Version May 2024
INTRODUCTION — Stress cardiomyopathy (also called apical ballooning syndrome, takotsubo cardiomyopathy, broken heart syndrome, and stress-induced cardiomyopathy) is a syndrome characterized by transient regional systolic dysfunction of the left ventricle (LV), mimicking myocardial infarction (MI), but in the absence of angiographic evidence of obstructive coronary artery disease or acute plaque rupture [1,2]. In most cases of stress cardiomyopathy, the regional wall motion abnormality extends beyond the territory perfused by a single epicardial coronary artery.
Stress cardiomyopathy was first described in 1990 in Japan and has since been increasingly recognized around the world [1,3-9]. The term "takotsubo" is taken from the Japanese name for an octopus trap, which has a shape that is similar to the systolic apical ballooning appearance of the LV in the most common and typical form of this disorder (movie 1 and movie 2); mid and apical segments of the LV are depressed, and there is hyperkinesis of the basal walls. Midventricular type (movie 3) and focal variants have also been described. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy", section on 'Approach to diagnosis'.)
This topic will review the management and prognosis of stress cardiomyopathy. The epidemiology, pathogenesis, clinical manifestations, and diagnosis of stress cardiomyopathy are discussed separately. (See "Clinical manifestations and diagnosis of stress (takotsubo) cardiomyopathy".)
MANAGEMENT
Approach to management — Stress cardiomyopathy is generally a transient disorder that is managed with supportive therapy. Conservative treatment and resolution of the physical or emotional stress usually result in rapid resolution of symptoms, although some patients develop acute complications such as shock and acute heart failure (HF) that require intensive therapy. Appropriate management of shock varies depending upon whether significant left ventricular outflow tract (LVOT) obstruction is present. HF management during acute presentation and following stabilization is generally performed according to standard guidelines for HF with reduced ejection fraction (HFrEF) except that particular care is taken to avoid volume depletion and vasodilator therapy in patients with LVOT obstruction. Recommendations for anticoagulation to prevent thromboembolism in patients with stress cardiomyopathy with LV thrombus or severe LV systolic dysfunction are similar to those for patients post-MI.
Hypotension and shock — Approximately 5 to 10 percent of patients with stress cardiomyopathy develop cardiogenic shock [8,10]. Factors associated with the development of shock include younger age, lower LV ejection fraction (LVEF) and a physical trigger. Among patients with shock, in hospital mortality is almost 10-fold higher compared with those without shock [11]. In-hospital mortality from shock is lower in stress cardiomyopathy (15 versus 37 percent) compared with acute MI [10,12]. Mortality during follow-up remains higher, but whether this is a consequence of shock or higher comorbidity burden is unknown [11,13]. The development of shock may not correlate with the extent of left or right ventricular systolic dysfunction [14]. One explanation for discordance between ventricular dysfunction and risk of shock is that some shock is caused by LVOT obstruction, which has been described in 10 to 25 percent of patients with stress cardiomyopathy [15-18].
Since management of shock differs depending upon whether LVOT obstruction is present, patients who are in shock should undergo urgent echocardiography to assess for LVOT obstruction. In some cases, LVOT obstruction is accompanied by systolic anterior motion of the mitral valve and mitral regurgitation, similar to that seen in hypertrophic cardiomyopathy [16,17].
Without left ventricular outflow tract obstruction — We suggest cautious fluid resuscitation for patients with hypotension without significant pulmonary congestion (with or without LVOT obstruction). Patients without significant LVOT obstruction who are hypotensive due to LV systolic dysfunction may require inotropic therapy (eg, dobutamine or dopamine) as a temporizing measure. Since the condition is potentially caused by catecholamine excess, the impact of sympathomimetics remains to be established. In a patient with hypotension due to pump failure, inotropic agents may induce LVOT obstruction, but the degree is usually mild [5]. Inotropic therapy should be discontinued in patients who develop moderate to severe LVOT obstruction; a change in the therapeutic approach is not necessary if mild LVOT obstruction develops. (See "Treatment of acute decompensated heart failure: Specific therapies", section on 'Management of hypotensive patients'.)
