Syncope, Vasovagal
Conditions
Keywords
Vasovagal syncope, Cardioneuroablation, Midodrine
Brief summary
This is a prospective, international multi-center, open-labeled, randomized trial. The investigator speculated that CNA prevents more patients with moderate to severe VVS from syncope recurrence compared to midodrine.
Detailed description
Nearly 40% of people faint at least once in their life, and vasovagal syncope (VVS) is the most common cause. Study shows that VVS accounts for 66% of syncope in the Emergency Room. The early peak incidence is around 15 years for young women and a later significant rise in visits for both sexes over the age of 65 years. Patients with frequent syncope have a markedly reduced quality of life, similar to that of patients with severe rheumatoid arthritis or chronic low back pain. Vasovagal syncope is characterized by paroxysmal hypotension and/or bradycardia. Multiple hypotheses have been suggested as the mechanism of VVS, hence the treatment was diverse. The current therapy suggested by guidelines includes diet, counter-pressure maneuvers, beta-blockers, fludrocortisone, serotonin reuptake inhibitors, midodrine, and permanent pacemakers. Cardioneuroablation (CNA) which modified the cardiac autonomic nervous system through catheter ablation shows encouraging results in preventing syncope recurrence. Experience from our center also suggested that CNA was highly effective, with a syncope-free rate of nearly 80% for 4-year follow-up; however, the studies were non-randomized with no control group. A recent single-center randomized control study has reported that CNA was superior to non-pharmacology therapy for syncope prevention. The investigators are hereby willing to compare the effectiveness of CNA to drug therapy in a multi-center randomized control fashion. The objective of this trial is to determine the role of CNA and midodrine therapy in the prevention of syncope recurrence in patients with vasovagal syncope and provide evidence for clinical treatment strategies. Participants will be randomized to either CNA plus patient education (diet, avoidance trigger, physical counter-pressure maneuvers) or midodrine therapy plus patient education. Randomization will be carried out with interactive web response system stratified by center. The participants were followed up at 7 days, 3 months, 6 months, 12 months and 24 months respectively after ablation procedure, to observe whether there were recurrent syncope and /or pre-syncope (including the time and frequency of recurrent syncope, inducing factors, and whether complicated with fall injury, etc.), and to reassessed tilt test, 24-hour ambulatory electrocardiogram and fill in Euroqol (EQ-5D) and ISQL quality of life score form. To evaluate the safety and efficacy of cardiac nerve ablation in the prevention of refractory vasovagal syncope. The tilt test, the changes of vagus nerve function and the improvement of quality of life before and after were analyzed and compared.
Interventions
PROCEDURECardioneuroablation
The left atrium model was established under the guidance of three-dimensional mapping. Atrial septum puncture、left atrium mapping and right atrium mapping will be performed according to standard EP lab protocol. The location of GPs will be detected with HAFE potential (duration ≥ 50ms， deflections ≥ 4 times， amplitude ≥ 0.7mV) and high frequency stimulation (HFS; 30 Hz, 20 mV, pulse width 2ms) through positive vasovagal response (transient ventricular asystole, atrioventricular block, or R-R interval increased by 30%) . Saline Irrigated-tip catheter with pressure monitoring will be applied for the procedure, and radiofrequency energy is limited to 40W and 43℃ for at least 30s at each site. The ablation endpoint for each GP is defined as the complete elimination of all targeted HAFE potential and elimination of positive vasovagal response. The endpoint of the procedure was that the heart rate reach 75% of the maximum heart rate in atropine test.
Midodrine will start dosing with 5 mg of the study drug 3 times daily, 4 hours apart, during daylight hours.Dose with be adjusted within a range of 2.5 mg twice daily, 4 hours apart, up to 10 mg, 3 times daily, every 4 hours. The optimal dose ranging be completed within the first 2 weeks. If intolerable symptoms persisted despite dose reductions, the drug will be withdrawn, and the patient was released from the study.
Sponsors
Beijing Chao Yang Hospital
RenJi Hospital
Yeditepe University Hospital
First Affiliated Hospital Xi'an Jiaotong University
First Affiliated Hospital, Sun Yat-Sen University
Ningbo No. 1 Hospital
Fuwai Yunnan Cardiovascular Hospital
Henan Provincial People's Hospital
China National Center for Cardiovascular Diseases
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥ 18 years of age 2. Calgary Syncope Symptom Score ≥ -2 points 3. Positive response to head-up tilt test 4. With syncope episodes more than 3 times in the preceding year 5. A proven failure of non-pharmacologic treatment, including reassurance regarding the benign prognosis, education about the avoidance of situations and triggers initiating syncope， application of PCM during the occurrence of prodromal symptoms, and lifestyle modifications（adequate fluid intake and salt supplementation）， according to the guideline 6. Willingness to comply with follow-up requirements and to sign the informed consent
Exclusion criteria
1. Complied with other causes of syncope, including postural hypotension, aortic stenosis, sick sinus node syndrome, high-grade atrioventricular block, ventricular arrhythmias, pulmonary hypertension, hypertrophic cardiomyopathy, transient ischemic attack, epilepsy, sequelae of cerebral infarction or cerebral hemorrhage, subclavian vein steal syndrome and drug-induced syncope. 2. Complied with congenital heart disease, valvular heart disease, cardiomyopathy, and diabetes. 3. History of cardiac catheter ablation, peacemaker implantation and cardiac surgery. 4. History of midodrine usage, or compiled with contradiction of midodrine, including urine retention, hypertension (Bp≥140/90mmHg), glaucoma， renal dysfunction. 5. Life expectancy \<1 year for any medical condition 6. Pregnancy or breast-feeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with syncope recurrence during follow-up | 12 month after randomization | Syncope was defined as a transient loss of consciousness and complete recovery in a very short time. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with pre-syncope during follow-up | 12 month after randomization | Pre-syncope was defined as the prodrome before syncope, such as dizziness, sweating，dyspnea, and paleness, and patients did not actually fall down. We documented each time that syncope occurred. The severeity of the prodrome will be assessed with a standardized questionnaire CPF. |
| Quality of life measure by Impact of Syncope on Quality of Life（ISQL）questionnaire | 6 month after randomization | The difference in quality of life between the two groups as compared to baseline by using the standardized ISQL (Impact of Syncope on Quality of Life) questionnaire. The ISQL score was ranged from 0 to 57 points, and higher points represented more severe impaired quality of life. |
| Results of Head-up tilt test | 12 month after randomization | The difference in the rate of head-up tilt test induced syncope between the two groups. The positive results of head-upright tilt test were defined by VASIS standard. The examination will be performed at each investigative center. |
| Blood pressure measured with 24 hours monitoring | 6 month after randomization | The difference in blood pressure between the two groups as compared to baseline. Both systolic and diastolic blood pressure were assessed. The device provided to patients prior to discharge or at outpatient visits will be used for this assessment. |
Countries
China
Contacts
Primary Contactyan Yao, PhD
Backup Contactlihui Zheng, PhD
Outcome results
None listed