The Downside of Right Ventricular Apical Pacing

The right ventricular (RV) apex has been the standard pacing site since the development of implantable pacemaker technology. Although RV pacing was initially only utilized for the treatment of severe bradyarrhythmias usually due to complete heart block, today the indications for and implantation of RV pacing devices is dramatically larger. Recently, the adverse effects of chronic RV apical pacing have been described including an increased risk of heart failure and death. This review details the detrimental effects of RV apical pacing and their shared hemodynamic pathophysiology. In particular, the role of RV apical pacing induced ventricular dyssynchrony is highlighted with a specific focus on differential outcome based upon QRS morphology at implant

Effectiveness of cardiac resynchronization therapy by the frequency of revascularization procedures in ischemic cardiomyopathy patients

Background: It is not known whether the number of revascularizations modifies clinical outcomes in patients with ischemic cardiomyopathy (ICM) implanted with cardiac resynchronization therapy defibrillator (CRT-D) vs. an implantable cardioverter-defibrillator (ICD)-only. Methods: In Multicenter Automatic Defibrillator Implantation Trial-Cardiac Resynchronization Therapy (MADIT-CRT), we evaluated the effect of CRT-D vs. ICD-only on heart failure (HF) or death, on ventricular tachycardia (VT), ventricular fibrillation (VF) or death, and on reverse remodeling in 592 ICM patients with left bundle branch block, by the number of pre-enrollment revascularizations (0, 1 or ≥ 2 revascularizations). Results: There was a risk reduction of HF/death with CRT-D vs. ICD-only in all three sub-groups: ICM with no need for revascularization (HR 0.51 [0.26–1.02]; p = 0.055), ICM with 1 revascularization (HR 0.45 [0.30–0.70]; p < 0.001), and ICM with 2 or more revas­cularizations (HR 0.37 [0.20–0.66]; p < 0.001). Similarly, there was a risk reduction of VT/ /VF/death with CRT-D vs. ICD-only in patients with no need for revascularization (HR 0.55 [0.31–0.99]; p = 0.044); with 1 revascularization (HR 0.77 [0.51–1.18]; p = 0.23); or with ≥ 2 revascularizations (HR 0.63 [0.34–1.17]; p = 0.14). There was a similar degree of left ventricular reverse remodeling in all three subgroups (p > 0.05 for LVESV, LVEDV, and LAV percent change at 1-year follow-up). Conclusions: In ICM patients, CRT-D is associated with a reduction in HF or death and VT/VF or death — irrespective of the frequency of pre-enrollment revascularization procedures — and is accompanied by a similar degree of beneficial left ventricular reverse remodeling.

CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis

A single G protein–coupled receptor (GPCR) can activate multiple signaling cascades based on the binding of different ligands. The biological relevance of this feature in immune regulation has not been evaluated. The chemokine-binding GPCR CXCR3 is preferentially expressed on CD4+ T cells, and canonically binds 3 structurally related chemokines: CXCL9, CXCL10, and CXCL11. Here we have shown that CXCL10/CXCR3 interactions drive effector Th1 polarization via STAT1, STAT4, and STAT5 phosphorylation, while CXCL11/CXCR3 binding induces an immunotolerizing state that is characterized by IL-10hi (Tr1) and IL-4hi (Th2) cells, mediated via p70 kinase/mTOR in STAT3- and STAT6-dependent pathways. CXCL11 binds CXCR3 with a higher affinity than CXCL10, suggesting that CXCL11 has the potential to restrain inflammatory autoimmunity. We generated a CXCL11-Ig fusion molecule and evaluated its use in the EAE model of inflammatory autoimmune disease. Administration of CXCL11-Ig during the first episode of relapsing EAE in SJL/J mice not only led to rapid remission, but also prevented subsequent relapse. Using GFP- expressing effector CD4+ T cells, we observed that successful therapy was associated with reduced accumulation of these cells at the autoimmune site. Finally, we showed that very low doses of CXCL11 rapidly suppress signs of EAE in C57BL/6 mice lacking functional CXCL11

Qual a Contribuiçao do Tilt Training (treinamento postural) na Prevençao da Síncope Vasovagal?

