Physiologic risk stratification is important to long-term mortality, complications, and readmission in thoracic endovascular aortic repair.

Use of the American Society of Anesthesiologists (ASA) physical status classification is important for periprocedural risk stratification. However, the collective effect after adjustment for the Society for Vascular Surgery (SVS) medical comorbidity grading system on long-term all-cause mortality, complications, and discharge disposition is unknown. We examined these associations in patients after thoracic endograft placement. Data from three thoracic endovascular aortic repair (TEVAR) trials through 5 years of follow-up were included. Patients with acute complicated type B dissection (n = 50), traumatic transection (n = 101), or descending thoracic aneurysm (n = 66) were analyzed. The patients were stratified into three groups according to the ASA class: I-II, III, and IV. Multivariable proportional hazards regression models were used to examine the effect of ASA class on 5-year mortality, complications, and rehospitalizations after adjustment for SVS risk score and potential confounders. The largest proportion of patients treated by TEVAR across the ASA groups (n = 217) was ASA IV (n = 97; 44.7%; P < .001), followed by ASA III (n = 83; 38.2%) and ASA I-II (n = 37; 17.1%). Among the ASA groups, the ASA I-II patients were, on average, 6 years younger than those with ASA III and 3 years older than those with ASA IV (ASA I-II: age, 54.3 ± 22.0 years; ASA III: age, 60.0 ± 19.7 years; ASA IV: age, 51.0 ± 18.4 years; P = .009). Multivariable adjusted 5-year outcome models showed that ASA class IV, independent of the SVS score, conferred an increased risk of mortality (hazard ratio [HR], 3.83; 95% confidence interval [CI], 1.19-12.25; P = .0239) and complications (HR, 4.53; 95% CI, 1.69-12.13; P = .0027) but not rehospitalization (HR, 1.84; 95% CI, 0.93-3.68; P = .0817) compared with ASA class I-II. Procedural ASA class is associated with long-term outcomes among post-TEVAR patients, independent of the SVS score. The ASA class and SVS score remain important to patient counseling and postoperative outcomes beyond the index operation.

ITGB2 (Integrin ß2) Immunomodulatory Gene Variants in Premature Infants With Necrotizing Enterocolitis.

ABSTRACT: Aberrant toll-like receptor (TLR) activation is central to necrotizing enterocolitis (NEC) pathogenesis. ß2 integrins regulate TLR signaling, and integrin ß2 (ITGB2) deficiency causes TLR hyperresponsiveness. To test the hypothesis that ITGB2 genetic variants modulate NEC susceptibility, we sequenced the exonic ITGB2 locus to compare the prevalence of deleterious variants among 221 preterm infants with and without NEC. ITGB2 variants were not associated with NEC in our entire cohort (NEC [9/56] versus controls [16/165], P = 0.19) or in extremely low birthweight infants (ELBW, controls [7.9%] versus NEC [18.2%]; P = 0.11) but were increased compared to the populace (4.5%, gnomad.broadinstitute.org). Combined annotation-dependent depletion -predicted deleterious ITGB2 variants increased proportionately with increasing NEC severity in ELBW infants (controls [6.7%] versus medical NEC [16.7%] versus surgical NEC [19%] (P = 0.03). Although ITGB2 variants were not associated with NEC in our preterm cohort, subgroup analysis showed a trend towards enrichment with NEC severity in ELBW infants.

Twenty-two Years of Pediatric Musculoskeletal Firearm Injuries: Adverse Outcomes for the Very Young.

BACKGROUND: Firearm injuries are a significant cause of morbidity and mortality for children in the United States. The purpose of this study is to investigate the 22-year experience of pediatric firearm-related musculoskeletal injuries at a major pediatric level 1 hospital and to analyze the risk of adverse outcomes in children under 10 years of age. METHODS: An institutional review board-approved, retrospective cohort analysis was conducted on pediatric firearm-related musculoskeletal injuries at our institution from 1995 to 2017. A total of 189 children aged 0 to 18 years were identified using International Classification of Diseases, 9th Revision/10th Revision codes, focusing on musculoskeletal injuries by firearms. Exclusion criteria were primary treatment at an outside hospital, isolated nonmusculoskeletal injuries (eg, traumatic brain injury), and death before orthopaedic intervention. Two cohorts were included: age below 10 years and age 10 years and above. Primary outcome measure was a serious adverse outcome (death, growth disturbance, amputation, or impairment). Standard statistical analysis was used for demographic data, along with linear mixed models and multivariable logistic regression for adverse outcome. RESULTS: Of the 189 children, 46 (24.3%) were below 10 years of age and 143 (75.7%) were 10 years and above. Fifty-two (27.5%) of the total group had an adverse outcome, with 19 (41.3%) aged below 10 years and 33 (23.1%) aged 10 years and above (P=0.016). Adverse outcomes were 3 deaths, 17 growth disturbances, 7 amputations, and 44 impairments. For those below 10 years of age, rural location (P=0.024), need for surgical treatment (P=0.041), femur injury (P=0.032), peripheral nerve injury (P=0.006), and number of surgeries (P=0.022) were associated with an adverse outcome. CONCLUSIONS: Over one fourth of survivors of musculoskeletal firearm injuries had an adverse outcome. Children 10 years and above represent the majority of firearm injuries in our population; however, when injured, those below 10 years are more likely to have an adverse outcome. LEVEL OF EVIDENCE: Level III.

