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1.
JAMA ; 332(3): 204-213, 2024 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-38900490

RESUMO

Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest [UCA]; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia [CPVT]), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS (P < .001). The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination. Although the median change in QT interval was longer in CRDS cases (P = .002), an overlap between the cases and controls was present. The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.


Assuntos
Eletrocardiografia , Humanos , Camundongos , Estudos de Casos e Controles , Masculino , Animais , Feminino , Adulto , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/etiologia , Parada Cardíaca/etiologia , Parada Cardíaca/diagnóstico , Cálcio/metabolismo , Cálcio/sangue , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatologia , Taquicardia Supraventricular/etiologia , Pessoa de Meia-Idade , Modelos Animais de Doenças , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Adolescente , Adulto Jovem , Canal de Liberação de Cálcio do Receptor de Rianodina/genética
2.
Pacing Clin Electrophysiol ; 46(12): 1447-1454, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37997450

RESUMO

BACKGROUND: Cardiac implantable electronic devices (CIEDs) are routinely implanted using intravenous drugs for sedation. However, some patients are poor candidates for intravenous sedation. OBJECTIVE: We present a case series demonstrating the safety and efficacy of a novel, ultrasound-guided nerve block technique that allows for pre-pectoral CIED implantation. The targets are the supraclavicular nerve (SCN) and pectoral nerve (PECS1). METHODS: We enrolled 20 patients who were planned for new CIED implantation. Following US-localization of the SCN and PECS1, local anesthetic (LA) was instilled at least 30-60 min pre-procedure. Successful nerve block was determined if < 5 mL of intraprocedural LA was used, along with lack of sensation with skin and deep tissue pinprick. Optional sedation was offered to patients' pre-procedure if discomfort was reported. RESULTS: Seventeen patients (85%) had a successful periprocedural nerve block, with only three patients exceeding 5 mL of LA. SCN and PECS1 success occurred in 19 (95%) and 18 (90%) patients, respectively. The overall success of nerve block by fulfilling all the criteria was demonstrated in 17 out of 20 patients (85%). Patients who reported no pain (VAS score = 0) were distributed as follows: 13 patients (65%) in the immediate post-procedure interval, 18 patients (90%) at the 1 h post-implant interval, and 14 patients (70%) at the 24 h post- implant interval. The median cumulative VAS score was 0 (IQR = 0 - 1). There were no reported significant adverse effects. CONCLUSION: SCN and PECS1 nerve blocks are safe and effective for patients undergoing CIED implantation to minimize or eliminate the use of intravenous sedation.


Assuntos
Analgesia , Bloqueio Nervoso , Humanos , Projetos Piloto , Bloqueio Nervoso/métodos , Manejo da Dor , Anestésicos Locais/uso terapêutico
3.
Europace ; 24(6): 948-958, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34964475

RESUMO

AIMS: Complexity of the ventricular tachycardia (VT) substrate and the size and thickness of infarction area border zones differ based on location of myocardial infarctions (MIs). These differences may translate into heterogeneity in the effectiveness of treatments. This study aims to examine the influence of infarct location on the effectiveness of VT ablation in comparison with escalated pharmacological therapy in patients with prior MI and antiarrhythmic drug (AAD)-refractory VT. METHODS AND RESULTS: VANISH trial participants were categorized based on the presence or absence of an inferior MI scar. Inverse probability of treatment weighted Cox models were calculated for each subgroup. Of 259 randomized patients (median age 69.8 years, 7.0% women), 135 had an inferior MI and 124 had a non-inferior MI. Among patients with an inferior MI, no statistically significant difference in the composite primary outcome of all-cause mortality, appropriate implantable cardioverter-defibrillator (ICD) shock, and VT storm was detected between treatment arms [adjusted hazard ratio (aHR) 0.80, 95% confidence interval (CI) 0.51-1.20]. In contrast, patients with non-inferior MIs had a statistically significant reduction in the incidence of the primary outcome with ablation (aHR 0.48, 95% CI 0.27-0.86). In a sensitivity analysis of anterior MI patients (n = 83), a trend towards a reduction in the primary outcome with ablation was detected (aHR 0.50, 95% CI 0.23-1.09). CONCLUSION: The effectiveness of VT ablation versus escalated AADs varies based on the location of the MI. Patients with MI scars located only in non-inferior regions of the ventricles derive greater benefit from VT ablation in comparison to escalation of AADs in reducing VT-related events.


