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Background: Mutations in genes encoding ion channels or sarcomeric proteins are an important cause of hereditary cardiac disease. However, the severity of the resultant disease varies considerably even among those with an identical mutation. Such clinical variation is often thought to be explained largely by differences in genetic background or 'modifier genes'. We aimed to test the prediction that identical genetic backgrounds result in largely similar clinical expression of a cardiac disease causing mutation, by studying the clinical expression of mutations causing cardiac disease in monozygotic twins. Methods: We compared first available clinical information on 46 monozygotic twin pairs and 59 control pairs that had either a hereditary cardiomyopathy or channelopathy. Results: Despite limited power of this study, we found significant heritability for corrected QT interval (QTc) in long QT syndrome (LQTS). We could not detect significant heritability for structural traits, but found a significant environmental effect on thickness of the interventricular septum in hypertrophic cardiomyopathy. Conclusions: Our study confirms previously found robust heritability for electrical traits like QTc in LQTS, and adds information on low or lacking heritability for structural traits in heritable cardiomyopathies. This may steer the search for genetic modifiers in heritable cardiac disease.
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AIMS: Despite our prior report suggesting heart failure (HF) risk reduction from cardiac resynchronization therapy with defibrillator (CRT-D) in mild HF patients with higher left ventricular ejection fraction (LVEF > 30%), data on mortality benefit in this cohort are lacking. We aimed to assess long-term mortality benefit from CRT-D in mild HF patients by LVEF > 30%. METHODS AND RESULTS: Among 1274 patients with mild HF and left bundle branch block enrolled in MADIT-CRT, we analysed long-term effects of CRT-D vs. implantable cardioverter defibrillator (ICD) therapy only, and reverse remodelling to CRT-D (left ventricular end-systolic volume percent change ≥ median at 1 year), on all-cause mortality and HF for the LVEF ≤ 30% and LVEF > 30 subgroups using Kaplan-Meier and Cox analyses. During long-term follow-up, CRT-D vs. ICD was associated with reduction in all-cause mortality in both patients with LVEF > 30% and LVEF ≤ 30% [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.25-0.85, P = 0.036 vs. HR 0.69, 95% CI 0.49-0.98, P = 0.013, interaction P = 0.261]. The efficacy of CRT-D vs. ICD only to reduce HF was similar in those with LVEF above and below 30% (HR 0.36, 95% CI 0.35-0.61, P < 0.001 vs. HR 0.46, 95% CI 0.35-0.61, P < 0.001; interaction P = 0.342). Patients with CRT-D-induced reverse remodelling had significant mortality reduction when compared to ICD, with either LVEF > 30% or LVEF ≤ 30% (HR 0.17 and 0.39), but no mortality benefit was seen in patients with less reverse remodelling. HF events, however, were reduced in both CRT-D-induced high and low reverse remodelling vs. ICD only, in both LVEF subgroups. CONCLUSIONS: In MADIT-CRT, left bundle branch block patients with higher LVEF (> 30%) derive long-term mortality benefit from CRT-D when exhibiting significant reverse remodelling. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID NCT00180271, NCT01294449, and NCT02060110.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Efeitos Adversos de Longa Duração , Volume Sistólico , Remodelação Ventricular , Idoso , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/etiologia , Terapia de Ressincronização Cardíaca/métodos , Terapia de Ressincronização Cardíaca/estatística & dados numéricos , Desfibriladores Implantáveis , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Humanos , Estimativa de Kaplan-Meier , Efeitos Adversos de Longa Duração/etiologia , Efeitos Adversos de Longa Duração/mortalidade , Efeitos Adversos de Longa Duração/patologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
AIMS: Prospective data regarding the role of implantable cardioverter-defibrillator (ICD) for the primary prevention of sudden cardiac death in patients with long QT syndrome (LQTS) is scarce. Herein, we explore the prospective Rochester LQTS ICD registry to assess the risk for appropriate shock in primary prevention in a real-world setting. METHODS AND RESULTS: We studied 212 LQTS patients that had ICD implantation for primary prevention. Best-subsets proportional-hazards regression analysis was used to identify clinical variables that were associated with the first appropriate shock. Conditional models of Prentice, Williams, and Peterson were utilized for the analysis of recurrent appropriate shocks. During a median follow-up of 9.2 ± 4.9 years, there were 42 patients who experienced at least one appropriate shock and the cumulative probability of appropriate shock at 8 years was 22%. QTc ≥ 550 ms [hazard ratio (HR) 3.94, confidence interval (CI) 2.08-7.46; P < 0.001) and prior syncope on ß-blockers (HR 1.92, CI 1.01-3.65; P = 0.047) were associated with increased risk of appropriate shock. History of syncope while on ß-blocker treatment (HR 1.87, CI 1.28-2.72; P = 0.001), QTc 500-549 ms (HR 1.68, CI 1.10-2.81; P = 0.048), and QTc ≥ 550 ms (HR 3.66, CI 2.34-5.72; P < 0.001) were associated with increased risk for recurrent appropriate shocks, while ß-blockers were not protective (HR 1.03, CI 0.63-1.68, P = 0.917). LQT2 (HR 2.10, CI 1.22-3.61; P = 0.008) and multiple mutations (HR 2.87, CI 1.49-5.53; P = 0.002) were associated with higher risk for recurrent shocks as compared with LQT1. CONCLUSION: In this prospective ICD registry, we identified clinical and genetic variables that were associated appropriate shock risk. These data can be used for risk stratification in high-risk patients evaluated for primary prevention with ICD.
