The Society of Thoracic Surgeons Congenital Heart Surgery Database: 2023 Update on Outcomes and Research.

The Society of Thoracic Surgeons (STS) Congenital Heart Surgery Database (CHSD) continues to be the most comprehensive database of congenital and pediatric cardiothoracic surgical procedures in the world and contains information on 664,210 operations as of June 30, 2023. The 35th harvest of the STS CHSD data was undertaken in Spring 2023, spanning the 4-year period January 1, 2019, through December 31, 2022, and included 144,919 operations performed at 114 participating sites in North America. The harvest analysis was successfully executed by the STS Research and Analytic Center. The overall unadjusted mortality rate was 2.68% and has remained stable over the 4 years included in the current harvest window. Mortality is highest in neonates (7.4%) and lowest in children (1.1%). As in prior analyses, observed mortality and postoperative length of stay in the database increase with an increase in STS-European Association for Cardio-Thoracic Surgery (STAT) Congenital Heart Surgery Mortality Categories. This quality report summarizes contemporary outcomes, provides the odds ratios for the CHSD risk model variables based on this analysis, and describes on-going efforts to improve data collection and augment analytical approaches. Lastly, 5 research publications completed in the last year using data from the CHSD are also summarized.

A multi-dimensional approach to identifying high performing trauma centers across the United States.

INTRODUCTION: The differentiators of centers performing at the highest level of quality and patient safety are likely both structural and cultural. We aimed to combine five indicators representing established domains of trauma quality, and to identify and describe the structural characteristics of consistently performing centers. METHODS: Using ACS-TQIP data from 2017-2020, we evaluated five quality measures across several care domains for adult patients in level I and II trauma centers; 1) time to operating room (OR) for patients with abdominal gunshot wounds (GSW) and shock, 2) proportion of patients receiving timely venous thromboembolism (VTE) prophylaxis, 3) failure to rescue (death following a complication), 4) major hospital complications, and 5) mortality. Overall performance was summarized as a composite score incorporating all measures. Centers were ranked from highest to lowest performer. Principal Component Analysis (PCA) showed the influence of each indicator on overall performance and supported the composite score approach. RESULTS: We identified 272 level I and II centers, with 28 and 27 centers in the top and bottom 10%, respectively. Patients treated in high performing centers had significant lower rates of death major complications, and failure to rescue, compared to low performing centers (p < 0.001). The median time to OR for GSW was almost half that in high compared to low performing centers, and rates of timely VTE prophylaxis were over two-fold greater (p < 0.001). Top performing centers were more likely to be level I centers and cared for a higher number of severely injured patients per annum. Each indicator contributed meaningfully to the variation in scores and centers tended to perform consistently across most indicators. CONCLUSIONS: The combination of multiple indicators across dimensions of quality sets a higher standard for performance evaluation and allows the discrimination of centers based on structural elements, specifically level 1 status, and trauma center volume. LEVEL OF EVIDENCE: Prognostic and Epidemiological, III.

Benchmarking Pediatric Trauma Care in Mixed Trauma Centers: Adult Risk-Adjusted Mortality Is Not a Reliable Indicator of Pediatric Outcomes.

