To the best of our knowledge we conducted the largest single study analysis dedicated to NSTEMITO phenomenon (16,209 patients). The previous meta-analyses on this topic included 10,415 patients (7 studies) and 17,212 patients (25 studies) with NSTEMITO respectively.6–7
Our study results suggest that NSTEMITO may be considered as an intermediate condition between NSTEMINTO and STEMITO. However, the following features make NSTEMITO group exceptional:
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The longest time delay to obtain proper medical care (patients with NSTEMITO reached FMC when STEMITO patients had already finished their PCI),
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LCx as the most frequent infarct related artery,
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The worst final result of PCI.
Numerous studies showing the differences in baseline clinical presentation between patients with STEMI and NSTEMI. In the OPERA Registry correlates of mid- and long term mortality were similar for NSTEMI and STEMI patients.8 This leads to the conclusion that we should not consider STEMI and NSTEMI as two different diseases but rather as a ischemic continuum due to subtotal or total occlusion of coronary artery with different ECG manifestation.9–10 Total occlusion of IRA can occur in both STEMI and NSTEMI patients. There are numerous studies which have compared acute total occlusion of IRA with non-total occlusion of IRA but mostly within NSTEMI subset of patients.11–12 Our goal was to compare three manifestations of acute MI: NSTEMINTO, NSTEMITO and STEMITO thus for the first time we have compared three groups instead of two.
Considering the baseline characteristic, patients with NSTEMITO in our study constituted an intermediate group between NSTEMINTO and STEMITO. In comparison to STEMITO they were older and had higher prevalence of cardiovascular risk factors and chronic diseases. When comparing NSTEMITO to NSTEMINTO, they were younger and had lower prevalence of cardiovascular risk factors and chronic diseases. These findings are in accordance with other studies, where patients with NSTEMI, in comparison to STEMI, were older and had more often chronic diseases.13–14 According to the baseline characteristic our NSTEMITO group was definitely closer to STEMITO than NSTEMINTO group. Patients with STEMINTO were excluded due to large group heterogeneity. To summarize the results of prehospital management, participants with NSTEMITO generally were not considered as candidates for direct transportation to the Cath lab in contrary to STEMITO patients (9.41% vs 25.69%). Additionally, ischemia-time, i.e. time from pain to balloon inflation, as well as time from FMC to balloon inflation were longer in NSTEMITO than in STEMITO group. Duration of ischemia is a major determinant of infarct size and subsequent mortality.3,15 In almost all studies included in the meta-analysis of Khan et al. patients with NSTEMITO had a mean delay to invasive procedure longer than 24 hours and in comparison to NSTEMINTO increased risk of both major adverse cardiovascular events and mortality.6 Mean time from pain to inflation in our study was approximately 30 hours (data not presented) and also was similar to presented by Khan et. al.6
Time from pain to FMC was the longest in NSTEMITO group, even longer than in NSTEMINTO group. In NSTEMITO group patients postponed decision to seek medical help probably because of younger age (than in NSTEMINTO group) and lack of previous experience with stenocardial pain. Longer time delay from pain to FMC in NSTEMITO than in STEMITO may be explained by lower severity of symptoms due to lower extent of ischemia in case of LCx occlusion (typical for NSTEMITO in our study) in contrary to LAD or dominant RCA occlusion typical for STEMITO.
Time delay to achieve the opening of the occluded artery in NSTEMITO group in comparison to STEMITO was amplified during in-hospital management what is noticeable as the pronounced difference (almost three times longer median time from FMC to balloon inflation in NSTEMITO group).
In contrast, patients with NSTEMITO in comparison to NSTEMINTO were earlier considered as candidates for invasive management. The potential explanation is more severe clinical presentation caused by total artery occlusion. Higher frequency of cardiac arrest before admission and more advanced Killip class in NSTEMITO group than in NSTEMINTO group in our study confirms this hypothesis. Similar results were obtained by Shin et al. in the COREA-AMI Registry.16 Other commonly used parameter of time delay in MI is the percentage of patients who receive PCI within 120 min. since the onset of symptoms. In the study of Terkelsen et al. approximately 50% of STEMI patients had balloon inflation within 120 min.17 In our study almost 70% of STEMITO, but only 25% of NSTEMITO patients had PCI within 120 minutes. Terkelsen and other investigators confirmed that time delay to PCI worsened prognosis causing increased risk of mortality especially in patients with totally occluded artery.3,15,17
In our NSTEMI patients approximately 20% had acute coronary artery occlusion which is less than previously reported by Khan (25.5%) and Hung (34%).6–7 This difference may be explained by the fact that we defined NSTEMITO more restrictive, analysing only patients with TIMI 0 flow, whereas Khan and Hung included patients with TIMI 0–1. Previous studies examining the distribution of occluded artery in NSTEMITO patients indicated RCA or LCx being mostly responsible artery for NSTEMITO.6–7 In our study we found that LCx is the most typical localization of the culprit lesion responsible for MI in the NSTEMITO group. The distribution of the IRA differs between trials when STEMI cases are compared to NSTEMI, i.e. in STEMI there is underrepresentation of LCx as IRA,18 whereas in NSTEMITO occlusion of LAD occurs the least often.7,19 We must acknowledge that ECG has unsatisfactory sensitivity to diagnose coronary artery total occlusion, especially in posterolateral distribution.20 It has been shown that the presence of STE on ECG enables to detect acute coronary TO in 70%-92% of cases for the LAD and RCA, but the ability of 12 lead ECG to diagnose LCx-related MI with coronary occlusion of IRA is below 50%.2,21 Explanation is that LCx supplies the region of the heart placed more distally to the chest wall with no corresponding leads in standard ECG.
In our study patients with NSTEMITO demonstrated more severe clinical condition on admission than those with NSTEMINTO (more advanced Killip class, higher prevalence of death and cardiac arrest prior admission or during invasive procedure, no-reflow phenomenon), which is in concordance with prior studies showing that prognosis of patients with total occlusion without ST segment elevation is worse than in NSTEMINTO patients.6–7 We confirmed that the outcome after PCI (lower frequency of achieving TIMI 3 and higher frequency of TIMI 0) in NSTEMITO is even inferior to STEMITO. Possible explanation is that unrecognized acute coronary artery occlusion is associated with high morbidity and mortality15 and the outcome in this group is worse than in those who received timely revascularization.11,22
Two additional results of our study in NSTEMITO group are noteworthy, i.e.: increased total radiation dose and higher amount of contrast media during PCI compared with both STEMITO and NSTEMINTO. It may be due to predominance of LCx as IRA in NSTEMITO. Fetterly et al. showed that PCI of LCx correlates with increased total radiation dose due to anatomy and need for specific oblique projections consuming higher radiation doses.23 Furthermore, it has been proven that patients with longer time to reperfusion (NSTEMITO patients in our study) are prone to receive significantly more contrast media during PCI.24
Study limitations
Our study has several limitations. First, we should deduce very cautiously about detailed in-hospital prognosis because our analysis is based on data from the structured registry of prespecified clinical and periprocedural data spectrum only, without longitudinal follow-up, but with the largest number of evaluated patients. Second, the registry was created and fulfilled by several operators, also quality of data depends on their individual knowledge; however only the most experienced operators collected the data.