Patients with persistent hypotension with symptoms or evidence of consequent end-organ hypoperfusion despite optimization of filling pressures and inotropic therapy may require vasopressor therapy. In this setting, invasive monitoring can be helpful to assess filling pressures and systemic vascular resistance. (See "Pulmonary artery catheterization: Indications, contraindications, and complications in adults", section on 'Indications'.)
Mechanical circulatory support (eg, intraaortic balloon counterpulsation [IABP], percutaneous continuous-flow device) is the preferred therapy when there is marked LV dysfunction associated with severe hypotension or shock [5]. (See "Treatment of acute decompensated heart failure: Specific therapies", section on 'Management of hypotensive patients' and "Intraaortic balloon pump counterpulsation".)
With left ventricular outflow tract obstruction — In contrast to hypotension due only to pump failure, hypotension associated with moderate to severe LVOT obstruction should not be treated with inotropic agents, because they can worsen the degree of obstruction [5,16].
The recommended approach to patients with stress cardiomyopathy with moderate to severe LVOT obstruction is similar to that for patients with hypertrophic cardiomyopathy with LVOT obstruction and hemodynamic collapse. Therapy includes the use of beta blockers, which can improve hemodynamics by causing resolution of the obstruction. In addition, in the absence of significant pulmonary congestion, preload should be increased with leg elevation and fluid resuscitation [15,16].
In patients with LVOT obstruction and severe hypotension who either do not tolerate or do not adequately respond to beta blockers, an alpha agonist may be added with caution and close monitoring. Phenylephrine is a pure alpha-adrenergic agonist that may reduce the gradient by increasing afterload, thereby improving overall hemodynamics. This treatment may be helpful to support blood pressure while a beta blocker is administered to reduce inotropy. However, the vasoconstrictive effects of alpha agonists may be harmful, particularly in those patients who can be prone to coronary vasospasm. Thus, if phenylephrine is used, it should be done with a high degree of caution and very close monitoring of hemodynamics and tissue perfusion. The utility of noncatecholamine agents such as vasopressin or terlipressin in this setting is unknown at this time, but these may be considered as alternative vasopressors.
In patients with LVOT obstruction with severe hypotension that is unresponsive to initial medical therapy and volume resuscitation, we suggest the use of an IABP. As with patients in shock due to pump failure, those with LVOT obstruction may benefit from an IABP, although there is a slight risk that afterload reduction from the IABP will worsen the degree of obstruction [5], so the effect of IABP on the LVOT gradient should be evaluated [17]. (See "Intraaortic balloon pump counterpulsation".)
Heart failure — Acute HF is managed according to standard recommendations, which include supplemental oxygen and assisted ventilation as needed, intravenous diuretics to treat volume overload, and vasodilator therapy as needed to correct elevated filling pressures and/or LV afterload. Volume depletion and vasodilator therapy should be avoided in patients with LVOT obstruction. (See "Treatment of acute decompensated heart failure: Specific therapies".)
There are no specific randomized trial data to define an optimal medical regimen for stress cardiomyopathy. We treat hemodynamically stable patients with standard medications for HF with reduced ejection fraction, especially as the diagnosis may not be definitive at the time of presentation. These include beta blocker therapy and, for patients without LVOT obstruction, an angiotensin converting enzyme (ACE) inhibitor (or angiotensin II receptor blocker [ARB]) and diuretics as necessary to treat volume overload [15]. Observational data have suggested that acute use of beta blockers may not improve in-hospital mortality. In a retrospective analysis of 2672 patients, 423 had beta blocker therapy initiated within the first two days, and this group did not have reduced 30-day in-hospital mortality [19].
Stress cardiomyopathy is a transient disorder, and the appropriate duration of medical therapy is not known given the lack of clinical trial data. We generally treat patients with a medical regimen appropriate for HFrEF until there is recovery of systolic function, which occurs in one to four weeks in most cases. Since the condition may recur, we favor continuing adrenergic blockade with either beta blockers or combined alpha and beta blockers indefinitely in the absence of contraindications or intolerance.
