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Novel diagnostic methods and potential treatments in cardiovascular autonomic dysfunction

Kharraziha, Isabella LU orcid (2024) In Lund University, Faculty of Medicine Doctoral Dissertation Series
Abstract
General Aim: To investigate novel diagnostic tools and treatment options for cardiovascular autonomic dysfunction (CVAD) patients, focusing on syncope, orthostatic intolerance, and heart failure (HF).

Background: CVAD includes common clinical entities such as vasovagal syncope (VVS) postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). Also, CVAD plays an important role in HF. Monitoring of cerebral tissue oxygenation (SctO2) during orthostasis may aid in understanding mechanisms in CVAD. For POTS, studies indicate autoimmune activity against G-protein coupled receptors (GPCRs), however, data is sparse. Exercise training is recommended in POTS, but little is known about clinical... (More)
General Aim: To investigate novel diagnostic tools and treatment options for cardiovascular autonomic dysfunction (CVAD) patients, focusing on syncope, orthostatic intolerance, and heart failure (HF).

Background: CVAD includes common clinical entities such as vasovagal syncope (VVS) postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). Also, CVAD plays an important role in HF. Monitoring of cerebral tissue oxygenation (SctO2) during orthostasis may aid in understanding mechanisms in CVAD. For POTS, studies indicate autoimmune activity against G-protein coupled receptors (GPCRs), however, data is sparse. Exercise training is recommended in POTS, but little is known about clinical implementation.

Subjects: Patients in paper 1-4 (n=68-342) are from the Syncope Study of Unselected Population in Malmö (SYSTEMA), a cohort of patients evaluated for syncope and orthostatic intolerance at Skåne University Hospital (SUS), Malmö, Sweden. Paper 3 also includes patients (n=61) from the HeArt and bRain failure inVESTigation study (HARVEST) of admitted HF patients from SUS. Study 5 will include POTS-patients (n=200) from the Syncope Unit, SUS.

Methods and Results: Patients underwent active standing or head-up tilt test (HUT). Non-invasive cerebral oximetry measured SctO2 during HUT in paper 1, 3 and 4. GPCR activity in POTS versus controls and its association with symptoms were studied (paper 2). A cross-over study protocol of a 16-week exercise program was constructed. POTS (p=0.023) and HF patients (p<0.001) had lower SctO2 during orthostasis compared to SYSTEMA participants with normal HUT. Older patients with VVS and OH exhibited lower SctO2 prior to syncope than younger patients (p<0.01). Proteins activating adrenergic, muscarinic, and nociceptin receptors were highly predictive of POTS (Area-under-the-curve
0.88; 95% confidence interval 0.80-0.97).

Conclusion: Cerebral deoxygenation during orthostasis is notable in POTS, VVS, OH and HF, and may relate to aging in VVS and OH. The role of altered SctO2 in HF therapy and cognitive function should be further examined. High GPCR activity is predictive of POTS supporting autoimmune involvement. Exercise training in POTS warrants further studies for effective clinical implementation. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Associate Professor Johan Engdahl, Associate professor, Department of Clinical Sciences, Karolinska Institutet.
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Autonomic nervous system, Postural orthostatic tachycardia syndrome, Tilt-table test, Cerebrovascular circulation, G-protein coupled receptors, Exercise, Vasovagal syncope, Orthostatic hypotension, Heart failure, Orthostatic intolerance
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
issue
2024-100
pages
88 pages
publisher
Lund University, Faculty of Medicine
defense location
Kvinnoklinikens aula, Jan Waldenströms gata 47, Skånes Universitetssjukhus i Malmö. Join by Zoom: https://lu-se.zoom.us/j/66254922105
defense date
2024-09-27 09:00:00
ISSN
1652-8220
ISBN
978-91-8021-596-1
language
English
LU publication?
yes
id
7052698e-5376-4c1c-a98d-fee95d4dc91b
date added to LUP
2024-08-20 12:38:48
date last changed
2024-09-09 12:31:43
@phdthesis{7052698e-5376-4c1c-a98d-fee95d4dc91b,
  abstract     = {{General Aim: To investigate novel diagnostic tools and treatment options for cardiovascular autonomic dysfunction (CVAD) patients, focusing on syncope, orthostatic intolerance, and heart failure (HF).<br/><br/>Background: CVAD includes common clinical entities such as vasovagal syncope (VVS) postural orthostatic tachycardia syndrome (POTS) and orthostatic hypotension (OH). Also, CVAD plays an important role in HF. Monitoring of cerebral tissue oxygenation (SctO2) during orthostasis may aid in understanding mechanisms in CVAD. For POTS, studies indicate autoimmune activity against G-protein coupled receptors (GPCRs), however, data is sparse. Exercise training is recommended in POTS, but little is known about clinical implementation.<br/><br/>Subjects: Patients in paper 1-4 (n=68-342) are from the Syncope Study of Unselected Population in Malmö (SYSTEMA), a cohort of patients evaluated for syncope and orthostatic intolerance at Skåne University Hospital (SUS), Malmö, Sweden. Paper 3 also includes patients (n=61) from the HeArt and bRain failure inVESTigation study (HARVEST) of admitted HF patients from SUS. Study 5 will include POTS-patients (n=200) from the Syncope Unit, SUS.<br/><br/>Methods and Results: Patients underwent active standing or head-up tilt test (HUT). Non-invasive cerebral oximetry measured SctO2 during HUT in paper 1, 3 and 4. GPCR activity in POTS versus controls and its association with symptoms were studied (paper 2). A cross-over study protocol of a 16-week exercise program was constructed. POTS (p=0.023) and HF patients (p&lt;0.001) had lower SctO2 during orthostasis compared to SYSTEMA participants with normal HUT. Older patients with VVS and OH exhibited lower SctO2 prior to syncope than younger patients (p&lt;0.01). Proteins activating adrenergic, muscarinic, and nociceptin receptors were highly predictive of POTS (Area-under-the-curve<br/>0.88; 95% confidence interval 0.80-0.97).<br/><br/>Conclusion: Cerebral deoxygenation during orthostasis is notable in POTS, VVS, OH and HF, and may relate to aging in VVS and OH. The role of altered SctO2 in HF therapy and cognitive function should be further examined. High GPCR activity is predictive of POTS supporting autoimmune involvement. Exercise training in POTS warrants further studies for effective clinical implementation.}},
  author       = {{Kharraziha, Isabella}},
  isbn         = {{978-91-8021-596-1}},
  issn         = {{1652-8220}},
  keywords     = {{Autonomic nervous system; Postural orthostatic tachycardia syndrome; Tilt-table test; Cerebrovascular circulation; G-protein coupled receptors; Exercise; Vasovagal syncope; Orthostatic hypotension; Heart failure; Orthostatic intolerance}},
  language     = {{eng}},
  number       = {{2024-100}},
  publisher    = {{Lund University, Faculty of Medicine}},
  school       = {{Lund University}},
  series       = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
  title        = {{Novel diagnostic methods and potential treatments in cardiovascular autonomic dysfunction}},
  url          = {{https://lup.lub.lu.se/search/files/193676549/Isabella_Kharraziha_-WEBB.pdf}},
  year         = {{2024}},
}