Quantification of Epicardial Adipose Tissue Volume and Attenuation for Cardiac CT Scans Using Deep Learning in a Single Multi-Task Framework.

Background: Recent studies have shown that epicardial adipose tissue (EAT) is an independent atrial fibrillation (AF) prognostic marker and has influence on the myocardial function. In computed tomography (CT), EAT volume (EATv) and density (EATd) are parameters that are often used to quantify EAT. While increased EATv has been found to correlate with the prevalence and the recurrence of AF after ablation therapy, higher EATd correlates with inflammation due to arrest of lipid maturation and with high risk of plaque presence and plaque progression. Automation of the quantification task diminishes the variability in readings introduced by different observers in manual quantification and results in high reproducibility of studies and less time-consuming analysis. Our objective is to develop a fully automated quantification of EATv and EATd using a deep learning (DL) framework. Methods: We proposed a framework that consists of image classification and segmentation DL models and performs the task of selecting images with EAT from all the CT images acquired for a patient, and the task of segmenting the EAT from the output images of the preceding task. EATv and EATd are estimated using the segmentation masks to define the region of interest. For our experiments, a 300-patient dataset was divided into two subsets, each consisting of 150 patients: Dataset 1 (41,979 CT slices) for training the DL models, and Dataset 2 (36,428 CT slices) for evaluating the quantification of EATv and EATd. Results: The classification model achieved accuracies of 98% for precision, recall and F 1 scores, and the segmentation model achieved accuracies in terms of mean ( ± std.) and median dice similarity coefficient scores of 0.844 ( ± 0.19) and 0.84, respectively. Using the evaluation set (Dataset 2), our approach resulted in a Pearson correlation coefficient of 0.971 ( R 2 = 0.943) between the label and predicted EATv, and the correlation coefficient of 0.972 ( R 2 = 0.945) between the label and predicted EATd. Conclusions: We proposed a framework that provides a fast and robust strategy for accurate EAT segmentation, and volume (EATv) and attenuation (EATd) quantification tasks. The framework will be useful to clinicians and other practitioners for carrying out reproducible EAT quantification at patient level or for large cohorts and high-throughput projects.

Case report: Antidromic atrioventricular reentrant tachycardia and underlying Ebstein anomaly.

Multiple accessory pathways (APs) can develop in patients with Ebstein anomaly. Rarely, these APs can participate in antidromic atrioventricular reentrant tachycardia (AVRT) which can be life-threatening and requires unique considerations for acute management and ultimate ablation. These considerations are discussed herein.

Rationale and design of OPT-RATE AF: A randomized clinical trial of increased physiologic pacing rates in heart failure with preserved ejection fraction.

Cardiac physiologic pacing (CPP) after atrioventricular node (AVN) ablation for persistent atrial fibrillation (AF) has improved outcomes in patients with heart failure with reduced and preserved ejection fraction (HFpEF). Emerging evidence suggests patients with HFpEF benefit from higher heart rates, yet the optimal pacing rate after AVN ablation remains unknown. OPT-RATE AF is a prospective, randomized crossover study of patients with HFpEF following AVN ablation for persistent AF (NCT06445439). Approximately 60 patients with AF and AVN ablation, CPP, and HF with left ventricular ejection fraction ≥50% will be enrolled. Participants will be randomly assigned 1:1 to a pacing lower rate limit of 60 beats-per-minute (bpm) for 3 months and then switched to a rate of 80 bpm for 3 months, and vice versa. The primary endpoint is change in exercise capacity assessed by the 6-minute walk test. Notable secondary outcomes will include change in Kansas City Quality of Life Questionnaire (KCCQ-12), creatinine and natriuretic peptide, and clinical events. Patient mortality and HF hospitalizations will be recorded at each phase. EKG, echocardiogram, pacemaker interrogation, and primary and secondary outcomes will be recorded at baseline, 3 months, and 6 months. Study enrollment is ongoing and estimated to be completed by 2026. OPT-RATE AF is a randomized clinical trial that will determine the effect of a higher pacing rate in patients with persistent AF and HFpEF following AVN ablation and/or CPP. Study findings will provide insight on the role of chronotropy in improving QoL and other important cardiovascular outcomes.

