Method for prediction of risk of cardiovascular complications following ischemic stroke

FIELD: medicine.

SUBSTANCE: heart rate variability is assessed. The assessment procedure involves 24-hour Holter monitoring on the 21st day from the moment of the ischemic stroke occurred. And if observing brady-arrhythmias presented by degree 2-3 atrio-ventricular block or degree 2-3 sinoatrial block and sinus pauses of more than 2 sec long, a high risk of cardiovascular fatal complications following the ischemic stroke is predicted.

EFFECT: method provides the high informative and flexible prediction of the risk of cardiovascular fatal complications following the ischemic stroke in the patients with cerebrovascular, cardiac, endocrine comorbidities.

3 tbl, 3 ex

 

The invention relates to medicine, in particular, neurology and cardiology in the treatment of patients with stroke.

Stroke due to high levels of mortality and disability of patients represents a major problem in modern medicine. Stroke after coronary heart disease (CHD) is the second most common cause of death worldwide (Murray C. J., Lopez A. D. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 349:1436-1442). Mortality of stroke patients in the early stages (30-day) reaches 32-42%, and in the first year after onset of the disease increases to 48-63% (Suslin H. A., Varakin Y. Y., Vereshchagin N. In. Vascular brain disease: Epidemiology. The basics of prevention. M, Medpress-inform, 2006. - 256 S.). In several large studies have shown that in patients after ischemic stroke are the leading causes of death from cardiac causes (Broderick J. P., Phillips, S. J., OTallon W. M. et al. Relationship of cardiac disease to stroke occurrence, recurrence, and mortality. Stroke 1992; 23:1250-1256; M. S. Dhamoon et al. Risk of myocardial infarction or vascular death after first ischemic stroke. Stroke 2007; 38:1752-1758). The reason is that most patients with ischemic stroke detected associated cardiac pathology: CHD, revocandi different etiology, the vices and disorders of heart rhythm (D. Bartko et al. The heart and the brain. Aspects of their interrelations. Vnitr Lek. 1996; 42:482-489). It is also expected that in jivamukti after stroke is affected by the dysfunction of the autonomic regulation of the heart (Robinson T. G. et al. Cardiac baroreceptor sensitivity predicts long-term outcome after acute ischemic stroke. Stroke 2003; 34:705-712).

From a clinical point of view the direct cause of cardiac death in the General clinical practice are cardiac arrhythmias: ventricular tachyarrhythmias and bradyarrhythmia (Kuller L., Lilienfeld A. An epidemiological study of sudden and unexpected deaths in adults. Medicine 1967; 46:341). The cause of cardiac arrest is called the primary atrial ventricular paroxysmal ventricular tachycardia and primary asistoliei (Bayes de Luna A., Guindo Soldevila J. Sudden cardiac death. MCR, Barcelona, 1989).

Reports about the prognostic value of life-threatening ventricular arrhythmias in patients with ischemic stroke not numerous (Lown C., Verrier, R. L. Neural activity and ventricular fibrillation. N. Engl. J. Med. 1976; 294:1165-1170; Limacina I. N. Cerebrocortical syndrome. Bulletin of Arrhythmology, 2009; 58:26-34). It was shown that the presence of ventricular arrhythmias in patients with ischemic stroke is associated with increased mortality (Davis A. M., A. M. Natelson Brain-heart interaction. The neurocardiology of arrhythmia and sudden cardiac death. Those. Heart. Inst. J. 1993; 20:158-169; Colivicchi F. et al. Prognostic implications of right-sided insular damage, cardiac autonomic derangement, and arrhythmias after acute ischemic stroke. Stroke 2005; 36:1710-1715). However, these studies included only patients in the acute phase of ischemic stroke, and evaluated the risk of sudden cardiac death. At the same time in the distant post-stroke period, the reasons for the deaths can be also repeat the haunted brain disorders.

As a prototype we have used the work Colivicchi F. et al. Prognostic implications of right-sided insular damage, cardiac autonomic derangement, and arrhythmias after acute ischemic stroke. Stroke 2005; 36:1710-1715. Authors within 1 year, conducting surveillance of patients undergoing first stroke, followed by analysis of prognostic significance in relation to risk of death indicators of heart rate variability (HRV) and unstable ventricular tachycardia. In the multivariate analysis identified the adverse prognostic significance of reducing the standard deviation of the R-interval (SDNN) of less than 100 MS and unstable ventricular tachycardia in relation to increased mortality (cardiovascular and due to other reasons) for 1 year after a stroke.

It should be noted that the main aim of this study was to demonstrate an independent effect of destruction of certain brain structures (right island) on post-stroke prognosis. Therefore, these studies have had strict selection criteria. So, included patients only with the first stroke, a cerebral ischemic lesion, absence of diabetes mellitus (DM), cardiac or pulmonary pathology, clinically significant arrhythmias. However, this sample of patients does not reflect the real situation, with the seat in everyday clinical practice. In addition, it is shown that the increased risk of fatal cardiovascular complications after a stroke is stored not only in the first year, and over longer periods of time (Makikallio A. M. et al. Heart rate dynamics predict poststroke mortality. Neurology 2004; 62:1822-1826).

