Dysautonomia In Patients Research Articles

Assessing Full Stomach Prevalence with Ultrasound Following Preoperative Fasting in Diabetic Patients with Dysautonomia: A Comparative Observational Study.

Traditionally, diabetics have been considered patients with a high risk of aspiration due to having delayed gastric emptying; However, the evidence concerning residual gastric volume (GV) in fasting diabetic patients is inconsistent. This study aimed to compare the fasting GV of diabetic patients with or without dysautonomia with control patients scheduled for elective surgery using gastric ultrasound. This bicentric prospective single-blinded case-control study was conducted at 2 university hospitals in Spain. Patients aged over 18 years, classified as American Society of Anesthesiologists (ASA) physical statuses I to III and having similar fasting statuses, were included in the study. The primary outcome was to compare the prevalence of risk stomach using the Perlas gastric content grading scale evaluated by ultrasound in the 3 groups. Secondary outcomes included the measurement of cross-sectional area (CSA) and GV in the right lateral decubitus (RLD) position, as well as the prevalence of solid gastric residue. A total of 289 patients were recruited for the study, comprising 145 diabetic patients (83 of whom had dysautonomia) and 144 patients in the control group. The percentage of patients classified as Perlas grade 2 was 13.2% in the control group, 16.1% in diabetic patients without dysautonomia, and 22.9% in diabetic patients with dysautonomia (P = .31). Antral CSA was significantly higher in diabetic patients with dysautonomia (6.5 [4.8-8.4]) compared to the control group (5.4 [4.0-7.2]; P = .04). However, no significant differences were observed between groups in residual GV. Among diabetic patients with dysautonomia, 12% exhibited solid gastric residue, which was twice the percentage observed in diabetic patients without dysautonomia (4.8%) and 3 times higher than that in the control group (3.5%; P = .03). The presence of dysautonomia was associated with an increased odds ratio of solid gastric residue (odds ratio [OR], 3.37; 95% confidence interval [CI], 1.28-8.87; P = .01) after adjusting for confounding factors. This study offers insights into the relationship between dysautonomia in patients with diabetes mellitus and the presence of full stomach, underscoring the significance of preoperative gastric ultrasound evaluation in managing perioperative risks in this population.

Value of 123I-MIBG SPECT for the assessment of dysautonomia in patients with long COVID

Value of 123I-MIBG SPECT for the assessment of dysautonomia in patients with long COVID

Vagal dysautonomia in patients with Chagas disease and mortality: 14-year results of a population cohort of the elderly

IntroductionGreat part of Chagas disease (ChD) mortality occurs due to ventricular arrhythmias, and autonomic function (AF) may predict unfavorable outcomes. We aimed to evaluate the predictive value of AF indexes in ChD patients. MethodsThe Bambuí Study of Aging is a prospective cohort of residents ≥60 years at study onset (1997), in the southeastern Brazilian city of Bambuí (15,000 inhabitants). Consented participants underwent annual follow-up visits, and death certificates were tracked. AF was assessed by the maximum expiration on minimum inspiration (E:I) ratio during ECG acquisition and by heart rate variability indices: SDRR (standard deviation of adjacent RR intervals) and RMSSD (square root of the mean of the sum of squares of the differences between adjacent RR intervals)), calculated using a computer algorithm. Cox proportional hazards regression was performed to access the prognostic value of AF indexes, expressed as terciles, for all-cause mortality, after adjustment for demographic, clinical and ECG variables. ResultsFrom 1742 qualifying residents, 1000 had valid AF tests, being 321 with ChD. Among these, median age was 68 (64–74) years, and 32.5% were men. In Cox survival analyses, only SDRR was associated with all-cause mortality in non-adjusted models: SDRR (hazard ratio (HR): 1.26 (95% CI 1.08–1.47), p < 0.001), E:I ratio (HR: 1.13 (95% CI 0,98–1.31), p = 0.10) and RMSSD (HR: 0.99 (0.86–1.16), p = 0.95). After adjustment for sex and age, none of the indexes remained as independent predictors. ConclusionAmong elderly patients with ChD, AF indexes available in this cohort were not independent predictors of 14-year mortality.

