 |
|
Association of Long QT Syndrome Loci and Cardiac Events Among Patients Treated With  -Blockers
Silvia G. Priori, MD, PhD;
Carlo Napolitano, MD, PhD;
Peter J. Schwartz, MD;
Massimiliano Grillo, MD;
Raffaella Bloise, MD;
Elena Ronchetti, PhD;
Cinzia Moncalvo, MD;
Chiara Tulipani, MD;
Alessia Veia, MD;
Georgia Bottelli, BS;
Janni Nastoli, BS
JAMA. 2004;292:1341-1344.
ABSTRACT
| |
Context Data on the efficacy of  -blockers in the 3 most common genetic long QT syndrome (LQTS) loci are limited.
Objective To describe and assess outcome in a large systematically genotyped population of -blocker–treated LQTS patients.
Design, Setting, and Patients Consecutive LQTS-genotyped patients (n = 335) in Italy treated with -blockers for an average of 5 years.
Main Outcome Measures Cardiac events (syncope, ventricular tachycardia/torsades de pointes, cardiac arrest, and sudden cardiac death) while patients received -blocker therapy according to genotype.
Results Cardiac events among patients receiving -blocker therapy occurred in 19 of 187 (10%) LQT1 patients, 27 of 120 (23%) LQT2 patients, and 9 of 28 (32%) LQT3 patients (P<.001). The risk of cardiac events was higher among LQT2 (adjusted relative risk, 2.81; 95% confidence interval [CI], 1.50-5.27; P = .001) and LQT3 (adjusted relative risk, 4.00; 95% CI, 2.45-8.03; P<.001) patients than among LQT1 patients, suggesting inadequate protection from -blocker therapy. Other important predictors of risk were a QT interval corrected for heart rate that was more than 500 ms in patients receiving therapy (adjusted relative risk, 2.01; 95% CI, 1.16-3.51; P = .01) and occurrence of a first cardiac event before the age of 7 years (adjusted RR, 4.34; 95% CI, 2.35-8.03; P<.001).
Conclusion Among patients with genetic LQTS treated with -blockers, there is a high rate of cardiac events, particularly among patients with LQT2 and LQT3 genotypes.
INTRODUCTION
Long QT syndrome (LQTS) is a genetic disease characterized by prolonged ventricular repolarization, syncope, ventricular arrhythmias, and sudden death,1-3 often precipitated by emotion or exercise. Primarily according to nonrandomized trial evidence, -blockers are considered first-line prophylactic therapy,4 whereas patients refractory to -blockers may be treated with left-sided cardiac sympathetic denervation, pacemakers, or implantable cardioverter defibrillators.1, 5-8 The hypothesis that the efficacy of therapy may vary according to the genetic form of the disease has been proposed7 but not thoroughly investigated.
Three genetic loci account for nearly 98% of genetically characterized patients. In this investigation, we sought to describe and assess outcomes of -blocker–treated patients affected by the 3 most common genetic loci of LQTS9: LQT1, LQT2, and LQT3, caused by genetic defects on KCNQ1, KCNH2, and SCN5A genes.
METHODS
Study Population and Data Collection
The study population included 335 genotyped LQT1, LQT2, or LQT3 patients treated with long-term -blocker therapy. For each patient, data on personal and family history, cardiac events, and therapy were systematically recorded at each visit or medical contact. The specific -blocker used, as well as dose, was at the discretion of the treating physician. LQTS-related cardiac events included unexplained syncope, torsades de pointes, ventricular tachycardia, aborted cardiac arrest, and sudden cardiac death. All patients or their guardians provided written informed consent for clinical and genetic evaluation. The protocol was approved by the institutional review board of the Policlinico S. Matteo and of the Maugeri Foundation, Pavia, Italy.
Genetic Analysis
Patients were consecutively genotyped at the Molecular Cardiology Laboratories of the Maugeri Foundation as carriers of a single mutation on KCNQ1, KCNH2, or SCN5A genes; carriers of double mutations, representing on average 3% to 5% of the patients, were excluded from the study.