Early real-world implant experience with a helix-fixation ventricular leadless pacemaker.

BACKGROUND: Roughly one in six patients receiving conventional transvenous pacemaker systems experience significant complications within 1 year of implant, mainly due to the transvenous lead and subcutaneous pocket. A new helix-fixation single-chamber ventricular leadless pacemaker (LP) system capable of pre-deployment exploratory electrical mapping is commercially available. Such an LP may mitigate complications while streamlining the implantation. In this study, the initial real-world implant experience of the helix-fixation LP was evaluated following its commercial release. METHODS: In patients indicated for single-chamber right ventricular pacing, helix-fixation Aveir VR LPs (Abbott, Abbott Park, IL) were implanted using the dedicated loading tool, introducer, and delivery catheter. Implant procedural characteristics, electrical parameters, and any 30-day procedure-related adverse events of consecutive implant attempts were retrospectively evaluated. RESULTS: A total of 167 patients with Class I indication for permanent pacing received implants in four North American centers (57% male, 70 years old). Pre-fixation electrical mapping of potential sites allowed repositioning to be avoided in 95.7% of patients. Median [interquartile range] LP procedure and fluoroscopy durations were 25.5 min [20.0, 35.0] and 5.7 min [4.0, 9.2], respectively. Pacing capture threshold, sensed R-wave amplitude, and impedance were 0.8 V [0.5, 1.3], 9.0 mV [6.0, 12.0], and 705 Ω [550, 910], respectively. Implantation was successful in 98.8% of patients, with 98.2% free from acute adverse events. CONCLUSIONS: The initial, real-world experience of the helix-fixation ventricular leadless pacemaker demonstrated safe and efficient implantation with minimal repositioning, viable electrical metrics, and limited acute complications.

Using machine learning to enhance prediction of atrial fibrillation recurrence after catheter ablation.

Background: Traditional risk scores for recurrent atrial fibrillation (AF) following catheter ablation utilize readily available clinical and echocardiographic variables and yet have limited discriminatory capacity. Use of data from cardiac imaging and deep learning may help improve accuracy and prediction of recurrent AF after ablation. Methods: We evaluated patients with symptomatic, drug-refractory AF undergoing catheter ablation. All patients underwent pre-ablation cardiac computed tomography (cCT). LAVi was computed using a deep-learning algorithm. In a two-step analysis, random survival forest (RSF) was used to generate prognostic models with variables of highest importance, followed by Cox proportional hazard regression analysis of the selected variables. Events of interest included early and late recurrence. Results: Among 653 patients undergoing AF ablation, the most important factors associated with late recurrence by RSF analysis at 24 (+/-18) months follow-up included LAVi and early recurrence. In total, 5 covariates were identified as independent predictors of late recurrence: LAVi (HR per mL/m2 1.01 [1.01-1.02]; p < .001), early recurrence (HR 2.42 [1.90-3.09]; p < .001), statin use (HR 1.38 [1.09-1.75]; p = .007), beta-blocker use (HR 1.29 [1.01-1.65]; p = .043), and adjunctive cavotricuspid isthmus ablation [HR 0.74 (0.57-0.96); p = .02]. Survival analysis demonstrated that patients with both LAVi >66.7 mL/m2 and early recurrence had the highest risk of late recurrence risk compared with those with LAVi <66.7 mL/m2 and no early recurrence (HR 4.52 [3.36-6.08], p < .001). Conclusions: Machine learning-derived, full volumetric LAVi from cCT is the most important pre-procedural risk factor for late AF recurrence following catheter ablation. The combination of increased LAVi and early recurrence confers more than a four-fold increased risk of late recurrence.

A Unique Case of Central Line Fracture Due to Laser Lead Extraction.

Transvenous laser-assisted lead extraction is successful, with a low procedural complication rate for a wide range of indications. Here, we report a case of right internal jugular triple-lumen central venous catheter fracture and subsequent embolism to the right pulmonary artery during laser lead extraction that was successfully retrieved with a gooseneck snare. (Level of Difficulty: Advanced.).

