Clinical Aspects of Type 3 Long-QT Syndrome: An International Multicenter Study.

Background: Risk stratification in patients with type 3 long-QT syndrome (LQT3) by clinical and genetic characteristics and effectiveness of β-blocker therapy has not been studied previously in a large LQT3 population.

Methods: The study population included 406 LQT3 patients with 51 sodium channel mutations; 391 patients were known to be event free during the first year of life and were the focus of our study. Clinical, electrocardiographic, and genetic parameters were acquired for patients from 7 participating LQT3 registries.

New Mexico Community Health Councils: Documenting Contributions to Systems Changes.

Context: Coalition research has shifted from delineating structures and processes to identifying intermediate, systems changes (e.g., changes in policies) that contribute to longterm community health improvement.

Risk for life-threatening cardiac events in patients with genotype-confirmed long-QT syndrome and normal-range corrected QT intervals.

Objectives: This study was designed to assess the clinical course and to identify risk factors for life-threatening events in patients with long-QT syndrome (LQTS) with normal corrected QT (QTc) intervals.

Background: Current data regarding the outcome of patients with concealed LQTS are limited.

Methods: Clinical and genetic risk factors for aborted cardiac arrest (ACA) or sudden cardiac death (SCD) from birth through age 40 years were examined in 3,386 genotyped subjects from 7 multinational LQTS registries, categorized as LQTS with normal-range QTc (≤ 440 ms [n = 469]), LQTS with prolonged QTc interval (> 440 ms [n = 1,392]), and unaffected family members (genotyped negative with ≤ 440 ms [n = 1,525]).

Relation between renal function and response to cardiac resynchronization therapy in Multicenter Automatic Defibrillator Implantation Trial--Cardiac Resynchronization Therapy (MADIT-CRT).

Background: Cardiorenal interactions have been shown to affect outcome in heart failure patients but were not related to response to cardiac resynchronization therapy (CRT).

Objective: The purpose of this study was to test our hypothesis that assessment of markers of prerenal failure may help identify mildly symptomatic HF patients with diminished effective circulating blood volume who will benefit from CRT.

Methods: The benefit of CRT with a defibrillator (CRT-D) as compared with defibrillator-only therapy in reducing the risk of HF or death was assessed by renal function parameters (including serum creatinine [SCr], blood urea nitrogen [BUN], and the ratio of BUN to SCr [BUN:SCr], dichotomized at median values and into approximate quartiles) among 1,803 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy.

Risk factors for recurrent heart failure events in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II).

Unlabelled: Risk Factors for Recurrent Heart Failure.

Background: This study was designed to identify risk factors for recurrent heart failure (HF) events in patients with ischemic left ventricular dysfunction enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II).

Methods And Results: The Prentice, Williams, and Peterson (PWP) statistical model was utilized to identify and compare risk factors for 1 or ≥ 2 HF hospitalizations among 1,218 patients with ischemic left ventricular dysfunction enrolled in the MADIT-II trial.

Genotype-phenotype aspects of type 2 long QT syndrome.

Objectives: The purpose of this study was to investigate the effect of location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in type 2 long QT syndrome (LQTS).

Background: Previous studies were limited by population size in their ability to examine phenotypic effect of location, type, and topology.

Methods: Study subjects included 858 type 2 LQTS patients with 162 different KCNH2 mutations in 213 proband-identified families.

Phenotypic variability in Caucasian and Japanese patients with matched LQT1 mutations.

Background: Ethnic differences may affect the phenotypic expression of genetic disorders. However, data regarding the effect of ethnicity on outcome in patients with genetic cardiac disorders are limited. We compared the clinical course of Caucasian and Japanese long QT type-1 (LQT1) patients who were matched for mutations in the KCNQ1 gene.

Risk factors for aborted cardiac arrest and sudden cardiac death in children with the congenital long-QT syndrome.

Background: The congenital long-QT syndrome (LQTS) is an important cause of sudden cardiac death in children without structural heart disease. However, specific risk factors for life-threatening cardiac events in children with this genetic disorder have not been identified.

Methods And Results: Cox proportional-hazards regression modeling was used to identify risk factors for aborted cardiac arrest or sudden cardiac death in 3015 LQTS children from the International LQTS Registry who were followed up from 1 through 12 years of age.

Long-QT syndrome after age 40.