BACKGROUND: Trauma center benchmarking has become standard practice for assessing quality. The American College of Surgeons adult trauma center verification standards do not specifically require participation in a pediatric-specific benchmarking program. Centers that treat adults and children may therefore rely solely on adult benchmarking metrics as a surrogate for pediatric quality. This study assessed discordance between adult and pediatric mortality within mixed trauma centers to determine the need to independently report pediatric-specific quality metrics. STUDY DESIGN: A cohort of trauma centers (n = 493, including 347 adult-only, 44 pediatric-only, and 102 mixed) that participated in the American College of Surgeons TQIP in 2017 to 2018 was analyzed. Center-specific observed-to-expected mortality estimates were calculated using TQIP adult inclusion criteria for 449 centers treating adults (16 to 65 years) and using TQIP pediatric inclusion criteria for 146 centers treating children (0 to 15 years). We then correlated risk-adjusted mortality estimates for pediatric and adult patients within mixed centers and evaluated concordance of their outlier status between adults and children. RESULTS: The cohort included 394,075 adults and 97,698 children. Unadjusted mortality was 6.1% in adults and 1.2% in children. Mortality estimates had only moderate correlation ( r = 0.41) between adult and pediatric cohorts within individual mixed centers. Mortality outlier status for adult and pediatric cohorts was discordant in 31% (32 of 102) of mixed centers (weighted Kappa statistic 0.06 [-0.11 to 0.22]), with 78% (23 of 32) of discordant centers having higher odds of mortality for children than for adults (6 centers with average adult mortality and high pediatric mortality and 17 centers with low adult mortality and average pediatric mortality, p < 0.01). CONCLUSIONS: Adult mortality is not a reliable surrogate for pediatric mortality in mixed trauma centers. Incorporation of pediatric-specific benchmarks should be required for centers that admit children.

Impact of Diabetes Mellitus on Benefit of ß-Blocker Therapy After Myocardial Infarction.

Beta blockers are uniformly recommended for all patients after myocardial infarction (MI), including those with diabetes mellitus (DM). This study assesses the impact of ß-blocker type and dosing on survival in patients with DM after MI. A cohort of 6,682 patients in the Outcomes of Beta-blocker Therapy After Myocardial INfarction registry were discharged after MI. In this cohort, 2,137 patients had DM (32%). Beta-blocker dose was indexed to the target daily dose used in randomized clinical trials and reported as percentage. Dosage groups were: no ß blocker, >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of the target dose. The overall mean discharge ß-blocker dose in patients with DM was 42.7 ± 34.1% versus 35.9 ± 27.4% in patients without DM (p <0.0001). Patients with DM were prescribed carvedilol at a higher rate than those without DM (27.8% vs 19.6%). The 3-year mortality estimates were 24.4% and 12.8% for patients with DM versus without DM (p <0.0001), respectively, with an unadjusted hazard ratio = 1.820 (confidence interval 1.587 to 2.086, p <0.0001). Patients with DM in the >12.5% to 25% dose category had the highest survival rates, whereas patients in the >50% dose had the lowest survival rate among patients discharged on ß blockers (p <0.0001). In the multivariable analysis among patients with DM after MI, all ß-blocker dose categories demonstrated lower mortality than no therapy; however, only the >12.5% to 25% dose had a statistically significant hazard ratio 0.450 (95% confidence interval 0.224 to 0.907, p = 0.025). In patients with DM, there was no statistically significant difference in 3-year mortality among those treated with metoprolol versus carvedilol. In conclusion, our analysis in patients with DM after MI suggested a survival benefit from ß-blocker therapy, with no apparent advantage to high- versus low-dose ß-blocker therapy; although, physicians tended to prescribe higher doses in patients with DM. There was no survival benefit for carvedilol over metoprolol in patients with DM.

Determinants of Early and Late In-Hospital Mortality After Acute Myocardial Infarction: A Subanalysis of the OBTAIN Registry.

BACKGROUND: Predictors of in-hospital mortality after myocardial infarction (MI) have been reported dichotomously: survival vs death. Predictors of time from admission to death have not been reported. METHODS: A total of 7335 patients were enrolled in a prospective multicentre registry of acute MI. In-hospital mortality was classified by time from admission as acute (≤ 2 days), subacute (3 to 7 days), late (8 to 14 days), and very late (≥ 15 days) to identify factors associated with time to death in patients who died before discharge. Patient and MI characteristics, in-hospital interventions, and electrocardiographic findings were screened for differences in time to in-hospital death. RESULTS: In-hospital death affected 351 patients (4.8%). Mean age was 72.0 ± 12.4 years, and 40.5% were female patients. Median survival was 5 days (interquartile range: 2-12), and 41% of in-hospital deaths occurred after 1 week. Cardiac biomarkers and ejection fraction were not related to time to in-hospital death. Previous MI, systolic blood pressure, pharmacologic therapy, and interventional treatments were different among the 4 groups. The factors associated with late in-hospital death were coronary artery bypass graft surgery (CABG), new-onset atrial fibrillation or flutter, heart failure or pulmonary edema, bleeding, and lung disease. Acute and subacute in-hospital death was associated with ST-elevation MI, lower systolic blood pressure, and cardiac arrest on admission. CABG was performed in 12% of post-MI patients who died in hospital. CONCLUSIONS: Clinical risk factors for in-hospital mortality evolve over time immediately after acute MI. Understanding the time-dependent risk factors may allow for the development of new approaches to curtail the "later" in-hospital mortality.