DNA was extracted from peripheral blood lymphocytes and amplified with primer pairs for KCNQ1, KCNH2, and SCN5A. Genetic analysis was performed by standard methods: denaturating high-performance liquid chromatography (Wave Transgenomics, Omaha, Neb) was performed on polymerase chain reaction–amplified DNA, encompassing the entire open reading frame of each gene, by using intronic primers. When abnormal chromatograms were identified, double-strand sequencing of amplified genomic DNA (ABI Prism 310; Applied Biosystems, Foster City, Calif) of the corresponding amplicon was performed. In addition to the previously reported polymorphisms, all DNA variants causing coding variations and occurring in more than 1 in 100 of the control population (400 healthy controls; ie, 800 alleles) were considered polymorphisms.
Statistical Analysis
All analyses were performed with the SPSS 11.0 statistical package (SPSS Inc, Chicago, Ill). Statistical significance was set at P .05. Genetic loci–related differences for continuous variables were assessed by using 1-way analysis of variance, with post hoc analysis with the Tukey test, whereas differences for categorical variables were assessed with the Pearson  2 test. Survival analyses included construction of Kaplan-Meier plots with comparisons with the log-rank 2 test, as well as forward-selection Cox proportional hazards modeling. We considered sex, QT interval corrected for heart rate (QTc), occurrence of cardiac events before therapy, age at first cardiac event before therapy, family history of sudden death, and genotype as candidate variables.
RESULTS
Population Characteristics
The 335 genotyped LQTS patients were from 187 families with mutations on KCNQ1 (LQT1; n = 187), KCNH2 (LQT2; n = 120), or SCN5A (LQT3; n = 28) genes treated with -blockers. Before therapy, 159 of 335 (47%) experienced cardiac events. The mean (SD) age at initiation of -blocker therapy was 21 (17) years (interquartile range, 8.5-31.7 years); the median follow-up for patients without events and receiving -blocker therapy was 4.7 years (range, 0.6-36 years). As summarized in Table 1, no differences among LQT1, LQT2, and LQT3 patients were observed in age, age at initiation of therapy, observation time while receiving -blockers, and age at first cardiac event before therapy. However, LQT1 patients had a shorter QTc interval. Data for type of -blocker and dosage per kilogram of body weight were available for 266 individuals: 69% of them were treated with either propranolol (average daily dose, 2.2 [SD, 1.04] mg/kg) or nadolol (average daily dose, 1.2 [SD, 0.5] mg/kg ); there were no dosage differences among the 3 genotypes (P = .31).
|
|
|
|
Table 1. Clinical Characteristics of the Study Population According to Genotype*
|
|
|
Cardiac Events in Patients Receiving -Blocker Therapy
There were 55 patients (16%) who experienced cardiac events while receiving -blocker therapy, of whom 14 (25%) had a cardiac arrest; 4 sudden cardiac deaths occurred (1 LQT1 and 3 LQT3). Events were not evenly distributed in the 3 loci, with LQT1 having the lowest incidence of cardiac events (LQT1: 19/187 [10%]; LQT2: 27/120 [23%]; and LQT3: 9/28 [32%]; P = .001) (Table 1 and Figure 1).
|
|
|
|
Figure. Kaplan-Meier Analysis of Event-Free Survival
Kaplan-Meier analysis of cumulative cardiac event-free survival in genotyped long QT syndrome patients receiving -blockers according to the genetic variant of the disease (log-rank P<.001). The definition of events includes syncope, cardiac arrest, and sudden cardiac death. LQT1 indicates long QT syndrome type 1; LQT2, long QT syndrome type 2; LQT3, long QT syndrome type 3.
