Clinical Features and Outcomes of Patients With Malignancy and Takotsubo Syndrome: Observations From the International Takotsubo Registry

Victoria L Cammann, Annahita Sarcon, Katharina J Ding, Burkhardt Seifert, Ken Kato, Davide Di Vece, Konrad A Szawan, Sebastiano Gili, Stjepan Jurisic, Beatrice Bacchi, Jozef Micek, Antonio H Frangieh, L Christian Napp, Milosz Jaguszewski, Eduardo Bossone, Rodolfo Citro, Fabrizio D'Ascenzo, Jennifer Franke, Michel Noutsias, Maike Knorr, Susanne Heiner, Christof Burgdorf, Wolfgang Koenig, Holger Thiele, Carsten Tschöpe, Lawrence Rajan, Guido Michels, Roman Pfister, Alessandro Cuneo, Claudius Jacobshagen, Mahir Karakas, Adrian Banning, Florim Cuculi, Richard Kobza, Thomas A Fischer, Tuija Vasankari, K E Juhani Airaksinen, Rafal Dworakowski, Christoph Kaiser, Stefan Osswald, Leonarda Galiuto, Wolfgang Dichtl, Clément Delmas, Olivier Lairez, John D Horowitz, Martin Kozel, Petr Widimský, Petr Tousek, David E Winchester, Ekaterina Gilyarova, Alexandra Shilova, Mikhail Gilyarov, Ibrahim El-Battrawy, Ibrahim Akin, Christian Ukena, Johann Bauersachs, Burkert M Pieske, Gerd Hasenfuß, Wolfgang Rottbauer, Ruediger C Braun-Dullaeus, Grzegorz Opolski, Philip MacCarthy, Stephan B Felix, Martin Borggrefe, Carlo Di Mario, Filippo Crea, Hugo A Katus, Heribert Schunkert, Thomas Münzel, Michael Böhm, Jeroen J Bax, Abhiram Prasad, Jerold Shinbane, Thomas F Lüscher, Frank Ruschitzka, Jelena R Ghadri, Christian Templin, Victoria L Cammann, Annahita Sarcon, Katharina J Ding, Burkhardt Seifert, Ken Kato, Davide Di Vece, Konrad A Szawan, Sebastiano Gili, Stjepan Jurisic, Beatrice Bacchi, Jozef Micek, Antonio H Frangieh, L Christian Napp, Milosz Jaguszewski, Eduardo Bossone, Rodolfo Citro, Fabrizio D'Ascenzo, Jennifer Franke, Michel Noutsias, Maike Knorr, Susanne Heiner, Christof Burgdorf, Wolfgang Koenig, Holger Thiele, Carsten Tschöpe, Lawrence Rajan, Guido Michels, Roman Pfister, Alessandro Cuneo, Claudius Jacobshagen, Mahir Karakas, Adrian Banning, Florim Cuculi, Richard Kobza, Thomas A Fischer, Tuija Vasankari, K E Juhani Airaksinen, Rafal Dworakowski, Christoph Kaiser, Stefan Osswald, Leonarda Galiuto, Wolfgang Dichtl, Clément Delmas, Olivier Lairez, John D Horowitz, Martin Kozel, Petr Widimský, Petr Tousek, David E Winchester, Ekaterina Gilyarova, Alexandra Shilova, Mikhail Gilyarov, Ibrahim El-Battrawy, Ibrahim Akin, Christian Ukena, Johann Bauersachs, Burkert M Pieske, Gerd Hasenfuß, Wolfgang Rottbauer, Ruediger C Braun-Dullaeus, Grzegorz Opolski, Philip MacCarthy, Stephan B Felix, Martin Borggrefe, Carlo Di Mario, Filippo Crea, Hugo A Katus, Heribert Schunkert, Thomas Münzel, Michael Böhm, Jeroen J Bax, Abhiram Prasad, Jerold Shinbane, Thomas F Lüscher, Frank Ruschitzka, Jelena R Ghadri, Christian Templin

Abstract

Background Clinical characteristics and outcomes of takotsubo syndrome (TTS) patients with malignancy have not been fully elucidated. This study sought to explore differences in clinical characteristics and to investigate short- and long-term outcomes in TTS patients with or without malignancy. Methods and Results TTS patients were enrolled from the International Takotsubo Registry. The TTS cohort was divided into patients with and without malignancy to investigate differences in clinical characteristics and to assess short- and long-term mortality. A subanalysis was performed comparing long-term mortality between a subset of TTS patients with or without malignancy and acute coronary syndrome (ACS) patients with or without malignancy. Malignancy was observed in 16.6% of 1604 TTS patients. Patients with malignancy were older and more likely to have physical triggers, but less likely to have emotional triggers compared with those without malignancy. Long-term mortality was higher in patients with malignancy (P<0.001), while short-term outcome was comparable (P=0.17). In a subanalysis, long-term mortality was comparable between TTS patients with malignancies and ACS patients with malignancies (P=0.13). Malignancy emerged as an independent predictor of long-term mortality. Conclusions A substantial number of TTS patients show an association with malignancy. History of malignancy might increase the risk for TTS, and therefore, appropriate screening for malignancy should be considered in these patients. Clinical Trial Registration URL: http://www.clinicaltrial.gov. Unique identifier: NCT01947621.