Translation of the Frailty Paradigm from Older Adults to Children with Cardiac Disease.

Children and adolescents with cardiac disease (CCD) have significant morbidity and lower quality of life. However, there are no broadly applicable tools similar to the frailty score as described in the elderly, to define functional phenotype in terms of physical capability and psychosocial wellbeing in CCD. The purpose of this study is to investigate the domains of the frailty in CCD. We prospectively recruited CCD (8-17.5 years old, 70% single ventricle, 27% heart failure, 12% pulmonary hypertension; NYHA classes I, II and III) and age and gender matched healthy controls (total n = 56; CCD n = 34, controls n = 22; age 12.6 ± 2.6 years; 39.3% female). We measured the five domains of frailty: slowness, weakness, exhaustion, body composition and physical activity using developmentally appropriate methods. Age and gender-based population norms were used to obtain Z scores and percentiles for each measurement. Two-tailed t-tests were used to compare the two groups. The CCD group performed significantly worse in all five domains of frailty compared to healthy controls. Slowness: 6-min walk test with Z score -3.9 ± 1.3 vs -1.4 ± 1.3, p < 0.001; weakness: handgrip strength percentile 18.9 ± 20.9 vs 57.9 ± 26.0, p < 0.001; exhaustion: multidimensional fatigue scale percentile 63.7 ± 13.5 vs 83.3 ± 14.4, p < 0.001; body composition: height percentile 43.4 ± 29.5 vs 71.4 ± 25.2, p < 0.001, weight percentile 46.0 ± 36.0 vs 70.9 ± 24.3, p = 0.006, BMI percentile 48.4 ± 35.5 vs 66.9 ± 24.2, p = 0.04, triceps skinfold thickness 41.0 ± 24.0 vs 54.4 ± 22.1, p = 0.04; physical activity: pediatric activity questionnaire score 2 ± 0.6 vs 2.7 ± 0.6, p < 0.001. The domains of frailty can be quantified in children using developmentally appropriate methods. CCD differ significantly from controls in all five domains, supporting the concept of quantifying the domains of frailty. Larger longitudinal studies are needed to study frailty in CCD and examine if it predicts adverse health outcomes.Clinical Trial Registration: The ClinicalTrials.gov identification number is NCT02999438. https://clinicaltrials.gov/ct2/show/NCT02999438.

Using liver elastography to diagnose sinusoidal obstruction syndrome in pediatric patients undergoing hematopoetic stem cell transplant.

Sinusoidal obstruction syndrome (SOS) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Traditional ultrasound (US) has poor sensitivity and specificity. US shear wave elastography (SWE) is a newer technology that measures liver stiffness. This is a single-institution, prospective cohort study evaluating SWE in patients younger than 21 years who received HSCT from December 2015 through June 2017. SOS was defined using the modified Seattle criteria. Subjects had US with SWE at three scheduled time points. t-tests were used to assess for difference between the groups and ROC curves were generated. Twenty-five patients were included. Five subjects developed SOS. At day +5 HSCT, SOS patients had SWE velocities that increased by 0.25 ± 0.21 m/s compared to 0.02 ± 0.18 in patients without SOS (p = 0.020). At day +14, SOS patients had SWE velocities that significantly increased by 0.91 m/s ± 1.14 m/s compared to 0.03 m/s ± 0.23 m/s in patients without SOS (p = 0.010). SWE SOS diagnosis occurred on average 9 and 11 days before clinical and conventional US diagnosis, respectively. Patients who develop SOS have increased liver stiffness compared to patients who do not develop SOS. SWE changes occur before other imaging and clinical findings of SOS.

