63-year-old woman with acute chest pain

Mayo Clin Proc. • April 2006;81(4):537-540 • www.mayoclinicproceedings.com 537

RESIDENTS’ CLINICRESIDENTS‘ CLINIC

*Resident in Internal Medicine, Mayo School of Graduate Medical Education,Mayo Clinic College of Medicine, Rochester, Minn.

†Adviser to residents and Consultant in Cardiovascular Diseases, Mayo ClinicCollege of Medicine, Rochester, Minn.

See end of article for correct answers to questions.

Individual reprints of this article are not available. Address correspondence toAbhiram Prasad, MD, Division of Cardiovascular Diseases, Mayo Clinic Col-lege of Medicine, 200 First St SW, Rochester, MN 55905 (e-mail: [email protected]).

© 2006 Mayo Foundation for Medical Education and Research

63-Year-Old Woman With Acute Chest Pain

JOSEPH C. VAGLIO, JR, MD, MBA*; A DAM M. REYBURN, MD*; AND ABHIRAM PRASAD, MD†

A 63-year-old woman with a history of hypertension,nicotine dependence, and paroxysmal supraventricu-

lar tachycardia presented to the emergency departmentwith acute substernal chest pain and tachycardia. The pa-tient described the pain as dull pressure (severity rated as 5on a scale of 0 to 10) that radiated to her neck and left armand was associated with profound weakness and dyspnea.She had recently experienced paroxysmal supraventriculartachycardia during recovery from open reduction and inter-nal fixation of a right subtrochanteric femoral fracture.Medical therapy had been unsuccessful, and the patient wasscheduled to undergo radiofrequency ablation. She deniedany history of chest discomfort or coronary artery disease.

The patient’s cardiac medications were diltiazem (con-trolled release) at 240 mg/d and atenolol at 25 mg/d. Bothdrugs had been discontinued in preparation for the ablation.Additional medications included acetaminophen/oxyco-done (325/5 mg) as needed for pain control. She reported a30-pack-year smoking history and denied alcohol use.Physical examination revealed an anxious-appearingwoman with vital signs notable for tachycardia (pulse rate,120/min) and hypertension (blood pressure, 210/70 mm Hgon the left and 190/80 mm Hg on the right). Carotidupstrokes were normal, and no jugular venous distentionwas evident. Cardiac examination revealed a nondisplacedpoint of maximal impact and normal heart sounds withoutmurmurs. She had no clubbing, cyanosis, or edema, and herlungs were clear to auscultation.

1. Which one of the following would not be included inthe initial differential diagnosis of this patient’s chestpain?

a. Gastroesophageal reflux diseaseb. Peptic ulcer diseasec. Pulmonary embolusd. Acute cholecystitise. Acute myocardial infarction

Reflux disease, a common cause of epigastric discom-fort, can mimic cardiac pain and should be considered inthis patient. Other upper gastrointestinal tract disorders,including peptic ulcer disease, can also cause abdominalpain that is referred to the chest. However, the acuteonset, symptom characteristics, and lack of associationwith eating exclude peptic ulcer disease from the initialdifferential diagnosis in this patient. Her postoperativestatus and recent tachycardia place her at increased riskfor a pulmonary embolus, which should be strongly con-sidered as a cause of her tachycardia, dyspnea, and chestpain. Acute cholecystitis can also present as chest painand must be included in the patient’s differential diagno-sis. However, the most important consideration in thispatient with substernal chest pain is acute myocardialinfarction. The possible life-threatening consequences ofa coronary event and the classic constellation of signs andsymptoms (chest pain radiating to the arm and neck,tachycardia, dyspnea, and weakness) necessitate a rapidcardiac evaluation.

Laboratory tests revealed the following (referenceranges shown in brackets): leukocytosis (white blood cellcount, 11.5 × 109/L [3.5-10.5 × 109/L]), an elevated tropo-nin T level (0.32 ng/mL [≤0.03 ng/mL]), and an elevatedcreatine kinase-MB fraction (8.2 ng/mL [<6.2 ng/mL]).Electrocardiography (ECG) showed a 2- to 3-mm ST-seg-ment elevation in leads V

2 through V

6.

