Risk Factors for Pediatric Asthma Readmissions: A Systematic Review.

OBJECTIVE: To systematically review the literature on pediatric asthma readmission risk factors. STUDY DESIGN: We searched PubMed/MEDLINE, CINAHL, Scopus, PsycINFO, and Cochrane Central Register of Controlled Trials for published articles (through November 2019) on pediatric asthma readmission risk factors. Two authors independently screened titles and abstracts and consensus was reached on disagreements. Full-text articles were reviewed and inclusion criteria applied. For articles meeting inclusion criteria, authors abstracted data on study design, patient characteristics, and outcomes, and 4 authors assessed bias risk. RESULTS: Of 5749 abstracts, 74 met inclusion criteria. Study designs, patient populations, and outcome measures were highly heterogeneous. Risk factors consistently associated with early readmissions (≤30 days) included prolonged length of stay (OR range, 1.1-1.6) and chronic comorbidities (1.7-3.2). Risk factors associated with late readmissions (>30 days) included female sex (1.1-1.6), chronic comorbidities (1.5-2), summer discharge (1.5-1.8), and prolonged length of stay (1.04-1.7). Across both readmission intervals, prior asthma admission was the most consistent readmission predictor (1.3-5.4). CONCLUSIONS: Pediatric asthma readmission risk factors depend on the readmission interval chosen. Prior hospitalization, length of stay, sex, and chronic comorbidities were consistently associated with both early and late readmissions. TRIAL REGISTRATION: CRD42018107601.

Coronary microvascular dysfunction is related to abnormalities in myocardial structure and function in cardiac amyloidosis.

OBJECTIVES: The purpose of this study was to test the hypothesis that coronary microvascular function is impaired in subjects with cardiac amyloidosis. BACKGROUND: Effort angina is common in subjects with cardiac amyloidosis, even in the absence of epicardial coronary artery disease (CAD). METHODS: Thirty-one subjects were prospectively enrolled in this study, including 21 subjects with definite cardiac amyloidosis without epicardial CAD and 10 subjects with hypertensive left ventricular hypertrophy (LVH). All subjects underwent rest and vasodilator stress N-13 ammonia positron emission tomography and 2-dimensional echocardiography. Global left ventricular myocardial blood flow (MBF) was quantified at rest and during peak hyperemia, and coronary flow reserve (CFR) was computed (peak stress MBF/rest MBF) adjusting for rest rate pressure product. RESULTS: Compared with the LVH group, the amyloid group showed lower rest MBF (0.59 ± 0.15 ml/g/min vs. 0.88 ± 0.23 ml/g/min; p = 0.004), stress MBF (0.85 ± 0.29 ml/g/min vs. 1.85 ± 0.45 ml/g/min; p < 0.0001), and CFR (1.19 ± 0.38 vs. 2.23 ± 0.88; p < 0.0001) and higher minimal coronary vascular resistance (111 ± 40 ml/g/min/mm Hg vs. 70 ± 19 ml/g/min/mm Hg; p = 0.004). Of note, almost all subjects with amyloidosis (>95%) had significantly reduced peak stress MBF (<1.3 ml/g/min). In multivariable linear regression analyses, a diagnosis of amyloidosis, increased left ventricular mass, and age were the only independent predictors of impaired coronary vasodilator function. CONCLUSIONS: Coronary microvascular dysfunction is highly prevalent in subjects with cardiac amyloidosis, even in the absence of epicardial CAD, and may explain their anginal symptoms. Further study is required to understand whether specific therapy directed at amyloidosis may improve coronary vasomotion in amyloidosis.

Imaging cardiac amyloidosis: a pilot study using ¹8F-florbetapir positron emission tomography.

