Tanya S. Kenkre

Cardiac magnetic resonance myocardial perfusion reserve index is reduced in women with coronary microvascular dysfunction. A National Heart, Lung, and Blood Institute-sponsored study from the Women's Ischemia Syndrome Evaluation.

Background—Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). Although traditional noninvasive stress imaging is often normal in CMD, cardiac MRI may be able to detect CMD in this population. Methods and Results—Vasodilator stress cardiac MRI was performed in 118 women with suspected CMD who had undergone CRT and 21 asymptomatic reference subjects. Semi-quantitative evaluation of the first-pass perfusion images was completed to determine myocardial perfusion reserve index (MPRI). The relationship between CRT findings and MPRI was examined by Pearson correlations, logistic regression, and sensitivity/specificity. Symptomatic women had lower mean pharmacological stress MPRI compared with reference subjects (1.71±0.43 versus 2.23±0.37; P<0.0001). Lower MPRI was predictive of ≥1 abnormal CRT variables (odds ratio =0.78 [0.70, 0.88], P<0.0001, c-statistic 0.78 [0.68, 0.88]). An MPRI threshold of 1.84 predicted CRT abnormality with sensitivity 73% and specificity 74%. Conclusions—Noninvasive cardiac MRI MPRI can detect CMD defined by invasive CRT. Further work is aimed to optimize the noninvasive identification and management of CMD patients. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00832702.Background— Women with signs and symptoms of ischemia and no obstructive coronary artery disease often have coronary microvascular dysfunction (CMD), diagnosed by invasive coronary reactivity testing (CRT). Although traditional noninvasive stress imaging is often normal in CMD, cardiac MRI may be able to detect CMD in this population. Methods and Results— Vasodilator stress cardiac MRI was performed in 118 women with suspected CMD who had undergone CRT and 21 asymptomatic reference subjects. Semi-quantitative evaluation of the first-pass perfusion images was completed to determine myocardial perfusion reserve index (MPRI). The relationship between CRT findings and MPRI was examined by Pearson correlations, logistic regression, and sensitivity/specificity. Symptomatic women had lower mean pharmacological stress MPRI compared with reference subjects (1.71±0.43 versus 2.23±0.37; P <0.0001). Lower MPRI was predictive of ≥1 abnormal CRT variables (odds ratio =0.78 [0.70, 0.88], P <0.0001, c-statistic 0.78 [0.68, 0.88]). An MPRI threshold of 1.84 predicted CRT abnormality with sensitivity 73% and specificity 74%. Conclusions— Noninvasive cardiac MRI MPRI can detect CMD defined by invasive CRT. Further work is aimed to optimize the noninvasive identification and management of CMD patients. Clinical Trial Registration— URL: . Unique identifier: [NCT00832702][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00832702&atom=%2Fcirccvim%2F8%2F4%2Fe002481.atom

Anxiety associations with cardiac symptoms, angiographic disease severity, and healthcare utilization: The NHLBI-sponsored Women's Ischemia Syndrome Evaluation

BACKGROUND Anxiety is common among patients presenting with suspected coronary artery disease (CAD). In a sample of women with signs and symptoms of ischemia, we examined three anxiety markers as predictors of CAD endpoints including: 1) cardiac symptom indicators; 2) angiographic CAD severity; and 3) healthcare utilization (cardiac hospitalizations and 5-year cardiovascular [CVD] healthcare costs). METHODS Participants completed a baseline protocol including coronary angiogram, cardiac symptoms, psychosocial measures and a median 5.9-year follow-up to track hospitalizations. We calculated CVD costs based on cardiac hospitalizations, treatment visits, and CVD medications. Anxiety measures included anxiolytic medication use, Spielberger Trait Anxiety Inventory (STAI) scores, and anxiety disorder treatment history. RESULTS The sample numbered 514 women with anxiety measure data and covariates (mean age=57.5 [11.1]). One in five (20.4%) women reported using anxiolytic agents. Anxiety correlated with cardiac symptom indicators (anxiolytic use with nighttime angina and nitroglycerine use; STAI scores and anxiety disorder treatment history with nighttime angina, shortness of breath, and angina frequency). Anxiety disorder treatment history (but not STAI scores or anxiolytics) predicted less severe CAD. Anxiolytic use (but not STAI scores or anxiety disorder treatment history) predicted hospitalizations for chest pain and coronary catheterization (HRs=2.0, 95% CIs=1.1-4.7). Anxiety measures predicted higher 5-year CVD costs (+9.0-42.7%) irrespective of CAD severity. CONCLUSIONS Among women with signs and symptoms of myocardial ischemia, anxiety measures predict cardiac endpoints ranging from cardiac symptom severity to healthcare utilization. Based on these findings, anxiety may warrant greater consideration among women with suspected CAD.

