Published online before print December 31, 2008, doi: 10.1161/CIRCULATIONAHA.108.772533
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(Circulation. 2009;119:215-221.)
© 2009 American Heart Association, Inc.
Arrhythmia/Electrophysiology |
High Efficacy of β-Blockers in Long-QT Syndrome Type 1
Contribution of Noncompliance and QT-Prolonging Drugs to the Occurrence of β-Blocker Treatment "Failures"
From the Departments of Medicine, LDS Hospital and University of Utah, Salt Lake City (G.M.V., C.B., L.Z.); Department of Cardiology, IRCCS Fondazione Policlinico S. Matteo (P.J.S., C.S., L.C.) and University of Pavia (P.J.S., S.G.P.), Pavia, Italy; Laboratory of Cardiovascular Genetics, IRCCS Instituto Auxologico, Milan, Italy (P.J.S.); Cardiovascular Genetics Laboratory, Hatter Institute for Cardiovascular Research, Department of Medicine, University of Cape Town, South Africa (P.J.S.); Service de Cardiologie, Hôpital Lariboisière, Paris, France (I.D.); Departments of Cardiology (H.S.) and Medicine (K.P.), Helsinki University, Helsinki, Finland; Hôpital Robert-Debré, Paris, France (J.-M.L.); Hôpital Necker Enfant Maladies, Paris, France (E.V.); and Molecular Cardiology, IRCCS Fondazione S. Maugeri, Pavia, Italy (S.G.P., C.N.).
Correspondence to G. Michael Vincent, MD, 324 10th Ave, Suite 127, Salt Lake City, UT 84103. E-mail g.michael.vincent{at}intermountainmail.org
Received February 11, 2008; accepted October 6, 2008.
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Abstract |
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Background— β-Blocker efficacy in long-QT syndrome type 1 is good but variably reported, and the causes of cardiac events despite β-blocker therapy have not been ascertained.
Methods and Results— This was a retrospective study of the details surrounding cardiac events in 216 genotyped long-QT syndrome type 1 patients treated with β-blocker and followed up for a median time of 10 years. Before β-blocker, cardiac events occurred in 157 patients (73%) at a median age of 9 years, with cardiac arrest (CA) in 26 (12%). QT-prolonging drugs were used by 17 patients; 9 of 17 (53%) had CA compared with 17 of 199 nonusers (8.5%; odds ratio, 12.0; 95% confidence interval, 4.1 to 35.3; P<0.001). After β-blocker, 75% were asymptomatic, and cardiac events were significantly reduced (P<0.001), with a median event count (quartile 1 to 3) per person of 0 (0 to 1). Twelve patients (5.5%) suffered CA/sudden death, but 11 of 12 (92%) were noncompliant (n=8), were on a QT-prolonging drug (n=2), or both (n=1) at the time of the event. The risk for CA/sudden death in compliant patients not taking QT-prolonging drugs was dramatically less compared with noncompliant patients on QT-prolonging drugs (odds ratio, 0.03; 95% confidence interval, 0.003 to 0.22; P=0.001). None of the 26 patients with CA before β-blocker had CA/sudden death on β-blockers.
Conclusions— β-Blockers are extremely effective in long-QT syndrome type 1 and should be administered at diagnosis and ideally before the preteen years. β-Blocker noncompliance and use of QT-prolonging drug are responsible for almost all life-threatening "β-blocker failures." β-Blockers are appropriate therapy for asymptomatic patients and those who have never had a CA or β-blocker therapy. Routine implantation of cardiac defibrillators in such patients does not appear justified.
