The Cardiology Update took place again this year in Davos, covered in winter snow. Among other things, it was about acute coronary syndrome. New strategies of early diagnosis in acute myocardial infarction were discussed. Could a new algorithm that makes inclusion and exclusion diagnosis possible within an hour soon find application in clinical practice? Results from large studies presented at ESC 2014 suggest this.
“Early diagnosis of acute myocardial infarction is critical, but remains an unmet goal for many patients presenting to the emergency department with chest pain,” said Prof. Christian Müller, MD, Cardiology, University Hospital Basel. Delayed inclusion diagnosis (rule-in) causes morbidity and mortality to increase because evidence-based therapy occurs later. The delayed diagnosis of exclusion (rule-out) results in a longer stay in the emergency department, higher costs, and increased patient concern.
In principle, three diagnostic tools are available in the emergency department: history (including chest pain characteristics), ECG, and cardiac troponins (cTn). A problem with previous cTn assays was that values often showed no elevation in the first hours of acute myocardial infarction. In recent years, however, much more sensitive and precise assays have been developed, the “high-sensitivity” cTn methods (hs-cTn). Due to the sensitivity of these tests, cTn are now also detectable in the majority of healthy individuals, so the detection limit is significantly lower. In addition, a more precise statement is possible as to which values are normal and which are pathological; the 99th percentile of a healthy reference population serves as the threshold. Early diagnosis of acute myocardial infarction is thus improved (especially exclusion diagnosis). Instead of the terms “troponin-positive” or “troponin-negative,” detectable levels are the norm and must be distinguished from elevated levels. Minimal cTn elevations missed with the earlier assay can be accurately collected with the highly sensitive method. It therefore allows a quantitative, not only qualitative statement.
The diagnostic superiority of the new assays was demonstrated in a prospective, multicenter, blinded study of 718 emergency patients with suspected acute myocardial infarction [1]. In particular, patients with recent chest pain benefited.
Larger diagnostic spectrum
However, the higher sensitivity does not necessarily make the diagnosis easier, on the contrary: While a massive acute myocardial infarction is very likely with large amounts of troponin in the blood and thus the positive predictive value is also high, the newly detectable minor elevations represent a differential diagnostic challenge. The positive predictive value decreases.
“Nevertheless, together with the ECG and the medical history, the highly sensitive tests can improve the exclusion diagnosis, but also the inclusion diagnosis,” he said. It is important not to get confused in the face of the expanded possibilities, but to make the most of the advantages of the new processes.
When to test?
The specific application or indicated frequency of hs-cTn measurement in clinical practice is therefore a matter of debate. Conventional cTn assays require repeat testing six hours after the first result, which delays the time to diagnosis. In comparison, the ESC Guidelines 2011 (IB) recommend an hs-cTn assay at the time of presentation and after three hours for the rule-out diagnosis. The results of a prospective observational study with 872 emergency patients with acute chest pain now indicate a further reduction in waiting time [2]. The authors tested an algorithm that is currently not used clinically and is viewed ambivalently by experts: Instead of repeating the test after three hours, they repeated it after only one hour. The authors defined the algorithm and the corresponding values (baseline and absolute changes after one hour) on the basis of half of the patients and validated them on the basis of the other half:
- Of the 436 patients from the second cohort, 60% could be excluded from the diagnosis of acute myocardial infarction (rule-out). They had a baseline hs-cTnT level below 12 ng/l and an absolute change of less than 3 ng/l within the measurement hour.
- 17% were included (rule-in). They had a baseline hs-cTnT level of ≥52 ng/l and an absolute change of at least 5 ng/l within the measurement hour.
- The 23% who could not be categorized into either group were in the “observational zone.”
Two independent cardiologists made the final diagnosis. The sensitivity and negative predictive value of the algorithm were 100% (rule-out), specificity was 97%, and positive predictive value was 84% (rule-in). In the “observational zone,” the prevalence of acute myocardial infarction was 8%.
The authors concluded that in a total of 77% of patients, the new method would allow a definite diagnosis of exclusion and an accurate diagnosis of inclusion in a short time. Early hospital discharge of those patients with exclusion diagnosis was also justified – this because 30-day mortality was only 0.2% here, a significant difference from the 4.7% in the rule-in group. Compared with the group with exclusion diagnosis, those in the observation group and those with inclusion diagnosis showed an approximate 7- resp. 24-fold increase in the risk of death (the latter increase was significant). The difference held over two years: HR 5.8 (95%CI, 2.7-12.5, p<0.001) resp. 8.3 (95%CI, 3.9-17.9, p<0.001) compared with the rule-out group.
Data situation is becoming increasingly robust
TRAPID-AMI, another large international study, reviewed the same algorithm in 1282 emergency chest pain patients. The results were presented at the ESC Congress 2014 in Barcelona:
- Of 1282 patients, 63% could be excluded from the diagnosis of acute myocardial infarction (rule-out). The negative predictive value was 99.1%.
- 14% were included (rule-in). The positive predictive value was 77%.
- Again, the 30-day mortality rate of the rule-out group was significantly lower than the mortality rate of the other two groups.
Another validation study shows comparable values. So the data in favor of the 1-hour algorithm is now very solid. Now randomized clinical trials with associated mortality data are needed to confirm the results. In TRAPID-AMI, patients were not treated based on test results. Furthermore, the algorithm has only been tested with one particular assay (hs-cTnT, Elecsys® 2010, Roche Diagnostics). Thus, it is not clear whether the algorithm can be extended to other highly sensitive assays. Similarly, emergency patients must be distinguished from patients in primary care practices. Nevertheless, the 1-hour algorithm shows promising results in a short time in about three quarters of patients with acute chest pain and should therefore be further explored.
Source: Cardiology Update, February 8-12, 2015, Davos
Literature:
- Reichlin T, et al: Early diagnosis of myocardial infarction with sensitive cardiac troponin assays. N Engl J Med 2009 Aug 27; 361(9): 858-867.
- Reichlin T, et al: One-hour rule-out and rule-in of acute myocardial infarction using high-sensitivity cardiac troponin T. Arch Intern Med 2012 Sep 10; 172(16): 1211-1218.
CARDIOVASC 2015; 14(2): 27-28
