Citalopram,QTc Interval Prolongation,and Torsade de Pointes. How Should We Apply the Recent FDA Ruling?

Recently, both the manufacturer of citalopram and the US Food and Drug Administration have warned health care providers and patients about new information implicating drug-induced QTc interval prolongation and torsade de pointes when using citalopram in doses >40 mg/day. This warning is not placed in the context of either benefits or risks in real-world clinical practice, leaving clinicians with an untenable choice between depriving patients of high-dose citalopram or malpractice litigation. We reviewed the literature and found no cases of citalopram-induced sudden cardiac death among patients taking up to 60 mg/day of citalopram and free of risk factors for QTc interval prolongation and torsade de pointes. Because psychotropic drug-induced sudden cardiac death is an outlier in the absence of identified risk factors for QTc interval prolongation and torsade de pointes, we do not believe current Phase 3 and Phase 4 studies provide sufficient information to limit current prescribing practices for citalopram (20 mg to 60 mg/day). We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, torsade de pointes, and sudden cardiac death so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as citalopram.     

Amiodarone in patients with previous drug-mediated torsade de pointes. Long-term safety and efficacy

The safety and efficacy of long-term amiodarone therapy were examined in 12 patients who had previously developed torsade de pointes as a complication of previous antiarrhythmic therapy. The QTc intervals were determined at the time of torsade de pointes (570 +/- 40 ms), after 7 days of amiodarone loading (490 +/- 70 ms), and after 3 months of chronic amiodarone administration (580 +/- 80 ms). Compared to a drug-free control period, QTc was significantly prolonged (P less than 0.05) at the time of torsade de pointes, after amiodarone loading, and after 3 months of amiodarone therapy. The QTc intervals at the time of torsade de pointes and after chronic amiodarone treatment were not significantly different. At 16 +/- 7 months of follow-up, all patients remained free of subsequent torsade de pointes, syncope, or sudden death. In addition, 5 of 6 patients with a history of sustained ventricular tachycardia remained free from arrhythmic recurrence despite persistence of inducible ventricular tachycardia during programmed stimulation studies done before discharge. We conclude that amiodarone can often be used safely and effectively in patients who have previously had an episode of drug-mediated torsade de pointes. Amiodarone-induced QTc prolongation, even when marked, does not predict recurrent torsade de pointes. These observations also suggest that the propensity for a drug to produce this arrhythmia is dependent on other electrophysiologic effects in addition to its ability to simply lengthen repolarization.     

Pause-dependent torsade de pointes following acute myocardial infarction: a variant of the acquired long QT syndrome

OBJECTIVES: We report on a previously unrecognized form of the long QT syndrome (QT interval prolongation and pause-dependent polymorphic ventricular tachycardia [VT]) entirely related to myocardial infarction (MI). BACKGROUND: Polymorphic VT in the setting of acute MI generally occurs during the hyperacute phase, is related to ischemia, and is not associated with QT prolongation. Although QT prolongation after MI is well described, typical pause-dependent polymorphic VT (torsade de pointes) secondary to uncomplicated MI was previously unknown. METHODS: Of 434 consecutive admissions for acute MI, 8 patients had progressive QT prolongation that led to typical torsade de pointes. None of these patients had active ischemia or other known causes of QT prolongation. These patients were compared with 100 consecutive patients with uncomplicated MI who served as controls. RESULTS: The incidence of torsade de pointes following MI was 1.8% (95% confidence interval 0.8% to 3.6%). The QTc intervals of patients and controls were similar on admission. The QTc lengthened by day 2 in both groups, but more so in patients with torsade de pointes (from 470 +/- 46 to 492 +/- 57 ms [p < 0.05] and from 445 +/- 58 to 558 +/- 84 ms, respectively [p < 0.01]). Maximal QT prolongation and torsade de pointes occurred 3 to 11 days after infarction. Therapy included defibrillation, magnesium, lidocaine and beta-blockers. Three patients required rapid cardiac pacing. The long-term course was uneventful. CONCLUSIONS: Infarct-related torsade de pointes is uncommon but potentially lethal. An acquired long QT syndrome should be considered in patients recovering from MI who experience polymorphic VT as specific therapeutic measures are mandatory.     

