Takotsubo cardiomyopathy in elderly female trauma patients: a case series

Originally reported in Japan in 1990, Takotsubo cardiomyopathy is a syndrome characterized by acute left ventricular wall motion abnormalities with a hallmark transient apical ballooning leading to left ventricular systolic dysfunction [1, 2]. Commonly mistaken for an acute coronary syndrome (ACS), it can present with transient cardiac ischemia-like symptoms such as chest pain and shortness of breath with electrocardiogram (ECG) changes of ST segment elevation in the absence of significant coronary artery disease. Biochemical markers of cardiac injury (troponin I and T, creatinine kinase, and myoglobin) are usually elevated [2]. The clinical presentation can range from mild symptoms to severe pulmonary edema and cardiogenic shock [3]. With prompt recognition and management, there is usually a good prognosis and low mortality regardless of the severity of the clinical presentation [4].

The incidence of Takotsubo cardiomyopathy has been reported in around 2% of patients presenting with symptoms suggestive of ACS [5]. It appears to more common in people between the ages of 65 and 70 and in postmenopausal women [6]. Although the pathogenesis is not fully understood, there is evidence to suggest that sympathetic stimulation is integral [1, 7]. Increased plasma catecholamine levels in the setting of Takotsubo cardiomyopathy are usually precipitated by an event related to acute physical illness or emotional stress [7].

For patients presenting following trauma, in urgent need of operative management, the clinical conundrum relates to the concern that these patients are contemporaneously experiencing an ACS. The symptoms, signs, and investigations usually result in delays to operative management and heightened anxiety of the anesthetic risk. Differentiating Takotsubo cardiomyopathy from an ACS may prevent operative delays and avoid inappropriate management.

In this paper we present three cases of Takotsubo cardiomyopathy observed in elderly females admitted to a major trauma center following falls.

In our case series, the patients fulfilled the criteria for the diagnosis of Takotsubo cardiomyopathy based on a precipitating physical stressor in the setting of trauma as a trigger, elevated troponin levels, ST segment changes on ECG, and reversible left ventricular dysfunction on echocardiogram, with recovery prior to discharge. These characteristics are part of the InterTAK diagnostic score which assesses the diagnostic likelihood of Takotsubo cardiomyopathy [8]. The demographics of our cases are in line with previous reports where 90% of cases occur in females with the majority over the age of 60 [9].

Emotional stressors account for approximately 15–40% of cases of Takotsubo cardiomyopathy, whereas physiological triggers such as acute medical illness or surgery have been reported in up to 70% of cases [10]. In elderly patients presenting following trauma, Takotsubo cardiomyopathy may be multifactorial. In addition to the trauma causing emotional distress, the peri- and postoperative phases and underlying medical illness may act as physiological stressors, particularly in elderly patients with multiple comorbidities [11].

The etiology of Takotsubo cardiomyopathy is not fully understood. Several hypotheses derived from observational studies have suggested the importance of the vascular and myocardial response to stress. Initially, multivessel coronary vasospasm was thought to explain the acute ventricular dysfunction seen in Takotsubo cardiomyopathy. However, in the majority of cases, there was no reported spontaneous coronary artery spasm or inducible vasospasm in follow-up studies [12‐14]. Intravascularly, there appears to be no association between Takotsubo cardiomyopathy and acute atherosclerotic plaque rupture seen in ACS [15].

In patients with Takotsubo cardiomyopathy, catecholamine levels in the blood were found to be approximately ten times higher than normal, suggesting the importance of catecholamines in mediating cardiac injury [16]. This is also supported by conditions associated with raised catecholamines such as pheochromocytoma and thyrotoxicosis being associated with Takotsubo cardiomyopathy [17, 18]. An increased sensitivity of beta-adrenergic receptors to levels of catecholamines in the myocardium during periods of stress may be responsible for the pathophysiological findings in Takotsubo cardiomyopathy, particularly in the apical myocardium where higher densities of beta-adrenergic receptors are found [19]. Estrogen usually leads to a suppression of beta-adrenergic receptor expression in the ventricular myocardium [20]. In postmenopausal women, the loss of estrogen leads to an increased response to beta-adrenergic receptor agonists, which may account for the gender differences in the incidence of Takotsubo cardiomyopathy.