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Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Síndrome do QT Longo/terapia , Prevenção Primária/instrumentação , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Antiarrítmicos/uso terapêutico , Criança , Pré-Escolar , Morte Súbita Cardíaca/etiologia , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Síndrome do QT Longo/genética , Síndrome do QT Longo/mortalidade , Síndrome do QT Longo/fisiopatologia , Masculino , Minnesota , Mutação , Falha de Prótese , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVES: The authors aimed to evaluate the association of left ventricular (LV) lead location and long-term outcomes in MADIT-CRT (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy). BACKGROUND: There is limited data on the association of lead location with long-term clinical outcomes in patients with cardiac resynchronization therapy with defibrillator (CRT-D). METHODS: The LV lead location was classified in 797 patients with CRT-D, in 569 patients with left bundle branch block (LBBB), in 228 patients with non-LBBB, and in 505 patients with an implantable cardioverter-defibrillator (ICD) only. Leads were classified into apical (n = 83) and non-apical (n = 486); with the non-apical LV leads further categorized into anterior (n = 99) and posterior/lateral (n = 387) within LBBB. All-cause mortality and heart failure (HF) events were assessed using Kaplan-Meier and Cox analyses. RESULTS: In CRT-D patients with LBBB and posterior/lateral LV lead location, there was an association with a significant reduction in long-term all-cause mortality (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.37 to 0.79; p = 0.001), and HF events (HR: 0.44, 95% CI: 0.33 to 0.60; p < 0.001) compared to an ICD only, accompanied with better LV reverse remodeling. CRT-D patients with LBBB and an anterior LV lead location were shown to be associated with a significant reduction in HF events compared to an ICD only (anterior HR: 0.50, 95% CI: 0.30 to 0.82; p = 0.006); however, no association with mortality reduction was observed from CRT-D versus an ICD only. CRT-D was not associated with improved outcomes in non-LBBB patients, regardless of LV lead location. CONCLUSIONS: In mild HF patients with LBBB and an implanted CRT-D, lateral/posterior, and anterior LV lead locations are similarly associated with reduction in the risk of HF or death events compared to ICD alone. Mortality benefit derived from CRT-D is associated only with patients with lateral/posterior LV lead location. An apical LV lead location should be avoided due to the early risk of death whenever possible. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT], NCT00180271; Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy Post Approval Registry [MADIT-CRT-PAR], NCT01294449; and MADIT-CRT Long-Term International Follow-Up Registry - Europe, NCT02060110).
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Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Idoso , Bloqueio de Ramo/terapia , Terapia de Ressincronização Cardíaca/efeitos adversos , Terapia de Ressincronização Cardíaca/mortalidade , Terapia de Ressincronização Cardíaca/estatística & dados numéricos , Desfibriladores Implantáveis/efeitos adversos , Desfibriladores Implantáveis/estatística & dados numéricos , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/etiologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Remodelação VentricularRESUMO
BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). OBJECTIVES: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. METHODS: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. RESULTS: Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. CONCLUSIONS: In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).
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Fármacos Cardiovasculares/uso terapêutico , Desfibriladores Implantáveis/tendências , Ranolazina/uso terapêutico , Taquicardia Ventricular/prevenção & controle , Fibrilação Ventricular/prevenção & controle , Idoso , Desfibriladores Implantáveis/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/epidemiologia , Fibrilação Ventricular/fisiopatologiaRESUMO
BACKGROUND: The WEARIT-II Registry demonstrated efficacy and safety of the wearable cardioverter defibrillator (WCD) for at-risk cardiac patients. However, 1-year outcomes in this population have not been reported. METHODS: The WEARIT-II Registry enrolled 2,000 U.S. patients prescribed the WCD. One-year mortality data from start of WCD use were prospectively collected for 1,846 patients (93%). Outcome data were analyzed by disease etiology and implantable cardioverter defibrillator (ICD) implantation following WCD use. RESULTS: During 12 months of follow-up, 73 patients died (4%). Kaplan-Meier survival analysis showed differences in all-cause mortality from WCD prescription between patients with ischemic versus nonischemic cardiomyopathy versus congenital/inherited heart disease (4% vs 3% vs 7%, P = 0.013). Patients with ventricular arrhythmia events during WCD use had a higher 1-year mortality (10% vs 3%, P = 0.042). Renal disease, increasing age, prior syncope, and nonbeta-blocker use predicted mortality. One-year mortality was similar in patients who did versus did not receive an ICD following WCD use in ischemic (3% vs 4%, P = 0.470) and nonischemic cardiomyopathy (3% vs 3%, P = 0.892). Patients with congenital/inherited heart disease with no implanted ICD had a trend toward a higher rate of mortality than those who received an ICD (8% vs 3%, P = 0.082). Multivariate models confirmed these findings. CONCLUSION: One-year follow-up from the WEARIT-II Registry shows an overall good survival in patients prescribed the WCD. Short-term use of WCD allows appropriate risk stratification for decision on an ICD implantation in at-risk ischemic and nonischemic cardiomyopathy patients. Congenital/inherited heart disease patients had a higher risk of 1-year mortality even without an implanted ICD post-WCD.