National evaluation of the association between stay-at-home orders on mechanism of injury and trauma admission volume.

BACKGROUND: The COVID-19 pandemic had numerous negative effects on the US healthcare system. Many states implemented stay-at-home (SAH) orders to slow COVID-19 virus transmission. We measured the association between SAH orders on the injury mechanism type and volume of trauma center admissions during the first wave of the COVID-19 pandemic. METHODS: All trauma patients aged 16 years and older who were treated at the American College of Surgeons Trauma Quality Improvement Program participating centers from January 2018-September 2020. Weekly trauma patient volume, patient demographics, and injury characteristics were compared across the corresponding SAH time periods from each year. Patient volume was modeled using harmonic regression with a random hospital effect. RESULTS: There were 166,773 patients admitted in 2020 after a SAH order and an average of 160,962 patients were treated over the corresponding periods in 2018-2019 in 474 centers. Patients presenting with a pre-existing condition of alcohol misuse increased (13,611 (8.3%) vs. 10,440 (6.6%), p <0.001). Assault injuries increased (19,056 (11.4%) vs. 15,605 (9.8%)) and firearm-related injuries (14,246 (8.5%) vs. 10,316 (6.4%)), p<0.001. Firearm-specific assault injuries increased (10,748 (75.5%) vs. 7,600 (74.0%)) as did firearm-specific unintentional injuries (1,318 (9.3%) vs. 830 (8.1%), p<0.001. In the month preceding the SAH orders, trauma center admissions decreased. Within a week of SAH implementation, hospital admissions increased (p<0.001) until a plateau occurred 10 weeks later above predicted levels. On regional sub-analysis, admission volume remained significantly elevated for the Midwest during weeks 11-25 after SAH order implementation, (p<0.001).

The association between gun shows and firearm injuries: An analysis of 259 gun shows across 23 US cities.

Guns shows are estimated to account for 4-9% of firearm sales in the US. Increased regulation of firearm sales at gun shows has been proposed as one approach to reducing firearm injury rates. This study evaluated the association between gun shows and local firearm injury rates. Data regarding the date and location of gun shows from 2017 to 2019 were abstracted from the Big Show Journal. Firearm injury rates were estimated using discharges from trauma centers serving counties within a 25-mile radius of each gun show. Clinical data were derived from the National Trauma Databank (NTDB). We used Poisson regression modeling to adjust for potential confounders including seasonality. We evaluated injury rates before and after 259 gun shows in 23 US locations using firearm injury data from 36 trauma centers. There were 1513 hospitalizations for firearm injuries pre-gun show and 1526 post-gun show. The adjusted mean 2-week rate of all-cause firearm injury per 1,000,000 person-years was 1.79 (1.16-2.76) before and 1.82 (1.18-2.83) after a gun show, with an incident rate ratio of 1.02 (0.94, 1.08). The adjusted mean 2-week rate did not vary significantly by intent after a gun show, (p = 0.24). Within two weeks after a gun show, rates of hospitalization for all-cause firearm injury do not increase significantly within the surrounding communities. The relatively small increase in available firearms after a show and the short time horizon evaluated may account for the absence of an association between gun show firearm sales and local firearm injury rates.

Time to OR for patients with abdominal gunshot wounds: A potential process measure to assess the quality of trauma care?

