Мобильная версия

Международный неврологический журнал Том 19, №2, 2023

Особливості структурно-функціонального стану серця в пацієнтів з аритміями залежно від вираженості когнітивних розладів

Авторы: S.M. Stadnik (1), O.M. Radchenko (2)
(1) — Military Medical Clinical Center of the Western Region, Lviv, Ukraine
(2) — Danylo Halytsky Lviv National Medical University, Lviv, Ukraine

Рубрики: Неврология

Разделы: Клинические исследования

Мета: встановити залежність змін когнітивної сфери від особливостей структурно-функціонального стану серця та центральної гемодинаміки в пацієнтів з аритміями. Матеріали та методи. Обстежено 139 осіб із різними клінічними формами аритмій. У всіх пацієнтів проводили розширене нейропсихологічне тестування й дослідження центральної гемодинаміки. Стан центральної гемодинаміки оцінювали шляхом ультразвукового обстеження серця. Вивчали стан внутрішньосерцевої гемодинаміки, структурні зміни різних відділів серця, на підставі яких визначали тип ремоделювання серця. Визначали кореляцію гемодинамічних показників із результатами нейропсихологічного тестування. Результати. У пацієнтів із легкими когнітивними розладами (КР) показник скоротливості міокарда лівого шлуночка (ЛШ) суттєво не відрізнявся від такого в осіб без КР, проте в пацієнтів із помірними КР був на 9,6 % нижчим (р = 0,044). У хворих із помірними КР наростала дилатація лівих відділів серця (кінцево-діастолічний об’єм — на 16,5 %, р = 0,049; ліве передсердя — на 9,9 %, р = 0,049), що поряд із посиленням гіпертрофії міжшлуночкової перетинки на 12,8 % (р = 0,048) і задньої стінки ЛШ на 12,9 % (р = 0,048) призводило до підвищення тиску в легеневій артерії на 24,8 % (р = 0,015). При КР частіше виявляли концентричну (42,2 %) і ексцентричну (22,6 %) гіпертрофію ЛШ (p = 0,048 і р = 0,027), в осіб без КР переважало концентричне ремоделювання ЛШ (p = 0,037). У хворих із легкими КР реєстрували вищі значення ударного об’єму (на 8,3 %, р = 0,049) порівняно з особами без КР. Однак за показниками хвилинного об’єму, серцевого індексу і загального периферичного судинного опору відмінності були недостовірними (р > 0,05). У пацієнтів із помірними КР мало місце підвищення ударного й хвилинного об’єму на 7,6 (р = 0,043) і 14,9 % (р = 0,014) відповідно порівняно з особами без КР. Показники центральної гемодинаміки мали найбільший вплив на сферу уваги, регуляторні функції, зорово-просторовий і мнестичний дефіцит. Найбільші співвідношення шансів щодо розвитку КР установлені для фракції викиду ЛШ (2,52; 95% довірчий інтервал 1,82–3,29, p < 0,001). Висновки. Виявлені асоціації когнітивної дисфункції, центральної гемодинаміки і ремоделювання серця важливі для оптимізації індивідуалізованого підходу до ведення пацієнтів і прогнозування розвитку КР.