|
|
|
In a multivariable model, important predictors of time free of events were first cardiac event before therapy in early childhood (age 7 years), QTc more than 500 ms in patients receiving therapy, and genetic locus other than LQT1 (Table 2). When we combined patients with LQT2 and LQT3, they were at substantially increased risk for cardiac events compared with those with LQT1 (18/187 [10%] vs 36/148 [24%]; odds ratio, 2.8; 95% confidence interval [CI], 1.6-5.2; P<.001). Similarly, LQT2 and LQT3 patients were at increased risk for cardiac arrest or sudden cardiac death compared with those with LQT1 (8% vs 1%; odds ratio, 8.1; 95% CI, 1.8-37; P = .001). Four of 14 patients experiencing cardiac arrest while receiving therapy had been asymptomatic before therapy; thus, cardiac arrest was their first symptom of LQTS.
|
|
|
|
Table 2. Significant Predictors of Cardiac Events and Cardiac Arrest for Patients Receiving Therapy (N = 335)
|
|
|
These results were confirmed in a supplementary analysis of the 187 probands of each family to correct for a possible confounding effect introduced by the presence of family members. In another supplementary analysis, we found that LQT2 or LQT3 genotype was associated with a higher risk of cardiac events in patients receiving -blockers, even after excluding patients who had a cardiac arrest before therapy (49 events: 2/183 LQT1, 7/110 LQT2, and 3/23 LQT3; odds ratio, 2.15; 95% CI, 1.2-4.2; P = .002).
COMMENT
Prophylactic therapy with -blockers is the mainstay treatment for LQTS patients. In our large series, however, we found a high rate of cardiac events in patients receiving -blocker therapy, particularly for patients with LQT2 and LQT3 genotypes. These observations are troubling and suggest that, for some patients, genotyping may be useful for identifying candidates for more aggressive interventions, possibly including defibrillator implantation.
Our findings are consistent with existing evidence that genetic background may influence the severity of the disease and its clinical manifestations before treatment.10 In 1985, Schwartz4 provided the first data indicating that a subset of LQTS patients was not fully protected by -blockers. In 2000, Moss et al7 further quantified this worrisome phenomenon and, reporting data on 139 genotyped patients, introduced the concept that the response to -blockers may be modulated by genetic substrate. We have extended those observations by showing in a large systematically genotyped -blocker–treated cohort a gradient of risk from LQT1 to LQT2 to LQT3 genotypes. Furthermore, we have shown that in addition to genotype, other important predictors of cardiac events in patients receiving therapy include QTc interval and younger age at a first pretherapy cardiac event.
Because no randomized trial data exist, our findings about the value of defibrillator implantation in -blocker–treated LQTS patients who have not experienced a cardiac arrest cannot be considered conclusive. Nonetheless, these findings suggest that prophylactic defibrillator therapy may be a reasonable addition to -blockers in patients with LQT2 or LQT3 genotypes. However, a decision to implant a defibrillator in LQT2 and LQT3 patients in the absence of definitive randomized trial evidence is a complex one that requires consideration of important issues such as the implantable cardioverter defibrillator's impact on quality of life of young patients, high complication rates, the acceptance of the device by patients and their families as an alternative, and the incomplete but additional protection by left-sided cardiac sympathetic stimulation.5 Furthermore, it is unlikely that -blocker therapy could be safely discontinued after defibrillator implantation.
This study is based on an observational registry and is subject to all the inherent limitations of such an analysis. Because LQTS is a relatively rare disease, it is unlikely that large-scale randomized trial data will become available soon, meaning that evaluation and treatment of these patients must occur in a setting of incomplete evidence. Furthermore, approximately 40% of LQTS patients cannot be genotyped on the known loci, so for these patients, -blockers remain the recommended therapy.
AUTHOR INFORMATION
| |
Corresponding Author: Silvia G. Priori, MD, PhD, Molecular Cardiology, Maugeri Foundation, University of Pavia, Via Ferrata 8, 27100 Pavia, Italy (spriori{at}fsm.it).
