Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy

Caroline Scally, Amelia Rudd, Alice Mezincescu, Heather Wilson, Janaki Srinivasan, Graham Horgan, Paul Broadhurst, David E. Newby, Anke Henning, Dana K. Dawson

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Abstract

BACKGROUND: Takotsubo cardiomyopathy is an increasingly recognized acute heart failure syndrome precipitated by intense emotional stress. Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction, the long-term clinical and functional consequences of takotsubo cardiomyopathy are ill-defined.METHODS: In an observational case-control study, we recruited 37 patients with prior (>12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and comorbidity-matched control subjects. Patients completed the Minnesota Living with Heart Failure Questionnaire. All participants underwent detailed clinical phenotypic characterization, including serum biomarker analysis, cardiopulmonary exercise testing, echocardiography, and cardiac magnetic resonance including cardiac 31P-spectroscopy.RESULTS: Participants were predominantly middle-age (64±11 years) women (97%). Although takotsubo cardiomyopathy occurred 20 (range 13-39) months before the study, the majority (88%) of patients had persisting symptoms compatible with heart failure (median of 13 [range 0-76] in the Minnesota Living with Heart Failure Questionnaire) and cardiac limitation on exercise testing (reduced peak oxygen consumption, 24±1.3 versus 31±1.3 mL/kg/min, P<0.001; increased VE/VCO2 slope, 31±1 versus 26±1, P=0.002). Despite normal left ventricular ejection fraction and serum biomarkers, patients with prior takotsubo cardiomyopathy had impaired cardiac deformation indices (reduced apical circumferential strain, ‒16±1.0 versus ‒23±1.5%, P<0.001; global longitudinal strain, ‒17±1 versus ‒20±1%, P=0.006), increased native T1 mapping values (1264±10 versus 1184±10 ms, P<0.001), and impaired cardiac energetic status (phosphocreatine/γ-adenosine triphosphate ratio, 1.3±0.1 versus 1.9±0.1, P<0.001).CONCLUSIONS: In contrast to previous perceptions, takotsubo cardiomyopathy has long-lasting clinical consequences, including demonstrable symptomatic and functional impairment associated with persistent subclinical cardiac dysfunction. Taken together our findings demonstrate that after takotsubo cardiomyopathy, patients develop a persistent, long-term heart failure phenotype.CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02989454.
Original languageEnglish
Pages (from-to)1039-1048
Number of pages9
JournalCirculation
Volume137
Issue number10
Early online date11 Nov 2017
DOIs
Publication statusPublished - 6 Mar 2018

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Takotsubo Cardiomyopathy
Heart Failure
Stroke Volume
Biomarkers
Exercise
Phosphocreatine
Serum
Psychological Stress
Oxygen Consumption
Echocardiography
Case-Control Studies
Comorbidity
Spectrum Analysis
Magnetic Resonance Spectroscopy
Adenosine Triphosphate
Clinical Trials
Phenotype

Keywords

  • cardiac energetics
  • cardiopulmonary exercise testing
  • broken heart syndrome
  • stress-induced cardiomyopathy
  • takotsubo

Cite this

Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy. / Scally, Caroline; Rudd, Amelia; Mezincescu, Alice; Wilson, Heather; Srinivasan, Janaki; Horgan, Graham; Broadhurst, Paul; Newby, David E.; Henning, Anke; Dawson, Dana K.

In: Circulation, Vol. 137, No. 10, 06.03.2018, p. 1039-1048.

