History

Fact Explanation
Syncope Stress induced syncope is a common symptom of long QT syndrome(LQTS)[1][2][3][4][5][6][9]
Cardiac arrest Can be the presenting symptom of some patients with LQTS[1][2][5][6][8]
Palpitations Cardiac rhythm abnormalities can occur in patients with LQTS that will be perceived by patients as palpitations[6]
Seizures Can be the presentation in some patients with LQTS, especially those with bigenic mutations. Patients with Romano-Ward syndrome can present with syncope, seizures, and sudden death associated with QT prolongation[5][6][9][11]
Sudden cardiac death Sudden cardiac death can occur in patients with LQTS due to torsade de pointes and ventricular fibrillation and may be the only presentation in 30-40% of patients with LQTS. Studies have shown that sudden cardiac events occur in these patients just after acute arousal events such as vigorous exercise, emotional stress, loud noise etc. [1][2][3][5][6][7][8][9]
Family history of cardiac arrest in a young person Is a feature suggestive of congenital LQTS [2][3][6][7][8]
Family history of sudden cardiac death That occurred particularly at a young age, is an important factor found in patients with congenital LQTS [1][2][6][8]
Congenital sensorineural deafness or having a family history of hearing deficit If this is present together with Long QT syndrome could be due to Jervell and Lange-Nielsen Syndrome[10]
History of using medication such as salbutamol, amantadine, amitriptyline, macrolides, sotolol etc These drugs can prolong QT interval and it is important to exclude their use in a patient presenting with a sudden cardiac event[1][2][4]
Patients presenting with a collection of features such as congenital heart diseases, cognitive and behavioral problems, musculoskeletal diseases, seizures, distinctive cranio-facial abnormalities and immune dysfunction May be seen in those with Timothy syndrome (Also called LQT8)[7]
References
  1. PETER J. SCHWARTZ. Practical issues in the management of the long QT syndrome: focus on diagnosis and therapy. Swiss Med Wkly[online] 2013;143:w13843 [viewed on 27 June 2014] Available from; http://www.smw.ch/content/smw-2013-13843/
  2. MEYER. JS, MEHDIRAD A, SALEM BI, JAMRY WA, KULIKOWSKA A, KULIKOWSKI P. Sudden Arrhythmia Death Syndrome: Importance of the Long QT Syndrome. Am Fam Physician[online] 2003 Aug 1;68(3):483-488[viewed on 26 June 2014] Available from; http://www.aafp.org/afp/2003/0801/p483.html
  3. GYSEL M, CRYSTAL A, HANCOX JC, METHOT M, BARANCHUK A. Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy Case Rep Cardiol [online] 2014:213842 [viewed 26 June 2014] Available from: doi:10.1155/2014/213842
  4. Combined List of All QTdrugs and the List of Drugs to Avoid for Patients with Congenital Long QT Syndrome. Crediblemeds[online] 2013[viewed on 27 June 2014] Available from: http://crediblemeds.org/everyone/composite-list-all-qtdrugs/?rf=US
  5. TAKAHASHI K, SHIMIZU W, MIYAKE A, NABESHIMA T, NAKAYASHIRO M, GANAHA H. High Prevalence of the SCN5A E1784K Mutation in School Children With Long QT Syndrome Living on the Okinawa Islands. Circ J [online] 2014 May 28 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24871449
  6. IMMY JJ, CHEN CY, YEH HM, CHIU WY, YU CC, LIU YB, TSAI CT, LO LW, YEH SF, LAI LP. Clinical characteristics of patients with congenital long QT syndrome and bigenic mutations. Chin Med J (Engl) [online] 2014, 127(8):1482-6 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24762593
  7. FRöHLER S, KIESLICH M, LANGNICK C, FELDKAMP M, OPGEN-RHEIN B, BERGER F, WILL JC, CHEN W. Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2) BMC Med Genet [online] :48 [viewed 26 June 2014] Available from: doi:10.1186/1471-2350-15-48
  8. BHUIYAN ZA, AL-SHAHRANI S, AL-AAMA J, WILDE AA, MOMENAH TS. Congenital Long QT Syndrome: An Update and Present Perspective in Saudi Arabia Front Pediatr [online] :39 [viewed 26 June 2014] Available from: doi:10.3389/fped.2013.00039
  9. SADRNIA S, YOUSEFI P, JALALI L. Correlation between seizure in children and prolonged QT interval ARYA Atheroscler [online] 2013 Jan, 9(1):7-10 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653254
  10. Tranebjaerg L, Samson RA, Green GE. Jervell and Lange-Nielsen Syndrome. 2002 Jul 29 [Updated 2012 Oct 4]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1405/
  11. Alders M, Mannens MMAM. Romano-Ward Syndrome. 2003 Feb 20 [Updated 2012 May 31]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1129/

