Coronary Microvascular Dysfunction in Takotsubo Syndrome: Subtype-Specific Patterns Revealed by Invasive Assessment

Background/Objectives: Coronary microvascular dysfunction (CMD) is considered a key mechanism of Takotsubo syndrome (TTS), but its phenotype-specific territorial distribution remains unclear. This study investigated CMD within the left anterior descending artery (LAD) and left circumflex/obtuse marginal/ramus intermedius (LCx/OM/RI) territories in apical (AP) and midventricular (MV) TTS. Methods: In this prospective single-centre study, 31 patients with acute TTS were enrolled (median age, 71 years; 93.5% women; 20 AP and 11 MV). During the acute phase, coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and fractional flow reserve (FFR) were assessed invasively in both territories. CMD was defined as CFR ≤ 2 and/or IMR > 25; the neutral descriptive subtypes Pattern A (CFR ≤ 2 with IMR ≤ 25) and Pattern B (CFR ≤ 2 with IMR > 25) were distinguished. Results: FFR was ≥0.80 in all patients, excluding haemodynamically significant epicardial disease; at least one abnormal microvascular parameter was present in 26/31 patients (83.9%). LAD-CFR was significantly lower in AP than in MV TTS (1.6 vs. 2.6; p = 0.003), whereas LCx/OM/RI-CFR did not differ (1.6 vs. 1.5; p = 0.679). Bifocal CFR reduction predominated in AP TTS (55.0% vs. 9.1%; p = 0.020), whereas isolated LCx/OM/RI involvement occurred only in MV TTS (45.5% vs. 0.0%; p = 0.003). Pattern B in the LAD territory was more common in AP TTS (50.0% vs. 9.1%; p = 0.047). Conclusions: In this cohort, TTS showed a phenotype-specific territorial distribution of CMD: the apical phenotype predominantly involved Pattern B in the LAD territory, whereas the midventricular phenotype showed isolated LCx/OM/RI involvement within the interrogated left coronary circulation. These hypothesis-generating findings suggest phenotype-associated differences that require confirmation in larger, adequately powered cohorts.