Immunomodulation of T- and NK-cell Responses by a Bispecific Antibody Targeting CD28 Homolog and PD-L1.

Checkpoint blockade therapies targeting PD-1/PD-L1 and CTLA-4 are clinically successful but also evoke adverse events due to systemic T-cell activation. We engineered a bispecific, mAb targeting CD28 homolog (CD28H), a newly identified B7 family receptor that is constitutively expressed on T and natural killer (NK) cells, with a PD-L1 antibody to potentiate tumor-specific immune responses. The bispecific antibody led to T-cell costimulation, induced NK-cell cytotoxicity of PD-L1-expressing tumor cells, and activated tissue-resident memory CD8+ T cells. Mechanistically, the CD28H agonistic arm of the bispecific antibody reduced PD-L1/PD-1-induced SHP2 phosphorylation while simultaneously augmenting T-cell receptor signaling by activating the MAPK and AKT pathways. This bispecific approach could be used to target multiple immune cells, including CD8+ T cells, tissue-resident memory T cells, and NK cells, in a tumor-specific manner that may lead to induction of durable, therapeutic antitumor responses.

Risk stratification with longitudinal neutrophil to lymphocyte ratio assessment after left ventricular assist device implantation.

INTRODUCTION: Inflammatory processes are well-characterized risk factors in cardiovascular disease including advanced heart failure. Previous studies have utilized individual white cell subtypes in risk analysis, and a recent study has focused on the efficacy of the neutrophil-to-lymphocyte ratio in evaluating negative outcomes following left ventricular assist device implantation. To investigate the interaction between the left ventricular assist device and white cell counts, we assessed longitudinal changes in neutrophil-to-lymphocyte ratio following left ventricular assist device implantation. METHODS: This retrospective study included 100 patients who underwent left ventricular assist device implantation between 2012 and 2013. The neutrophil-to-lymphocyte ratio was calculated prior to left ventricular assist device implantation, daily for the first 30 postoperative days, and at the first two postoperative outpatient visits. Preoperative demographic and clinical data were collected for all patients. RESULTS: The mean neutrophil-to-lymphocyte ratio immediately before left ventricular assist device implantation was 5.2 ± 4.9. After surgery, the neutrophil-to-lymphocyte ratio decreased asymptotically, from a peak of 29.2 on postoperative day 1 to 4.1 at the second outpatient visit ( p < 0.001). Lack of improvement in the neutrophil-to-lymphocyte ratio at postoperative day 10 was associated with increased length of stay, right heart failure, and a trend toward worsened survival. CONCLUSION: Our results indicate a significant inflammatory response to implantation of the left ventricular assist device, a known effect. The magnitude of this response may be effectively and easily monitored over time using the neutrophil-to-lymphocyte ratio. In general, approximately 30 days is required for the neutrophil-to-lymphocyte ratio to return to preoperative levels. After several months, the neutrophil-to-lymphocyte ratio improves to below preoperative levels. It is possible that this reduction reflects the reversal of various heart failure-mediated inflammatory processes following left ventricular assist device implantation.

Preoperative Nutritional Assessment with the Prognostic Nutrition Index in Patients Undergoing Left Ventricular Assist Device Implantation.

The prognostic nutritional index (PNI) is a simple metric that uses serum albumin and total lymphocyte count to provide a basic indicator for nutritional status. It has recently garnered attention as a prognosticator of outcomes in many types of cancer. We investigated the utility of the PNI as a marker for poor outcomes following left ventricular assist device (LVAD) implantation. Two hundred eighty-eight consecutive patients implanted with continuous-flow LVADs were included. Prognostic nutritional index was calculated for all patients (PNI = [10 × serum albumin {g/dl}] + [0.005 × total lymphocytes {1,000/µl}]). The population was split into two groups based on median PNI; group 1 with PNI <30 and group 2 with PNI ≥30. Mean age was 60.3 years in group 1 and 59.8 years in group 2. There were no significant differences between groups in terms of age, gender, ethnicity, or comorbidities. The mean PNI for the group as a whole was 30.1 ± 4.6, indicating pervasive malnutrition in this group of advanced heart failure patients. Group 1 had significantly longer postoperative length of stay than did group 2 (27.42 ± 19.31 vs. 21.66 ± 15.0 days; p = 0.008). Patients in group 1 also had higher rates of right ventricular failure (37.8% vs. 25.5%; p = 0.025). A multivariate model indicated that PNI less than 30 was associated with a 12.2% reduction in postoperative survival (Hazard Ratio: 0.888; confidence interval [CI]: 0.795-0.993; p = 0.037). Our results suggest that the PNI may be an indicator for worsened outcomes in patients with advanced heart failure. These patients, who often suffer from chronic malnutrition, may experience worsened outcomes because of associated neurohormonal, muscular, and metabolic derangements.