Keywords: acute coronary syndrome; broken heart syndrome; cancer; malignancy; outcome; takotsubo syndrome.

Figures

Figure 1
Figure 1
Study flowchart. Flowchart summarizes patients’ selection and respective analyses of the study. ACS indicates acute coronary syndrome; TTS, takotsubo syndrome.
Figure 2
Figure 2
Prevalence of malignancy. Prevalence of malignancy in the total study cohort of TTS patients (left column), subcohort of TTS (middle column) and ACS (right column) shows an increased prevalence of malignancy in TTS when compared with ACS.10 If a patient had a history of >1 malignancy then the patient was categorized into all respective groups of malignancies. ACS indicates acute coronary syndrome; TTS, takotsubo syndrome.
Figure 3
Figure 3
Short‐ and long‐term outcome in takotsubo patients with and without malignancy. Kaplan–Meier survival analysis demonstrated a comparable 30‐day survival of TTS patients with and without malignancy (P=0.17, inset), while long‐term mortality was significantly higher in TTS patients with malignancy than in TTS patients without malignancy (P<0.001). TTS indicates takotsubo syndrome.
Figure 4
Figure 4
Long‐term outcome in takotsubo syndrome and acute coronary syndrome according to presence or absence of malignancy. Kaplan–Meier survival analysis showed that patients with malignancy had significantly worse outcome than those without malignancy both in patients with TTS and ACS. In addition, TTS patients with malignancy had a comparable long‐term outcome with ACS patients with malignancy (P=0.13) and TTS patients without malignancy also showed a comparable outcome with ACS patients without malignancy (P=0.54). ACS indicates acute coronary syndrome; TTS, takotsubo syndrome.
Figure 5
Figure 5
Univariable (A) and multivariable (B) predictors of long‐term mortality in takotsubo syndrome. Results of the multivariable Cox‐regression in the total cohort of TTS patients showed that age >70 years, atrial fibrillation, maximum troponin >10x ULN, maximum creatinine kinase >10x ULN, left ventricular ejection fraction <45%, malignancy, neurologic disorders, and psychiatric disorders are independent predictors of long‐term mortality. Error bars represent 95% CI. Black rhombi indicate statistical significance; grey rhombi not statistically significant. CI indicates confidence interval; HR, hazard ratio; ULN, upper limit of the normal range.

