| 1. |
- Hall, Juliette, et al.
(författare)
-
Detection of G Protein-Coupled Receptor Autoantibodies in Postural Orthostatic Tachycardia Syndrome Using Standard Methodology
- 2022
-
Ingår i: Circulation. - 1524-4539. ; 146:8, s. 613-622
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a disorder of orthostatic intolerance that primarily affects women of childbearing age. The underlying pathophysiology of POTS is not fully understood, but it has been suggested that autoimmunity may play a role. The aim of this study was to compare concentrations of autoantibodies to cardiovascular G protein-coupled receptors between patients with POTS and healthy controls.METHODS: Sera were collected from 116 patients with POTS (91% female; mean age, 29 years) and 81 healthy controls (84% female; mean age, 27 years) from Calgary, Canada, and Malmö, Sweden. Samples were evaluated for autoantibodies to 11 receptors (adrenergic, muscarinic, angiotensin II, and endothelin) using a commercially available enzyme-linked immunosorbent assay.RESULTS: Autoantibody concentrations against all of the receptors tested were not significantly different between controls and patients with POTS. The majority of patients with POTS (98.3%) and all controls (100%) had α1 adrenergic receptor autoantibody concentrations above the seropositive threshold provided by the manufacturer (7 units/mL). The proportion of patients with POTS versus healthy controls who fell above the diagnostic thresholds was not different for any tested autoantibodies. Receiver operating characteristic curves showed a poor ability to discriminate between patients with POTS and controls.CONCLUSION: Patients with POTS and healthy controls do not differ in their enzyme-linked immunosorbent assay-derived autoantibody concentrations to cardiovascular G protein-coupled receptors. These findings suggest that these tests are not useful for establishing the role of autoimmunity in POTS.
|
|
| 2. |
- Kharraziha, Isabella, et al.
(författare)
-
Cerebral Oximetry in Syncope and Syndromes of Orthostatic Intolerance
- 2019
-
Ingår i: Frontiers in Cardiovascular Medicine. - : Frontiers Media SA. - 2297-055X. ; 6
-
Forskningsöversikt (refereegranskat)abstract
- Cerebral autoregulation is crucial for maintaining cerebral blood flow and perfusion. In recent years, the importance of cerebral oxygenation in syncope and orthostatic intolerance (OI) has received increased attention. Cerebral tissue oxygenation can be measured by using near-infrared spectroscopy (NIRS), which determines the ratio of oxygenated hemoglobin to total hemoglobin in cerebral tissue. NIRS is non-invasive technology using near-infrared light, which displays real-time cerebral tissue oxygenation. Normal values of cerebral tissue oxygenation in healthy subjects are 60 to 80%. Head-up tilt test (HUT) offers the opportunity to observe the haemodynamic changes precipitating syncope and is, today, the standard method for the evaluation of syncope and orthostatic intolerance syndromes. In previous studies where NIRS was applied during HUT, a significant decrease in cerebral tissue oxygenation both prior to and during loss-of-consciousness in vasovagal syncope (VVS) has been observed. Interestingly, cerebral tissue oxygenation appears to decrease even before haemodynamic changes can be observed. Apart from VVS, cerebral tissue oxygenation decreases during orthostatic provocation in patients with orthostatic hypotension (OH) and postural orthostatic tachycardia syndrome (POTS), in the latter even in the absence of hypotension. Importantly, decline of cerebral tissue oxygenation in VVS and POTS during HUT may not correlate with hemodynamic changes. In this mini review, we summarize the current knowledge of the application of cerebral oximetry in syncope and orthostatic intolerance syndromes, discuss its likely value as a clinical diagnostic tool and also emphasize its potential in the understanding of the relevant pathophysiology.
|
|
| 3. |
- Kharraziha, Isabella, et al.
