Clinical cardiologists are encountering an important challenge in the caring of families with inherited cardiac diseases. The majority of the inherited cardiac diseases causing sudden death express themselves at variable ages in the form of altered muscle function (i.e hypertrophic or dilated cardiomyopathy) or in the form of arrhythmias (i.e. Brugada syndrome, long QT syndrome). However, it is not uncommon that the first sign of the disease may actually be sudden cardiac death, even before the identification of clear clinical abnormalities. In this last decade, with more than 50 new disease-associated genes identified, the possibility of genetic testing has opened a new opportunity to disease diagnosis and prevention. Clinical and genetic research is continuously on-going not only to identify those at risk, but to better define their level or risk still with limited success.
Author(s): Josep Brugada, Pedro Brugada, Ramon Brugada
Edition: 1st Edition.
Publisher: Springer
Year: 2010
Language: English
Pages: 340
Cover......Page p0001.djvu
Front......Page p0002.djvu
Part I : Sudden Unexplained Death......Page p0015.djvu
1.1 Magnitude of the Problem......Page p0016.djvu
1.3 Diagnostic Considerations and Role of the Molecular Autopsy......Page p0017.djvu
1.4 Conclusions......Page p0018.djvu
2.1 Introduction......Page p0020.djvu
2.2.1 Sodium and Potassium Cardiac Channelopathies......Page p0021.djvu
2.2.2 Serotonin Transporter (5-HTT)......Page p0022.djvu
2.2.4 Infection and Inflammation......Page p0023.djvu
2.3.1 Sociodemographic Factors......Page p0024.djvu
2.3.3 Tobacco, Illicit Drug, and Alcohol Use......Page p0025.djvu
2.3.4 Infant Sleep Practices and Environment......Page p0026.djvu
2.3.8 Recurrence of SIDS in Siblings......Page p0027.djvu
2.4 Phenotypes Associated with Increased Risk for SIDS......Page p0028.djvu
2.5 Gene–Environment Interactions......Page p0029.djvu
2.6 Summary......Page p0030.djvu
Part II : Arrhythmias and sudden cardiac death.The initial investigation......Page p0035.djvu
3.3 Etiology of Syncope......Page p0036.djvu
3.5.1 History and Physical Examination......Page p0039.djvu
3.6.4 Tilt Test......Page p0040.djvu
3.7.1 Electrophysiological Study......Page p0041.djvu
3.8 Diagnostic Approach of Unexplained Syncope......Page p0042.djvu
Arrhythmias and Sudden Cardiac Death in Adult Congenital Heart Disease......Page p0047.djvu
4.1 Atrial Septal Defect......Page p0048.djvu
4.3 Atrioventricular Canal Defect......Page p0051.djvu
4.5 L-Transposition of the Great Arteries (L-TGA)......Page p0052.djvu
4.7 Heterotaxy Syndromes......Page p0053.djvu
4.8 Single Ventricle Physiology......Page p0054.djvu
4.9 Fontan Palliation......Page p0056.djvu
4.10 Tetralogy of Fallot......Page p0057.djvu
4.11 D-Transposition of the Great Arteries (D-TGA)......Page p0059.djvu
4.12 Summary......Page p0061.djvu
5.1 Athlete’s Heart: Anatomical and Electrical Considerations......Page p0067.djvu
5.1.2 Right Ventricular Involvement......Page p0068.djvu
5.2.4 Changes in ST Segment......Page p0069.djvu
5.3 Sudden Death and Ventricular Arrhythmias......Page p0070.djvu
5.4.1 Differentiating HCM and Athlete’s Heart......Page p0071.djvu
5.5.1 Sport Eligibility......Page p0072.djvu