PURPOSE: Cardiac amyloidosis, a restrictive heart disease with high mortality and morbidity, is underdiagnosed due to limited targeted diagnostic imaging. The primary aim of this study was to evaluate the utility of (18)F-florbetapir for imaging cardiac amyloidosis. METHODS: We performed a pilot study of cardiac (18)F-florbetapir PET in 14 subjects: 5 control subjects without amyloidosis and 9 subjects with documented cardiac amyloidosis. Standardized uptake values (SUV) of (18)F-florbetapir in the left ventricular (LV) myocardium, blood pool, liver, and vertebral bone were determined. A (18)F-florbetapir retention index (RI) was computed. Mean LV myocardial SUVs, target-to-background ratio (TBR, myocardial/blood pool SUV ratio) and myocardial-to-liver SUV ratio between 0 and 30 min were calculated. RESULTS: Left and right ventricular myocardial uptake of (18)F-florbetapir were noted in all the amyloid subjects and in none of the control subjects. The RI, TBR, LV myocardial SUV and LV myocardial to liver SUV ratio were all significantly higher in the amyloidosis subjects than in the control subjects (RI median 0.043 min(-1), IQR 0.034 - 0.051 min(-1), vs. 0.023 min(-1), IQR 0.015 - 0.025 min(-1), P = 0.002; TBR 1.84, 1.64 - 2.50, vs. 1.26, IQR 0.91 - 1.36, P = 0.001; LV myocardial SUV 3.84, IQR 1.87 - 5.65, vs. 1.35, IQR 1.17 - 2.28, P = 0.029; ratio of LV myocardial to liver SUV 0.67, IQR 0.44 - 1.64, vs. 0.18, IQR 0.15 - 0.35, P = 0.004). The myocardial RI, TBR and myocardial to liver SUV ratio also distinguished the control subjects from subjects with transthyretin and those with light chain amyloid. CONCLUSION: (18)F-Florbetapir PET may be a promising technique to image light chain and transthyretin cardiac amyloidosis. Its role in diagnosing amyloid in other organ systems and in assessing response to therapy needs to be further studied.

Targeted deletion of fibrinogen like protein 1 reveals a novel role in energy substrate utilization.

Fibrinogen like protein 1(Fgl1) is a secreted protein with mitogenic activity on primary hepatocytes. Fgl1 is expressed in the liver and its expression is enhanced following acute liver injury. In animals with acute liver failure, administration of recombinant Fgl1 results in decreased mortality supporting the notion that Fgl1 stimulates hepatocyte proliferation and/or protects hepatocytes from injury. However, because Fgl1 is secreted and detected in the plasma, it is possible that the role of Fgl1 extends far beyond its effect on hepatocytes. In this study, we show that Fgl1 is additionally expressed in brown adipose tissue. We find that signals elaborated following liver injury also enhance the expression of Fgl1 in brown adipose tissue suggesting that there is a cross talk between the injured liver and adipose tissues. To identify extra hepatic effects, we generated Fgl1 deficient mice. These mice exhibit a phenotype suggestive of a global metabolic defect: Fgl1 null mice are heavier than wild type mates, have abnormal plasma lipid profiles, fasting hyperglycemia with enhanced gluconeogenesis and exhibit differences in white and brown adipose tissue morphology when compared to wild types. Because Fgl1 shares structural similarity to Angiopoietin like factors 2, 3, 4 and 6 which regulate lipid metabolism and energy utilization, we postulate that Fgl1 is a member of an emerging group of proteins with key roles in metabolism and liver regeneration.

Incremental prognostic value of gated Rb-82 positron emission tomography myocardial perfusion imaging over clinical variables and rest LVEF.

OBJECTIVES: This investigation sought to study the incremental value of gated rubidium (Rb)-82 positron emission tomography (PET) myocardial perfusion imaging (MPI) over clinical variables for predicting survival and future cardiac events. BACKGROUND: The prognostic value of Rb-82 PET-MPI and left ventricular ejection fraction (LVEF) reserve (stress minus rest LVEF) is not well defined. METHODS: 1,432 consecutive patients undergoing gated rest/vasodilator stress rubidium-82 PET were followed up for at least 1 year. Of these, rest and peak stress LVEF and LVEF reserve were available in 985 patients. Cardiac events (CE) including cardiac death or nonfatal myocardial infarction and all-cause death were assessed. RESULTS: Over a mean follow-up of 1.7 +/- 0.7 years, 83 (5.8%) CE and 140 (9.7%) all-cause death were observed. There was an increase in risk for both end points with an increasing percentage of abnormal and ischemic myocardium. With normal, mild, moderate, or severely ischemic scans, the observed annualized rates of CE were 0.7%, 5.5%, 5%, and 11% and of all-cause death were 3.3%, 7.2%, 6.9%, and 12.5%, respectively. In 985 patients with peak stress gated data, the observed annualized rates of CE (2.1% vs. 5.3%, p < 0.001) and all-cause death (4.3% vs. 9.2%, p < 0.001) were higher in patients with an LVEF reserve <0% compared with those with an LVEF reserve >or=0%. On Cox proportional hazards analysis, after consideration of clinical, historical, and rest LVEF information, stress PET results and LVEF reserve yielded incremental prognostic value with respect to both CE and all-cause death. CONCLUSIONS: Vasodilator stress Rb-82 PET-MPI provides incremental prognostic value to historical/clinical variables and rest LVEF to predict survival free of CE and all-cause death. An increasing percentage of ischemia on PET-MPI is associated with an increase in the risk of CE and all-cause death. Left ventricular ejection fraction reserve provides significant independent and incremental value to Rb-82 MPI for predicting the risk of future adverse events.

