AIMS: Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. METHODS AND RESULTS: Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In-hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long-term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long-term mortality (hazard ratio 2.12, 95% confidence interval 1.33-3.38; P = 0.002). CONCLUSIONS: The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in-hospital course and a worse long-term outcome.

1st Department of Cardiology Medical University of Gdansk Gdansk Poland

1st Department of Medicine Faculty of Medicine University Medical Centre Mannheim University of Heidelberg Mannheim Germany

Advanced Heart Failure and Transplantation Center University Medical Center Ljubljana Ljubljana Slovenia

Cardiocenter 3rd Faculty of Medicine Charles University Prague University Hospital Kralovske Vinohrady Prague Czech Republic

Cardiology Department Santa Maria University Hospital Lisbon School of Medicine Universidade de Lisboa Lisbon Portugal

Center for Cardiology Cardiology 1 University Medical Center Mainz Mainz Germany

Center for Molecular Cardiology Schlieren Campus University of Zurich Zurich Switzerland

Centro Cardiologico Monzino IRCCS Milan Italy

Clinic for Cardiology and Pneumology Georg August University of Goettingen Goettingen Germany

Department of Cardiology and Angiology Hannover Medical School Hannover Germany

Department of Cardiology and Cardiac Imaging Center University Hospital of Rangueil Toulouse France

Department of Cardiology Basil Hetzel Institute Queen Elizabeth Hospital University of Adelaide Adelaide Australia

Department of Cardiology Centro Hospitalar Universitário de São João E P E Porto Portugal

Department of Cardiology Charité Campus Rudolf Virchow Berlin Germany

Department of Cardiology Chiba Emergency Medical Center Chiba Japan

Department of Cardiology Christchurch Hospital Christchurch New Zealand

Department of Cardiology Heidelberg University Hospital Heidelberg Germany

Department of Cardiology John Radcliffe Hospital Oxford University Hospitals Oxford UK

Department of Cardiology Kantonsspital Frauenfeld Frauenfeld Switzerland

Department of Cardiology Kantonsspital Lucerne Lucerne Switzerland

Department of Cardiology Kantonsspital St Gallen St Gallen Switzerland

Department of Cardiology Kantonsspital Winterthur Winterthur Switzerland

Department of Cardiology King's College Hospital London UK

Department of Cardiology Leiden University Medical Centre Leiden The Netherlands

Department of Cardiology Medical University of Warsaw Warsaw Poland

Department of Cardiology University Heart Center University Hospital of Zurich Raemistrasse 100 Zurich 8091 Switzerland

Department of Cardiology University Hospital of Basel Basel Switzerland

Department of Cardiovascular Diseases Mayo Clinic Rochester MN USA

Department of Cardiovascular Medicine Chiba University Graduate School of Medicine Chiba Japan

Department of General and Interventional Cardiology University Heart Center Hamburg Hamburg Germany

Department of Internal Medicine 1 Cardiology University Hospital Olomouc Olomouc Czech Republic

Department of Internal Medicine 1 JenaUniversity Hospital Friedrich Schiller University Jena Jena Germany

Department of Internal Medicine 2 Cardiology University of Ulm Medical Center Ulm Germany

Department of Internal Medicine 2 University Medical Center Regensburg Regensburg Germany

Department of Internal Medicine 3 Division of Cardiology Angiology and Intensive Medical Care University Hospital Halle Martin Luther University Halle Wittenberg Halle Germany

Department of Internal Medicine 3 Heart Center University of Cologne Cologne Germany

Department of Internal Medicine B University Medicine Greifswald Greifswald Germany

Department of Internal Medicine Cardiology Heart Center Leipzig University Hospital Leipzig Germany

Deutsches Herzzentrum München Technische Universität München Munich Germany

Division of Cardiology A O U San Luigi Gonzaga Turin Italy

Division of Cardiology Antonio Cardarelli Hospital Naples Italy

Division of Cardiology Department of Medical Sciences AOU Città della Salute e della Scienza University of Turin Turin Italy

Division of Cardiology Heart and Vascular Center University of Iowa Iowa City Iowa USA

