Retrospective Diagnosis of Congenital Long QT Syndrome in a Patient With Febrile Syncope

Patient Case Presentation

A 72-year-old man presented to a level-1 urban trauma center by ambulance after a witnessed syncopal event. The syncope was sudden and without prodrome, resulting in facial injuries. He was feeling well until the day before when he developed fever and chills. History was obtained from his family who witnessed the event and emergency medical services because the patient did not recall the events preceding the syncope. The patient’s medical history included hyper-tension and prostate cancer with robotic prostatectomy.

Triage and initial physical examination were remarkable for temperature, 38.6°C (101.4°F); blood pressure 137/82 mm Hg; heart rate 88 beats per minute; respiratory rate 18 breaths per minute; and oxygen saturation 98% on room air. On examination, he was febrile, awake, and conversant. A brief primary survey revealed the following: orbital ecchymosis bilaterally with swelling of the lower lip and small mucosal laceration without active bleeding, c-collar in place, no chest wall tenderness, lungs clear, no heart murmur, mild suprapubic tenderness, and moving all extremities purposefully.

Because of his age and head trauma, the patient was quickly expedited to computed tomography where he had his head, cervical spine, and facial bones examined. Routine laboratory tests, including blood and urine cultures for possible sepsis, and a 12-lead electrocardiogram (ECG) were obtained. The ECG at this time was notable for a corrected QT-interval of 538 ms without other prominent derangement. When he returned to the ED resuscitation room after imaging was completed, the nurse noted that the patient was unresponsive. The emergency nurse placed the patient on the cardiac monitor, which demonstrated an undulating wide complex tachycardia consistent with torsades de pointes (TdP). The emergency nurse administered 1 precordial thump and promptly defibrillated the patient with 200 biphasic joules. The patient immediately regained consciousness and returned to a normal sinus rhythm.

The emergency care team administered empiric antibiotic coverage with intravenous (IV) cefTRIAXone, IV crystalloid fluids, and oral acetaminophen. The patient was admitted to the cardiac critical care unit for further monitoring of his dysrhythmia and sepsis. He was ultimately diagnosed with Escherichia coli sepsis, based on the results of both urine and blood cultures.

The patient had an uneventful stay in the critical care unit. He was started on an oral β-blocker. His IV antibiotics were transitioned to oral cefdinir. A more comprehensive family history was obtained, which revealed the patient had previously passed out twice with fever. His biological son had died unexpectedly in his sleep at the age of 30. In addition, his biological niece had died in infancy. Her crib death had been previously attributed to sudden infant death syndrome. The patient was referred for genetic testing and cardiology follow-up for possible implantable cardioverter-defibrillator placement. Follow-up testing concluded that the patient had an underlying congenital long QT syndrome (c-LQTS).

Long QT SYNDROME

ETIOLOGY

LQTS is a common genetic disorder that predisposes patients to sudden cardiac death, with a prevalence of 1 in 2,000 live births.¹ The pathognomonic feature is a prolonged QT or corrected QT (QTc) interval on an ECG, >470 ms in men, >480 ms in women, and often-times much longer.² QT prolongation is associated with a number of important illnesses, such as stroke, myocardial infarction, metabolic derangements, renal failure, and hypothyroidism.³ This prolongation, which functionally represents an elongation of the ventricular repolarization, is common in critically ill patients and is associated with up to a 300% increase in mortality.³ The common pathway of sudden cardiac death secondary to LQTS is the following: TdP, a form of polymorphic ventricular tachycardia that occurs when a prolonged QT interval causes a R-on-T phenomenon in which the subsequent R wave lands on the late T wave, inducing ventricular tachycardia (Figure 1).

FIGURE 1.

Prolonged QT causing torsades via R on T mechanism.

c-LQTS is the result of 16 disease-causing mutations associated with 15 separate genes.⁴ There are 3 main types of LQTS involving mutations in potassium and sodium channels (Figure 2). The remainder of LQTS constitute ≤1% of the total cases and encompass mutations affecting other electrolyte gating channels, adapter proteins, which link the cell membrane to the overall cytoskeleton, or kinase activity.⁴ Most cases are inherited via an autosomal dominant pattern, meaning subsequent generations have up to a 50% risk of inheriting this disease from a parent. There is variable expressivity and incomplete penetrance; those who have the genetic mutation, therefore, may not ever have symptoms or even manifest prolonged QTc on their ECG. LQTS is an elusive diagnosis, in part, because of this variable genetic penetrance, such as in the phenotypic expression across generations of this family. Most patients with LQTS experience diagnosable signs and symptoms in childhood and adolescence, but these cases may be mistaken for benign syncope and seizure.

FIGURE 2.

