Cryoballoon Pulmonary Vein Isolation for the Treatment of Atrial Fibrillation and Issues in Follow-up Management

Since the fi rst publication proving the causal relation between electrically active muscular sleeves in the pulmonary veins (PV) and the triggering of paroxysmal atrial fi brillation (AF) by ectopic beats originating from them, numerous endocardial ablation techniques have been used to eliminate this arrhythmia. Although well established as a standard procedure in the treatment of atrial fi brillation, point-to-point radiofrequency ablation remains a challenging procedure, in which manual operator skills and experience is highly variable. This currently translates in variable success rates and high complication rates, making the risk-benefi t evaluation of this procedure diffi cult to assess. Several devices have been engineered to simplify the circumferential ablation, with the aim of permitting less experienced operator to achieve the endpoint of PV isolation with reasonable procedure and fl uoroscopy times, and without a higher risk of complications

Electro-anatomical mapping of the left atrium before and after cryothermal balloon isolation of the pulmonary veins

Introduction: The 28 mm cryoballoon catheter is a device used for pulmonary vein isolation (PVI). The aim of this study was to evaluate the extent of the ablation in the antral regions of the left atrium. Methods and Results: Eighteen patients with drug refractory, symptomatic, paroxysmal AF were enrolled. A 3D electroanatomic reconstruction of the left atrium was made before and after successful PVI with the 28 mm cryoballoon. Markers were placed at the ostium. Sixteen patients were mapped. Fourteen patients had 4 veins each, and 2 patients had a common ostium of the left sided veins. All separate ostia were isolated in the antral region. The two common ostia showed ostial isolation. There was a significant difference in vein size between the common (29 and 31 mm) and the separate ostia (19∈±∈4 mm) (p∈<∈0.01). The performance of an additional segmental ablation if balloon PVI did not eliminate all electrical activity, did not influence the extent of the ablation. The earliest left atrial activation during sinus rhythm was located in the superior septal region before ablation in all patients. After ablation, two patients showed a substantial downward shift towards the middle and inferior septal region respectively (NS). Four patients demonstrated a slight downward shift of the first activation. Conclusions: In cryoballoon PVI, the majority of the veins undergo antral isolation. Veins with a diameter larger than the balloon, are isolated ostially. In individual cases, the left atrial activation sequence appears to be altered after ablation

ICDs at higher age and clinical risk factors

Background The implantable cardioverter defibrillator (ICD) is effective in preventing sudden cardiac death. However, in elderly patients (aged 75 years or older) the role of ICDs is still not well-defined and controversial. Methods We retrospectively analysed all clinical and survival data of all ICD patients who were ≥75 years at the date of implantation in the Erasmus MC, Rotterdam, the Netherlands and the University Hospital, Basel, Switzerland. Kaplan- Meier survival analysis was performed, and mortality predictors were identified. Mortality of the cohort was compared with a random sample of patients aged 60-70 years originating from the same database and to an age- and sex-matched cohort of Dutch persons. Results The study cohort consisted of 179 patients aged 75 years or older who were implanted between February 1999 and July 2008. The median follow-up time was 2.0 (IQR 2.8) years. Survival rates after 1, 2 and 3 years were 87, 82, 75 %, respectively. Survival was similar for primary and secondary prevention. Mortality in this study population could be predicted by combining four clinical risk factors: QRS duration >120 ms, NYHA class > II, renal failure and atrial fibrillation (AF). Survival was worse compared with the group of ICD patients aged 60-70 years and to the age- and sex-matched group of elderly persons. However, survival was not significantly worse when comparing elderly ICD patients without additional risk factors to the general population. Conclusions Elderly patients still have an acceptable survival probability independent of prevention indication, certainly if there are no additional clinical risk factors. The presence or absence of additional clinical risk factors should be taken into account when making the decision for imp

Adenosine testing after cryoballoon pulmonary vein isolation improves long-term clinical outcome

Background Adenosine infusion after pulmonary vein isolation (PVI) with radiofrequency energy reveals dormant muscular sleeves and predicts atrial fibrillation (AF) recurrence. The aim of our study was to determine whether adenosine could reveal dormant PV sleeves after cryoballoon isolation and study its effect on long-term recurrence of AF. Methods Patients with paroxysmal AF underwent cryoballoon PVI. After PVI, adenosine 25 mg was infused to test for dormant muscular sleeves in each vein. If reconnection under adenosine was shown, further cryoballoon ablation was performed until no more reconnection occurred. Follow-up was performed with ECG, 24-h Holter recording, and a symptom questionnaire at three monthly intervals. Transtelephonic Holter monitoring was performed for 1 month before and 3 months after PVI. Patients who underwent cryoballoon PVI without adenosine administration were used as controls for comparison. Results In the study group (n034, 24 males), adenosine revealed dormant sleeves in 9/132 (8 %) veins, and 7/34 (21 %) patients. All but one vein was further treated until the dormant sleeves were isolated. During a mean follow-up of 520±147 days, 23/34 (68 %) patients were free of AF without antiarrhythmic drugs (AADs). In the control group (n065, 46 males), 29/65 (46 %) were free of AF without AADs. There were significantly less AF recurrences in the study group (p00.04). Conclusions Adenosine administration after cryoballoon PVI reveals dormant muscular sleeves in 21 % of patients. Clinical follow-up shows that adenosine testing is effective in reducing AF recurrence after cryoballoon ablation