Efficacy of Inpatient Rehabilitation After Left Ventricular Assist Device Implantation.

BACKGROUND: Left ventricular assist devices (LVADs) have become an increasingly popular and effective means for treating advanced heart failure. LVAD implantation requires extensive surgery and postoperative rehabilitation. The Functional Independence Measure (FIM) has been used to quantify functional gains in numerous patient populations, including those with stroke and spinal cord injury. This study investigated functional improvements in patients undergoing LVAD implantation using the FIM score. OBJECTIVE: To assess functional improvements in patients with advanced heart failure who underwent LVAD implantation. DESIGN: Retrospective. SETTING: Inpatient rehabilitation unit. SUBJECTS: Ninety consecutive patients who received acute inpatient rehabilitation after continuous flow LVAD implantation. METHODS: Demographic, laboratory, and functional outcomes data including inpatient rehabilitation unit (IRU) length of stay (LOS), discharge disposition, and FIM score were collected for all patients. Paired t-tests were used to assess change in functional measures and laboratory data. MAIN OUTCOME MEASURES: Primary outcome measures included FIM gain, FIM efficiency, discharge disposition, rates of readmission after discharge from rehabilitation, and LOS in the rehabilitation unit. RESULTS: The FIM gain was statistically significant at 28.4 ± 12.3 (P < .001) and compared favorably with benchmarks for mean FIM gains at our facility (26.4), regionally (21.5), and nationally (22.7) for patients admitted to IRUs with a cardiac diagnosis. FIM efficiency (FIM gain/IRU LOS) was 1.9 ± 1.0 compared with the mean FIM efficiency at our facility (2.2), regionally (2.1), and nationally (2.2). Seventy-four percent (n = 67) of patients were discharged directly home after inpatient rehabilitation, 17% (n = 16) were readmitted to the acute hospital service, and 8% (n = 7) required additional rehabilitation at a subacute rehabilitation facility. The IRU LOS was 16.2 ± 6.9 days. CONCLUSIONS: Our study indicates that most patients with an LVAD achieve clinically meaningful functional gains from acute inpatient rehabilitation, with the majority of patients being discharged home. Further studies need to be performed to analyze clinical outcomes after acute inpatient rehabilitation. LEVEL OF EVIDENCE: IV.

Relationship Between Handgrip Strength and Length of Stay for Left Ventricular Assist Device Implantation.

BACKGROUND: Advanced heart failure is associated with a wide range of physiological derangements, including muscular deterioration, weight loss, and cardiac cachexia. These conditions, as well as poor nutrition status, have been shown to affect the quality of outcomes in patients who undergo left ventricular assist device (LVAD) implantation. Noting that handgrip strength has been shown to be an effective indicator of poor functional status, muscular strength, and nutrition, we investigated its use as a tool for prediction of length of stay (LOS) in patients undergoing LVAD implantation. MATERIALS AND METHODS: Handgrip strength was measured in 90 patients undergoing evaluation for LVAD implantation using the Jamar Hand Dynamometer. Handgrip strength was normalized to body weight (HGS:BW), and patients were divided into 2 groups: those with HGS:BW <28.5% and those with HGS:BW ≥28.5%. Clinical data and length of stay were compared between groups. RESULTS: Patients with lower HGS:BW tended to have worsened clinical indicators of heart failure severity, including reduced ejection fraction, serum albumin, and hemoglobin and increased B-type natriuretic peptide and white blood cell count. Lower HGS:BW was an independent predictor for increased LOS. CONCLUSION: Handgrip strength measurement at the bedside is a simple and effective means of assessing functional status and risk for increased LOS following LVAD implantation, which may aid in preoperative evaluation of LVAD candidacy.

Loss of Immune Tolerance Is Controlled by ICOS in Sle1 Mice.

