The Effect of Diabetes on Pathologic Complete Response Among Patients With Esophageal Cancer.

Diabetes is a common comorbidity in the U.S. and is associated with adverse outcomes in a variety of disease processes. Other cancer specialties have shown an association of diabetes with poor oncologic outcomes. We hypothesized that pathologic complete response (pCR) would be less likely among diabetic patients with esophageal cancer who underwent neoadjuvant chemoradiation therapy followed by esophagectomy resulting in worse overall survival (OS). We performed a retrospective chart review at 2 high-volume academic hospitals of all patients with esophageal cancer who received neoadjuvant chemoradiation therapy followed by esophagectomy from 2010-2019. Patients were excluded if they had histology other than squamous cell carcinoma or adenocarcinoma, did not receive multi-agent chemotherapy or received a radiation dose <39.6 Gy. The primary outcome of interest was pCR and secondary outcome was OS. Multivariable logistic regression was used to assess the likelihood of pCR and Cox hazard analysis was used to assess OS. In total, 244 patients met inclusion criteria: 190 (77.9%) were non-diabetic and 54 (22.1%) were diabetic. Diabetic and non-diabetic patients were similar in age, sex, institution where they received treatment, ASA class, comorbidities, histologic sub-type, clinical T and N stage, chemotherapy regimen and radiation dose. Diabetic patients were more likely to have a higher body mass index (29.1 vs 25.9, p < 0.001) and hypertension (87.0% vs 47.9%, p < 0.001). On univariable analysis, diabetes was the only factor associated with decreased likelihood of pCR (p = 0.04). Multivariable analysis showed diabetes was again the only factor associated with a decreased likelihood of pCR (OR 0.32, p = 0.03). Cox survival analysis showed that older age (HR 1.03, p = 0.02) and overall posttreatment pathologic stage 2 (HR 2.16, p = 0.03), stage 3 (HR 3.25, p < 0.001), and stage 4 (HR 5.75, p < 0.001) compared to pCR were associated with worse OS, however diabetes alone had no effect (HR 1.01, p = 0.98). This multi-institutional study shows that diabetes adversely affects pCR in patients receiving neoadjuvant treatment for esophageal cancer. Almost a quarter of patients with esophageal cancer have diabetes suggesting implications for management of these patients. Future studies are warranted to determine the optimal neoadjuvant treatment strategy for esophageal cancer patients with diabetes.

Intraoperative Cytology for Video-Assisted Thoracic Surgery: A Quality Improvement Analysis.

BACKGROUND: Frozen section is a standard of care procedure during thoracic surgery when an immediate diagnosis is needed. An alternative procedure is intraoperative cytology. Video-assisted thoracic surgery is currently widely used for thoracic surgical procedures. The aim of this study was to assess intraoperative cytology together with frozen section for accuracy, turnaround time, and total response time during video-assisted thoracic surgery. METHODS: We included patients having video-assisted thoracic surgery between August 2018 and February 2019 at our institution. A cytopathologist and a surgical pathologist independently performed intraoperative cytology and frozen sections, respectively. Final histologic diagnosis was the reference standard. Intraoperative cytology, frozen section turnaround, and total response times were analyzed. RESULTS: A total of 52 specimens from 27 patients were included. The intraoperative cytology correlated with final histology in 98% of cases. Frozen section correlated with final histology in 100% of cases. Intraoperative cytology turnaround and total response times were equal (mean, 4.35 minutes; range, 2-15 minutes). Mean frozen section turnaround and response times were 26.2 minutes (range, 9-61 minutes) and 36.7 minutes (range, 16-90 minutes), respectively. We found a statistically significant difference between intraoperative cytology and frozen section turnaround time and total response times (P < .001). CONCLUSIONS: This study highlights that intraoperative cytology could be as accurate as frozen section and considerably faster during video-assisted thoracic surgery (P < .001). Total response time could potentially be used as a quality metric for video-assisted thoracic surgery.

Optimising rapid on-site evaluation-assisted endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes: The real-time cytopathology intervention process.

