Role of the central autonomic nervous system intrinsic functional organisation and psychosocial factors in primary microvascular angina and Takotsubo syndrome Author: Magdalena Maria Cattaneo1 2, Emanuele Pravatà3, Micol Provenzi4, Marco Moccetti5, Alain Kaelin3, Isabella Sudano6, Luigi Biasucci7, Camilla Gallino8, Costanzo Limoni9, Carlo Calanchini10, Augusto Gallino8 11, Filippo Crea7, Mattia Cattaneo5 8 Affiliation: <sup>1</sup> Cardiovascular Research, Hospital of San Giovanni, Bellinzona, Switzerland cattaneo.magdalena@gmail.com. <sup>2</sup> Internal Medicine, Hospital of San Giovanni, Bellinzona, Switzerland. <sup>3</sup> Neuroradiology, Neurocenter of Southern Switzerland, Lugano, Switzerland. <sup>4</sup> Psychology, Psycho-Educational Center, Stabio, Switzerland. <sup>5</sup> Cardiology, Cardiocentro Ticino, Lugano, Switzerland. <sup>6</sup> Cardiology, University Heart Center, Zurich, Switzerland. <sup>7</sup> Cardiology, Catholic University of Sacred Heart, Rome, Italy. <sup>8</sup> Cardiovascular Research, Hospital of San Giovanni, Bellinzona, Switzerland. <sup>9</sup> Biostatistics, University of Applied Sciences and Arts of Southern Switzerland, Lugano, Switzerland. <sup>10</sup> Psychiatry, Hospital Malcantonese Castelrotto, Castelrotto, Switzerland. <sup>11</sup> Cardiology, University of Zurich, Zurich, Switzerland. Conference/Journal: Open Heart Date published: 2020 Jul Other: Volume ID: 7 , Issue ID: 2 , Pages: e001315 , Special Notes: doi: 10.1136/openhrt-2020-001315. , Word Count: 279 PMID: 32727853 DOI: 10.1136/openhrt-2020-001315 Free article Abstract Introduction and objective: Dysfunctional central autonomic nervous system network (CAN) at rest may result in aberrant autonomic responses to psychosocial stressors. We hypothesised that patients with primary microvascular angina (MVA) or Takotsubo syndrome (TTS) would exhibit a peculiar functional organisation of the CAN, potentially associated with psychological patterns. Methods: Patients underwent a psychosocial evaluation: a clinical diagnostic interview, Millon Clinical Multiaxial Inventory III, State-Trait Anxiety Inventory form Y and Short Form 36 Health Survey (SF-36). The strength of intrinsic functional connectivity (FC) between various nodes of the CAN was investigated using cerebral resting state functional MRI (RS-fMRI). Results: We evaluated 50 (46 women) stable patients: 16 patients with MVA, 17 patients with TTS and 17 patients with previous acute myocardial infarction (AMI). Compared with AMI, patients with MVA showed a lower (higher impairment) SF-36 Body-Pain score (p 0.046) and a higher SF-36 Mental-Health score (p 0.039). Patients with TTS showed the strongest FC between two nodes of the CAN (sympathetic midcingulate cortex and parasympathetic primary motor area) (F 6.25, p 0.005) using RS-fMRI. Conclusions: The study implements an innovative collaborative research among cardiologists, neuroscientists and psychiatrists ('Neuro-psycho-heart Team'). MVA showed a discrepancy between the highest level of self-reported body pain and the best mental health score, which might suggest a mechanism of somatisation. TTS exhibited an increased functional integration between two areas of the CAN involved in interoceptive pain awareness and negative emotional status. We implemented an innovative research collaboration among cardiologists, neuroscientists and psychiatrists. These data are hypothesis generating and suggest potential prospective investigations on pathophysiology and implementation of psychotherapy and stress-reducing techniques as therapeutic strategies. Trial registration number: NCT02759341. Keywords: autonomic regulation; cardiomyopathy apical; endothelial function; microvascular; syndrome X; interoception