ICOS, a member of the CD28 family, represents a key molecule that regulates adaptive responses to foreign Ags. ICOS is prominently expressed on T follicular helper (TFH) cells, a specialized CD4(+) T cell subset that orchestrates B cell differentiation within the germinal centers and humoral response. However, the contribution of ICOS and TFH cells to autoantibody profiles under pathological conditions has not been thoroughly investigated. We used the Sle1 lupus-prone mouse model to examine the role of ICOS in the expansion and function of pathogenic TFH cells. Genetic deletion of ICOS impacted the expansion of TFH cells in B6.Sle1 mice and inhibited the differentiation of B lymphocytes into plasma cells. The phenotypic changes observed in B6.Sle1-ICOS-knockout mice were also associated with a significant reduction in class-switched IgG, and anti-nucleosomal IgG-secreting B cells compared with B6.Sle1 animals. The level of vascular cell adhesion protein 1, a molecule that was shown to be elevated in patients with SLE and in lupus models, was also increased in an ICOS-dependent manner in Sle1 mice and correlated with autoantibody levels. The elimination of ICOS-expressing CD4(+) T cells in B6.Sle1 mice, using a glyco-engineered anti-ICOS-depleting Ab, resulted in a significant reduction in anti-nucleosomal autoantibodies. Our results indicate that ICOS regulates the ontogeny and homeostasis of B6.Sle1 TFH cells and influences the function of TFH cells during aberrant germinal center B cell responses. Therapies targeting the ICOS signaling pathway may offer new opportunities for the treatment of lupus and other autoimmune diseases.

Acute Cellular Rejection and C4d Positivity in Heart Transplantation : A Manifestation of Asymptomatic Antibody-Mediated Rejection?

OBJECTIVES: The role of routine C4d staining in endomyocardial biopsy specimens is uncertain. The implications of a diagnosis of acute cellular rejection (ACR) with a positive C4d with or without any evidence of antibody-mediated rejection (AMR) are unclear. This study sought to evaluate a distinct phenotype of ACR+/C4d+ in AMR- patients. METHODS: Data on C4d, ACR, and AMR were collected. Donor-specific antibody (DSA), panel-reactive antibody (PRA), flow crossmatch, and data on ACR and AMR episodes were also reviewed. RESULTS: Thirty-five patients were followed. Group I with C4d+ biopsy specimens was compared with group II with C4d- biopsy specimens. ACR greater than 1R was higher in group I compared with group II (50% vs 7.4%; P = .01). Clinical suspicion of AMR, positive retrospective crossmatches, and detection of de novo DSA were also higher in group I. CONCLUSIONS: Our result indicate that C4d and ACR positivity in posttransplant patients may be a harbinger of a subclinical form of asymptomatic AMR.

Intraoperative bronchoscopic visualization of left ventricular assist device thrombus.

Despite advancements in left ventricular assist device (LVAD) design and clinical management, device thrombosis remains a pertinent complication. Limited imaging makes precise visualization of clot location and shape very challenging. We report the usage of videobronchoscopic exploration of explanted LVADs for direct visualization of clot in two patients. This technique is a rapid and inexpensive means of improving our understanding of LVAD clot formation and may be useful in surgical exploration of inflow and outflow tracts during LVAD exchange.

Acoustic Characterization of Axial Flow Left Ventricular Assist Device Operation In Vitro and In Vivo.

The use of left ventricular assist devices (LVADs), implantable pumps used to supplement cardiac output, has become an increasingly common and effective treatment for advanced heart failure. Although modern continuous-flow LVADs improve quality of life and survival more than medical management of heart failure, device malfunction remains a common concern. Improved noninvasive methods for assessment of LVAD function are needed to detect device complications. An electronic stethoscope was used to record sounds from the HeartMate II axial flow pump in vitro and in vivo. The data were then uploaded to a computer and analyzed using two types of acoustic analysis software. Left ventricular assist device acoustics were quantified and were related to pump speed, acoustic environment, and inflow and outflow graft patency. Peak frequency values measured in vivo were found to correlate strongly with both predicted values and in vitro measurements (r > 0.999). Plots of the area under the acoustic spectrum curve, obtained by integrating over 50 Hz increments, showed strong correlations between in vivo and in vitro measurements (r > 0.966). Device thrombosis was found to be associated with reduced LVAD acoustic amplitude in two patients who underwent surgical device exchange.

Changes in Spirometry After Left Ventricular Assist Device Implantation.