2. Which one of the following diagnostic tests or therapieswould be the most appropriate next step in the evalua-tion of this patient?

a. Abdominal computed tomographyb. Transthoracic echocardiographyc. Empirical nonsteroidal anti-inflammatory drug therapyd. Empirical treatment of gastroesophageal reflux disease

with a proton pump inhibitore. Emergent cardiac catheterization

Numerous intra-abdominal sources (reflux disease,cholecystitis, peptic ulcer disease, etc) must be consideredas a cause of this patient’s symptoms. However, in thesetting of ECG changes and elevated cardiac biomarkers,abdominal computed tomography would not be indicatedas the most appropriate next step. Furthermore, the lack ofaccompanying symptoms, such as nausea, vomiting, diar-rhea, or association with eating, argues against a gas-trointestinal etiology. Transthoracic echocardiography

For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.

Mayo Clin Proc. • April 2006;81(4):537-540 • www.mayoclinicproceedings.com538

RESIDENTS’ CLINIC

would be useful to evaluate cardiac function in this patientbut is not the best test in this acute setting. Although apericardial rub or costal tenderness could suggest peri-carditis or costochondritis that would respond to treatmentwith nonsteroidal anti-inflammatory drugs, this patient’spresentation and clinical findings are not suggestive ofthese conditions. Likewise, if no cardiac or pulmonarysource is identified, empirical treatment with a protonpump inhibitor may be indicated, but not in patients inwhom an acute cardiac cause is suspected. Emergent car-diac catheterization to identify a possible acute coronarycause of the symptoms would be the most appropriate nextstep.

The patient underwent emergency cardiac catheteriza-tion. Angiography revealed no acute obstructions in thecoronary arteries and only mild diffuse atherosclerosis.However, left ventriculography showed an ejection frac-tion of 34% and moderate to severe hypokinesis of theapical septal and apical segments of the left ventricle.

3. Which one of the following is the most likely explana-tion for this patient’s ECG changes, elevated cardiacbiomarkers, and reduced left ventricular function?

a. Myocarditisb. Left ventricular aneurysmc. ST-segment elevation myocardial infarctiond. Left ventricular apical ballooning syndromee. Cardiac tamponade

Patients with myocarditis can present with a variety ofECG changes, including ST-segment elevation, elevatedcardiac biomarkers, and normal coronary anatomy onangiography, and have reduced left ventricular function.However, the dysfunction is generally global, which wasnot the case in our patient. Left ventricular aneurysmsform as a result of a healed transmural myocardial infarc-tion and can lead to ST elevations in the anterior leadson ECG. In our patient, left ventriculography did notshow an aneurysm. The presumed diagnosis in this case,which led to urgent catheterization, was ST-segmentelevation myocardial infarction. However, the patient’snear-normal coronary anatomy is inconsistent with thiscondition. The presentation and objective data are consis-tent with a diagnosis of left ventricular apical ballooningsyndrome, a cardiac condition characterized by acutechest pain, ST-segment elevation, mildly elevated cardiacenzymes, and apical hypokinesis in the absence of obvi-ous occlusive coronary artery disease. Cardiac tamponadeoccurs when fluid collects within the pericardial sacand is associated with hypotension, sinus tachycardia,and pulsus paradoxus. This diagnosis was not supportedby the clinical or cardiac catheterization findings in ourpatient.

The patient was stabilized and transferred to the coro-nary care unit for continued cardiac monitoring.

4. Which one of the following treatments is not a reason-able option for the patient at this time?

a. Vasodilatorsb. Hemodynamic monitoringd. β-blockersd. Coronary artery bypass graftinge. Anticoagulation

When left ventricular apical ballooning syndrome isdiagnosed, treatment is mainly supportive care for thesymptoms of chest pain, dyspnea, and congestive heartfailure. In this patient, vasodilators were used to provideafterload reduction. Diuretics are also indicated for patientswith evidence of volume overload or heart failure. Con-tinuous cardiac monitoring should be used to detect atrialand ventricular dysrhythmias and hemodynamic instabil-ity. Temporary use of β-blockers may be useful for thetreatment of hypertension, heart failure, or dysrhythmias.Because angiography was negative for occlusive coronaryartery disease in this patient, bypass grafting would not beindicated. To prevent left ventricular mural thrombusformation, short-term anticoagulation should be consid-ered, especially for patients with severe left ventriculardysfunction.

