RESUMEN
BACKGROUND: The Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT) showed a greater benefit with respect to mortality at 5 years among patients who received cardiac-resynchronization therapy (CRT) than among those who received implantable cardioverter-defibrillators (ICDs). However, the effect of CRT on long-term survival is not known. METHODS: We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more (or a paced QRS duration of 200 msec or more) to receive either an ICD alone or a CRT defibrillator (CRT-D). We assessed long-term outcomes among patients at the eight highest-enrolling participating sites. The primary outcome was death from any cause; the secondary outcome was a composite of death from any cause, heart transplantation, or implantation of a ventricular assist device. RESULTS: The trial enrolled 1798 patients, of whom 1050 were included in the long-term survival trial; the median duration of follow-up for the 1050 patients was 7.7 years (interquartile range, 3.9 to 12.8), and the median duration of follow-up for those who survived was 13.9 years (interquartile range, 12.8 to 15.7). Death occurred in 405 of 530 patients (76.4%) assigned to the ICD group and in 370 of 520 patients (71.2%) assigned to the CRT-D group. The time until death appeared to be longer for those assigned to receive a CRT-D than for those assigned to receive an ICD (acceleration factor, 0.80; 95% confidence interval, 0.69 to 0.92; P = 0.002). A secondary-outcome event occurred in 412 patients (77.7%) in the ICD group and in 392 (75.4%) in the CRT-D group. CONCLUSIONS: Among patients with a reduced ejection fraction, a widened QRS complex, and NYHA class II or III heart failure, the survival benefit associated with receipt of a CRT-D as compared with ICD appeared to be sustained during a median of nearly 14 years of follow-up. (RAFT ClinicalTrials.gov number, NCT00251251.).
Asunto(s)
Terapia de Resincronización Cardíaca , Desfibriladores Implantables , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Estimación de Kaplan-Meier , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular Izquierda , Electrocardiografía , Estudios de Seguimiento , Factores de TiempoRESUMEN
BACKGROUND: Recurrent ventricular tachycardia (VT) in patients with prior myocardial infarction is associated with adverse quality of life and clinical outcomes, despite the presence of implanted defibrillators (ICDs). Suppression of recurrent VT can be accomplished with antiarrhythmic drug therapy or catheter ablation. The Ventricular Tachycardia Antiarrhythmics or Ablation In Structural Heart Disease 2 (VANISH2) trial is designed to determine whether ablation is superior to antiarrhythmic drug therapy as first line therapy for patients with ischemic cardiomyopathy and VT. METHODS: The VANISH2 trial enrolls patients with prior myocardial infarction and VT (with one of: ≥1 ICD shock; ≥3 episodes treated with antitachycardia pacing (ATP) and symptoms; ≥5 episodes treated with ATP regardless of symptoms; ≥3 episodes within 24 hours; or sustained VT treated with electrical cardioversion or pharmacologic conversion). Enrolled patients are classified as either sotalol-eligible, or amiodarone-eligible, and then are randomized to either catheter ablation or to that antiarrhythmic drug therapy, with randomization stratified by drug-eligibility group. Drug therapy, catheter ablation procedures and ICD programming are standardized. All patients will be followed until two years after randomization. The primary endpoint is a composite of mortality at any time, appropriate ICD shock after 14 days, VT storm after 14 days, and treated sustained VT below detection of the ICD after 14 days. The outcomes will be analyzed according to the intention-to-treat principle using survival analysis techniques RESULTS: The results of the VANISH2 trial are intended to provide data to support clinical decisions on how to suppress VT for patients with prior myocardial infarction. CLINICALTRIALS: gov registration NCT02830360.
