Cardiac channelopathies are a group of inherited arrhythmia syndromes caused by mutations in genes encoding ion channel proteins. They can cause potentially lethal arrhythmias in structurally normal hearts. The document discusses several specific channelopathies in detail, including Brugada syndrome and long QT syndrome. Brugada syndrome is characterized by ST elevation in the right precordial leads and increases the risk of ventricular arrhythmias. It is caused by mutations reducing sodium channel function. Long QT syndrome prolongs cardiac repolarization and increases risks of syncope, seizures and sudden cardiac death, with triggers varying by genotype. It is caused by mutations reducing potassium channel function or increasing sodium channel function. Accurate diagnosis, risk stratification, medical
Sudden cardiac death in structurally normal heartsYasmeen Kamal
Potential causes of sudden cardiac death without structural heart disease include long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization syndrome, idiopathic ventricular fibrillation, commotio cordis, and familial sudden cardiac death. These conditions are often genetic and can result in fatal arrhythmias. Evaluation of survivors and families of victims is important to determine the cause and provide appropriate treatment such as an implantable cardioverter-defibrillator.
Brugada Syndrome is a inherited sodium channel disorder leading to life threatening ventricular fibrillation in young population. diagnosis and ICD therapy could be life saving.
This document discusses Uhl's anomaly and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). It presents a case study of a 50-year-old man with palpitations and ventricular ectopic beats. Key differences between Uhl's anomaly and ARVD/C are described. Uhl's anomaly is a rare congenital disorder characterized by a thin-walled right ventricle, while ARVD/C is an inherited cardiomyopathy characterized by structural abnormalities and fatty infiltration of the right ventricle myocardium. Diagnostic criteria for ARVD/C include family history, electrocardiogram abnormalities, arrhythmias on monitoring, and structural changes seen on imaging like echocard
The document discusses Brugada Syndrome, which is a genetic heart condition characterized by abnormal ECG patterns that can lead to sudden cardiac death. It provides guidance on diagnosing and managing the disease. The diagnosis is made based on characteristic ECG patterns seen in the right precordial leads. Resuscitated cardiac arrest or cardiac syncope require implantation of an ICD. Asymptomatic patients should be advised of lifestyle measures and genetic testing can help with family screening. Risk stratification of asymptomatic patients considers factors like spontaneous ECG patterns and history of syncope.
Brugada Syndrome is a genetic cardiac condition characterized by abnormal ECG patterns and an increased risk of sudden cardiac death. It is caused by mutations in the SCN5A gene which encodes sodium channels, resulting in conduction abnormalities. The condition is diagnosed based on distinctive ECG patterns, especially Type 1 patterns which are diagnostic. Management involves lifestyle modifications and ICD implantation for high-risk patients based on symptoms and ECG markers. Prognosis depends on risk factors like spontaneous Type 1 patterns or history of cardiac events.
The document discusses sudden cardiac death (SCD) in various populations. It notes that SCD accounts for 12-15% of natural deaths and almost 90% have cardiac causes. The peak ages for SCD are within the first year of life and between 45-75 years. The most common causes of SCD in children are congenital heart defects while in those over 35 it is coronary heart disease. Rare causes like hypertrophic cardiomyopathy also contribute to SCD in young adults. Exercise-related SCD is often due to congenital anomalies or premature heart disease in young and older athletes respectively.
Brugada syndrome is a genetic heart condition characterized by abnormal ECG patterns and risk of sudden cardiac death. It is caused by mutations in genes encoding sodium channels. The condition is diagnosed through ECG showing ST segment elevation in leads V1-V3. Treatment involves implanting an ICD to detect and treat lethal arrhythmias with shocks. Prognosis depends on risk stratification and treatment.
This document presents a case study of a 33-year-old man admitted to the coronary care unit with chest pain. His electrocardiogram shows a type 1 Brugada pattern, suggestive of Brugada syndrome. Immediate management includes physical examination and cardiac monitoring. Further investigations like imaging and genetic testing aim to confirm the diagnosis and exclude other causes. Risk stratification for Brugada syndrome considers factors like history of syncope, electrocardiogram pattern, and response to programmed stimulation. Long-term advice centers on avoiding triggers that increase arrhythmia risk, such as certain drugs and fever.
Sudden cardiac death in structurally normal heartsYasmeen Kamal
Potential causes of sudden cardiac death without structural heart disease include long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome, early repolarization syndrome, idiopathic ventricular fibrillation, commotio cordis, and familial sudden cardiac death. These conditions are often genetic and can result in fatal arrhythmias. Evaluation of survivors and families of victims is important to determine the cause and provide appropriate treatment such as an implantable cardioverter-defibrillator.
Brugada Syndrome is a inherited sodium channel disorder leading to life threatening ventricular fibrillation in young population. diagnosis and ICD therapy could be life saving.
This document discusses Uhl's anomaly and arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). It presents a case study of a 50-year-old man with palpitations and ventricular ectopic beats. Key differences between Uhl's anomaly and ARVD/C are described. Uhl's anomaly is a rare congenital disorder characterized by a thin-walled right ventricle, while ARVD/C is an inherited cardiomyopathy characterized by structural abnormalities and fatty infiltration of the right ventricle myocardium. Diagnostic criteria for ARVD/C include family history, electrocardiogram abnormalities, arrhythmias on monitoring, and structural changes seen on imaging like echocard
The document discusses Brugada Syndrome, which is a genetic heart condition characterized by abnormal ECG patterns that can lead to sudden cardiac death. It provides guidance on diagnosing and managing the disease. The diagnosis is made based on characteristic ECG patterns seen in the right precordial leads. Resuscitated cardiac arrest or cardiac syncope require implantation of an ICD. Asymptomatic patients should be advised of lifestyle measures and genetic testing can help with family screening. Risk stratification of asymptomatic patients considers factors like spontaneous ECG patterns and history of syncope.
Brugada Syndrome is a genetic cardiac condition characterized by abnormal ECG patterns and an increased risk of sudden cardiac death. It is caused by mutations in the SCN5A gene which encodes sodium channels, resulting in conduction abnormalities. The condition is diagnosed based on distinctive ECG patterns, especially Type 1 patterns which are diagnostic. Management involves lifestyle modifications and ICD implantation for high-risk patients based on symptoms and ECG markers. Prognosis depends on risk factors like spontaneous Type 1 patterns or history of cardiac events.
The document discusses sudden cardiac death (SCD) in various populations. It notes that SCD accounts for 12-15% of natural deaths and almost 90% have cardiac causes. The peak ages for SCD are within the first year of life and between 45-75 years. The most common causes of SCD in children are congenital heart defects while in those over 35 it is coronary heart disease. Rare causes like hypertrophic cardiomyopathy also contribute to SCD in young adults. Exercise-related SCD is often due to congenital anomalies or premature heart disease in young and older athletes respectively.
