Prevalence of thrombophilic disorders in takotsubo patients: the (ThROmbophylia in TAkotsubo cardiomyopathy) TROTA study

Abstract

Takotsubo cardiomyopathy (TTC) pathophysiology is still unclear. A transient intracoronary thrombosis dissolved at the time of angiography has been hypothesized. We aimed to evaluate the prevalence of thrombophilic disorders in TTC patients. In 75 TTC women, 75 age- and sex-matched acute coronary syndrome (ACS) patients, both enrolled during the acute phase, and in 75 control subjects, we compared the prevalence of congenital and acquired thrombophilic alterations and the values of clotting and endothelial activation biomarkers. Some parameters were re-assessed 1 month after the acute phase in TTC patients. No significant difference between the three groups was observed in factor II (G20210A) and V (G1691A) polymorphisms prevalence. Homocysteine levels were significantly higher in ACS patients vs. TTC and control subjects. Lipoprotein(a) values trended to be higher in TTC patients vs. control subjects, though not significantly. Other thrombophilic alterations in TTC patients were similar to that previously reported in healthy women. Von Willebrand factor and plasminogen activator inhibitor-1 were significantly higher in TTC and in ACS patients than controls. Clotting activation biomarkers were not statistically different between TTC patients and controls. During follow-up, in TTC patients, endothelial damage indices significantly decreased while clotting activation biomarkers remained unchanged. In conclusion, our results, showing a rate of thrombophilic alterations in TTC patients similar to control subjects, do not support the transient intracoronary thrombus hypothesis. However, several endothelial damage markers and lipoprotein(a) were higher in TTC patients vs. controls suggesting a role of endothelial dysfunction and of other factors concurring to hyperviscosity, as recently hypothesized.

Short- and Long-Term Incidence of Thromboembolic Events in Takotsubo Syndrome as Compared With Acute Coronary Syndrome

“…27 Several endothelial markers, clotting activation biomarkers (von Willebrand factor and plasminogen), and lipoprotein a levels were higher in patients with TTS as compared with the healthy population, suggesting a role of endothelial dysfunction and similar pathologies contributing to the hyperviscosity of blood flow in TTS. 28 One potential explanation for the high rate of thromboembolic events in TTS compared with ACS might be due to the fact that the recovery from impaired LV function is much earlier than in the setting of an ACS. However, in the long term, the risk of thromboembolism is higher in TTS compared with ACS.…”

“…16 Even more, it has been reported that thrombus formation is a common finding in the right ventricle, especially in TTS cases with right ventricular involvement. 28 Additionally, in rare cases, tumor or thrombus formation may challenge physicians, leading to overlooking thrombus formation. 29,30 In rare cases, the use of computed tomography and cardiac magnetic resonance imaging might be required to rule out intraventricular thrombus.…”

Takotsubo Stress Syndrome and Intracoronary Thromboembolic Occlusion: Fact or Myth?

“…No significant alterations have been seen in thrombophilic factors in takotsubo syndrome on serology [1] and no plaque rupture has been noted on intravascular ultrasound [2]. However, Pawlowski, et al described vulnerable plaque surface, platelet activity and subsequent thrombus formation in virtual histology intravascular ultrasound evaluation of the left anterior descending coronary artery in slight or non-significant lesions [3].…”

Genetic and Epigenetic Factors of Takotsubo Syndrome: a Systematic Review

“…Current literature has focused on the possible existence of associations between TTS and single nucleotide polymorphisms (SNPs) in genes associated with sympathetic stress. Several studies analysing polymorphisms potentially involved in the pathogenesis of TTS have been published (Table 2) [21][22][23][24][25][26][27][28][29][30][31][32][33].…”