(författare)
-
Effect of aging on cerebral tissue oxygenation in relation to reflex syncope
- 2021
-
Ingår i: Europace. - : Oxford University Press (OUP). - 1532-2092. ; 23:Supplement 3
-
Konferensbidrag (refereegranskat)abstract
- Background: There is an increased susceptibility to syncope with aging attributed to age-related physiological impairments. Cerebral oxime-try non-invasively measures cerebral tissue oxygenation (SctO2) and has been shown to be valuable in syncope evaluation. SctO2 has beenfound to decrease with aging but it is unknown whether the decrease in SctO2 is related to increased susceptibility to syncope during ortho-static provocation. By measuring SctO2 during head up tilt test (HUT) we can study age-related differences in SctO2 and their impact ondeveloping reflex syncope.Purpose: To investigate the effect of age on the cerebral tissue oxygenation threshold for syncope and presyncope among patients withvasovagal syncope.Methods: Non-invasive haemodynamic monitoring and near-infrared spectroscopy (NIRS) were applied during head-up tilt (HUT) in 139vasovagal syncope patients (mean [SD] 45[17] years, 60% female), and 82 control patients with a normal response to HUT (45[18] years,61% female). Group differences in SctO2 and systolic blood pressure (SBP) during HUT in supine position, after 3 and 10 min of HUT, 30seconds prior to syncope ("presyncopal phase") and during syncope in different age groups (<30, 30-60 and >60 years) were comparedusing one-way ANOVA and Tukey"s multiple comparison test. Associations between age and SctO2 were studied using linear regressionmodels adjusted for sex and concurrent SBP.Results: Lower SctO2 in supine position was associated with increasing age among controls (B=-0.085, p = 0.010) but not among VVS pa-tients (B=-0.036, p = 0.114). No age-related differences in SctO2 were found after 3 and 10 minutes of HUT and during syncope. MeanSctO2 (%) during the presyncopal phase decreased over the advancing age groups (<30: 66.9 ± 6.2, 30-60: 64.5 ± 6.1, >60: 62.2 ± 5.8; p = 0.009 for inter-group comparison). In contrast, mean SBP during the presyncopal phase did not differ by age groups (<30: 85.6 ± 21.8, 30-60:77.6 ± 19.7, >60: 77.6 ± 20.8 mmHg, p = 0.133). Age was associated with lower SctO2 during the presyncopal phase after adjusting for sexand SBP (B = 0.096, p = 0.001).Conclusion: Older VVS patients have lower cerebral tissue oxygenation in the presyncopal phase compared with younger patients inde-pendently of systolic blood pressure. These results suggest either that with imminent reflex syncope cerebral tissue oxygenation diminishesmore with advancing age or that cerebral deoxygenation is better tolerated by older reflex syncope patients.
|
|
| 4. |
- Kharraziha, Isabella, et al.
(författare)
-
Impaired cerebral oxygenation in heart failure patients at rest and during head-up tilt testing
- 2021
-
Ingår i: ESC Heart Failure. - : Wiley. - 2055-5822. ; 8:1, s. 586-594
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: Heart failure (HF) confers potentially negative effects on the brain and autonomic nervous system. The measurement cerebral tissue oxygen saturation (SctO2 ) may aid in understanding such effects. We aimed to investigate if compensated HF affects SctO2 at rest and during orthostatic challenge.METHODS AND RESULTS: Non-invasive haemodynamic monitoring and near-infrared spectroscopy were applied during head-up tilt (HUT) in 61 HF patients [mean (SD) 71 (11) years, 82% male, New York Heart Association (NYHA) class I-III] and 60 controls [60 (12) years, 42% male). Group differences in continuous variables were compared using Student's t-test. Associations between HF and SctO2 were studied using multivariable linear regression models adjusted for age, sex, diabetes, smoking, systolic blood pressure (SBP), and heart rate in supine position and after 10 min of HUT. Mean SctO2 was lower in HF patients compared with controls both in the supine position (67 vs. 71%; P < 0.001) and after 10 min of HUT (64 vs. 69%; P < 0.001). The HUT-induced SctO2 decrease was greater in HF patients compared with controls (P = 0.026). SBP did not change in neither HF patients nor controls during HUT, whereas diastolic blood pressure and heart rate increased in both groups. HF was associated with lower SctO2 in supine (B = -2.5%, P = 0.023) and after 10 min of HUT (B = -2.6%, P = 0.007) after multivariable adjustments.CONCLUSIONS: Cerebral tissue oxygenation is lower in HF patients both at rest and during orthostasis compared with subjects without HF. Future studies should test if the lower cerebral oxygenation associates with negative prognosis and with impaired cognitive function.
|
|
| 5. |
- Kharraziha, Isabella, et al.
