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Previous Volume 339:960-965 October 1, 1998 Number 14 Next

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ABSTRACT

Background The congenital long-QT syndrome, caused by mutations in cardiac potassium-channel genes (KVLQT1 at the LQT1 locus and HERG at the LQT2 locus) and the sodium-channel gene (SCN5A at the LQT3 locus), has distinct repolarization patterns on electrocardiography, but it is not known whether the genotype influences the clinical course of the disease.

Methods We determined the genotypes of 541 of 1378 members of 38 families enrolled in the International Long-QT Syndrome Registry: 112 had mutations at the LQT1 locus, 72 had mutations at the LQT2 locus, and 62 had mutations at the LQT3 locus. We determined the cumulative probability and lethality of cardiac events (syncope, aborted cardiac arrest, or sudden death) occurring from birth through the age of 40 years according to genotype in the 246 gene carriers and in all 1378 members of the families studied.

Results The frequency of cardiac events was higher among subjects with mutations at the LQT1 locus (63 percent) or the LQT2 locus (46 percent) than among subjects with mutations at the LQT3 locus (18 percent) (P<0.001 for the comparison of all three groups). In a multivariate Cox analysis, the genotype and the QT interval corrected for heart rate were significant independent predictors of a first cardiac event. The cumulative mortality through the age of 40 among members of the three groups of families studied was similar; however, the likelihood of dying during a cardiac event was significantly higher (P<0.001) among families with mutations at the LQT3 locus (20 percent) than among those with mutations at the LQT1 locus (4 percent) or the LQT2 locus (4 percent).

Conclusions The genotype of the long-QT syndrome influences the clinical course. The risk of cardiac events is significantly higher among subjects with mutations at the LQT1 or LQT2 locus than among those with mutations at the LQT3 locus. Although cumulative mortality is similar regardless of the genotype, the percentage of cardiac events that are lethal is significantly higher in families with mutations at the LQT3 locus.

The identification of three mutant genes at loci LQT1, LQT2, and LQT3 associated with the long-QT syndrome was largely made possible by the study of patients enrolled in the International Long-QT Syndrome Registry.^5,7,8,9 During the past 18 years, 728 families with clinically identified long-QT syndrome have been enrolled and followed as part of the registry. The broad spectrum of clinical manifestations among patients enrolled in the registry was an indication of the heterogeneity of the disease before the disease was linked to multiple loci. We have previously reported that the electrocardiographic phenotypes¹³ and factors triggering cardiac events^14,15 differ in the three genetically distinct forms of long-QT syndrome. In the current study, we evaluated the clinical course of the long-QT syndrome on the basis of the genotype in members of the registry.

Methods

Study Population

The study subjects were enrolled in the International Long-QT Syndrome Registry⁵ by four centers (in Rochester, N.Y.; Pavia, Italy; Salt Lake City; and Jerusalem, Israel). Genetic testing for the long-QT syndrome was performed in 541 members of 38 large families selected from the registry, since to be successful linkage analysis requires large families. There were 10 families with mutations at the LQT1 locus in which 9 probands and 242 relatives were genetically tested, 22 families with mutations at the LQT2 locus in which all probands and 127 relatives underwent genetic testing, and 6 families with mutations at the LQT3 locus in which 5 probands and 136 relatives were tested. Most of the known mutations were originally identified in patients enrolled in the registry.^7,8,9 Blood samples were obtained from the study subjects for the purpose of linkage and mutation analyses. The mutations were identified with the use of standard genetic tests.^7,8,9 All subjects or their guardians provided informed consent for the genetic and clinical studies.

We also compared the phenotypic features of all 1378 enrolled members of the 38 families, on the basis of the assumption that the phenotype — and therefore the genotype — of affected members of a given family would be the same as that of the proband. This assumption was supported by our own data showing that 209 members of 38 families had the same mutation as their respective probands and that for the various genotypes, the proportions of carriers among genetically tested subjects were similar. Different intragenic mutations, including deletions, splice-donor mutations, and missense mutations, have been identified in some pedigrees.^7,8,9,16 This study was intended to explore the clinical course of the long-QT syndrome not on the basis of specific intragenic mutations, but on the basis of the mutated gene locus (LQT1, LQT2, or LQT3), reflecting abnormalities in potassium-channel or sodium-channel function.

Phenotypic Characterization

Detailed pedigrees were constructed for each family. A clinical history and a 12-lead electrocardiogram were obtained at the time of enrollment of each family member in the registry. On these base-line electrocardiograms, the duration of the QT and RR intervals in lead II (or lead I or III if the QT interval was not measurable in lead II) was determined, and the QT interval, corrected for heart rate (QTc) according to Bazett's formula, was determined.¹⁷ Clinical data were recorded on prospectively designed forms and included information on demographic characteristics, personal and family history of disease, electrocardiographic findings, therapy, follow-up, and end points.

End Points

The following cardiac events were included as end points: syncopal events (fainting spells with transient loss of consciousness), aborted cardiac arrest (requiring defibrillation), and death. Only events occurring from birth through the age of 40 years were included in the analysis to limit possible confounding effects of coronary artery disease and other cardiovascular conditions on the outcome. Surviving family members were asked about the clinical circumstances surrounding the death of their relatives, the presence of preexisting medical problems, and the abruptness of the event. Unexpected, sudden death (i.e., death without warning) that occurred through the age of 40 without a known cause was categorized as related to the long-QT syndrome.

Since numerous patients with the long-QT syndrome had multiple cardiac events, we also evaluated the severity and lethality of cardiac events in the 38 families. We determined the percentage of subjects who had had multiple cardiac events, since this value is a reflection of the severity of the disease. We assessed the lethality of cardiac events by dividing the number of deaths related to the long-QT syndrome by the total number of cardiac events. To determine the natural course of the disease, we assessed cardiac events that occurred before treatment with beta-blockers was begun.

Statistical Analysis

The clinical features of the three groups identified on the basis of the genotype — LQT1, LQT2, or LQT3 — were compared with use of analysis of variance, the Kruskal–Wallis rank test, and the chi-square test, as appropriate. The cumulative probability of a first cardiac event (syncope, aborted cardiac arrest, or death) in the first 40 years of life was determined for the three groups with use of the life-table method of Kaplan and Meier,¹⁸ and the results were compared with the log-rank test with the Bonferroni correction for multiplicity. Cox multivariate survivorship analyses¹⁹ were performed to evaluate the significance and independence of the genotype as a predictor of cardiac events through the age of 40 in carriers of mutations, after adjustment for sex, QTc, and heart rate.

