Preface

Chapter 8 **Breijo Electrocardiographic Pattern 145** Francisco R. Breijo-Márquez

**Neonates 161**

**VI** Contents

Karnika Senthilkumar

**Management 177**

Chapter 9 **Central Venous Catheter-Induced Cardiac Arrhythmias in**

Chapter 10 **Drug Abuse-Induced Cardiac Arrhythmias: Mechanisms and**

Lakshmi Prabha, Anwar Khan, Mahmoudh Galal, Yaser El Saba and

Sana Ouali, Omar Guermazi, Fatma Guermazi, Manel Ben Halima, Selim Boudiche, Nadim Khedher, Fathia Meghaieth, Abdeljalil Farhati, Noureddine Larbi and Mohamed Sami Mourali

Cardiac arrhythmia is a very complex disorder that could change both quality and quantity of life. In this book titled *Cardiac Arrhythmias*, authors from different geographical regions contributed to the advancement of this field of cardiac arrhythmias. This book is divided into two sections—atrial and nonatrial arrhythmias. In atrial arrhythmias, authors have de‐ scribed various aspects including genetics, clinical aspects, and surgical management of at‐ rial fibrillation. Similarly, in nonatrial arrhythmias, authors described new patterns of ECG including Breijo pattern. Common clinical scenarios like drug-induced arrhythmias will be very helpful for the readers. Our authors have also worked diligently to provide practical tips to the readers to prevent life-threatening cardiac arrhythmias induced by central venous catheterization. In the past few decades, there is a rapid development of new mapping and ablation techniques. In this book, we have excellent review chapters describing the clinical approach, mapping techniques, troubleshooting, and ablation methods for atrial arrhyth‐ mias and ventricular arrhythmias. These chapters are supported with excellent ECGs, elec‐ trograms, fluoroscopic pictures, and 3D electro-anatomic mapping images. These chapters are written by experienced and acclaimed experts in their field and hence will provide a comprehensive and authoritative review in those respective topics. I am very confident that these articles will be used as reference articles by the clinicians whether they are trainees, physicians, advanced care providers, or anyone involved in patient care.

This work was possible mainly because of the diligent and meticulous work of the authors. I sincerely thank them for all their sincere effort to spread the knowledge. I am deeply indebt‐ ed to Mr. Julian Virag, Author Service Manager at IntechOpen, for his continuous support. He put out many fires and facilitated timely publication of this book. I am also very thankful for the editorial assistance provided by the IntechOpen team. May the fruits of our labor, including the publishing team and contributors, serve the field of cardiac arrhythmias.

This book is dedicated to my mother Jana, the source of my inspiration and for being the ever-dependable platform, and to my son Shawn, who fills my life with joy and happiness and gives me the confidence that every generation is better than the previous one.

> **Umashankar Lakshmanadoss MD, CCDS, FHRS** Cardiac Electrophysiologist Ballad CVA Heart Institute Kingsport, TN, USA

**Section 1**

**Atrial Arrhythmias**

**Section 1**

**Atrial Arrhythmias**

**Chapter 1**

**Provisional chapter**

**Gene Polymorphisms Associated with Atrial Fibrillation**

Atrial fibrillation (AF), which causes severe health problems, is a multi-factor disorder and is increasing day by day. AF is known to be one of the most common cardiac arrhythmias in clinical practice. AF can also be described as a cardiac dysrhythmia that causes severe cardiovascular morbidity and mortality. AF is known as an independent risk factor for death and it occurs a significant risk of morbidity due to stroke. There are many diseases that contribute to the development of AF. Diseases such as aging, heart failure, heart valve disorders, myocardial infarction, hypertension and diabetes mellitus are important factors in the development of structural AF. It is a known fact that AF prevalence increases with age. The mechanism underlying of AF is not fully understood, but genetic factors play an important role in the pathogenesis of this disease. There have been many studies aimed at investigating the genetic basis of AF, especially in recent years. In these studies, many mutations and variants have emerged which are identified as genetic risk factors in the development of AF. Identification of gene polymorphisms that play a role in the development of AF will be an important guide in the development