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Doenças Cardiovasculares/terapia , Cardioversão Elétrica/instrumentação , Dispositivos Eletrônicos Vestíveis , Idoso , Doenças Cardiovasculares/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Análise de Sobrevida , Resultado do Tratamento , Estados UnidosRESUMO
INTRODUCTION: Data on inappropriate and appropriate ICD therapy, and efficacy of ICD programing strategies by race are limited. METHODS: In MADIT-RIT, we evaluated the risk of ICD therapy by race, and the efficacy of high rate cut-off ventricular tachycardia (VT) zone ≥200 beats per minute (bpm) (Arm B), or 60 seconds delay in VT zone 170-199 bpm (Arm C), compared to 2.5 seconds delay at 170 bpm (Arm A) among black and white patients. RESULTS: MADIT-RIT enrolled 272 (20%) black and 1119 (80%) white patients. The risk of inappropriate therapy was similar among blacks and whites, HR 1.25, 95% CI (0.82-1.93), P = 0.30. High rate cut-off or delayed VT therapy was associated with significant reductions in inappropriate therapy among whites, Arm B versus Arm A, HR 0.15, 95% CI (0.08-0.29), P < 0.0001, Arm C versus Arm A, HR 0.19, 95% CI (0.11-0.33), P < 0.001, and black individuals Arm B versus Arm A, HR 0.24, 95% CI (0.01-0.56), P = 0.0001, Arm C versus Arm A, HR 0.30, 95% CI (0.13-0.68), P = 0.004, P interaction > 0.10). However, delayed VT therapy was associated with a trend toward greater reduction in appropriate therapy in black individuals, HR 0.08, 95% CI (0.03-0.27), P < 0.0001 relative to white individuals, HR 0.27, 95% CI (0.16-0.43), P < 0.0001, P interaction = 0.077. CONCLUSION: In MADIT-RIT, high rate and delayed detection ICD programming provided similar benefit with reductions in both inappropriate therapy and unnecessary appropriate therapy among black and white individuals. CLINICALTRIALS. GOV IDENTIFIER: NCT00947310.
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População Negra , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Disparidades em Assistência à Saúde/etnologia , Taquicardia Ventricular/terapia , População Branca , Potenciais de Ação , Negro ou Afro-Americano , Cardioversão Elétrica/efeitos adversos , Europa (Continente)/epidemiologia , Feminino , Frequência Cardíaca , Humanos , Israel/epidemiologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , América do Norte/epidemiologia , Desenho de Prótese , Falha de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etnologia , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Procedimentos DesnecessáriosRESUMO
BACKGROUND: Long-QT (LQT) syndrome mutation carriers have higher risk of cardiac events than unaffected family members even in the absence of QTc prolongation. Changes in T-wave morphology may reflect penetrance of LQT syndrome mutations. We aimed to assess whether T-wave morphology may improve risk stratification of LQT2 mutation carriers with normal QTc interval. METHODS: LQT2 mutation carriers with QTc <460 ms in men and <470 ms in women (n=154) were compared with unaffected family members (n=1007). Baseline ECGs recorded at age ≥18 years underwent blinded assessment. Flat, notched, or negative T waves in leads II or V5 were considered abnormal. Cox regression analysis was performed to assess the association between T-wave morphology, the presence of mutations in the pore region of KCNH2, and the risk of cardiac events defined as syncope, aborted cardiac arrest, defibrillator therapy, or sudden cardiac death. Sex-specific associations were estimated using interactions terms. RESULTS: LQT2 female carriers with abnormal T-wave morphology had significantly higher risk of cardiac events compared with LQT2 female carriers with normal T waves (hazard ratio, 3.31; 95% confidence interval, 1.68-6.52; P=0.001), whereas this association was not significant in men. LQT2 men with pore location of mutations have significantly higher risk of cardiac events than those with nonpore mutations (hazard ratio, 6.01; 95% confidence interval, 1.50-24.08; P=0.011), whereas no such association was found in women. CONCLUSIONS: The risk of cardiac events in LQT2 carriers with normal QTc is associated with abnormal T-wave morphology in women and pore location of mutation in men. The findings further indicate sex-specific differences in phenotype and genotype relationship in LQT2 patients.
