Sonya Aggarwal

Patterns and prognosis of all components of the J-wave pattern in multiethnic athletes and ambulatory patients

BACKGROUND Despite recent concern about the significance of the J-wave pattern (also often referred to as early repolarization) and the importance of screening in athletes, there are limited rigorous prognostic data characterizing the 3 components of the J-wave pattern (ST elevation, J waves, and QRS slurs). We aim to assess the prevalence, patterns, and prognosis of the J-wave pattern among both stable clinical and athlete populations. METHODS We retrospectively studied 4,041 electrocardiograms from a multiethnic clinical population from 1997 to 1999 at the Veterans Affairs Palo Alto Health Care System. We also examined preparticipation electrocardiograms of 1,114 Stanford University varsity athletes from 2007 to 2008. Strictly defined criteria for components of the J-wave pattern were examined. In clinical subjects, prognosis was assessed using the end point of cardiovascular death after 7 years of follow-up. RESULTS Components of the J-wave pattern were most prevalent in males; African Americans; and, particularly, athletes, with the greatest variations demonstrated in the lateral leads. ST elevation was the most common. Inferior J waves and slurs, previously linked to cardiovascular risk, were observed in 9.6% of clinical subjects and 12.3% of athletes. J waves, slurs, or ST elevation was not associated with time to cardiovascular death in clinical subjects, and ST-segment slope abnormalities were not prevalent enough in conjunction with them to reach significance. CONCLUSIONS J waves, slurs, or ST elevation was not associated with increased hazard of cardiovascular death in our large multiethnic, ambulatory population. Even subsets of J-wave patterns, recently proposed to pose a risk of arrhythmic death, occurred at such a high prevalence as to negate their utility in screening.

Limitations of Current AHA Guidelines and Proposal of New Guidelines for the Preparticipation Examination of Athletes.

Objective:To examine the prevalence of athletes who screen positive with the preparticipation examination guidelines from the American Heart Association, the AHA 12-elements, in combination with 3 screening electrocardiogram (ECG) criteria. Design:Observational cross-sectional study. Setting:Stanford University Sports Medicine Clinic. Participants:Total of 1596 participants, including 297 (167 male; mean age, 16.2 years) high school athletes, 1016 (541 male; mean age, 18.8 years) collegiate athletes, and 283 (mean age, 26.3 years) male professional athletes. Main Outcome Measures:Athletes were screened using the 8 personal and family history questions from the AHA 12-elements. Electrocardiograms were obtained for all participants and interpreted using Seattle criteria, Stanford criteria, and European Society of Cardiology (ESC) recommendations. Results:Approximately one-quarter of all athletes (23.8%) had at least 1 positive response to the AHA personal and family history elements. High school and college athletes had similar rates of having at least 1 positive response (25.9% vs 27.4%), whereas professional athletes had a significantly lower rate of having at least 1 positive response (8.8%, P < 0.05). Females reported more episodes of unexplained syncope (11.4% vs 7.5%, P = 0.017) and excessive exertional dyspnea with exercise (11.1% vs 6.1%, P = 0.001) than males. High school athletes had more positive responses to the family history elements when compared with college athletes (P < 0.05). The percentage of athletes who had an abnormal ECG varied between Seattle criteria (6.0%), Stanford criteria (8.8%), and ESC recommendations (26.8%). Conclusions:Many athletes screen positive under current screening recommendations, and ECG results vary widely by interpretation criteria. Clinical Relevance:In a patient population without any adverse cardiovascular events, the currently recommended AHA 12-elements have an unacceptably high rate of false positives. Newer screening guidelines are needed, with fewer false positives and evidence-based updates.

Albumin and Neutrophil-Lymphocyte Ratio (NLR) Predict Survival in Patients With Pancreatic Adenocarcinoma Treated With SBRT