**Keywords:** AF, cardiac arrhythmia, gene polymorphism, related diseases, PCR

AF, which has a significant morbidity and mortality rate, is a multifactorial disorder as one of the most common cardiac arrhythmias [1, 2]. This cardiac arrhythmia affects 1–2% of the general population. AF is an increasingly prevalent dysrhythmia and is associated with many cardiac risk factors. Disorders such as hypertensive, ischemic or structural heart diseases are

> © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: 10.5772/intechopen.76920

Nevra Alkanli, Arzu Ay and Suleyman Serdar Alkanli

Nevra Alkanli, Arzu Ay and Suleyman Serdar Alkanli

of new therapies for the treatment of this condition.

**Gene Polymorphisms Associated with Atrial** 

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.76920

**Fibrillation**

**Abstract**

**1. Introduction**

important risk factors for AF [3].

#### **Gene Polymorphisms Associated with Atrial Fibrillation Gene Polymorphisms Associated with Atrial Fibrillation**

DOI: 10.5772/intechopen.76920

Nevra Alkanli, Arzu Ay and Suleyman Serdar Alkanli Nevra Alkanli, Arzu Ay and Suleyman Serdar Alkanli

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.76920

#### **Abstract**

Atrial fibrillation (AF), which causes severe health problems, is a multi-factor disorder and is increasing day by day. AF is known to be one of the most common cardiac arrhythmias in clinical practice. AF can also be described as a cardiac dysrhythmia that causes severe cardiovascular morbidity and mortality. AF is known as an independent risk factor for death and it occurs a significant risk of morbidity due to stroke. There are many diseases that contribute to the development of AF. Diseases such as aging, heart failure, heart valve disorders, myocardial infarction, hypertension and diabetes mellitus are important factors in the development of structural AF. It is a known fact that AF prevalence increases with age. The mechanism underlying of AF is not fully understood, but genetic factors play an important role in the pathogenesis of this disease. There have been many studies aimed at investigating the genetic basis of AF, especially in recent years. In these studies, many mutations and variants have emerged which are identified as genetic risk factors in the development of AF. Identification of gene polymorphisms that play a role in the development of AF will be an important guide in the development of new therapies for the treatment of this condition.

**Keywords:** AF, cardiac arrhythmia, gene polymorphism, related diseases, PCR

#### **1. Introduction**

AF, which has a significant morbidity and mortality rate, is a multifactorial disorder as one of the most common cardiac arrhythmias [1, 2]. This cardiac arrhythmia affects 1–2% of the general population. AF is an increasingly prevalent dysrhythmia and is associated with many cardiac risk factors. Disorders such as hypertensive, ischemic or structural heart diseases are important risk factors for AF [3].

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

The underlying mechanisms in the development of AF are still not fully understood, but a heterogeneous model plays an important role in the pathophysiology of this disease. This heterogeneous model is based on the interaction of multiple substrates and triggers [3].

necrosis and susceptible fibrosis. RAAS is functioning via angiotensin II. Angiotensin II is involved in the elevation of blood pressure in the systemic arterial and venous systems and in the increase of blood return to the heart. It increases the central sympathetic activity by increasing the oscillation from the sympathetic nerve endings. Thus, synthesis and release of aldosterone is regulated. RAAS, which plays a role in atrial remodeling and pathogenesis of AF, is an important regulator. There are not many studies aiming to investigate the relationship between RAAS gene polymorphisms and the risk of developing AF. In a study conducted by Tsai et al., it was determined that the polymorphisms occurring in RAAS genes increased the susceptibility to AF development as a result of association with environmental factors leading to elevated atrial pressures. RAAS gene polymorphisms include ACE insertion/deletion (I/D), AGT (G-217A, A-20C, G-7A, M235T and T174M) and ATR1 A1166C gene polymorphisms. In a study aiming to investigate the association of these polymorphisms with AF, in exon 2 of the AGT gene, the M235 allele, a significant relationship was found between haploids associated with the G-6 and G-217 alleles in the promoter