Given these circumstances, there is a need of finding a universal predictor of increased risk of cardiovascular fatal complications such as sudden death after ischemic stroke in a real patient, burdened with previous cerebrovascular, cardiac, endocrine diseases to personify preventive measures and improve remote prognosis of the disease and increase life expectancy of the patient.

The technical result of the invention is highly informative and versatility of the risk prediction of cardiovascular fatal complications after ischemic stroke in patients with concomitant cerebrovascular, cardiac, endocrine diseases at an early stage of the disease (21 days from the time of stroke).

The technical result is achieved by the fact that for predicting the risk of cardiovascular fatal complications after ischemic stroke patient, assess the heart rate variability by daily Holter monitoring (HM) n is 21 days from the date of development of ischemic stroke and bradyarrythmia in the form of atrioventricular block grade 2-3 or sinoatrial blockade 2-3 degrees and sinus pauses longer than 2 seconds forecast high risk of cardiovascular fatal complications after ischemic stroke.

The method is as follows. All patients with ischemic stroke and concomitant cerebrovascular, and/or cardiac and/or endocrine diseases to identify the risk of cardiovascular fatal complications after ischemic stroke spend HMM daily for 21 days from the date of development of ischemic stroke. To conduct HMM used domestic cardioregulatory "Cartotecnica 4000" and "Cartotecnica-04 (INCART, St. Petersburg) with the three-channel ECG recording (lead V4, Y, V6). Upon detection of bradyarrythmia in the form of atrioventricular (AV) blockade 2-3 degree or sinoatrial (SA) blockade of 2-3 degrees and sinus pauses longer than 2 seconds predict a high risk of cardiovascular fatal complications after ischemic stroke. Based on these data, carry out the necessary measures for the timely removal of bradyarrythmia, such as the implantation of the electric car of biostimulator mode "on demand" with a pulse frequency of 60 beats per minute.

Thus, using the presence of bradyarrythmia as a universal prognostic factor of cardiovascular fatal complications is promising to improve the life prognosis of patients who NTA.

Only observation was included 148 patients with ischemic stroke; of these, 94 (64%) males and 54 (36%) women. Patient age at the time of inclusion in the study ranged from 22 to 83 years, on average - 60±14 years. Available in patients with concomitant cardiovascular pathology are presented in table 1.

Heart disease (rheumatic, degenerative)
Table 1
Diseases of cardiovascular system in patients with ischemic stroke
Disease of cardiovascular systemThe number of patients (%)
Hypertension129 (87%)
Atherosclerosis124 (84%)
Acute disorders of cerebral circulation in history26 (18%)
Chronic heart failure87 (59%)
Ischemic heart disease49 (33%)
Paroxysmal form of atrial fibrillation34 (23%)
Diabetes mellitus32 (22%)
20 (14%)
Mitral valve prolapse, open oval window18 (12%)
Infectious endocarditis4 (3%)

All patients underwent daily HMMM performed using a wearable portable monitor with a continuous recording of ECG within 24 hours. To exclude acute cerebrogenic influences on HRV HMM was performed on the 21st day from the moment of the stroke. Used domestic cardioregulatory "Cartotecnica 4000" and "Cartotecnica-04 (INCART, St. Petersburg) with the three-channel ECG recording (lead V4, Y, V6). Implemented continuous recording during the whole observation time providing visual information about the ECG anywhere in the record.

On the basis of 24-hour ECG recording studied all heart rhythm disturbances and the state of HRV. Episodes of transient AV block grade 2-3 or SA blockade 2-3 degree, sinus pauses longer than 2 seconds were classified as bradyarrhythmia.

Computer statistical processing of the obtained results was carried out on the basis of the software package STATISTICA 7.0 (StatSoft, USA). To identify predictors of adverse outcome (fatal complications) was the curves of time of occurrence of cardiovascular death (according to the method of Kaplan-Meier), and we used a regression analysis models the proportional risk of Coke. Multivariate analysis was preceded by a one-factor. In multivariate analysis included variables for which the values of the criterion of statistical significance in univariate analysis was <0,05, as well as characteristics that could be associated with the study outcome according to previous studies. Multivariate regression analysis was carried out step-by-step method. Statistically significant differences were considered when p<0,05.

The duration of the prospective follow-up ranged from 1 year to 10 years, averaged 35±12 months. During the observation time in 15 (10%) patients registered cardiovascular death (table.2).