Examination

Fact Explanation
Bradycardia Seen in some patients with LQTS[3]
Arrhythmia A life-threatening tachyarrhythmia known as torsades de pointes can arise in patients with congenital LQTS [1][2]
Hearing loss Can be found in patients with Jervell and Lange-Nielsen Syndrome[6]
Syndactyly Is seen in patients with Timothy syndrome[4]
Presence of features such as short stature and scoliosis, periodic paralysis, dysmorphic features, ventricular arrhythmias Is seen in patients having Andersen-Tawil Syndrome (formerly LQT7)[5]
References
  1. MEYER. JS, MEHDIRAD A, SALEM BI, JAMRY WA, KULIKOWSKA A, KULIKOWSKI P. Sudden Arrhythmia Death Syndrome: Importance of the Long QT Syndrome. Am Fam Physician[online] 2003 Aug 1;68(3):483-488[viewed on 26 June 2014] Available from; http://www.aafp.org/afp/2003/0801/p483.html
  2. GYSEL M, CRYSTAL A, HANCOX JC, METHOT M, BARANCHUK A. Multifactorial QT Interval Prolongation and Takotsubo Cardiomyopathy Case Rep Cardiol [online] 2014:213842 [viewed 26 June 2014] Available from: doi:10.1155/2014/213842
  3. TAKAHASHI K, SHIMIZU W, MIYAKE A, NABESHIMA T, NAKAYASHIRO M, GANAHA H. High Prevalence of the SCN5A E1784K Mutation in School Children With Long QT Syndrome Living on the Okinawa Islands. Circ J [online] 2014 May 28 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24871449
  4. FRöHLER S, KIESLICH M, LANGNICK C, FELDKAMP M, OPGEN-RHEIN B, BERGER F, WILL JC, CHEN W. Exome sequencing helped the fine diagnosis of two siblings afflicted with atypical Timothy syndrome (TS2) BMC Med Genet [online] :48 [viewed 26 June 2014] Available from: doi:10.1186/1471-2350-15-48
  5. TESTER DJ, ACKERMAN MJ. GENETICS OF LONG QT SYNDROME Methodist Debakey Cardiovasc J [online] 2014, 10(1):29-33 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4051331
  6. Tranebjaerg L, Samson RA, Green GE. Jervell and Lange-Nielsen Syndrome. 2002 Jul 29 [Updated 2012 Oct 4]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2014. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1405/

Differential Diagnoses

Fact Explanation
Hypertrophic cardiomyopathy Will have clinical features such as syncope, palpitations, sudden cardiac death etc[2]
Vasovagal syncope Most common in children and adolescents. An important differential diagnosis to be considered in young patients presenting with syncope[3]
Drug-induced QT prolongation An important differential diagnosis as there is a number of drugs that can cause QT prolongation[1]
QT prolongation following myocardial infarction(MI) Life-threatening arrhythmias including QT prolongation and torsades de pointes can develop following MI[6]
Brugada syndrome A rare cardiac arrhythmia associated with sudden cardiac death[4]
Arrhythmogenic right ventricular dysplasia An inherited disorder associated with ventricular arrhythmia and sudden cardiac death[5]
References
  1. BILL ZEPF. Drug-induced Prolongation of the QT Interval.Am Fam Physician[online] 2005 Jan 1;71(1):164-166[viewed on 26 June 2014] Available from; http://www.aafp.org/afp/2005/0101/p164.html
  2. AHMED W, AKHTAR N, BECH-HANSSEN O, MAHDI BA, OTAIBI TA, FADEL BM. Hypertrophic cardiomyopathy in the Saudi Arabian population: Clinical and echocardiographic characteristics and outcome analysis J Saudi Heart Assoc [online] 2014 Jan, 26(1):7-13 [viewed 26 June 2014] Available from: doi:10.1016/j.jsha.2013.08.003
  3. SHIM SH, PARK SY, MOON SN, OH JH, LEE JY, KIM HH, HAN JW, LEE SJ. Baseline heart rate variability in children and adolescents with vasovagal syncope. Korean J Pediatr [online] 2014 Apr, 57(4):193-8 [viewed 26 June 2014] Available from: doi:10.3345/kjp.2014.57.4.193
  4. BRUGADA R, CAMPUZANO O, SARQUELLA-BRUGADA G, BRUGADA J, BRUGADA P. BRUGADA SYNDROME. Methodist Debakey Cardiovasc J [online] 2014 Jan, 10(1):25-28 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24932359
  5. SALLAM K, KODO K, WU JC. Modeling inherited cardiac disorders. Circ J [online] 2014, 78(4):784-94 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24632794
  6. CROTTI L, HU D, BARAJAS-MARTINEZ H, DE FERRARI GM, OLIVA A, INSOLIA R, POLLEVICK GD, DAGRADI F, GUERCHICOFF A, GRECO F, SCHWARTZ PJ, VISKIN S, ANTZELEVITCH C. Torsades de pointes following acute myocardial infarction: evidence for a deadly link with a common genetic variant. Heart Rhythm [online] 2012 Jul, 9(7):1104-12 [viewed 26 June 2014] Available from: doi:10.1016/j.hrthm.2012.02.014