References

    1. Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, Cammann VL, Crea F, Galiuto L, Desmet W, Yoshida T, Manfredini R, Eitel I, Kosuge M, Nef HM, Deshmukh A, Lerman A, Bossone E, Citro R, Ueyama T, Corrado D, Kurisu S, Ruschitzka F, Winchester D, Lyon AR, Omerovic E, Bax JJ, Meimoun P, Tarantini G, Rihal C, Y‐Hassan S, Migliore F, Horowitz JD, Shimokawa H, Luscher TF, Templin C. International expert consensus document on takotsubo syndrome (Part I): clinical characteristics, diagnostic criteria, and pathophysiology. Eur Heart J. 2018;39:2032–2046.
    1. Akashi YJ, Goldstein DS, Barbaro G, Ueyama T. Takotsubo cardiomyopathy: a new form of acute, reversible heart failure. Circulation. 2008;118:2754–2762.
    1. Kato K, Lyon AR, Ghadri JR, Templin C. Takotsubo syndrome: aetiology, presentation and treatment. Heart. 2017;103:1461–1469.
    1. Ghadri JR, Ruschitzka F, Luscher TF, Templin C. Takotsubo cardiomyopathy: still much more to learn. Heart. 2014;100:1804–1812.
    1. Templin C, Napp LC, Ghadri JR. Takotsubo syndrome: underdiagnosed, underestimated, but understood? J Am Coll Cardiol. 2016;67:1937–1940.
    1. De Pasquale MD, Mastronuzzi A, De Sio L, Serra A, Grimaldi C, Chinali M, Giordano U. Transient global ventricular dysfunction in an adolescent affected by pancreatic adenocarcinoma. BMC Pediatr. 2016;16:99.
    1. Smith SA, Auseon AJ. Chemotherapy‐induced takotsubo cardiomyopathy. Heart Fail Clin. 2013;9:233–242, x.
    1. Malley T, Watson E. A case of takotsubo cardiomyopathy after chemotherapy. Oxf Med Case Reports. 2016;2016:55–58.
    1. Munoz E, Iliescu G, Vejpongsa P, Charitakis K, Karimzad K, Lopez‐Mattei J, Yusuf SW, Marmagkiolis K, Iliescu C. Takotsubo stress cardiomyopathy: “Good news” in cancer patients? J Am Coll Cardiol. 2016;68:1143–1144.
    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, Tschope C, Schultheiss HP, Laney CA, Rajan L, Michels G, Pfister R, Ukena C, Bohm 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, Luscher TF. Clinical features and outcomes of takotsubo (stress) cardiomyopathy. N Engl J Med. 2015;373:929–938.
    1. Ghadri JR, Kato K, Cammann VL, Gili S, Jurisic S, Di Vece D, Candreva A, Ding KJ, Micek J, Szawan KA, Bacchi B, Bianchi R, Levinson RA, Wischnewsky M, Seifert B, Schlossbauer SA, Citro R, Bossone E, Munzel T, Knorr M, Heiner S, D'Ascenzo F, Franke J, Sarcon A, Napp LC, Jaguszewski M, Noutsias M, Katus HA, Burgdorf C, Schunkert H, Thiele H, Bauersachs J, Tschope C, Pieske BM, Rajan L, Michels G, Pfister R, Cuneo A, Jacobshagen C, Hasenfuss G, Karakas M, Koenig W, Rottbauer W, Said SM, Braun‐Dullaeus RC, Banning A, Cuculi F, Kobza R, Fischer TA, Vasankari T, Airaksinen KEJ, Opolski G, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Crea F, Dichtl W, Empen K, Felix SB, Delmas C, Lairez O, El‐Battrawy I, Akin I, Borggrefe M, Horowitz J, Kozel M, Tousek P, Widimsky P, Gilyarova E, Shilova A, Gilyarov M, Winchester DE, Ukena C, Bax JJ, Prasad A, Bohm M, Luscher TF, Ruschitzka F, Templin C. Long‐term prognosis of patients with takotsubo syndrome. J Am Coll Cardiol. 2018;72:874–882.
    1. Burgdorf C, Kurowski V, Bonnemeier H, Schunkert H, Radke PW. Long‐term prognosis of the transient left ventricular dysfunction syndrome (tako‐tsubo cardiomyopathy): focus on malignancies. Eur J Heart Fail. 2008;10:1015–1019.
    1. Sattler K, El‐Battrawy I, Lang S, Zhou X, Schramm K, Tulumen E, Kronbach F, Roger S, Behnes M, Kuschyk J, Borggrefe M, Akin I. Prevalence of cancer in takotsubo cardiomyopathy: short and long‐term outcome. Int J Cardiol. 2017;238:159–165.
    1. Ghadri JR, Cammann VL, Templin C. The International Takotsubo Registry: rationale, design, objectives, and first results. Heart Fail Clin. 2016;12:597–603.
    1. Prasad A, Lerman A, Rihal CS. Apical ballooning syndrome (tako‐tsubo or stress cardiomyopathy): a mimic of acute myocardial infarction. Am Heart J. 2008;155:408–417.
    1. Girardey M, Jesel L, Campia U, Messas N, Hess S, Imperiale A, Blondet C, Trinh A, Ohlmann P, Morel O. Impact of malignancies in the early and late time course of takotsubo cardiomyopathy. Circ J. 2016;80:2192–2198.
    1. Burgdorf C, Kurowski V, Radke PW. Long‐term prognosis of transient left ventricular ballooning syndrome and cancer. Heart Lung. 2011;40:472.
    1. Song BG. Comment on “long‐term prognosis of transient left ventricular ballooning syndrome and cancer”. Heart Lung. 2011;40:270.
    1. Burgdorf C, Nef HM, Haghi D, Kurowski V, Radke PW. Tako‐tsubo (stress‐induced) cardiomyopathy and cancer. Ann Intern Med. 2010;152:830–831.
    1. Han X, Zhou Y, Liu W. Precision cardio‐oncology: understanding the cardiotoxicity of cancer therapy. NPJ Precis Oncol. 2017;1:31.
    1. Lutz JM, Francisci S, Mugno E, Usel M, Pompe‐Kirn V, Coebergh JW, Bieslka‐Lasota M; Group EW . Cancer prevalence in central Europe: the EUROPREVAL study. Ann Oncol. 2003;14:313–322.
    1. Song BG, Hahn JY, Cho SJ, Park YH, Choi SM, Park JH, Choi SH, Choi JH, Park SW, Lee SH, Gwon HC. Clinical characteristics, ballooning pattern, and long‐term prognosis of transient left ventricular ballooning syndrome. Heart Lung. 2010;39:188–195.
    1. Ghadri JR, Wittstein IS, Prasad A, Sharkey S, Dote K, Akashi YJ, Cammann VL, Crea F, Galiuto L, Desmet W, Yoshida T, Manfredini R, Eitel I, Kosuge M, Nef HM, Deshmukh A, Lerman A, Bossone E, Citro R, Ueyama T, Corrado D, Kurisu S, Ruschitzka F, Winchester D, Lyon AR, Omerovic E, Bax JJ, Meimoun P, Tarantini G, Rihal C, Y‐Hassan S, Migliore F, Horowitz JD, Shimokawa H, Luscher TF, Templin C. International expert consensus document on takotsubo syndrome (Part II): diagnostic workup, outcome, and management. Eur Heart J. 2018;39:2047–2062.
    1. Morel O, Messas N, Imperiale A, Blondet C, Jesel L. Cancer and takotsubo syndrome: a need to explore a very complex association‐ reply. Circ J. 2016;81:124.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner