Intro: Amyloidosis leads to a wide range of disorders: vascular, cardiac, neuropathic, digestive, renal and others. These impairments are a source of disability, altered autonomy and quality of life, as well as stress and anxiety. The literature review demonstrates the positive impact of complementary approaches on these multiple symptoms of disabling chronic illnesses, as well as the efficacy of Shiatsu, attested by Evidence Based Medicine in a number of international studies. As part of a project to improve patient care and take better account of their needs and persistent, chronic symptoms, we thought of integrating Shiatsu targeted at amyloidosis symptoms as a complementary therapy. How can Shiatsu help patients with amyloidosis? What effect does Shiatsu have on amyloidosis patients' quality of life and their various symptoms? Hypothesis/Objective: Demonstrate the beneficial impact of three targeted Shiatsu sessions versus "comfort" Shiatsu on symptoms in cardiac amyloidosis patients with severe symptoms. To demonstrate the beneficial short-term impact of a targeted SHIATSU session on neuro-cardio-vascular physiological parameters and symptoms in patients with cardiac amyloidosis compared with comfort Shiatsu and no Shiatsu. To demonstrate the beneficial impact of three targeted Shiatsu sessions versus "comfort" Shiatsu and no Shiatsu on symptoms (fatigue, sleep, pain, anxiety, depression dyspnea, digestive disorders, nausea) and quality of life in cardiac amyloidosis patients with severe symptoms. Evaluate patient satisfaction with shiatsu. Assess tolerance to shiatsu.

Method: Randomized, controlled, superiority, single-center, double-blind study comparing the effects of "targeted" Shiatsu sessions on amyloidosis symptoms with the effects of "comfort" (non-targeted) Shiatsu sessions. Population: patients with amyloidosis (TTR, WT, AL) hospitalized or followed at the Centre de référence Amyloses-Cardiaques (Cardiogen branch) at the CHU Henri Mondor in Créteil, France. 108 patients in total: Shiatsu group (78 patients, 26 AL, 26 TTR, 26 WT), Comfort Shiatsu (39), Targeted Shiatsu (39), No Shiatsu group (30). Comparison group: Comfort Shiatsu group. Expected number of inclusions per center per month: 4.5, duration: 2 years. Primary endpoint: Reduction in total ESAS symptom score at 48 hours after third shiatsu session. Secondary endpoints: 20% improvement in heart rate variability measured with the e-patch; 20% improvement in skin conductance and variability measured with the SUDOSCAN. Overall score on the EQ-5D scale; Overall score on the MINNESOTA scale; Improvement of the questionnaire score corresponding to the symptom targeted by the Shiatsu session by 2 points (patient's dominant symptom ≥ 3 on the EESE-R), i.e. : on the Minnesota for the dominant symptom dyspnea; on the EESE-R for the dominant digestive symptoms "Digestive disorders"; on the QCD for the dominant symptom pain; Improvement of at least one global score on the BFI, HADS or LSEQ scales.

Inclusion visit (D0) The study will be offered to patients undergoing consultation as part of their routine care. At D0: Once consent has been signed, the patient will complete the questionnaires (MINNESOTA, EESE-R, EQ-5D, QCD, BFI, LSEQ, HADS). Measurement with the SUDOSCAN will be performed. The e-patch will be performed continuously for 48 hours. For patients in the Shiatsu group, the EESE-R questionnaire will be sent to the CRU for randomization. This will be carried out by an open-label CRA independent of the study. The results of the randomization are forwarded to the Shiatsu specialists of the group in which the patient is included (targeted or comfort). The CRA from the clinical research team at the Centre welcomes the patient and refers him or her to the shiatsu specialist who has been instructed to give either comfort shiatsu or shiatsu targeting a dominant symptom, depending on the outcome of the randomization. The patient will receive a Shiatsu session (Shiatsu group) according to his group (targeted Shiatsu or comfort Shiatsu). Research follow-up visits Visit 1 (D1) and Visit 2 (D2). At D1 in hospital, a second measurement with the SUDOSCAN will be taken at 24 hours from the Shiatsu session or from inclusion (group without Shiatsu), 2 measurements at 24H and 48H. On D2, a third measurement with the SUDOSCAN will be taken 48 hours after the Shiatsu session or inclusion (non-Shiatsu group). The patient will complete the following questionnaires: EESE-R and modified TAQ (if applicable). Visit 3 (D7±1 day). Group without Shiatsu: nothing. Shiatsu group: patient will receive a 2nd Shiatsu session given by a Shiatsu specialist (D7±1 day) and will complete the modified TAQ questionnaire 48 hours after the session (D9±1 day). Visit 4 (D14±1 day): At D14±1 day, the patient will receive a 3rd Shiatsu session given by a Shiatsu specialist (D14 ±1 day) and will complete the modified TAQ questionnaire 48 hours after the session (D16 ±1 day). Telephone visits Telephone contact 1 (D16 ±1 day). At D16±1 day, the patient's first telephone follow-up at 48 hours after the Shiatsu session will be carried out (TEC, ARC) in order to complete the following questionnaires with him/her: MINNESOTA, EESE-R, EQ-5D, QCD, BFI, LSEQ, HADS, modified TAQ (if applicable). Telephone contact 2 (D31 ±1 day). At D31±1 day, the patient's second telephone follow-up will be carried out by TEC or ARC in order to complete the following questionnaires with the patient: MINNESOTA, EESE-R, EQ-5D, QCD, BFI, LSEQ, HADS.

Conclusion: The expected benefits for patients are: An improvement in quality of life and symptoms (appetite, nausea, digestive disorders, sleep, fatigue, anxiety-depression, pain) and balancing of the ANS autonomic nervous system, weakened by the progression of pathologies and hospitalization.