INTRODUCTION: Lymph node sampling by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the state of art procedure for staging the mediastinum and hilar regions in lung cancer patients. Our experience of implementing the real-time cytopathology intervention (RTCI) process for intraoperative EBUS-TBNAs is presented. This study is aimed to describe in detail the RTCI process for EBUS-TBNAs, and assess its utility and diagnostic yield before and after its implementation in parallel to conventional rapid on-site evaluation (c-ROSE). METHODS: A retrospective review of all EBUS-TBNAs between July 2016 and July 2017 at the University of Rochester Medical Center was performed. Final diagnoses, patient clinical data, and number of non-diagnostic samples (NDS) were reviewed. The numbers of NDS obtained from EBUS-TBNAs with no cytology assistance (NCA), with RTCI and with c-ROSE were analysed. RESULTS: Non-diagnostic lymph node samples were found in 20 out of 116 (17%), three out of 114 (2.6%) and 33 out of 286 (11.5%) cases with NCA, RTCI and c-ROSE, respectively. Application of statistical analysis revealed significant difference in the NDS between the groups of cases in the operating room with NCA and RTCI (P = .005). The different settings and variables between the cases performed using RTCI in the operating room and those assisted with c-ROSE in the bronchoscopy suite preclude legitimate comparison. CONCLUSION: Our results indicate that the use of RTCI could yield a significantly low proportion of NDS when assisting EBUS-TBNA of mediastinal and hilar lymph node for lung cancer patients enhancing the diagnostic efficiency of the procedure.

Esophagectomy Following Endoscopic Resection of Submucosal Esophageal Cancer: a Highly Curative Procedure Even with Nodal Metastases.

BACKGROUND: Despite the increased risk for nodal disease, definitive endoscopic resection is being increasingly offered for lesions invasive into the submucosa based on the success with intramucosal tumors. The aim of this study was to evaluate survival after esophagectomy alone for confirmed submucosal tumors after endoscopic resection. METHODS: Patients from seven centers in the USA who underwent esophagectomy for submucosal tumors removed with endoscopic resection were analyzed. Nodal involvement was correlated with recurrence and survival. RESULTS: We identified 23 patients with submucosal esophageal adenocarcinoma. Esophagectomy was performed at a median of 2 months (Interquartile range 1-3) after the endoscopic resection. There was no postoperative mortality. Positive nodal disease was seen in 26 % of patients on final pathology. At a median of 37 months (Interquartile range 25-55), 91 % of patients were alive and free of disease. The disease-specific 5-year survival was 88 %. Disease-specific 5-year survival was 67 % in patients with positive nodal metastases and 100 % in those without (p = 0.159). CONCLUSIONS: Esophagectomy is curative in the majority of patients with submucosal tumors even in the presence of nodal metastases. These data serve as a benchmark for comparison when considering extending the indications for therapeutic endoscopic resection for submucosal tumors in the future.

Survival in Patients With Esophageal Adenocarcinoma Undergoing Trimodality Therapy Is Independent of Regional Lymph Node Location.

BACKGROUND: The American Joint Committee on Cancer Cancer Staging Manual 7th Edition esophageal cancer staging was derived from outcomes of patients undergoing esophagectomy alone and eliminated nodal location from its schema. A limitation of this staging system is that it has not been validated in the setting of multimodality therapy for esophageal cancer. In addition, nodal location continues to influence treatment decisions. The aim of our study was to evaluate outcomes of patients with distal esophageal or gastroesophageal junction (GEJ) adenocarcinoma undergoing trimodality therapy and assess the effect of nodal location on survival. METHODS: This multiinstitutional retrospective study assessed patients with clinically node-positive (cN+) distal esophageal/GEJ adenocarcinoma treated with trimodality therapy between January 2002 and December 2011. Nodal stations were classified as paratracheal, subcarinal, celiac, lower esophageal, paraaortic, supraclavicular, or perigastric/perihepatic. Overall survival (OS) was estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed to identify variables associated with OS. RESULTS: A total of 196 cN+ patients met the study criteria. The most prevalent metastatic nodal location was in the perigastric region, present in 141 patients (72%); paratracheal nodal involvement was present in 19 patients (10%). None of the nodal stations was significantly associated with OS on univariable analysis. Multivariable analysis identified age (hazard ratio [HR], 1.036; p = 0.001), male sex (HR, 2.39; p = 0.003), pathologic ypT3 (HR, 1.81; p = 0.048), and ypN3 (HR, 2.93; p = 0.003) as being significantly associated with survival. CONCLUSIONS: The location of cN+ regional node disease in patients with distal esophageal or GEJ adenocarcinoma was not predictive of survival after trimodality therapy. Age, sex, pathologic tumor depth, and the number of involved nodes were independent predictors of survival. Patients with cN+ cancers should not be deprived of potentially curative surgical resection based solely on the location of regional nodal disease.