Abstract 17642: Takotsubo Cardiomyopathy After Guillian Barre Syndrome

Introduction: Guillian Barre Syndrome (GBS) has the potential to cause acute and long-term cardiac effects. Takotsubo Cardiomyopathy(TCM) is a life-threatening manifestation of dysautonomia in patients with GBS, although infrequently reported in the literature. We present a case of TCM in the setting of GBS. Case Presentation: A 54-year-old woman with no past history presented with progressive ascending bilateral lower limb weakness, numbness and paraesthesia following a recent chest infection. On exam, she had reduced motor power and absent deep tendon reflexes. MRI brain was normal. CSF analysis revealed albuminocytologic dissociation(1a). Nerve Conduction Studies(NCS) showed severe sensorimotor polyneuropathy with demyelinating features suggestive of GBS. She was treated with plasmapheresis. The next day, she developed respiratory failure and was hemodynamically unstable with persistent tachycardia and labile blood pressure. ECG showed sinus tachycardia with ST-segment depression(1b). Chest CT was normal. Echocardiogram showed moderate anterolateral hypokinesia with an ejection fraction(EF) of 30%. Coronary angiography showed no significant arterial stenosis, suggesting TCM with a diagnostic TCM score of 59 (1c,1d). She received steroids, furosemide and norepinephrine. Repeat ECG and echocardiogram on day 11 were normal with improved EF (52%).This was followed by a Cardiac MRI which was normal (1e). Discussion: The precise etiology of TCM in GBS is unknown and is believed to be related to a complex interplay of autonomic dysfunction, catecholamine release and inflammation. Although rare, TCM is a fatal complication of GBS, warranting urgent evaluation and management. Sudden onset hemodynamic instability and new onset ECG changes may raise the suspicion of TCM in GBS and must be ruled out. Early diagnosis and treatment can improve the patient’s prognosis.

The Relationship between Paresthesia and the Presence of Cardiac Dysautonomia in Patients with Post-COVID-19 Syndrome: A Preliminary Observational Study.

Post-Coronavirus disease 2019 (Post-COVID-19) syndrome has neurological symptoms related to the dysfunction of the autonomous nerve system. However, a pathogenic relationship between post-COVID-19 syndrome and dysautonomia still remains to be demonstrated. Establishing a pathogenic relationship between paresthesia and the presence of cardiac dysautonomia in patients with post-COVID-19 syndrome is the objective of this study. This observational study was carried out in the neurophysiology service wing of the Juan Bruno Zayas Hospital, Santiago de Cuba, in Cuba. The patients were recruited through a post-COVID-19 clinic at the same hospital. A variability study of cardiac frequency and a test of autonomic cardiovascular reflexes was carried out, which is composed of deep breathing, orthostatism, and the Valsalva maneuver. The variability parameters of the cardiac frequency, the expiration-inspiration ratio between deep breaths, and the Valsalva Index showed no statistically significant differences between healthy participants and those with post-COVID-19 syndrome. During the Valsalva maneuver, there was a greater cardiac frequency response in participants with post-COVID-19 syndrome than in healthy subjects. The difference in supine and standing blood pressure was significantly minor in patients with post-COVID-19 syndrome. The logarithm of high frequency (log HF) increased significantly in patients with paresthesia when compared to patients without paresthesia. In the autonomic function tests, no signs of dysautonomia were found in patients with post-COVID-19 syndrome. The presence of paresthesias is associated with differences in cardiac vagal activity, which may suggest that damage to peripheral sensory nerve fibers could be associated with an affectation to autonomic fibres.