5.8.1 Paroxysmal Supraventricular Tachycardia and Ventricular Preexcitation......Page p0073.djvu
5.8.2 Atrial Fibrillation and Atrial Flutter......Page p0074.djvu
5.9 Screening Athletes......Page p0075.djvu
5.10.2 Rhythm Disorders......Page p0077.djvu
5.12 Differences in Race......Page p0078.djvu
5.13 Syncope in Athletes......Page p0079.djvu
6.1.2.5 QRS Complex......Page p0083.djvu
6.2 Ventricular Repolarization Components......Page p0085.djvu
6.2.2 QT Interval......Page p0086.djvu
6.3.2 ECG Parameters in Congenital LQTS......Page p0087.djvu
6.5 Electrophysiological Mechanism......Page p0089.djvu
6.8.2 Main ECG Features......Page p0091.djvu
6.8.2.1 ECG with Modified Protocol......Page p0092.djvu
6.9.2 Electrocardiographic Characterization......Page p0093.djvu
6.10.2 Electrocardiographic Features......Page p0096.djvu
6.11 Clue for Electrocardiographic Diagnosis of CPVT......Page p0099.djvu
7.1.1 The Range of Pathology......Page p0101.djvu
7.1.2 Methods of Investigation......Page p0103.djvu
7.3.1 External Examination of the Body......Page p0104.djvu
7.3.2.3 The Standard Gross Examination of the Heart......Page p0105.djvu
7.4.2 Toxicology......Page p0107.djvu
7.5.1 Coronary Artery Disease......Page p0108.djvu
7.5.2.1 Hypertrophic Cardiomyopathy......Page p0109.djvu
7.5.2.2 Arrhythmogenic Right Ventricular Dysplasia......Page p0110.djvu
7.5.3.2 Hypersensitivity Myocarditis......Page p0112.djvu
7.5.3.5 Sarcoidosis......Page p0113.djvu
7.5.4 Sudden Cardiac Death in the Absence of Autopsy Findings......Page p0114.djvu
7.6 Forensic Report and Clinico-Pathological Summary......Page p0116.djvu
7.7 Conclusions......Page p0117.djvu
Part III : Cardiac genetic syndromes......Page p0121.djvu
8.1 Introduction......Page p0122.djvu
8.3 Mendelian Traits......Page p0123.djvu
8.4 Genetic Linkage Studies......Page p0124.djvu
8.5 Genetic Association Studies for Complex Traits......Page p0125.djvu
8.6 Challenges of Genetic Association Studies......Page p0127.djvu
8.7 In Conclusion......Page p0128.djvu
9.3 Diagnostic Tools......Page p0130.djvu
9.6 Autosomal Dominant Long QT Syndrome (Romano-Ward Syndrome)......Page p0132.djvu
9.9 Risk Stratification......Page p0134.djvu
9.10.3 Other Treatment Options......Page p0135.djvu
9.11 Prevention......Page p0136.djvu
10.2 Diagnostic Criteria and General Characteristics......Page p0139.djvu
10.3 Genetics of the Brugada Syndrome......Page p0141.djvu
10.4.1 Gender Differences......Page p0142.djvu
10.4.2 Children......Page p0144.djvu
10.5 ECG and Modulating Factors......Page p0145.djvu
10.6 Diagnostic Tools: Drug Challenge......Page p0147.djvu
10.7 Prognosis and Risk Stratification......Page p0148.djvu
10.8.2 Pharmacological Options......Page p0151.djvu
11.2 Clinical Diagnosis......Page p0157.djvu
11.4 Risk Stratification Parameters......Page p0160.djvu
11.6 Genetic Basis......Page p0161.djvu
11.7 Role of Genetics in Diagnosis, Risk Stratification and Therapy......Page p0162.djvu
11.8.1 Clinical Case Presentation......Page p0163.djvu
12.2 Clinical Diagnosis......Page p0165.djvu
12.3 Differential Diagnosis......Page p0166.djvu
12.5 Therapeutic Approach to the Disease......Page p0167.djvu
