The“Broken Heart Syndrome”: Understanding Takotsubo Cardiomyopathy

What are the pathophysiology, diagnosis, treatment, and prognosis of this cardiomyopathy?The damaging effects of stress on the cardiovascular system are widely documented and accepted by the general public and the medical community. A specific syndrome of stress-related reversible cardiomyopathy, however, has recently been observed with greater frequency. Increasingly referred to as the “broken heart syndrome,” this condition mimics myocardial infarction in patients without obstructive coronary artery disease. Initial signs and symptoms resemble those of acute coronary syndrome; chest pain, dyspnea, electrocardiographic (ECG) changes, and elevated levels of cardiac biomarkers are common.1It is important for critical care nurses to be aware of this syndrome and what differentiates it from classic acute myocardial infarction. Proper understanding will guide appropriate assessment, monitoring, management, and education of patients.The hallmark of the syndrome is a characteristic transient contractile abnormality of the left ventricle causing a balloonlike morphology that can be detected with left ventricular angiography or contrast echocardiography. Damage of the left ventricle causes a contractile defect of the apex of the heart. During systole, or ventricular contraction, ventricular imaging shows a rounded, hypokinetic apex with a narrow, hypercontracted base (Figure 1). This phenomenon was first described in 1991 by Dote et al,2 who named the syndrome “takotsubo-like cardiomyopathy” because the appearance resembles a pot historically used in Japan to catch octopus (tako in Japanese means octopus; tsubo means pot). The cardiac dysfunction is transient, and the left ventricle returns to normal and contractile function is restored within days to weeks.2Terms used to describe this syndrome in published reports include transient left ventricular apical ballooning, stress cardiomyopathy, and ampulla cardiomyopathy.3 In this article, I use the term takotsubo [tah-ku-su-bu] cardiomyopathy. I describe the pathophysiology of takotsubo cardiomyopathy, signs and symptoms, diagnosis, treatment, and prognosis. A case report is included.The National Heart, Lung, and Blood Institute estimated that in 2007 in the United States, about 1.2 million people would have a myocardial infarction.4 Akashi et al5 reported that takotsubo cardiomyopathy may account for about 1% of all acute myocardial infarctions, suggesting that about 12 000 Americans might have had the syndrome in 2007. Bybee et al,6 in a review of the literature, reported that the syndrome accounted for 1.5% and 2.2% of Q-wave and ST-segment acute coronary syndrome, respectively, in the patients studied.Most patients who have takotsubo cardiomyopathy are postmenopausal women.1,7 Gianni et al1 reviewed 14 studies and found that of 286 patients with the syndrome, 254 (89%) were female. The mean age of the patients was 68.5 years. Of the 14 studies, 11 included data on risk factors for coronary disease. Figure 2 compares the presence of risk factors in patients with takotsubo cardiomyopathy and patients with coronary artery disease. Cardiovascular risk factors are generally present to a lesser degree in patients with takotsubo cardiomyopathy than in patients with coronary artery disease.1,8Severe reversible left ventricular dysfunction (myocardial stunning) in patients without marked coronary disease is thought to be caused by excessive exposure to catecholamines mediated by exaggerated sympathetic stimulation.7 Although this situation is known to occur in critically ill patients in the absence of coronary artery disease9 (Table 1), the takotsubo variant involves patients in their usual state of health, often after an episode of emotional or physical distress.The pathophysiological mechanisms associated with takotsubo cardiomyopathy remain unclear, although broadly speculated on. The most accepted theory is catecholamine excess due to activation of sympathetic tone. Other theories considered include ischemia from multivessel coronary spasm or a transient atherosclerotic plaque.Patients with takotsubo cardiomyopathy can have abnormally high serum levels of circulating catecholamines.7 Wittstein et al7 monitored plasma levels of epinephrine, norepinephrine, and dopamine in patients with takotsubo cardiomyopathy on hospital days 1 and 2. Levels were also measured in patients hospitalized with classic myocardial infarction. Patients with takotsubo cardiomyopathy had levels 7 to 34 times as high as published normal values and 2 to 3 times as high as the levels in patients with classic