Key Words: arrhythmia • death, sudden • heart arrest • long-QT syndrome • syncope • torsade de pointes
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Introduction |
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Beta-Blockers have long been the primary therapy for inherited long-QT syndrome (LQTS),1 but despite good, although variably reported, efficacy,2–6 a small number of cardiac arrests and sudden deaths occur.3–6 Whether these events are due to inherent limitations of β-blocker or avoidable factors is unknown. Implantable cardioverter-defibrillators (ICDs) are being used increasingly in LQTS patients, and these "failures" are used to justify implantation in patients without a cardiac arrest and even as initial therapy, including in children and teenagers in whom ICDs produce many complications7–10 and impair quality of life without always preventing sudden death.8,11,12
Editorial p 204
Clinical Perspective p 221
According to registries of ICDs in LQTS,12,13 the majority of patients receiving an ICD had not suffered a cardiac arrest, 25% to 40% had not been treated with β-blockers before implantation, and some patients were even asymptomatic.12–14 In recent reports, only a minority of LQTS patients receiving ICDs for "high-risk" status (defined as prior cardiac arrest or symptoms on β-blockers) received an appropriate ICD discharge during follow-up, indicating limited usefulness of these criteria for predicting subsequent events.14,15
Responsiveness to β-blockers varies according to genotype.3,5,16 We chose to focus our study on long-QT syndrome type 1 (LQT1) because it is the most prevalent form of LQTS and because β-blockers are most effective in LQT1. High β-blocker efficacy is predicted in LQT1 because mutations impair the IKs current and increase risk during sympathetic activation and tachycardia. Indeed, 90% of lethal events of LQT1 patients occur during physical or emotional stress.16
Our main objective was to clarify whether life-threatening cardiac events on β-blocker therapy are due to inherent limitations of these drugs or to avoidable causes. This was done by quantifying the influence of 2 potential culprits: incomplete compliance with the prescribed β-blocker regimen and the use of QT-prolonging drugs or other drugs to be avoided by LQTS patients as defined by the Arizona Center for Education and Research on Therapeutics program (http://www.qtdrugs.org).
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Methods |
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Study Population
We retrospectively evaluated 216 genotyped LQT1 patients with 105 different mutations from our 4 databases, some of which began enrollment in the early 1970s. Selection criteria included that we personally followed up the patient for LQTS, prescribed and managed the β-blocker, and followed up the patient for a minimum of 2 years after β-blocker initiation, unless the subject suffered a sudden death or cardiac arrest before 2 years of follow-up, in which case they were included. Although we prescribed and adjusted β-blockers during follow-up, other physicians prescribed various medications for different conditions.
Some of the subjects in our study were included in prior publications that reported on β-blocker effectiveness.2,3,5 However, information on β-blocker noncompliance and the use of QT-prolonging drugs was unknown and thus unreported at the time of those publications. Therefore, the present findings on β-blocker efficacy and the causes of "β-blocker failures," β-blocker noncompliance and the use of QT prolonging drugs, are completely new and previously unreported findings.
Clinical data were recorded on predesigned forms and included age, gender, QTc from the initial ECG, age at symptom onset, diagnosis, β-blocker treatment, number and type of cardiac events from birth to the time of the study, and type and dose of β-blocker used and other LQTS therapy.
Cardiac Events
Cardiac events included syncope, aborted cardiac arrest, and sudden cardiac death. The definition of cardiac arrest required the presence of resuscitation efforts (cardiopulmonary resuscitation, any responder, or shock) before any apparent sign of recovery of consciousness or spontaneous recovery from a protracted syncope with hypoxic neurological injury. Arrhythmia documentation was not required. This definition may overstate cardiac arrest prevalence because some patients with early bystander "resuscitation" might have recovered spontaneously and would otherwise have been reported to have syncope. Sudden death was defined as sudden, unexpected death without any known cause. All cardiac events that we judged to be LQTS related and occurred during the entire observation time were considered; thus, late-onset (>40 years) cardiac events, which would have been missed if the traditional LQTS time horizon from birth to 40 years of age had been followed, were included.
The number of patients with each type of cardiac event before and after β-blocker treatment is reported by the most severe symptom (sudden death, then cardiac arrest, then syncope) occurring for each patient.
Compliance With β-Blocker Therapy and QT-Prolonging Drug Use
Compliance refers to the persistence over time with the prescribed β-blocker regimen. Information on compliance and the use of any QT-prolonging drug was collected for all patients regardless of their clinical status and determined from patient records and conversations with patients, spouses, or parents, not by any objective measure (eg, plasma level assessment). These data were tabulated separately for the pre-β-blocker and post-β-blocker periods. We focused on the sudden death and cardiac arrest cases because of their practical importance. Because they were uncommon and very memorable, we could accurately determine whether each patient was on or off β-blockers and was or was not using a QT-prolonging drug at the time of each event. For syncope, this retrospective assessment was similarly accurate in those patients with only 1 to a few events. In those with larger numbers of syncope over a period of years, compliance or use of a QT-prolonging drug at the time of a particular syncope was obviously less certain. Consequently, for classification and comparison purposes, these patients were coded as noncompliant if they reported missing their β-blocker for 7 consecutive days or more per year or using a QT-prolonging drug in close proximity to the event. Eighteen patients missed taking their β-blockers for 1 to 6 days; according to the above definition of noncompliance, these 18 were categorized as compliant.
