(Circulation. 2001;103:89.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
Genotype-Phenotype Correlation in the Long-QT Syndrome
Gene-Specific Triggers for Life-Threatening Arrhythmias
From the Department of Cardiology (P.J.S., C.S., R.B.), Policlinico S. Matteo IRCCS and University of Pavia, Pavia, Italy; Molecular Cardiology Laboratories (S.G.P., C.N.), IRCCS Fondazione "S. Maugeri," Pavia, Italy; Department of Medicine (A.J.M., W.Z., J.L.R.), University of Rochester School of Medicine and Dentistry, Rochester, NY; Department of Medicine (M.V., K.W.T.), University of Utah School of Medicine (Salt Lake City); Service de Cardiologie (I.D., P.C.), Hôpital Lariboisière, Paris, France; INSERM U523 (P.G., K.S.), Institut de Myologie, IFR "Coeur Muscle et Vaisseaux" No. 14, Groupe Hospitalier Pitié-Salpêtrière, Paris, France; Medizinische Klinik und Poliklinik (G.B., W.H., E.S.-B.), Innere Medizin C, Kardiologie, and Institute for Arteriosclerosis Research, Westfälische Wilhelms Universität Münster, Münster, Germany; Howard Hughes Medical Institute (M.T.K.), University of Utah, Salt Lake City, Utah; Phoebe Willingham Muzzy Pediatric Molecular Cardiology Laboratory (J.A.T.), Baylor College of Medicine, Texas Children’s Hospital, Houston, Tex; Children’s Hospital (A.H.B., D.W.), Genetic Division, Boston, Mass; Department of Internal Medicine (P.B., V.C., C.C.), University of Stellenbosch and Tygerberg Hospital, Tygerberg, Republic of South Africa; Experimental and Molecular Cardiology Group (A.A.M.W.), Academisch Medisch Centrum Amsterdam, and the Interuniversity Cardiology Institute, the Netherlands; Division of Cardiology (L.T.), Department of Medicine, University of Helsinki, Helsinki, Finland; and Department of Internal Medicine (M.H.L.), University of Michigan School of Medicine (Ann Arbor).
Correspondence to Peter J. Schwartz, MD, Department of Cardiology, Policlinico S Matteo IRCCS, V le Golgi, 19, 27100 Pavia, Italy. E-mail PJQT{at}compuserve.com
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Abstract |
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Background—The congenital long-QT syndrome (LQTS) is caused by mutations on several genes, all of which encode cardiac ion channels. The progressive understanding of the electrophysiological consequences of these mutations opens unforeseen possibilities for genotype-phenotype correlation studies. Preliminary observations suggested that the conditions ("triggers") associated with cardiac events may in large part be gene specific.
Methods and Results—We identified 670 LQTS patients of known genotype (LQT1, n=371; LQT2, n=234; LQT3, n=65) who had symptoms (syncope, cardiac arrest, sudden death) and examined whether 3 specific triggers (exercise, emotion, and sleep/rest without arousal) differed according to genotype. LQT1 patients experienced the majority of their events (62%) during exercise, and only 3% occurred during rest/sleep. These percentages were almost reversed among LQT2 and LQT3 patients, who were less likely to have events during exercise (13%) and more likely to have events during rest/sleep (29% and 39%). Lethal and nonlethal events followed the same pattern. Corrected QT interval did not differ among LQT1, LQT2, and LQT3 patients (498, 497, and 506 ms, respectively). The percent of patients who were free of recurrence with ß-blocker therapy was higher and the death rate was lower among LQT1 patients (81% and 4%, respectively) than among LQT2 (59% and 4%, respectively) and LQT3 (50% and 17%, respectively) patients.
Conclusions—Life-threatening arrhythmias in LQTS patients tend to occur under specific circumstances in a gene-specific manner. These data allow new insights into the mechanisms that relate the electrophysiological consequences of mutations on specific genes to clinical manifestations and offer the possibility of complementing traditional therapy with gene-specific approaches.
Key Words: death, sudden • genetics • ion channels • long-QT syndrome • nervous system, autonomic
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Introduction |
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The identification between 1995 and 19961 2 of 3 of the genes responsible for the congenital long-QT syndrome (LQTS)3 4 5 6 and the realization that they all encode ion channels involved in the control of repolarization1 2 fostered the concept that LQTS may represent a unique model for the study of genotype-phenotype correlation in hereditary arrhythmogenic disorders. Interest in this correlation has been further stimulated by the demonstration that the mutations identified in these genes produce either gain or loss of function, resulting in an excess of late inward sodium current or in reduced outward potassium current.1 2 These ionic alterations lengthen action potential duration and explain the prolonged QT interval characteristic of LQTS.
Within months of the identification of the first 2 LQTS genes, HERG and SCN5A, some of the present authors7 reported gene-specific differential degrees of QT interval shortening in response to Na+ channel blockade and to heart rate increases. We also noted a seemingly different pattern in the conditions associated with syncope and cardiac arrest. Specifically, although 6 of 7 LQT3 patients (those with mutations in SCN5A, the cardiac Na+ channel gene) experienced their cardiac events at rest or during sleep, all 5 LQT2 patients (those with mutations in HERG, the gene that encodes the rapid component of the delayed rectifier potassium current [IKr]) experienced their events during emotion or exercise. If confirmed, this finding might have implications for the management of LQTS patients of known genotype. We warned against making extrapolations from such a small study and committed ourselves to test this intriguing observation in a population of symptomatic patients of known genotype that was sufficiently large to allow safe and definitive conclusions. This commitment constitutes the focus of the present study.
The identification in 1996 of KvLQT1, a K+ channel gene that, when coexpressed with minK, produces the slow component of the delayed rectifier potassium current (IKs), allowed us to extend the comparison to LQT1, the LQTS subtype with mutations on KvLQT1.1 2
Here, we report the analysis of the triggers involved in the precipitation of major cardiac events in 670 LQTS patients, all symptomatic and of known genotype, who are of the LQT1, LQT2, and LQT3 subtypes.
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Methods |
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For the present study, we (1) identified patients of known genotype, (2) selected among them those who experienced major cardiac events, and (3) further selected the patients whose cardiac events had been associated with, or triggered by, well-defined conditions.
Patients who were of known genotype but were asymptomatic were not considered for inclusion into the study. Because the same electrophysiological mechanism, torsade de pointes (TdP), of varying duration underlies the tachyarrhythmias of LQTS and because all these tachyarrhythmias have a life-threatening potential, we did not distinguish among syncope, cardiac arrest, or sudden cardiac death in the main analysis. However, we also separately analyzed the lethal events. Data were collected on specifically prepared forms. Whenever possible, direct contacts were established to verify the information; special care was taken for patients with multiple events, and in large part, we followed procedures that have been previously described.8 9
The LQTS International Registry contributed 50% of the patients, and 50% originated mostly from the BIOMED LQTS Research Group but also from individual physicians.
