Takotsubo cardiomyopathy (TC) was described for the first time in the 1990 in Japan. This cardiomyopathy affects usually postmenopausal woman and it is often related to physical or emotional stress [
TC presentation is “acute coronary syndrome-like” with chest pain, electrocardiographic alterations, left ventricle (LV) systolic dysfunction, and minimal troponin elevation and represents 1-2% of the ST-segment elevation myocardial infarction. Coronary angiography reveals normal or near-normal coronary arteries and the ventricle function usually recovers in a few weeks. The typical pattern of TC shows apical dysfunction (apical ballooning) at echocardiography and ventriculography, but other morphologies of TC are reported [
Our study evaluated the role of MVD in TC assessing the flow and the perfusion at coronary angiography. We compared these results to another setting of supposed MVD like microvascular angina (MVA) and a control group (CG).
We retrospectively screened 42 consecutive patients with TC presented at our centre from October 2013 to January 2017. Out of 42 patients, we selected 27 cases. 15 patients were excluded because coronary angiography was not long enough to study myocardial perfusion with the blush score. Diagnosis of TC was achieved according to the presence of all 4 Mayo Clinic criteria [ Transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid segments with or without apical involvement: the regional wall motion abnormalities extend beyond a single epicardial vascular distribution Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture New electrocardiographic abnormalities (ST-segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin Absence of pheochromocytoma or myocarditis.
27 age- and sex-matched patients with MVA were selected as a second group. MVA diagnosis was defined according to these features: typical chest pain according to the ESC guidelines [
The CG included 27 age- and sex-matched patients with atypical chest pain and normal coronary arteries at the angiography.
Angiograms were acquired with Philipp Allura FD 10 X-ray machine at 15 frames/sec using a manual injection of 5–10 mL of contrast. Iomeron 350 (Bracco Imaging Deutschland) or Ultravist 370 (Bayer Pharma) was used as a dye. For every patient the angiogram with no or minimal overlapping of the territories perfused by each vessel was selected and analysed offline. Qualitative assessment of epicardial coronary flow was measured using Thrombolysis In Myocardial Infarction (TIMI) flow criteria [
Myocardial blush is the myocardial opacification resulting from injection of contrast into the coronary vessels and it depends on the microcirculation resistance if there is no evidence of obstructive (more than 70%) epicardial coronary stenosis. Qualitative assessment (blush score) was measured according to Van’t Hof et al. [
TIMI, TFC, blush grade, and QuBE were angiographically analysed by one interventional cardiology, a second assessment of all variables was repeated by a second observer blinded to the clinical data.
Frequencies and percentages are given for quantitative variables. Variables were expressed as mean ± standard deviation (SD) or as median and interquartile range (IQR). Normality was tested by Shapiro-Wilk test. Categorical variables were expressed as percentages and analysed by two-tailed Fisher’s exact test. The proportion of the categorical variables was compared using a chi-square analysis. Continuous variables were expressed as mean ± SD and compared with the Student’s
This is an observational study; all patients provided informed consent for the coronary angiography due to clinical indication.
Clinical characteristics of study population are presented in Table
Baseline characteristics of the patients.
TC ( | MVA ( | CG ( | | |
---|---|---|---|---|
Age | | | | NS |
Female | 23 (85%) | 23 (85%) | 23 (85%) | NS |
Caucasian | 27 (100%) | 27 (100%) | 27 (100%) | NS |
Hypertension | 15 (55%) | | 20 (74%) | NS |
Diabetes Mellitus | 3 (11%) | 5 (18%) | 3 (11%) | NS |
Hypercholesterolemia | 15 (55%) | 13 (48%) | 16 (59%) | NS |
Current Smoking | 10 (37%) | 6 (22%) | 8 (30%) | NS |
EF, % | | | | |
Menopause | 26 (96%) | | | |
Emotional trigger | 6 (22%) | | | |
Physical trigger | 11 (40%) | | | |
Apical pattern | 23 (85%) | | | |
LVOT obstruction | 3 (11%) | | | |
Troponin | | | | |
ST-segment elevation | 11 (40%) | | | |
Prolonged | 9 (33%) | | | |
EF ≤ 35% | 17 (63%) | | | |
Inotropic support | 6 (22%) | | | |
In-hospital death | 3 (11%) | | | |
TC: Takotsubo cardiomyopathy; MVA: microvascular angina; CG: control group; LVOT: left ventricle outflow tract obstruction; EF: ejection fraction. NS: nonsignificant;
Seventeen (63%) patients had severe reduction of ejection fraction and six of them required inotropic support for low cardiac output with a rate of in-hospital death of 11%.
Qualitative study of the TIMI flow in the LAD was lower in TC than in the CG (
Coronary flow evaluation in the three groups.