Intravenous Immunoglobulin Therapy for Autoimmune Dysautonomia in children: A Case Series (P10-5.013)

<h3>Objective:</h3> To assess the efficacy of intravenous immunoglobulin (IVIG) therapy in Autoimmune Dysautonomia <h3>Background:</h3> IVIG has been successfully used in the past for pain management and Autoimmune Gastric Dysmotility Disorder (AGID) of adult patients with suspected autoimmune etiology. However, the literature on efficacy of IVIG in children is scarce. <h3>Design/Methods:</h3> A retrospective review of AGID patients treated with IVIG was conducted. All symptoms were reviewed. <h3>Results:</h3> Patient 1 was positive for IgM TS-HDS Ab. Patients 2 and 3 were positive for Neuronal Acetylcholine Receptor Ganglionic (alpha-3) Ab. Patients 1 and 2 had Small Fiber Neuropathy diagnosis. Age at diagnosis of patients 1, 2, and 3 were 14, 17.25, and 16.5 years, respectively. Duration of treatment for patient 3 was 6 months, and 1 year for patients 1 and 2. Post treatment, patient 1 did not require venting of J tube; though still dependent on Total Parenteral Nutrition (TPN). Patient 1 is no longer dependent on enemas, as distal colonic and antroduodenal contractions have normalized. Esophageal dysmotility remains unchanged. Abdominal pain and distention, Postural Orthostatic Tachycardia Syndrome (POTS), and neuropathic pain improved. Patient 2 presented with intractable vomiting and POTS. She was dependent on Nasogastric tube (NG) feedings due to vomiting and was on cyproheptadine, erythromycin, bethanechol, amitriptyline, and prucalopride. Post treatment, vomiting resolved and all but prucalopride were discontinued. Colonic motility has not been re-assessed, however constipation, abdominal distention, and pain resolved. Polyethylene glycol and Bisacodyl were discontinued. Likewise, her POTS resolved. Patient 3 had hyperadrenergic POTS, persistent vomiting, and constipation, suffering a 4 kg weight loss. Following treatment, her vomiting and constipation improved, regaining 3.5 kg. Activity levels and orthostatic dizziness improved, and midodrine and fludrocortisone were discontinued. <h3>Conclusions:</h3> IVIG is an effective treatment for autoimmune dysautonomia in patients with positive IgM TS-HDS Ab and N-AchR Ganglionic (alpha-3) Ab. <b>Disclosure:</b> Mr. Bolufer has nothing to disclose. Dr. Prakash has nothing to disclose.

582 - Recurrent dysautonomia in patients with neuromyelitis optica spectrum disorders; a case report

582 - Recurrent dysautonomia in patients with neuromyelitis optica spectrum disorders; a case report

Effect of RNAi therapeutics patisiran and vutrisiran on orthostatic hypotension due to dysautonomia in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy

Effect of RNAi therapeutics patisiran and vutrisiran on orthostatic hypotension due to dysautonomia in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy

Abstract 11419: Prognostic Value of Vagal Dysautonomia in Patients With Chagas Disease: 14-year Results of a Population Cohort of the Elderly