We identified 670 patients of the LQT1, LQT2, and LQT3
subtypes; 418 (62%) had been directly genotyped. The remaining 252
(38%) patients had their genotype attributed with certainty because
(1) they were obligate gene carriers or (2) they fulfilled both the
rigorous criteria (score 
4) for definite clinical diagnosis of
LQTS10 and were first- or
second-degree relatives of genotyped patients. The few available LQT5
and LQT6 patients were not included.
Triggers: Definitions and Rationale
For purposes of analysis, we identified 3 distinct
conditions, or triggers, associated with the onset of cardiac events:
exercise, emotion, and rest or sleep without arousal. The choice of
these "classified" triggers was based on the following
pathophysiological considerations.
Physical stress, or exercise, is a clear-cut condition without possibility of misinterpretation. It is either witnessed or narrated by the patient. It represents a condition associated with progressively increasing heart rate and with the release of both neural and circulating catecholamines.
The opposite condition is represented by events that occurred during sleep or rest in the presumed absence of any known arousal. This can be established for the survivors, whereas for patients found dead in bed, it is impossible to rule out an arousal before sudden death. However, sleep is not a uniformly quiet state, because periods of REM sleep are associated with abrupt increases in sympathetic activity. Events at rest were included only when the absence of a known arousal was combined with a truly resting condition (eg, lying in bed awake or in an armchair), with the exclusion of television watching, driving, and sitting in school. These events usually occur at relatively long cardiac cycles and with a modest amount of circulating catecholamines.
Between these 2 extremes, we introduced emotional stress, that is, stressful events and arousals that occur during normal daily activities (fear, anger) and arousals that occur at rest or during sleep (sudden noise, startle). This condition is usually characterized by an abrupt neurally mediated release of norepinephrine that occurs while the heart rate is relatively low and without allowance of time for QT adaptation to faster rates.
Several patients (22%) had 2 classified triggers (eg, during exercise and during emotions), and only 2 (0.4%) had 3 triggers. To avoid selection bias, where there were multiple trigger mechanisms, each of the separate triggers was included in the analysis. Sometimes the triggers were unknown or "other" (ie, outside the 3 main conditions), such as during anesthesia, fever, menses, or pregnancy-related events.
The possibilities that lethal events (sudden death and documented cardiac arrest) might differ from syncope in their gene-specific relation to triggers and that the sex effect on the time of occurrence of the first event11 might differ between genotypes were considered. The sex analysis included all patients and all triggers, including those different from the classified ones.
Response to Therapy
The relation observed between genotype and specific
triggers also suggested that the response to ß-blockers might be in
part gene specific.
Data on therapy were available for 494 patients (74%),
which also includes patients who received no treatment (in large part
representing the sudden deaths that occurred before diagnosis).
The treatment modality used for most patients (n=300) was ß-blockers,
and we limited our analysis to those patients (n=271, 90%) for whom
precise information was available regarding both therapy and outcome.
Patients were not included in this analysis if the dosage of
ß-blockers was 
0.5
mg·kg–1·d–1
(n=2) and if therapy had been discontinued for >1 month. We also
excluded 2 patients with cardiac arrest in association with a
QT-prolonging drug and with non–LQTS-related
surgery.
Statistical Analysis
A comparison among the patients of ECG variables was
performed using the t test for
independent samples and ANOVA with Bonferroni’s correction for
multiple comparisons. Differences in other clinical features were
assessed by the 
2 method and Fisher’s
exact test for dichotomous variables. Survival curves that represent
cumulative event rates were obtained by using the Kaplan-Meier
life-tables and were compared by the log-rank test. Data are given as
mean±1 SD, and differences were accepted as significant for
P<0.05.
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Results |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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We determined the genotype of 670 symptomatic LQTS patients (Table 1
).
Table 2 shows the number of patients with unknown trigger,
with 1 of the 3 classified triggers, and with other nonclassifiable
triggers. In 200 cases (30%), it was either not possible to identify
with certainty the trigger involved (n=116) or the trigger differed
from the 3 main categories chosen for analysis (n=84). Cardiac events
were induced by 2 different triggers in only 10% of LQT3 patients
compared with 25% of LQT1 patients
(P=0.04) and 20% of LQT2
patients (NS). Of clinical relevance, among the 105 patients with 2
triggers, only 2 (2%) had events in "opposite" conditions (ie,
exercise and sleep/rest without arousal).
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There was no difference between the triggers for the genotyped patients and for the obligate gene carriers whose genotype had not been documented.
Triggers and Cardiac Events
Figure 1 shows the relation among the 3 subgroups, the 3
classified triggers, and other triggers. The pattern for LQT1 is very
distinctive, with most events (62%) occurring during exercise and only
a very small minority (3%) occurring during rest/sleep. This is in
sharp contrast with the pattern shown by LQT3 patients, for whom only
13% of the events occurred during exercise and 39% occurred at
sleep/rest. LQT2 patients have an intermediate pattern, with only 13%
occurring during exercise and most of the remainder (43%) occurring
with emotional stress.
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The frequency of lethal events (cardiac arrest and sudden death) was affected by the genotype; the rate increased from 28% for LQT1 to 40% for LQT2 to 49% for LQT3 patients. This high mortality rate depends on the noninclusion of asymptomatic patients.
The pattern observed for lethal events was similar to that
for all events (ie, including syncope), but it did accentuate the
differences between LQT1 versus LQT2 and LQT3.
Figure 2 shows that 68% of lethal events occurred during
exercise for LQT1, whereas this never occurred for LQT2 and occurred in
only 4% of cases for LQT3 patients. By contrast, 49% and 64% of
lethal events occurred during rest/sleep without arousal for LQT2 and
LQT3 patients, respectively, whereas this occurred in only 9% of cases
for LQT1 patients.
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Specific Triggers
Auditory stimuli were rare (2%) among LQT1 patients
and relatively frequent (26%) among LQT2
(P<0.001). They also occurred
in LQT3 (7%) less frequently than in LQT2 (P=0.002)
but more frequently than in LQT1 (P=0.07)
(Table 3). Conversely, 80% of the patients with events that
occurred after auditory stimuli were LQT2 patients. Of note, in LQT2
patients, most of these events (64%) occurred during
sleep.
