The Long QT Syndrome - Research Paper Example

The Long QT Syndrome The Long QT Syndrome The Long QT Syndrome (LQTS) is a hereditary oriented disorder that is highly characterised by immense QT intervals. It often leads to intense cardiac events such as cardiac death or syncope. It is caused by an imbalance of the electrolytes and use of drugs such as antiarrhythmics, antimicrobials, and antihistamines among others. The phenotypic features of the LQTS include deafness, prolonged QT intervals, polymorphic ventricular tachycardia and arrhythmia. There are thirteen genes that are associated with the disorder, and with the complexity that comes with testing it, there is a need for counselling. Consequently, patients will be in a better position to manage the disease by taking the right drugs, avoiding triggers such as strenuous exercises, and consuming the right diet, mostly one that is rich in potassium. This paper has discussed in length the history, diagnosis, management, treatment, genetics, and the phenotypic features of LQTS. The Long QT Syndrome Introduction The congenital Long QT Syndrome (LQTS) is a genetic heart disorder that is caused by the malfunction of the cardiac channels. It is a lethal ailment that is associated with torsade de pointes and ventricular tachyarrhythmias as a result of prolonged repolarisation (Furushima et al., 2009). Research shows that approximately 4,000 people die in the US every year as a result of this disorder. The affected persons inhibit signs of delayed repolarisation and sudden cardiac arrests. Various scholars argue that the LQTS has genetic related causes in roughly 75% of the people who are diagnosed with the condition. Therefore, it is usually inherited with an autosomal recessive and dominant trait. It is alleged that one of the main causes of cardiac arrests mostly in children and young people is the LQTS; hence, there is a need to come up with mechanisms in which it can be managed (Schwartz, Crotti & Insolia, 2014; Skinner, 2013). This discourse gives an in-depth analysis of the disorder, including its historical discovery, its phenotypic features, diagnosis, and genetic testing as well as counselling considerations. In addition, it will give limelight to management and treatment of the person affected by such disorder. Historical Discovery of the Disorder Meissner in Leipzig described the first documented case related to LQTS in the year 1856. He alleged that a deaf girl had died after reports showed that her teacher had yelled at her. On receiving the news, the parents claimed that the girl’s older brother who was equally deaf had died after undergoing an intense flight. On the same note, in 1901, an Uruguan family is reported to have collapsed and died and in 1937, Munro and Latham that five children coming from the same family suffered from grave spells and one of them died noted it. Moreover, in the year 1953, a deaf boy who had frequent syncope exhibited numerous phonotypic features of LQTS such as increased QT interval and bradycardia among others. This happened before the Electrocardiogram (ECG) had been invented but it clearly describes a case related to Jervell and Lange-Nielsen Syndrome. Later on, after the invention of the ECG by Fred Nielsen and Jervell, they later described another variant that was characterised with normal hearing and called it Romano-Ward Syndrome (Zumhagen, 2012; Vizgirda, 1999). The LQTS is a life threatening condition that causes sudden death among the youths and the old people. Research shows that children and adults with prolonged QTC are at high risk of having LQTS and suffering from other life threatening episodes such as cardiac arrests (Horr et al., 2010). Since the year 1975, hereditary variants such as the Jervell and Lange-Nielsen Syndrome, which is characterised by deafness and the Romano-Ward Syndrome, have been included in the study of LQTS. The LQTS is an important condition to study because it is a lethal disorder; hence, symptomatic patients that are left without treatment have high rates of mortality. Nevertheless, with the right therapy and treatments, the rate of mortality is reduced. The condition is caused by using drugs such as antiarrhythmics, which include medications such as quinidine, disopyramide, propafenone, and amiodarone among others. Other types of drugs are antimicrobials, which include itraconazole, chloquine, trimethprin, and erythmycin. There are also antihistamines and fluvoxamine, glibenclamide, domperidone, and amitriptyline among others. Apart from drugs, other causes are imbalance of the electrolyte and severe bradycardia. However, it can be managed by using drugs such as beta-blockers and modifying one’s lifestyle (Zumhagen, 2012). Phenotypic Features of the LQTS Today, results show that there are increased cases of cardiac events among people with LQTS, which is characterised by extended QT intervals and other related characteristics such as polymorphic ventricular tachycardia and arrhythmia. The disorder can be acquired due to abnormalities of the metabolic, response to drugs, and bradyarrhythmias. The Torsades de Pointes (TdP) is an example of a ventricular tachycardia that is associated with any type of LQTS. Patients show clinical phenotypes such as sinus arrhythmia, bradycardia, delayed conduction, and ventricular fibrillation among others (Furushima et al., 2009). There are two inherited forms