Asunto(s)
Antiarrítmicos , Cardiomiopatías , Ablación por Catéter , Isquemia Miocárdica , Taquicardia Ventricular , Humanos , Taquicardia Ventricular/terapia , Antiarrítmicos/uso terapéutico , Ablación por Catéter/métodos , Cardiomiopatías/complicaciones , Cardiomiopatías/terapia , Isquemia Miocárdica/complicaciones , Masculino , Femenino , Desfibriladores Implantables , Persona de Mediana Edad , Amiodarona/uso terapéutico , Resultado del Tratamiento , Sotalol/uso terapéutico , Terapia CombinadaRESUMEN
BACKGROUND: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and can be challenging to treat. Pharmacologically based rhythm control of AF has not proven to be superior to rate control. Ablation-based rhythm control was compared with rate control to evaluate if clinical outcomes in patients with HF and AF could be improved. METHODS: This was a multicenter, open-label trial with blinded outcome evaluation using a central adjudication committee. Patients with high-burden paroxysmal (>4 episodes in 6 months) or persistent (duration <3 years) AF, New York Heart Association class II to III HF, and elevated NT-proBNP (N-terminal pro brain natriuretic peptide) were randomly assigned to ablation-based rhythm control or rate control. The primary outcome was a composite of all-cause mortality and all HF events, with a minimum follow-up of 2 years. Secondary outcomes included left ventricular ejection fraction, 6-minute walk test, and NT-proBNP. Quality of life was measured using the Minnesota Living With Heart Failure Questionnaire and the AF Effect on Quality of Life. The primary analysis was time-to-event using Cox proportional hazards modeling. The trial was stopped early because of a determination of apparent futility by the Data Safety Monitoring Committee. RESULTS: From December 1, 2011, to January 20, 2018, 411 patients were randomly assigned to ablation-based rhythm control (n=214) or rate control (n=197). The primary outcome occurred in 50 (23.4%) patients in the ablation-based rhythm-control group and 64 (32.5%) patients in the rate-control group (hazard ratio, 0.71 [95% CI, 0.49-1.03]; P=0.066). Left ventricular ejection fraction increased in the ablation-based group (10.1±1.2% versus 3.8±1.2%, P=0.017), 6-minute walk distance improved (44.9±9.1 m versus 27.5±9.7 m, P=0.025), and NT-proBNP demonstrated a decrease (mean change -77.1% versus -39.2%, P<0.0001). Minnesota Living With Heart Failure Questionnaire demonstrated greater improvement in the ablation-based rhythm-control group (least-squares mean difference of -5.4 [95% CI, -10.5 to -0.3]; P=0.0036), as did the AF Effect on Quality of Life score (least-squares mean difference of 6.2 [95% CI, 1.7-10.7]; P=0.0005). Serious adverse events were observed in 50% of patients in both treatment groups. CONCLUSIONS: In patients with high-burden AF and HF, there was no statistical difference in all-cause mortality or HF events with ablation-based rhythm control versus rate control; however, there was a nonsignificant trend for improved outcomes with ablation-based rhythm control over rate control. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01420393.
Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Insuficiencia Cardíaca , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/cirugía , Humanos , Calidad de Vida , Volumen Sistólico , Resultado del Tratamiento , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Achieving bi-directional conduction block, as assessed by differential pacing and change in activation along tricuspid annulus (TA), across the cavo-tricuspid isthmus (CTI), is considered a satisfactory end point during catheter ablation of atrial flutter (AFL). AIM: To assess role of subclinical conduction by observing polarity reversal of local bipolar signals from RS to QR pattern lateral to the line of ablation, in predicting recurrence of CTI dependant AFL after ablation in patients with bidirectional conduction block. METHOD AND RESULTS: Of 683 patients undergoing ablation of CTI dependent AFL, 73 (10.6%) patients underwent redo flutter ablation and were evaluated further. The mean age was 60.8 years and 51% were males. Evidence of bidirectional block by differential pacing and change is activation along multipolar catheter and reversal of local bipolar signals from RS to QR pattern lateral to the line of ablation, during the 1st and subsequent procedure, were studied. 60% patients had confirmed bidirectional block of which 71% had lack of voltage reversal, at the end of 1st procedure. All patients with bidirectional block with lack of reversal of bipolar signals, after the first procedure had recurrence of AFL whereas only 3/11 (27%) people with bidirectional block and with absence of subclinical conduction had recurrence of AFL. CONCLUSION: Achieving bidirectional conduction block is not sufficient to prevent recurrence of AFL after CTI ablation. Reversal of local bipolar signals, from RS to QR pattern along with achieving bidirectional conduction delay would reduce recurrence of AFL, post ablation.
