Method of predicting risk of cardiac complications after ischemic stroke

FIELD: medicine.

SUBSTANCE: estimation of the heart rate variability is realised by a method of 24-hour Holter monitoring of the 21st day from the moment of ischemic stroke development. After that, the power of a low-frequency spectrum is determined by means of spectral analysis and, if its value is lower than 117 ms2, a high risk of cardiac complications after the ischemic stroke is predicted.

EFFECT: method makes it possible to increase the accuracy of predicting a risk of development of cardiac complications after the ischemic stroke due to the identification of a certain LF value, an independent prognostic factor.

2 ex, 4 tbl, 2 dwg

 

The invention relates to medicine, in particular, to neurology and cardiology in the treatment of patients who have suffered a stroke.

Stroke after coronary heart disease (CHD) is the second most frequent cause of death in the world (C. J. Murray, A. D. Lopez Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 349: 1436-1442). In several large studies and meta-analyses have shown that in patients who have had an ischemic stroke, the frequency of cardiac complications prevails over the frequency of repeated brain disorders (E. Touze et al. Risk of myocardial infarction and vascular death after transient ischemic attack and ischemic stroke: A systematic review and meta-analysis. Stroke 2005; 36: 2748-2755; M. S. Dhamoon et al. Recurrent stroke and cardiac risks after first ischemic stroke: The Northen Manhattan Study. Neurology 2006; 66: 641-646). Stroke is considered as an independent prognostic factor for cardiac events on a par with coronary artery disease, diabetes mellitus (DM), peripheral atherosclerosis, etc. (S. Chaturvedi stroke Should be considered both a brain attack and a heart attack? The Stroke. 2007; 38: 1713-1714; M. S. Dhamoon, M. S. Elkind Inclusion of stroke as an outcome and risk equivalent in risk scores for primary and secondary prevention of vascular diseases. The Circulation. 2010; 121: 2071-2078). So, in one study, for 2 years after stroke was found a significant increase in the risk of myocardial infarction (mi) even in the absence of clinical manifestations of CHD (Towfighi, A. et al. Utility of the Framingham coronary heart disease risk score for predicting cardiac risk after stroke. Stroke. 2012; 43: 2942-2947).

� most patients with ischemic stroke, there is a concomitant latent or manifest coronary atherosclerosis, which may explain the increased risk of coronary complications in the post-stroke period (Amarenco P. et al. Prevalence of coronary atherosclerosis in patients with cerebral infarction. The Stroke. 2011; 42: 22-29). Another probable prognostic factors for cardiac events is called direct cerebral damage, and one of the possible mechanisms of its implementation can be a persistent disorder of autonomic regulation of heart rhythm (Robinson T. G. et al. Cardiac baroreceptor sensitivity predicts long-term outcome after acute ischemic stroke. Stroke 2003; 34: 705-712). Heart rate is the best indicator of changes in the state of the autonomic nervous system, therefore, the study of heart rate variability (BCP) as an indicator of Autonomous regulation, and impact on cardiac prognosis after ischemic stroke, are of practical importance (Makikallio A. M. et al. Heart rate dynamics predict poststroke mortality. Neurology 2004; 62: 1822-1826).

Studies of heart rate variability (BCP) in ischemic stroke as a predictor of risk of sudden cardiac death (BCC) was largely limited to the study of the effect of localization of brain lesions on the state of the autonomic nervous system (S. L. Tokgozoglu et al. Effect of stroke localization on cardiac autonomic balance and sudden death. Stroke 1999; 30: 1307-1311). The design of the research was based on the hypothesis that topical features cerebral semices�wow lesions cause rough down the sympatho-vagal interactions, that may be associated with the development of cardiac arrhythmias. It is shown that involvement in the defeat of the right hemisphere of the brain, especially the right islet greatly increases the likelihood of sudden cardiac death (Naver N. K. et al. Reduced heart rate variability after right-sided stroke. Stroke 1996; 27: 247-251). In another prospective study BCC and ROME were more often registered in the group of patients with ischemic stroke and the defeat of the left island (S. Laowattana et al. Left insular stroke is associated with adverse cardiac outcome. Neurology. 2006; 66: 477-483). In increased mortality (cardiovascular and other causes) in the distant post-stroke period was also identified prognostic role of reduction of an indicator BCP, as the standard deviation of normal RR-intervals (SDNN) (F. Colivicchi et al. Prognostic implications of right-sided insular damage, cardiac autonomic derangement, and arrhythmias after acute ischemic stroke. Stroke 2005; 36: 1710-1715).