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Canal de Potássio ERG1/genética , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Síndrome do QT Longo/genética , Mutação , Potenciais de Ação , Adulto , Morte Súbita Cardíaca/etiologia , Canal de Potássio ERG1/metabolismo , Eletrocardiografia , Feminino , Predisposição Genética para Doença , Parada Cardíaca/genética , Parada Cardíaca/fisiopatologia , Sistema de Condução Cardíaco/metabolismo , Humanos , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/metabolismo , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Minnesota , Penetrância , Fenótipo , Prognóstico , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores Sexuais , Síncope/genética , Síncope/fisiopatologia , Fatores de TempoRESUMO
Aims: Data on outcomes in patients using the wearable cardioverter-defibrillator (WCD) > 90 days are limited. We aimed to analyse the clinical course of patients with WCD use ≤90 days vs. WCD use >90 days. Methods and results: We assessed arrhythmia events during WCD use, and ejection fraction (EF) improvement/implantable cardioverter-defibrillator (ICD) implantation at the end of WCD use in patients with WCD use ≤90 days vs. WCD use >90 days enrolled in the WEARIT-II registry, further assessed by disease aetiology (ischaemic vs. non-ischaemic vs. congenital/inherited heart disease). There were 981 (49%) patients with WCD use >90 days, and 1019 patients with WCD use ≤90 days (median 120 vs. 55 days). There was a lower incidence of sustained ventricular tachycardia/ventricular fibrillation (VT/VF) events (11 vs. 50 events per 100 patient-years, P < 0.001), WCD treated VT/VF events (1 vs. 8 events per 100 patient-years, P < 0.001), and non-sustained VT events (21 vs. 51 events per 100 patient-years, P = 0.008) with WCD use >90 vs. WCD use ≤90 days. Non-ischaemic cardiomyopathy patients presented with similar rates of sustained VT/VF events during WCD use >90 vs. ≤90 days (13.4 vs. 13.7 events per 100 patient-years, P = 0.314), while most of these events terminated spontaneously. One-third of the patients with extended WCD use further improved their EF and they were not implanted with an ICD, with similar rates among ischaemic and non-ischaemic patients. Conclusions: In WEARIT-II, patients with extended WCD use >90 days remain at risk for ventricular arrhythmia events. One-third of the patients with WCD use >90 days further improved their EF, avoiding the need to consider ICD implantation.
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Morte Súbita Cardíaca/prevenção & controle , Desfibriladores , Cardioversão Elétrica/instrumentação , Taquicardia Ventricular/terapia , Fibrilação Ventricular/terapia , Dispositivos Eletrônicos Vestíveis , Idoso , Morte Súbita Cardíaca/etiologia , Cardioversão Elétrica/efeitos adversos , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Fatores de Risco , Taquicardia Ventricular/complicações , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/mortalidade , Fatores de Tempo , Resultado do Tratamento , Fibrilação Ventricular/complicações , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/mortalidadeRESUMO
AIM: There is limited information on the outcomes after primary prevention implantable cardioverter-defibrillator (ICD) implantation in patients with heart failure (HF) and diabetes. This analysis evaluates the effectiveness of a strategy of ICD plus medical therapy vs. medical therapy alone among patients with HF and diabetes. METHODS AND RESULTS: A patient-level combined-analysis was conducted from a combined dataset that included four primary prevention ICD trials of patients with HF or severely reduced ejection fractions: Multicenter Automatic Defibrillator Implantation Trial I (MADIT I), MADIT II, Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE), and Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). In total, 3359 patients were included in the analysis. The primary outcome of interest was all-cause death. Compared with patients without diabetes (n = 2363), patients with diabetes (n = 996) were older and had a higher burden of cardiovascular risk factors. During a median follow-up of 2.6 years, 437 patients without diabetes died (178 with ICD vs. 259 without) and 280 patients with diabetes died (128 with ICD vs. 152 without). ICDs were associated with a reduced risk of all-cause mortality among patients without diabetes [hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.46-0.67] but not among patients with diabetes (HR 0.88, 95% CI 0.7-1.12; interaction P = 0.015). CONCLUSION: Among patients with HF and diabetes, primary prevention ICD in combination with medical therapy vs. medical therapy alone was not significantly associated with a reduced risk of all-cause death. Further studies are needed to evaluate the effectiveness of ICDs among patients with diabetes.