Torsade de pointes: the long-short initiating sequence and other clinical features: observations in 32 patients

The clinical setting, precipitating factors, electrocardiographic features and response to treatment of 32 patients with torsade de pointes were reviewed. Thirty-one patients had underlying cardiac disease and 30 patients had a previous underlying cardiac arrhythmia. Antiarrhythmic medications, often in association with electrolyte abnormalities (such as hypokalemia and hypomagnesemia) were the most common precipitating factors. In 22 of 26 patients, the serum drug levels of the antiarrhythmic agents were found to be within the therapeutic range. However, before the administration of agents known to prolong the QT interval, 20 of the 32 patients had, either alone or in combination, baseline prolongation of the QT interval, hypokalemia or hypomagnesemia. All patients had QTc interval prolongation (mean 0.59 second) immediately before the development of torsade de pointes. Marked lability of T wave morphology was frequently noted. Cardiac pacing was the only consistently effective mode of therapy. A characteristic long-short ventricular cycle length as the initiating sequence was found in 41 of 44 episodes of torsade de pointes. Reported data support the high frequency of this electrocardiographic feature of torsade de pointes in which its onset could be analyzed. It is suggested that this electrocardiographic characteristic will aid in both establishing the diagnosis of torsade de pointes and distinguishing it from other polymorphic forms of ventricular tachycardia.     

Precordial QT interval dispersion as a marker of torsade de pointes. Disparate effects of class Ia antiarrhythmic drugs and amiodarone.

BACKGROUND. Patients with a history of class Ia drug-induced torsade de pointes have been treated with chronic amiodarone without recurrence of torsade de pointes despite comparable prolongation of the QT interval. We hypothesized that in such patients, class Ia drugs cause nonhomogeneous prolongation of cardiac repolarization times, whereas amiodarone causes homogeneous prolongation of cardiac repolarization times. METHODS AND RESULTS. Thirty-eight consecutive patients who received both class Ia drug therapy and chronic amiodarone therapy were evaluated. Standard 12-lead ECGs at baseline and during each therapy were used to calculate precordial QT interval dispersion (maximum QT in leads V1 through V6 minus minimum QT leads V1 through V6) as a measure of regional variabilities in ventricular repolarization times. Nine of these patients had torsade de pointes during class Ia drug therapy. In these nine patients, class Ia drug therapy and amiodarone significantly prolonged the maximum QT interval to comparable extents. However, class Ia drug therapy but not amiodarone therapy significantly increased precordial QT interval dispersion (101 +/- 37 versus 49 +/- 26 msec; baseline, 44 +/- 12 msec; p = 0.002). In the 29 patients without class Ia drug-induced torsade de pointes, neither class Ia drug therapy nor amiodarone therapy significantly increased QT interval dispersion (50 +/- 6 versus 69 +/- 7 msec; baseline, 54 +/- 5 msec). None of the patients with class Ia drug-induced torsade de pointes had recurrent torsade de pointes during chronic amiodarone therapy. CONCLUSIONS. An increase in regional QT interval dispersion during class Ia antiarrhythmic drug therapy is associated with torsade de pointes. Chronic amiodarone therapy in patients with a history of class Ia drug-induced torsade de pointes produces comparable maximum QT interval prolongation but does not increase QT interval dispersion. This characteristic may explain its apparent safe use in patients with a history of class Ia drug-induced torsade de pointes.     

Left cardiac sympathectomy prevents exercise-induced QTc prolongation in congenital long QT syndrome

Congenital long QT syndrome (LQTS) is a group of ion channel disorders of ventricular myocytes caused by mutations of genes that encode these ion channels. The main clinical features of LQTS are syncope, cardiac arrest and QT prolongation on body surface electrocardiogram. The present study reports on the case of a 42-year-old female patient with a 10-year history of LQTS and syncopal attacks resistant to beta-blocker therapy. Treadmill exercise testing in this patient increased the corrected QT interval (QTc) from 0.48 s to 0.54 s and reduced the amplitude of the T wave. Left cardiac sympathectomy did not affect the resting heart rate or QTc but it prevented exercise-induced T wave reduction and QTc prolongation. Therefore, sympathetic activation plays a key role in exerciseinduced QT prolongation and changes in T wave morphology in patients with congenital LQTS.     

Clinical and therapeutic aspects of congenital and acquired long QT syndrome.

