Most anesthesiologists are well aware of the adverse effects of cardiac surgery, especially the use of cardiopulmonary bypass, on the brains of our patients. In this issue of Anesthesia & Analgesia our attention is redirected, to the potential adverse effects of the brain on the heart, by two case reports of the recently described syndrome of “Transient Left Ventricular Apical Ballooning (TLVAB)” (“Tako-Tsubo-like cardiomyopathy”) occurring after noncardiac surgery (1) and associated with subarachnoid hemorrhage (SAH) (2). Cushing was one of the first to call attention to the effect of the brain on the heart over a century ago, and most anesthesiologists are acquainted with the not infrequent evidence of cardiac abnormalities (electrocardiogram [ECG] changes, elevated enzymes, left ventricular [LV] dysfunction) associated with brain injury (especially with SAH and brain death). However, it is likely that few anesthesiologists were aware of this new syndrome (TLVAB) until publication of these two case reports. It frequently mimics acute myocardial infarction, is often preceded by emotional or physiologic stress, and is thought to be mediated by excessive sympathetic discharge from the central nervous system (CNS).
The perioperative appearance of this entity raises many issues for all anesthesiologists, not just those concentrating on cardiac, neurological, or critical care anesthesia; for instance, which cases should be included in this syndrome? What is its pathophysiology? When should it be suspected? How can it be diagnosed and differentiated from conventional unstable coronary artery disease? And can or should the anesthesia management of these patients differ from that of patients with acute coronary artery syndromes resulting from atherosclerotic coronary artery disease?
TLVAB was first recognized and described in the Japanese literature by Sato et al. (3), who proposed the term “tako-tsubo-like cardiomyopathy” because the left ventriculogram at end-systole resemble the Japanese octopus trap (tako = octopus, tsubo = pot) (Fig. 1). Other terms that have been used include ampulla cardiomyopathy, stress cardiomyopathy, reversible LV dysfunction, reversible myocardial contractility abnormalities, and broken heart syndrome. Key features include presentation as an acute coronary syndrome (e.g., typical chest pain, precordial ST segment elevation, elevated cardiac enzymes—although these are usually low compared with usual myocardial infarcts), mainly (80%–94%) occurs in elderly women, is associated with this peculiar regional wall motion abnormality (predominantly apical and mid ventricular, with transient hyperkinesia of the base). TLVAB is generally associated with a good outcome, although arrhythmias, ventricular rupture, mural thrombus and embolization and even recurrence have been reported. Transient but sometimes severe LV failure (pulmonary edema, cardiogenic shock) is common, and there have been deaths. All of this occurs in the absence of demonstrable, hemodynamically significant, fixed coronary artery lesions (5–8) Abe and Kondo (9) and Bybee et al. (5) (the Mayo Clinic criteria) have defined the criteria for making the clinical diagnosis of TLVAB.
The pathophysiology of TLVAB is unknown, but many hypotheses have been proposed, and it may have several different mechanism and causes. Most authors note its relationship to stress (emotional or physical/physiologic) and attribute it to enhanced sympathetic activity originating in the CNS, which results in high levels of catecholamines in the blood and/or high levels of norepinephrine released directly into the myocardium by sympathetic nerves that terminate in the myocardium. Catecholamines may mediate their adverse effects on the heart by increasing myocardial oxygen demands beyond supply, inducing vasospasm in the epicardial coronaries (10,11) or plaque rupture (12), causing transient dynamic LV outflow tract obstruction (8,13,14), altering the microvasculature, or by direct myocyte injury. It has been known for nearly 50 years that high levels of catecholamines can cause myocyte injury. Ako et al. (15) have reviewed the evidence of reversible microvascular endothelial dysfunction and its resemblance to cardiac syndrome X. Emotional and physical stresses are known to alter microvascular function, the coagulation cascade, and markers of inflammation (16).