Further study is needed to identify effective therapy in patients with stress cardiomyopathy. Observational data suggest that beta blocker therapy may not prevent this condition or its recurrence [20]. Over 30 percent of 1750 patients in the International Takotsubo Registry study were taking beta blockers when they developed the condition [8]. There was no evidence of survival benefit at one year from use of a beta blocker at discharge. In addition, 29 of the 57 patients who subsequently developed recurrent stress cardiomyopathy were taking beta blockers at the time of the second event. In contrast, use of an ACE inhibitor or ARB was associated with improved survival at one year. However, a later Mayo Clinic study of 265 patients with stress cardiomyopathy found no association between beta blocker and ACE inhibitor use at discharge and survival [21]. These observational findings are hypothesis generating and are not sufficient to define therapy.
Thromboembolism — The potential risk of intraventricular thrombus formation and systemic embolization should be addressed in patients with LV thrombus or severe LV systolic dysfunction. Echocardiography (and cardiac magnetic resonance imaging if available) should include evaluation for potential thrombus as well as assessment of the extent of wall motion abnormality. Ventricular thrombus was identified in 1.3 percent of the 1750 patients with stress cardiomyopathy in the International Takotsubo Registry study [8].
Scant data are available to guide anticoagulant therapy to prevent thromboembolism in patients with stress cardiomyopathy:
●Indirect data are available from randomized trials of anticoagulation to prevent LV thrombus in patients with acute MI. As discussed in detail separately, these trials found that approximately 10 days of anticoagulation reduced the incidence of LV thrombus. (See "Left ventricular thrombus after acute myocardial infarction", section on 'Prevention of embolic events'.)
●The use of anticoagulation to prevent embolization in patients with known LV thrombus is supported by indirect data from observational studies in patients with LV thrombus after MI. In these studies, anticoagulation during a period of four to six months was associated with a reduced rate of embolization. (See "Left ventricular thrombus after acute myocardial infarction", section on 'Prevention of embolic events'.)
We recommend anticoagulation with a vitamin K antagonist (warfarin) if intraventricular thrombus is detected, with a suggested duration of approximately three months. The duration of anticoagulation may be modified based on the rate of recovery of cardiac function and resolution of the thrombus. For patients without thrombus but with severe LV systolic dysfunction (ie, ejection fraction <30 percent) and low bleeding risk, we suggest anticoagulation with vitamin K antagonist (warfarin) until akinesis or dyskinesis has resolved or for three months, whichever is shorter.
Standard recommendations for antiplatelet therapy apply to patients with coexisting coronary atherosclerosis [15,22].
PROGNOSIS
In-hospital mortality and complications — Although most patients with stress cardiomyopathy recover, the risk of severe in-hospital complications is similar to that in patients with acute coronary syndrome [8]. As an example, the risk of a composite of catecholamine use, cardiogenic shock, the use of invasive or noninvasive ventilation, cardiopulmonary resuscitation, and death was 19.1 percent in patients with stress cardiomyopathy in the International Takotsubo Registry study versus 19.3 percent in a control group of patients with acute coronary syndrome [8]. In-hospital mortality rates have ranged from 0 to 8 percent (4.1 percent in the International Takotsubo Registry study) [5,8,15,23,24].
A National Inpatient Sample study of 88,849 stress cardiomyopathy patients found that frequency of complications was higher (38.2 versus 32.6 percent) compared with acute MI. Complications included acute HF and shock, acute kidney injury, arrhythmia, vascular access complications, ventricular and papillary muscle rupture, tamponade, and stroke. Stress cardiomyopathy patients had higher rates of acute HF (29 versus 16.6 percent) and strokes (0.5 versus 0.2 percent), but lower rates of other complications. In-hospital mortality was lower in stress cardiomyopathy (2.6 versus 3.1 percent) [10].
A preliminary report proposed a risk score to predict the likelihood of acute HF based on the presence or absence of the following three variables: age >70 years, presence of a physical stressor, and LVEF <40 percent [25]. In the development cohort of 118 patients, the likelihood of developing acute HF was <10 percent in the absence of these risk factors. With one, two, or three risk factors present, the risk was approximately 28, 58, and 85 percent, respectively. A similar gradient of risk was observed when the risk score was applied to the 52 patients in the validation cohort.
Patients who survive the acute episode typically recover systolic ventricular function within one to four weeks [5,6,23,26,27]. In two series, for example, the mean LVEF increased from 29 percent at presentation to 63 percent at a mean of six days [5] and from a median of 20 percent at presentation to 60 percent at two to four weeks [26].
