Physical exercise or cognitive behavioural therapy for takotsubo cardiomyopathy: a randomised controlled trial

Abstract Background Patients with takotsubo cardiomyopathy present acutely with symptoms indicative of an acute myocardial infarction. Despite apparent ‘normalisation’ of heart function, many patients develop heart failure with preserved ejection fraction, characterised by impaired cardiac energetic status and cardiac limitation on cardiopulmonary exercise testing. In heart failure of other aetiologies, patients’ functional status can be improved with exercise training. In addition, psychiatric disorders including anxiety or depression are more common in patients with takotsubo cardiomyopathy, suggesting that some patients might benefit from a combined psycho-cardiological rehabilitation. Purpose As there is no evidence base to inform the management of patients with takotsubo cardiomyopathy, in this randomised controlled trial we assessed the role of behavioural modifications after a recent index event. Methods In a prospective multi-centre clinical trial conducted between February 2020 and August 2023, patients with acute takotsubo cardiomyopathy were randomised 1:1:1 to physical exercise training, cognitive behavioural therapy or standard care for 12 weeks after index presentation. The primary endpoint was resting phosphocreatine/gamma-adenosine triphosphate ratio (PCr/yATP) assessed by 31P-magnetic resonance spectroscopy. Secondary endpoints were peak oxygen consumption (peak VO2) on cardiopulmonary exercise testing, 6-minute walk distance, left ventricular global longitudinal strain and patient-reported symptoms. Between groups differences in post-to-pre intervention changes in end-points were compared. Results Seventy-six participants were recruited: median age was 66 years and 91% were women. As shown in Figure 1, compared with standard care, the primary endpoint of myocardial PCr/yATP ratio was improved by physical exercise training (0.4, 95% confidence interval 0.1–0.8; p=0.016) and with cognitive behavioural therapy (0.3 0.01 – 0.7; p=0.043). Both physical exercise training and cognitive behavioural therapy also improved peak VO2 (4.2 1.6–6.8 and 3.7 1.1 – 6.2 mL/min/kg; p=0.003 and 0.007 respectively) and 6-minute walk distance (92.6 24.7–160.6 and 73.3 7.9–138.8 m; p=0.009 and 0.029, respectively) compared to standard care. There were no differences in global longitudinal strain or symptom burden. Conclusion In this randomised controlled trial, a 12-week cardiac rehabilitation with behavioural modification (physical exercise training or cognitive behavioural therapy) delivered to patients with acute takotsubo cardiomyopathy led to improvements in resting left ventricular high energy phosphate metabolism and cardio-respiratory functional capacity. We have shown that behavioural modification strategies after takotsubo cardiomyopathy can enhance the metabolic and functional recovery of the heart, supporting the use of these cardiac rehabilitation strategies for these patients.Figure 1