Altered Cardiac Autonomic Regulation in Individuals with Myasthenia Gravis—A Systematic Review and Meta-Analysis

Abstract

The aim of this systematic review with meta-analysis was to determine differences in cardiovascular autonomic parameters between patients with myasthenia gravis (MG) and healthy controls (HCs). Two reviewers searched four electronic databases, namely PubMed, Web of Science, EMBASE, and SCOPUS, from database inception to 7 July 2023 for studies investigating cardiovascular autonomic parameters in MG vs. HCs. A random-effects meta-analysis was performed to compute Hedges’ g ± 95% confidence intervals (CI). Out of a total of 2200 records, 8 observational studies with a sample size of 301 patients with MG and 454 HCs were included in the systematic review. Meta-analysis revealed lower values of expiration/inspiration ratio (g = −0.45, I2 = 74.7), baroreflex sensitivity (g = −0.56, 95%CI −0.80, −0.33; I2 = 0.3), percentage of adjacent NN intervals differing by more than 50 ms (g = −1.2, I2 = 82.8), square root of the mean of squared differences between successive beat intervals (g = −1.94, I2 = 95.1), mean of the standard deviations of all NN intervals (g = −0.83, 95%CI −1.37, −0.28; I2 = 55.5), and high frequency of HRV during tilt (g = −0.75, 95%CI −0.11, −0.39; I2 = 0). MG patients vs. HCs had higher systolic blood pressure (g = 0.39; I2 = 56.1), sympathovagal balance at rest/during tilt (LF/HF-RRIsupine, g = 0.44; I2 = 0; LF/HF-RRItilt, g = 0.86; I2 = 0; LF/HFtilt, g = 0.40; I2 = 0). As a group, MG patients have altered cardiac autonomic function, including decreased parasympathetic function, lower baroreflex sensitivity, and higher sympathovagal balance at rest and during orthostatic challenges.

Correlation between Cardiovascular Autonomic and Pulmonary Ventilation Functions in Myasthenia Gravis Patients

“…In terms of cardiac autonomic function, MG patients exhibited a decreased HRV (HF and PSD), a lower BRS, a higher prevalence of abnormal cardiovagal function test results (the Valsalva ratio or E/I ratio), and a tendency toward a slightly higher but not statistically significant sympathovagal balance compared with that in HCs. These results partially corroborate the findings from our recent meta-analysis [20] involving 301 MG patients and 454 healthy controls, in which we confirmed a decreased parasympathetic function, reduced BRS, and increased sympathovagal balance at rest and during orthostatic challenges in patients with MG. However, some differences in our study may result from variations in sample size and disease severity.…”

“…In the present study, we found that age, FVC (% pred ), and TLC (% pred ) were independent predictors (with R 2 values ranging from 0.48 to 0.49) of the lower HR response to deep breathing (E/I ratio) in MG patients. These findings may partly explain the high heterogeneity in MG studies that assess the E/I ratio [20]. Our results are consistent with those of previous studies that link diminished cardiovagal tone and/or increased sympathetic activity at the sinus node with reduced pulmonary function [24].…”

“…Several cardiac manifestations have been reported in association with MG, including left cardiac autonomic imbalance, ventricular abnormalities, myocarditis, cardiac arrhythmia, and heart failure [12,[17][18][19]. A recent meta-analysis showed that as a group, MG patients have an altered cardiac autonomic function, including a decreased parasympathetic function, lower baroreflex sensitivity (BRS), and higher sympathovagal balance at rest and during orthostatic challenges [20]. Furthermore, reduced BRS and decreased lung function have been linked to an increased risk of cardiovascular mortality [21,22].…”

Frequency and severity of autonomic dysfunction assessed by objective hemodynamic responses and patient-reported symptoms in individuals with myasthenia gravis

“…However, most studies have focused primarily on cardiovascular autonomic dysfunction. A recent meta-analysis of more than 300 patients with MG showed decreased cardiovascular parasympathetic function, and higher sympathovagal balance, supporting cardiac autonomic dysfunction ( Zawadka-Kunikowska et al, 2023b ).…”

“…For laboratory quantification, the Ewing battery and the Composite Autonomic Scoring Scale (CASS) ( Cheshire et al, 2021 ), developed by Low (2003) are widely used as standard tests for assessing autonomic function ( Cheshire et al, 2021 ). Cardiac autonomic dysfunction has been identified in patients with MG, often with limited use of Valsalva maneuvers (VMs) which reflect cardiovagal and adrenergic function, or a lack of autonomic evaluations using the CASS scoring ( Zawadka-Kunikowska et al, 2023b ). There are conflicting findings regarding the relationship between autonomic questionnaires and autonomic function tests (AFTs) or CASS.…”