Statistical Analysis
For continuous variables, data are expressed as mean and SD; whenever the distribution was skewed, medians with the first quartile and third quartiles were reported. Comparison of these variables among groups was performed by t test or by its nonparametric equivalent. Discrete variables were presented as absolute and relative frequencies, along with binomial exact 95% confidence intervals (CIs), and compared by Fisher exact test. To compare the numbers of patients with any cardiac event and the event counts before and after β-blocker therapy was started, the McNemar test and the Wilcoxon signed-rank test were used. Incidence rates with 95% CIs were computed by dividing the number of patients with any first event by the total number of person-years. Similarly, event counts per person-year were calculated and presented as mean yearly events with exact 95% CIs based on a Poisson distribution. Number of events >30 in a given patient was counted as 30. The influence of the use of QT-prolonging drugs, compliance with β-blocker therapy, or both on the risk of experiencing cardiac arrest and arrest/sudden death before and while on therapy was determined by a logistic regression model. Odds ratios and 95% CIs were computed while controlling for demographic (gender) and clinical (baseline QTc, prior history of symptoms) characteristics of the patients.
All authors had full access to and take full responsibility for the integrity of the data. All authors have read and agree to the manuscript as written.
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Results |
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Population Characteristics
Baseline characteristics of the study population are shown in Table 1. Most (138, 64%) were female subjects who were more frequent users of QT-prolonging drugs than male subjects. Age at the time of data review ranged from 4 to 76 years, with a median age of 26 years (18 to 42 years). QT drug users were older at their first event and consequently started β-blocker therapy at a later age compared with the non-QT drug users. A pretreatment baseline ECG was available for 182 patients (84%). Mean QTc was 495±46 ms (range, 400 to 680 ms) without significant difference (P=0.29) between asymptomatic (490±48 ms) and symptomatic (498±46 ms) patients. Only 1 patient had Jervell, Lange-Nielsen syndrome; 215 had the Romano-Ward form.
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Decisions on the β-blocker dose varied by centers; dose and maximum heart rate on Holter or exercise test were the commonly used methods. The initial β-blocker drugs prescribed were propranolol (48%) and nadolol (36%), together accounting for the initial treatment of 84% of the patients. Other agents used were atenolol (9%) and metoprolol (3%), and a few patients received bisoprolol, acebutolol, or pindolol. Fifty-six patients (26%) changed to a different β-blocker, mostly (57%) from propranolol to nadolol. The final mean doses for the commonly used β-blocker were 2.2±1.1 mg/kg for propranolol and 1.7±0.79 mg/kg for nadolol.
QT-prolonging and other potentially proarrhythmic medications used by the study population encompassed almost all drug classes that should be avoided by LQTS patients, including antipsychotic and antidepressant agents, antiarrhythmics, antihistaminics, antibiotics, antifungals, antimalarials, 
-blocking agents, stimulants, and diuretics.
Pre-β-Blocker Period
None of the patients received an ICD or left cardiac sympathetic denervation in the pre-β-blocker period.
Cardiac Events
The occurrence and type of cardiac events in the pre-β-blocker period and their relationship to the use of QT-prolonging drugs are shown in Table 2. Over a median observation time from birth to start of β-blocker therapy of 12.5 years (7 to 26), 157 patients (73%) became symptomatic, with a median age at first episode of 9 years (5 to 14; mean, 13±13 years). Twenty-six patients (12%), 85% female, had at least 1 cardiac arrest; 24 of them also had syncope; 131 (61%) had syncope only. A median number of 1 event per patient (0 to 4) was observed, corresponding to a mean yearly rate of 0.19 events per patient (95% CI, 0.18 to 0.21). In this highly symptomatic population, only 6 patients (3%) had 
30 events, whereas 50 (23%) had just 1 event. In the 157 patients with symptoms, both the age at diagnosis (12 years [7 to 29 years]) and the age at the start of β-blocker therapy (15 years [9 to 29 years]) were significantly more advanced than in those without symptoms in the pre-β-blocker period (4 years [<1 to 13 years] and 7 years [<1 to 15 years], respectively; P<0.001 for both). These figures reflect the fact that some patients were diagnosed and started on β-blocker therapy following an event that occurred after 40 years of age; nonetheless, these differences remained significant also when patients with only cardiac events before 40 years of age were considered.