The Durability of Endoscopic Therapy for Treatment of Barrett's Metaplasia, Dysplasia, and Mucosal Cancer After Nissen Fundoplication.

INTRODUCTION: Radiofrequency ablation (RFA) ± endoscopic resection (EMR) is an established treatment strategy for neoplastic Barrett's and intramucosal cancer. Most patients are managed with proton pump inhibitors. The incidence of recurrent Barrett's metaplasia, dysplasia, or cancer after complete eradication is up to 43 % using this strategy. We hypothesize the addition of fundoplication should result in a lower recurrence rates after complete eradication. METHODS: Multi-institutional retrospective review of patients undergoing endotherapy followed by Nissen fundoplication RESULTS: A total of 49 patients underwent RFA ± EMR followed by Nissen fundoplication. Complete remission of intestinal metaplasia (CR-IM) was achieved in 26 (53 %) patients, complete remission of dysplasia (CR-D) in 16 (33 %) patients, and 7 (14 %) had persistent neoplastic Barrett's. After fundoplication, 18/26 (70 %) remained in CR-IM. An additional 10/16 CR-D achieved CR-IM and 4/7 with persistent dysplasia achieved CR-IM. One patient progressed to LGD while no patient developed HGD or cancer. CONCLUSION: Endoscopic therapy for Barrett's dysplasia and/or intramucosal cancer followed by fundoplication results in similar durability of CR-IM to patients being managed with PPIs alone after endoscopic therapy. However, fundoplication may be superior in preventing further progression of disease and the development of cancer. Fundoplication is an important strategy to achieve and maintain CR-IM, and facilitate eradication of persistent dysplasia.

Neoadjuvant treatment response in negative nodes is an important prognosticator after esophagectomy.

BACKGROUND: The current American Joint Committee on Cancer Seventh Edition (AJCC7) pathologic staging for esophageal adenocarcinoma (EAC) is derived from data assessing the outcomes of patients having undergone esophagectomy without neoadjuvant treatment and has unclear significance in patients who have received multimodality therapy. Lymph nodes with evidence of neoadjuvant treatment effect without residual cancer cells may be observed and are not traditionally considered in pathologic reports, but may have prognostic significance. METHODS: All patients who underwent esophagectomy after completing neoadjuvant therapy for EAC at our institution between 2006 and 2012 were reviewed. Slides of pathologic specimens were reexamined for locoregional treatment-response nodes lacking viable cancer cells but with evidence of acellular mucin pools, central fibrosis, necrosis, or calcifications suggesting prior tumor involvement. Kaplan-Meier survival functions were estimated, and Cox proportional hazards regression models were used to compare staging models. RESULTS: Ninety patients (82 men) underwent esophagectomy after neoadjuvant therapy for EAC (mean age, 61.8 ± 8.9 years). All patients received preoperative chemotherapy, and 50 patients also underwent preoperative radiotherapy. Median Kaplan-Meier survival was 55.6 months, and 5-year survival was 35% (95% confidence interval, 19% to 62%). A total of 100 treatment-response nodes were found in 38 patients. For patients with limited nodal disease (62 ypN0-N1), the presence of treatment-response nodes was associated with significantly worse survival (p = 0.03) compared with patients lacking such nodes. Adjusting for patient age and AJCC7 pathologic stage showed the presence of treatment-response nodes significantly increased the risk of death (hazard ratio, 2.7; 95% confidence interval, 1.1 to 6.9; p = 0.04). When stage-adjusted survival was modeled, counting treatment-response nodes as positive nodes offered a better model fit than ignoring them. CONCLUSIONS: Treatment-response lymph nodes detected from esophagectomy specimens in patients having undergone neoadjuvant chemotherapy or combined chemoradiation for EAC provide valuable prognostic information, particularly in patients with limited nodal disease. The current practice of considering lymph nodes lacking viable cancer cells, but with evidence of tumor necrosis, as pathologically negative likely results in understaging. Future efforts at revising the staging system for EAC should consider incorporating treatment-response lymph nodes in the analysis.

24-h multichannel intraluminal impedance-pH monitoring may be an inadequate test for detecting gastroesophageal reflux in patients with mixed typical and atypical symptoms.

