durusoy, MD,b Murat Samsa, MD,b Armagan Altun, MD(b)
a Department of Cardiology, School of Medicine, Marmara University, Istanbul, Turkey
b Department of Cardiology, School of Medicine, Trakya University, Edirne, Turkey
Received 29 September 2007
* Corresponding author. Marmara Universitesi Tip Fakutesi Hastanesi, Altunizade, Istanbul, Turkey. Tel.: +90 216 327 10 10; fax: +90 212 327 60 35.
E-mail address: [email protected]
Copyright Churchill Livingstone Inc., Medical Publishers Jul/Aug 2008
(c) 2008 Journal of Electrocardiology. Provided by ProQuest LLC. All rights Reserved.