Expression of HBME-1 and CD56 in follicular variant of papillary carcinoma in children: An immunohistochemical study and their diagnostic utility.

Papillary thyroid carcinoma (PTC) is the most common differentiated thyroid cancer in children; and the follicular variant is the second most common variant after the classic subtype. The histological appearance of follicular variant of papillary thyroid cancer (FVPTC), can be mimicked by benign follicular nodules. Pediatric pathologists encountering such lesions with FVPTC-like appearance may err on diagnosing the benign lesions as malignant. In adult patients, several immunohistochemical markers have emerged recently as a useful adjunct to distinguish differentiated thyroid carcinomas from benign follicular lesions. We undertook an inter-institutional retrospective study to establish the diagnostic utility of immunohistochemical staining for HBME-1, Galectin-3 and CD56 in differentiating FVPTC from its benign mimics, follicular adenoma and adenomatoid nodules, in children. Our specific aim of the project was to define the sensitivity and specificity of the three antibodies in FVPTC. Based on institutional diagnoses, a total of 66 cases were obtained: 32 FVPTC and 34 benign follicular nodules that comprised of 23 follicular adenoma and 11 adenomatoid nodules. Five investigators, who were blinded to the original diagnoses, independently reviewed the slides following pre-determined criteria and semi-quantitatively scoring the immunohistochemical staining. The immunohistochemical staining revealed that a combination of positive HBME-1 and negative CD56 result gave 100% specificity and positive predictive value in distinguishing FVPTC from benign follicular nodules. However, the antibody combination suffered from a lower sensitivity (50%). We used a cutoff of 25% positivity of tumor cells in determining positivity of tumor cells to an antibody. In conclusion, our study found a very high specificity and strong positive predictive value for the combination of HBME-1 and CD56 immunohistochemical stains in distinguishing FVPTC from benign follicular lesions.

Adolescent Reproductive Health Care: Views and Practices of Pediatric Hospitalists.

BACKGROUND AND OBJECTIVES: Many hospitalized adolescents are at increased risk for pregnancy complications due to an underlying medical condition, however sexual risk assessment is not consistently performed in this setting. While adolescents and their parents are supportive of sexual health discussion in the inpatient setting, a thorough understanding of factors that influence provision of this care among pediatric hospital physicians is lacking. This formative information is needed to facilitate efforts to improve and standardize clinical care provision. Our objective is to assess the frequency and factors that influence the provision of adolescent sexual and reproductive care by pediatric hospitalists. METHODS: We performed a cross-sectional computerized survey of hospitalists at 5 pediatric hospitals who cared for ≥1 adolescent (14-21 years old) in the past year. Sexual and reproductive care practices were assessed by using a 76-item novel survey informed by the theory of planned behavior. We used descriptive statistics to summarize the data. RESULTS: Sixty-eight pediatric hospitalists participated (49% response rate): 78% were women and 65% were aged <40 years. Most (69%) reported treating >46 adolescents annually, including many who are at an increased risk for pregnancy complications due to teratogenic medication use or a comorbid condition. A majority felt that sexual and reproductive services are appropriate, although many endorsed barriers, including concern about follow-up after emergency contraception (63%) and time constraints (53%). Most reported insufficient knowledge regarding contraception (59%), desired contraception education (57%), and were likely to increase contraceptive provision if provided education (63%). Hospitalists rarely provided condoms or referral for an intrauterine device. CONCLUSIONS: Pediatric hospitalists frequently care for adolescents who are at risk for pregnancy complications and generally agree that reproductive care is appropriate in the inpatient setting. With these findings, we highlight the critical need for effective comprehensive reproductive health service interventions that are tailored to address the numerous actionable barriers identified in this study.

Improving Wait Time for Patients in a Pediatric Echocardiography Laboratory - a Quality Improvement Project.