Previous cases have been reported of patients with Takotsubo cardiomyopathy in the setting of trauma [21, 22] and in elderly patients with hip fractures requiring operative management [14, 23]. Optimal timing of urgent surgery in the setting of Takotsubo cardiomyopathy is not known, with ranges from 48 hours to 6 days post admission, as seen in our cases. In both our cases associated with hip fractures, patients made a full recovery despite differing time to surgical fixation. Delays in surgery may lead to increasing analgesia requirements, increased hospital-acquired infections, and delayed mobilization and rehabilitation, which may contribute to a prolonged length of hospital stay and potential increased mortality [24]. The Best Practice Tariff for hip fractures was introduced to ensure that operative management of these fractures occurred within 36 hours of admission [25].

Patients with Takotsubo cardiomyopathy who are admitted with raised troponin levels and ECG changes of ST elevation, as in our cases, are often initially managed as ACS and given dual antiplatelet therapy. This is of particular importance in patients presenting following trauma and in those requiring surgery [11, 23]. Takotsubo cardiomyopathy has also been reported in patients following brain trauma [26‐28], with the majority of ECG changes (ST segment deviation, T wave abnormalities, QT prolongation) being reported in patients with severe subarachnoid hemorrhage [29]. In these patients, management with dual antiplatelet therapy, including clopidogrel, may contribute to a further delay of urgent surgery and increased risk in perioperative bleeding, increased need for blood transfusions, and infection [30].

To combat this, prompt assessment by a cardiologist and early echocardiography may help in reaching an early diagnosis of Takotsubo cardiomyopathy, avoiding delay to urgent surgical management. While coronary angiography is the optimal imaging modality for excluding high-grade coronary stenosis, in some patients, this may not be suitable. In patients who are frail with life-threatening comorbidities, invasive angiography may be associated with considerable risk [6]. Noninvasive CT coronary angiography (CTCA) may be considered an alternative imaging modality in these patients. A study in 11 patients with suspected Takotsubo cardiomyopathy showed use of a contemporary CTCA ruled out significant coronary artery disease in 80% of patients [31]. Further studies are required to determine whether it can be used early in the management of Takotsubo cardiomyopathy to prevent delays in patients requiring surgery.

The management of Takotsubo cardiomyopathy is based upon identifying patients with adverse features secondary to complications. For patients with hypotension and cardiogenic shock, prompt assessment of whether left ventricular outflow obstruction exists will determine the suitability of inotropic support [6]. Beta-blockers have not been shown to reduce mortality in patients with heart failure secondary to Takotsubo cardiomyopathy and should be avoided in patients with bradycardia and QTc prolongation due to the risk of pause-dependent torsades de pointes [32, 33]. For patients presenting with acute heart failure, diuretics and prognostic medical therapy (angiotensin-converting enzyme inhibitors, aldosterone antagonists) are the mainstay of management. The majority of patients will present without complications, in which case the management is supportive and prognostic medical therapy can be considered [32]. Their impact on prognosis and recurrence of Takotsubo cardiomyopathy is not fully known. Antiplatelet therapy has been shown to reduce major adverse cardiovascular events during hospitalization [34]; however, the impact of its long-term use is unknown, particularly in elderly patients with Takotsubo cardiomyopathy [32].

Since its initial reports in 1990, Takotsubo cardiomyopathy is being increasingly reported, particularly in elderly females following trauma. The severity of this syndrome ranges from mild symptoms, as presented in our cases, to life-threatening cardiogenic shock and pulmonary edema. It remains an important differential diagnosis for ACS. For patients requiring surgical management, delays in the diagnosis of Takotsubo cardiomyopathy may lead to postponement of urgent operative management. This may impact on length of hospital stay, time to recovery, as well as increased morbidity and mortality, not only due to the delays but to the use of antiplatelet medication. To aid the prompt diagnosis of Takotsubo cardiomyopathy in patients requiring surgery, we advocate a multidisciplinary approach with combined decision making from physicians, cardiologists, anesthetists, and surgical teams.