Asunto(s)
Aleteo Atrial , Ablación por Catéter , Bloqueo Cardíaco , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aleteo Atrial/cirugía , Ablación por Catéter/métodos , Frecuencia Cardíaca , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Analgesia , Bloqueo Nervioso , Humanos , Proyectos Piloto , Bloqueo Nervioso/métodos , Manejo del Dolor , Anestésicos Locales/uso terapéuticoRESUMEN
PURPOSE OF REVIEW: Heart failure (HF) and atrial fibrillation (AF) frequently co-exist, with the prevalence of AF increasing in patients with more advanced HF symptoms. When present, AF increases morbidity and mortality in patients with HF. The purpose of this review is to examine emerging evidence addressing the value of restoration and maintenance of sinus rhythm in patients with HF. RECENT FINDINGS: Earlier trials comparing a rhythm control strategy with antiarrhythmic drugs have failed to demonstrate benefit in patients with HF and reduced ejection fraction. More recent trials, including the recently published RAFT-AF, utilizing catheter ablation for rhythm control, have shown greater promise, possibly due to reduced medication-related side effects and higher efficacy in maintaining sinus rhythm. A strategy of sinus rhythm maintenance with catheter ablation appears to improve mortality, reduce HF events and improve quality of life in patients with AF and HF.
Asunto(s)
Fibrilación Atrial , Ablación por Catéter , Insuficiencia Cardíaca , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Humanos , Calidad de Vida , Resultado del TratamientoRESUMEN
BACKGROUND: Advanced generation ablation technologies have been developed to achieve more effective pulmonary vein isolation (PVI) and minimize arrhythmia recurrence after atrial fibrillation (AF) ablation. METHODS: We randomly assigned 346 patients with drug-refractory paroxysmal AF to contact force-guided radiofrequency ablation (CF-RF; n=115), 4-minute cryoballoon ablation (Cryo-4; n=115), or 2-minute cryoballoon ablation (Cryo-2; n=116). Follow-up was 12 months. The primary outcome was time to first documented recurrence of symptomatic or asymptomatic atrial tachyarrhythmia (AF, atrial flutter, or atrial tachycardia) between days 91 and 365 after ablation or a repeat ablation procedure at any time. Secondary end points included freedom from symptomatic arrhythmia and AF burden. All patients received an implantable loop recorder. RESULTS: One-year freedom from atrial tachyarrhythmia defined by continuous rhythm monitoring was 53.9%, 52.2%, and 51.7% with CF-RF, Cryo-4, and Cryo-2, respectively (P=0.87). One-year freedom from symptomatic atrial tachyarrhythmia defined by continuous rhythm monitoring was 79.1%, 78.2%, and 73.3% with CF-RF, Cryo-4, and Cryo-2, respectively (P=0.26). Compared with the monitoring period before ablation, AF burden was reduced by a median of 99.3% (interquartile range, 67.8%-100.0%) with CF-RF, 99.9% (interquartile range, 65.3%-100.0%) with Cryo-4, and 98.4% (interquartile range, 56.2%-100.0%) with Cryo-2 (P=0.36). Serious adverse events occurred in 3 patients (2.6%) in the CF-RF group, 6 patients (5.3%) in the Cryo-4 group, and 7 patients (6.0%) in the Cryo-2 group, with no significant difference between groups (P=0.24). The CF-RF group had a significantly longer procedure duration but significantly shorter fluoroscopy exposure (P<0.001 vs cryoballoon groups). CONCLUSIONS: In this multicenter, randomized, single-blinded trial, CF-RF and 2 different regimens of cryoballoon ablation resulted in no difference in 1-year efficacy, which was 53% by time to first recurrence but >98% burden reduction as assessed by continuous cardiac rhythm monitoring. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01913522.
Asunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter , Criocirugía , Anciano , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/fisiopatología , Femenino , Fluoroscopía , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
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.).
Asunto(s)
Amiodarona/administración & dosificación , Antiarrítmicos/administración & dosificación , Cardiomiopatías/complicaciones , Ablación por Catéter , Taquicardia Ventricular/terapia , Anciano , Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Cardiomiopatías/mortalidad , Ablación por Catéter/efectos adversos , Desfibriladores Implantables , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/complicaciones , Recurrencia , Prevención Secundaria , Taquicardia Ventricular/tratamiento farmacológicoRESUMEN
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.
Asunto(s)
Fibrilación Atrial/diagnóstico , Fibrilación Atrial/terapia , Determinación de la Presión Sanguínea/tendencias , Presión Sanguínea/fisiología , Ablación por Catéter/tendencias , Anciano , Fibrilación Atrial/fisiopatología , Determinación de la Presión Sanguínea/métodos , Ablación por Catéter/métodos , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del TratamientoRESUMEN
BACKGROUND: Catheter ablation (CA) is an established therapy for atrial fibrillation (AF). Studies regarding long-term real-world outcomes post-CA have inconsistently accounted for oral anticoagulation (OAC). OBJECTIVES: To describe patterns of OAC use post-CA and to compare the OAC-adjusted long-term risk of stroke and major bleeding in AF patients with and without CA. METHODS: A population-based cohort of AF patients was constructed in Quebec and Ontario, Canada (1999-2014). Propensity score matching was performed to determine the incidence rates of stroke and major bleeding among those undergoing CA, adjusted for time-dependent OAC use. RESULTS: From the entire cohort, 6391 patients were identified as having undergone CA as compared to 482 977 patients who did not. Of these, 1240 patients with government medical insurance undergoing CA were matched with 2427 patients without CA. Post-CA, 78%, 65%, and 61% remained on an OAC at 1, 2, and 5 years, while 75%, 71%, and 68% of patients not undergoing CA were on OACs at 1, 2, and 5 years. At follow-up, there was no statistically significant difference for stroke (adjusted hazard ratio [HR], 0.88; 95% CI, 0.63 to 1.21) or major bleeding (adjusted HR, 0.88; 95% CI, 0.73 to 1.06). CONCLUSION: No evidence was found that CA significantly decreases the risk of stroke or major bleeding when adjusting for OAC use over time. It may be prudent to continue anticoagulation post-CA based on patient-risk profile until randomized trials demonstrate both reduced stroke rates with CA, and improved safety (balancing stroke and bleeding risk) with OAC discontinuation post-CA.
