Stress cardiomyopathy pathophysiology

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Stress cardiomyopathy Microchapters



Historical Perspective




Differentiating Stress Cardiomyopathy from other Diseases

Epidemiology and Demographics

Risk Factors


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Unstable angina/non ST elevation myocardial infarction in Stress (Takotsubo) Cardiomyopathy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Dima Nimri, M.D. [2] Arzu Kalayci, M.D. [3]


The pathogenesis of stress cardiomyopathy is not completely understood. However, the most accepted theory behind it is thought to be due to catecholamine surge, which are thought to contribute to myocardial necrosis and stunning seen in stress cardiomyopathy. On biopsy, findings include an inflammatory infiltrate, fibrosis and formation of contraction bands, which may or may not be associated with myocardial necrosis. Stress cardiomyopathy is associated with various neurological and psychological conditions.


The cause of stress cardiomyopathy is unknown. Several theories have been postulated to explain the pathophysiology behind it:[1][2][3][4]

Catecholamine Cardiotoxicity:

The etiology of stress cardiomyopathy appears to involve the response of the myocardium to a hyperadrenergic state. The syndrome is often preceded by significant emotional and physical stress. Serum catecholamines may be markedly elevated in patients with stress cardiomyopathy with levels greater than seen in patients with thrombotic ST elevation myocardial infarction or congestive heart failure, though this is not always present. Thus, it has been postulated that catecholamine excess contributes at least in part to the pathophysiology, and that catecholamines may cause direct myonecrosis.[5] It is thought that myocardial stunning seen in stress cardiomyopathy is largely mediated by the effects of epinephrine.[6]

Multi-vessel Epicardial Coronary Artery Spasms:

This theory is not well accepted, as it has been noted that multi-vessel epicardial coronary artery vasospasm does not correlate with the areas of myocardium that are hypokinetic.

Coronary Microvascular Impairment

Myocardial stunning can occur because of microvascular spasm or direct myocardial toxicity of catecholamines. [7] [8]

Mid-cavity or Left Ventricular Outflow Tract Obstruction

Dynamic mid-cavity or left ventricular outflow tract obstruction may induce the apical dysfunction.

Microscopic Pathology

The histological findings on myocardial biopsy in patients with stress cardiomyopathy include:[9][10]


There are no identified genes linked to the development of stress cardiomyopathy. However, there are cases of stress cardiomyopathy occurring among first degree relatives (among 2 sisters and among a patient and her mother), which point out to a possible genetic link to this condition.[11][12][13] In addition, genetic variation in adrenergic receptors and signaling pathways may be associated with stress cardiomyopathy.[14][15][16][17]

Associated Conditions

  • Many neurological and psychiatric conditions are associated with the development of stress cardiomyopathy. These include:[18]
  • It can also be associated with malignancies.[25]


