Takotsubo Syndrome: Pathophysiology, Emerging Concepts, and Clinical Implications

Abstract

Takotsubo syndrome is a condition characterized by acute transient left ventricular systolic dysfunction, which at presentation can be challenging to distinguish from acute myocardial infarction. Although previously thought to be a benign, self-limiting condition, recent studies have confirmed that patients with takotsubo syndrome have persistent subtle ongoing cardiac dysfunction, and many continue to have limiting symptoms despite restoration of left ventricular ejection fraction. Moreover, these patients have a substantial burden of morbidity and mortality, as well, with high rates of subsequent major adverse cardiovascular events that approach those of patients with acute coronary syndrome. The mechanisms behind this condition remain elusive. Despite substantial research, the medical community continues to have an incomplete understanding of its underlying pathogenesis and pathophysiology. Catecholamine-induced myocardial injury is the most established and well-known theory, but this does not explain all the clinical features and presentations of the condition, and numerous other pathways and abnormalities are emerging. Because of the poor understanding of its underlying pathophysiology, there is a lack of evidence-based interventions to treat the acute episode, to avoid recurrences, and to prevent major adverse cardiovascular events. This highlights the need for further research to gain a better understanding of the underlying pathophysiology to inform appropriate randomized controlled trials of interventions targeting the causative pathways. Only then can evidence-based management strategies be established to improve clinical outcomes of this potentially lethal condition.

Serotonin Syndrome Induced Tako-Tsubo Syndrome

“…The exact pathophysiologic mechanism of Tako-tsubo syndrome is unknown with multiple theories postulated including catecholamine-induced cardiotoxicity and microvascular dysfunction [ 1 ]. This condition can resemble an acute coronary syndrome (ACS) as both conditions may present with acute onset chest pain, dyspnea, and electrocardiogram changes, most notably acute ST segment elevations [ 2 ]. The diagnosis of Tako-tsubo syndrome is challenging in part due to similarities in presentation to an ACS [ 2 ].…”

“…This condition can resemble an acute coronary syndrome (ACS) as both conditions may present with acute onset chest pain, dyspnea, and electrocardiogram changes, most notably acute ST segment elevations [ 2 ]. The diagnosis of Tako-tsubo syndrome is challenging in part due to similarities in presentation to an ACS [ 2 ]. The most utilized diagnostic criteria used is from the Mayo Clinic and requires that patients have echocardiographic findings of temporary hypokinesis, dyskinesis, or akinesis of the left ventricle; lack of coronary artery disease (CAD); acute electrocardiographic (ECG) changes or elevations in cardiac troponins; and no presence of pheochromocytoma or myocarditis [ 3 ].…”

Myocardial work and takotsubo syndrome: stress affects work

“…Similar cases have subsequently been reported in western countries [ 2 – 4 ] and found in adults of all ages and also in children. Etiology and pathophysiology are still not fully understood and, although initially thought to be a relatively benign condition, this syndrome is now known to be associated with considerable short-term morbidity and small but important long-term mortality risk [ 5 ]. In the fourth universal definition of myocardial infarction TTS is classified as myocardial injury but not infarction [ 6 ].…”

“…Diagnosis of TTS can be challenging because the clinical presentation is often similar to acute coronary syndromes and prompt cardiac imaging is required due to rapid normalization of LV ejection fraction. The Mayo Clinic diagnostic criteria [ 5 ] originally described in 2004 and modified in 2008 are the most used in clinical practice and research. The International Takotsubo Registry (Inter-TAK) diagnostic score [ 8 ] was designed to help clinicians differentiate takotsubo syndrome from acute coronary syndrome.…”

“…Intravascular ultrasound may aid to rule out plaque rupture, which is not a feature of takotsubo syndrome. Echocardiography can also help to support the diagnosis (severity and extent of wall motion abnormalities) and detect potential complications [ 5 ]. Typically, the wall motion abnormality is not limited to one arterial territory differentiating it from acute myocardial infarction.…”