Brugada syndrome is a genetic heart condition characterized by abnormal ECG patterns and risk of sudden cardiac death. It is caused by mutations in genes encoding sodium channels. The condition is diagnosed through ECG showing ST segment elevation in leads V1-V3. Treatment involves implanting an ICD to detect and treat lethal arrhythmias with shocks. Prognosis depends on risk stratification and treatment.
This document presents a case study of a 33-year-old man admitted to the coronary care unit with chest pain. His electrocardiogram shows a type 1 Brugada pattern, suggestive of Brugada syndrome. Immediate management includes physical examination and cardiac monitoring. Further investigations like imaging and genetic testing aim to confirm the diagnosis and exclude other causes. Risk stratification for Brugada syndrome considers factors like history of syncope, electrocardiogram pattern, and response to programmed stimulation. Long-term advice centers on avoiding triggers that increase arrhythmia risk, such as certain drugs and fever.
This document provides information on a case of Brugada syndrome in a 70-year-old female patient. Key details include:
- The patient presented with a month of fever and breathlessness and was referred for ECG changes. Exams found wheezing and tremors.
- Tests included a normal echocardiogram and negative troponin. A Holter monitor found no arrhythmias.
- The document then provides background on Brugada syndrome, including its genetic basis, ECG patterns, diagnosis, management with ICDs and drugs, and drugs to avoid due to risk of arrhythmias.
Brugada Syndrome was first described in 1992 and is characterized by ST-segment elevation in the right precordial leads and risk of sudden cardiac death. It is caused by mutations that result in loss of function of the cardiac sodium channel. Diagnosis requires a type 1 ECG pattern with coved ST elevation of ≥2 mm in ≥1 right precordial lead, either spontaneously or after sodium channel blocker administration. Implantable cardioverter defibrillator placement is the primary treatment for those who experience symptoms or induced arrhythmias due to high risk of sudden death. Lifestyle modifications and sodium channel blockers like quinidine may also be used for prevention and treatment of arrhythmias.
This document discusses channelopathies, focusing on Brugada syndrome and long QT syndrome. It describes:
- The types of channelopathies including Brugada syndrome, long QT syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia.
- The ion channel mutations that cause each condition, such as loss of function mutations in SCN5A causing Brugada syndrome and gain of function mutations in SCN5A causing long QT syndrome type 3.
- The clinical features, diagnosis, and management of Brugada syndrome and long QT syndrome. Risk stratification and indications for ICD placement are also covered.
This document provides an overview of sudden cardiac death, including its definition, epidemiology, risk factors, etiologies, clinical features, management, and prevention. Some key points include:
- Sudden cardiac death is defined as natural death from cardiac causes within 1 hour of symptom onset. It accounts for about 50% of cardiovascular deaths.
- Risk factors include increasing age, male sex, coronary heart disease, smoking, elevated cholesterol, emotional stress, depression, low socioeconomic status, and left ventricular dysfunction.
- Transient factors like ischemia, electrolyte abnormalities, drugs, and autonomic influences can trigger lethal arrhythmias in those with underlying structural heart issues. Antiarrhythmic drugs in particular carry
Long QT Syndrome is a genetic disorder characterized by a prolonged QT interval on electrocardiogram (ECG) and risk of ventricular arrhythmias. It can be congenital due to mutations in ion channel genes or acquired due to certain medications. Clinical presentation includes syncope, seizures or cardiac arrest triggered by exertion or emotions. Diagnosis involves measuring the corrected QT interval on ECG. Treatment involves beta blockers, left cardiac sympathetic denervation, implantable cardioverter-defibrillator or targeted pharmacology depending on risk factors. Prognosis is poor without treatment but can be improved with medications and devices.
This document discusses different types of channelopathies, which are inherited arrhythmogenic diseases caused by mutations in ion channel genes. It summarizes the definitions, epidemiology, clinical manifestations, risk stratification approaches, and management recommendations for several major channelopathies:
- Long QT syndrome is associated with prolonged cardiac repolarization and can cause syncope or cardiac arrest. Risk stratification considers clinical factors and genetic testing, and management includes beta-blockers and ICDs.
- Brugada syndrome causes ST segment elevation and is a common cause of sudden cardiac death. Risk is assessed based on symptoms and ECG patterns, and ICDs are often recommended for high-risk patients.
- Cate
This document provides an overview of various cardiac arrhythmia syndromes including Brugada syndrome, long QT syndrome, short QT syndrome, arrhythmogenic right ventricular dysplasia, Wolff-Parkinson-White syndrome, and hypertrophic cardiomyopathy. It discusses the clinical features, ECG findings, diagnostic criteria, and disposition for each condition. Key advice includes carefully examining leads V1-V3 for abnormalities, being aware of rare conditions like short QT syndrome, and consulting cardiology when these complex syndromes are suspected.
IDENTIFICATION AND APPROACH TO BRADYARRHYTHMIAS .pptxDr Dravid m c
Explanation of SA Nodal and AV nodal block , ECG changes , identification clinical features and presentation of patients to emergency department, their approach and medical linea of treatment
Brugada Syndrome is a genetic cardiac condition characterized by abnormal ECG patterns and risk of sudden cardiac death. It is caused by mutations in the SCN5A gene which encodes cardiac sodium channels. Patients typically present with syncope or sudden death and have a distinctive pattern on ECG of ST segment elevation in leads V1-V3. Risk stratification focuses on history of symptoms like syncope as inducible arrhythmias on electrophysiological study have poor predictive value. Treatment involves medical management with quinidine or device therapy with an ICD for high-risk patients. Lifestyle modifications like avoiding fever or medications that affect sodium channels are also recommended.
Basic science and forensic pathology aspects of cardiac conduction system dis...Luchengam
This document provides an overview of cardiac conduction system disorders from both a basic science and forensic pathology perspective. It discusses arrhythmias, their causes, types and potential symptoms. Sudden cardiac death is also examined, with the most common cause being coronary artery disease. Non-atherosclerotic causes are more prevalent in younger victims and can include channelopathies, cardiomyopathies and other structural abnormalities. The morphology of sudden cardiac death is outlined, with most cases associated with significant coronary atherosclerosis but acute myocardial infarction only present in a minority of cases. Forensic examination of the cardiac conduction system can provide insights into underlying causes of death in select circumstances.
This document discusses sudden cardiac death (SCD), providing information on:
- SCD is an unexpected death from cardiac causes within one hour of symptoms. It often occurs in people with known or unknown heart disease.