Depression, dietary habits, and cardiovascular events among women with suspected myocardial ischemia.

BACKGROUND Dietary habits and depression are associated with cardiovascular disease risk. Patients with depression often report poor eating habits, and dietary factors may help explain commonly observed associations between depression and cardiovascular disease. METHODS From 1996 to 2000, 936 women were enrolled in the Womens Ischemia Syndrome Evaluation at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (median follow-up, 5.9 years) for adverse outcomes (cardiovascular disease death, heart failure, myocardial infarction, stroke). Participants completed a protocol including coronary angiography (coronary artery disease severity) and depression assessments (Beck Depression Inventory scores, antidepressant use, and depression treatment history). A subset of 201 women (mean age, 58.5 years; standard deviation, 11.4) further completed the Food Frequency Questionnaire for Adults (1998 Block). We extracted daily fiber intake and daily servings of fruit and vegetables as measures of dietary habits. RESULTS In separate Cox regression models adjusted for age, smoking, and coronary artery disease severity, Beck Depression Inventory scores (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.10), antidepressant use (HR, 2.4; 95% CI, 1.01-5.9), and a history of treatment for depression (HR, 2.4; 95% CI, 1.1-5.3) were adversely associated with time to cardiovascular disease outcomes. Fiber intake (HR, 0.87; 95% CI, 0.78-0.97) and fruit and vegetable consumption (HR, 0.36; 95% CI, 0.19-0.70) were associated with a decreased time to cardiovascular disease event risk. In models including dietary habits and depression, fiber intake and fruit and vegetable consumption remained associated with time to cardiovascular disease outcomes, whereas depression relationships were reduced by 10% to 20% and nonsignificant. CONCLUSIONS Among women with suspected myocardial ischemia, we observed consistent relationships among depression, dietary habits, and time to cardiovascular disease events. Dietary habits partly explained these relationships. These results suggest that dietary habits should be included in future efforts to identify mechanisms linking depression to cardiovascular disease.

Comparison of low and high dose intracoronary adenosine and acetylcholine in women undergoing coronary reactivity testing: Results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Women with signs and symptoms of myocardial ischemia who are referred for invasive coronary angiography often have no evidence of obstructive coronary artery disease (CAD) [1]. Forty-five to sixty percent of these patients have abnormal coronary vasomotion due to endothelial or non-endothelial dependent macro- or microvascular coronary dysfunction [1–3]. Abnormal coronary vasomotion is linked with adverse cardiovascular outcomes, suggesting that additional coronary reactivity testing (CRT), beyond standard angiography, is needed in clinical practice to appropriately risk stratify these patients [2–6]. CRT with intra-coronary adenosine and acetylcholine (ACh) is used to identify vascular dysfunction, yet ascending dosing of these agents is time-consuming. We aimed to determine if 1) coronary flow reserve (CFR) was different after low or high dose adenosine, and 2) change in coronary artery cross sectional area (CSA) and coronary blood flow (CBF) was different after low or high dose ACh.

Ten-Year Mortality in the WISE Study (Women’s Ischemia Syndrome Evaluation)

Background— The WISE study (Women’s Ischemia Syndrome Evaluation) was a prospective cohort study of 936 clinically stable symptomatic women who underwent coronary angiography to evaluate symptoms and signs of ischemia. Long-term mortality data for such women are limited. Methods and Results— Obstructive coronary artery disease (CAD) was defined as ≥50% stenosis on angiography by core laboratory. We conducted a National Death Index search to assess the mortality of women who were alive at their final WISE contact date. Death certificates were obtained. All deaths were adjudicated as cardiovascular or noncardiovascular by a panel of WISE cardiologists masked to angiographic data. Multivariate Cox proportional hazards regression was used to identify significant independent predictors of mortality. At baseline, mean age was 58±12 years; 176 (19%) were non-white, primarily black; 25% had a history of diabetes mellitus, 59% hypertension, 55% dyslipidemia, and 59% had a body mass index ≥30. During a median follow-up of 9.5 years (range, 0.2–11.5 years), a total of 184 (20%) died. Of these, 115 (62%) were cardiovascular deaths; 31% of all cardiovascular deaths occurred in women without obstructive CAD (<50% stenosis). Independent predictors of mortality were obstructive CAD, age, baseline systolic blood pressure, history of diabetes mellitus, history of smoking, elevated triglycerides, and estimated glomerular filtration rate. Conclusions— Among women referred for coronary angiography for signs and symptoms of ischemia, 1 in 5 died from predominantly cardiac pathogeneses within 9 years of angiographic evaluation. A majority of the factors contributing to the risk of death seem to be modifiable by existing therapies. Of note, 1 in 3 of the deaths in this cohort occurred in women without obstructive CAD, a condition often considered benign and without guideline-recommended treatments. Clinical trials are needed to provide treatment guidance for the group without obstructive CAD.

