Several studies have shown that the commonest underlying etiology of patients presenting with suspected ACS and unobstructed coronary arteries is myocarditis. The prevalence of myocarditis is variable and ranges from 15 to 75 % [16‐18, 19••, 20•, 21••, 22•, 23•, 24•, 25•]. This large variation is probably due to the CMR imaging sequences being used and the timing of the scan from the acute presentation. The use of T2-weighted images for assessment of myocardial edema/inflammation and imaging patients early from the onset of symptoms increases the diagnostic pick-up rate given that some abnormalities as myocardial edema/inflammation may be reversible and resolve with time. Use of T2-weighted images for assessment of myocardial edema and scanning the patients within 2 weeks from the onset of symptom increases the diagnostic pick up rate [30••].

The non-invasive imaging diagnosis of myocarditis and myocardial inflammation always represented a diagnostic challenge because diagnosis is based on indirect signs like myocardial swelling, wall motion abnormality, and pericardial effusion, particularly with echocardiography [31]. Endomyocardial biopsy (EMB) still represents the gold standard for the diagnosis of myocarditis. Recently, several studies have validated CMR against EMB [18, 32••, 33], suggesting that CMR can have a promising role in the diagnostic pathway of these patients [34‐39].

EMB is an invasive procedure and not widely available and has several limitations including low sensitivity and specificity due to sampling errors. This has fostered the increasing interest on the role of CMR in these patients. A recent Expert Position Statement of the European Society of Cardiology (ESC) confirms the important diagnostic role of CMR in patients with suspected myocarditis [40••]. Whilst CMR cannot replace EMB, there is agreement that it can be offered in clinically stable patients prior to EMB. CMR-guided EMB, i.e. obtaining the biopsy specimen from the LGE scar, can improve the diagnostic rate of the disease, as demonstrated by Mahrholdt et al. [41].

Recently, a consensus paper has defined the recommendations on the use of CMR in myocarditis [42] which led the establishment of the “Lake Louise criteria” diagnostic criteria. In particular, the CMR findings are consistent with the diagnosis of myocarditis if two of three sequences demonstrating myocardial edema, hyperemia, and fibrosis are positive.

Novel parametric mapping techniques like, native T1 mapping, extracellular volumes of distribution (ECV) and T2 mapping, currently mainly used for research, have recently shown promising results in the diagnostic assessment of myocarditis [43••]. Recent studies by Ferreira and Piechnik et al. [44••, 45••] demonstrated that native T1 mapping has a superior diagnostic role compared to conventional T2-weighted imaging, and an equivalent performance to LGE. Native T1 mapping can also display the typical non-ischemic patterns in acute myocarditis, without the need for gadolinium contrast agents [46••]. Radunski et al. recently demonstrated the utility of ECV quantification, as a measure of interstitial fibrosis in both acute and subacute, severe myocarditis [47••]. They compared the diagnostic performance of T2, T1, and ECV as novel quantitative tissue markers compared to the Lake Louise criteria. ECV quantification together with LGE imaging significantly improved the diagnostic accuracy of CMR compared with the Lake Louise criteria [47••].

Acute MI with unobstructed coronary artery is a common clinical situation and is the second most common etiology in this cohort of patients (5–29 %) [16‐18, 19••, 20•, 21••, 22•, 23•, 24•, 25•]. Several different patho-physiological mechanisms have been proposed to explain this phenomenon, e.g. rupture or erosion of a vulnerable plaque (causing transitory occlusion that resolves spontaneously, without leaving any residual visible intracoronary lesion), and distal vessels or small-caliber side branches disease. Other mechanisms including distal embolisation, coronary vasospasm, inflammation, or coronary dissections are rarely associated. Myocardial infarction can be diagnosed on CMR by identifying either a subendocardial or transmural LGE pattern in a typical coronary artery territory [29]. CMR can provide information on whether the myocardial infarction is acute/sub-acute orchronic. Acute ischaemic myocardial injury leads to myocardial edema, which can be delineated with T2-weighted imaging. Establishing the diagnosis in the presence of MI with unobstructed coronary arteries is very important, particularly so that appropriate management can be tailored. This can represent a plaque event or an extra-coronary embolic event. Review of coronary angiogram and coronary plaques, and excluding other sources of emboli (for example: exclude a patent foramen ovale as a potential contributor to a paradoxical embolic MI) often follows this diagnosis by CMR.