The long QT syndrome is characterized by prolongation of the corrected QT (QTc) interval on the surface electrocardiogram. It is associated with precipitation of a polymorphic ventricular tachycardia, torsade de pointes, which may cause sudden death. The syndrome is a disorder of cardiac repolarization caused by the alterations in the transmembrane potassium and sodium currents. Six genetic loci for the congenital forms of the syndrome have been identified; sporadic cases occur because of spontaneous mutations. Acquired causes of the long QT syndrome include drugs, electrolyte imbalance, toxins, marked bradycardia, subarachnoid hemorrhage, stroke, myocardial ischemia, protein-sparing fasting, autonomic neuropathy, and human immunodeficiency virus disease. Clinical symptoms are the result of the precipitation of torsade de pointes and range from such minor symptoms as dizziness to syncope and sudden death. Short-term treatment is aimed at preventing the recurrences of torsade de pointes and includes intravenous magnesium and potassium administration, temporary cardiac pacing, and correction of electrolyte imbalance; rarely, intravenous isoproterenol is indicated. Long-term management includes use of beta-blockers, permanent pacemaker placement, and cardioverter-defibrillator implantation. Asymptomatic patients are treated if under the age of 40 years at the time of diagnosis.     

QT interval prolongation, torsade de pointes and renal disease

Torsade de pointes is a form of polymorphic ventricular tachycardia occurring in a setting of prolonged QT interval on surface electrocardiogram. Several non-antiarrhythmic drugs including antibiotic and antipsychotic agents have been shown to prolong cardiac repolarization predisposing to torsade de pointes ventricular tachycardia. Blockade of the delayed rectifier (repolarising) potassium current and drug interactions with inhibitors of the cytochromes P450 (CYP)-mediated metabolism are the most common underlying mechanisms. Many antiarrhythmic drugs have been also implicated in prolonging QT interval and triggering torsades de pointes, especially during chronic therapy or in case of acute high dose toxicity. Progressive renal disease is associated from the earliest stages with increased QT interval and dispersal and with an increased risk of cardiovascular death, specifically sudden death. It has also been reported that cCorrected QT (QTc) interval prolongation and torsade de pointes are associated with end-stage renal disease (ESRD) and that they can be a cause of sudden death in ESRD. We present a case of torsade de pointes in a 82-year-old Italian woman with chronic renal failure.     

QT interval prolongation and torsade de pointes induced by propofol and hypoalbuminemia

We report the case of a 70-year-old man presenting with the development of torsade de pointes (TDP) during infusion of propofol in the setting of severe hypoalbuminemia. TDP developed 15 hours after the beginning of a standard infusion of propofol, following the development of a prominent U wave and prolongation of the QTc interval. While the serum concentrations of electrolytes were within normal ranges, serum albumin as low as 1.4 mg/dL was observed. TDP disappeared during the infusion of isoproterenol, and QTc normalized after the discontinuation of propofol. We hypothesize that hypoalbuminemia increased the free fraction of propofol, causing marked QTc prolongation and TDP.     

遗传性长 QT 综合征的药物及器械治疗

遗传性长 QT 综合征（long-QT syndrome,LQTS）以心电图上 QT 间期延长及其相关的尖端扭转型室性心动过速（torsade de pointes,TdP）为特征,易导致心脏性猝死。它的危险因素有 QTc 长度、基因型、晕厥史等。LQTS 的治疗手段包括β受体阻滞剂治疗、外科心脏左侧交感神经节切除术（LCSD）、心脏起搏治疗以及植入式心律转复除颤器（ICD）治疗。β受体阻滞剂治疗是 LQTS 治疗的基石;心脏起搏治疗适用于伴有心动过缓的 LQTS,可明显降低心脏事件的复发率,但不降低死亡率。对高危的 LQTS 应植入 ICD,皮下 ICD 并发症较少,值得推广。LCSD 技术实用性较差,更适用于 ICD 植入后频繁电击治疗的患者。     

QTc prolongation as a surrogate for drug-induced arrhythmias: fact or fallacy?