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Swimming, as a trigger, was particularly frequent among LQT1
patients; it occurred in 33% of patients with a known trigger (107 of
320). By contrast, it was exceptionally rare (1 of 176, 0.6%) among
LQT2 patients and absent among LQT3 patients. Of the patients who
experienced cardiac events while swimming, 99% were of LQT1
(Table 3
).
Corrected QT Duration and Triggers
Corrected QT (QTc) measurements were available for 517
(77%) patients
(Figure 3). The 3 subgroups have very similar average
values; furthermore, LQT1 and LQT2, but not LQT3, female patients have
longer durations.
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Time to First Event and Genotype
For 626 patients (93%), we knew the exact age at which
the first cardiac event occurred. This allowed to generate curves that
show the time interval from birth to the first major cardiac event for
the 3 subgroups
(Figure 4). LQT1 patients were the earliest to have symptoms;
54% of them become symptomatic before age 10. By contrast, 50% of
LQT2 and LQT3 patients were still asymptomatic at age 16.
Figure 4 reflects that the present study includes only
symptomatic patients.
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We also constructed Kaplan-Meyer time-to-event curves
specific for the 3 classified triggers within each genotype
(Figure 5); they were obviously limited to patients with 1
trigger only. For LQT1 patients through age 8, exercise and emotion
occurred at the same time; thereafter, the events triggered by exercise
occurred earlier, so by the age of 20, 94% of the patients who were
destined to experience events with exercise had them, whereas this was
true for only 68% of the patients who were destined to experience
episodes during emotional stress. Sleep-related events tended to occur
markedly later, and by age 20, 50% of patients still had not
experienced a first episode; however, this represents a small subgroup.
The patterns for LQT2 and LQT3, despite a similar trend, are less
distinct, and the separation between triggers is no longer
statistically significant.
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Among LQT1 patients, male patients had their first event
much earlier than female patients
(P<0.0001), with the 2 curves
beginning to differentiate by age 5 and remaining well distinct over
time
(Figure 6). Among LQT2 and LQT3 patients, this pattern was
just a nonsignificant trend.
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ß-Blocker Therapy and Genotype
Of the 162 LQT1 patients treated with ß-blockers and
for whom adequate information was available, 131 (81%) had no
recurrences
(Table 4). Among those (19%) with recurrences, there were 7
cardiac arrests/sudden deaths, representing 4% of the population
treated and 23% of those with recurrences.
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The success rate of ß-blocker therapy, as assessed on the basis of recurrences, was lower among LQT2 (P<0.001) and LQT3 (P=0.05) patients.
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Discussion |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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This study demonstrates that life-threatening arrhythmias in LQTS patients do not occur at random and that the probability for these events to occur under specific circumstances varies in a gene-specific manner. The unique dimensions of the study, in terms of the number of patients of known genotype who have also experienced a major cardiac event, ensure the validity of the observations and the possibility of extrapolation of these results to all LQTS patients with mutations on these 3 genes.
The results provide new insights into the mechanisms that relate the molecular abnormalities to the onset of lethal arrhythmias and suggest gene-specific approaches to decrease arrhythmic risk.
Findings and Mechanisms
The first difference that emerges from an examination
of the patterns of association between various triggering conditions
and genotype is that LQT2 patients are more similar to LQT3 patients
than to LQT1 patients. Because both LQT1 and LQT2 patients have
mutations of K+ channels, this was initially
surprising. The most likely explanation lies in the common denominator
for LQT2 and LQT3: the presence of a normal
IKs
current.
IKs is
activated by fast heart rates and by catecholamines and shortens
ventricular repolarization, thus providing a physiological protection
against the possibility of reentrant arrhythmias at fast rates. This
may help explain why compared with LQT1 patients, LQT2 and LQT3
patients are at relatively low risk during exercise. This pattern is
further accentuated when the analysis is limited to lethal events, and
the similarity between LQT2 and LQT3 becomes quite
impressive.
Experimental observations12 and preliminary clinical data on QT changes during exercise7 and nighttime13 provide additional explanations for the low risk during exercise and the high risk during sleep of LQT3 patients. A significant reduction in action potential duration during rapid pacing was observed in the cellular model for LQT3 but not in the model that mimics LQT2.12 A potential explanation is available.2 With rapid rates, Na+ accumulates in the cell, lowering the Na+ gradient across the membrane and, consequently, the magnitude of INa. The effect of such a reduction would be negligible during the rising phase of the action potential, when INa is of overwhelming magnitude. However, the plateau INa contribution of the mutant channels is of much smaller magnitude due to delayed inactivation of INa and could be significantly affected by such changes. Of importance, this current operates at a critical time, when the action potential is determined by a delicate balance of small currents.1 2 Thus, a reduction in INa during this phase, as can result from faster heart rates, could shorten action potential duration and, hence, the QT interval.
LQT3 patients tend to have shortened QT intervals, much more than normal, during exercise-induced tachycardia and to have significant QT prolongations at long cycle lengths.7 They also have considerably prolonged QT intervals during nighttime, whereas this seems to happen to a lesser degree for LQT2 patients and not at all for LQT1 patients.13 Confirmation of these preliminary data would help to explain the current findings, including the intriguing propensity of LQT3 patients to experience major arrhythmic events while they are asleep.
LQT1 patients, with malfunctioning IKs channels, are expected to shorten their QT intervals during tachycardia less effectively than normal individuals. The superimposition of a major catecholamine release, as happens during exercise, without a proper QT adaptation (ie, QT shortening), sets the stage for early afterdepolarizations, which may then lead to TdP via reentry. This concept is supported by an experimental model for LQT1 in which IKs blockade greatly enhances the probability of TdP in the presence of catecholamines.14
Among these symptomatic LQT1, LQT2, and LQT3 patients, the QT interval was equally prolonged. The apparent discrepancy from our previous report15 is explained by the fact that it included both symptomatic and asymptomatic patients.
We also extended previous observations on the age and sex dependence of first cardiac events.11 The earlier occurrence of cardiac events among male patients reported for nongenotyped LQTS patients is indeed mostly dependent on LQT1. This trend is present across genotypes but is much less distinct among LQT2 and LQT3 patients, where, at variance with LQT1, the difference between sexes is no longer evident after age 20.
Implications for Clinical Management
These novel findings allow a more tailored approach to
the management of LQTS patients on the basis of genotype.
The greater probability of becoming symptomatic under one condition does not exclude the possibility of a cardiac event occurring under different circumstances. Nevertheless, patients of a given genotype are more or less likely to experience cardiac events under well-defined conditions; this can provide guidance for diagnostic procedures and for gene-specific approaches to management. Indeed, 65% of the patients continue to experience their cardiac events under conditions similar to their first classified event.
