Is Atrial Sensing of Ventricular Far-Field Signals Important in Single-Lead VDD Pacing?

In single-lead VDD pacing the atrial sensitivity frequently is programmed to sensitive values. Atrial sensing of ventricular far-field signals should be reduced by differential atrial sensing. The aim of the study was to evaluate the effectiveness of this approach. Methods: The study included 10 patients with a single-lead VDD pacemaker (Thera 8948, Lead 5032). The atrial sensitivity was set to its most sensitive value of 0.18 mV and the telemetered intraatrial EGM was continuously recorded. After atrial tracked ventricular pacing, VVI pacing was performed with pacing rates from 100 to 160 beats/min in steps of 10 beats/min and up to 165 beats/min. The peak-to-peak amplitudes of P waves (P) and ventricular far-field signals (VFFS) were measured from the recordings. The ratio P/VFFS that defines the atrial signal-to-noise ratio was calculated, and the time from stimulus to maximum of the far-field signals amplitude (Tmax) was measured. Results: P measured 0.98 ± 0.76 mV. A VFFS was visible in the atrial channel in all patients with an amplitude of 0.45 ± 0.25 mV (range 0.01–1.0 mV), independent of the pacing rate. The ratio P/VFFS was 3.9 ± 4.2 (range 0.9–21.0). Tmax measured 99.4 ± 15.2 ms during sinus rhythm. A rate dependent shortening of Tmax to 92.7 ± 11.2 ms at 140 beats/min was observed (P = 0.001). At rates above 140 beats/min no further shortening occurred. Conclusion: Ventricular far-field signals are measurable in the atrial channel of VDD systems and may reach considerable amplitudes, which are not rate dependent. Although differential sensing provides favorable P waves to ventricular far-field signal ratios, refractory periods are needed to avoid far-field sensing. The rate dependent shortening of the ventricular signal can be detected in the atrial channel in VDD pacing.     

Cryoablation at Growing Myocardium: No Evidence of Coronary Artery Obstruction or Intimal Plaque Formation Early and Late after Energy Application

Background: Animal studies and clinical observations have demonstrated that radiofrequency current application at growing myocardium may result in coronary artery obstruction. Recently, cryoenergy has emerged as an effective alternative to radiofrequency ablation of arrhythmogenic substrates in pediatric patients. Up to now, there has been a lack of experimental data concerning the effects of cryoenergy application at growing myocardium.
Methods: During general anesthesia, selective coronary angiography of the right and left coronary artery was performed in 10 piglets (age: 6 weeks, body weight: 14–18 kg). Subsequently, cryoenergy was delivered at −75°C for 4 minutes using a 7-F catheter with a 6-mm-tip electrode at the atrial aspect of the tricuspid valve annulus in a posterior and lateral position. Additional cryoenergy lesions were induced via a retrograde approach at the lateral and posterior atrial and ventricular aspect of the mitral valve annulus, respectively. Five animals were restudied after 48 hours by coronary angiography and intracoronary ultrasound and in the remaining five piglets after 3 and 6 months, respectively.
Results: Selective coronary angiography and intracoronary ultrasound studies did not demonstrate any evidence for coronary artery obstruction after 48 hours, 3 months, or 6 months after cryoenergy application. In addition, histological examinations of the cryolesions after 48 hours and after 6 months did not demonstrate any intimal proliferations of the coronary arteries, respectively.
Conclusions: By means of the present study, we did not observe any affection of the coronary arteries after cryoenergy application at growing myocardium in young piglets.     