Patients with acute MI need long-term clinical follow-up and secondary atherosclerotic prevention treatment. In addition, CMR can provide further valuable prognostic information in this setting, including myocardial wall motion, global function, perfusion, and viability.

Cardiomyopathy is the third common cause of suspected ACS with unobstructed coronary arteries. According to literature TCM is the most frequent and occurs in 10–15 % of this patients group [16‐18, 19••, 20•, 21••, 22•, 23•, 24•, 25•]. Occasionally, dilated cardiomyopathy or hypertrophic cardiomyopathy may also present with chest pain with unobstructed coronaries.

TCM or stress cardiomyopathy is a subtype of MI with unobstructed coronary artery, and defined by the characteristic wall motion abnormality that is, by definition, reversible and transient. The condition usually has a favorable prognosis compared to the other conditions. It is often, but not always, provoked by an emotional stress or respiratory distress. Several mechanisms have been hypothesized for TCM, including plaque disruption, multivessel spasm, baroreflex abnormalities, and catecholamine toxicity. It remains unclear whether TCM occurs due to one or multiple mechanisms in individual patients.

TCM is characterized by mid-cavity to apical regional wall motion abnormalities (“apical ballooning”) with sparing of the left ventricular basal segments. This can be identified by LV angiogram, as well as transthoracic echocardiography. The added diagnostic value of CMR is in its (1) high spatial resolution, 3D image acquisition, and (2) non-invasive myocardial tissue characterization. The former results in a clear detection of cardiac chambers and endocardial contours, whilst the latter allows the detection of myocardial edema (markedly present in TCM) and myocardial scarring (usually absent in TCM) [48••]. Typically, T2-weighted sequences are used to image myocardial edema and it commonly identifies the presence of circumferential and transmural myocardial edema of the apical to mid-cavity myocardium matching with the regional wall motion abnormalities [49••]. Since myocardial edema is a transient phenomenon, it is advisable that CMR imaging is carried out within the first few weeks from the acute presentation. Myocardial edema resolves in 2–3 months without any myocardial scarring and with complete functional recovery [49••]. A few studies have shown the presence of subtle late gadolinium enhancement in TCM [50•], but experimental data shows that delayed washout of gadolinium may be caused by increased interstitial water content such that associated with transient myocardial edema [51]. The subtle changes are called myocardial edema-related LGE and they do not represent myocardial necrosis. The distribution of myocardial edema matching the wall motion abnormalities with no or subtle LGE helps in distinguishing TCM from myocardial infarction and myocarditis.

ACS with unobstructed coronary arteries is a common clinical entity encountered in day-to-day clinical practice. The mean age of presentation is usually lower than ACS with obstructed coronaries [52•]. Except for cigarette smoking [53], the common risk factors for CAD such as hypertension, diabetes mellitus, and hyperlipidemia are less present than in the obstructed coronary artery group [54]. ACS with unobstructed coronaries poses a clinical dilemma, as the underlying diagnosis is variable and often unclear. Accurate diagnosis is not only important for initiation of appropriate treatment, but may also have long-term implications for the patient. Contrary to popular belief, the 1-year mortality in the overall group was shown to be non-negligible in a recent systematic review [15••]. Diagnosis is crucial as a completely normal CMR scan is associated with a good prognosis as demonstrated by the study by Chopard et al. [21••]. CMR and its unique non-invasive myocardial tissue characterization do not just have a diagnostic role but it has a potential role in risk stratification.