Generalizable Framework for Atrial Volume Estimation for Cardiac CT Images Using Deep Learning With Quality Control Assessment.

OBJECTIVES: Cardiac computed tomography (CCT) is a common pre-operative imaging modality to evaluate pulmonary vein anatomy and left atrial appendage thrombus in patients undergoing catheter ablation (CA) for atrial fibrillation (AF). These images also allow for full volumetric left atrium (LA) measurement for recurrence risk stratification, as larger LA volume (LAV) is associated with higher recurrence rates. Our objective is to apply deep learning (DL) techniques to fully automate the computation of LAV and assess the quality of the computed LAV values. METHODS: Using a dataset of 85,477 CCT images from 337 patients, we proposed a framework that consists of several processes that perform a combination of tasks including the selection of images with LA from all other images using a ResNet50 classification model, the segmentation of images with LA using a UNet image segmentation model, the assessment of the quality of the image segmentation task, the estimation of LAV, and quality control (QC) assessment. RESULTS: Overall, the proposed LAV estimation framework achieved accuracies of 98% (precision, recall, and F1 score metrics) in the image classification task, 88.5% (mean dice score) in the image segmentation task, 82% (mean dice score) in the segmentation quality prediction task, and R 2 (the coefficient of determination) value of 0.968 in the volume estimation task. It correctly identified 9 out of 10 poor LAV estimations from a total of 337 patients as poor-quality estimates. CONCLUSIONS: We proposed a generalizable framework that consists of DL models and computational methods for LAV estimation. The framework provides an efficient and robust strategy for QC assessment of the accuracy for DL-based image segmentation and volume estimation tasks, allowing high-throughput extraction of reproducible LAV measurements to be possible.

Sinus node sparing novel hybrid approach for treatment of inappropriate sinus tachycardia/postural sinus tachycardia: multicenter experience.

BACKGROUND: The ideal treatment of inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) still needs to be defined. Medical treatments yield suboptimal results. Endocardial catheter ablation of the sinus node (SN) may risk phrenic nerve damage and open-heart surgery may be accompanied by unjustified invasive risks. METHODS: We describe our first multicenter experience of 255 consecutive patients (235 females, 25.94 ± 3.84 years) having undergone a novel SN sparing hybrid thoracoscopic ablation for drug-resistant IST (n = 204, 80%) or POTS (n = 51, 20%). As previously described, the SN was identified with 3D mapping. Surgery was performed through three 5-mm ports from the right side. A minimally invasive approach with a bipolar radiofrequency clamp was used to ablate targeted areas while sparing the SN region. The targeted areas included isolation of the superior and the inferior caval veins, and a crista terminalis line was made. All lines were interconnected. RESULTS: Normal sinus rhythm (SR) was restored in all patients at the end of the procedure. All patients discontinued medication during the follow-up. After a blanking period of 6 months, all patients presented stable SR. At a mean of 4.07 ± 1.8 years, normal SN reduction and chronotropic response to exercise were present. In the 51 patients initially diagnosed with POTS, no syncope occurred. During follow-up, pericarditis was the most common complication (121 patients: 47%), with complete resolution in all cases. Pneumothorax was observed in 5 patients (1.9%), only 3 (1.1%) required surgical drainage. Five patients (1.9%) required a dual-chamber pacemaker due to sinus arrest > 5 s. CONCLUSIONS: Preliminary results of this multicenter experience with a novel SN sparing hybrid ablation of IST/POTS, using surgical thoracoscopic video-assisted epicardial ablation combined with simultaneous endocardial 3D mapping may prove to be an efficient and safe therapeutic option in patients with symptomatic drug-resistant IST and POTS. Importantly, in our study, all patients had a complete resolution of the symptoms and restored normal SN activity.

Prognostic value of left atrial size in hypertensive African Americans undergoing stress echocardiography.

