Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients.

BACKGROUND: Diagnosing obstructive coronary artery disease (CAD) in at-risk patients can be challenging and typically requires both noninvasive imaging methods and coronary angiography, the gold standard. Previous studies have suggested that peripheral blood gene expression can indicate the presence of CAD. OBJECTIVE: To validate a previously developed 23-gene, expression-based classification test for diagnosis of obstructive CAD in nondiabetic patients. DESIGN: Multicenter prospective trial with blood samples obtained before coronary angiography. (ClinicalTrials.gov registration number: NCT00500617) SETTING: 39 centers in the United States. PATIENTS: An independent validation cohort of 526 nondiabetic patients with a clinical indication for coronary angiography. MEASUREMENTS: Receiver-operating characteristic (ROC) analysis of classifier score measured by real-time polymerase chain reaction, additivity to clinical factors, and reclassification of patient disease likelihood versus disease status defined by quantitative coronary angiography. Obstructive CAD was defined as 50% or greater stenosis in 1 or more major coronary arteries by quantitative coronary angiography. RESULTS: The area under the ROC curve (AUC) was 0.70 ± 0.02 (P < 0.001); the test added to clinical variables (Diamond-Forrester method) (AUC, 0.72 with the test vs. 0.66 without; P = 0.003) and added somewhat to an expanded clinical model (AUC, 0.745 with the test vs. 0.732 without; P = 0.089). The test improved net reclassification over both the Diamond-Forrester method and the expanded clinical model (P < 0.001). At a score threshold that corresponded to a 20% likelihood of obstructive CAD (14.75), the sensitivity and specificity were 85% and 43% (yielding a negative predictive value of 83% and a positive predictive value of 46%), with 33% of patient scores below this threshold. LIMITATION: Patients with chronic inflammatory disorders, elevated levels of leukocytes or cardiac protein markers, or diabetes were excluded. CONCLUSION: A noninvasive whole-blood test based on gene expression and demographic characteristics may be useful for assessing obstructive CAD in nondiabetic patients without known CAD. PRIMARY FUNDING SOURCE: CardioDx.

Understanding barriers to home-based and self-care in-center hemodialysis.

Despite superior outcomes and lower associated costs, relatively few patients with end-stage renal disease undergo self-care or home hemodialysis. Few studies have examined patient- and physician-specific barriers to self-care and home hemodialysis in the modern era. The degree to which innovative technology might facilitate the adoption of these modalities is unknown. We surveyed 250 patients receiving in-center hemodialysis and 51 board-certified nephrologists to identify key barriers to adoption of self-care and home hemodialysis. Overall, 172 (69%) patients reported that they were "likely" or "very likely" to consider self-care hemodialysis if they were properly trained on a new hemodialysis system designed for self-care or home use. Nephrologists believed that patients were capable of performing many dialysis-relevant tasks, including: weighing themselves (98%), wiping down the chair and machine (84%), clearing alarms during treatment (53%), taking vital signs (46%), and cannulating vascular access (41%), but thought that patients would be willing to do the same in only 69%, 34%, 31%, 29%, and 16%, respectively. Reasons that nephrologists believe patients are hesitant to pursue self-care or home hemodialysis do not correspond in parallel or by priority to reasons reported by patients. Self-care and home hemodialysis offer several advantages to patients and dialysis providers. Overcoming real and perceived barriers with new technology, education and coordinated care will be required for these modalities to gain traction in the coming years.

Results of human factors testing in a novel Hemodialysis system designed for ease of patient use.

Introduction Home hemodialysis has not been widely adopted despite superior outcomes relative to conventional in-center hemodialysis. Patients receiving home hemodialysis experience high rates of technique failure owing to machine complexity, training burden, and the inability to master treatments independently. Methods We conducted human factors testing on 15 health care professionals (HCPs) and 15 patients upon release of the defined training program on the Tablo™ Hemodialysis System. Each participant completed one training and one testing session conducted in a simulated clinical environment. Training sessions lasted <3 hours for HCPs and <4 hours for patients, with an hour break between sessions for knowledge decay. During the testing session, we recorded participant behavior and data according to standard performance and safety-based criteria. Findings Of 15 HCPs, 10 were registered nurses and five patient care technicians, with a broad range of dialysis work experience and no limitations other than visual correction. Of 15 patients (average age 48 years), 13 reported no limitations and two reported modest limitations-partial deafness and blindness in one eye, respectively. The average error rate was 4.4 per session for HCPs and 2.9 per session for patients out of a total possible 1,710 opportunities for errors. Despite having received minimal training, neither HCPs nor patients committed safety-related errors that required mitigation; rather, we noted only minor errors and operational difficulties. Discussion The Tablo™ Hemodialysis System is easy to use, and may help to enable self-care and home hemodialysis in settings heretofore associated with high rates of technique failure.

