Point Of Ablation Research Articles

Simplifying atrial fibrillation ablation: How far can we go?

The procedural end point of electrical isolation of the pulmonary veins (PVs) for the treatment of atrial fibrillation (AF) has been debated extensively. After identifying the PVs as the dominant arrhythmogenic site of paroxysmal AF, 2 fundamentally different approaches to the interventional treatment of AF were introduced. Haissaguerre et al developed a technique to electrically isolate the PVs by targeting electrophysiological (EP) breakthroughs from the left atrium to the PVs guided by a circular mapping catheter. In contrast, Pappone et al implemented an anatomical approach that used circumferential ablation lines around the PVs guided by a 3-dimensional mapping system. This latter approach used the procedural end point of local electrogram amplitude reduction on the line and assessment of voltage maps within the encircled area but not the demonstration of PV isolation. For a considerably long time, these 2 different approaches separated the EP community in terms of AF ablation into 2 fractions according to their affinity to either of these techniques. Subsequently, 2 independent groups performed each a prospective randomized trial comparing the 2 approaches. However, these 2 studies ultimately did not clarify which one of the approaches is the more effective and therefore more appropriate technique. In contrast, the completely divergent results of the 2 studies further heated up this debate. Interestingly, although no additional clarifying data were published afterward, the 2007 Heart Rhythm Society/European Heart Rhythm Association/European Cardiac Arrhythmia Society consensus documents recommended for the first time that in AF ablation approaches targeting the PVs, complete electrical isolation should be the goal. With this statement, discussions on whether electrical isolation should be used as the EP end point of PV ablation abated subsequently. The contemporary approach to PV isolation consolidates the combination of both techniques, a wide circumferential linear ablation around the ipsilateral PVs with the end point of electrical isolation guided by a circular PV mapping catheter. Recently, the German Gap-AF (AFNET 1) study demonstrated

Blood Pressure and Autonomic Responses to Electrical Stimulation of the Renal Arterial Nerves Before and After Ablation of the Renal Artery

Radiofrequency (RF) catheter ablation of the renal artery is therapeutic in patients with drug-refractory essential hypertension. This study was designed to examine the role of the renal autonomic nerves and of RF application from inside the renal artery in the regulation of blood pressure (BP). An open irrigation catheter was inserted into either the left or right renal artery in 8 dogs. RF current (17 ± 2 watts) was delivered to one renal artery. Electrical autonomic nerve stimulation was applied to each renal artery before and after RF ablation. BP, heart rate, indices of heart rate variability, and serum catecholamines were analyzed. Before RF ablation, electrical autonomic nerve stimulation of either renal artery increased BP from 150 ± 16/92 ± 15 to 173 ± 21/105 ± 16 mm Hg. After RF ablation, BP increased similarly when the nonablated renal artery was electrically stimulated, although the rise in BP was attenuated when the ablated renal artery was stimulated. Serum catecholamines and sympathetic nerve indices of heart rate variability increased when electrical autonomic nerve stimulation was applied before RF ablation and to the nonablated renal artery after RF ablation, although it changed minimally when the ablated renal artery was stimulated, suggesting interconnectivity between afferent renal nerve stimulation and systemic sympathetic activity. Renal artery angiogram showed no apparent injury after RF ablation. In conclusion, electrical stimulation of the renal arterial autonomic nerves increases BP via an increase in central sympathetic nervous activity. This response might be used to determine the target ablation site and end point of renal artery RF ablation.