BACKGROUND: Left atrial (LA) enlargement is a marker of increased risk in the general population undergoing stress echocardiography. African American (AA) patients with hypertension are known to have less atrial remodeling than whites with hypertension. The prognostic impact of LA enlargement in AA with hypertension undergoing stress echocardiography is uncertain. AIM: To investigate the prognostic value of LA size in hypertensive AA patients undergoing stress echocardiography. METHODS: This retrospective outcomes study enrolled 583 consecutive hypertensive AA patients who underwent stress echocardiography over a 2.5-year period. Clinical characteristics including cardiovascular risk factors, stress and echocardiographic data were collected from the electronic health record of a large community hospital. Treadmill exercise and Dobutamine protocols were conducted based on standard practices. Patients were followed for all-cause mortality. The optimal cutoff value of antero-posterior LA diameter for mortality was assessed by receiver operating characteristic analysis. Cox regression was used to determine variables associated with outcome. RESULTS: The mean age was 57 ± 12 years. LA dilatation was present in 9% (54) of patients (LA anteroposterior ≥ 2.4 cm/m2). There were 85 deaths (15%) during 4.5 ± 1.7 years of follow-up. LA diameter indexed for body surface area had an area under the curve of 0.72 ± 0.03 (optimal cut-point of 2.05 cm/m2). Variables independently associated with mortality included age [P = 0.004, hazard ratio (HR) 1.34 (1.10-1.64)], tobacco use [P = 0.001, HR 2.59 (1.51-4.44)], left ventricular hypertrophy [P = 0.001 , HR 2.14 (1.35-3.39)], Dobutamine stress [P = 0.003, HR 2.12 (1.29-3.47)], heart failure history [P = 0.031, HR 1.76 (1.05-2.94)], LA diameter ≥ 2.05 cm/m2 [P = 0.027, HR 1.73 (1.06-2.82)], and an abnormal stress echocardiogram [P = 0.033, HR 1.67 (1.04-2.68)]. LA diameter as a continuous variable was also independently associated with mortality but LA size ≥ 2.40 cm/m2 was not. CONCLUSION: LA enlargement is infrequent in hypertensive AA patients when traditional reference values are used. LA enlargement is independently associated with mortality when a lower than "normal" threshold (≥ 2.05 cm/m2) is used.

The combination of coronary sinus ostial atresia/abnormalities and a small persistent left superior vena cava-Opportunity for left ventricular lead implantation and unrecognized source of thromboembolic stroke.

BACKGROUND: Coronary sinus (CS) ostial atresia/abnormalities prevent access to the CS from the right atrium (RA) for left ventricular (LV) lead implantation. Some patients with CS ostial abnormalities also have a small persistent left superior vena cava (sPLSVC). OBJECTIVE: The purpose of this study was to describe CS ostial abnormalities and sPLSVC as an opportunity for LV lead implantation and unrecognized source of stroke. METHODS: Twenty patients with CS ostial abnormalities and sPLSVC were identified. Clinical information, imaging methods, LV lead implantation techniques, and complications were summarized. RESULTS: Forty percent had at least 1 previously unsuccessful LV lead placement. In 70%, sPLSVC was identified by catheter manipulation and contrast injection in the left brachiocephalic vein, and in 30% by levophase CS venography. In 30%, sPLSVC was associated with drainage from the CS into the left atrium (LA). When associated with CS ostial abnormalities, the sPLSVC diameter averaged 5.6 ± 3 mm. sPLSVC was used for successful LV lead implantation in 90% of cases. In 80%, the LV lead was implanted down sPLSVC, and in 20%, sPLSVC was used to access the CS from the RA. Presumably because of unrecognized drainage from the CS to the LA, 1 patient had a stroke during implantation via sPLSVC. CONCLUSION: When CS ostial abnormalities prevent access to the CS from the RA, sPLSVC can be used to successfully implant LV leads. In some, the CS partially drains into the LA and stroke can occur spontaneously or during lead intervention. It is important to distinguish sPLSVC associated with CS ostial abnormalities from isolated PLSVC.

Three-dimensional stress echocardiography: the promise and limitations of volumetric imaging.