Results

Among the 541 subjects who underwent genotyping, 112 had mutations at the LQT1 locus, 72 had mutations at the LQT2 locus, and 62 had mutations at the LQT3 locus. Their clinical characteristics are shown in Table 1. There was a higher percentage of female subjects in the LQT2 group than in the other two groups. The mean heart rate and the incidence of bradycardia were not significantly different among the three groups. The mean QTc was significantly longer in the LQT3 group than in the other groups (P=0.03): 48 percent of the subjects in the LQT3 group had a QTc of more than 500 msec, as compared with 33 percent of subjects in the LQT1 group and 28 percent of subjects in the LQT2 group (P=0.06). The QTc was as low as 400 to 430 msec in some carriers of the long-QT syndrome. The treatments were similar in the three groups except that cardiac pacing was not used in the LQT1 group.

View this table: [in this window] [in a new window]   Table 1. Characteristics of the 246 Subjects with a Mutant Long-QT Syndrome Gene.

 
The LQT1 and LQT2 groups had a significantly higher frequency (Table 1) and cumulative probability (Figure 1) of cardiac events than the LQT3 group. By the age of 15 years, 53 percent of subjects in the LQT1 group, 29 percent of those in the LQT2 group, and 6 percent of those in the LQT3 group had had a first cardiac event (Figure 1). Thirty-seven percent of subjects in the LQT1 group and 36 percent of those in the LQT2 group had had multiple cardiac events, as compared with 5 percent of subjects in the LQT3 group (P<0.001). Multivariate Cox regression analysis of the 246 gene carriers indicated that after adjustment for base-line QTc, those with mutations at the LQT1 or LQT2 locus had a risk of a first cardiac event through the age of 40 years that was three to five times as high as that of subjects in the LQT3 group (Table 2). The risk of a first cardiac event was also higher in the LQT1 group than in the LQT2 group (hazard ratio, 1.58; P=0.03).

View larger version (5K): [in this window] [in a new window]   Figure 1. Kaplan–Meier Estimate of the Cumulative Probability of a Cardiac Event in the LQT1, LQT2, and LQT3 Groups. The P value was computed with the log-rank test. The numbers of subjects at risk are given for each decade of age.

 

View this table: [in this window] [in a new window]   Table 2. Multivariate Analysis of Genotype and QTc as Predictors of a First Cardiac Event through the Age of 40 in 246 Subjects with a Mutant Long-QT Syndrome Gene.

 
A longer QTc was associated with an increased risk of cardiac events (hazard ratio, 1.06 per 10-msec increase in QTc; P=0.003) (Table 2), and this association was independent of the genotype. Sex, heart rate, and interactions between sex and genotype and between QTc and genotype were not statistically significant prognostic factors. However, examination of the data indicated a higher-than-expected incidence of events among male subjects in the LQT1 group, and analysis of this particular interaction yielded a hazard ratio of 1.77 (P=0.03). Since the effect of sex in the LQT2 group was in the opposite direction (more cardiac events in female than in male subjects) and was not significant, no overall effect of sex was identified.

Cardiac events that occurred through the age of 40 years before beta-blocker therapy was instituted were assessed in all 1378 enrolled members of the 38 families, regardless of whether genotyping had been performed (Table 3). Members of families with mutations at the LQT1 locus had the highest frequency of cardiac events, and members of families with mutations at the LQT3 locus had the lowest frequency (P=0.001). Multiple cardiac events were also more frequent in members of families with mutations at the LQT1 or LQT2 locus than in members of families with mutations at the LQT3 locus (P=0.002). Multivariate Cox regression analysis (data not shown) of 851 family members for whom electrocardiographic data were available yielded similar results, confirming that the risk of cardiac events was higher in families with mutations at the LQT1 or LQT2 locus than in families with mutations at the LQT3 locus and that the QTc was an independent predictor of the likelihood of a first cardiac event. As shown in Figure 2, the likelihood of cardiac events could be predicted on the basis of both the QTc and the genotype.

View this table: [in this window] [in a new window]   Table 3. Incidence of Cardiac Events through the Age of 40 in the 38 Families Studied.

 

View larger version (4K): [in this window] [in a new window]   Figure 2. Percentage of Subjects with Cardiac Events According to the QTc in Family Members of Genotyped Families.

 
Although there were significant differences in the frequency of cardiac events among the three groups, the overall frequency of death related to the long-QT syndrome was similar, 3 to 4 percent in each group (Table 3). The cumulative probability of death from the long-QT syndrome through the age of 40 was also similar among the groups (Figure 3).

View larger version (4K): [in this window] [in a new window]   Figure 3. Kaplan–Meier Estimate of the Cumulative Probability of Death Related to the Long-QT Syndrome in the LQT1, LQT2, and LQT3 Groups. There were no significant differences in cumulative mortality rates among the groups at the age of 40 (P=0.91). At the age of 15, the rates were 2.9 percent in the LQT1 group, 0.4 percent in the LQT2 group, and 1.5 percent in the LQT3 group (P=0.006 by the log-rank test).

 
Since the patients with the long-QT syndrome have an increased risk of sudden death, we evaluated the lethality of cardiac events in families with known genotypes. Twenty percent of all cardiac events were fatal in the LQT3 group, as compared with 4 percent in the LQT1 group and 4 percent in the LQT2 group (P<0.001).

Discussion

We have previously shown that the three genotypes of the long-QT syndrome are associated with distinctive repolarization patterns.¹³ In the current study, we found evidence that the clinical course of disease in families with the three genotypes also differs. Subjects with mutations at the LQT1 or LQT2 locus, which lead to abnormalities of the delayed inwardly rectifying potassium channel, had a significantly higher likelihood of cardiac events than subjects with the SCN5A mutation at the LQT3 locus, which leads to sodium-channel abnormalities. Younger age at onset and a higher likelihood of recurrent cardiac events were also observed in the subjects in the LQT1 and LQT2 groups.

We found a wide range of QTc values (from 400 to 640 msec) among carriers of the gene for the long-QT syndrome, as has been reported in previous studies.^13,20,21 Since previous studies of patients with the long-QT syndrome who had not undergone genotyping^5,22 showed a significant association between the QTc and the probability of cardiac events, we evaluated the effect of the genotype and the QTc on the probability of cardiac events in 246 gene carriers. Multivariate Cox regression analysis showed that the genotype was an independent predictor of a first cardiac event. In other words, the risk of cardiac events among patients with the long-QT syndrome who have similar QTc values differs depending on the genotype, and within each group, patients with a longer QTc have a higher risk of cardiac events than those with a shorter QTc. Therefore, in an evaluation of the risk of cardiac events in patients with the long-QT syndrome whose genotype is known, both the gene locus and the QTc need to be considered.

