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Malignancies and outcome in Takotsubo syndrome: a meta-analysis study on cancer and stress cardiomyopathy

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Abstract

Takotsubo syndrome (TTS) can be induced by a large variety of physical/emotional triggers; several cases, however, are related to either an overt or occult malignancy, as shown in retrospective studies and case reports. The aim of this study was therefore to evaluate the clinical outcome of patients with TTS and cancer in a meta-analysis study. In June 2018, a Pubmed systematic research was conducted for studies assessing outcome in patients with TTS and cancer. We assessed Mantel-Haenszel pooled estimates of risk ratios (RRs) and 95% confidence intervals (CIs) for adverse events at follow-up. After paper retrieval, four studies were included in the meta-analysis, with a total of 123,563 patients. The prevalence of current or previous malignancy among patients admitted with TTS was 6.7% (8258 patients). When compared to control patients, patients with cancer showed an increased risk of clinical events (RR 3.24, 95% CI 3.04–3.45, p < 0.01). The risk of in-hospital events was significantly higher in the cancer group (RR 2.08 95% CI, 1.50–2.87, p < 0.01) and was mainly due to higher need for respiratory support (RR 1.67, 95% CI, 1.58–1.77, p < 0.01). The risk of adverse events at follow-up was also higher in the cancer group (RR 3.30, 95% CI 3.09–3.51, p < 0.01). Cancer, either history or active, is associated with an increased risk of adverse events in TTS.

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References

  1. 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 373:929–938

    Article  CAS  PubMed  Google Scholar 

  2. Smith SA, Auseon AJ (2013) Chemotherapy-induced takotsubo cardiomyopathy. Heart Fail Clin 9:233–242

    Article  PubMed  Google Scholar 

  3. Giza DE, Lopez-Mattei J, Vejpongsa P, Munoz E, Iliescu G, Kitkungvan D, Hassan SA, Kim P, Ewer MS, Iliescu C (2017) Stress-induced cardiomyopathy in Cancer patients. Am J Cardiol 120:2284–2288

    Article  PubMed  Google Scholar 

  4. Möller C, Stiermaier T, Graf T, Eitel C, Thiele H, Burgdorf C, Eitel I (2017) Prevalence and long-term prognostic impact of malignancy in patients with Takotsubo syndrome: research letter. EurJ Heart Fail 20(4):816–818

  5. Sattler K, El-Battrawy I, Lang S, Zhou X, Schramm K, Tülümen E, Kronbach F, Röger S, Behnes M, Kuschyk J, Borggrefe M, Akin I (2017) Prevalence of cancer in Takotsubo cardiomyopathy: short and long-term outcome. Int J Cardiol 238:159–165

    Article  CAS  PubMed  Google Scholar 

  6. Girardey M, Jesel L, Campia U, Messas N, Hess S, Imperiale A, Blondet C, Trinh A, Ohlmann P, Morel O (2016) Impact of malignancies in the early and late time course of Takotsubo cardiomyopathy. Circ J 80:2192–2198

    Article  PubMed  Google Scholar 

  7. Joy PS, Guddati AK, Shapira I (2018) Outcomes of Takotsubo cardiomyopathy in-hospitalized cancer patients. J Cancer Res Clin Oncol 144:1539–1545

    Article  PubMed  Google Scholar 

  8. Gingles C, Leslie S, Harvey R (2010) A case of Takotsubo's cardiomyopathy and multiple endocrine neoplasia 2A syndrome. Clin Endocrinol 73:827–829

    Article  Google Scholar 

  9. Kim HS, Chang WI, Kim YC, Yi SY, Kil JS, Hahn JY, Kang M, Lee MS, Lee SH (2007) Catecholamine cardiomyopathy associated with paraganglioma rescued by percutaneous cardiopulmonary support: inverted Takotsubo contractile pattern. Circ J 71:1993–1995

