Pregbalin induced recurrent syncopal attacks with prolong QT interval

Abstract

Long QT syndrome may lead to fatal dysrhythmia. Prolongation of QT interval due to pregabalin has been shown in rats and no data is available in humans. We report a 80‐year‐old female patient using pregabalin. She was presented to emergency room with syncope attacks. Her admission electrocardiography demonstrated prolonged QT interval. After excluding the possible causes of the long QT syndrome, we attributed prolonged QT interval to pregabalin therapy. After discontinuation of pregabalin QT interval returned to normal range and patient experienced no further syncope attacks. It is first time for documentation of prolonged QT due to pregabalin in humans.

1. INTRODUCTION

Long QT syndrome is characterized by prolonged QT interval on electrocardiography (ECG). It may lead to fatal dysrhythmia such as polymorphic ventricular tachycardia. Long QT syndrome usually results from medications or electrolyte disorders such as hypopotassemia. Long QT interval is defined as a QT interval >0.45 s in males and >0.47 s in females. In the acquired form, the underlying pathology needs to be treated first. Correction of electrolyte imbalance or discontinuation of the medication, if it is medication‐associated, brings QT interval within the normal range (Moss, 2003). In the literature, long QT syndrome was reported due to numerous medications, which resulted in ventricular tachycardia (Haverkamp et al., 2000). In the present case, we attributed prolonged QT interval to pregabalin therapy. First time the present case showed that pregabalin can cause prolonged QT interval even at normal doses in humans.

2. CASE REPORT

An 80‐year‐old female patient visited the emergency room with chest pain and syncope. The patient has had two syncope attacks lasting for one minute. The patient's vital signs were stable. On her physical examination, auscultation of the lungs revealed rale in the basal segments of both lungs. Her detailed anamnesis was unremarkable except for hypertension (perindopril 5 mg, amlodipin 5 mg). In addition, the patient visited neurologists 2 months ago for burning sensation in her feet and pregabalin (150 mg 2 × 1) has been commenced for neuropathic pain. Her biochemical parameters were within the normal range excluding elevated troponin level (troponin at admission: 0.535 ng/ml, peak troponin: 1.276 ng/ml). ECG illustrated normal sinus rhythm with 1 mm ST elevation on leads V₁, V₂, and V₃ and prolonged QT interval (QTc: 501 ms) (Figure 1). Being diagnosed with decompensated heart failure, long QT syndrome and acute coronary syndrome, the patient was admitted to the coronary intensive care unit. Diuretic (furosemide 20 mg vial T.I.D.) was started for heart failure; and pregabalin was stopped and beta‐blocker (metoprolol 50 mg tb/day) was started for long QT interval. The patient, who has been receiving diuretic therapy, developed hypopotassemia (admission potassium level 4.2 mEq/L, lowest potassium level was: 3.3 mEq/L). Along with hypopotassemia, QTc interval was further prolonged (QTc:701 ms) (Figure 2) together with deep negative T wave. K⁺ was increased to the normal range by decreasing the dose of diuretic therapy and replacing K⁺. The patient with long QT interval on the ECG experienced five syncope attacks and one sensation of palpitation over the course of monitoring in the coronary intensive care unit. The patient's monitor recorded polymorphic ventricular tachycardia for five times during syncope attacks and atrial fibrillation for one time during sensation of palpitation (Figure 3). Both ventricular tachycardia and atrial fibrillation attacks spontaneously ceased without treatment. Transthoracic echocardiography revealed normal wall motion, mild left ventricular hypertrophy (LVMI: 121 gr/m²) and preserved left ventricular systolic function (LVEF: 55%). Considering acute coronary syndrome, coronary angiography was performed and noncritical stenoses were detected in the coronary arteries. ECG monitoring of the patient showed that prolonged QT interval regressed to the normal range (Figure 4). The patient experienced no further syncope or palpitation attacks as QT interval regressed to the normal range.

Figure 1.

Admission ECG. QTc: 501 ms; 1 mm ST segment elevation can be seen on derivations V₁, V₂, and V₂ (K: 4.2 mEq/L)

Figure 2.

Hypopotassemia aggravated long QT: QTc: 701 ms; Deep symmetrical T wave inversion (K: 3.3 mEq/L)

Figure 3.

(a, b) Multimorphic ventricular tachycardia ECG samples recorded during syncope events. (c) Paroxysmal atrial fibrillation. ECG sample recorded during the palpitation feeling reported by patient

Figure 4.

After QTc normalized syncope attacks were not seen anymore. QTc: 320 ms

3. DISCUSSION

For the first time, the present case showed that pregabalin can cause prolonged QT interval even at normal doses in humans. ECG monitoring should be recommended for the patients undergoing pregabalin therapy, if necessary. Furthermore, pregabalin itself, which is commenced as an auxiliary medication for the treatment of epilepsy (Baldwin et al., 2015; Bhusal, Diomampo, & Magrey, 2016) can be the cause of next syncope by prolonging the QT interval. Prolonged QT interval should be excluded during epileptic attacks in the patients receiving pregabalin for epilepsy. Pregabalin is a gamma‐aminobutyric acid analogue it acts by blocking L‐type calcium canals resulting in decreased level of neurotransmitters such as substance p, norepinephrine, and glutamate (Baldwin et al., 2015; Bhusal et al., 2016). Most common side effects of pregabalin include dizziness, sensation of numbness and blurred vision. Although cardiac side effects primarily include heart failure and peripheral edema (Page, Cantu, Lindenfeld, Hergott, & Lowes, 2008), Aksakal et al. (2012) reported pregabalin‐induced complete AV block. In their experimental research on rats, Alp et al. (2008) demonstrated that pregabalin not only increases the heart rate but also prolongs QT interval on ECG. In this study, female gender, advanced age, heart failure, hypopotassemia due to diuretic therapy, the presence of left ventricle hypertrophy and paroxysmal atrial fibrillation were the predisposing risk factors for pregabalin‐associated prolonged QT interval.

Hypopotassemia is the most common electrolyte abnormality encountered in clinical practice. The most feared consequence of hypopotassemia is the development of torsades de pointes (TdP). Etiology of TdP is usually multifactorial (Zeltser et al., 2003). There are lots of reports that showing a close relationship between hypopotassemia and TdP. For example, the case series have been reported by Digby, et al. which consisted of 11 patients presenting four tertiary care hospital with long QT and ≥2 risk factors for developing long QT. Nine patients developed TdP. All patients with TdP had an electrolyte abnormality. Eight patients use a diuretic and all of them had severe hypopotassemia (K < 3 mmol/L) (Digby et al., 2011). In our case; although pregabalin causes QT prolongation, hypopotassemia associated with the use of diuretics further extends QT and accelerates the development of TdP.

4. CONCLUSION

Pregabalin can cause prolonged QT interval even at normal doses in human. ECG monitoring should be recommended for the patients undergoing pregabalin therapy who are prone to long QT syndrome.

CONFLICT OF INTEREST

None declared.

Adar A, Cakan F, Önalan O. Pregbalin induced recurrent syncopal attacks with prolong QT interval. Ann Noninvasive Electrocardiol. 2018;23:e12489 10.1111/anec.12489