BACKGROUND: The detection of gastroesophageal reflux (GERD) via pH testing is the key component of the evaluation of patients considered for antireflux surgery. Two common pH testing systems exist, a multichannel, intraluminal impedance-pH monitoring (MII-pH) catheter, and wireless (Bravo(®)) capsule; however, discrepancies between the two systems exist. In patients with atypical symptoms, MII-pH catheter is often used preferentially. We aimed to elucidate the magnitude of this discrepancy and to assess the diagnostic value of MII-pH and the Bravo wireless capsule in a population of patients with mixed respiratory and typical symptoms. METHODS: The study population consisted of 66 patients tested with MII-pH and Bravo pH testing within 90 days between July 2009 and 2013. All patients presented with laryngo-pharyngo-respiratory (LPR) symptoms. Patient demographics, symptomatology, manometric and endoscopic findings, and pH monitoring parameters were analyzed. Patients were divided into four comparison groups: both pH tests positive, MII-pH negative/Bravo positive, MII-pH positive/Bravo negative, and both pH tests negative. RESULTS: Nearly half of the patients (44%) had discordant pH test results. Of these, 90% (26/29) had a negative MII-pH but positive Bravo study. In this group, the difference in the DeMeester score was large, a median of 29.3. These patients had a higher BMI (28.5 vs. 26.1, p = 0.0357), were more likely to complain of heartburn (50 vs. 23%, p = 0.0110), to have a hiatal hernia, (85 vs. 53%, p = 0.0075) and a structurally defective lower esophageal sphincter (LES, 85 vs. 58%, p = 0.0208). CONCLUSIONS: In patients with LPR symptoms, we found a high prevalence of discordant esophageal pH results, most commonly a negative MII-pH catheter and positive Bravo. As these patients exhibited characteristics consistent with GERD (heartburn, defective LES, hiatal hernia), the Bravo results are likely true. A 24-h MII-pH catheter study may be inadequate to diagnose GERD in this patient population.

Comparison of cancer-associated genetic abnormalities in columnar-lined esophagus tissues with and without goblet cells.

OBJECTIVE: To determine and compare the frequency of cancer-associated genetic abnormalities in esophageal metaplasia biopsies with and without goblet cells. BACKGROUND: Barrett's esophagus is associated with increased risk of esophageal adenocarcinoma (EAC), but the appropriate histologic definition of Barrett's esophagus is debated. Intestinal metaplasia (IM) is defined by the presence of goblet cells whereas nongoblet cell metaplasia (NGM) lacks goblet cells. Both have been implicated in EAC risk but this is controversial. Although IM is known to harbor genetic changes associated with EAC, little is known about NGM. We hypothesized that if NGM and IM infer similar EAC risk, then they would harbor similar genetic aberrations in genes associated with EAC. METHODS: Ninety frozen NGM, IM, and normal tissues from 45 subjects were studied. DNA copy number abnormalities were identified using microarrays and fluorescence in situ hybridization. Targeted sequencing of all exons from 20 EAC-associated genes was performed on metaplasia biopsies using Ion AmpliSeq DNA sequencing. RESULTS: Frequent copy number abnormalities targeting cancer-associated genes were found in IM whereas no such changes were observed in NGM. In 1 subject, fluorescence in situ hybridization confirmed loss of CDKN2A and amplification of chromosome 8 in IM but not in a nearby NGM biopsy. Targeted sequencing revealed 11 nonsynonymous mutations in 16 IM samples and 2 mutations in 19 NGM samples. CONCLUSIONS: This study reports the largest and most comprehensive comparison of DNA aberrations in IM and NGM genomes. Our results show that IM has a much higher frequency of cancer-associated mutations than NGM.

Eliminating a need for esophagectomy: endoscopic treatment of Barrett esophagus with early esophageal neoplasia.

