Objectives The purpose of this study was to compare the efficiency, cost, and safety of a diagnostic strategy employing early coronary computed tomographic angiography (CCTA) to a strategy employing ...rest-stress myocardial perfusion imaging (MPI) in the evaluation of acute low-risk chest pain. Background In the United States, >8 million patients require emergency department evaluation for acute chest pain annually at an estimated diagnostic cost of >$10 billion. Methods This multicenter, randomized clinical trial in 16 emergency departments ran between June 2007 and November 2008. Patients were randomly allocated to CCTA (n = 361) or MPI (n = 338) as the index noninvasive test. The primary outcome was time to diagnosis; the secondary outcomes were emergency department costs of care and safety, defined as freedom from major adverse cardiac events in patients with normal index tests, including 6-month follow-up. Results The CCTA resulted in a 54% reduction in time to diagnosis compared with MPI (median 2.9 h 25th to 75th percentile: 2.1 to 4.0 h vs. 6.3 h 25th to 75th percentile: 4.2 to 19.0 h, p < 0.0001). Costs of care were 38% lower compared with standard (median $2,137 25th to 75th percentile: $1,660 to $3,077 vs. $3,458 25th to 75th percentile: $2,900 to $4,297, p < 0.0001). The diagnostic strategies had no difference in major adverse cardiac events after normal index testing (0.8% in the CCTA arm vs. 0.4% in the MPI arm, p = 0.29). Conclusions In emergency department acute, low-risk chest pain patients, the use of CCTA results in more rapid and cost-efficient safe diagnosis than rest-stress MPI. Further studies comparing CCTA to other diagnostic strategies are needed to optimize evaluation of specific patient subsets. (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment CT-STAT; NCT00468325 )
Network inference is a valuable approach for gaining mechanistic insight from high-dimensional biological data. Existing methods for network inference focus on ranking all possible relations (edges) ...among all measured quantities such as genes, proteins, metabolites (features) observed, which yields a dense network that is challenging to interpret. Identifying a sparse, interpretable network using these methods thus requires an error-prone thresholding step which compromises their performance. In this article we propose a new method, DEKER-NET, that addresses this limitation by directly identifying a sparse, interpretable network without thresholding, improving real-world performance. DEKER-NET uses a novel machine learning method for feature selection in an iterative framework for network inference. DEKER-NET is extremely flexible, handling linear and nonlinear relations while making no assumptions about the underlying distribution of data, and is suitable for categorical or continuous variables. We test our method on the Dialogue for Reverse Engineering Assessments and Methods (DREAM) challenge data, demonstrating that it can directly identify sparse, interpretable networks without thresholding while maintaining performance comparable to the hypothetical best-case thresholded network of other methods.
BACKGROUNDThe utility of performing early myocardial revascularization among patients presenting with inducible myocardial ischemia and low left ventricular ejection fraction (LVEF) is currently ...unknown. OBJECTIVESIn this study, we sought to assess the relationship between stress-induced myocardial ischemia, revascularization, and all-cause mortality (ACM) among patients with normal vs low LVEF. METHODSWe evaluated 43,443 patients undergoing stress-rest single-photon emission computed tomography myocardial perfusion imaging from 1998 to 2017. Median follow-up was 11.4 years. Myocardial ischemia was assessed for its interaction between early revascularization and mortality. A propensity score was used to adjust for nonrandomization to revascularization, followed by multivariable Cox modeling adjusted for the propensity score and clinical variables to predict ACM. RESULTSThe frequency of myocardial ischemia varied markedly according to LVEF and angina, ranging from 6.7% among patients with LVEF ≥55% and no typical angina to 64.0% among patients with LVEF <45% and typical angina (P < 0.001). Among 39,883 patients with LVEF ≥45%, early revascularization was associated with increased mortality risk among patients without ischemia and lower mortality risk among patients with severe (≥15%) ischemia (HR: 0.70; 95% CI: 0.52-0.95). Among 3,560 patients with LVEF <45%, revascularization was not associated with mortality benefit among patients with no or mild ischemia, and was associated with decreased mortality among patients with moderate (10%-14%) (HR: 0.67; 95% CI: 0.49-0.91) and severe (≥15%) (HR: 0.55; 95% CI: 0.38-0.80) ischemia. CONCLUSIONSWithin this cohort, early myocardial revascularization was associated with a significant reduction in mortality among both patients with normal LVEF and severe inducible myocardial ischemia and patients with low LVEF and moderate or severe inducible myocardial ischemia.
This study sought to assess whether the frequency of inducible myocardial ischemia during stress-rest single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has changed ...over time.
The prevalence of cardiac death and other clinical cardiac events have declined in recent decades, but heretofore no study has examined if there has been a temporal change in the frequency of inducible myocardial ischemia during cardiac stress testing.
We assessed 39,515 diagnostic patients undergoing stress-rest MPI between 1991 and 2009. Patients were assessed for change in demographics, clinical symptoms, risk factors, and frequency of abnormal and ischemic SPECT-MPI.