myocardial infarction.7Histological examination of biopsy samples from the affected left ventricle of patients with takotsubo cardiomyopathy have shown contraction band necrosis, which is associated with clinical states of catecholamine excess.4 Catecholamine excess has reversible toxic effects on myocardium that have been documented in cases of pheochromocytoma (a catecholamine-secreting tumor).10 In takotsubo cardiomyopathy, the apex of the left ventricle appears to be selectively vulnerable to these effects. The basal segments are spared, suggesting a difference in sympathetic innervation or andrenergic receptor sensitivity in the apex.6 The exact mechanism of catecholamine-induced damage and selective apical involvement is not yet understood.One of the first theories for the cause of takotsubo cardiomyopathy was multivessel coronary spasm.3 Coronary spasm can cause ischemia in the absence of obstructive coronary artery disease, and occlusive spasm causes transmural ischemia with ST-segment elevation.11(p1160) Feasibly, multivessel coronary artery spasm could account for the diffuse takotsubo defect. Many researchers5,6,7,12,13 have tested the spasm theory by performing angiography during persistent ST-segment elevation and did not observe or provoke any spasm. Bybee et al,6 in a systematic review of 7 studies, identified 3 studies in which provocable multivessel spasm occurred in 13 of 73 patients (18%) with the syndrome who were tested. This result suggests that although spasm may play a role in takotsubo cardiomyopathy, it does not explain most cases.Although obstructive coronary artery disease (>50% narrowing) is ruled out by angiography, some researchers hypothesize that a ruptured coronary plaque could be the underlying cause of takotsubo cardiomyopathy.14 Spontaneous intermittent occlusion and recanalization of coronary arteries due to a combination of thrombosis and vasoconstriction are common during early acute coronary syndrome.14 Can a ruptured plaque cause severe or total coronary occlusion that then undergoes spontaneous recanalization before angiography?In classic myocardial infarction, the size of the infarct corresponds to the amount of myocardium supplied by the obstructed artery. In takotsubo cardiomyopathy, the area of affected myocardium is much larger than the normal distribution of a single coronary artery. Involvement of more myocardium than could be supplied by a single artery seems to negate the possibility of transient coronary occlusion. Ibanez et al14 used intravascular ultrasound to image the LAD in 5 patients with takotsubo cardiomyopathy. Although all patients had less than 50% stenosis on angiograms, intravascular ultrasound showed ulcerated atherosclerotic lesions in each patient’s LAD. Further evaluation of the LAD in these patients showed that the artery bent around the apex and extended along the diaphragmatic left ventricle. Ibanez et al14 proposed that in patients with a “well-developed” LAD such as those studied, widespread apical akinesis can be caused by transient occlusion; implying that takotsubo cardiomyopathy in these patients is essentially an aborted myocardial infarction.Another confounding variable is that takotsubo cardiomyopathy occurs predominantly in postmenopausal women. Does a difference exist between the sexes in the psychological response to stress that triggers an abnormal physiological change? Is the cardiovascular system of women physiologically or anatomically more sensitive than that of men to catecholamines? Sex hormones may influence the sympathetic nervous system and may affect coronary vasoreactivity or the tendency to spasm. Perhaps endothelial dysfunction, known to worsen after menopause (because of lowered estrogen levels) further increases vulnerability to sympathetically mediated myocardial stunning.1Patients with takotsubo cardiomyopathy have signs and symptoms suggestive of acute coronary syndrome, usually chest pain, dyspnea, ST-segment changes on ECGs, and elevated levels of cardiac biomarkers.3,6,15,16 Degree of symptom severity varies widely. Because of acute left ventricular dysfunction, some patients have pulmonary edema or cardiogenic shock.1,3,7 Onset of signs and symptoms is usually sudden and usually occurs after an emotional stressor such as the death of a loved one or a physical stressor such as an asthma attack (Table 2). A systematic review1 of 254 patients with takotsubo cardiomyopathy indicated that 27% had an emotional stressor, 39% had a physical stressor, and 34% could not identify a stressor.The most common ECG finding in takotsubo cardiomyopathy is ST-segment elevation, typically in the