Международный неврологический журнал Том 19, №1, 2023
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Вплив імплантації електрокардіостимулятора на неврологічну симптоматику та когнітивні функції пацієнтів iз брадіаритміями
Авторы: S.M. Stadnik
Military Medical Clinical Center of the Western Region, Lviv, Ukraine
Рубрики: Неврология
Разделы: Клинические исследования
Версия для печати
Резюме
Метою нашої роботи було дослідити неврологічну симптоматику й когнітивний статус пацієнтів із брадіаритміями після імплантації електрокардіостимуляторa (ЕКС) у ранньому періоді та протягом лонгітудинального дослідження. Матеріали та методи. Сорок шість пацієнтів із різними формами брадіаритмій розподілені на 2 групи залежно від терапії: 1-ша група — 29 осіб, яким проведена первинна імплантація ЕКС; 2-га група — 17 пацієнтів, яким для корекції брадіаритмій застосовували медикаментозну терапію. Огляд пацієнтів проводили на початку лікування, через 10 днів, 6 і 12 місяців. Оцінка ефективності лікування грунтувалася на динаміці неврологічної симптоматики, когнітивних функцій, показників центральної та церебральної гемодинаміки, маркерів системного запалення. Результати. У хворих 1-ї групи спостерігалося більш виражене регресування неврологічної симптоматики порівняно з пацієнтами 2-ї групи. На фоні імплантації ЕКС відмічено значне покращення всіх когнітивних функцій: пам’яті, уваги, швидкості мовлення, зорово-просторового та симультанного гнозису, мовленнєвої активності, а також емоційного статусу. Поліпшення показників центральної та церебральної гемодинаміки після імплантації ЕКС полягали насамперед у позитивному міокардіальному ремоделюванні, збільшенні швидкісних показників кровотоку по екстра- й інтракраніальних відділах сонних артерій. Позитивна клінічна динаміка поєднувалася із вірогідним зниженням умісту прозапальних цитокінів, що свідчило про зменшення активності імунного запалення. Висновки. Імплантація ЕКС покращує неврологічний статус і сприяє зменшенню вираженості когнітивних та афективних розладів у хворих із брадіаритміями за рахунок покращення систолодіастолічних характеристик лівого шлуночка, скоротливої функції міокарда лівого шлуночка, центральної гемодинаміки, функціонального стану мозкового кровотоку, зниження активності імунного запалення.
Background. The purpose of our work was to investigate the neurological symptoms and cognitive status of patients with bradyarrhythmias after pacemaker implantation in the early period and during a longitudinal study. Materials and methods. Forty-six patients with various forms of bradyarrhythmias are divided into 2 groups depending on the therapy: group 1 — 29 people who underwent primary pacemaker implantation; group 2 — 17 individuals who were treated with drug therapy to correct bradyarrhythmias. Patients were examined at baseline, after 10 days, 6 and 12 months. The assessment of treatment effectiveness was based on the dynamics of neurological symptoms, cognitive functions, indicators of central and cerebral hemodynamics, markers of systemic inflammation. Results. The patients of the group 1 had a more pronounced regression of neurological symptoms compared to those in the group 2. Against the background of pacemaker implantation, a significant improvement of all cognitive functions was noted: memory, attention, speaking rate, visual-spatial and simultaneous gnosis, speech activity, as well as emotional status. The improvement of central and cerebral hemodynamic parameters revealed after pacemaker implantation consisted, first of all, in positive myocardial remodeling, an increase in blood flow velocity in the extra- and intracranial sections of the carotid arteries. Positive clinical dynamics was combined with a significant decrease in the content of proinflammatory cytokines, which indicated a decrease in the activity of immune inflammation. Conclusions. Pacemaker implantation improves neurological status, contributes to the reduction of the severity of cognitive and affective disorders in patients with bradyarrhythmias due to the improvement of the left ventricular systolic and diastolic characteristics, the contractile function of the myocardium of the left ventricle, central hemodynamics, the functional state of cerebral blood flow, and a decrease in the activity of immune inflammation.
Ключевые слова
когнітивні розлади; атріовентрикулярна блокада; синдром слабкості синусового вузла; фібриляція передсердь; електрокардіостимулятор
cognitive disorders; atrioventricular block; sick sinus syndrome; atrial fibrillation; pacemaker
Introduction
Disorders of higher brain functions are one of the most urgent medical and social problems, as they lead to a decrease in the quality of life, disorders of social and professional activity of a person, and with a long course — to the development of dementia and complete social maladaptation [1–4].
