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

Circ Heart Fail. 2026 Mar;19(3):e013229. doi: 10.1161/CIRCHEARTFAILURE.125.013229. Epub 2025 Dec 3.

Abstract

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.

Keywords: Takotsubo cardiomyopathy; cardiac rehabilitation; cognitive behavioral therapy; exercise; heart failure.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Cognitive Behavioral Therapy* / methods
  • Exercise Therapy* / methods
  • Exercise Tolerance
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxygen Consumption
  • Prospective Studies
  • Recovery of Function
  • Takotsubo Cardiomyopathy* / physiopathology
  • Takotsubo Cardiomyopathy* / psychology
  • Takotsubo Cardiomyopathy* / therapy
  • Treatment Outcome
  • Ventricular Function, Left

Associated data

  • ClinicalTrials.gov/NCT04425785