A systematic review on the triggers and clinical features of type 2 myocardial infarction

Abstract Little is known about the correlation between triggering factors, clinical characteristics, diagnosis, and prognosis of patients with type 2 myocardial infarction (T2MI). The triggers and features of T2MI are linked to its diagnosis and prognosis. The Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines were followed. A structured search of three databases (PubMed, Embase, and Medline) was undertaken to identify peer‐reviewed articles related to the triggers and clinical features of T2MI published between January 2012 and August 2018. Seven retrospective cohort studies and seven prospective cohort studies involving 3867 patients with T2MI were included. All selected studies were rated as being of high or acceptable quality. Nine studies revealed that the leading trigger of T2MI was arrhythmia, especially tachyarrhythmia. Six studies revealed that the proportion of single‐trigger T2MIs was higher than that of multiple triggers and two studies showed that two‐trigger cases formed the majority of multiple trigger cases. All included studies found that a greater prevalence of T2MI in the older population. Thirteen studies revealed that the patients with T2MI often had a previous relevant medical history. The leading trigger of T2MI is arrhythmia, especially tachyarrhythmia, and the majority of cases arise from a single trigger. Two‐trigger is the most common form of multiple‐trigger T2MI, which often occurs in older patients with cardiovascular risk factors or comorbidities. Non‐cardiovascular causes may be the triggering factors and are strongly associated with the diagnosis, treatment, and prognosis of T2MI.

The inclusion criteria were as follows: (a) the definition, different causes, and baseline features of T2MI were mentioned; (b) an available clinical database was used; and (c) the study design met the requirement of high or acceptable quality assessment; especially, the single-and multiple-trigger T2MI should be both included in selected studies. The exclusion criteria were as follows: (a) duplicate reporting; (b) lack of outcome data; and (c) non-English publication.
Two investigators (G.Q.W. and N.Z.) independently evaluated the titles and abstracts of the articles retrieved using the search strategy.
Abstracts that did not meet the inclusion criteria or met exclusion criteria were discarded. We selected the remaining studies for fulltext evaluation and data extraction. Any disagreements regarding the inclusion or exclusion of a study were solved by consensus, and, if doubt persisted, a third reviewer (J.P.L.) evaluated the reference.
Therefore, we extracted data on the different causes of T2MI, which contained arrhythmia, anemia, respiratory failure, hypotension, infection and sepsis, heart failure, hypertension, postoperative factors, and other factors. Additionally, the data of multi-trigger T2MI was extracted from selected studies.

| RESULTS
Our literature search identified 7386 articles corresponding to the key terms; 7306 were excluded because they were not relevant based on the title and abstract. The full text of 80 articles was evaluated and 14 articles were ultimately included in this review. After screening the reference list of all included articles, no articles were added to this review. A detailed description of the selection process is presented in   To evaluate the quality of included studies, we applied the improved Newcastle-Ottawa Quality Assessment Scale (NOS) for nonrandomized studies. 11 All prospective or retrospective cohort studies received a rating of high (NOS ≥7) or acceptable quality (NOS ≥6) in this systematic review, respectively.
The baseline clinical characteristics and treatment of patients with T2MI are summarized in Table 1 Figure 2 shows the comparison between the single-and multipletrigger T2MI in six selected studies and shows that the proportion of single-trigger T2MI was higher than that of multiple-trigger T2MI, while Figure 3 shows that 2-trigger T2MI constituted the majority of multiple-trigger cases. 15,16

| DISCUSSION
A key finding of this review is that the clinical characteristics of patients with T2MI, which were similar to those of found by Gupta et al. 25 Patients with T2MI were older, more often men, more frequently presented with NSTEMI, and had a higher prevalence of cardiovascular risk factors or comorbidities, such as hypertension, smoking, dyslipidemia, diabetes, obesity, heart failure, impaired renal function, anemia, coronary artery disease, atrial fibrillation, cancer, peripheral artery disease, and chronic obstructive pulmonary disease.
In this review, most selected studies revealed that the number of men with T2MI was higher than that of women, while a reduced number T A B L E 1 (Continued) of studies found the opposite. 17 24 Few studies confirm that T2MI has worse outcomes independent of severe concomitant diseases. On the other hand, patients with T2MI were less likely to undergo coronary angiography (CAG) or PCI or to receive secondary preventive treatment than patients with T1MI. The impact of anti-thrombotic and/or antiplatelet therapy, as well as the role of reperfusion in patients with T2MI due to mild atherosclerotic coronary stenosis might be beneficial or effective, but in patients without plaque rupture this benefit is uncertain and there might even be a detrimental effect or contraindication to treatment in many cases. 19,29 Otherwise, patients with T2MI often receive specific treatments for concomitant diseases, such as anticoagulants for atrial fibrillation or diuretics for heart failure. Regardless of the definition, we agree that the optimal medical therapy should be based on the cause of T2MI.
This review systematically evaluated T2MI triggers and listed the leading cause and other common causes, especially in single-trigger cases; our findings also shed light on the underlying etiologies, which may help improve the decision regarding treatment options. In the TRACER trial, the most frequent potential provoking factor for T2MI was tachyarrhythmia (38.2%), which is consistent with our findings. 30 A meta-analysis also demonstrated that the most common associated arrhythmia was tachyarrhythmia, especially atrial fibrillation, in patients with T2MI. 25  There are several limitations to this systematic review. First, it is based on a relatively small number of selected patients. T2MI cases are not representative of the local population they were been derived from, and the study population is heterogeneous. The study period is narrow and might not be able to represent the whole spectrum of patients with T2MI adequately. In addition, selection bias may be present due to the heterogeneity of included patients due to the subjectivity of the diagnostic criteria for T2MI and to the different diagnostic methods used. 33

| CONCLUSION
The leading trigger of T2MI was arrhythmia, especially tachyarrhythmia, and single-trigger cases represented the majority of cases. Among multiple-trigger cases of T2MI, two-trigger cases are the most common. T2MI often occurs in older patients with cardiovascular risk factors or comorbidities. As for the triggering factors, non-cardiovascular causes are closely related to the diagnosis and prognosis of T2MI. Furthermore, the optimal medical therapy should be decided based on the trigger of T2MI. Although recent data are promising, more prospective randomized controlled studies are necessary to verify the impact of different triggers on the diagnosis, treatment, and prognosis of T2MI.