when: (i) vasospasm is angiographically reproduced with provocative testing, along with (ii) symptoms and (iii) ST changes during testing.
Endothelial dysfunction, which underlies isolated coronary vasospasm, may also occur at the microvascular level and manifest as diffuse microvascular constriction, not visible angiographically, or as insufficient microvascular dilatation during stress.
E. MI with non-obstructed coronary arteries (MINOCA)
About 6-10% of patients presenting with a picture of type 1 MI have normal coronary arteries or insignificant CAD (<50% obstructive; 50% being considered obstructive in MI, unlike the 70% cutoff in stable CAD). This prevalence is higher among women and younger patients; up to 15% of women presenting with a type 1 MI picture have no CAD.19-27 The picture is mostly a NSTEMI picture, but up to a third of cases are STEMI, and half of the patients have completely normal angiographic appearance of the coronary arteries.19 This phenomenon is coined MINOCA and may be due to any of the following processes:19,23
1 True type 1 infarction from:plaque rupture or plaque erosion that has embolized distally without leaving any significant stenosis; or thrombosed then recanalized with antithrombotic therapy (or spontaneously). As such, intracoronary imaging often needs to be performed to assess moderate or hazy irregular stenoses in ACS.overlooked occlusion of a branch vessel, such as a diagonal or OM, particularly when it is a flush occlusioncoronary embolus (in patients with AF or severe LV dysfunction) or spontaneous coronary thrombosis from thrombophilia
2 Infarction from isolated coronary spasm or microvascular disease17-19
3 Myopericarditis
4 Takotsubo cardiomyopathy
5 Overlooked type 2 MI mechanisms:Hypertension with diastolic dysfunction and elevated LVEDPPulmonary embolismTachyarrhythmia, or unsuspected hyperthyroidism
Troponin elevation is generally mild, <1 ng/ml, in overlooked type 2 MI, but may be severe in the other processes 1-4.
Work-up with cardiac MRI - Cardiac MRI is a central investigation in MINOCA. In an analysis of all comers with MINOCA, MRI established the diagnosis in most patients (three main diagnoses: myocarditis 33%, infarction 24%, and takotsubo 16%);19 ~25% did not have significant MRI abnormality (myocardial injury too small, <1 gram?). In two studies of patients with severely elevated troponin (up to 27 ng/ml, mean 9 ng/ml) and unobstructed coronary arteries, cardiac MRI established the diagnosis in 90% of patients (myocarditis 60%, infarction 15%, and takotsubo ~14%).26,27 **
Other work-up- In a cohort of 145 women with MINOCA (median angiographic stenosis 30%), OCT showed plaque disruption in 46% of the cases, at times in an angiographically normal coronary segment and even in some patients with a fully normal coronary angiogram.20 An even higher prevalence of plaque disruption, >50%, was seen in another OCT study of men and women with MINOCA.21 MRI showed an ischemic pattern in most (75%) but not all of these plaque disruption cases. Yet MRI detected an ischemic pattern in an additional 25% of patients, missed by OCT, coronary vasospasm being the likely culprit in this subset. Half the time, ischemic edema was seen with no LGE.
Regarding coronary artery vasospasm, one meta-analysis showed that vasospasm, macro- or microvascular, was inducible in 27% of patients with MINOCA, suggesting that it is a common pathogenetic mechanism in MINOCA.19 In a contemporary study of MINOCA patients, coronary vasospasm was induced in 46% of them.18
Beware of microvascular dysfunction diagnosis in MINOCA: microvascular dysfunction may be a consequence of the myocardial injury, not the cause of it.
Thrombophilia was detected in 14% of MINOCA patients19 (but beware that factor V Leiden and factor II mutation are also prevalent in normal subjects, 5% and 2%, respectively).
Prognosis- Most studies suggest that MI patients without significant CAD have good long-term outcomes,22-25 particularly if the coronary arteries are angiographically normal,22,24 with a 6-month risk of death of < 1% and death/MI of ~2%. One review suggests a more guarded prognosis, albeit better than MI with obstructive CAD with half of its 12-month mortality.19 The finding of plaque disruption on OCT does not dictate stenting if stenosis <50%, but rather aggressive antiplatelet and statin therapy.
Consider the diagnosis of coronary embolus in patients with AF or severe LV dysfunction who present with a large troponin rise yet no obstructive CAD.
Beware of the misuse of the term MINOCA. The term MINOCA does not apply to patients with type 2 MI context or non-MI troponin elevation. It only applies to those with type 1 MI presentation.
F. Unstable angina
Unstable angina is traditionally defined as any of the following clinical presentations, with or without ECG evidence of ischemia and with a normal troponin:
Crescendo exertional angina: angina that increases in frequency, intensity, or duration, often requiring a more frequent use of nitroglycerin
New-onset (< 2 months) severe exertional angina, occurring during normal activities performed at a normal pace
True resting angina of ACS will generally result in a troponin rise. In case of a serially negative troponin, and even more so, serially undetectable troponin (< 0.003–0.01 ng/ml), ACS is very unlikely, and the 30-day risk of coronary events is < 0.5%. 28-30 In the current era of sensitive troponin, resting chest pain is generally either MI or non-cardiac pain (+/- vasospastic angina), not unstable angina.
Unstable angina and NSTEMI are grouped together as non-ST-segment elevation ACS (NSTE-ACS). However, it must be noted that unstable angina has a much better prognosis than NSTEMI, particularly that many patients labeled as unstable angina do not actually have true angina, and if they do, the underlying CAD is stable CAD, sometimes severe, but not ACS.4,31 In fact, in the current era of highly sensitive troponin assays, a true ACS with coronary thrombosis or resting pain is accompanied by a troponin rise. Unstable angina is, thus, a vanishing entity. 32
The patient either has non-cardiac pain, stable angina (sometimes severe), or true ACS with positive troponin. The negative troponin, truly “unstable angina” is rare and is more in the realm of severe or progressive stable angina than unstable CAD with plaque rupture.
G. Additional notes: definition of reinfarction, type 3 MI, post-PCI MI (type 4 MI), and post-CABG MI (type 5 MI)
In patients with a recent infarction (a few days earlier), the diagnosis of reinfarction relies on:
CK or CK-MB re-elevation, as they normalize faster than troponin, or
Change in the downward trend of troponin (re-increase > 20% above the nadir)1
Type 3 MI is defined as sudden death with preceding clinical and ECG features suggestive of MI, such as VF.
In the post-PCI context, MI is diagnosed by a troponin elevation > 5× normal, along with ischemic ST changes or Q waves, new wall motion abnormality, or angiographic evidence of procedural
