Pacemaker Effect With Closed Loop Sensor in Neuromodulated Syncope Refractory to Medical Therapy
Pacemaker Effect With Closed Loop Sensor in Neuromodulated Syncope Refractory to Medical Therapy
Vasovagal syncope is an entity frequently in the emergency services, its treatment includes
 pharmacological and non-pharmacological measures, and in some severe cases, requires the
 implantation of cardiac stimulation devices, specifically, those pacemakers that have
 closed-loop sensors (CLS).

 This research is an intervention study, multi-institutional, randomized and double blind that
 will be carried out in patients older than 18 years, with a diagnosis of neurally mediated
 type 1, 2A or 2B syncope documented in a tilting table test, who have had at least 2 syncope
 in the last year and that significantly affects the quality of life despite the use of
 pharmacological and non-pharmacological non-interventionist therapy.

 This study aims to evaluate the effect of cardiac pacing therapy with CLS pacemakers on
 quality of life, recurrence of syncope and pre-syncopal symptoms in patients with a diagnosis
 of neurally mediated syncope in this group of patients.
Syncope is defined as a loss of consciousness with inability to maintain the postural tone,
 with subsequent spontaneous recovery and without neurological sequelae. This occurs due to
 cerebral hypoperfusion by two mechanisms: 1) decreased cardiac output, usually due to
 bradycardia, and 2) hypotension due to decreased peripheral vascular resistance. An incidence
 of 6.2 per 1000 persons / year has been calculated, constitutes 2% of the reasons for
 consultation by emergency department and is found in 40% of the hospitalized participants.
 Its prevalence increases with age and is clearly influenced by the presence or absence of
 heart disease. The most frequent etiology is vasovagal, which has a benign course, with a
 mortality that does not exceed the expected for the general population. However, up to 21.6%
 have recurrences, which affects the quality of life and can generate physical injuries,
 especially in the geriatric population. The pathophysiology is not completely clear, it is
 thought that orthostasis has an important mechanism by decreasing the venous return,
 therefore, this leads to a vigorous contraction of the myocardium in the presence of a little
 filled heart chamber, it can stimulate the mechanoreceptors and thus precipitate the Bezold
 Jarisch reflex, which results in paradoxical hypotension and bradycardia.

 The management can be variable, and will depend on the patient's response, from conservative
 strategies such as changes in lifestyle, avoiding triggers, abortive maneuvers in the case of
 prodromes, and some drugs (fludrocortisone) to cardiac stimulation devices such as
 pacemakers. Cardiac stimulation has been studied in participants with cardioinhibitory
 response in the Tilt test with divergent results, especially with the use of conventional
 pacemakers that monitor the fall in heart rate. Interestingly, an other type of pacemakers,
 those with closed handle sensor (CLS), that measures the impedance through each beat, which
 is related to myocardial contractility, in this way it could detect changes in the
 contractility that precede the cardioinhibitory response, and thus guarantee a good cardiac
 output and avoid syncope.

 The use of cardiac stimulation therapy has been proposed as an effective strategy in
 participants with recurrent syncope and refractory to pharmacological and non-pharmacological
 measures, a special group are those with a cardioinhibitory response with asystole greater
 than 6 seconds, however, this benefit it could be extrapolated to those of mixed commitment.
 In the world, there is no definitive consensus on the level of recommendation for the
 implantation of pacemakers with CLS in this disease, however, based on the pathophysiology,
 studies of the disease and technical elements on the functioning of these devices, they have
 come implanting in Colombia and in the world with apparent good results in the quality of
 life of the participants, syncope-free event rate, longer time to the first syncope and
 improvement in hemodynamic parameters in the Tilt Test. In Colombia, more research is needed
 to confirm or reject this assertion.

 General objective: Evaluate the effect of cardiac pacing therapy with CLS pacemakers on
 quality of life, recurrence of syncope and pre-syncopal symptoms of participants with a
 diagnosis of neurally mediated syncope (with mixed response or inhibitory cardio) refractory
 to pharmacological and non-pharmacological management, in six health care centers in the city
 of Medellín.