There was a marked progressive decline in the prevalence of abnormal SPECT studies, from 40.9% in 1991 to 8.7% in 2009 (p < 0.001). Similarly, the prevalence of ischemic SPECT-MPI declined, from 29.6% to 5.0% (p < 0.001), as did the prevalence of severe ischemia. The decline of SPECT-MPI abnormality occurred among all age and symptom subgroups, falling to only 2.9% among recent exercising patients without typical angina. We also noted a progressive trend toward performing more pharmacological rather than exercise stress in all age and weight groups, and pharmacological stress was more likely than exercise to be associated with SPECT-MPI abnormality (odds ratio: 1.43, 95% confidence interval: 1.3 to 1.5; p < 0.001).
Over the past 2 decades, the frequency and severity of abnormal stress SPECT-MPI studies has progressively decreased. Notably, the frequency of abnormal SPECT-MPI is now very low among exercising patients without typical angina. These findings suggest the need for developing more cost-effective strategies for the initial work-up of patients who are presently at low risk for manifesting inducible myocardial ischemia during cardiac imaging procedures.
Although pre-revascularization ischaemia testing is recommended, the interaction between the extent of ischaemia and myocardial scar with performance of revascularization on patient survival is ...unclear.
We identified 13 969 patients who underwent adenosine or exercise stress SPECT myocardial perfusion scintigraphy (MPS). The percent myocardium ischaemic (%I) and fixed (%F) were calculated using 5 point/20-segment MPS scoring. Patients lost to follow-up (2.8%) were excluded leaving 13 555 patients 35% with history (Hx) of known coronary artery disease (CAD), 65% exercise stress, 61% male, age 66 ± 12. Follow-up was performed at 12-18 months for early revascularization and at >7 years for all-cause death (ACD) (mean follow-up 8.7 ± 3.3 years). All-cause death was modelled using Cox proportional hazards modelling adjusting for logistic-based propensity scores, MPS, revascularization, and baseline characteristics. During FU, 3893 ACD (29%, 3.3%/year) and 1226 early revascularizations (9.0%) occurred. After risk-adjustment, a three-way interaction was present between %I, early revascularization, and HxCAD, such that %I identified a survival benefit with early revascularization in patients without prior myocardial infarction (MI), whereas no such benefit was present in patients with prior MI (overall model χ(2)= 3932, P < 0.001; interaction P < 0.021). Further modelling revealed that after excluding patients with scar >10% total myocardium, %I identified a survival benefit in all patients.
In this large observational series with long-term follow-up, patients with significant ischaemia and without extensive scar were likely to realize a survival benefit from early revascularization. In contrast, the survival of patients with minimal ischaemia was superior with medical therapy without early revascularization.
Abstract Objectives This study aims to assess the correlations among coronary artery calcium (CAC), self-reported exercise, and mortality in asymptomatic patients. Background The interaction between ...reported exercise habits and CAC scores for predicting clinical risk is not yet well known. Methods We followed 10,690 asymptomatic patients who underwent CAC scanning. Patients were divided into 4 groups based on a single-item self-reported exercise. Mean follow-up was 8.9 ± 3.5 years for the occurrence of all-cause mortality (ACM). Results Annualized ACM progressively increased with increasing CAC score (p < 0.001) and decreasing exercise (p < 0.001). Among patients with CAC scores of 0, ACM was low regardless of the amount of exercise. Among patients with CAC scores from 1 to 399, there was a stepwise increase in ACM for each reported decrement in exercise, and this difference was markedly more pronounced among patients with CAC scores ≥400. Compared with highly active patients with a CAC score of 0, highly sedentary patients with CAC scores ≥400 had a 3.1-fold increase (95% confidence interval: 1.35 to 7.11) in adjusted ACM risk. Our single-item physical activity questionnaire was also predictive of risk factors and clinical and lipid profile measurements. Conclusions In asymptomatic patients, self-reported exercise is a significant predictor of long-term outcomes. Prognostic value of the reported exercise is additive to the increasing degree of underlying atherosclerosis. Among patients with high CAC scores, exercise may play a protective role, whereas reported minimal or no exercise substantially increases clinical risk. Our results suggest there is clinical utility for the use of a simple single-item exercise questionnaire for such assessments.
River network structure influences many important population and community processes. Previous work examining ecological dynamics in river networks has focused on within‐trophic‐level dynamics, with ...less emphasis on food‐web interactions. Yet, trophic interactions in rivers are influenced by processes that may interact with network structure and position.
Using a spatially explicit consumer–resource model, we explore how trophic dynamics are influenced by the branching nature of river networks. We focus on cases where the consumer–resource interaction is prone to temporal oscillations and periodic low population sizes. In these cases, we find that the influence of network structure and dispersal can reduce temporal variability and increase persistence of consumers and resources at the metacommunity scale.
The effects of network structure and dispersal on our observed metacommunity dynamics result from asynchrony among dynamics of local communities: when asynchronous local fluctuations are averaged, consumer–resource dynamics become less variable and bounded higher above zero at regional spatial scales. Fluctuations synchronise across clusters of linked local communities.
Communities that connect to only one other downstream community typically vary independently of other patches and show high variability, while communities that are linked to multiple upstream and downstream habitats show greater clustering and less variability. These patterns suggest that headwater versus mainstem locations in river networks may show different levels of population variability and thus differential responses to management and restoration efforts.