Introduction: The cardiac form is the main responsible for morbidity and mortality of Chagas disease (ChD), given its prevalence and unpredictable clinical evolution. A great part of ChD mortality occurs due to sudden ventricular arrhythmias, and the frequently observed autonomic dysfunction may be associated with unfavorable outcomes. We aimed to evaluate the predictive value of autonomic dysfunction indexes in ChD patients. Methods: The Bambuí Study of Aging is a prospective cohort of residents ≥60 years at study onset (1997), living in the southeastern Brazilian city of Bambuí (15,000 inhabitants). Consented participants underwent annual follow-up visits, and death certificates were tracked. For assessment of respiratory sinus arrhythmia (E:I ratio), patients were instructed to breathe deeply in a 10-second cycle (5 inhales and 5 exhales) while ECG was recorded. Heart rate variability indices (SDRR (standard deviation of adjacent RR intervals) and RMSSD (square root of the mean of the sum of squares of the differences between adjacent RR intervals)) were calculated using a computer algorithm, supervised by an independent cardiologist blinded to clinical data. Multivariable regression was performed to access the prognostic value of autonomic dysfunction indexes, expressed as tertiles, for all-cause mortality, after adjustment for demographic, clinical and ECG variables. Results: From 1,742 qualifying residents, 1,606 were enrolled, being 557 with positive ChD serology. Among these, mean age was 68 (64-74) years, and 32.5% were men. The most frequent ECG abnormality was right bundle branch block (23.2%). In 14 years, loss-to-follow-up was 7.9% and overall mortality was 51.9%. At total 321 ChD patients had valid autonomic indexes measurements. In univariate analyses, measurements of autonomic function predicted all-cause death: E:I ratio (HR: 1.20 (95% CI 1.09-1.33)), SDRR (HR: 1.26 (95% CI 1.14-1.40)) and RMSSD (HR: 1.12 (1.01-1.23)). After adjustment for sex, age and cardiovascular risk factors, none of these indexes remained as independent predictors of mortality. Conclusions: In a long-term cohort of elderly patients with ChD, abnormalities in autonomic function indexes were not independent predictors of 14-year mortality.

Effect of RNAi therapeutics patisiran and vutrisiran on orthostatic hypotension due to dysautonomia in patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy

Abstract Background Hereditary transthyretin-mediated (hATTR) amyloidosis, also known as ATTRv amyloidosis, is a rapidly progressive, multisystem disease. Orthostatic hypotension, due to autonomic neuropathy, is a common yet hard-to-treat disease manifestation in patients with hATTR amyloidosis. Fatigue, muscle weakness, and deterioration in cardiac function further exacerbate orthostatic symptoms. Efficacy of RNAi therapeutics patisiran and vutrisiran was assessed in patients with hATTR amyloidosis with polyneuropathy across the APOLLO (NCT01960348), Global Open-Label Extension (OLE) (NCT02510261), and HELIOS-A (NCT03759379) studies, respectively. Purpose Evaluate the quantitative effect of patisiran and vutrisiran on orthostatic hypotension in patients with hATTR amyloidosis with polyneuropathy. Methods In APOLLO, patients were randomised 2:1 to patisiran 0.3 mg/kg or placebo, IV q3w. Patients who completed APOLLO (APOLLO-placebo, APOLLO-patisiran) were eligible to enrol into the ongoing Global OLE (patisiran 0.3 mg/kg IV q3w). In HELIOS-A, patients were randomised 3:1 to vutrisiran (25 mg SC q3m) or patisiran (0.3 mg/kg IV q3w; reference group). Primary endpoint for APOLLO and HELIOS-A was change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7) vs APOLLO placebo at M18 (APOLLO) and M9 (HELIOS-A). Orthostatic hypotension was evaluated using the postural blood pressure (PBP) component of mNIS+7, calculated as the mean of 2 supine readings of systolic BP [SBP, mmHg] taken 15 min apart minus the lowest SBP upon standing at 1, 3, and 5 min. A smaller reduction in observed SBP between supine and upright readings indicated an improved PBP. Results APOLLO enrolled 225 patients (placebo, n=77; patisiran, n=148), Global OLE 211 and HELIOS-A 164 (vutrisiran, n=122; patisiran, n=42). At baseline, the severity of orthostatic hypotension was similar between within-study treatment arms in APOLLO and HELIOS-A. In APOLLO, patisiran-treated patients showed PBP improvement or stabilization from baseline to M18 (mean [SD] change in SBP: baseline, −17.6 [19.4]; M18, −13.5 [16.8]) and was maintained at Global OLE 36m (−13.4 [15.6]). In contrast, placebo-treated patients in APOLLO had an increased change in PBP over 18m (baseline, −17.5 [16.5]; M18, −20.4 [16.9]); their PBP improved after patisiran initiation (Global OLE 36m, −16.6 [18.1]). In HELIOS-A, stabilization in PBP was observed in the vutrisiran arm (baseline, −11.2 [14.0], M18, −11.7 [14.6]). In the smaller patisiran arm, while the change in PBP increased, the value remained in the normal range (baseline, −11.6 [17.2]; M18, −14.2 [15.5]). Patisiran and vutrisiran have acceptable safety profiles. Conclusions PBP analyses quantify the benefits of RNAi therapeutics patisiran and vutrisiran on autonomic function in patients with hATTR amyloidosis with polyneuropathy. The increase in change in PBP to a symptomatic range without treatment indicates the importance of early intervention. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Alnylam Pharmaceuticals

