Myocardial Contractile Function Recovery, Systemic Inflammation, and Prognosis in Takotsubo Syndrome
論文ID: CJ-21-0322
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論文ID: CJ-21-0322
Takotsubo syndrome (TTS) was first described approximately 20 years ago as a unique cardiomyopathy resembling myocardial infarction (MI),1,2 but unlike MI, cardiac function improves and so TTS was initially thought to be a benign disease. However, a review3 reported an in-hospital mortality rate of approximately 4–5%, comparable to that for acute MI. The 2 main reasons for death are a lack of evidence-based treatment and comorbidities. TTS prognosis is greatly influenced by non-cardiac diseases, with triggering diseases worsening the patient’s prognosis.4,5
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The cause and pathogenesis of TTS remain unclear. The reasons for delayed improvement in cardiac function are also unclear, although the prognosis of patients with TTS is not poor. Although the left ventricular ejection fraction (LVEF) recovers rapidly and spontaneously in TTS, the long-term clinical and functional consequences are unclear. TTS is thought to have long-term effects on regional myocardial damage, even if LVEF improves. In their study assessing the presence of prolonged cardiac dysfunction in the chronic phase of TTS, Scally et al6 performed echocardiography, cardiac magnetic resonance imaging (MRI), and exercise testing in 37 patients. They reported the long-term clinical consequences of TTS, including persistent latent cardiac dysfunction and impaired exercise capacity.
Why does TTS not restore normal cardiac function in the chronic phase? The delayed myocardial recovery may be mediated by inflammation, edema, and fibrosis. Schwarz et al7 enrolled 52 patients with TTS and evaluated the recovery of cardiac function over 4 months by echocardiography and cardiac MRI. Despite normalization of the overall LVEF, focal LV systolic and diastolic deformation abnormalities persisted after acute events. Although myocardial edema partially subsided, fibrosis persisted after 4 months. Those findings suggest continued regional myocardial dysfunction in the chronic phase, even in cases of TTS with a good clinical course. Therefore, the effects of regional inflammation, edema, and fibrosis in the myocardium may be lead to chronic TTS without improvement in cardiac function.
However, recent studies have reported that B-type natriuretic peptide (BNP) may be more involved than inflammation in the progression of myocardial damage. An observational study on the course of cardiac function and inflammation after TTS8 reported poor regional myocardial contractile dysfunction even after 3 months, which was associated with high BNP levels. However, those authors observed no association between regional myocardial contraction and levels of systemic inflammatory markers (i.e., high-sensitivity C-reactive protein).
Other studies have also suggested that BNP, rather than inflammation, may be involved in the chronic phase of myocardial damage. Neil et al9 investigated whether myocardial edema had resolved at 3 months after TTS onset; T2-weighted imaging showed persistent elevation of inflammation. Although a direct correlation was found between the T2-weighted signal and plasma normetanephrine and NT-proBNP levels, there was no correlation between the T2-weighted signal and the levels of systemic inflammatory markers. These findings suggest that TTS is associated with slowly improving edema, which is itself associated with inflammation of the entire myocardium. However, there is a dissociation between myocardial edema images and the levels of systemic inflammatory markers.
Why is there no association between myocardial edema and systemic inflammatory markers? In this issue of the Journal, Matsushita et al10 report that systemic inflammation may interfere with the improvement of cardiac function in TTS. They conducted a retrospective observational study to investigate factors that might contribute to incomplete recovery in TTS. Of the 407 patients with TTS, 66 had an LVEF <50% in the chronic phase. The factors associated with this incomplete recovery were low LVEF and high CRP levels at discharge. They also reported that the incomplete recovery group showed an increased risk of cardiovascular death. The authors also report the absence of troponin in the myocardium at hospital discharge, when inflammation levels were still high. Their study found that a troponin-negative sustained inflammatory response was associated with a high risk for delayed recovery of cardiac function. This result suggested that not only local inflammation in the myocardium but also peripheral inflammation may contribute to prolonged cardiac dysfunction.
The mechanisms by which systemic inflammation of peripheral organs prevents improvement of cardiac function in TTS are unknown and remain to be addressed. The relationship between TTS and inflammation is shown in the Figure. Acute-phase TTS is triggered by emotional or physical factors, and inflammation in TTS should be considered to follow 1 of 2 pathways: (1) involves inflammation of the myocardium, as assessed by conventional MRI and myocardial biopsy, often with a positive cardiac troponin finding; (2) includes peripheral tissue inflammation due to cardiac damage as well as inflammation of peripheral organs, leading to conditions such as pneumonia. However, the relationship between the recovery of cardiac function and systemic inflammation in TTS remains unclear and requires further study.
Myocardial systolic function recovery and systemic inflammation in Takotsubo syndrome. Regional myocardial and peripheral inflammation may be associated with incomplete recovery of cardiac systolic function in the chronic phase.
K.Y. has nothing to disclose.
Y.J.A. is a member of Circulation Journal’s Editorial Team.