Author Contributions: Drs Priori, Grillo, Bloise, Napolitano, and Schwartz had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Priori, Napolitano, Schwartz.
Acquisition of data: Napolitano, Grillo, Bloise, Ronchetti, Moncalvo, Tulipani, Veia, Bottelli, Nastoli.
Analysis and interpretation of data: Priori, Napolitano, Schwartz, Grillo, Bloise, Ronchetti, Moncalvo, Tulipani, Veia, Nastoli.
Drafting of the manuscript: Priori, Napolitano, Schwartz, Bloise, Moncalvo, Veia, Bottelli, Nastoli.
Critical revision of the manuscript for important intellectual content: Priori, Napolitano, Schwartz, Grillo, Bloise, Ronchetti, Tulipani.
Statistical analysis: Priori, Napolitano, Grillo, Bloise, Ronchetti, Moncalvo, Tulipani, Veia, Bottelli.
Obtained funding: Priori, Schwartz.
Administrative, technical, or material support: Priori, Schwartz, Nastoli.
Study supervision: Priori, Napolitano, Schwartz.
Funding/Support: This work was supported in part by Telethon grant GP0227Y01, "Ricerca Finalizzata" DG-RSVE-RF2001-1862 and RF2002/1290, Fondi per fli Investimenti della Ricerca di Base RBNE01XMP4_006, Co-Finanziamento 2001067817_003, and Cassa di Risparmio delle Province Lombarde grant 2001.3009/10.9079.
Role of the Sponsor: The study sponsor provided an unrestricted educational grant that covered the costs of some of the data entry. The sponsor had no role regarding the decision to publish. The sponsor did not see the submitted manuscript and is not aware of the data obtained as the result of our analysis.
Acknowledgment: We thank Paola Baiardi, PhD, for assistance in the statistical analysis and Francesca Giovannoni, BS, for assistance in the organization of the data collection and entry.
Financial Disclosure: Dr Priori serves on the advisory board of Guidant-Europe and Medtronic-Europe.
Author Affiliations: Molecular Cardiology, IRCCS Fondazione Maugeri (Drs Priori, Napolitano, Grillo, Bloise, Ronchetti, Moncalvo, Tulipani, and Veia and Mss Bottelli and Nastoli); Department of Cardiology, IRCCS Policlinico S. Matteo (Dr Schwartz); and University of Pavia (Drs Priori and Schwartz), Pavia, Italy.
REFERENCES
1. Romano C, Gemme G, Pongiglione R. Aritmie cardiache rare dell'età pediatrica. Clin Pediatr. 1963;45:656-683.
2. Ward OC. A new familial cardiac syndrome in children. J Ir Med Assoc. 1964;54:103-106.
PUBMED
3. Schwartz PJ, Priori SG, Napolitano C. The long QT syndrome. In: Zipes DP, Jalife J, eds. Cardiac Electrophysiology From Cell to Bedside. Philadelphia, Pa: WB Saunders Co; 2000:597-615.
4. Priori SG, Aliot E, Blomstrom-Lundqvist C, et al. Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J. 2001;22:1374-1450.
FREE FULL TEXT
5. Schwartz PJ, Priori SG, Cerrone M, et al. Left cardiac sympathetic denervation in the management of high-risk patients affected by the long QT syndrome. Circulation. 2004;109:1826-1833.
FREE FULL TEXT
6. Groh WJ, Silka MJ, Oliver RP, Halperin BD, McAnulty JH, Kron J. Use of implantable cardioverter-defibrillator in the congenital long QT syndrome. Am J Cardiol. 1996;78:703-706.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
7. Moss AJ, Zareba W, Hall WJ, et al. Effectiveness and limitations of beta-blocker therapy in congenital long-QT syndrome. Circulation. 2000;101:616-623.
FREE FULL TEXT
8. Schwartz PJ, Priori SG, Spazzolini C, et al. Genotype-phenotype correlation in the long QT syndrome: gene-specific triggers for life threatening arrhythmias. Circulation. 2001;103:89-95.
