Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial

Aminorroaya, Arya; Tavolinejad, Hamed; Sadeghian, Saeed; Jalali, Arash; Alaeddini, Farshid; Emkanjoo, Zahra; Mollazadeh, Reza; Bozorgi, Ali; Oraii, Saeed; Kiarsi, Mohamadreza; Shahabi, Javad; Akbarzadeh, Mohammad Ali; Rahimi, Behzad; Joharimoghadam, Adel; Mohsenizade, Abolfazl; Mohammadi, Roghayeh; Oraii, Alireza; Ariannejad, Hamid; Apakuppakul, Sanatcha; Ngarmukos, Tachapong; Tajdini, Masih

doi:10.1016/j.ahj.2021.03.002

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…Midodrine hydrochloride was utilized for VVS children in multiple studies [ 7 , 19 – 21 ]. However, the effectiveness of unselected use of midodrine hydrochloride on VVS in children varied.…”

Section: Discussionmentioning

confidence: 99%

Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study

Du,

Li,

Zhang

et al. 2023

Eur J Pediatr

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Serum uric acid (UA) level has been proven to be related to several cardiovascular and metabolic diseases. In the present study, we examined if baseline serum UA level could predict the therapeutic efficacy of midodrine hydrochloride on vasovagal syncope (VVS) in children. The pediatric VVS patients who received midodrine hydrochloride from November 2008 to October 2022 were enrolled. After a median treatment duration of 3 months, the therapeutic effect was evaluated. According to the patients’ responses to midodrine hydrochloride, which was determined by the recurrence of syncope, they were divided into effective and ineffective groups. The baseline variables were explored using univariable and multivariate logistic analysis. The predictive efficacy was assessed by receiver operating characteristic curve (ROC), precision-recall curve (PR), Hosmer–Lemeshow test, calibration curve, and decision curve analysis (DCA). Totally, 53 participants were included in the study. Among the 51 patients who were successfully followed up, 29 (56.9%) responded to midodrine hydrochloride (effective group), and the other 22 (43.1%) failed to respond to midodrine hydrochloride (ineffective group). The participants in effective group had lower baseline serum UA level than those in ineffective group (276.5 ± 73 μmol/L vs. 332.7 ± 56 μmol/L, p = 0.004). Multivariable logistic analysis showed that serum UA was associated with the therapeutic response (odds ratio (OR): 0.985, 95% confidence interval (CI): 0.974–0.997, p = 0.01). ROC analysis indicated that using baseline serum UA < 299 μmol/L as a threshold value yielded a sensitivity of 77.3% and a specificity of 79.3% in predicting the treatment response to midodrine hydrochloride. The area under the PR curve was 0.833. Hosmer–Lemeshow test yielded a p value of 0.58, and calibration plot indicated that the model was well-fitted. DCA demonstrated that treatment decision depending on the baseline serum UA level resulted in a favorable net benefit. Conclusion: This pilot study suggested that the baseline serum UA level could be taken as a predictor of therapeutic effect of midodrine hydrochloride on VVS in children. What is Known:• Empirical and unselected use of midodrine hydrochloride has an unfavorable therapeutic effect on VVS in children. Serum uric acid (UA) is closely linked to cardiovascular events. What is New:• A low baseline serum UA level successfully predicts the therapeutic effectiveness of midodrine hydrochloride on VVS in children.

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Section: Discussionmentioning

confidence: 99%

Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study

Du,

Li,

Zhang

et al. 2023

Eur J Pediatr

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“…We evaluated patients with VVS who presented to the syncope unit 12,13,25 of Tehran Heart Center, 26 Tehran, Iran, for a head-up tilt table test (HUTT) from February 2020 to February 2021 as the case group. The control group was selected from the population-based Tehran Cohort Study (TeCS) on adult inhabitants of Tehran.…”

