CMR Reveals the Influence of Trigger and Classification on the Myocardial Tissue Response in Takotsubo Syndrome

The pathogenesis of Takotsubo syndrome (TTS) is poorly understood, but differences in outcome depending on the triggering factor imply differences in the pathophysiology. Beyond the established trigger-based InterTAK (International Takotsubo Registry) classification, the newly proposed distinction between primary and secondary TTS aims to differentiate emotionally primed heart dysfunction from TTS driven by direct myocardial injury. To explore these potential differences, we utilized cardiovascular magnetic resonance imaging to assess left ventricular function, myocardial edema, and myocardial injury across the InterTAK classification and between primary and secondary TTS.

For this multicenter cohort study, 110 patients (95% women, age 66±12 years) from the InterTAK registry were included who received cardiovascular magnetic resonance 3 (interquartile range, 2-5) days after symptom onset. Cardiovascular magnetic resonance included assessment of myocardial function, edema (T2-weighted spin-echo and T2-mapping when available), and late gadolinium enhancement.

No significant differences were observed in left ventricular volumes, function, or mass across the 3 InterTAK groups or between primary and secondary TTS. Patients with emotional triggers exhibited significantly larger myocardial edema (72% versus 60% for physical triggers; P<0.01), supported by higher T2-mapping values in a subset of 22 patients with T2-mapping. In multivariable regression, only emotional trigger (P<0.01) and the absence of coronary artery disease (P=0.04) were independently associated with the extent of myocardial edema. Secondary TTS showed a higher prevalence of focal or patchy late gadolinium enhancement (primary 19%, secondary 54%; P<0.01). In multivariable logistic regression, secondary TTS (P<0.01) and early cardiovascular magnetic resonance (P=0.02) were associated with the presence of any late gadolinium enhancement.

TTS due to emotional stress is associated with larger myocardial edema, and secondary TTS exhibited late gadolinium enhancement more frequently, indicative of direct myocardial damage. These findings suggest that emotionally primed heart dysfunction and direct myocardial injury contribute to TTS pathophysiology to varying extents, influenced by both the triggering factor and preexisting conditions.