FREE FULL TEXT
9. Keating MT, Sanguinetti MC. Molecular and cellular mechanisms of cardiac arrhythmias. Cell. 2001;104:569-580.
FULL TEXT
|
WEB OF SCIENCE
| PUBMED
10. Priori SG, Schwartz PJ, Napolitano C, et al. Risk stratification in the long QT syndrome. N Engl J Med. 2003;348:1866-1874.
FREE FULL TEXT
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Genotype-Phenotype Aspects of Type 2 Long QT Syndrome.
Shimizu et al.
J Am Coll Cardiol 2009;54:2052-2062.
ABSTRACT
| FULL TEXT
Routine electrocardiogram and medical history in syncope: a simple approach can identify most high-risk patients
Cerrone and Priori
Europace 2009;11:1411-1412.
FULL TEXT
Clinical Implications for Patients With Long QT Syndrome Who Experience a Cardiac Event During Infancy.
Spazzolini et al.
J Am Coll Cardiol 2009;54:832-837.
ABSTRACT
| FULL TEXT
Drug-Sensitized Zebrafish Screen Identifies Multiple Genes, Including GINS3, as Regulators of Myocardial Repolarization
Milan et al.
Circulation 2009;120:553-559.
ABSTRACT
| FULL TEXT
Re-evaluating the efficacy of {beta}-adrenergic agonists and antagonists in long QT-3 syndrome through computational modelling
Ahrens-Nicklas et al.
Cardiovasc Res 2009;82:439-447.
ABSTRACT
| FULL TEXT
Advances in the prevention of sudden cardiac death in the young
Shephard and Semsarian
Ther Adv Cardiovasc Dis 2009;3:145-155.
ABSTRACT
Treating the Long-QT Syndrome in the Era of Implantable Defibrillators
Viskin and Halkin
Circulation 2009;119:204-206.
FULL TEXT
High Efficacy of {beta}-Blockers in Long-QT Syndrome Type 1: Contribution of Noncompliance and QT-Prolonging Drugs to the Occurrence of {beta}-Blocker Treatment "Failures"
Vincent et al.
Circulation 2009;119:215-221.
ABSTRACT
| FULL TEXT
CHAPTER 9 Genetics of Cardiovascular Diseases
Priori et al.
ESC Textbook of Cardiovascular Medicine 2009;2:med-9780199566990-chapter-med-9780199566990-chapter.
ABSTRACT
| FULL TEXT
Malignant Perinatal Variant of Long-QT Syndrome Caused by a Profoundly Dysfunctional Cardiac Sodium Channel
Wang et al.
Circ Arrhythm Electrophysiol 2008;1:370-378.
ABSTRACT
| FULL TEXT
Therapeutic Strategies for Long-QT Syndrome: Does the Molecular Substrate Matter?
Ruan et al.
Circ Arrhythm Electrophysiol 2008;1:290-297.
FULL TEXT
Congenital long QT syndrome: Considerations for primary care physicians
LEVINE et al.
Cleveland Clinic Journal of Medicine 2008;75:591-600.
ABSTRACT
| FULL TEXT
Importance of Knowing the Genotype and the Specific Mutation When Managing Patients With Long-QT Syndrome
Moss and Goldenberg
Circ Arrhythm Electrophysiol 2008;1:219-226.
FULL TEXT
Genotyping Has a Minor Role in Selecting Therapy for Congenital Long-QT Syndromes at Present
Vincent
Circ Arrhythm Electrophysiol 2008;1:227-233.
FULL TEXT
Antiarrhythmic properties of a rapid delayed-rectifier current activator in rabbit models of acquired long QT syndrome
Diness et al.
Cardiovasc Res 2008;79:61-69.
ABSTRACT
| FULL TEXT
Long QT syndrome.