TH-284. Dysautonomia in patients recovered from COVID-19

TH-284. Dysautonomia in patients recovered from COVID-19

Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies.

IntroductionOn March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting.ObjectiveTo conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines.ResultsAutonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done.ConclusionSymptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.

Prevalence and patterns of symptoms of dysautonomia in patients with long-COVID syndrome: A cross-sectional study.

BackgroundThe association between autonomic dysfunction and long‐COVID syndrome is established. However, the prevalence and patterns of symptoms of dysautonomia in long‐COVID syndrome in a large population are lacking.ObjectiveTo evaluate the prevalence and patterns of symptoms of dysautonomia in patients with long‐COVID syndrome.MethodsWe administered the Composite Autonomic Symptom Score 31 (COMPASS‐31) questionnaire to a sample of post‐COVID‐19 patients who were referred to post‐COVID clinic in Assiut University Hospitals, Egypt for symptoms concerning for long‐COVID syndrome. Participants were asked to complete the COMPASS‐31 questionnaire referring to the period of more than 4 weeks after acute COVID‐19.ResultsWe included 320 patients (35.92 ± 11.92 years, 73% females). The median COMPASS‐31 score was 26.29 (0–76.73). The most affected domains of dysautonomia were gastrointestinal, secretomotor, and orthostatic intolerance with 91.6%, 76.4%, and 73.6%, respectively. There was a positive correlation between COMPASS‐31 score and long‐COVID duration (p < 0.001) and a positive correlation between orthostatic intolerance domain score and post‐COVID duration (p < 0.001). There was a positive correlation between orthostatic intolerance domain score and age of participants (p = 0.004). Two hundred forty‐seven patients (76.7%) had a high score of COMPASS‐31 >16.4. Patients with COMPASS‐31 >16.4 had a longer duration of long‐COVID syndrome than those with score <16.4 (46.2 vs. 26.8 weeks, p < 0.001).ConclusionsSymptoms of dysautonomia are common in long‐COVID syndrome. The most common COMPASS‐31 affected domains of dysautonomia are gastrointestinal, secretomotor, and orthostatic intolerance. There is a positive correlation between orthostatic intolerance domain score and patients' age.

Autonomic symptoms are predictive of dementia with Lewy bodies

IntroductionAutonomic symptoms are common in patients with dementia with Lewy bodies (DLB). Although autonomic dysfunction is considered as one of the primary early markers in patients with DLB, there are few studies that examine the timing of the onset of autonomic symptoms in these patients. The purpose of the current study was to evaluate the time of onset of autonomic symptoms in patients with DLB using a questionnaire. MethodsAutonomic symptoms were evaluated in patients with DLB using the Scales for Outcomes in Parkinson's disease - autonomic (SCOPA-Aut) questionnaire. Time of the onset of autonomic symptoms of patients with DLB was also assessed relative to that of memory loss. ResultsA total of 106 patients with DLB were included. The most frequent symptom of dysautonomia in patients with DLB was constipation (60.4%), followed by orthostatic dizziness (33%), urinary frequency (30.2%), and daytime hyperhidrosis (22.6%). The gastrointestinal system was the most prominent system of autonomic dysfunction in patients with DLB. Orthostatic dizziness, daytime hyperhidrosis, and constipation all preceded the onset of memory loss by 0.2 ± 4.9, 3.3 ± 8.6, and 3.7 ± 9.2 years, respectively, while urinary incontinence occurred 1.7 ± 1.5 years following the onset of memory loss. ConclusionMany autonomic symptoms precede the onset of memory loss in patients with DLB, especially constipation and daytime hyperhidrosis. These symptoms can facilitate an early diagnosis of patients with DLB.

