Cardiac autonomic dysfunction in Takotsubo cardiomyopathy: an observational study

Abstract Takotsubo syndrome (TTS), commonly perceived as a benign and reversible condition has received attention due to emerging registry data revealing its prognosis to be comparable to acute coronary syndrome (ACS). Following ACS, a notable subset of patients develops autonomic dysfunction, whith unfavourable prognostic implications. Periodic repolarization dynamics (PRD) and deceleration capacity (DC), derived from ECG signals, are parameters capable of quantifying cardiac autonomic function. In this study, we aimed to assess autonomic dysfunction in patients with TTC in comparison to ST-elevation myocardial infarction (STEMI) patients. Consecutive patients diagnosed with TTS were prospectively recruited into an observational, single-centre cohort study. All patients underwent a 30-minute high-resolution ecg recording. Subsequent recordings were conducted at 4 and 12 months post-acute event. PRD and DC as markers for sympathetic and parasympathetic activity, respectively, were assessed using established methods. The control group comprised patients with STEMI. Statistical comparisons between groups were performed using the Mann-Whitney U-test, with a corrected significance level for multiple testing of α< .017. Between July 2021 and December 2023, 57 patients diagnosed with TTS were recruited (interquartile range [IQR]) 69.0 years (62.0-78.0), 98.3% women. A control group was derived from a pre-existing cohort of STEMI patients, matched through propensity score matching to adjust for age and sex (median age [IQR]: 69.0 [59.0-76.0] years, 98.3% women). At baseline, there was no significant difference in PRD between TTS patients and controls (median [IQR]: TTS: 5.28deg² [3.43-9.93], STEMI: 4.40deg² [2.24-7.21]; p = .04). However, at 4 months post-acute event, PRD was notably higher in TTS patients compared to controls (median [IQR]: TTS: 5.20deg² [2.71-8.17], STEMI: 2.63deg² [1.86-4.92]; p = .011). Interestingly, at 12-month follow-up, PRD in TTS patients did not differ from that of controls (median [IQR]: TTS: 4.55deg² [2.89-8.40], STEMI: 4.15deg² [2.42-6.85]; p = .68). Regarding DC, no significant differences were observed between TTS and STEMI patients at any time point (baseline: median [IQR]: TTS: 3.95 ms [2.27-5.51], STEMI: 3.52 ms [2.30-7.24], p = .51; 4 months: median [IQR]: TTS: 6.63 ms [4.59-8.64], STEMI: 7.41 ms [4.63-9.25], p = .39; 12 months: median [IQR]: TTS: 4.98 ms [4.19-6.67], STEMI: 7.48 ms [4.92-10.28], p = .17). Patients with TTS show substantial signs of cardiac autonomic dysfunction, similar or even higher than acute STEMI patients. This dysfunction persists even up to 4 months after the acute event, whereas STEMI patients show recovery of autonomic function in this 4 month period. DC remained consistent between TTS and STEMI patients across all time points. Further research elucidating the long-term implications of these autonomic alterations is warranted to refine risk stratification and therapeutic strategies in TTS management.