Takotsubo syndrome (TTS) and its variants represent a form of acute heart failure (HF), typically reversible, secondary to a catecholaminergic myocardial storm, and without evidence of obstructive coronary atherosclerotic disease (CAD) to explain the left ventricle (LV) dysfunction. Diagnostic criteria have been established, reviewed by various societies, and mentioned in several reviews on the subject [1]. In the acute phase, the symptoms and signs of TTS are indistinguishable from those of type 1 ST-segment elevation myocardial infarction (STEMI) or atherosclerotic events, as 76% of TTS patients experience chest pain and 44% present with ST-segment elevation [1]. Initially, it was suggested that these two entities were mutually exclusive; however, it is now recognized that stable or unstable CAD may coexist with TTS, either concomitantly or as a trigger [2]. In cohorts evaluating TTS patients, 41.2% were found to have non-obstructive CAD, while 23% had obstructive CAD [2–5].

Differentiating these two conditions can be particularly challenging. In such cases, cardiac magnetic resonance (CMR) imaging plays a pivotal role, being especially useful in the acute phase. Several findings have been documented in the literature, including a combination of typical contractility abnormalities, myocardial edema, and the absence of late gadolinium enhancement (LGE) [6, 7]. It remains unclear whether the presence of TTS alongside a significant but non-occlusive coronary lesion would necessitate primary intervention [2]. An acute coronary syndrome (ACS) may be the initial event, subsequently triggering TTS, but alternatively, TTS could precipitate a type 1 STEMI through a sympathetic discharge that causes vasoconstriction and plaque rupture [2].

The exact pathophysiology of TTS remains unclear, though significant advances have been made in understanding the syndrome. One central hypothesis is that intense sympathetic activation and elevated circulating catecholamine levels play a critical role in TTS. Acute episodes are often triggered by stress or physical illness, with patients showing signs of intense sympathetic activation. Elevated plasma catecholamine levels, especially in patients with pheochromocytoma or those receiving catecholamine-based treatments, support this hypothesis [1, 5, 8]. These findings suggest that excessive sympathetic stimulation contributes to the pathophysiology of TTS, leading to reversible myocardial dysfunction [5, 8].

The diagnostic criteria for TTS, according to the InterTAK registry, include: 1) clinical evidence of transient LV dysfunction, with apical or mid-ventricular hypokinesia or akinesia on echocardiography; 2) the absence of significant coronary artery obstruction, confirmed by coronary angiography; 3) the absence of pre-existing conditions that could explain the ventricular dysfunction, such as myocardial infarction or myocarditis; 4) the presence of an emotional or physical trigger, often with initial chest pain or angina, particularly in postmenopausal women [5, 7]. Spontaneous recovery of ventricular function is common within weeks to months. The InterTAK score, used to assess the risk and severity of the syndrome, assigns points for factors such as age, sex, presence of coronary artery disease, type of trigger (emotional or physical), and the extent of ventricular dysfunction, with a score greater than 70 points indicating a high probability of TTS [7, 8].

We present an unusual case of TTS with concomitant ACS, confirmed by transthoracic echocardiogram (TE) and CMR during the acute episode. The edema resolved within three months, but transmural LGE persisted, as evidenced in the initial event.

This case highlights a diagnostic challenge in cardiology, where two entities with remarkably similar clinical presentations are difficult to differentiate in practice: TTS and type 1 STEMI. According to the 2004 Mayo Clinic diagnostic criteria, which considered both entities to be mutually exclusive, our patient would have been diagnosed with ACS only [9]. However, these criteria were revised in 2008 to account for the coexistence of the two entities, and later, a cohort study revealed that such an association is not as rare as previously thought [2, 10].

Differentiating the two entities or recognizing their association is not straightforward, as there is considerable overlap in pathophysiological, clinical, and diagnostic characteristics. Emotional and physical triggering factors can occur in both situations, and one may precipitate the other [2]. In patients with ACS, troponin and creatine kinase-MB (CK-MB) levels are elevated [7, 11, 12]. In TTS, CK-MB typically shows mild elevations, while brain natriuretic peptide (BNP) levels increase significantly, which was not observed in this ACS case [11, 12]. Comparing echocardiography with coronary angiography is crucial; in ACS, segmental ventricular dysfunction correlates with the anatomy of the coronary artery responsible for the acute event [7, 11]. In TTS, however, regional ventricular dysfunction typically does not adhere to the coronary anatomy, often extending beyond the boundaries of the affected artery [11]. If TTS is associated with CAD, CMR plays a fundamental role in addition to comparing echocardiography with coronary angiography. The presence of subendocardial or transmural LGE indicates myocardial necrosis, confirming an acute coronary event [7, 11]. Patient follow-up is also critical, as recovery of myocardial function and reduction in myocardial edema across various walls should raise suspicion for TTS [11].

This patient had a non-obstructive coronary lesion in the LAD artery, but the ventricular dysfunction observed on ventriculography and echocardiography extended beyond the LAD territory. CMR showed edema in multiple walls, but LGE was only present in the lower apical segment, consistent with the lesion in the LAD. At the 90-day follow-up, the complete resolution of the edema compared to the previous exam, alongside persistent LGE in the lower apical segment, supports the hypothesis of TTS associated with type 1 STEMI. This is further corroborated by the recovery of ventricular function in regions not compatible with the LAD lesion, while myocardial necrosis persisted in a segment consistent with the LAD lesion.

The treatment of TTS and ACS shares similarities in managing complications such as HF and arrhythmias, utilizing beta-blockers, diuretics, mineralocorticoid antagonists, ACE inhibitors, and, when necessary, advanced mechanical support in cases of cardiogenic shock. However, therapeutic strategies differ in the acute phase. The management of TTS primarily involves supportive care, with an emphasis on preventing recurrence and monitoring for arrhythmias and HF. In the presence of CAD, aspirin and statins are indicated. In contrast, the management of ACS includes dual antiplatelet therapy, anticoagulation, and early revascularization of the target vessel to reduce mortality and prevent HF [7, 13].

In conclusion, TTS is a challenging diagnosis, particularly when associated with CAD. Therefore, the combined evaluation of echocardiography and coronary angiography is crucial, as it allows for comparison between the territory of the affected coronary artery and the dysfunctional myocardial segment. Additionally, CMR evaluation of LGE, myocardial edema, and segmental contractility changes play an important role in aiding the differential diagnosis.