There was a significantly higher risk of cardiac events among male subjects in the LQT1 group, and a nonsignificantly higher risk was identified among female subjects in the LQT2 group. The small number of cardiac events in the LQT3 group precluded meaningful conclusions regarding sex. Although the mechanism underlying this finding is unclear, there is preliminary evidence that sex-hormone activity may modulate specific ion-channel kinetics and the response of beta-adrenergic receptors to triggering stimuli.^23,24

Further evidence of the genotype-related differences in the risk of cardiac events was provided by the multivariate Cox analysis of the risk of cardiac events before the initiation of beta-blocker treatment among 1378 enrolled members of the 38 families studied, rather than just those who underwent genotyping. This analysis provides insight into the natural course of the disease in families with a history of the long-QT syndrome without potential bias due to the selection of family members on the basis of genetic testing or electrocardiographic findings.

The frequency of death related to the long-QT syndrome in families with a history of the disease was similar regardless of the genotype (3 to 4 percent, with a cumulative mortality rate of 6 to 8 percent by the age of 40 years), despite the fact that there were significant differences in the frequency of cardiac events among the three groups. Since the analysis included all family members and since only approximately half of all family members are likely to be carriers of this autosomal dominant disorder, the actual mortality rate in affected patients was substantially underestimated.

The cumulative probability of cardiac events at the age of 40 differed significantly among the three groups, yet the cumulative mortality rate at the age of 40 was similar. This potential discrepancy suggests that the lethality of cardiac events — the risk of death during a cardiac event — differs in the three groups. It was significantly higher in the LQT3 group than in the LQT1 and LQT2 groups (P<0.001). The difference in the lethality of cardiac events between patients with potassium-channel abnormalities and those with sodium-channel abnormalities may relate to the electrophysiologic mechanisms of the onset and self-termination of torsade de pointes in these abnormalities.²⁵ Torsade de pointes in an experimental model of an LQT3-based sodium-channel abnormality (induced by the administration of the neurotoxin antopleurin) was associated with a significantly higher transmural dispersion of repolarization than in a model of an LQT2-based potassium-channel abnormality (induced by the administration of sotalol or almokalant).^26,27 Our observation of increased lethality of cardiac events in patients with the SCN5A mutation may suggest the need for more aggressive treatment of these patients. Gene-specific therapy with class Ib sodium-channel blockers appears to be promising in these patients.^27,28,29

We cannot draw any conclusions regarding the prevalence of specific mutations in patients with the long-QT syndrome, since the 38 families with a history of long-QT syndrome who were recruited for genetic screening were initially selected because of their large size, an advantage for linkage analysis. Systematic genetic screening is needed to establish the prevalence of specific mutations. The higher lethality of cardiac events in patients with mutations at the LQT3 locus may contribute to a potential underrepresentation of such patients among patients with a diagnosis of the long-QT syndrome. The frequency of cardiac events decreased after the initiation of beta-blocker therapy (data not shown), but the number of cardiac events in these patients was too small to allow a clinically relevant interpretation of the effectiveness of beta-blockers in the three groups.

The results of this study demonstrate that the genotype of the long-QT syndrome influences both the probability and the lethality of cardiac events, independently of the QTc.

Supported in part by research grants (HL-33843 and HL-51618) from the National Institutes of Health.

Source Information

From the Departments of Medicine (W.Z., A.J.M., E.H.L.), Community and Preventive Medicine (J.L.R.), and Biostatistics (W.J.H.), University of Rochester School of Medicine and Dentistry, Rochester, N.Y.; Centro di Fisiologia Clinica e Ipertensione, University of Milan, and Ospedale Maggiore Istituto di Ricovero e Cura a Carattene Scientifico, Milan, Italy (P.J.S.); the Department of Cardiology, University of Pavia, and Policlinico San Matteo, Istituto di Ricovero e Cura a Carattene Scientifico, Pavia, Italy (P.J.S.); LDS Hospital, Salt Lake City (G.M.V.); Molecular Cardiology Foundation S. Maugeri, Pavia, Italy (S.G.P.); the Department of Cardiology, University of Perugia, Perugia, Italy (E.H.L.); Bikur Cholim Hospital, University of Jerusalem, Jerusalem, Israel (J.B.); the Department of Pediatrics, Baylor College of Medicine, Texas Children's Hospital, Houston (J.A.T.); Howard Hughes Medical Institute, University of Utah, Salt Lake City (M.T.K.); and the Arrhythmia Center, Sinai Hospital, Detroit (M.H.L.). Other authors were Mark L. Andrews, B.B.A. (Department of Community and Preventive Medicine, University of Rochester School of Medicine and Dentistry, Rochester, N.Y.), Carlo Napolitano, M.D. (Centro di Fisiologia Clinica e Ipertensione, University of Milan, and Ospedale Maggiore Istituto di Ricovero e Cura a Carattene Scientifico, Milan, Italy), Katherine Timothy and Li Zhang, M.D. (LDS Hospital, Salt Lake City), Aharon Medina, M.D. (Bikur Cholim Hospital, University of Jerusalem, Jerusalem, Israel), and Jean W. MacCluer, Ph.D. (Southwest Foundation for Biomedical Research, San Antonio, Tex.).

Address reprint requests to Dr. Zareba at the Heart Research Follow-up Program, Box 653, University of Rochester Medical Center, Rochester, NY 14642-8653.