Background. The purpose of our work was to find out the dependence of changes in the cognitive sphere on the features of the structural and functional state of the heart and central hemodynamics in patients with arrhythmias. Material and methods. We have examined 139 patients with different clinical forms of arrhythmias. All of them underwent extended neuropsychological testing and central hemodynamic studies. The state of central hemodynamics was assessed by an ultrasound examination of the heart. The state of intracardiac hemodynamics, structural changes in various parts of the heart were evaluated; based on this, the type of heart remodeling was determined. Correlations of hemodynamic indicators with the results of neuropsychological testing were evaluated. Results. In patients with mild cognitive disorders (CD), the left ventricular myocardial contractility index did not differ significantly from that in patients without CD, but in people with moderate CD it was 9.6 % lower (p = 0.044). With moderate CD, the dilatation of the left parts of the heart increased (end-diastolic volume — by 16.5 %, p = 0.049; left atrium — by 9.9 %, p = 0.049), which, along with increased hypertrophy of the interventricular septum by 12.8 % (p = 0.048) and of the left ventricular posterior wall by 12.9 % (p = 0.048), led to an increase in the pulmonary artery pressure by 24.8 % (p = 0.015). Among patients with CD, concentric (42.2 %) and eccentric (22.6 %) left ventricular hypertrophy was more often detected (p = 0.048 and p = 0.027); in those without CD, concentric remodeling of the left ventricle prevailed (p = 0.037). In patients with mild CD, higher stroke volume was recorded — by 8.3 % (p = 0.049) compared to those without CD. However, according to indicators of cardiac output, cardiac index and total peripheral vascular resistance, differences were unreliable (p > 0.05). Patients with moderate CD reported an increase in stroke volume and cardiac output by 7.6 (p = 0.043) and 14.9 % (p = 0.014), respectively, compared to those without CD. Indicators of central hemodynamics had the greatest impact on the sphere of attention, regulatory functions, visual-spatial and mnestic deficits. The highest odds ratio for the development of CD were found for left ventricular ejection fraction (2.52, 95% confidence interval: 1.82–3.29, p < 0.001). Conclusions. The identified associations of cognitive dysfunction, central hemodynamics and heart remodeling are important for optimizing an individualized approach to patient management and predicting the development of CD.

Ключевые слова

аритмії; когнітивні розлади; центральна гемодинаміка; ремоделювання серця

arrhythmias; cognitive disorders; central hemodynamics; heart remodeling

doi: http://dx.doi.org/10.22141/2224-0713.19.2.2023.997

Introduction

Cognitive dysfunctions are one of the most common neurological disorders [1, 2]. The most powerful risk factor for the development of cognitive dysfunction is considered to be elderly and senile age [3, 4]. Hypertension is an important predictor of cognitive disorders (CD) [5]. At the same time, less attention is paid to the role of arrhythmias. CD in patients with arrhythmias occurs in 26–80 % of cases [6, 7]. Moderate impairment of cognitive functions in patients with arrhythmias is found most often [8–10]. Neuropsychological examination of patients with arrhythmias reveals violations of executive functions, attention, memory, a decrease in the rate of mental reactions, as well as visual-spatial disorders [11].

Currently, one of the causes of CD is considered to be cerebral hypoperfusion as a result of impaired systemic hemodynamics [4, 12]. Unregulated heart rate in arrhythmias leads to a decrease in cardiac output by 25–45 %. Hemodynamic insufficiency in arrhythmias causes qualitative chan-ges in the blood: according to F. Alani, already at 95 bpm, there is a pronounced decrease in arterial oxygen saturation. Prolonged arrhythmia is accompanied by an enlargement of heart chambers and the inclusion of a myocardial mechanism for the development of circulatory failure. Progressive changes in the myocardium lead to the development of severe damage, defined as tachycardiomyopathy. Arrhythmia is accompanied by a decrease in coronary blood flow by 40 %, cerebral — by 23–28 %, while the risk of stroke increases by 18 times. Mortality in the acute period of stroke in patients with arrhythmias is about 2 times higher than in those without arrhythmias [13].

Cardiohemodynamic characteristics are one of the most important components that ensure the adequacy of cerebral perfusion. The total volume of cerebral blood flow is determined not only by the levels of systemic blood pressure and heart rate, but also by the cardiac output and the input impedance of the arterial system, which can be indirectly judged by the amount of afterload [14].

It is advisable to evaluate central hemodynamics in patients with arrhythmias and without concomitant pathologies that could have a significant impact on cognitive functions and cerebral blood flow.

An integrated approach to the study of the mechanisms of CD development in patients with arrhythmias, their early diagnosis, the choice of the correct strategy for the treatment of arrhythmias can slow down the progression of cognitive deficits, which will make it possible to 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 determined its aim.