Enhanced assessment of chest pain and related symptoms in the primary care setting through the use of a novel personalized medicine genomic test: results from a prospective registry study.

Novel approaches for assessing patients with chest pain and related symptoms may improve outpatient care. The REGISTRY I study measured the impact of a personalized gene expression score (GES) on subsequent cardiac referral decisions by primary care providers. Of the 342 stable, nonacute patients evaluated, the mean age was 55 years, 53% were female, and mean (SD) GES was 16 (±10) (range = 1-40). Low GES (≤15), indicating a low current likelihood of obstructive coronary artery disease (CAD), was observed in 49% of patients. After clinical covariate adjustment, each 10-point GES decrease was associated with a 14-fold decreased odds of cardiac referral (P < .0001). Low GES patients had 94% reduced odds of referral relative to elevated GES patients (P < .0001), with follow-up supporting a favorable safety profile. This genomic-based test demonstrated clinical utility by guiding decision making during assessment of symptomatic patients with suspected obstructive CAD.

Utility of a genomic-based, personalized medicine test in patients presenting with symptoms suggesting coronary artery disease.

PURPOSE: Better methods are needed to assess patients presenting with symptoms suggestive of obstructive coronary artery disease (CAD). We hypothesized that the use of a gene expression score (GES) would lead to a change in the diagnostic evaluation. METHODS: The Primary Care Providers Use of a Gene Expression Test in Coronary Artery Disease Diagnosis (IMPACT-PCP) trial (clinical trial identifier NCT01594411, clinicaltrials.gov) was a prospective study of stable, nonacute, nondiabetic patients presenting with chest pain and related symptoms at 4 primary care practices. All patients underwent GES testing, with clinicians documenting their planned diagnostic strategy both before and after GES. The GES was derived from a peripheral blood draw measuring expression of 23 genes and has been shown to have a 96% negative predictive value for excluding the diagnosis of obstructive CAD. RESULTS: Of the 251 study patients, 140 were women (56%); the participants had a mean age of 56 years (standard deviation, 13.0) and a mean body mass index of 30 mg/kg(2) (standard deviation, 6.7). The mean GES was 16 (range, 1-38), and 127 patients (51%) had a low GES ([ltqeu]15). A change in the diagnostic testing pattern before and after GES testing was noted in 145 of 251 patients (58% observed vs. 10% predefined expected change; P < .001). CONCLUSIONS: Incorporation of the GES into the diagnostic workup showed clinical utility above and beyond conventional clinical factors by optimizing the patient's diagnostic evaluation.

The clinical utility of gene expression testing on the diagnostic evaluation of patients presenting to the cardiologist with symptoms of suspected obstructive coronary artery disease: results from the IMPACT (Investigation of a Molecular Personalized Coronary Gene Expression Test on Cardiology Practice Pattern) trial.

Accurate, noninvasive evaluation for obstructive coronary artery disease (CAD) remains challenging and inefficient. In this study, 171 patients presenting with stable chest pain and related symptoms without a history of CAD were referred to 6 cardiologists for evaluation. In the prospective cohort of 88 patients, the cardiologist's diagnostic strategy was evaluated before and after gene expression score (GES) testing. The GES is a validated, quantitative blood-based diagnostic test measuring peripheral blood cell expression levels of 23 genes to determine the likelihood of obstructive CAD (at least 1 vessel with ≥ 50% angiographic coronary artery stenosis). The objective of the study was to measure the effect of the GES on diagnostic testing using a pre/post study design. There were 83 prospective patients evaluable for study analysis, which included 57 (69%) women, mean age 53 ± 11 years, and mean GES 12.5 ± 9. Presenting symptoms were classified as typical angina, atypical angina, and noncardiac chest pain in 33%, 60%, and 7% of patients (n = 27, 50, and 6), respectively. After GES, changes in diagnostic testing occurred in 58% of patients (n = 48, P < 0.001). Of note, 91% (29/32) of patients with decreased testing had low GES (≤ 15), whereas 100% (16/16) of patients with increased testing had elevated GES (P < 0.001). A historical cohort of 83 patients, matched to the prospective cohort by clinical factors, had higher diagnostic test use compared with the post-GES prospective cohort (P < 0.001). In summary, the GES showed clinical utility in the evaluation of patients with suspected obstructive CAD presenting to the cardiologist's office.