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The Brain and the Heart

Hessel, Eugene A. II, MD, FACS

Section Editor(s): Hogue, Charles W. Jr; London, Martin J.

doi: 10.1213/01.ane.0000229719.39592.8c
Cardiovascular Anesthesia: Cardiovascular and Thoracic Education: Editorial
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From the Department of Anesthesiology and Surgery (Cardiothoracic), University of Kentucky College of Medicine, Lexington, Kentucky.

This article has supplementary material on the Web site:www.anesthesia-analgesia.org.

Accepted for publication May 11, 2006.

Address correspondence and reprint requests to Eugene A. Hessel, MD, Professor, Anesthesiology and Surgery (Cardio-thoracic), University of Kentucky, 800 Rose St., Lexington, KY 40536. Address e-mail to ehessel@uky.edu.

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.

Figure 1.

Figure 1.

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).

Figure 2.

Figure 2.

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.

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ADDENDUM

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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REFERENCES

1. Lentschener C, Vignaux O, Spaulding C, et al. Early postoperative tako-tsubo-like left ventricular dysfunction (Transient left ventricular apical ballooning syndrome). Anesth Analg 2006;103:580–2.
2. Otoma S, Sugita M, Shimoda O, Terasaki H. Two cases of “transient left ventricular apical ballooning syndrome” associated with subarachnoid hemorrhage. Anesth Analg 2006;103:583–6.
3. Sato H, Tateishi H, Uchida T. Takotsubo-type cardiomyopathy due to multivessel spasm. In: Kodama, K, Haze K, Hon M, eds. Clinical aspect of myocardial injury: from ischemia to heart failure [in Japanese]. Kagakuhyouronsha 1990:56–64.
4. Kurisu S, Sato H, Kawagoe T, et al. Tako-tsubo-like left ventricular dysfunction with ST-segment elevation: a novel cardiac syndrome mimicking acute myocardial infarction. Am Heart J 2002;143:448–55.
5. 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;141:858–6.
6. Dec GW. Recognition of the apical ballooning syndrome in the United States. Circulation 2005;111:388–90.
7. Donohue D, Mohammad-Reza M. Clinical characteristics and demographics and prognosis of transient left ventricular apical ballooning syndrome. Heart Failure Rev 2005;10:311–6.
8. Desmet W. Dynamic LV obstruction in apical ballooning syndrome: the chicken or the egg? Eur J Echocardiogr 2006;7:1–3.
9. Abe Y, Kondo M. Apical ballooning of the left ventricle: a distinct entity? Heart 2003;89:974–6.
10. Maseri A. Myocardial stunning due to sudden emotional stress. N Engl J Med 2005;353:1923.
11. Upadya SP, Hoq SM, Pannala R, et al. Tako tsubo cardiomyopathy (transient left ventricular apical ballooning): case report of a myocardial perfusion echocardiogram study. J Am Soc Echocardiogr 2005;18:883.
12. Ibanez B, Navarro F, Cordoba M, et al. Tako-tsubo transient left ventricular apical ballooning: is intravascular ultrasound the key to resolve the enigma? Heart 2005;91:102–4.
13. Villareal R, Achari A, Wilansky S, Wilson J. Antero-apical stunning and left ventricular outflow tract obstruction. Mayo Clin Proc 2001;76:79–83.
14. Merli E, Sutcliffe S, Gori M, Sutherland GG. Tako-Tsubo cardiomyopathy: new insights into the possible underlying pathophysiology. Eur J Echocardiogr 2006;7:53.