Histórico: A síncope vasovagal é um dos quadros clínicos mais comuns em adultos jovens. Estudos anteriores demonstram a eficiência do tilt training (treinamento postural) no tratamento desse transtorno clínico. Realizou-se um estudo prospectivo e randomizado com o objetivo de avaliar a contribuiçao do tilt training no tratamento de adultos jovens acometidos pela síncope vasovagal. Métodos: Quarenta e seis soldados, 25 dos quais do sexo masculino, média de idade de 19,4 ± 0,8 anos e diagnóstico clínico de síncope vasovagal pelo tilt test, foram divididos aleatoriamente em dois grupos: um grupo controle e outro submetido a tilt training diariamente, por três meses. Nos dois grupos, os participantes foram instruídos a aumentar a ingestao de líquidos e sal e evitar situaçoes indutoras da síncope, tais como permanecer em pé por períodos longos. Resultados: A adesao ao programa de treinamento, caracterizada pela realizaçao de 50% ou mais das sessoes diárias de tilt training, foi de 91% durante o primeiro mês, caindo para 58% nos três meses. Os que realizaram o treinamento apresentaram uma média (distância interquartílica) de 5,0 episódios de síncope (0,5 a 16,0) durante um ano de acompanhamento, enquanto o grupo controle apresentou média de 2,0 episódios (0 a 6,0; P = 0,737). Após a randomizaçao, nao houve diferença significativa no tempo de ocorrência do primeiro episódio de síncope entre os dois grupos: média de 1,0 por mês (0,5 a 2,0) no grupo em tratamento e 0,8 (0,5 a 2,0) no grupo controle (P = 0,336). Conclusoes: A realizaçao diária do tilt training, aliada às modificaçoes de estilo de vida, nao produziu melhora no resultado do tratamento de adultos jovens com síncope vasovagal. Verificou-se ainda a dificuldade de obter boa adesao ao programa de treinamento postural

Qual a Contribuiçao do Tilt Training (treinamento postural) na Prevençao da Síncope Vasovagal?

Histórico: A síncope vasovagal é um dos quadros clínicos mais comuns em adultos jovens. Estudos anteriores demonstram a eficiência do tilt training (treinamento postural) no tratamento desse transtorno clínico. Realizou-se um estudo prospectivo e randomizado com o objetivo de avaliar a contribuiçao do tilt training no tratamento de adultos jovens acometidos pela síncope vasovagal. Métodos: Quarenta e seis soldados, 25 dos quais do sexo masculino, média de idade de 19,4 ± 0,8 anos e diagnóstico clínico de síncope vasovagal pelo tilt test, foram divididos aleatoriamente em dois grupos: um grupo controle e outro submetido a tilt training diariamente, por três meses. Nos dois grupos, os participantes foram instruídos a aumentar a ingestao de líquidos e sal e evitar situaçoes indutoras da síncope, tais como permanecer em pé por períodos longos. Resultados: A adesao ao programa de treinamento, caracterizada pela realizaçao de 50% ou mais das sessoes diárias de tilt training, foi de 91% durante o primeiro mês, caindo para 58% nos três meses. Os que realizaram o treinamento apresentaram uma média (distância interquartílica) de 5,0 episódios de síncope (0,5 a 16,0) durante um ano de acompanhamento, enquanto o grupo controle apresentou média de 2,0 episódios (0 a 6,0; P = 0,737). Após a randomizaçao, nao houve diferença significativa no tempo de ocorrência do primeiro episódio de síncope entre os dois grupos: média de 1,0 por mês (0,5 a 2,0) no grupo em tratamento e 0,8 (0,5 a 2,0) no grupo controle (P = 0,336). Conclusoes: A realizaçao diária do tilt training, aliada às modificaçoes de estilo de vida, nao produziu melhora no resultado do tratamento de adultos jovens com síncope vasovagal. Verificou-se ainda a dificuldade de obter boa adesao ao programa de treinamento postural

The influence of left ventricular ejection fraction on the effectiveness of cardiac resynchronization therapy: MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy).