12.8 Controversial Issues in Clinical Diagnosis and Management......Page p0168.djvu
13.2 Clinical Presentation......Page p0171.djvu
13.3.1 Task Force Diagnostic Criteria......Page p0172.djvu
13.3.2 Molecular Genetic Diagnosis......Page p0173.djvu
13.4.2 Therapy......Page p0176.djvu
13.4.3 Programmed Ventricular Stimulation......Page p0177.djvu
14.1.1 Genetic Mechanisms......Page p0180.djvu
14.2.2 Atrial Fibrillation Associated with Genetic Alterations in Potassium Currents......Page p0181.djvu
14.3 Genetic Predisposition to Nonfamilial AF......Page p0182.djvu
14.4 Future......Page p0183.djvu
14.5 Clinical Implications in Familial Atrial Fibrillation......Page p0184.djvu
15.2 Epidemiology and Genetic Basis......Page p0186.djvu
15.4 Clinical Diagnosis......Page p0188.djvu
15.5 Differential Diagnosis......Page p0189.djvu
15.6 Diagnosis......Page p0190.djvu
15.7 Genetic Basis......Page p0192.djvu
15.9.1 Pharmacological Therapy......Page p0193.djvu
15.10 Asymptomatic Left Ventricular Dysfunction......Page p0194.djvu
15.11 Genetic Counseling......Page p0195.djvu
15.12 Unresolved Questions......Page p0196.djvu
16.2 Clinical Manifestations......Page p0198.djvu
16.3 Clinical Diagnosis......Page p0199.djvu
16.4 Molecular Genetics......Page p0200.djvu
16.5 Risk Factors for SCD in HCM......Page p0201.djvu
16.6 Genetic Testing and SCD in HCM......Page p0203.djvu
16.7 Evaluation and Management of Risk of SCD......Page p0204.djvu
16.8 Concluding Remarks......Page p0205.djvu
17.1 Introduction......Page p0209.djvu
17.2.2 Lipoproteins, Apolipoproteins, Receptors, and Processing Enzymes......Page p0210.djvu
17.2.3 Lipoprotein Metabolism and Transport......Page p0213.djvu
17.3.1 Definitions......Page p0216.djvu
17.3.2 Genetic Lipoprotein Disorders......Page p0219.djvu
17.3.3 Hypobetalipoproteinemia and Abetalipoproteinemia......Page p0222.djvu
17.4.2 Laboratory Test and Their Orders......Page p0224.djvu
17.4.4 Gene Therapy......Page p0225.djvu
18.3 Marfan Syndrome......Page p0228.djvu
18.4 The Fibrillin-1 Gene and Type-1 Fibrillinopathies......Page p0229.djvu
18.5 Loeys Dietz Syndrome......Page p0231.djvu
18.6 Other Hereditary Forms of Thoracic Aortic Aneurysm and Dissection......Page p0232.djvu
18.7 Bicuspid Aortic Valve......Page p0233.djvu
18.8 Clinical Management......Page p0234.djvu
19.2 Limitations to Classification of Secondary Cardiomyopathies......Page p0238.djvu
19.3 The Elusive Concept of Hypertrophy......Page p0239.djvu
19.4 Hypertrophy in Children......Page p0240.djvu
19.5.1 Intracellular Lipid Accumulation in the Heart (Mitochondrial Disorders)......Page p0241.djvu
19.5.2 Intracellular Glycogen Accumulation in the Heart with Mild or No Systemic Manifestations......Page p0242.djvu
19.5.3 Intracellular Glycogen Accumulation in the Heart with Systemic Manifestations......Page p0243.djvu
19.6.1 Fatty Acid Oxidation Disorders......Page p0245.djvu
19.6.2.1 Danon Disease......Page p0246.djvu
19.6.2.2 Fabry’s Disease......Page p0249.djvu
19.6.2.3 Pompe’s Disease......Page p0250.djvu
19.6.2.4 PRKAG2 Mutations......Page p0252.djvu
19.6.3 Other Mitochondrial Diseases with Emphasis on Maternally Inherited Cardiomyopathy (MICM) and Kairnes-Sayre syndrome......Page p0255.djvu
