Materiały źródłowe

• #1 Brugada Syndrome – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-brugada-syndrome-articulo-13145482

  In fact, Brugada syndrome is the cause of 4% to 12% of all SCD and up to 20% of SCD that occur in normal heart. […] Various experimental studies have enabled the mechanisms involved in the development of the 2 main characteristics of Brugada syndrome to be elucidated, namely: the typical ECG morphology, and the susceptibility to VF and SCD. […] A decrease in INa, the disorder more frequently observed in mutations in SCN5A associated with Brugada syndrome, leads to an imbalance between the positive inward and outward currents at the end of phase 1 of the cell action potential. […] The ion current imbalance at the end of phase 1 of the action potential also explains the susceptibility to develop ventricular arrhythmias in Brugada syndrome, which would arise via a phase 2 reentry mechanism. […] The concept of an imbalance between inward and outward ion currents, defining the pathological substrate of Brugada syndrome, has many applications.

• #2 Brugada Syndrome: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/16813-brugada-syndrome

  Brugada syndrome is a disease that can cause an abnormal rhythm in your hearts lower chambers (ventricles). This irregular heart rhythm, ventricular fibrillation (v-fib), prevents your heart from pumping blood to your brain. When this happens, you faint. […] V-fib can lead to sudden cardiac death. This often happens while youre at rest or asleep. Out of all the sudden cardiac deaths that happen, researchers blame Brugada syndrome for 4% of them. […] Brugada syndrome causes include an unknown cause or a genetic one. About 70% of people with Brugada syndrome dont have a known genetic mutation. […] Some people have a genetic variation in one of 18 or more genes, most often in SCN5A. These variations interfere with heartbeat signal conduction in your heart. […] It only takes one copy of an affected gene from one parent to inherit Brugada syndrome. Any child of someone with a Brugada-related gene variation has a 50% chance of having it, too.

• #3 Brugada Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519568/

  When Brugada syndrome was first described, it was thought to be only in structurally normal hearts. However, newer research revealed right ventricular outflow tract abnormalities, such as an increase in adipose tissue and fibrosis. These structural abnormalities support the depolarization disorder model as a possible cause of slower conduction in the right ventricular outflow tract. Nonetheless, whether these structural abnormalities account for the arrhythmias caused in Brugada syndrome or that they are the result of the disease and aging process is still a matter of debate.

• #4 Pathogenesis and Management of Brugada Syndrome: Recent Advances and Protocol for Umbrella Reviews of Meta-Analyses in Major Arrhythmic Events Risk Stratification

  https://www.mdpi.com/2077-0383/11/7/1912

  BrS was previously described as an autosomal-dominant inherited disorder with incomplete penetrance, and absent or benign structural heart abnormalities. The lack of significant structural heart disease in BrS patients may be visualized by echocardiography, angiography, or ventriculography. However, magnetic resonance imaging in subgroups of patients with BrS revealed enlarged right ventricular (RV) volumes, increased RV outflow tract (RVOT) area, or mild RV wall motion abnormalities. The pathomechanism observed in BrS patients involves depolarization and repolarization abnormalities, inflammation of myocytes, and fibrosis in RVOT and/or RV. A recent study performed on whole hearts from deceased patients, whose SCD was accounted to BrS, showed biventricular myocardial fibrosis, especially in the epicardium of the RVOT. RV myocardium in a number of patients with BrS type 1 ECG pattern have showed histological changes comparable to arrhythmogenic RV cardiomyopathy (ARVC), and indicate possible autoimmune causes of myocardial inflammation in BrS patients.

• #5 Brugada Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/163751-overview

  Brugada syndrome is an example of a channelopathy, a disease caused by an alteration in the transmembrane ion currents that together constitute the cardiac action potential. Specifically, in 10-30% of cases, mutations in the SCN5A gene, which encodes the cardiac voltage-gated sodium channel Nav 1.5, have been found. These loss-of-function mutations reduce the sodium current (INa) available during the phases 0 (upstroke) and 1 (early repolarization) of the cardiac action potential. […] This decrease in INa is thought to affect the right ventricular endocardium differently from the epicardium. Thus, it underlies both the Brugada ECG pattern and the clinical manifestations of the Brugada syndrome. […] The exact mechanisms underlying the ECG alterations and arrhythmogenesis in Brugada syndrome are disputed.

• #6 Brugada Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519568/

  Brugada syndrome is a genetic disease that predisposes patients to fatal cardiac arrhythmias. […] The first genetic association with Brugada syndrome discovered was a loss-of-function mutation in the cardiac voltage-gated sodium channel gene SCN5A. It is thought to be found in 15-30% of Brugada Syndrome cases. […] The exact mechanism for Brugada Syndrome is not clear. There are two main physiologic hypotheses that have been suggested: the repolarization disorder and the depolarization disorder models. According to the repolarization disorder model, the decrease in sodium current secondary to the loss-of-function sodium channel mutation causes the right ventricular epicardium’s action potential to have a deeper notch when compared to the action potential of the endocardium. This difference in current can lead to the typical EKG finding of Brugada syndrome and subsequent fatal arrhythmias. The depolarization disorder model, on the other hand, suggests that the EKG findings of Brugada syndrome are secondary to a delay in depolarization due to slow conduction in the right ventricular outflow tract.

• #7 Pathogenesis and Management of Brugada Syndrome: Recent Advances and Protocol for Umbrella Reviews of Meta-Analyses in Major Arrhythmic Events Risk Stratification

  https://www.mdpi.com/2077-0383/11/7/1912

  Genetic etiology, identified in about 14–34% cases, is primarily associated with sodium voltage-gated channel alpha subunit 5 (SCN5A) gene mutation affecting cardiac channels. SCN5A gene encodes for the α-subunit of the sodium channels in the heart and mutations in the gene lead to reduced expression of Nav1.5 α-subunit proteins, loss of functional sodium channels, and impaired phase 0 action potential. At present, other genes have been identified as susceptibility genes for BrS, and BrS is now considered an oligogenic or polygenic disease. […] Currently, potassium, chloride, and calcium ion channels involved in the cardiac depolarization and repolarization process have also been described as associated with channelopathies caused by the dysfunction of regulatory proteins. For example, excess outflow of potassium current during early repolarization or reduced inward current via calcium channels may contribute to BrS pathophysiology. The reduced inward current flow of sodium in BrS patients may result in prolonged PR (PQ) interval, first degree atrioventricular block, slow cardiac conduction (intraventricular and His–Purkinje), phase 2 reentry and premature repolarization, low-amplitude and high-frequency electrical activity in RVOT epicardium (late potentials), and ventricular arrhythmias.