Research output: Contribution to journalArticle

Scally, Caroline ; Rudd, Amelia ; Mezincescu, Alice ; Wilson, Heather ; Srinivasan, Janaki ; Horgan, Graham ; Broadhurst, Paul ; Newby, David E. ; Henning, Anke ; Dawson, Dana K. / Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy. In: Circulation. 2018 ; Vol. 137, No. 10. pp. 1039-1048.
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abstract = "BACKGROUND: Takotsubo cardiomyopathy is an increasingly recognized acute heart failure syndrome precipitated by intense emotional stress. Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction, the long-term clinical and functional consequences of takotsubo cardiomyopathy are ill-defined.METHODS: In an observational case-control study, we recruited 37 patients with prior (>12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and comorbidity-matched control subjects. Patients completed the Minnesota Living with Heart Failure Questionnaire. All participants underwent detailed clinical phenotypic characterization, including serum biomarker analysis, cardiopulmonary exercise testing, echocardiography, and cardiac magnetic resonance including cardiac 31P-spectroscopy.RESULTS: Participants were predominantly middle-age (64±11 years) women (97{\%}). Although takotsubo cardiomyopathy occurred 20 (range 13-39) months before the study, the majority (88{\%}) of patients had persisting symptoms compatible with heart failure (median of 13 [range 0-76] in the Minnesota Living with Heart Failure Questionnaire) and cardiac limitation on exercise testing (reduced peak oxygen consumption, 24±1.3 versus 31±1.3 mL/kg/min, P<0.001; increased VE/VCO2 slope, 31±1 versus 26±1, P=0.002). Despite normal left ventricular ejection fraction and serum biomarkers, patients with prior takotsubo cardiomyopathy had impaired cardiac deformation indices (reduced apical circumferential strain, ‒16±1.0 versus ‒23±1.5{\%}, P<0.001; global longitudinal strain, ‒17±1 versus ‒20±1{\%}, P=0.006), increased native T1 mapping values (1264±10 versus 1184±10 ms, P<0.001), and impaired cardiac energetic status (phosphocreatine/γ-adenosine triphosphate ratio, 1.3±0.1 versus 1.9±0.1, P<0.001).CONCLUSIONS: In contrast to previous perceptions, takotsubo cardiomyopathy has long-lasting clinical consequences, including demonstrable symptomatic and functional impairment associated with persistent subclinical cardiac dysfunction. Taken together our findings demonstrate that after takotsubo cardiomyopathy, patients develop a persistent, long-term heart failure phenotype.CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02989454.",
keywords = "cardiac energetics, cardiopulmonary exercise testing, broken heart syndrome, stress-induced cardiomyopathy, takotsubo",
author = "Caroline Scally and Amelia Rudd and Alice Mezincescu and Heather Wilson and Janaki Srinivasan and Graham Horgan and Paul Broadhurst and Newby, {David E.} and Anke Henning and Dawson, {Dana K.}",
note = "The HEROIC study was funded by the British Heart Foundation Project Grant no. PG/15/108/31928 (D.K.D.), the Josephine Lansdell British Medical Association 2015 Award (D.K.D.), and the Chief Scientist Office CGA-16-4 Catalytic Grant (D.K.D). D.E.N. is supported by the British Heart Foundation (CH/09/002) and a Wellcome Trust Senior Investigator Award (WT103782AIA).",
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TY - JOUR

T1 - Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy

AU - Scally, Caroline

AU - Rudd, Amelia

AU - Mezincescu, Alice

AU - Wilson, Heather

AU - Srinivasan, Janaki

AU - Horgan, Graham

AU - Broadhurst, Paul

AU - Newby, David E.

AU - Henning, Anke

AU - Dawson, Dana K.

N1 - The HEROIC study was funded by the British Heart Foundation Project Grant no. PG/15/108/31928 (D.K.D.), the Josephine Lansdell British Medical Association 2015 Award (D.K.D.), and the Chief Scientist Office CGA-16-4 Catalytic Grant (D.K.D). D.E.N. is supported by the British Heart Foundation (CH/09/002) and a Wellcome Trust Senior Investigator Award (WT103782AIA).