Serum proteome profiles revealed dysregulated proteins and mechanisms associated with fibromyalgia syndrome in women

Fibromyalgia syndrome (FM) is a multifactorial disorder whose pathogenesis and diagnosis are poorly understood. This study investigated differential serum proteome profiles in patients with FM and healthy pain-free controls and explored the association between serum proteome and clinical profiles in patients with FM. Twenty patients with FM (according to the American College of Rheumatology criteria, 2010) and 20 healthy pain-free controls were recruited for optimized quantitative serum proteomics analysis. The levels of pain, pressure pain threshold, sleep, anxiety, depression, and functional status were evaluated for patients with FM. We identified 22 proteins differentially expressed in FM when compared with healthy pain-free controls and propose a panel of methyltransferase-like 18 (METTL18), immunoglobulin lambda variable 3–25 (IGLV3–25), interleukin-1 receptor accessory protein (IL1RAP), and IGHV1OR21-1 for differentiating FM from controls by using a decision tree model (accuracy: 0.97). In addition, we noted several proteins involved in coagulation and inflammation pathways with distinct expression patterns in patients with FM. Novel proteins were also observed to be correlated with the levels of pain, depression, and dysautonomia in patients with FM. We suggest that upregulated inflammation can play a major role in the pathomechanism of FM. The differentially expressed proteins identified may serve as useful biomarkers for diagnosis and evaluation of FM in the future.

Retrograde nerve growth factor signaling abnormalities in familial dysautonomia.

Familial dysautonomia (FD) is the most prevalent form of hereditary sensory and autonomic neuropathy (HSAN). In FD, a germline mutation in the Elp1 gene leads to Elp1 protein decrease that causes sympathetic neuron death and sympathetic nervous system dysfunction (dysautonomia). Elp1 is best known as a scaffolding protein within the nuclear hetero-hexameric transcriptional Elongator protein complex, but how it functions in sympathetic neuron survival is very poorly understood. Here, we identified a cytoplasmic function for Elp1 in sympathetic neurons that was essential for retrograde nerve growth factor (NGF) signaling and neuron target tissue innervation and survival. Elp1 was found to bind to internalized TrkA receptors in an NGF-dependent manner, where it was essential for maintaining TrkA receptor phosphorylation (activation) by regulating PTPN6 (Shp1) phosphatase activity within the signaling complex. In the absence of Elp1, Shp1 was hyperactivated, leading to premature TrkA receptor dephosphorylation, which resulted in retrograde signaling failure and neuron death. Inhibiting Shp1 phosphatase activity in the absence of Elp1 rescued NGF-dependent retrograde signaling, and in an animal model of FD it rescued abnormal sympathetic target tissue innervation. These results suggest that regulation of retrograde NGF signaling in sympathetic neurons by Elp1 may explain sympathetic neuron loss and physiologic dysautonomia in patients with FD.

Vitamin D, vitamin D binding protein, vitamin D receptor levels and cardiac dysautonomia in patients with multiple sclerosis: a cross-sectional study.