of the LQTS, which vary when it comes to the type of inheritance and the absence or presence of loss in hearing. These include Jervell and Lange-Nielsen and Romano-Ward Syndrome. The Romano-Ward Syndrome is characterised by phenotypic features such as dominance of the autosomal with a variable penetrance. On the other hand, the Jervell Lange-Nielsen Syndrome is directly associated with deafness. In that case, in regard to pathological features, it is rational to argue that the LQTS is caused by prolonged repolarisation of the myocyte; hence, resulting to increased QT intervals on the ECG and sudden cardiac death. Various LQTS subtype exhibit diverse pathological features. For instance, the KVLQT1 is associated with acute emotional reactions. In addition, the HERG gene shows features such as low amplitude of the T wave. There is also the SCNSA gene in which symptoms are exhibited when one is at rest rather when they are excited. It is also associated with sudden cardiac arrests and death mostly by young people who are below the age of 40 years. Moreover, LQT2 patients that have mutations of the HERG gene have increased risks of suffering from cardiac events (Zareba, 2002). Research shows that patients with the genetic subtype LQT1 have exertional- triggered signs and symptoms. Medics argue that swimming is a major trigger of the condition. In that case, numerous patients with a history of drowning or nearly drowning have a defective KCNQ1 gene. Other major triggers apart from swimming are anger, running, fright, and shock. It is understood that LQT1 mutations often cause a defective channel; thus, the shortening of the QT to increase the heart rate ends up being impaired and the QTC tends to lengthen during exercise. The common ECG result in LQT1 is a prolonged duration of the T wave. There is also the LQT2 phenotype, which is triggered by telephone ring or the sound of an alarm clock. In that case, this indicates that there is a presence of KCNH2 gene defect, which encodes the subunit a of the potassium channels (Krishnan et al., 2011). One of the phenotypic features of LQT2 is postpartum cardiac events. In regard to LQT3 phenotype, it is determined that rest and sleep are the main triggers; hence, the SCN5A gene impairs inactivation, causing continuous re-openings and prolonged duration of the QT interval. Research reveals patients with LQT1, LQT2 and LQT3 have diverse ECG manifestations with different T wave patterns; thus, reflecting some aspects of abnormalities in sodium and potassium ion channels functioning (Zareba et al, 2003, pp. 1149-1150). Genetics of the Disorder There are thirteen genes that are associated with LQTS, of which six of them encode pore- forming ion channels. The six genes include KCNQ1, KCNH2, KCNJ2, SCN5A, KCNJ5 and CACNAIC. The rest encode regular proteins and include KCNE1, KCNE2, SCN4B, ANKB, AKAP9, CAV3, and SNTA1. However, the three most common ones are KCNH2 or LQ2 and SCN5A or the LQT3, which account for approximately 75% of the mutations (Zumhagen, 2012). Moreover, it is important to note that the electrocardiographic QT interval is a representative of both the repolarisation, as well as the depolarisation phases of the cardiac actions. Therefore, several ion channels determine the duration of the interval. For instance, decrease in potassium repolarisation or increase in the calcium depolarisation leads to extended QT intervals. In that case, it is rational to allege that genes are responsible for the execution of some cardiac events (Schwartz, Crotti & Insolia, 2014). Diagnosis of the Disorder It is argued that in most cases, physicians do not find it difficult to diagnose the LQTS. However, there are rare and complex cases such as those suffering from LQT8, which require the evaluation of various variables as well as when diagnosing children (Moric-Janiszwska et al., 2006). In 1985, the diagnostic criterion for the disorder was proposed. This has remained valid until today. However, other approach such as Schwartz score, which was introduced in the year 2006, has yielded more fruits. Therefore, researchers argue that the use of the 1985 criterion in the modern era has led to underestimation of those persons who have been identified as having being affected (Schwartz, Crotti & Insolia, 2014 According to Vizgirda (1999), findings related to physical examination do not necessarily indicate a sound diagnosis of the LQTS. However, some patients are seen to present more bradycardia and others suffer from hearing loss. In addition, other symptoms that may be exhibited after physical examination are abnormalities of the skeletal among those with LQT7 and behavioural problems, heart diseases, dysfunction of the immune system, and musculoskeletal diseases among those with LQ78. Various scholars argue that the heart rate that is above 450ms and 460ms in male and female patients respectively and an absence of heart disease or use of drugs is associated with the LQTS. However, it ought to be noted that in case a patient has a normal QT interval, that does not mean that they are excluded from the diagnosis. For instance, KCNQ1 mutation carriers or LQT1 can have a normal QT interval but at the same time have prolonged intervals in scenario whereby there is increased sympathetic activation or increased heart rates. Moreover, in clinical diagnosis, the LQTS is usually suspected in cases of Spatially