 Specific objectives

 -  Sociodemographically and clinically characterize the study population.

 -  Evaluate the impact on quality of life, pre and post implant.

 -  Measure the occurrence of episodes of syncope, pre and post implant.

 -  Assess the reduction of pre-syncopal symptoms.

 -  Evaluate if the mode and programming functions influence the appearance of syncopes and
 recurrences.

 -  Determine the average time that elapses from the implantation of the CLS pacemaker until
 the first episode of syncope.

 Interventions of participants

 -  A: participants who will be activated the CLS function one month after implantation of
 the pacemaker. They will be reevaluated after 4 months and will be changed to DDD-R mode
 for another 4 months, when the results will be analyzed to define the final form of
 reprogramming.

 -  B: patient to whom, one month after the implantation of the pacemaker, the R function
 will be activated. They will be reevaluated after 4 months and will be switched to
 DDD-CLS mode for another 4 months, when they will be evaluated again and the results
 will be analyzed for define final form of reprogramming.

 Participants will be contacted through the electrophysiology service of "CES Cardiology" in
 Medellín, Colombia.

 The calculation of the sample size was carried out probabilistically with the following
 parameters and based on the previous studies: Power 80%, confidence: 95%, expected proportion
 of group 1: 72%, expected proportion group2: 99% What gave the following results:
 intervention A: 26 participants, intervention B: 26 participants. Total sample: 52
 participants.

 Selection of participants All participants will be recruited and who meet all the inclusion
 criteria and none of the exclusion criteria will be selected by one of the members of the
 research team previously trained on the Plan of Clinical Research and that has been
 designated to perform this type of tasks.

 Estimated time to include participants The inclusion of all participants requires
 approximately 6 months. The anticipated duration of this study is 27 months. This will depend
 on the inclusion rate.

 Informed consent process: It will be prepared by the principal investigator, with the
 information indicated in article 15 of resolution 8430.

 -  It will be reviewed by the Human Research Ethics Committee of the CES University and can
 only be signed by the patient, researchers and witnesses when it is approved.

 -  Indicate the names and contact forms of the principal investigators and who should be
 contacted in case of any difficulty or adverse event.

 -  It must be signed by two witnesses and by the research subject or his legal
 representative. If the research subject does not know how to sign, he will print his
 fingerprint and in his name he will sign another person that he designates.

 -  It will be prepared in duplicate, leaving a copy in the possession of the research
 subject or his legal representative.

 Blinding of the study: The programming modes of the intracardiac devices can only be known
 through the use of specific reprogramming equipment provided by each generating company of
 the device. In the case of pacemakers with CLS, their only manufacturer is Biotronik, so they
 provide a device that connects with the device that the patient has implanted. Unless the
 reprogramming card is delivered, neither the patient nor another person will be able to
 establish the programming mode.

 In this way the people who will be in contact with the programming of the device will be:

 Electrophysiologist in charge of implanting the device: it could be any of the members of the
 CES Cardiology group with this training, it will implant the device and leave it in DDD-CLS
 mode to start the first month or washing time. This electrophysiologist will not make any
 scheduled visits or reprogram the device in any of his visits.

 Electrophysiologist commissioned the visit by electrophysiology within each of the visits
 scheduled and listed above: professional in charge of programming the devices as established
 by the paper envelopes generated in the random assignment. It will be the only person who
 will know the way of programming during the 8 months of intervention and will not disclose
 this information to the patient or their relatives.

 Main co-investigators: they will not know the way of programming the device nor will they
 attend the part of the visit that performs electrophysiology. In another office and before or
 after the program, they will evaluate the patient clinically and ask the questions included
 in the scales of quality of life used.

 The person who will analyze the information: will know the process. The patient: He will not
 know the programming mode of his device, that is, he will not know if he is in DDD - CLS or
 DDD - R. This study will be double blind.