3
Table 2
Causes of cardiovascular death during the period of prospective follow-up
Causes of cardiovascular deathThe number of deceased patients (n=15)
Re ischemic stroke7
Acute heart failure3
Sudden cardiac death
Acute myocardial infarction2

When comparative analysis was obtained a number of qualitative differences between survivors and deceased patients. To clarify the prognostic significance using univariate analysis was calculated relative risk of cardiovascular fatal complications and it is shown that with the increase associated with age of 67 years, SDNN <71 MS and the presence of bradyarrythmia.

It is obvious that the influence of prognostic factors may be in some cases combined and overlap, while their presence in one patient. Why was performed multivariate analysis using models is proportional to the risk of Coke to determine independent factors high risk of cardiovascular fatal complications after ischemic stroke based on identified predictors according to univariate analysis (age of 67 years and the presence of bradyarrythmia). Also carried out the adjustment of patients according to the duration of the observation, gender, stroke in history, received medical therapy, presence of hypertension, diabetes, ischemic heart disease, chronic heart failure, atrial fibrillation and atherosclerosis. When assessing the impact on the increased incidence of cardiovascular deaths in many of the factor models, the most significant and the only statistically significant was the impact of bradyarrythmia (p=0,044976).

Table 3
Prognostic factors associated with cardiovascular fatal complications in the post-stroke period
BetaStandardt-valueexponentWaldP
Age >670,7726170,5463841,414062,1654261,9995530,157355
The bradyarrhythmia1,4613530,7288682,004964,3117894,0198690,044976
SDNN <71 MS0,1484260,7689990,193011,1600060,0372530,846951

Thus, bradyarrhythmia in the form of atrioventricular block grade 2-3 or sinoatrial blockade 2-3 degrees and sinus pauses lifespan is using more than 2 seconds are an independent risk factor for cardiovascular fatal complications in the distant post-stroke period. Prognostic value of bradyarrythmia persists after adjustment for other prognostic factors, i.e., is an independent factor high risk of cardiovascular fatal complications after ischemic stroke.

Examples of implementation of the method

Example 1: the Patient Z., 72 years old, underwent acute ischemic stroke on the background of arterial hypertension and coronary heart disease: postinfarction cardiosclerosis. On the 21st day from the moment of development of ischemic stroke was conducted daily HMMM. According to his results were detected bradyarrhythmia three episodes SA blockade of 2 degrees with periods of sinus pauses up to 2.2 seconds. These data were factor 8 increased risk of cardiovascular fatal complications after ischemic stroke. The patient was offered surgery to implant a pacemaker, which the patient refused. After discharge from hospital the patient was on the basis of antihypertensive, antithrombotic, and lipid-lowering therapy. However, this therapy has not been sufficient to prevent fatal complications, and after 16 months, the patient died as a result of repeated extensive stroke on the background of bradyarrythmia.

Example 2: the Patient M, 69, suffered acute ischemic stroke on the background paroxysmal form of atrial fibrillation. At 21 days the t stage of ischemic stroke was conducted daily HMMM. According to the results of the episodes bradyarrythmia not found that testified in favor of the absence of risk of cardiovascular fatal complications after ischemic stroke. After discharge from hospital the patient was on the basis of drug therapy, including therapy with oral anticoagulants. Within 4 years prospective follow-up the patient is alive, cardiovascular disorders is not registered.

Example 3: Patient U., 76 years, suffered repeated ischemic stroke on the background of diabetes mellitus and chronic heart failure. On the 21st day from the moment of development of ischemic stroke was conducted daily HMMM. Results revealed bradyarrhythmia in 7 episodes of AV block 2nd degree with periods of sinus pauses up to 2.8 seconds. This was a factor in increased risk of cardiovascular fatal complications after ischemic stroke. The patient was implanted with a pacemaker mode "on demand" with a frequency of 60 pulses per minute. After discharge from hospital the patient carefully follows all the recommendations. Within 3 years prospective follow-up of recurrent fatal cardiovascular complications the patient has not occurred.

Thus, in comparison with the known method of assessing HRV in patients with first stroke without accompanying for the of olivani have the opportunity to predict the risk of cardiovascular fatal complications HMM method with analysis of bradyarrythmia. The use of inexpensive methods for standard specified conditions allows us to predict the risk of cardiovascular fatal complications such as death in the post-stroke period in patients with different comorbidities already 21 days from the date of development of ischemic stroke. The proposed method daily CHILLER with automatic analysis of bradyarrythmia is informative and universal in predicting the risk of cardiovascular fatal complications that can help to optimize the management of the patient post-stroke period to increase the duration of his life.

A method for predicting the risk of cardiovascular fatal complications after ischemic stroke, namely, that the patient assess heart rate variability, characterized in that the evaluation of heart rate variability is carried out by daily Holter monitoring in 21 days from the date of development of ischemic stroke and bradyarrythmia in the form of atrioventricular block grade 2-3 or sinoatrial blockade 2-3 degrees and sinus pauses longer than 2 seconds predict a high risk of cardiovascular fatal complications after ischemic stroke.



 

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5 ex

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