Over the past several years, endoscopic ablation and resection have become a new standard of care in the management of Barrett esophagus (BE) with high-grade dysplasia (HGD) or intramucosal adenocarcinoma (IMC). Risk factors for failure of endoscopic therapy and the need for subsequent esophagectomy have not been well elucidated. The aims of this study were to determine the efficacy of radiofrequency ablation (RFA) with or without endoscopic mucosal resection (EMR) in the management of BE with HGD or IMC, to discern factors predictive of endoscopic treatment failure, and to assess the effect of endoscopic therapies on esophagectomy volume at our institution. Data were obtained retrospectively for all patients who underwent endoscopic therapies or esophagectomy for a diagnosis of BE with HGD or IMC in our department between January 1, 2004, and December 31, 2012. Complete remission (CR) of BE or HGD or IMC was defined as 2 consecutive biopsy sessions without BE or HGD or IMC and no subsequent recurrence. Recurrence was defined by the return of BE or HGD or IMC after initial remission. Progression was defined as worsening of HGD to IMC or worsening of IMC to submucosal neoplasia or beyond. Overall, 57 patients underwent RFA with or without EMR for BE with HGD (n = 45) or IMC (n = 12) between 2007 and 2012, with a median follow-up duration of 35.4 months (range: 18.5-52.0 months). The 57 patients underwent 181 ablation sessions and more than half (61%) of patients underwent EMR as a component of treatment. There were no major procedural complications or deaths, with only 2 minor complications including 1 symptomatic stricture requiring dilation. Multifocal HGD or IMC was present in 43% (25/57) of patients. CR of IMC was achieved in 100% (12/12) at a median of 6.1 months, CR of dysplasia was achieved in 79% (45/57) at a median of 11.5 months, and CR of BE was achieved in 49% (28/57) at a median of 18.4 months. Following initial remission, 28% of patients (16/57) had recurrence of dysplasia (n = 12) or BE (n = 4). Progression to IMC occurred in 7% (4/57). All patients without CR continue endoscopic treatment. No patient required esophagectomy or developed metastatic disease. Overall, 6 patients died during the follow-up interval, none from esophageal cancer. Factors associated with failure to achieve CR of BE included increasing length of BE (6.0 ± 0.6 vs 4.0 ± 0.6cm, P = 0.03) and shorter duration of follow-up (28.5 ± 3.8 months vs 49.0 ± 5.8 months, P = 0.004). Shorter surveillance duration (17.8 ± 7.6 months vs 63.9 ± 14.4 months, P = 0.009) and shorter follow-up (21.1 ± 6.1 months vs 43.2 ± 4.1 months) were the only significant factors associated with failure to eradicate dysplasia. Our use of esophagectomy as primary therapy for BE with HGD or IMC has diminished since we began using endoscopic therapies in 2007. From a maximum of 16 esophagectomies per year for early Barrett neoplasia in 2006, we performed only 3 esophageal resections for such early disease in 2012, all for IMC, and we have not performed an esophagectomy for HGD since 2008. Although recurrence of BE or dysplasia/IMC was not uncommon, RFA with or without EMR ultimately resulted in CR of IMC in all patients, CR of HGD in the majority (79%), and CR of BE in nearly half (49%). No patient treated endoscopically for HGD or IMC subsequently required esophagectomy. In patients with BE with HGD or IMC, RFA and EMR are safe and highly effective. The use of endoscopic therapies appears justified as the new standard of care in most cases of BE with early esophageal neoplasia.

Gastroesophageal reflux disease, proton-pump inhibitor use and Barrett's esophagus in esophageal adenocarcinoma: Trends revisited.

PURPOSE: Screening for esophageal adenocarcinoma (EAC) has not become policy in part over concerns in identifying the high-risk group. It is often claimed that a significant proportion of patients developing EAC do not report preexisting reflux symptoms or prior treatment for gastroesophageal reflux disease (GERD). As such, our aim was to assess the prevalence of GERD symptoms, proton pump inhibitor (PPI) use and Barrett's esophagus (BE) and their impact on survival in patients undergoing esophagectomy for EAC. METHODS: The study population consisted of 345 consecutive patients who underwent esophagectomy for EAC between 2000 and 2011 at a university-based medical center. Patients with a diagnosis of esophageal squamous cell carcinoma and those who underwent esophagectomy for benign disease were excluded. The prevalence of preoperative GERD symptoms, defined as presence of heartburn, regurgitation or epigastric pain, PPI use (>6 months) and BE, defined by the phrases "Barrett's esophagus," "intestinal epithelium," "specialized epithelium," or "goblet cell metaplasia" in the patients' preoperative clinical notes were retrospectively collected. Overall long-term and stage-specific survival was compared in patients with and without the presence of preoperative GERD symptoms, PPI use, or BE. RESULTS: The majority of patients (64%; 221/345) had preoperative GERD symptoms and a history of PPI use (52%; 179/345). A preoperative diagnosis of BE was present in 34% (118/345) of patients. Kaplan-Meier survival analysis revealed a marked survival advantage in patients undergoing esophagectomy who had preoperative GERD symptoms, PPI use or BE diagnosis (P ≤ .001). The survival advantage remained when stratified for American Joint Committee on Cancer stage in patients with preoperative PPI use (P = .015) but was less pronounced in patients with GERD symptoms or BE (P = .136 and P = .225, respectively). CONCLUSION: These data show that the oft-quoted statistic that the majority of patients with EAC do not report preexisting GERD or PPI use is false. Furthermore, a diagnosis of BE is present in a surprisingly high proportion of patients (34%). There is a distinct survival advantage in patients with preoperative GERD symptoms, PPI use, and BE diagnosis, which may not be simply owing to earlier stage at diagnosis. Screening may affect survival outcomes in more patients with EAC than previously anticipated.