BACKGROUND: Prolonged wait times for echocardiograms in the outpatient pediatric cardiology clinic led to patient and provider dissatisfaction at our institution. The aims of this project were to measure our baseline performance with regard to echocardiogram wait time (EWT), to implement a formal quality improvement (QI) program to improve EWT, and to measure the impact of QI on EWT. METHODS: A QI team was formed comprising of cardiologists (A.P., T.S.), sonographer (A.W.), and QI mentor (J.M.). EWT was defined as time in minutes from initiation of the order in the electronic medical record to start of the echocardiogram. Goal EWT was set as ≤ 20 minutes for 90% patients. Flowcharts were created after process observation to identify sources of potential delay contributing to EWT. QI methodology such as driver diagrams were utilized to identify interventions, which were then implemented and studied as Plan-Do-Study-Act cycles. RESULTS: Sequential interventions included early start time, huddles involving clinic and echo laboratory staff, patient tracking system, and repurposing of a clinic room for echo. EWT was tracked for 840 patients. Mean EWT was 22.5 ± 17.5 minutes at baseline and decreased to 15.3 ± 7.8 minutes postintervention (P < 0.001). Postintervention, 81% of the patients waited < 20 minutes for their echo, and 98% patients waited < 30 minutes, compared with baseline numbers of 62% and 76%, respectively (P < 0.001). CONCLUSIONS: We were able to utilize QI methodology to derive interventions and track changes, resulting in quantifiable improvement in EWT in a busy pediatric echo laboratory.

Lipoprotein (a): Examination of Cardiovascular Risk in a Pediatric Referral Population.

Atherosclerotic cardiovascular disease (CVD), a leading cause of death globally, has origins in childhood. Major risk factors include family history of premature CVD, dyslipidemia, diabetes mellitus, and hypertension. Lipoprotein (a) [Lp(a)], an inherited lipoprotein, is associated with premature CVD, but its impact on cardiovascular health during childhood is less understood. The objective of the study was to examine the relationship between Lp(a), family history of premature CVD, dyslipidemia, and vascular function and structure in a high-risk pediatric population. This is a single-center, cross-sectional study of 257 children referred to a preventive cardiology clinic. The independent variable, Lp(a), separated children into high-Lp(a) [Lp(a) ≥ 30 mg/dL] and normal-Lp(a) groups [Lp(a) < 30 mg/dL]. Dependent variables included family history of premature CVD; dyslipidemia, defined as low-density lipoprotein cholesterol > 130 mg/dL, high-density lipoprotein cholesterol (HDL-C) < 45 mg/dL, triglycerides (TG) > 100 mg/dL; and vascular changes suggesting early atherosclerosis, as measured by carotid-femoral pulse wave velocity (PWV) and carotid artery intima-media thickness (CIMT). Of the 257 children, 110 (42.8%) had high Lp(a) and 147 (57.2%) had normal Lp(a). There was a higher prevalence of African-American children in the high-Lp(a) group (19.3%) compared to the normal-Lp(a) group (2.1%) (p < 0.001). High Lp(a) was associated with positive family history of premature CVD (p = 0.03), higher-than-optimal HDL-C (p = 0.02), and lower TG (p < 0.001). There was no difference in PWV or CIMT between groups. High Lp(a) in children is associated with family history of premature CVD and is prevalent in African-American children. In children with high Lp(a), promotion of intensive lifestyle modifications is prudent to decrease premature CVD-related morbidity.

Interstage Outcomes in Infants With Single Ventricle Heart Disease Comparing Home Monitoring Technology to Three-Ring Binder Documentation: A Randomized Crossover Study.

BACKGROUND: Interstage outcomes for infants with single ventricle remain suboptimal. We have previously described a tablet PC-based platform Cardiac High Acuity Monitoring Program (CHAMP) for remote monitoring which provides immediate access to data, videos, and instant alerts to our single ventricle care team. METHODS: This study compares traditional three-ring binder monitoring (Binder) to CHAMP using a randomized crossover design to evaluate mortality, resource utilization, and caregiver experience. At discharge, all single ventricle infants were monitored using Binder and randomized to receive CHAMP at either one or two months postdischarge. One month after randomization, caregivers could choose either Binder or CHAMP for the remainder of the interstage period. Caregivers experience was recorded using surveys. RESULTS: Enrollment included 31 single ventricle infants from May 2014 to June 2015. There was no interstage mortality over 4,911 total interstage days (median: 144/patient). Of 73 readmissions, 45 were unplanned. Of the initial 23 unplanned readmissions, 13 were found to have been based on data obtained exclusively through CHAMP (as instant alerts or based on data review) rather than caregiver concerns. Due to concerns regarding patient safety, additional enrollment was stopped. The CHAMP use was associated with significantly fewer unplanned intensive care unit days/100 interstage days, shorter delays in care, lower resource utilization at readmissions, and lower incidence of interstage growth failure and was preferred by a majority of caregivers. CONCLUSIONS: These findings suggest that CHAMP may offer benefits over Binder (improved interstage outcomes, delays in care, and caregiver experience). These findings should be tested across multiple centers in larger populations.

Post-ligation cardiac syndrome is associated with increased morbidity in preterm infants.