precordial leads5 (Figure 4), but ECGs can have normal findings or show T-wave abnormalities or Q waves5 (Figure 5). Evolutionary changes sometimes occur in the first few days, including resolution of the ST-segment elevation with development of diffuse and often deep T-wave inversion that involves most leads.15Most patients with takotsubo cardiomyopathy have elevated levels of cardiac biomarkers, although usually not to the extent associated with classic myocardial infarction.6 In the Global Use of Strategies to Open Occluded Arteries in Acute Coronary Syndromes (GUSTO IIa) troponin substudy,17 222 patients with classic myocardial infarction associated with ECG changes were studied. Their levels of CKMB and troponin and the degrees of elevation above the upper limit of normal were examined. Among these patients, 95% had more than a 2-fold increase in CKMB level and more than a 3- to 11-fold increase in troponin level.17 Gianni et al,1 in a review of 14 studies on patients with takotsubo cardiomyopathy, found 6 studies in which troponin levels were measured and 3 studies in which CKMB levels were measured. The troponin level was elevated in 106 of 123 patients (86.2%), and the CKMB level was elevated in 17 of 23 (73.9%),1 well below the expected 95% elevation that occurs in patients with classic myocardial infarction. Kazuki et al13 compared 10 patients who had takotsubo cardiomyopathy with 16 patients who had classic acute coronary syndrome. The mean elevation of levels of cardiac biomarkers in acute coronary syndrome was 10 times that in the patients with takotsubo cardiomyopathy. The mean level of CKMB (normal, 25 IU/L) in patients with takotsubo cardiomyopathy was 34 IU/L (SD, 23) compared with a mean of 326 IU/L (SD, 98) in patients with acute coronary syndrome.13No way currently exists to immediately distinguish the signs and symptoms of takotsubo cardiomyopathy from those of myocardial infarction caused by acute coronary thrombosis. Urgent cardiac catheterization is often performed. A diagnosis of takotsubo cardiomyopathy is suspected when obstructive coronary disease is not present to explain the patient’s degree of left ventricular dysfunction. Diagnosis is confirmed by observation of the typical octopus pot morphology of the left ventricle. Identification of a triggering emotional or physical stressor is considered supportive of but not necessary to the diagnosis.15 An echocardiogram must be obtained within days or weeks after the acute phase to confirm that abnormalities have reversed. Table 3 summarizes the clinical findings that lead to a diagnosis of takotsubo cardiomyopathy.Because takotsubo cardiomyopathy is initially indistinguishable from classic acute coronary syndrome, immediate treatment should include management of coronary ischemia and pulmonary edema. This management includes continuous telemetry monitoring and administration of aspirin, anticoagulants with direct thrombin inhibition and or glycoprotein IIb/IIa receptor inhibition, nitrates, β-blockers, and diuretics. Once takotsubo cardiomyopathy is diagnosed, treatment is primarily supportive. Akashi et al5 noted complete reversal of contractile abnormalities and recovery with no treatment. Aspirin can be discontinued unless coronary disease or peripheral vascular disease is concomitant. β-Blockers may be continued long-term to protect against catecholamine sensitivity, which may predispose to this syndrome. Heparin and coumadin should be used if apical thrombus is present, or a severe apical defect makes thrombus formation likely.6Most complications of takotsubo cardiomyopathy occur during the acute phase of illness. Late complications are rare because the syndrome is reversible and the damage is not permanent. The reported complication rate is about 19%.16 Heart failure and pulmonary edema occur in 3% to 46% of patients, and mortality rates are 1%6,17 to approximately 3%.16 Reported complications are summarized in Table 4.Patients with left-ventricular failure can require mechanical support with intra-aortic counterpulsation by balloon pump during the acute phase. Adrenergic agents are usually avoided to prevent additional catecholamine stimulation. Diuretics are often helpful for pulmonary edema and fluid overload. Standard therapy for left ventricular dysfunction should be initiated, including use of angiotensin-converting enzyme inhibitors and β-blockers.Heparin and warfarin may be used to treat or prevent left ventricular apical thrombus, which is a risk of significant left ventricular dysfunction. Apical thrombi form because of stasis of blood in the akinetic segments. This same protocol is used to