In the majority of works on the study of cognitive deficit (CD), the role arterial hypertension and cerebral atherosclerosis in its occurrence was investigated [5–8]; however, the impact of arrhythmias on the development of cognitive deficits has not been sufficiently studied.
Currently, both medical and surgical methods of treatment are used to treat cardiac arrhythmias. One of the most promising and effective of them is the implantation of permanent pacemakers [9]. There is isolated information about the effect of pacemaker implantation on cognitive functions (CF) [10, 11]. At the same time, there are no comparative data on the state of CF in patients with implanted pacemaker and medical correction of bradyarrhythmias.
Choosing the right treatment strategy for bradyarrhythmias can slow the progression of cognitive deficits, which will improve not only the clinical status of patients, but also their prognosis. The above positions determined the relevance of the chosen direction of research and its purpose.
The purpose of our work was to investigate the neurolo-gical symptoms and cognitive status of patients with bradyarrhythmias after pacemaker implantation in the early period and during of a longitudinal study.
Materials and methods
We examined 46 patients (mean age 66.1 ± 3.7 years) who were divided into 2 groups: group 1 — 29 patients who underwent primary implantation of pacemaker; group 2 — 17 patients who were treated with drug therapy to correct bradyarrhythmias (in acute forms — 0.1% solution of atropine sulfate intravenously 1–2 ml or 0.05% solution of alupent by intravenous drip 5.0 per 200.0 physiological solution; for chronic and protracted forms — zelenin: 30 drops 3 times a day).
It is obvious that the patients of the group 2 also needed the implantation of a permanent pacemaker, and drug the-rapy cannot be an alternative to their treatment. However, part of the patients in this group were at the stage of wai-ting for pacemaker implantation, another part categorically refused surgical intervention, fearing the negative impact of a foreign object in the body on the general well-being, part explained their refusal by the lack of funds for its installation.
Among the indications for pacemaker implantation, there were: third-degree atrioventricular block — 19 (65.5 %) patients, sick sinus syndrome (SSS) — 6 (20.7 %), bradysystolic variant of permanent atrial fibrillation — 4 (13.8 %) cases. Patients with atrioventricular block and SSS were implanted in the DDDR mode (dual-chamber rate-adaptive atrioventricular stimulation), patients with bradyarrhythmias — in the VVIR mode (isolated rate-adaptive ventricular stimulation).
Underlying conditions, which led to the development of arrhythmias, were ischemic heart disease and/or essential hypertension in 31 (67.4 %) patients, non-coronary myocardial diseases — in 12 (26.1 %), chronic rheumatic heart disease — in 3 (6.5 %) cases.
Patients of the group 1 during the study after pacemaker implantation did not have their own rhythm faster than the programmed pacemaker, and a fixed baseline pacemaker rhythm was continuously recorded. The frequency of stimulation in the examined patients was within physiological li-mits and corresponded to 60–70 beats per minute.
During the first 2 weeks from the start of treatment, patients of both groups were hospitalized and received standard therapy, which included hypotensive, hypolipidemic, and antithrombotic drugs. After discharge from the hospital, all patients were observed on an outpatient basis for 12 months. Patients were reexamined after 10 days, 6 and 12 months. During the specified period, a detailed clinical and paraclinical examination was carried out. The evaluation of treatment effectiveness was based on the dynamics of neurological symptoms, CF, indicators of central and cerebral hemodynamics, markers of systemic inflammation. During the year, all patients received outpatient treatment recommended upon discharge from the hospital.
In 10.3 % of patients of the group 1, complications in the early postoperative period were observed: increased body temperature, hematoma of the implantation site, vein thrombosis in the arm on the side of implantation. This coincided with literature data, according to which infectious complications in the early postoperative period accompany 0.02 to 12 % of implantations [12].
During 12 months of observation, 6 (13 %) patients dropped out of the study at different times. In 1 (3.4 %) patient of the group 1 and in 2 (11.8 %) patients of the group 2, the cause of withdrawal was acute cerebrovascular accident. Three (3.5 %) people died: in the group 1 — one (3.4 %) patient (cause of death was pulmonary embolism), in the group 2 — two (17.6 %) patients (due to acute myocardial infarction and acute cerebrovascular accident). Thus, after a year of observation, 40 patients remained in the study (Table 1).