Goldenberg and Moss
J Am Coll Cardiol 2008;51:2291-2300.
ABSTRACT
| FULL TEXT
The Year in Review of Clinical Cardiac Electrophysiology
Scheinman and Keung
J Am Coll Cardiol 2008;51:2075-2081.
FULL TEXT
ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices) Developed in Collaboration With the American Association for Thoracic Surgery and Society of Thoracic Surgeons
Epstein et al.
J Am Coll Cardiol 2008;51:e1-e62.
FULL TEXT
ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): Developed in Collaboration With the American Association for Thoracic Surgery and Society of Thoracic Surgeons
Writing Committee Members et al.
Circulation 2008;117:e350-e408.
FULL TEXT
Risk Factors for Aborted Cardiac Arrest and Sudden Cardiac Death in Children With the Congenital Long-QT Syndrome
Goldenberg et al.
Circulation 2008;117:2184-2191.
ABSTRACT
| FULL TEXT
Long-QT Syndrome After Age 40
Goldenberg et al.
Circulation 2008;117:2192-2201.
ABSTRACT
| FULL TEXT
Clinical indications for genetic testing in familial sudden cardiac death syndromes: an HRUK position statement
Heart Rhythm UK Familial Sudden Death Syndromes St
Heart 2008;94:502-507.
ABSTRACT
| FULL TEXT
Antiarrhythmic vs. pro-arrhythmic effects depending on the intensity of adrenergic stimulation in a canine anthopleurin-A model of type-3 long QT syndrome
Chinushi et al.
Europace 2008;10:249-255.
ABSTRACT
| FULL TEXT
Long-QT Syndrome
Roden
NEJM 2008;358:169-176.
FULL TEXT
The fight against sudden cardiac death: consensus guidelines as a reference
Rossenbacker et al.
Eur Heart J Suppl 2007;9:I50-I58.
ABSTRACT
| FULL TEXT
The Common Long-QT Syndrome Mutation KCNQ1/A341V Causes Unusually Severe Clinical Manifestations in Patients With Different Ethnic Backgrounds: Toward a Mutation-Specific Risk Stratification
Crotti et al.
Circulation 2007;116:2366-2375.
ABSTRACT
| FULL TEXT
Long QT Syndrome in Children: Not One Disease Anymore
Balaji
J Am Coll Cardiol 2007;50:1341-1342.
FULL TEXT
Long QT Syndrome in Children in the Era of Implantable Defibrillators
Etheridge et al.
J Am Coll Cardiol 2007;50:1335-1340.
ABSTRACT
| FULL TEXT
Gating Properties of SCN5A Mutations and the Response to Mexiletine in Long-QT Syndrome Type 3 Patients
Ruan et al.
Circulation 2007;116:1137-1144.
ABSTRACT
| FULL TEXT
Long QT Syndrome in Adults
Sauer et al.
J Am Coll Cardiol 2007;49:329-337.
ABSTRACT
| FULL TEXT
Prevalence of Long-QT Syndrome Gene Variants in Sudden Infant Death Syndrome
Arnestad et al.
Circulation 2007;115:361-367.
ABSTRACT
| FULL TEXT
Effects of L-type Ca2+ channel antagonism on ventricular arrhythmogenesis in murine hearts containing a modification in the Scn5a gene modelling human long QT syndrome 3
Thomas et al.
J. Physiol. 2007;578:85-97.
ABSTRACT
| FULL TEXT
Sudden Death and Long-QT Syndrome
Saarel
AAP Grand Rounds 2006;16:62-63.
FULL TEXT
Altered Na+ Channels Promote Pause-Induced Spontaneous Diastolic Activity in Long QT Syndrome Type 3 Myocytes
Fredj et al.
Circ. Res. 2006;99:1225-1232.
ABSTRACT
| FULL TEXT
Genotype-Specific Onset of Arrhythmias in Congenital Long-QT Syndrome: Possible Therapy Implications
Tan et al.
