Introduction

The history of research into the issue of morphofunctional interrelationships between the cardiovascular and central nervous systems dates back to 1552 BCE, as evidenced by the Papyrus Ebers, an ancient Egyptian compilation of medical knowledge [1]. Over the past few decades, there has been a significant increase in the interest of researchers in this area, owing to the varied clinical manifestations of cardiovascular disorders, their primary contribution to the structure of morbidity and mortality in the population [2, 3]. The findings from several scientific studies indicate the occurrence and subsequent progression of cognitive impairment (CI) among patients with chronic heart failure (CHF), atrial fibrillation, and, of course, hypertension. Simultaneously, it has been established that these conditions can act as direct contributors to the development of morphological and functional alterations in the central nervous system [4, 5]. One of the primary pathogenic mechanisms underlying the development of CI following myocardial infarction (MI) appears to be a reduction in myocardial contractility, which leads to compromised systemic blood flow and cerebral hypoperfusion. In addition, impaired cerebral perfusion can occur due to myocardial dysfunction, leading to increased venous pressure, impaired cerebrospinal fluid absorption, and its accumulation in cerebrospinal fluid spaces. It is also important to consider other potential causes. Other mechanisms that may contribute to the development of CI in MI and CHF: are increased levels of components of the renin-angiotensin-aldosterone system and changes in the concentration of thrombin/antithrombin complex, which can lead to microembolization of cerebral vessels, as mentioned in scientific literature [6].

According to some research, MI has the potential to induce neuroinflammatory and neurodegenerative processes in the brain, probably through the activation of pro-inflammatory cytokines [7, 8]. However, the potential impact of varying degrees of arrhythmias, such as supraventricular and ventricular extrasystoles, on the development of CIs appears to have been understudied.

Certainly, severe disturbances in cardiac rhythm and conduction of the heart, such as paroxysmal ventricular tachycardia or complete atrioventricular block, often result in acute disturbances of the central nervous system. These disturbances can manifest clinically as Morgagni-Adams-Stokes attacks. However, the issue of whether extrasystole, frequently occurring in individuals with diverse cardiac conditions, may contribute to the progression of pathological neurological alterations remains a subject of exploration within the contemporary medical field. In this context, it appears particularly pertinent to investigate the potential interconnections between brain function and cardiac activity in individuals experiencing acute MI (AMI). As is well-documented, a wide range of cardiac rhythm and conduction abnormalities are frequently observed among this patient population.

To investigate the clinical and functional relationships between cognitive function, the severity of daytime premature contractions, and echocardiographic parameters in patients with a history of single old MI (OMI) and recent AMI.

Materials and methods

The study was conducted in accordance with the requirements of the Helsinki Declaration of the World Medical Association (2013) and the provisions of biomedical ethics, according to the Geneva Convention on Human Rights (1997), approved by the local ethics committee at the Federal State Budgetary Educational Institution of Higher Education “Saratov State Medical University named after V.I. Razumovsky” of the Ministry of Health of Russia.

A total of 52 patients with coronary heart disease were included in the study. These patients were divided into two groups: the main group and the comparison group. All participants had controlled arterial hypertension and compensated CHF II-III functional class (FC) according to the New York Heart Association (NYHA) functional classification. The main group consisted of 32 patients who had experienced an AMI within the past 7 days. The patients in this group were aged between 42 and 65 years, with an average age of 64 years. Of these, 20 were men and 12 were women. The exclusion criteria for the study were: age over 65, diabetes mellitus, any history of cancer, stroke or transient ischemic attack (TIA), dementia [Mini-Mental State Examination (MMSE) score less than 24], Alzheimer’s disease, hemodynamically significant stenosis of the arteries in the head and neck, sick sinus syndrome, the use of psychoactive substances or alcohol, and any other conditions that the opinion of the researcher, can independently influence the development and/or progression of CI. In this study, patients with atrial fibrillation of any type were excluded (the results of Holter monitoring and all patients’ historical data were carefully analyzed to detect atrial fibrillation) as it is one of the factors contributing to the development/prognosis of cognitive disorders [9]. Additionally, the study did not include patients with MI complicated by cardiogenic shock, acute heart failure, or life-threatening arrhythmias. The comparison group consisted of 20 patients who had suffered a single MI suffered more than one year ago and were aged between 48 and 65 years (with an average age of 57). Of these, 12 were male and 8 were female. The exclusion criteria for this group were similar to those for the main patient group.

In addition to a general clinical examination, all patients underwent echocardiography (ECHO-CG), which assessed the parameters of the right and left heart chambers. These included the left ventricular end-diastolic dimension (LVEDD), the left atrial end-systolic dimension (LAESD), the left ventricular ejection fraction (LVEF), the local myocardial contractility, and the presence of hypokinetic and akinetic zones. The left ventricular mass index (LVMI) and systolic pulmonary artery pressure (sPAP) were also determined.