OBJECTIVES: The goal of this study was to evaluate the influence of left ventricular (LV) lead position on the risk of ventricular tachyarrhythmia in patients undergoing cardiac resynchronization therapy (CRT). BACKGROUND: Left ventricular ejection fraction (LVEF) is a surrogate marker of heart failure (HF) status and associated risk. Data on the effectiveness of cardiac resynchronization therapy with defibrillator (CRT-D) in patients with mild HF and better LVEF are limited. METHODS: In the MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy) study, the echocardiography core laboratory assessed baseline LVEF independent of the enrolling centers and identified a range of LVEFs, including those >30% (i.e., beyond the eligibility criteria). Echocardiographic response with CRT, defined as percent change in left ventricular end-diastolic volume (LVEDV), was analyzed in 3 prespecified LVEF groups: >30%, 26% to 30%, and 30% (in the range of 30.1% to 45.3%); 914 patients (50.5%) with LVEF 26% to 30%; and 199 patients with LVEF 30%: 22.3%; LVEF 26% to 30%: 20.1%; and LVEF 30% (hazard ratio [HR]: = 0.56 [95% confidence interval (CI): 0.39 to 0.82], p = 0.003), LVEF 26% to 30% (HR: 0.67: [95% CI: 0.50 to 0.90], p = 0.007), and LVEF 0.1). CONCLUSIONS: In MADIT-CRT, the clinical benefit of CRT was evident regardless of baseline LVEF, including those with LVEF >30%, whereas the echocardiographic response was increased with increasing LVEF, indicating that CRT might benefit patients with better LVEF. (Multicenter Automatic Defibrillator Implantation With Cardiac Resynchronization Therapy [MADIT-CRT]; NCT00180271)

Risk Factors for Recurrent Syncope and Subsequent Fatal or Near-Fatal Events in Children and Adolescents With Long QT Syndrome

ObjectivesWe aimed to identify risk factors for recurrent syncope in children and adolescents with congenital long QT syndrome (LQTS).BackgroundData regarding risk assessment in LQTS after the occurrence of the first syncope episode are limited.MethodsThe Prentice-Williams-Peterson conditional gap time model was used to identify risk factors for recurrent syncope from birth through age 20 years among 1,648 patients from the International Long QT Syndrome Registry.ResultsMultivariate analysis demonstrated that corrected QT interval (QTc) duration (≥500 ms) was a significant predictor of a first syncope episode (hazard ratio: 2.16), whereas QTc effect was attenuated when the end points of the second, third, and fourth syncope episodes were evaluated (hazard ratios: 1.29, 0.99, 0.90, respectively; p < 0.001 for the null hypothesis that all 4 hazard ratios are identical). A genotype-specific subanalysis showed that during childhood (0 to 12 years), males with LQTS type 1 had the highest rate of a first syncope episode (p = 0.001) but exhibited similar rates of subsequent events as other genotype-sex subsets (p = 0.63). In contrast, in the age range of 13 to 20 years, long QT syndrome type 2 females experienced the highest rate of both first and subsequent syncope events (p < 0.001 and p = 0.01, respectively). Patients who experienced ≥1 episodes of syncope had a 6- to 12-fold (p < 0.001 for all) increase in the risk of subsequent fatal/near-fatal events independently of QTc duration. Beta-blocker therapy was associated with a significant reduction in the risk of recurrent syncope and subsequent fatal/near-fatal events.ConclusionsChildren and adolescents who present after an episode of syncope should be considered to be at a high risk of the development of subsequent syncope episodes and fatal/near-fatal events regardless of QTc duration