OBJECTIVE: The influence of post-ligation cardiac syndrome (PLCS), a complication of patent ductus arteriosus (PDA) ligations, on neonatal outcomes is unknown. The purpose of this study was to determine the risks of PLCS on severe pulmonary morbidity and severe retinopathy of prematurity (ROP). STUDY DESIGN: Retrospective cohort study of infants who underwent a PDA ligation between 2006 and 2015. Data were collected on patients with and without PLCS. The primary outcome was the difference in severe bronchopulmonary dysplasia (BPD) between groups. Secondary outcomes included discharge with home oxygen and severe ROP. RESULT: A total of 100 infants that underwent PDA ligation during the study period were included in the study; 31 (31%) neonates developed PLCS. In adjusted analysis, PLCS was associated with increased risk for severe BPD (RR 1.67, 95% CI: 1.15-2.42) and home oxygen therapy (RR: 1.47, 95% CI: 1.09-1.99) only. No association with severe ROP was seen (RR: 1.48; 95% CI: 0.87-2.52). CONCLUSION: PLCS is associated with severe neonatal pulmonary morbidity, but not with severe ROP. Further investigation is warranted to validate these results.

Interpreting measurements of cardiac function using vendor-independent speckle tracking echocardiography in children: a prospective, blinded comparison with catheter-derived measurements.

BACKGROUND: Adult studies demonstrate that echocardiographic measurements of cardiac function using speckle tracking correlate with invasive measurements, but such data in the pediatric population are sparse. Our aim was to compare speckle-derived measures of cardiac function to measurements routinely obtained by cardiac catheterization in children. METHODS: Echocardiograms were performed on the day of cardiac catheterization. Using Tomtec 2D Cardiac Performance Analysis, longitudinal strain (LS), longitudinal strain rate (LSR), early diastolic LSR, and ejection fraction (EF) for the right and left ventricle (RV and LV) were calculated via speckle tracking. Global LS and LSR were calculated for the LV. These results were compared to cardiac index, maximum ventricular dp/dt (max dp/dt), ventricular end-diastolic pressure (EDP), and pulmonary capillary wedge pressure (PCWP) obtained by fluid-filled catheters. A blinded observer performed all echo measurements. RESULTS: Fifty studies were performed on 28 patients ages 4 months to 20 years old. Their diagnoses included cardiac transplant (48 studies), repaired AV septal defect (1), and dilated cardiomyopathy (1). RVEDP ranged from 2 to 22 mm Hg (median=6) and PCWP ranged from 6 to 32 mmHg (median 10). LV global LS and LV 2-chamber LSR by speckle-tracking negatively correlated with LV max dp/dt (LV global LS R=-.83, P=.001; LV 2-chamber LSR R=-.69, P=.009). RV LS weakly correlated with max dp/dt (R=.363, P=.002). Early diastolic strain rate did not correlate with EDP in either ventricle. CONCLUSION: Speckle-derived measurements of function in the LV have stronger correlation than the RV to catheter-derived measures. LV global LS has the strongest correlation with invasive function measures in children.

Value-Based Benefit Design to Improve Medication Adherence for Employees with Anxiety or Depression.

BACKGROUND: Through reduced out-of-pocket costs and wellness offerings, value-based benefit design (VBBD) is a promising strategy to improve medication adherence and other health-related outcomes across populations. There is limited evidence, however, of the effectiveness of these policy-level changes among individuals with anxiety or depression. OBJECTIVES: To assess the impact of a multifaceted VBBD policy that incorporates waived copayments, wellness offerings, and on-site services on medication adherence among plan members with anxiety or depression, and to explore how this intervention and its resulting improved adherence affects other health-related outcomes. METHODS: A retrospective longitudinal pre/post design was utilized to measure outcomes before and after the VBBD policy change. Repeated measures statistical regression models with correlated error terms were utilized to evaluate outcomes among employees of a self-insured global health company and their spouses (N = 529) who had anxiety or depression after the VBBD policy change. A multivariable linear regression model was chosen as the best fit to evaluate a change in medication possession ratio (MPR) after comparing parameters for several distributions. The repeated measures multivariable regression models were adjusted for baseline MPR and potential confounders, including continuous age, sex, continuous modified Charlson Comorbidity Index, and the continuous number of prescriptions filled that year. The outcomes were assessed for the 1 year before the policy change (January 1, 2011, through December 31, 2011) and for 2 years after the change (January 1, 2012, through December 31, 2013). The primary outcome was a change in MPR. The secondary outcomes included healthcare utilization, medical or pharmacy costs, the initiation of medication, generic medication use, and employee absenteeism (the total number of sick days). RESULTS: The implementation of the VBBD strategy was associated with a significant increase in average MPR (0.65 vs 0.61 in the pre-VBBD period; P = .004), the initiation of new medications for anxiety or depression (31.4% vs 29.5%, respectively; P = .033), and the filling of generic medications for anxiety or depression (85.1% vs 80.5%, respectively; P <.001). A multivariable adjusted analysis revealed a 0.05 increase in MPR after the benefit enhancement (P = .002). Healthcare utilization, costs, and absenteeism were not statistically different before and after the VBBD policy change. CONCLUSION: The VBBD strategy was associated with improved medication adherence and cost-conscious medication use. Future analyses should explore whether these trends persist over time, and if they can further impact healthcare utilization, cost, and absenteeism.