15. Ako J, Sudhir K, Farouque O, et al. Transient left ventricular dysfunction under severe stress: brain-heart relationship revisited. Am J Med 2006;119:10–15.
16. Connelly K, MacIsaac A, Jelinek MV. The “tako-tsubo” phenomenon and myocardial infarction. South Med J 2006;99:2–3.
17. Mori H, Ishikawa S, Kojima S, et al. Increased responsiveness of left ventricular apical myocardium to adrenergic stimuli. Cardiovasc Res 1993;27:192–8.
18. Pierpont GL, DeMasater EG, Reynolds S, et al. Ventricular myocardial catecholamines in primates. J Lab Clin Med 1985;106:205–10.
19. Kline RC, Swanson DP, Wieland DM, et al. Myocardial imaging in man with I-123 metaiodobenzylguanidine. J Nucl Med 1981;22:129–32.
20. Zaroff JG, Rordorf G, Ogilvy CS, Picard MH. Regional patterns of left ventricular systolic dysfunction after subarachnoid hemorrhage: evidence for neurally mediated cardiac injury. J Am Soc Echo 2000;13:774–9.
21. Haghi D, Papavassiliu T, Fluchter S, et al. Variant form of the acute apical ballooning syndrome (takotsubo cardiomyopathy): observations on a novel entity. Heart 2006;92:392–4.
22. Bonnemeier H, Schafer U, Schunkert H. Apical ballooning without apical ballooning. Eur Heart J 2006 Feb 23; [Epub ahead of print].
23. Robles P, Alonso M, Huelmos AI, et al. Atypical transient left ventricular ballooning without involvement of apical segment. Circ 2006;113:e686–8.
24. Elsesber AA, Prasad A, Bybee KA, et al. Transient cardiac apical ballooning syndrome: prevalence and clinical implications of right ventricular involvement. J Am Coll Cardiol 2006;47:1082–3.
25. Ramakrishna G, Ravi BS, Chandrasekaran K. Apical ballooning syndrome in a postoperative patient with normal microvascular perfusion by myocardial contrast echocardiography. Echocardiography 2005;22:606–10.
26. Spes C, Knape A, Mudra H. Recurrent tako-tsubo-like left ventricular dysfunction (apical ballooning) in a patient with pheochromocytoma: a case report. Clin Res Cardiol 2006;95:307–11.
27. Poh KK, Chan MY, Chiba B-L. Images in cardiology:. reversible left ventricular apical ballooning after head injury. Clin Cardiol 2005;28:30.
28. Handlin LR, Kindrea LH, Beauchamp GD, et al. Reversible left ventricular dysfunction after subarachnoid haemorrhage. Am Heart J 1993;126:235–40.
29. Kuroiwa T, Morita H, Tanabe H, Ohta T. Significance of ST segment elevation in electrocardiograms in patients with ruptured cerebral aneurysms. Acta Neurochir (Wien) 1995;133:141–6.
30. Chang PC, Lee SH, Hung HF, et al. Transient ST elevation and left ventricular asynergy associated with normal coronary artery and Tc-99m PYP myocardial infarct scan in subarachnoid hemorrhage. Internat J Cardiology 1998;63:189–92.
31. Abi-Saleh B, Iskandar SB, Schoondyke JW, Fahrig S. Tako-tsubo syndrome as a consequence of transient ischemic attack. Rev Cardiovasc Med 2006;7:37–41.
32. Park JH, Kang SJ, Song JK, et al. Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU. Chest. 2005;128:296–302.
33. Haghi D, Fluechter S, Suselbeck T, et al. Takotsubo cardiomyopathy (acute left ventricular apical ballooning syndrome) occurring in the intensive care unit. Intensive Care Med 2006;32:1069–74.
34. Ako J, Honda Y, Fitzgerald PJ. Transient left ventricular apical ballooning (Letter). Ann Intern Med 2005;142:678.
35. Sato K, Masuda T, Izumi T. Subarachnoid hemorrhage and myocardial damage: clinical and experimental studies. Jpn Heart J 1999;40:683–701.