Does a Weekly Didactic Conference Improve Resident Performance on the Pediatric Domain of the Orthopaedic In-Training Examination?

Background: Performance on the Orthopaedic In-training Examination (OITE) has been correlated with performance on the written portion of the American Board of Orthopaedic Surgery examination. Herein we sought to discover whether adding a regular pediatric didactic lecture improved residents’ performance on the OITE’s pediatric domain. Methods: In 2012, a didactic lecture series was started in the University of Pittsburgh Medical Center (UPMC) Hamot Orthopaedic Residency Program (Hamot). This includes all topics in pediatric orthopaedic surgery and has teaching faculty present, and occurs weekly with all residents attending. A neighboring program [UMPC Pittsburgh (Pitt)] shares in these conferences, but only during their pediatric rotation. We sought to determine the effectiveness of the conference by comparing the historic scores from each program on the pediatric domain of the OITE examination to scores after the institution of the conference, and by comparing the 2 programs’ scores. Results: Both programs demonstrated improvement in OITE scores. In 2008, the mean examination score was 19.6±4.3 (11.0 to 30.0), and the mean percentile was 57.7±12.6 (32.0 to 88.0); in 2014, the mean examination score was 23.5±4.2 (14.0 to 33.0) and the mean percentile was 67.1±12.1 (40.0 to 94.0). OITE scores and percentiles improved with post graduate year (P<0.0001). Compared with the preconference years, Hamot residents answered 3.99 more questions correctly (P<0.0001) and Pitt residents answered 2.93 more questions correctly (P<0.0001). Before the conference, site was not a predictor of OITE score (P=0.06) or percentile (P=0.08); there was no significant difference found between the mean scores per program. However, in the postconference years, site did predict OITE scores. Controlling for year in training, Hamot residents scored higher on the OITE (2.3 points higher, P=0.003) and had higher percentiles (0.07 higher, P=0.004) than Pitt residents during the postconference years. Conclusions: This study suggests that adding a didactic pediatric lecture improved residents’ scores on the OITE and indirectly suggests that more frequent attendance is associated with better scores. Level of Evidence: Level III—retrospective case-control study.

Sudden Cardiac Death in Women With Suspected Ischemic Heart Disease, Preserved Ejection Fraction, and No Obstructive Coronary Artery Disease: A Report From the Women's Ischemia Syndrome Evaluation Study.

Background Sudden cardiac death (SCD) is often the first presentation of ischemic heart disease; however, there is limited information on SCD among women with and without obstructive coronary artery disease (CAD). We evaluated SCD incidence in the WISE (Womens Ischemia Syndrome Evaluation) study. Methods and Results Overall, 904 women with suspected ischemic heart disease with preserved ejection fraction and core laboratory coronary angiography were followed for outcomes. In case of death, a death certificate and/or a physician or family narrative of the circumstances of death was obtained. A clinical events committee rated all deaths as cardiovascular or noncardiovascular and as SCD or non‐SCD. In total, 96 women (11%) died over a median of 6 years (maximum: 8 years). Among 65 cardiovascular deaths, 42% were SCD. Mortality per 1000 person‐hours increased linearly with CAD severity (no CAD: 5.8; minimal: 15.9; obstructive: 38.6; P<0.0001). However, the proportion of SCD was similar across CAD severity: 40%, 58%, and 38% for no, minimal, and obstructive CAD subgroups, respectively (P value not significant). In addition to traditional risk factors (age, diabetes mellitus, smoking), a history of depression (P=0.018) and longer corrected QT interval (P=0.023) were independent SCD predictors in the entire cohort. Corrected QT interval was an independent predictor of SCD in women without obstructive CAD (P=0.033). Conclusions SCD contributes substantially to mortality in women with and without obstructive CAD. Corrected QT interval is the single independent SCD risk factor in women without obstructive CAD. In addition to management of traditional risk factors, these data indicate that further investigation should address mechanistic understanding and interventions targeting depression and corrected QT interval in women.

Coagulation Profile of Patients with Adolescent Idiopathic Scoliosis Undergoing Posterior Spinal Fusion.