Long-term mortality and morbidity — However, the risk of adverse events in this older adult population continues after hospital discharge, as illustrated by the following studies:
●In the International Takotsubo Registry study, which included 1750 patients, the composite rate of major adverse cardiac and cerebrovascular events (including death, stroke, or transient ischemic attack) during the first 30 days after admission was 7.1 percent [8]. During long-term follow-up, the rate of death from any cause was 5.6 percent per patient-year, and the rate of major adverse cardiac and cerebrovascular events was 9.9 percent per patient-year, but no control population was available for comparison.
●In a series of 136 patients, all-cause mortality of stress cardiomyopathy patients was increased compared with an age- and sex-matched general population; however, the excess mortality was predominantly in the first year and was predominantly due to noncardiac causes [28], with the most common causes being cancer, chronic obstructive pulmonary disease (COPD), and sepsis [29]. The importance of noncardiac conditions was confirmed in an analysis of a Mayo clinic cohort of 265 patients with stress cardiomyopathy in which cancer, physical trigger, and a history of depression were independent predictors of one-year mortality [21]. The lowest mortality was in patients with an emotional trigger and the highest in those with a physical trigger, including a major neurological disorder [30].
●A series of 174 patients with 15 years of follow-up found that in-hospital mortality was similar to that in a matched group of patients with acute MI (hazard ratio [HR] 1.06, 95% CI 0.81-1.38), but the risk of cardiovascular rehospitalization was lower in the stress cardiomyopathy group (HR 0.79, 95% CI 0.66-0.95) [31]. Compared with matched population controls admitted for noncardiovascular diagnoses, patients with stress cardiomyopathy had higher rates of in-hospital mortality (HR 1.59, 95% CI 1.21-2.09), cardiovascular rehospitalization (HR 2.71, 95% CI 2.24-3.28), and hospitalization for stress and anxiety disorder (HR 1.86, 95% CI 1.21-2.85). Associations between stress cardiomyopathy and these adverse outcomes were strongest during the first few years after initial admission for stress cardiomyopathy.
●Many patients experience ongoing cardiovascular symptoms. In a study from the Mayo Clinic, 31 out of 100 patients reported chest pain following discharge, and in 12 it resulted in hospitalization during a mean follow-up duration of 4.4 years [32].
Recurrence rates — In cohort studies, the yearly risk of recurrence was approximately 1 to 2 percent per year. The triggers of stress cardiomyopathy and the regions involved can differ between the index event and a recurrence [8,20,32-35]. Factors associated with recurrence have not been established.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Heart failure in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Stress cardiomyopathy (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Approach to management – Stress cardiomyopathy is generally a transient disorder managed with supportive therapy. Conservative treatment and resolution of physical or emotional stress usually results in rapid resolution of symptoms, although some patients develop acute complications such as shock and acute heart failure (HF) that require intensive therapy. (See 'Approach to management' above.)
•Heart failure – In patients with stress cardiomyopathy, HF management during acute presentation and following stabilization is generally according to standard guidelines for HF with reduced ejection fraction (HFrEF) except that particular care is taken to avoid volume depletion and vasodilator therapy in patients with left ventricular outflow tract (LVOT) obstruction. (See 'Heart failure' above.)
•Thromboembolism – For patients with stress cardiomyopathy with intraventricular thrombus, we recommend anticoagulation (Grade 1B). We typically anticoagulate for three months, with the duration of anticoagulation modified based on the rate of recovery of cardiac function and resolution of the thrombus. (See 'Thromboembolism' above.)
For patients without thrombus but with severe LV dysfunction (ie, ejection fraction <30 percent) and low bleeding risk, we suggest anticoagulation until the akinesis or dyskinesis has resolved or for three months, whichever is shorter (Grade 2C). (See 'Thromboembolism' above.)
●Prognosis – In-hospital mortality is approximately 3 to 4 percent. Patients who survive the acute episode typically recover systolic LV function within one to four weeks. (See 'Prognosis' above.)
Patients who survive an episode of stress cardiomyopathy have a risk of recurrence of approximately 1 to 2 percent per year. (See 'Prognosis' above.)
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