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Inclusion criteria without research assistance:
1. The patient’s ability to make productive contact with the doctor to assess the cognitive status.
2. Voluntary informed consent of the patient or, if necessary, the consent of the person caring for the patient.
Criteria for excluding patients from the study:
1. Lack of voluntary informed consent of the patient.
2. Other possible causes of CD, in addition to cerebrovascular disease: Parkinson’s disease and parkinsonism syndrome, Huntington’s disease, Wilson-Konovalov disease, normal pressure hydrocephalus, brain tumors (primary and metastatic), neuroinfections, epilepsy, demyelinating di-seases, Alzheimer’s disease, frontotemporal degeneration, dementia with Lewy bodies.
3. Brain injuries and their consequences, which are the only cause of cognitive deficit.
4. A history of acute disorders of cerebral blood circulation.
5. Unstable angina, myocardial infarction during the last 3 months.
6. Diseases accompanied by pronounced chronic inflammation (infectious, dermatological) and purulent-septic complications.
7. Any somatic diseases in the stage of decompensation, mental pathology or alcoholism (including: daily consumption of more than 30 ml of alcohol during the last 3 months), drug addiction.
8. The use of drugs that have a potentially negative effect on intellectual and cognitive functions (neuroleptics, tricyclic antidepressants, benzodiazepines, central cholinolytics, barbiturates, antiepileptic drugs).
Neurological examination included clarification of complaints with an emphasis on impaired memory, attention, speech and other cognitive functions, emotional instability. Objective neurological examination was performed according to the generally accepted method. A formalized score was used to assess the severity of symptoms. The absence of a symptom on the scale was given 0 points, a mild symptom — 1 point, a moderate symptom — 2 points, a significant symptom — 3 points. After treatment, the patient assessed the severity of the corresponding complaints according to the following scheme: 3 points — the symptom remained at the previous level, 2 points — the severity of the symptom decreased, 1 point — the symptom decreased significantly and 0 points — the symptom regressed. If the symptom worsened during the-rapy, 4 points were set.
Neuropsychological examination included the following tests: Mini-Mental State Examination (MMSE) (Folstein M. et al., 1975), Frontal Assessment Battery (FAB) (Dubois B. et al., 2000), Dementia Rating Scale (DRS) (Mattis S., 1976), 10 words (Luria A.R., 1969), 5 words (Grober E. et al., 1988), verbal association (Kazdin A., 1982), Judgment of Line Orientation (Benton A., 1975), unpainted objects (Luria A.R., 1969), clock dra-wing (Sunderland T. et al., 1989), Trail Making Test (Reitan R.M., 1958), Boston Naming Test (Kaplan J. et al., 1978), Spielberger-Hanin anxiety self-assessment scale (Spielberger C.D. et al., 1976), Beck Depression Inventory (Beck A.T. et al., 1975) [13].
The study of central hemodynamics consisted of two-dimensional transthoracic echocardiography in the mode of pulsed wave tissue Doppler using an ultrasound scanner LOGIQ 500 MD (Japan) according to standard methods. The study of cerebral hemodynamics, Doppler ultrasound were performed on a Doppler device MyLab-25 (Esaote S.p.A., Italy) according to standard methods. The blood flow velocities (peak systolic (Vps), end-diastolic (Ved), mean velocity (Vm)) and indices of vascular resistance (pulsatility index (PI) and resistance index (RI)) in the middle cerebral artery were studied.
To assess the inflammatory profile, the blood levels of cytokines such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay on a biochemical analyzer Immulite 1000 (Siemens AG, Germany). The level of С-reactive protein (CRP) was determined by immunoturbidimetric method on the biochemical analyzer Cobas Integra 400 plus (Roche, Switzerland).
The results of statistical processing of quantitative variables are represented by the mean and standard deviations (M ± SD). The study used application packages Statistica for Windows v.8.0 (StatSoft Inc., USA, 2012) in accordance with the recommendations for processing the results of biomedical research.
Results and discussion
Over the course of a year, patients in both groups were assessed for the presence of hard endpoints (Table 2). The frequency of cardiovascular and cerebrovascular events during the 1-year observation period in the group 2 was higher than in that of the group 1 (p > 0.05).
Thus, drug therapy for the correction of bradyarrhythmias was inferior to the effectiveness of pacemaker implantation, increasing the risk of vascular events by 3.3 times (OR 3.34, CI 2.44–4.37, p = 0.002).