The purpose of our study was to reveal the dependence of changes in the cognitive sphere on the features of the structural and functional state of the heart and central hemodynamics in patients with arrhythmias.

Materials and methods

We examined 139 patients aged 30 to 75 years (mean age 63.8 ± 4.3 years) with various forms of arrhythmias: 69 with persistent (paroxysmal) form of atrial fibrillation (AF), 32 with permanent AF, 24 with atrioventricular block (AVB) degree II–III and 14 patients with sick sinus syndrome.

Underlying diseases, which led to the development of arrhythmias, were: ischemic heart disease and/or essential hypertension — 93 (66.9 %) cases, non-coronary myocardial diseases — 22 (15.8 %), chronic rheumatic heart disease — 9 (6.5 %), thyroid pathology — 7 (5.0 %) patients. Idiopathic arrhythmias were detected in 8 (5.8 %) patients. The criterion of idiopathic (alone) arrhythmia was considered the absence of an explicit structural substrate of heart damage.

Inclusion criteria: age to 75 years, the presence of arrhythmias verified by clinical data, echocardiography (ECG), daily ECG monitoring; patient’s ability to carry out productive contact with a doctor to evaluate cognitive status; voluntary informed consent.

Exclusion criteria: the absence of a voluntary informed patient’s consent; vascular dementia (total score on Mini-Mental State Examination (MMSE) < 24, Frontal Assessment Battery (FAB) < 11, Mattis Dementia Rating Scale (DRS) < 115); other possible causes of cognitive impairment, including cerebrovascular disease: Parkinson’s disease and parkinsonian syndrome, Huntington’s disease, Wilson-Konovalov disease, normal pressure hydrocephalus, brain tumors (primary and metastatic), neuroinfections, epilepsy, demyelinating diseases, Alzheimer’s disease, frontotemporal degeneration, dementia with Lewy bodies; brain injuries and their consequences, which are the only cause of cognitive deficits; acute cerebrovascular disorders; unstable angina, myocardial infarction during the last 3 months; any somatic diseases in the stage of decompensation, mental illness or alcoholism (including daily consumption of more than 30 ml of alcohol for the last 3 months), narcotic deposition. Criteria for the need to maximize the effect on the results of the study of pathology with proven action on cognitive functions were evaluated.

Neuropsychological examination included following tests: MMSE (Folstein M. et al., 1975), FAB (Dubois B. et al., 2000), DRS (Mattis S., 1976), 10 words test (Luria A.R., 1969), 5 words test (Grober E. et al., 1988), verbal association test (Kazdin A., 1982), Judgment of Line Orientation (Benton A., 1975), unpainted objects (Luria A.R., 1969), clock drawing test (Sunderland T. et al., 1989), Trail Making Test (Reitan R.M., 1958), Boston Naming Test (Kaplan J. et al., 1978) [15].

The study of central hemodynamics included two-dimensional transthoracic echocardiography on Logiq-500 M (Japan) using a sector sensor with a frequency of 2–10 MHz according to a standard protocol. Quantitative assessment of the structure and function of cardiac chambers was performed according to the recommendations of the American Society of Echocardiography (2006) and the European Association of Echocardiography (2006). From the parasternal and apical positions along the left ventricular (LV) long axis in the M-mode, the dimensions of the left atrium (LA), state of the mitral and aortic valves, interventricular septal thickness (IST), LV posterior wall thickness (PWT), the end-systolic size (ESS), end-diastolic size (EDS) were determined. The criterion for LV hypertrophy was left ventricular mass index (LVMI) over 125 g/m2 for men and over 110 g/m2 for women. Based on the received data, the following indicators were calculated: LV end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), cardiac output (CO), cardiac index (CI), ejection fraction (EF), total peripheral vascular resistance (TPVR), relative wall thickness (RWT) [16].

Based on the indicators of RWT and LVMI, the geometric model of the LV was evaluated and the types of its remodeling were identified: normal geometry (NG) — with a normal LVMI and RWT < 0.45; eccentric hypertrophy (EH) was determined when LVMI was greater than normal and RWT < 0.45; concentric hypertrophy (CH) — with LVMI greater than normal and RWT > 0.45; concentric remodeling (CR) — with normal LVMI and RWT > 0.45 [16].