The patient was treated with supportive therapy andsteadily improved.

5. Which one of the following is the most common poten-tial complication to watch for in this patient?

a. Left heart failureb. Sudden deathc. Dynamic outflow obstructiond. Ventricular arrhythmiae. Mural thrombus formation

The most commonly reported clinical complication ofleft ventricular apical ballooning syndrome is left heartfailure.1 Thus, management may require hemodynamicmonitoring, diuretics, and inotropic medications. Only afew cases of sudden death have been reported. Other infre-quent complications are hypotension and reduced cardiacoutput secondary to a dynamic left ventricular outflow tractobstruction resulting from the combination of hypokineticapical and midventricular segments and hyperdynamicbasal segments. Given their vastly different therapeuticrequirements, early echocardiographic differentiation be-tween pump failure and obstructive hemodynamic im-pairment is essential for effective management. Otheruncommonly reported complications include mitral re-gurgitation, ventricular arrhythmias, left ventricular mu-ral thrombus formation, and free wall rupture.1,2


Mayo Clin Proc. • April 2006;81(4):537-540 • www.mayoclinicproceedings.com 539

RESIDENTS’ CLINIC

After an uneventful 5-day hospital course, the pa-tient’s symptoms resolved, and she was discharged home.Echocardiography 6 weeks later showed complete re-covery of left ventricular function, and the patient wasasymptomatic.

DISCUSSION

Originally reported in Japan by Dote et al,3 transient leftventricular apical ballooning syndrome is a cardiac condi-tion that mimics the clinical presentation of an acute coro-nary syndrome. Numerous case series have shown consis-tent clinical characteristics, including ischemia-like chestpain and dyspnea, ST-segment elevation and evolutionaryT-wave inversion on ECG, mildly elevated levels of car-diac biomarkers, and transient apical and midventricularregional wall motion abnormalities.3-6 However, thesefindings occur in the absence of obstructive coronaryatherosclerosis. Reports show predominance in post-menopausal women, and most episodes occur after aphysical or emotional stress. The characteristic left ven-tricular wall motion abnormalities and decreased sys-tolic function typically resolve rapidly (days to weeks).Although the prognosis for most patients with this syn-drome is favorable, several isolated deaths have beenreported.5,7

The optimal treatment of patients with transient leftventricular apical ballooning syndrome has not been wellcharacterized because of limited clinical data. Presumably,most patients undergo emergency diagnostic cardiac cath-eterization to evaluate the possibility of ST-segment eleva-tion acute myocardial infarction. After the initial acutepresentation, appropriate management is primarily sup-portive. Aspirin therapy is indicated if coronary atheroscle-rosis is also present. Short-term treatment with β-blockersmay be appropriate if the syndrome was precipitated bymental or physical stress. Hemodynamic monitoring is in-dicated in patients with hypotension, and short-term antico-agulation may be considered to prevent mural thrombosisformation.

The prognosis for patients with transient left ventricularapical ballooning syndrome is favorable, with most pa-tients regaining normal systolic ventricular function withinseveral months. Furthermore, recurrence of the syndromeappears to be rare, occurring in less than 10% of reportedcases. Little is known about emergent treatment of thecondition, and no evidence currently exists to guide effec-tive long-term care. Supportive therapy is indicated untilsymptoms of heart failure have resolved. Follow-up echo-cardiographic evaluation is commonly conducted to ensureadequate resolution of systolic left ventricular dysfunction.Whether prolonged medical therapy or routine cardiac sur-

veillance could provide additional benefit remains unclear.Further study is needed to characterize the optimal long-term management of the condition.