The critical role of an impairment of IKs in the facilitation of adrenergic-dependent arrhythmias has implications for therapy. Indeed, 88% of LQT1 patients were at risk during conditions of sympathetic hyperactivity, exercise, or emotions. Thus, antiadrenergic interventions were expected to be particularly effective for them. They did very well with ß-blocker therapy; >80% remained free from recurrences, with a total mortality rate of 4%. Only a few LQT1 patients will require therapy other than antiadrenergic intervention.
Most LQT1 patients experience their events during exercise; accordingly, not only should they not engage in competitive sports, like all LQTS patients, but also physical stress should be avoided or limited, compatible with quality of life. Swimming, identified early as an important trigger for LQTS patients16 and recently for LQT1 patients,8 is a major risk factor (triggering an event in 33% of them), and without supervision, swimming should be avoided. Because LQT1 patients are endangered by high heart rates, pacemaker therapy is not advised.
LQT3 patients are at higher risk at longer cycle lengths. This raises concerns, not yet supported by evidence, regarding the use of ß-blockers because of the attendant reduction in heart rate. The prevention of norepinephrine release remains important, but it is effectively and more safely achieved with selective left cardiac sympathetic denervation,17 which does not reduce heart rate.18 LQT3 patients may benefit from pacemakers, which would also allow the safe use of ß-blockers, because their QT interval tends to shorten significantly at faster heart rates; accordingly, recreational physical activity may not have to be withheld, except for those who have already experienced events during exercise. The long-term value of Na+ channel blockers in this group, proposed in 1995,7 remains to be tested. Even though the data regarding therapy for LQT3 patients remain numerically limited, their high mortality rate despite therapy, and particularly at the first episode,5 suggests the consideration of internal cardioverter-defibrillator implantation; the combination with left sympathectomy would reduce the probability of lethal arrhythmias while providing a safety net.
Gene-specific management for LQT2 is more problematic. Suggestions that increases in extracellular K+ concentration may be beneficial are hindered by the difficulties in achieving high [K] with chronic oral therapy. These patients are at a relatively low risk during exercise. The occurrence of cardiac events either at sleep/rest without arousal or during exercise, given the extremely low probability of their occurrence under both conditions, can identify the triggers associated with the highest risk. A comparison with LQT1 patients suggested that auditory stimuli are specific for LQT219 ; our data, which demonstrate their occurrence mostly during sleep, support but also qualify that concept by confirming the high prevalence of auditory stimuli as triggers for LQT2 and by showing their significant role also for LQT3 patients. The experimental prevention with ß-blocker therapy of life-threatening arrhythmias triggered by a loud noise suggests their effectiveness also for LQT2 patients at risk under this specific condition. The efficacy of ß-blockers in LQT2 patients was already proposed.10 Finally, the high risk associated with auditory stimuli makes the removal of telephones and alarm clocks from patient bedrooms advisable.
The cumulative survival curves demonstrate that the age at which LQTS becomes clinically manifest is also gene specific, with LQT1 patients being the youngest to experience cardiac events; 86% of them experience their first episode by age 20. In contrast, symptomatic LQT2 and LQT3 patients are also at risk of the onset of cardiac events later in life. Although data for only symptomatic patients are presented here, when dealing with asymptomatic patients of known genotype, it may now be possible to consider their probability of ever becoming symptomatic on the basis of their age. This allows further refinement in management strategy.
Study Limitations
This study has the limitations that are unavoidable
with multiple data sources, such as occurs in any registry or large
multicenter studies. Due to organizational complexity, data
collection forms were very simple, with only information essential for
the present study on triggers. Data on secondary objectives, such as
response to therapy, should be regarded as hypothesis generating, and
will require specific analysis with additional information.
Nevertheless, the very large number of genotyped symptomatic patients
allows to safe conclusions to be drawn regarding the main aspects of
the study.
Conclusions
This uniquely large cooperative study has allowed us to
gather information on an unprecedented number of LQTS patients, all
with major cardiac events and all of known genotype. In the
investigation of hereditary arrhythmogenic disorders, this is the
largest data set ever used for genotype-phenotype correlation studies.
It provides definitive evidence for gene-specific differences in the
propensity to life-threatening arrhythmias under specific conditions
and offers insights into some of the underlying mechanisms. It also
provides the rationale for a novel approach toward the prevention of
sudden death in LQTS on the basis of the integration of
experience-supported therapies (ß-blockers, left cardiac sympathetic
denervation, pacemakers, implantable cardioverter-defibrillators) with
behavioral recommendations and therapeutic choices dictated by
gene-specific
considerations.
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Acknowledgments |
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This work was supported in part by grants NIH HL-33843 and HL-51618, CEE BMH4-CT96-0028, Telethon 1058, PROGRES 4P009D, NHS 95.014, and ICIN project 27. The following investigators have contributed to aspects of the study: MacDonald Dick II, Debra Francovich, Marco Hördt, Pamela S. Karnes, Emanuela H. Locati, Mark Russell, Melvin M. Scheinman, Julia Sunkomat, and Heikki Swan. We are also grateful to Pinuccia De Tomasi for expert editorial support.
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Footnotes |
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Guest Editor for this article was Douglas P. Zipes, MD, Indiana University School of Medicine, Indianapolis, Ind.
Received June 5, 2000; revision received August 9, 2000; accepted August 14, 2000.