References

1. Jervell A, Lange-Nielsen F. Congenital deaf-mutism, functional heart disease with prolongation of the Q-T interval and sudden death. Am Heart J 1957;54:59-68. [CrossRef][Medline]
2. Romano C, Gemme G, Pongiglione R. Aritmie cardiache rare dell'eta' pediatrica. II. Accessi sincopali per fibrillazione ventricolare parossistica. Clin Pediatr (Bologna) 1963;45:656-661. [Medline]
3. Ward OC. New familial cardiac syndrome in children. J Ir Med Assoc 1964;103-6.
4. Schwartz PJ, Periti M, Malliani A. The long Q-T syndrome. Am Heart J 1975;89:378-390. [CrossRef][Medline]
5. Moss AJ, Schwartz PJ, Crampton RS, et al. The long QT syndrome: prospective longitudinal study of 328 families. Circulation 1991;84:1136-1144. [Free Full Text]
6. Schwartz PJ, Moss AJ, Vincent GM, Crampton RS. Diagnostic criteria for the long QT syndrome: an update. Circulation 1993;88:782-784. [Free Full Text]
7. Wang Q, Curran ME, Splawski I, et al. Positional cloning of a novel potassium channel gene: KVLQT1 mutations cause cardiac arrhythmias. Nat Genet 1996;12:17-23. [CrossRef][Medline]
8. Curran ME, Splawski I, Timothy KW, Vincent GM, Green ED, Keating MT. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell 1995;80:795-803. [CrossRef][Medline]
9. Wang Q, Shen J, Splawski I, et al. SCN5A mutations cause an inherited cardiac arrhythmia, long QT syndrome. Cell 1995;80:805-811. [CrossRef][Medline]
10. Barhanin J, Lesage F, Guillemare E, Fink M, Lazdunski M, Romey G. K_vLQT1 and IsK (minK) proteins associate to form the I_Ks cardiac potassium current. Nature 1996;384:78-80. [CrossRef][Medline]
11. Splawski I, Tristani-Firouzi M, Lehmann MH, Sanguinetti MC, Keating MT. Mutations in the hminK gene cause long QT syndrome and suppress I_Ks function. Nat Genet 1997;17:338-340. [Medline]
12. Schott JJ, Charpentier F, Peltier S, et al. Mapping of a gene for long QT syndrome to chromosome 4q25-27. Am J Hum Genet 1995;57:1114-1122. [Medline]
13. Moss AJ, Zareba W, Benhorin J, et al. ECG T-wave patterns in genetically distinct forms of the hereditary long QT syndrome. Circulation 1995;92:2929-2934. [Free Full Text]
14. Hajj Ali R, Zareba W, Rosero SZ, et al. Adrenergic triggers and non-adrenergic factors associated with cardiac events in long QT syndrome patients. Pacing Clin Electrophysiol 1997;20:1072-1072.abstract [CrossRef]
15. Schwartz PJ, Matteo PS, Moss AJ, et al. Gene-specific influence on the triggers for cardiac arrest in long QT syndrome. Circulation 1997;96:Suppl I:I-212.abstract 
16. McDonald TV, Yu Z, Ming Z, et al. A minK-HERG complex regulates the cardiac potassium current I_Kr. Nature 1997;388:289-292. [CrossRef][Medline]
17. Bazett HC. An analysis of time-relations of electrocardiograms. Heart 1920;7:353-370.
18. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
19. Cox DR. Regression models and life-tables. J R Stat Soc [B] 1972;34:187-220.
20. Vincent GM, Timothy KW, Leppert M, Keating M. The spectrum of symptoms and QT intervals in carriers of the gene for the long-QT syndrome. N Engl J Med 1992;327:846-852. [Abstract]
21. Lehmann MH, Timothy KW, Frankovich D, et al. Age-gender influence on rate-corrected QT interval and the QT-heart rate relation in families with genotypically characterized long QT syndrome. J Am Coll Cardiol 1997;29:93-99. [Abstract]
22. Zareba W, Moss AJ, le Cessie S, et al. Risk of cardiac events in family members of patients with long QT syndrome. J Am Coll Cardiol 1995;26:1685-1691. [Abstract]
23. Drici MD, Burklow TR, Haridasse V, Glazer RI, Woosley RL. Sex hormones prolong the QT interval and downregulate potassium channel expression in the rabbit heart. Circulation 1996;94:1471-1474. [Free Full Text]
24. Boyle MB, MacLusky NJ, Naftolin F, Kaczmarek LK. Hormonal regulation of K⁺-channel messenger RNA in rat myometrium during oestrus cycle and in pregnancy. Nature 1987;330:373-375. [CrossRef][Medline]
25. Shimizu W, Antzelevitch C. Characteristics of spontaneous as well as stimulation-induced torsade de pointes in LQT2 and LQT3 models of the long QT syndrome. Circulation 1997;96:Suppl I:I-554.abstract
26. el-Sherif N, Caref EB, Yin H, Restivo M. The electrophysiological mechanism of ventricular arrhythmias in the long QT syndrome: tridimensional mapping of activation and recovery patterns. Circ Res 1996;79:474-492. [Free Full Text]
27. Shimizu W, Antzelevitch C. Sodium channel block with mexiletine is effective in reducing dispersion of repolarization and preventing torsade de pointes in LQT2 as well as LQT3 models of the long-QT syndrome. Circulation 1997;96:2038-2047. [Free Full Text]
28. Schwartz PJ, Priori SG, Locati EH, et al. Long QT syndrome patients with mutations of the SCN5A and HERG genes have differential responses to Na⁺ channel blockade and to increases in heart rate: implications for gene-specific therapy. Circulation 1995;92:3381-3386. [Free Full Text]
29. Rosero SZ, Zareba W, Robinson JL, Moss AJ. Gene-specific therapy for long QT syndrome: QT shortening with lidocaine and tocainide in patients with mutation of the sodium-channel gene. Ann Noninvasive Electrocardiol 1997;2:274-8.