Clinical presentation of myocarditis can be varied ranging from benign disease with preserved cardiac function to more aggressive form associated with severe LV/RV dysfunction (like giant cell myocarditis). Recent literature on myocarditis delineates its possible malignant side. Myocarditis was the third leading cause of sudden death after hypertrophic cardiomyopathy and congenital/atherosclerotic coronary artery disease, as demonstrated in a clinical case series of sudden deaths in young competitive athletes [55]. Myocarditis is responsible for 5 to 20 % of sudden deaths as demonstrated in the autopsy studies of young adults [56]. It may also resolve spontaneously without specific treatment in patients presenting with mild symptoms and minimal ventricular dysfunction [40••]. In up to 30 % of cases, biopsy-proven myocarditis can progress to DCM and is associated with a poor prognosis [40••]. CMR with its superior tissue characterization property can delineate the severity of myocarditis, thereby guiding in the management and in risk stratification. A recent study by Grun et al. has shown the presence of LGE is the best independent predictor of all-cause mortality and of cardiac mortality in 222 consecutive patients with biopsy proven viral myocarditis [57••]. LGE performed better than the traditional markers like LV ejection fraction, LV end diastolic volume, and NYHA symptom class. Moreover, normal CMR in patients with clinically suspected myocarditis, is associated with a good prognosis independent of their clinical symptoms and other findings [58••]. Thus CMR may help to distinguish a benign from malignant form of myocarditis. Prompt CMR diagnosis of an aggressive myocarditis may led to in initiation of appropriate therapy like immunosuppressants, early referral for myocardial biopsy or help in MR guided biopsy. Response to immunosuppressive therapy has been reported mainly in chronic virus-negative forms, in giant cell myocarditis, and in active myocarditis defined as autoimmune (e.g. virus-negative and autoantibody positive) [40••].

CMR can also help in risk stratification in MI. In addition to help achieving the diagnosis, the better tissue characterization properties allow accurate assessment of infarct size (LGE) and myocardial salvage. The area of myocardial edema delineated by T2-weighted CMR corresponds to the myocardial area at risk (AAR). The presence and extent of myocardial salvage can also be derived with CMR by subtracting the infarcted area from the AAR [59]. There is increasing data on the prognostic value of CMR-derived infarct size and myocardial salvage [60, 61•]. Microvascular obstruction (MVO), characterized by hypoenhanced core within myocardial infarction scar (hyperenhancement) on rest first-pass perfusion or LGE imaging, can occasionally be demonstrated. The presence and extent of MVO after AMI is associated with adverse LV remodeling and poor clinical outcome [62‐64], and myocardial segments with MVO at presentation are more likely to develop wall thinning and fail to demonstrate functional recovery [65]. Nijveldt et al. confirmed that MVO in LGE proved a more powerful predictor of global and regional functional recovery than the transmural extent of infarction.

CMR can potentially diagnose the complications of MI. CMR is superior to echocardiography for the identification of ventricular thrombi, particularly when they are small and apical. They are easily identifiable early after contrast administration when both the cavity and the myocardium still appear bright, whilst the thrombus appears hypointense (lack of contrast uptake given that it is avascular) [66, 67]. CMR is also able to detect other complications of MI including ventricular aneurysm, pseudoaneurysm, papillary muscle infarction with subsequent mitral regurgitation, etc.

Although TCM is usually considered to be a benign reversible condition, its arrhythmic risk is increasingly recognized. There are promising new CMR analyses which may help to risk stratify the patients with potential higher arrhythmic risk [68••].

Deep T-wave inversion and QTc interval prolongation on ECG may be observed in TCM [69•, 70]. Malignant arrhythmias including torsades de pointes (TdP) caused by repolarization abnormalities and QTc prolongation, can be seen in up to 8 % of cases [71••]. In one meta-analysis, sudden cardiac death (SCD) after TCM has been reported in 1.1 % during the index episode, with a further 0.5 % of patients suffering a SCD weeks to months later [72••]. The study primarily looked at the relationship between TCM and ventricular arrhythmias, reviewing a total 816 published cases. VF was reported in 15 cases (prevalence of 1.8 %) and VT was reported in 18 (2.2 %) [72••].

The T-wave inversion and QT interval prolongation in typical TCM is thought to be caused by an intra-cardiac gradient (apico-basal) of myocardial edema which, in turn, gives rise to regional dispersion of action potential durations [73]. A study by Perazzolo Marra et al. looked at the ECG and CMR findings in 20 consecutive TCM patients. A linear correlation of the apical-basal ratio of T2-weighted signal intensity with ECG repolarization indices such as negative T-wave magnitude, sum of the amplitudes of negative T-waves, and maximum corrected QT interval has been shown [49••]. Interestingly, the repolarization changes were unrelated to either late gadolinium enhancement or quantitative cine parameters. Hence, the T2-weighted signal intensity gradient can be potentially used as a marker of malignant arrhythmia.

CMR can also provide additional information on the presence of LV apical thrombus, valvular abnormalities, and LV outflow tract obstruction. Some of these findings are also directly linked to adverse prognosis.