Division of Cardiology Kimitsu Central Hospital Kisarazu Japan

Division of Cardiovascular Medicine Department of Medicine College of Medicine University of Florida Gainesville FL USA

Division of Cardiovascular Medicine Keck School of Medicine University of Southern California Los Angeles CA USA

DZHK partner site Greifswald Greifswald Germany

DZHK partner site Hamburg Kiel Luebeck Hamburg Germany

DZHK Partner Site Heidelberg Mannheim Mannheim Germany

DZHK partner site Munich Heart Alliance Munich Germany

FB Mathematics and Computer Science University of Bremen Bremen Germany

Fondazione Policlinico Universitario A Gemelli IRCCS Rome Italy

Heart and Vascular Centre Bad Bevensen Bad Bevensen Germany

Heart Center Turku University Hospital University of Turku Turku Finland

Heart Department University Hospital 'San Giovanni di Dio e Ruggi d'Aragona' Salerno Italy

Intensive Coronary Care Unit Moscow City Hospital 1 named after N Pirogov Moscow Russia

Internal Medicine Cardiology Angiology and Pneumology Magdeburg University Magdeburg Germany

Klinik für Innere Medizin 3 Universitätsklinikum des Saarlandes Homburg Germany

Krankenhaus 'Maria Hilf' Medizinische Klinik Stadtlohn Germany

Local Health Unit n 8 Cardiology Unit Arzignano Vicenza Italy

Pulmonary Division University Hospital of Zurich Zurich Switzerland

Royal Brompton and Harefield Hospitals Trust and Imperial College London UK

Section of Cardiac Electrophysiology Department of Medicine University of California San Francisco San Francisco CA USA

Service de Cardiologie Hôpitaux Universitaires de Genève Geneva Switzerland

Structural Interventional Cardiology Careggi University Hospital Florence Italy

TJ Health Partners Heart and Vascular Glasgow KY USA

University Hospital for Internal Medicine 3 Medical University Innsbruck Innsbruck Austria

Zobrazit více v PubMed

Tsuchihashi K, Ueshima K, Uchida T, Oh‐mura N, Kimura K, Owa M, Yoshiyama M, Miyazaki S, Haze K, Ogawa H, Honda T, Hase M, Kai R, Morii I. Angina pectoris‐myocardial infarction investigations in Japan: transient left ventricular apical ballooning without coronary artery stenosis: a novel heart syndrome mimicking acute myocardial infarction. J Am Coll Cardiol 2001; 38: 11–18. PubMed

Lyon AR, Bossone E, Schneider B, Sechtem U, Citro R, Underwood SR, Sheppard MN, Figtree GA, Parodi G, Akashi YJ, Ruschitzka F, Filippatos G, Mebazaa A, Omerovic E. Current state of knowledge on takotsubo syndrome: a position statement from the Taskforce on Takotsubo Syndrome of the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 2016; 18: 8–27. PubMed

Akashi YJ, Musha H, Kida K, Itoh K, Inoue K, Kawasaki K, Hashimoto N, Miyake F. Reversible ventricular dysfunction takotsubo cardiomyopathy. Eur J Heart Fail 2005; 7: 1171–1176. PubMed

Citro R, Radano I, Parodi G, Di Vece D, Zito C, Novo G, Provenza G, Bellino M, Prota C, Silverio A, Antonini‐Canterin F, Rigo F, Vriz O, Galasso G, Bossone E, Salerno‐Uriarte J, Piscione F. Long‐term outcome in patients with takotsubo syndrome presenting with severely reduced left ventricular ejection fraction. Eur J Heart Fail 2019; 21: 781–789. PubMed

Kato K, Lyon AR, Ghadri JR, Templin C. Takotsubo syndrome: aetiology, presentation and treatment. Heart 2017; 103: 1461–1469. PubMed