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QT-Prolonging Drug Use
Seventeen patients received a QT-prolonging drug, and 9 (53%; 95% CI, 28 to 77) suffered a cardiac arrest. In 3 patients, the arrest occurred after 40 years of age. In contrast, just 17 (8.5%; 95% CI, 5 to 13) of the 199 patients who used no QT-prolonging drugs had cardiac arrest (Figure, A). Thus, the use of QT-prolonging drugs was associated with a markedly increased risk of cardiac arrest compared with patients not on these drugs (unadjusted odds ratio, 12.0; 95% CI, 4.1 to 35.3; P<0.001). The magnitude and significance of this excessive risk remained unaltered after adjustment for baseline QTc (
500 versus >500 ms; Table 1); thus, QTc was not a significant contributor to the outcome. Although we could not estimate the effect of gender, it is of note that all 9 patients with cardiac arrest associated with a QT-prolonging drug were female.
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Post-β-Blocker Period
As shown in Table 3, no significant differences were observed in gender, pre-β-blocker history of symptoms, and QTc interval between the β-blocker compliant/no cardiac arrest QT-prolonging drug use group and the noncompliant/QT-prolonging drug user group. One patient had left cardiac sympathetic denervation. Three patients received an ICD during the post-β-blocker period: 1 because of an inability to tolerate a full therapeutic dose of β-blocker as a result of asthma, 1 with syncope on a low dose of β-blocker because of side effects, and 1 because of a syncopal episode while noncompliant with β-blocker. The 2 patients who had an ICD as a result of β-blocker tolerance issues had no ICD discharges during follow-up. The patient with a syncope while noncompliant had just 1 ICD discharge, an appropriate discharge during a cardiac arrest after an antidepressant overdose accompanied by hypokalemia.
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Cardiac Events
Table 2 shows the dramatic effect of β-blocker therapy on the number and types of cardiac events and their relationship with compliance and QT-prolonging drug use. Over a median observation time on β-blocker therapy of 10 years (6 to 15.5), a median number of 0 events per patient (0 to 1) occurred, corresponding to a mean yearly rate of 0.06 events per patient (95% CI, 0.05 to 0.07), as shown in Table 4, demonstrating that β-blocker therapy was associated with a significant and dramatic reduction in both the number of patients with any event and the cardiac event count. Most patients (162 of 216, 75%) had no events while on therapy. Within this group, 49 previously asymptomatic subjects remained free of events over a median follow-up time on β-blocker of 7 years (5 to 9.5 years). Their mean baseline QTc was 484±37 ms. Most of them had been diagnosed and started on β-blocker therapy in childhood, half before 7 years of age. On the other hand, 54 of 216 patients (25%) had cardiac events; 82% had experienced symptoms in the pre-β-blocker period. Their post-β-blocker symptoms began at a median of 3 years (1 to 6) after the start of therapy, and, by most severe event, 42 had syncope only, 6 had aborted cardiac arrest, and 6 had sudden death. More than half (57%) had just 1 event, and none had 30 events. Among the 12 with cardiac arrest/sudden death, 1 had experienced cardiac arrest before β-blockers, and for 9 (75%), arrest or sudden death was the first event while on therapy. Importantly, none of the 26 patients who had a pre-β-blocker cardiac arrest had sudden death while taking β-blockers, and none had received an ICD. Compared with the 49 lifelong-asymptomatic patients (mean baseline QTc, 484±37 ms), no significant difference was observed in those who had syncope only (499±52 ms) or life-threatening events (499±63 ms).
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β-Blocker Compliance and QT-Prolonging Drug Use
Eleven of the 12 patients (92%) with cardiac arrest or sudden death were noncompliant (n=8), on a QT-prolonging drug (n=2), or both (n=1) at the time of the event. The only sudden death in a β-blocker-compliant patient not taking QT-prolonging drugs occurred as a first event in the only patient in the series with Jervell, Lange-Nielsen syndrome, known to be a more severe form of LQT1 with a higher incidence of life-threatening events.1,17 He was a previously asymptomatic 9-year-old boy reported as fully compliant on 1.0 mg · kg–1 · d–1 atenolol, perhaps a small dose for Jervell, Lange-Nielsen syndrome, and a potentially less effective β-blocker.4 He had been started on propranolol shortly after birth and was switched to atenolol 3 years before his death. Among the 35 noncompliant patients, all 8 fatal or near-fatal events occurred after long-standing withdrawal of β-blocker therapy (21 days) despite a β-blocker prescription at adequate doses. Among the 18 patients who missed 1 to 6 consecutive days (median, 2 days) of β-blocker per year and by our definition were classified as compliant, none had cardiac arrest or sudden death.
