Practical Cardiovascular Medicine. Elias B. Hanna

It is not specific for MI definition in this setting.

      C. Non-ischemic myocardial injury (also called “non-MI troponin elevation”)

In this case, myocardial injury occurs because of a demand-supply imbalance similar to type 2 MI but less profound and with less CAD, or because of a direct cardiomyocyte injury (trauma, myocarditis, rhabdomyolysis, cytokines and neurohormones in shock, stroke, or post-operative states). This injury may be chronic with steady, chronic troponin elevation (e.g., advanced kidney disease or cardiomyopathy).^*

      Therapy is directed towards the primary insult. The cardiac prognosis depends on the presence of CAD and is generally better than type 2 MI, as CAD is less likely.¹⁰

      D .Coronary vasospasm and microvascular dysfunction

      It was initially hypothesized by Prinzmetal and then demonstrated in a large series that coronary vasospasm and vasospastic angina most often occur in patients with significant CAD at the site of a significant and sometimes unstable atherosclerotic obstruction.^13-15 In fact, a ruptured plaque is commonly accompanied by vasospasm, as the activated platelets and leukocytes release vasoconstrictors.

      Vasospasm also frequently occurs without obstructive coronary atherosclerosis and may lead to chronic vasospastic angina. In fact, in the current era, the term “coronary vasospasm” is mainly used to identify this “isolated coronary vasospasm” with no severe CAD. Indeed, isolated vasospasm is frequently the underlying disease process in patients with typical angina or MI yet no significant CAD.^16-19 The diagnosis is definitely made 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