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References |
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 R. C. Ahrens-Nicklas, C. E. Clancy, and D. J. Christini Re-evaluating the efficacy of {beta}-adrenergic agonists and antagonists in long QT-3 syndrome through computational modelling Cardiovasc Res, June 1, 2009; 82(3): 439 - 447. [Abstract] [Full Text] [PDF]
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 W.-Y. Chuang, Y.-T. Chuang, and K.-C. Ueng Fourteen-Year Follow-up in a Teenager with Congenital Long QT Syndrome Masquerading as Idiopathic Generalized Epilepsy J Am Board Fam Med, May 1, 2009; 22(3): 331 - 334. [Abstract] [Full Text] [PDF]
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 R. Shephard and C. Semsarian Advances in the prevention of sudden cardiac death in the young Therapeutic Advances in Cardiovascular Disease, April 1, 2009; 3(2): 145 - 155. [Abstract] [PDF]
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 I. Iniesta, R. Yotti, and A. Garcia-Pastor Transient loss of consciousness with convulsions in two young adults with potentially fatal underlying heart disease: syncope versus seizures BMJ Case Reports, March 20, 2009; 2009(mar19_1): bcr0620080285 - bcr0620080285. [Abstract] [Full Text]
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 G. M. Vincent, P. J. Schwartz, I. Denjoy, H. Swan, C. Bithell, C. Spazzolini, L. Crotti, K. Piippo, J.-M. Lupoglazoff, E. Villain, et al. 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" Circulation, January 20, 2009; 119(2): 215 - 221. [Abstract] [Full Text] [PDF]
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 J.-P. Couderc, S. Kaab, M. Hinterseer, S. McNitt, X. Xia, A. Fossa, B. M. Beckmann, S. Polonsky, and W. Zareba Baseline Values and Sotalol-Induced Changes of Ventricular Repolarization Duration, Heterogeneity, and Instability in Patients With a History of Drug-Induced Torsades de Pointes J. Clin. Pharmacol., January 1, 2009; 49(1): 6 - 16. [Abstract] [Full Text] [PDF]
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 S. Nattel Delayed-rectifier potassium currents and the control of cardiac repolarization: Noble and Tsien 40 years after J. Physiol., December 15, 2008; 586(24): 5849 - 5852. [Full Text] [PDF]
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 D. W. Wang, L. Crotti, W. Shimizu, M. Pedrazzini, F. Cantu, P. De Filippo, K. Kishiki, A. Miyazaki, T. Ikeda, P. J. Schwartz, et al. Malignant Perinatal Variant of Long-QT Syndrome Caused by a Profoundly Dysfunctional Cardiac Sodium Channel Circ Arrhythmia Electrophysiol, December 1, 2008; 1(5): 370 - 378. [Abstract] [Full Text] [PDF]
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 R. J. Kirk, J. L. Hung, S. R. Horner, and J. T. Perez Implications of Pharmacogenomics for Drug Development Experimental Biology and Medicine, December 1, 2008; 233(12): 1484 - 1497. [Abstract] [Full Text] [PDF]
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 K. E. Odening, O. Hyder, L. Chaves, L. Schofield, M. Brunner, M. Kirk, M. Zehender, X. Peng, and G. Koren Pharmacogenomics of anesthetic drugs in transgenic LQT1 and LQT2 rabbits reveal genotype-specific differential effects on cardiac repolarization Am J Physiol Heart Circ Physiol, December 1, 2008; 295(6): H2264 - H2272. [Abstract] [Full Text] [PDF]
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Y. Ruan, N. Liu, C. Napolitano, and S. G. Priori Therapeutic Strategies for Long-QT Syndrome: Does the Molecular Substrate Matter? Circ Arrhythmia Electrophysiol, October 1, 2008; 1(4): 290 - 297. [Full Text] [PDF]
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 M. D Tobin, M. Kahonen, P. Braund, T. Nieminen, C. Hajat, M. Tomaszewski, J. Viik, R. Lehtinen, G A. Ng, P. W Macfarlane, et al. Gender and effects of a common genetic variant in the NOS1 regulator NOS1AP on cardiac repolarization in 3761 individuals from two independent populations Int. J. Epidemiol., October 1, 2008; 37(5): 1132 - 1141. [Abstract] [Full Text] [PDF]
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 E. LEVINE, S. Z. ROSERO, A. S. BUDZIKOWSKI, A. J. MOSS, W. ZAREBA, and J. P. DAUBERT Congenital long QT syndrome: Considerations for primary care physicians Cleveland Clinic Journal of Medicine, August 1, 2008; 75(8): 591 - 600. [Abstract] [Full Text] [PDF]
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A. J. Moss and I. Goldenberg Importance of Knowing the Genotype and the Specific Mutation When Managing Patients With Long-QT Syndrome Circ Arrhythmia Electrophysiol, August 1, 2008; 1(3): 219 - 226. [Full Text] [PDF]
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G. M. Vincent Genotyping Has a Minor Role in Selecting Therapy for Congenital Long-QT Syndromes at Present Circ Arrhythmia Electrophysiol, August 1, 2008; 1(3): 227 - 233. [Full Text] [PDF]
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 E. R. Behr, C. Dalageorgou, M. Christiansen, P. Syrris, S. Hughes, M. T. Tome Esteban, E. Rowland, S. Jeffery, and W. J. McKenna Sudden arrhythmic death syndrome: familial evaluation identifies inheritable heart disease in the majority of families Eur. Heart J., July 1, 2008; 29(13): 1670 - 1680. [Abstract] [Full Text] [PDF]
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 A. E. Epstein, J. P. DiMarco, K. A. Ellenbogen, N.A. M. Estes III, R. A. Freedman, L. S. Gettes, A. M. Gillinov, G. Gregoratos, S. C. Hammill, D. L. Hayes, et al. 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 J. Am. Coll. Cardiol., May 27, 2008; 51(21): e1 - e62. [Full Text] [PDF]
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A. E. Epstein, J. P. DiMarco, K. A. Ellenbogen, N.A. M. Estes III, R. A. Freedman, L. S. Gettes, A. M. Gillinov, G. Gregoratos, S. C. Hammill, D. L. Hayes, et al. 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 Circulation, May 27, 2008; 117(21): e350 - e408. [Full Text] [PDF]
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I. Goldenberg, A. J. Moss, D. R. Peterson, S. McNitt, W. Zareba, M. L. Andrews, J. L. Robinson, E. H. Locati, M. J. Ackerman, J. Benhorin, et al. Risk Factors for Aborted Cardiac Arrest and Sudden Cardiac Death in Children With the Congenital Long-QT Syndrome Circulation, April 29, 2008; 117(17): 2184 - 2191. [Abstract] [Full Text] [PDF]