The Agilis Sheath in Typical Atrial Flutter Ablation Trial

Background: In general is it believed that use of a deflectable sheath can enhance tissue contact or improve catheter manipulation for ablation of challenging cavotricuspid anatomy. We sought to determine if use of a St. JudeAgilis sheath®− lead to improvedcontact force, faster procedures or greater efficacy in typical right atrial flutter ablation. Method: We performed cavotricuspid isthmus ablation with a pressure sensing catheter on 20 patients with isthmus dependant flutter and randomised them to use, or no use of an Agilis sheath. For the purpose of contact force assessment, the isthmus was divided into peri-annular, mid isthmus and venacaval zones. The proceduralist was blinded to contact force readings and the end point of ablation was bidirectional isthmus block with >50% prolongation of the transisthmus interval. Results: After 10min of ablation, four patients in the control group crossed over to use of an Agilis sheath. On intention to treat analysis bidirectional isthmus block was achieved in 9/10 patients with use of the Agilis sheath and 10/10 patients without (p=NS). Results were as follows.

The National Heart Foundation of Australia Consensus Statement on Catheter Ablation as a Therapy for Atrial Fibrillation

Background: In general is it believed that use of a deflectable sheath can enhance tissue contact or improve catheter manipulation for ablation of challenging cavotricuspid anatomy. We sought to determine if use of a St. JudeAgilis sheath®− lead to improvedcontact force, faster procedures or greater efficacy in typical right atrial flutter ablation. Method: We performed cavotricuspid isthmus ablation with a pressure sensing catheter on 20 patients with isthmus dependant flutter and randomised them to use, or no use of an Agilis sheath. For the purpose of contact force assessment, the isthmus was divided into peri-annular, mid isthmus and venacaval zones. The proceduralist was blinded to contact force readings and the end point of ablation was bidirectional isthmus block with >50% prolongation of the transisthmus interval. Results: After 10min of ablation, four patients in the control group crossed over to use of an Agilis sheath. On intention to treat analysis bidirectional isthmus block was achieved in 9/10 patients with use of the Agilis sheath and 10/10 patients without (p=NS). Results were as follows.

Bi-directional block is superior to non-inducibility in predicting freedom from atrial fibrillation after pulmonary vein isolation

There is variability in the endpoints used with the different approaches to pulmonary vein (PV) isolation. Elimination of PVP recorded inside the targeted PV antrum indicates inlet block and is considered the 1st indicator of a successful PV isolation, however this may not be sufficient to predict non recurrence of AF. To compare the efficacy of two end points, pulmonary vein (PV) entrance block with non-inducibility (NI) Vs achieving PV bi-directional (BD) block in terms of freedom of AF after PV isolation (PVI) for paroxysmal/persistent atrial fibrillation (AF). We included 58 consecutive patients (pts) who underwent PVI for symptomatic AF. In all pts, the end point of ablation was abolishing PV potentials (PVP) in the PVs followed by testing for bidirectional block (defined by both loss of PVP and failure to conduct to the LA by pacing at 10 mA and from 10 bipolar pairs of electrodes on a circular catheter positioned at the entrance of the PV) and/or NI of AF (by burst atrial pacing). Bidirectional block was achieved in 40 patients (69%) while Non inducibility was achieved in 36 (58.5%) patients with an overlap of achieving both endpoints in 18 (31%) patients. Over a follow up period of 17 ± 11 months, 34 pts (85%) in group I Vs 22 (62%) in group II were free of AF. Correlation showed significant relation between BD block (OR = 8.07, P = 0.004) Vs NI of AF post-PVI (OR = 2.8, P = 0.095) in predicting freedom from AF at follow up. Achieving BD block improves results and may predict maintenance of sinus rhythm more than NI of AF after PVI. It can be used as an electrophysiological endpoint alternative to or in conjunction with non inducibility in AF ablation procedures.