It should be noted that the main goal for the majority of the work was to demonstrate an independent effect of lesions of brain structures on the state of the BCP and post-stroke prognosis. Therefore, these studies have had stringent criteria, for example did not include patients with recurrent stroke, diabetes, previous cerebral changes, cardiac arrhythmias, respiratory problems. However, most patients with ischemic lesion th�IOD of the brain revealed a concomitant cardiac, broncho-pulmonary, endocrine pathology, the presence of stroke in anamnesis that can have an influence on the course of post-stroke period and the survival of patients.

As a prototype we used the work Makikallio A. M. et al. "Heart rate dynamics predict poststroke mortality". Neurology 2004; 62: 1822-1826, where in patients after stroke within a 7-year prospective study analyzed all causes of death, including cardiac disorders. In the study of temporal and spectral characteristics of BCP identified the importance of reducing the logarithmic derivative of the composite spectrum is very low (VLF) and ultra low frequency (ULF) BCP as a predictor of increased mortality in the distant post-stroke period. However, the study patients were selected only with the first stroke, not having other cerebrovascular disease. Was evaluated only fatal cases. Logarithmic derivative of the composite spectrum of the VLF and ULF were studied only in relation to mortality in different categories studied, including healthy individuals and cardiac patients (J. T. Bigger Jr. et al. Power law behavior of RR-interval variability in healthy middle-aged persons, patients with recent acute myocardial infarction, and patients with heart transplants. Circulation 1996; 93: 2142-2151). In addition, physiological interpretation and prognostic value of the actual low-frequency components of the BCP (VLF and ULF) are unknown and require further and�exercise (heart rate Variability. Standards of measurement, physiological interpretation and clinical use. The working group of the European society of Cardiology and the North American society of pacing and electrophysiology., Bulletin of Arrhythmology, 1999; 11: 53-78).

With this background, the need arose of finding a universal predictor of increased risk of any cardiac events after ischemic stroke to personalize preventive measures and improve long-term prognosis of the disease.

The technical result of the invention is highly informative and versatility predict the risk of cardiac 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 in that the patient on day 21 of ischemic stroke with daily continuous Holter monitoring (HM) perform spectral analysis of BCP and evaluate the values of the power at low frequencies (LF). When identifying power bass<117 MS2predict high risk for cardiac events after ischemic stroke and carry out a correction of drug therapy for the prevention of heart problems.

Method OS�Westlake as follows. All patients on day 21 of ischemic stroke was performed daily migraine with the BCP assessment by spectral analysis. Analysis in the frequency domain (power spectral density) shows periodic oscillations of the signals of heart rate in the context of different frequencies and amplitudes; and also provides information about the relative intensity fluctuations (called variation or power) of the sinus rhythm of the heart. Power in the low frequency range reflects the low frequency component of the BCP that characterizes sympathetic tone. For the spectral analysis used domestic cardioregulatory "Cartotecnica 4000" and "Cartotecnica-04 (INCART, St. Petersburg) with three-channel ECG recording (leads V4, Y, V6). When detected at 21 days from the date of ischaemic stroke power bass<117 MS2was diagnosed with high risk for cardiac events after ischemic stroke and had taken the necessary measures for their prevention. Thus, the use of the power values of LF<117 MS2as a universal prognostic factor for cardiac events may be promising for the personification of preventive measures and improved prognosis of a patient's life.

Only observation was included 148 patients with ischemic stroke; of these, 94 64%) males and 54 (36%) women. The age of patients at the time of inclusion in the study ranged from 22 to 83 years; mean age was 60±14 years. Atherothrombotic stroke was diagnosed in 56 (38%) patients, cardioembolic - 38 (26%), lacunar - in 42 (28%) patients. In 5 (3%) patients were found to have other refined subtypes (hemodynamic and hemorheological microinclusion), 7 (5%) patients the cause of stroke has not been clarified (cryptogenic stroke). Available in patients with concomitant cardiovascular disease are presented in table 1.

All patients underwent daily Holter performed using a wearable portable monitor with continuous recording of ECG within 24 hours. To exclude acute cerebrogenic effects on BCP HMM was carried out on 21-22 days from the time of stroke. Used domestic cardioregulatory "Cartotecnica 4000" and "Cartotecnica-04 (INCART, St. Petersburg) with three-channel ECG recording (leads V4, Y, V6). Implemented continuous recording during the whole observation time providing visual information about the ECG anywhere in the record.

