COVID-19: A double threat to takotsubo cardiomyopathy and spontaneous coronary artery dissection?

Med Hypotheses. 2021 Jan:146:110410. doi: 10.1016/j.mehy.2020.110410. Epub 2020 Nov 22.


Coronavirus disease 2019 (COVID-19) is an ongoing pandemic that has affected millions of individuals worldwide. Prior studies suggest that COVID-19 may be associated with an increased risk for various cardiovascular disorders, such as myocardial injury, arrhythmia, acute coronary syndrome, and venous thromboembolism. Early reports of non-COVID-19 patients have described the concurrence of takotsubo cardiomyopathy (TTC) and spontaneous coronary artery dissection (SCAD). However, the interplay between COVID-19, TTC and SCAD has not been well established. We herein propose two sets of two-hit hypotheses for the development of SCAD and TTC in the context of COVID-19. The first two-hit hypothesis explains the development of SCAD, in which TTC-associated formation of vulnerable coronary substrate serves as the first hit (predisposing factor), and COVID-19-associated inflammation and vascular disruption serves as the second hit (precipitating factor). The second two-hit hypothesis is proposed to explain the development of TTC, in which SCAD-associated formation of vulnerable myocardial substrate serves as the first hit, and COVID-19-associated sympathetic overactivity serves as the second hit. Under this conceptual framework, COVID-19 poses a double threat for the development of SCAD (among patients with underlying TTC) as well as TTC (among patients with underlying SCAD), thereby forming a reciprocal causation. This hypothesis provides a rationale for the joint assessment of TTC and SCAD in COVID-19 patients with pertinent cardiovascular manifestations.

Keywords: Acute coronary syndrome; COVID-19; Spontaneous coronary artery dissection; Stress cardiomyopathy; Takotsubo cardiomyopathy.

Publication types

  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • COVID-19 / complications*
  • COVID-19 / epidemiology
  • Causality
  • Coronary Vessel Anomalies / epidemiology
  • Coronary Vessel Anomalies / etiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Cardiovascular*
  • Pandemics
  • Risk Factors
  • SARS-CoV-2* / pathogenicity
  • Takotsubo Cardiomyopathy / epidemiology
  • Takotsubo Cardiomyopathy / etiology*
  • Vascular Diseases / congenital*
  • Vascular Diseases / epidemiology
  • Vascular Diseases / etiology

Supplementary concepts

  • Coronary Artery Dissection, Spontaneous