Assuntos
Ablação por Cateter , Desfibriladores Implantáveis , Infarto do Miocárdio , Taquicardia Ventricular , Idoso , Antiarrítmicos/uso terapêutico , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Cicatriz/etiologia , Feminino , Humanos , Masculino , Infarto do Miocárdio/tratamento farmacológico , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgia , Resultado do Tratamento
4.
Europace ; 24(7): 1112-1118, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-35030257

RESUMO

AIMS: Catheter ablation is superior to escalated antiarrhythmic drugs among patients with ventricular tachycardia (VT) and prior myocardial infarction (MI). However, it is uncertain whether clinical VT characteristics, should influence choice of therapy. The purpose of this study was to evaluate whether presentation with electrical storm and the clinical VT cycle length predicted response to ablation vs. escalated antiarrhythmic therapy. METHODS AND RESULTS: All patients enrolled in the Ventricular Tachycardia Ablation vs. Escalated Antiarrhythmic Drug Therapy in Ischaemic Heart Disease (VANISH) trial were included. The association between VT cycle length and presentation with electrical storm and the primary outcome of death, subsequent VT storm or appropriate ICD shock was evaluated. Among the study population of 259 patients, escalated antiarrhythmic drug therapy had worse outcomes for those presenting with a VT cycle length >400 ms [<150 b.p.m., 89/259, hazard ratio (HR) 1.7 (1.02-3.13)]. This effect was more pronounced among those taking amiodarone at baseline [HR of 2.22 (1.19-4.16)]. Presentation with VT storm (32/259) did not affect the primary outcome between groups. However, those presenting with VT storm on amiodarone had a trend towards worse outcomes with escalated antiarrhythmic therapy [HR 4.31 (0.55-33.93)]. CONCLUSION: The VT cycle length can influence response to either ablation or escalated drug therapy in patients with VT and prior MI. Those with slow VT had improved outcomes with ablation. Patients presenting with electrical storm demonstrated similar outcomes to the overall trial population, with a trend to benefit of catheter ablation, particularly in those on amiodarone.


Assuntos
Amiodarona , Ablação por Cateter , Infarto do Miocárdio , Taquicardia Ventricular , Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Ablação por Cateter/métodos , Humanos , Infarto do Miocárdio/complicações , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/tratamento farmacológico , Taquicardia Ventricular/cirurgia , Resultado do Tratamento
5.
Circulation ; 141(6): 429-439, 2020 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-31941373

RESUMO

BACKGROUND: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration. METHODS: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. RESULTS: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P<0.001). ECG penetrance for heterozygous genotype positive family members was 20.7% (29/140). A definite arrhythmic event was experienced in 16.9% (15/89) of heterozygous probands in comparison with 1.4% (2/140) of family members (adjusted hazard ratio [HR] 11.6 [95% CI, 2.6-52.2]; P=0.001). Event incidence did not differ significantly for Type 2 Jervell and Lange-Nielsen syndrome patients relative to the overall heterozygous cohort (10.5% [2/19]; HR 1.7 [95% CI, 0.3-10.8], P=0.590). The cumulative prevalence of the 32 KCNE1 variants in the Genome Aggregation Database, which is a human database of exome and genome sequencing data from now over 140 000 individuals, was 238-fold greater than the anticipated prevalence of all LQT5 combined (0.238% vs 0.001%). CONCLUSIONS: The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT prolongation, however, the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for Type 2 Jervell and Lange-Nielsen syndrome patients.


Assuntos
Síndrome do QT Longo , Penetrância , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Sistema de Registros , Adolescente , Adulto , Morte Súbita Cardíaca , Cardioversão Elétrica , Eletrocardiografia , Feminino , Parada Cardíaca/genética , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Parada Cardíaca/terapia , Humanos , Síndrome do QT Longo/genética , Síndrome do QT Longo/mortalidade , Síndrome do QT Longo/fisiopatologia , Síndrome do QT Longo/terapia , Masculino , Pessoa de Meia-Idade
6.
Europace ; 23(6): 844-850, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-33682005

RESUMO

AIMS: Atrial fibrillation (AF) is a complex heritable disease whose genetic underpinnings remain largely unexplained, though recent work has suggested that the arrhythmia may develop secondary to an underlying atrial cardiomyopathy. We sought to evaluate for enrichment of loss-of-function (LOF) and copy number variants (CNVs) in genes implicated in ventricular cardiomyopathy in 'lone' AF. METHODS AND RESULTS: Whole-exome sequencing was performed in 255 early onset 'lone' AF cases, defined as arrhythmia onset prior to 60 years of age in the absence of known clinical risk factors. Subsequent evaluations were restricted to 195 cases of European genetic ancestry, as defined by principal component analysis, and focused on a pre-defined set of 43 genes previously implicated in ventricular cardiomyopathy. Bioinformatic analysis identified 6 LOF variants (3.1%), including 3 within the TTN gene, among cases in comparison with 4 of 503 (0.80%) controls [odds ratio: 3.96; 95% confidence interval (CI): 1.11-14.2; P = 0.033]. Further, two AF cases possessed a novel heterozygous 8521 base pair TTN deletion, confirmed with Sanger sequencing and breakpoint validation, which was absent from 4958 controls (P = 0.0014). Subsequent cascade screening in two families revealed evidence of co-segregation of a LOF variant with 'lone' AF. CONCLUSION: 'Lone' AF cases are enriched in rare LOF variants from cardiomyopathy genes, findings primarily driven by TTN, and a novel TTN deletion, providing additional evidence to implicate atrial cardiomyopathy as an AF genetic sub-phenotype. Our results also highlight that AF may develop in the context of these variants in the absence of a discernable ventricular cardiomyopathy.