    Article  PubMed  Google Scholar 

  10. Pelliccia F, Parodi G, Greco C, Antoniucci D, Brenner R, Bossone E, Cacciotti L, Capucci A, Citro R, Delmas C, Guerra F, Ionescu CN, Lairez O, Larrauri-Reyes M, Lee PH, Mansencal N, Marazzi G, Mihos CG, Morel O, Nef HM, Nunez Gil IJ, Passaseo I, Pineda AM, Rosano G, Santana O, Schneck F, Song BG, Song JK, Teh AW, Ungprasert P, Valbusa A, Wahl A, Yoshida T, Gaudio C, Kaski JC (2015) Comorbidities frequency in Takotsubo syndrome: an international collaborative systematic review including 1109 patients. Am J Med 128:654.e11–654.e19

    Article  Google Scholar 

  11. Burgdorf C, Kurowski V, Bonnemeier H, Schunkert H, Radke PW (2008) Long-term prognosis of the transient left ventricular dysfunction syndrome (Tako-Tsubo cardiomyopathy): focus on malignancies. Eur J Heart Fail 10:1015–1019

    Article  PubMed  Google Scholar 

  12. Crocetti E, De Angelis R, Buzzoni C, Mariotto A, Storm H, Colonna M, Zanetti R, Serraino D, Michiara M, Cirilli C, Iannelli A, Mazzoleni G, Sechi O, Sanoja Gonzalez ME, Guzzinati S, Capocaccia R, Dal Maso L (2013) AIRTUM working group. Cancer prevalence in United States, Nordic countries, Italy, Australia, and France: an analysis of geographic variability. Br J Cancer 109:219–228

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. El-Sayed AM, Brinjikji W, Salka S (2012) Demographic and co-morbid predictors of stress (takotsubo) cardiomyopathy. Am J Cardiol 110:1368–1372

    Article  PubMed  Google Scholar 

  14. Capocaccia R, Colonna M, Corazziari I, De Angelis R, Francisci S, Micheli A, Mugno E (2002) EUROPREVAL working group. Measuring cancer prevalence in Europe: the EUROPREVAL project. Ann Oncol 13:831–839

    Article  CAS  PubMed  Google Scholar 

  15. Shin KJ, Lee YJ, Yang YR, Park S, Suh PG, Follo MY, Cocco L, Ryu SH (2016) Molecular mechanisms underlying psychological stress and cancer. Curr Pharm Des 22:2389–2402

    Article  CAS  PubMed  Google Scholar 

  16. Borchert T, Hübscher D, Guessoum CI, Lam TD, Ghadri JR, Schellinger IN, Tiburcy M, Liaw NY, Li Y, Haas J, Sossalla S, Huber MA, Cyganek L, Jacobshagen C, Dressel R, Raaz U, Nikolaev VO, Guan K, Thiele H, Meder B, Wollnik B, Zimmermann WH, Lüscher TF, Hasenfuss G, Templin C, Streckfuss-Bömeke K (2017) Catecholamine-dependent β-adrenergic signaling in a pluripotent stem cell model of Takotsubo cardiomyopathy. J Am Coll Cardiol 70:975–991

    Article  CAS  PubMed  Google Scholar 

  17. Eitel I, Moeller C, Munz M, Stiermaier T, Meitinger T, Thiele H, Erdmann J (2017) Genome-wide association study in takotsubo syndrome - preliminary results and future directions. Int J Cardiol 236:335–339

    Article  PubMed  Google Scholar 

  18. Santoro F, Stiermaier T, Tarantino N, De Gennaro L, Moeller C, Guastafierro F, Marchetti MF, Montisci R, Carapelle E, Graf T, Caldarola P, Thiele H, Di Biase M, Brunetti ND, Eitel I (2017) Left ventricular thrombi in Takotsubo Syndrome: incidence, predictors, and management: results from the GEIST (German Italian stress cardiomyopathy) registry. J Am Heart Assoc 6(12). https://doi.org/10.1161/JAHA.117.006990

  19. Franco TH, Khan A, Joshi V, Thomas B (2008) Takotsubo cardiomyopathy in two men receiving bevacizumab for metastatic cancer. Ther Clin Risk Manag 4:1367–1370

    Article  PubMed  PubMed Central  Google Scholar 

  20. Miyoshi S, Takeda Y, Ro S, Masaki H, Hojo M, Sugiyama H (2015) Takotsubo cardiomyopathy and subsequent seizures induced by flexible bronchoscopy. Respir Care 60:e151–e154