- Autopsies show most SCD victims had prior heart attacks or coronary artery disease. About 92% of SCD victims do not survive.
- Risk factors for SCD include age, male sex, family history of heart disease, smoking, diabetes, and high blood pressure. EKG abnormalities like prolonged QT also increase risk.
- Causes of SCD include coronary artery disease, cardiomyopathies, genetic conditions, and electrical issues in the heart. The most common mechanism is
MOLECULAR ASPECTS OF CARDIAC CHANNELOPATHIESmukund joshi
This document discusses cardiac channelopathies, which are clinical syndromes that affect the cardiovascular electrical system due to mutations in genes encoding ion channels. Some examples of channelopathies mentioned are long QT syndrome, short QT syndrome, and Brugada syndrome. The prevalence of channelopathies in the general population is estimated to be between 1 in 2000 to 1 in 3000. Interpreting genetic testing results for channelopathies can be challenging given limitations such as many mutations being unknown or private to families. Future research directions discussed include gaining more understanding of genetic structures and phenotypes of channelopathies and developing new diagnostic and gene-specific treatment strategies.
The Long QT Syndrome: Overview and Management The Long QT Syndrome: Overvie...MedicineAndFamily
Long QT Syndrome is a genetic disorder characterized by a prolonged QT interval on electrocardiogram that can cause dangerous arrhythmias and sudden cardiac death. Symptoms include unexplained fainting, seizures, or sudden death, especially with exercise or emotions. Treatment involves beta blockers, implantable cardioverter defibrillators, or left stellate ganglionectomy depending on risk level and genotype. Ongoing research seeks to better understand genotype-phenotype relationships and develop mutation-specific therapies.
This document discusses the classification and management of ventricular arrhythmias. It is divided into sections on classification by clinical presentation, electrocardiography, disease entity. Management of VT in structurally abnormal hearts is discussed, including those related to coronary artery disease, dilated cardiomyopathy, bundle branch reentrant tachycardia, arrhythmogenic right ventricular dysplasia, and other conditions. Clinical presentation, mechanisms, diagnostic testing, and treatment options are summarized for each condition.
Brugada Syndrome is a genetic disorder characterized by abnormal ECG patterns and increased risk of ventricular arrhythmias. It is caused by mutations in genes encoding sodium channels. Typical ECG findings include ST elevation in leads V1-V3. Risk factors include spontaneous type 1 ECG pattern, family history of sudden cardiac death, and inducible arrhythmias on electrophysiology study. Diagnosis requires type 1 ECG pattern plus symptoms or family history of events.
Cardiac channelopathies are genetic disorders characterized by altered cardiac excitability without structural heart involvement. Major channelopathies include long QT syndrome (LQTS), Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), and short QT syndrome. LQTS results from mutations affecting genes controlling myocardial cell excitability and commonly involves potassium channel genes. It presents with prolonged QT interval and symptoms include syncope. Treatment involves beta-blockers and ICD implantation in high-risk patients. Brugada syndrome causes a distinctive ECG pattern and risk of sudden cardiac death. CPVT causes adrenergic-dependent ventricular arrhythmias during exercise or stress.
How to recognise and manage idiopathic ventricular tachycardia (nhịp nhanh thất)SoM
This document summarizes common forms of idiopathic ventricular tachycardia. It discusses how right ventricular outflow tract VT and left ventricular outflow tract VT are the most common forms, often presenting as nonsustained, repetitive monomorphic VT in younger patients. Treatment may include medications like beta-blockers or verapamil, but catheter ablation has over a 90% success rate. Distinguishing idiopathic VT from other conditions is important as treatment differs. The prognosis is generally excellent for idiopathic VT patients.
Brugada Syndrome is a genetic cardiac condition characterized by an abnormal ECG pattern and increased risk of sudden cardiac death. It is caused by mutations that result in loss of function of cardiac ion channels, most commonly sodium channels encoded by SCN5A. The ECG typically shows ST segment elevation in leads V1-V3. Brugada Syndrome presents variably from asymptomatic to sudden cardiac death, usually during sleep. Drug challenges may help diagnose when the ECG is unclear. An ICD is recommended for those with symptoms or inducible arrhythmias on electrophysiological study to prevent sudden death.
Sudden cardiac death is defined as natural death from cardiac causes that occurs abruptly within one hour of the onset of symptoms. It accounts for about 50% of cardiovascular deaths with an annual incidence of 250,000 cases in the US and 7 lakh cases in India. Risk factors include increasing age, male sex, and underlying heart diseases such as coronary artery disease, cardiomyopathies, and cardiac channelopathies. Management involves cardiopulmonary resuscitation, defibrillation if ventricular fibrillation is detected, and administration of antiarrhythmic drugs. Strategies for prevention include implantable cardioverter-defibrillators, catheter ablation, antiarrhythmic medications like beta-blockers, and surgical interventions tailored to
This document provides information on a case of Brugada syndrome in a 70-year-old female patient. Key details include:
- The patient presented with a month of fever and breathlessness and was referred for ECG changes. Exams found wheezing and tremors.
- Tests included a normal echocardiogram and negative troponin. A Holter monitor found no arrhythmias.
- The document then provides background on Brugada syndrome, including its genetic basis, ECG patterns, diagnosis, management with ICDs and drugs, and drugs to avoid due to risk of arrhythmias.
Brugada Syndrome was first described in 1992 and is characterized by ST-segment elevation in the right precordial leads and risk of sudden cardiac death. It is caused by mutations that result in loss of function of the cardiac sodium channel. Diagnosis requires a type 1 ECG pattern with coved ST elevation of ≥2 mm in ≥1 right precordial lead, either spontaneously or after sodium channel blocker administration. Implantable cardioverter defibrillator placement is the primary treatment for those who experience symptoms or induced arrhythmias due to high risk of sudden death. Lifestyle modifications and sodium channel blockers like quinidine may also be used for prevention and treatment of arrhythmias.
This document discusses channelopathies, focusing on Brugada syndrome and long QT syndrome. It describes:
- The types of channelopathies including Brugada syndrome, long QT syndrome, short QT syndrome, and catecholaminergic polymorphic ventricular tachycardia.
- The ion channel mutations that cause each condition, such as loss of function mutations in SCN5A causing Brugada syndrome and gain of function mutations in SCN5A causing long QT syndrome type 3.
- The clinical features, diagnosis, and management of Brugada syndrome and long QT syndrome. Risk stratification and indications for ICD placement are also covered.
This document provides an overview of sudden cardiac death, including its definition, epidemiology, risk factors, etiologies, clinical features, management, and prevention. Some key points include:
- Sudden cardiac death is defined as natural death from cardiac causes within 1 hour of symptom onset. It accounts for about 50% of cardiovascular deaths.