• #8 Brugada syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/brugada-syndrome/

  Brugada syndrome can be caused by mutations in one of several genes. The most commonly mutated gene in this condition is SCN5A, which is altered in approximately 30 percent of affected individuals. This gene provides instructions for making a sodium channel, which normally transports positively charged sodium atoms (ions) into heart muscle cells. This type of ion channel plays a critical role in maintaining the heart’s normal rhythm. Mutations in the SCN5A gene alter the structure or function of the channel, which reduces the flow of sodium ions into cells. A disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of Brugada syndrome. […] Mutations in other genes can also cause Brugada syndrome. Together, these other genetic changes account for less than two percent of cases of the condition. Some of the additional genes involved in Brugada syndrome provide instructions for making proteins that ensure the correct location or function of sodium channels in heart muscle cells. Proteins produced by other genes involved in the condition form or help regulate ion channels that transport calcium or potassium into or out of heart muscle cells. As with sodium channels, proper flow of ions through calcium and potassium channels in the heart muscle helps maintain a regular heartbeat. Mutations in these genes disrupt the flow of ions, impairing the heart’s normal rhythm.

• #9 KEGG DISEASE: Brugada syndrome

  https://www.genome.jp/dbget-bin/www_bget?H00728

  The Brugada syndrome (BRS) is an autosomal dominant genetic disorder that is characterised by abnormal electrocardiogram (ECG) findings and an increased risk of sudden cardiac death. […] Mutations in nine genes (SCN5A, GPD1L, CACNA1C, CACNB2, SCN1B, KCNE3, SCN3B, HCN4, and KCND3) are known to cause BRS. […] In approximately 20% of the cases BRS is caused by mutations in the SCN5A gene, encoding the cardiac sodium channel. […] Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. […] Functional effects of KCNE3 mutation and its role in the development of Brugada syndrome. […] A mutation in the beta 3 subunit of the cardiac sodium channel associated with Brugada ECG phenotype.

• #10 Genetic and Molecular Mechanisms in Brugada Syndrome

  https://www.mdpi.com/2073-4409/12/13/1791

  The debate regarding the predominant electrophysiological mechanism of BrS has largely revolved around the repolarization versus depolarization hypotheses. […] Genetic variations in the SCN5A gene, affecting the inward current during phase 0, are implicated in approximately a quarter of Brugada syndrome (BrS) cases, leading to a slower upstroke and delayed action potential formation that significantly contributes to ventricular arrhythmogenesis. […] The sodium channel is a voltage-gated, complex structure consisting of multiple subunits. […] Loss-of-function variants in SCN5A are commonly associated with Brugada syndrome (BrS). […] The GPD1-L protein is closely linked, structurally and functionally, to the Na v 1.5 sodium channel. […] The dynamic nature of the ECG can sometimes hide the characteristic patterns of BrS, proposing the use of sodium channel blockers for diagnostic purposes. […] The current understanding of the genetic and molecular mechanisms underlying BrS is limited.

• #11 Pathogenesis and Management of Brugada Syndrome | Encyclopedia MDPI

  https://encyclopedia.pub/entry/21844

  Brugada syndrome (BrS) is a primary electrical disease associated with arrhythmias and an elevated risk of sudden cardiac death (SCD). […] BrS was previously described as an autosomal-dominant inherited disorder with incomplete penetrance, and absent or benign structural heart abnormalities. […] The pathomechanism observed in BrS patients involves depolarization and repolarization abnormalities, inflammation of myocytes, and fibrosis in RVOT and/or RV. […] Genetic etiology, identified in about 14–34% cases, is primarily associated with sodium voltage-gated channel alpha subunit 5 (SCN5A) gene mutation affecting cardiac channels. […] Currently, potassium, chloride, and calcium ion channels involved in the cardiac depolarization and repolarization process have also been described as associated with channelopathies caused by the dysfunction of regulatory proteins.

• #12 Brugada syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/brugada-syndrome/

  Brugada syndrome can be caused by mutations in one of several genes. The most commonly mutated gene in this condition is SCN5A, which is altered in approximately 30 percent of affected individuals. This gene provides instructions for making a sodium channel, which normally transports positively charged sodium atoms (ions) into heart muscle cells. This type of ion channel plays a critical role in maintaining the heart’s normal rhythm. Mutations in the SCN5A gene alter the structure or function of the channel, which reduces the flow of sodium ions into cells. A disruption in ion transport alters the way the heart beats, leading to the abnormal heart rhythm characteristic of Brugada syndrome. […] Mutations in other genes can also cause Brugada syndrome. Together, these other genetic changes account for less than two percent of cases of the condition. Some of the additional genes involved in Brugada syndrome provide instructions for making proteins that ensure the correct location or function of sodium channels in heart muscle cells. Proteins produced by other genes involved in the condition form or help regulate ion channels that transport calcium or potassium into or out of heart muscle cells. As with sodium channels, proper flow of ions through calcium and potassium channels in the heart muscle helps maintain a regular heartbeat. Mutations in these genes disrupt the flow of ions, impairing the heart’s normal rhythm.

• #13 Brugada syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/brugada-syndrome/

  In affected people without an identified gene mutation, the cause of Brugada syndrome is often unknown. In some cases, certain drugs may cause a nongenetic (acquired) form of the disorder. Drugs that can induce an altered heart rhythm include medications used to treat some forms of arrhythmia, a condition called angina (which causes chest pain), high blood pressure, depression, and other mental illnesses. Abnormally high blood levels of calcium (hypercalcemia) or potassium (hyperkalemia), as well as unusually low potassium levels (hypokalemia), also have been associated with acquired Brugada syndrome. In addition to causing a nongenetic form of this disorder, these factors may trigger symptoms in people with an underlying mutation in SCN5A or another gene.

