Fetal Heart Block: A New Experimental Model to Assess Fetal Pacing

Epicardial fetal pacing via thoracotomy has the potential of being a safer and more reliable procedure to treat congenital complete heart block (CHB) associated with fetal hydrops refractory to medical therapy. To assess the acute electrophysiological characteristics of two ventricular epicardial leads, a new experimental model of fetal heart block induced by cryosurgical ablation of the AV node without the need for fetal cardiac bypass was performed in 12 pregnant ewes at 110–115 days gestation. A modified screw-in lead (1½ turns) was used in six fetal lambs and a stitch-on lead in the other six lambs. CHB was achieved in 100% of the fetal lambs, with no ventricular escape rate noticed in any of the lambs. The acute stimulation thresholds were consistently low for both leads, with lower values for the screw-in lead at pulse duration below 0.9 msec (P < 0.03). Current measured at voltage threshold with pulse width below 0.5 msec was lower for the screw-in lead (P < 0.048). Stimulation resistance, measured during constant-voltage pacing, was not statistically different between the two leads (441.8 ± 13.7 Ω for the screw-in lead vs 480.2 ± 59.2 Ω for the stitch-on lead). No significant differences (P > 0.20) were found in R wave amplitude between the two electrodes. Slew rates were significantly higher in the screw-in group than in the stitch-on group (1.40 ± 0.2 vs 0.62 ± 0.2 V/sec, P = 0.04). This model of CHB is a simple and reproducible method to assess fetal pacing. We find the screw-in electrode to be a better option when fetal pacing is indicated.     

A New Nonfluoroscopic Navigation System to Guide Pulmonary Vein Isolation

Different techniques have been proposed to treat atrial fibrillation (AF) by catheter ablation. This study compares a new three-dimensional (3D) nonfluoroscopic navigation system with conventional fluoroscopy to guide pulmonary vein (PV) isolation. A total of 60 consecutive patients with paroxysmal or persistent AF were randomly assigned to 3D-guided ablation (group 1, n = 30), versus conventional fluoroscopy guidance ablation (group 2, n = 30). Complete PV isolation was achieved in both groups. The mean duration of fluoroscopy exposure (22 ± 8 vs 56 ± 10 minutes), and radiofrequency delivery (5 ± 1 vs 10 ± 3 minutes) were significantly shorter in group 1 than in group 2, P < 0.05 for both comparisons). The mean procedural time in group 1 was longer (225 ± 15 minutes) than in group 2 (156 ± 10 minutes, P < 0.05) due to the learning curve and time spent to generate the 3D maps. Over a mean follow-up of 7 ± 2 months, 6 patients (20%) in group 2 had AF recurrences compared to 3 patients (10%) in group 1 (ns). The new nonfluoroscopic 3D system allows a high-resolution reconstruction of the left atrium and PVs. It significantly reduces the mean radiofrequency delivery and fluoroscopy times as opposed to ablation performed under fluoroscopy guidance.     

Activated Pyrolytic Carbon Tip Pacing Leads: An Alternative to Steroid-Eluting Pacing Leads?

Pyrolytic carbon technology is known for its excellent mechanical properties and electrical conductivity; it is particularly biocompatible and does not require high production costs. The Sorin S100/4 lead is a ventricular passive fixation lead with a hemispherical electrode surface area of 4 mm²; the stimulating tip is made of a graphite core coated by a thin activated pyrolytic carbon layer. We evaluated the acute and medium-term performance of the unipolar version of this lead in 65 patients. At implantation, pacing threshold (at 0.5 ms) was 0.26 ± 0.08 V; pacing impedance (at 5 V and 0.5 ms) was 537 ± 94 Ω and Ft wave amplitude was 15.0 ± 5.5 mV. No lead related complications (dislodgment, perforation, exit block, etc.) occurred in any patient; one patient presented with a wire fracture after 26 months, due to subclavian crush syndrome. Follow-up procedures were performed at 1 week, and 2-, 10-, 18-, and 30-months postimplant. Since the leads were connected to pacemakers from different manufacturers, either voltage or duration thresholds were measured, In approximately two thirds of the patients, with an output of 2.5 V, a mean duration threshold of 0.16 ± 0.13 ms at 1 week, 0.12 ± 0.08 ms at 2 months, 0.11 ± 0.06 ms at 10 months, 0.09 ± 0.06 ms at 18 months, and 0.07 ± 0.03 ms at 30 months, was measured. In the remaining one-third of the patients, a comparable voltage threshold trend was measured. The mean pacing impedance showed a transient drop at 1 week, and then increased to a plateau of about 600 fl reached after 10 months. No sensing defect occurred in any patient. Our data show good acute and intermediate-term results of the S100/4 lead; the early rise in threshold was remarkably blunted. Activated pyrolytic carbon tip leads might therefore be considered as a possible, inexpensive alternative to steroideluting leads.     

