THI Scientists Identify Common Respiratory Diseases That Trigger Takotsubo Syndrome

In the Molecular Cardiology Research Laboratories at the Texas Heart Institute (THI), scientists perform basic research to understand the molecular mechanisms of heart disease and to find ways to improve the treatments available for patients with cardiovascular disease. One area of their research is takotsubo syndrome (TTS), which is an acute transient cardiovascular condition characterized by localized left ventricular dysfunction.


TTS, which was first described in 1990, can be induced by severe emotional or physical stress. Because the primary symptoms of TTS are chest pain and shortness of breath, it is often misdiagnosed as a heart attack. Although patients with TTS may have obstructive coronary artery disease that blocks blood flow to the heart, the presence of coronary lesions cannot fully explain the observed ventricular dysfunction in TTS. Given that TTS has been recently recognized as having a high risk of mortality, understanding and identifying the triggers of TTS are critical for managing the care of these patients.


Recent studies have pointed to an association between respiratory disease and TTS. Respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma are highly prevalent, affecting more than 5% and 8% of the general population, respectively. Other respiratory illnesses, including pneumonia, pulmonary embolism, and lung cancer, are common conditions that require hospitalization. Given that these respiratory conditions are associated with TTS, the possibility remains that they may also trigger TTS and affect its clinical course.


To understand the complex relationship between respiratory disease and TTS, Drs. Richard A. F. Dixon, Qi Liu, and Su Pan of the Molecular Cardiology Research Laboratories at THI and their collaborators performed a comprehensive systematic review of the literature, analyzing the available evidence for the association between TTS and common respiratory illnesses, including COPD, asthma, pneumonia, pulmonary embolism, and lung cancer. Their findings were recently published in European Heart Journal Open.


After performing searches in multiple databases, the THI researchers identified 99 studies containing a total of 108 patients that met the criteria for their analysis. In these studies, patients must have been hospitalized for one of the above-mentioned respiratory conditions and found to have TTS at the time of admission. Among the TTS cases, 39.8% were associated with obstructive lung disease (including COPD and asthma), and 38.9% were associated with pneumonia (including COVID-19 and other pneumonia). Relatively fewer cases of TTS were associated with pulmonary embolism (11.1%) or lung cancer (10.2%).


In addition, the THI researchers compared their data to those reported by Templin et al. (Templin, C. et al., N Engl J Med 2015;373:929-938) in a study of patients with any TTS (ie, not just patients with respiratory disease and TTS). Importantly, patients with coexisting respiratory disease and TTS from the THI analysis had a higher in-hospital mortality rate than did patients with any type of TTS in the study by Templin et al. (12.5% vs. 4.1%, P<0.001). Together, these findings support that obstructive lung disease and pneumonia are respiratory triggers of TTS and that patients with coexisting respiratory disease and TTS have an even higher risk of mortality than patients with any TTS.


Few large-scale studies have evaluated the association between respiratory disease and TTS. Until now, the data supporting these observations have been limited. As Dr. Dixon, Director Emeritus of the Molecular Cardiology Research Laboratories at THI points out, “Patients with acute respiratory conditions make up a large percentage of ER visits and hospitalizations in the United States.

These findings bring attention to this unique subset of patients with coexisting respiratory disease and TTS and will help raise awareness of the special clinical considerations that need to be made when managing the care of these patients.” One consideration is that concurrently diagnosing TTS in patients with respiratory disease can be challenging and may be delayed because of the atypical presentation of TTS. A high degree of clinical suspicion is required to make an accurate diagnosis and initiate the appropriate therapy. In addition, medications and invasive procedures used in managing respiratory disease may contribute to TTS development. Because the suggested pathophysiology of TTS varies with each respiratory condition, future prospective studies are needed to investigate the underlying mechanisms of TTS development for each respiratory disease.

As Dr. Dixon concludes, “Our data show the potential impact of coexisting respiratory disease and TTS on mortality, as well as morbidity, complications, hospitalization, outcomes, and hospital length of stay. The next crucial step will be to perform additional studies so that we can move closer to establishing appropriate guidelines for managing respiratory disease concurrent with TTS.”


Read Report

Li P, Wang Y, Liang J, Zuo X, Li Q, Sherif AA, Zhang J, Xu Y, Huang Z, Dong M, Teng C, Pan S, Dixon RAF, Wei X, Wu L, Jin C, Cai P, Dai Q, Ma J, Liu Q, European Heart Journal Open, Volume 2, Issue 2, March 2022, oeac009,

News Story By Nicole Stancel, PhD, ELS(D)

Pictured:  Drs. Qi Liu, Richard A. F. Dixon, and Su Pan