• #14 Brugada Syndrome: Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/16813-brugada-syndrome

  Brugada syndrome is a disease that can cause an abnormal rhythm in your hearts lower chambers (ventricles). This irregular heart rhythm, ventricular fibrillation (v-fib), prevents your heart from pumping blood to your brain. When this happens, you faint. […] V-fib can lead to sudden cardiac death. This often happens while youre at rest or asleep. Out of all the sudden cardiac deaths that happen, researchers blame Brugada syndrome for 4% of them. […] Brugada syndrome causes include an unknown cause or a genetic one. About 70% of people with Brugada syndrome dont have a known genetic mutation. […] Some people have a genetic variation in one of 18 or more genes, most often in SCN5A. These variations interfere with heartbeat signal conduction in your heart. […] It only takes one copy of an affected gene from one parent to inherit Brugada syndrome. Any child of someone with a Brugada-related gene variation has a 50% chance of having it, too.

• #15 Brugada syndrome: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/brugada-syndrome/

  In affected people without an identified gene mutation, the cause of Brugada syndrome is often unknown. In some cases, certain drugs may cause a nongenetic (acquired) form of the disorder. Drugs that can induce an altered heart rhythm include medications used to treat some forms of arrhythmia, a condition called angina (which causes chest pain), high blood pressure, depression, and other mental illnesses. Abnormally high blood levels of calcium (hypercalcemia) or potassium (hyperkalemia), as well as unusually low potassium levels (hypokalemia), also have been associated with acquired Brugada syndrome. In addition to causing a nongenetic form of this disorder, these factors may trigger symptoms in people with an underlying mutation in SCN5A or another gene.

• #16 Brugada Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519568/

  Brugada syndrome is a genetic disease that predisposes patients to fatal cardiac arrhythmias. […] The first genetic association with Brugada syndrome discovered was a loss-of-function mutation in the cardiac voltage-gated sodium channel gene SCN5A. It is thought to be found in 15-30% of Brugada Syndrome cases. […] The exact mechanism for Brugada Syndrome is not clear. There are two main physiologic hypotheses that have been suggested: the repolarization disorder and the depolarization disorder models. According to the repolarization disorder model, the decrease in sodium current secondary to the loss-of-function sodium channel mutation causes the right ventricular epicardium’s action potential to have a deeper notch when compared to the action potential of the endocardium. This difference in current can lead to the typical EKG finding of Brugada syndrome and subsequent fatal arrhythmias. The depolarization disorder model, on the other hand, suggests that the EKG findings of Brugada syndrome are secondary to a delay in depolarization due to slow conduction in the right ventricular outflow tract.

• #17 Brugada Syndrome – Core EM

  https://coreem.net/core/brugada-syndrome/

  Pathophysiology not completely understood. […] Many different genes have been implicated in Brugada syndrome, involving mutations in the sodium channels as well as the calcium and potassium channels. […] 3 different hypotheses exist for mechanism of Brugada syndrome: (Sieira J et al.) […] Repolarization: an outward shift in balance of current in right ventricular epicardium results in repolarization abnormalities, leading to closely coupled premature beats which can lead to ventricular arrhythmia. […] Depolarization: conduction delay in the right ventricular outflow tract (RVOT) creates abnormal current leading to ventricular arrhythmia. […] Neural crest: the RVOT has different embryologic origin than rest of the heart, and abnormal expression of these cells could lead to both a depolarization delay and abnormal repolarization in the RVOT.

• #18 Brugada Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519568/

  Brugada syndrome is a genetic disease that predisposes patients to fatal cardiac arrhythmias. […] The first genetic association with Brugada syndrome discovered was a loss-of-function mutation in the cardiac voltage-gated sodium channel gene SCN5A. It is thought to be found in 15-30% of Brugada Syndrome cases. […] The exact mechanism for Brugada Syndrome is not clear. There are two main physiologic hypotheses that have been suggested: the repolarization disorder and the depolarization disorder models. According to the repolarization disorder model, the decrease in sodium current secondary to the loss-of-function sodium channel mutation causes the right ventricular epicardium’s action potential to have a deeper notch when compared to the action potential of the endocardium. This difference in current can lead to the typical EKG finding of Brugada syndrome and subsequent fatal arrhythmias. The depolarization disorder model, on the other hand, suggests that the EKG findings of Brugada syndrome are secondary to a delay in depolarization due to slow conduction in the right ventricular outflow tract.

• #19 Brugada Syndrome – Revista Española de Cardiología (English Edition)

  https://www.revespcardiol.org/en-brugada-syndrome-articulo-13145482

  In fact, Brugada syndrome is the cause of 4% to 12% of all SCD and up to 20% of SCD that occur in normal heart. […] Various experimental studies have enabled the mechanisms involved in the development of the 2 main characteristics of Brugada syndrome to be elucidated, namely: the typical ECG morphology, and the susceptibility to VF and SCD. […] A decrease in INa, the disorder more frequently observed in mutations in SCN5A associated with Brugada syndrome, leads to an imbalance between the positive inward and outward currents at the end of phase 1 of the cell action potential. […] The ion current imbalance at the end of phase 1 of the action potential also explains the susceptibility to develop ventricular arrhythmias in Brugada syndrome, which would arise via a phase 2 reentry mechanism. […] The concept of an imbalance between inward and outward ion currents, defining the pathological substrate of Brugada syndrome, has many applications.