Given the results of calculations, the types of hemodynamics were determined: hyperkinetic — CI > 3.55 l/min • m2, TPVR < 1600 dyn • cm/s–5; eukinetic — CI 2.5–3.55 l/min • m2, TPVR > 1600 dyn • cm/s–5; hypokinetic — CI < 2.5 l/min • m2, TPVR > 1600 dyn • cm/s–5.

Left ventricular diastolic function was assessed in the Doppler electrocardiography mode. The peak velocity of early (E) and late diastolic LV filling (A), the E/A ratio (< 1 or > 2 cm/s) were determined. The following types of LV diastolic dysfunction were distinguished: rigid, pseudonormal, restrictive. Rigid type was diagnosed when the E/A ratio was below the age norm, pseudonormal — when it changed from normal age indicators to < 1 on the background of the Valsalva test, restrictive — when the E/A ratio increased sharply [16].

Statistical analysis was carried out using standard database management programs data. Results are given as arithmetic mean (M) and its standard error (m). Statistical significance of the difference was determined using Student’s t-test, and categorical data — by the χ2 criterion. Pearson correlation coefficient (r) was calculated using univariate analysis. P < 0.05 was statistically significant. To find differences in frequencies, the odds ratio (OR) was calculated. A 95% confidence interval (CI) was calculated for the indicators of OR. It was considered reliable if the CI did not contain an odds ratio equal to 1 [17].

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

The neuropsychological pattern of patients with arrhythmias is represented by neurodynamic and regulatory disorders, manifested by impaired executive function, auditory-speech memory, spatial gnosis, perception, concentration, decreased speed of psychomotor processes. These disorders in most cases were moderate (44.6 %) and mild (36.0 %). Mild CD were more often found in patients with persistent (paroxysmal) AF (OR = 1.47, 95% CI: 1.13–1.88, p = 0.036), moderate CD — with a permanent AF (OR = 2.15, 95% CI: 1.45–3.32, p < 0.001) and with AVB degree II–III (OR = 2.62, 95% CI: 1.51–4.13, p < 0.001) (Fig. 1).

In patients with persistent (paroxysmal) AF, disorders of the neurodynamic component of cognitive activity have been detected, which did not become significant cognitive impairment and did not affect professional and social acti-vity. In patients with a permanent AF, disorders of regulatory functions come to the fore, forming a polymodal cognitive deficit with a relatively uniform impairment of all cognitive functions. In patients with bradyarrhythmias, the leading neuropsychological mechanism of cognitive disorders is the insufficiency of voluntary regulation of activity against the background of reduced general mental activity, manifested by a significant decrease in cognitive function, most pronounced in AVB.

LV hypertrophy was found in 90 (79.6 %) patients with CD and in 19 (73.1 %) without CD. The average LVMI is significantly higher in patients with moderate CD (154.2 ± ± 9.3 g/m2) compared to those without CD (130.2 ± 7.8 g/m2) (р = 0.049).

In patients with mild CD, the left ventricular myocardial contractility index didn’t differ significantly from that in patients without CD, but in moderate CD it was 9.6 % lower (p = 0.044). In patients with moderate CD, the dilatation of the left parts of the heart increased (EDV — by 16.5 %, p = 0.049; LA — by 9.9 %, p = 0.049), which, along with increased hypertrophy of the interventricular septum by 12.8 % (p = 0.048) and of the left ventricular posterior wall by 12.9 % (p = 0.048), led to an increase in the pulmonary artery pressure (PAP) by 24.8 % (p = 0.015) (Table 1).

Analysis of the frequency of LV remodeling in patients with CD showed that in most cases pathological types of LV geometry were detected — CH (42.5 %) and EH (23 %). It should be noted that CH and EH compared to other types of remodeling were more often observed in moderate CD (p = 0.048 and p = 0.027). In patients with CD compared to those without CD more favorable concentric remodeling was less often registered (p = 0.037) (Table 1).