QTc prolongation is commonly used as a surrogate for drug-induced torsade de pointes (TdP) because it is frequently associated with TdP. However, TdP can also occur in the absence of QTc prolongation or even when QTc is shortened. In the absence of disturbances of lambda-TRIaD (lambda: cardiac wavelength, Triangulation, Reverse use dependence, Instability and Dispersion; TRIaD) QTc prolongation can be antiarrhythmic. In the presence of disturbances of lambda-TRIaD, QTc prolongation still reduces proarrhythmia but frequently cannot overcome the proarrhythmic effect induced by lambda-TRIaD disturbances. Safety evaluation focused upon QTc prolongation (antiarrhythmic parameter) instead of disturbances of lambda-TRIaD (proarrhythmic parameters), is scientifically incorrect. Such evaluation can impede the development of highly valuable drugs, while not recognizing agents that disturb lambda-TRIaD and hereby endanger patient safety. It must be concluded that the century old proposal by Lewis that prolongation of action potential duration and refractory period can be antiarrhythmic is still correct, provided it is not contaminated by disturbances of lambda-TRIaD.     

Ciprofloxacin-induced acquired long QT syndrome

Quinolone antibiotics have potentially serious proarrhythmic effects. The effects on intracardiac potassium channels result in QT interval prolongation, leading to torsades de pointes. Evidence suggests fluoroquinolones cause QT-mediated proarrhythmia, and weak evidence links ciprofloxacin with QT-mediated arrhythmias. Ciprofloxacin may be given to select patients because the agent is believed to be safer than other drugs in its class. We report two cases of unexplained cardiac arrest temporally related to ciprofloxacin administration. Two female patients (ages 44 and 67 years) developed marked QTc prolongation (QTc 590 and 680 ms) within 24 hours of ciprofloxacin administration, with recurrent syncope and documented torsades de pointes requiring defibrillation. The patients previously were stable with sotalol and amiodarone therapy for supraventricular arrhythmia without obvious QTc prolongation prior to ciprofloxacin therapy. Marked QTc prolongation and subsequent proarrhythmia became a clinical concern only after initiation of ciprofloxacin. In both cases, the QTc normalized after cessation of ciprofloxacin. Ciprofloxacin may cause QTc prolongation and rarely torsades de pointes. This effect is of particular concern in patients with predisposing factors, such as concomitant medications or underlying heart disease reflecting decreased repolarization reserve.     

Prevalence and determinants of QT interval prolongation in medical inpatients

Background: QT interval prolongation carries an increased risk of torsade de pointes and death. Aim: We sought to determine the prevalence of QT prolongation in medical inpatients and to identify determinants of this condition. Methods: We enrolled consecutive patients who were admitted to the internal medicine ward and who had an electrocardiogram performed within 24 h of admission. We collected information on baseline patient characteristics and the use of QT‐prolonging drugs. Two blinded readers manually measured the QT intervals. QT intervals were corrected for heart rate using the traditional Bazett formula and the linear regression‐based Framingham formula. We used logistic regression to identify patient characteristics and drugs that were independently associated with QTc prolongation. Results: Of 537 inpatients, 22.3% had a prolonged QTc based on the Bazett formula. The adjusted odds for QTc prolongation based on the Bazett correction were significantly higher in patients who had liver disease (OR 2.9, 95% CI: 1.5–5.6), hypokalaemia (OR 3.3, 95% CI: 1.9–5.6) and who were taking ≥1 QT‐prolonging drug at admission (OR 1.7, 95% CI: 1.1–2.6). Overall, 50.8% of patients with QTc prolongation received additional QT‐prolonging drugs during hospitalisation. Conclusions: The prevalence of QTc prolongation was high among medical inpatients but depended on the method used to correct for heart rate. The use of QT‐prolonging drugs, hypokalaemia and liver disease increased the risk of QTc prolongation. Many patients with QTc prolongation received additional QT‐prolonging drugs during hospitalisation, further increasing the risk of torsade de pointes and death.     

Electrocardiographic evidence of ventricular repolarization remodelling during atrial fibrillation.

