Person: Stevenson, William
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Stevenson
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William
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Stevenson, William
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Publication Direct Comparison of Adjacent Endocardial and Epicardial Electrograms: Implications for Substrate Mapping(Blackwell Publishing Ltd, 2013) Tokuda, Michifumi; Tedrow, Usha; Inada, Keiichi; Reichlin, Tobias; Michaud, Gregory F.; John, Roy M.; Epstein, Laurence M.; Stevenson, WilliamBackground: Analysis of unipolar voltage maps has been used to detect epicardial scar, but data to define optimal parameters to identify scar remote from the recording site is limited. This study compares the characteristics of electrograms at endocardial sites adjacent to abnormal epicardial sites. Methods and Results: Data obtained from endocardial and epicardial electroanatomical maps of 31 patients with scar‐related ventricular tachycardia were reviewed. Five hundred twenty‐three pairs of endo‐ and epicardial points were selected according to predefined criteria. The endocardial points adjacent to epicardial scar (bipolar voltage <1.5 mV) had smaller unipolar voltage than those distant from epicardial scar (P<0.001). In multivariable analysis, unipolar voltage was the only endocardial electrogram predictor of epicardial scar (P<0.001, OR 0.94, 95% CI 0.93 to 0.97). An endocardial unipolar amplitude <4.4 mV in the right ventricular (RV) (sensitivity 93%, specificity 76%) and <5.1 mV in the left ventricular (LV) (sensitivity 91%, specificity 75%) was the optimal cutoff predicting epicardial scar. Applying these thresholds to electroanatomical maps, revealed a good match between endocardial unipolar abnormality and epicardial scar for 67% of LV and 75% of RV maps, respectively, but notably poor matches occurred in 8 (29%) maps (7 with nonischemic cardiomyopathy). Site‐by‐site correlations were better for ischemic than nonischemic cardiomyopathy. Conclusions: This study supports the contention that unipolar electrograms are capable of indicating overlying epicardial scar during endocardial mapping, but illustrates limitations that appear to differ with nonischemic as compared to ischemic cardiomyopathy. The presence of epicardial arrhythmia substrate cannot be excluded by analysis of unipolar endocardial maps in some patients.Publication Effect of Late Gadolinium Enhancement on the Recovery of Left Ventricular Systolic Function After Pulmonary Vein Isolation(John Wiley and Sons Inc., 2016) Addison, Daniel; Farhad, Hoshang; Shah, Ravi; Mayrhofer, Thomas; Abbasi, Siddique Akbar; John, Roy M.; Michaud, Gregory F.; Jerosch‐Herold, Michael; Hoffmann, Udo; Stevenson, William; Kwong, Raymond; Neilan, TomasBackground: The factors that predict recovery of left ventricular (LV) systolic dysfunction among patients with atrial fibrillation (AF) are not completely understood. Late gadolinium enhancement (LGE) of the LV has been reported among patients with AF, and we aimed to test whether the presence LGE was associated with subsequent recovery of LV systolic function among patients with AF and LV dysfunction. Methods and Results: From a registry of 720 consecutive patients undergoing a cardiac magnetic resonance study prior to pulmonary vein isolation (PVI), patients with LV systolic dysfunction (ejection fraction [EF] <50%) were identified. The primary outcome was recovery of LVEF defined as an EF >50%; a secondary outcome was a combined outcome of subsequent heart failure (HF), admission, and death. Of 720 patients, 172 (24%) had an LVEF of <50% prior to PVI. The mean LVEF pre‐PVI was 41±6% (median 43%, range 20% to 49%). Forty‐three patients (25%) had LGE (25 [58%] ischemic), and the extent of LGE was 7.5±4% (2% to 19%). During follow‐up (mean 42 months), 91 patients (53%) had recovery of LVEF, 68 (40%) had early recurrence of AF, 65 (38%) had late AF, 18 (5%) were admitted for HF, and 23 died (13%). Factors associated with nonrecovery of LVEF were older age, history of myocardial infarction, early AF recurrence, late AF recurrence, and LGE. In a multivariable model, the presence of LGE and any recurrence of AF had the strongest association with persistence of LV dysfunction. Additionally, all patients without recurrence of AF and LGE had normalization of LVEF, and recovery of LVEF was associated with reduced HF admissions and death. Conclusions: In patients with AF and LV dysfunction undergoing PVI, the absence of LGE and AF recurrence are predictors of