• #20 Brugada Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/163751-overview

  The repolarization-defect theory is based on the fact that right ventricular epicardial cells display a more prominent notch in the action potential than endocardial cells. This is thought to be due to an increased contribution of the transient outward current (Ito) to the action potential waveform in that tissue. […] A decrease in INa accentuates this difference, causing a voltage gradient during repolarization and the characteristic ST elevations on ECG. […] When the usual relative durations of repolarization are not altered, the T wave remains upright, causing a saddleback ECG pattern (type 2 or 3). When the alteration in repolarization is sufficient to cause a reversal of the normal gradient of repolarization, the T wave inverts, and the coved (type 1) ECG pattern is seen. […] In a similar way, a heterogeneous alteration in cardiac repolarization may predispose to the development of reentrant arrhythmias, termed phase 2 reentry, that can clinically cause ventricular tachycardia and ventricular fibrillation.

• #21 Genetic and Molecular Mechanisms in Brugada Syndrome

  https://www.mdpi.com/2073-4409/12/13/1791

  Brugada syndrome is a rare hereditary arrhythmia disorder characterized by a distinctive electrocardiogram pattern and an elevated risk of ventricular arrhythmias and sudden cardiac death in young adults. […] The underlying electrophysiological mechanism of Brugada syndrome requires further investigation, with current theories focusing on abnormalities in repolarization, depolarization, and current-load match. […] The current understanding of the pathophysiology of BrS has evolved significantly in recent years. The widely supported mechanism for BrS suggests that it is primarily caused by a repolarization disorder, characterized by abnormal shortening of the epicardial action potential duration. […] Evidence suggests that BrS is associated with the amplification of intrinsic heterogeneities of the AP between epicardial and endocardial myocytes.

• #22 Brugada Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/163751-overview

  The repolarization-defect theory is based on the fact that right ventricular epicardial cells display a more prominent notch in the action potential than endocardial cells. This is thought to be due to an increased contribution of the transient outward current (Ito) to the action potential waveform in that tissue. […] A decrease in INa accentuates this difference, causing a voltage gradient during repolarization and the characteristic ST elevations on ECG. […] When the usual relative durations of repolarization are not altered, the T wave remains upright, causing a saddleback ECG pattern (type 2 or 3). When the alteration in repolarization is sufficient to cause a reversal of the normal gradient of repolarization, the T wave inverts, and the coved (type 1) ECG pattern is seen. […] In a similar way, a heterogeneous alteration in cardiac repolarization may predispose to the development of reentrant arrhythmias, termed phase 2 reentry, that can clinically cause ventricular tachycardia and ventricular fibrillation.

• #23 The Brugada Syndrome – Diagnosis, Clinical Implications and Risk Stratification | ECR Journal

  https://www.ecrjournal.com/articles/brugada-syndrome-diagnosis-clinical-implications-and-risk-stratification?language_content_entity=en

  The Brugada syndrome (BrS) is a hereditary arrhythmic syndrome manifesting as syncope or sudden cardiac death (SCD) in individuals without overt structural heart disease. […] The cellular basis of the BrS is still not fully understood. […] According to the repolarisation theory, reduction of the inward Na+ current leads to unopposed transient outward (Ito) current in some epicardial regions of the right ventricular outflow tract (RVOT), which causes either delayed expression of the action potential (AP) dome and epicardial AP prolongation or loss of the dome and AP shortening. […] There is also mounting evidence from experimental, histopathological, computational, clinical electrophysiological and imaging studies for the presence of conduction abnormalities in the RVOT and their importance for the genesis of ventricular arrhythmias in BrS.

• #24 Brugada Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/163751-overview

  The repolarization-defect theory is based on the fact that right ventricular epicardial cells display a more prominent notch in the action potential than endocardial cells. This is thought to be due to an increased contribution of the transient outward current (Ito) to the action potential waveform in that tissue. […] A decrease in INa accentuates this difference, causing a voltage gradient during repolarization and the characteristic ST elevations on ECG. […] When the usual relative durations of repolarization are not altered, the T wave remains upright, causing a saddleback ECG pattern (type 2 or 3). When the alteration in repolarization is sufficient to cause a reversal of the normal gradient of repolarization, the T wave inverts, and the coved (type 1) ECG pattern is seen. […] In a similar way, a heterogeneous alteration in cardiac repolarization may predispose to the development of reentrant arrhythmias, termed phase 2 reentry, that can clinically cause ventricular tachycardia and ventricular fibrillation.

• #25 Brugada Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/163751-overview

  The repolarization-defect theory is based on the fact that right ventricular epicardial cells display a more prominent notch in the action potential than endocardial cells. This is thought to be due to an increased contribution of the transient outward current (Ito) to the action potential waveform in that tissue. […] A decrease in INa accentuates this difference, causing a voltage gradient during repolarization and the characteristic ST elevations on ECG. […] When the usual relative durations of repolarization are not altered, the T wave remains upright, causing a saddleback ECG pattern (type 2 or 3). When the alteration in repolarization is sufficient to cause a reversal of the normal gradient of repolarization, the T wave inverts, and the coved (type 1) ECG pattern is seen. […] In a similar way, a heterogeneous alteration in cardiac repolarization may predispose to the development of reentrant arrhythmias, termed phase 2 reentry, that can clinically cause ventricular tachycardia and ventricular fibrillation.

• #26 Management of patients with a Brugada ECG pattern

  https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-7/Management-of-patients-with-a-Brugada-ECG-pattern

  To date, the most accepted theory to explain the ECG changes and the arrhythmogenic basis of BS is based on the effect of the decrease of the inward positive currents (Na+, Ca+2) on the potassium transient outward current (Ito), whose expression levels vary across the myocardium layers (epicardium-endocardium). These changes in the ionic imbalance are responsible for the modification of the morphology of the cardiac action potential (presenting a remarked notch during the Phase 1, otherwise called 'loss of dome’), the typical ECG changes. These changes constitute the electrophysiological basis of the increased susceptibility of these patients to present episodes of polymorphic VT and/or VF (by a mechanism of Phase-2 reentry).

• #27 Brugada Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/163751-overview

  An alternative hypothesis, the depolarization/conduction disorder model, proposes that the typical Brugada ECG findings can be explained by slow conduction and activation delays in the right ventricle (in particular in the right ventricular outflow tract). […] One study used ajmaline provocation to elicit a type 1 Brugada ECG pattern in 91 patients, and found that the repolarization abnormalities were concordant with the depolarization abnormalities and appeared to be secondary to the depolarization changes.