AIMS: Some atrial fibrillation (AF) patients develop excessive QTc prolongation and torsade de pointes when they take QTc-prolonging antiarrhythmic drugs (class IA/III) immediately after termination of AF. We hypothesized that this is caused by changes in ventricular repolarization during AF. We aimed to establish whether such 'ventricular repolarization remodelling' occurs. METHODS AND RESULTS: We studied all patients who visited our cardiac emergency room with AF and converted to sinus rhythm (SR) in a 30 months' period. We defined four groups: (i) no antiarrhythmic drugs, electrical cardioversion (n = 30), (ii) no antiarrhythmic drugs, spontaneous AF termination (n = 19), (iii) antiarrhythmic drugs, electrical cardioversion (n = 29), and (iv) antiarrhythmic drugs, spontaneous AF termination (n = 9). We studied QTc duration at SR before AF (SR(baseline)), immediately after termination of AF (SR(postAF)), and at follow-up (SR(followup): > or =7 days after SR(postAF)). Moreover, we studied determinants of QTc prolongation at SR(postAF). We found that, in all groups, QTc at SR(postAF) was significantly and transiently prolonged compared with SR(baseline). Although of limited magnitude on average (approximately 5%), the increase was substantial (approximately 15%) in some individuals. The only independent predictor of the magnitude of QTc prolongation was QTc duration at SR(baseline); this relation had a negative correlation. CONCLUSION: AF causes ventricular repolarization remodelling, resulting in QTc prolongation. QTc prolongation is substantial in some patients and may render these patients vulnerable to pro-arrhythmia from class IA/III antiarrhythmic drugs immediately after termination of AF.     

Torsade de pointes due to noncardiac drugs: most patients have easily identifiable risk factors

Numerous medications, including drugs prescribed for noncardiac indications, can lead to QT prolongation and trigger torsade de pointes. Although this complication occurs only rarely, it may have lethal consequences. It is therefore important to know if patients with torsade de pointes associated with noncardiac drugs have risk factors that are easy to identify. We reviewed reports of drug-induced torsade de pointes and analyzed each case of torsade de pointes associated with a noncardiac drug for the presence of risk factors for the long QT syndrome that can be easily identified from the medical history or clinical evaluation (female gender, heart disease, electrolyte disturbances, excessive dosing, drug interactions, and history of familial long QT syndrome). We identified 249 patients with torsade de pointes caused by noncardiac drugs. The most commonly identified risk factor was female gender (71%). Other risk factors were frequently present (18%-41%). Virtually all patients had at least 1 of these risk factors, and 71% of patients had 2 or more risk factors. Our study suggests that almost all patients with torsade de pointes secondary to noncardiac drugs have risk factors that can be easily identified from the medical history before the initiation of therapy with the culprit drug.     

Citalopram induced torsade de pointes, a rare life threatening side effect

Acquired Long QT syndrome is a disorder caused by medications, electrolyte imbalances, and drug interactions. This syndrome is associated with an increased risk of a characteristic life-threatening cardiac arrhythmia, known as torsade de pointes (TdP). In the setting of Long QT syndrome (LQTS), selective serotonin reuptake inhibitors (SSRIs) can precipitate TdP. We report the first case of LQTS and TdP induced by citalopram in the United States. After discontinuation of citalopram, the QT/QTc interval normalized after 3 days and resolved further episodes of TdP. Patients on citalopram should be monitored closely for QT/QTc interval to prevent torsade de pointes.     

Torsade de pointes during loading with amiodarone

Torsade de pointes represents a potential complication of chronicamiodarone therapy. Several reports have emphasized the needfor a loading dose in order to achieve therapeutic blood levelsrapidly. We report a case of torsade de pointes following asingle oral dose of amiodarone (1400 mg or 30 mg kg^–1)administered after short intravenous loading for preventionof paroxysmal atrial flutter. Torsades de pointes were precededand associated with marked QT prolongation and bradycardia.This report suggests that careful monitoring of patients undergoingoral amiodarone loading is necessary.     

获得性QT间期延长伴尖端扭转型室性心动过速52例临床分析

目的 总结获得性QT间期延长伴尖端扭转型室性心动过速(扭转型室速)患者的危险因素、心电图特征、治疗方法,为临床医生正确识别和处理提供帮助.方法以"扭转型室速"及"QT间期延长"检索阜外心血管病医院1990至2010年病历库,统计获得性扭转型室速患者的临床资料.结果总计52例获得性扭转型室速,其中67.3%有基础心脏病,59.6%存在电解质紊乱,36.5%应用利尿剂,28.8%应用延长QT间期的抗心律失常药.治疗前后平均QTc分别为(571±93)ms及(456±50)ms,所有患者均经补钾、补镁治疗,32.7%应用异丙肾上腺素,13.5%接受临时起搏治疗.结论获得性扭转型室速多发生于电解质紊乱及应用延长QT间期药物的患者.高危患者应监测心电图及QTc变化,注意有预警价值的表现,有助于早期识别并正确治疗.