Purpose: To determine if pretreatment nutritional status and inflammatory markers correlate with survival in patients with locally advanced pancreatic adenocarcinoma treated with stereotactic body radiotherapy (SBRT). Materials and Methods: We retrospectively reviewed 208 patients with newly diagnosed, locally advanced pancreatic adenocarcinoma treated with SBRT at our institution from 2002 to 2014. Laboratory values were collected before SBRT, including hemoglobin, platelets, albumin, red blood cell, white blood cell, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio, and tumor markers CA 19-9 and CEA. Patients were followed every 3 months with computed tomography (CT) and/or positron emission tomography-CT imaging to monitor for local recurrence and overall survival (OS). Results: Median follow-up after SBRT was 7.5 months (interquartile range, 4.6 to 12.0 mo) for all patients. Median OS for patients with NLR>5 compared with NLR⩽5 was 6.9 and 8.5 months, respectively (P=0.0057). On univariate analysis, receipt of chemotherapy (P=0.05, hazard ratio [HR]=0.69), increased albumin (P=0.002, HR=0.64), increased red blood cell (P=0.05, HR=0.75), increased lymphocyte count (P=0.002, HR=0.66), decreased CEA (P=0.01, HR=0.96), and NLR⩽5 (P=0.01, HR=0.65) correlated with improved OS. On multivariate analysis, higher albumin (P=0.03, HR=0.70), receipt of chemotherapy (P=0.007, HR=0.56), and NLR⩽5 (P=0.02, HR=0.66) correlated with better survival. Conclusions: Preradiotherapy low albumin levels and NLR>5 correlate with decreased survival in patients with locally advanced pancreatic adenocarcinoma treated with SBRT, indicating the prognostic value of systemic inflammatory markers (such as NLR) and a role of nutritional supplementation to improve outcomes in these patients. Further investigation is warranted.

Prognostic value of midtreatment FDG-PET in oropharyngeal cancer.

Prognostic metabolic imaging indices are needed for risk stratification for patients with locally advanced oropharyngeal cancer.

Spectrum of ST amplitude: athletes and an ambulatory clinical population

BACKGROUND AND PURPOSE To augment data guiding thresholds for myocardial ischemia and cardiac risk, we studied resting ST amplitude in ambulatory patients and collegiate athletes. METHODS We analyzed 4041 ECGs from ambulatory visits at the Veterans Affairs in Palo Alto, California from 1997 to 1999 and 1114 screening ECGs from Stanford University athletes in 2007-2008. Using the PR interval as the isoelectric line and >95μV and<-45μV (visually equivalent to 1mm and 0.5mm) to define ST elevation and depression, ST amplitude was measured at QRS-end. RESULTS ST elevation was most prevalent in males, African Americans, and athletes (87% of male athletes in anterior leads). ST depression was rare in athletes and, among patients, associated with time to cardiovascular death in lateral leads (age-adjusted HR of 1.9, p<0.001). CONCLUSIONS ST amplitude differs by gender, age, race, and athletic status, which should be considered when developing guidelines for ECG interpretation.

The long-term prognostic value of the ST depression criteria for ischemia recommended in the universal definition of myocardial infarction in 43,661 veterans

BACKGROUND The third Universal Definition of Myocardial Infarction (UDMI) includes electrocardiographic criteria for ischemia, specifying horizontal or down-sloping ST depression ≥0.05 mV in two contiguous electrocardiogram (ECG) leads. We used the surrogate of cardiovascular (CV) death to evaluate the criteria. METHODS We collected computerized ST amplitude measurements, in different lead groupings, from the resting ECGs of 43,661 patients collected between 1987 and 1999 at the Palo Alto VA. There were 3929 (9.0%) cardiac deaths over a mean follow-up of 7.6 (SD 3.8) years. RESULTS We found that horizontal or down-sloping ST depressions in contiguous leads, depending upon the lead groupings, had sensitivities ranging from 1% to 5%, specificities exceeding 99%, and relative risks for CV death ranging from 3.1 to 7.0 (p<0.001 for each individual relative risk) while horizontal or down-sloping ST depressions in a single lead had comparable values. We found that up-sloping ST depressions had greater sensitivities than horizontal or down-sloping ST depressions. Additionally, we found that ST depressions isolated to the inferior or anterior leads, without concomitant lateral depressions, were poor predictors of CV death. CONCLUSION These findings reinforce and further characterize the value of ST depressions for predicting CV death. Furthermore, if these findings can be reproduced in the acute setting, they would undermine the requirement for contiguous lead depressions with slope assessment as well as prioritize ST depression in V4, V5, and V6 when assessing for myocardial ischemia.