Table 1.
Diseases of the cardiovascular system
The disease cardio-vessel�stop system The number of patients (%)
Hypertension129 (87%)
Atherosclerosis124 (84%)
Chronic heart failure87 (59%)
Coronary heart disease49 (33%)
Paroxysmal atrial fibrillation34 (23%)
Diabetes mellitus32 (22%)
Stroke in anamnesis26 (18%)
Heart disease (rheumatic, degenerative)20 (14%)
Mitral valve prolapse, patent foramen ovale18 (12%)
Infectious endocarditis4 (3%)

Using spectral analysis BCP in accordance with the recommendations of the working group of the European society of cardiology and North American society of pacing and electrophysiology (heart rate Variability. Standards of measurement, physiological interpretation and clinical use. Working GRU�PA European society of Cardiology and the North American society of pacing and electrophysiology. Bulletin of Arrhythmology 1999; 11: 53-78) based on 24-hour ECG recording in the present work analyzed the spectral characteristics of the BCP, such as power (MS2) in the range of high frequencies (HF, 0.15 to 0.4 Hz, the average level of parasympathetic activity of the regulation), low-frequency oscillations (LF, 0.04 to 0.15 Hz, the average activity level of the sympathetic and parasympathetic link).

Computer statistical processing of the obtained results was performed using the software package STATISTICA 7.0 (StatSoft, USA). To identify predictors of adverse outcome of the disease curves were constructed the time of the occurrence of cardiac complications (Kaplan-Meier) and was also used regression analysis in the Cox proportional hazard models. Multivariate analysis was preceded by a one-factor. In multivariate analysis included variables for which values of the criterion of statistical significance in the univariate analysis amounted to <0,05. Multivariate regression analysis was performed step-by-step method. Statistically significant differences were considered when p values<0,05.

When comparing the values of the median, 25 - and 75-percentiles of performance woofers in patients undergoing (1) and not endured cardiac complications (0), set the threshold parameter - LF≤117 MS2. (Fig.1).

Further analysis of survival of patients without cardiac complications (Kaplan-Meier) depending on the values of LF to assess the predictive role of threshold. As "cutting points" of quantitative traits were selected values of variables, providing the optimal balance of sensitivity and specificity. Selected adverse prognostic variables were included in univariate regression analysis was made of those for which the relationship with unfavorable outcome was most pronounced. To identify risk factors were constructed time curves of unfavourable outcome (Kaplan-Meier). The proportion of patients without cardiac complications in the post-stroke period depending on the performance LF power spectrum shown in figure 2.

As can be seen, the divergence of the curves characterizing a 50% proportion of patients free from cardiac complications, as compared to less bass 117 MS2occurred significantly earlier. In other patients with LF is equal to or more than 117 MS2the complication rate was significantly lower and did not exceed 29% with continued follow-up (up to 10 years).

The duration of a prospective study after ischemic stroke ranged from 1 year to 10 years, averaged 35±12 months. During the observed� " s 17 (11,5%) patients registered 19 cardiac complications (tab.2).

Table 2.
Cardiac complications for the period of prospective study
Cardiac complicationsThe number of cases (Σ=19)
Unstable angina7
Acute heart failure5
Myocardial infarction4
Sudden cardiac death3

For benchmarking was received by a number of qualitative differences between patients who underwent cardiac complications and without them. To clarify the prognostic significance using univariate analysis for each trait was calculated relative risk (RR) of cardiac complications and obtained statistically significant values, p-values and confidence intervals (CI) (table.3).

Table 3.
Prognostic factors and relative risk of cardiac complications after stroke
IndexThe PRp95% CI
Age >67of 1.740,005-0,03-1,00
The defeat of the island3,140,009-0,85-3,139
Stroke in anamnesis2,3120,040,08-1,6
Power WOOFER <117 MS20,460,0040,24-0,889
The power of the HF <43 MS20,550,02from 0.3 to 0.98

Clearly, 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 Cox proportional hazard models to determine independent predictors of cardiac events after ischemic stroke based on the identified predictors according to univariate analysis. Also carried out the adjustment of patients according to the duration of the observation�tion, gender, subtype of stroke, get medical therapy, the presence of hypertension, diabetes, ischemic heart disease, chronic heart failure, atrial fibrillation and atherosclerosis, (PL.4).

Table 4.
Multivariate analysis of prognostic factors for cardiac events in post-stroke period

IndexBetaStandardt-valueexponentWaldp
Age >670,971250,535041,815282,6412433,29520,0694
The defeat of the island0,983960,604481,627782,6750342,64960,1035
Stroke in anamnesis0,83594 0,574421,455272,3069862,11780,1456
Power WOOFER <117 MS2-1,92010,50199-2,374560,3036115,63850,0175
The power of the HF <43 MS2-0,549490,64218-0,855670,5772400,73210,3921

The table columns contain the values of the following parameters of the Cox model: 1. Beta - coefficient (measurement) when the relevant factor in the regression equation. The value of the coefficient is the contribution of the corresponding factor in the cumulative risk. 2. Standard - the standard error of the coefficient estimates. 3. t-value - value of the t-criterion for the estimate of the coefficient (the ratio of the estimate of the coefficient to its standard error). 4. exponent - value exp(Beta) - values of the relative risk associated with a change factor of n units. 5. Wald - value of the Wald criterion for the estimate of the coefficient. 6. p - value the probability of error of the coefficient estimates.