Assuntos
Fibrilação Atrial , Cardiomiopatias , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/genética , Cardiomiopatias/diagnóstico , Cardiomiopatias/genética , Variações do Número de Cópias de DNA , Predisposição Genética para Doença , Heterozigoto , Humanos , Fenótipo
7.
Am Heart J ; 220: 246-252, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31911261

RESUMO

Approximately 5% of patients with sarcoidosis have clinically manifest cardiac involvement. Clinical features of Cardiac Sarcoidosis are dependent on the location, extent, and activity of the disease. First line therapy is usually with prednisone and this is recommended based on clinician experience, expert opinion and small observational cohorts. There are no published clinical trials in cardiac sarcoidosis and multiple experts in the field have called for randomized clinical trials to answer important patient care questions. Corticosteroid are associated with multiple adverse effects including hypertension, diabetes, weight gain, osteoporosis, and increased risk of infections. In contrast Methotrexate is generally well tolerated and is increasingly used in other forms of sarcoidosis. OBJECTIVES: The Cardiac Sarcoidosis Multi-Center Randomized Controlled Trial (CHASM CS-RCT; NCT03593759) is a multicenter randomized controlled trial designed to evaluate the optimal initial treatment strategy for patients with active cardiac sarcoidosis. We hypothesize that (1) a low dose prednisone/methotrexate combination will have non-inferior efficacy to standard dose prednisone and that (2) the low dose prednisone/ methotrexate combination will result in significantly better quality of life than standard dose prednisone, as a result of reduced burden of side effects. METHODS/DESIGN: Eligible study subjects will have active clinically manifest cardiac sarcoidosis presenting with one or more of the following clinical findings: advanced conduction system disease, significant sinus node dysfunction, non-sustained or sustained ventricular arrhythmia, left ventricular dysfunction or right ventricular dysfunction. Subjects will be randomized in a 1:1 ratio to prednisone 0.5 mg/kg/day for 6 months (maximum dose 30 mg daily) OR to prednisone 20 mg daily for 1 month, then 10 mg daily for 1 month, then 5 mg daily for one month then stop AND methotrexate 15-20 mg once weekly for 6 months. The primary endpoint is summed perfusion rest score on 6-month PET (blinded core-lab review). The summed perfusion rest score is measure of myocardial fibrosis/scar. The design is non-inferiority with a sample size of 97 per group. DISCUSSION: Given the multiorgan system potential adverse side effects of prednisone, proving noninferiority of an alternate regimen would be sufficient to make the alternative compare favorably to standard dose steroids. This is the first ever clinical trial in cardiac sarcoidosis and thus in addition to the listed goals of the trial, we will also establish a multi-center, multinational cardiac sarcoidosis clinical trials network. Such a collaborative infrastructure will enable a new era of high quality data to guide physicians when treating cardiac sarcoidosis patients.


Assuntos
Cardiomiopatias/tratamento farmacológico , Glucocorticoides/administração & dosagem , Metotrexato/administração & dosagem , Prednisona/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Sarcoidose/tratamento farmacológico , Cardiomiopatias/complicações , Esquema de Medicação , Quimioterapia Combinada , Estudos de Equivalência como Asunto , Glucocorticoides/efeitos adversos , Humanos , Estudos Multicêntricos como Assunto , Prednisona/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Projetos de Pesquisa , Sarcoidose/complicações
8.
J Cardiovasc Electrophysiol ; 31(10): 2751-2758, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32713090

RESUMO

INTRODUCTION: We sought to explore the relationship between ventricular tachycardia (VT) and premature ventricular complex (PVC) burden (from implantable cardioverter-defibrillator diagnostics), before and during corticosteroid use in patients with newly diagnosed clinically manifest cardiac sarcoidosis (CS). METHODS: A single-centre, prospective cohort study was performed in consecutive patients who met all of the following criteria: (1) presentation with clinically manifest CS, (2) abnormal myocardial fluoro-deoxyglucose (FDG) uptake on positron emission tomography scan, (3) plan for implantation with implantable cardioverter-defibrillator device that reports accurate PVC count, (4) plan to initiate corticosteroids after the device healing period. Data were collected during each device interrogation visit for all patients in the study. For each inter-visit period the total number of episodes of VT-sustained and nonsustained, and the number of PVCs was obtained. Each inter-visit period was classified into one of the following three periods: (1) New diagnosis of treatment-naive active disease without corticosteroids during the period. (2) Known treatment-naive active disease with corticosteroids initiated during the inter-visit period. (3) On corticosteroid therapy during the entire period. RESULTS: A total of 20 patients with a mean age of 59.7 ± 7.7 years were recruited and 82 inter-visit periods were analyzed. All patients were corticosteroid responders based on FDG uptake. The maximum left ventricular standardized uptake value was 11.14 ± 5.19 before corticosteroid initiation and 4.07 ± 0.88 after (p < .001). Patients with active untreated CS had an average of 496.4 ± 879.1 PVCs per day. After treatment with corticosteroids, the average PVC count increased to 1332.4 ± 1865.7/day during Period 2 (p = .036) and to 1590.1 ± 2362.2 per day during Period 3 (p = .008). There was also a statistically significant increase in episodes of nonsustained ventricular tachycardia (NSVT) before and after treatment with corticosteroids (p = .017). There were too few episodes of sustained ventricular arrhythmia to analyze. Overall, 18 out of 20 patients (90%) had an increase in PVC burden after corticosteroid initiation. CONCLUSION: This study demonstrated, on average, a threefold increase in daily PVC count in clinically manifest CS patients during treatment with corticosteroids compared to pretreatment. There was also a significant increase in episodes of NSVT. Clinicians and patients with active manifest CS should be aware that corticosteroids are unlikely to lead to a reduction in the burdens of PVC and NSVT.