Patient-Specific Modeling of Corneal Refractive Surgery Outcomes and Inverse Estimation of Elastic Property Changes

The purpose of this study is to develop a 3D patient-specific finite element model (FEM) of the cornea and sclera to compare predicted and in vivo refractive outcomes and to estimate the corneal elastic property changes associated with each procedure. Both eyes of a patient who underwent laser-assisted in situ keratomileusis (LASIK) for myopic astigmatism were modeled. Pre- and postoperative Scheimpflug anterior and posterior corneal elevation maps were imported into a 3D corneo-scleral FEM with an unrestrained limbus. Preoperative corneal hyperelastic properties were chosen to account for meridional anisotropy. Inverse FEM was used to determine the undeformed corneal state that produced <0.1% error in anterior elevation between simulated and in vivo preoperative geometries. Case-specific 3D aspheric ablation profiles were simulated, and corneal topography and spherical aberration were compared at clinical intraocular pressure. The magnitude of elastic weakening of the residual corneal bed required to maximize the agreement with clinical axial power was calculated and compared with the changes in ocular response analyzer (ORA) measurements. The models produced curvature maps and spherical aberrations equivalent to in vivo measurements. For the preoperative property values used in this study, predicted elastic weakening with LASIK was as high as 55% for a radially uniform model of residual corneal weakening and 65% at the point of maximum ablation in a spatially varying model of weakening. Reductions in ORA variables were also observed. A patient-specific FEM of corneal refractive surgery is presented, which allows the estimation of surgically induced changes in corneal elastic properties. Significant elastic weakening after LASIK was required to replicate clinical topographic outcomes in this two-eye pilot study.

Chronic Atrial Fibrillation Is a Biatrial Arrhythmia

Background— Termination of chronic atrial fibrillation (CAF) can be achieved by catheter ablation using a stepwise approach. However, there are limited data on the contribution of the right atrium to the CAF process. Furthermore, the prognostic value of CAF termination remains unclear. Methods and Results— Eighty-eight patients (61�10 years of age) underwent de novo ablation of CAF in 2006 at our institution. The ablation procedure was performed sequentially in the following order: pulmonary vein isolation, defragmentation of the left atrium, coronary sinus, and right atrium. Attempted procedural end point was termination of CAF. Consecutive arrhythmias occurring after AF termination were mapped, and ablation was attempted. AF termination was achieved in 68 (77%) patients: in 37 (55%) patients it occurred in the left atrium, in 18 (26%) patients in the right atrium, and in 13 (19%) patients in the coronary sinus. In 54 patients, at least one redo was performed (total number of procedures: 154). After the first redo, another 30 patients were in sinus rhythm (total 63), 8 patients were in atrial tachycardia (AT), and 17 patients were in AF. Another 11 patients underwent a second redo. After a mean follow-up of 20�4 months, 71 (81%) patients were in sinus rhythm, 1 (1%) patient was in AT, and 16 (18%) patients were in AF. Patients with CAF termination had predominantly ATs as recurrent arrhythmias (83%), whereas those without mainly presented with recurrent CAF (85%). The overall success rate in patients with CAF termination was 95% compared with 5% of patients without CAF termination in 2 procedures (n=12). In almost all redo procedures attributable to AT, at least 1 AT during redo was documented previously. Conclusions— AF termination is a prognostic important end point of catheter ablation for CAF. Termination of AF was achieved in both atria and the coronary sinus, suggesting a biatrial substrate of CAF. Subsequent arrhythmias often recur during follow-up and, therefore, should be targeted for ablation.

Catheter Ablation for Atrial Fibrillation

▪ Abstract Atrial fibrillation is frequently disabling and resistant to antiarrhythmic drugs. Curative treatment by catheter-based ablation has been shown to be feasible either by achieving long linear lesions, mainly in the left atrium, or by targeting the initiating focus, most frequently in the pulmonary veins. This paper reviews the different ablation approaches, their results, potential complications, and relative merits.