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Six months after pacemaker implantation, a tendency to decrease in the need for taking diuretics and prolonged nitrates was found, which indicated a favorable course of heart and coronary insufficiency. In addition, the number of patients who regularly took statins increased significantly, which also led to a more favorable course of coronary artery disease and regression of CD. Pacemaker implantation had no effect on the frequency of prescribing antiplatelet agents — their doses remained unchanged at all stages of observation. An increase in the frequency of prescription and dose of β-blockers or amiodarone up to the six-month follow-up period and a decrease at the one-year stage of the study after pacemaker implantation were noted. Thus, pacemaker implantation does not cancel, but modifies drug therapy taking into account the degree of arterial hypertension and heart rate.
Patients of both groups presented an average of 4–5 complaints before the start of therapy, which were evaluated: in the group 1 — 12.8 ± 2.2 points, in the group 2 — 12.5 ± 2.1 points (p = 0.92). Against the background of treatment, patients of the group 1 noted an improvement in their well-being after 12 months: decreased headache, dizziness, noise in the head, general weakness, syncopal and vestibular pa-
roxysms, increased exercise tolerance. In the group 1, a decrease in the intensity of complaints by 39.1 % (p = 0.047) was found compared to the baseline. In the group 2, the total assessment of complaints increased by 8.7 % (p = 0.69) (Fig. 1).
In the early stages of treatment, patients of the group 1 reported a significant reduction of cephalic syndrome by 2.3 ± 0.6 to 0.9 ± 0.3 points (p = 0.041), vestibulo-atactic — from 2.6 ± 0.8 to 0.7 ± 0.3 points (p = 0.03), cochleovestibular — from 2.0 ± 0.5 to 0.7 ± 0.3 points (p = 0.03), paroxysmal — from 2.2 ± 0.6 to 0.6 ± 0.2 points (p = 0.014), dyssomnic syndrome — from 2.6 ± 0.7 to 0.8 ± 0.3 points (p = 0.022). The dynamics of other syndromes were unreliable. The analysis of indicators in the patients of the group 2 revealed an unreliable decrease in cephalic syndrome — from 2.2 ± 0.7 to 1.8 ± 0.6 points (p = 0.67), vestibulo-atactic — from 2.5 ± 0.8 to 2.3 ± 0.7 points (p = 0.85), cochleovestibular — from 2.5 ± 0.8 to 2.1 ± 0.6 points (p = 0.69), paroxysmal — from 2.1 ± 0.6 to 1.9 ± 0.5 points (p = 0.8), dyssomnic syndrome — from 2.5 ± 0.7 to 2.3 ± 0.6 points (p = 0.83) (Fig. 2).
In the group 1, regression of syncopal states, Morgagni-Adams-Stokes syndrome, vestibular paroxysms was observed throughout the entire period; reduction of cephalgia and vestibulopathy was noted. In the patients of the group 2, a tendency to decrease in neurological symptoms was recorded in the early stages of treatment, but in the distant period, its increase was observed.
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The subjective clinical effect of the therapy on neurological complaints in most patients began to manifest itself on day 2–3 after pacemaker implantation. After 10 days, a significant improvement was noted by 17.2 % of patients, moderate — by 27.6 %, minor — by 31.0 %, no changes — by 24.2 %; after 6 months: a significant improvement — 11.1 %, moderate — 18.6 %, slight — 29.6 %, no changes — 29.6 %, deterioration — 11.1 %; after 12 months: a significant improvement — 8 %, moderate — 12 %, slight — 24 %, no change — 32 %, deterioration — 24 %.
The patients of the group 2 had the following results: after 10 days, a moderate improvement was noted in 11.8 % of cases, slight improvement in 23.5 %, no changes in 58.8 %, deterioration in 5.9 %; after 6 months: a moderate improvement — 6.7 %, slight — 13.3 %, no changes — 46.7 %, deterioration — 33.3 %; after 12 months: a moderate improvement — 7.7 %, insignificant — 7.7 %, no changes — 30.8 %, deterioration — 53.8 % (Fig. 3).
Thus, in the group 1 after 10 days, 75.8 % of patients had positive results, after 6 and 12 months, there was a downward trend. In the group 2, positive results after 10 days of treatment were obtained only in a third of patients, the effectiveness of the treatment decreased thereafter.
