Causes of Takotsubo Cardiomyopathy
Takotsubo cardiomyopathy is primarily caused by profound emotional or physical stressors that trigger an adrenergically mediated process, characterized by supraphysiological elevations of plasma catecholamines leading to transient left ventricular dysfunction.1
Primary Triggering Factors
- Emotional stressors are common precipitating events for takotsubo cardiomyopathy, particularly in postmenopausal women 1
- Physical stressors including acute medical illness, surgery, or other physiological stress can trigger the syndrome 1
- Postmenopausal status is a significant risk factor, with 96% of cases occurring in women ≥50 years of age 1
Pathophysiological Mechanisms
- Catecholamine surge is the primary proposed mechanism, with documented supraphysiological elevations of plasma catecholamines during acute episodes 1
- β2-adrenergic receptor signaling switch from Gs to Gi protein signaling occurs with high levels of circulating epinephrine, which is protective against apoptosis but causes negative inotropy 1
- Regional differences in adrenergic receptor density explain the characteristic apical involvement, as the ventricular apex has increased β2-adrenergic receptor density despite relatively sparse sympathetic innervation 1
- Microvascular vasospasm may contribute to the pathophysiology 1
- Impaired fatty acid metabolism has been implicated in the development of the syndrome 1
- Transient left ventricular outflow tract obstruction can occur and contribute to the clinical presentation 1
- Base-to-apex perfusion gradient differences in myocardial blood flow have been postulated as contributing factors 1
Specific Triggers and Associated Conditions
- Acute medical illness including neurological conditions, respiratory failure, or sepsis 1
- Surgical procedures and other invasive medical interventions 1
- Severe electrolyte disturbances such as hyponatremia have been reported as triggers 2
- Chemotherapy and other medications that affect catecholamine levels or sensitivity 1
- Endocrine disorders including thyroid dysfunction, which can alter cardiovascular response to catecholamines 1
Clinical Characteristics and Risk Factors
- Female predominance with approximately 90% of cases occurring in women 1, 3
- Mean age of 66.8 years with most cases occurring in postmenopausal women 1
- Pre-existing psychiatric disorders such as anxiety and depression may increase susceptibility 1
- Absence of significant coronary artery disease is characteristic, though some patients may have incidental coronary atherosclerosis 1
Variant Forms
- Apical ballooning is the classic presentation, but other patterns have been described 1
- Mid-ventricular variant with sparing of the apex and base 1
- Basal variant (inverse takotsubo) with hyperkinesis of the apex 1
- Right ventricular involvement can occur and is associated with more complications and worse outcomes 4
Understanding these causes and mechanisms is essential for proper diagnosis and management of takotsubo cardiomyopathy, which should be considered in patients presenting with apparent acute coronary syndrome but with nonobstructive coronary arteries on angiography 1.