BACKGROUND: Abdominal gunshot wounds (GSWs) require rapid assessment and operative intervention to reduce the risk of death and complications. We sought to determine if time to the operating room (OR) might be a useful process measure for the assessment of trauma care quality. We evaluated the facility benchmark time to OR for patients with serious injury and whether this was associated with lower rates of complications and mortality. METHODS: We evaluated time to OR for adult patients with an abdominal GSW presenting in shock to American College of Surgeons Trauma Quality Improvement Program centers from 2015 to 2020. We calculated the 75th percentile time to the OR for each center and characterized centers as average, slow, or fast. We compared patient and facility characteristics across outlier status, as well as risk-adjusted complications and mortality using hierarchical multivariable logistic regression models. RESULTS: There were 4,027 patients in 230 centers that met the inclusion criteria. Mortality was 28%. There were 61 (27%) fast and 52 (23%) slow centers. The median time for slow centers was 83 minutes (68-94 minutes) compared with fast centers, 35 minutes (32-38 minutes). Injury Severity Score and emergency department vital signs were similar across centers. Fast hospitals had higher total case volumes, more cases per surgeon, and were more likely to be Level I centers. Patients cared for in these centers had similar risk-adjusted rates of complications and mortality. CONCLUSION: Time to OR for patients with abdominal GSWs and shock might be a useful process measure to evaluate rapid decision making and OR access. Surgeon and center experience as measured by annual case volumes, coupled with a rapid surgical response required through Level I trauma center standards might be contributory. There was no association between outlier status and complications or mortality suggesting other factors apart from time to the OR are of greater significance. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.

Exercise based assessment of cardiac autonomic function in type 1 versus type 2 diabetes mellitus.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that is associated with increased mortality. Exercise-based assessment of autonomic function has identified diminished parasympathetic reactivation after exercise in type 2 DM. It is postulated herein, that this would be more prominent among those with type 1 DM. METHODS: Sixteen subjects with type 1 DM (age 32.9 ± 10.1 years), 18 subjects with type 2 DM (55.4 ± 8.0 years) and 30 controls (44.0 ± 11.6 years) underwent exercise-based assessment of autonomic function. Two 16-min submaximal bicycle tests were performed followed by 45 min of recovery. On the second test, atropine (0.04 mg/kg) was administered near end-exercise so that all of the recovery occurred under parasympathetic blockade. Plasma epinephrine and norepinephrine levels were measured at rest, during exercise, and during recovery. RESULTS: There were no differences in resting or end-exercise heart rates in the three groups. Parasympathetic effect on RR-intervals during recovery (p < 0.03) and heart rate recovery (p = 0.02) were blunted in type 2 DM. Type 1 DM had higher baseline epinephrine and norepinephrine levels (p < 0.03), and exhibited persistent sympathoexcitation during recovery. CONCLUSIONS: Despite a longer duration of DM in the study patients with type 1 versus type 2 DM, diminished parasympathetic reactivation was not noted in type 1 DM. Instead, elevation in resting plasma catecholamines was noted compared to type 2 DM and controls. The variable pathophysiology for exercise-induced autonomic abnormalities in type 1 versus type 2 DM may impact prognosis.

One-Year Landmark Analysis of the Effect of Beta-Blocker Dose on Survival After Acute Myocardial Infarction.