Mild CD was diagnosed in 14 (30.4 %) patients, mode-rate — in 26 (56.5 %), and severe CD — in 6 (13.1 %) cases. The frequency of affective disorders in patients with bradyarrhythmias was 85.6 %.
The profile and severity of detected CF abnormalities in both groups corresponded to the general results of testing as a whole for the group of patients with bradyarrhythmias. A decrease in memory (mainly in the form of disorders of vo-
luntary reproduction), speaking rate, level of attention, violation of the nominative function of speech and visual-spatial gnosis were revealed.
Before the beginning of the study, 21 (72.4 %) patients of the group 1 complained of memory loss, 18 (62.1 %) — attention deterioration, 13 (44.8 %) — speaking rate reduction, 15 (51.7 %) — of reduced level of wakefulness. In the group 2, 12 (70.6 %) patients complained of reduced memory, 10 (58.8 %) — impaired attention, 7 (41.2 %) — reduced speaking rate, 8 (47.1 %) — of reduced level of wakefulness.
Before the end of the clinical observation, the patients of the group 1 showed positive dynamics: a decrease in complaints of memory loss was detected in 11 (52.4 %) cases, an increase in attention — in 10 (55.5 %), improvement in speech functions — in 6 (46.1 %), increased level of wakefulness — in 10 (66.7 %) patients. Overall in the group, 16 (64.0 %) people had an improvement in CF, 6 (24.0 %) patients maintained it at the previous level, and only in 3 (12.0 %) cases, there was a tendency to worsen neuropsychological indicators, which is associated with the emergence for the first time after pacemaker implantation of patients’ excessive anxiety about its work and with some limitation of their usual way of life.
In the distant period after pacemaker implantation, a reliable improvement of CF was observed, both compared to the baseline indicators and indicators of the early period. A significant decrease in the severity of CD was observed after 6 months regardless of the pacemaker implantation mode. This was facilitated by the gradual adaptation of patients to pacemaker implantation and softening of the psycho-emotional reaction, as well as the reprogramming of pacemaker implantation parameters, which caused a decrease in the level of CD and somato-vegetative symptoms. A particularly pronounced positive dynamics was noted in patients with implanted pacemaker, who initially had a higher level of CD. Thus, with VVIR stimulation, the reduction in CD was 43.7 %, and with DDDR stimulation — 56.3 %.
No significant dynamics of clinical manifestations was observed in the early stages of treatment in the group 2, but later, a tendency to CF deterioration was noted. There was no improvement in CF, in 3 (23.1 %) patients, CF were at the previous level, and their worsening was detected in 10 (76.9 %) cases.
In the group 1, the MMSE score increased by 2.4 % (p = 0.52) on the day 10 of treatment and by 8.7 % (p = 0.024) on the 12th month treatment. In the group 2, the MMSE score increased unreliably by 0.4 % on the day 10 (p = 0.91) and progressively decreased by 2.5 % (p = 0.58) on the 12th month. In the group 1, in all subtests, reliable positive dynamics was found compared to the baseline. In the group 2, accor-ding to all subtests, there was a deterioration of CF (Table 3).
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In the group 1, the FAB score on the day 10 of treatment increased by 5.7 % (p = 0.31), and on the 12th month — by 13.7 % (p = 0.016); in the group 2 — on the day 10 of treatment, it did not change and amounted to 13.4 ± 0.6 points, on the 12th month — decreased by 4.5 % (p = 0.61). In the group 1, according to the subtests “conceptualization” (p = 0.031) and “dynamic praxis” (p = 0.049), a reliable positive dynamics was revealed starting from 6th month of observation. In the patients of the group 2, on the day 10 of treatment, only “conceptualization” and “verbal fluency” improved (p = 0.81).
The DRS score in the group 1 on the tenth day of treatment increased by 1.9 % (p = 0.62), and on the 12th month — by 10 % (p = 0.037), in the group 2 — on the day 10 of treatment, it increased by 0.3 % (p = 0.99), and on the 12th month — decreased by 1.4 % (p = 0.96). In the group 1, according to all subtests, reliable positive dynamics was found after 6 months compared to the baseline. The patients of the group 2 had an unreliable worsening of indicators for all subtests (p > 0.05).
In the group 1, the indicators of hearing, speech and visual memory improved significantly from the 6th month (p < 0.05). In the group 2, direct and delayed reproduction after 10 days of treatment practically did not change, but in the remote period, there was a tendency to decrease (p > 0.05).