The results of the multivariate analysis by Cox (table 4) show�Lee, during the assessment of the impact on the increased risk of cardiac complications in multivariate models only statistically significant (p=0,0175) was the effect of power bass<117 MS2.

Thus, the power values of LF<117 MS2are independent prognostic factor for cardiac events after ischemic stroke. Prognostic value of power bass<117 MS2persisted after the introduction of amendments to other risk factors, i.e. is an independent predictor of increased risk of cardiac complications after stroke.

An example implementation of the method:

Example 1: Patient G., aged 59, had an acute ischemic stroke in the atherosclerosis of cerebral vessels. On the 21st day from the date of ischaemic stroke was conducted HMM daily. According to the results of the LF power was 57 MS2that equates to a high risk of cardiac complications in the post-stroke period. After discharge from hospital the patient received antihypertensive and antithrombotic drugs. After 10 months, suffered acute myocardial infarction. Was hospitalized, where the basic treatment added lipid-lowering drugs (statins). In the next 2 years of follow-up cardiac complications were not registered.

Example 2: Patient M., 63, suffered an acute ischemic cerebrovascular disease on the background of diabetes mellitus and chronic heart failure. On the 21st day from the date of ischaemic stroke was conducted HMM daily. According to the results of the LF power amounted to 249 MS2that was consistent with a low risk of cardiac complications in the post-stroke period. After discharge from hospital the patient was on basic drug therapy. Within 3 years of prospective study of cardiac complications the patient is not registered.

Thus, there is the ability to predict the risk of cardiac complications method HMM daily using automated spectral analysis of the BCP and the study of the power spectrum of LF to 21 days from the date of ischaemic stroke. The use of inexpensive standard methods for the given conditions allows to identify patients with increased risk of cardiac complications in the post-stroke period. The proposed method HMM daily with automatic spectral analysis of the BCP and the study of LF power spectrum is informative in the prediction of the risk of cardiac complications, which will help to optimize the management of the patient in the post-stroke period to improve cardiovascular prognosis.

Method prog�of Osinovaya risk for cardiac events after ischemic stroke namely that patients underwent assessment of heart rate variability (HRV), characterized in that the evaluation of HRV is carried out by a method of daily Holter monitoring in 21 days from the date of ischaemic stroke, then use spectral analysis to determine the low-frequency power spectrum and when the value is less 117 MS2predict a high risk of cardiac complications after stroke.



 

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EFFECT: providing the more effective differential diagnostics of cardiogenic myocardial ischemia and ileocecal-cardial inhibitory reflex with underlying ileocecal patency.

1 ex

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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

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1 tbl, 4 ex

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3 dwg

FIELD: medicine, cardiology.

SUBSTANCE: one should register a standard electrocardiogram (ECG) and measure the duration of a "P"-wave. Moreover, it is necessary to conduct daily ECG monitoring to calculate single, paired and group atrial extrasystoles. Then one should calculate diagnostic coefficient DC by the following formula: DC=DC1+DC2+DC3+DC4, DC1 =-8.8 at duration of "P"-wave below 106 msec, 9.3 at duration of "P"-wave above 116 msec, -3.5 at duration of "P"-wave ranged 106-116 msec. DC2=-1.9 at the absence of group atrial extrasystoles during a day, 8.3 -at daily quantity of group atrial extrasystoles being above 4, 2.5 - at daily quantity of group atrial extrasystoles ranged 1-4. DC3=-2.9 at daily quantity of paired atrial extrasystoles being below 3, 8.1 - at daily quantity of paired extrasystoles being above 35, -1.4 - at daily quantity of paired atrial extrasystoles ranged 3-35. DC4=-5.1 at daily quantity of single atrial extrasystoles being below 15, 4.3 - at daily quantity of single atrial extrasystoles being above 150, -1.0 - at daily quantity of single atrial extrasystoles ranged 15-150, if DC is above or equal to 13 one should diagnose high risk for the development of paroxysmal atrial fibrillation, in case if DC is below or equal -13 it is possible to diagnose no risk for the development of paroxysmal atrial fibrillation, and if DC is above -13 and below 13 - the diagnosis is not established.

EFFECT: higher sensitivity of diagnostics.

5 ex

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