Bones in the heart skeleton of the otter (Lutra lutra)

In most mammalian species the cardiac skeleton is composed of coarse collagen fibres, fibrocartilage, and pieces of hyaline cartilage. Bone, the os cordis, is a regular constituent of the ruminant heart. The cardiac skeleton of the otter ( Lutra lutra ) has not previously been described. The skeleton in 30 otter hearts was studied by x-ray analysis and light microscopy. Serial sections were cut parallel to the atrioventricular plane and histochemical staining methods were performed to identify connective tissue fibres, glycosaminoglycans, mineral deposits, and bone. Age and sex of the animals under investigation were considered. The otter heart skeleton was composed of coarse collagen fibres with intercalated pieces of fibrous and/or hyaline cartilage, calcified cartilage, and lamellar bone with red or white marrow. Pieces of hyaline cartilage were not clearly defined: a perichondrial layer was missing and coarse connective tissue continuously transformed into fibrous and hyaline cartilage. In both sexes the amount of cartilage and bone were found to increase with age.
Our results establish the presence of bony material in the heart skeleton of the otter, a small mammalian species. This finding indicates that differentiation of bone is not exclusively related to the size of the organ. Increasing amounts of calcified cartilage and bone correlated with increasing age.     

Iterative Cardiac Output Measurement for Optimizing Cardiac Resynchronization Therapy: A Randomized,Blinded, Crossover Study

Background: Many invasive and noninvasive methods have been proposed for guiding optimal programming of cardiac resynchronization therapy (CRT) devices. However, results are not satisfying. Preliminary results suggest that cardiac output (CO) measurements using inert gas rebreathing (IGR) might be an eligible method to tailor atrioventricular (AV) and ventriculo‐ventricular (VV) programming. The aims of the present study were: (1) to evaluate whether an optimization of CRT can be obtained by noninvasive CO measurements and (2) to evaluate whether acute hemodynamic improvements obtained by this approach relate into increase in cardiac exercise capacity. Methods: In 24 patients on CRT, iterative VV‐ and AV‐delay optimization was done using the IGR method. This blinded, randomized, crossover study compared the responses to optimization during two periods: a 4‐week optimized and a 4‐week standard programming. Exercise capacity after optimization was assessed after each period by New York Heart Association (NYHA) classification, a 6‐minute walking test, and quality of life (QoL) questionnaire. Results: CO could be determined by IGR in all patients. The NYHA class decreased by 17.8% (2.8 ± 0.3 vs 2.3 ± 0.4, P < 0.001), the mean (± standard deviation) distance walked in 6 minutes was 9.3% greater after optimization (456 ± 140 m vs 417 ± 134 m, P < 0.001), and the QoL improved by 14.5% (41.8 ± 10.4 vs 36.5 ± 9.5, P < 0.001). The portion of responders to CRT increased from 66.5% to 87.5%. Conclusion: CRT optimization by iterative CO measurements leads to an increase in CO and an improvement of exercise capacity. Our results suggest that this method might become an important additive tool to adjust CRT programming. (PACE 2010; 33:1188–1194)     

Contrary Roles of IL-4 and IL-12 on IL-10 Production and Proliferation of Human Tumour Reactive T Cells

The cytokine profile of tumour reactive T cells is likely to play a central role in their function. However, little is known about how cytokine patterns of tumour reactive T cells can be regulated. Here, the authors investigated the influence of exogenous regulatory cytokines in addition to interleukin-2 (IL-2) on cytokine patterns and the proliferation of T cells recognizing an autologous sarcoma cell line. In this system, IL-4 and IL-12 showed the most polarizing influences on tumour reactive T cells. Exogenous IL-4 induced a predominant production of IL-4 while decreasing the interferon-γ (IFN-γ) and IL-10 production by tumour reactive T cells. It also stimulated the growth of tumour reactive CD4⁺ T cell clones. In contrast, IL-12 substantially increased the production of IL-10 and IFN-γ. This was accompanied by a growth inhibition of tumour reactive T cells. The growth of CD4⁺ tumour reactive T cells was also suppressed by exogenous IL-10. This study shows that cytokine patterns and proliferation tumour reactive T cells can be significantly influenced by exogenous cytokines and confirms the hypothesis of a negative feedback loop of IL-12 by the induction of IL-10 in the context of human tumour reactive T cells.     