• #28 Brugada Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519568/

  Brugada syndrome is a genetic disease that predisposes patients to fatal cardiac arrhythmias. […] The first genetic association with Brugada syndrome discovered was a loss-of-function mutation in the cardiac voltage-gated sodium channel gene SCN5A. It is thought to be found in 15-30% of Brugada Syndrome cases. […] The exact mechanism for Brugada Syndrome is not clear. There are two main physiologic hypotheses that have been suggested: the repolarization disorder and the depolarization disorder models. According to the repolarization disorder model, the decrease in sodium current secondary to the loss-of-function sodium channel mutation causes the right ventricular epicardium’s action potential to have a deeper notch when compared to the action potential of the endocardium. This difference in current can lead to the typical EKG finding of Brugada syndrome and subsequent fatal arrhythmias. The depolarization disorder model, on the other hand, suggests that the EKG findings of Brugada syndrome are secondary to a delay in depolarization due to slow conduction in the right ventricular outflow tract.

• #29 Brugada Syndrome: Practice Essentials, Background, Pathophysiology

  https://emedicine.medscape.com/article/163751-overview

  An alternative hypothesis, the depolarization/conduction disorder model, proposes that the typical Brugada ECG findings can be explained by slow conduction and activation delays in the right ventricle (in particular in the right ventricular outflow tract). […] One study used ajmaline provocation to elicit a type 1 Brugada ECG pattern in 91 patients, and found that the repolarization abnormalities were concordant with the depolarization abnormalities and appeared to be secondary to the depolarization changes.

• #30 Brugada Syndrome – Core EM

  https://coreem.net/core/brugada-syndrome/

  Pathophysiology not completely understood. […] Many different genes have been implicated in Brugada syndrome, involving mutations in the sodium channels as well as the calcium and potassium channels. […] 3 different hypotheses exist for mechanism of Brugada syndrome: (Sieira J et al.) […] Repolarization: an outward shift in balance of current in right ventricular epicardium results in repolarization abnormalities, leading to closely coupled premature beats which can lead to ventricular arrhythmia. […] Depolarization: conduction delay in the right ventricular outflow tract (RVOT) creates abnormal current leading to ventricular arrhythmia. […] Neural crest: the RVOT has different embryologic origin than rest of the heart, and abnormal expression of these cells could lead to both a depolarization delay and abnormal repolarization in the RVOT.

• #31 The Brugada Syndrome – Diagnosis, Clinical Implications and Risk Stratification | ECR Journal

  https://www.ecrjournal.com/articles/brugada-syndrome-diagnosis-clinical-implications-and-risk-stratification?language_content_entity=en

  A third hypothesis unifying the above two explains the BrS with abnormal expression of the neural crest cells during the embryological development of the RVOT. […] From electrocardiographic point of view, the characteristic elevation of the J point and ST segment of the type 1 Brugada ECG pattern results from early relative (intracellular) positivity of the unaffected zone (RVOT endocardium according to the repolarisation theory or normally activated myocardium outside the RVOT according to the depolarisation theory), whereas the negative T wave is an expression of late epicardial relative (intracellular) positivity in the affected RVOT zone due to either prolongation of the epicardial APs or its delayed activation. […] The symptoms associated with the BrS are due to re-entry ventricular arrhythmias typically arising in the affected zone of the RV.

• #32 Brugada Syndrome: Progress in Genetics, Risk Stratification and Management | AER Journal

  https://www.aerjournal.com/articles/brugada-syndrome-progress-genetics-risk-stratification-and-management?language_content_entity=en

  Brugada syndrome (BrS) is one of the most common causes of sudden cardiac death in normal structural heart individuals. […] Future studies are required to increase understanding of the pathogenesis of this disease and to guide clinical practice. […] The complexity of this disease has also been increasingly recognised, with controversies and uncertainties awaiting future studies. […] There are three major mechanistic models explaining the electric abnormality in BrS, namely the repolarisation, depolarisation and neural crest models. […] Despite their differences, all three models agree that the major region of pathology is the right ventricular outflow tract (RVOT). […] Evidence has revealed structural derangement of the right ventricle in BrS. […] Histological evidence of substantial fibrosis in the RVOT epicardium, corresponding to a low expression of Cx43, was found in the hearts (from autopsy or explanted hearts) of BrS individuals.

• #33 Brugada Syndrome: Progress in Genetics, Risk Stratification and Management | AER Journal

  https://www.aerjournal.com/articles/brugada-syndrome-progress-genetics-risk-stratification-and-management?language_content_entity=en

  A recent study has further shown that RVOT electroanatomical alterations (a low-voltage area) correlate with myocardial inflammation and arrhythmia vulnerability, supporting the hypothesis that BrS is a combination of electrical and structural disease. […] The concept of the connexome connects the two diseases. […] Accumulating evidence has shown that these structures are closely interconnected and interdependent for anchorage and stabilisation. […] Therefore, sodium channel activity could be affected by the disruption of any connexome components. […] This review summarises progress in the understanding and management of BrS in recent years. […] Not only has new knowledge been acquired in the genetics and molecular mechanisms of BrS, but recent years have also seen progress made in risk stratification as well as the development of promising new therapies, including epicardial ablation for BrS. […] Future studies are needed to further clarify the pathogenesis of this complex disease and to guide clinical practice, including genetic testing, risk stratification and selection of therapies.

• #34 Brugada Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK519568/

  When Brugada syndrome was first described, it was thought to be only in structurally normal hearts. However, newer research revealed right ventricular outflow tract abnormalities, such as an increase in adipose tissue and fibrosis. These structural abnormalities support the depolarization disorder model as a possible cause of slower conduction in the right ventricular outflow tract. Nonetheless, whether these structural abnormalities account for the arrhythmias caused in Brugada syndrome or that they are the result of the disease and aging process is still a matter of debate.

