Background: Takotsubo syndrome (TTS) is characterized by specific wall motion abnormalities in the absence of corresponding lesions of the coronary arteries. Although acute myocardial infarction is the most important differential diagnosis of TTS, its pathophysiological cause is very distinct. One often proposed pathophysiological explanation of TTS is an acute severe microvascular dysfunction. The aim of our study was to test this hypothesis as well as to assess whether the microvascular dysfunction in the context of TTS of transient nature.

Methods: The angiographically derived indices of myocardial resistance (caIMR) of the main three coronary arteries of 100 TTS patients were assessed using a new software that allows retrospective evaluation and compared with the caIMR of healthy control vessels, via the Student’s t-test. The caIMR of non-culprit vessels of 71 propensity-score matched patients with ST-elevation myocardial infarction served as the healthy control, as non-culprit vessels have previously been shown to be healthy in the context of the caIMR. An analysis of variance (ANOVA) was performed to determine whether the caIMR of the three coronary vessels of TTS patients differed significantly from each other, with a subsequent post hoc Tukeys test to compare the caIMR between pairs of two of the vessels. In 10 patients, follow-up caIMR could be determined (follow-up coronary angiography without any cardiac event) and compared with the respective event-caIMR with a paired t-test. A two-sided P value < 0.05 was considered statistically significant.

Results: caIMR in each of the three coronary arteries was significantly higher compared to the respective non-culprit (“healthy”) vessels of the control group with highest values in the circumflex artery (RCX: caIMR during TTS 50.6 +/- 17.8 vs. 27.0 +/- 11.7 in the control group) followed by the left anterior descending artery (LAD: caIMR during TTS 44.9 +/- 20.3 vs. 21.6 +/- 9.6 in the control group) and the lowest values measured in the right coronary artery (RCA: caIMR during TTS 41.4 +/- 15.1 vs. 22.3 +/- 12.0 in the control group). Comparing all three main vessels in the TTS cohort, we could detect a significant difference in the caIMR (50.6 (RCX) vs. 44.9 (LAD) vs. 41.4 (RCA), p=0.026). However, when comparing each coronary to another, only the difference between RCX and RCA remained statistically significant (50.6 (RCX) vs. 41.4 (RCA), p=0.002). caIMR normalized in all patients at follow-up (LAD: mean caIMR during event 34.5 +/- 5.6 vs. 19.6 +/- 5.7 at follow-up; RCX: mean caIMR during event 42.4 +/- 10.9 vs. 25.7 +/- 10.4 at follow-up; RCA: mean caIMR during event 32.0 +/- 9.2 vs. 20.2 +/- 6.2 at follow-up

Conclusion: Whereas apical and midventricular TTS have specific wall motion abnormalities that would indicate microvascular dysfunction in specific coronary distribution areas, microvascular dysfunction affects all three mainvessels. Moreover, the microvascular dysfunction is transient with caIMR values normalizing over time. Our findings further strengthen the hypothesis that TTS is due to a severe transient microvascular dysfunction, which might play an important role in the development of therapeutic strategies for fulminant TTS.