The composition and extent of coronary artery plaque detected by multislice computed tomographic angiography provides incremental prognostic value in patients with suspected coronary artery disease.

Multislice computed tomographic coronary angiography (CTCA) provides accurate noninvasive assessment of coronary artery disease (CAD). However, data on the prognostic value of CTCA in patients with suspected CAD are only beginning to emerge. The aim of the study was to assess the prognostic value of CTCA in patients with suspected CAD. Patients (males = 259, females = 235; mean age 58.2 ± 9.8 years) with suspected CAD who underwent 16- or 64-slice CTCA were followed for 1,308 ± 318 days for cardiac death, nonfatal myocaridal infarction (MI) and late (>90 days after CTCA) revascularization. Patient outcomes were related to clinical and CTCA data. Cox proportional-hazards model was applied in stepwise forward fashion to identify outcome predictors. Coronary artery plaque was found in 340 patients. Cardiac events occurred in 40 patients including cardiac death (n = 9), nonfatal MI (n = 8) and late revascularization (n = 23). A multivariable analysis identified the following independent predictors for adverse cardiac events: obstructive plaque in a proximal coronary artery segment (hazard ratio (HR) 2.73; 95% confidence interval (CI): 1.35-5.54; P = 0.005), the number of segments with noncalcified plaque(s) (HR 1.53 per segment; 95%CI: 1.21-1.92; P < 0.001), the number of segments with mixed plaque(s) (HR 1.56 per segment; 95%CI: 1.27-1.92; P < 0.001) and the number of segments with calcified plaque(s) (HR 1.21 per segment; 95%CI: 1.07-1.37; P = 0.002). In patients with suspected CAD, both the extent and composition of atherosclerotic plaque as determined by CTCA are prognostic of subsequent cardiac events.

Extent of RV dysfunction and myocardial infarction assessed by CMR are independent outcome predictors early after STEMI treated with primary angioplasty.

OBJECTIVES: The aim of this study was to assess the prognostic value of right ventricular (RV) involvement diagnosed by cardiac magnetic resonance (CMR) early after ST-elevation myocardial infarction (STEMI). BACKGROUND: CMR allows accurate and reproducible RV assessment. However, there is a paucity of data regarding the prognostic value of RV involvement detected by CMR early after STEMI. METHODS: Ninety-nine patients (77 men, mean age 57 ± 11 years) who underwent CMR 3 to 5 days after STEMI treated with primary angioplasty were followed for 1,150 ± 337 days for cardiac events (cardiac death, nonfatal myocardial infarction [MI], and hospitalizations due to decompensated heart failure). Cox proportional hazards model was applied in stepwise forward fashion to identify outcome predictors. Event-free survival was estimated by Kaplan-Meier method and compared between groups by the log-rank test. RESULTS: Cardiac events occurred in 34 patients (7 cardiac deaths, 8 MIs, 26 hospitalizations). By multivariable analysis, the independent outcome predictors were left ventricular (LV) MI transmurality index (hazard ratio: 1.03 per 1%; 95% confidence interval: 1.01 to 1.04; p = 0.001), RV ejection fraction (RVEF) (hazard ratio: 1.46 per 10% decrease; 95% confidence interval: 1.05 to 2.02; p = 0.03), and RVMI extent (hazard ratio: 1.50 per each infarcted RV segment; 95% confidence interval: 1.11 to 2.01; p = 0.007). Compared with clinical data (global chi-square = 5.2), LV ejection fraction [LVEF] (global chi-square = 11.1), RVEF (global chi-square = 17.1), LVMI transmural extent (global chi-square = 26.0), and RVMI extent (global chi-square = 34.9) improved outcome prediction in sequential Cox model analysis (p < 0.05 for all steps). RVEF stratified risk in patients with LVEF <40% in whom the 4-year event-free survival was 66.7% for RVEF ≥40% and 40.0% for RVEF <40% (p < 0.05). CONCLUSIONS: The extent of RVMI and RV dysfunction assessed early after STEMI are independent outcome predictors, which provide incremental prognostic value to clinical data, LV systolic function, and infarct burden. Measurement of RVEF may be particularly useful to stratify risk in patients with depressed LV function after STEMI.