• #35 Brugada Syndrome: Progress in Genetics, Risk Stratification and Management | AER Journal

  https://www.aerjournal.com/articles/brugada-syndrome-progress-genetics-risk-stratification-and-management?language_content_entity=en

  A recent study has further shown that RVOT electroanatomical alterations (a low-voltage area) correlate with myocardial inflammation and arrhythmia vulnerability, supporting the hypothesis that BrS is a combination of electrical and structural disease. […] The concept of the connexome connects the two diseases. […] Accumulating evidence has shown that these structures are closely interconnected and interdependent for anchorage and stabilisation. […] Therefore, sodium channel activity could be affected by the disruption of any connexome components. […] This review summarises progress in the understanding and management of BrS in recent years. […] Not only has new knowledge been acquired in the genetics and molecular mechanisms of BrS, but recent years have also seen progress made in risk stratification as well as the development of promising new therapies, including epicardial ablation for BrS. […] Future studies are needed to further clarify the pathogenesis of this complex disease and to guide clinical practice, including genetic testing, risk stratification and selection of therapies.

• #36 Brugada Syndrome: Progress in Genetics, Risk Stratification and Management | AER Journal

  https://www.aerjournal.com/articles/brugada-syndrome-progress-genetics-risk-stratification-and-management?language_content_entity=en

  A recent study has further shown that RVOT electroanatomical alterations (a low-voltage area) correlate with myocardial inflammation and arrhythmia vulnerability, supporting the hypothesis that BrS is a combination of electrical and structural disease. […] The concept of the connexome connects the two diseases. […] Accumulating evidence has shown that these structures are closely interconnected and interdependent for anchorage and stabilisation. […] Therefore, sodium channel activity could be affected by the disruption of any connexome components. […] This review summarises progress in the understanding and management of BrS in recent years. […] Not only has new knowledge been acquired in the genetics and molecular mechanisms of BrS, but recent years have also seen progress made in risk stratification as well as the development of promising new therapies, including epicardial ablation for BrS. […] Future studies are needed to further clarify the pathogenesis of this complex disease and to guide clinical practice, including genetic testing, risk stratification and selection of therapies.

• #37 Pathogenesis and Management of Brugada Syndrome: Recent Advances and Protocol for Umbrella Reviews of Meta-Analyses in Major Arrhythmic Events Risk Stratification

  https://www.mdpi.com/2077-0383/11/7/1912

  A recent study identified autoantibodies in the myocardium of BrS patients against cardiac proteins (α-actin, skeletal α-actin, connexin-43, keratin) and observed abnormal expression of Nav1.5 α-subunit proteins. Another study reported distinct elevation (apolipoprotein E, clusterin, prothrombin, vitamin-D-binding protein, complement-factor H, voltage-dependent anion-selective channel protein 3, vitronectin) or reduction (alpha-1-antitrypsin, angiotensinogen, fibrinogen) in plasma proteome of BrS patients and relatives with SCN5A Q1118X gene mutation compared to their healthy family members without the gene mutation, as well as antithrombin-III post-translational modifications.

• #38 The Brugada Syndrome – Diagnosis, Clinical Implications and Risk Stratification | ECR Journal

  https://www.ecrjournal.com/articles/brugada-syndrome-diagnosis-clinical-implications-and-risk-stratification?language_content_entity=en

  Currently there are only limited data suggesting that other ECG parameters may indicate increased arrhythmic risk. […] The development of sustained VT/VF in the BrS is likely a complex event resulting from interaction between the arrhythmic substrate (repolarisation and depolarisation abnormalities) and various triggering and modifying factors.

• #39 Brugada syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Brugada_syndrome

  Brugada syndrome (BrS) is a genetic disorder in which the electrical activity of the heart is abnormal due to channelopathy. It increases the risk of abnormal heart rhythms and sudden cardiac death. The abnormal heart rhythms seen in those with Brugada syndrome often occur at rest, and may be triggered by a fever. […] The individual heart muscle cells communicate with each other with electrical signals that are disrupted in those with Brugada syndrome. As a genetic condition, the syndrome is ultimately caused by changes to a person’s DNA, known as genetic mutations. The first mutations described in association with Brugada syndrome were in a gene responsible for a protein or ion channel that controls the flow of sodium ions through the cell membrane of heart muscle cells the cardiac sodium channel. Many of the genetic mutations that have subsequently been described in association with Brugada syndrome influence the sodium current in some way, or affect other ionic currents.

• #40 Brugada Syndrome | Arrhythmias – MedSchool

  https://medschool.co/diseases/arrhythmias/brugada-syndrome

  Brugada syndrome is an inherited condition that strongly predisposes to sudden cardiac death. The condition is autosomal dominant in inheritance and involves a loss of function mutation in sodium channels, predominantly affecting the right ventricle. […] Drug Triggers of Arrhythmia in Brugada Syndrome […] Antiarrhythmics – flecainide, procainamide […] Psychotropics – amitriptyline, nortriptyline, lithium […] Anaesthetics – local anaesthetics, propofol […] Substances – alcohol, cannabis, cocaine.

• #41 Brugada Syndrome and Carbohydrate Metabolism – MedCrave online

  https://medcraveonline.com/JCCR/brugada-syndrome-and-carbohydrate-metabolism.html

  Brugada syndrome is an arrhythmogenic and autosomal dominant disease with incomplete penetrance that may cause syncope and sudden cardiac death in young individuals with a normal heart. […] There are many factors contributing to the syndrome, including genetic factors, cellular and ionic mechanisms abnormalities, exercise, carbohydrate (CHO) and blood electrolyte. […] Based on Thai ministry of Public Health report in 1990 there was an association between a large meal of glutinous (sticky) rice or carbohydrates ingested on the night of death in Brugada syndrome victims. […] Some investigators have reported that a glucose load, glucose alone, glucose combined with insulin infusion, and Thai high glycemic index (HGI) meals influenced ST-segment elevation in Brugada syndrome patients. […] A reduction in INa or ICaL or an increase in Ito and/or any other potassium current may cause the changes of the configuration of the action potential notch that leads to J-point elevation on the ECG.