The Role of Left Atrial Muscular Bundles in Catheter Ablation of Atrial Fibrillation

We sought to investigate the imaging of the left atrial (LA) muscular bundle and the relationship between the bundle and inducibility of tachyarrhythmia after pulmonary vein isolation (PVI). Noninducibility is used as a clinical end point of atrial substrate ablation after PVI. However, little is known about the role of the LA muscular bundles in tachyarrhythmia after PVI. Forty-three consecutive patients with paroxysmal atrial fibrillation who underwent catheter ablation were included. Bi-atrial isochronal mapping was performed with the NavX system (St. Jude Medical Inc., St. Paul, Minnesota) during sinus rhythm. After 4 PVI, inducible organized LA flutter with or without transforming to atrial fibrillation (AF) (LA flutter/AF) was ablated with additional lines at the roof and/or mitral isthmus. The existence of bilateral muscular bundles was an independent predictor of LA flutter/AF after PVI (p = 0.02). Patients with LA flutter/AF after PVI had a greater index of the double potentials (5.4 +/- 3.4% vs. 2.8 +/- 1.8%, p = 0.006) and interpotential interval (33 +/- 5 ms vs. 29 +/- 4 ms, p = 0.02) than without LA flutter/AF. The muscular bundles were identified in 28% patients using 16-slice multidetector computed tomography, which were identical to the isochrone map. Patients with noninducible LA flutter/AF after PVI plus the additional linear ablation had a lower recurrence rate as compared with the patients without it (19% vs. 75%, p = 0.02). Left atrial muscular bundles may provide a conduction block line and barrier, which is important for the formation of LA flutter/AF after PVI. The noninducibility of LA flutter/AF achieved after additional linear ablation may contribute to a better outcome in RF ablation of paroxysmal atrial fibrillation.

The management of atrial fibrillation in heart failure

The development of atrial fibrillation (AF) can greatly complicate the course of heart failure (HF). Although recent trials have indicated the nonsuperiority of a rhythm control strategy in the general population with AF, this may not apply to patients with HF. We feel strongly that AF be treated aggressively in patients with HF, defaulting toward an initial rhythm control strategy, to avoid the hemodynamic detriment of irregular rapid ventricular response and the development of tachycardia-related myopathy. The index episode is treated with cardioversion and antiarrhythmic therapy. If significant benefit is demonstrated, the rhythm control strategy is maintained, to the point of catheter ablation for AF if necessary. If there is no change in cardiac performance or symptoms after cardioversion, strict rate control is enforced, to the point of atrioventricular node ablation and pacing if necessary.

A Tailored Approach to Catheter Ablation of Paroxysmal Atrial Fibrillation

Because the genesis of atrial fibrillation (AF) is multifactorial and variable, an ablation strategy that involves pulmonary vein isolation and/or a particular set of ablation lines may not be equally effective or efficient in all patients with AF. A tailored strategy that targets initiators and drivers of AF is a possible alternative to a standardized lesion set. Catheter ablation was performed in 153 consecutive patients (mean age, 56+/-11 years) with symptomatic paroxysmal AF with the use of an 8-mm tip radiofrequency ablation catheter. The esophagus was visualized with barium. The pulmonary veins and left atrium were mapped during spontaneous or induced AF. Arrhythmogenic pulmonary veins were isolated or encircled. If AF was still present or inducible, complex electrograms in the left atrium, coronary sinus, and superior vena cava were targeted for ablation. The end point of ablation was absence of frequent atrial ectopy and spontaneous AF during isoproterenol infusion and noninducibility of AF. Routine energy applications near the esophagus were avoided. During follow-up, left atrial flutter developed in 19% of patients and was still present in 10% at >12 weeks of follow-up. A repeat ablation procedure was performed in 18% of patients. During a mean follow-up of 11+/-4 months, 77% of patients were free from AF and/or atrial flutter without antiarrhythmic drug therapy. Pericardial tamponade or transient neurological events occurred in 2% of procedures. A tailored ablation strategy that only targets triggers and drivers of AF is feasible and eliminates paroxysmal AF in approximately 80% of patients.