PURPOSE OF REVIEW: Three-dimensional (3D) volumetric imaging has potential advantages in stress echocardiography, including the ability to provide an unlimited number of planes for analysis and more rapid acquisition than conventional two-dimensional (2D) imaging. This review focuses on the advantages and disadvantages of 3D volumetric imaging and the current and future role of the technique in stress echocardiography. RECENT FINDINGS: Three-dimensional volumetric imaging uniformly shortens the time required for acquisition of stress images. The success of imaging is high with pharmacologic stress but the feasibility is not established with exercise stress. The lower spatial and temporal resolution of 3D imaging and artifacts introduced by suboptimal subvolume integration are limitations of the current 3D technique. The ability to provide more planes for analysis has not been clearly shown to improve the accuracy of stress echocardiography. However, 3D imaging eliminates apical foreshortening, which is common with 2D imaging, and may improve detection of apical wall motion abnormalities. SUMMARY: In general, 3D imaging has shown rates of success and accuracy comparable to those of 2D imaging in pharmacologic stress echocardiography. Further studies are needed in larger and more heterogeneous patient populations. As improvements in 3D technology continue, successful application of the technique to exercise echocardiography is likely. Development of automated image registration, quantitative analysis techniques, and single beat acquisition is needed to fully exploit the potential of 3D imaging in the stress laboratory.

Inhibition of p53-murine double minute 2 interaction by nutlin-3A stabilizes p53 and induces cell cycle arrest and apoptosis in Hodgkin lymphoma.

PURPOSE: p53 is frequently expressed but rarely mutated in Hodgkin and Reed-Sternberg (HRS) cells of Hodgkin's lymphoma (HL). p53 protein levels are regulated by murine double minute 2 (MDM2) through a well-established autoregulatory feedback loop. In this study, we investigated the effects of nutlin-3A, a recently developed small molecule that antagonizes MDM2 and disrupts the p53-MDM2 interaction, on p53-dependent cell cycle arrest and apoptosis in cultured HRS cells. EXPERIMENTAL DESIGN: HL cell lines carrying wild-type (wt) or mutated p53 gene were treated with the potent MDM2 inhibitor nutlin-3A or a 150-fold less active enantiomer, nutlin-3B. RESULTS: We show that nutlin-3A, but not nutlin-3B, stabilizes p53 in cultured HRS cells carrying wt p53 gene resulting in p53-dependent cell cycle arrest and apoptosis. Cell cycle arrest was associated with up-regulation of the cyclin-dependent kinase inhibitor p21. Nutlin-3A-induced apoptotic cell death was accompanied by Bax and Puma up-regulation and caspase-3 cleavage and was abrogated, in part, by inhibition of caspase-9 and caspase-3 activity. By contrast, no effects on cell cycle or apoptosis were found in HL cell lines harboring mutated p53 gene. Furthermore, combined treatment with nutlin-3A and doxorubicin revealed enhanced cytotoxicity in HRS cells with wt p53 gene. Blocking of nuclear export by leptomycin B, or inhibition of proteasome by MG132, stabilized p53 at a level comparable with that of nutlin-3A treatment in HRS cells with wt p53. CONCLUSIONS: These data suggest that nutlin-3A stabilized p53 by preventing MDM2-mediated p53 degradation in HRS cells. wt p53 stabilization and activation by nutlin-3A may be a novel therapeutic approach for patients with HL.

Utility of Invasive Electrophysiology Studies in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

Permanent pacemaker (PPM) implantation remains common after transcatheter aortic valve implantation (TAVI). Invasive electrophysiology studies (EPSs) may reduce PPM implantation rates by identifying patients who do not require long-term pacing. At our institution, a new strategy in which patients with equivocal indications for pacing underwent EPSs to determine the need for PPM implantation was adopted. We compared baseline demographics, TAVI procedural details, and outcomes in patients without any conduction disturbance after TAVI, patients with new PPM implantation, and patients with EPS ± new PPM implantation. After exclusion for preexisting PPMs, of a total of 614 consecutive TAVI patients, 117 (19.1%) required new PPM implantation for unequivocal pacing indications, and 95 (15.5%) underwent EPSs. Of those patients who underwent EPSs, 28 (29.5%) required PPM implantation and 67 (70.5%) did not. The overall rate of new PPM implantation was higher for self-expanding versus balloon-expandable valves (34.0% vs 19.9%, p = 0.0011). PPM implantation increased intensive care and hospital length of stay compared with patients without any conduction disturbance (10.7 ± 8.3 vs 8.5 ± 6.4 days, p = 0.003). A negative EPS did not prolong length of stay. There were no significant differences in 30-day and 1-year mortality between groups. In conclusion, among TAVI patients with new-onset conduction disturbance, EPS is a safe strategy to identify those who require PPM implantation and those in whom PPMs can be avoided.

