Abstract
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. 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. 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). 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. URL: https://clinicaltrials.gov. Unique identifier: NCT02989454.
Highlights
Takotsubo cardiomyopathy is an increasingly recognized acute heart failure syndrome precipitated by intense emotional stress
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
Summary
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. The data-analytic methods and study materials will be made available to other researchers for purposes of reproducing the results or replicating these findings. This was an observational cross-sectional case-control study of patients with prior (>12 months) takotsubo cardiomyopathy. All cases had to have a previously established diagnosis of takotsubo cardiomyopathy fulfilling the Mayo Clinic[5] and the European Society of Cardiology‒Heart Failure Association criteria,[6] plus evidence of absence of fibrosis on cardiac magnetic resonance imaging. The study was approved by the Institutional Review Board (North of Scotland Research Ethics Committee), and all subjects gave written informed consent
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