- Risk factors include increasing age, male sex, coronary heart disease, smoking, elevated cholesterol, emotional stress, depression, low socioeconomic status, and left ventricular dysfunction.
- Transient factors like ischemia, electrolyte abnormalities, drugs, and autonomic influences can trigger lethal arrhythmias in those with underlying structural heart issues. Antiarrhythmic drugs in particular carry
Long QT Syndrome is a genetic disorder characterized by a prolonged QT interval on electrocardiogram (ECG) and risk of ventricular arrhythmias. It can be congenital due to mutations in ion channel genes or acquired due to certain medications. Clinical presentation includes syncope, seizures or cardiac arrest triggered by exertion or emotions. Diagnosis involves measuring the corrected QT interval on ECG. Treatment involves beta blockers, left cardiac sympathetic denervation, implantable cardioverter-defibrillator or targeted pharmacology depending on risk factors. Prognosis is poor without treatment but can be improved with medications and devices.
This document discusses different types of channelopathies, which are inherited arrhythmogenic diseases caused by mutations in ion channel genes. It summarizes the definitions, epidemiology, clinical manifestations, risk stratification approaches, and management recommendations for several major channelopathies:
- Long QT syndrome is associated with prolonged cardiac repolarization and can cause syncope or cardiac arrest. Risk stratification considers clinical factors and genetic testing, and management includes beta-blockers and ICDs.
- Brugada syndrome causes ST segment elevation and is a common cause of sudden cardiac death. Risk is assessed based on symptoms and ECG patterns, and ICDs are often recommended for high-risk patients.
- Cate
This document provides an overview of various cardiac arrhythmia syndromes including Brugada syndrome, long QT syndrome, short QT syndrome, arrhythmogenic right ventricular dysplasia, Wolff-Parkinson-White syndrome, and hypertrophic cardiomyopathy. It discusses the clinical features, ECG findings, diagnostic criteria, and disposition for each condition. Key advice includes carefully examining leads V1-V3 for abnormalities, being aware of rare conditions like short QT syndrome, and consulting cardiology when these complex syndromes are suspected.
IDENTIFICATION AND APPROACH TO BRADYARRHYTHMIAS .pptxDr Dravid m c
Explanation of SA Nodal and AV nodal block , ECG changes , identification clinical features and presentation of patients to emergency department, their approach and medical linea of treatment
Brugada Syndrome is a genetic cardiac condition characterized by abnormal ECG patterns and risk of sudden cardiac death. It is caused by mutations in the SCN5A gene which encodes cardiac sodium channels. Patients typically present with syncope or sudden death and have a distinctive pattern on ECG of ST segment elevation in leads V1-V3. Risk stratification focuses on history of symptoms like syncope as inducible arrhythmias on electrophysiological study have poor predictive value. Treatment involves medical management with quinidine or device therapy with an ICD for high-risk patients. Lifestyle modifications like avoiding fever or medications that affect sodium channels are also recommended.
Basic science and forensic pathology aspects of cardiac conduction system dis...Luchengam
This document provides an overview of cardiac conduction system disorders from both a basic science and forensic pathology perspective. It discusses arrhythmias, their causes, types and potential symptoms. Sudden cardiac death is also examined, with the most common cause being coronary artery disease. Non-atherosclerotic causes are more prevalent in younger victims and can include channelopathies, cardiomyopathies and other structural abnormalities. The morphology of sudden cardiac death is outlined, with most cases associated with significant coronary atherosclerosis but acute myocardial infarction only present in a minority of cases. Forensic examination of the cardiac conduction system can provide insights into underlying causes of death in select circumstances.
This document discusses sudden cardiac death (SCD), providing information on:
- SCD is an unexpected death from cardiac causes within one hour of symptoms. It often occurs in people with known or unknown heart disease.
- Autopsies show most SCD victims had prior heart attacks or coronary artery disease. About 92% of SCD victims do not survive.
- Risk factors for SCD include age, male sex, family history of heart disease, smoking, diabetes, and high blood pressure. EKG abnormalities like prolonged QT also increase risk.
- Causes of SCD include coronary artery disease, cardiomyopathies, genetic conditions, and electrical issues in the heart. The most common mechanism is
MOLECULAR ASPECTS OF CARDIAC CHANNELOPATHIESmukund joshi
This document discusses cardiac channelopathies, which are clinical syndromes that affect the cardiovascular electrical system due to mutations in genes encoding ion channels. Some examples of channelopathies mentioned are long QT syndrome, short QT syndrome, and Brugada syndrome. The prevalence of channelopathies in the general population is estimated to be between 1 in 2000 to 1 in 3000. Interpreting genetic testing results for channelopathies can be challenging given limitations such as many mutations being unknown or private to families. Future research directions discussed include gaining more understanding of genetic structures and phenotypes of channelopathies and developing new diagnostic and gene-specific treatment strategies.
The Long QT Syndrome: Overview and Management The Long QT Syndrome: Overvie...MedicineAndFamily
Long QT Syndrome is a genetic disorder characterized by a prolonged QT interval on electrocardiogram that can cause dangerous arrhythmias and sudden cardiac death. Symptoms include unexplained fainting, seizures, or sudden death, especially with exercise or emotions. Treatment involves beta blockers, implantable cardioverter defibrillators, or left stellate ganglionectomy depending on risk level and genotype. Ongoing research seeks to better understand genotype-phenotype relationships and develop mutation-specific therapies.
This document discusses the classification and management of ventricular arrhythmias. It is divided into sections on classification by clinical presentation, electrocardiography, disease entity. Management of VT in structurally abnormal hearts is discussed, including those related to coronary artery disease, dilated cardiomyopathy, bundle branch reentrant tachycardia, arrhythmogenic right ventricular dysplasia, and other conditions. Clinical presentation, mechanisms, diagnostic testing, and treatment options are summarized for each condition.
Brugada Syndrome is a genetic disorder characterized by abnormal ECG patterns and increased risk of ventricular arrhythmias. It is caused by mutations in genes encoding sodium channels. Typical ECG findings include ST elevation in leads V1-V3. Risk factors include spontaneous type 1 ECG pattern, family history of sudden cardiac death, and inducible arrhythmias on electrophysiology study. Diagnosis requires type 1 ECG pattern plus symptoms or family history of events.
Cardiac channelopathies are genetic disorders characterized by altered cardiac excitability without structural heart involvement. Major channelopathies include long QT syndrome (LQTS), Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), and short QT syndrome. LQTS results from mutations affecting genes controlling myocardial cell excitability and commonly involves potassium channel genes. It presents with prolonged QT interval and symptoms include syncope. Treatment involves beta-blockers and ICD implantation in high-risk patients. Brugada syndrome causes a distinctive ECG pattern and risk of sudden cardiac death. CPVT causes adrenergic-dependent ventricular arrhythmias during exercise or stress.