Circulation 2006;114:2096-2103.
ABSTRACT
| FULL TEXT
Does Pregnancy Increase Cardiac Risk for LQT1 Patients With the KCNQ1-A341V Mutation?
Heradien et al.
J Am Coll Cardiol 2006;48:1410-1415.
ABSTRACT
| FULL TEXT
Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome.
Hobbs et al.
JAMA 2006;296:1249-1254.
ABSTRACT
| FULL TEXT
Corrected QT Variability in Serial Electrocardiograms in Long QT Syndrome: The Importance of the Maximum Corrected QT for Risk Stratification
Goldenberg et al.
J Am Coll Cardiol 2006;48:1047-1052.
ABSTRACT
| FULL TEXT
QT Interval Duration Remains a Major Risk Factor in Long QT Syndrome Patients
Locati
J Am Coll Cardiol 2006;48:1053-1055.
FULL TEXT
ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death)
Developed in Collaboration With the European Heart et al.
J Am Coll Cardiol 2006;48:e247-e346.
FULL TEXT
ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society
Writing Committee Members et al.
Europace 2006;8:746-837.
FULL TEXT
Effects of Beta-Blocker Therapy on Ventricular Repolarization Documented by 24-h Electrocardiography in Patients With Type 1 Long-QT Syndrome
Viitasalo et al.
J Am Coll Cardiol 2006;48:747-753.
ABSTRACT
| FULL TEXT
Cost-effectiveness of neonatal ECG screening for the long QT syndrome
Quaglini et al.
Eur Heart J 2006;27:1824-1832.
ABSTRACT
| FULL TEXT
Molecular Underpinning of "Good Luck"
Priori and Napolitano
Circulation 2006;114:360-362.
FULL TEXT
Dental treatment of patients with long QT syndrome
Karp and Moss
Journal of the American Dental Association 2006;137:630-637.
ABSTRACT
| FULL TEXT
Epinephrine QT Stress Testing in the Evaluation of Congenital Long-QT Syndrome: Diagnostic Accuracy of the Paradoxical QT Response
Vyas et al.
Circulation 2006;113:1385-1392.
ABSTRACT
| FULL TEXT
Role of Genetic Analyses in Cardiology: Part I: Mendelian Diseases: Cardiac Channelopathies
Priori and Napolitano
Circulation 2006;113:1130-1135.
ABSTRACT
| FULL TEXT
The Jervell and Lange-Nielsen Syndrome: Natural History, Molecular Basis, and Clinical Outcome
Schwartz et al.
Circulation 2006;113:783-790.
ABSTRACT
| FULL TEXT
Genetic Testing in the Long QT Syndrome: Development and Validation of an Efficient Approach to Genotyping in Clinical Practice
Napolitano et al.
JAMA 2005;294:2975-2980.
ABSTRACT
| FULL TEXT
Efficient Genotyping for Congenital Long QT Syndrome
Kaufman
JAMA 2005;294:3027-3028.
FULL TEXT
Phenotypic Variability and Unusual Clinical Severity of Congenital Long-QT Syndrome in a Founder Population
Brink et al.
Circulation 2005;112:2602-2610.
ABSTRACT
| FULL TEXT
Genetics of cardiac arrhythmias
Wilde and Bezzina
Heart 2005;91:1352-1358.
FULL TEXT
The long QT syndrome: Therapeutic implications of a genetic diagnosis
Shimizu
Cardiovasc Res 2005;67:347-356.
ABSTRACT
| FULL TEXT
The year in clinical electrophysiology
Scheinman and Keung
J Am Coll Cardiol 2005;45:790-795.
FULL TEXT
Cardiac repolarization. The long and short of it
Antzelevitch
Europace 2005;7:S3-S9.
ABSTRACT
| FULL TEXT
How Effective Are Beta-Blockers for Long-QT Syndrome?
Journal Watch Cardiology 2004;2004:3-3.
FULL TEXT
|
