Abstract Body (Do not enter title and authors here): Introduction:
Preliminary data suggest that patients with takotsubo syndrome (TTS) have altered activation of stress-related brain regions. The medial prefrontal cortex (mPFC) plays a central role in processing stress-related information and initiating the associated cardiovascular response. The aim of this study is to determine whether changes in mPFC hemodynamics are present in patients with TTS during the acute hospitalization compared to in recovery, and whether mPFC hemodynamics correlate with cardiac function and peak oxygen consumption (peak VO₂), a measure of cardiorespiratory fitness and a strong predictor of cardiovascular outcomes.
Methods:
Medial prefrontal cortex (mPFC) hemodynamics were evaluated non-invasively with near-infrared spectroscopy in patients hospitalized with TTS and controls. TTS patients were then reassessed 90±30 days after discharge (follow-up). We assessed mPFC hemodynamics for ten minutes with the patient resting in the semi-fowler position. In follow-up, a symptom-limited cardiopulmonary exercise test was also completed to assess peak VO₂. Comparisons were assessed with Wilcoxon or Mann-Whitney testing as appropriate, and correlations were made with Spearman rank testing. Data are median [IQR].
Results:
Patients with TTS (n=14) were assessed during hospitalization (LVEF: 34 [28-40] %, troponin I: 1,392 [405-2,626] ng/L, BNP: 873 [459-996] pg/mL). Controls were matched for age, sex, and LVEF to TTS patients at follow-up. We observed significantly lower mPFC hemodynamics in TTS (48 [43-53] μM) compared to controls (63 [58-69] μM; p=0.008; Fig 1A). At follow-up (n=9), cardiac function in TTS improved (LVEF: 57 [53-60] %, troponin I: 3 [3-5] ng/L, BNP: 32 [24-72] pg/mL), however, mPFC hemodynamics were not different from hospitalization (46 [39-55] μM; p=0.65) and remained significantly reduced compared to controls (p=0.004). Peak VO₂ in TTS (18 [17-23] ml.kg^-1.min^-1) was also significantly reduced compared to controls (30 [28-32] ml.kg^-1.min^-1; p=0.006), and peak VO₂ correlated with mPFC hemodynamics in follow-up (R=0.37; p=0.04; n=11; Fig 1B).
Conclusion:
These data suggest that in TTS, mPFC hemodynamics are reduced during hospitalization and remain reduced in follow-up. Further, peak VO₂ is poor in those with TTS and positively correlates with mPFC hemodynamics. Additional research is needed to address how mPFC hemodynamics may influence cardiorespiratory fitness in TTS.