Background: Previous studies that assessed the risk of life-threatening cardiac events in patients with congenital long-QT syndrome (LQTS) have focused mainly on the first 4 decades of life, whereas the clinical course of this inherited cardiac disorder in the older population has not been studied.

Methods And Results: The risk of aborted cardiac arrest or death from age 41 though 75 years was assessed in 2759 subjects from the International LQTS Registry, categorized into electrocardiographically affected (corrected QT interval [QTc] > or = 470 ms), borderline (QTc 440 to 469 ms), and unaffected (QTc < 440 ms) subgroups. The affected versus unaffected adjusted hazard ratio for aborted cardiac arrest or death was 2.

Inappropriate implantable cardioverter-defibrillator shocks in MADIT II: frequency, mechanisms, predictors, and survival impact.

Objectives: This study sought to identify the incidence and outcome related to inappropriate implantable cardioverter-defibrillator (ICD) shocks, that is, those for nonventricular arrhythmias.

Background: The MADIT (Multicenter Automatic Defibrillator Implantation Trial) II showed that prophylactic ICD implantation improves survival in post-myocardial infarction patients with reduced ejection fraction. Inappropriate ICD shocks are common adverse consequences that may impair quality of life.

Mechanisms of ventricular fibrillation initiation in MADIT II patients with implantable cardioverter defibrillators.

Background: The availability of stored intracardiac electrograms from implantable defibrillators (ICDs) has facilitated the study of the mechanisms of ventricular tachyarrhythmia onset. This study aimed to determine the patterns of initiation of ventricular fibrillation (VF) in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II patients along with associated electrocardiogram (ECG) parameters and clinical characteristics.

Methods: Examination of stored electrograms enabled us to evaluate the rhythm preceding each episode of VF and to calculate (intracardiac) ECG parameters including QT, QT peak (QTp), coupling interval, and prematurity index.

Risk stratification for primary implantation of a cardioverter-defibrillator in patients with ischemic left ventricular dysfunction.

Objectives: The study was designed to develop a simple risk stratification score for primary therapy with an implantable cardioverter-defibrillator (ICD).

Background: Current guidelines recommend primary ICD therapy in patients with a low ejection fraction (EF). However, the benefit of the ICD in the low EF population may not be uniform.

Ventricular arrhythmia storms in postinfarction patients with implantable defibrillators for primary prevention indications: a MADIT-II substudy.

Background: Much of prognostic implications of ventricular arrhythmia storms remain unclear.

Objective: We evaluated the risk associated with electrical storm in patients with defibrillators in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) study.

Methods: Electrical storm was defined as > or =3 episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) in 24 hours.

Improved survival associated with prophylactic implantable defibrillators in elderly patients with prior myocardial infarction and depressed ventricular function: a MADIT-II substudy.

Introduction: We aim to evaluate the mortality benefit from defibrillator therapy in eligible elderly patients. Effective primary prevention of sudden cardiac death with implantable cardioverter defibrillators is well demonstrated in patients with coronary disease and depressed ventricular function.

Methods And Results: Among 1,232 patients enrolled with prior infarct and left ventricular ejection fraction < or = 0.

Clinical aspects of type-1 long-QT syndrome by location, coding type, and biophysical function of mutations involving the KCNQ1 gene.

Background: Type-1 long-QT syndrome (LQTS) is caused by loss-of-function mutations in the KCNQ1-encoded I(Ks) cardiac potassium channel. We evaluated the effect of location, coding type, and biophysical function of KCNQ1 mutations on the clinical phenotype of this disorder.

Methods And Results: We investigated the clinical course in 600 patients with 77 different KCNQ1 mutations in 101 proband-identified families derived from the US portion of the International LQTS Registry (n=425), the Netherlands' LQTS Registry (n=93), and the Japanese LQTS Registry (n=82).

Inverse relationship of blood pressure levels to sudden cardiac mortality and benefit of the implantable cardioverter-defibrillator in patients with ischemic left ventricular dysfunction.

Objectives: This study was designed to evaluate the relationship among blood pressure (BP) levels, risk of sudden cardiac death (SCD), and benefit of the implantable cardioverter-defibrillator (ICD) in patients with ischemic left ventricular (LV) dysfunction.

Background: Low BP has been shown to be associated with increased mortality in patients with LV dysfunction and heart failure. We hypothesized that increasing BP levels are associated with a reduction in the risk of SCD in this population, thereby limiting ICD efficacy in a lower-risk subset.

Long QT syndrome and pregnancy.

