Value of a short non-contrast CMR protocol in MINOCA

Acute coronary syndrome (ACS) is a leading cause of mortality, with coronary artery disease representing its most common origin [1, 2]. However, it is estimated that 7 to 15% of patients presenting with an ACS have myocardial damage but no obstructed coronary arteries or other clinically evident reasons that might justify the acute presentation. To describe such clinical scenario, the term myocardial infarction with non-obstructive coronary arteries (MINOCA) was established [3, 4].

According to the European Society of Cardiology (ESC) guidelines and American College of Cardiology/American Heart Association (ACC/AHA) Joint Committee [3‐5], cardiac magnetic resonance (CMR) is a key diagnostic technique in the algorithm for the differential diagnosis of patients with MINOCA for its ability to characterize the myocardium in addition to the morphofunctional evaluation. CMR was found to detect the underlying etiology in 74–87% of cases [6‐9] and to change the clinical diagnosis in around 50% of patients [6]. CMR should, however, be performed within few days of symptom onset [9], since a delayed evaluation may result in a false-negative evaluation for edema resolution [10] and a delayed diagnosis may have a negative impact on the patient’s prognosis [7]. Unfortunately, CMR is not widely practiced, particularly in emergency settings, since it needs a lengthy acquisition time and requires the administration of contrast medium, which is not always desirable.

In recent years, the application of new CMR techniques, such as mapping sequences, revolutionized the CMR scenario since they can characterize the myocardium in an accurate and quantitative mode. These sequences provide a wide range of additional information, from edema to fibrosis, that opens up the possibility of a gadolinium-free protocol combining T2-based imaging with T1 mapping [11‐15]. A protocol requiring reduced acquisition time with comparable diagnostic accuracy as standard contrast-enhanced CMR is highly desirable to speed up the diagnostic work-up in MINOCA patients, especially when the administration of contrast agents is contraindicated (i.e., patients with renal insufficiency or specific allergies).

To the best of our knowledge, the diagnostic value of a short non-contrast CMR (ShtCMR) protocol in patients with MINOCA has not yet been investigated. Hence, we planned a retrospective study aimed at evaluating how the diagnostic performance of a ShtCMR protocol lasting around 20 min without contrast agent compared with that of a matched standard comprehensive CMR (StdCMR) protocol on patients admitted to the emergency department for MINOCA.

One hundred seventy-nine MINOCA patients constituted the final study cohort. Table 1 presents the population characteristics and relative CMR findings. CMRs were performed 5 ± 4 days after symptom onset (troponin T peak 1651 ± 2368 ng/mL, normal range < 14 ng/mL), leading to the diagnosis of 95 (55.3%) acute myocarditis, 35 (19.6%) myocardial infarction, 29 (16.2%) takotsubo cardiomyopathy, 3 (1.7%) others, and 13 (7.3%) negative exams.

CMR has a crucial role in patients with a working diagnosis of MINOCA for addressing the correct diagnosis as recommended by the European and American guidelines [3, 5]. However, the StdCMR protocol requires a lengthy acquisition time and the administration of contrast medium and may not always be available or possible in emergency settings. A ShtCMR without contrast agent could be a possible alternative in some cases, provided it has the necessary reliability.

Our study compared the performance of a ShtCMR with that of its matched StdCMR in 179 cases of MINOCA patients. The ShtCMR considered lasts about 20 min and does not require contrast agent; it includes long-axis cine sequences for morphofunctional ventricular assessment and native T1, T2 mapping, and T2-STIR for tissue characterization in several cases.

The main finding of our study was the good agreement of the diagnoses performed with ShtCMR with the parallel StdCMR ones. It also evidenced that the confidence of the reader in the interpretation of the myocardial damage without use of contrast medium increased such agreement. Specifically, ShtCMR allowed reaching the same diagnosis as StdCMR in 85% of patients when interpreted by expert readers (rising from 66% for poor confidence to 99% for good, p = 0.0001) and 73% (p = 0.01) by non-expert ones (60% for poor vs 89% for good confidence, p = 0.0001).

These results might envision the implementation of a tailored approach which may avoid the use of contrast media in cases of good diagnostic confidence, thus allowing a shorter scanning time. In fact, based on the expert readers’ opinion, ShtCMR could have been sufficient to reach a diagnosis in 102/179 cases (57%) potentially leading to 41 h of scanning time saved (about 30%) at the cost of less than 1% incorrect diagnoses. Caution is however needed before considering any extension to clinical practice, since our results evidenced some issues related to an underestimation of the extent of the pathology and of volumes and overestimation of the ejection fraction.