Investigations - for Diagnosis

Fact Explanation
Electrocardiography(ECG) The most helpful ECG finding is prolongation of QT interval for more than 0.46 seconds. In addition there can be other changes such as torsade de pointes, T wave alternans, notched T wave in three leads etc[2][3][5]
Genetic Testing The common mutations related to the long QT syndrome are in three genetic loci termed KCNQ1 (LQT1), KCNH2 (LQT2) and SCN5A (LQT3). LQT1 and LQT2 are potassium channel genes and LQT3 is a sodium channel gene. Some studies has shown that LQT1 mutations to be the least hazardous. LQT2 and LQT3 mutations were associated with a relatively high risk of cardiac events. These can be identified by genetic testing[3][4][5][7]
Serum Electrolytes Serum levels of potassium, calcium and magnesium are done in patients who present with QT prolongation to eliminate secondary reasons for repolarization abnormalities, as hypocalcemia, hypokalemia or hypomagnesia can precipitate similar arrythmias[2][3]
Echocardiography This is done to exclude the presence of any structural abnormality in the heart which can trigger arrhythmia[6]
References
  1. MOREY SS. AHA Assesses the Impact of Genotyping on Diagnosis of Genetic Cardiac Disease. Am Fam Physician[online] 1999 May 15;59(10):2915-2918[viewed on 26 June 2014] Available from; http://www.aafp.org/afp/1999/0515/p2915.html
  2. MEYER. JS, MEHDIRAD A, SALEM BI, JAMRY WA, KULIKOWSKA A, KULIKOWSKI P. Sudden Arrhythmia Death Syndrome: Importance of the Long QT Syndrome. Am Fam Physician[online] 2003 Aug 1;68(3):483-488[viewed on 26 June 2014] Available from; http://www.aafp.org/afp/2003/0801/p483.html
  3. PETER J. SCHWARTZ. Practical issues in the management of the long QT syndrome: focus on diagnosis and therapy. Swiss Med Wkly[online] 2013;143:w13843 [viewed on 27 June 2014] Available from; http://www.smw.ch/content/smw-2013-13843/
  4. IMMY JJ, CHEN CY, YEH HM, CHIU WY, YU CC, LIU YB, TSAI CT, LO LW, YEH SF, LAI LP. Clinical characteristics of patients with congenital long QT syndrome and bigenic mutations. Chin Med J (Engl) [online] 2014, 127(8):1482-6 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24762593
  5. BHUIYAN ZA, AL-SHAHRANI S, AL-AAMA J, WILDE AA, MOMENAH TS. Congenital Long QT Syndrome: An Update and Present Perspective in Saudi Arabia Front Pediatr [online] :39 [viewed 26 June 2014] Available from: doi:10.3389/fped.2013.00039
  6. SHAH BN. Echocardiography in the Era of Multimodality Cardiovascular Imaging Biomed Res Int [online] 2013:310483 [viewed 26 June 2014] Available from: doi:10.1155/2013/310483
  7. TESTER DJ, ACKERMAN MJ. GENETICS OF LONG QT SYNDROME. Methodist Debakey Cardiovasc J [online] 2014 Jan, 10(1):29-33 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24932360