How to recognise and manage idiopathic ventricular tachycardia (nhịp nhanh thất)SoM
This document summarizes common forms of idiopathic ventricular tachycardia. It discusses how right ventricular outflow tract VT and left ventricular outflow tract VT are the most common forms, often presenting as nonsustained, repetitive monomorphic VT in younger patients. Treatment may include medications like beta-blockers or verapamil, but catheter ablation has over a 90% success rate. Distinguishing idiopathic VT from other conditions is important as treatment differs. The prognosis is generally excellent for idiopathic VT patients.
Brugada Syndrome is a genetic cardiac condition characterized by an abnormal ECG pattern and increased risk of sudden cardiac death. It is caused by mutations that result in loss of function of cardiac ion channels, most commonly sodium channels encoded by SCN5A. The ECG typically shows ST segment elevation in leads V1-V3. Brugada Syndrome presents variably from asymptomatic to sudden cardiac death, usually during sleep. Drug challenges may help diagnose when the ECG is unclear. An ICD is recommended for those with symptoms or inducible arrhythmias on electrophysiological study to prevent sudden death.
Sudden cardiac death is defined as natural death from cardiac causes that occurs abruptly within one hour of the onset of symptoms. It accounts for about 50% of cardiovascular deaths with an annual incidence of 250,000 cases in the US and 7 lakh cases in India. Risk factors include increasing age, male sex, and underlying heart diseases such as coronary artery disease, cardiomyopathies, and cardiac channelopathies. Management involves cardiopulmonary resuscitation, defibrillation if ventricular fibrillation is detected, and administration of antiarrhythmic drugs. Strategies for prevention include implantable cardioverter-defibrillators, catheter ablation, antiarrhythmic medications like beta-blockers, and surgical interventions tailored to
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
Cell Therapy Expansion and Challenges in Autoimmune DiseaseHealth Advances
There is increasing confidence that cell therapies will soon play a role in the treatment of autoimmune disorders, but the extent of this impact remains to be seen. Early readouts on autologous CAR-Ts in lupus are encouraging, but manufacturing and cost limitations are likely to restrict access to highly refractory patients. Allogeneic CAR-Ts have the potential to broaden access to earlier lines of treatment due to their inherent cost benefits, however they will need to demonstrate comparable or improved efficacy to established modalities.
In addition to infrastructure and capacity constraints, CAR-Ts face a very different risk-benefit dynamic in autoimmune compared to oncology, highlighting the need for tolerable therapies with low adverse event risk. CAR-NK and Treg-based therapies are also being developed in certain autoimmune disorders and may demonstrate favorable safety profiles. Several novel non-cell therapies such as bispecific antibodies, nanobodies, and RNAi drugs, may also offer future alternative competitive solutions with variable value propositions.
Widespread adoption of cell therapies will not only require strong efficacy and safety data, but also adapted pricing and access strategies. At oncology-based price points, CAR-Ts are unlikely to achieve broad market access in autoimmune disorders, with eligible patient populations that are potentially orders of magnitude greater than the number of currently addressable cancer patients. Developers have made strides towards reducing cell therapy COGS while improving manufacturing efficiency, but payors will inevitably restrict access until more sustainable pricing is achieved.
Despite these headwinds, industry leaders and investors remain confident that cell therapies are poised to address significant unmet need in patients suffering from autoimmune disorders. However, the extent of this impact on the treatment landscape remains to be seen, as the industry rapidly approaches an inflection point.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central19various
Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central Clinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa CentralClinic ^%[+27633867063*Abortion Pills For Sale In Tembisa Central
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Local Advanced Lung Cancer: Artificial Intelligence, Synergetics, Complex Sys...Oleg Kshivets
Overall life span (LS) was 1671.7±1721.6 days and cumulative 5YS reached 62.4%, 10 years – 50.4%, 20 years – 44.6%. 94 LCP lived more than 5 years without cancer (LS=2958.6±1723.6 days), 22 – more than 10 years (LS=5571±1841.8 days). 67 LCP died because of LC (LS=471.9±344 days). AT significantly improved 5YS (68% vs. 53.7%) (P=0.028 by log-rank test). Cox modeling displayed that 5YS of LCP significantly depended on: N0-N12, T3-4, blood cell circuit, cell ratio factors (ratio between cancer cells-CC and blood cells subpopulations), LC cell dynamics, recalcification time, heparin tolerance, prothrombin index, protein, AT, procedure type (P=0.000-0.031). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and N0-12 (rank=1), thrombocytes/CC (rank=2), segmented neutrophils/CC (3), eosinophils/CC (4), erythrocytes/CC (5), healthy cells/CC (6), lymphocytes/CC (7), stick neutrophils/CC (8), leucocytes/CC (9), monocytes/CC (10). Correct prediction of 5YS was 100% by neural networks computing (error=0.000; area under ROC curve=1.0).
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
A proprietary approach developed by bringing together the best of learning theories from Psychology, design principles from the world of visualization, and pedagogical methods from over a decade of training experience, that enables you to: Learn better, faster!
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Our backs are like superheroes, holding us up and helping us move around. But sometimes, even superheroes can get hurt. That’s where slip discs come in.
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd...Donc Test
TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version TEST BANK For Community and Public Health Nursing: Evidence for Practice, 3rd Edition by DeMarco, Walsh, Verified Chapters 1 - 25, Complete Newest Version Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Study Guide Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Stuvia Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Test Bank For Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Pdf Download Course Hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Answers Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Ebook Download Course hero Community and Public Health Nursing: Evidence for Practice 3rd Edition Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Chapters Download Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Pdf Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Study Guide Questions and Answers Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Ebook Download Stuvia Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Questions Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Studocu Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Quizlet Community and Public Health Nursing: Evidence for Practice 3rd Edition Test Bank Stuvia
2. INTRODUCTION
• Group of inherited arrhythmogenic diseases (IADs)
caused by mutation on genes encoding for ion channel
proteins and proteins that regulate ion channels.
• Potentially lethal and inheritable arrhythmia syndromes
with the propensity to produce fatal arrhythmias in the
setting of a structurally normal heart can occur.
3. • There is Incomplete penetrance and variable expressivity -
distinctive ECG patterns may be concealed.
• Although rare, they are potentially fatal but preventable
causes of sudden cardiac death (SCD).
• In fact, it is now recognized that almost one third of autopsy-
negative sudden unexplained death (SUD) in young persons
and approximately 10% of sudden infant death syndrome
(SIDS) stem from these genetically inherited cardiac
channelopathies.
