ACHAIKI IATRIKI | 2021; 40(4): 198–204
Original research article
Ioannis Vogiatzis, Evangelos Sdogkos, Eustathios Koulouris, Sarantis Pittas, Konstantinos Koutsampasopoulos
Department of Cardiology, General Hospital of Veroia, Veroia, Greece
Received: 31 May 2021; Accepted: 08 Sep 2021
Corresponding author: Dr. Ioannis Vogiatzis, General Hospital of Veroia, Department of Cardiology, Veroia 59100, Greece, Tel. +30 2331351253, +30 6944276230, E-mail: firstname.lastname@example.org
Key words: Neurocardiogenic syncope, non-pharmacological treatment, quality of life
Background: Neurocardiogenic syncope is a common cause of syncope and is found in 50% of patients hospitalized because of syncope. Neurocardiogenic syncope is not a life-threatening situation; however, it may lead to injuries and an impaired quality of life. Initial treatment of neurocardiogenic syncope consists of adequate fluid and salt intake, regular exercise and implementation of special exercises. The aim of the study is the evaluation of the effects of therapy in patients with a history of syncope episodes.
Methods: Sixty-eight patients (33 men and 35 women, mean age 45.8+15.6 years) with a history of syncope episodes and positive tilt test, with a diagnosis of neurocardiogenic syncope, entered the study. All participants followed a non-pharmacological therapeutic intervention which included counseling to change lifestyle along with daily special exercises. The effectiveness of this non-pharmacological treatment in the reduction of syncope episodes and improvement of quality of life, using a general questionnaire (EQ-5D) was evaluated.
Results: Our sample had fewer syncope episodes on average, at 3, 6 and 12 months of non-pharmacological treatment compared to the last year before treatment (0.3+0.48 versus 3.9+0.9 / p=0.003). Quality of life was improved over time with greater improvement in patients who had fewer recurrences.
Conclusion: In patients with a history of neurocardiogenic syncope, non-pharmacological therapy has the benefit of reducing new episodes and ameliorating quality of life.
Syncope is a sudden and transient loss of consciousness and postural tonus followed by a quick and spontaneous recovery. It is caused by an acute decrease in systemic arterial blood pressure and cerebral blood flow . Reflex syncope is caused by systemic arterial hypotension resulting from reflex vasodilation, bradycardia, or both . Neurocardiogenic syncope, mediated by emotional or orthostatic stress, is the most common cause of reflex syncope [2-3]. Neurocardiogenic syncope (NS), also known as vasovagal or neurally-mediated syncope, is a common cause of syncope and is found in 50% of patients hospitalized because of syncope. Neurocardiogenic syncope is not life-threatening and its only consequences are injuries and reduced quality of life. Recently, it was found that quality of life (QOL) in patients who suffered from NS was poor compared with healthy people . It is typically triggered by environmental, physical or mental stress, with an estimated lifetime prevalence of 35% . It is diagnosed by obtaining a detailed history and performing a head-up tilt test, with or without drug provocation. Widely accepted measures, not confirmed to be effective, include explanations of the underlying mechanism, patient education, reassurance emphasizing the generally benign nature of the disorder, recognition of premonitory manifestations and avoidance of triggers. Several studies have been performed about its management. Initial treatment of neurocardiogenic syncope consists of adequate fluid and salt intake, regular exercise and implementation of special exercises (physical counterpressure maneuvers i.e. muscle tensing) which are recommended as the first line of treatment for neurocardiogenic syncope in current syncope management guidelines [6-8].
The aim of the present study is the evaluation of the effects of treatment in patients with a history of syncope episodes and positive tilt test.
Sixty-eight patients (33 men and 35 women, mean age 45.8+15.6 years), with a history of recurrent syncope episodes (>2 episodes and positive head-up tilt-table test – HUT-test) were studied prospectively, in whom the diagnosis was neurocardiogenic syncope (based on the definition of the syncope management guidelines of the European Society of Cardiology). Patients were referred to the Syncope Unit in the Department of Cardiology. Patients with orthostatic hypotension, suspected or confirmed heart disease with a high likelihood of cardiac syncope, steal syndrome, episodes of loss of consciousness due to other reasons than neurocardiogenic syncope, were excluded. In the same manner, patients receiving medications that could interfere with treatment response or patients with orthopedic and functional limitations that could prevent them from performing exercises, were excluded.
Diagnosis was based on the head-up tilt (HUT) test. Tilt test has become a widely accepted method in the clinical evaluation of patients with syncope. Its duration is 30 to 45 min at 60 to 80 degrees and is widely accepted in laboratories for evaluating adult patients. Diagnostic specificity is 80 to 100%, however sensitivity, in contrast, does not exceed 40 to 70%. Isoproterenol or nitrates are the most common agents applied for pharmacologic provocation .
After diagnosis, patients followed a program of non-pharmacological therapy, with counseling to change lifestyle alongside daily special exercises . Initially, all patients were informed about the benign nature of their condition and the potential risks, such as accidents, downfalls, etc. and were advised with general guidelines on the way they could avoid everything it could trigger syncope (eg emotional stress). They were asked to avoid certain conditions, such as alcohol, caffeine or nicotine consumption and to drink at least 2.0 L of water per day .