Discordant Alternans (SDA) among people who are below the age of 40 years. In addition, syncope or SDA when one is having physical or emotional stress can be used to suggest that one has LQT-3 (Zumhagen, et al., 2012). It is also important to perform genetic tests in case the cardiologist suspects the patient of having LQTS. Therefore, genetic diagnosis includes giving information about the patient’s clinical history, the duration of QT interval, family history, and examination of the T wave morphology. It is also vital to note that performing of genotyping is crucial even in scenarios whereby the symptoms are not evident. Therefore, genetic testing is not done solely for patients who have had cases of cardiac arrests and fainting but rather ought to be conducted after consulting with the cardiologist. Therefore, there is a need for genetic counselling to ensure that the right procedure is followed and there are no mishaps (Zumhagen et al., 2012; Furushima et al., 2009). Testing and Counselling Considerations Diagnostic tests in patients suspected of suffering from LQTS include testing of the levels of magnesium and serum potassium, the functioning of the thyroid, and a thorough genetic testing of both the patient as well as the family members. In addition, they undergo electrocardiography tests. Moreover, standing tests offer more diagnostic information on patients suffering from the disorder. Various scholars also avow that family members and patients undergo through epinephrine infusion. Numerous tests that have been performed earlier reveals that infusion of epinephrine is usually affirmative for LQTS patients in cases whereby the QT is prolonged by approximately 30ms at 0.10 kg per minute and in complex cases where the QT is increased to 29ms (Krahn et al., 2014). The components of counselling in regard to LQTS include education concerning genetic testing and inheritance and giving advice on the medical adjustments and options that are available. Scholars argue that the need for information is one of the major desires that are expressed by families that have hereditary conditions. Therefore, genetic counselling is imperative even in cases whereby genetic testing is not required or possible as the information offered may serve as a revelation to those who might be at risk. The complexity that comes with genetic testing shows that indeed counselling is essential; thus, the patients and their healthcare provider get to understand the implications as well as the limitations of the findings for both families and specific individuals. Moreover, patients suffering from stress-oriented dysrhythmias benefit from counselling interventions since they learn on the effective strategies for managing stress (Vizgirda, 1999). Moreover, there is a need for persons suffering from LQTS to attend counselling sessions with their cardiologists and psychiatrists. This is because it is highly likely that they suffer from depression and anxiety caused by the condition. It is also important to note that medication for the disorder and the maintenance process can prove to be expensive; hence, the likelihood of such patients being stressed is high. Counselling is also vital in ensuring that patients take the right measures to reduce cases of cardiac arrests and deaths. This means that in counselling, they will be advised on the right medications to use and those that they should avoid. On the same note, they are given a list of activities that they are not supposed to do such as swimming, engaging in sporting events for instance, running among others. It is also in counselling where they get a chance to learn on ways they can control their moods, which result in immense anger or excitement and can trigger the condition. In that case, attending counselling is imperative since this is the place in which they are advised on ways they can modify their lifestyles. For instance, avoiding strenuous exercises can help in reducing risks that are associated with fainting. This also means that they get to have the right medications and avoid those that trigger anomalous heart rhythms such as those used to treat allergies, high blood pressure, infections, depression, and arrhythmias among others. Consequently, they will end up taking drugs such as beta-blockers that decreases the risks of the condition by slowing down the heart rhythm. When it comes to lifestyle changes, the counselling sessions also give the patients an opportunity to ask questions in regard to the right diet. For instance, most of the people who have LQTS benefit from adding a lot of potassium in their daily meal such as eating bananas or consuming potassium supplements. Therefore, counselling will ensure patients take the right diet and avoid developing ventricular dysrhythmias as a result of an abnormal pattern caused by excitation of the cardiac (Vizgirda, 1999). Moreover, before tests are done, a genetic counsellor should be consulted to advise the family members and the patient on what ought to be disclosed and the reason behind the tests. This will reduce cases of resistance that come with lack of proper information; hence increasing the chance of survival among the patients. This means that the counselling will also help in establishing individual genetic status on time; thus, early treatment can commence in case they are gene carriers. Similarly, patients and their relatives who are at