LVEF recovery and LVEF recovery in AF with associated reduction in subsequent death and heart failure.Publication Graft Site Microenvironment Determines Dendritic Cell Trafficking Through the CCR7-CCL19/21 Axis(The Association for Research in Vision and Ophthalmology, 2016) Hua, Jing; Stevenson, William; Dohlman, Thomas H.; Inomata, Takenori; Tahvildari, Maryam; Calcagno, Narghes; Pirmadjid, Negar; Sadrai, Zahra; Chauhan, Sunil; Dana, RezaPurpose The graft site microenvironment has a profound effect on alloimmunity and graft survival. We aimed to study the kinetics and phenotype of trafficking antigen-presenting cells (APC) to the draining lymph nodes (DLNs) in a mouse model of corneal transplantation, and to evaluate the homing mechanisms through which graft site inflammation controls APC trafficking. Methods: Allogeneic donor corneas were transplanted onto inflamed or quiescent graft beds. Host- (YAe+) and donor (CD45.1+ or eGFP+)-derived APCs were analyzed by flow cytometry. Protein and mRNA expression of the CC chemokine receptor (CCR)7 ligands CCL19 and CCL21 were assessed using ELISA and Real-Time qPCR, respectively. Transwell migration assay was performed to assess the effect of DLNs isolated from hosts with inflamed graft beds on mature bone marrow–derived dendritic cells (BMDCs). Results: We found that inflamed graft sites greatly promote the trafficking of both recipient- and graft-derived APCs, in particular mature CCR7+ CD11c+ dendritic cells (DC). CCL19 and CCL21 were expressed at significantly higher levels in the DLNs of recipients with inflamed graft beds. The supernatant of DLNs from recipients with inflamed graft beds induced a marked increase in mature DC migration compared with supernatant from recipients with quiescent graft beds in a transwell assay. This effect was abolished by neutralizing CCL19 or CCL21. These data suggest that graft site inflammation increases the expression of CCR7 ligands in the DLNs, which promote mature DC homing and allorejection. Conclusions: We conclude that the graft site microenvironment plays a critical role in alloimmunity by determining DC trafficking through the CCR7-CCL19/21 axis.Publication Gamma-Irradiation Reduces the Allogenicity of Donor Corneas(Association for Research in Vision and Ophthalmology (ARVO), 2012) Stevenson, William; Cheng, Sheng-Fu; Emami-Naeini, Parisa; Hua, Jing; Paschalis, Eleftherios I.; Dana, Reza; Saban, Daniel R.Purpose. To evaluate the utility and allogenicity of gamma-irradiated corneal allografts. Methods. Corneal buttons were harvested from C57BL/6 mice and decellularized with gamma irradiation. Cell viability was assessed using TUNEL and viability/cytotoxicity assays. Orthotopic penetrating keratoplasty was performed using irradiated or nonirradiated (freshly excised) C57BL/6 donor grafts and BALB/c or C57BL/6 recipients. Graft opacity was assessed over an 8-week period and graft survival was evaluated using Kaplan-Meier survival curves. Mixed-lymphocyte reactions and delayed-type hypersensitivity assays were performed to evaluate T-cell alloreactivity. Real-time PCR was used to investigate the corneal expression of potentially pathogenic T-helper 1, 2, and 17 cell-associated cytokines. Results. Corneal cells were devitalized by gamma irradiation as evidenced by widespread cellular apoptosis and plasma membrane disruption. Nonirradiated allograft and isograft rates of survival were superior to irradiated allograft and isograft rates of survival (P < 0.001). Mixed lymphocyte reactions demonstrated that T-cells from irradiated allograft recipients did not exhibit a secondary alloimmune response (P < 0.001). Delayed-type hypersensitivity assays demonstrated that irradiated allografts did not elicit an alloreactive delayed-type hypersensitivity response in graft recipients (P ≤ 0.01). The corneal expression of T-helper 1, 2, and 17 cell-associated cytokines was significantly lower in failed irradiated allografts than rejected nonirradiated allografts (P ≤ 0.001). Conclusions. Gamma-irradiated corneas failed to remain optically clear following murine penetrating keratoplasty; however, gamma irradiation reduced the allogenicity of these corneas, potentially supporting their use in procedures such as anterior lamellar keratoplasty or keratoprosthesis implantation.Publication Cardiac MRI with Concurrent Physiological Monitoring Using MRI-Compatible 12-Lead ECG(BioMed Central, 2012) Tse, Zion; Dumoulin, Charles; Clifford, Gari D; Oster, Julien; Jerosch-Herold, Michael; Kwong, Raymond; Stevenson, William; Schmidt, Ehud Jeruham