SCN5A mutations in the S5–S6 region cause brugada syndrome and cardiac conduction disturbances

SCN5A gene mutations can lead to ion channel defects which can cause cardiac conduction disturbances. In the presence of specific ECG characteristics, this mutation is called Brugada syndrome. Many drugs are associated with adverse events, making anesthesia in patients with SCN5A gene mutations or Brugada syndrome challenging. In this case report, we describe a pregnant patient with this mutation who received epidural analgesia using low dose ropivacaine and sufentanil during labour.

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Regulation of Cardiac Conduction and Arrhythmias by Ankyrin/Spectrin-Based Macromolecular Complexes

Journal of Cardiovascular Development and Disease ◽

10.3390/jcdd8050048 ◽

2021 ◽

Vol 8 (5) ◽

pp. 48

Author(s):

Drew Nassal ◽

Jane Yu ◽

Dennison Min ◽

Cemantha Lane ◽

Rebecca Shaheen ◽

...

Keyword(s):

Ion Channels ◽

Cardiac Disease ◽

Conduction System ◽

Cytoskeletal Proteins ◽

Cardiac Conduction ◽

Proper Function ◽

Cardiac Conduction System ◽

Loss Of Function ◽

Macromolecular Complexes ◽

Conduction Disturbances

The cardiac conduction system is an extended network of excitable tissue tasked with generation and propagation of electrical impulses to signal coordinated contraction of the heart. The fidelity of this system depends on the proper spatio-temporal regulation of ion channels in myocytes throughout the conduction system. Importantly, inherited or acquired defects in a wide class of ion channels has been linked to dysfunction at various stages of the conduction system resulting in life-threatening cardiac arrhythmia. There is growing appreciation of the role that adapter and cytoskeletal proteins play in organizing ion channel macromolecular complexes critical for proper function of the cardiac conduction system. In particular, members of the ankyrin and spectrin families have emerged as important nodes for normal expression and regulation of ion channels in myocytes throughout the conduction system. Human variants impacting ankyrin/spectrin function give rise to a broad constellation of cardiac arrhythmias. Furthermore, chronic neurohumoral and biomechanical stress promotes ankyrin/spectrin loss of function that likely contributes to conduction disturbances in the setting of acquired cardiac disease. Collectively, this review seeks to bring attention to the significance of these cytoskeletal players and emphasize the potential therapeutic role they represent in a myriad of cardiac disease states.

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Brugada Syndrome: Fatal Consequences of a Must-Not-Miss Diagnosis

Critical Care Nurse ◽

10.4037/ccn2021499 ◽

2021 ◽

Vol 41 (5) ◽

pp. 15-22

Author(s):

L. Douglas Smith ◽

Sarah Gast ◽

Danielle F. Guy

Keyword(s):

At Risk ◽

Critical Care ◽

Sudden Cardiac Death ◽

Ventricular Arrhythmia ◽

Brugada Syndrome ◽

Cardiac Death ◽

Lifestyle Modification ◽

Genetic Disorder ◽

Cardiac Conduction ◽

St Segment Elevation

Background Brugada syndrome is a genetic disorder of cardiac conduction that predisposes patients to spontaneous ventricular arrhythmia and sudden cardiac death. Although Brugada syndrome is one of the most common causes of sudden cardiac death, patients presenting with the syndrome often go misdiagnosed. This error has potentially fatal consequences for patients, who are at risk for sudden cardiac death without appropriate management. Objective To increase the critical care professional’s knowledge of Brugada syndrome through detailed description of the characteristic electrocardiographic findings, an algorithmic approach to electrocardiogram evaluation, and a case report of a patient with a previously missed diagnosis of Brugada syndrome. The essential concepts of epidemiology, pathophysiology, clinical presentation, risk stratification, and management are reviewed for critical care professionals who may encounter patients with the syndrome. Diagnosis Patients typically present with syncope or cardiac arrest and an abnormal electrocardiographic finding of ST-segment elevation in the precordial leads. The diagnosis of Brugada syndrome centers on identification of its electrocardiographic characteristics by critical care professionals who routinely evaluate electrocardiograms. Critical care professionals, especially nurses and advanced practice nurses, should be proficient in recognizing the electrocardiographic appearance of Brugada syndrome and initiating appropriate management. Interventions Management strategies include prevention of sudden cardiac death through lifestyle modification and placement of an implantable cardioverter-defibrillator. Critical care professionals should be aware of commonly used medications that may exacerbate ventricular arrhythmia and place patients at risk for sudden cardiac death. Conclusion Increased awareness of Brugada syndrome among critical care professionals can decrease patient morbidity and mortality.

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Sodium channel kinetic changes that produce Brugada syndrome or progressive cardiac conduction system disease

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01025.2005 ◽

2007 ◽

Vol 292 (1) ◽

pp. H399-H407 ◽

Cited By ~ 33

Author(s):

Zhu-Shan Zhang ◽

Joseph Tranquillo ◽

Valentina Neplioueva ◽

Nenad Bursac ◽

Augustus O. Grant

Keyword(s):

Action Potential ◽

Sodium Channel ◽

Brugada Syndrome ◽

Sodium Current ◽

Conduction System ◽

Cardiac Conduction ◽

Cardiac Conduction System ◽

Wild Type ◽

System Disease ◽

Conduction System Disease

Some mutations of the sodium channel gene NaV1.5 are multifunctional, causing combinations of LQTS, Brugada syndrome and progressive cardiac conduction system disease (PCCD). The combination of Brugada syndrome and PCCD is uncommon, although they both result from a reduction in the sodium current. We hypothesize that slow conduction is sufficient to cause S-T segment elevation and undertook a combined experimental and theoretical study to determine whether conduction slowing alone can produce the Brugada phenotype. Deletion of lysine 1479 in one of two positively charged clusters in the III/IV inter-domain linker causes both syndromes. We have examined the functional effects of this mutation using heterologous expression of the wild-type and mutant sodium channel in HEK-293-EBNA cells. We show that ΔK1479 shifts the potential of half-activation, V1/2m, to more positive potentials ( V1/2m = −36.8 ± 0.8 and −24.5 ± 1.3 mV for the wild-type and ΔK1479 mutant respectively, n = 11, 10). The depolarizing shift increases the extent of depolarization required for activation. The potential of half-inactivation, V1/2h, is also shifted to more positive potentials ( V1/2h = −85 ± 1.1 and −79.4 ± 1.2 mV for wild-type and ΔK1479 mutant respectively), increasing the fraction of channels available for activation. These shifts are quantitatively the same as a mutation that produces PCCD only, G514C. We incorporated experimentally derived parameters into a model of the cardiac action potential and its propagation in a one dimensional cable (simulating endo-, mid-myocardial and epicardial regions). The simulations show that action potential and ECG changes consistent with Brugada syndrome may result from conduction slowing alone; marked repolarization heterogeneity is not required. The findings also suggest how Brugada syndrome and PCCD which both result from loss of sodium channel function are sometimes present alone and at other times in combination.

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