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• Hofman, N., Wilde, A. A.M., Kaab, S., van Langen, I. M., Tanck, M. W.T., Mannens, M. M.A.M., Hinterseer, M., Beckmann, B.-M., Tan, H. L. (2007). Diagnostic criteria for congenital long QT syndrome in the era of molecular genetics: do we need a scoring system?. Eur Heart J 28: 575-580 [Abstract] [Full Text]  
• Sauer, A. J., Moss, A. J., McNitt, S., Peterson, D. R., Zareba, W., Robinson, J. L., Qi, M., Goldenberg, I., Hobbs, J. B., Ackerman, M. J., Benhorin, J., Hall, W. J., Kaufman, E. S., Locati, E. H., Napolitano, C., Priori, S. G., Schwartz, P. J., Towbin, J. A., Vincent, G. M., Zhang, L. (2007). Long QT Syndrome in Adults. J Am Coll Cardiol 49: 329-337 [Abstract] [Full Text]  
• Stokoe, K. S., Thomas, G., Goddard, C. A., Colledge, W. H., Grace, A. A., Huang, C. L.-H. (2007). Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/{Delta} murine hearts modelling long QT syndrome 3. J. Physiol. 578: 69-84 [Abstract] [Full Text]  
• Imboden, M., Swan, H., Denjoy, I., Van Langen, I. M., Latinen-Forsblom, P. J., Napolitano, C., Fressart, V., Breithardt, G., Berthet, M., Priori, S., Hainque, B., Wilde, A. A. M., Schulze-Bahr, E., Feingold, J., Guicheney, P. (2006). Female Predominance and Transmission Distortion in the Long-QT Syndrome. NEJM 355: 2744-2751 [Abstract] [Full Text]  
• Fredj, S., Lindegger, N., Sampson, K. J., Carmeliet, P., Kass, R. S. (2006). Altered Na+ Channels Promote Pause-Induced Spontaneous Diastolic Activity in Long QT Syndrome Type 3 Myocytes. Circ. Res. 99: 1225-1232 [Abstract] [Full Text]  
• Vatta, M., Ackerman, M. J., Ye, B., Makielski, J. C., Ughanze, E. E., Taylor, E. W., Tester, D. J., Balijepalli, R. C., Foell, J. D., Li, Z., Kamp, T. J., Towbin, J. A. (2006). Mutant Caveolin-3 Induces Persistent Late Sodium Current and Is Associated With Long-QT Syndrome. Circulation 114: 2104-2112 [Abstract] [Full Text]  
• Tan, H. L., Bardai, A., Shimizu, W., Moss, A. J., Schulze-Bahr, E., Noda, T., Wilde, A. A. M. (2006). Genotype-Specific Onset of Arrhythmias in Congenital Long-QT Syndrome: Possible Therapy Implications. Circulation 114: 2096-2103 [Abstract] [Full Text]  
• Hobbs, J. B., Peterson, D. R., Moss, A. J., McNitt, S., Zareba, W., Goldenberg, I., Qi, M., Robinson, J. L., Sauer, A. J., Ackerman, M. J., Benhorin, J., Kaufman, E. S., Locati, E. H., Napolitano, C., Priori, S. G., Towbin, J. A., Vincent, G. M., Zhang, L. (2006). Risk of aborted cardiac arrest or sudden cardiac death during adolescence in the long-QT syndrome.. JAMA 296: 1249-1254 [Abstract] [Full Text]  
• Goldenberg, I., Mathew, J., Moss, A. J., McNitt, S., Peterson, D. R., Zareba, W., Benhorin, J., Zhang, L., Vincent, G. M., Andrews, M. L., Robinson, J. L., Morray, B. (2006). Corrected QT Variability in Serial Electrocardiograms in Long QT Syndrome: The Importance of the Maximum Corrected QT for Risk Stratification. J Am Coll Cardiol 48: 1047-1052 [Abstract] [Full Text]  
• Locati, E. T. (2006). QT Interval Duration Remains a Major Risk Factor in Long QT Syndrome Patients. J Am Coll Cardiol 48: 1053-1055 [Full Text]  
• Developed in Collaboration With the European Heart, , Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A. E., Chaitman, B., Fromer, M., Gregoratos, G., Klein, G., Moss, A. J., Myerburg, R. J., Priori, S. G., Quinones, M. A., Roden, D. M., Silka, M. J., Tracy, C., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Antman, E. M., Anderson, J. L., Hunt, S. A., Halperin, J. L., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B., Priori, S. G., Blanc, J.-J., Budaj, A., Camm, A. J., Dean, V., Deckers, J. W., Despres, C., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J. L., Zamorano, J. L. (2006). 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). J Am Coll Cardiol 48: e247-e346 [Full Text]  
• Monnig, G., Eckardt, L., Wedekind, H., Haverkamp, W., Gerss, J., Milberg, P., Wasmer, K., Kirchhof, P., Assmann, G., Breithardt, G., Schulze-Bahr, E. (2006). Electrocardiographic risk stratification in families with congenital long QT syndrome. Eur Heart J 27: 2074-2080 [Abstract] [Full Text]  
• Writing Committee Members, , Zipes, D. P., Camm, A. J., Borggrefe, M., Buxton, A. E., Chaitman, B., Fromer, M., Gregoratos, G., Klein, G., Moss, A. J., Myerburg, R. J., Priori, S. G., Quinones, M. A., Roden, D. M., Silka, M. J., Tracy, C., ESC Committee for Practice Guidelines, , Priori, S. G., Blanc, J.-J., Budaj, A., Camm, A. J., Dean, V., Deckers, J. W., Despres, C., Dickstein, K., Lekakis, J., McGregor, K., Metra, M., Morais, J., Osterspey, A., Tamargo, J. L., Zamorano, J. L., ACC/AHA Task Force Members, , Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Antman, E. M., Anderson, J. L., Hunt, S. A., Halperin, J. L., Nishimura, R., Ornato, J. P., Page, R. L., Riegel, B. (2006). 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. Europace 8: 746-837 [Full Text]  
• Quaglini, S., Rognoni, C., Spazzolini, C., Priori, S. G., Mannarino, S., Schwartz, P. J. (2006). Cost-effectiveness of neonatal ECG screening for the long QT syndrome. Eur Heart J 27: 1824-1832 [Abstract] [Full Text]  
• Priori, S. G., Napolitano, C. (2006). Molecular Underpinning of "Good Luck". Circulation 114: 360-362 [Full Text]  
