***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Background —The congenital long-QT syndrome ( LQTS ) is caused by mutations on several genes , all of which encode cardiac ion channels . The progressive underst and ing 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 & bgr;-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 BACKGROUND beta-blockers are routinely prescribed in congenital long-QT syndrome ( LQTS ) , but the effectiveness and limitations of beta-blockers in this disorder have not been evaluated . METHODS AND RESULTS The study population comprised 869 LQTS patients treated with beta-blockers .  Effectiveness of beta-blockers was analyzed during matched periods before and after starting beta-blocker therapy , and by survivorship methods to determine factors associated with cardiac events while on prescribed beta-blockers . After initiation of beta-blockers , there was a significant ( P<0.001 ) reduction in the rate of cardiac events in prob and s ( 0.97+/-1.42 to 0.31+/-0.86 events per year ) and in affected family members ( 0 . 26+/-0.84 to 0.15+/-0.69 events per year ) during 5-year matched periods . On-therapy survivorship analyses revealed that patients with cardiac symptoms before beta-blockers ( n=598 ) had a hazard ratio of 5.8 ( 95 % CI , 3.7 to 9.1 ) for recurrent cardiac events ( syncope , aborted cardiac arrest , or death ) during beta-blocker therapy compared with asymptomatic patients ; 32 % of these symptomatic patients will have another cardiac event within 5 years while on prescribed beta-blockers . Patients with a history of aborted cardiac arrest before starting beta-blockers ( n=113 ) had a hazard ratio of 12.9 ( 95 % CI , 4.7 to 35.5 ) for aborted cardiac arrest or death while on prescribed beta-blockers compared with asymptomatic patients ; 14 % of these patients will have another arrest ( aborted or fatal ) within 5 years on beta-blockers . CONCLUSIONS beta-blockers are associated with a significant reduction in cardiac events in LQTS patients . However , syncope , aborted cardiac arrest , and LQTS-related death continue to occur while patients are on prescribed beta-blockers , particularly in those who were symptomatic before starting this therapy BACKGROUND Eight r and omized trials have evaluated whether the prophylactic use of an implantable cardioverter-defibrillator ( ICD ) improves survival  among patients who are at risk for sudden death due to left ventricular systolic dysfunction but who have not had a life-threatening ventricular arrhythmia . We assessed the  cost-effectiveness  of the ICD in the population s represented in these primary -prevention trials . METHODS We developed a Markov model of the cost , quality of life , survival , and incremental cost-effectiveness of the prophylactic implantation of an ICD , as compared with control therapy , among patients with survival and mortality rates similar to those in each of the clinical trials . We modeled the efficacy of the ICD as a reduction in the relative risk of death on the basis of the hazard ratios reported in the individual clinical trials . RESULTS Use of the ICD increased lifetime costs in every trial . Two trials -- the Coronary Artery Bypass Graft ( CABG ) Patch Trial and the Defibrillator in Acute Myocardial Infa rct ion Trial (DINAMIT)--found that the prophylactic implantation of an ICD did not reduce the risk of death and thus was both more expensive and less effective than control therapy . For the other six trials -- the Multicenter Automatic Defibrillator Implantation Trial ( MADIT ) I , MADIT II , the Multicenter Unsustained Tachycardia Trial ( MUSTT ) , the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation ( DEFINITE ) trial , the Comparison of Medical Therapy , Pacing , and Defibrillation in Heart Failure ( COMPANION ) trial , and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)--the use of an ICD was projected to add between 1.01 and 2.99 quality -adjusted life-years ( QALY ) and between 68,300 dollars and 101,500 dollars in cost . Using base-case assumptions , we found that the cost-effectiveness of the ICD as compared with control therapy in these six population s ranged from 34,000 dollars to 70,200 dollars per QALY gained . Sensitivity analyses showed that this cost-effectiveness ratio would remain below 100,000 dollars per QALY as long as the ICD reduced mortality for seven or more years . CONCLUSIONS Prophylactic implantation of an ICD has a cost-effectiveness ratio below 100,000 dollars per QALY gained in population s in which a significant device-related reduction in mortality has been demonstrated INTRODUCTION Implantable cardioverter defibrillators ( ICDs ) are increasingly being used in high-risk long QT syndrome ( LQTS ) patients , but there are limited data regarding clinical experience with this therapeutic modality . The aim of this study is to describe the clinical characteristics of 125 LQTS patients treated with ICDs compared with LQTS patients having similar risk indications who were not treated with ICDs .  