Background Although beta-blockers are recommended following myocardial infarction (MI), the benefits of long-term treatment have not been established. The study's aim was to evaluate beta-blocker efficacy by dose in 1-year post-MI survivors. Methods and Results The OBTAIN (Outcomes of Beta-Blocker Therapy After Myocardial Infarction) registry included 7057 patients with acute MI, with 6077 one-year survivors. For this landmark analysis, beta-blocker dose status was available in 3004 patients and analyzed by use (binary) and dose at 1 year after MI. Doses were classified as no beta-blocker and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target doses used in randomized clinical trials. Age was 63 to 64 years, and approximately two thirds were men. Median follow-up duration was 1.05 years (interquartile range, 0.98-1.22). When analyzed dichotomously, beta-blocker therapy was not associated with improved survival. When analyzed by dose, propensity score analysis showed significantly increased mortality in the no-beta-blocker group (hazard ratio,1.997; 95% CI, 1.118-3.568; P<0.02), the >0% to 12.5% group (hazard ratio, 1.817; 95% CI, 1.094-3.016; P<0.02), and the >25% to 50% group (hazard ratio, 1.764; 95% CI, 1.105-2.815; P<0.02), compared with the >12.5% to 25% dose group. The mortality in the full-dose group was not significantly higher (hazard ratio, 1.196; 95% CI, 0.687-2.083). In subgroup analyses, only history of congestive heart failure demonstrated significant interaction with beta-blocker effects on survival. Conclusions This analysis suggests that patients treated with >12.5% to 25% of the target dose used in prior randomized clinical trials beyond 1 year after MI may have enhanced survival compared with no beta-blocker and other beta-blocker doses. A new paradigm for post-MI beta-blocker therapy is needed that addresses which patients should be treated, for how long, and at what dose.

Comparison of Metoprolol Versus Carvedilol After Acute Myocardial Infarction.

Beta-blockers are typically prescribed following myocardial infarction (MI), but no specific beta-blocker is recommended. Of 7,057 patients enrolled in the OBTAIN multi-center registry of patients with acute MI, 4142 were discharged on metoprolol and 1487 on carvedilol. Beta-blocker dose was indexed to the target daily dose used in randomized clinical trials (metoprolol-200 mg; carvedilol-50 mg), reported as %. Beta-blocker dosage groups were >0% to12.5% (n = 1,428), >12.5% to 25% (n = 2113), >25% to 50% (n = 1,392), and >50% (n = 696). The Kaplan-Meier method was used to calculate 3-year survival. Correction for baseline differences was achieved by multivariable adjustment. Patients treated with carvedilol were older (64.4 vs 63.3 years) and had more comorbidities: hypertension, diabetes, prior MI, congestive heart failure, reduced left ventricular ejection fraction, and a longer length of stay. Mean doses for metoprolol and carvedilol did not significantly differ (37.2 ± 27.8% and 35.8 ± 31.0%, respectively). The 3-year survival estimates were 88.2% and 83.5% for metoprolol and carvedilol, respectively, with an unadjusted HR = 0.72 (p <0.0001), but after multivariable adjustment HR = 1.073 (p = 0.43). Patients in the >12.5% to 25% dose category had improved survival compared with other dose categories. Subgroup analysis of patients with left ventricular ejection fraction ≤40%, showed worse survival with metoprolol versus carvedilol (adjusted HR = 1.281; 95% CI: 1.024 to 1.602, p = 0.03). In patients with left ventricular ejection fraction >40%, there were no differences in survival with carvedilol versus metoprolol. In conclusion, overall survival after acute MI was similar for patients treated with metoprolol or carvedilol, but may be superior for carvedilol in patients with left ventricular ejection fraction ≤40%.

Simulation-based training is associated with lower risk-adjusted mortality in ACS pediatric TQIP centers.

BACKGROUND: Although use of simulation-based team training for pediatric trauma resuscitation has increased, its impact on patient outcomes has not yet been shown. The purpose of this study was to determine the association between simulation use and patient outcomes. METHODS: Trauma centers that participate in the American College of Surgeons (ACS) Pediatric Trauma Quality Improvement Program (TQIP) were surveyed to determine frequency of simulation use in 2014 and 2015. Center-specific clinical data for 2016 and 2017 were abstracted from the ACS TQIP registry (n = 57,916 patients) and linked to survey responses. Center-specific risk-adjusted mortality was estimated using multivariable hierarchical logistic regression and compared across four levels of simulation-based training use: no training, low-volume training, high-volume training, and survey nonresponders (unknown training use). RESULTS: Survey response rate was 75% (94/125 centers) with 78% of the responding centers (73/94) reporting simulation use. The average risk-adjusted odds of mortality was lower in centers with a high volume of training compared with centers not using simulation (odds ratio, 0.58; 95% confidence interval, 0.37-0.92). The times required for resuscitation processes, evaluations, and critical procedures (endotracheal intubation, head computed tomography, craniotomy, and surgery for hemorrhage control) were not different between centers based on levels of simulation use. CONCLUSION: Risk-adjusted mortality is lower in TQIP-Pediatric centers using simulation-based training, but this improvement in mortality may not be mediated by a reduction in time to critical procedures. Further investigation into alternative mediators of improved mortality associated with simulation use is warranted, including assessment of resuscitation quality, improved communication, enhanced teamwork skills, and decreased errors. LEVEL OF EVIDENCE: Therapeutic/care management, Level III.