    Article  PubMed  Google Scholar 

  21. Gomella PT, Frazier H (2016) Takotsubo stress-induced cardiomyopathy following robotic radical cystectomy. Can J Urol 23:8234–8236

    PubMed  Google Scholar 

  22. Singh SB, Harle IA (2014) Takotsubo cardiomyopathy secondary in part to cancer-related pain crisis: a case report. J Pain Symptom Manag 48:137–142

    Article  Google Scholar 

  23. Ledowski T, Reimer M, Chavez V, Kapoor V, Wenk M (2012) Effects of acute postoperative pain on catecholamine plasma levels, hemodynamic parameters, and cardiac autonomic control. Pain 153:759–764

    Article  CAS  PubMed  Google Scholar 

  24. De Gennaro L, Brunetti ND, Ruggiero M, Rutigliano D, Campanella C, Santoro F, Guaricci AI, Di Biase M, Caldarola P (2015) Vagotonia, cancer, and fluid depletion in Takotsubo cardiomyopathy: the "not" good, the bad and the ugly. Int J Cardiol 179:193–194

    Article  PubMed  Google Scholar 

  25. El-Battrawy I, Borggrefe M, Takotsubo Syndrome AI (2018) Cancer. Am J Cardiol 121:777

    Article  PubMed  Google Scholar 

  26. Santoro F, Tarantino N, Ferraretti A, Ieva R, Musaico F, Guastafierro F, Di Martino L, Di Biase M, Brunetti ND (2016) Serum interleukin 6 and 10 levels in Takotsubo cardiomyopathy: increased admission levels may predict adverse events at follow-up. Atherosclerosis 254:28–34

    Article  CAS  PubMed  Google Scholar 

  27. Stein B, Frank P, Schmitz W, Scholz H, Thoenes M (1996) Endotoxin and cytokines induce direct cardiodepressive effects in mammalian cardiomyocytes via induction of nitric oxide synthase. J Mol Cell Cardiol 28:1631–1639

    Article  CAS  PubMed  Google Scholar 

  28. Paran E, Neumann L, Cristal N (1992) Effects of mental and physical stress on plasma catecholamine levels before and after beta-adrenoceptor blocker treatment. Eur J Clin Pharmacol 43:11–15

    Article  CAS  PubMed  Google Scholar 

  29. Miller JW, Selhub J, Joseph JA (1996) Oxidative damage caused by free radicals produced during catecholamine autoxidation: protective effects of O-methylation and melatonin. Free Radic Biol Med 21:241–249

    Article  CAS  PubMed  Google Scholar 

  30. Modi S, Baig W (2009) Radiotherapy-induced Tako-tsubo cardiomyopathy. Clin Oncol 21:361–362

    Article  CAS  Google Scholar 

  31. Santoro F, Tarantino N, Pellegrino PL, Caivano M, Lopizzo A, Di Biase M, Brunetti ND (2014) Cardiovascular sequelae of radiation therapy. Clin Res Cardiol 103:955–967

    Article  PubMed  Google Scholar 

  32. Branco AF, Moreira AC, Cunha-Oliveira T, Couto R, Sardao VA, Rizvanov AA, Palotas A, Oliveira PJ (2014) β-Adrenergic over-stimulation and cardio-myocyte apoptosis: two receptors, one organelle, two fates? Curr Drug Targets 15:956–964

    Article  CAS  PubMed  Google Scholar 

  33. Kaneko M, Matsumoto Y, Hayashi H, Kobayashi A, Yamazaki N (1994) Oxygen free radicals and calcium homeostasis in the heart. Mol Cell Biochem 139:91–100

    Article  CAS  PubMed  Google Scholar 

  34. Yoshida T, Taguchi D, Fukuda K, Shimazu K, Inoue M, Murata K, Shibata H (2017) Incidence of hypophosphatemia in advanced cancer patients: a recent report from a single institution. Int J Clin Oncol 22:244–249

    Article  CAS  PubMed  Google Scholar 

  35. Ariyoshi N, Nogi M, Ando A, Watanabe H, Umekawa S (2016) Hypophosphatemia-induced cardiomyopathy. Am J Med Sci 352:317–323