Electrocardiography (ECG) and 24-hour Holter monitoring were performed to count the total number of premature atrial contractions (PACs) and premature ventricular contractions (PVCs) per day. The daily distribution of these complexes, as well as the number of right- and left-sided PVCs, was recorded. The gradation of PVCs according to the Lown-Wolff classification, the duration of compensatory pauses, and the coupling intervals of PACs and PVCs were also assessed. Finally, the corrected QT interval was measured.

Neuropsychological research methods were used to evaluate cognitive functions. The cognitive functions were assessed via Wechsler Verbal and Nonverbal Scale of Ability (V and VII subtests) and Bourdon test (Dot Cancellation Test). To exclude dementia, the MMSE scale—a brief scale assessing mental status, was used. Holter monitoring and assessment of the patient’s cognitive function were conducted three to four days following the onset of AMI. For the control group of patients, these assessments were also carried out within one day.

Results

The main clinical characteristics of the patient groups are presented in Table 1.

There were no significant differences in the clinical, demographic, physical, or gender characteristics of the patients included in the study (Table 1).

The results of the tests evaluating cognitive functions and the main echocardiographic parameters in patients with AMI and those with a single MI more than one year ago (control group) are presented in Table 2. Analysis of variance revealed a number of significant differences in cognitive test parameters between the patients in the main group and the comparison group. Patients with AMI performed worse on Wechsler Subtests 5 and 7 (p < 0.05). The Bourdon Correction Test showed that the speed and accuracy of their performance, as well as their level of concentration, were lower in patients of the AMI group (p < 0.05). No significant differences were found between the quantitative echocardiographic indicators of the two groups during analysis of variance.

When conducting a canonical correlation analysis on the main group of patients, a statistically significant and sufficiently strong relationship was identified between the indicators of cognitive tests (results of the Wechsler subtests 5 and 7 and the Bourdon correction test) and ECHO-CG parameters (LVMI, LAESD, LVEDD, sPAP) (R = 0.62; p = 0.04). Regarding the comparison group, a similar statistical analysis did not reveal any statistically significant associations between the groups of cognitive test scores and the aforementioned echocardiographic parameters (R = 0.73; p = 0.40). Additionally, through paired correlation analysis using the Gamma coefficient, statistically significant relationships between ECHO-CG features and cognitive test results among patients in the main group were identified. Specifically, LVEF was associated with poorer performance on Wechsler subtests 5 and 7 (R = 0.35 and R = 0.30 respectively), as well as lower concentration, attention switching index, and accuracy index in the Bourdon test (R = 0.20; R = 0.27; R = 0.23, respectively).

A negative correlation was observed between the results of the MMSE test and certain ECHO-CG parameters, such as LVEF, LAESD, sPAP, and the presence of areas of local myocardial contractile dysfunction (R = 0.53; R = –0.22; R = –0.27; R = –0.62, respectively). Additionally, paired correlation analysis revealed weak but statistically significant associations: patients with myocardial akinesia areas performed significantly worse on Wechsler Subtests 5 and 7 than patients with hypokinetic zones of the myocardium (R Gamma = 0.31; –0.34). A negative correlation was also found between the Wechsler subtest 5 score and the LAESD score (R Gamma = –0.34).

In the comparison group, weak statistical associations were identified using paired correlation analysis (using the Gamma coefficient). Patients with lower LVEF demonstrated worse results in attention switching and the accuracy index when performing the Bourdon correction test (R = –0.29; R = 0.27, respectively). The results of the MMSE were worse in patients with areas of impaired local myocardial contractility (R = –0.60).

In addition, within the main group of subjects, statistically significant correlations were identified using paired correlation analysis between higher levels of FC CHF and poorer results on cognitive tests, specifically: lower scores on Wechsler Subtests 5 and 7 (R Gamma = –0.56; –0.45, respectively), lower speed on the Bourdon Correction Test (R Gamma = –0.70), and a lower MMSE score (R = –0.68). It should be noted that among patients in the comparison group, only a single correlation was identified between FC CHF and MMSE scores using this analysis (R = –0.60).

When conducting a multivariate analysis including body mass index (BMI), LVEF, LAESD, LVEDD in the model for the main group of patients, we found the following statistically significant relationships: the worst score on the Wechsler subtest 7 was associated with lower LVEF and larger LAESD (p = 0.0008 and p = 0.034, respectively). However, in the comparison group, the multivariate analysis did not reveal any statistically significant relationships between cognitive test scores and echocardiographic parameters.