Wischnewsky MB, Candreva A, Bacchi B, Cammann VL, Kato K, Szawan KA, Gili S, D'Ascenzo F, Dichtl W, Citro R, Bossone E, Neuhaus M, Franke J, Sorici‐Barb I, Jaguszewski M, Noutsias M, Knorr M, Heiner S, Burgdorf C, Kherad B, Tschope C, Sarcon A, Shinbane J, Rajan L, Michels G, Pfister R, Cuneo A, Jacobshagen C, Karakas M, Koenig W, Pott A, Meyer P, Arroja JD, Banning A, Cuculi F, Kobza R, Fischer TA, Vasankari T, Airaksinen KEJ, Napp LC, Budnik M, Dworakowski R, MacCarthy P, Kaiser C, Osswald S, Galiuto L, Chan C, Bridgman P, Beug D, Delmas C, Lairez O, El‐Battrawy I, Akin I, Gilyarova E, Shilova A, Gilyarov M, Kozel M, Tousek P, Winchester DE, Galuszka J, Ukena C, Poglajen G, Carrilho‐Ferreira P, Hauck C, Paolini C, Bilato C, Prasad A, Rihal CS, Liu K, Schulze PC, Bianco M, Jorg L, Rickli H, Nguyen TH, Kobayashi Y, Bohm M, Maier LS, Pinto FJ, Widimsky P, Borggrefe M, Felix SB, Opolski G, Braun‐Dullaeus RC, Rottbauer W, Hasenfuss G, Pieske BM, Schunkert H, Thiele H, Bauersachs J, Katus HA, Horowitz J, Di Mario C, Munzel T, Crea F, Bax JJ, Luscher TF, Ruschitzka F, Ghadri JR, Templin C. Prediction of short‐ and long‐term mortality in takotsubo syndrome: the InterTAK Prognostic Score. Eur J Heart Fail 2019; 21: 1469–1472. PubMed

Sharkey SW, Windenburg DC, Lesser JR, Maron MS, Hauser RG, Lesser JN, Haas TS, Hodges JS, Maron BJ. Natural history and expansive clinical profile of stress (tako‐tsubo) cardiomyopathy. J Am Coll Cardiol 2010; 55: 333–341. PubMed

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. Comorbidities frequency in takotsubo syndrome: an international collaborative systematic review including 1109 patients. Am J Med 2015; 128: 654 e11–654 e19. PubMed

Manfredini R, Fabbian F, Giorgi AD, Pala M, Menegatti AM, Parisi C, Misurati E, Tiseo R, Gallerani M, Salmi R, Bossone E. Heart and lung, a dangerous liaison‐Tako‐tsubo cardiomyopathy and respiratory diseases: a systematic review. World J Cardiol 2014; 6: 338–344. PubMed PMC

Ghadri JR, Bataisou RD, Diekmann J, Luscher TF, Templin C. First case of atypical takotsubo cardiomyopathy in a bilateral lung‐transplanted patient due to acute respiratory failure. Eur Heart J Acute Cardiovasc Care 2015; 4: 482–485. PubMed

Landefeld K, Saleh Q, Sander GE. Stress cardiomyopathy in the setting of COPD exacerbation. J Investig Med High Impact Case Rep 2015; 3: 2324709615612847. PubMed PMC

Hawkins NM, Petrie MC, Macdonald MR, Jhund PS, Fabbri LM, Wikstrand J, McMurray JJ. Heart failure and chronic obstructive pulmonary disease the quandary of beta‐blockers and beta‐agonists. J Am Coll Cardiol 2011; 57: 2127–2138. PubMed

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, Clinical Features LTF. Outcomes of takotsubo (stress) cardiomyopathy. N Engl J Med 2015; 373: 929–938. PubMed

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. PubMed

Leitner LM. Dopamine metabolism in the rabbit carotid body in vitro: effect of hypoxia and hypercapnia. Adv Exp Med Biol 1993; 337: 183–190. PubMed

Low JM, Gin T, Lee TW, Fung K. Effect of respiratory acidosis and alkalosis on plasma catecholamine concentrations in anaesthetized man. Clin Sci (Lond) 1993; 84: 69–72. PubMed

Offner B, Czachurski J, Konig SA, Seller H. Different effects of respiratory and metabolic acidosis on preganglionic sympathetic nerve activity. J Appl Physiol (1985) 1994; 77: 173–178. PubMed