The exact cause of this acute stress-induced cardiacdysfunction is unknown. Although the precise mechanismis unclear, exaggerated sympathetic stimulation is thoughtto be a central cause of the syndrome. In one study, patientswith left ventricular apical ballooning syndrome had supra-physiologic levels of plasma catecholamines and stress-related neuropeptides, higher than the levels seen in pa-tients with acute myocardial infarction.8 A proposedmechanism is sympathetic-mediated epicardial vasospasmresulting in ischemia. Previous studies have shown thatincreased sympathetic tone associated with mental stresscan cause coronary vasospasm in patients without underly-ing coronary artery disease.9 An alternative hypothesis in-volves catecholamine-associated coronary microvasculardysfunction. Patients who underwent invasive measure-ment of coronary flow reserve after diagnosis were noted tohave diffusely abnormal coronary microvascular func-tion.10 Another proposed mechanism is neurogenically me-diated myocardial stunning.11,12

Universal diagnostic criteria for transient left ventricu-lar apical ballooning syndrome have not been established.Recently, a diagnostic algorithm was proposed1 that in-cluded 4 criteria: (1) transient regional wall motion abnor-malities of the left ventricular apical and midventricularsegments, (2) absence of obstructive coronary disease orplaque rupture, (3) new ST-segment elevation and/or T-wave inversion, and (4) absence of an obvious alternativecause (recent head trauma, extensive intracranial bleed-ing, myocarditis, pheochromocytoma, hypertrophic car-diomyopathy). All 4 suggested criteria must be met toestablish a diagnosis of transient left ventricular apicalballooning syndrome.

Although uncommon, transient left ventricular apicalballooning syndrome must be considered in the differentialdiagnosis of patients presenting with ST-segment elevationand suspected acute coronary syndromes. Clinical suspi-cion for this condition should be particularly high in pa-tients whose symptoms, ECG abnormalities, and biochemi-cal markers are highly suggestive of coronary ischemia inthe setting of nonobstructive atherosclerotic disease.Prompt recognition and aggressive supportive treatmentare indicated, and recovery of systolic function can beexpected. Future studies are needed to determine the opti-mal management of this increasingly recognized cardiacsyndrome.

REFERENCES1. Bybee KA, Kara T, Prasad A, et al. Systematic review: transient left

ventricular apical ballooning: a syndrome that mimics ST-segment elevationmyocardial infarction. Ann Intern Med. 2004;141:858-865.


Mayo Clin Proc. • April 2006;81(4):537-540 • www.mayoclinicproceedings.com540

RESIDENTS’ CLINIC

2. Yasuga Y, Inoue M, Takeda Y, et al. Tako-tsubo-like transient leftventricular dysfunction with apical thrombus formation: a case report [inJapanese]. J Cardiol. 2004;43:75-80.

3. Dote K, Sato H, Tateishi H, Uchida T, Ishihara M. Myocardial stunningdue to simultaneous multivessel coronary spasms: a review of 5 cases [inJapanese]. J Cardiol. 1991;21:203-214.

4. Kawai S, Suzuki H, Yamaguchi H, et al. Ampulla cardiomyopathy(‘Takotusbo’ cardiomyopathy)—reversible left ventricular dysfunction: withST segment elevation [published correction appears in Jpn Circ J. 2000;64:237]. Jpn Circ J. 2000;64:156-159.

5. Tsuchihashi K, Ueshima K, Uchida T, et al, Angina Pectoris-MyocardialInfarction Investigations in Japan. Transient left ventricular apical ballooningwithout coronary artery stenosis: a novel heart syndrome mimicking acutemyocardial infarction. J Am Coll Cardiol. 2001;38:11-18.

6. Akashi YJ, Tejima T, Sakurada H, et al. Left ventricular rupture associ-ated with Takotsubo cardiomyopathy. Mayo Clin Proc. 2004;79:821-824.

7. Desmet WJ, Adriaenssens BF, Dens JA. Apical ballooning of the leftventricle: first series in white patients. Heart. 2003;89:1027-1031.

8. Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features ofmyocardial stunning due to sudden emotional stress. N Engl J Med. 2005;352:539-548.

9. Lacy CR, Contrada RJ, Robbins ML, et al. Coronary vasoconstrictioninduced by mental stress (simulated public speaking). Am J Cardiol. 1995;75:503-505.

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

11. Singal PK, Kapur N, Dhillon KS, Beamish RE, Dhalla NS. Role of freeradicals in catecholamine-induced cardiomyopathy. Can J Physiol Pharmacol.1982;60:1390-1397.

12. Mann DL, Kent RL, Parsons B, Cooper G IV. Adrenergic effects on thebiology of the adult mammalian cardiocyte. Circulation.1992;85:790-804.

Correct answers: 1. b, 2. e, 3. d, 4. d, 5. a


63-year-old woman with acute chest pain

Documents