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Advancements in the diagnostic workup, prognostic evaluation, and treatment of takotsubo syndrome

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Abstract

Takotsubo syndrome (TTS) is an acute and mostly reversible cardiomyopathy that mimics an acute coronary syndrome with left ventricular (LV) systolic dysfunction without relevant obstructive coronary artery disease. Its prevalence is probably underestimated and reaches 1.2–2% in patients with acute coronary syndrome undergoing coronary catheterization. Although supraphysiological epinephrine levels have been associated with TTS, the detailed pathophysiology is incompletely understood. Chest pain is the most common clinical presentation; however, cardiac decompensation, cardiogenic shock, and sudden cardiac death due to ventricular fibrillation may also be the first clinical manifestations. Patients are mostly postmenopausal women, in whom the condition is commonly associated with emotional triggers; however, men have a higher prevalence of TTS being associated with physical triggers, which has a worse prognosis compared with TTS associated with emotional triggers. As a diagnosis of exclusion, TTS has no single definitive diagnostic test. According to the distribution of LV wall motion abnormalities, various morphological subtypes have been identified. The final diagnosis depends on cardiac imaging with left ventricular angiography during acute heart catheterization, as well as on echocardiography and cardiac magnetic resonance. Most patients recover completely, albeit several factors have been associated with worse prognosis. Management is based on observational data, while randomized multicenter studies are still lacking. This review provides a general overview of TTS and focuses on the hypothesized pathophysiology, and especially on current practices in diagnosis, prognosis, and treatment.

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Abbreviations

ACE:

Angiotensin-converting enzyme

ACS:

Acute coronary syndrome

CAD:

Coronary artery disease

ECV:

Extracellular volume

EGE:

Early gadolinium enhancement

EMB:

Endomyocardial biopsies

CMR:

Cardiac magnetic resonance

LGE:

Late gadolinium enhancement

LVEF:

Left ventricular ejection fraction

LVOTO:

Left ventricular outflow tract obstruction

MINOCA:

Myocardial infarction without obstructive coronary arteries

InterTAK Registry:

International Takotsubo Registry

LV:

Left ventricular

MMP:

Matrix metalloproteinase

MR:

Mitral regurgitation

RV:

Right ventricular

RWMAs:

Right ventricular wall motion abnormalities

STIR:

Short tau inversion recovery

TIMP:

Tissue inhibitor of metalloproteinases

TTS:

Takotsubo syndrome

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Acknowledgments

We would like to thank Dr. John Palios, Department of Cardiac CMR, Metropolitan Hospital, Athens, Greece, and Dr. Maria Mademli, 2nd Department of Radiology, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece, for providing us with some of the MRI images.

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  1. Muhammad Ali and Angelos G. Rigopoulos contributed equally to this work.

Authors and Affiliations

  1. Mid-German Heart Center, Department of Internal Medicine III, Division of Cardiology, Angiology and Intensive Medical Care, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle (Saale), Germany

    Muhammad Ali, Angelos G. Rigopoulos, Marios Matiakis, Hannes Melnyk, Elena Abate, Mammad Mammadov, Jan Lukas Prüser, Daniel Sedding & Michel Noutsias

  2. Department of Thoracic and Cardiovascular Surgery, Klinikum Braunschweig, Brunswick, Germany

    Khaldoun Ali

  3. 2nd Cardiology Department, National and Kapodistrian University of Athens, Attikon Hospital, Rimini 1, Haidari, GR-12462, Athens, Greece

    Ignatios Ikonomidis & George Makavos

  4. Preventive Cardiology and Rehabilitation Unit, DSB 29 “S. Gennaro dei Poveri Hospital”, I-80136, Naples, Italy

    Renato de Vecchis

  5. Department of Radiology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, 06120, Halle (Saale), Germany

    Walter Wohlgemuth

  6. Interventional Cardiology and Cardiology Department, Mediterraneo Hospital, Ilias Street 8-12, Glyfada, GR-16675, Athens, Greece

    Athanassios Manginas

  7. Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany

    Boris Bigalke

  8. Onassis Cardiac Surgery Center, 50 Esperou Street, Palaeo Faliro, GR-17561, Athens, Greece

    Sophie Mavrogeni

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  1. Muhammad Ali
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Correspondence to Michel Noutsias.

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Conflict of interest

MN has received grants from the Deutsche Forschungsgemeinschaft (DFG) through the Sonderforschungsbereich Transregio 19 “Inflammatory Cardiomyopathy” (SFB TR19) (TP B2) and the University Hospital Giessen and Marburg Foundation Grant “T cell functionality” (UKGM 10/2009). MN is the local p.i. of the InterTAK Registry (until 2017: University Hospital Jena; since 2017: University Hospital Halle). MN has been a consultant to the IKDT (Institute for Cardiac Diagnosis and Therapy GmbH, Berlin) 2004–2008 and has received honoraria for presentations and/or participated in advisory boards from Abbot, Abiomed, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Fresenius, Miltenyi Biotec, Novartis, Pfizer, and Zoll. AR and MA have received honoraria for presentations from AstraZeneca. All the other authors declare that they have no conflict of interest.

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Ali, M., Rigopoulos, A.G., Ali, K. et al. Advancements in the diagnostic workup, prognostic evaluation, and treatment of takotsubo syndrome. Heart Fail Rev 25, 757–771 (2020). https://doi.org/10.1007/s10741-019-09843-9

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