Sudden Death After Hospitalization for Heart Failure With Reduced Ejection Fraction (from the EVEREST Trial).

Patients with chronic heart failure with reduced ejection fraction (HFrEF) benefit from medical and device therapies targeting sudden cardiac death (SCD). Contemporary estimates of SCD risk after hospitalization for heart failure are limited. We describe the incidence, timing, and clinical predictors of SCD after hospitalization for HFrEF (≤40%) in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan) trial. Multiple logistic regression analyses tested >30 baseline covariates (including treatment randomization, demographics, comorbid conditions, natriuretic peptides, ejection fraction, and medical and device therapies) to identify predictors of 1-year SCD. Of the 4,024 trial patients discharged alive (97%), there were 268 who experienced SCD (7%) and 703 who experienced non-SCD (17%) during median follow-up of 9.9 months. Implantable cardioverter defibrillator use at baseline was 14.5%. Estimates of SCD at 1, 3, 6, and 12 months were 0.8%, 2.3%, 4.1%, and 7.4%, respectively. Most patients were readmitted before SCD (n = 147, 55%). Male gender, black race, diabetes mellitus, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker use were potential predictors of 1-year SCD after hospitalization for HFrEF (all p <0.10); however, this final model demonstrated poor discrimination (C-statistic 0.57). In conclusion, in the EVEREST trial, patients hospitalized for HFrEF faced risks of 1-year postdischarge SCD of 7%, which accrued gradually over time, and were balanced with high competing risks of nonsudden death (17%). Traditional clinical characteristics fail to adequately predict SCD risk. Further data are needed to identify patients at greatest relative risk for SCD (compared with non-SCD) after hospitalization for HFrEF.

Plasma renin activity, response to aliskiren, and clinical outcomes in patients hospitalized for heart failure: the ASTRONAUT trial.

AIMS: The direct renin inhibitor, aliskiren, is known to reduce plasma renin activity (PRA), but whether the efficacy of aliskiren varies based on an individual's baseline PRA in patients hospitalized for heart failure (HF) is presently unknown. We characterized the prognostic value of PRA and determined if this risk is modifiable with use of aliskiren. METHODS AND RESULTS: This pre-specified neurohormonal substudy of ASTRONAUT analysed all patients hospitalized for HF with ejection fraction (EF) ≤40% with available baseline PRA data (n = 1306, 80.9%). Risk associated with baseline PRA and short-term changes in PRA from baseline to 1 month was modelled with respect to 12-month clinical events. Median baseline PRA was 3.0 (interquartile range 0.6-16.4) ng/mL/h. Aliskiren significantly reduced PRA early after treatment initiation through 12-month follow-up compared with placebo (P < 0.001). The lowest baseline PRA quartile (<0.6 ng/mL/h) was independently predictive of lower all-cause mortality [adjusted hazard ratio (HR) 0.50, 95% confidence interval (CI) 0.31-0.81] and the composite of cardiovascular mortality and HF hospitalization (adjusted HR 0.57, 95% CI 0.40-0.79). Delta log-normalized PRA (from baseline to 1 month) was not predictive of either primary endpoint at 12 months (P ≥ 0.43). The prognostic value of baseline PRA and short-term changes in PRA did not vary by randomization to aliskiren or placebo (interaction P ≥ 0.13). CONCLUSIONS: Plasma renin activity is reduced early and durably by aliskiren, but this did not translate into improved clinical outcomes in ASTRONAUT. Baseline PRA or short-term reduction in PRA do not identify a subgroup who may preferentially benefit from direct renin inhibition. Clinical Trial Registration ClinicalTrials.gov Unique Identifier: NCT00894387.