4. • Comprehensive management include diagnosing and
treating the proband and identifying and protecting
affected family members.
• Accurate diagnosis is of critical importance based on
history and ECG findings.
• Molecular advances in the field of cardiovascular
genetics have uncovered the underlying genetic basis
responsible for many inherited cardiac arrhythmia
syndromes.
• Theoretically, genetic testing is the “gold standard” to
determine the preventive and follow-up plan, therapeutic
strategy and prognostic estimation for these patients.
7. Ion Channel Mutations
Loss of Function
SCN5A Brugada
IKs LQT1
IKr LQT2
Gain of Function
SCN5A LQT3
IKs ShortQT
IKr ShortQT
4
0
1 2
3
Na
Ca > Na
IKr & IKs
(Ito)
IK1
4
8. Brugada syndrome (BrS)
• Brugada syndrome (BrS) is an heritable arrhythmia syndrome
characterized by an ECG pattern consisting of coved-type ST-
segment elevation (≥2 mm) followed by a negative T wave in
the right precordial leads V1 through V3 (often referred to as
type 1 Brugada ECG pattern) .
• There is increased risk for SCD resulting from episodes of
polymorphic ventricular tachyarrhythmias.
• The penetrance and expressivity of the disorder are highly
variable, ranging from lifelong asymptomatic individuals to
SCD during the first year of life.
9. • BrS is generally considered a disorder involving young
male adults, greatest among Southeast Asian men.
• The arrhythmogenic manifestation first occurring at an
average age of 40 years.
• However, BrS has been demonstrated in children and
infants.
• Prevalence- 1–5 per 10,000 worldwide [highest
in Southeast Asia]
• SCD typically occurs during sleep.
12. Genetic Basis
• BrS is inherited as an autosomal dominant trait, although
more than half of BrS cases may be sporadic.
• Approximately 20% to 30% of BrS cases result from loss-of-
function mutations in the SCN5A-encoded cardiac sodium
channel and are classified as Brugada syndrome type 1
(BrS1).
• To date, 18 genes have been implicated in BrS pathogenicity,
but only SCN5A shows a significant contribution to the
disease.
14. Pathophysiology
•Decreases in the inward
sodium(INa)
•And increases in
the outward (Ito)potassium
current produce the BrS
phenotype.
15. Pathophysiology
■ RV epicardium Ito conc. is
maximum, hence there is brugada
pattern Action potential notch in
Right sided leads.
■ Since there is an increased
contribution of the transient
outward current (Ito) in this area,
this discriminating
electrophysiological mechanism
has been thought to be associated
with ST- segment elevation
(Jwave) and T wave inversion in
BrS.
■ Prolongation of repolarization in
the right ventricular epicardial
(Epi), but not endocardial (Endo),
cells results in T-wave inversion in
the surface electrocardiogram .
16. Mechanism of arrhythmia in Brugada Syndrome
• Phase 2 reentry has been
implicated in the genesis of
VT-VF associated with
Brugada syndrome.
• Heterogeneous loss of the
action potential dome during
the plateau phase (phase 2) in
the right ventricular
epicardium, leads to a
marked dispersion of
repolarization and
refractoriness and the
potential for phase 2 reentry.
17. Reentry
• Electrical activity during each normal cardiac cycle begins in
the sinoatrial node and continues until the entire heart has
been activated.
• Each cell becomes activated in turn, and the cardiac
impulse dies out when all fibers have been discharged and
are completely refractory.
• During this absolute refractory period, the cardiac impulse
has “no place to go.”
• It must be extinguished and restarted by the next sinus
impulse.
• If, however, a group of fibers not activated during the initial
wave of depolarization recovers excitability in time to be
reactivated before the impulse dies out, the fibers may
serve as a link to reexcite areas that were just discharged
and have now recovered from the initial depolarization.
18. Diagnosis
Type 1 pattern pronounced elevation of
the J point
coved – type ST- segment elevation >2 mm
changes in > 1 right precordial lead (V1 to
V3),
placed in the second, third, or fourth
intercostal space,
occurring spontaneously is diagnostic.
19. Diagnosis
Only type 1 is diagnostic of BrS.
•Type 2 and Type 3 a type 2 or 3 pattern
is only diagnostic when it converts to a type
1 pattern with class I drug provocation
with one additional clinical feature:
• documented VF or VT,
•syncope of probable arrhythmic cause,
•family history of SCD before age 45,
•family history of Brugada type 1
pattern, or
•nocturnal agonal respirations.
20. Drug Challange
■ Pharmacological provocation should only be performed
when the baseline ECG is not diagnostic of BS (in the
absence of a diagnostic type 1 ECG pattern ).
■ Intravenous administration of Na+ channel blocking drugs
like ajmaline, flecainide and procainamide, are useful in
bringing out Type 1 Brugada pattern on the ECG when ECG
changes are not diagnostic.
■ There is no advantage of performing it in the presence of
Type 1 BS pattern in the baseline ECG.
■ Drug administration should be stopped if:
■ Type 1 pattern becomes apparent on the
ECG
■ Patient develops ventricular arrhythmias
■ QRS widens to 130% of the baseline
21.
22. Role of EP study in BS
• EPS to risk-stratify patients remain controversial.
• EPS may be considered in asymptomatic patients with type 1
Brugada pattern.
• An ICD should be considered if such a patient has inducible
VT/VF with two or less extrastimuli.
Genetic Testing
• Mutations in SCN5A account for 18% to 28% of BrS cases,
voltage-gated calcium channel accounting for about another
13%.
• A variety of mutations in other genes have been rarely
reported.
• Genetic testing may not be helpful in risk stratification,
• although it can be helpful in family screening if there is an
identifiable causative mutation.
23. Risk stratification
HIGH RISK GROUP
•A spontaneous ECG pattern of BrS (type 1),
•a history of syncope,
•Patients presenting with aborted sudden death
•Atrial fibrillation and QRS fragmentation
25. Management
Avoid
■ A febrile state
■ hyperkalemia
■ class ia antiarrhythmic drugs
■ Vagotonic agents
■ Beta- adrenergic antagonists
■ Tricyclic antidepressants
■ Antihistamines
■ Cocaine
all can induce ECG aggravation andVT/VF
26. Management
ICD implantation is warranted in patients with BrS with
• Aborted SCD or spontaneous VT/VF (class I indication) or
• with a history of syncope (class IIa).
• ICD implantation may be considered in patients with a type 1
ECG pattern and inducible VT/VF with two or less extrastimuli
on EPS.
27. • Ablation in the epicardium of the anterior RV outflow tract
can normalize the ECG and suppress VT, eliminating the Ito-
rich area.