The results on the tests for the assessment of speaking rate in the patients of the group 1 were significantly better than in the group 2: the average score on the literal associations test in the group 1 increased by 6.8 % (p = 0.62) on the day 10 and by 40.6 % (p = 0.003) on the 12th month; on the categorical associations test — increased by 7.3 % (p = 0.59) after 10 days and by 35.7 % (p = 0.009) on the 12th month. In the group 2, positive dynamics was observed only after 10 days (p = 0.88 and p = 0.9), in the future, the indicators tended to worsen.
Performance of Judgment of Line Orientation and unpainted objects in the group 1 significantly improved after 6 months (p = 0.049 and p = 0.044), in the group 2, it wor-sened from the 6th month of treatment (p > 0.05). The score on the Judgment of Line Orientation improved by 18.9 % (p = 0.001) after 12 months in the group 1, in the group 2, it worsened by 4.9 % (p = 0.21). Thus, in the group 1, patients noted a significant improvement in optical-spatial gnosis. On the unpainted objects test, the results in the group 1 after 12 months increased by 17.8 % (p = 0.04), in the group 2 — decreased by 2.7 % (p = 0.64).
After 6 months, patients of the group 1 performed the clock drawing test significantly better compared to the baseline (by 14 %, p = 0.047). In the group 2, there was an unreliable deterioration, starting from the 6th month (by 2.5 %, p = 0.69).
Indicators of attention according to Trail Making Test improved unreliably in the group 2 after 10 days (p > 0.05). After 6 and 12 months of treatment, there was a tendency to their worsening. In the group 1, a significant improvement was noted at the late stages of observation (p < 0.05). Performance of block A in the group 1 improved by 2.3 % (p = 0.77) after 10 days, after 6 months — by 13.8 % (p = 0.049), after 12 months — by 27.2 % (p = 0.001); in the group 2, indicators worsened in the late period (p = 0.92 and p = 0.69). The score on block B in the group 1 improved by 2.2 (p = 0.8), 16.2 (p = 0.049) and 33.2 % (p = 0.001), respectively; in the group 2, deterioration of indicators was noted in the late periods (p = 0.84 and p = 0.70).
Nominative speech function in the patients of the group 1 was restored already 10 days after pacemaker implantation: the frequency of literal clues when performing the Boston Naming Test decreased by 8.3 % (p = 0.66), after 6 months — by 33.3 % (p = 0.044), after 12 months — by 63.9 % (p = 0.001); in the group 2, deterioration of indicators was detected in the late period, by 4.1 (p = 0.84) and 5.4 % (p = 0.72), respectively. The frequency of categorical clues in the group 1 decreased: after 10 days — by 17 % (p = 0.46), after 6 months — by 43.4 % (p = 0.038), after 12 months — by 66 % (p = 0.003). In the group 2, an unreliable deterioration of indicators was observed in the late periods of observation: after 6 months — by 3.7 % (p = 0.88), after 12 months — by 7.1 % (p = 0.78) (Table 3).
In both groups, the indicators of the transition from one clinical stage of cognitive impairment to another du-ring the entire period of the study were analyzed. Before the end of the study, only 2 (8.0 %) patients in the group 1 and 6 (46.2 %) in the group 2 had a lower diagnostic category. The frequency of CF deterioration within 12 months from the beginning of the study in the group 1 was six times lower than that of the group 2 (OR 5.93; CI 2.18–9.85; p = 0.017).
Thus, an improvement of CF was noted 10 days after pacemaker implantation, and after 6 months, there was a recovery of neuropsychological processes. Against the background of pacemaker implantation, positive dynamics was noted for all tests, while statistically significant changes in CF were detected on the 6th month of observation. Against the background of drug correction in bradyarrhythmias, unreliable positive dynamics was noted after 10 days according to the MMSE, DRS, 10 words, verbal associations, unpainted objects, clock drawing test, Trail Making Test; however, in the distant periods of treatment, deterioration on all of them was observed.
In the group 1 on day 10, an increase in the level of reactive anxiety and depression was noted, which is associated with the patients’ experiences regarding the intervention, with a feeling of their own inferiority due to the pacemaker implantation and difficulties in adapting to new living conditions. Patients perceived pacemaker as a foreign object in the body, experienced an unreliable situation in life, dependence on pacemaker, were in a state of anxious anticipation of pacemaker failure and recurrence of arrhythmia attacks. After the pacemaker implantation, the patients considered themselves seriously ill, were afraid of returning home from the hospital, and did not make active life plans.