Three most common types of congenital long QT syndrome with associated triggers and disease-causing genetic mutations (for medication list, see Table 2).

LQTS is rare in the elderly. Prolonged QTc is still problematic in this age group and is primarily related to poly-pharmacy and electrolyte derangements, rather than congenital. In addition to the direct effects of medications on the QT interval, many medications exert an indirect effect through potassium depletion. Examples include diuretics, which can deplete stores of potassium, and medications with anorexia side effects, which can prevent adequate potassium repletion through diet. Thus, syncope in the elderly may be due to TdP as a result of the medical and social etiology, rather than a genetic mutation.

ASSESSMENT AND MONITORING

The case presented in this article demonstrates clinician vigilance and vigor needed for diagnosing LQTS prior to the sentinel event, which is death or fatal ventricular dysrhythmia 50% of the time. Clinician critical thinking and awareness are essential, as LQTS may present as benign syncope or seizure, and the diagnosis is often missed.⁵ When preemptory symptoms occur, they are often prompted by medications (Table 1), electrolyte derangements, exercise, fever, and even seeming benign events such as sleep and emotional responses.⁴ These triggers depend on the type of LQTS; LQT1 is predominantly triggered by exercise, and LQT2-LQT3, largely by emotions, medications, and sleep.⁴

TABLE 1.

DOSE mnemonic for long QT syndrome

Mnemonic	Meaning
D	Drug (QTc prolonging drugs)
O	Overdose
S	Slow rhythm
E	Electrolyte disturbance

A commonly cited mnemonic, DOSE, can assist clinicians in determining who may be acutely at risk of developing TdP: Drug (medications that predispose to TdP), Overdose (medications that cause bradycardia or that predispose to TdP), Slow rhythm (slower rhythms have longer repolarization periods and can lead to TdP), and Electrolyte derangement (see Table 1).⁵

The list of medications that can cause prolongation of the QT are many, however, several are worth discussing because of their prevalence in the emergency department (Table 2).^6–8 Electrolyte derangements that prolong QT intervals include hypokalemia, hypomagnesemia, and hypocalcemia. Conditions predisposing patients to these electrolyte abnormalities include malnutrition/dehydration, gastrointestinal illness, diuretic therapy, and disorders of calcium metabolism such as primary and acquired hypoparathyroidism.

TABLE 2.

Common ED medications that prolong the QT interval

Class/category	Medication examples
Antiemetics
5-HT3 antagonists	Ondansetron, granisetron
Dopamine antagonists	Metoclopramide, prochlorperazine
Antipsychotics
Butyrophenones	Haloperidol, droperidol
Phenothiazines	chlorproMAZINE, fluPHENAZine
Atypicals	OLANZapine, risperiDONE, qUEtiapine, ziprasidone
Antibiotics
Macrolides	Azithromycin, erythromycin, clarithromycin
Fluoroquinolones	ciprofloxacin, levoFLOXacin, moxifloxacin
Extended spectrum β lactams	Piperacillin-tazobactam, ampicillin-sulbactam
Antifungal medications	fluconazole, ketoconazole
Antidepressants
Tricyclics	Amitriptyline, nortriptyline
Selective serotonin reuptake inhibitors	Citalopram, sertraline
Analgesics
Mu receptor agonists	Methadone, traMADol
Nonsteroidal anti-inflammatories	Ketorolac, celecoxib
Antiarrhythmics
Class Ia	Procainamide, quiNIDine
Class III	Amiodarone

Morbidity from TdP is linked to the result of a 2- or 3-hit hypothesis: the congenitally prolonged QT interval is worsened by a combination of electrolyte derangement, medications, exercise, and/or emotional stress. An example would be an athlete with LQTS suffering from dehydration and hypokalemia, in which subsequent exercise may cause TdP and sudden cardiac death. Up to 20% of patients with LQTS will have normal QTc on a standard ECG and suffer sudden cardiac death on the initial presentation of disease.² A number of otherwise unexplained drownings may be explained by the effects of temperature mediated surprise and/or exercise-induced QTc prolongation.⁹

DIAGNOSIS

Diagnosis is rarely made on the first encounter. Once there is suspicion for c-LQTS, the Schwartz score can be used to calculate a risk of having LQTS and the need for further diagnostic testing (Table 3). The Schwartz score uses a combination of ECG findings (QTc interval, T-wave alternans, notched T waves, and relative bradycardia) and clinical and family histories.¹⁰ Depending on the level of suspicion, additional clinical testing includes stress ECG testing, provocative drug testing, Holter monitoring, and sometimes genetic testing on the index case.³ Once a diagnosis is made, molecular genetic testing can be performed to determine the exact abnormality followed by familial cascade screening of first degree relatives.