Assuntos
Desfibriladores Implantáveis , Sarcoidose , Taquicardia Ventricular , Complexos Ventriculares Prematuros , Corticosteroides/efeitos adversos , Criança , Humanos , Estudos Prospectivos , Sarcoidose/diagnóstico por imagem , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/diagnóstico por imagem
9.
J Cardiovasc Electrophysiol ; 31(12): 3207-3214, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32936492

RESUMO

INTRODUCTION: Septal accessory pathway (AP) ablation can be challenging due to the complex anatomy of the septal region. The decision to access the left atrium (LA) is often made after failure of ablation from the right. We sought to establish whether the difference between ventriculo-atrial (VA) time during right ventricular (RV) apical pacing versus the VA during tachycardia would help establish the successful site for ablation of septal APs. METHODS: Intracardiac electrograms of patients with orthodromic reciprocating tachycardia (ORT) using a septal AP with successful catheter ablation were reviewed. The ∆VA was the difference between the VA interval during RV apical pacing and the VA interval during ORT. The difference in the VA interval during right ventricular entrainment and ORT (StimA-VA) was also measured. RESULTS: The median ∆VA time was significantly less in patients with a septal AP ablated on the right side compared with patients with a septal AP ablated on the left side (12 ± 19 vs. 56 ± 10 ms, p < .001). The StimA-VA was significantly different between the two groups (22 ± 14 vs. 53 ± 9 ms, p < .001). The ∆VA and StimA-VA were always ≤ 40 ms in patients with non-decremental septal APs ablated from the right side and always greater than 40 ms in those with septal APs ablated from the left. CONCLUSION: ΔVA and StimA-VA values identified with RV apical pacing in the setting of ORT involving a septal AP predict when left atrial access will be necessary for successful ablation.


Assuntos
Feixe Acessório Atrioventricular , Ablação por Cateter , Taquicardia por Reentrada no Nó Atrioventricular , Feixe Acessório Atrioventricular/cirurgia , Fascículo Atrioventricular , Ablação por Cateter/efeitos adversos , Eletrocardiografia , Sistema de Condução Cardíaco/diagnóstico por imagem , Sistema de Condução Cardíaco/cirurgia , Humanos , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia
10.
N Engl J Med ; 375(2): 111-21, 2016 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-27149033

RESUMO

BACKGROUND: Recurrent ventricular tachycardia among survivors of myocardial infarction with an implantable cardioverter-defibrillator (ICD) is frequent despite antiarrhythmic drug therapy. The most effective approach to management of this problem is uncertain. METHODS: We conducted a multicenter, randomized, controlled trial involving patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite the use of antiarrhythmic drugs. Patients were randomly assigned to receive either catheter ablation (ablation group) with continuation of baseline antiarrhythmic medications or escalated antiarrhythmic drug therapy (escalated-therapy group). In the escalated-therapy group, amiodarone was initiated if another agent had been used previously. The dose of amiodarone was increased if it had been less than 300 mg per day or mexiletine was added if the dose was already at least 300 mg per day. The primary outcome was a composite of death, three or more documented episodes of ventricular tachycardia within 24 hours (ventricular tachycardia storm), or appropriate ICD shock. RESULTS: Of the 259 patients who were enrolled, 132 were assigned to the ablation group and 127 to the escalated-therapy group. During a mean (±SD) of 27.9±17.1 months of follow-up, the primary outcome occurred in 59.1% of patients in the ablation group and 68.5% of those in the escalated-therapy group (hazard ratio in the ablation group, 0.72; 95% confidence interval, 0.53 to 0.98; P=0.04). There was no significant between-group difference in mortality. There were two cardiac perforations and three cases of major bleeding in the ablation group and two deaths from pulmonary toxic effects and one from hepatic dysfunction in the escalated-therapy group. CONCLUSIONS: In patients with ischemic cardiomyopathy and an ICD who had ventricular tachycardia despite antiarrhythmic drug therapy, there was a significantly lower rate of the composite primary outcome of death, ventricular tachycardia storm, or appropriate ICD shock among patients undergoing catheter ablation than among those receiving an escalation in antiarrhythmic drug therapy. (Funded by the Canadian Institutes of Health Research and others; VANISH ClinicalTrials.gov number, NCT00905853.).