 Random assignment Through computer-based randomization programs, 26 participants will be
 assigned to the group of participants who, in the month of implantation, will be programmed
 in DDD-CLS mode and 26 participants who will be programmed in DDD-R mode one month after
 implantation. The randomization will be known by the investigating epidemiologist who will
 activate the randomization program and the electrophysiologist who will program the patient.
 Initial randomized programming modes will be delivered in sealed envelopes to the
 electrophysiologist who will program the patient.

 Procedures The clinical trial will be conducted in accordance with the Clinical Research
 Plan. All those who participate in the conduct of the clinical study will be qualified by
 training, training or experience to carry out their tasks and this training should be
 documented in an appropriate manner. The clinical study will not begin until it receives
 written approval from the Ethics Committee and the relevant regulatory authorities and all
 necessary documentation has been collected. Procedures during the time of intervention. Once
 the patient enters the health center with criteria to participate in the study, as long as it
 does not meet any of the exclusion criteria and has signed the informed consent (the
 participant or a legal representative in case this is not in conditions to sign).

 Starting point: Prior to implanting the device. Between the day of implantation and the first
 month (at which time the initial visit will take place) will be the washing or "wash out"
 process in which the device will be left in DDD-CLS mode until the start visit.

 Start visit: One month after implanting the device. It includes two parts: Evaluation by
 electrophysiology and Clinical evaluation.

 Visit # 1: It will happen 4 months after the start visit. It includes two parts: Evaluation
 by electrophysiology and Clinical evaluation.

 Visit # 2: Finally, a final check (visit # 2) will be made 8 months after the start visit and
 4 months after the visit # 1. It includes two parts: Evaluation by electrophysiology and
 Clinical evaluation.

 Procedures during the time following the end of the intervention: At the end of the 8 months
 in which the information on the mode of reprogramming was recorded and these modes were
 reversed, the follow-up will continue for 12 more months counted from visit # 2 as follows:

 -  Visit # 3: It will take place 6 months after the visit # 2 and 14 months after the
 initial visit. The patient will be evaluated clinically (without pacemaker programming)
 by one of the researchers who will apply the SFSQ and SF-36 quality of life scales.

 -  Visit # 4: It will take place 12 months after the visit # 2 and 20 months after the
 initial visit. The patient will be evaluated clinically (without pacemaker programming)
 by one of the researchers who will apply the SFSQ and SF-36 quality of life scales.

 After this the study ends.

 Procedures in case of Adverse Events: In the event of any adverse event related or not to the
 implant or use of the device or any condition of the patient, the patient must notify the
 group of researchers in the contact telephone numbers that are delivered and according to the
 severity and needs of the event will be cited in an additional visit for clinical evaluation
 and / or electrophysiology or will be redirected to the CES Clinic if the event or situation
 requires management in the emergency department or intrahospital service. Each of these
 adverse events must be reported on a form and a communication sent within 72 hours after the
 group of researchers had knowledge of the Human Research Ethics Committee of the CES
 University, making the event known to all. the details.
Inclusion Criteria:

 -  Over 18 years.

 -  Diagnosis of neurally mediated syncope with a tilting table test (Tilt test) that
 demonstrates a mixed (type 1) or cardioinhibitory response (Type 2A and 2B).

 -  Negative impact on work and social life.

 -  Non-respondent to pharmacological therapy (Fludrocortisone 0.1mg / 24 hours for 3
 months) and non-pharmacological (exercise, hydration and consumption of more than 3
 months) is due to a cardiologist who has performed a strict stricture over time.

 -  At least 2 episodes of syncope in the last year.

 Exclusion Criteria:

 -  Complete atrioventricular block.

 -  Second degree ventricular atrial block.

 -  Bradycardia syndrome - tachycardia.

 -  Disease of the sinus node.

 -  Arrhythmia (bradycardia or tachycardia that generate syncope and / or low cardiac
 output).

 -  Syncope due to hypersensitivity of the carotid sinus.

 -  Syncope with Tilt Test that demonstrates depressant vasopressor response (type 3).

 -  Refusal of the patient, his relatives or the attending physician to participate in the
 study.