Vitamin D is a pleiotropic steroid hormone that modulates the autonomic balance. Its deficiency has been described as an environmental risk factor for multiple sclerosis (MS). The aim of this study was to investigate the serum levels of vitamin D, vitamin D binding protein (VDBP) and vitamin D receptors (VDR) and to evaluate cardiac dysautonomia in MS patients due to bidirectional interaction between vitamin D and the autonomic nervous system. The current cross-sectional study was conducted on 26 patients with relapsing-remitting MS and on 24 healthy controls. Twenty-four-hour ambulatory blood pressure variability (BPV) was calculated and the participants were evaluated for orthostatic hypotension and supine hypertension. Serum levels of vitamin D, VDBP and VDR were measured. The mean serum vitamin D level was significantly lower in MS patients than in controls (p = 0.044); however there was no significant difference in terms of VDR and VDBP levels between the groups. Supine hypertension and orthostatic hypotension were significant and the 24-hour systolic BPV was significantly decreased in patients with MS (p < 0.05) compared to controls. No correlation was found between vitamin D, VDBP and VDR with supine hypertension, orthostatic hypotension and systolic BPV values (p > 0.05). Also, there was a negative correlation between VDBP and the EDSS (p = 0.039, r = -0.406). There was no correlation between orthostatic hypotension, supine hypertension and systolic BPV values and serum vitamin D, VDBP and VDR in MS patients. Future prospective studies with large number of patients may help us to better understand the relationship between vitamin D and the autonomic nervous system.

P2733Prognostic value of cardiac dysautonomia in AL amyloidosis

Abstract Introduction Cardiac involvement is the major prognostic factor in patients with light chain amyloidosis (AL). Cardiac dysautonomia can occur early in amyloidosis and can be assess by Iodine-123-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Its prognostic value has been shown in TTR amyloidosis but is unknown in AL amyloidosis. We aimed to evaluate the prognosis impact of cardiac dysautonomia in patients with AL amyloidosis. Methods We carried out a prospective study in consecutive patients with biopsy-proven AL amyloidosis. All patients underwent clinical examination, EKG, echocardiography, cardiac MRI and biological tests. The 2012 Mayo clinic prognostic classification was calculated by using blood levels of NT-proBNP, cardiac T troponin and the differential of free light chains as recommended. The sympathetic cardiac innervation was assessed by using 123I-MIBGscintigraphy and measurement of the heart-to-mediastinum uptake ratio (late H/M) in the anterior view of the chest. A cardiac denervation was defined by late H/M &lt;1.8 4h after injection of 3 MBq/kg of 123I-MIBG. The primary end-point was all-cause mortality during follow-up. Results Fifty consecutive patients with AL amyloidosis were included. The median age was 68 years old [58–73]. By using both echocardiography and MRI, cardiac involvement was diagnosed in 33 patients (66%) and thirteen of these patients were NYHA class III or IV. By using Mayo clinic classification, patients were I, II, III and IV classes in 9 (18%), 14 (28%), 16 (32%) and 11 (22%) cases respectively. According to echocardiographic data, the median wall thickness of left ventricle was 13 mm [12–15]. The late H/M was 1.51 [1.33–1.67]. Cardiac denervation was found in 44 patients (88%). The 6 patients (12%) with a normal late H/M had no cardiac amyloidosis involvement. During a median follow-up of 24 months, 9 patients (18%) died. The area under the ROC curve of late H/M for predicting death was 0.74 (CI 95% 0.58–0.86). According to this curve, the best threshold was 1.44 and 7 of the 9 patients who died had late H/M ≤1.44. The figure shows the 2 year-survival according to late H/M. Late H/M ≤1.44 predicted all-cause death irrespective of the Mayo clinic classification: HR 8.0 (CI 95% 2.1–63) after adjustment on the Mayo clinic score (p=0.005). In addition, unplanned hospitalization for heart failure occurred in 8 patients with late H/M ≤1.44 versus 3 patients with late H/M &gt;1.44 (p=0.03). Survival according to late H/M Conclusion Late H/M ≤1.44 is predictive of adverse outcomes in patients with AL amyloidosis, independently of the Mayo Clinic prognostic classification.

Cardiac dysautonomia in depression - heart rate variability biofeedback as a potential add-on therapy.