Assuntos
Amiodarona/administração & dosagem , Antiarrítmicos/administração & dosagem , Cardiomiopatias/complicações , Ablação por Cateter , Taquicardia Ventricular/terapia , Idoso , Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Cardiomiopatias/mortalidade , Ablação por Cateter/efeitos adversos , Desfibriladores Implantáveis , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Recidiva , Prevenção Secundária , Taquicardia Ventricular/tratamento farmacológico
11.
Circulation ; 135(19): 1788-1798, 2017 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-28228428

RESUMO

BACKGROUND: Radiofrequency catheter ablation for atrial fibrillation has become an important therapy for AF; however, recurrence rates remain high. We proposed to determine whether aggressive blood pressure (BP) lowering prevents recurrent atrial fibrillation (AF) after catheter ablation in patients with AF and a high symptom burden. METHODS: We randomly assigned 184 patients with AF and a BP >130/80 mm Hg to aggressive BP (target <120/80 mm Hg) or standard BP (target <140/90 mm Hg) treatment before their scheduled AF catheter ablation. The primary outcome was symptomatic recurrence of AF/atrial tachycardia/atrial flutter lasting >30 seconds, determined 3 months beyond catheter ablation by a blinded end-point evaluation. RESULTS: The median follow-up was 14 months. At 6 months, the mean systolic BP was 123.2±13.2 mm Hg in the aggressive BP treatment group versus 135.4±15.7 mm Hg (P<0.001) in the standard treatment group. The primary outcome occurred in 106 patients, 54 (61.4%) in the aggressive BP treatment group compared with 52 (61.2%) in the standard treatment group (hazard ratio=0.94; 95% confidence interval, 0.65-1.38; P=0.763). In the prespecified subgroup analysis of the influence of age, patients ≥61 years of age had a lower primary outcome event rate with aggressive BP (hazard ratio=0.58; 95% confidence interval, 0.34-0.97; P=0.013). There was a higher rate of hypotension requiring medication adjustment in the aggressive BP group (26% versus 0%). CONCLUSIONS: In this study, this duration of aggressive BP treatment did not reduce atrial arrhythmia recurrence after catheter ablation for AF but resulted in more hypotension. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00438113.


Assuntos
Fibrilação Atrial/diagnóstico , Fibrilação Atrial/terapia , Determinação da Pressão Arterial/tendências , Pressão Sanguínea/fisiologia , Ablação por Cateter/tendências , Idoso , Fibrilação Atrial/fisiopatologia , Determinação da Pressão Arterial/métodos , Ablação por Cateter/métodos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Resultado do Tratamento
12.
J Cardiovasc Electrophysiol ; 29(3): 421-434, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29316012

RESUMO

BACKGROUND/OBJECTIVE: We compared health-related quality of life (HRQoL) in patients randomized to escalated therapy and those randomized to ablation for ventricular tachycardia in the VANISH trial. METHODS: HRQoL was assessed among VANISH patients at baseline and 3-, 6-, and 12-month follow-up visits. Four validated instruments were used: the SF-36, the implanted cardioverter defibrillator (ICD) Concerns questionnaire (ICDC), the Hospital Anxiety and Depression Scale (HADS), and the EuroQol five dimensions questionnaire (EQ-5D). Linear mixed-effects modeling was used for repeated measures with SF-36, HADS, ICDC, and EQ-5D as dependent variables. In a second model, treatment was subdivided by amiodarone use prior to enrollment. RESULTS: HRQoL did not differ significantly between those randomized to ablation or escalated therapy. On subgroup analysis, improvement in SF-36 measures was seen at 6 months in the ablation group for social functioning (63.5-69.3, P = 0.03) and energy/fatigue (43.0-47.9, P = 0.01). ICDC measures showed a reduction in ICD concern in the ablation group at 6 months (10.4-8.7, P = 0.01) and a reduction in ICD concern in the escalated therapy group at 6 months (10.9-9.4, P = 0.04). EQ-5D measures showed a significant improvement in overall health in ablation patients at 6 months (63.4-67.3, P = 0.04). CONCLUSION: Patients in the VANISH study randomized to ablation did not have a significant change in quality of life outcomes compared to those randomized to escalated therapy. Some subgroup findings were significant, as those randomized to ablation showed persistent improvement in SF-36 energy/fatigue and ICD concern, and transient improvement in SF-36 social functioning and EQ-5D overall health.