Incidence and Significance of Early Recurrences Associated with Different Ablation Strategies for AF: A STAR‐AF Substudy

Early Recurrence in STAR‐AF. Background: Early recurrences of atrial tachyarrhythmias (ERAT) are common after atrial fibrillation (AF) ablation, and predict late recurrences (LR). We sought to determine the impact of different ablation strategies on ERAT and LR. Methods and Results: The STAR‐AF trial randomized 100  patients with paroxysmal or persistent AF to ablation of complex fractionated electrograms (CFAE) alone, pulmonary vein isolation (PVI) alone, or combined PVI + CFAE. Patients were followed for 12  months. ERAT was defined as any recurrence of AF, atrial tachycardia, or flutter (AT/AFL) >30 seconds during the first 3  months of follow‐up. LR was defined as any recurrence of AF/AT/AFL >30 seconds 3–12  months post. Forty‐nine patients experienced ERAT. The index ablation strategy was the only independent predictor of ERAT on multivariate analysis (HR 2.24 PVI vs PVI + CFAE; and HR 2.65 CFAE vs PVI + CFAE). Fifty‐two patients experienced LR. The presence of ERAT (HR 3.23), the use of antiarrhythmic drug (AAD) in the first 3  months postablation (HR 2.85), and the index ablation strategy were independently associated with LR (HR 3.42 PVI vs PVI + CFAE; HR 4.72 CFAE vs PVI + CFAE). Thirty‐five of 49 (71%) patients with ERAT and 17 (33%) of 51  patients without ERAT had LR (P  < 0.0001). Among patients with ERAT, increased left atrium size (HR 1.08), the use of AAD in the first 3  months postablation (HR 2.86) and the index ablation strategy were independently associated with LR (HR 4.77 PVI vs PVI + CFAE; HR 4.45 CFAE vs PVI + CFAE). Conclusion: ERAT is common following AF ablation and is strongly associated with LR. Although CFAE ablation alone results in higher rates of early and LR, the addition of CFAE to PVI results in increased long‐term success without an increase in ERAT. (J Cardiovasc Electrophysiol, Vol. 23, pp. 1295‐1301, December 2012)     

Production and characterization of human monoclonal antibodies against Schistosoma mansoni

We have produced a panel of human monoclonal antibodies (MoAb) from patients infected with Schistosoma mansoni in order to analyse more carefully the human immune response to this helminth infection. This study describes the production, characterization and analysis of these MoAbs. Briefly, peripheral blood mononuclear cells from chronically infected patients were (1) isolated and stimulated with parasite antigens in vitro, (2) positively selected for B-cells on anti-Ig columns, and (3) then transformed with Epstein-Barr virus (EBV). Once EBV cell lines were established, they were selected for anti-S. mansoni antibodies using an ELISA, cloned, retested and then fused with the mouse-human heteromyeloma SHM-D33. In this study, we describe five MoAbs which have different antigenic specificities for life-cycle stages based on ELISA to soluble crude antigen preparations, membrane immunofluorescence on whole intact organisms, and immunofluorescent staining of cryostat frozen sections. The importance of these reagents with regard to the human immune response to S. mansoni is currently being evaluated.     

Immunological Response of Guinea Pigs Sensitized With Homologous Antigens

ABSTRACT: The chemical composition of some “immunologically” pure antigens isolated from guinea pig testis and spermatozoa was correlated with their antigenic behavior. Their immunological responses were compared to select the best materials for a further isolation of chemically pure antigens. The glycoprotein extracted from the spermatozoa (T Gly) has the highest immunological potency and seems to be a T and B, depending antigen, able to induce high humoral and cell responses producing germinal cell damage, testicular lesions, and aspermatogenesis.     

Solid-phase synthesis of chicken vasoactive intestinal peptide by a mild procedure using Nα-9-fluorenylmethyloxycarbonyl amino acids

The octacosapeptide amide corresponding to the entire amino acid sequence of chicken vasoactive peptide (VIP) was assembled on a p-benzyloxybenzylamine resin support using the base-labile 9-fluorenylmethyloxycarbonyl as N^α-protecting group, cleaved by mild acid treatment, and purified by gel-filtration and ion-exchange chromatography. The symmetrical anhydride coupling was employed and monitored by two independent methods, and acetic anhydride termination was incorporated to minimize formation of deletion peptides. The homogeneity of the final product, obtained in 18% yield, was assessed by t.l.c., disc electrophoresis, amino-terminal amino acid analysis, and amino acid analyses of acid and enzyme hydrolysates. The purified chicken VIP was shown to be active on gastric acid secretion and on pancreatic blood flow. Previously reported ring closure of the Asp-Asn unit seemed to be at a minimum, owing to the mild basic and acid treatments.     

Multicenter Clinical Evaluation of a New SSIR Pacemaker

A multicenter clinical evaluation of Sorin Swing 100, a new SSIR pacemaker with a gravimetric sensor, was performed by seven different centers enrolling a total of 89 patients, 56 men and 33 women, mean age 73.1 years, for pacemaker implantion (73 patients) or pacemaker replacement (16 patients). Pacing mode was VVIR in 73 patients and AAIR in 16. The behavior of pacing rate was evaluated 3 months after the implant by performing a 24-hour Holter monitor, an exercise stress test, and tests for the assessment of mechanical external interference (MEI). A physiological behavior of the paced rate was always observed during Holter monitoring. In 52 completely paced patients mean diurnal, nocturnal, and maximal heart rate were, respectively, 74.9 ± 5.7 ppm, 58.1 ± 5.8 ppm, and 113.4 ± 12.7 ppm; a paced rate exceeding 100 ppm was reached on the average 5.6 times/Holter monitor. In all but two patients the sleep rate (55 ppm) was reached during the night or long resting time. During exercise stress test a direct correlation between the increase in pacing rate and the increase in workload was observed; the mean maximal heart rate reached in 49 completely paced patients was, respectively, 102.8 ± 9 ppm in 17 patients who accomplished stage 1, 116.2 ± 13.6 ppm in 28 patients who accomplished stage 2, and 133 ± 6.7 ppm in 10 patients who accomplished stage 3 of the Bruce protocol. MEI testing never increased the pacing rate over the noise rate (10 ppm over the basic rate). In only seven patients the results obtained suggested to change the nominal set up of the pacemaker. Our experience clearly indicates that Swing 100 is an effective, reliable, and easy to use SSIR pacemaker. The availability of the sleep rate allows a more physiological pattern of pacing rate and can lead to significant energy saving.