Many other questions remain unanswered: Why does TLVAB mainly involve women and why does it predominantly affect the apex? Dec (6) suggested that the latter may be related to the fact that the LV apex is particularly vulnerable to catecholamine-mediated toxicity (17), that the LV apex does not have the three-layered myocardial structure characteristic of the rest of the ventricular wall, that there is a base to apex perfusion gradient, that the apex behaves as a border zone when myocardial blood flow is impaired, and, last, that the apical region more easily loses its elasticity. However, others have noted a paucity of sympathetic nerve terminals in the LV apex (18,19) to explain apical sparing observed in some cases of transient regional wall motion abnormalities after SAH (20). Furthermore, not all cases of this same apparent syndrome of stress-induced reversible regional myocardial dysfunction exhibit apical dysfunction. In some cases the apex is spared and the mid-portion or even the base of the LV is affected (21–23), whereas in one third of cases in another series the right ventricular apex was involved (24) This led the Mayo Clinic group (24) to suggest that the name be changed to “transient cardiac apical ballooning syndrome,” but this does not address the fact that, in some cases, the apex is spared. Female propensity may be related to different hormonal environment (16). On the other hand, the fact that only a few individuals (mainly females) exposed to similar degrees of emotional or physical stresses develop this syndrome suggests a genomic predisposition (see addendum).
TLVAB is commonly referred to as an example of “myocardial stunning” because of its pattern of recovery. However, myocardial stunning specifically refers to prolonged but reversible LV dysfunction that follows a brief period of myocardial ischemia. It is not clear that TLVAB is preceded by ischemia, although some have suggested brief microvascular dysfunction and/or a severe imbalance between myocyte oxygen supply and demand as a result of catecholamine stimulation in its pathogenesis. Whether the type of muscle injury encountered in TLVAB is significantly different from conventional postischemic myocardial stunning is yet to be resolved.
Typical cases of TLVAB have been reported after surgery (25), pheochromocytoma (26), head injury (27), SAH (although described before the syndrome was generally recognized) (28–30), transient ischemic attack (31) and in patients admitted to medical intensive care units (ICUs) (32,33).
Many authors have excluded the LV dysfunction associated with SAH from the definition of TLVAB (5,8,9). However, Ako et al. (34) take exception to this. They reviewed and compared the clinical syndromes of tako-tsubo-like LV dysfunction and the LV dysfunction that follows acute brain injury, as well as animal models of each (15) (see their Table 1) and suggest that these are simply examples of a range of disorders and that the definition should be more inclusive and should encompass conditions with a similar clinical picture and patterns of ventricular dysfunction that appear to be initiated by CNS stimulation. I agree with Ako et al. and believe that, at least for the present, we can learn more about these various syndromes of reversible LV dysfunction by “lumping” rather than dividing.
Between 50% and 90% of patients experiencing a SAH exhibit ECG changes; 20%–50% have elevated troponin levels, 10%–20% have transient abnormal LV function (global or regional), 20%–30% experience pulmonary edema, some of which may be a result of LV dysfunction, and 2%–5% experience cardiogenic shock. The incidences of all of these cardiac abnormalities are directly related to severity of SAH (Hunt and Hess grade) and, although associated with adverse outcome, are rarely the cause of mortality (35–43). These changes have also been hypothesized to be a result of the effects of sympathetic hyperactivity on the myocardium (44).
Doubt regarding the relationship of the LV dysfunction found in patients with SAH to TLVAB was raised by the study of Zaroff et al. (20), who observed global hypokinesis in 9 of 30 patients with SAH who had abnormal LV function by echocardiography and apical sparing in 57% of those with regional wall motion abnormalities. However, “classic” TLVAB has been described in two case reports of elderly female patients after SAH (28,30) (Fig. 2) and in 23 additional patients reported by Kono et al. (45) and Kuroiwa et al. (29). Of the 52 other cases (exclusive of Zaroff et al.'s 30 cases) of SAH with abnormal LV function (ventriculogram or echocardiogram) reported in the literature, approximately 56% exclusively involved the apex and 19% involved the apex (usually predominantly) as well as other walls, whereas only 10% spared the apex and 15% had global hypokinesis (28–30,44–56). The gender distribution (71% females) matches the gender distribution for SAH and thus seems not as predominantly associated with female gender as in other cases of TLVAB. Also, ST elevations were reported in only 60% of patients with LV dysfunction associated with SAH, although the Osaka Medical College group observed LV apical hypokinesis or akinesis in all 30 of their patients who had ST segment elevation associated with SAH (29,45).