Asunto(s)
Anticoagulantes/administración & dosificación , Fibrilación Atrial/terapia , Ablación por Catéter , Hemorragia/epidemiología , Accidente Cerebrovascular/prevención & control , Administración Oral , Anciano , Anticoagulantes/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/epidemiología , Ablación por Catéter/efectos adversos , Toma de Decisiones Clínicas , Bases de Datos Factuales , Esquema de Medicación , Femenino , Hemorragia/inducido químicamente , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Ontario/epidemiología , Quebec/epidemiología , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Ablación por Catéter , Calidad de Vida , Taquicardia Ventricular/terapia , Anciano , Amiodarona/efectos adversos , Antiarrítmicos/efectos adversos , Ansiedad/diagnóstico , Ansiedad/prevención & control , Ansiedad/psicología , Australia , Ablación por Catéter/efectos adversos , Emociones , Europa (Continente) , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , América del Norte , Conducta Social , Encuestas y Cuestionarios , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Taquicardia Ventricular/psicología , Factores de Tiempo , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Venas Pulmonares/cirugía , Anciano , Fibrilación Atrial/diagnóstico por imagen , Fibrilación Atrial/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Venas Pulmonares/diagnóstico por imagen , RecurrenciaRESUMEN
BACKGROUND: Stimulation of phospholipase Cß (PLCß) by the activated α-subunit of Gq (Gαq) constitutes a major signaling pathway for cellular regulation, and structural studies have recently revealed the molecular interactions between PLCß and Gαq. Yet, most of the PLCß-interacting residues identified on Gαq are not unique to members of the Gαq family. Molecular modeling predicts that the core PLCß-interacting residues located on the switch regions of Gαq are similarly positioned in Gαz which does not stimulate PLCß. Using wild-type and constitutively active chimeras constructed between Gαz and Gα14, a member of the Gαq family, we examined if the PLCß-interacting residues identified in Gαq are indeed essential. RESULTS: Four chimeras with the core PLCß-interacting residues composed of Gαz sequences were capable of binding PLCß2 and stimulating the formation of inositol trisphosphate. Surprisingly, all chimeras with a Gαz N-terminal half failed to functionally associate with PLCß2, despite the fact that many of them contained the core PLCß-interacting residues from Gα14. Further analyses revealed that the non-PLCß2 interacting chimeras were capable of interacting with other effector molecules such as adenylyl cyclase and tetratricopeptide repeat 1, indicating that they could adopt a GTP-bound active conformation. CONCLUSION: Collectively, our study suggests that the previously identified PLCß-interacting residues are insufficient to ensure productive interaction of Gα14 with PLCß, while an intact N-terminal half of Gα14 is apparently required for PLCß interaction.
Asunto(s)
Subunidades alfa de la Proteína de Unión al GTP Gq-G11/química , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/metabolismo , Fosfolipasa C beta/metabolismo , Subunidades alfa de la Proteína de Unión al GTP Gq-G11/genética , Células HEK293 , Humanos , Modelos Moleculares , Simulación del Acoplamiento Molecular , Unión Proteica , Estructura Secundaria de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMEN
PURPOSE OF REVIEW: Heart failure and atrial fibrillation are both common cardiac conditions that share multiple risk factors. Heart failure is a risk for atrial fibrillation and atrial fibrillation is a risk for heart failure. The need to understand the interplay between these two cardiac conditions and the effectiveness of management options becomes increasingly relevant. RECENT FINDINGS: Recent studies have focused on the prognostic nature of atrial fibrillation and heart failure, the questionable utility of digoxin and beta-blocker therapy when heart failure and atrial fibrillation coexist, and the efficacy of cardiac ablation and resynchronization therapy with concomitant heart failure and atrial fibrillation. SUMMARY: The predominant questions that require further attention with respect to atrial fibrillation and heart failure are whether catheter ablation and rhythm control offers benefit in a high-risk heart failure population with respect to mortality or heart failure reduction, and whether cardiac resynchronization therapy implantation truly benefits the subgroup of candidate patients with permanent atrial fibrillation. Large randomized multicentre studies are currently ongoing to address these important questions.