Left ventricular assist devices (LVADs) are increasingly being used as life-saving therapy in patients with end-stage heart failure. The changes in spirometry following LVAD implantation and subsequent unloading of the left ventricle and pulmonary circulation are unknown. In this study, we explored long-term changes in spirometry after LVAD placement. In this retrospective study, we compared baseline preoperative pulmonary function test (PFT) results to post-LVAD spirometric measurements. Our results indicated that pulmonary function tests were significantly reduced after LVAD placement (forced expiratory volume in one second [FEV1 ]: 1.9 vs.1.7, P = 0.016; forced vital capacity [FVC]: 2.61 vs. 2.38, P = 0.03; diffusing capacity of the lungs for carbon monoxide [DLCO]: 14.75 vs. 11.01, P = 0.01). Subgroup analysis revealed greater impairment in lung function in patients receiving HeartMate II (Thoratec, Pleasanton, CA, USA) LVADs compared with those receiving HeartWare (HeartWare, Framingham, MA, USA) devices. These unexpected findings may result from restriction of left anterior hemi-diaphragm; however, further prospective studies to validate our findings are warranted.

Results of the destination therapy post-food and drug administration approval study with a continuous flow left ventricular assist device: a prospective study using the INTERMACS registry (Interagency Registry for Mechanically Assisted Circulatory Support).

OBJECTIVES: A post-approval (PA) study for destination therapy (DT) was required by the Food and Drug Administration (FDA) to determine whether results with the HeartMate (HM) II (Thoratec, Pleasanton, California) left ventricular assist device (LVAD) in a commercial setting were comparable to results during the DT multicenter pivotal clinical trial. BACKGROUND: New device technology developed in the clinical research setting requires validation in a real-world setting. METHODS: The PA study was a prospective evaluation of the first 247 HM II patients identified pre-operatively as eligible for DT in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) registry. Patients were enrolled from January to September 2010 at 61 U.S. centers and followed for 2 years. A historical comparison group included patients (n = 133 at 34 centers) enrolled in the primary data cohort in the DT pivotal trial (TR). Survival rates and adverse events for the PA group were obtained from the INTERMACS registry. RESULTS: Baseline characteristics were similar for PA versus TR. Forty-five percent of PA patients were in INTERMACS profiles 1 to 2 and 28% were in profile 3. Adverse events in the PA group were similar or lower than those in the TR group, including improvements in device-related infection (0.22 vs. 0.47) and post-operative bleeding requiring surgery (0.09 vs. 0.23) events per patient-year. Kaplan-Meier survival at 2 years was 62% (PA group) versus 58% (TR group). PA group survival at 1 and 2 years was 82 ± 5% and 69 ± 6% for INTERMACS profiles 4 to 7 (n = 63) versus 72 ± 3% and 60 ± 4% for profiles 1 to 3 (n = 184). The median length of stay after surgery was reduced by 6 days in the PA group versus the TR group. CONCLUSIONS: Results in a commercial patient care setting for the DT population supported the original pivotal clinical trial findings regarding the efficacy and risk profile of the HM II LVAD. Survival was best in patients who were not inotrope-dependent (INTERMACS profiles 4 to 7).

Impact of cardiovascular magnetic resonance on management and clinical decision-making in heart failure patients.

BACKGROUND: Cardiovascular magnetic resonance (CMR) can provide important diagnostic and prognostic information in patients with heart failure. However, in the current health care environment, use of a new imaging modality like CMR requires evidence for direct additive impact on clinical management. We sought to evaluate the impact of CMR on clinical management and diagnosis in patients with heart failure. METHODS: We prospectively studied 150 consecutive patients with heart failure and an ejection fraction ≤ 50% referred for CMR. Definitions for "significant clinical impact" of CMR were pre-defined and collected directly from medical records and/or from patients. Categories of significant clinical impact included: new diagnosis, medication change, hospital admission/discharge, as well as performance or avoidance of invasive procedures (angiography, revascularization, device therapy or biopsy). RESULTS: Overall, CMR had a significant clinical impact in 65% of patients. This included an entirely new diagnosis in 30% of cases and a change in management in 52%. CMR results directly led to angiography in 9% and to the performance of percutaneous coronary intervention in 7%. In a multivariable model that included clinical and imaging parameters, presence of late gadolinium enhancement (LGE) was the only independent predictor of "significant clinical impact" (OR 6.72, 95% CI 2.56-17.60, p=0.0001). CONCLUSIONS: CMR made a significant additive clinical impact on management, decision-making and diagnosis in 65% of heart failure patients. This additive impact was seen despite universal use of prior echocardiography in this patient group. The presence of LGE was the best independent predictor of significant clinical impact following CMR.

