Electrophysiological markers predicting impeding AV‐block during ablation of atrioventricular nodal reentry tachycardia

1 Background

Radiofrequency (RF) ablation of the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT) is occasionally complicated with atrioventricular block (AVB) often predicted by junctional beats (JB) with loss of ventriculo‐atrial (VA) conduction.

2 Methods

We analyzed retrospectively 153 patients undergoing ablation of SP for typical AVNRT. Patients were divided into two age groups: 127 ≤ 70 years and 26 > 70 years. We analyzed the interval between the atrial electrogram in the His‐bundle position and the distal ablation catheter [A(H)‐A(RFd)] and between the distal ablation catheter and the proximal coronary sinus catheter [A(RFd)‐A(CS)] before RF applications with and without JB. We evaluated if these intervals can be used as predictors of JB incidence and also of JB with loss of VA conduction. We also assessed if age influences the risk of loss of VA conduction.

3 Results

The A(H)‐A(RFd) and A(RFd)‐A(CS) intervals were significantly shorter in RF applications causing JB than those without JB (33 ± 11 ms vs 39 ± 9 ms, P < 0.001, 14 ± 9 ms vs 20 ± 7 ms, P < 0.001, respectively). The A(H)‐A(RFd) and A(RFd)‐A(CS) intervals were also significantly shorter in RFs causing JB with VA block than those with VA conduction (29 ± 11 ms vs 35 ± 11 ms, P < 0.001, 8 ± 8 ms vs 17 ± 8 ms, P < 0.001, respectively). Patients > 70 years had shorter intervals (36 ± 11 ms vs 29 ± 8 ms, P  =  0.012, 17 ± 8 ms vs 13 ± 7 ms, P  =  0.027, respectively), while VA block was more common in this age group.

4 Conclusions

The A(H)‐A(RFd) and A(RFd)‐A(CS) intervals can be used as markers for predicting JB occurrence as well as impending AVB. JB with loss of VA conduction occur more often in older patients possibly due to a higher position of SP.     

Current and Emerging Treatment Modalities for Leber’s Hereditary Optic Neuropathy: A Review of the Literature

Introduction

The purpose of this review is to present the current and emerging treatment alternatives for Leber’s hereditary optic neuropathy (LHON), emphasizing the most recent use of idebenone and stem cells or gene therapy.

Methods

A comprehensive literature review was performed at the PubMed database regarding the various treatment modalities for LHON.

Results

Treatment modalities for LHON include nutritional supplements, activators of mitochondrial biogenesis, brimonidine, and symptomatic and supportive treatment, but nowadays attention is being paid to idebenone and gene therapy or stem cells.

Conclusion

The treatment of LHON remains challenging, given the nature of the disease and its prognosis.

     

Sensitivity and specificity for primary Sjögren's syndrome of IgA and IgG anti-alpha-fodrin antibodies detected by ELISA

OBJECTIVE: To investigate the sensitivity and specificity of anti-alpha-fodrin antibodies in patients with primary Sj?gren's syndrome (pSS). METHODS: IgA and IgG anti-alpha-fodrin antibodies were measured in the sera of 80 patients with pSS, 60 blood donors matched for age and sex, 50 patients with systemic lupus erythematosus (SLE), 30 with rheumatoid arthritis (RA), 20 with systemic sclerosis (SSc), and 10 with polymyositis or dermatomyositis (PM/DM) by an ELISA method employing recombinant human alpha-fodrin as antigen. RESULTS: The sensitivity of IgA and IgG anti-alpha-fodrin antibodies for pSS was 32.50% and 21.25%, respectively. When the prevalence of these antibodies in patients with SLE, RA, SSc, and PM/DM was evaluated, we observed specificity of these antibodies of 68.18% and 79.09%, respectively. The sensitivity and specificity for pSS of the combined determination of IgA and IgG anti-alpha-fodrin antibodies were 40% and 58.18%, respectively. CONCLUSION: The prevalences of IgA and IgG anti-alpha-fodrin antibodies in our patients with pSS and other chronic autoimmune diseases have induced us to doubt their use as diagnostic markers of pSS.     

Occidental beriberi and sudden death

Beriberi, thiamine deficiency, is classified as "dry" (neurologic) or "wet" (cardiovascular) and may be mixed. Deficiency of this vitamin may be nutritional or secondary to alcohol intoxication. In Western societies (occidental beriberi), the disorder is more commonly observed in long-term alcohol abusers. However, it may go undiagnosed because it is relatively uncommon. In some cases (acute cardiovascular beriberi), early treatment with parenteral vitamin B1 is required to prevent the development of low-output state and sudden death. We report a case of occidental beriberi with fatal outcome despite therapy.     

