Physical Exercise or Cognitive Behavioral Therapy for Takotsubo Cardiomyopathy: A Randomized Controlled Trial

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. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04425785.