  1. Akashi YJ, Goldstein DS, Barbaro G, Ueyama T (2008). "Takotsubo cardiomyopathy: a new form of acute, reversible heart failure". Circulation. 118 (25): 2754–62. doi:10.1161/CIRCULATIONAHA.108.767012. PMC 4893309. PMID 19106400.
  2. Goico A, Chandrasekaran M, Herrera CJ (2016). "Novel developments in stress cardiomyopathy: From pathophysiology to prognosis". Int. J. Cardiol. 223: 1053–1058. doi:10.1016/j.ijcard.2016.08.241. PMID 27611570.
  3. Testa M, Feola M (2014). "Usefulness of myocardial positron emission tomography/nuclear imaging in Takotsubo cardiomyopathy". World J Radiol. 6 (7): 502–6. doi:10.4329/wjr.v6.i7.502. PMC 4109102. PMID 25071891.
  4. Ramaraj R (2007). "Stress cardiomyopathy: aetiology and management". Postgrad Med J. 83 (982): 543–6. doi:10.1136/pgmj.2007.058776. PMC 2600114. PMID 17675548.
  5. Wittstein IS, Thiemann DR, Lima JA; et al. (2005). "Neurohumoral features of myocardial stunning due to sudden emotional stress". N. Engl. J. Med. 352 (6): 539–48. doi:10.1056/NEJMoa043046. PMID 15703419.
  6. Lyon AR, Rees PS, Prasad S, Poole-Wilson PA, Harding SE (2008). "Stress (Takotsubo) cardiomyopathy--a novel pathophysiological hypothesis to explain catecholamine-induced acute myocardial stunning". Nat Clin Pract Cardiovasc Med. 5 (1): 22–9. doi:10.1038/ncpcardio1066. PMID 18094670.
  7. Gianni M, Dentali F, Grandi AM, Sumner G, Hiralal R, Lonn E (2006). dbfrom=pubmed& "Apical ballooning syndrome or takotsubo cardiomyopathy: a systematic review" Check |url= value (help). Eur Heart J. 27 (13): 1523–9. doi:10.1093/eurheartj/ehl032. PMID 16720686.
  8. Nef HM, Möllmann H, Kostin S, Troidl C, Voss S, Weber M; et al. (2007). "Tako-Tsubo cardiomyopathy: intraindividual structural analysis in the acute phase and after functional recovery". Eur Heart J. 28 (20): 2456–64. doi:10.1093/eurheartj/ehl570. PMID 17395683.
  9. Akashi YJ, Goldstein DS, Barbaro G, Ueyama T (2008). "Takotsubo cardiomyopathy: a new form of acute, reversible heart failure". Circulation. 118 (25): 2754–62. doi:10.1161/CIRCULATIONAHA.108.767012. PMC 4893309. PMID 19106400.
  10. Brenner ZR, Powers J (2008). "Takotsubo cardiomyopathy". Heart Lung. 37 (1): 1–7. doi:10.1016/j.hrtlng.2006.12.003. PMID 18206521.
  11. Pison L, De Vusser P, Mullens W (2004). "Apical ballooning in relatives". Heart. 90 (12): e67. doi:10.1136/hrt.2004.046813. PMC 1768596. PMID 15547001.
  12. Kumar G, Holmes DR, Prasad A (2010). ""Familial" apical ballooning syndrome (Takotsubo cardiomyopathy)". Int. J. Cardiol. 144 (3): 444–5. doi:10.1016/j.ijcard.2009.03.078. PMID 19375184.
  13. Ikutomi M, Yamasaki M, Matsusita M, Watari Y, Arashi H, Endo G, Yamaguchi J, Ohnishi S (2014). "Takotsubo cardiomyopathy in siblings". Heart Vessels. 29 (1): 119–22. doi:10.1007/s00380-013-0345-y. PMID 23563753.
  14. Handy AD, Prasad A, Olson TM (2009). "Investigating genetic variation of adrenergic receptors in familial stress cardiomyopathy (apical ballooning syndrome)". J Cardiol. 54 (3): 516–7. doi:10.1016/j.jjcc.2009.08.008. PMID 19944334.
  15. Sharkey SW, Maron BJ, Nelson P, Parpart M, Maron MS, Bristow MR (2009). "Adrenergic receptor polymorphisms in patients with stress (tako-tsubo) cardiomyopathy". J Cardiol. 53 (1): 53–7. doi:10.1016/j.jjcc.2008.08.006. PMID 19167638.
  16. Novo G, Giambanco S, Guglielmo M, Arvigo L, Sutera MR, Giambanco F, Evola S, Vaccarino L, Bova M, Lio D, Assennato P, Novo S (2015). "G-protein-coupled receptor kinase 5 polymorphism and Takotsubo cardiomyopathy". J Cardiovasc Med (Hagerstown). 16 (9): 639–43. doi:10.2459/JCM.0000000000000120. PMID 25010510.
  17. Goodloe AH, Evans JM, Middha S, Prasad A, Olson TM (2014). "Characterizing genetic variation of adrenergic signalling pathways in Takotsubo (stress) cardiomyopathy exomes". Eur. J. Heart Fail. 16 (9): 942–9. doi:10.1002/ejhf.145. PMID 25132214.
  18. Templin C, Ghadri JR, Diekmann J, Napp LC, Bataiosu DR, Jaguszewski M, Cammann VL, Sarcon A, Geyer V, Neumann CA, Seifert B, Hellermann J, Schwyzer M, Eisenhardt K, Jenewein J, Franke J, Katus HA, Burgdorf C, Schunkert H, Moeller C, Thiele H, Bauersachs J, Tschöpe C, Schultheiss HP, Laney CA, Rajan L, Michels G, Pfister R, Ukena C, Böhm M, Erbel R, Cuneo A, Kuck KH, Jacobshagen C, Hasenfuss G, Karakas M, Koenig W, Rottbauer W, Said SM, Braun-Dullaeus RC, Cuculi F, Banning A, Fischer TA, Vasankari T, Airaksinen KE, Fijalkowski M, Rynkiewicz A, Pawlak M, Opolski G, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Crea F, Dichtl W, Franz WM, Empen K, Felix SB, Delmas C, Lairez O, Erne P, Bax JJ, Ford I, Ruschitzka F, Prasad A, Lüscher TF (2015). "Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy". N. Engl. J. Med. 373 (10): 929–38. doi:10.1056/NEJMoa1406761. PMID 26332547.
  19. Lee VH, Connolly HM, Fulgham JR, Manno EM, Brown RD, Wijdicks EF (2006). "Tako-tsubo cardiomyopathy in aneurysmal subarachnoid hemorrhage: an underappreciated ventricular dysfunction". J. Neurosurg. 105 (2): 264–70. doi:10.3171/jns.2006.105.2.264. PMID 17219832.
  20. Le Ven F, Pennec PY, Timsit S, Blanc JJ (2011). "Takotsubo syndrome associated with seizures: an underestimated cause of sudden death in epilepsy?". Int. J. Cardiol. 146 (3): 475–9. doi:10.1016/j.ijcard.2010.12.028. PMID 21194774.
  21. Sharp RP, Welch EB (2011). "Takotsubo cardiomyopathy as a complication of electroconvulsive therapy". Ann Pharmacother. 45 (12): 1559–65. doi:10.1345/aph.1Q393. PMID 22116995.
  22. Riera M, Llompart-Pou JA, Carrillo A, Blanco C (2010). "Head injury and inverted Takotsubo cardiomyopathy". J Trauma. 68 (1): E13–5. doi:10.1097/TA.0b013e3181469d5b. PMID 19065115.
  23. Yoshimura S, Toyoda K, Ohara T, Nagasawa H, Ohtani N, Kuwashiro T, Naritomi H, Minematsu K (2008). "Takotsubo cardiomyopathy in acute ischemic stroke". Ann. Neurol. 64 (5): 547–54. doi:10.1002/ana.21459. PMID 18688801.
  24. Summers MR, Lennon RJ, Prasad A (2010). "Pre-morbid psychiatric and cardiovascular diseases in apical ballooning syndrome (tako-tsubo/stress-induced cardiomyopathy): potential pre-disposing factors?". J. Am. Coll. Cardiol. 55 (7): 700–1. doi:10.1016/j.jacc.2009.10.031. PMID 20170799.

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