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Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Diabetes Mellitus/epidemiologia , Insuficiência Cardíaca/terapia , Prevenção Primária/métodos , Volume Sistólico/fisiologia , Comorbidade/tendências , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Feminino , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologiaRESUMO
INTRODUCTION: Adverse electrical remodeling (AER), represented here as the sum absolute QRST integral (SAI QRST), has previously been shown to be directly associated with the risk for ventricular arrhythmia (VA). Cardiac resynchronization therapy (CRT) is known to reduce the risk for VA through various mechanisms, including reverse remodeling, and we aimed to evaluate the association between baseline AER and the risk for VA in CRT recipients. METHODS AND RESULTS: The study population comprised 961 CRT-D implanted patients from the MADIT CRT study. The relationship between SAI QRST, VA risk, and VA risk/death was evaluated as a continuous and as a categorical variable-tertiles (T1 ≤ 0.527, T2 0.528-0.766, T3 > 0.766). In a multivariable model, AER was inversely associated with the risk of VA. Each unit increase in SAI QRST was associated with 64% (P = 0.007) and 54% (P = 0.003) decrease in the risk of VA and VA/death, respectively. Patients with high SAI QRST (T3) and medium SAI QRST (T2) had 52% (P < 0.001) and 32% (P = 0.027) reduced risk for VA and 44% (P = 0.002) and 26% (P = 0.055) reduced risk for VA/death as compared with patients with low SAI QRST (T1), respectively. CONCLUSION: In CRT implanted patients with mild heart failure, baseline AER was inversely associated with the risk for VA and VA/death; this is a finding that contradicts the relationship previously reported in non-CRT implanted patients. We theorize that CRT may abate the process of AER; however, characterization of this mechanism requires further study.
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Remodelamento Atrial/fisiologia , Terapia de Ressincronização Cardíaca/efeitos adversos , Cardiomiopatias/fisiopatologia , Cardiomiopatias/terapia , Desfibriladores Implantáveis/efeitos adversos , Taquicardia Ventricular/fisiopatologia , Idoso , Terapia de Ressincronização Cardíaca/métodos , Cardiomiopatias/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/etiologiaRESUMO
BACKGROUND: Use of the wearable cardioverter-defibrillator (WCD) in older patients has not been described previously. OBJECTIVE: The purpose of this study was to assess WCD wear time, risk of arrhythmic events during WCD use, and implantable cardioverter-defibrillator (ICD) implantation rates after the end of WCD use in patients with age ≥65 years vs <65 years. METHODS: We stratified 1732 patients with ischemic and nonischemic cardiomyopathy from the Prospective Registry of Patients Using the Wearable Defibrillator Registry into 2 subgroups by age: those with age ≥65 years and those with age <65 years. Wear time, arrhythmic events, and end-of-use decisions, specifically ICD implantation or improvement in ejection fraction, were evaluated for each age group. RESULTS: There were 722 patients with age ≥65 years (41.7%) and 1010 patients with age <65 years (58.3%). Daily WCD wear time was longer in the older population (median 22.8 h/d (IQR 21.5 - 23.2) vs 22.3 h/d (IQR 19.5 - 23.0); P < .001). Patients with age ≥65 years experienced higher event rates, per 100 patient-years, for any sustained ventricular tachycardia/ventricular fibrillation (31.95 vs 9.82; P = .027) and ventricular tachycardia/ventricular fibrillation treated with WCD shock (6.92 vs 2.37; P = .034), particularly with ischemic cardiomyopathy. Younger patients experienced a trend toward a higher event rate for atrial arrhythmias with nonischemic cardiomyopathy (150.07 vs 74.86; P = .055). At the end of WCD use, ICD implantation was more frequent in older patients (41.8% vs 36.5%; P = .034). CONCLUSION: Older patients had good compliance with the WCD, presented with more frequent ventricular arrhythmias, and were more likely to receive an ICD at the end of WCD use. The WCD may play a role in risk stratification of the older population.
Assuntos
Cardiomiopatias/terapia , Morte Súbita Cardíaca/prevenção & controle , Cardioversão Elétrica/instrumentação , Cooperação do Paciente , Sistema de Registros , Taquicardia Ventricular/terapia , Dispositivos Eletrônicos Vestíveis , Idoso , Cardiomiopatias/complicações , Cardiomiopatias/fisiopatologia , Morte Súbita Cardíaca/etiologia , Eletrocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taquicardia Ventricular/complicações , Taquicardia Ventricular/fisiopatologia , Resultado do TratamentoRESUMO
BACKGROUND: Although cardiac resynchronization therapy (CRT) is beneficial in heart failure patients with left bundle branch block, 30% of these patients do not respond to the therapy. Identifying these patients before implantation of the device is one of the current challenges in clinical cardiology. METHODS: We verified the diagnostic contribution and an optimized computerized approach to measuring ventricular electrical activation delay (VED) from body surface 12-lead ECGs. We applied the method to ECGs acquired before implantation (baseline) in the MADIT-CRT trial (Multicenter Automatic Defibrillator Implantation-Cardiac Resynchronization Therapy). VED values were dichotomized using its quartiles, and we tested the association of VED values with the MADIT-CRT primary end point of heart failure or death. Multivariate Cox proportional models were used to estimate the risk of study end points. In addition, the association between VED values and hemodynamic changes after CRT-D implantation was examined using 1-year follow-up echocardiograms. RESULTS: Our results showed that left bundle branch block patients with baseline VED <31.2 ms had a 35% risk of MADIT-CRT end points, whereas patients with VED ≥31.2 ms had a 14% risk (P<0.001). The hazard ratio for predicting primary end points in patients with low VED was 2.34 (95% confidence interval, 1.53-3.57; P<0.001). Higher VED values were also associated with beneficial hemodynamic changes. These strong VED associations were not found in the right bundle branch block and intraventricular conduction delay cohorts of the MADIT-CRT trial. CONCLUSIONS: Left bundle branch block patients with a high baseline VED value benefited most from CRT, whereas left bundle branch block patients with low VED did not show CRT benefits.