The development of aortic insufficiency in continuous-flow left ventricular assist device-supported patients.

BACKGROUND: Significant aortic insufficiency (AI) after left ventricular assist device (LVAD) placement affects device performance and end-organ perfusion. This study examined the development and progression of AI after implantation of continuous-flow LVAD. METHODS: Seventy-nine patients undergoing Heart Mate II (Thoratec Corp, Pleasanton, CA) LVAD implantation for predominantly destination therapy (n = 69 [87%]) were examined. Preoperative and postoperative echocardiograms for all patients were reviewed at the intervals of 0 to 3, 3 to 6, 6 to 12, 12 to 18, and 18 to 24 months. AI was graded on an interval scale of 0, none; 0.5, trivial; 1, mild; 1.5, mild to moderate; 2, moderate; 2.5, moderate to severe; and 3, severe. Development and progression of AI were analyzed. RESULTS: The incidence of significant AI (mild or greater) was 52% (n = 41). Median time to AI development was 187 days. The median duration of VAD support was 761 days. Mild AI developed in 41 patients (52%). No severe AI developed. In the Cox regression model (hazard ratio [95% confidence interval]), aortic valve closure (2.51 [1.06 to 5.89]; p = 0.03), and age (1.04 [1.008 to 1.08]; p = 0.01) were independent predictors of AI development. There was no difference in mortality rates in the two groups (p = 0.40 by log-rank test). A mixed-model linear regression analysis showed a significant overall progression of AI over time (ß ± standard error, 0.06 ± 0.02; p = 0.006). CONCLUSIONS: AI develops over time in a significant number of Heart Mate II LVAD patients. AI is more common in patients with closed aortic valves and in the older age group. As more patients require long-term VAD support, the development of AI will need careful attention and monitoring.

Experience with noncardiac surgery in destination therapy left ventricular assist devices patients.

Continuous flow left ventricular assist devices (CF-LVAD) are increasing the life expectancy of patients with advanced heart failure, with these patients undergoing more noncardiac operations after implantation. The purpose of this study was to determine the safety of noncardiac operations in destination therapy CF-LVAD patients. In a retrospective study of 110 CF-LVAD patients, we reviewed 36 patients who underwent 63 noncardiac operations 315.1 ± 333.5 days after LVAD placement. Fifty-four (84%) operations were elective and 10 were emergent. The mean age of the cohort was 61.4 ± 11.4 years, with the majority (81%) being men. Most patients (n = 24, 38%) underwent total abdominal operation. Of the 36 patients in the study, 23 (63.8%) patients required one surgical procedure, and 13(36.1%) patients underwent more than one procedure. Six critically ill patients (16%) of 37 expired within 30 days after emergent operation. Our study demonstrates overall good clinical outcomes with minimal intraoperative complications in LVAD patients undergoing noncardiac surgeries, except an increased propensity for intra- and postoperative transfusion of blood products because of complex coagulopathies.

Early cardiac allograft vasculopathy: are the viruses to blame?

This paper describes a case of early (7 months after transplant) cardiac allograft vasculopathy. This-43-year-old (CMV positive, EBV negative) female patient underwent an orthotopic heart transplant with a (CMV negative, EBV positive) donor heart. She had a history of herpes zoster infection and postherpetic neuralgia in the past. The patient's panel reactive antibodies had been almost undetectable on routine surveillance testing, and her surveillance endomyocardial biopsies apart from a few episodes of mild-to-moderate acute cellular rejection (treated adequately with steroids) never showed any evidence of humoral rejection. The postoperative course was complicated by multiple admissions for upper respiratory symptoms, and the patient tested positive for entero, rhino, and coronaviruses serologies. During her last admission (seven months postoperatively) the patient developed mild left ventricular dysfunction with an ejection fraction of 40%. The patient's endomyocardial biopsy done at that time revealed concentric intimal proliferation and inflammation resulting in near-total luminal occlusion in the epicardial and the intramyocardial coronary vessels, suggestive of graft vasculopathy with no evidence of rejection, and the patient had a fatal ventricular arrhythmia.

Incidence and management of gastrointestinal bleeding with continuous flow assist devices.