Robotic Magnetic Navigation for Atrial Fibrillation Ablation

We assessed feasibility of magnetic catheter guidance in patients with atrial fibrillation (AF) undergoing circumferential pulmonary vein ablation (CPVA). No data are available on feasibility of remote navigation for AF ablation. Forty patients underwent CPVA for symptomatic AF using the NIOBE II remote magnetic system (Stereotaxis Inc., St. Louis, Missouri). Ablation was performed with a 4-mm tip, magnetic catheter (65 degrees C, maximum 50 W, 15 s). The catheter tip was guided by a uniform magnetic field (0.08-T), and a motor drive (Cardiodrive unit, Stereotaxis Inc.). Left atrium maps were created using an integrated CARTO RMT system (Stereotaxis Inc.). End point of ablation was voltage abatement >90% of bipolar electrogram amplitude. Remote ablation was successful in 38 of 40 patients without complications. The median mapping and ablation time was 152.5 min (range, 90 to 380 min) but was much longer in the first 12 patients (192.5 min vs. 148 min; p = 0.012). Median ablation time was 49.5 min (range, 17 to 154 min), but it was much shorter in the last 28 patients than in the first 12 patients (49 min vs. 70 min; p = 0.021). Patients receiving remote ablation had longer procedure times than control patients (p < 0.001) with similar mapping time but shorter ablation time on right-sided pulmonary veins. Many more mapping points regardless of their location were collected remotely (p < 0.001). Remote magnetic navigation for AF ablation is safe and feasible with a short learning curve. Although all procedures were performed by a highly experienced operator, remote AF ablation can be performed even by less experienced operators.

Noninducibility of atrial fibrillation as an end point of left atrial circumferential ablation for paroxysmal atrial fibrillation. A randomized study

Noninducibility of atrial fibrillation as an end point of left atrial circumferential ablation for paroxysmal atrial fibrillation. A randomized study

Noninducibility of Atrial Fibrillation as an End Point of Left Atrial Circumferential Ablation for Paroxysmal Atrial Fibrillation

An anatomic approach of left atrial radiofrequency circumferential ablation (LACA) to encircle the pulmonary veins is often effective in eliminating paroxysmal atrial fibrillation (AF). However, no electrophysiological end points other than voltage abatement and/or conduction slowing or block across ablation lines have been used. It has been unclear whether noninducibility of AF is a clinically useful end point. In 100 patients with paroxysmal AF (mean age, 55+/-10 years), LACA to encircle the left- and right-sided pulmonary veins was performed during AF, with additional ablation lines in the posterior left atrium and mitral isthmus, with an 8-mm-tip catheter. After completion of this lesion set, sinus rhythm was present, and AF lasting >60 seconds was not inducible in 40 patients (40%; group 1). The 60 patients in whom AF was still present or who still had inducible AF were randomly assigned to no further ablation (group 2; 30 patients) or to additional ablation lines along the left atrial septum, roof, and/or anterior wall where there were fractionated electrograms (group 3; 30 patients). In group 3, AF was rendered noninducible in 27 of 30 patients (90%). At a 6-month follow-up, 67% of patients in group 2 were free of AF without drug therapy compared with 86% of patients in group 3. (P=0.05, log-rank test). Left atrial flutter occurred in 17% and 27% of patients in each group, respectively (P=0.3). After LACA in patients with paroxysmal AF, AF usually can be rendered noninducible by additional ablation at sites of fractionated electrograms. Noninducibility of AF attained by additional electrogram-guided left atrial ablation may be associated with a better midterm clinical outcome than when AF is still inducible after LACA alone.

Usefulness of CT During Renal Arteriography: A Case of Percutaneous Radiofrequency Ablation for Renal Cell Carcinoma

A 64-year-old man with a unilateral 15 mm diameter renal cell carcinoma underwent percutaneous radiofrequency ablation (RFA) assisted by CT during renal arteriography (angio-CT). Prior to placement of the needle electrode, a 5 Fr angio-catheter was placed in the right renal artery, and angio-CT was performed before, during and after the procedure. Since multiple angio-CT can be performed using a small amount of diluted contrast agent, RFA can be monitored without impairing renal function. As a result, this imaging combination was found to be useful for determining the end point of ablation.