Recently Park et al. (32) detected TLVAB in 28% of medical patients admitted to their ICU in a prospective study in which they performed transthoracic echocardiography in all patients on admission. However, unlike previously described series of TLVAB, most of their patients were males (65%), and only 20% had ST segment changes (elevation in only 3 patients). Coronary angiography was not performed, but myocardial perfusion scans were normal in 10 of 11 patients in whom they were done. These data suggest that this syndrome may be more prevalent in critically ill patients (and perhaps also in perioperative patients) than previously suspected. However, in a retrospective review, Haghi et al. (33) found six cases of typical tako-tsubo cardiomyopathy (all underwent coronary angiography) in their medical ICU over an 18-mo period. Five presented with evidence of cardiac depression. Half were males. During this period of time approximately 600 patients were admitted to their ICU (Haghi, personal communication), which suggests a considerably lower incidence in the ICU than found by Park et al. (32).
In summary, regional (and global) LV dysfunction may be occurring more frequently during critical illness (and perioperatively) than previously suspected. It behaves like myocardial stunning in that it is rapidly reversible and is thought to be initiated by excessive activation of the sympathetic nervous system. One distinguishable pattern is that of TLVAB. Whether TLVAB is a unique syndrome or merely one example of a spectrum of transient ventricular dysfunction associated with several types of CNS stimulation (and one that may involve other parts of the ventricles) is yet to be resolved. As pointed out by Conti (57), clearly not all LV apical abnormalities represent tako-tsubo syndrome. Other types are LV aneurysm, noncompaction, and apical hypertrophy.
Until further information becomes available—and we hope that studies such as those of Lentschener et al., Otomo et al., Park et al. (32) and Haghi et al. (33) will stimulate further studies—what can we conclude at present? One's first response when confronted by a patient who may have this syndrome (e.g., typical echocardiogram) should be to rule out the more common cause of acute coronary syndrome, i.e., acute myocardial infarction/ischemia resulting from atherosclerotic coronary artery disease, which has different prognostic (high risk of adverse outcome) and management (defer surgery if possible, consider coronary intervention) implications. Making this differential diagnosis will benefit from the advice of a knowledgeable cardiologist and may require a coronary arteriogram. If the patient is thought to have TLVAB syndrome (instead of atherosclerotic myocardial ischemia/infarction), the management implications are likely quite different. First the prognosis appears to be much better, although dysrhythmias, heart failure, and even cardiogenic shock may occur. If we can extrapolate from the SAH experience and other series, the probability of cardiac death is low. The LV dysfunction is likely to recover rapidly (within a reasonable time to delay nonemergent surgery). Aggressive intervention is to be encouraged and, unlike in patients with ongoing ischemia or hemodynamically significant epicardial coronary artery disease, the use of inotropic therapy is not likely to be detrimental but rather helpful. If dynamic LV outflow tract obstruction is a contributing or causal factor, then intravascular volume expansion, vasoconstrictor therapy, and β-adrenergic receptor blocker therapy may be warranted. Finally, if surgery cannot be delayed, limited evidence suggests that it will be reasonably well tolerated. However, these are only conjectures on my part, and we eagerly await more data on which to base rational management.
Added to proof: A recent paper from the group at the University of California in San Francisco (Zaroff JG, Pawlikowska L, Miss JC, et al. Adrenoreceptor polymorphism and the risk of cardiac injury and dysfunction after subarachnoid hemorrhage. Stroke 2006;37:1680–5) has offered data that supports the hypothesis that there may be a genetic predisposition (polymorphism of adrenoreceptors) for cardiac injury associated with acute CNS disease (SAH). (Also see editorial by AM Naidech that accompanied this article on page 1635.)
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