In 31 (27.4 %) patients with CD and in 4 (15.4 %) without CD, diffuse myocardial hypokinesia was detected. The studied groups did not significantly differ in the frequency of local hypokinesia of the LV myocardium — 16 (14.1 %) and 2 (7.7 %) cases, respectively (p = 0.06).

The most common valvular disorder, mitral valve insufficiency, was found in 44 (38.9 %) patients with CD and in 9 (34.6 %) without CD (p = 0.07). The others were aortic insufficiency (9 (20.4 %) and 2 (22.2 %) cases, respectively, p = 0.07), insufficiency of the tricuspid valve (7 (15.9 %) and 1 (11.1 %), p = 0.06), mitral stenosis (2 (4.5 %) and 1 (11.1 %), p = 0.06) and aortic stenosis stage 1–2 (2 (4.5 %) and 1 (11.1 %) case, respectively, p = 0.06).

In 86 (76.1 %) patients with CD, LV diastolic dysfunction was detected, which in 27 (31.4 %) cases was combined with hypokinesia or paradoxical septal and left ventricular wall motion. Among patients without CD, the LV diastolic dysfunction was detected in 15 (57.7 %) cases. Mitral valve regurgitation of a functional nature was present in 16.8 % of patients with CD and in 7.7 % without CD, aortic regurgitation — in 9.7 and 7.7 %, respectively, tricuspid regurgitation — in 15 and 11.5 %, with a parallel increase in the pulmonary blood flow and an increase in the pulmonary artery pressure up to 41.5 ± 3.3 mm Hg.

Indicators of transmitral blood flow in moderate CD were characterized by a significantly lower peak late diastolic filling velocity than in patients without CD (р = 0.007) with an increase in the ratio of peak velocities — E/A, which indicated a violation of the LV diastolic function, mainly by the pseudonormal type (Fig. 2).

With mild CD, the E/A ratio was higher compared to that in patients without CD (p = 0.31), which indicated the predominance of the rigid type of the LV diastolic dysfunction.

In mild CD, higher values of SV were recorded — by 8.3 % (p = 0.049) compared to patients without CD; how-ever, the differences were not reliable according to the indicators of CO, CI and TPVR (p > 0.05). In patients with moderate CD, an increase in SV and CO was recorded by 7.6 (p = 0.043) and 14.9 % (p = 0.014), respectively, compared to patients without CD. However, this did not provide a sufficient level of CI and TPVR whose differences from the indicators of patients without CD were unreliable (p > 0.05) (Table 2).

The level of compensatory changes in patients with CD was insufficient, the hypokinetic type of blood circulation prevailed (61.1 %), which created conditions for the progression of brain ischemia and hypoxia. Hyperkinetic type was detected in 20.3 % of patients, eukinetic type — in 18.6 %. In patients without CD, the hyperkinetic type of hemodynamics was observed in 26.9 % of cases, eukinetic — in 42.3 %, and hypokinetic — in 30.8 %.

Thus, in patients with CD against the background of arrhythmias, an increase in the LA volume and the LV myocardial mass, a decrease in the total pumping function and hemodynamic performance of the heart were recorded. Hemodynamic disorders should be considered as a manifestation of a hyperkinetic type of blood circulation.

Cognitive functions of patients with arrhythmias are more related to the LV EF. Correlations were found between the LV EF and severity of CD according to the following tests: MMSE (r = 0.39, p = 0.006), FAB (r = 0.41, p = 0.002), DRS (r = 0.32, p = 0.027), delayed reproduction in the tests of 10 words (r = 0.37, p = 0.01), 5 words (r = 0.33, p = 0.016), clock drawing (r = 0.40, p = 0.012), Trail Making Test, block A (r = –0.35, p = 0.024), categorical (r = 0.33, p = 0.034) and literal (r = 0.31, p = 0.028) associations, ca-tegorical prompts (r = –0.35, p = 0.021).