Prognostic significance of MUC-1 expression in systemic anaplastic large cell lymphoma.

Systemic anaplastic large cell lymphoma (ALCL) frequently carries the t(2;5)(p23;q35) and overexpresses anaplastic lymphoma kinase (ALK). MUC-1, a highly glycosylated transmembrane protein, is detected in normal and malignant epithelial cells and has been associated with a poorer patient survival in various human malignancies. We have shown previously that MUC-1 is expressed as a consequence of t(1;14)(q21;32) in a subset of diffuse large B-cell lymphomas. ALCLs are known to express MUC-1, but its clinical significance is undefined. For this study, eligible patients with ALCL were HIV negative, received anthracycline-containing regimens, and had pretreatment archival tissue. Expression of MUC-1 and ALK was determined immunohistochemically after heat-induced antigen retrieval. A 10% cutoff for MUC-1 positivity was used. We identified 63 patients with systemic ALCL (22 ALK+, 41 ALK-) with a median age of 47 years, and 41 were male. MUC-1 was detected in 16 of 22 (73%) ALK-positive and 20 of 41 (49%) ALK-negative ALCL (P = 0.06, chi(2) test). MUC-1 expression was not associated with apoptotic rate as detected by terminal deoxynucleotidyl transferase-mediated nick end labeling assay or proliferation index as evaluated by MIB-1 antibody. For 48 patients with ALCL (16 ALK+, 32 ALK-) and complete clinical follow-up, 5-year progression-free survival (PFS) was 39.7% for patients with MUC-1-positive tumors versus 75.2% (P = 0.027 by Log-rank) for patients with MUC-1-negative tumors. For the ALK-negative ALCL group of 32 patients, the 5-year PFS was 26 versus 70.8% for patients with MUC-1-positive versus MUC-1-negative tumors (P = 0.0096 by Log-rank). For the ALK-positive ALCL group of 16 patients, the 5-year PFS was 52 versus 100% for patients with MUC-1-positive versus MUC-1-negative tumors (P, not significant). In summary, MUC-1 is frequently expressed in systemic ALCL, and its expression is associated with significantly inferior outcome in patients untreated previously with ALK-negative tumors. Future studies should explore the underlying molecular mechanisms of MUC-1 expression in these tumors and its role as a target for novel therapeutic strategies.

Quantitative real-time polymerase chain reaction for monitoring minimal residual disease in patients with advanced indolent lymphomas treated with rituximab, fludarabine, mitoxantrone, and dexamethasone.

Fludarabine and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) are active against indolent lymphomas. We have previously shown the safety and efficacy of the combination of FND (fludarabine/mitoxantrone/dexamethasone) in relapsed and subsequently untreated patients with stage IV indolent lymphomas. Currently, we treat patients with stage IV indolent lymphomas who are previously untreated, younger than 60 years, human immunodeficiency virus-negative, and have adequate organ and marrow function with FND and random assignment to concurrent or delayed administration of rituximab. We have developed a quantitative real-time polymerase chain reaction assay for t(14;18). With 1 microg of DNA, this assay detects 0.6 copies in 55% of reactions, as expected for the Poisson distribution. When 1microg of DNA was analyzed in duplicate, cells with the t(14;18) were detected in peripheral blood of 22% of 152 volunteer blood donors. Quantitation showed that numbers of t(14;18) cells were higher than the statistical upper normal limit (mean of all volunteer values plus standard deviations) in 2% of volunteer blood donors. By contrast, 36% of blood or marrow specimens from follicular lymphoma patients were positive, and the number of cells with t(14;18) was higher than the normal upper limit in 26%. The presence of cells with t(14;18) and their numbers are prospectively quantitated in blood and marrow of patients treated with FND plus rituximab to determine their clinical significance both at presentation and during therapy.