We aimed to investigate if early revascularization in patients with suspected coronary artery disease can be effectively predicted by integrating clinical data and quantitative image features derived ...from perfusion SPECT (MPS) by machine learning (ML) approach.
713 rest 201Thallium/stress 99mTechnetium MPS studies with correlating invasive angiography with 372 revascularization events (275 PCI/97 CABG) within 90 days after MPS (91% within 30 days) were considered. Transient ischemic dilation, stress combined supine/prone total perfusion deficit (TPD), supine rest and stress TPD, exercise ejection fraction, and end-systolic volume, along with clinical parameters including patient gender, history of hypertension and diabetes mellitus, ST-depression on baseline ECG, ECG and clinical response during stress, and post-ECG probability by boosted ensemble ML algorithm (LogitBoost) to predict revascularization events. These features were selected using an automated feature selection algorithm from all available clinical and quantitative data (33 parameters). Tenfold cross-validation was utilized to train and test the prediction model. The prediction of revascularization by ML algorithm was compared to standalone measures of perfusion and visual analysis by two experienced readers utilizing all imaging, quantitative, and clinical data.
The sensitivity of machine learning (ML) (73.6% ± 4.3%) for prediction of revascularization was similar to one reader (73.9% ± 4.6%) and standalone measures of perfusion (75.5% ± 4.5%). The specificity of ML (74.7% ± 4.2%) was also better than both expert readers (67.2% ± 4.9% and 66.0% ± 5.0%, P < .05), but was similar to ischemic TPD (68.3% ± 4.9%, P < .05). The receiver operator characteristics areas under curve for ML (0.81 ± 0.02) was similar to reader 1 (0.81 ± 0.02) but superior to reader 2 (0.72 ± 0.02, P < .01) and standalone measure of perfusion (0.77 ± 0.02, P < .01).
ML approach is comparable or better than experienced readers in prediction of the early revascularization after MPS, and is significantly better than standalone measures of perfusion derived from MPS.
Expression of phenotypic plasticity depends on reaction norms adapted to historic selective regimes; anthropogenic changes in these selection regimes necessitate contemporary evolution or declines in ...productivity and possibly extinction. Adaptation of conditional strategies following a change in the selection regime requires evolution of either the environmentally influenced cue (e.g., size-at-age) or the state (e.g., size threshold) at which an individual switches between alternative tactics. Using a population of steelhead (Oncorhynchus mykiss) introduced above a barrier waterfall in 1910, we evaluate how the conditional strategy to migrate evolves in response to selection against migration. We created 9 families and 917 offspring from 14 parents collected from the above- and below-barrier populations. After 1 year of common garden-rearing above-barrier offspring were 11% smaller and 32% lighter than below-barrier offspring. Using a novel analytical approach, we estimate that the mean size at which above-barrier fish switch between the resident and migrant tactic is 43% larger than below-barrier fish. As a result, above-barrier fish were 26% less likely to express the migratory tactic. Our results demonstrate how rapid and opposing changes in size-at-age and threshold size contribute to the contemporary evolution of a conditional strategy and indicate that migratory barriers may elicit rapid evolution toward the resident life history on timescales relevant for conservation and management of conditionally migratory species.
SPECT myocardial perfusion imaging plays a central role in coronary artery disease diagnosis, but concerns exist regarding its radiation burden. Compared with standard Anger SPECT (A-SPECT) cameras, ...new high-efficiency (HE) cameras with specialized collimators and solid-state cadmium-zinc-telluride detectors offer potential to maintain image quality (IQ), while reducing administered activity and thus radiation dose to patients. No previous study has compared IQ, interpretation, total perfusion deficit (TPD), or ejection fraction (EF) in patients receiving both ultra-low-dose (ULD) imaging on an HE SPECT camera and standard low-dose (SLD) A-SPECT imaging.
We compared ULD HE SPECT with SLD A-SPECT imaging by dividing the rest dose in 101 patients at 3 sites scheduled to undergo clinical A-SPECT myocardial perfusion imaging using a same day rest-stress (99m)Tc protocol. Patients underwent HE SPECT imaging after an initial approximately 130-MBq (3.5 mCi) dose and SLD-A-SPECT imaging after the remainder of the planned dose. Images were scored visually by 2 masked readers for IQ and summed rest score. TPD and EF were assessed quantitatively.
Mean activity was 134 MBq (3.62 mCi) for ULD HE SPECT (effective dose, 1.15 mSv) and 278 MBq (7.50 mCi, 2.39 mSv) for SLD A-SPECT. Overall IQ was superior for ULD HE SPECT (P < 0.0001), with twice as many studies graded excellent quality. Extracardiac activity and overall perfusion assessment were similar. Between-method correlations were high for summed rest score (r = 0.87), TPD (r = 0.91), and EF (r = 0.88).
ULD HE SPECT rest imaging correlates highly with SLD A-SPECT. It has improved image quality, comparable extracardiac activity, and achieves radiation dose reduction to 1 mSv for a single injection.
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