Scally C; Rudd A; Mezincescu A; Wilson H; Srivanasan J; Horgan G;
Broadhurst P; Newby DE; Henning A; Dawson DK.

Circulation. 137(10):1039-1048, 2018 03 06.

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/gamma-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.