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

Figure 1. Comparison of CFR values in the LAD territory (left) and the LCx/OM/RI territory (right) between the apical (AP, blue) and midventricular (MV, red) TTS phenotypes. The boxplot shows the median, interquartile range (IQR), and whiskers (1.5 × IQR); dots represent individual patient values. The dotted line indicates the CFR threshold of 2. * p < 0.05. AP, apical phenotype; MV, midventricular phenotype; CFR, coronary flow reserve; LAD, left anterior descending artery; LCx/OM/RI, left circumflex artery/obtuse marginal branch/ramus intermedius; IQR, interquartile range; TTS, Takotsubo syndrome.

Figure 2. Relationship between CFR values in the LAD territory (x-axis) and the LCx/OM/RI territory (y-axis) in individual patients. Dashed lines indicate the CFR threshold of 2 and delineate four quadrants corresponding to the patterns of territorial distribution of reduced CFR. The downward arrow (↓) denotes reduced CFR (≤2). AP, apical phenotype; MV, midventricular phenotype; CFR, coronary flow reserve; LAD, left anterior descending artery; LCx/OM/RI, left circumflex artery/obtuse marginal branch/ramus intermedius; TTS, Takotsubo syndrome.

Figure 3. Distribution of individual IMR (x-axis) and CFR (y-axis) values in the LAD territory according to TTS phenotype. Dashed lines indicate the thresholds of CFR = 2 and IMR = 25, delineating four CMD subtypes. No CMD: CFR > 2 and IMR ≤ 25; isolated IMR elevation: CFR > 2 and IMR > 25; Pattern A: CFR ≤ 2 and IMR ≤ 25; Pattern B: CFR ≤ 2 and IMR > 25. AP, apical phenotype; MV, midventricular phenotype; CFR, coronary flow reserve; IMR, index of microcirculatory resistance; CMD, coronary microvascular dysfunction.

Figure 4. Distribution of individual IMR (x-axis) and CFR (y-axis) values in the LCx/OM/RI territory according to TTS phenotype. Dashed lines indicate the thresholds of CFR = 2 and IMR = 25, delineating four CMD subtypes. No CMD: CFR > 2 and IMR ≤ 25; isolated IMR elevation: CFR > 2 and IMR > 25; Pattern A: CFR ≤ 2 and IMR ≤ 25; Pattern B: CFR ≤ 2 and IMR > 25. AP, apical phenotype; MV, midventricular phenotype; CFR, coronary flow reserve; IMR, index of microcirculatory resistance; CMD, coronary microvascular dysfunction.

Figure 5. Distribution of CMD subtypes in the LAD territory according to TTS phenotype. Values are expressed as the proportion of patients (%) in each group. The asterisk (*) indicates a statistically significant difference between phenotypes (p < 0.05); all p-values are unadjusted and should be interpreted as exploratory. Subtype analysis of the LCx/OM/RI territory showed no phenotype-specific differences in any of the four categories (all p = 1.000). The upward arrow (↑) denotes elevated IMR (>25). AP, apical phenotype; MV, midventricular phenotype; CMD, coronary microvascular dysfunction; IMR, index of microcirculatory resistance.

Figure 6. Individual trajectories of left ventricular ejection fraction (LVEF) from admission to week 12 in patients with apical (AP, left, blue) and midventricular (MV, right, red) TTS phenotypes. The bold line indicates the group median; open symbols indicate median values at each time point. The dotted line indicates the lower limit of normal LVEF (55%). Admission LVEF is shown only for patients with complete follow-up data (AP: n = 16; MV: n = 11); therefore, the AP admission median (43.5%) differs slightly from that shown in Table 2 (42%), which includes all 20 patients with the AP phenotype. AP, apical phenotype; MV, midventricular phenotype; LVEF, left ventricular ejection fraction; TTS, Takotsubo syndrome.