Thus, patients with AMI have more severe CI than those with single MI that occurred more than one year ago.

The findings from 24-hour Holter ECG monitoring in patients with AMI did not significantly differ from those of the comparison group. This lack of difference may be attributed to the specific selection criteria for the study, including the exclusion of patients with complicated MI [10]. Additionally, patients with arrhythmias (for example, ventricular tachycardia, atrial fibrillation, and others) were also excluded, as these conditions, according to the literature, can significantly affect the clinical condition and hemodynamics of patients [11].

When conducting a paired correlation analysis in the main group of patients several statistically significant relationships were revealed. Specifically, it was found that the higher the total number of PVCs, both during the day and at night, the lower the MMSE score and the lower the concentration of attention when performing the Bourdon correction test at the 6th minute (R Kendall Tau = –0.42; –0.44; –0.41, respectively; R Kendall Tau = –0.25; –0.33, respectively). The higher the gradation of PVCs according to Lown-Wolf, the lower the MMSE and Wechsler subtest 5 (R = –0.34; R = –0.33, respectively). A greater number of PACs, both during the day and at night, was associated with lower results of the Wechsler subtest 5 (R Gamma = 0.41; 0.35; 0.38). A longer corrected QT interval was associated with the lower MMSE score (R = –0.33).

A multivariate analysis with the inclusion of BMI, LVEF, LAESD, and LVEDD in the model among the main group of patients revealed a statistically significant independent association between the number of PVCs, both during the day and night, and the results of the Wechsler Subtest 7 (p = 0.028). In the comparison group, statistically significant weak correlations were revealed during paired correlation analysis: a greater number of PACs was associated with lower scores on the Wechsler 5 and Wechsler 7 subtests (R Kendall Tau = –0.35; –0.24, respectively). Additionally, the higher number of PACs was correlated with the lower MMSE score (R Gamma = –0.33).

When conducting a multivariate analysis, it was determined that the studied parameters of Holter monitoring, ECHO-CG, and cognitive testing in patients with AMI and single OMI did not significantly depend on the patient’s age, gender, body weight, or height. Therefore, the findings of the study indicate a negative, moderate although statistically significant correlation between the rate of extrasystolic cardiac arrhythmias and cognitive function in patients with AMI.

Discussion

The findings of the study indicate that MI is an independent risk factor for the development and progression of CI, which is in line with previous literature [12, 13]. It has been demonstrated that the severity of cognitive decline depends on the age of MI (acute or old). Specifically, patients who experience acute phase of AMI have a greater degree of cognitive deficit compared to those with the single MI that is more than one year old. Among other factors, extrasystolic heart arrhythmias (PVCs and PACs) may contribute directly to the formation of cognitive dysfunction in patients after AMI. These arrhythmias are typically considered clinically insignificant, but their severity and frequency throughout the day have been linked to the severity of CI. Conversely, in patients with a history of single OMI, premature cardiac contractions are significantly less linked to CI. Therefore, given the lack of substantial differences between the parameters of 24-hour ECG monitoring in both groups of patients, it becomes evident that extrasystoles, which are clinically insignificant in the context of chronic coronary heart disease, in the acute phase of MI can contribute to the development or progression of cognitive deficit.

One of the possible explanations for this phenomenon may be changes in hemodynamics, both intracardiac and systemic, that occur with premature contraction’s heart rhythm disorders. As mentioned above, there is practically no information on studies in the literature of a similar focus. There is only a mention in a few works whose results allow us to assume the nature of pathogenetic interactions between the brain and premature contractions of the heart. In 1999, a research group led by G. Schmidt conducted a study to assess turbulence of heart rhythm, reflecting fluctuations in sinus cycle following PVC (acceleration of sinus rhythm following PVC with subsequent deceleration back to initial values) [14].

Two parameters are proposed: the onset of turbulence (magnitude of sinus rhythm acceleration) and slope of turbulence (intensity of sinus rhythm deceleration). The onset index of turbulence is associated with unrecoverable ion channels in cardiomyocytes at the time of premature ectopic contraction, leading to shortening of an action potential. As a result, it has been established that premature cardiac contractions are associated with incomplete diastolic filling of heart chambers, which leads to a decrease in stroke volume and myocardial contractility according to the Frank-Starling mechanism, causing activation of aortic and carotid baroreceptors and subsequent increase in heart rate. In addition, PVCs are known to be accompanied by a disruption of the synchronous functioning of the ventricles, depending on the location of the PVCs (in the right or left ventricle). Desynchronization of the ventricles contributes to a change in the pressure gradient between them.

Furthermore, intraventricular asynchronism results in a reduction in cardiac output due to the asynchronous contraction of ventricular walls.