Apoptotic rate in peripheral T-cell lymphomas. A study using a tissue microarray with validation on full tissue sections.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of non-Hodgkin lymphomas with a wide spectrum of clinicopathologic features, and apoptosis mechanisms may have a role in lymphomagenesis. We assessed apoptotic rate (AR) in 112 PTCLs using a tissue microarray developed in our laboratory and a modified terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. The mean AR was 1.47% +/- 1.38% for the entire group of PTCLs (range, 0.06%-5.15%), and AR varied significantly among different tumor types. In mycosis fungoides, the mean AR was 0.74%; angioimmunoblastic T-cell lymphoma, 1.02%; PTCL, not otherwise specified, 1.38%; cutaneous anaplastic large cell lymphoma (ALCL), 1.41%; anaplastic lymphoma kinase protein (ALK)-negative ALCL, 1.43%; extranodal natural killer/T-cell lymphoma of nasal type, 2.04%; ALK-positive ALCL, 2.95%; and enteropathy-type T-cell lymphoma, 3.06%. Mean AR was higher in PTCL with large cell vs small/medium cell morphologic features (1.66% +/- 1.1% vs 0.99% +/- 1.0%). In a subset of 33 PTCLs, the tissue microarray results comparedfavorably with those obtained in full tissue sections. We conclude that the highest ARs in PTCLs are found in enteropathy-type T-cell lymphoma and ALK-positive ALCL, and that AR can be assessed reliably by using a tissue microarray.

Improving prediction of outcomes in African Americans with normal stress echocardiograms using a risk scoring system.

Cardiovascular mortality is high in African Americans, and those with normal results on stress echocardiography remain at increased risk. The aim of this study was to develop a risk scoring system to improve the prediction of cardiovascular events in African Americans with normal results on stress echocardiography. Clinical data and rest echocardiographic measurements were obtained in 548 consecutive African Americans with normal results on rest and stress echocardiography and ejection fractions ≥50%. Patients were followed for myocardial infarction and death for 3 years. Predictors of cardiovascular events were determined with Cox regression, and hazard ratios were used to determine the number of points in the risk score attributed to each independent predictor. During follow-up of 3 years, 47 patients (8.6%) had events. Five variables-age (≥45 years in men, ≥55 years in women), history of coronary disease, history of smoking, left ventricular hypertrophy, and exercise intolerance (<7 METs in men, <5 METs in women, or need for dobutamine stress)-were independent predictors of events. A risk score was derived for each patient (ranging from 0 to 8 risk points). The area under the curve for the risk score was 0.82 with the optimum cut-off risk score of 6. Among patients with risk scores ≥6, 30% had events, compared with 3% with risk score <6 (p <0.001). In conclusion, African Americans with normal results on stress echocardiography remain at significant risk for cardiovascular events. A risk score can be derived from clinical and echocardiographic variables, which can accurately distinguish high- and low-risk patients.

Chronotropic incompetence on dobutamine stress echocardiography in candidates for a liver transplant.

OBJECTIVES: We evaluated dobutamine stress echocardiography as an initial screening test for a cardiac evaluation before a liver transplant. MATERIALS AND METHODS: We retrospectively examined 111 liver transplant candidates who had undergone previous cardiac evaluation; 30 of whom had undergone a liver transplant. RESULTS: Eighty patients (72.1%) completed a dobutamine stress echocardiography (41 chronotropically competent, 39 incompetent), while 31 patients (27.9%) required us to terminate early. Overall, 68 patients (61%) were on ß-blockers (21 required early dobutamine stress echocardiography termination, 30 chronotropically incompetent, and 17 competent). Patient results were normal. Thirty patients underwent a liver transplant. Among candidates requiring termination of early dobutamine stress echocardiography, posttransplant cardiac events included 1 fatal acute myocardial infarction, 1 nonfatal acute myocardial infarction, and 1 idiopathic cardiomyopathy. Among chronotropically incompetent patients, 2 patients had transient bradycardia, and among those who were chronotropically competent, 1 had refractory atrial fibrillation, and 1 had transient bradycardia. CONCLUSIONS: Nearly 50% of patients with end-stage liver disease may not reach the target heart rate. Early termination of dobutamine stress echocardiography because of cardiac symptoms or significant echocardiographic changes have more effect in predicting postoperative cardiac events, but further evaluation is required even if their target heart rate is close to that desired. Lower target heart rate may be acceptable in chronotropically incompetent individuals provided they are asymptomatic, have no echocardiographic changes, or cardiovascular risk factors, especially if they are on ß-blockers.