    Article  PubMed  Google Scholar 

  36. Yasar ZA, Kirakli C, Yilmaz U, Ucar ZZ, Talay F (2014) Can non-thyroid illness syndrome predict mortality in lung cancer patients? A prospective cohort study. Horm Cancer 5:240–246

    Article  CAS  PubMed  Google Scholar 

  37. Katzeff HL, Powell SR, Ojamaa K (1997) Alterations in cardiac contractility and gene expression during low-T3 syndrome: prevention with T3. Am J Phys 273:E951–E956

    CAS  Google Scholar 

  38. Herrmann J, Yang EH, Iliescu CA, Cilingiroglu M, Charitakis K, Hakeem A, Toutouzas K, Leesar MA, Grines CL, Marmagkiolis K (2016) Vascular toxicities of Cancer therapies: the old and the new -an evolving avenue. Circulation 133:1272–1289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Klag T, Cantara G, Ong P, Kaufmann M, Sechtem U, Athanasiadis A (2014) Epicardial coronary artery spasm as cause of capecitabine-induced takotsubo cardiomyopathy. Clin Res Cardiol 103:247–250

    Article  PubMed  Google Scholar 

  40. Stewart T, Pavlakis N, Ward M (2010) Cardiotoxicity with 5-fluorouracil and capecitabine: more than just vasospastic angina. Intern Med J 40:303–307

    Article  CAS  PubMed  Google Scholar 

  41. Herrmann J, Yang EH, Iliescu CA, Cilingiroglu M, Charitakis K, Hakeem A, Toutouzas K, Leesar MA, Grines CL, Marmagkiolis K (2016) VascularToxicities of Cancer therapies: the old and the new -an evolving avenue. Circulation 133:1272–1289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Ng KH, Dearden C, Gruber P (2015 Mar) Rituximab-induced Takotsubo syndrome: more cardiotoxic than it appears? BMJ Case Rep 2:2015

    Google Scholar 

  43. Damodaran S, Mrozek E, Liebner D, Kendra K (2014) Focal takotsubo cardiomyopathy with high-dose interleukin-2 therapy for malignant melanoma. J Natl Compr Cancer Netw 12:1666–1670

    Article  Google Scholar 

  44. Finkel MS, Oddis CV, Jacob TD, Watkins SC, Hattler BG, Simmons RL (1992) Negative inotropic effects of cytokines on the heart mediated by nitric oxide. Science 257:387–389

    Article  CAS  PubMed  Google Scholar 

  45. Chen Z, Venkat P, Seyfried D, Chopp M, Yan T, Chen J (2017) Brain-heart interaction: cardiac complications after stroke. Circ Res 121:451–468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Mazzeo AT, Micalizzi A, Mascia L, Scicolone A, Siracusano L (2014) Brain-heart crosstalk: the many faces of stress-related cardiomyopathy syndromes in anaesthesia and intensive care. Br J Anaesth 112:803–815

    Article  CAS  PubMed  Google Scholar 

  47. Addington J, Freimer M (2016) Chemotherapy-induced peripheral neuropathy: an update on the current understanding. F1000Res;5. Faculty Rev-1466. https://doi.org/10.12688/f1000research.8053.1

  48. Geue K, Brähler E, Faller H, Härter M, Schulz H, Weis J, Koch U, Wittchen HU, Mehnert A (2018 Apr 12) Prevalence of mental disorders and psychosocial distress in German adolescent and young adult cancer patients (AYA). Psychooncology 27:1802–1809

    Article  PubMed  Google Scholar 

  49. Grassi L, Caruso R, Mitchell AJ, Sabato S, Nanni MG (2018 Apr 16) Screening for emotional disorders in patients with cancer using the brief symptom inventory (BSI) and the BSI-18 versus a standardized psychiatric interview (the World Health Organization composite international diagnostic interview). Cancer 124:2415–2426

    Article  PubMed  Google Scholar 

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Brunetti, N.D., Tarantino, N., Guastafierro, F. et al. Malignancies and outcome in Takotsubo syndrome: a meta-analysis study on cancer and stress cardiomyopathy. Heart Fail Rev 24, 481–488 (2019). https://doi.org/10.1007/s10741-019-09773-6

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