Moreover, they were instructed to a daily training program consisting of isometric contraction maneuvers (Figure 1, Figure 2) and standing in a special position for 10 minutes (Figure 3) [10,12]. The whole training program lasted for about 20 minutes daily. The combined effect of information, lifestyle changes and the training program was estimated.
Figure 1. Isometric Exercises of the arms. A: Grip trial, B: Tension of the arms.
Figure 2. (A, B): Isometric Exercises of the legs.
Figure 3. Standing trial. The back of the patient lays on the wall and the legs lie 15-30 cm from the wall.
Patients were asked to note the date and the symptoms of probable recurrences. At 1, 3, 6, and 12 months after inclusion, patients informed the medical personnel about syncopal recurrence, the frequency of physical exercises and also their effectiveness. Patients were contacted by telephone or were seen at the outpatient department of the Syncope Unit.
Quality of Life (QoL)
At the same time, QoL was estimated using a general questionnaire (EQ-5D), before intervention initiation and at 1 month, 3 months, 6 and 12 months of follow-up.
The questionnaire consists of two parts, the descriptive system which includes 5 dimensions (mobility, self-care, usual activities, pain – discomfort, anxiety – depression each of which is rated in a 3-point scale) and the EQ visual analogue scale (EQ-VAS) to estimate the patients’ current health status from zero to one hundred. EQ-5D has been extensively used in a large number of clinical studies of cardiovascular disease patients and is one of the most reliable instruments for measuring quality of life, both in the general population and in particular subgroups suffering from specific diseases . The structure and the features of the EQ-5D in recording quality of life have been extensively described .
Each patient completed the questionnaire at his/hers first visit, before application of the program and then at one, three, six and twelve months, during the follow-up period. Patients completed the questionnaires on their own, in a separate room, or with the assistance of laboratory staff on the days they had to come to their appointment during the follow-up period. The values calculated using the EQ-5D range between -0.594, which indicates serious problems in mobility, self-care, usual activities, pain – discomfort, stress – depression, and 1 which indicates the absence of any problems. On the contrary, death which in our case was not observed has a value of 0 .
In case of lost values or questionnaires, the last observation was used. About 12% of the questionnaires had missed responses, but due to their small number it was not considered to affect the overall evaluation model.
Moreover, patients during their visits were completed a set of questions referring to:
1) Their general health status
2) Frequency and impact of symptoms due to recurrences of arrhythmia (0 = never, 1 = rarely, 2 = sometimes, 3 = often, 4 = always).
3) Severity of symptoms due to recurrences of arrhythmia (1 = mild, 2 = moderate, 3 = severe).
4) Number of visits to Health Units and Health Services consumption (Hospitals, Health Centers, outpatients services).
This information was used as a specific tool to measure quality of life, in accordance with a recent study evaluating the impact of atrial fibrillation recurrences on quality of life .
The study’s protocol was approved by the Ethical Committee of the Hospital of Veroia (13/2010) and all patients provided written informed consent.
Analysis was performed using the statistical package SPSS 19.00 (SPSS Inc., Chicago, Ill, USA). Initially, an estimation of the normality of the distribution of quantitative variables using the Kolmogorov-Smirnoff test (population >50 individuals) was performed. For comparison of continuous variables, the t-test and the non-parametric Mann-Whitney test were used, while the x2 test and the Fischer test were used to assess differences in the distribution of categorical variables. The visualization of the time of syncope recurrences was achieved with the Kaplan-Meier curve. The variables that were significantly associated with syncope recurrences were introduced in a multivariable regression model (Cox regression model) to calculate the relative risk and 95% confidence interval (95% CI). The probability p < 0.05 (2- way) was considered statistically significant.
The sample’s baseline characteristics are shown in Table 1. The mean age of the population was 46 years and 48.5% were males. The mean follow-up time was 12 months.
Patients had fewer syncope episodes on average, at 1, 3, 6 and 12 months of non-pharmacological treatment compared to the last year before treatment (0.3+0.48 versus 3.9+0.9 / p=0.003). In the same way, trauma and fractures due to syncopal episodes were decreased significantly. Thirty patients (44.12%) had experienced a syncopal episode during the follow-up period. The mean time until a new syncopal episode after the counseling period was 46.5 days. Using Cox regression analysis, it was found that the number of syncopal episodes before the counseling period were independent factors for syncopal recurrence (>3 episodes per year, HR=1.34 – CI=1.15-2.56, p=0.03).
Forty-two patients (80.77%) reported that they followed the instructions and all of them found them beneficial.
Quality of life was improved during the follow-up period compared with the baseline (Figure 4), with a greater improvement in patients who had fewer recurrences. These patients reported an improvement in severity and frequency of symptoms in questionnaires (Figure 5).
Figure 4. Quality of life index before intervention and during the follow-up period as it was estimated with EQ-5D questionnaire.
Figure 5. Alterations of frequency and severity of symptoms during the follow-up period according to the questionnaires.
Neurocardiogenic syncope (NCS) is a temporal functional abnormality of the Autonomic Nervous System (ANS) which affects mainly younger persons, especially women, presenting without signs of structural heart disease or other neurological abnormality. Patients complaining about frequent episodes, present with limitations of daily activities and especially their jobs, significantly affecting their quality of life .
Various medications have been proposed as a definite therapy including b-blockers, fludrocortisone, serotonin reuptake inhibitors. The results are poor and disappointing on many occasions [18-20].
In addition, a variety of non-pharmacological measures have been proposed, as patient education and lifestyle modifications, including the avoidance of triggering factors such as hot environment, humid atmosphere and prolonged standing, an increase of water consumption during the day, normal food intake and the use of exercises that prevent syncopal episodes. An informative and instructive discussion with the patient about the benign nature and prognosis represents the first step in the management of neurocardiogenic syncope [21,22]
A multicenter, randomized clinical trial, showed that vasovagal syncopal patients who received conventional therapy plus training in exercise protocols had a lower syncope burden than the control group . This means that the exercise protocol is a safe, effective, and low-cost intervention, which should be used as first-line treatment for patients with neurocardiogenic syncope.
The efficacy of non-pharmacological measures in managing NCS was obvious in the current study. The frequency and severity of symptoms were decreased and as a result, patients’ quality of life was improved.
In various studies [24,25] the favorable effect of programs encompassing physical counterpressure maneuvers was clear and marked in comparison with patients that received only lifestyle advice or pharmaceutical therapy. Studies [4,26] have shown that the results of these therapies are disappointing.
After a positive tilt test, the patients were given instructions to perform lifestyle modifications and an exercise program. A session protocol [maximum duration of 30min- hour] includes a presentation of the program’s purpose and session structure, an analysis of simple physiology and vasovagal reflexes and a demonstration and explanation of the maneuvers. In various studies, physical exercise and all these measures have shown a decreased or elimination of syncopal recurrences [24,25]. These exercises and protocols besides their favorable effect on the impact of the autonomic nervous system on the cardiovascular system in patients suffering from NCS, may also expand the circulatory blood volume and increase the muscle tone in the lower limbs. As a result, the systolic and diastolic volumes are increased and the excitation of ventricular C fibers, responsible for triggering NCS is obvious . In our study general instructions for the avoidance of triggering factors, an increase of water, other liquids and salt intake and the performance of physical counterpressure maneuvers were advised. It is concluded that these measures could be used as first-line treatment for patients with neurocardiogenic syncope. In the above study 40 patients (58.82%) did not present any symptoms during the 12-month follow-up period in contrast to other studies where patients relapsed during the follow-up period. This could be explained by the fact that the patients included were severely affected, with several syncopal episodes before their participation to the study. It is known that the burden of syncopal episodes is a predictor of relapses .
On the other hand, it is widely known that physical and psychosomatic functions are altered in patients with NCS. Sheldon et al.  reported a proportional decrease of syncopal episodes due to better management, better knowledge regarding the pathophysiology of syncope, greater reassurance and advice around the management of episodes and vigorous application of the exercises.
As a result, patients were assured that symptoms are decreased or disappeared and this leads to quality-of-life improvement as it is recorded in self-report questionnaires, at least six months after the beginning of the program. In previous studies, [29,30] Qol was assessed only after treatment initiation in groups of patients with different health issues and different diagnoses and treatment. In our study, Qol was assessed in different time intervals during the follow-up period.
General Qol, as it was estimated with the generic questionnaire EQ-5D, was significantly improved during the follow-up period. Moreover, the severity and frequency of symptoms were improved gradually. All Qol parameters are expected to improve if patients are reassured that they will have no syncopal episode or if they can manage them successfully.
Limitations of the study. In the study, none of the patients received any pharmacological treatment. Syncopal episodes before and after the application of the program were compared and this requires a certain caution from the patients in recording the episodes. Many of them, suffering from NCS, come to the hospital after symptom deterioration. As a result, any improvement in symptomatology would resemble a success. The collected data were subjective, as the self-reported measures of QoL, which could be subject to bias and misinterpretation.
In patients with a history of neurocardiogenic syncope, non-pharmacological therapy has the benefit of reducing new episodes and enhancing quality of life. This kind of therapy should be recommended to all patients with NCS, however, some of them need additional therapy.
The authors would like to thank Dr. Athina Kotsani, Director of ERL Department of Hospital of Veroia, for her valuable contribution to Figures 1,2,3 designing.
Conflict of interest disclosure
None to declare
Declaration of funding sources
None to declare
Author contributions: IV, conception and design, analysis and interpretation of the data, drafting of the article, critical revision of the article for important intellectual content, final approval of the article; ES, conception and design, analysis and interpretation of the data, drafting of the article; EK and SP, conception and design, analysis and interpretation of the data, drafting of the article; KK, conception and design, analysis and interpretation of the data, drafting of the article, critical revision of the article for important intellectual content.
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