• Karp, J. M., Moss, A. J. (2006). Dental treatment of patients with long QT syndrome. Journal of the American Dental Association 137: 630-637 [Abstract] [Full Text]  
• Cesario, D. A., Dec, G. W. (2006). Implantable Cardioverter- Defibrillator Therapy in Clinical Practice. J Am Coll Cardiol 47: 1507-1517 [Abstract] [Full Text]  
• Anastasakis, A., Kotta, C.-M., Kyriakogonas, S., Wollnik, B., Theopistou, A., Stefanadis, C. (2006). Phenotype reveals genotype in a Greek long QT syndrome family.. Europace 8: 241-244 [Abstract] [Full Text]  
• Roberts, R. (2006). Genomics and Cardiac Arrhythmias. J Am Coll Cardiol 47: 9-21 [Abstract] [Full Text]  
• Kaufman, E. S. (2005). Efficient Genotyping for Congenital Long QT Syndrome. JAMA 294: 3027-3028 [Full Text]  
• Brink, P. A., Crotti, L., Corfield, V., Goosen, A., Durrheim, G., Hedley, P., Heradien, M., Geldenhuys, G., Vanoli, E., Bacchini, S., Spazzolini, C., Lundquist, A. L., Roden, D. M., George, A. L. Jr, Schwartz, P. J. (2005). Phenotypic Variability and Unusual Clinical Severity of Congenital Long-QT Syndrome in a Founder Population. Circulation 112: 2602-2610 [Abstract] [Full Text]  
• Krahn, A. D., Gollob, M., Yee, R., Gula, L. J., Skanes, A. C., Walker, B. D., Klein, G. J. (2005). Diagnosis of Unexplained Cardiac Arrest: Role of Adrenaline and Procainamide Infusion. Circulation 112: 2228-2234 [Abstract] [Full Text]  
• Wilde, A. A M, Bezzina, C. R (2005). Genetics of cardiac arrhythmias. Heart 91: 1352-1358 [Full Text]  
• Shimizu, W. (2005). The long QT syndrome: Therapeutic implications of a genetic diagnosis. Cardiovasc Res 67: 347-356 [Abstract] [Full Text]  
• Tester, D. J., Ackerman, M. J. (2005). Sudden infant death syndrome: How significant are the cardiac channelopathies?. Cardiovasc Res 67: 388-396 [Abstract] [Full Text]  
• Beaufort-Krol, G. C.M., van den Berg, M. P., Wilde, A. A.M., van Tintelen, J. P., Viersma, J. W., Bezzina, C. R., Bink-Boelkens, M. Th.E. (2005). Developmental Aspects of Long QT Syndrome Type 3 and Brugada Syndrome on the Basis of a Single SCN5A Mutation in Childhood. J Am Coll Cardiol 46: 331-337 [Abstract] [Full Text]  
• Beery, T. T. (2005). The Genetics of Cardiac Arrhythmias. Biol Res Nurs 6: 249-261 [Abstract]  
• Moss, A. J., Schwartz, P. J. (2005). 25th Anniversary of the International Long-QT Syndrome Registry: An Ongoing Quest to Uncover the Secrets of Long-QT Syndrome. Circulation 111: 1199-1201 [Full Text]  
• Rossenbacker, T., Mubagwa, K., Jongbloed, R. J., Vereecke, J., Devriendt, K., Gewillig, M., Carmeliet, E., Collen, D., Heidbuchel, H., Carmeliet, P. (2005). Novel Mutation in the Per-Arnt-Sim Domain of KCNH2 Causes a Malignant Form of Long-QT Syndrome. Circulation 111: 961-968 [Abstract] [Full Text]  
• Hwang, H W, Chen, J J, Lin, Y J, Shieh, R C, Lee, M T, Hung, S I, Wu, J Y, Chen, Y T, Niu, D M, Hwang, B T (2005). R1193Q of SCN5A, a Brugada and long QT mutation, is a common polymorphism in Han Chinese. J. Med. Genet. 42: e7-e7 [Full Text]  
• Khalameizer, V., Pancheva, N., Reizin, L., Ovsyshcher, I. E. (2005). "Benign" course and malignant clinical presentations of congenital long QT syndrome. Europace 7: 50-53 [Abstract] [Full Text]  
• Shimizu, W., Horie, M., Ohno, S., Takenaka, K., Yamaguchi, M., Shimizu, M., Washizuka, T., Aizawa, Y., Nakamura, K., Ohe, T., Aiba, T., Miyamoto, Y., Yoshimasa, Y., Towbin, J. A., Priori, S. G., Kamakura, S. (2004). Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: Multicenter study in Japan. J Am Coll Cardiol 44: 117-125 [Abstract] [Full Text]  
• Maron, B. J., Chaitman, B. R., Ackerman, M. J., Bayes de Luna, A., Corrado, D., Crosson, J. E., Deal, B. J., Driscoll, D. J., Estes, N.A. M. III, Araujo, C. G. S., Liang, D. H., Mitten, M. J., Myerburg, R. J., Pelliccia, A., Thompson, P. D., Towbin, J. A., Van Camp, S. P., for the Working Groups of the American Heart Assoc, (2004). Recommendations for Physical Activity and Recreational Sports Participation for Young Patients With Genetic Cardiovascular Diseases. Circulation 109: 2807-2816 [Abstract] [Full Text]  
• Tian, X.-L., Yong, S. L, Wan, X., Wu, L., Chung, M. K, Tchou, P. J, Rosenbaum, D. S, Van Wagoner, D. R, Kirsch, G. E, Wang, Q. (2004). Mechanisms by which SCN5A mutation N1325S causes cardiac arrhythmias and sudden death in vivo. Cardiovasc Res 61: 256-267 [Abstract] [Full Text]  
• Etheridge, S. P., Compton, S. J., Tristani-Firouzi, M., Mason, J. W. (2003). A new oral therapy for long QT syndrome: Long-term oral potassium improves repolarization in patients with HERG mutations. J Am Coll Cardiol 42: 1777-1782 [Abstract] [Full Text]  
• Antezano, E. S., Hong, M. (2003). Sudden Cardiac Death. J Intensive Care Med 18: 313-329 [Abstract]  
• Ellinor, P. T., Milan, D. J., MacRae, C. A., Priori, S. G., Schwartz, P. J., Napolitano, C. (2003). Risk Stratification in the Long-QT Syndrome. NEJM 349: 908-909 [Full Text]  
• Zareba, W., Moss, A. J., Locati, E. H., Lehmann, M. H., Peterson, D. R., Hall, W. J., Schwartz, P. J., Vincent, G. M., Priori, S. G., Benhorin, J., Towbin, J. A., Robinson, J. L., Andrews, M. L., Napolitano, C., Timothy, K., Zhang, L., Medina, A., International Long QT Syndrome Registry, (2003). Modulating effects of age and gender on the clinical course of long QT syndrome by genotype. J Am Coll Cardiol 42: 103-109 [Abstract] [Full Text]  