(författare)
-
Monitoring of cerebral oximetry in patients with postural orthostatic tachycardia syndrome
- 2019
-
Ingår i: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology. - : Oxford University Press (OUP). - 1532-2092. ; 21:10, s. 1575-1583
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS : Postural orthostatic tachycardia syndrome (POTS) is a disorder of unknown aetiology characterized by orthostatic intolerance and tachycardia with diverse other symptoms, including neurocognitive deficits. Cerebral oximetry non-invasively measures cerebral tissue saturation (SctO2) and has been shown to be informative in syncope evaluation. We aimed to assess SctO2 in POTS patients and those with normal response to orthostatic provocation, relative to haemodynamic parameters and symptoms.METHODS AND RESULTS : Thirty-four patients with POTS (29.1 ± 9.5 years; 26 females) and 34 age-/sex-matched controls with normal head-up tilt tests (HUTs) were included. SctO2 at rest and during HUT were compared between POTS and controls. The relation between SctO2, systolic blood pressure (SBP), and heart rate (HR) during HUT was linearly assessed. SctO2 values were related to dizziness or syncope during HUT. The minimum SctO2-value during HUT was lower (65.4 ± 5.6 vs. 68.2 ± 4.2%, P = 0.023) and changes in SctO2 from supine to minimum HUT value were more pronounced in POTS patients (-5.7 ± 2.9% vs. -4.3 ± 2.1%, P = 0.028). Decrease in SBP from supine to minimum HUT value (P = 0.004) and increase in HR from supine to HUT value at 3 min (P = 0.022) correlated with more pronounced SctO2 decrease in POTS but not controls. SctO2 did not predict syncope or dizziness during HUT.CONCLUSION : Postural orthostatic tachycardia syndrome patients have lower cerebral tissue saturation during orthostatic provocation compared with those subjects having normal haemodynamic response to tilt. Orthostatic decrease in cerebral saturation only weakly correlates with HR increase and does not predict vasovagal reflex in POTS. Other hitherto unknown factors may affect cerebral tissue saturation in POTS.
|
|
| 6. |
- Kharraziha, Isabella
(författare)
-
Novel diagnostic methods and potential treatments in cardiovascular autonomic dysfunction
- 2024
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)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 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-curve0.88; 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.
|
|
| 7. |
- Kharraziha, Isabella, et al.
(författare)
-
Serum Activity Against G Protein-Coupled Receptors and Severity of Orthostatic Symptoms in Postural Orthostatic Tachycardia Syndrome
- 2020
-
Ingår i: Journal of the American Heart Association. - 2047-9980. ; 9:15
-
Tidskriftsartikel (refereegranskat)abstract
- Background Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate increase on standing and orthostatic intolerance. Previous data indicate autoimmune involvement. We studied serum activity against G protein-coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell-based assay. Methods and Results Forty-eight patients with POTS (aged 28.6±10.5 years; 44 women) and 25 healthy individuals (aged 30.7±8.6 years; 21 women) were included. The 10-item Orthostatic Hypotension Questionnaire (OHQ) was completed by 33 patients with POTS and all controls. Human embryonic kidney 293 cells overexpressing one G protein-coupled receptor: adrenergic α1 receptor, adrenergic β2 receptor, cholinergic muscarinic type 2 receptor, and opioid receptor-like 1 were treated with sera from all patients. Receptor response was analyzed using a β-arrestin-linked transcription factor driving transgenic β-lactamase transcription by fluorescence resonance energy transfer method. Receiver operating characteristic curves were constructed. G protein-coupled receptor activation was related to OHQ indices in linear regression models. Sera from patients with POTS activated all 4 receptors to a higher degree compared with controls (P<0.01 for all). The area under the curve was 0.88 (0.80-0.97, P<0.001) combining all 4 receptors. Adrenergic α1 receptor activation associated with OHQ composite score (β=0.77 OHQ points per SD of activity, P=0.009) and with reduced tolerability for prolonged standing (P=0.037) and walking for short (P=0.042) or long (P=0.001) periods. All 4 receptors were associated with vision problems (P<0.05 for all). Conclusions Our results indicate the presence of circulating proteins activating adrenergic, muscarinic, and nociceptin receptors in patients with POTS. Serum-mediated activation of these receptors has high predictive value for POTS. Activation of adrenergic α1 receptor is associated with orthostatic symptoms severity in patients with POTS.
|
|
| 8. |
- Kharraziha, Isabella, et al.
(författare)
-
The Influence of Age on Cerebral Tissue Oxygenation in Vasovagal Syncope and Orthostatic Hypotension
- 2022
-
Ingår i: Journal of Clinical Medicine. - : MDPI AG. - 2077-0383. ; 11:15, s. 1-12
-
Tidskriftsartikel (refereegranskat)abstract
- Age-related physiological impairment increases susceptibility to syncope. We tested the hypotheses that cerebral oxygenation during orthostatic provocation, as well as the level at which syncope occurs, differs according to age. Non-invasive hemodynamic monitoring and cerebral oximetry were applied during a head-up tilt test in 139 patients with vasovagal syncope (mean (SD) 45, (17) years, 60%-female); 121 patients with orthostatic hypotension (61.4 (19.2) years, 49.6%-female); and 82 patients with a negative head-up tilt test (45 (18) years, 61%-female). Group differences in cerebral tissue oxygenation levels and systolic blood pressure were assessed in supine at 3 and 10 min of orthostatic provocation, 30 s before (i.e., presyncopal phase) and during syncope in age groups of <30, 30–60, and >60 years. During the head-up tilt test, cerebral tissue oxygenation at the presyncopal phase decreased with age, both in patients with vasovagal syncope (<30 years: 66.9 ± 6.2, 30–60: 64.5 ± 6.1, >60: 62.2 ± 5.8%; p = 0.009) and orthostatic hypotension (<30: 67.4 ± 4.4, 30–60: 61.6 ± 6.2, >60: 57.5 ± 3.9; p < 0.001). Mean systolic blood pressure at the presyncopal phase did not differ according to age. Cerebral oxygenation prior to syncope in older individuals with vasovagal syncope and orthostatic hypotension is lower compared with younger individuals independently of systolic blood pressure. This suggests that the level of cerebral oxygenation at which syncope is elected is lower in older individuals.
|
|
| 9. |
- Memarian, Ensieh, et al.