RESUMEN
AIMS: Cardiac resynchronization therapy (CRT) with or without a defibrillator reduces morbidity and mortality in selected patients with heart failure (HF) but response can be variable. We sought to identify pre-implantation variables that predict the response to CRT in a meta-analysis using individual patient-data. METHODS AND RESULTS: An individual patient meta-analysis of five randomized trials, funded by Medtronic, comparing CRT either with no active device or with a defibrillator was conducted, including the following baseline variables: age, sex, New York Heart Association class, aetiology, QRS morphology, QRS duration, left ventricular ejection fraction (LVEF), and systolic blood pressure. Outcomes were all-cause mortality and first hospitalization for HF or death. Of 3782 patients in sinus rhythm, median (inter-quartile range) age was 66 (58-73) years, QRS duration was 160 (146-176) ms, LVEF was 24 (20-28)%, and 78% had left bundle branch block. A multivariable model suggested that only QRS duration predicted the magnitude of the effect of CRT on outcomes. Further analysis produced estimated hazard ratios for the effect of CRT on all-cause mortality and on the composite of first hospitalization for HF or death that suggested increasing benefit with increasing QRS duration, the 95% confidence bounds excluding 1.0 at â¼140 ms for each endpoint, suggesting a high probability of substantial benefit from CRT when QRS duration exceeds this value. CONCLUSION: QRS duration is a powerful predictor of the effects of CRT on morbidity and mortality in patients with symptomatic HF and left ventricular systolic dysfunction who are in sinus rhythm. QRS morphology did not provide additional information about clinical response. CLINICALTRIALSGOV NUMBERS: NCT00170300, NCT00271154, NCT00251251.
Asunto(s)
Bloqueo de Rama/terapia , Terapia de Resincronización Cardíaca/métodos , Insuficiencia Cardíaca/terapia , Anciano , Bloqueo de Rama/fisiopatología , Causas de Muerte , Desfibriladores Implantables , Femenino , Insuficiencia Cardíaca/fisiopatología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados Aleatorios como Asunto , Volumen Sistólico/fisiología , Resultado del Tratamiento , Disfunción Ventricular Izquierda/fisiopatología , Disfunción Ventricular Izquierda/terapiaRESUMEN
Importance: Catheter ablation is associated with reduced heart failure (HF) hospitalization and death in select patients with atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). However, the benefit in patients with HF with preserved ejection fraction (HFpEF) is uncertain. Objective: To investigate whether catheter ablation for AF is associated with reduced HF-related outcomes according to HF phenotype. Data Source: A systematic search of MEDLINE, Embase, and Cochrane Central was conducted among studies published from inception to September 2023. Study Selection: Parallel-group randomized clinical trials (RCTs) comparing catheter ablation with conventional rate or rhythm control therapies in patients with HF, New York Heart Association functional class II or greater, and a history of paroxysmal or persistent AF were included. Pairs of independent reviewers screened 7531 titles and abstracts, of which 12 RCTs and 4 substudies met selection criteria. Data Extraction and Synthesis: Data were abstracted in duplicate according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Pooled effect estimates were calculated using random-effects Mantel-Haenszel models. Interaction P values were used to test for subgroup differences. Main Outcomes and Measures: The primary outcome was HF events, defined as HF hospitalization, clinically significant worsening of HF, or unscheduled visits to a clinician for treatment intensification. Secondary outcomes included cardiovascular and all-cause mortality. Results: A total of 12 RCTs with 2465 participants (mean [SD] age, 65.3 [9.7] years; 658 females [26.7%]) were included; there were 1552 participants with HFrEF and 913 participants with HFpEF. Compared with conventional rate or rhythm control, catheter ablation was associated with reduced risk of HF events in HFrEF (risk ratio [RR], 0.59; 95% CI, 0.48-0.72), while there was no benefit in patients with HFpEF (RR, 0.93; 95% CI, 0.65-1.32) (P for interaction = .03). Catheter ablation was associated with reduced risk of cardiovascular death compared with conventional therapies in HFrEF (RR, 0.49; 95% CI, 0.34-0.70) but a differential association was not detected in HFpEF (RR, 0.91; 95% CI, 0.46-1.79) (P for interaction = .12). Similarly, no difference in the association of catheter ablation with all-cause mortality was found between HFrEF (RR vs conventional therapies, 0.63; 95% CI, 0.47-0.86) and HFpEF (RR vs conventional therapies, 0.95; 95% CI, 0.39-2.30) groups (P for interaction = .39). Conclusions and Relevance: This study found that catheter ablation for AF was associated with reduced risk of HF events in patients with HFrEF but had limited or no benefit in HFpEF. Results from ongoing trials may further elucidate the role of catheter ablation for AF in HFpEF.