3 DISCUSSION
TTC is an acute reversible myocardial injury first reported by Sato et al. in 1990. The term “takotsubo” means an octopus fishing pot in Japanese that has a round bottom and a narrow neck, and it is similar to the shape of the heart in TTC. TTC is triggered by emotional (negative and positive) or physical stress, including asthma exacerbation. Symptoms similar to those of myocardial infarction have been observed in patients with TTC, without coronary artery stenosis [3,8,9].
The pathophysiology of stress cardiomyopathy is unclear and may involve several mechanisms. One pathway involves high circulating catecholamines released by the sympathetic nerves under stress, including respiratory diseases. Sato et al. showed that microvascular dysfunction and coronary artery spasms cause TTC.
As most patients with TTC are postmenopausal women, estrogen deprivation has been proposed as a cause in several hypotheses [20], whereas some studies have reported abnormalities in the central autonomic nervous system [10].
Although TTC has a good prognosis, patients with TTC sometimes develop heart failure, arrhythmia, systemic embolism, cardiogenic shock, and cardiac rupture, which might be fatal. Underlying diseases triggering TTC increase mortality (12.2% vs. 1.1% in patients without preexisting diseases) [6]. Our patient did not have cardiac complications; however, adequate treatment for asthma was required.
Dyspnea is a common symptom in respiratory illnesses and TTC; therefore, electrocardiography and echocardiography should be performed before the use of SABAs or adrenaline.
Infection with SARS-CoV-2, a novel virus that was first reported in Wuhan, China in 2019, might trigger asthma flare-up; however, the SARS-CoV-2 polymerase chain reaction test of the patient was negative, indicating that she was not infected with SARS-CoV-2. COVID-19 aggravates many diseases; therefore, vaccines have been developed and implemented rapidly worldwide to reduce the risk of progression and death. mRNA-based COVID-19 vaccines are effective and safe. Nonetheless, adverse events associated with the vaccines are not completely understood. Almost all COVID-19 vaccines used in Japan are mRNA-based.
TTC has been reportedly triggered by mRNA-based COVID-19 vaccines [11,12,13] or the influenza vaccine [12,14]. However, our patient had status asthmaticus, and the vaccination did not seem directly of TTC, despite her symptoms being common to both diseases.
Colaneri et al. reported a case of asthma exacerbation triggered by an mRNA-based COVID-19 vaccine [1]. mRNA-based vaccines promote secretion of type I interferons and that increased interferon-I production is associated with asthma exacerbation [15,16]. Nappi et al. reported a case in which two doses of the adenovirus-vectored vaccine ChAdOx1 (Astra Zeneca) progressively worsened asthma and a subsequent dose of the COVID-19 vaccine mRNA-1273 (Moderna) triggered eosinophilic granulomatosis with polyangiitis [17]. Regardless of the type of vaccine, COVID-19 vaccination itself may exacerbate asthma.
Hence, we concluded that the mRNA-based vaccine enhanced asthma exacerbation and TTC onset in our patient. However, our study was limited because the relationship between asthma exacerbation and mRNA-based COVID-19 vaccines is currently difficult to demonstrate directly. Thus, more reports and further studies are required.
Between February 17, 2021, and July 25, 2021, 74,137,348 patients received the BNT162b2 vaccine in Japan. Among these, 219 (0.0003%) cases of asthma attacks were reported to the Japanese Ministry of Health, Labour, and Welfare, which indicates a low incidence [18].
Pfaar et al. reported that patients taking biologicals for asthma do not have an increased risk of allergic reactions following COVID-19 vaccination [19].