In the group 2, a decrease in the levels of reactive anxiety (p = 0.86) and depression (p = 0.92) was noted on day 10, but they did not reach normal values (Table 4).
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In the distant period, a positive effect of pacemaker implantation on the emotional state of patients with bradyarrhythmias was found. The elimination of arrhythmias, the feeling of “protection” of a patient with installed pacemaker contributed to the reduction of the level of anxiety. It should be noted that personal anxiety is a more stable psychological indicator; therefore, a more pronounced decrease in reactive anxiety during re-examination is explained by the therapeutic intervention that took place. Patients noted an increase in the level of optimism, increased confidence in the favorable outcome of the disease.
Psycho-emotional status of the patients of the group 1 was characterized by a moderate level of anxiety. This was due to to the chronicity of cardiac pathology and the idea of the reliability of the pacemaker. The indicated disorders were determined by the effectiveness of pacemaker implantation and the state of myocardial and hemodynamic homeostasis. With satisfactory indicators of the latter, especially in patients with dual-chamber stimulation, the anxiety profile was within normal values, which reflected adapted anxiety and optimistic attitudes towards the treatment.
In the group 2, the level of anxiety and depression increased after 6 and 12 months. This indicated the presence of maladjustment of the anxiety-phobic type, which can largely be explained by somatogenic influences.
Thus, pacemaker implantation in the treatment of patients with bradyarrhythmias reliably improved the degree of recovery of memory, attention, speaking rate, visual-spatial and simultaneous gnosis, speech activity, emotional status. Medical correction of bradyarrhythmias did not reliably improve patients’ CF until day 10 of treatment, and thereafter their cognitive status worsened.
In the group 1, regardless of the pacemaker regime, an unreliable improvement of intracardiac hemodynamic indicators was noted in the early period, but later, the average end-systolic volume, end-diastolic volume decreased reliably. Pacemaker implantation was accompanied by an improvement in the pumping and contractile function of the left ventricle. A significant increase in the left ventricular ejection fraction by 17.9 % (p = 0.009) was observed in the group 1, in the group 2, its decreased by 3.7 % (p = 0.49). In the group 1, normalization of heart rate led to a significant increase of cardiac output 10 days, 6 and 12 months after pacemaker implantation — by 44.2 (p = 0.028), 49.1 (p = 0.015) and 50.9 % (p = 0.017), respectively, and the reduction of total peripheral vascular resistance — by 45.4 (p = 0.008), 51.5 (p = 0.003) and 53.5 % (p = 0.002), respectively.
After 10 days of the pacemaker implantation, an improvement in the blood flow velocity was recorded, however, the differences compared to the baseline were unreliable. In the late period, there was a statistically significant improvement in extracranial artery parameters after 6 months: an increase in Vрs of the common carotid arteries (CCAs) — by 14.4 % (p = 0.042), Vm of the CCAs — by 16.1 % (p = 0.049), Vрs of the internal carotid arteries (ICAs) — by 12.4 % (p = 0.037), Vm of the ICAs — by 14.2 % (p = 0.041), as well as an unreliable decrease in RI and PI (p = 0.05) compared to preoperative data; after 12 months: an increase in Vрs of the CCAs — by 24.2 % (p = 0.001), Vm of the CCAs — by 27.7 % (p = 0.001), Vрs of the ICAs — by 25 % (p = 0.001), Vm of the ICAs — by 27.4 % (p = 0.001), as well as a decrease in RI of the CCAs and PI of the ICAs — by 8.9 (p = 0.03) and 7.7 % (p = 0.04), respectively. Similarly, the hemodynamics of the intracranial arteries changed after 6 months: an increase in Vps of the middle cerebral arteries (MCAs) — by 9.6 % (p = 0.047), Vm of the MCAs — by 13.9 % (p = 0.042), Vрs of the vertebral arteries (VAs) — by 17.3 % (p = 0.036), Vm of the VAs — by 19 % (p = 0.024) and a decrease in RI and PI (p = 0.06) compared to initial indicators; after 12 months: an increase in Vps of the MCAs — by 17.5 % (p = 0.001), Vm of the MCAs — by 23.8 % (p = 0.001), Vрs of the VAs — by 30.3 % (p = 0.001), Vm of the VAs — by 32.1 % (p = 0.001) and a decrease in RI of the MCAs and PI of the VAs — by 17.4 (p = 0.001) and 6.4 % (p = 0.08), respectively.