• Tateyama, M., Kurokawa, J., Terrenoire, C., Rivolta, I., Kass, R.S. (2003). Stimulation of Protein Kinase C Inhibits Bursting in Disease-Linked Mutant Human Cardiac Sodium Channels. Circulation 107: 3216-3222 [Abstract] [Full Text]  
• Glatter, K. A., Chiamvimonvat, N. (2003). Tachy- or Bradyarrhythmias: Implications for Therapeutic Intervention in LQT3 Families. Circ. Res. 92: 941-943 [Full Text]  
• Priori, S. G., Schwartz, P. J., Napolitano, C., Bloise, R., Ronchetti, E., Grillo, M., Vicentini, A., Spazzolini, C., Nastoli, J., Bottelli, G., Folli, R., Cappelletti, D. (2003). Risk Stratification in the Long-QT Syndrome. NEJM 348: 1866-1874 [Abstract] [Full Text]  
• Moss, A. J. (2003). Long QT Syndrome. JAMA 289: 2041-2044 [Full Text]  
• Al-Khatib, S. M., LaPointe, N. M. A., Kramer, J. M., Califf, R. M. (2003). What Clinicians Should Know About the QT Interval. JAMA 289: 2120-2127 [Abstract] [Full Text]  
• Fabritz, L., Kirchhof, P., Franz, M. R, Nuyens, D., Rossenbacker, T., Ottenhof, A., Haverkamp, W., Breithardt, G., Carmeliet, E., Carmeliet, P. (2003). Effect of pacing and mexiletine on dispersion of repolarisation and arrhythmias in {Delta}KPQ SCN5A (long QT3) mice. Cardiovasc Res 57: 1085-1093 [Abstract] [Full Text]  
• Shimizu, W., Noda, T., Takaki, H., Kurita, T., Nagaya, N., Satomi, K., Suyama, K., Aihara, N., Kamakura, S., Sunagawa, K., Echigo, S., Nakamura, K., Ohe, T., Towbin, J. A., Napolitano, C., Priori, S. G. (2003). Epinephrine unmasks latent mutation carriers with LQT1 form of congenital long-QT syndrome. J Am Coll Cardiol 41: 633-642 [Abstract] [Full Text]  
• Moric, E., Herbert, E., Trusz-Gluza, M., Filipecki, A., Mazurek, U., Wilczok, T. (2003). The implications of genetic mutations in the sodium channel gene (SCN5A). Europace 5: 325-334 [Abstract] [Full Text]  
• Wehrens, X. H.T., Vos, M. A., Doevendans, P. A., Wellens, H. J.J. (2002). Novel Insights in the Congenital Long QT Syndrome. ANN INTERN MED 137: 981-992 [Abstract] [Full Text]  
• Viitasalo, M., Oikarinen, L., Swan, H., Vaananen, H., Glatter, K., Laitinen, P. J., Kontula, K., Barron, H. V., Toivonen, L., Scheinman, M. M. (2002). Ambulatory Electrocardiographic Evidence of Transmural Dispersion of Repolarization in Patients With Long-QT Syndrome Type 1 and 2. Circulation 106: 2473-2478 [Abstract] [Full Text]  
• Chinushi, M., Kasai, H., Tagawa, M., Washizuka, T., Hosaka, Y., Chinushi, Y., Aizawa, Y. (2002). Triggers of ventricular tachyarrhythmias and therapeutic effects of nicorandil in canine models of LQT2 and LQT3 syndromes. J Am Coll Cardiol 40: 555-562 [Abstract] [Full Text]  
• Roden, D. M. (2002). The problem, challenge and opportunity of genetic heterogeneity in monogenic diseases predisposing to sudden death. J Am Coll Cardiol 40: 357-359 [Full Text]  
• Noda, T., Takaki, H., Kurita, T., Suyama, K., Nagaya, N., Taguchi, A., Aihara, N., Kamakura, S., Sunagawa, K., Nakamura, K., Ohe, T., Horie, M., Napolitano, C., Towbin, J.A., Priori, S.G., Shimizu, W. (2002). Gene-specific response of dynamic ventricular repolarization to sympathetic stimulation in LQT1, LQT2 and LQT3 forms of congenital long QT syndrome. Eur Heart J 23: 975-983 [Abstract] [Full Text]  
• Papadatos, G. A., Wallerstein, P. M. R., Head, C. E. G., Ratcliff, R., Brady, P. A., Benndorf, K., Saumarez, R. C., Trezise, A. E. O., Huang, C. L.-H., Vandenberg, J. I., Colledge, W. H., Grace, A. A. (2002). From the Cover: Slowed conduction and ventricular tachycardia after targeted disruption of the cardiac sodium channel gene Scn5a. Proc. Natl. Acad. Sci. USA 99: 6210-6215 [Abstract] [Full Text]  
• Vatta, M., Dumaine, R., Varghese, G., Richard, T. A., Shimizu, W., Aihara, N., Nademanee, K., Brugada, R., Brugada, J., Veerakul, G., Li, H., Bowles, N. E., Brugada, P., Antzelevitch, C., Towbin, J. A. (2002). Genetic and biophysical basis of sudden unexplained nocturnal death syndrome (SUNDS), a disease allelic to Brugada syndrome. Hum Mol Genet 11: 337-345 [Abstract] [Full Text]  
• Priori, S. G., Aliot, E., Blomstrom-Lundqvist, C., Bossaert, L., Breithardt, G., Brugada, P., Camm, J. A., Cappato, R., Cobbe, S. M., Di Mario, C., Maron, B. J., McKenna, W. J., Pedersen, A. K., Ravens, U., Schwartz, P. J., Trusz-Gluza, M., Vardas, P., Wellens, H. J. J., Zipes, D. P. (2002). TASK FORCE ON SUDDEN CARDIAC DEATH, EUROPEAN SOCIETY OF CARDIOLOGY: Summary of Recommendations. Europace 4: 3-18 [Abstract]  
• Huikuri, H. V., Castellanos, A., Myerburg, R. J. (2001). Sudden Death Due to Cardiac Arrhythmias. NEJM 345: 1473-1482 [Full Text]  
• Ackerman, M. J., Siu, B. L., Sturner, W. Q., Tester, D. J., Valdivia, C. R., Makielski, J. C., Towbin, J. A. (2001). Postmortem Molecular Analysis of SCN5A Defects in Sudden Infant Death Syndrome. JAMA 286: 2264-2269 [Abstract] [Full Text]  
• Halkin, A., Roth, A., Lurie, I., Fish, R., Belhassen, B., Viskin, S. (2001). Pause-dependent torsade de pointes following acute myocardial infarction: A variant of the acquired long QT syndrome. J Am Coll Cardiol 38: 1168-1174 [Abstract] [Full Text]  
• Exner, D. V., Klein, G. J., Prystowsky, E. N. (2001). Primary Prevention of Sudden Death With Implantable Defibrillator Therapy in Patients With Cardiac Disease: Can We Afford to Do It? (Can We Afford Not To?). Circulation 104: 1564-1570 [Full Text]  