risk of any inherited disorder are advised on its impact as well as its nature. They are also given options related to treatment and management (Vizgirda, 1999). Management and Treatment The main goal behind treating the LQTS is to ensure that life-threatening episodes are minimised such as abnormal rhythms of the heart as well as fainting spells. The type of medicine prescribed depends with the type of LQTS that one has. For instance, physicians recommend sodium channel blocker drugs for persons who have LQT3. Research shows that so far, there is no treatment that has addressed the main cause of the LQTS. However, it is alleged that one way in which the symptoms such as cardiac arrests can be minimised and managed effectively is by using antiadrenergic oriented measures such as taking of beta-blockers drugs. In addition, patients can undergo device therapy that involves the use of pacemakers and cardioverter-defibrillators that are implantable. For instance, the use of implantable cardioverter- defibrillator is necessary in reducing cases of shocks and cardiac attacks. Consequently, such measures are crucial in helping reduce the risks associated with cardiac events. Patients should also use beta-adrenergic blocking agents drugs such as nadolol, atenolol, metaprolol, and propranolol. Such agents are of the essence in barring particular contraindications. However, although all blockers have some positive aspect, it is argued that the most effective are nadolol and propranolol. For instance, propranolol is the most widely used medication in which a patient is required to take 2 to 3 mg/kg per day and in malignant cases the dosage is supposed to be increased to 4mg/kg (Schwartz, Crotti & Insolia, 2014). It is also important to note that patients suffering from LQTS should not engage in competitive sports or have strenuous exercises. This is because such measures aggravate their condition. It is also imperative that they avoid asthma and anaesthetic medications and antibiotics. Other medications that should be avoided among this group include gastrointestinal medications such as cisapride, antifungal drugs for instance itraconazole, and medications that are taken due to loss of potassium such as indapamide. Therefore, it is sound to argue that all patients that have LQTS should avoid all forms of medication that tend to prolong their QT intervals or tend to reduce the magnesium and potassium serum levels. In the year 1985, a study was conducted among 233 patients on the use of therapeutic measures. Results revealed that there was an increase in survival rates among those who underwent surgical anti-adrenergic or pharmacological therapy, as compared to those who were not under any treatment (Schwartz, Crotti & Insolia, 2014). On the same note, various scholars argue that sudden increase of the sympathetic activity is the main trigger of arrhythmias in most of the LQTS patients. Therefore, offering antiadrenergic therapies is vital in ensuring protection. Related data shows that the concept was supported in 1985 among 233 patients, whereby, it was determined that mortality at 15 years during the first syncope was 9% among the group that was treated using the therapy and over 53% among those who were not treated or used other therapies. Therefore, the data reveals that such therapies are able to radically modify the prognosis for patients with LQTS (Schwartz, Crotti & Insolia, 2014). Another paramount treatment is the Left Cardiac Sympathetic Denervation (LCSD). It requires the removal of four to five thoracic ganglia. It is significant as it decreases the number of cardiac arrests from approximately 99 to 45%. In addition, it helps patients as it reduces cases of lethal arrhythmias by removing the main triggers and adjusting the substrate. It is also essential as it plays a major role in reducing the QT dispersion levels. However, it ought to be understood that such treatments should begin by using the beta-blockers unless there are known contraindications (Zumhagen, 2012). Conclusion Research shows that the LQTS mostly affects the youths; hence, there is a need for families and patients to be tested early to avoid its impacts. In addition, counselling is necessary as it offers a platform in which families can get more information related to genetic disorders and develop affirmative ways in which they can modify their lifestyles. It is obvious from research that various medications and disproportion of the electrolytes lead to LQTS, thus, patients should be advised on the right medications and ways in which they can manage their lifestyles to ensure optimum results. References Furushima, H., Chinushi, M., Sato, A., Aizawa, Y., Kikuchi, A., Takakuwa, K&Tanaka, K (2009). Fetal Atrioventricular Block and Postpartum Augmentative QT Prolongation in a Patient with Long-QT Syndrome With KCNQ1 Mutation. Journal of Cardiovascular Electrophysiol, 21(10):1170-1173. Horr, S., Goldenberg, I., Moss, A., Uchi, J., Barsheshet, A., Connelly, H., Gray, D., Zareba, W & Lopes, C. (2010). Ion Channel Mechanism Related to Sudden Cardiac Death in Phenotype-Negative Long QT Syndrome Genotype-Phenotype Correlations of the KCNQ1 (S349W) Mutation. Journal of Cardiovascular Electrophysiology, 22(2): 193-200. Moric-Janiszewska, E., Loskot, G., Loskot, M., Weglarz, G., Hollek, A. & Sztdlowski, L. (2006). 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