Management - General Measures

Fact Explanation
Avoid competitive sports Strenuous activities, vigorous exercise, swimming etc can trigger sudden cardiac events in patients with long QT syndrome. Therefore they are advised to avoid competitive sports and stressful activities[1]
Avoid drugs that prolong QT interval Certain medication such as some antihistamines, macrolides, antifungal agents, psychotrophic agents etc. (see above) should be avoided in these patients as they prolong QT interval and worsen their disease[1][2]
References
  1. MEYER. JS, MEHDIRAD A, SALEM BI, JAMRY WA, KULIKOWSKA A, KULIKOWSKI P. Sudden Arrhythmia Death Syndrome: Importance of the Long QT Syndrome. Am Fam Physician[online] 2003 Aug 1;68(3):483-488[viewed on 26 June 2014] Available from; http://www.aafp.org/afp/2003/0801/p483.html
  2. Combined List of All QTdrugs and the List of Drugs to Avoid for Patients with Congenital Long QT Syndrome. Crediblemeds[online] 2013[viewed on 27 June 2014] Available from;http://crediblemeds.org/everyone/composite-list-all-qtdrugs/?rf=US

Management - Specific Treatments

Fact Explanation
Beta-blockers Beta-blockers are effective in preventing cardiac events in a majority of patients but some continue to develop cardiac events despite treatment[3][4][5][7]
Pacemakers Implanted cardiac pacemakers can eliminate arrhythmogenic bradycardias, decrease irregularities in heart-rate and diminish the risk of torsade de pointes ventricular tachycardia. Can be used in combination with beta blockade[2][3][4][5]
Implantable Cardioverter-Defibrillators(ICD) These are designed to detect and treat life-threatening arrhythmias, and have been proven to be highly effective in preventing sudden cardiac death (SCD), particularly in individuals who have a strong family history of SCD. [1][6][7]
Left cardiac sympathetic denervation Done for high-risk patients with long QT syndrome, who experience recurrent cardiac events despite maximal therapy on beta-blockers. The procedure decreases the risk of cardiac events but does not completely eliminate their occurrence. Therefore, it is limited to very high risk patients without adequate response to implantable devices or beta-blockers[5][7]
References
  1. MINTU P. TURAKHIA. Sudden Cardiac Death and Implantable Cardioverter-Defibrillators. Am Fam Physician[online] 2010 Dec 1;82(11):1357-1366[viewed on 27 June 2014] Available from; http://www.aafp.org/afp/2010/1201/p1357.html
  2. GABRIEL GREGORATOS. Indications and Recommendations for Pacemaker Therapy. Am Fam Physician[online] 2005 Apr 15;71(8):1563-1570[viewed on 27 June 2014] Available from; http://www.aafp.org/afp/2005/0415/p1563.html
  3. MEYER. JS, MEHDIRAD A, SALEM BI, JAMRY WA, KULIKOWSKA A, KULIKOWSKI P. Sudden Arrhythmia Death Syndrome: Importance of the Long QT Syndrome. Am Fam Physician[online] 2003 Aug 1;68(3):483-488[viewed on 26 June 2014] Available from; http://www.aafp.org/afp/2003/0801/p483.html
  4. TAKAHASHI K, SHIMIZU W, MIYAKE A, NABESHIMA T, NAKAYASHIRO M, GANAHA H. High Prevalence of the SCN5A E1784K Mutation in School Children With Long QT Syndrome Living on the Okinawa Islands. Circ J [online] 2014 May 28 [viewed 26 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/24871449
  5. SCHWARTZ PJ, MOSS AJ.25th Anniversary of the International Long-QT Syndrome Registry;An Ongoing Quest to Uncover the Secrets of Long-QT Syndrome. Circulation[online] 2005; 111: 1199-1201[viewed on 27 June 2014] Available from; http://circ.ahajournals.org/content/111/9/1199.full
  6. AKERSTRöM F, ARIAS MA, PACHóN M, PUCHOL A, JIMéNEZ-LóPEZ J. Subcutaneous implantable defibrillator: State-of-the art 2013 World J Cardiol [online] 2013 Sep 26, 5(9):347-354 [viewed 26 June 2014] Available from: doi:10.4330/wjc.v5.i9.347
  7. PETER J. SCHWARTZ. Practical issues in the management of the long QT syndrome: focus on diagnosis and therapy. Swiss Med Wkly[online] 2013;143:w13843 [viewed on 27 June 2014] Available from; http://www.smw.ch/content/smw-2013-13843/