Pre-discharge and early post-discharge troponin elevation among patients hospitalized for heart failure with reduced ejection fraction: findings from the ASTRONAUT trial.

AIMS: Troponin levels are commonly elevated among patients hospitalized for heart failure (HF), but the prevalence and prognostic significance of early post-discharge troponin elevation are unclear. This study sought to describe the frequency and prognostic value of pre-discharge and post-discharge troponin elevation, including persistent troponin elevation from the inpatient to outpatient settings. METHODS AND RESULTS: The ASTRONAUT trial (NCT00894387; http://www.clinicaltrials.gov) enrolled hospitalized HF patients with ejection fraction ≤40% and measured troponin I prior to discharge (i.e. study baseline) and at 1-month follow-up in a core laboratory (elevation defined as >0.04 ng/mL). This analysis included 1469 (91.0%) patients with pre-discharge troponin data. Overall, 41.5% and 29.9% of patients had elevated pre-discharge [median: 0.09 ng/mL; interquartile range (IQR): 0.06-0.19 ng/mL] and 1-month (median: 0.09 ng/mL; IQR: 0.06-0.15 ng/mL) troponin levels, respectively. Among patients with pre-discharge troponin elevation, 60.4% had persistent elevation at 1 month. After adjustment, pre-discharge troponin elevation was not associated with 12-month clinical outcomes. In contrast, 1-month troponin elevation was independently predictive of increased all-cause mortality [hazard ratio (HR) 1.59, 95% confidence interval (CI) 1.18-2.13] and cardiovascular mortality or HF hospitalization (HR 1.28, 95% CI 1.03-1.58) at 12 months. Associations between 1-month troponin elevation and outcomes were similar among patients with newly elevated (i.e. normal pre-discharge) and persistently elevated levels (interaction P ≥ 0.16). The prognostic value of 1-month troponin elevation for 12-month mortality was driven by a pronounced association among patients with coronary artery disease (interaction P = 0.009). CONCLUSIONS: In this hospitalized HF population, troponin I elevation was common during index hospitalization and at 1-month follow-up. Elevated troponin I level at 1 month, but not pre-discharge, was independently predictive of increased clinical events at 12 months. Early post-discharge troponin I measurement may offer a practical means of risk stratification and should be investigated as a therapeutic target.

Influence of atrial fibrillation on post-discharge natriuretic peptide trajectory and clinical outcomes among patients hospitalized for heart failure: insights from the ASTRONAUT trial.

AIMS: Change in NT-proBNP level is a common surrogate endpoint in early phase heart failure (HF) trials, but whether this endpoint is influenced by atrial fibrillation/flutter (AFF) is unclear. METHODS AND RESULTS: This analysis included 1358 patients from the ASTRONAUT trial, which randomized patients hospitalized for HF with EF ≤40% to aliskiren or placebo in addition to standard care. Patients were stratified by presence of AFF on baseline ECG. NT-proBNP was measured longitudinally by a core laboratory at baseline, 1 month, 6 months, and 12 months. Compared with non-AFF patients, AFF patients experienced greater reduction from baseline in log-transformed NT-proBNP (interaction P < 0.001), but this difference was not significant after adjustment (interaction P = 0.726). The ability of aliskiren to lower NT-proBNP during follow-up differed by AFF status (interaction P = 0.001), with aliskiren lowering NT-proBNP more than placebo among non-AFF patients only. After adjustment, baseline AFF was not associated with mortality or HF hospitalization at 12 months (all P ≥ 0.152). CONCLUSION: In this hospitalized HF cohort, AFF status did not influence post-discharge NT-proBNP trajectory or clinical outcomes after adjustment for patient characteristics. Aliskiren lowered follow-up NT-proBNP levels in patients without AFF, but had no influence among patients with AFF. This study generates the hypothesis that the ability of a HF trial to meet an NT-proBNP defined endpoint may be influenced by the prevalence of AFF in the population. Because aliskiren did not improve outcomes in patients without AFF, this analysis suggests changes in NT-proBNP induced by investigational therapies may be dissociated from clinical effects.

