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Coronary microvascular dysfunction in Takotsubo syndrome and associations with left ventricular function

Ekenbäck, Christina ; Nickander, Jannike ; Jokhaji, Fadi ; Tornvall, Per ; Engblom, Henrik LU ; Spaak, Jonas and Persson, Jonas (2023) In ESC Heart Failure 10(4). p.2395-2405
Abstract

Aims: Coronary microvascular dysfunction (CMD) has been proposed as an important pathophysiological mechanism in Takotsubo syndrome (TTS). Our aims were (i) to evaluate and compare levels of CMD in patients with TTS and patients with ischaemia and no obstructive coronary arteries (INOCA) and (ii) to investigate associations between CMD and clinical parameters, left ventricular function, and coronary atherosclerosis in TTS. Methods and results: We conducted a prospective study of 27 female TTS patients and an equally sized, age- and gender-matched, cohort of INOCA patients. Coronary microvascular function was quantified invasively using the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve... (More)

Aims: Coronary microvascular dysfunction (CMD) has been proposed as an important pathophysiological mechanism in Takotsubo syndrome (TTS). Our aims were (i) to evaluate and compare levels of CMD in patients with TTS and patients with ischaemia and no obstructive coronary arteries (INOCA) and (ii) to investigate associations between CMD and clinical parameters, left ventricular function, and coronary atherosclerosis in TTS. Methods and results: We conducted a prospective study of 27 female TTS patients and an equally sized, age- and gender-matched, cohort of INOCA patients. Coronary microvascular function was quantified invasively using the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve ratio (RRR). CMD was defined as IMR ≥ 25 and/or CFR ≤ 2. In the TTS patients, left ventricular function was assessed with echocardiography and cardiovascular magnetic resonance (CMR) imaging, and coronary atherosclerosis was visualized with intravascular ultrasound with near-infrared spectroscopy (IVUS-NIRS). The incidence of CMD was higher in the TTS patients than in the INOCA cohort (78% vs. 44%, P = 0.01), with higher IMR (30 vs. 14, P = 0.002), lower CFR (1.8 vs. 2.8, P = 0.009), and lower RRR (2.1 vs. 3.5, P = 0.003). In apical compared with midventricular TTS, IMR was numerically higher (50 vs. 28, P = 0.20), whereas CFR and RRR were lower (1.5 vs. 2.5, P = 0.003 and 1.6 vs. 2.7, P = 0.01, respectively). Global longitudinal strain and global circumferential strain, assessed with CMR imaging, were more impaired in apical than in midventricular TTS (−11 vs. −14, P < 0.001 and −12 vs. −15, P = 0.049, respectively). In the TTS patients, CFR and RRR correlated with echocardiography-derived (R2 = 0.15, P = 0.002 and R2 = 0.18, P = 0.007, respectively) and CMR-derived (R2 = 0.09, P = 0.025 and R2 = 0.10, P = 0.038, respectively) ejection fraction. CFR and RRR correlated inversely with CMR-derived end-diastolic volume index, end-systolic volume index, and left ventricular mass index. IMR, CFR, and RRR were not associated with measures of coronary atherosclerosis derived by IVUS-NIRS. Conclusions: Coronary microvascular dysfunction is common in patients with TTS and more frequent than in patients with INOCA. CMD in TTS is more severe in the apical compared with the midventricular phenotype of the syndrome, is associated with left ventricular function, but is unrelated to coronary atherosclerosis. Our results support the notion of CMD as a key mediator in TTS.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiovascular magnetic resonance imaging, Coronary flow reserve, Coronary microvascular dysfunction, Index of microcirculatory resistance, Ischaemia and no obstructive coronary arteries, Takotsubo syndrome
in
ESC Heart Failure
