In a variable proportion of patients presenting with ST-segment elevation myocardial infarction, ranging from 5% to 50%, primary percutaneous coronary intervention achieves epicardial coronary artery reperfusion but not myocardial reperfusion, a condition known as no-reflow. Of note, no-reflow is associated with a worse prognosis at follow-up. The phenomenon has a multifactorial pathogenesis including: distal embolization, ischemia-reperfusion injury, and individual predisposition of coronary microcirculation to injury. Moreover, it is spontaneously reversible in some patients, thus suggesting that it might be amenable to treatment also when we fail to prevent it. Several recent studies have shown that biomarkers and other easily available clinical parameters can predict the risk of no-reflow and can help in the assessment of the multiple mechanisms of the phenomenon. Several therapeutic strategies have been tested for the prevention and treatment of no-reflow. In particular, thrombus aspiration before stent implantation prevents distal embolization and has been recently shown to improve myocardial perfusion and clinical outcome as compared with the standard procedure. However, it is conceivable that the relevance of each pathogenetic component of no-reflow is different in different patients, thus explaining the occurrence of no-reflow despite the use of mechanical thrombus aspiration. Thus, in this review article, for the first time, we propose a personalized management of no-reflow on the basis of the assessment of the prevailing mechanisms of no-reflow operating in each patient.

Myocardial infarction (MI) with no obstructive coronary atherosclerosis (MINOCA) is a syndrome with different causes. Its prevalence ranges between 5 and 25% of all MIs. The prognosis is extremely variable, depending on the causes of MINOCA. Clinical history, echocardiography, coronary angiography, and left ventriculography represent the first-level diagnostic investigations. Nevertheless, additional tests are required in order to establish its specific cause, thus allowing an appropriate risk stratification and treatment. We review pathogenesis, diagnosis, prognosis, and therapy of MINOCA and propose an algorithm for its management.

We thank Dr Fearon for his interest in our review article on primary microvascular angina (MVA). We agree with him that invasive methods would provide more complete information about presence and characteristics of coronary microvascular dysfunction in patients with chest pain and normal coronary arteries.However, although small, the risk of serious adverse events with invasive tests cannot be regarded as absent, 1,2 and it may raise particular concerns when considering the excellent outcome of patients with MVA 3 and the lack of any evidence that invasive assessment of coronary microvascular dysfunction may predict major cardiac events (eg, cardiac death or acute myocardial infarction) in these patients. 2,4 Moreover, a reliable assessment of coronary microvascular dysfunction can now be obtained noninvasively, an approach that, besides being safer, is also cheaper than invasive methods, which is not irrelevant in the present era of economic constraints.As we observe in our review, in most patients with angina and normal coronary arteries the most cost-effective way to confirm the diagnosis of MVA is to assess coronary flow reserve by transthoracic echo-Doppler of the left anterior descending coronary artery, which has been shown to give sufficiently reliable results and can also be easily repeated in follow-up. 5 Importantly, we believe that, in patients for whom a careful assessment of the clinical history suggests MVA, the presence of a reduced coronary flow reserve by this method, together with the absence of transient regional wall motion abnormalities on dipyridamole/ dobutamine stress test despite reproduction of angina and STsegment depression, might be taken as diagnostic of MVA, even in the absence of coronary angiographic data.Notably, even more accurate information could be obtained by dipyridamole or dobutamine cardiovascular magnetic resonance, which, however, is at present a less available and more expensive diagnostic method.Thus, although we agree that invasive methods remain the gold standard for the morphological and functional assessment of coronary circulation and can find application to assess coronary microvascular dysfunction in selected patients, we believe that practical and clinical issues make them unsuitable for a widespread routine use in patients with suspected MVA. DisclosuresNone. Gaetano

AMI is followed by enhanced spontaneous mobilization of BMSC, in particular, in patients on statin therapy and following a primary percutaneous intervention. More importantly persistent spontaneous mobilization of BMSC might contribute to determine a more favourable post-AMI remodelling.