T-Wave Alternans, Heart Rate Turbulence, and Ventricular Ectopy in Standard versus Daily Hemodialysis: Results from the FHN Daily Trial.

BACKGROUND: Hemodialysis (HD) patients are at high risk of sudden cardiac death (SCD). HD 6-times/week (6x/wk) may reduce SCD risk compared to usual 3-times/week HD (3x/wk) by mechanisms unknown. T-wave alternans (TWA), heart rate turbulence (HRT), and ventricular ectopy (VE) are elevated in HD patients, but their response to 6x/wk HD has not been assessed. METHODS: Baseline and 1-year Holter recordings were analyzed from enrollees in the Frequent Hemodialysis Network Daily Trial, a randomized trial comparing 3x/wk to 6x/wk in 245 chronic HD patients. TWA, HRT, and VE were assessed using MARS software. RESULTS: Sixty-eight patients (34 with 6x/wk) had complete baseline and 1-year Holter recordings. Mean age was 50 ± 13 years and 38% were female. Maximum TWA in the 3x/wk and 6x/wk groups were 52.4 µV at baseline and 51.2 µV at 1-year versus 54.0 and 49.9 µV, respectively (P = 0.28). The proportion of abnormal HRT (scores of 1 or 2) in the 3x/wk group decreased from 65% to 56% at 1-year versus 53% to 53% in the 6x/wk group (P = 0.58). Mean %VE changed from 1.6% to 2.9% in the 3x/wk group from baseline to 1-year and from 2.1% to 3.7% in the 6x/wk group (P = 0.85). CONCLUSIONS: There were no significant differences in HRT or VE at 1-year in chronic HD patients randomized to 6x/wk versus 3x/wk and a trend in TWA reduction. Additional studies are needed to evaluate the impact and mechanisms of SCD in HD.

Timing of Pharmacologic Venous Thromboembolism Prophylaxis in Severe Traumatic Brain Injury: A Propensity-Matched Cohort Study.

BACKGROUND: Patients with severe traumatic brain injury (sTBI) are at high risk for developing venous thromboembolism (VTE). Nonetheless, pharmacologic VTE prophylaxis is often delayed out of concern for precipitating extension of intracranial hemorrhage (ICH). The purpose of this study was to compare the effectiveness of early vs late VTE prophylaxis in patients with sTBI, and to characterize the risk of subsequent ICH-related complication. STUDY DESIGN: Adults with isolated sTBI (head Abbreviated Injury Scale score ≥3 and total Glasgow Coma Scale score ≤8) who received VTE prophylaxis with low-molecular-weight or unfractionated heparin were derived from the American College of Surgeons Trauma Quality Improvement Program (2012 to 2014). Patients were divided into EP (<72 hours) or LP (≥72 hours) groups. Propensity score matching was used to minimize selection bias. The primary end point was VTE (pulmonary embolism or deep vein thrombosis). Secondary outcomes were defined as late neurosurgical intervention (≥72 hours) or death. RESULTS: We identified 3,634 patients with sTBI. Early prophylaxis was given in 43% of patients. Higher head injury severity, presence of ICH, and early neurosurgery were associated with late prophylaxis. Propensity score matching yielded a well-balanced cohort of 2,468 patients. Early prophylaxis was associated with lower rates of both pulmonary embolism (odds ratio = 0.48; 95% CI, 0.25-0.91) and deep vein thrombosis (odds ratio = 0.51; 95% CI, 0.36-0.72), but no increase in risk of late neurosurgical intervention or death. CONCLUSIONS: In this observational study of patients with sTBI, early initiation of VTE prophylaxis was associated with decreased risk of pulmonary embolism and deep vein thrombosis, but no increase in risk of late neurosurgical intervention or death. Early prophylaxis may be safe and should be the goal for each patient in the context of appropriate risk stratification.