JunB expression is a common feature of CD30+ lymphomas and lymphomatoid papulosis.

JunB is a member of the Jun family of proteins that are components of the AP-1 transcription factor complex. AP-1 is involved in cell proliferation and apoptosis. Recent evidence suggests that Hodgkin and Reed-Sternberg cells overexpress JunB and that JunB facilitates constitutive CD30 expression by binding to an AP-1 site in the CD30 promoter. In this study we surveyed JunB expression in a variety of CD30+ lymphoma types including 42 cases of anaplastic large cell lymphoma, 36 classical Hodgkin lymphoma, 15 cutaneous anaplastic large cell lymphoma, and 11 CD30+ diffuse large B-cell lymphoma. In addition, seven cases of nodular lymphocyte-predominant Hodgkin lymphoma and 42 diffuse large B-cell lymphoma, known to be CD30-, were analyzed. JunB expression was assessed using tissue microarrays, immunohistochemistry and a monoclonal antibody specific for JunB. Expression of JunB was observed in 41 of 42 cases of anaplastic large cell lymphoma, including all 21 cases positive for anaplastic lymphoma kinase and 20 of 21 (95%) negative for anaplastic lymphoma kinase. JunB was also expressed in all cases of classical Hodgkin lymphoma, cutaneous anaplastic large cell lymphoma and CD30+ diffuse large B-cell lymphoma, and in lymphomatoid papulosis. By contrast, all nodular lymphocyte-predominant Hodgkin lymphomas and diffuse large B-cell lymphomas that were CD30- were also JunB-. We conclude that JunB is expressed in virtually all CD30+ lymphomas and is a potential target for experimental therapy in patients with these tumors.

Quantitative real-time polymerase chain reaction for monitoring minimal residual disease in patients with advanced indolent lymphomas treated with rituximab, fludarabine, mitoxantrone, and dexamethasone.

Fludarabine and rituximab (Rituxan; Genentech, Inc, South San Francisco, CA, and IDEC Pharmaceuticals, San Diego, CA) are active against indolent lymphomas. We have previously shown the safety and efficacy of the combination of FND (fludarabine/mitoxantrone/dexamethasone) in relapsed and subsequently untreated patients with stage IV indolent lymphomas. Currently, we treat patients with stage IV indolent lymphomas who are previously untreated, younger than 60 years, human immunodeficiency virus-negative, and have adequate organ and marrow function with FND and random assignment to concurrent or delayed administration of rituximab. We have developed a quantitative real-time polymerase chain reaction assay for t(14;18). With 1 µg of DNA, this assay detects 0.6 copies in 55% of reactions, as expected for the Poisson distribution. When 1µg of DNA was analyzed in duplicate, cells with the t(14;18) were detected in peripheral blood of 22% of 152 volunteer blood donors. Quantitation showed that numbers of t(14;18) cells were higher than the statistical upper normal limit (mean of all volunteer values plus standard deviations) in 2% of volunteer blood donors. By contrast, 36% of blood or marrow specimens from follicular lymphoma patients were positive, and the number of cells with t(14;18) was higher than the normal upper limit in 26%. The presence of cells with t(14;18) and their numbers are prospectively quantitated in blood and marrow of patients treated with FND plus rituximab to determine their clinical significance both at presentation and during therapy. Semin Oncol 29 (suppl 2):48-55. Copyright © 2002 by W.B. Saunders Company.