Genetic Variants of Human Granzyme B Predict Transplant Outcomes after HLA Matched Unrelated Bone Marrow Transplantation for Myeloid Malignancies

Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G), the A and G alleles represent wild type QPY and RAH mutant variants, respectively. In this study, we analyzed the impact of granzyme B polymorphisms on transplant outcomes in recipients undergoing unrelated HLA-fully matched T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The granzyme B genotypes were retrospectively analyzed in a cohort of 613 pairs of recipients with hematological malignancies and their unrelated donors. In patients with myeloid malignancies consisting of acute myeloid leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41–0.89; P = 0.01) as well as transplant related mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27–0.86, P = 0.01). The recipient G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI, 0.47–0.99; P = 0.05) and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI, 0.35–1.06; P = 0.08). Granzyme B polymorphism did not have any effect on the transplant outcomes in patients with lymphoid malignancies consisting of acute lymphoid leukemia and malignant lymphoma. These data suggest that there is an association between the granzyme B genotype and better clinical outcomes in patients with myeloid malignancies after unrelated BMT

Acquisition of the pulmonary venous and left atrial anatomy with non-contrast-enhanced MRI for catheter ablation of atrial fibrillation: Usefulness of two-dimensional balanced steady-state free precession

Background: Usually, the pulmonary venous and left atrial (PV–LA) anatomy is assessed with contrast-enhanced computed tomographic imaging for catheter ablation of atrial fibrillation (AF). A non-contrast-enhanced magnetic resonance (MR) imaging method has not been established. Three-dimensional balanced steady-state free precession (3D b-SSFP) sequences cannot visualize the PV–LA anatomy simultaneously because of the signal intensity defect of pulmonary veins. We compared two-dimensional (2D) b-SSFP sequences with 3D b-SSFP sequences in depicting the PV–LA anatomy with non-contrast-enhanced MR imaging for AF ablation. Methods: Eleven healthy volunteers underwent non-contrast-enhanced MR imaging with 3D b-SSFP and 2D b-SSFP sequences. The MR images were reconstructed on the 3D PV–LA surface image. Two experienced radiological technicians independently scored the multiplanar reformatted (MPR) images on a scale of 1–4 (from 1, not visualized, to 4, excellent definition). The overall score was a sum of 5 segments (LA and 4 PVs). Results: In the 2D b-SSFP method, MR imaging was successfully performed, and the 3D PV–LA surface image was precisely reconstructed in all healthy volunteers. The image score was significantly higher in the 2D b-SSFP method compared to the 3D b-SSFP method (19 [19; 20] vs. 12 [11; 15], p=0.004, for both observers). No PV signal intensity defects occurred in the 2D b-SSFP method. Conclusions: The 2D b-SSFP sequence was more useful than the 3D b-SSFP sequence in adequately depicting the PV–LA anatomy

Factors involved in correct analysis of intracardiac electrograms captured by Medtronic Inc. pacemakers during tachycardias

Background: To thoroughly investigate the diagnostic information obtained by pacemakers, it is important that the stored intracardiac electrograms (EGMs) are analyzed. However, in Medtronic pacemakers, only a single intracardiac recording channel is available and thus EGM channel selection is critical. Methods: The study population comprised 150 patients who underwent implantation of Medtronic's dual chamber pacemakers with a single intracardiac EGM memory channel. We first set the electrogram channel to “summed,” and the automatic EGM diagnosis during the tachycardia was compared with the manual analysis findings. When the results were not identical for the 2 methods, the atrial EGM (AEGM) and ventricular EGM channels were sequentially selected and the results of each EGM selection were compared to conclude which channel was more valuable for diagnosis of high-rate episodes. The post-ventricular atrial blanking (PVAB) period was adjusted to the shortest interval with a relevant margin to avoid any far-field R wave over-sensing. Results: A total of 130 patients were eventually enrolled. High-rate episodes were observed in 115/130 patients (88%). The results of the automated tachycardia diagnosis obtained using the “summed” EGM differed from those obtained manually in 43/115 patients (37%). Changing the intracardiac EGM channel from “summed” to “AEGM” enabled a much better manual diagnosis with intracardiac EGMs because of improved atrial potential sensing, clearer manifestation of atrial electrograms within the PVAB, and more prominent atrial electrograms fused with the ventricular potentials. The ventricular EGM channel was not as useful as the AEGM channel for tachycardia diagnosis. Conclusions: In Medtronic pacemakers with single intracardiac EGM channel recording capability, AEGM is the most useful of the 3 EGM channel settings; PVAB should also be set to a much shorter value to achieve a more accurate automatic diagnosis

Incidence of esophageal injury after pulmonary vein isolation in patients with a low body mass index and esophageal temperature monitoring at a 39 °C setting

Background: Esophageal injury following catheter ablation of atrial fibrillation (AF) is reported to occur in 35% of patients. Even with a low energy setting (20–25 W), lesions develop in 10% of patients. Body mass index (BMI) has been reported to be a predictor of esophageal injury, indicating that patients with a low BMI (<24.9 kg/m2) are at a higher risk. We hypothesized that catheter ablation with a lower energy setting of 20 W controlled by esophageal temperature monitoring (ETM) at 39 °C could prevent esophageal injury even in patients with a BMI <24.9 kg/m2. Methods: Twenty patients with AF were included (age, 63±8 years; BMI, 22.9±1.3 kg/m2, left atrium diameter, 44±11 mm). If the esophageal temperature probe registered a temperature of >39 °C, radiofrequency (RF) application was stopped immediately. RF application could be performed in a “point by point” manner for a maximum of 20 s. Endoscopy was performed 1–5 days after ablation. Results: Esophageal mucosal injury was not observed in any patient in the study. Conclusions: Catheter ablation using ETM reduced the incidence of esophageal injuries, even in patients with a low BMI

Visualizing radiofrequency lesions using delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation: A modification of the method used by the University of Utah group

Background: Atrial tissue fibrosis has previously been identified using delayed-enhancement MRI (DE-MRI) in patients with atrial fibrillation (AF). Although the clinical importance of DE-MRI is well recognized, the visualization of atrial fibrosis and radiofrequency (RF) lesions has still not been achieved in Japan, primarily because of the differences in contrast agents, volume-rendering tools, and technical experience. The objective of this study was to visualize RF lesions by using commercially available tools. Methods: DE-MRI was performed in 15 patients who had undergone AF ablation (age, 59±4 years, left atrium diameter, 40±2 mm). Specific parameters for MR scanning obtained from previous reports were modified. Results: Of the 15 images, the images of three patients were uninterpretable owing to low image quality. RF lesions could be visualized in 8 (67%) of the 12 patients. Conclusions: In the current study, we successfully demonstrated that RF lesions could be visualized in Japanese patients using DE-MRI, although only commercially available tools were used