The cardiac sodium channel NaV1.5, encoded by SCN5A, generates the inward sodium current required for myocardial excitability and impulse conduction. Loss-of-function mutations of NaV1.5 have been implicated in inherited arrhythmia syndromes, including Brugada syndrome, progressive cardiac conduction disease, and congenital sick sinus syndrome. The common SCN5A polymorphism H558R has reported minor allele frequencies ranging from 9.2% to 29% across ethnic groups, whereas S524Y has been described in individuals of African ancestry with a minor allele frequency of approximately 3.3%. Two splice variants of human SCN5A, one lacking a glutamine at position 1077 (Q1077del) and one containing Q1077, exist in every human in a 2:1 mRNA transcript ratio. We engineered these two polymorphisms in both backgrounds and reported that when S524Y and H558R were expressed in the Q1077del variant, current densities were normal. In the Q1077 variant, however, the current densities showed a dramatic reduction compared to those in the Q1077del variant or WT-Q1077. We previously reported that incubation with the antiarrhythmic drug mexiletine "rescued" expression deficiencies in the Brugada syndrome. Cells expressing S524Y/Q1077 and H558R/Q1077 were incubated for 48 h with or without mexiletine (500 μM), followed by drug washout before electrophysiological assessment. Mexiletine significantly increased current density for both S524Y/Q1077 and H558R/Q1077 compared with untreated cells, restoring current density to levels comparable to WT-Q1077. Flow cytometry using a FLAG-tagged channel demonstrated that mexiletine-mediated rescue was associated with increased cell-surface expression. The magnitude of the expression defects caused by H558R and S524Y in the Q1077 splice background is similar to that observed with arrhythmia-associated SCN5A mutations, and we show for the first time that the defects for both polymorphisms can be rescued with mexiletine. Although it is unknown whether they result in heightened arrhythmia susceptibility in patients homozygous for the minor allele, our result may have implications for therapy for mutations with loss-of-function phenotypes modified by these common polymorphisms.

An 83-year-old woman with a history of severe mitral and tricuspid valve regurgitation requiring surgical repair, sick sinus syndrome status after permanent pacemaker placement, and paroxysmal atrial fibrillation presented to the hospital for outpatient right heart catheterization as part of an evaluation for pulmonary hypertension and severe tricuspid regurgitation. During the procedure, the patient began to expectorate a large volume of blood. A rapid response was called due to concerns for respiratory compromise, and the patient was emergently intubated for airway protection. She was subsequently transported to the appropriate unit for further diagnostic studies.

Papillary fibroelastoma (PFE) is the most common benign primary cardiac tumor in adults, yet its occurrence on the Coumadin ridge remains exceptionally rare. Here, we report a case of an 86-year-old woman with paroxysmal atrial fibrillation, sick sinus syndrome, and a dual-chamber pacemaker who was found to have methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. On transesophageal echocardiography (TEE), an 11 × 9 mm highly mobile, pedunculated mass with frond-like appearance was found attached to the Coumadin ridge that had the characteristic of PFE. A prior cardiac CT from 2021 confirmed that the mass had been present for at least four years, ruling out acute infective endocarditis. Given the patient's advanced age and significant comorbidities, surgical resection was deferred in favor of conservative management with serial imaging surveillance. This case highlights the importance of multimodality cardiac imaging (particularly three-dimensional TEE and cardiac CT) in characterizing cardiac masses, distinguishing PFE from endocarditic vegetations, and guiding individualized management in high-surgical-risk patients.

Transient loss of consciousness has overlapping cardiac and neurologic causes, and distinguishing syncope from seizure can be difficult. The co-occurrence of a primary cardiac rhythm disorder with a possible coexisting epileptic process is infrequently reported, as most cases instead describe one condition mimicking or triggering the other. We present a case of a 77-year-old woman with hypertension, hyperlipidemia, and paroxysmal atrial fibrillation who awoke with an abnormal chest sensation, a dream-like experience, and urinary incontinence and was admitted for evaluation of a possible seizure. Continuous telemetry captured a 50-second sinus arrest (initially reported as an eight-second pause), followed by an episode of atrial fibrillation with rapid ventricular response, establishing tachy-brady syndrome secondary to severe sinus node dysfunction. The patient underwent dual-chamber pacemaker implantation. Routine electroencephalography performed the following day showed occasional left temporal focal slowing and sharp waves without captured seizures, raising concern for possible focal epilepsy; incidentally identified right-sided meningiomas were discordant with the left temporal focus. The prolonged sinus arrest occurred during sleep without accompanying clinical seizures and showed a tachy-brady pattern typical of intrinsic sinus node disease, arguing against ictal asystole. Although the telemetry findings strongly supported intrinsic sinus node dysfunction, the interictal EEG abnormalities raised the possibility of an additional epileptogenic tendency. The patient was started on levetiracetam for a provisional diagnosis of epilepsy, pending reassessment. This case illustrates that a cardiac rhythm disorder and a possible coexisting epileptic process can occur together and that identifying one etiology should not preclude investigation of the other. Clinicians should maintain a low threshold for both continuous cardiac monitoring and EEG in patients with atypical transient loss of consciousness, as findings favoring one diagnosis do not preclude the other.