Depressive disorders are among the most important health problems and are predicted to constitute the leading cause of disease burden by the year 2030. Aside significant impact on quality of life, psychosocial well-being and socioeconomic status of affected patients, depression is associated with impaired cardiovascular health and increased mortality. The link between affective and cardiovascular disease has largely been attributed to dysregulation of the autonomic nervous system resulting in a chronic shift toward increased sympathetic and decreased parasympathetic activity and, consecutively, cardiac dysautonomia. Among proposed surrogate parameters to capture and quantitatively analyze this shift, heart rate variability (HRV) and baroreflex sensitivity have emerged as reliable tools. Attenuation of these parameters is frequently seen in patients suffering from depression and is closely linked to cardiovascular morbidity and mortality. Therefore, diagnostic and therapeutic strategies were designed to assess and counteract cardiac dysautonomia. While psychopharmacological treatment can effectively improve affective symptoms of depression, its effect on cardiac dysautonomia is limited. HRV biofeedback is a non-invasive technique which is based on a metronomic breathing technique to increase parasympathetic tone. While some small studies observed beneficial effects of HRV biofeedback on dysautonomia in patients with depressive disorders, larger confirmatory trials are lacking. We reviewed the current literature on cardiac dysautonomia in patients suffering from depression with a focus on the underlying pathophysiology as well as diagnostic workup and treatment.

Increased Prevalence of Autonomic Dysfunction in Patients With Eosinophilic Gastrointestinal Disorders

Introduction: Eosinophilic gastrointestinal disorders (EGIDs) are characterized by eosinophilic inflammation in the GI tract. These include eosinophilic esophagitis (EoE), gastritic (EG), gastroenteritis (EGE), and colitis (EC). Studies have linked EGIDs with atopic conditions, connective tissue disorders, and autoimmune disorders, but the association between EGIDs and autonomic dysfunction has not been extensively described. Methods: We identified adult patients in the EoE/EGID database at UNC who also had a diagnosis of comorbid autonomic dysfunction (postural orthostatic tachycardia syndrome or gastroparesis). The electronic medical record was abstracted for data regarding their EGID and autonomic dysfunction, including demographic information, disease characteristics and diagnostic information, treatments, and presence of other comorbidities. Results: We identified 7 patients who had EGID and dysautonomia. All were Caucasian and 5 were female. There were 4 patients with EoE alone, 2 with EoE overlapping with EGE, and 1 with EG overlapping with EC. All patients had POTS, and 2 also had gastroparesis. In regard to POTS, 6 of the patients sought treatment with an autonomic dysfunction specialist. The most common treatments included liberalized fluid and salt intake, exercise, corticosteroids (hydrocortisone, fludrocortisone) and pyridostigmine. Onset of autonomic symptoms coincided with onset of EGID symptoms in 3 patients or with an acute EGID flare in 3. Oral viscous budesonide, targeted dietary elimination, and/or manual endoscopic dilations were sufficient to control EGID for 4 of the patients. However, 3 patients required systemic steroids to control EGID. In no cases did successful control of EGID lead to improvement of autonomic symptoms. Two subjects had both comorbid Ehlers-Danlos syndrome (EDS) and mast cell activation syndrome (MCAS). Using the UNC EoE/EGID database (n=560 adults), we calculated a prevalence of POTS in EGID patients as 7/560 = 1.25%, compared to the estimated previously published 0.17% prevalence of POTS in the general population. Conclusion: In a large database of adult EoE/EGID patients, we found a higher than expected prevalence of autonomic dysfunction, suggesting an association between the two conditions, though the underlying mechanism is unclear. Therefore, providers should consider comorbid dysautonomia in patients with EGID, particular when symptoms persist despite treatment.334_A Figure 1. Patient demographics, type of eosinophilic gastrointestinal disorder (EGID), dysautonomia, and other comorbidities in our cohort of seven patients with comorbid EGID and dysautonomia. EoE = eosinophilic esophagitis EGE = eosinophilic gastroenteritis EG = eosinophilic gastritis EC = eosinophilic colitis POTS = postural orthostatic tachycardia syndrome334_B Figure 2. Frequency of presenting symptoms and attempted treatments for postural orthostatic tachycardia syndrome (POTS) in our cohort of seven patients with comorbid eosinophilic gastrointestinal disorder (EGID) and dysautonomia.