Panel B in the Figure shows that compliance with β-blocker and no use of QT- prolonging drugs dramatically reduce the probability of suffering cardiac arrest or sudden death from 27.5% (95% CI, 15 to 44) to 0.6% (95% CI, 0.014 to 3; P<0.001) in noncompliant patients on QT-prolonging drugs. When demographic and clinical characteristics are controlled for, a striking reduction in risk was observed (odds ratio, 0.03; 95% CI, 0.003 to 0.22; P=0.001); neither the pre-β-blocker QTc interval (500 versus >500 ms) nor a history of previous symptoms or gender was significantly associated with the risk of arrest or sudden death during therapy, although all 3 patients with life-threatening events occurring on QT-prolonging drugs were female. Similar results were observed when the analysis was limited to noncompliant patients.
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Discussion |
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This is the first study to address the critical question of whether cardiac arrests and sudden deaths among LQT1 patients treated with β-blockers are due to incomplete efficacy of the therapy or to the avoidable causes of noncompliance or the use of drugs that should be avoided by LQTS patients.
The previous studies that have called attention to β-blocker limitations3–6 used intention-to-treat analysis, the gold standard for assessing the effectiveness of therapy in clinical trials. However, for the practicing clinician and patients dealing with a disease associated with sudden and life-threatening events, what really matters is knowing what can be expected if the prescribed therapeutic regimen is carefully and rigorously followed. Our findings show that the reasons for β-blocker failure are β-blocker noncompliance and the concurrent administration of QT-prolonging drugs, the latter involving almost exclusively female patients known to be at higher risk than male patients for cardiac events while on QT-prolonging drug.18–20
Only 1 patient had sudden death while reportedly compliant and on no QT-prolonging drug, a striking reduction of >90% in the risk for life-threatening events compared with patients who were prescribed β-blockers but were noncompliant, taking QT-prolonging drugs, or both. This is a powerful reminder of the importance of following the prescribed β-blocker therapy and avoiding QT-prolonging drugs.
Study Strengths and Limitations
The major strength of this study was our ability to identify noncompliant patients and those receiving QT-prolonging drugs and to relate these findings to cardiac events. This was made possible by the long-standing personal relationships we had with most patients and families. Limitations included the small sample size of the comparison groups, and the relatively small number of events limited the power of the multivariate analysis in evaluating the predictive value of potential confounding factors. A further potential limitation was error in patient recollection about compliance with therapy21,22 and the association of events with the use of QT-prolonging drugs or use of QT-prolonging drugs that were not associated with events. However, the high clinical severity and unequivocal classification of the prespecified end points of cardiac arrest and sudden death make these events quite memorable, minimizing this concern, as does the observation that the difference in the incidence of cardiac arrest and sudden death between the 2 groups is so large that errors of recollection by a few of the patients would not alter the validity of the findings.
We suspect the prevalence of these 2 causes of β-blocker failure was similar in prior studies,3–6 but an evaluation of their influence on events in the other LQTS genotypes is warranted.
Implications
The study provides major recommendations for improving the care of LQT1 patients. The first is to eliminate β-blocker noncompliance and the use of QT-prolonging drugs. The present data clearly show that LQT1 patients who take their β-blocker as prescribed and use no QT-prolonging drug are at extremely low risk for life-threatening events. If an event does occur while a patients is on β-blocker, physicians should question noncompliance or the use of a QT-prolonging drug and should confirm and correct these risk behaviors before recommending alternative therapy if possible. The second is to reexamine the risk-to-benefit relationships of β-blocker therapy versus ICDs using the high efficacy of β-blockers demonstrated in this study in the β-blocker benefit analysis and the complications associated with ICDs,10 their costs, and their impact on quality of life in the ICD risk analysis. Our present data indicate that β-blockers are the appropriate initial therapy for most asymptomatic LQT1 patients and those with a syncopal episode off β-blocker—in other words, those who have never had β-blocker therapy or cardiac arrest. In fact, our data show that even patients who had cardiac arrest off β-blocker have a very low incidence (none in our series of 26 patients) of repeat cardiac arrest or sudden death while taking their β-blocker and avoiding QT-prolonging drugs. Those with syncope despite β-blocker should be carefully informed about the risks and outcomes with adjustments to the β-blocker dose and formulation, ICD implantation, and left cardiac sympathetic denervation.23 Those who demonstrate or voice a high likelihood of β-blocker noncompliance should be considered for ICD or left cardiac sympathetic denervation intervention. Third is to emphasize early and presymptomatic diagnosis to provide prophylactic β-blocker therapy during the high-risk preteen through teenage years. Because it is not possible to accurately predict risk in asymptomatic children and young persons, all those without contraindications should be administered prophylactic β-blockers that are regularly adjusted for growth and any LQTS symptoms.