Among 125 LQTS patients with ICDs , there were 54 cardiac arrest survivors , 19 patients who had ICDs implanted due to recurrent syncope despite beta-blocker therapy , and 52 patients with ICDs implanted due to other reasons , including syncope and LQTS-related sudden death in a close family member . Patients with cardiac arrest and those with recurrent syncope despite beta-blocker therapy ( n = 73 ) were compared to 161 LQTS patients who had similar indications ( 89 cardiac arrest and 72 recurrent syncope despite beta-blocker therapy ) but did not receive ICDs .  Total mortality was the endpoint of the analysis . There was 1 ( 1.3 % ) death in 73 ICD patients followed an average of 3 years , whereas there were 26 deaths ( 16 % ) in non-ICD patients during mean 8-year follow-up ( P = 0.07 from log rank test from Kaplan-Meier curves ) . CONCLUSION ICDs provide an important therapeutic option to prevent sudden arrhythmic death in high-risk LQTS patients . A long-term prospect i ve study is needed to determine the benefit of this therapeutic modality in LQTS patients Background The Long QT Syndrome ( LQTS ) is an infrequently occurring familial disorder in which affected individuals have electrocardiographic QT interval prolongation and a propensity to veiltricular tachyarrhythmic syncope and sudden death . We prospect ively investigated the clinical characteristics and the long-term course of 3,343 individuals from 328 families in which one or more members were identified as affected with LQTS ( QTc > 0.44 sec½ ) . Methods and Results The first member of a family to be identified with LQTS , the prob and , was usually brought to medical attention because of a syncopal episode during childhood or teenage years . Prob and s ( n = 328 ) were younger at first contact ( age 21 ± 15 years ) , more likely to be female ( 69%o ) , and had a higher frequency of preenroilment syncope or cardiac arrest with resuscitation ( 80 % ) , congenital deafness ( 7 % ) , a resting heart rate less than 60 beats/min ( 31 % ) , QTc ≥ 0.50 sec½ ( 52 % ) , and a history of ventricular tachyarrhythmia ( 47 % ) than other affected ( n = 688 ) and unaffected ( n = 1,004 ) family members . Arrhythmogenic syncope often occurred in association with acute physical , emotional , or auditory arousal . The syncopal episodes were frequently misinterpreted as a seizure disorder . By age 12 years , 50 % of the prob and s had experienced at least one syncopal episode or death . The rates of postenrollment syncope ( one or more episodes ) and probable LQTS-related death ( before age 50 years ) for prob and s ( n = 235 ; average follow-up 54 months per patient ) were 5.0 % per year and 0.9 % per year , respectively ; these event rates were considerably higher than those observed among affected and unaffected family members . Conclusions Among 232 prob and s and 1,264 family members with prospect i ve follow-up , three factors made significant independent contributions to the risk of subsequent syncope or probable LQTS-related death before age 50 years , whichever occurred first ( Cox hazard ratio ; 95 % confidence limits ) : 1 ) QTc ( 1.052 ; 1.017 , 1.088 ) , 2 ) history of cardiac event ( 3.1 ; 1.3 , 7.2 ) , and 3 ) heart rate ( 1.017 ; 1.004 , 1.031 ) . The findings from this prospect i ve longitudinal study highlight the clinical features , risk factors , and course of LQTS AIMS To evaluate the effect of beta-blockers in children with long QT syndrome ( LQTS ) we review ed the outcome of 122 patients ( pts ) . METHODS LQTS was diagnosed in 24 neonates and in 98 pts aged 0.5 - 15 years . Diagnosis was made because of syncope in 51 pts , bradycardia in 10 neonates and family history in 61 pts . The longest QTc ranged from 400 to 700 ms . Thirteen pts had 2:1 atrioventricular block and /or ventricular arrhythmias . Screening for mutations was performed in 118 pts . All children were treated with beta-blockers , annually checked by exercise testing and /or 24 h ECG monitoring . RESULTS Four pts died . Survivors were followed-up for 1 - 18 years ( 7.5 + /- 5.3 years ) . Five neonates and 3 older pts received a  prophylactic pacemaker  ( 1 death ) so that only 111/122 pts survived and were followed-up with beta-blockers alone . None of them died and five experienced a non-fatal cardiac event . There was no cardiac event among pts who were diagnosed because of familial history and among symptomatic KCNQ1 pts who were effectively treated with beta-blockers . CONCLUSION The outcome of children with LQTS under effective beta-blockers is favourable . Persisting arrhythmia or symptoms despite beta-blockers should aim at identifying other genotypes than KCNQ1 
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Among them , genetic testing in the early detection of LQTS was cost-effective compared with no testing in symptomatic cases and not cost-effective when compared with watchful waiting in asymptomatic first-degree relatives of patients with established LQTS although it reached cost-effectiveness in higher risk subgroups , whereas ECG testing in neonates was highly cost-effective when compared with any screening strategy .
LQTS profiling and patients ' stratification have the potential to improve the disease management .