Baseline Left Ventricular Ejection Fraction Associated with Symptom Improvements in Both Children and Adolescents with Postural Tachycardia Syndrome Under Metoprolol Therapy
Postural tachycardia syndrome (POTS) is a common form of orthostatic intolerance (OI) characterized by excessive orthostatic tachycardia. It predominantly affects older children and adolescents, with an incidence of approximately 6.80% in this population. POTS significantly impacts physical health, psychological well-being, and quality of life. The condition is often triggered by rapid changes from a supine to an upright position or prolonged standing, leading to symptoms such as dizziness, headache, fatigue, blurred vision, chest tightness, palpitations, hand tremors, and syncope. The diagnosis of POTS is confirmed by an increase in heart rate (HR) of ≥40 beats per minute (bpm) or a maximum HR of ≥130 bpm for children aged 6–12 years or ≥125 bpm for adolescents aged 13–18 years during the first 10 minutes of a standing test or head-up tilt test, without orthostatic hypotension.
Beta-blockers, particularly metoprolol, are a cornerstone in the management of POTS. However, the efficacy of metoprolol varies, with symptom improvement observed in only about 57.10% to 57.89% of children. This variability underscores the need for predictive biomarkers to guide personalized treatment strategies. Previous studies have identified several potential predictors of metoprolol response, including plasma concentrations of norepinephrine, copeptin, and C-type natriuretic peptide, as well as HR variability assessed via 24-hour Holter monitoring. However, these markers are either invasive or time-consuming, limiting their clinical utility. Therefore, there is a pressing need for stable, non-invasive, and easily accessible indicators to predict treatment response in children and adolescents with POTS.
Left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) are echocardiography-derived parameters that reflect the contractile function of the left ventricle. These markers are relatively stable, non-invasive, and easily obtainable. LVEF and LVFS are influenced by sympathetic activity and catecholamine levels, which are implicated in the pathophysiology of POTS. Given the role of sympathetic hyperactivity in POTS, we hypothesized that baseline LVEF and LVFS values might predict the therapeutic response to metoprolol in children and adolescents with POTS.
This retrospective study aimed to investigate the association between pre-treatment baseline LVEF and LVFS values and symptom improvement following metoprolol therapy in children and adolescents with POTS. The study included 51 patients diagnosed with POTS who received metoprolol therapy at Peking University First Hospital between November 2010 and July 2019. All patients underwent a standing test or basic head-up tilt test and cardiac echocardiography before treatment. Treatment response was evaluated three months after initiating metoprolol therapy, based on the reduction in symptom scores (SS). Responders were defined as those with a decrease in SS of ≥2 points, while non-responders had a decrease of <2 points.
The demographic and hemodynamic characteristics of responders and non-responders were compared. No significant differences were observed in terms of sex, age, height, weight, body mass index (BMI), pre-treatment baseline HR, systolic and diastolic blood pressure (BP), maximum HR during standing, HR increase from supine to upright position, or urine specific gravity (Usg). However, responders had significantly higher baseline LVEF (71.09% ± 4.44% vs. 67.17% ± 4.88%, t = -2.789, P = 0.008) and LVFS values (40.00 [38.00, 42.00]% vs. 36.79% ± 4.11%, Z = -2.542, P = 0.010) compared to non-responders.
Correlation analysis revealed that baseline LVEF and LVFS values were positively correlated with the decrease in symptom scores (DSS) (r = 0.378, P = 0.006; r = 0.363, P = 0.009, respectively). Multivariable logistic regression analysis, adjusted for sex, age, BMI, LVEF, and LVFS, demonstrated that LVEF was independently associated with the likelihood of response to metoprolol therapy. Each 1% increase in baseline LVEF was associated with a 21% higher likelihood of response to metoprolol treatment (odds ratio: 1.201, 95% confidence interval: 1.039–1.387, P = 0.013).
The findings of this study suggest that pre-treatment baseline LVEF and LVFS values are associated with symptom improvement following metoprolol therapy in children and adolescents with POTS. Specifically, higher baseline LVEF values predict a better therapeutic response to metoprolol. This is consistent with the hypothesis that sympathetic hyperactivity, reflected by elevated LVEF, is a key factor in the pathophysiology of POTS and a determinant of metoprolol efficacy.
The study has several limitations, including its retrospective design, small sample size, and short follow-up period. Additionally, direct measurements of blood volume were not performed. Future multicenter studies with larger sample sizes and longer follow-up periods are needed to validate these findings and explore the underlying mechanisms.
In conclusion, baseline LVEF is a promising, non-invasive predictor of treatment response to metoprolol in children and adolescents with POTS. Evaluation of LVEF before initiating metoprolol therapy may help identify patients who are more likely to benefit from this treatment, thereby guiding personalized therapeutic strategies and improving clinical outcomes.
doi.org/10.1097/CM9.0000000000001698
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