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I. Goldenberg, A. J. Moss, J. Bradley, S. Polonsky, D. R. Peterson, S. McNitt, W. Zareba, M. L. Andrews, J. L. Robinson, M. J. Ackerman, et al. Long-QT Syndrome After Age 40 Circulation, April 29, 2008; 117(17): 2192 - 2201. [Abstract] [Full Text] [PDF]
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 Heart Rhythm UK Familial Sudden Death Syndromes St Clinical indications for genetic testing in familial sudden cardiac death syndromes: an HRUK position statement Heart, April 1, 2008; 94(4): 502 - 507. [Abstract] [Full Text] [PDF]
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P. J. Schwartz, E. Vanoli, L. Crotti, C. Spazzolini, C. Ferrandi, A. Goosen, P. Hedley, M. Heradien, S. Bacchini, A. Turco, et al. Neural control of heart rate is an arrhythmia risk modifier in long QT syndrome. J. Am. Coll. Cardiol., March 4, 2008; 51(9): 920 - 929. [Abstract] [Full Text] [PDF]
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M. Chinushi, D. Izumi, K. Iijima, S. Ahara, S. Komura, H. Furushima, Y. Hosaka, and Y. Aizawa Antiarrhythmic vs. pro-arrhythmic effects depending on the intensity of adrenergic stimulation in a canine anthopleurin-A model of type-3 long QT syndrome Europace, February 1, 2008; 10(2): 249 - 255. [Abstract] [Full Text] [PDF]
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 D. M. Roden Long-QT Syndrome N. Engl. J. Med., January 10, 2008; 358(2): 169 - 176. [Full Text] [PDF]
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 L. Chen, M. L. Marquardt, D. J. Tester, K. J. Sampson, M. J. Ackerman, and R. S. Kass Mutation of an A-kinase-anchoring protein causes long-QT syndrome PNAS, December 26, 2007; 104(52): 20990 - 20995. [Abstract] [Full Text] [PDF]
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L. Crotti, C. Spazzolini, P. J. Schwartz, W. Shimizu, I. Denjoy, E. Schulze-Bahr, E. V. Zaklyazminskaya, H. Swan, M. J. Ackerman, A. J. Moss, et al. 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 Circulation, November 20, 2007; 116(21): 2366 - 2375. [Abstract] [Full Text] [PDF]
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 P. J. Mohler and X. H. T. Wehrens Mechanisms of Human Arrhythmia Syndromes: Abnormal Cardiac Macromolecular Interactions Physiology, October 1, 2007; 22(5): 342 - 350. [Abstract] [Full Text] [PDF]
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C. Antzelevitch Role of spatial dispersion of repolarization in inherited and acquired sudden cardiac death syndromes Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2024 - H2038. [Abstract] [Full Text] [PDF]
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Y. Ruan, N. Liu, R. Bloise, C. Napolitano, and S. G. Priori Gating Properties of SCN5A Mutations and the Response to Mexiletine in Long-QT Syndrome Type 3 Patients Circulation, September 4, 2007; 116(10): 1137 - 1144. [Abstract] [Full Text] [PDF]
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N. van Dijk, M. C. Boer, T. De Santo, N. Grovale, A. J.J. Aerts, L. Boersma, and W. Wieling Daily, weekly, monthly, and seasonal patterns in the occurrence of vasovagal syncope in an older population Europace, September 1, 2007; 9(9): 823 - 828. [Abstract] [Full Text] [PDF]
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C. Antzelevitch Ionic, molecular, and cellular bases of QT-interval prolongation and torsade de pointes Europace, September 1, 2007; 9(suppl_4): iv4 - iv15. [Abstract] [Full Text] [PDF]
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 T. A. Beery, K. A. Shooner, and D. W. Benson Neonatal Long QT Syndrome Due to a De Novo Dominant Negative hERG Mutation Am. J. Crit. Care., July 1, 2007; 16(4): 416 - 412. [Abstract] [Full Text] [PDF]
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V. L. Vetter Clues or Miscues?: How to Make the Right Interpretation and Correctly Diagnose Long-QT Syndrome Circulation, May 22, 2007; 115(20): 2595 - 2598. [Full Text] [PDF]
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N. W. Taggart, C. M. Haglund;, D. J. Tester, and M. J. Ackerman Diagnostic Miscues in Congenital Long-QT Syndrome Circulation, May 22, 2007; 115(20): 2613 - 2620. [Abstract] [Full Text] [PDF]
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F. Suto, W. Zhu, A. Chan, and G. J. Gross IKr and IKs remodeling differentially affects QT interval prolongation and dynamic adaptation to heart rate acceleration in bradycardic rabbits Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1782 - H1788. [Abstract] [Full Text] [PDF]
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R. Seth, A. J. Moss, S. McNitt, W. Zareba, M. L. Andrews, M. Qi, J. L. Robinson, I. Goldenberg, M. J. Ackerman, J. Benhorin, et al. Long QT Syndrome and Pregnancy J. Am. Coll. Cardiol., March 13, 2007; 49(10): 1092 - 1098. [Abstract] [Full Text] [PDF]
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 A. Bell and K. McLeod Not so funny turns Arch. Dis. Child. Ed. Pract., February 1, 2007; 92(1): ep7 - ep13. [Full Text] [PDF]
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M. Arnestad, L. Crotti, T. O. Rognum, R. Insolia, M. Pedrazzini, C. Ferrandi, A. Vege, D. W. Wang, T. E. Rhodes, A. L. George Jr, et al. Prevalence of Long-QT Syndrome Gene Variants in Sudden Infant Death Syndrome Circulation, January 23, 2007; 115(3): 361 - 367. [Abstract] [Full Text] [PDF]
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K. S. Stokoe, G. Thomas, C. A. Goddard, W. H. Colledge, A. A. Grace, and C. L.-H. Huang Effects of flecainide and quinidine on arrhythmogenic properties of Scn5a+/{Delta} murine hearts modelling long QT syndrome 3 J. Physiol., January 1, 2007; 578(1): 69 - 84. [Abstract] [Full Text] [PDF]
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G. Thomas, I. S. Gurung, M. J. Killeen, P. Hakim, C. A. Goddard, M. P. Mahaut-Smith, W. H. Colledge, A. A. Grace, and C. L.-H. Huang 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 J. Physiol., January 1, 2007; 578(1): 85 - 97. [Abstract] [Full Text] [PDF]
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 S. Fredj, N. Lindegger, K. J. Sampson, P. Carmeliet, and R. S. Kass Altered Na+ Channels Promote Pause-Induced Spontaneous Diastolic Activity in Long QT Syndrome Type 3 Myocytes Circ. Res., November 24, 2006; 99(11): 1225 - 1232. [Abstract] [Full Text] [PDF]
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H. L. Tan, A. Bardai, W. Shimizu, A. J. Moss, E. Schulze-Bahr, T. Noda, and A. A. M. Wilde Genotype-Specific Onset of Arrhythmias in Congenital Long-QT Syndrome: Possible Therapy Implications Circulation, November 14, 2006; 114(20): 2096 - 2103. [Abstract] [Full Text] [PDF]