TU-AB-BRA-10: Prognostic Value of Intra-Radiation Treatment FDG-PET and CT Imaging Features in Locally Advanced Head and Neck Cancer

Purpose: To predict response to radiation treatment using computational FDG-PET and CT images in locally advanced head and neck cancer (HNC). Methods: 68 patients with State III-IVB HNC treated with chemoradiation were included in this retrospective study. For each patient, we analyzed primary tumor and lymph nodes on PET and CT scans acquired both prior to and during radiation treatment, which led to 8 combinations of image datasets. From each image set, we extracted high-throughput, radiomic features of the following types: statistical, morphological, textural, histogram, and wavelet, resulting in a total of 437 features. We then performed unsupervised redundancy removal and stability test on these features. To avoid over-fitting, we trained a logistic regression model with simultaneous feature selection based on least absolute shrinkage and selection operator (LASSO). To objectively evaluate the prediction ability, we performed 5-fold cross validation (CV) with 50 random repeats of stratified bootstrapping. Feature selection and model training was solely conducted on the training set and independently validated on the holdout test set. Receiver operating characteristic (ROC) curve of the pooled Result and the area under the ROC curve (AUC) was calculated as figure of merit. Results: For predicting local-regional recurrence, our model built on pre-treatment PET of lymph nodes achieved the best performance (AUC=0.762) on 5-fold CV, which compared favorably with node volume and SUVmax (AUC=0.704 and 0.449, p<0.001). Wavelet coefficients turned out to be the most predictive features. Prediction of distant recurrence showed a similar trend, in which pre-treatment PET features of lymph nodes had the highest AUC of 0.705. Conclusion: The radiomics approach identified novel imaging features that are predictive to radiation treatment response. If prospectively validated in larger cohorts, they could aid in risk-adaptive treatment of HNC.

Severe Chest Wall Toxicity From Cryoablation in the Setting of Prior Stereotactic Ablative Radiotherapy.

We present the case of a 42-year-old woman with metastatic synovial sarcoma of parotid origin, treated definitively with chemoradiation, who subsequently developed oligometastatic disease limited to the lungs. She underwent multiple left and right lung wedge resections and left lower lobectomy, followed by right lower lobe stereotactic ablative radiotherapy (SABR), 54 Gy in three fractions to a right lower lobe lesion abutting the chest wall. Two years later, she was treated with cryoablation for a separate right upper lobe nodule abutting the chest wall. Two months later, she presented with acute shortness of breath, pleuritic chest pain, decreased peripheral blood O2 saturation, and productive cough. A computed tomography (CT) scan demonstrated severe chest wall necrosis in the area of recent cryoablation that, in retrospect, also received a significant radiation dose from her prior SABR. This case demonstrates that clinicians should exercise caution in using cryoablation when treating lung tumors abutting a previously irradiated chest wall. Note: Drs. Loo and Shah contributed equally as co-senior authors.

The long-term prognostic value of the Q wave criteria for prior myocardial infarction recommended in the universal definition of myocardial infarction

BACKGROUND We sought to characterize the prognostic value of the third universal definition of myocardial infarction (UDMI) and ≥40msec Q wave criteria. METHODS We evaluated hazard ratios (HR) with 95% confidence intervals (CI) for cardiovascular (CV) death for computerized Q wave measurements from the electrocardiograms of 43,661 patients collected from 1987 to 1999 at the Palo Alto VA. There were 3929 (9.0%) CV deaths over a mean follow-up of 7.6 (±3.8) years. RESULTS The risk of CV death for Q waves ≥40msec in any two contiguous leads in any lead group was equivalent to or higher than that for contiguous UDMI Q waves, with HR 2.44 (95% CI 2.15-4.11) and HR 2.42 (95% CI (2.18-3.42), respectively. CONCLUSIONS The UDMI Q wave criteria do not provide an advantage over ≥40msec Q waves at predicting CV death.

Probabilistic Prognostic Estimates of Survival in Metastatic Cancer Patients (PPES-Met) Utilizing Free-Text Clinical Narratives

We propose a deep learning model - Probabilistic Prognostic Estimates of Survival in Metastatic Cancer Patients (PPES-Met) for estimating short-term life expectancy (>3 months) of the patients by analyzing free-text clinical notes in the electronic medical record, while maintaining the temporal visit sequence. In a single framework, we integrated semantic data mapping and neural embedding technique to produce a text processing method that extracts relevant information from heterogeneous types of clinical notes in an unsupervised manner, and we designed a recurrent neural network to model the temporal dependency of the patient visits. The model was trained on a large dataset (10,293 patients) and validated on a separated dataset (1818 patients). Our method achieved an area under the ROC curve (AUC) of 0.89. To provide explain-ability, we developed an interactive graphical tool that may improve physician understanding of the basis for the model’s predictions. The high accuracy and explain-ability of the PPES-Met model may enable our model to be used as a decision support tool to personalize metastatic cancer treatment and provide valuable assistance to the physicians.