Contemporary use of dual antiplatelet therapy for preventing cardiovascular events.

OBJECTIVES: CHARISMA was a landmark randomized clinical trial that failed to demonstrate a benefit of dual antiplatelet therapy (DAPT) over aspirin alone for preventing cardiovascular events. However, subgroup analyses of the trial found fewer major adverse cardiovascular events (MACEs) for patients with established cardiovascular disease but more MACEs for patients with multiple risk factors without established cardiovascular disease. Our objective was to examine DAPT use in contemporary clinical practice after publication of CHARISMA results. STUDY DESIGN: Retrospective analysis of a large clinical registry of outpatient cardiovascular visits to over 1000 physicians that collected data on patient clinical history, symptoms, vital signs, and medications. METHODS: Clinical characteristics and prescription rates of aspirin and clopidogrel were compared for patients with established cardiovascular disease and for patients with only multiple cardiovascular risk factors. Prescription of DAPT by calendar quarter was evaluated from 2008 to 2011 using multivariable Poisson regression models. RESULTS: Of 167,839 patients with established cardiovascular disease, 20.5% were prescribed both aspirin and clopidogrel. Of 20,478 patients with multiple risk factors but no known cardiovascular disease, 3.5% were prescribed both aspirin and clopidogrel. Across 14 calendar quarters, prescription rates of DAPT did not change significantly for patients with established CVD but decreased for patients with multiple risk factors with an incidence rate ratio of 0.77. CONCLUSIONS: Use of DAPT is modest in patients with established cardiovascular disease, for whom the CHARISMA trial suggested decreased MACEs, and prescription rates have remained stable over time. Use of DAPT in patients with multiple risk factors only, for whom CHARISMA suggested that DAPT may lead to increased MACE, was low and decreased over time.

Blood transfusion during acute myocardial infarction: association with mortality and variability across hospitals.

BACKGROUND: Blood transfusion is controversial for anemic patients with acute myocardial infarction (AMI), with some previous studies reporting increased risk of transfusion-associated mortality. OBJECTIVES: The goal of this study was to examine variability in blood transfusions across hospitals and the relationship between blood transfusion and in-hospital mortality in a large, contemporary cohort of consecutive AMI patients. METHODS: Among 34,937 AMI hospitalizations from 57 centers, patients receiving at least 1 packed red blood cell transfusion were compared with those who were not transfused. Using 45 disease severity, comorbidity, laboratory, and in-hospital treatment variables, we propensity matched patients who did and did not receive a packed red blood cell transfusion. A conditional logistic regression model was used to identify the association between transfusion and in-hospital mortality. RESULTS: A total of 1,778 patients (5.1%) had at least 1 transfusion. In unadjusted analyses, transfusion was associated with higher in-hospital mortality (odds ratio: 2.05 [95% confidence interval: 1.76 to 2.40]). The vast majority of patients (91.1%) with and without transfusion had nonoverlapping propensity scores, reflecting incomparable clinical profiles. Thus, they were excluded from the propensity-matched analyses. After propensity matching those with overlapping scores, blood transfusion was associated with a reduced risk of in-hospital death (odds ratio: 0.73 [95% confidence interval: 0.58 to 0.92]). CONCLUSIONS: The majority of patients undergoing blood transfusion in clinical practice cannot be matched with nontransfused patients due to their markedly different clinical profiles. Among comparable patients, blood transfusion was associated with a lower risk of in-hospital mortality. These findings suggest that previous observational reports of increased mortality with transfusion may have been influenced by selection bias, and they highlight the need for randomized trials to establish the role of transfusion during AMI.