Objectives: This study was designed to investigate the clinical course of women with long QT syndrome (LQTS) throughout their potential childbearing years.

Background: Only limited data exist regarding the risks associated with pregnancy in women with LQTS.

Methods: The risk of experiencing an adverse cardiac event, including syncope, aborted cardiac arrest, and sudden death, during and after pregnancy was analyzed for women who had their first birth from 1980 to 2003 (n = 391).

Physical functioning and mental well-being in association with health outcome in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial II.

Aims: The association of psychosocial and physical factors with health outcome in patients with congestive heart failure (CHF) has not been fully explored. The aim of this study was to assess the physical and mental health in relationship to health outcome in post-infarction patients with advanced left ventricular dysfunction.

Methods And Results: A total of 1058 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT II) completed the Medical Outcome Trust Short Form (SF-12) at baseline.

Corrected QT variability in serial electrocardiograms in long QT syndrome: the importance of the maximum corrected QT for risk stratification.

Objectives: We evaluated the incremental prognostic information provided by multiple corrected QT (QTc) measurements on serial electrocardiograms (ECGs) in patients with the inherited long QT syndrome (LQTS).

Background: A baseline QTc of > or =500 ms has been shown to be associated with increased risk of cardiac events among LQTS patients. However, the value of QTc measurements on follow-up ECGs in risk assessment has not been determined.

Relations among renal function, risk of sudden cardiac death, and benefit of the implanted cardiac defibrillator in patients with ischemic left ventricular dysfunction.

Implanted cardioverter defibrillator therapy has been shown to be associated with a significant reduction in the risk of sudden cardiac death (SCD) in patients with ischemic left ventricular dysfunction. However, data on the relation between renal function and SCD in this population are limited, and the effect of renal dysfunction on the implanted cardioverter defibrillator benefit has not been determined. We performed a retrospective analysis of the outcome associated with renal dysfunction, as determined by the estimated glomerular filtration rate (eGFR), in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial-II.

Causes and consequences of heart failure after prophylactic implantation of a defibrillator in the multicenter automatic defibrillator implantation trial II.

Background: Implantable cardioverter-defibrillator (ICD) therapy may be associated with an increased risk for heart failure (HF). The present study evaluated the frequency, causes, and consequences of HF after ICD implantation.

Methods And Results: We performed a retrospective analysis of the clinical factors and outcomes associated with postenrollment HF events in 1218 patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial II.

Cigarette smoking and the risk of supraventricular and ventricular tachyarrhythmias in high-risk cardiac patients with implantable cardioverter defibrillators.

Introduction: Nicotine elevates serum catecholamine concentration and is therefore potentially arrhythmogenic. However, the effect of cigarette smoking on arrhythmic risk in coronary heart disease patients is not well established.

Methods And Results: The risk of appropriate and inappropriate defibrillator therapy by smoking status was analyzed in 717 patients who received an implantable cardioverter defibrillator (ICD) in the Multicenter Automatic Defibrillator Implantation Trial-II.

The cost effectiveness of implantable cardioverter-defibrillators: results from the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

Objectives: We sought to evaluate the cost implications of the implantable cardioverter-defibrillator (ICD), using utilization, cost, and survival data from the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

Background: This trial showed that prophylactic implantation of a defibrillator reduces the rate of mortality in patients who experienced a previous myocardial infarction and low left ventricular ejection fraction. Given the size of the eligible population, the cost effectiveness of the ICD has substantial implications.

Time dependence of defibrillator benefit after coronary revascularization in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

Objectives: The study was designed to assess the effect of elapsed time from coronary revascularization (CR) on the benefit of the implantable cardioverter-defibrillator (ICD) and the risk of sudden cardiac death (SCD) in patients with ischemic left ventricular dysfunction.

Background: The ICD improves survival in appropriately selected high-risk cardiac patients by 30% to 54%. However, in the Coronary Artery Bypass Graft (CABG)-Patch trial no evidence of improved survival was shown among a similar population of patients in whom an ICD was implanted prophylactically at the time of elective CABG.

Reduction in ventricular tachyarrhythmias with statins in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

Objectives: We evaluated whether statins have anti-arrhythmic effects by exploring the association of statin use with appropriate implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia/ventricular fibrillation (VT/VF) in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II.

Background: A few studies have suggested that lipid-lowering drugs may have anti-arrhythmic effects in patients with coronary artery disease.

Methods: Patients receiving an ICD (n = 654; U.