prevent thrombus in patients with ventricular aneurysms as a complication of classic myocardial infarction.19 Warfarin can be discontinued once ventricular function has returned to normal.6Patients with takotsubo cardiomyopathy are at risk for obstruction of the left ventricular outflow tract (LVOT).1 The LVOT is the path that blood takes along the septal wall as the blood is being ejected from the left ventricle through the aortic valve. Obstruction of this pathway is caused by exaggerated contraction of the base of the ventricle when hypokinesis of the apex occurs. The unbalanced contraction of the ventricle reduces the size of the outflow tract, resulting in acceleration of blood flow through this pathway during systole. Accelerated flow decreases the pressure above the neighboring mitral valve, causing a suctioning effect of the anterior mitral valve leaflet toward the septum. This “systolic anterior motion” of the mitral valve toward the septum causes further LVOT obstruction,20 which can cause hypotension. Echocardiography or catheterization of the left side of the heart is used to diagnose this complication. The hypotension of LVOT obstruction can be managed in several ways. β-Blockers can reduce the hypercontractility of the base and lessen the degree of obstruction. β-Blockers also increase ventricular filling during diastole. Reduction in pressure gradient between the left ventricular apex and outflow tract has been observed after intravenous injection of pro-pranolol.3 Increased blood volume increases the functional size of the outflow tract and reduces the obstruction.20 Intravenous fluids can be used to increase volume if the patient does not have pulmonary edema.Overall, without significant comorbid diseases, prognosis for patients with takotsubo cardiomyopathy is good once the acute phase has passed. Recommendations for follow-up include echocardiography at approximately 4 to 6 weeks after discharge to document normalization of left ventricular function. Complete resolution of contractile abnormalities within weeks is characteristic of this syndrome, so another diagnosis should be considered for patients with persistent contractile abnormalities.Reoccurrence of takotsubo cardiomyopathy is considered rare and has been reported in no more than 10% of cases.15 Gianni et al1 identified 4 studies documenting a mean recurrence rate of 3.5%. However, the syndrome has been documented for a relatively short time, and so the natural history remains largely unknown. Patients should be followed up regularly as outpatients.Takotsubo cardiomyopathy is an important health issue involving postmenopausal women without severe coronary artery disease and often without classic risk factors for coronary artery disease. Patients are affected suddenly, with no warning, often at a time of crisis in their life. Health care providers should be prepared to provide education and counseling to patients with this unique diagnosis. Takotsubo cardiomyopathy should be considered when patients have signs and symptoms of acute coronary syndrome and appear to be at low risk for coronary artery disease, especially if a stressful event occurred before the onset of the signs and symptoms.Nursing care of patients with takotsubo cardiomyopathy involves monitoring hemodynamic status, providing supportive measures, and watching for complications. Nurses need a thorough understanding of the nature of the syndrome and what distinguishes it from classic myocardial infarction. Education of patients and their families about the nature of the syndrome, including its reversibility and low rate of recurrence, is imperative. Expectation for a full recovery will be reassuring to patients and their families. Assessing effective coping is important, especially if a major emotional stressor was the precipitant of the syndrome. The added stress of being ill and hospitalized requires continued psychological support. Patients must be educated on the importance of outpatient follow-up for repeat echocardiography to confirm resolution.If mild or moderate coronary disease was detected during angiography, the patient should also be counseled on risk-factor modification for coronary artery disease.Further research is needed to clarify the pathophysiology of takotsubo cardiomyopathy, especially in relationship to women. Also important is distinguishing any potentially modifiable risk factors. Additionally, future research should focus on techniques for differentiating takotsubo cardiomyopathy from classic acute coronary syndrome and on establishing standardized criteria for diagnosis and clinical guidelines for treatment and follow-up.