Variation in the incidence of hospital-acquired anemia during hospitalization with acute myocardial infarction (data from 57 US hospitals).

Development of hospital-acquired anemia (HAA) during acute myocardial infarction may be related to processes of care and is associated with poor outcomes. Little is known about variation in the incidence of HAA across hospitals or the hospital characteristics associated with HAA. We studied 17,676 patients with acute myocardial infarction without anemia at admission, defining HAA as a hemoglobin decline below anemia diagnostic thresholds and moderate-to-severe HAA as a hemoglobin decline to <11 g/dl. We calculated median rate ratios (MRRs), the median value of the relative risk (RR) for HAA for 2 patients with identical characteristics presenting to 2 randomly selected hospitals, to identify variation in HAA adjusting for patient characteristics. Separate models were fit to test the association between hospital characteristics and HAA. HAA (57.5%) and moderate-to-severe HAA (20.1%) were common. The incidence of HAA varied substantially across hospitals and remained significant after multivariable adjustment (any HAA: MRR 1.09, 95% confidence interval (CI) 1.07 to 1.13; moderate-to-severe HAA: MRR 1.27, 95% CI 1.19 to 1.39). Adjusting for patient characteristics, teaching status (RR 0.91, 95% CI 0.84 to 0.97 vs nonteaching status), and region (Northeast vs Midwest: RR 1.10, 95% CI 1.01 to 1.19; West vs Midwest: RR 1.19, 95% CI 1.06 to 1.33, respectively) was associated with risk of HAA. Teaching status (RR 0.7, 95% CI 0.6 to 0.9 vs nonteaching status) and region (South vs Midwest: RR 1.3, 95% CI 1.0 to 1.5) were independently associated with moderate-to-severe HAA. In conclusion, we observed significant variability in the incidence of HAA across hospitals and found a lower risk of HAA at teaching centers, suggesting that qualitative studies of the relation between HAA and processes of care are needed to identify targets for quality improvement.

New-onset atrial fibrillation after acute myocardial infarction and its relation to admission biomarkers (from the TRIUMPH registry).

Atrial fibrillation (AF) is an independent predictor of mortality after acute myocardial infarction (AMI). We analyzed the relation between biomarkers linked to myocardial stretch (NT-pro-brain natriuretic peptide [NT-proBNP]), myocardial damage (Troponin-T [TnT]), and inflammation (high-sensitivity C-reactive protein [hs-CRP]) and new-onset AF during AMI to identify patients at high risk for AF. In a prospective multicenter registry of AMI patients (from the Translational Research Investigating Underlying disparities in recovery from acute Myocardial infarction: Patients' Health status registry), we measured NT-proBNP, TnT, and hs-CRP in patients without a history of AF (n = 2,370). New-onset AF was defined as AF that occurred during the index hospitalization. Hierarchical multivariate logistic regression models were used to determine the association of biomarkers with new-onset AF, after adjusting for other covariates. New-onset AF was documented in 114 patients with AMI (4.8%; mean age 58 years; 32% women). For each twofold increase in NT-proBNP, there was an 18% increase in the rate of AF (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03 to 1.35; p <0.02). Similarly, for every twofold increase in hs-CRP, there was a 15% increase in the rate of AF (OR 1.15, 95% CI 1.02 to 1.30; p = 0.02). TnT was not independently associated with new-onset AF (OR 0.96, 95% CI 0.85 to 1.07; p = 0.3). NT-proBNP and hs-CRP were independently associated with new in-hospital AF after MI, in both men and women, irrespective of race. Our study suggests that markers of myocardial stretch and inflammation, but not the amount of myocardial necrosis, are important determinants of AF in the setting of AMI.

Prevalence of traditional cardiac risk factors and secondary prevention among patients hospitalized for acute myocardial infarction (AMI): variation by age, sex, and race.