Data on rigorously shortened CMR protocols is rare. Nadjiri et al [20] evaluated a shortened protocol based on T1 mapping and cine images in 160 individuals, finding that 70% of patients required contrast medium to complete the diagnostic process, in contrast to 34% (for the expert reader) and 43% (for the non-expert reader) of patients in our study population.

Hirschberg et al [15] evaluated the performance of a short CMR protocol without contrast agent in cardiomyopathy patients. As in our study, the scan time with ShtCMR was much shorter (23 vs. 48 min), and 92% of patients with suspected non-ischemic cardiomyopathies were diagnosed without contrast medium.

Even fewer data exist on short CMR protocols for MINOCA patients. Ferreira et al [21] showed that native T1 mapping can detect typical non-ischemic patterns with high sensitivity (90%) and specificity (88%) in patients with acute myocarditis and speculated that gadolinium-free CMR using cine and T1-mapping for tissue characterization may be possible in that setting. These findings are consistent with the revised Lake Louise criteria [12] which reported that a gadolinium-free protocol, combining T2-based CMR with T1 mapping, could be very appealing and effective in circumstances when contrast agents are not desirable. Vermes et al [13] evaluated 30 takotsubo patients and 34 controls, finding that a ShtCMR with mapping approaches techniques ensured high diagnosis accuracy, even if in Takotsubo patients there is usually no late enhancement [22].

The late gadolinium enhancement technique is important not only for diagnosis but also for prognosis in all heart diseases [23, 24]. With ShtCMR, LGE evaluation is not possible, and the extent of myocardial involvement is underestimated. This may be related to susceptibility to artifacts of the mapping technique especially in emergency patients with limited possibility of collaboration, which makes it harder to estimate the affected myocardial segments. However, the emergence and incorporation of mapping techniques in the evaluation of cardiac patients could make up for this deficit, both for their diagnostic and prognostic significance [25, 26].

Finally, in patients with MINOCA, assessing LV volume, wall motion, and ejection fraction is crucial for prognosis and therapy [3, 12, 27]. Bi-planar measurement is attractive because it only requires two views, reducing acquisition and processing time. Geometric assumptions limit biplane MRI. In our study, LV sizes were underestimated by 2–4 mL and LVEF was overestimated. Our findings are consistent with those of Huttin et al [28], who evaluated 100 patients with acute myocardial infarction and compared LV volume and EF with short-axis and long-axis techniques, finding a 63% reduction in acquisition/analysis time at the expense of a “systematic” underestimation of LVEDV (about 4 mL) and an overestimation of EF of about 5%.

Regarding the performance of readers with different experience, as one might expect, the less experienced readers had more difficulties with ShtCMR than the more experienced ones, but when the data is sub-analyzed for the different diagnoses, the difference was statistically significant only in the myocardial infarction group. We can speculate that for these patients, the diagnosis with ShtCMR without contrast medium may be hindered by the more difficult identification of the transmural distribution of the injury. In fact, the excellent specificity of LGE in providing a diagnosis is driven by the clear identification of the injured myocardial layer. Without contrast agent, edema can be subtler in relation to the severity of the damage or to the time delay from the symptom onset with unclear distribution pattern, and the presence of a microvascular obstruction may lead to a false absence of transmural distribution with subsequent misinterpretation of the injury as subendocardial/non ischemic. Additionally, the lack of short-axis cine images may affect the correct assessment of wall motion alteration. Nevertheless, in takotsubo cardiomyopathy, where the diagnosis is mainly guided by the identification of the typical contractile pattern, the presence of the apical ballooning is well explored with long axes cine images [27].

Our study has some limitations. Firstly, it is a retrospective study, even if the inclusion of consecutive patients from three different hospitals supports the robustness of the results. Second, we did not examine the contribution of the different sequences to the diagnosis, but made a diagnosis based on all sequences together without distinction. This approach was chosen because there is greater likelihood of reproducing the real approach used in clinical practice. Finally, the extent of the injury was assessed only qualitatively rather than quantitatively, so it is not possible to assess if differences are due to different degrees of severity.

In conclusion, ShtCMR was found to be a debatable alternative to the StdCMR in patients with MINOCA. Such a strategy could reduce time and resources without altering the patient’s diagnosis while also increasing the number of patients who can be scanned. However, this solution for being routinely acceptable requires the presence during scanning of an expert team able to quickly determine whether contrast administration is required. Alternatively, we may offer patients a first-stage ShtCMR and then, if necessary, add the contrast-enhanced part at a later scan.