X-linked severe combined immunodeficiency with γδT cells

A patient with X-linked severe combined immunodeficiency (X-SCID) was found to have a deletion mutation of a four base pair in the transmembrane domain of the IL-2 receptor γ chain gene, a subunit shared by the receptors for IL-4, IL-7, IL-9, and IL-15 (common γ chain; γc). He had very few αβT cells but had a considerable number of γδT cells in his peripheral blood. Fluorescence in situ hybridization (FISH) analysis showed that the γδT cells in his peripheral blood were not of maternal origin. He had received a Bacillus Calmette-Guerin (BCG) vaccination before recognition of the disease, and the BCG infection remained quiescent with no reaction for 19 months. After successful bone marrow transplantation, the site of the BCG vaccination showed a reaction, and live BCG were detected. It is useful to consider the relationship between the existence of γδT cells and BCG in this case, and it is suggested that γδT cells may be, in a given situation, less dependent on the γc chain than are αβT cells.     

Long‐Term Results after Carotid Stent Implantation

Background

Though carotid artery stenting (CS) has gained popularity as an alternative to carotid endarterectomy, studies examining long‐term results are limited.

Methods

All consecutive patients who underwent unilateral CS between 7/1993 and 8/2005 with no or non‐significant contralateral stenosis were included. Follow‐up with duplex sonography and/or angiography and neurological assessment was performed at 6 and/or 12 months. Thereafter, annually, a questionnaire was sent to the patients and their referring physicians.

Results

Two‐hundred and seventy‐nine patients underwent CS. In 99% of procedures stent delivery was successful. The periprocedural major and minor stroke rates were 2.2%, respectively. The periprocedural major stroke or death rate was 2.9%. Median clinical follow‐up was 49 ± 32 months (range: 30 days–12.1 years). Excluding perioperative (<30 days) events, the annual major and minor stroke rate was 1.3% and the annual ipsilateral major and minor stroke rate was 0.6%. In symptomatic and asymptomatic patients, the annual major and minor stroke rates were 2.2% and 0.8%, respectively, and the ipsilateral major and minor stroke rates were 1.1% and 0.3%, respectively. There was no significant difference between ipsilateral and contralateral major or minor strokes at long‐term follow‐up. At last sonographic follow‐up (median 36 ± 32 months), restenosis rates for symptomatic and asymptomatic stenoses were 5% and 3%, respectively.

Conclusion

The results of our study demonstrate very low long‐term cerebral event rates after CS supporting the long‐term safety of CS. Importantly, there was no significant difference in long‐term ipsilateral versus contralateral cerebral events lending support to the hypothesis of plaque stabilization.

     

Improved Sensing Signals After Endocardial Defibrillation with a Redesigned Integrated Sense Pace Defibrillation Lead

Adequate sensing is a basic requirement for appropriate therapy with ICDs. Integrated sense pace defibrillation leads, which facilitate ICD implantation, show a close proximity of sensing and defibrillation electrodes that might affect the sensing signal amplitude by the high currents of internal defibrillation. In 99 patients, we retrospectively examined two integrated sense pace defibrillation leads, eitherboth with a distance of 6 mm between the tip of the lead (sensing cathode) and the right ventricular defibrillation electrode (sensing anode) or one with a distance of 12 mm. Three seconds after a shock of 20 J, mean sensing signal amplitude during sinus rhythm (SR) decreased from 10.5 ± 4.3 mVto 5.1 ± 3.7 mV (P < 0.001) for the 6-mm lead, but showed no significant decrease for the 12-mm lead. The degree of signal reduction was inversely related to the time passed since defibrillation. Significant differences in reduction of sensing signal amplitude concerning monophasic and biphasic shocks could not be observed. Mean sensing signal amplitude of VF after shocks that failed to terminate it decreased in the same order as during SR (from 8.3 ± 4.1 mV to 4.1 ± 3.2 mV), but resulted in no failure of redetection during ongoing VF. DFTs did not differ for the 6-mm and the 12-mm lead. In conclusion, close proximity of the right ventricular defibrillation coil to the sensing tip of an integrated sense pace defibrillation lead causes energy and time related reductions in sensing signal amplitude after defibrillation, and might cause undersensing in the postshock period. A new lead design with a more proximal position of the right ventricular defibrillation coil avoids these problems without impairing DFTs.