Assuntos
Amiodarona/uso terapêutico , Antiarrítmicos/uso terapêutico , Ablação por Cateter , Qualidade de Vida , Taquicardia Ventricular/terapia , Idoso , Amiodarona/efeitos adversos , Antiarrítmicos/efeitos adversos , Ansiedade/diagnóstico , Ansiedade/prevenção & controle , Ansiedade/psicologia , Austrália , Ablação por Cateter/efeitos adversos , Emoções , Europa (Continente) , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte , Comportamento Social , Inquéritos e Questionários , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/psicologia , Fatores de Tempo , Resultado do Tratamento
13.
J Cardiovasc Electrophysiol ; 27(11): 1298-1303, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27510229

RESUMO

INTRODUCTION: Radiofrequency (RF) ablation in thicker regions of the left atrium (LA) may require increased ablation energy in order to achieve effective transmural lesions. Consequently, many cases of recurrent atrial fibrillation (AF) postablation may be due to thicker-than-normal atrial tissue. The aim of this study was to test the hypotheses that patients with recurrent AF have thicker tissue overall and that electrical reconnection is more likely in regions of thicker tissue. METHODS AND RESULTS: Retrospective analysis was performed on 86 CT images acquired preoperatively from a cohort of 119 patients who had undergone RF ablation for AF. Of these, 33 patients experienced recurrence of AF within 1 year of initial treatment and 29 returned for a repeat ablation. For each patient, LA wall thickness (LAWT) was measured from the images in 12 anatomical regions using custom software. Patients with recurrent AF had larger LAWT compared to successfully treated patients (1.6 ± 0.6 mm vs. 1.5 ± 0.5 mm, P < 0.001) and reconnection was found to be at regions of thicker tissue (1.6 ± 0.6 mm, P = 0.038) compared to nonreconnected regions (1.5 ± 0.5 mm). The superior right posterior wall of the LA was significantly related to both recurrence (P = 0.048) and reconnection (P = 0.014). CONCLUSION: Increased LAWT has a small but significant effect on postablation recurrence and reconnection. Measures of LAWT may facilitate appropriate dosing of RF energy, but other factors will be critical in transmural lesion formation and ablation success.

14.
J Cardiovasc Electrophysiol ; 27(3): 298-302, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26538372

RESUMO

BACKGROUND: A full circumferential set of antral lesions is not always required for bidirectional pulmonary vein conduction block. It is unknown whether a partial lesion set that isolates the veins will have clinical success rates similar to a full circumferential lesion set, and if procedural times or procedural risk will be affected. METHODS: We performed a prospective, randomized clinical trial to test the hypothesis that a partial lesion set that isolates the pulmonary veins has comparable clinical success rate and shorter procedure times compared to a strategy of completing the circumferential lesion set once the veins are isolated. RESULTS: A total of 119 patients were enrolled, 59 randomized to circumferential ablation, and 60 to segmental. Mean age was 58.3 ± 10.1, 77% male. Mean procedure time was 221.0 ± 46.9 minutes in circumferential and 224.7 ± 51.3 in segmental (P = 0.68). Twelve-month freedom from AF recurrence was 61.3% overall, 64.4% in circumferential, and 58.3% in segmental (P = 0.50). Among 25 segmental patients with AF recurrence, 23 underwent second ablation. Among 33 areas of conduction recovery, 23 (70%) occurred in segments ablated at first procedure and 10 (30%) in segments not previously ablated, suggesting reversible conduction block from edema. CONCLUSION: No difference in AF recurrence or procedure time is detectable in a sample of 119 patients randomized to segmental or circumferential antral ablation to achieve pulmonary vein isolation. Second ablation procedures confirmed that some antral sites do not require ablation. A segmental approach results in unacceptably high rates of untargeted or recovered antral sites to make this approach feasible.


Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Idoso , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Veias Pulmonares/diagnóstico por imagem , Recidiva
15.
J Genet Couns ; 24(4): 558-64, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25273952

RESUMO

The acceptance and yield of family screening in genotype-negative long QT syndrome (LQTS) remains incompletely characterized. In this study of family screening for phenotype-definite Long QT Syndrome (LQTS, Schwartz score ≥3.5), probands at a regional Inherited Cardiac Arrhythmia clinic were reviewed. All LQTS patients were offered education by a qualified genetic counselor, along with materials for family screening including electronic and paper correspondence to provide to family members. Thirty-eight qualifying probands were identified and 20 of these had family members who participated in cascade screening. The acceptance of screening was found to be lower among families without a known pathogenic mutation (33 vs. 77 %, p = 0.02). A total of 52 relatives were screened; fewer relatives were screened per index case when the proband was genotype-negative (1.7 vs. 3.1, p = 0.02). The clinical yield of screening appeared to be similar irrespective of gene testing results (38 vs. 33 %, p = 0.69). Additional efforts to promote family screening among gene-negative long QT families may be warranted.