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E. Schulze-Bahr Arrhythmia Predisposition: Between Rare Disease Paradigms and Common Ion Channel Gene Variants J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A67 - A78. [Abstract] [Full Text] [PDF]
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M. J. Heradien, A. Goosen, L. Crotti, G. Durrheim, V. Corfield, P. A. Brink, and P. J. Schwartz Does Pregnancy Increase Cardiac Risk for LQT1 Patients With the KCNQ1-A341V Mutation? J. Am. Coll. Cardiol., October 3, 2006; 48(7): 1410 - 1415. [Abstract] [Full Text] [PDF]
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 C.-u. Choe, E. Schulze-Bahr, A. Neu, J. Xu, Z. I. Zhu, K. Sauter, R. Bahring, S. Priori, P. Guicheney, G. Monnig, et al. C-terminal HERG (LQT2) mutations disrupt IKr channel regulation through 14-3-3{epsilon} Hum. Mol. Genet., October 1, 2006; 15(19): 2888 - 2902. [Abstract] [Full Text] [PDF]
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M. A. Perhonen, P. Haapalahti, S. Kivisto, A.-M. Hekkala, H. Vaananen, H. Swan, and L. Toivonen Effect of physical training on ventricular repolarization in type 1 long QT syndrome: a pilot study in asymptomatic carriers of the G589D KCNQ1 mutation Europace, October 1, 2006; 8(10): 894 - 898. [Abstract] [Full Text] [PDF]
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M. Stengl, C. Ramakers, D. W. Donker, A. Nabar, A. V. Rybin, R. L.H.M.G. Spatjens, T. van der Nagel, W. K.W.H. Wodzig, K. R. Sipido, G. Antoons, et al. Temporal patterns of electrical remodeling in canine ventricular hypertrophy: Focus on IKs downregulation and blunted {beta}-adrenergic activation Cardiovasc Res, October 1, 2006; 72(1): 90 - 100. [Abstract] [Full Text] [PDF]
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I. Goldenberg, J. Mathew, A. J. Moss, S. McNitt, D. R. Peterson, W. Zareba, J. Benhorin, L. Zhang, G. M. Vincent, M. L. Andrews, et al. Corrected QT Variability in Serial Electrocardiograms in Long QT Syndrome: The Importance of the Maximum Corrected QT for Risk Stratification J. Am. Coll. Cardiol., September 5, 2006; 48(5): 1047 - 1052. [Abstract] [Full Text] [PDF]
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E. T. Locati QT Interval Duration Remains a Major Risk Factor in Long QT Syndrome Patients J. Am. Coll. Cardiol., September 5, 2006; 48(5): 1053 - 1055. [Full Text] [PDF]
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Developed in Collaboration With the European Heart, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. 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., September 5, 2006; 48(5): e247 - e346. [Full Text] [PDF]
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Writing Committee Members, D. P. Zipes, A. J. Camm, M. Borggrefe, A. E. Buxton, B. Chaitman, M. Fromer, G. Gregoratos, G. Klein, A. J. Moss, et al. 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, September 1, 2006; 8(9): 746 - 837. [Full Text] [PDF]
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M. Viitasalo, L. Oikarinen, H. Swan, H. Vaananen, J. Jarvenpaa, H. Hietanen, J. Karjalainen, and L. Toivonen Effects of Beta-Blocker Therapy on Ventricular Repolarization Documented by 24-h Electrocardiography in Patients With Type 1 Long-QT Syndrome J. Am. Coll. Cardiol., August 15, 2006; 48(4): 747 - 753. [Abstract] [Full Text] [PDF]
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S. Quaglini, C. Rognoni, C. Spazzolini, S. G. Priori, S. Mannarino, and P. J. Schwartz Cost-effectiveness of neonatal ECG screening for the long QT syndrome Eur. Heart J., August 1, 2006; 27(15): 1824 - 1832. [Abstract] [Full Text] [PDF]
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S. G. Priori and C. Napolitano Molecular Underpinning of "Good Luck" Circulation, August 1, 2006; 114(5): 360 - 362. [Full Text] [PDF]
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 J. M. Karp and A. J. Moss Dental treatment of patients with long QT syndrome J Am Dent Assoc, May 1, 2006; 137(5): 630 - 637. [Abstract] [Full Text] [PDF]
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K. L. Dodge-Kafka, L. Langeberg, and J. D. Scott Compartmentation of Cyclic Nucleotide Signaling in the Heart: The Role of A-Kinase Anchoring Proteins Circ. Res., April 28, 2006; 98(8): 993 - 1001. [Abstract] [Full Text] [PDF]
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A. Anastasakis, C.-M. Kotta, S. Kyriakogonas, B. Wollnik, A. Theopistou, and C. Stefanadis Phenotype reveals genotype in a Greek long QT syndrome family. Europace, April 1, 2006; 8(4): 241 - 244. [Abstract] [Full Text] [PDF]
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H. Vyas, J. Hejlik, and M. J. Ackerman Epinephrine QT Stress Testing in the Evaluation of Congenital Long-QT Syndrome: Diagnostic Accuracy of the Paradoxical QT Response Circulation, March 21, 2006; 113(11): 1385 - 1392. [Abstract] [Full Text] [PDF]
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S. G. Priori and C. Napolitano Role of Genetic Analyses in Cardiology: Part I: Mendelian Diseases: Cardiac Channelopathies Circulation, February 28, 2006; 113(8): 1130 - 1135. [Abstract] [Full Text] [PDF]
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P. J. Schwartz, C. Spazzolini, L. Crotti, J. Bathen, J. P. Amlie, K. Timothy, M. Shkolnikova, C. I. Berul, M. Bitner-Glindzicz, L. Toivonen, et al. The Jervell and Lange-Nielsen Syndrome: Natural History, Molecular Basis, and Clinical Outcome Circulation, February 14, 2006; 113(6): 783 - 790. [Abstract] [Full Text] [PDF]
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 A. A. Fossa, T. Wisialowski, and K. Crimin QT Prolongation Modifies Dynamic Restitution and Hysteresis of the Beat-to-Beat QT-TQ Interval Relationship during Normal Sinus Rhythm under Varying States of Repolarization J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 498 - 506. [Abstract] [Full Text] [PDF]
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 O. Casis, S.-P. Olesen, and M. C. Sanguinetti Mechanism of Action of a Novel Human ether-a-go-go-Related Gene Channel Activator Mol. Pharmacol., February 1, 2006; 69(2): 658 - 665. [Abstract] [Full Text] [PDF]
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G. Berecki, J. G. Zegers, Z. A. Bhuiyan, A. O. Verkerk, R. Wilders, and A. C. G. van Ginneken Long-QT syndrome-related sodium channel mutations probed by the dynamic action potential clamp technique J. Physiol., January 15, 2006; 570(2): 237 - 250. [Abstract] [Full Text] [PDF]