(författare)
-
Associations between physical activity and ankle-brachial index: the Swedish CArdioPulmonary bioImage Study (SCAPIS)
- 2024
-
Ingår i: BMC CARDIOVASCULAR DISORDERS. - : BMC. - 1471-2261. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background The ankle-brachial index (ABI) is the ratio of the ankle and brachial systolic blood pressures. In the clinical setting, low ABI (< 0.9) is an indicator of peripheral atherosclerosis, while high ABI (> 1.4) is a sign of arterial stiffness and calcification. The purpose of the current study was to investigate the association between ABI and physical activity levels, measured by accelerometer. Methods The Swedish CArdioPulmonary bioImage Study (SCAPIS) is a Swedish nationwide population-based cross-sectional cohort for the study of cardiovascular and pulmonary diseases, in which individuals aged 50-64 years were randomly invited from the general population. The study population with data on ABI, physical activity, and sedentary time based on accelerometry was 27,737. Differences between ABI categories and associations to sedentary behavior, moderate to vigorous physical activity (MVPA), and other metabolic characteristics were compared. ABI was categorized as low, ABI <= 0.9, borderline, ABI 0.91-0.99, normal, ABI 1.0-1.39, and high, ABI >= 1.4. Results Prevalence of low ABI was higher in the most sedentary quartiles compared to the least sedentary (0.6% vs. 0.1%, p < 0.001). The most sedentary individuals also exhibited higher BMI, higher prevalence of diabetes and hypertension. The proportion of wake time spent in MVPA was lowest in those with low ABI (0.033 +/- 0.004; p < 0.001) and highest in those with ABI > 1.4 (0.069 +/- 0.001; p < 0.001) compared to those with normal ABI. Compared to normal ABI, the proportion of sedentary time was highest in those with low ABI (0.597 +/- 0.012; p < 0.001) and lowest in those with ABI > 1.4 (0.534 +/- 0.002; p = 0.004). Conclusion This population-based study shows that middle-aged individuals with ABI > 1.4 have the highest level of physical activity, while individuals with a lower ABI, especially those with ABI < 0.9, are less active and spend more time sedentary. Future studies are needed to understand the relationships between ABI, physical activity, and the risk of peripheral arterial and cardiovascular disease in the general population.
|
|
| 10. |
- Memarian, Ensieh, et al.
(författare)
-
Associations between physical activity and autonomic function during deep breathing test : the Swedish CArdioPulmonary bioImage Study (SCAPIS).
- 2023
-
Ingår i: Clinical Autonomic Research. - : Springer. - 0959-9851 .- 1619-1560. ; 33:4, s. 411-420
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The deep breathing test (DBT) is a sensitive test of cardiovagal function. The aim of this study was to explore associations between physical activity and sedentary time, measured by accelerometer, and autonomic function, using DBT.METHODS: In the Swedish Cardio-Pulmonary bioImage Study, men and women aged 50-64 were randomly invited from the general population. A total of 4325 subjects who underwent DBT and assessment of physical activity and sedentary time by accelerometery were included. ECG files from 1-min DBT were used to calculate measures of respiratory sinus arrhythmia [RSA; expiration-inspiration (E-I) difference and E/I ratio], heart rate variability [HRV; root mean square of successive differences (RMSSD), standard deviation of heart rates and mean circular resultant]. Low RSA and HRV was defined as the lowest 10% in the population.RESULTS: For accelerometer-assessed physical activity, there were significant associations between high percentage of sedentary time and low E/I (p < 0.01), and low RMSSD (p < 0.01) in an age- and sex-adjusted model, and between percentage of sedentary time and low RMSSD (p = 0.04) in a risk factor-adjusted model. Low RMSSD was less common in those with a high percentage of moderate to vigorous physical activity (p = 0.04, after risk-factor adjustment). These associations became non-significant when further adjusting for heart rate.CONCLUSION: We report associations between degree of physical activity and indices of autonomic dysfunction in a large population. The relationships were no longer significant after adjustments for heart rate, indicating that the relationship between physical activity and cardiovagal function partly is accounted for by reduced heart rate.
|
|