Abstract：

Objective Risk factors, ECG characteristics and treatment options of patients with Torsade de Points associated with acquired QT prolongation are summarized in this study. Method Using "torsade de points" and "QT prolongation" as the keywords to search the inpatients database from 1990 -2010 of Fuwai hospital, 52 eligible patients were included in this analysis. Results Structural heart diseases were found in 67.3% and electrolyte disorders in 59. 6% patients, 36. 5% patients received diuretic therapy and 28. 8% received antiarrhythmic drugs which might induce prolonged QT interval The mean QTc was (571 ±93)ms and (456 ±50)ms before and after treatment. All patients received potassium and magnesium supplement. Isoproterenol was used in 32. 7% patients. 13.5% patients received temporary pacing therapy. Conclusions Torsade de points and acquired QT interval prolongation was often associated with electrolyte disorders and drugs causing QT prolongation. ECG and QTc should be intensively monitored for high risk patients. Early awareness of the warning signs might contribute to early recognition and proper treatment of patients with Torsade de Points associated with acquired QT prolongation.     

QTc abnormalities in deliberate self-poisoning with moclobemide

BACKGROUND: Several medications have been found to prolong the QT interval in overdose. This can predispose to torsade de pointes-type ventricular tachycardia. AIMS: To analyse the effects of moclobemide deliberate self-poisoning on the length of both QT and corrected QT (QTc) intervals. METHODS: Electrocardiograms (ECG) of all patients presenting to a regional toxicology service with moclobemide ingestion were reviewed. Cases where a cardiotoxic agent was coingested were excluded. QT and QTc parameters were compared with a comparison group of patients ingesting paracetamol or benzodiazepines. RESULTS: Of 75 patients where ECG were available, the median ingested dose was 4.5 g (interquartile range (IQR): 2.4-7.5; range: 0.6-18 g) and the median age was 34 years (IQR: 26-44). The mean QT interval was 415 ms (standard deviation (SD): 51 ms) with a mean QTc of 459 ms (SD: 44 ms), and were prolonged compared with the comparison group. Twelve female patients had a QTc > 500 ms and in seven of these causality was established based on a pre- or post-ECG with a QTc < 500 ms. Only 10% of the moclobemide cases had a heart rate (HR) > 100 beats per minute, making overcorrection of HR by Bazett's formula an unlikely cause of the findings. No cardiac arrythmias were observed other than one case of first-degree heart block. CONCLUSIONS: Moclobemide prolongs the QT and QTc intervals in overdose and a 12-lead ECG should be done on all moclobemide deliberate self-poisonings. Continuous cardiac monitoring for what is otherwise a relatively benign overdose would appear to be an inappropriate use of resources but can be considered in patients with a QTc > 500 ms or with known risks for QT prolongation.     

Whole‐exome sequencing reveals microsatellite DNA markers for response to dofetilide initiation in patients with persistent atrial fibrillation: A pilot study

Background

Dofetilide is a class III antiarrhythmic drug effective for the treatment of atrial fibrillation (AF). Dofetilide initiation (DI) associates with corrected QT interval (QTc) prolongation. Significant QTc prolongation during DI mandates dose adjustment or discontinuation of the drug. Microsatellite DNA are novel genetic markers associated with congenital and acquired health conditions.

Hypothesis.

DNA microsatellite polymorphism may associate with QTc response to dofetilide initiation in patients with persistent AF.

Methods

We performed whole‐exome sequencing in a cohort of patients with persistent AF undergoing DI. Electrocardiographic variables and clinical data were assessed. We defined patients as eligible for DI when no significant QTc prolongation (>20% compared with baseline) was seen with a 500‐μg dose. We defined patients as ineligible for DI when significant QTc prolongation was seen during DI with 500 μg. We investigated polymorphisms for 11 919 DNA microsatellite loci in relation to QTc response to DI.

Results

During the study, 14 consecutive patients with persistent AF presenting for DI were enrolled. Whole‐exome sequencing revealed 14 different microsatellite loci in the 2 groups. All genes or proximal genes that harbor these loci are known to have expression in the human heart. Two genes, MYH6 and TRAK2, are known to have expression in the atria. TRAK2 is known to interact with KCNJ2, the inward‐rectifier potassium channel 1.

Conclusions

Microsatellite DNA polymorphisms seem to associate with QTc response to DI therapy in patients with persistent AF who are deemed otherwise eligible for dofetilide therapy.