TABLE 3.

Schwartz criteria to calculate long QT syndrome risk

ECG finding	Score, points
QTc duration* (Bazett formula)
≥480 ms	3
460–479 ms	2
450–459 ms (men only)	1
Torsades de pointes	2
T-wave alternans	1
Notched T wave in 3 leads	1
HR <2nd percentile for age	0.5
Clinical history
Syncope†
With stress/exertion	2
Without stress	1
Congenital deafness	0.5
Family history‡
Family member with definite LQTS	1
Unexplained sudden cardiac death < age 30	0.5

Scoring: ≤1, low probability of LQTS; 2–3, intermediate probability of LQTS; ≥4, high probability of LQTS.

ECG, electrocardiogram; HR, heart rate; LQTS, long QT syndrome.

^*In absence of drugs or conditions that affect QTc.

^†Mutually exclusive.

^‡Cannot be same family member to count both family history categories.

PREVENTION AND TREATMENT

Treatment for LQTS is multimodal and targeted toward both the genotype and phenotype.^11,12 First, there is an emphasis on avoiding known triggers including QT-prolonging medications, electrolytes aberrancies, and extra cautiousness during exercise and illness that increase the risk of fever.¹¹ Athletes are recommended to seek consultation from an LQTS specialist before returning to sports.¹¹

Pharmacotherapy includes initiation of a β-blocker, even in most asymptomatic patients, except those with explicit contraindications such as severe asthma, brady-cardia, and atrioventricular nodal blockade.¹¹ The mechanism of β-blocker protection against LQTS is its antiadrenergic properties, which not only decrease the risk of tachydysrhythmias but also decrease the QT interval. In the largest trial to date comparing β-blockers, none were substantially superior, except in the case of LQT2 in which nadolol would be the drug of choice.¹² Clinical symptoms while on β-blockers connotes an increased risk, and other therapies that can be considered include other medications (such as mexiletine), cardiac sympathetic denervation, and/or placement of an implantable cardioverter-defibrillator.¹¹

In acute management, commercial cardiac monitoring equipment to continuously measure QT intervals is available; however, guidelines on its use limit recommendations to those patients started on antiarrhythmic medications, which predispose to TdP, or in those patients with known prolonged QT who are started on other medications, which may prolong the interval.¹³ Whereas these represent general guidelines, there are many clinical scenarios in the emergency department in which QT monitoring may be appropriate, including initiation of antiarrhythmic agents or addition of antipsychotics.

Patient Case Conclusion

After hospital discharge, the patient was seen by electrophysiology specialists, and genetic samples for channelopathies testing were sent to a specialized laboratory. He was started on nadolol, and all family members were tested. He eventually received an implantable cardioverter-defibrillator, and his symptomatic family members were diagnosed and treated. His sepsis resolved with appropriate antibiotic treatment and hospital and follow-up care.

Emergency Nursing Implications

LQTS is a complex disease with presentation possible at any point of life. Emergency clinician critical thinking and vigilance for LQTS can save the lives of both patients and their family members. This critical thinking and vigilance should focus on clues in the patient history, ECG and cardiac monitoring, and relevant pharmacotherapy (Table 2). We recommend emergency clinicians use the ASK, MONITOR, TREAT, AND REFER process for LQTS. ASK if any family members passed away suddenly. If the patient has experienced a syncopal event with no prodrome, ASK if they have started any new medications recently. MONITOR the ECG. If the QTc is prolonged, maintain cardiac monitor and/or consider continuous QTc monitoring if history is highly concerning. TREAT to replace electrolytes, hydrate, and do not administer any medications that could further prolong the QTc interval. REFER the patient to cardiology for consideration of genetic testing when appropriate and provide family resources if the LQTS disease diagnosis is made. In 1 study, only 53% of families were properly informed of an inherited cardiac condition.¹⁴ This highlights the need for family counseling and guidance around this issue. More provider and patient resources about LQTS and other forms of sudden arrhythmia death syndromes can be found at the Sudden Arrhythmia Death Syndrome Foundation website, http://www.sads.org.¹⁵

Contribution to Emergency Nursing Practice.

• The current literature on congenital long QT syndrome (LQTS) indicates that the diagnosis is often missed in the emergency department and has a wide range of presentations.

• This article contributes information on LQTS for the purpose of increasing awareness of the subtle presentation of LQTS and the implication for familial testing, particularly the unique presentation of a febrile older adult.

• Key implications for emergency nursing practice found in this article are the signs in a patient’s history that suggest LQTS as a possible underlying pathology in patients who present with syncope, seizures, and/or sudden cardiac arrest and the recognition of the high-risk features.