PY - 2018/3/6

Y1 - 2018/3/6

N2 - BACKGROUND: Takotsubo cardiomyopathy is an increasingly recognized acute heart failure syndrome precipitated by intense emotional stress. Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction, the long-term clinical and functional consequences of takotsubo cardiomyopathy are ill-defined.METHODS: In an observational case-control study, we recruited 37 patients with prior (>12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and comorbidity-matched control subjects. Patients completed the Minnesota Living with Heart Failure Questionnaire. All participants underwent detailed clinical phenotypic characterization, including serum biomarker analysis, cardiopulmonary exercise testing, echocardiography, and cardiac magnetic resonance including cardiac 31P-spectroscopy.RESULTS: Participants were predominantly middle-age (64±11 years) women (97%). Although takotsubo cardiomyopathy occurred 20 (range 13-39) months before the study, the majority (88%) of patients had persisting symptoms compatible with heart failure (median of 13 [range 0-76] in the Minnesota Living with Heart Failure Questionnaire) and cardiac limitation on exercise testing (reduced peak oxygen consumption, 24±1.3 versus 31±1.3 mL/kg/min, P<0.001; increased VE/VCO2 slope, 31±1 versus 26±1, P=0.002). Despite normal left ventricular ejection fraction and serum biomarkers, patients with prior takotsubo cardiomyopathy had impaired cardiac deformation indices (reduced apical circumferential strain, ‒16±1.0 versus ‒23±1.5%, P<0.001; global longitudinal strain, ‒17±1 versus ‒20±1%, P=0.006), increased native T1 mapping values (1264±10 versus 1184±10 ms, P<0.001), and impaired cardiac energetic status (phosphocreatine/γ-adenosine triphosphate ratio, 1.3±0.1 versus 1.9±0.1, P<0.001).CONCLUSIONS: In contrast to previous perceptions, takotsubo cardiomyopathy has long-lasting clinical consequences, including demonstrable symptomatic and functional impairment associated with persistent subclinical cardiac dysfunction. Taken together our findings demonstrate that after takotsubo cardiomyopathy, patients develop a persistent, long-term heart failure phenotype.CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02989454.

AB - BACKGROUND: Takotsubo cardiomyopathy is an increasingly recognized acute heart failure syndrome precipitated by intense emotional stress. Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction, the long-term clinical and functional consequences of takotsubo cardiomyopathy are ill-defined.METHODS: In an observational case-control study, we recruited 37 patients with prior (>12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and comorbidity-matched control subjects. Patients completed the Minnesota Living with Heart Failure Questionnaire. All participants underwent detailed clinical phenotypic characterization, including serum biomarker analysis, cardiopulmonary exercise testing, echocardiography, and cardiac magnetic resonance including cardiac 31P-spectroscopy.RESULTS: Participants were predominantly middle-age (64±11 years) women (97%). Although takotsubo cardiomyopathy occurred 20 (range 13-39) months before the study, the majority (88%) of patients had persisting symptoms compatible with heart failure (median of 13 [range 0-76] in the Minnesota Living with Heart Failure Questionnaire) and cardiac limitation on exercise testing (reduced peak oxygen consumption, 24±1.3 versus 31±1.3 mL/kg/min, P<0.001; increased VE/VCO2 slope, 31±1 versus 26±1, P=0.002). Despite normal left ventricular ejection fraction and serum biomarkers, patients with prior takotsubo cardiomyopathy had impaired cardiac deformation indices (reduced apical circumferential strain, ‒16±1.0 versus ‒23±1.5%, P<0.001; global longitudinal strain, ‒17±1 versus ‒20±1%, P=0.006), increased native T1 mapping values (1264±10 versus 1184±10 ms, P<0.001), and impaired cardiac energetic status (phosphocreatine/γ-adenosine triphosphate ratio, 1.3±0.1 versus 1.9±0.1, P<0.001).CONCLUSIONS: In contrast to previous perceptions, takotsubo cardiomyopathy has long-lasting clinical consequences, including demonstrable symptomatic and functional impairment associated with persistent subclinical cardiac dysfunction. Taken together our findings demonstrate that after takotsubo cardiomyopathy, patients develop a persistent, long-term heart failure phenotype.CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02989454.

KW - cardiac energetics

KW - cardiopulmonary exercise testing

KW - broken heart syndrome

KW - stress-induced cardiomyopathy

KW - takotsubo

U2 - 10.1161/CIRCULATIONAHA.117.031841

DO - 10.1161/CIRCULATIONAHA.117.031841

M3 - Article

VL - 137

SP - 1039

EP - 1048

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 10

ER -