Compression stockings for treating vasovagal syncope (COMFORTS-II) trial: Rationale and design of a triple-blind, multi-center, randomized controlled trial.

BACKGROUND: Reduced venous return is an important trigger of vasovagal syncope (VVS). Elastic compression stockings (ECS) can modify venous return and be of therapeutic interest; however, evidence for ECS efficacy in VVS is scarce. This randomized controlled trial was designed to address the issue. METHODS: COMFORTS-II is a multicenter, triple-blind, parallel design, randomized controlled trial aimed to assess the efficacy of ECS in preventing VVS recurrences. Using central online randomization, 268 participants will be allocated to 2 arms (1:1 ratio), wearing intervention ECS (25-30 mm Hg pressure) or sham ECS (≤10 mm Hg pressure). All participants will receive standard VVS treatment in the form of education, and lifestyle modification recommendations (drinking 2-3 l/d of fluids and consuming 10 g/d-roughly half a tablespoon-of table salt). Adherence to ECS treatment will be evaluated through diary sheets, and compared between study arms. Follow-up continues for 1 year, and is conducted via a 24/7 phone line available to patients and trimonthly visits. The co-primary outcomes are proportion of participants with any syncopal recurrence and time to first syncopal episode. Secondary outcomes include frequency of VVS spells, time intervals between recurrences, and incidence of any patient-reported adverse effects. CONCLUSION: To the best of our knowledge, COMFORTS-II is the first clinical trial to assess ECS efficacy among patients with VVS, addressing an important gap in evidence for VVS treatments.

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.

BACKGROUND: The cornerstone of the treatment of vasovagal syncope (VVS) is lifestyle modifications; however, some patients incur life-disturbing attacks despite compliance with these treatments which underscores the importance of pharmacological interventions. METHODS: In this open-label multi-center randomized controlled trial, we are going to randomize 1375 patients with VVS who had ≥2 syncopal episodes in the last year into three parallel arms with a 2:2:1 ratio to receive midodrine, fludrocortisone, or no medication. All patients will be recommended to drink 2 to 3 liters of fluids per day, consume 10 grams of NaCl per day, and practice counter-pressure maneuvers. In medication arms, patients will start on 5 mg of midodrine TDS or 0.05 mg of fludrocortisone BD. After one week the dosage will be up-titrated to midodrine 30 mg/day and fludrocortisone 0.2 mg/day. Patient tolerance will be the principal guide to dosage adjustments. We will follow-up the patients on 3, 6, 9, and 12 months after randomization. The primary outcome is the time to first syncopal episode. Secondary outcomes include the recurrence rate of VVS, time interval between first and second episodes, changes in quality of life (QoL), and major and minor adverse drug reactions. QoL will be examined by the 36-Item Short Form Survey questionnaire at enrollment and 12 months after randomization. CONCLUSION: The COMFORTS trial is the first study that aims to make a head-to-head comparison between midodrine and fludrocortisone, against a background of lifestyle modifications for preventing recurrences of VVS and improving QoL in patients with VVS.

Indications and Effectiveness of ICD for Primary and Secondary Prevention in Patients Admitted in Ahvaz Imam Khomeini Hospital since 2017.

Background: Implantable cardioverter-defibrillators (ICDs) have been established for primary and secondary prevention of fatal arrhythmias and effectively reduce the rate of sudden cardiac death (SCD). This study aims to evaluate the indications and effectiveness of ICD for primary and secondary prevention of SCD. Materials and Methods: This retrospective study was conducted on 229 patients (136 for primary and 93 for secondary prevention) with ICD implantations in Imam Khomeini Hospital, Ahvaz, between 2017 and 2020. The incidence of arrhythmic events after implantation of ICDs was saved in electrograms, and the performed treatments (antitachycardia pacing (ATP)/shock) were recorded from the device memory. Results: The indications for ICD implantation in primary and secondary prevention were different (P < 0.0001). The most common cause of ICD implantation for primary prevention was ischemic cardiomyopathy (ICMP, 90.4%) and for secondary prevention was ICMP (58.1%) followed by dilated cardiomyopathy (31.2%). During ICD implantation, 54 patients (39.7%) with ICD implantation for primary prevention and 50 patients (53.8%) for secondary prevention had arrhythmia (P = 0.043). The rate of appropriate therapies in patients with secondary prevention was higher than the primary prevention (57.9% vs. 42.1%), while the rate of inappropriate treatments in patients with primary prevention indication was more than the secondary prevention (63% vs. 37%) (P = 0.060). Conclusions: ICMP was the main cause of ICD implantation for the prevention of SCD in both groups. At follow-up, the high prevalence of appropriate ICD therapy was observed in both groups, and this risk was slightly higher in the secondary prevention group.