Gamble DT; School of Medicine and Dentistry, University of Aberdeen, United Kingdom.
Ross J; Khan H; Cheyne L; Rudd A; Srivanasan J; Horgan G; Hogg
D; Myint PK; Newby DE; Williams C; Gray SR; Dawson D

Circulation: Heart Failure. 19(3):e013229, 2026 Mar.

BACKGROUND: Takotsubo cardiomyopathy is an acute cardiac emergency
presenting with severe left ventricular dysfunction. Physical exercise
training or cognitive behavioral therapy may enhance myocardial recovery
after takotsubo cardiomyopathy.

METHODS: In a prospective multicenter clinical trial conducted between
February 2020 and August 2023, patients with acute takotsubo
cardiomyopathy were randomized 1:1:1 to physical exercise training,
cognitive behavioral therapy, or standard care for 12 weeks after index
presentation. The primary end point was resting phosphocreatine/gamma-ATP
ratio assessed by 31P-magnetic resonance spectroscopy. Secondary end
points were the rate of oxygen consumption at peak exercise on
cardiopulmonary exercise testing, 6-minute walk distance, left ventricular
global longitudinal strain, and the Minnesota Living With Heart Failure
Questionnaire. Twelve-week changes in outcome were compared between
allocated trial interventions.

RESULTS: Seventy-six participants were recruited: the median age was 66
years, and 91% were women. Compared with standard care, the primary end
point of myocardial phosphocreatine/gamma-ATP ratio was improved by
physical exercise training (0.4 [95% CI, 0.1-0.8]; P=0.016) and cognitive
behavioral therapy (0.3 [0.01-0.7]; P=0.043). Both physical exercise
training and cognitive behavioral therapy improved rate of oxygen
consumption at peak exercise (4.7 [1.4-8.0] and 4.0 [1.5-6.4] mL/min per
kg; P=0.001 and 0.004, respectively) and 6-minute walk distance (92.6
[24.7-160.6] and 73.3 [7.9-138.8] m; P=0.004 and 0.029, respectively)
compared with standard care. There were no differences in global
longitudinal strain or symptom burden.

CONCLUSIONS: In patients with acute takotsubo cardiomyopathy, a 12-week
intervention with exercise training or cognitive behavioral therapy
improved left ventricular myocardial energetics and exercise performance
without demonstrable effects on symptoms of heart failure