• Ablation may be considered in patients with frequent ICD
shocks (class IIb).
• Quinidine can normalize the ECG and suppress the VT,
presumably by blocking the transient outward potassium
current (Ito), or perhaps a late sodium current.
• Quinidine has been effective in patients with frequent or
storms of VT/VF on ICD (Class IIb). and
• in patients who qualify for an ICD but either refuse or are
otherwise contraindicated (class IIa).
28. • In patients with VT storm secondary to Brugada
syndrome, low-dose isoproterenol can also be
effective in suppressing the arrhythmia.
30. • Congenital long-QT syndrome (LQTS) comprises a distinct
group of cardiac channelopathies characterized by delayed
repolarization of the myocardium, QT prolongation (QTc
>480 msec as the 50th percentile among individuals with
genetically confirmed LQTS).
• There is increased risk for syncope, seizures, and sudden
cardiac death (SCD) in the setting of a structurally normal
heart and otherwise healthy individual.
• The incidence of LQTS may exceed 1 in 2500 persons.
31. • Individuals with LQTS may or may not manifest QT
prolongation on a resting 12-lead surface electrocardiogram
(ECG).
• Most common presenting symptom: unexplained syncope
• Hallmark arrhythmia: Torsade de pointesVT
• LQTS may explain approximately 20% of autopsy-negative SUD
in young persons and 10% of SIDS cases.
32. Genetic Basis
• LQTS is a genetically heterogeneous disorder largely inherited in an
autosomal dominant pattern, previously known as “Romano-Ward
syndrome.”
• To date, hundreds of mutations have now been identified in 14
LQTS susceptibility genes.
• Approximately 75% of patients with a clinically robust diagnosis of
LQTS host either loss-of-function or gain-of-function mutations in
one of three major LQTS genes
• KCNQ1-encoded Iks potassium channel (LQT1, approximately 35%;
loss of function)
• KCNH2-encoded IKr potassium channel (LQT2, 30%; loss of
function), and
• SCN5A-encoded sodium channel (LQT3, 10%; gain of function).
• Approximately 5% to 10% of patients have multiple mutations in
these genes, and patients with multimutation LQTS present at a
younger age and with greater expressivity.
34. • Patient with the acquired of long QT interval
developing from various drugs may also have an
underlying genetic predisposition .
35. Pathophysiology
■ EAD (R onT VT)
has been implicated
in the genesis of VT-
VF associated with
LQTS.
36. Early After Depolarization(EAD)
■ EAD occurs when large inward current during
platue phase occurs resulting in prolongation of
plateau.This provides time for reactivation of
Ical. It is this second phase of reactivation of
inward Ical that produces EAD by depolarizing
cell membrane.
■ A delicate balance between depolarizing and
repolarizing currents controls the plateaue
phase of theAP.An increase in inward current
and or decrease in outward current may induce
EADs.
■ Example include persistently inward INa in LQT3
and reduced Ikr in LQT2 and Iks in LQT1
■ EADs can trigger a propagated response and
thus elicit an extra beat ,which can initiate a
tachycardia.
39. LQTS: Presentation
■ Most common presenting symptom:
unexplained syncope.
■ Syncope on exertion in pediatric
patients should be considered
malignant until proven otherwise.
■ History & ECG:
– Onset and offset of syncopal episode
– Siblings, or family members with
unexplained syncope or sudden
death
– Family history of “seizures” or congenital deafness
– ProlongedQTc on ECG
40. Triggering Events for
Syncope or SCD
■ 3 main factors contributing to
syncope orSCD
– Exercise (LQT1), especially swimming
– Emotions or emotional stress (LQT2)
– Events occurring
during sleep or at rest,
with or without arousal
(LQT3)
42. • Among the 221 symptomatic LQT1 patients, their first
cardiac event was most often associated with exercise
(62%), followed by emotions (26%), sleep (3%), and
nonspecific (10%) triggers.
• Whereas the 204 symptomatic LQT2 patients most often
had their first event associated with emotions (43%) or
sleep(29%), and only 13% of the symptomatic LQT2
patients had an exercise-induced first event.
• In addition, LQT1 male patients younger than 13 years had
an almost threefold increase in risk for exercise triggered
events, whereas LQT1 females age 13 and older had a 3.5-
fold increase in risk for sleep/rest nonarousal events.
46. Management
• For LQTS patients who don’t have syncope, complex
ventricular arrhythmias, a family history of SCD, or a QTc
interval of 500 milliseconds or more, no therapy or
treatment with a beta blocker is generally recommended.
• In asymptomatic patients but with h/o complex
ventricular arrhythmias, a family history of early SCD, or
a QTc interval of 500 milliseconds or more, beta
adrenoceptor blockers such as nadolol at maximally
tolerated doses are recommended.
47. • For both LQT1 and LQT2 patients, beta blockade was
associated with a pronounced 71% (LQT2 patients) to
78% (LQT1 patients) reduction in the risk for exercise-
triggered cardiac events,
• but had no statistically significant effect on the apparent
risk for arousal- or sleep/rest-triggered events.
• For LQT3 targeting the pathologic late sodium current
with agents such as mexiletine, flecainide, and ranolazine
may represent a gene-specific therapeutic option.
48. • ICD is indicated In patients with syncope or aborted
sudden death.
• These patients should also be treated with concomitant beta
blockers.
• Use of an ICD in patients without syncope but with a long QT
interval and a strong family history of SCD is still controversial.
• Implantation of a permanent pacemaker to prevent the
bradycardia or pauses that may predispose to the
development of TdP may be indicated.
49. • Left-sided cervicothoracic sympathetic
ganglionectomy that interrupts the stellate ganglion and
the first three or four thoracic ganglia may be helpful and can
be done thorascopically.
• For patients with the acquired form and TdP, IV magnesium
and atrial or ventricular pacing are initial choices.
• Avoidance of precipitating drugs is mandatory.
50. Hereditary varients
■ Jervell and Lange-Nielsen syndrome(LQT10):
-most severe variant of LQTS (autosomal
recessive)
-longQT syndrome, associated with severe,
bilateral sensorineural hearing loss
-mutation on KCNQ1 or KCNE1 genes (LQT1- Iks)
- 90% have cardiac event by age 3
-ICD should be seriously considered
51. Andersen tawil syndrome: LQT7
• A rare, multisystem disorder.
• Characteristic triad : periodic paralysis, dysmorphic features,
and ventricular arrhythmias.
• Autosomal dominant , incomplete penetrance.
• The mean age of onset for periodic paralysis- 5 years and 13
years for cardiac symptoms.