• Wedekind, H., Smits, J. P.P., Schulze-Bahr, E., Arnold, R., Veldkamp, M. W., Bajanowski, T., Borggrefe, M., Brinkmann, B., Warnecke, I., Funke, H., Bhuiyan, Z. A., Wilde, A. A.M., Breithardt, G., Haverkamp, W. (2001). De Novo Mutation in the SCN5A Gene Associated With Early Onset of Sudden Infant Death. Circulation 104: 1158-1164 [Abstract] [Full Text]  
• Drici, M.-D. (2001). Influence of gender on drug-acquired long QT syndrome. Eur Heart J Suppl 3: K41-K47 [Abstract]  
• Wilde, A. A.M., Escande, D. (2001). LQT genotype-phenotype relationships: patients and patches. Cardiovasc Res 51: 627-629 [Full Text]  
• Priori, S.G., Aliot, E., Blomstrom-Lundqvist, C., Bossaert, L., Breithardt, G., Brugada, P., Camm, A.J., Cappato, R., Cobbe, S.M., Di Mario, C., Maron, B.J., McKenna, W.J., Pedersen, A.K., Ravens, U., Schwartz, P.J., Trusz-Gluza, M., Vardas, P., Wellens, H.J.J., Zipes, D.P. (2001). Task Force on Sudden Cardiac Death of the European Society of Cardiology. Eur Heart J 22: 1374-1450  
• Kimbrough, J., Moss, A. J., Zareba, W., Robinson, J. L., Hall, W. J., Benhorin, J., Locati, E. H., Medina, A., Napolitano, C., Priori, S., Schwartz, P. J., Timothy, K., Towbin, J. A., Vincent, G. M., Zhang, L. (2001). Clinical Implications for Affected Parents and Siblings of Probands With Long-QT Syndrome. Circulation 104: 557-562 [Abstract] [Full Text]  
• Lupoglazoff, J.M., Cheav, T., Baroudi, G., Berthet, M., Denjoy, I., Cauchemez, B., Extramiana, F., Chahine, M., Guicheney, P. (2001). Homozygous SCN5A Mutation in Long-QT Syndrome With Functional Two-to-One Atrioventricular Block. Circ. Res. 89 : e16-e21 [Abstract] [Full Text]  
• Towbin, J. A., Wang, Z., Li, H. (2001). Genotype and Severity of Long QT Syndrome. Drug Metab. Dispos. 29: 574-579 [Abstract] [Full Text]  
• Casimiro, M. C., Knollmann, B. C., Ebert, S. N., Vary, J. C. Jr., Greene, A. E., Franz, M. R., Grinberg, A., Huang, S. P., Pfeifer, K. (2001). Targeted disruption of the Kcnq1 gene produces a mouse model of Jervell and Lange- Nielsen Syndrome. Proc. Natl. Acad. Sci. USA 98: 2526-2531 [Abstract] [Full Text]  
• Lupoglazoff, J. M., Denjoy, I., Berthet, M., Neyroud, N., Demay, L., Richard, P., Hainque, B., Vaksmann, G., Klug, D., Leenhardt, A., Maillard, G., Coumel, P., Guicheney, P. (2001). Notched T Waves on Holter Recordings Enhance Detection of Patients With LQT2 (HERG) Mutations. Circulation 103: 1095-1101 [Abstract] [Full Text]  
• Piippo, K., Swan, H., Pasternack, M., Chapman, H., Paavonen, K., Viitasalo, M., Toivonen, L., Kontula, K. (2001). A founder mutation of the potassium channel KCNQ1 in long QT syndrome: Implications for estimation of disease prevalence and molecular diagnostics. J Am Coll Cardiol 37: 562-568 [Abstract] [Full Text]  
• Bezzina, C. R, Rook, M. B, Wilde, A. A.M (2001). Cardiac sodium channel and inherited arrhythmia syndromes. Cardiovasc Res 49: 257-271 [Full Text]  
• Schwartz, P. J., Priori, S. G., Spazzolini, C., Moss, A. J., Vincent, G. M., Napolitano, C., Denjoy, I., Guicheney, P., Breithardt, G., Keating, M. T., Towbin, J. A., Beggs, A. H., Brink, P., Wilde, A. A. M., Toivonen, L., Zareba, W., Robinson, J. L., Timothy, K. W., Corfield, V., Wattanasirichaigoon, D., Corbett, C., Haverkamp, W., Schulze-Bahr, E., Lehmann, M. H., Schwartz, K., Coumel, P., Bloise, R. (2001). Genotype-Phenotype Correlation in the Long-QT Syndrome : Gene-Specific Triggers for Life-Threatening Arrhythmias. Circulation 103: 89-95 [Abstract] [Full Text]  
• Priori, S. G., Bloise, R., Crotti, L. (2001). The long QT syndrome. Europace 3: 16-27  
• Nisam, S. (2001). A Prophylactic ICD? Who are the patients? What is the device?. Europace 3: 269-274  
• Wilde, A. A. M., Roden, D. M. (2000). Predicting the Long-QT Genotype From Clinical Data : From Sense to Science. Circulation 102: 2796-2798 [Full Text]  
• Vos, M. A., Gorenek, B., Verduyn, S.C., van der Hulst, F. F., Leunissen, J. D., Dohmen, L., Wellens, H. J. (2000). Observations on the onset of Torsade de Pointes arrhythmias in the acquired long QT syndrome. Cardiovasc Res 48: 421-429 [Abstract] [Full Text]  
• Priori, S. G., Napolitano, C., Gasparini, M., Pappone, C., Della Bella, P., Brignole, M., Giordano, U., Giovannini, T., Menozzi, C., Bloise, R., Crotti, L., Terreni, L., Schwartz, P. J. (2000). Clinical and Genetic Heterogeneity of Right Bundle Branch Block and ST-Segment Elevation Syndrome : A Prospective Evaluation of 52 Families. Circulation 102: 2509-2515 [Abstract] [Full Text]  
• Kass, R. S., Cabo, C. (2000). Channel structure and drug-induced cardiac arrhythmias. Proc. Natl. Acad. Sci. USA 97: 11683-11684 [Full Text]  
• Priori, S. G., Napolitano, C., Schwartz, P. J., Bloise, R., Crotti, L., Ronchetti, E. (2000). The Elusive Link Between LQT3 and Brugada Syndrome : The Role of Flecainide Challenge. Circulation 102: 945-947 [Abstract] [Full Text]  
• Dubin, A. M. (2000). Arrhythmias in the Newborn. NeoReviews 1: e146-151 [Full Text]  
• Schwartz, P. J., Priori, S. G., Dumaine, R., Napolitano, C., Antzelevitch, C., Stramba-Badiale, M., Richard, T. A., Berti, M. R., Bloise, R. (2000). A Molecular Link between the Sudden Infant Death Syndrome and the Long-QT Syndrome. NEJM 343: 262-267 [Full Text]