Pulmonary vein isolation using an occluding cryoballoon for circumferential ablation: Feasibility, complications, and short-term outcome

Aims: To assess safety, feasibility and short term outcome of pulmonary vein (PV) isolation in paroxysmal atrial fibrillation (AF) with a cryoballoon. Methods: We consecutively treated 57 patients with a double lumen 23 or 28 mm cryoballoon. The acute results, complications and follow-up over the first three months were analysed, using a comprehensive and intensive follow-up period. Results: During 57 procedures, 185 of 220 targeted PV's were successfully isolated using the cryoballoon (84%) (balloon group, 33 patients). In 33 veins (15%) an additional segmental isolation (hybrid group, 24 patients) was necessary with a standard cryocatheter to achieve isolation. The average procedure times were respectively 211 ± 108 and 261 ± 83 minutes (NS), the average fluoroscopy times 52 ± 36 and 66 ± 33 minutes (NS). The number of balloon applications did not differ between both groups: respectively a median 9 (4-18) and 10 (5-17) (NS). We observed four phrenic nerve paralysis after ablation of the right superior PV: two resolved immediately after cessation of the cryoenergy, one recovered after 3 months, one persisted up to 6 months. A daily transtelephonic rhythm recording showed a significant drop in mean AF burden from 24% to 10%, 8% and 5% during the three consecutive months of follow-up (p < 0.01 versus baseline). No differences were observed between the treatment groups. 34 patients (60%) were completely free from AF after a single procedure. Conclusions: Balloon cryoablation of the pulmonary veins with additional segmental isolation if necessary, is a good approach for patients presenting with paroxysmal AF, showing a significant reduction in AF burden after a single procedure. The major complication seems to be phrenic nerve paralysis after ablation of the right superior PV, but this is potentially reversible over several months

Practice guidelines on the use of erythropoiesis-stimulating agents in the treatment of chemotherapy induced anemia

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Flutter ablation with remote magnetic navigation: Comparison between the 8-mm tip, the irrigated tip and a manual approach

Introduction: Remote magnetic navigated ablation has proven its feasibility in a large group of arrhythmias. Until now only scarce data are available on the use for atrial flutter. In this study we compared remote magnetic navigation (RMN), using non-irrigated and irrigated tip catheters, to manual radiofrequency ablation for ablating typical atrial flutter. Methods: The 3 study groups consisted of 17 patients treated with RMN 8-mm tip; 14 patients with RMN irrigated tip; and 24 patients with a manual 8-mm tip. The primary outcome was the number of patients in whom bidirectional isthmus block could be obtained with 15 applications. Secondary end points were the median number of applications needed, the need to switch to a manual irrigated tip catheter, the procedural and fluoroscopy times. Results: There was no significant difference in the primary end point (RMN 8 mm-tip group: 59%, RMN irrigated tip group: 64% and manual group: 83%). The median number of applications needed to obtain block was higher in the RMN groups compared to the manual group. In 5 patients from the RMN 8-mm tip group, 1 in the RMN irrigated tip group and 1 in the manual group, a switch to a manually irrigated tip catheter was performed. There was no difference in fluoroscopy time, but procedural time was significantly longer in the RMN groups compared to the manual group (P = 0.03). Conclusions: The use of magnetic navigation for the ablation of atrial flutter is feasible but not superior to a manual approach. There was no difference concerning the primary end point of acute success within 15 applications. Overall, more applications were needed and procedure times were longer with RMN but RMN with the irrigating tip is promising

Establishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT) has remained controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice (previously injected with the MOPC315.BM myeloma cell line), based on a chronic graft-versus-host disease (GvHD) murine model. Methods and results: Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received 30 days later an allogeneic (B10.D2 donor) or autologous (Balb/cJ donor) transplantation by intravenous administration of bone marrow cells and splenocytes. We observed a graft-versus-myeloma effect in 94% of the allogeneic transplanted mice, as luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma evolution. Lower serum paraprotein levels and myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect, while allogeneic mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggest the involvement of effector memory CD4 and CD8 T cells in the GvM effect. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR V spectratyping analysis identified V families within CD4 and CD8 T cells which were associated with both GvM effects and GVHD, whereas other V families within CD4 T cells were associated exclusively with either GvM or GvHD responses. Conclusions: We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first immunocompetent murine model which is based on a MM model closely resembling human MM disease (bone marrow tropism, ...) and using allo-SCT after the disease establishment, as a curative treatmen