Stress-Induced Cardiomyopathy

Etiology and Pathogenesis

Although numerous associations exist between putative etiologies and stress-induced cardiomyopathy, the pathogenesis of the disease is not well understood. Because a variety of clinical circumstances have been temporally associated with stress-induced cardiomyopathy, it has been proposed that mediators, such as excess catecholamines, histamines, and/or cytokines that result from a variety of stresses, could cause coronary artery spasm, microvascular dysfunction, or direct myocardial toxicity. Any combination of these could result in the transient ECG changes, depressed LV function, and elevated cardiac biomarkers that characterize stress-induced cardiomyopathy. In addition, multiple studies have associated a lack of estrogen with the predominance of this condition in postmenopausal women.

Observational studies indicate that most cases of Takotsubo cardiomyopathy are preceded by either emotional (14%–38%) or physiological (17%–77%) stress. However, in the International Takotsubo Registry, up to 28% of patients had no evident trigger. The association with stress would be consistent with the hypothesis that increased catecholamine levels could cause microvascular dysfunction or myocardial toxicity. Studies that evaluated plasma norepinephrine found elevated levels in most patients with Takotsubo cardiomyopathy. One report measured the magnitude of plasma catecholamine release in Takotsubo cardiomyopathy compared with patients with myocardial infarction (MI). In this study, concentrations of both epinephrine (1264 pg/mL vs. 376 pg/mL) and norepinephrine (2284 pg/mL vs. 1100 pg/mL) were higher in patients with Takotsubo cardiomyopathy. Further support for a causative effect of catecholamines includes findings of transient myocardial perfusion abnormalities consistent with stunned myocardium or multivessel coronary artery vasospasm. In addition, endomyocardial biopsy specimens show histological signs of catecholamine toxicity in patients with stress cardiomyopathy.

Clinical Presentation

Many patients with stress-induced cardiomyopathy present with severe LV dysfunction and are critically ill as a result. The most common chief complaint in Takotsubo cardiomyopathy is chest pain at rest (33%–71%), with shortness of breath, syncope, and shock also reported. It is important to note if there may be a history of severe emotional distress, such as death of a family member or other significant psychological stress, in the clinical presentation. Critical medical or surgical illness, panic attacks, arguments, and other emotionally charged situations have been reported as triggering scenarios. Cardiogenic pulmonary edema may develop in stress cardiomyopathy, particularly with fluid resuscitation in the setting of sepsis, pancreatitis, trauma, or the postoperative period.

ECG findings typically mimic those in ST-segment elevation MI (STEMI) or other forms of acute coronary syndrome. The presentation of stress-induced cardiomyopathy may also result in ECG changes similar to those seen in intracranial hemorrhage, stroke, or head trauma, as well as deep symmetric T-wave inversions in the precordial leads with a prolonged QT interval. Acute systolic heart failure, cardiogenic shock, or dynamic LV outflow tract obstruction due to hyperdynamic basal segments (13%–18%) may also be part of the presentation.

Differential Diagnosis

Stress-induced cardiomyopathy typically presents with chest pain, respiratory distress, or pulmonary edema, in conjunction with LV dysfunction, ECG abnormalities, and elevated cardiac biomarkers. The clinical presentation of Takotsubo cardiomyopathy often mimics MI.

Acute coronary syndromes are far more common than stress-induced cardiomyopathy. For this reason, the clinician who is evaluating a patient with suspected Takotsubo cardiomyopathy should still consider MI a high possibility in the differential. The diagnosis of stress-induced cardiomyopathy most often involves ruling out significant coronary artery disease (CAD) by angiography. Acute pulmonary embolism may also be considered in the differential diagnosis. The possibility of myocarditis may be more difficult to distinguish from Takotsubo cardiomyopathy at times. Either a characteristic pattern of wall motion abnormalities, findings at angiography, or a rapidly improving clinical course can help to distinguish stress-induced cardiomyopathy from an acute coronary syndrome or myocarditis.

Diagnostic Approach

The diagnosis of stress-induced cardiomyopathy depends on an appropriate clinical history and the lack of evidence to support an alternative diagnosis. Clinical context, laboratory data, and the use of echocardiographic and angiographic imaging can help direct the clinician with the diagnosis.

Diagnostic criteria have been developed by a group at the Mayo Clinic. If all four of the following criteria are met, the diagnosis of stress cardiomyopathy can be confirmed:

• 1.

  Transient akinesis or dyskinesis of the LV apical and midventricular segments with regional wall motion abnormalities extending beyond a single epicardial vascular distribution. Exceptions are the focal and global variants.

• 2.

  Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture. If CAD is present, the diagnosis of stress cardiomyopathy can still be made if the wall motion abnormalities are not in the distribution of the CAD.

• 3.

  New ECG abnormalities (either ST-segment elevation or T-wave inversion) or modest elevation in cardiac troponin.

• 4.

  Absence of pheochromocytoma or myocarditis.