Assuntos
Testes Genéticos , Genótipo , Síndrome do QT Longo/genética , Aceitação pelo Paciente de Cuidados de Saúde , Adolescente , Adulto , Análise Mutacional de DNA , Feminino , Aconselhamento Genético/psicologia , Humanos , Londres , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/prevenção & controle , Síndrome do QT Longo/psicologia , Masculino , Pessoa de Meia-Idade , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Fenótipo
16.
Europace ; 16(12): 1847-51, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24833771

RESUMO

AIMS: Beta-blockers are the standard of care for the treatment of long QT syndrome (LQTS), and have been shown to reduce recurrent syncope and mortality in patients with type 1 LQTS (LQT1). Although beta-blockers have minimal effect on the resting corrected QT interval, their effect on the dynamics of the non-corrected QT interval is unknown, and may provide insight into their protective effects. METHODS AND RESULTS: Twenty-three patients from eight families with genetically distinct mutations for LQT1 performed exercise stress testing before and after beta-blockade. One hundred and fifty-two QT, QTc, and Tpeak-Tend intervals were measured before starting beta-blockers and compared with those at matched identical cycle lengths following beta-blockade. Beta-blockers demonstrated heart-rate-dependent effects on the QT and QTc intervals. In the slowest heart rate tertile (<90 b.p.m.), beta-blockade increased the QT and QTc intervals (QT: 405 vs. 409 ms; P = 0.06; QTc: 459 vs. 464 ms; P = 0.06). In the fastest heart rate tertile (>100 b.p.m.), the use of beta-blocker was associated with a reduction in both the QT and QTc intervals (QT: 367 vs. 358 ms; P < 0.0001; QTc: 500 vs. 486 ms; P < 0.0001). The Tpeak-Tend interval showed minimal change at slower heart rates (<90 b.p.m.) (93 vs. 87 ms; P = 0.09) and at faster heart rates (>100 b.p.m.) (87 vs. 84 ms; P = NS) following beta-blockade. CONCLUSION: Beta-blockers have heart-rate-dependent effects on the QT and QTc intervals in LQTS. They appear to increase the QT and QTc intervals at slower heart rates and shorten them at faster heart rates during exercise.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Eletrocardiografia/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Síndrome de Romano-Ward/tratamento farmacológico , Síndrome de Romano-Ward/fisiopatologia , Adulto , Teste de Esforço , Feminino , Humanos , Masculino , Síndrome de Romano-Ward/diagnóstico , Resultado do Tratamento
17.
Circulation ; 125(19): 2308-15, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22532593

RESUMO

BACKGROUND: The incidence of sudden cardiac death (SCD) and the management of this risk in patients with asymptomatic preexcitation remain controversial. The purpose of this meta-analysis was to define the incidence of SCD and supraventricular tachycardia in patients with asymptomatic Wolff-Parkinson-White ECG pattern. METHODS AND RESULTS: We performed a systematic search of prospective, retrospective, randomized, or cohort English-language studies in EMBASE and Medline through February 2011. Studies reporting asymptomatic patients with preexcitation who did not undergo ablation were included. Twenty studies involving 1869 patients met our inclusion criteria. Participants were primarily male with a mean age ranging from 7 to 43 years. Ten SCDs were reported involving 11 722 person-years of follow-up. Seven studies originated from Italy and reported 9 SCDs. The risk of SCD is estimated at 1.25 per 1000 person-years (95% confidence interval [CI], 0.57-2.19). A total of 156 supraventricular tachycardias were reported involving 9884 person-years from 18 studies. The risk of supraventricular tachycardia was 16 (95% CI, 10-24) events per 1000 person-years of follow-up. Children had numerically higher SCD (1.93 [95% CI, 0.57-4.1] versus 0.86 [95% CI, 0.28-1.75]; P=0.07) and supraventricular tachycardia (20 [95% CI, 12-31] versus 14 [95% CI, 6-25]; P=0.38) event rates compared with adults. CONCLUSION: The low incidence of SCD and low risk of supraventricular tachycardia argue against routine invasive management in most asymptomatic patients with the Wolff-Parkinson-White ECG pattern.


Assuntos
Morte Súbita Cardíaca/epidemiologia , Taquicardia Supraventricular/mortalidade , Síndrome de Wolff-Parkinson-White/mortalidade , Humanos , Incidência , Prevalência , Fatores de Risco
18.
J Cardiovasc Electrophysiol ; 24(12): 1354-60, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24016223

RESUMO

INTRODUCTION: Atrioventricular nodal reentrant tachycardia (AVNRT) is the most common supraventricular tachycardia referred for ablation. High success rates have been accompanied with a small risk of atrioventricular (AV) block. Cryoablation has been used as an alternative to radiofrequency (RF) ablation, but studies have been underpowered in comparing the 2 techniques. METHODS AND RESULTS: An electronic search and hand-search of reference lists for published and unpublished data was carried out. Comparative studies (cohort and randomized controlled trials) of RF versus cryoablation for AVNRT were identified independently by 2 reviewers. Searches were limited to English language human studies. The primary metameter was long-term AVNRT recurrence (>2 months postprocedure and ECG/electrophysiology study [EPS]-documented) and secondary metameters included acute procedural failure and AV block requiring pacing. A total of 5,617 patients in 14 trials were included in this systematic review. Acute procedural failure with cryoablation was slightly higher than with RF ablation, but the difference was not statistically significant (risk ratio [RR] 1.44 [95% confidence interval; CI 0.91-2.28], P = 0.12). Long-term recurrence was higher with cryoablation (RR 3.66 [95% CI 1.84-7.28], P = 0.0002) even after adjusting for larger (6 mm) cryocatheter tips, "insurance lesions" and longer (>6 months) follow-up duration. RF ablation for AVNRT was associated with permanent AV block in 0.75% of patients, but was not reported in any patients treated with cryoablation (n = 1066, P = 0.01). CONCLUSIONS: Cryoablation is a safe and effective treatment for AVNRT. Although late-recurrence is more common with cryoablation than with RF ablation, avoidance of permanent AVN block makes it an attractive option in patients where the avoidance of AV block assumes higher priority (such as children and young adults).