TC ( | MVA ( | CG ( | | |
---|---|---|---|---|
TIMI 3 LAD | 19 (70%) | 22 (81%) | 26 (96%) | |
TFC LAD | | | | |
TIMI 3 RCA | 27 (100%) | 27 (100%) | 27 (100%) | NS |
TFC RCA | | | | |
TIMI 3 LC | 27 (100%) | 25 (93%) | 27 (100%) | NS |
TFC LC | | | | |
TC: Takotsubo cardiomyopathy; MVA: microvascular angina; CG: control group; LAD: left anterior descending coronary artery; RCA: right coronary artery; LC: left circumflex coronary artery;
TIMI frame count in the LAD, RCA, and LC for the three groups. TC: Takotsubo cardiomyopathy; MVA: microvascular angina; CG: control group; TFC: TIMI frame count; LAD: left anterior descending coronary artery; RCA: right coronary artery; LC: left circumflex coronary artery; NS: nonsignificant.
No significant difference was reported between observers (
The qualitative evaluation of the blush score was significantly lower in the TC than in the other groups; a blush score of 3 was observed only in the 70% of the patients with TS versus all of them in the others groups (
Myocardial perfusion evaluation in the three groups.
TC ( | MVA ( | CG ( | | |
---|---|---|---|---|
Blush LAD | 19 (70%) | 27 (100%) | 27 (100%) | |
QuBE LAD | 8,9 (7,2–11,5) | 13,5 (10–16) | 11,4 (10–15,7) | |
Blush 3 RCA | 26 (96%) | 27 (100%) | 27 (100%) | NS |
QuBE RCA | 10 (7,7–12,4) | 11 (9–15,4) | 10,5 (7,7–13) | NS |
Blush 3 LC | 27 (100%) | 26 (96%) | 27 (100%) | NS |
QuBE LC | 10,4 (7,1–12,8) | 13 (10–17) | 11,5 (9,5–15) | NS |
TC: Takotsubo cardiomyopathy; MVA: microvascular angina; CG: control group; TFC: TIMI frame count; QuBE: Quantitative Blush Evaluator; LAD: left anterior descending coronary artery; RCA: right coronary artery; LC: left circumflex coronary artery;
Similarly, the quantitative blush evaluation with QuBE software in TC group showed a significant impairment of myocardial perfusion in the LAD compared to the others groups (TC 8,9 (7,2–11,5) versus CG 11,4 (10–15,7);
Quantitative blush assessment in the LAD, RCA, and LC for the three groups. TC: Takotsubo cardiomyopathy; MVA: microvascular angina; CG: control group; QuBE: Quantitative Blush Evaluator; LAD: left anterior descending coronary artery; RCA: right coronary artery; LC: left circumflex coronary artery; NS: nonsignificant. Red circle: mild outliers; red star: extreme outliers.
No significant difference was reported between observers (
Pathophysiology of TC has not been completely clarified. Several hypotheses have been proposed: transitory epicardial coronary spasm, myocarditis, alterations of the coronary microcirculation, catecholamine excess, sympathetic nervous system hyperactivity in a setting of estrogenic deficiency, and genetic predisposition [
In our study, we retrospectively studied angiographic analysis of coronary flow and myocardial perfusion in patients with TC compared to MVA and a CG to assess the possible role of MVD in TC. We compared the flow and the perfusion using both qualitative (TIMI flow, blush score) and quantitative technique (TFC, QuBE). Our patients data were typical for TC [
We reported increased LAD TFC (mean value of 22) and reduced QuBE value on the LAD territory (mean value of 9) even in the four patients without apical pattern of TS (midventricular pattern). These findings suggested that the flow and the perfusion on the LAD territory are impaired regardless of the morphological pattern. Other papers described the mismatch between the akinetic territory and the area affected by the microcirculatory dysfunction [
The coronary flow, as expected, was impaired in MVA patients for the underlying microvascular dysfunction.
Qualitative and quantitative data suggested that perfusion is impaired in TC compared with both the MVA and the CG, but only in the LAD region. No differences were reported in the blush and QuBE in the RCA and LC area in the three groups. Furthermore, the perfusion evaluated by QuBE in MVA patients was similar to the CG. This last data is probably due to the fact that the patients, at the time of the angiography, were at rest, in optimal medical therapy, and that the jeopardized area of ischemia, typical of MVA, did not allow finding out alteration in the blush with QuBE even if it is probably present.
According to the literature, controversial results about TFC in TC are reported: Khalid et al. observed that, in 16 TC patients, TFC was higher compared to controls in LAD artery, but not in the other vessels [
Our data confirmed deterioration of the epicardial flow in TC that it is probably due to MVD with a significant impairment of myocardial perfusion in LAD territory and this finding could not be related to morphological pattern of TC presentation.
Our study presents some limitations:
In conclusion, our study showed that the epicardial coronary flow is impaired in TC and in MVA compared to a CG, reflecting a MVD. However, it seemed to be related to myocardial perfusion defect only in the LAD area as proved by QuBE.
Takotsubo cardiomyopathy
Microvascular dysfunction
Microvascular angina
Control group
TIMI frame count
Quantitative Blush Evaluator
Left anterior descending artery
Right coronary artery
Left circumflex coronary artery
Ejection fraction.
All the authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
The authors have no conflicts of interest to declare.