19.6.3.1Kearns-Sayre syndrome (KSS)......Page p0258.djvu
19.7 Approaching the Child with Suspicion of Having an Inborn Error of the Metabolism (IEM) 77......Page p0259.djvu
19.7.2 Encephalopathy......Page p0260.djvu
19.7.3 Pathological Findings......Page p0261.djvu
Clinical Genetics in Congenital Heart Disease......Page p0264.djvu
20.1 Genetic Basis in CHD: Clinical Implications......Page p0265.djvu
20.2.1 Known Chromosomal Aberrations......Page p0266.djvu
Noonan Syndrome......Page p0267.djvu
20.2.4 Left Ventricular Outflow Tract Obstructions......Page p0268.djvu
20.2.5.1 Secundum ASD......Page p0269.djvu
20.2.8.2 Truncus Arteriosus/Interruption of the Aortic Arch......Page p0270.djvu
20.3 Conclusion......Page p0272.djvu
Part IV : Polygenic cardiovascular genetics......Page p0276.djvu
21.1 Introduction......Page p0277.djvu
21.2 The Complexity of Drug Effects......Page p0278.djvu
21.3.1 Cytochrome P450 2D6......Page p0279.djvu
21.3.3 Cytochrome P450 3A......Page p0280.djvu
21.4 Drug Transporters......Page p0281.djvu
21.5.1 Renin–Angiotensin–Aldosterone System Antagonists......Page p0282.djvu
21.5.2 Beta-Blockers......Page p0283.djvu
21.5.4 Statins......Page p0284.djvu
21.6.3 Life Habits......Page p0285.djvu
21.7 Pharmacogenomics: Hope or Hype?......Page p0286.djvu
22.2 Common Genetic Variants as Modifiers of Arrhythmia Risk in the Context of Monogenic Diseases......Page p0292.djvu
22.5 Searching for the Genetic Susceptibility to Common Cardiac Arrhythmias......Page p0293.djvu
23.2.1.1 Familial Aggregation Studies......Page p0300.djvu
23.3 Single Gene vs. Polygenic Disorders......Page p0301.djvu
23.4 Genetic Basis for Predisposition to Disease......Page p0302.djvu
23.7 Genome-Wide Case Control Association Studies: A New Era for Common Polygenic Disorders......Page p0303.djvu
23.10 The First Common Genetic Variant for CAD: 9p21 May Unravel a Novel Pathway......Page p0305.djvu
23.11 The Importance of Phenotyping and Selecting Controls......Page p0306.djvu
23.13 Personalized Medicine: The Beginning of a Reality......Page p0307.djvu
23.14 Functional Analysis of Genetic Variant: A Challenge for the Future......Page p0308.djvu
Part V : Ethical, legal and Social implications......Page p0311.djvu
24.1 Psycho-Social Effects of Genetic Testing......Page p0312.djvu
24.2 Living with Hereditary SCD Syndrome......Page p0313.djvu
24.3 The Firing of the ICD as Symptom......Page p0314.djvu
24.6 Future Directions......Page p0315.djvu
24.7 Conclusion......Page p0316.djvu
25.1 Introduction......Page p0318.djvu
25.3 Scope of the Problem......Page p0319.djvu
25.4 Premises......Page p0320.djvu
25.6 Recommendations......Page p0321.djvu
25.7 Implantable Cardioverter-Defibrillators......Page p0325.djvu
26.2 Sudden Cardiac Death and Genetics......Page p0328.djvu
26.3.1 Interpretation of Medical and Family Histories......Page p0329.djvu
26.3.2.1 Gene Targeting Applications and Challenges......Page p0330.djvu
26.3.2.2 Implications and Limitations of Results......Page p0331.djvu
26.4 Implications for the Immediate Family with a Known Mutation......Page p0332.djvu
26.4.2 Psychosocial Implications for the Family......Page p0333.djvu
26.5 Conclusion......Page p0334.djvu
Index......Page p0337.djvu