Education is the primary tool to improve β-blocker compliance and the avoidance of QT-prolonging drugs. The concerns about taking β-blockers by our patients included loss of physical prowess, fatigue, weight gain, depression, and aggravation of preexistent asthma. In addition, many patients on treatment remain or become asymptomatic, which may generate the false impression of a "cure," and a cavalier attitude may result in the frequent skipping or stopping of medication. To counter these possibilities, the high efficacy of β-blockers taken regularly and the high risk for arrest or sudden death among noncompliant patients, those using QT-prolonging drugs, or those who are noncompliant and using QT-prolonging drugs should be discussed regularly between physicians, patients, and families. In addition, once-daily medication regimens work best for improving compliance,21,22 and nadolol and long-acting propranolol were the most frequent β-blockers used. Furthermore, beginning β-blocker therapy with small doses and using small increments minimize side effects and allow gradual increases to the full β-blocker doses without significant side effects in most patients. The effective β-blocker dose varies by patient and is influenced by age, body size, drug metabolism, and drug interactions. Thus, no standard dose works for everyone. For nadolol, the range in this study was 0.5 to 3.5 mg/kg (mean, 1.7±0.79 mg/kg). These doses are similar to what has been reported in the literature and appear to be effective in most compliant patients. After the initial target dose has been achieved, it may be appropriate to evaluate efficacy by demonstrating that the characteristic abnormal prolongation of QTc after exercise24–27 has been minimized or corrected,28 showing that the maximum heart rate on exercise test or Holter has been decreased,2 and achieving symptom alleviation, with the dose increased as needed. As for QT-prolonging drugs, patients should take a regularly updated (www.qtdrugs.org) list of these drugs to each medical appointment for review with their physician(s) whenever any medication is recommended. No LQTS patient should receive QT-prolonging drugs unless absolutely necessary. Non-QT-prolonging alternatives should be used whenever available. When a QT-prolonging drug is thought to be necessary, the patient’s event history, the arrhythmogenic potential of the specific drug, and whether the patient is regularly taking an appropriate dose of a β-blocker should all be considered. In some instances, it may be appropriate to begin the drug in a monitored hospital setting unless the patient has an ICD in place. Particular caution should be exercised in female patients. Women in general are sensitive to these drugs and are more likely to experience the adverse arrhythmogenic effects,18–20 and they appear to receive more QT-prolonging drugs than male patients.29–31 The higher risk for females was evident in our study; of the 17 patients who took a QT-prolonging drug in the pre-β-blocker period, 9 had a cardiac arrest, and all were female.
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Acknowledgments |
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Sources of Funding
This work was supported in part by LDS Hospital-Deseret Foundation grants.
Disclosures
None.
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References |
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CLINICAL PERSPECTIVE
β-Blocker noncompliance, the use of QT-prolonging drugs, or both in combination are responsible for almost all cardiac events while patients are "on" β-blockers, rather than "β-blocker failures." Being β-blocker compliant and receiving no QT-prolonging drugs dramatically reduce cardiac events to a mean yearly rate of 0.06 (range, 0.05 to 0.07) for cardiac arrest or sudden death. This has equally important ramifications for the selection of therapy for long-QT syndrome type 1 patients. Being so efficacious, β-blockers should be the initial treatment for all asymptomatic patients at diagnosis, those with remote symptoms and those with syncope (and possible even a cardiac arrest) who were not on a β-blocker at the time of the event. Furthermore, early diagnosis and treatment, before the high-risk time of preteen through the 20s, is very important for preventing cardiac events, particularly cardiac arrest and sudden death. Physicians should carefully discuss the importance of full compliance with β-blockers and the avoidance of any QT-prolonging drugs at the time of first contact and indicate the danger of not adhering to these recommendations. This discussion should be repeated regularly during follow-up. Patients who will not or cannot take β-blockers may be candidates for implantable converter-defibrillators or left stellectomy therapy.
Circulation 2009 119: 201-203.
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