BACKGROUND: Modification of traditional cardiac risk factors is an important goal for patients after an acute myocardial infarction (AMI). Risk factor prevalence and secondary prevention efforts at discharge are well characterized among older patients; however, research is limited for younger and minority AMI populations, particularly among women. METHODS: Among 2369 AMI patients enrolled in a 19-center prospective study, we compared the prevalence and cumulative number of five cardiac risk factors (hypertension, hypercholesterolemia, current smoking, diabetes, obesity) by age, sex, and race. We also compared secondary prevention strategies at discharge for these risk factors, including prescription of antihypertensive or lipid-lowering medications and counseling on preventive behaviors (smoking cessation, diabetes management, diet/weight management). RESULTS: Approximately 93% of patients had ≥1 risk factor, 72% had ≥2 factors, and 40% had ≥3 factors. The prevalence of multiple risk factors was markedly higher for blacks than for whites within each age-sex group; black women had the greatest risk factor burden of any subgroup (60% of older black women and 54% of younger black women had ≥3 risk factors). Secondary prevention efforts for smoking cessation were less common for black compared with white patients, and younger black patients were less often prescribed antihypertensive and lipid-lowering medications compared with younger white patients. CONCLUSIONS: Multiple cardiac risk factors are highly prevalent in AMI patients, particularly among black women. Secondary prevention efforts, however, are less common for blacks compared to whites, especially among younger patients. Our findings highlight the need for improved risk factor modification efforts in these high-risk subgroups.

Association of low body temperature and poor outcomes in patients admitted with worsening heart failure: a substudy of the Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial.

AIMS: Risk stratification in patients admitted with worsening heart failure (HF) is essential for tailoring therapy and counselling. Risk models are available but rarely used, in part because many require laboratory and imaging results that are not routinely available. Body temperature is associated with prognosis in other illnesses, and we hypothesized that low body temperature would be associated with worse outcomes in patients admitted with worsening HF. METHODS AND RESULTS: The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial was an event-driven, randomized, double-blind, placebo-controlled study of tolvaptan in 4133 patients hospitalized for worsening HF with an EF <40%. Co-primary endpoints were all-cause mortality and cardiovascular (CV) death or HF rehospitalization. Body temperature was measured orally at randomization and entered in analyses both as a continuous variable and categorized into three groups (<36 °C, 36-36.5 °C, and >36.5 °C) using Cox regression models. The composite of CV death or HF rehospitalization occurred in 1544 patients within 1 year. For every 1 °C decrease in body temperature, the risk of adverse outcomes increased by 16% [hazard raio (HR) 1.16, 95% confidence interval (CI) 1.04-1.28], after adjustment for age, gender, race, systolic blood pressure, EF, blood urea nitrogen, and serum sodium. In fully adjusted analysis, the risk of adverse outcomes in the lowest body temperature group (<36 °C) was 51% higher than that of the index group (>36.5 °C) (HR 1.35, 95% CI 1.15-1.58). CONCLUSIONS: Low body temperature is an independent marker of poor cardiovascular outcomes in patients admitted with worsening HF and reduced EF.

Nuisance bleeding with prolonged dual antiplatelet therapy after acute myocardial infarction and its impact on health status.

OBJECTIVES: The purpose of this study was to examine the incidence of nuisance bleeding after AMI and its impact on QOL. BACKGROUND: Prolonged dual antiplatelet therapy (DAPT) is recommended after acute myocardial infarction (AMI) to reduce ischemic events, but it is associated with increased rates of major and minor bleeding. The incidence of even lesser degrees of post-discharge "nuisance" bleeding with DAPT and its impact on quality of life (QOL) are unknown. METHODS: Data from the 24-center TRIUMPH (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status) study of 3,560 patients, who were interviewed at 1, 6, and 12 months after AMI, were used to investigate the incidence of nuisance bleeding (defined as Bleeding Academic Research Consortium type 1). Baseline characteristics associated with "nuisance" bleeding and its association with QOL, as measured by the EuroQol 5 Dimension visual analog scale, and subsequent re-hospitalization were examined. RESULTS: Nuisance (Bleeding Academic Research Consortium type 1) bleeding occurred in 1,335 patients (37.5%) over the 12 months after AMI. After adjusting for baseline bleeding and mortality risk, ongoing DAPT was the strongest predictor of nuisance bleeding (rate ratio [RR]: 1.44, 95% confidence interval [CI]: 1.17 to 1.76 at 1 month; RR: 1.89, 95% CI: 1.35 to 2.65 at 6 months; and RR: 1.39, 95% CI: 1.08 to 1.79 at 12 months; p < 0.01 for all comparisons). Nuisance bleeding at 1 month was independently associated with a decrement in QOL at 1 month (-2.81 points on EuroQol 5 Dimension visual analog scale; 95% CI: 1.09 to 5.64) and nonsignificantly toward higher re-hospitalization (hazard ratio: 1.20; 95% CI: 0.95 to 1.52). CONCLUSIONS: Nuisance bleeding is common in the year after AMI, associated with ongoing use of DAPT, and independently associated with worse QOL. Improved selection of patients for prolonged DAPT may help minimize the incidence and adverse consequences of nuisance bleeding.