Assuntos
Potenciais de Ação , Bloqueio de Ramo/terapia , Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Eletrocardiografia , Insuficiência Cardíaca/terapia , Idoso , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/mortalidade , Bloqueio de Ramo/fisiopatologia , Terapia de Ressincronização Cardíaca/efeitos adversos , Terapia de Ressincronização Cardíaca/mortalidade , Tomada de Decisão Clínica , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Seleção de Pacientes , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
We have previously shown a reduction in HF events with cardiac resynchronization therapy with defibrillator (CRT-D) in patients with mild heart failure (HF) and diabetes mellitus (DM). It remains unknown whether HF remission in DM patients with CRT-D translates into reduced mortality. The effects of CRT-D versus an implantable cardioverter-defibrillator (ICD) alone to reduce long-term mortality were assessed in patients with left bundle branch block with DM (n = 386) and without DM (n = 982), enrolled in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT). We further subdivided DM patients by insulin and noninsulin therapy. Kaplan-Meier survival analyses and multivariate cox proportional hazards regression models were utilized. At the 7-year follow-up, CRT-D was associated with a lower mortality in DM patients compared with ICD alone (21% vs 42%, p = 0.02), similar to non-DM patients (16 vs 24%, p = 0.014). CRT-D was associated with a 41% reduction in the risk of long-term all-cause mortality in DM patients (hazard ratio [HR] 0.59, 95% confidence interval 0.36 to 0.96, p = 0.033) and a similar reduction in non-DM patients (HR 0.69, 95% confidence interval 0.48 to 0.99, p = 0.045, treatment-diabetes interaction p = 0.611). Among DM patients, mortality benefit was evident in insulin-treated patients only (HR 0.40, p = 0.030). Reductions in HF events were present in all groups. In the MADIT-CRT, patients with mild HF with DM derive significant long-term survival benefit from CRT-D, similar to those without DM. The mortality benefit from CRT-D within the DM subgroup seems to be confined to patients with insulin treated diabetes.
Assuntos
Bloqueio de Ramo/terapia , Terapia de Ressincronização Cardíaca , Complicações do Diabetes , Insuficiência Cardíaca/terapia , Mortalidade , Idoso , Bloqueio de Ramo/complicações , Dispositivos de Terapia de Ressincronização Cardíaca , Estudos de Casos e Controles , Desfibriladores Implantáveis , Diabetes Mellitus/tratamento farmacológico , Progressão da Doença , Feminino , Insuficiência Cardíaca/complicações , Humanos , Hipoglicemiantes/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Índice de Gravidade de DoençaRESUMO
BACKGROUND: A comprehensive report on the clinical course of the three major genotypes of the long QT syndrome (LQTS) in a large U.S. patient cohort is lacking. METHODS: Our study consisted of 1,923 U.S. subjects from the Rochester-based LQTS Registry with genotype-positive LQT1 (n = 879), LQT2 (n = 807), and LQT3 (n = 237). We evaluated the risk of a first cardiac event (syncope, aborted cardiac arrest, or sudden cardiac death, whichever occurred first) from birth through age 50 years. Cox proportional hazards regression models incorporating clinical covariates were used to assess genotype-specific risk of cardiac events. RESULTS: For all three genotypes, the cumulative probability of a first cardiac event increased most markedly during adolescence. Multivariate analysis identified proband status and QTc > 500 ms as predictors of cardiac events in all three genotypes, and males <14 years and females >14 years as predictors of cardiac events in LQT1 and LQT2 only. Beta-blockers significantly reduced the risk of cardiac events in LQT1 (HR: 0.49, p = .002) and LQT2 patients (HR: 0.48, p = .001). A trend toward beta-blocker benefit in reducing cardiac events was found in LQT3 females (HR: 0.32, p = .078), but not in LQT3 males (HR: 1.37, p = .611). CONCLUSION: Risk factors and outcomes in LQTS patients varied by genotype. In all three genotypes, proband status and prolonged QTc were risk factors for cardiac events. Younger males and older females experienced increased risk in LQT1 and LQT2 only. Beta-blockers were most effective in reducing cardiac events in LQT1 and LQT2, with a potential benefit in LQT3 females.