The most pronounced improvement was noted in patients with SSS, which consisted in a significant increase in the blood flow velocity in the extracranial arteries. When studying the dynamics of blood flow indicators in the intracranial arteries, no differences were found in patients depending on the type of bradyarrhythmia.
In the group 2, an unreliable deterioration of the blood flow velocity indicators in the extracranial and intracranial arteries was noted at various times during the entire observation period.
The inflammatory response manifested itself in CRP increase by 19.7 % (p = 0.35) in the early period after pacemaker implantation, but later the indicator decreased by 37.3 (p = 0.048) and 39.7 % (p = 0.03). During 10 days of the postoperative period, TNF-α increased by 41.8 % (p = 0.016), after 6 months decreased by 36 % (p = 0.019) and after 12 months — by 42.6 % (p = 0.006). In the early stages, IL-6 significantly increased by 38.8 % (p = 0.021), after 6 months decreased by 27.6 % (p = 0.044) and after 12 months — by 29.3 % (p = 0.032) (Table 5).
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In the group 2, the levels of pro-inflammatory markers tended to decrease after 10 days, and subsequently increased unreliably (p > 0.05).
Thus, an increase in inflammatory processes was detec-ted only in the early period after pacemaker implantation, in the remote period, the level of pro-inflammatory markers decreased significantly. In our opinion, these changes can be interpreted as follows: pacemaker implantation led to a decrease in the manifestations of heart failure due to the elimination of bradyarrhythmias and heart rhythm normalization.
The results of a comparative study on the effectiveness of permanent pacemaker implantation in patients with CD on the background of bradyarrhythmias indicate its advantages in slowing down the progression of cognitive deficits and dela-
ying or preventing its transition into the diagnostic category of dementia. Pacemaker implantation and restoration of a regular heart rhythm in patients with bradyarrhythmias in the early and late periods led to the elimination of syncopal states, Morgagni-Adams-Stokes syndrome, improvement of cognitive status and reduction of anxiety-depressive disorders by improving indicators of central and cerebral hemodynamics, which consisted in a positive myocardial remodeling, increased blood flow velocity in the extra- and intracranial sections of the carotid arteries, a decrease in the activity of systemic inflammation due to the suppression of pro-inflammatory cytokines.
A tendency to improve CF was registered on day 10 after pacemaker implantation; however, stabilization of the emotional background was noted in the remote period. The study showed the safety of pacemaker implantation: no new neurological symptoms were registered in any patient.
Patients who underwent only medical correction of bradyarrhythmias had prognostically dangerous indicators of cerebral hemodynamics. As a result, they should be included in the group at increased risk of developing severe CD. Therefore, follow-up of the specified group of patients and appropriate pathogenetic therapy are necessary.
Thus, the demonstrated beneficial effects of permanent pacemaker implantation on the neurological symptoms and CF make it possible to consider it not only as an effective method of bradyarrhythmia treatment, but also as a mean that has a cerebroprotective effect, which ultimately reduces the risk of developing dementia in these patients.
Conclusions
1. In patients implanted with a pacemaker, a more pronounced regression of neurological symptoms was observed compared to those in the group of drug correction of bradyarrhythmias. The most noticeable effect of cardiostimulation was observed for cephalic, vestibulo-atactic, dyssomnic and paroxysmal syndromes.
2. Against the background of pacemaker implantation, there was an improvement of all cognitive functions: me-mory, attention, speaking rate, visual-spatial and simultaneous gnosis, speech activity. Stabilization of the emotional background was noted in the remote period after pacemaker implantation.
3. The improvements in the parameters of central and cerebral hemodynamics after pacemaker implantation consisted in positive myocardial remodeling, an increase in the speed characteristics of blood flow in the extra- and intracranial sections of the carotid arteries.
4. Positive clinical dynamics in the process of pacemaker implantation were combined with a statistically significant decrease in the content of pro-inflammatory cytokines, which indicated a decrease in the activity of immune inflammation.
5. The assessment of the state of cognitive functions can be used as one of the additional indicators for the effectiveness of permanent pacemaker implantation in patients with bradyarrhythmias.
Received 10.01.2023
Revised 23.01.2023
Accepted 27.01.2023
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