Unexplained Syncope in Young Man With Inherited Arrhythmia Disorder

Why did a seemingly healthy young man pass out briefly, and then regain consciousness but with nausea, tightness in his chest, and a rapid heart rate? That's the question a medical team at Indiana University School of Medicine in Indianapolis faced when the patient, in his early 20s, presented to the emergency department with possible syncope, along with shaking.

In their report of the case in JAMA Cardiology, Asad J. Torabi, MD, and colleagues noted that the initial intake assessment revealed no relevant medical history. The patient's girlfriend said the patient had fallen asleep and when she tried to wake him, he had started shaking and then dropped to the ground.

When he came to, she said, he was fully conscious and mentally aware of his surroundings, but was flushed and complained of chest tightness and a racing heart. About 10 minutes later, he experienced a similar episode that lasted for 2 to 3 minutes, with involuntary twitching and muscle jerking.

Initial assessment at the ER showed he was not feverish, his blood pressure was 120/59 mm Hg, his heart rate was 85 beats per min, respiratory rate was 16 breaths per min, and oxygen saturation was 96% on room air. Heart sounds were normal and without murmurs.

Clinicians immediately performed several cardiovascular assessments, including an electrocardiogram (ECG) and transthoracic echocardiography, which showed his ejection fraction was 54%; he had mild dilation of the right ventricle (diameter 4.1 cm), and no evidence of heart valve dysfunction.

MRI of his heart did not reveal any right ventricle abnormalities, and right ventricle function appeared qualitatively normal. To assess the possibility that the recurrent syncopal episodes were related to epileptic seizures, neurology was consulted.

Brain MRI and ECG were performed, both showing normal results. In a subsequent discussion, the patient told clinicians that his second cousin had died suddenly in his early 20s after a cardiac episode of unknown cause.

Clinicians arrived at a diagnosis of Brugada type 1 syndrome with unexplained syncope, and decided that the next step should be placement of an implantable cardioverter defibrillator (ICD).

The patient underwent the procedure without incident, and a follow-up examination 7 days later showed he was recovering well and beginning to resume his regular activities.

Discussion

Torabi and co-authors noted that the ECG findings led to the correct diagnosis, since they were "consistent with spontaneous Brugada type 1 morphology with more than 2-mm coved ST-segment elevation in leads V1 and V2." The team urged clinicians assessing ECGs to be vigilant for the Brugada type 1 pattern as a potential cause of cardio-arrhythmogenic syncope.

The rare but serious condition is seen in the U.S. at an estimated rate of only about 0.03%. To diagnose the syndrome, the group suggested the proposed Shanghai Score System based on ECG findings, clinical history, family history, or genetic test results, with a score of more than 3.5 points indicating at least probable Brugada. Patients with Brugada type 1 may be asymptomatic, and in those cases require observation only.

A paper on risk stratification of asymptomatic Brugada patients referenced the multi-registry FINGER trial, which reported that approximately 64% of patients with Brugada syndrome are "asymptomatic at diagnosis."

Symptoms such as "unexplained cardiac arrest or polymorphic ventricular tachycardia or ventricular fibrillation arrest, nocturnal agonal respirations, atrial fibrillation/flutter in patients younger than 30 years of age, or syncope of uncertain etiology" require additional evaluation, Torabi and colleagues said.

They advised clinicians to consider the possibility of ventricular fibrillation when faced with unexplained syncope in a patient with Brugada syndrome. "The presence of suspected arrhythmogenic syncope alone in patients with Brugada syndrome with the spontaneous type 1 electrocardiogram pattern is a class 1 [guideline] indication for an implantable cardioverter defibrillator," the team added.

They also mentioned a "controversial" class 2B recommendation stating that before ICD placement, patients should have an electrophysiological evaluation to stratify their risk, suggesting that there may be a role for epicardial ablation in symptomatic patients whose condition is not responding to the ICD, or those suffering repeated ICD shocks.

Regarding their patient, the case report authors noted that on initial evaluation, although they had felt the possibility of seizures was lower in the differential diagnosis, a striking feature was the persistent muscle jerks, making convulsive syncope less likely. The conditional diagnosis, the authors said, was therefore based on a small margin of error, and after considering the options, the patient chose to "undergo transvenous ICD placement."

Still, the group acknowledged that "the decision to offer an ICD is not one to take lightly," particularly given the known risk of inappropriate shock from ICDs, which has a reported incidence of up to 6.6% over a median 2-year period.

Another concern to take into account is "the obstacle of generator changes in a young patient, which may be required within 5 to 10 years of device implantation, depending on the manufacturer used," the authors stated.

Another key consideration for patients who do not require pacing is whether to use a subcutaneous ICD -- "which has largely been shown to be noninferior to the transvenous system," Torabi and colleagues noted, adding that the decision depends primarily on patient preference.

They emphasized the benefits of taking a systematic, primarily guideline-based approach, in offering ICDs to patients -- "this played a large role in our decision to pursue such an extensive medical workup to validate the uncertain etiology of our patient's syncope," the team explained

In a published comment that followed the case report, Pedro Brugada, MD, PhD, of the University of Brussels, who along with his two brothers was the first to recognize the syndrome, wrote that while he agreed with the case authors' diagnostic and therapeutic process, he wanted to add three additional points:

• On the risk scoring system for Brugada syndrome, the patient's score was at least 4 points, meaning a 10-year risk of sudden death of 30%, which, Brugada said, supports the need for an ICD "irrespective of the results of an electrophysiological study (if it had been performed)"

• Brugada syndrome is an inherited arrhythmia disorder with an autosomal dominant pattern of inheritance

• "While the significance of many mutations can be considered unclear, many mutations in the gene SCN5A encoding for the cardiac sodium channel have been definitively related to the disease," Brugada wrote. "The finding of a significant mutation facilitates family screening and also opens the way for preimplant genetic diagnosis to prevent further transmission of abnormal genes"

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