Indicators of central hemodynamics had the greatest impact on attention, regulatory functions, visual-spatial and mnestic deficits. Correlations were found between SV and the total score on the MMSE (r = –0.31, р = 0.033), the “activity and perseverance” subtest of the DRS (r = –0.28, р = 0.042), Trail Making Test, block A (r = 0.29, p = 0.045); between CO and the “constructive praxis” subtest of DRS (r = –0.28, p = 0.041), delayed reproduction in the 10 words test (r = –0.32, p = 0.037), categorical associations (r = –0.35, p = 0.023); between CI and delayed reproduction in the 10 words test (r = –0.34, p = 0.025), clock drawing test (r = –0.32, p = 0.035); between TPVR and the “conceptualization” subtest of FAB (r = –0.37, p = 0.028), delayed reproduction in the 10 words test (r = –0.35, p = 0.03), Trail Making Test, block A (r = 0.30, p = 0.034).

A univariate analysis of the relationship between indicators of central hemodynamics and the risk of developing СD in patients with arrhythmias was conducted, it found that the highest odds ratio for the development of CD has the LV EF (Table 3).

Thus, the state of the cardiovascular system in patients with CD against the background of arrhythmias is characterized by the LV hypertrophy, diffuse changes, concentric hypertrophy and dilatation of the left chambers of the heart (mostly left atrium), initial signs of reduced LV systolic function, moderate pulmonary hypertension, the pre-

sence of degenerative changes in the mitral and aortic valves, pseudonormal type of diastolic dysfunction, the formation of a predominantly hypokinetic type of central hemodyna-mics. Early development of structural and functional LV disorders is characteristic for patients with moderate CD than for those with mild CD and without CD.

An increase in the frequency of the LV concentric and eccentric hypertrophy in patients with CD indicates an increase in the structural and geometric changes of the heart, which contributes not only to a violation of the geometric shape of the ventricle and an increase in the tension of its walls, but also to a further increase in myocardial stress. The presence of concentric and eccentric hypertrophy of the myocardium is an unfavorable factor for the development of CD.

Left ventricular diastolic dysfunction should be consi-dered a sensitive marker of both early and later myocardial damage. LV hypertrophy and remodeling with segmental changes in the structure cause a diastolic dysfunction, which contributes to the progression of heart failure and cognitive impairment.

Negative prognostic signs for the development of CD in patients with arrhythmias are an increase in the LVMI and RWT, LV concentric and eccentric hypertrophy, which is combined with a decrease in the LV EF and an increase in the size of the LA.

The identified associations of cognitive dysfunction and LV remodeling are important for optimizing an individua-lized approach to patient management and predicting both the arrhythmia itself and CD. On the one hand, violations of the structural and functional state of the myocardium cause the development of arrhythmia, on the other hand, arrhythmias contribute to the progression of remodeling and dysfunction of the myocardium, which is associated with an increased risk of CD.

Conclusions

1. Peculiarities of the structural and functional changes of the heart and central hemodynamics in patients with CD against the background of arrhythmias were the formation of left ventricular concentric and eccentric hypertrophy, left atrial enlargement, a decrease in the left ventricular systolic function, pseudonormal type of diastolic dysfunction, the formation of a predominantly hypokinetic type of central hemodynamics. More pronounced changes were found in patients with moderate CD.

2. The formation of cognitive disorders in patients with arrhythmias occurs against the background of restructu-

ring of the central hemodynamics (concentric and eccentric hypertrophy, a decrease in the left ventricular myocardial contractility (OR: 2.52, 95% CI: 1.82–3.29; p < 0.001) and cardiac output, an increase in the total peripheral vascular resistance).

3. Additional instrumental methods for examination of patients with arrhythmias, which includes the assessment of structural changes of the heart and hemodynamic indicators, ensures the pathogenetic validity of the differentiated prescription of effective therapy.

Received 02.04.2023

Revised 18.04.2023

Accepted 22.04.2023

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