No objective testing (NOT) rules offer simple clinical criteria for identifying emergency department patients with chest pain who do not need objective cardiac testing, a large multicenter validation study shows. "The major innovation in the early diagnosis of acute myocardial infarction (AMI), rapid high‐sensitivity cardiac troponin (hs‐cTn)-based algorithms, has also facilitated the selection of patients eligible for outpatient management," Dr. Christian Mueller of University Hospital Basel told Reuters Health by email. "However," he said, "it remains unclear which patients after rule out of AMI and early discharge should then undergo objective anatomic or functional cardiac testing for the detection of coronary artery disease (CAD)." "As some of these imaging modalities are associated with rare, but potentially severe adverse events as well as substantial cost, appropriate patient selection is of major medical and economic importance," he said. As reported in the Journal of the American Heart Association, Dr. Mueller and colleagues (Advantage Predictors of Acute Coronary Syndrome Evaluation Investigators) analyzed unselected patients presenting with acute chest pain to the emergency department from 2006-2018 to validate the three NOT rules. The primary end points were the safety and efficacy of the NOT rules for rule out of acute coronary syndrome or cardiovascular death within 30 days of follow-up. Among 3,500 patients included in the analysis, 2,374 (68%) were eligible for the NOT rules, as AMI was excluded on the basis of the 0/2-hour high-sensitivity cardiac troponin I (hs-cTnI) protocol - i.e., 0-and 2-hour hs-cTnI uniform cutoff <26.2 ng/L and nondiagnostic ECG without the Thrombolysis in Myocardial Infarction score. All three NOT rules performed well for rule out of ACS or cardiovascular death at 30 days (which occurred in 14% of patients). The first rule - weighted score, including age, sex, cardiovascular risk factors; previous myocardial infarction or known coronary artery disease; and nitrate use) had a sensitivity of 99.7%, a negative predictive value (NPV) of 99.8%, and an area under the receiver-operating characteristic curve of 0.81. The second rule (<50 years, no previous AMI or known coronary artery disease, <3 risk factors, and no nitrate use), as well as the simpler third rule (nitrate use omitted) best balanced safety and efficacy. Both identified 23% of patients at low risk with a sensitivity of 99.7% and an NPV of 99.8%. All three rules showed excellent safety for subgroups of patients at higher risk. By contrast, the rate of ACS or cardiovascular death was 18% at 30 days, 20% at 365 days, and 22% at 730 days in patients not meeting all criteria. The authors conclude, "4 simple clinical criteria (third NOT rule: aged <50 years, no previous AMI or known CAD, and <3 risk factors) identify a relevant proportion of patients (about 25%) at low risk of ACS or cardiovascular death up to 730 days. Accordingly, objective cardiac testing does not seem necessary in most of them." Dr. Harmony Reynolds, director of the Sarah Ross Soter Center for Women's Cardiovascular Research at NYU Langone Health in New York City, commented in an email to Reuters Health, "The likelihood of ACS or death from cardiovascular disease was lower than I would have expected in patients meeting the studied rules for not performing cardiac testing in the emergency room." "The results should be considered practice-changing (and) should facilitate faster discharges of low-risk patients," she said. That said, she noted, "this study only addressed patients who met the clinical no-objective-testing rules and had high-sensitivity troponin testing." "Older troponin tests are not the same," continued Dr. Reynolds, who coauthored the American Heart Association's 2019 Scientific Statement, "Contemporary Diagnosis and Management of Patients With Myocardial Infarction in the Absence of Obstructive Coronary Artery Disease. This may be particularly important for women, in whom previous research has shown that sex-specific troponin reference limits are particularly important for the accurate diagnosis of MI." "This study also did not report on the patients who had high sensitivity troponin levels above the upper reference limit," she added. "Clinicians should keep in mind that even a weakly positive troponin test in an otherwise low-risk patient is an important risk indicator that merits further evaluation," she said. "The clinical no-objective-testing rules should not be applied alone." The APACE study was supported in part by research grants from multiple drug companies and a number of coauthors reported receiving funds from these companies. —Marilynn Larkin Source
