Severe stress in an elderly woman causes a temporary "broken" heart

A 71-year-old white female presented to the emergency department (ED) for evaluation of chest pain. She reported that while she was sitting in church 2 hours earlier, she felt the sudden onset of crushing substernal chest pain, rated 10/10 in severity, radiating to both arms and associated with mild dyspnea, nausea, mild epigastric pain, and dizziness. The pain was worse with exertion and deep breaths and was without alleviating factors. She denied fever, cough, recent illness, recent travel, and recent leg swelling or pain. She had no history of smoking or tobacco use. Her medical history was significant for hyperlipidemia, hypothyroidism, and osteoarthritis. Current medications included levothyroxine, celecoxib, and a multivitamin. She denied a history of atherosclerotic coronary artery disease, diabetes, systemic inflammatory disorders, or hypercoagulability. She had no family history of early MI in first-degree relatives.

After triage, the patient was placed in a monitored bed. Vitals signs included a BP of 168/109 mm Hg, pulse of 119 beats per minute, respiratory rate of 20 breaths per minute, and oxygen saturation of 100% on room air. Temperature was 37.2°C (99°F). The physical examination revealed an anxious elderly female in mild discomfort; palpation produced midsternal and mild epigastric tenderness. The cardiovascular, pulmonary, and abdominal examinations were otherwise unremarkable. The patient was placed on oxygen via nasal cannula, IV access was established, and baseline laboratory tests—including troponin, D-dimer, and thyroid-stimulating hormone—were ordered, along with an ECG (see Figure 1) and chest radiographs. Because of concerns about acute coronary syndrome (ACS), nitroglycerin, 0.4 mg, was administered sublingually 3 times, along with chewable aspirin. Although the patient's pain improved after the medications were given, her systolic BP subsequently dropped to 70 mm Hg and she became presyncopal. These signs quickly improved after administration of 2 L of normal saline.

The initial ECG, when compared to a previously available ECG, revealed a distinct difference in the morphology of the ST segment in precordial leads V2 through V5. When the initial troponin level came back elevated at 1.58 ng/mL, a presumptive diagnosis of ACS and possible ST-elevation MI (STEMI) was made. Heparin and nitroglycerin drips were started in the ED, and a cardiology consultation was requested. 

The patient was admitted to the cardiology service and promptly taken to the cardiac catheterization laboratory, where coronary angiography revealed entirely normal coronary vessels without evidence of stenosis, thrombus, or vasospasm. Left ventriculography was then performed and demonstrated significant akinesis of the entire mid-distal left ventricular chamber with preserved basilar contractility (see Figure 2). The left ventricular ejection fraction (LVEF) was less than 20% and left ventricular end-diastolic pressures were elevated, consistent with cardiomyopathy. ST-segment elevations had resolved after catheterization, and T-wave inversions were first noted in the precordial leads 10 hours after the onset of pain.

The patient was transferred to the ICU in stable condition. The heparin and nitroglycerin drips were continued, and warfarin was started because of concerns about the potential for apical thrombus formation within the left ventricle. Other medications included carvedilol, 3.125 mg twice daily with aggressive titration, and lisinopril, 5 mg daily, for impaired left ventricular function (the dosage was limited by the patient's relative hypotension). The patient continued to experience intermittent chest pain, which was easily relieved with morphine and NSAIDs as needed. Daily ECGs revealed progression of T-wave inversion from precordial leads to a global pattern (see Figure 3). 

Upon further questioning, the patient reported that approximately 36 hours before the onset of chest pain, her husband had been involved in a motor vehicle collision. Upon learning of the accident, she became extremely distraught at the possibility that both her husband and a longtime family pet, also riding in the vehicle, had been harmed. She also admitted to being under significant emotional stress because of an important upcoming presentation she was to give at work. This history, coupled with the characteristic findings on angiography, led to a diagnosis of takotsubo cardiomyopathy.