Section: Data Sourcesmentioning

confidence: 99%

“…1,2 Therefore, it is encouraged to investigate the possible mechanisms as the basis of possible future interventions for treating VVS or at least a subgroup of these patients. 12,13 Increased serum levels of catecholamines might play a role in the pathophysiology of VVS, [14][15][16][17][18][19] and vitamin B12 deficiency may cause increased catecholamines through biochemically plausible mechanisms. 20,21 Moreover, there is some evidence on the association of vitamin B12 deficiency and VVS in pediatric patients; 22,23 however, no methodologically rigorous study has ever investigated this possible association in adult or elderly patients with VVS.…”

Section: Introductionmentioning

confidence: 99%

Association of Vitamin B12 and Folate Deficiency with Vasovagal Syncope: A Case-Control Study

Aminorroaya

Vasheghani‐Farahani²,

Tavolinejad³

et al. 2023

Preprint

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Aims: There is some clinical evidence of the association between vitamin B12 deficiency and vasovagal syncope (VVS) in pediatric patients. We aimed to investigate the possible association of vitamin B12 and folate deficiency with VVS in adults. Methods: In this case-control study, we included adult patients with VVS who presented to our tertiary syncope unit for a head-up tilt table test as the case group. We selected age- and sex-matched individuals without any history of syncope from the population-based Tehran Cohort Study as the control group. The exclusion criteria included but were not restricted to taking vitamin B supplements, carbamazepine, or phenobarbital, and sleeve gastrectomy. We measured and compared serum levels of vitamin B12, folate, and homocysteine. Results: From February 2020 to February 2021, we included 44 patients in the case group, matched with 44 controls, with a mean age of 37.9 years and 23 (52.3%) females in each group. There was no statistically significant difference between the study groups regarding vitamin B12 or folate deficiency, or their serum levels. The serum level of vitamin B12 was remarkably lower in patients with frequent VVS (≥3 lifetime episodes) compared to patients with infrequent VVS (<3 lifetime episodes) [233.8 (80.7) versus 305.2 (118.1) pg/mL; P=0.042] and this association remained significant after adjustment for possible confounders (P=0.026). Conclusion: We found no association between vitamin B12 or folate deficiency, or their serum levels and VVS; nevertheless, frequent VVS, compared to infrequent VVS, was associated with a lower serum vitamin B12.

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“…3 There is recruitment going on for the trial COMFORTS (comparison of outcomes with Midrodrine and Fludrocortisone for objective recurrence in treating syncope) [NCT04595942] which will give us a better picture regarding the benefit of pharmacological therapy in RS. 109 6. Pacing (with or without counteracting HS) A pacemaker may be indicated in a specific subset of the patients with RS.…”

Section: Treatmentmentioning

confidence: 99%

Evaluation and Management of Reflex Vasovagal Syncope—A Review

Udyavar

Deshpande

2021

Indian Journal of Clinical Cardiology

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Syncope is a symptom that is commonly encountered in the practice and may point to a cardiac or neurological diagnosis. The evaluation of syncope rests on a thorough clinical evaluation, aided by electrocardiogram (ECG) findings, followed by risk stratification of the particular case. Once high-risk factors have been ruled out, the patient can be further diagnosed as having a reflex syncope (RS), orthostatic hypotension, or cardiac syncope based on specific clues. If the initial evaluation is not confirmatory various diagnostic tests may be used to guide further management (eg, long-term ECG monitoring, tilt table testing, etc). The management should be based on the overall profile of the patient and not only on any single test. In this review, we discuss the evaluation of a patient with RS and give an overview of treatments available for the patients.

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Comparison of Outcomes with Midodrine and Fludrocortisone for Objective Recurrence in Treating Syncope (COMFORTS trial): Rationale and design for a multi-center randomized controlled trial

Cited by 6 publications

References 26 publications

Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study

Serum uric acid predicts therapeutic response to midodrine hydrochloride in children with vasovagal syncope: a pilot study

Association of Vitamin B12 and Folate Deficiency with Vasovagal Syncope: A Case-Control Study

Evaluation and Management of Reflex Vasovagal Syncope—A Review

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