BACKGROUND Blood loss and transfusion requirements during posterior spinal fusion for adolescent idiopathic scoliosis remain a concern. The mechanism of bleeding in these patients is poorly characterized. Thromboelastography is a comprehensive test of a patients coagulation system commonly used in cardiac surgical procedures. It has not been well studied for use in patients with adolescent idiopathic scoliosis. METHODS A prospective, observational study of the coagulation profile of patients with adolescent idiopathic scoliosis undergoing posterior spinal fusion is presented. Healthy patients with adolescent idiopathic scoliosis without a bleeding abnormality were analyzed during posterior spinal fusion. Standard coagulation laboratory and thromboelastogram measures were obtained at the time of the incision and at 1-hour intervals during the surgical procedure. Laboratory values were analyzed in relation to outcomes such as bleeding, transfusion, and a fibrinolysis score. RESULTS Fifty-eight patients were observed. Eighty-one percent of patients were female, the mean age was 13.5 years, a mean of 11.1 levels were fused, the median estimated blood loss was 645 mL, and 47% of patients received blood products. Overall, laboratory values remained stable throughout the surgical procedure. Mild increases in prothrombin time and partial thromboplastin time were observed, and platelets remained stable. From thromboelastogram analysis, an acceleration of clot formation (decreased reaction time) and a slight increase in clot lysis (increased lysis percentage at 30 minutes) were observed. A fibrinolysis score compiled from the presence of fibrin degradation products, the presence of D-dimers, and increased prothrombin time rose steadily over surgical time. The fibrinolysis score was predictive of both transfusion and greater estimated blood loss per level. CONCLUSIONS The stress of posterior spinal fusion induces a hypercoagulable state in patients with adolescent idiopathic scoliosis. Over the first 2 hours of a surgical procedure, varying degrees of fibrinolysis develop. Platelets and coagulation factors are not depleted. Our data support the use of antifibrinolytic therapy for patients with adolescent idiopathic scoliosis.

SRS-22r Scores in Non-Operated Adolescent Idiopathic Scoliosis Patients with Curves Greater than Forty Degrees.

Study Design. Case control comparative series. Objective. Describe surgical range adolescent idiopathic scoliosis (AIS) patients electing to forgo surgery and compare health-related quality-of-life outcomes to a similar cohort of operated AIS patients by the same single surgeon. Summary of Background Data. No data have been published either documenting SRS-22r scores of nonoperated patients with curves ≥40° or comparing these scores to a demographically similar operated cohort. Methods. Individuals with curves ≥40°, age ≥18 years, and electing to forgo surgery were identified. All patients completed an SRS-22r questionnaire. This nonoperated cohorts SRS-22r scores were compared to those of a large demographically similar cohort operated by the same surgeon. Group differences between the SRS-22r scores were evaluated by comparing these to published Minimal Clinically Important Differences (MCID) for the SRS-22r. Results. One hundred ninety subjects with nonoperated curves were compared to 166 individuals who underwent surgery. The nonoperated cohort averaged 23.5 years of age, averaged 7.7 years since curve reached 40°, and had an average 50° Cobb angle at last follow-up. No statistical significant differences were found between the groups on the Pain, Function, or Mental Health domains of the SRS-22r. Statistically significant differences in favor of the operative cohort were found for self-image, satisfaction, and total score. The observed group differences did not meet the established thresholds for minimal clinically important differences in any of the domain scores, the average total score, or raw scores. Conclusion. There are no meaningful clinically significant differences in SRS-22r scores at average 8-year follow-up between AIS patients with curves ≥40° treated with or without surgery. These data in conjunction with an absence of long-term evidence of serious medical consequences with nonsurgical management of curves ≥40° should encourage surgeons to reevaluate the benefits of routine surgical care. Level of Evidence: 3

Is There Value in Having Radiology Provide a Second Reading in Pediatric Orthopaedic Clinic

Background: The Joint Commission on Accreditation of Healthcare Organizations specifically mandates the dual interpretation of musculoskeletal radiographs by a radiologist in addition to the orthopaedist in all hospital-based orthopaedic clinics. Previous studies have questioned the utility of this practice. The purpose of this study was to further investigate the clinical significance of having the radiologist provide a second interpretation in a hospital-based pediatric orthopaedic clinic. Methods: A retrospective review was performed of all patients who had plain radiographs obtained in the pediatric orthopaedic clinic at an academic children’s hospital over a 4-month period. For each radiographic series, the orthopaedist’s note and the radiology interpretation were reviewed and a determination was made of whether the radiology read provided new clinically useful information and/or a new diagnosis, whether it recommended further imaging, or if it missed a diagnosis that was reflected in the orthopaedist’s note. The hospital charges associated with the radiology read for each study were also quantified. Results: The charts of 1570 consecutive clinic patients who were seen in the pediatric orthopaedic clinic from January to April, 2012 were reviewed. There were 2509 radiographic studies performed, of which 2264 had both a documented orthopaedist’s note and radiologist’s read. The radiologist’s interpretation added new, clinically important information in 1.0% (23/2264) of these studies. In 1.7% (38/2264) of the studies, it was determined that the radiologist missed the diagnosis or clinically important information that could affect treatment. The total amount of the professional fees charged for the radiologists’ interpretations was