volume
10
issue
4
pages
11 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • pmid:37218383
  • scopus:85159888432
ISSN
2055-5822
DOI
10.1002/ehf2.14394
language
English
LU publication?
yes
id
aef6e4e8-7cd1-4acb-8649-4e97ac80a26f
date added to LUP
2023-09-18 13:04:25
date last changed
2024-04-19 01:17:08
@article{aef6e4e8-7cd1-4acb-8649-4e97ac80a26f,
  abstract     = {{<p>Aims: Coronary microvascular dysfunction (CMD) has been proposed as an important pathophysiological mechanism in Takotsubo syndrome (TTS). Our aims were (i) to evaluate and compare levels of CMD in patients with TTS and patients with ischaemia and no obstructive coronary arteries (INOCA) and (ii) to investigate associations between CMD and clinical parameters, left ventricular function, and coronary atherosclerosis in TTS. Methods and results: We conducted a prospective study of 27 female TTS patients and an equally sized, age- and gender-matched, cohort of INOCA patients. Coronary microvascular function was quantified invasively using the index of microcirculatory resistance (IMR), coronary flow reserve (CFR), and resistive reserve ratio (RRR). CMD was defined as IMR ≥ 25 and/or CFR ≤ 2. In the TTS patients, left ventricular function was assessed with echocardiography and cardiovascular magnetic resonance (CMR) imaging, and coronary atherosclerosis was visualized with intravascular ultrasound with near-infrared spectroscopy (IVUS-NIRS). The incidence of CMD was higher in the TTS patients than in the INOCA cohort (78% vs. 44%, P = 0.01), with higher IMR (30 vs. 14, P = 0.002), lower CFR (1.8 vs. 2.8, P = 0.009), and lower RRR (2.1 vs. 3.5, P = 0.003). In apical compared with midventricular TTS, IMR was numerically higher (50 vs. 28, P = 0.20), whereas CFR and RRR were lower (1.5 vs. 2.5, P = 0.003 and 1.6 vs. 2.7, P = 0.01, respectively). Global longitudinal strain and global circumferential strain, assessed with CMR imaging, were more impaired in apical than in midventricular TTS (−11 vs. −14, P &lt; 0.001 and −12 vs. −15, P = 0.049, respectively). In the TTS patients, CFR and RRR correlated with echocardiography-derived (R<sup>2</sup> = 0.15, P = 0.002 and R<sup>2</sup> = 0.18, P = 0.007, respectively) and CMR-derived (R<sup>2</sup> = 0.09, P = 0.025 and R<sup>2</sup> = 0.10, P = 0.038, respectively) ejection fraction. CFR and RRR correlated inversely with CMR-derived end-diastolic volume index, end-systolic volume index, and left ventricular mass index. IMR, CFR, and RRR were not associated with measures of coronary atherosclerosis derived by IVUS-NIRS. Conclusions: Coronary microvascular dysfunction is common in patients with TTS and more frequent than in patients with INOCA. CMD in TTS is more severe in the apical compared with the midventricular phenotype of the syndrome, is associated with left ventricular function, but is unrelated to coronary atherosclerosis. Our results support the notion of CMD as a key mediator in TTS.</p>}},
  author       = {{Ekenbäck, Christina and Nickander, Jannike and Jokhaji, Fadi and Tornvall, Per and Engblom, Henrik and Spaak, Jonas and Persson, Jonas}},
  issn         = {{2055-5822}},
  keywords     = {{Cardiovascular magnetic resonance imaging; Coronary flow reserve; Coronary microvascular dysfunction; Index of microcirculatory resistance; Ischaemia and no obstructive coronary arteries; Takotsubo syndrome}},
  language     = {{eng}},
  number       = {{4}},
  pages        = {{2395--2405}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{ESC Heart Failure}},
  title        = {{Coronary microvascular dysfunction in Takotsubo syndrome and associations with left ventricular function}},
  url          = {{http://dx.doi.org/10.1002/ehf2.14394}},
  doi          = {{10.1002/ehf2.14394}},
  volume       = {{10}},
  year         = {{2023}},
}