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R. Roberts Genomics and Cardiac Arrhythmias J. Am. Coll. Cardiol., January 3, 2006; 47(1): 9 - 21. [Abstract] [Full Text] [PDF]
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M. Viitasalo, L. Oikarinen, H. Swan, K. A. Glatter, H. Vaananen, H. Fodstad, N. Chiamvimonvat, K. Kontula, L. Toivonen, and M. M. Scheinman Ratio of Late to Early T-Wave Peak Amplitude in 24-h Electrocardiographic Recordings as Indicator of Symptom History in Patients With Long-QT Syndrome Types 1 and 2 J. Am. Coll. Cardiol., January 3, 2006; 47(1): 112 - 120. [Abstract] [Full Text] [PDF]
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 C. Napolitano, S. G. Priori, P. J. Schwartz, R. Bloise, E. Ronchetti, J. Nastoli, G. Bottelli, M. Cerrone, and S. Leonardi Genetic Testing in the Long QT Syndrome: Development and Validation of an Efficient Approach to Genotyping in Clinical Practice JAMA, December 21, 2005; 294(23): 2975 - 2980. [Abstract] [Full Text] [PDF]
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E. S. Kaufman Efficient Genotyping for Congenital Long QT Syndrome JAMA, December 21, 2005; 294(23): 3027 - 3028. [Full Text] [PDF]
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M. Viitasalo, L. Oikarinen, H. Swan, K. A. Glatter, H. Vaananen, H. Fodstad, N. Chiamvimonvat, K. Kontula, L. Toivonen, and M. M. Scheinman Ratio of Late to Early T-Wave Peak Amplitude in 24-h Electrocardiographic Recordings as Indicator of Symptom History in Patients With Long-QT Syndrome Types 1 and 2 J. Am. Coll. Cardiol., December 13, 2005; (2005) j.jacc.2005.07.068v1. [Abstract] [Full Text] [PDF]
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T. Jespersen, M. Grunnet, and S.-P. Olesen The KCNQ1 Potassium Channel: From Gene to Physiological Function Physiology, December 1, 2005; 20(6): 408 - 416. [Abstract] [Full Text] [PDF]
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G. S. Ginsburg, M. P. Donahue, and L. K. Newby Prospects for Personalized Cardiovascular Medicine: The Impact of Genomics J. Am. Coll. Cardiol., November 1, 2005; 46(9): 1615 - 1627. [Abstract] [Full Text] [PDF]
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P. A. Brink, L. Crotti, V. Corfield, A. Goosen, G. Durrheim, P. Hedley, M. Heradien, G. Geldenhuys, E. Vanoli, S. Bacchini, et al. Phenotypic Variability and Unusual Clinical Severity of Congenital Long-QT Syndrome in a Founder Population Circulation, October 25, 2005; 112(17): 2602 - 2610. [Abstract] [Full Text] [PDF]
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A. A M Wilde and C. R Bezzina Genetics of cardiac arrhythmias Heart, October 1, 2005; 91(10): 1352 - 1358. [Full Text] [PDF]
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L. Crotti, A. L. Lundquist, R. Insolia, M. Pedrazzini, C. Ferrandi, G. M. De Ferrari, A. Vicentini, P. Yang, D. M. Roden, A. L. George Jr, et al. KCNH2-K897T Is a Genetic Modifier of Latent Congenital Long-QT Syndrome Circulation, August 30, 2005; 112(9): 1251 - 1258. [Abstract] [Full Text] [PDF]
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W. Shimizu The long QT syndrome: Therapeutic implications of a genetic diagnosis Cardiovasc Res, August 15, 2005; 67(3): 347 - 356. [Abstract] [Full Text] [PDF]
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D. J. Tester and M. J. Ackerman Sudden infant death syndrome: How significant are the cardiac channelopathies? Cardiovasc Res, August 15, 2005; 67(3): 388 - 396. [Abstract] [Full Text] [PDF]
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S. Kaab and E. Schulze-Bahr Susceptibility genes and modifiers for cardiac arrhythmias Cardiovasc Res, August 15, 2005; 67(3): 397 - 413. [Abstract] [Full Text] [PDF]
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G. C.M. Beaufort-Krol, M. P. van den Berg, A. A.M. Wilde, J. P. van Tintelen, J. W. Viersma, C. R. Bezzina, and M. Th.E. Bink-Boelkens 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., July 19, 2005; 46(2): 331 - 337. [Abstract] [Full Text] [PDF]
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J. Temple, P. Frias, J. Rottman, T. Yang, Y. Wu, E. E. Verheijck, W. Zhang, C. Siprachanh, H. Kanki, J. B. Atkinson, et al. Atrial Fibrillation in KCNE1-Null Mice Circ. Res., July 8, 2005; 97(1): 62 - 69. [Abstract] [Full Text] [PDF]
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L. Zhang, D. W. Benson, M. Tristani-Firouzi, L. J. Ptacek, R. Tawil, P. J. Schwartz, A. L. George, M. Horie, G. Andelfinger, G. L. Snow, et al. Electrocardiographic Features in Andersen-Tawil Syndrome Patients With KCNJ2 Mutations: Characteristic T-U-Wave Patterns Predict the KCNJ2 Genotype Circulation, May 31, 2005; 111(21): 2720 - 2726. [Abstract] [Full Text] [PDF]
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 R. D. Lane, C. Laukes, F. I. Marcus, M. A. Chesney, L. Sechrest, K. Gear, C. L. Fort, S. G. Priori, P. J. Schwartz, and A. Steptoe Psychological Stress Preceding Idiopathic Ventricular Fibrillation Psychosom Med, May 1, 2005; 67(3): 359 - 365. [Abstract] [Full Text] [PDF]
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 J R Skinner Is there a relation between SIDS and long QT syndrome? Arch. Dis. Child., May 1, 2005; 90(5): 445 - 449. [Full Text] [PDF]
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 D. J. Tester, L. J. Kopplin, W. Creighton, A. P. Burke, and M. J. Ackerman Pathogenesis of Unexplained Drowning: New Insights From a Molecular Autopsy Mayo Clin. Proc., May 1, 2005; 80(5): 596 - 600. [Abstract] [PDF]
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D. P. Zipes, M. J. Ackerman, N.A. M. Estes III, A. O. Grant, R. J. Myerburg, and G. Van Hare Task Force 7: Arrhythmias J. Am. Coll. Cardiol., April 19, 2005; 45(8): 1354 - 1363. [Full Text] [PDF]
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 T. T. Beery The Genetics of Cardiac Arrhythmias Biol Res Nurs, April 1, 2005; 6(4): 249 - 261. [Abstract] [PDF]
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C. Terrenoire, C. E. Clancy, J. W. Cormier, K. J. Sampson, and R. S. Kass Autonomic Control of Cardiac Action Potentials: Role of Potassium Channel Kinetics in Response to Sympathetic Stimulation Circ. Res., March 18, 2005; 96(5): e25 - e34. [Abstract] [Full Text] [PDF]
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