• #42 Brugada Syndrome and Carbohydrate Metabolism – MedCrave online

  https://medcraveonline.com/JCCR/brugada-syndrome-and-carbohydrate-metabolism.html

  Brugada syndrome is an arrhythmogenic and autosomal dominant disease with incomplete penetrance that may cause syncope and sudden cardiac death in young individuals with a normal heart. […] There are many factors contributing to the syndrome, including genetic factors, cellular and ionic mechanisms abnormalities, exercise, carbohydrate (CHO) and blood electrolyte. […] Based on Thai ministry of Public Health report in 1990 there was an association between a large meal of glutinous (sticky) rice or carbohydrates ingested on the night of death in Brugada syndrome victims. […] Some investigators have reported that a glucose load, glucose alone, glucose combined with insulin infusion, and Thai high glycemic index (HGI) meals influenced ST-segment elevation in Brugada syndrome patients. […] A reduction in INa or ICaL or an increase in Ito and/or any other potassium current may cause the changes of the configuration of the action potential notch that leads to J-point elevation on the ECG.

• #43 Brugada Syndrome and Carbohydrate Metabolism – MedCrave online

  https://medcraveonline.com/JCCR/brugada-syndrome-and-carbohydrate-metabolism.html

  According to the above information, the increasing of digestive related hormones and the CHO oxidation rate induced by having HGI or CHO load may result in abnormal metabolic and autonomic responses in these patients. […] In addition, an increasing of digestive related hormones and the CHO oxidation rate induced by having HGI or CHO load may result in abnormal metabolic and autonomic responses in these Brugada Syndrome patients.

• #44 Pathogenesis and management of Brugada syndrome | Nature Reviews Cardiology

  https://www.nature.com/articles/nrcardio.2016.143

  Brugada syndrome is an inherited disease responsible for a large number of sudden deaths in young people without structural heart anomalies. […] The pathophysiology of Brugada syndrome is unclear; repolarization-depolarization abnormalities underlying this disease can present with different features in different patients. […] A common electrocardiogram (ECG) phenotype seen in patients with Brugada syndrome might be the result of different pathophysiological mechanisms. […] The development of repolarization-depolarization abnormalities in patients with Brugada syndrome can involve genetic alterations, abnormal neural crest cell migration, improper gap junctional communication, or connexome abnormalities. […] Furthermore, risk stratification of this patient cohort is critical, and although some risk factors for Brugada syndrome have been frequently reported, several others remain unconfirmed. […] In this Review, we discuss the proposed mechanisms that underlie the development of Brugada syndrome and the current risk stratification and therapeutic options available for these patients.

• #45 Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility | Nature Genetics

  https://www.nature.com/articles/s41588-021-01007-6

  Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. […] The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. […] Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. […] Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.

• #46 Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility | Nature Genetics

  https://www.nature.com/articles/s41588-021-01007-6

  Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. […] The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. […] Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. […] Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings.

• #47 Brugada Syndrome: Progress in Genetics, Risk Stratification and Management | AER Journal

  https://www.aerjournal.com/articles/brugada-syndrome-progress-genetics-risk-stratification-and-management?language_content_entity=en

  A recent study has further shown that RVOT electroanatomical alterations (a low-voltage area) correlate with myocardial inflammation and arrhythmia vulnerability, supporting the hypothesis that BrS is a combination of electrical and structural disease. […] The concept of the connexome connects the two diseases. […] Accumulating evidence has shown that these structures are closely interconnected and interdependent for anchorage and stabilisation. […] Therefore, sodium channel activity could be affected by the disruption of any connexome components. […] This review summarises progress in the understanding and management of BrS in recent years. […] Not only has new knowledge been acquired in the genetics and molecular mechanisms of BrS, but recent years have also seen progress made in risk stratification as well as the development of promising new therapies, including epicardial ablation for BrS. […] Future studies are needed to further clarify the pathogenesis of this complex disease and to guide clinical practice, including genetic testing, risk stratification and selection of therapies.

• #48 Brugada Syndrome • LITFL • ECG Library Diagnosis

  https://litfl.com/brugada-syndrome-ecg-library/

  In a nutshell, Brugada syndrome is due to a mutation in the cardiac sodium channel gene. This is often referred to as a sodium channelopathy. Over 60 different mutations have been described so far and at least 50% are spontaneous mutations, but familial clustering and autosomal dominant inheritance has been demonstrated. […] ECG changes can be transient with Brugada syndrome and can also be unmasked or augmented by multiple factors: […] Pharmacological assessment has been suggested by some in Type 2 + 3 patterns, if Brugada syndrome is suspected clinically the administration of sodium channel blocking drugs may convert these non-diagnostic forms into the diagnostic type 1, however the sensitivity of this test is unknown and it would appear that this subgroup is at extremely low / no increased mortality when compared to the general population.

• #49 Brugada Syndrome – Brigham and Women’s Hospital

  https://www.brighamandwomens.org/heart-and-vascular-center/diseases-and-conditions/brugada-syndrome

  Still researchers believe that even when a drug appears to have caused it, these patients are predisposed to developing the condition due to genetic reasons. […] Brugada syndrome can be difficult to diagnose. […] Although it is usually detected on an electrocardiogram, sometimes the ECG findings are very subtle, which is why it is so important to see a specialist. […] Sometimes, certain medications are given to unmask the subtle changes that identify a person at risk for an arrhythmia. […] If someone has a history of fainting and is found to have Brugada syndrome, the likelihood that this person will experience recurring episodes of fainting or sudden cardiac death is up to 40 percent during the next 2-3 years. […] An ICD can detect and prevent the kind of arrhythmias responsible for causing patients to faint or die. […] When provided with an ICD, the rate of death in patients with Brugada syndrome has been 0 percent with up to 10 years follow-up.