• Mutations in KCNJ2 (loss of function of IK1 )
• ECG abnormalities include pronounced QTU prolongation,
prominent U waves, and ventricular ectopy, including
polymorphic ventricular tachycardia (VT), bigeminy, and
bidirectional VT.
52. Timothy syndrome: LQT8
• Timothy syndrome is an extremely rare (<30 patients described
worldwide), multisystem, highly lethal arrhythmia disorder.
• Is associated with both cardiac and extracardiac abnormalities.
• The typical cardiac manifestations of TS include fetal
bradycardia, extreme prolongation of the QT interval (QTc >500
msec) often with macroscopic T wave alternans and 2 : 1 AV
block at birth.
• Extracardiac abnormalities often consist of simple syndactyly
(webbing of toes and fingers), dysmorphic facial features,
abnormal dentition, immune deficiency, severe hypoglycemia,
and developmental delay (including autism).
• Currently, the majority of TS patients die before reaching
puberty.
• Mutations in CACNA1C (gain of function).
53. Ankyrin B Syndrome: LQT4
• Inherited cardiac arrhythmia, with an increased risk for SCD
associated with a prolonged QT interval and severe sinus
bradycardia.
• Loss-of-function mutations of ANK2.
• The ANK2 gene encodes ankyrin B protein, involved in
anchoring the Na+,K+-ATPase, Na+/Ca+ exchanger to
specialized microdomains in the cardiomyocyte transverse
tubules.
54. •Short-QT syndrome (SQTS), is a rare, inheritable
channelopathy characterised by abnormally short
QT interval (usually ≤320 msec), paroxysmal atrial
fibrillation, syncope, and an increased risk for SCD.
•Symptoms, including syncope and cardiac arrest, most
often occurred during periods of rest or sleep.
The typical ECG pattern consists of a QT interval of 320
milliseconds or less (QTc ≤340 msec) and tall, peaked T
waves in the precordial leads with either no or a short ST
segment present.
Short QT Syndrome
55.
56. Genetic Basis
• SQTS is most often inherited in an autosomal dominant
manner.
• 5 genes
• Gain of function mutations in K channel-
KCNH2 [IKr] (SQT1),
KCNQ1 [IKs] (SQT2),
KCNJ2 [IK1] (SQT3)
• Loss of function mutations in ICaL –
CACNA1C (SQT4)
CACNB2b (SQT5)
59. The ion channelopathies that cause SQTS not only abbreviate repolarization but
they significantly increase DISPERSIONOF REPOLARIZATION, thus creating the
cellular basis for both the substrate and trigger necessary for the initiation of
reentry
60. Clinical Presentation
■ Approximately 62% of the patients are symptomatic.
■ Cardiac arrest is the most frequently (34%) reported symptom, and in 28%
of patients it was the first clinical presentation.
■ Palpitations is the second most frequently reported symptom (31%),
followed by syncope (24%).
■ AF is the first presenting symptom in 17% of patients.
■ Strong family history of arrhythmic symptoms includingSCD is a common
finding
■ Many patients had frequent ventricular extrasystoles.
■ Approximately 38% patients were asymptomatic and were diagnosed due to
strong family history.
61. Diagnostic criteria includes
• QTc of 330 milliseconds or less or
• QTc of 360 milliseconds or less and at least one clinical
criterion: pathogenic mutation, family history of SQTS or SCD
before or at age 40, or survival of VT/VF arrest without heart
disease.
• In many patients with SQTS, the QT does not change with the
heart rate, and thus the conventional formulas for QT
correction may not apply to these patients.
• Other causes of SQTS, such as hyperkalemia, hypercalcemia,
hyperthermia, acidosis, and digitalis, should be excluded
62. Management
• ICDs are considered the treatment of choice in symptomatic
patients with SQTS to prevent SCD.
• AADs that prolong refractoriness have reportedly been
effective in some patients.
• In particular, quinidine was effective in patients with a gain-of-
function mutation in the HERG (KCNH2) gene.
63. Cholinergic Polymorphic Ventricular
Tachycardia(CPVT)
■ Lethal familial disease that usually manifests in childhood and
adolescence
■ Mortality among untreated patients is up to 30% by the age of
40yrs,SCD may be first presentation.
■ Stress induced or adrenergically-mediated bidirectional ventricular
tachycardia (biVT) or PMVT leading to syncope and/orSCD
■ Structurally intact heart and no ECG changes at rest.
■ Induced by exercise especially swimming
64. • Age of first presentation can range from infancy to 40
years.
• CPVT is potential lethality.
• There is presence of a positive family history of young
(<40 years) SCD for more than one third of CPVT
individuals and in as many as 60% of families hosting the
pathologic mutations.
• Moreover, approximately 15% of autopsy-negative SUD
in young persons and some cases of SIDS have been
attributed to CPVT.
65. Genetic Basis
• Inherited in an autosomal dominant
manner.
• Mutations in the RYR2-encoded
cardiac ryanodine receptor/calcium
release channel represent the most
common genetic subtype of CPVT
(CPVT1), accounting for 60% of
cases.
• Gain-of-function mutations in
RYR2 lead to leaky calcium release
channels and excessive calcium
release, particularly during
sympathetic stimulation that can
precipitate calcium overload,
delayed depolarizations, and
ventricular arrhythmias.
67. Delayed after Depolarizations
■ Delayed after depolarizations (DADs)
begin during phase 4, after
repolarization is completed but
before another action potential would
normally occur via the normal
conduction systems of the heart.
■ They are due to elevated cytosolic
calcium concentrations due to
increased leakage from SR.
This leads to intracellular Ca2+waves
and triggered activity (DADs).
68. Sign and Symptoms
• A presentation of exercise or stress induced syncope and a QTc
less than 460 milliseconds should always prompt first
consideration to rule out CPVT.
• As with LQT1, swimming is a potentially lethal arrhythmia-
precipitating trigger in CPVT.
• In fact, both LQT1 and CPVT have been shown to underlie
several cases of unexplained drowning or near-drowning in
young, healthy swimmers.
• During exercise, typical responses include initial sinus
tachycardia and ventricular extrasystoles, followed by salvoes of
monomorphic or bidirectional VT, which eventually lead to
polymorphic VT as exercise continues.
69. FIGURE. ECG obtained during an exercise treadmill test in a patient with
catecholaminergic polymorphic VT. A, During the early phase of exercise, short runs of
polymorphic VT and PVCs occur. B, With further exercise, bidirectional VT ensues.
70. Management
• The treatment of choice is beta blockers and an ICD.
• Left-sided or bilateral sympathectomy has been
reported to be effective in a few cases.
• Flecainide inhibits ryanodine receptor–mediated
calcium release and has had some clinical success.
• Patients with CPVT should be instructed to avoid
vigorous exercise.