BACKGROUND: Continuous flow left ventricular assist devices (CF-LVADs) have emerged as the standard of care for patients in advanced heart failure (HF) requiring long-term mechanical circulatory support. Gastrointestinal (GI) bleeding has been frequently reported within this population. METHODS: A retrospective analysis of 101 patients implanted with the Heart Mate II from January 2005 to August 2011 was performed to identify incidence, etiology, and management of GI bleeding. Univariate and multivariate regression analysis was conducted to identify related risk factors. RESULTS: A significant incidence of GI bleeding (22.8%) occurred in our predominantly destination therapy (DT) (93%) population. Fifty-seven percent of the patients with bleeding episodes bled from the upper GI (UGI) tract (with 54% bleeding from gastric erosions and 37% from ulcers/angiodysplasias), whereas 35% of patients bled from the lower GI (LGI) tract. Previous history of GI bleeding (odds ratio [OR], 22.7; 95% CI, 2.2-228.6; p=0.008), elevated international normalized ratio (INR) (OR, 3.9; CI, 1.2-12.9; p=0.02), and low platelet count (OR, -0.98; CI, 0.98 -0.99; p=0.001) were independent predictors of GI hemorrhage. Recurrent bleeding was more common in older patients (mean, 70 years; p=0.01). The majority of bleeders (60%) rebled from the same site. Management strategies included temporarily withholding anticoagulation, decreasing the speed of LVADs, and using octreotide. Octreotide did not impact the amount of packed red blood cells used, rebleeding rates, length of hospital stay, or all-cause mortality. Only 1 patient died as a direct consequence of GI bleeding. CONCLUSIONS: Multiple factors account for GI bleeding in patients on CF-VADs. A previous history of bleeding increases risk significantly and warrants careful monitoring.

Correlation of noninvasive markers of cardiac allograft rejection with endomyocardial biopsy: a case report.

Although endomyocardial biopsy remains the gold standard to diagnose cardiac allograft rejection, the search continues for clinical parameters that may aid in the early diagnosis of rejection. We report the case of a 29-year-old man who underwent orthotopic heart transplantation and subsequently had multifocal moderate allograft rejection. During the patient's hospital course, he exhibited a number of clinical parameters that served as important clues for the worsening rejection. After aggressive immunosuppression, the improvement of these markers hinted toward his eventual recovery.

Low-dose rituximab therapy for antibody-mediated rejection in a highly sensitized heart-transplant recipient.

Antibody-mediated rejection is the B-cell-mediated production of immunoglobulin G antibody against the transplanted heart. The currently available therapies for antibody-mediated rejection have had marginal success, and chronic manifestations of rejection can result in an increased risk of graft vasculopathy and perhaps require repeat transplantation. Rituximab, a monoclonal antibody directed against the CD20 receptor of B-lymphocytes and approved as therapy for lymphoma, can be used in heart-transplant patients for the management of antibody-mediated rejection. We present the case of a 52-year-old woman with high allosensitization (pre-transplantation panel reactive antibody level, 72%) who underwent successful orthotopic heart transplantation. Postoperatively, her acute antibody-mediated rejection with concomitant cellular rejection was successfully treated with low-dose rituximab. The patient died 5 months later because of multiple other medical problems. The present case suggests a role for low-dose rituximab as therapy for antibody-mediated rejection in heart-transplant patients.

Preoperative evaluation for bariatric surgery using transesophageal dobutamine stress echocardiography.

BACKGROUND: Bariatric surgery is an effective option for weight control in morbid obesity. The goal of this study was to assess cardiac risk prior to bariatric surgery using transesophageal-dobutamine stress echocardiography (TE-DSE). METHODS: 7 morbidly obese patients (mean BMI 67.7 +/- 15.6) were prospectively evaluated by TE-DSE prior to bariatric surgery. RESULTS: All patients underwent TE-DSE without complications. 6 of 7 patients had no evidence of ischemia on TE-DSE. One patient had abnormal TE-DSE showing inferior ischemia and was treated with beta-blockers and nitrates prior to surgery and had no complications. All patients underwent surgery without cardiac complications. 1 patient died at 18 days of sepsis. Over a mean follow-up period of 11 months, the 6 surviving patients have not experienced any cardiac events. Their average weight loss is 58.2 kg. CONCLUSION: TE-DSE is a valuable noninvasive technique for predicting cardiac risk in morbidly obese patients undergoing bariatric surgery.