Myocardial Infarction or Acute Coronary Syndrome With Non-obstructive Coronary Arteries and Sudden Cardiac Death

A Missing Connection

Nikolaos Kosmas; Antonis S. Manolis; Nikolaos Dagres; Efstathios K. Iliodromitis


Europace. 2020;22(9):1303-1310. 

In This Article

Abstract and Introduction


Myocardial infarction with non-obstructive coronary arteries or any acute coronary syndrome (ACS) with normal or near-normal (non-obstructive) coronary arteries (ACS-NNOCA) is an heterogeneous clinical entity, which includes different pathophysiology mechanisms and is challenging to treat. Sudden cardiac death (SCD) is a catastrophic manifestation of ACS that is crucial to prevent and treat urgently. The concurrence of the two conditions has not been adequately studied. This narrative review focuses on the existing literature concerning ACS-NNOCA pathophysiology, with an emphasis on SCD, together with risk and outcome data from clinical trials. There have been no large-scale studies to investigate the incidence of SCD within ACS-NNOCA patients, both early and late in the disease. Some pathophysiology mechanisms that are known to mediate ACS-NNOCA, such as atheromatous plaque erosion, anomalous coronary arteries, and spontaneous coronary artery dissection are documented causes of SCD. Myocardial ischaemia, inflammation, and fibrosis are probably at the core of the SCD risk in these patients. Effective treatments to reduce the relevant risk are still under research. ACS-NNOCA is generally considered as an ACS with more 'benign' outcome compared to ACS with obstructive coronary artery disease, but its relationship with SCD remains obscure, especially until its incidence and effective treatment are evaluated.


The majority of myocardial infarctions (MIs) are associated with obstructive coronary artery disease (CAD). In the decade of 1980s, the pioneering angiographic studies by De Wood et al. had already discovered that almost 5% of patients with acute MI did not have obstructive CAD.[1,2] This disease was subsequently named MI with non-obstructive coronary arteries (MINOCA) or MI with normal coronary arteries. Furthermore, there are patients who present with non-MI acute coronary syndrome (ACS) who also have no significant CAD detected at coronary angiography; all these patients have been recently grouped under the newly coined term of ACS with normal or near-normal (non-obstructive) coronary arteries (ACS-NNOCA).[3]

Sudden cardiac death (SCD) is responsible for over 4 million deaths worldwide every year, affecting both older and younger people.[4] Identifying the cause of SCD is challenging, because in older individuals multiple cardiovascular (CV) and non-CV conditions exist, making the attribution of the event to one of them difficult, while in younger persons, conditions such as inherited channelopathies or arrhythmias might be missed even on autopsy.[4]

There is currently a lack of any dedicated studies assessing the incidence of SCD within MINOCA/ACS-NNOCA patients, before and after the initiation of symptoms, and the risk of potentially lethal ventricular arrhythmias late after the index event. Large cohort studies presenting predictors of adverse outcomes (e.g. for MI, heart failure, stroke, total death, CV death) do not address the specific outcome of SCD.[5,6] Society guidelines and scientific statements have ostensibly neglected this important issue.[7–9] The purpose of this narrative review is to concentrate current knowledge concerning MINOCA/ACS-NNOCA and its pathophysiology, with a special focus on the clinical presentation of SCD in this setting.