Takotsubo cardiomyopathy, also known as left apical ballooning syndrome, stress-induced cardiomyopathy, and broken heart syndrome, is an increasingly reported entity in the United States. This distinct cardiac syndrome, first described by Sato and colleagues in Japan in 1990,1 is characterized by transient left ventricular dysfunction, elevated cardiac enzymes, and ECG changes that mimic acute MI (AMI).1-11 The name is taken from tako-tsubo, the Japanese name for a vessel with a narrow neck that is commonly used as an octopus trap (see Figure 4). The left ventricle takes the characteristic shape of this vessel during the acute phase of the syndrome. 

Although previously believed to be extremely rare, apical ballooning syndrome accounted for approximately 2.2% of cases of suspected ST-elevation ACS presenting to a single institution over a 2-year period.2 A review of multiple case series revealed a significant gender discrepancy, with 82% to 100% of patients being female. The average age of patients at presentation ranged from 62 to 75 years.3 Donohue and colleagues noted that 57% of those affected were Asian, followed by Caucasians at 40%.4

The pathophysiology of takotsubo cardiomyopathy is still poorly understood. Proposed mechanisms include endogenous catecholamine surge, multivessel coronary vasospasm, and coronary microvascular dysfunction.5 A significant emotional or physiologic stressor is the triggering event in most patients, as it was thought to be in this case. Physical stressors seem to be the precipitating factor more often than emotional stressors and may include asthma attacks, exacerbation of chronic systemic illnesses, or exhausting physical labor.3,6 Examples of emotional stressors have included the unexpected death of a loved one, arguments, devastating financial losses, and even natural disasters such as earthquakes.7,8 In one case report, COX-2 inhibitor therapy is suggested as the etiology of a patient's takotsubo cardiomyopathy.9 Considering our patient's use of celecoxib, futher investigation may be warranted to determine whether a potential relationship exists between COX-2 inhibitor therapy and takotsubo cardiomyopathy.

The clinical presentation can vary but most commonly includes ischemic ST-segment elevation on ECG (81%-100% of cases), substernal chest pain (33%-100% of cases), and dyspnea.3 ST-segment changes are most commonly found in the precordial leads.3,6 A comparison of ECGs in patients presenting with atherothrombotic STEMI versus left ventricular apical ballooning syndrome revealed no distinguishable differences.10 Cardiac biomarkers are frequently elevated in takotsubo cardiomyopathy, but these elevations are usually mild, as they were in our patient.

Invasive angiography can confirm the diagnosis. Characteristic findings include an akinetic apical wall and impaired left ventricular function; both obstructive coronary artery disease and evidence of acute plaque rupture will be absent. According to Bybee and colleagues, the average LVEF upon diagnosis ranged from 40% to 49%.3 In institutions lacking the ability to perform coronary angiography or percutaneous intervention, takotsubo cardiomyopathy can be indistinguishable from AMI. Currently, there is not enough evidence to support withholding thrombolytics in patients clinically suspected of having a stress-induced cardiomyopathy, as this condition cannot accurately be distinguished from AMI with ECG alone.5,10 

Management is primarily supportive once a diagnosis of takotsubo cardiomyopathy is made. Conservative measures include hydration and removal from the potentiating stressor. No consensus on optimal management exists because data are limited, but left ventricular systolic dysfunction is typically treated with ACE inhibitors, beta-blockers, aspirin, and diuretics, as required for volume overload secondary to left-sided heart failure. Anticoagulation therapy should be considered in the setting of significant left ventricular dysfunction because of reports of apical thrombus formation, and this therapy should be continued until left ventricular function returns to normal and the akinetic apical wall resolves.3

The prognosis for persons with takotsubo cardiomyopathy is generally favorable, with in-hospital mortality rates ranging from 0% to 8%.3 Most reported cases resolve within 1 to 4 weeks after diagnosis. Akashi and colleagues reported a mean time of 17.4 days until complete resolution of left ventricular dysfunction in five of seven patients with takotsubo cardiomyopathy,11 and Bybee's group reported an average follow-up LVEF of 60% to 76%.3 The most common complication was heart failure with or without pulmonary edema (3%-46%).3 Other reported complications include cardiogenic shock, ventricular arrhythmias, left ventricular thrombus formation, ventricular wall rupture, left ventricular outflow tract obstruction, and—rarely—death.3,4