Assuntos
Eletrocardiografia , Genótipo , Síndrome do QT Longo/genética , Síndrome do QT Longo/fisiopatologia , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , New York , Modelos de Riscos Proporcionais , Sistema de Registros , Fatores de Risco , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: The effects of right ventricular (RV) lead location and the combination of RV and left ventricular (LV) lead locations on long-term outcomes in patients receiving cardiac resynchronization therapy with defibrillator (CRT-D) are not well understood. METHODS: Our cohort consisted of 743 CRT-D patients from MADIT-CRT. We evaluated long-term death and combined heart failure or death (HF/death) in patients with non-apical RV vs. apical RV leads. We further assessed these long-term outcomes based on the combination of RV and LV leads, termed "RV-LV lead interaction." Patients with non-apical RV and apical LV leads and those with apical RV and non-apical LV leads were described to have "discordant RV and LV leads." Patients with RV and LV leads that were both non-apical or both apical were defined to have "concordant RV and LV leads." RESULTS: There were no differences in death and HF/death between patients with non-apical RV vs. apical RV leads. However, patients with non-apical RV and apical LV leads had higher mortality risk, relative to those with apical RV and non-apical LV leads (HR = 4.06, 95% CI 1.73-9.53, p = 0.001) as well as those with both leads in the non-apical (HR = 3.82, 95% CI 1.33-10.98, p = 0.013) or apical (HR = 3.40, 95% CI 1.24-9.37, p = 0.018) positions. There was no difference in HF/death by RV-LV lead sub-groups. CONCLUSION: Among CRT-D patients, long-term outcomes were similar for non-apical RV and apical RV leads. However, mortality risk was increased with discordant RV and LV leads, when a non-apical RV lead was combined with an apical LV lead.
Assuntos
Terapia de Ressincronização Cardíaca/mortalidade , Terapia de Ressincronização Cardíaca/métodos , Desfibriladores Implantáveis , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Idoso , Cateterismo Cardíaco/métodos , Causas de Morte , Ecocardiografia/métodos , Eletrocardiografia/métodos , Eletrodos Implantados , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Medição de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Rare, high-arousal negative emotions are known triggers of sudden death in individuals with preexisting heart disease. Whether everyday fluctuations in emotional arousal influence arrhythmia risk is unknown. METHODS: We studied 160 patients with the congenital long QT syndrome, 199 patients with coronary artery disease, and 2 groups of matched healthy volunteers (n = 52 and 50, respectively). Three-day home visits including a 12-hour Holter recording each day were completed. Subjects engaged in typical daily activities and were paged 10 times per day. On each occasion, subjects rated the intensity of 16 different emotions during the 5 minutes preceding the page. Holter data over those 5-minute epochs were analyzed for heart rate and QT interval corrected for heart rate (QTc). Analyses focused on within-subject covariation of momentary emotion and QTc. RESULTS: In patients with long QT syndrome, activated positive affect and activated negative affect were associated with QTc shortening, whereas low arousal positive affect (calm and relaxed) was associated with QTc lengthening, which at times exceeded 500 msec. Findings were not affected by beta-blocker status or observed in younger healthy subjects. Findings were 3 to 8 times stronger in the LQT2 genotype, known to be prone to emotion-induced events, relative to the LQT1 genotype. Findings in patients with long QT syndrome for activated positive affect and low arousal positive affect were replicated in patients with coronary artery disease relative to older healthy subjects. CONCLUSION: These findings suggest that even subtle changes in emotional arousal may alter repolarization reserve and contribute to sudden death risk in vulnerable individuals.
Assuntos
Afeto/fisiologia , Doença da Artéria Coronariana/fisiopatologia , Eletrocardiografia Ambulatorial , Frequência Cardíaca/fisiologia , Síndrome do QT Longo/fisiopatologia , Adulto , Estudos de Casos e Controles , Emoções/fisiologia , Feminino , Genótipo , Humanos , Síndrome do QT Longo/congênito , Síndrome do QT Longo/genética , Masculino , Pessoa de Meia-IdadeRESUMO
Aims: Discordant and concordant left bundle branch block (dLBBB/cLBBB) are characterized by negative or positive T waves, respectively, in lateral leads. We assessed if the two morphologies are associated with different clinical status and prognosis in patients with heart failure (HF) and current indication to Cardiac Resynchronization Therapy (CRT)/CRT-Defibrillator (CRT-D). Methods and results: Baseline electrocardiograms of 1270 patients with LBBB in the Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy cohort were analysed to identify dLBBB and cLBBB. The two groups were compared with respect to baseline clinical characteristics, primary endpoint (HF event or death), and secondary endpoint (ventricular tachycardia, ventricular fibrillation, or death) over a 3.5-year period, and benefit of CRT-D over implantable cardioverter defibrillator (ICD). dLBBB was identified in 909 (72%) patients, and cLBBB in 361 (28%). Patients with dLBBB were older, had more severe symptoms and systolic dysfunction, as well as higher brain natriuretic peptide. CRT-D was superior to ICD in patients with both LBBB morphologies. The occurrence of the primary outcome was significantly more frequent in patients with dLBBB than in those with cLBBB, both in the entire cohort (P = 0.005), and in the CRT-D arm (P = 0.002). There was a trend towards more frequent occurrence of the secondary endpoint in patients with dLBBB than in those with cLBBB, but statistical significance was not reached in the whole population or in the subgroup undergoing CRT-D. Among patients receiving CRT-D, dLBBB was an independent predictor of the primary endpoint. Conclusion: dLBBB morphology is associated with more severe HF clinical status and worse prognosis, even in patients receiving CRT-D, compared with cLBBB morphology.