Effect of scanning resolution and fluence fluctuation on femtosecond laser ablation of thin films

Femtosecond-pulse laser pulses have been shown to hold great potential for high-precision micromachining. Much research has been done to characterize the laser parameters for predicting the feature size, and the most important of these is the number of pulses incident at each point of ablation. Theoretical modeling, so far, has been restricted to a single point where the number of pulses incident at each point of ablation depends on the pulse-repetition rate and the dwell time of the laser beam at that machining point. However, to make the theoretical model useful, a laser scanning system with the ability to fabricate complex microfeatures is considered in this work. In this case, the scanning resolution determines the number of pulses incident at each scanning point. This has been taken into account while presenting a theoretical and experimental analysis of the effect of the scanning resolution on the threshold fluence of the material. Results of ablation on a gold thin film were subjected to theoretical analysis to predict the feature size. In addition, the effect of the energy fluctuation of the laser on the feature size has been evaluated to predict the minimum achievable feature size for a gold thin film.

Vapor-phase oxidation during pulsed laser deposition of SrBi2Ta2O9

Time-integrated optical emission spectroscopy has been used to observe the plume produced during pulsed laser deposition (PLD) in oxygen of the ferroelectric oxide SrBi2Ta2O9 (SBTO). Line emission from atomic and singly ionized target material was observed, together with emission from atomic oxygen. Band emission from strontium oxide was also observed. Spatially resolved analysis of oxide emission and atomic emission together with the assumption of an optically thin plasma plume distant from the point of ablation indicated that oxidation occurred most readily at the interface between the visible plume and the background gas. The oxide content in the visible plume was seen to increase as the plume passed through the background gas. Analysis of line intensity ratios and widths allowed the plasma electron temperature and density of the plume to be measured, with peak values of 7300 K and 1.2×1017 cm−3, respectively, measured at the laser spot. These results are of interest for the fabrication of SBTO thin fi...

Tracking dynamic conduction recovery across the cavotricuspid isthmus

OBJECTIVESWe sought to assess the dynamic temporal course of conduction recovery during and after radiofrequency (RF) catheter ablation of the cavotricuspid isthmus.BACKGROUNDAlthough cavotricuspid isthmus block is accepted as the best end point of ablation for typical flutter, conduction recovery is thought to underlie many eventual recurrences. Its time course and frequency have not been determined.METHODSIn a prospective group of 30 patients (26 men and 4 women, age 64 ± 12 years) undergoing ablation of typical flutter in the cavotricuspid isthmus, the morphology of the P wave during pacing from the low lateral right atrium after achievement of complete isthmus block was identified as a reference. Regression of this morphologic P wave change was confirmed to be associated with intracardiac evidence of the recovery of cavotricuspid isthmus conduction and was observed throughout the procedure both during ablation in sinus rhythm (n = 15, group B) and just after flutter termination (n = 15, group A).RESULTSStable complete isthmus block was achieved in all patients; 29 had a terminal positivity of the paced P wave. Flutter termination resulted in stable block and terminal P wave positivity in three patients, transient terminal P wave positivity and transient block despite continuing RF at the same site in five patients and no block in the remaining seven patients. Conduction recovery identified by recovery of P wave changes was nearly as common (48%) during ablation in sinus rhythm. Multiple recoveries were noted in some patients, and 72% of all recoveries occurred within 1 min. Conduction recovery was only rarely associated with coagulum, impedance elevation or pops.CONCLUSIONSConduction recovery in the cavotricuspid isthmus is common during and after ablation and can be accurately, dynamically and continuously observed by monitoring the recovery of the low lateral right atrial paced P wave change.

