There Is Much to Be Gained by Discarding Preconceived Notions
Article ID: CJ-16-0533
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Article ID: CJ-16-0533
Acute coronary syndromes (ACSs) are usually caused by atherosclerotic plaque rupture and subsequent coronary thrombus formation. Previous acute myocardial infarction (MI) angiographic studies have demonstrated the presence of significant obstructive coronary artery disease (CAD) in >95% of MI patients,1,2 thus leading to the general belief that an ischemic cardiac origin has to be excluded when significant coronary organic stenosis is not detected at angiography. However, recent multicenter ACS registries have reported that a sizable proportion of patients, particularly those without persisting ST-segment-elevation (NSTE-ACS), have no evidence of obstructive stenosis and coronary thrombosis that could cause acute myocardial ischemia. In the CRUSADE registry, 10.0% of 55,514 patients with NSTE-ACS were found to have absent or only angiographically mild coronary lesions.3 Similarly, 8.1% of subjects with NSTE-ACS enrolled in the ACUITY trial had non-obstructive CAD.4 More importantly, the outcome of those patients is likely to be not as good as commonly expected by the lack of obstructive atherosclerosis. In fact, in the ACUITY trial, the 1-year mortality rate was significantly higher in the patients with MI with no obstructive coronary atherosclerosis (MINOCA) than in those with obstructive CAD (5.2% vs. 1.6%; HR 3.44, CI 1.05–11.28; P=0.04).4 Therefore, in recent years, particular interest in the clinical features, mechanisms and outcomes of ACSs without obstructive coronary atherosclerosis has increased, and several research groups, which have a detailed knowledge of coronary functional disorders including epicardial coronary spasm and abnormalities of coronary microcirculation, have published sophisticated systematic review articles regarding MINOCA.5–7 Pasupathy et al5 performed a quantitative assessment of 28 publications using a meta-analytic approach to evaluate the prevalence, clinical features, and prognosis of MINOCA. The patients with MINOCA accounted for 6% of all AMI cases and were more likely to be younger, more often female, and less likely to have hyperlipidemia as compared with the patients with MI associated with obstructive CAD. All-cause mortality at 1 year was lower in the MINOCA group than in those with MI with obstructive CAD (4.5% vs. 6.7%). As they describe in their review, MINOCA could be considered as a working diagnosis that requires further exploration for the underlying cause. Based on the same standpoint, Niccoli et al6 presented a rational diagnostic algorithm of MINOCA. The first step is represented by clinical history, ECG, cardiac enzymes, echocardiography, coronary angiography, and left ventriculography. Regional wall motion abnormalities with an ‘epicardial pattern’, which is limited to a single epicardial coronary artery territory, indicate an epicardial cause of MINOCA, including coronary artery spasm8,9 and the presence of eccentric plaques with positive remodeling resulting in lack of obstructive CAD.10 On the other hand, regional wall motion abnormalities with a ‘microvascular pattern’, which extends beyond a single epicardial coronary artery territory, suggest a microvascular cause of MINOCA, including takotsubo syndrome,11 myocarditis,12 microembolism,13 and microvascular spasm.14 Thus, in the second step, additional tests such as intracoronary acetylcholine test, intracoronary imaging (eg, IVUS, OCT), cardiac magnetic resonance imaging, endomyocardial biopsy, and contrast-enhanced echocardiography, are considered individually to clarify the specific cause. However, there has not been a previous study that demonstrated the results of diagnostic work-up for those ACS patients with no obstructive CAD (NOCAD) in clinical practice.
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In this issue of the Journal, Lanza et al15 provide important information on the spectrum of clinical diagnoses as well as the predictors of clinical outcome in NSTE-ACS patients with NOCAD. In their study, they examined 178 patients admitted to a coronary care unit with an initial diagnosis of NSTE-ACS, but who had NOCAD at coronary angiography performed within 48 h of admission. The final diagnoses at discharge identified by work-ups based on the diagnostic algorithm of MINOCA included a variety of clinical presentations: true NSTE-ACS that involved transient coronary thrombosis formation at unstable plaque sites (0.56%), variant angina (10.1%), myocarditis (8.9%), takotsubo disease (7.9%), chest pain related to tachyarrhythmia (6.7%), and microvascular NSTE-ACS (56.2%) (Figure). During a follow-up period of 24.5±12 months, 21deaths (11.8%), most of which had non-coronary causes, occurred and readmission for non-fatal cardiovascular events also occurred in 36 patients (20.2%). Finally, they clarified that age was the only independent predictor for death, and non-coronary vascular disease was the only one for non-fatal cardiovascular events.
Final diagnoses in 178 patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and no obstructive coronary artery disease (NOCAD). When all other diagnoses are excluded at the end of diagnostic work-up, a final diagnosis of microvascular NSTE-ACS can be made.
Lanza et al have to be congratulated for this excellent study. They specifically confirmed the heterogeneity of causes of NSTE-ACS with NOCAD by performing appropriate tests based on their considerable experience in clinical practice of such ACS patients with NOCAD. Furthermore, their subjects, as shown by previous studies,4,5 also had a less favorable prognosis frequently determined by non-cardiovascular causes. We should not refuse to face the truth that the patency of coronary arteries never guarantees a brilliant future for those patients. In particular, to improve the long-term prognosis of patients with NSTE-ACS and NOCAD, we have to pay sufficient attention to their age and the presence and absence of complicating non-cardiac vascular diseases, which are the significant predictive factors first exposed by this study. In the future, we have to give in-depth consideration to microvascular NSTE-ACS, which accounted for almost half of the subjects of this study and was based on diagnoses of exclusion.
In conclusion, this thought-provoking study by Lanza et al15 shows that physicians should be challenged to make a correct diagnosis in NSTE-ACS patients with NOCAD, without mislabeling them as non-cardiac patients or with psychic disorders, for risk stratification and clinical management to improve their poor prognosis.
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