Wittstein IS, Thiemann DR, Lima JA, Baughman KL, Schulman SP, Gerstenblith G, Wu KC, Rade JJ, Bivalacqua TJ, Champion HC. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352: 539–548. PubMed

Bhowmik A, Seemungal TA, Sapsford RJ, Wedzicha JA. Relation of sputum inflammatory markers to symptoms and lung function changes in COPD exacerbations. Thorax 2000; 55: 629–630. PubMed PMC

Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P. Risk of myocardial infarction and stroke after acute infection or vaccination. N Engl J Med 2004; 351: 2611–2618. PubMed

Donaldson GC, Hurst JR, Smith CJ, Hubbard RB, Wedzicha JA. Increased risk of myocardial infarction and stroke following exacerbation of COPD. Chest 2010; 137: 1091–1097. PubMed

Surikow SY, Nguyen TH, Stafford I, Chapman M, Chacko S, Singh K, Licari G, Raman B, Kelly DJ, Zhang Y, Waddingham MT, Ngo DT, Bate AP, Chua SJ, Frenneaux MP, Horowitz JD. Nitrosative stress as a modulator of inflammatory change in a model of takotsubo syndrome. JACC Basic Transl Sci 2018; 3: 213–226. PubMed PMC

Mishra V, Banga J, Silveyra P. Oxidative stress and cellular pathways of asthma and inflammation: therapeutic strategies and pharmacological targets. Pharmacol Ther 2018; 181: 169–182. PubMed PMC

Marginean C, Popescu MS, Vladaia M, Tudorascu D, Pirvu DC, Petrescu F. Involvement of oxidative stress in COPD. Curr Health Sci J 2018; 44: 48–55. PubMed PMC

Salemi VM, Atik E, Kairalla RA, Queiroz EL, Rosa LV, Kalil Filho R. Takotsubo cardiomyopathy triggered by β(2) adrenergic agonist. J Bras Pneumol 2011; 37: 560–562. PubMed

Tornvall P, Collste O, Ehrenborg E, Jarnbert‐Petterson H. A case‐control study of risk markers and mortality in takotsubo stress cardiomyopathy. J Am Coll Cardiol 2016; 67: 1931–1936. PubMed

Chen S, Li Y, Zheng Z, Luo Q, Chen R. The analysis of components that lead to increased work of breathing in chronic obstructive pulmonary disease patients. J Thorac Dis 2016; 8: 2212–2218. PubMed PMC

Bellani G, Pesenti A. Assessing effort and work of breathing. Curr Opin Crit Care 2014; 20: 352–358. PubMed

Kallet RH, Hemphill JC 3rd, Dicker RA, Alonso JA, Campbell AR, Mackersie RC, Katz JA. The spontaneous breathing pattern and work of breathing of patients with acute respiratory distress syndrome and acute lung injury. Respir Care 2007; 52: 989–995. PubMed

Gift AG, Plaut SM, Jacox A. Psychologic and physiologic factors related to dyspnea in subjects with chronic obstructive pulmonary disease. Heart Lung 1986; 15: 595–601. PubMed

Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez‐Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P, Task Force M . 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J 2016; 37: 2129–2200. PubMed

Hoiseth AD, Neukamm A, Karlsson BD, Omland T, Brekke PH, Soyseth V. Elevated high‐sensitivity cardiac troponin T is associated with increased mortality after acute exacerbation of chronic obstructive pulmonary disease. Thorax 2011; 66: 775–781. PubMed

Gariani K, Delabays A, Perneger TV, Agoritsas T. Use of brain natriuretic peptide to detect previously unknown left ventricular dysfunction in patients with acute exacerbation of chronic obstructive pulmonary disease. Swiss Med Wkly 2011; 141: w13298. PubMed

Hawkins NM, Khosla A, Virani SA, McMurray JJ, FitzGerald JM. B‐type natriuretic peptides in chronic obstructive pulmonary disease: a systematic review. BMC Pulm Med 2017; 17: 11. PubMed PMC

Triggers, characteristics, and hospital outcome of patients with Takotsubo syndrome: 10 years experience in a large university hospital centre