• #50 Brugada Syndrome – Brigham and Women’s Hospital

  https://www.brighamandwomens.org/heart-and-vascular-center/diseases-and-conditions/brugada-syndrome

  Still researchers believe that even when a drug appears to have caused it, these patients are predisposed to developing the condition due to genetic reasons. […] Brugada syndrome can be difficult to diagnose. […] Although it is usually detected on an electrocardiogram, sometimes the ECG findings are very subtle, which is why it is so important to see a specialist. […] Sometimes, certain medications are given to unmask the subtle changes that identify a person at risk for an arrhythmia. […] If someone has a history of fainting and is found to have Brugada syndrome, the likelihood that this person will experience recurring episodes of fainting or sudden cardiac death is up to 40 percent during the next 2-3 years. […] An ICD can detect and prevent the kind of arrhythmias responsible for causing patients to faint or die. […] When provided with an ICD, the rate of death in patients with Brugada syndrome has been 0 percent with up to 10 years follow-up.

• #51 Brugada Syndrome: Progress in Genetics, Risk Stratification and Management | AER Journal

  https://www.aerjournal.com/articles/brugada-syndrome-progress-genetics-risk-stratification-and-management?language_content_entity=en

  A recent study has further shown that RVOT electroanatomical alterations (a low-voltage area) correlate with myocardial inflammation and arrhythmia vulnerability, supporting the hypothesis that BrS is a combination of electrical and structural disease. […] The concept of the connexome connects the two diseases. […] Accumulating evidence has shown that these structures are closely interconnected and interdependent for anchorage and stabilisation. […] Therefore, sodium channel activity could be affected by the disruption of any connexome components. […] This review summarises progress in the understanding and management of BrS in recent years. […] Not only has new knowledge been acquired in the genetics and molecular mechanisms of BrS, but recent years have also seen progress made in risk stratification as well as the development of promising new therapies, including epicardial ablation for BrS. […] Future studies are needed to further clarify the pathogenesis of this complex disease and to guide clinical practice, including genetic testing, risk stratification and selection of therapies.

• #52 Pathogenesis and management of Brugada syndrome | Nature Reviews Cardiology

  https://www.nature.com/articles/nrcardio.2016.143

  Brugada syndrome is an inherited disease responsible for a large number of sudden deaths in young people without structural heart anomalies. […] The pathophysiology of Brugada syndrome is unclear; repolarization-depolarization abnormalities underlying this disease can present with different features in different patients. […] A common electrocardiogram (ECG) phenotype seen in patients with Brugada syndrome might be the result of different pathophysiological mechanisms. […] The development of repolarization-depolarization abnormalities in patients with Brugada syndrome can involve genetic alterations, abnormal neural crest cell migration, improper gap junctional communication, or connexome abnormalities. […] Furthermore, risk stratification of this patient cohort is critical, and although some risk factors for Brugada syndrome have been frequently reported, several others remain unconfirmed. […] In this Review, we discuss the proposed mechanisms that underlie the development of Brugada syndrome and the current risk stratification and therapeutic options available for these patients.

• #53 Pathogenesis and management of Brugada syndrome | Nature Reviews Cardiology

  https://www.nature.com/articles/nrcardio.2016.143

  Brugada syndrome is an inherited disease responsible for a large number of sudden deaths in young people without structural heart anomalies. […] The pathophysiology of Brugada syndrome is unclear; repolarization-depolarization abnormalities underlying this disease can present with different features in different patients. […] A common electrocardiogram (ECG) phenotype seen in patients with Brugada syndrome might be the result of different pathophysiological mechanisms. […] The development of repolarization-depolarization abnormalities in patients with Brugada syndrome can involve genetic alterations, abnormal neural crest cell migration, improper gap junctional communication, or connexome abnormalities. […] Furthermore, risk stratification of this patient cohort is critical, and although some risk factors for Brugada syndrome have been frequently reported, several others remain unconfirmed. […] In this Review, we discuss the proposed mechanisms that underlie the development of Brugada syndrome and the current risk stratification and therapeutic options available for these patients.

• #54 Pathophysiological mechanisms of Brugada syndrome: depolarization disorder, repolarization disorder, or more? – PubMed

  https://pubmed.ncbi.nlm.nih.gov/15913579/

  After its recognition as a distinct clinical entity, Brugada syndrome is increasingly recognized worldwide as an important cause of sudden cardiac death. […] The pathophysiological mechanism of ST elevation and ventricular tachyarrhythmia, two phenomena strongly related, is controversial. Here, we review clinical and experimental studies as they provide evidence to support or disprove the two hypotheses on the mechanism of Brugada syndrome that currently receive the widest support: (1) nonuniform abbreviation of right ventricular epicardial action potentials („repolarization disorder”), (2) conduction delay in the right ventricular outflow tract („depolarization disorder”). […] Moreover, we review recent evidence to suggest that other derangements may also contribute to the pathophysiology of Brugada syndrome, in particular, right ventricular structural derangements. […] Rather than adhering to the notion that Brugada syndrome is a monofactorial disease, we should aim for clarification of the contribution of various pathophysiological mechanisms in individual Brugada syndrome patients and tailor therapy considering each of these mechanisms.

• #55 Pathophysiological mechanisms of Brugada syndrome: depolarization disorder, repolarization disorder, or more? – PubMed

  https://pubmed.ncbi.nlm.nih.gov/15913579/

  After its recognition as a distinct clinical entity, Brugada syndrome is increasingly recognized worldwide as an important cause of sudden cardiac death. […] The pathophysiological mechanism of ST elevation and ventricular tachyarrhythmia, two phenomena strongly related, is controversial. Here, we review clinical and experimental studies as they provide evidence to support or disprove the two hypotheses on the mechanism of Brugada syndrome that currently receive the widest support: (1) nonuniform abbreviation of right ventricular epicardial action potentials („repolarization disorder”), (2) conduction delay in the right ventricular outflow tract („depolarization disorder”). […] Moreover, we review recent evidence to suggest that other derangements may also contribute to the pathophysiology of Brugada syndrome, in particular, right ventricular structural derangements. […] Rather than adhering to the notion that Brugada syndrome is a monofactorial disease, we should aim for clarification of the contribution of various pathophysiological mechanisms in individual Brugada syndrome patients and tailor therapy considering each of these mechanisms.

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