Takotsubo Syndrome: Increased Incidence of Stress Cardiomyopathy During COVID-19

Takotsubo Syndrome: Increased Incidence of Stress Cardiomyopathy During COVID-19

Among the various cardiovascular sequalae associated with COVID-19, an increase in the number of cases of stress cardiomyopathy – also referred to as Takotsubo syndrome (TTS) – have been reported since the pandemic began. According to the results of a cohort study (N=1,914) published in July 2020 in JAMA Network Open, the incidence of stress cardiomyopathy increased roughly 4-fold in the early months of the pandemic, from 1.5%-1.8% to 7.8%.1

Risk Factors and Diagnosis

The growing number of TTS cases has been attributed both to the pathophysiology of COVID-19 infection and the multiple stressors related to the pandemic. In a study by Chang et al, COVID-19 infection was present in 66.7% of patients, while emotional triggers, psychiatric disorders, and neurologic disorders were reported in 33.3%, 12.1%, and 6.1% of patients, respectively.2

“Clearly being infected and its health sequela predominate, but also fear of infection, changes in lifestyle, loss of employment, grief of loss, and social isolation for prolonged periods are all involved,” explained Dr Eduardo de Marchena, MD, FACC, FACP, FSCAI, associate dean for international medicine, professor of medicine and surgery, and director of interventional cardiology at the University of Miami Miler School of Medicine in Miami.

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Some findings indicate a slight shift in predisposing factors for TTS during vs before the pandemic. While TTS has traditionally occurred primarily in older women with psychiatric or neurologic disorders, with psychological stress as the triggering factor, it has been “increasingly reported in the setting of physical stress (mostly COVID-19 pneumonia)–triggered male patients without psychiatric/neurologic disorders,” Chang et al stated.2

Nonetheless, the link between TTS and elevated levels of stress and anxiety is well-established. The increase in TTS cases more likely stems from the psychological, social, and economic distress related to the pandemic rather than direct mechanisms of viral involvement.1

Dr de Marchena notes the importance of remaining vigilant to the possibility of a TTS diagnosis, as the condition may present with nonspecific symptoms. TTS may be misdiagnosed as acute coronary syndrome (ACS) due to shared symptoms, including chest pain and dyspnea, along with signs of myocardial injury or ischemia on ECG and troponin elevations.3,4 The International Takotsubo (InterTAK) syndrome diagnostic criteria are used in the diagnosis of TTS, with coronary angiography representing the gold standard diagnostic tool in differentiating between TTS and ACS.5,4

Typical Outcomes

Limited findings have indicated high rates of complications and mortality in patients presenting with TTS among these recent cases. In a 2021 study of 123 patients with TTS, Chang et al found an overall in-hospital mortality rate of 23.3%, with higher mortality observed among men (38.7%) compared with women (13.9%).2 The prognosis is generally more favorable in patients with primary TTS (presenting for treatment due to TTS symptoms, usually with a clearly identifiable emotional trigger) compared to those with secondary TTS due to serious underlying illness or injury.4

Overall, TTS is “generally a transient disorder that is managed with supportive therapy,” said Dr Ahmad Jabri, MD, a cardiology fellow at MetroHealth in Cleveland, Ohio who served as lead author of the JAMA Network Open study while he was with the Cleveland Clinic.1 “Conservative treatment and resolution of the physical or emotional stress usually result in rapid resolution of symptoms, although some patients develop acute complications such as shock and acute heart failure that require intensive therapy.”

In February 2021, Dr de Marchena and colleagues published a case report describing 2 elderly women who presented with chest pain and ACS, who were ultimately diagnosed with stress cardiomyopathy triggered by increased pandemic-related emotional stress.6 The patients were treated with beta blockers and anxiolytics, and 1-month follow-up showed resolution on ECG, thus confirming these cases to be stress-mediated.

Another group reported a TTS patient who developed the symptoms of chest pain and dyspnea while watching an anxiety-provoking news program about the COVID-19 pandemic. “Symptoms resolved during the first few hours of hospitalization… [and she] was discharged with prescription of metoprolol and apixaban,” the authors wrote.4 “A follow-up echocardiogram 1 month later was entirely normal, with left ventricular ejection fraction of 75% and resolution of all previous anomalies including wall motion abnormalities, systolic anterior motion, and dynamic outflow tract gradient.”

A similar case report described a 71-year-old woman with TTS that appeared to be related to social isolation and emotional stressors related to reduced family contact during the pandemic.7

Key Considerations and Next Steps

“We should also question our patients about life stressors and encourage socialization either virtually or with safe in-person contact,” Dr de Marchena advised. “Obviously the effect of job loss, family tensions, and other issues are difficult to quantitate but should be discussed with patients, and social workers and community organizations can greatly assist in these areas as well.” 

He pointed to the need for urgent measures to help high-risk patients cope with ongoing stressors and thus potentially prevent the occurrence of TTS. Additional research is warranted to elucidate the mechanisms of TTS, as well as strategies for early recognition and treatment with both pharmacotherapy and psychotherapy.

“Research should also be done to gain insights into potential causes, such as adverse changes in population-scale mental health,” Dr Jabri added. “Such research may document a need for interventions to protect the emotional health of communities during widespread disasters.”


Jabri A, Kalra A, Kumar A, et al. Incidence of stress cardiomyopathy during the coronavirus disease 2019 pandemic. JAMA Netw Open. Published online July 9, 2020. doi:10.1001/jamanetworkopen.2020.14780Chang A, Wang YG, Jayanna MB, Wu X, Cadaret LM, Liu K. Mortality correlates in patients with Takotsubo syndrome during the COVID-19 pandemic. Mayo Clin Proc Innov Qual Outcomes. 2021;5(6):1050-1055. doi:10.1016/j.mayocpiqo.2021.09.008Casagrande M, Forte G, Favieri F, et al. The broken heart: The role of life events in Takotsubo syndrome. J Clin Med. 2021;10(21):4940. doi:10.3390/jcm10214940O’Keefe EL, Torres-Acosta N, O’Keefe JH, Sturgess JE, Lavie CJ, Bybee KA. Takotsubo syndrome: Cardiotoxic stress in the COVID era. Mayo Clin Proc Innov Qual Outcomes. 2020;4(6):775-785. doi:10.1016/j.mayocpiqo.2020.08.008Ghadri JR, Wittstein IS, Prasad A, et al. International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology. Eur Heart J. 2018;39(22):2032-2046. doi:10.1093/eurheartj/ehy076Kir D, Beer N, De Marchena EJ. Takotsubo cardiomyopathy caused by emotional stressors in the coronavirus disease 2019 (COVID-19) pandemic era. J Card Surg. Published online December 18, 2021. doi:10.1111/jocs.15251Rivers J, Ihle JF. COVID-19 social isolation-induced takotsubo cardiomyopathy. Med J Aust. Published online September 9, 2020. doi:10.5694/mja2.50770

This article originally appeared on The Cardiology Advisor

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