Novel approach to discriminate left bundle branch block from nonspecific intraventricular conduction delay using pacing-induced functional left bundle branch block

Purpose

Left bundle branch block (LBBB) has a predictive value for response to cardiac resynchronization therapy as reported by Zareba et al. (Circulation 123(10):1061–1072, 2011). However, based on ECG criteria, the discrimination between complete LBBB and nonspecific intraventricular conduction delay is challenging. We tested the hypothesis that discrimination can be performed using standard electrophysiological catheters and a simple stimulation protocol.

Methods

Fifty-nine patients were analyzed retrospectively. Patients were divided into groups of narrow QRS (n?=?20), wide QRS of right bundle branch block (RBBB) morphology (n?=?14), and wide QRS of LBBB morphology (n?=?25). Using a diagnostic catheter placed in the coronary sinus, left ventricular activation was assessed during intrinsic conduction as well as during right ventricular (RV) stimulation.

Results

In patients with narrow QRS and RBBB, the Q-LV/QRS ratio was 0.43?±?0.013 (n?=?20) and 0.41?±?0.026 (n?=?14), respectively. In patients with LBBB morphology, the Q-LV/QRS split up into a group of patients with normal (0.43?±?0.022, n?=?7) and a group with delayed left ventricular activation (0.75?±?0.016, n?=?18). By direct comparison of the Q-LV/QRS ratio during intrinsic conduction with the Q-LV/QRS ratio during RV pacing leading to a functional LBBB, a clear distinction between a group of “true LBBB” and another group of “apparent LBBB”/nonspecific intraventricular conduction delay (NICD) could be generated.

Conclusions

We present a novel and practical method that might facilitate discrimination between patients with apparent LBBB and true LBBB by comparing Q-LV/QRS ratios during intrinsic activation and during RV stimulation. Although this method can already be directly applied, validation by 3D electrical mapping and prospective correlation to cardiac resynchronization therapy (CRT) response will be required for further translation into clinical practice.

     

Respiratory virus infections in transplant recipients after reduced-intensity conditioning with Campath-1H: high incidence but low mortality

Respiratory virus infections can cause serious morbidity and mortality after conventional allogeneic stem cell transplantation. However, the incidence and outcome of these infections after reduced intensity conditioning has not been reported. Between 1997 and 2001, 35 episodes of respiratory virus infections were noted in 25 of 83 transplant recipients conditioned with fludarabine, melphalan and Campath-1H, and 80% of them received early antiviral therapy. Parainfluenza virus (PIV) 3 was the commonest isolate (45.7%) followed by respiratory syncytial virus (37%). Patients with myeloma were more susceptible to these infections [odds ratio (OR) 4.1, P = 0.01] which were often recurrent in patients with severe acute or chronic graft-versus-host disease (GVHD) (OR 10.6, P = 0.03). Infection within the first 100 d (OR 5.0, P = 0.05) and PIV 3 (OR 9.2, P = 0.01) isolation were risk factors for developing lower respiratory infection. Although more than half of the episodes progressed to lower respiratory infection, the mortality was only 8%. This could have been due to early initiation of antiviral therapy, but the attenuation of pulmonary damage due to the reduced-intensity conditioning, low incidence of GVHD and, paradoxically, the low CD4+ T-cell subset in this setting might also have been contributory factors.     

Poly(ethylene glycol)-block-cationic polylactide nanocomplexes of differing charge density for gene delivery

Representing a new type of biodegradable cationic block copolymer, well-defined poly(ethylene glycol)-block-cationic polylactides (PEG-b-CPLAs) with tertiary amine-based cationic groups were synthesized by thiol-ene functionalization of an allyl-functionalized diblock precursor. Subsequently the application of PEG-b-CPLAs as biodegradable vectors for the delivery of plasmid DNAs (pDNAs) was investigated. Via the formation of PEG-b-CPLA:pDNA nanocomplexes by spontaneous electrostatic interaction, pDNAs encoding luciferase or enhanced green fluorescent protein were successfully delivered to four physiologically distinct cell lines (including macrophage, fibroblast, epithelial, and stem cell). Formulated nanocomplexes demonstrated high levels of transfection with low levels of cytotoxicity and hemolysis when compared to a positive control. Biophysical characterization of charge densities of nanocomplexes at various polymer:pDNA weight ratios revealed a positive correlation between surface charge and gene delivery. Nanocomplexes with high surface charge densities were utilized in an in vitro serum gene delivery inhibition assay, and effective gene delivery was observed despite high levels of serum. Overall, these results help to elucidate the influence of charge, size, and PEGylation of nanocomplexes upon the delivery of nucleic acids in physiologically relevant conditions.