Assuntos
Bloqueio de Ramo , Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis/estatística & dados numéricos , Insuficiência Cardíaca , Idoso , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/etiologia , Terapia de Ressincronização Cardíaca/efeitos adversos , Terapia de Ressincronização Cardíaca/métodos , Terapia de Ressincronização Cardíaca/estatística & dados numéricos , Dispositivos de Terapia de Ressincronização Cardíaca , Eletrocardiografia/métodos , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Mortalidade , Avaliação de Resultados em Cuidados de Saúde , Prognóstico , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
Many antiseizure medications (ASMs) affect ion channel function. We investigated whether ASMs alter the risk of cardiac events in patients with corrected QT (QTc) prolongation. The study included people from the Rochester-based Long QT syndrome (LQTS) Registry with baseline QTc prolongation and history of ASM therapy (n = 296). Using multivariate Anderson-Gill models, we assessed the risk of recurrent cardiac events associated with ASM therapy. We stratified by LQTS genotype and predominant mechanism of ASM action (Na+ channel blocker and gamma-aminobutyric acid modifier.) There was an increased risk of cardiac events when participants with QTc prolongation were taking vs off ASMs (HR 1.65, 95% confidence interval [CI] 1.36-2.00, P < 0.001). There was an increased risk of cardiac events when LQTS2 (HR 1.49, 95% CI 1.03-2.15, P = 0.036) but not LQTS1 participants were taking ASMs (interaction, P = 0.016). Na+ channel blocker ASMs were associated with an increased risk of cardiac events in participants with QTc prolongation, specifically LQTS2, but decreased risk in LQTS1. The increased risk when taking all ASMs and Na+ channel blocker ASMs was attenuated by concurrent beta-adrenergic blocker therapy (interaction, P < 0.001). Gamma-aminobutyric acid modifier ASMs were associated with an increased risk of events in patients not concurrently treated with beta-adrenergic blockers. Female participants were at an increased risk of cardiac events while taking all ASMs and each class of ASMs. Despite no change in overall QTc duration, pharmacogenomic analyses set the stage for future prospective clinical and mechanistic studies to validate that ASMs with predominantly Na+ channel blocking actions are deleterious in LQTS2, but protective in LQTS1.
Assuntos
Anticonvulsivantes/efeitos adversos , Cardiopatias/induzido quimicamente , Síndrome do QT Longo/tratamento farmacológico , Antagonistas Adrenérgicos beta/efeitos adversos , Adulto , Estudos de Coortes , Eletrocardiografia , Feminino , GABAérgicos/efeitos adversos , Cardiopatias/fisiopatologia , Humanos , Síndrome do QT Longo/complicações , Síndrome do QT Longo/genética , Masculino , Fatores de Risco , Bloqueadores do Canal de Sódio Disparado por Voltagem/efeitos adversosRESUMO
BACKGROUND: Frequent ventricular ectopy on preimplantation Holter has been associated with attenuated benefit from cardiac resynchronization therapy (CRT). However, it is unclear whether ectopic burden measured post-CRT implantation can be utilized to evaluate long-term prognosis. We aimed to describe the association between post-CRT implantation ectopic burden and subsequent risk of clinical outcomes. METHODS: At the 12-month follow-up visit, 24-hour Holter recordings were performed in 698 CRT-D patients from the MADIT-CRT study. The mean number of ventricular premature complexes (VPCs/hour) was calculated. High ectopic burden was defined as >10 VPCs/hour and low burden as ≤10 VPCs/hour. Multivariate Cox proportional hazards models were utilized to assess the association between 12-month ectopic burden and the risk of the end points of heart failure (HF) or death and ventricular tachyarrhythmias (VT/VF). RESULTS: At 12 months, 282 (40%) patients presented with low ectopic burden and 416 (60%) patients presented with high ectopic burden. The 3-year risk of HF/death and VT/VF was lower in patients with a low burden (7% and 8%) and significantly higher (25% and 24%) in patients with high burden. In multivariate analyses, patients with a high ectopic burden had approximately threefold increased risk of both HF/death (HR=2.76 [1.62-4.70], p < .001) and VT/VF (HR=2.79 [1.69-4.58], p < .001). CONCLUSION: In CRT-D patients with mild heart failure, high ectopic burden at 12-month follow-up was associated with a high 3-year risk of HF/death and VT/VF and threefold increased risk as compared to patients with low burden. Ectopic burden at 12 months may be a valuable approach for evaluating long-term prognosis.