3797 Long term outcome of endoscopic therapy for sphincter of oddi dysfunction.

Long-term outcomes after sphincterotomy (ES) for SOD are not well known, especially for pancreatic (P) as well as biliary (B) ES. Clinical predictors of outcome other than duct dilation or LFT abnormalities are not well clarified. Methods:We prospectively studied 126 consecutive patients treated over 3 yr for SOD (recurrent pain suspected to be from structural or functional P/B sphincter abnormality, +/- any clinical evidence of P/B abnormality): 92% female, 87% post-chole, 41% nl LFT's + nondilated B duct (type III), 19% recurrent pancreatitis, and 18% with prior B ES elsewhere. SO manometry (mano) was done in 87%. All pts had B ES; indication for P ES was abnl P mano or hx pancreatitis, usually reserved for poor response to B ES. Nonresponders had repeat ERCP to point of total ablation of the treated sphincter(s). Pts graded final pain relief on a 5-point Likert scale: with excellent (total resolution) or good (substantially better) = improved, and fair (minor improvement), poor (no change) or very poor (worse) = not improved. Results: Of 121 pts with 1-4 yr f/u, 83 (69%) were improved: 61 (50%) required more than 1 ERCP, and 49 (40%) P ES. Final improvement occurred in 78% of pts requiring only 1 ERCP, but also in 60% of pts requiring 2-6 total ERCP's. Response was similar for type III vs others (62% v 73%), but more (50% v 34%) required P ES. Of 27 variables examined, multivariate predictors (p 1 ERCP. Not predictive were: abnl B or P enzymes, dilated B or P ducts, abnormal B mano, prior B ES elsewhere, chronic pancreatitis by EUS/ERP, location/duration or hospitalization for pain, depression, IBS, or other concomitant pain syndrome. Conclusion: Endoscopic treatment of SOD resulted in long term improvement in about 2/3 pts, using biliary ES in all plus selective pancreatic ES. Repeated ERCP's were required in half of pts and salvaged 60% of nonresponders to initial ES. Response was similar for type III (pain only) as for other pts, and traditional classification based on abnormal enzymes and duct dilation did not predict outcome. Clinical features including younger age, daily narcotic use, and gastroparesis did lessen likelihood of response. These results highlight the importance of global clinical assessment, pancreatic mano and ES, and repeated ERCP in order to achieve optimal outcomes for SOD

Treatment of Autoimmune Disease by Intense Immunosuppressive Conditioning and Autologous Hematopoietic Stem Cell Transplantation

Multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis are immune-mediated diseases that are responsive to suppression or modulation of the immune system. For patients with severe disease, immunosuppression may be intensified to the point of myelosuppression or hematopoietic ablation. Hematopoiesis and immunity may then be rapidly reconstituted by reinfusion of CD34+progenitor cells. In 10 patients with these autoimmune diseases, autologous hematopoietic stem cells were collected from bone marrow or mobilized from peripheral blood with either granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide and G-CSF. Stem cells were enriched ex vivo using CD34+ selection and reinfused after either myelosuppressive conditioning with cyclophosphamide (200 mg/kg), methylprednisolone (4 g) and antithymocyte globulin (ATG; 90 mg/kg) or myeloablative conditioning with total body irradiation (1,200 cGy), methylprednisolone (4 g), and cyclophosphamide (120 mg/kg). Six patients with multiple sclerosis, 2 with systemic lupus erythematosus, and 2 with rheumatoid arthritis have undergone hematopoietic stem cell transplantation. Mean time to engraftment of an absolute neutrophil count greater than 500/μL (0.5 × 109/L) and a nontransfused platelet count greater than 20,000/μL (20 × 109/L) occurred on day 10 and 14, respectively. Regimen-related nonhematopoietic toxicity was minimal. All patients improved and/or had stabilization of disease with a follow-up of 5 to 17 months (median, 11 months). We conclude that intense immunosuppressive conditioning and autologous T-cell–depleted hematopoietic transplantation was safely used to treat these 10 patients with severe autoimmune disease. Although durability of response is as yet unknown, all patients have demonstrated stabilization or improvement.