Value of vasodilator left ventricular ejection fraction reserve in evaluating the magnitude of myocardium at risk and the extent of angiographic coronary artery disease: a 82Rb PET/CT study.

UNLABELLED: Our aim was to determine the value of vasodilator left ventricular ejection fraction (LVEF) reserve (stress ejection fraction - rest ejection fraction) in evaluating the magnitude of myocardium at risk and the anatomic extent of underlying severe coronary artery disease (CAD). METHODS: We studied 510 consecutive patients with suspected CAD undergoing gated rest and vasodilator stress (82)Rb PET/CT. Patients were categorized as having no perfusion abnormalities, mild, moderate, or severe reversible perfusion defects. In a subgroup of 68 patients with coronary angiography, patients were categorized as having 0-vessel, 1-vessel, 2-vessel, or left main/3-vessel disease. RESULTS: Patients without coronary risk factors who comprised our control group as well as patients with coronary risk factors and normal perfusion demonstrated a high LVEF reserve (7% +/- 7% and 5% +/- 6%, respectively). The mean LVEF reserve was negative (-0.2% +/- 8%) in patients with severe reversible defects and in patients with 3-vessel (-6% +/- 8%) and left main (-8% +/- 5%) disease. Among the clinical and scintigraphic variables studied, male sex, rest ejection fraction, and increasing magnitude of myocardium at risk predicted a lower LVEF reserve, whereas LVEF reserve was the only independent predictor of left main/3-vessel disease (P = 0.008). An LVEF reserve of more than +5% had a positive predictive value of only 41% but a negative predictive value of 97% for excluding severe left main/3-vessel CAD. CONCLUSION: During (82)Rb PET/CT, LVEF increases with vasodilator stress in patients without significant stress-induced perfusion defects or severe left main/3-vessel CAD. A high LVEF reserve appears to be an excellent tool to exclude left main/3-vessel CAD noninvasively.

Prognostic value of SPECT myocardial perfusion imaging in patients with elevated cardiac troponin I levels and atypical clinical presentation.

BACKGROUND: We determined the prognostic value of myocardial perfusion imaging (MPI) in patients with atypical clinical presentations and unexpected elevation of cardiac troponin I (cTnI) levels. METHODS AND RESULTS: In 156 consecutive patients with atypical presentations for acute coronary syndromes (ACS) and elevated cTnI levels undergoing MPI within 30 days, rates of all-cause mortality (100% follow-up; median follow-up, 611 days) and 6-month cardiac death and nonfatal myocardial infarction (96% follow-up; median follow-up, 167 days) were determined. The mean age of the patients was 68 +/- 14 years. The majority of the study cohort (96%) was at low to intermediate clinical risk for ACS (Thrombolysis in Myocardial Infarction score for unstable angina/non-ST-segment elevation myocardial infarction <5). The overall event rate was high, with 45 deaths (28.8%). There were 13 cardiac deaths/nonfatal myocardial infarctions in 6 months (8.3%). A normal MPI result was associated with a high event-free survival rate, whereas an abnormal MPI result was associated with a 3-fold and 7-fold higher risk of all-cause mortality and 6-month cardiac events, respectively. An abnormal MPI result was an independent predictor of all-cause death. CONCLUSIONS: In patients with cTnI elevation and a low to intermediate risk for ACS, a normal MPI result portends a good prognosis. Patients with abnormal MPI results have a higher 6-month cardiac event rate and a worse survival rate.