Gene Polymorphisms Associated with Atrial Fibrillation http://dx.doi.org/10.5772/intechopen.76920 5

The 21-kilobase pair (kbp) long ACE gene locates on chromosome 17q23. This gene consists of 26 exons and 25 introns. The ACE (I/D) gene polymorphism is characterized by I/D of 287 base pairs in the 16th intron of the ACE gene. The genotypes of ACE (I/D) gene polymorphism differ in terms of ACE plasma and tissue levels. The DD genotype of the ACE (I/D) gene polymorphism is associated with high cellular ACE activity, which leads to myocardial fibrosis, so myocardial fibrosis develops. There are studies showing that ACE (I/D) gene polymorphism is associated with the risk of developing AF. There is a positive relationship between DD genotype and ACE activity of ACE (I/D) gene polymorphism. As a result of this relationship, angiotensin II level increases and myocardial hypertrophy, arrhythmia can develop. In the study carried out by Zhang and colleagues found a significant association between DD genotype of the ACE (I/D) gene polymorphism and increased AF. In another study conducted by Topal et al., a significant relationship was found between the incidence of ACE Alu D and

One of the ACE gene polymorphisms from the AF associated genes is the ACE 2350G/A (rs4343) polymorphism, and this polymorphism has a significant effect on the plasma ACE concentration. The ACE 2350G/A (rs4343) gene polymorphism is a synonymous mutation that is accepted as silent. There is insufficient study to investigate the relationship between ACE 2350G/A (rs4343) gene polymorphism and the risk of developing AF. In a study conducted by Jiang et al. in a Chinese population, the A allele of ACE 2350G/A (rs4343) gene polymorphism has been associated with the risk of developing AF in patients with essential hypertension. ACE 2350G/A (rs4343) polymorphic locus do not effect expression directly of ACE mRNA or it has not functional variant. It is assumed that there may be link imbalance between this fragment and an unknown DNA fragment acting as a muffler. In order to be able to identify gene loci in this linkage disequilibrium, a large number of studies have to be performed [1].

region and AF development risk [4, 5].

**2.2. ACE 2350G/A (rs4343) gene polymorphism**

**2.1. ACE (I/D) gene polymorphism**

increased AF [2].

There are many studies showing that genetic factors play an important role in the pathogenesis of AF. Monogenic mutations known to be associated with AF have been identified. A total of 25 gene mutations proven to be associated with AF have been identified. Genome-wide association studies (GWAS) have been conducted to investigate AF genetics, and these studies have shown that single nucleotide polymorphisms play a very important role in the development of AF. Several single nucleotide polymorphisms associated with AF predisposition have been identified in these GWAS studies [3].

AF is an electrical disease caused by defects in ionic currents, and a variety of studies have been undertaken to determine the genetic causes of these electrical illnesses. Studies conducted to investigate the hereditary predisposition of AF found that the development of AF in pups with AF detected in their parents was found. Even though disorders such as hypertension, myocardial infarction and diabetes mellitus, which are important risk factors for the development of AF, are regulated, they still have the risk of developing fourfold AF [3].

In many genetic studies, variants known to be associated with AF have emerged. These variants are formed as a result of abnormalities in genes encoding cardiac gap junctions, signaling molecules, ion channels and auxiliary subunits. In addition, gene polymorphisms may cause loss of function in genes that encode proteins contributing to cardiac depolarization or repolarization leading to AF's increased sensitivity, are also genetic risk factors that play an important role in the development of AF [3].

The purpose of this chapter is to give general information about AF and compiling the studies made with the aim of determining the gene polymorphisms that can play an important role in the development of AF.