36. Parekh N, Venkatesh B, Cross D, et al. Cardiac troponin I predicts myocardial dysfunction in aneurysmal subarachnoid hemorrhage. J Am Coll Cardiol 2000;36:1328–35.
37. Sakr YL, Ghosn I, Vincent JL. Cardiac manifestation after subarachnoid hemorrhage: A systematic review of the literature. Prog Cardiovasc Dis 2002;45:67–80.
38. Macmillan CS, Grant IS, Andrews PJ. Pulmonary and cardiac sequelae of subarachnoid haemorrhage: time for active management? Intens Care Med 2002;28:1012–23.
39. Arab D, Yahia AM, Qureshi AI. Cardiovascular manifestations of acute intracranial lesions: pathophysiology, manifestations, and treatment. J Intens Care Med 2003;18:119–29.
40. Homma S, Grahame-Clarke C. Myocardial damage in patients with subarachnoid hemorrhage. Stroke 2004;35:552–3.
41. Tung P, Kopelnik A, Banki N, et al. Predictors of neurocardiogenic injury after subarachnoid hemorrhage. Stroke 2004;35:548–53.
42. Macrea LM, Tramer MR, Walder B. Spontaneous subarachnoid hemorrhage and serious cardiopulmonary dysfunction: a systematic review. Resuscitation 2005;65:139–48.
43. Naidech AM, Kreiter KJ, Janjua N, et al. Cardiac troponin elevation, cardiovascular morbidity, and outcome after subarachnoid hemorrhage. Circulation. 2005;112:2851–56.
44. Banki NM, Kopelnik A, Dae MW, et al. Acute neurocardiogenic injury after subarachnoid hemorrhage. Circulation 2005;112:3314–9.
45. Kono T, Morita H, Kuroiwa T, et al. Left ventricular wall motion abnormalities in patients with subarachnoid hemorrhage: neurogenic stunned myocardium. J Am Coll Cardiol 1994;24:636–40.
46. Pollick C, Cujec B, Parker S, Tator C. Left ventricular wall motion abnormalities in subarachnoid hemorrhage: an echocardiographic study. JACC 1988;12:600–5.
47. Davies KR, Gelb AW, Manninem PH, et al. Cardiac function in aneurismal subarachnoid hemorrhage: a study of electrocardiographic and echocardiographic abnormalities. BJA 1991;67:58–63.
48. Yuki K, Kodama Y, Onda J, et al. Coronary vasospasm following subarachnoid hemorrhage as a cause of stunned myocardium. J Neurosurg 1991;75:308–11.
49. Mayer SA, Li Mandri G, Sherman D, et al. Electrocardiographic markers of abnormal left ventricular wall motion in acute subarachnoid hemorrhage. J Neurosurg 1995;83:889–96.
50. Parr MJA, Finfer SR, Morgan MK. Lesson of the week: reversible cardiogenic shock complicating subarachnoid haemorrhage. BMJ 1996;313:681–3.
51. Dominguez H, Torp-Pedersen C. Subarachnoid haemorrhage with transient myocardial injury and normal coronary arteries. Scand Cardiovasc J 1999;33:245–7.
52. Donaldson JW, Pritz MB. Myocardial stunning secondary to aneurismal subarachnoid hemorrhage. Surg Neurol 2001;55:12–6.
53. Hirsch GA, Haldman AW, Wittstein IS, et al. ST-segment elevation in an unresponsive patient. Images in cardiovascular medicine. Circulation 2003;108:e165–6.
54. Jain R, Deveikis J, Thompson BG. Management of patients with stunned myocardium associated with subarachnoid hemorrhage. AJNR Am J Neuroradiol 2004;25:126–9.
55. Cheng TO. Subarachnoid hemorrhage mimicking acute myocardial infarction. Int J Cardiol 2004;95:361–2.
56. de Chazal ID, Parham WD 3rd, Liopynis P, Wijdicks EF. Delayed cardiogenic shock and acute lung injury after aneurysmal subarachnoid hemorrhage. Anesth Analg 2005;100:1147–9.
57. Conti CR. Four left ventricular apical abnormalities. Clin Cardiol 2006;29:50–1.
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