Assuntos
Ablação por Cateter , Criocirurgia , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia , Bloqueio Atrioventricular/etiologia , Ablação por Cateter/efeitos adversos , Criocirurgia/efeitos adversos , Humanos , Seleção de Pacientes , Recidiva , Fatores de Risco , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Fatores de Tempo , Resultado do Tratamento
19.
J Cardiovasc Electrophysiol ; 24(1): 47-52, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22909255

RESUMO

INTRODUCTION: It has been suggested that the cavotricuspid isthmus (CTI) is composed of discrete muscle bundles with preferred paths of conduction. An ablation technique targeting high-voltage local electrograms (maximum voltage guided or MVG technique) has been described with the aim of preferentially targeting the muscle bundles. We hypothesized that the MVG technique could provide isthmus block even if the high voltage targets were clearly separated on different ablation lines. In contrast, conduction over a continuous sheet of muscle would require a single continuous ablation line. METHODS: Twenty-two consecutive patients (mean age 65 ± 11.7, 5 females) underwent ablation using the MVG technique on 2 noncontiguous lines in the CTI. Ablation lesions were first applied at the septal aspect of the CTI, targeting only the ventricular (anterior) aspect of the annulus. A line distinctly lateral and noncontiguous to the first was then chosen to target high voltage potentials on the atrial (posterior) aspect of the CTI. RESULTS: Complete CTI block was achieved in all study patients without complication. A mean of 7.8 ± 3.7 ablation lesions were required. Mean ablation time was 401.0 ± 414.5 seconds. CONCLUSION: Two nonoverlapping incomplete lines of ablation in the CTI consistently lead to bidirectional conduction block. This further supports the hypothesis that conduction over the CTI occurs over discrete muscle bundles. These bundles can be targeted individually for ablation without the need to ablate a continuous line over the CTI.


Assuntos
Flutter Atrial/fisiopatologia , Flutter Atrial/cirurgia , Sistema de Condução Cardíaco/fisiopatologia , Sistema de Condução Cardíaco/cirurgia , Condução Nervosa , Valva Tricúspide/fisiopatologia , Valva Tricúspide/cirurgia , Idoso , Medicina Baseada em Evidências , Feminino , Humanos , Masculino , Resultado do Tratamento
20.
J Cardiovasc Electrophysiol ; 24(9): 1015-20, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23691991

RESUMO

BACKGROUND: Targeted mutation site-specific differences have correlated C-loop missense mutations with worse outcomes and increased benefit of beta-blockers in LQT1. This observation has implicated the C-loop region as being mechanistically important in the altered response to sympathetic stimulation known to put patients with LQT1 at risk of syncope and sudden cardiac death. OBJECTIVE: The objective of this study was to determine if there is mutation site-specific response to sympathetic stimulation and beta-blockers using exercise testing. METHODS: This study is a retrospective review of LQT1 patients undergoing exercise testing at 3 academic referral centers. RESULTS: A total of 123 patients (age 28 ± 17 years, 59 male) were studied including 34 patients (28%) with C-loop mutations. There were no significant differences in supine, standing, peak exercise and 1-minute recovery QTc duration between patients with C-loop mutations and patients with alternate mutation sites. In 37 patients that underwent testing on and off beta-blockers, beta-blocker use was associated with a significant reduction in supine, standing and peak exercise QTc. This difference was not seen in the small group of patients (7/37) with C-loop mutations. There was no difference in QTc at 1 and 4 minutes into recovery. CONCLUSIONS: Genetically confirmed LQT1 patients in this study cohort with C-loop mutations did not demonstrate the expected increase in QTc in response to exercise, or resultant response to beta-blocker. The apparent increased risk of cardiac events associated with C-loop mutation sites and the marked benefit received from beta-blocker therapy are not reflected by exercise-mediated effects on QTc in this study population.


Assuntos
Teste de Esforço/métodos , Canal de Potássio KCNQ1/genética , Mutação de Sentido Incorreto/genética , Fenótipo , Síndrome de Romano-Ward/diagnóstico , Síndrome de Romano-Ward/genética , Adolescente , Adulto , Membrana Celular/genética , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Síndrome de Romano-Ward/fisiopatologia , Adulto Jovem
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