Our patient's chest pain resolved within 24 hours, and the remainder of her hospital stay was unremarkable. Transthoracic echocardiography was performed before discharge and revealed a large segment of mid-anterior to apex wall akinesis, along with mid-inferior posterior wall akinesis with an LVEF of approximately 30%. The patient was discharged home 3 days after admission on an outpatient regimen of warfarin, carvedilol, candesartan, simvastatin, and aspirin. She was seen for follow up 1 week after discharge and reported no complaints. An echocardiogram obtained at that time revealed mild apical akinesis, which was much improved from the study done 1 week earlier. Another echocardiogram was performed 5 weeks after discharge and demonstrated normal left ventricular size and function with an LVEF of 65%. ECG revealed global T-wave inversions. Warfarin therapy was subsequently discontinued, as were carvedilol and candesartan. The patient continued to take aspirin, 81 mg daily. Two months after her admission, she was doing well, without recurrence of symptoms. JAAPA

Disclaimer: The opinions or assertions contained in this article are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense.

Aspirin

Candesartan (Atacand)

Carvedilol (Coreg)

Celecoxib (Celebrex)

Heparin

Levothyroxine

Lisinopril (Prinivil, Zestril)

Morphine

Nitroglycerin, IV

Nitroglycerin, sublingual

Simvastatin (Zocor)

Warfarin (Coumadin, Jantoven)

---

1. Sato H, Tateishi H, Uchida T, et al. Tako-tsubo-like left ventricular dysfunction due to multivessel coronary spasm. In: Kodama K, Haze K, Hori M, eds. Clinical Aspect of Myocardial Injury: From Ischemia to Heart Failure [in Japanese]. Tokyo, Japan: Kagakuhyoronsha Publishing Co; 1990:56-64.

2. Bybee KA, Prasad A, Barsness GW, et al. Clinical characteristics and thrombolysis in myocardial infarction frame counts in women with transient left ventricular apical ballooning syndrome. Am J Cardiol. 2004;94:343-346.

3. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left ventricular apical ballooning: a syndrome that mimics ST-segment elevation myocardial infarction. Ann Intern Med. 2004; 141(11):858-865.

4. Donohue D, Movahed MR. Clinical characteristics, demographics, and prognosis of transient left ventricular apical ballooning syndrome. Heart Fail Rev. 2005;10(4):311-316.

5. Reeder GS. Stress-induced (takotsubo) cardiomyopathy. In: UpToDate. Rose BD, ed. Waltham, MA: UpToDate; 2007. http://www.uptodate.com.

6. Gianni M, Dentali F, Grandi AM, et al. Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review. Eur Heart J. 2006;27(13):1523-1529.

7. Sharkey SW, Lesser JR, Zenovich AG, et al. Acute and reversible cardiomyopathy provoked by stress in women from the United States. Circulation. 2005;111(4):472-479. 

8. Sato M, Fujita S, Saito A, et al. Increased incidence of transient left ventricular apical ballooning (so-called ‘takotsubo' cardiomyopathy) after the mid-Niigata Prefecture earthquake. Circ J. 2006;70(8):947-953.

9. Ker J, Van Wyk CJ. A case of takotsubo cardiomyopathy precipitated by lumiracoxib, a selective COX-2 inhibitor. Cardiovasc J Afr. 2007;18(6):383-384. 

10. Bybee KA, Motiei A, Syed IS, et al. Electrocardiography cannot reliably differentiate transient left ventricular ballooning syndrome from anterior ST-segment elevation myocardial infarction. J Electrocardiol. 2007;40(1):38.e1-6.

11. Akashi YJ, Nakazawa K, Sakakibara M, et al. The clinical features of takotsubo cardiomyopathy. Q J Med. 2003;96(8):563-573.