RU2744354C1 - METHOD FOR DETERMINING THE NORMAL AND PATHOLOGICAL REACTION OF THE CORRECTD QTc INTERVAL DURING EXERCISE TESTING - Google Patents

Abstract

FIELD: cardiology/functional diagnostics.

SUBSTANCE: invention relates to medicine, namely to cardiology, to functional diagnostic. Measurement of QT interval is carried out, QTc is calculated according to A. Sagie's formula. Based on the data obtained, a regression line is plotted on the graph according to the formula QTc = a(RR)+b, where a is the slope coefficient, b is the shift coefficient (intercept), and the dependence of the QTc duration on the RR interval is estimated. When the QTc interval is "shortened" in response to a decrease in the RR interval (a> -0.079), the QT response is considered normal. When the QTc interval is “lengthened” (a -0.079), the reaction is considered pathological.

EFFECT: method improves accuracy of detecting the latent syndrome of the shortened QT interval or the latent syndrome of the extended QT interval in patients with normal or borderline QTc values ​​on the resting electrocardiogram.

1 cl, 5 dwg, 2 tbl, 1 ex

Description

The invention relates to medicine, in particular to cardiology, to functional diagnostics and can be used to identify syndromes of an extended and shortened QT interval.

Sudden cardiac death (SCD) is currently an urgent problem throughout the world. Every year 17 million people die from cardiovascular diseases worldwide, of which 25% are from sudden cardiac death (SCD). In Russia, 200–250 thousand people die from WSS annually [1].

[3] Однако это не единственный метод для вычисления QTc. В 1920 году, почти одновременно с Н.С. Bazett, L.S. Fridericia предложил свой метод вычисления:

[4]For patients with cardiovascular diseases, changes in the repolarization processes in the myocardium are of great prognostic importance [2]. One of the significant causes of SCD is a change in the duration of the QT interval - both its lengthening and shortening. However, it is known that the QT interval depends on the heart rate (HR). Normally, with an increase in heart rate, the QT interval shortens, and with a decrease in heart rate, it lengthens. In this regard, to assess the QT interval, not absolute values are used, but corrected by heart rate, bringing its value to a heart rate of 60 beats per minute. The generally accepted formula for calculating the corrected QT interval (QTc) is N.C. Bazett:

[3] However, this is not the only method for calculating QTc. In 1920, almost simultaneously with N.S. Bazett, LS Fridericia proposed his own calculation method:

[four]

Later, linear formulas for calculating QTc were proposed:

A. Sagie: QTc = QT + 0.154 * (l-RR) (where QTc is the corrected QT interval, QT is the measured QT interval, RR is the distance between two subsequent QRS complexes in seconds) [5]

M. Hodges: QTc = QT + 1.75 (HRC-60) (QT in ms, HR in beats per minute), [6]

J. Karjalainen: for heart rate <60 beats per minute QTc = 392 * (QT) / (0.116 * (R-R) +277), [7]

- for a heart rate of 60-100 beats per minute QTc = 392 * (QT) / (0.156 * (R-R) +236),

- for heart rate> 100 beats per minute QTc = 392 * (QT) / (0.384R-R) +99).

According to the recommendations of the European Society of Cardiology for the treatment of patients with ventricular arrhythmias and the prevention of sudden cardiac death, long QT interval syndrome (LQT) is established by the QTc values determined by the formula of N.S. Bazett, in the following cases [8]:

1. When QTc≥480 ms is detected on 12-channel ECG, re-registration

2. The diagnosis should be considered in the presence of a corrected QT interval ≥460 ms upon repeated recording of a 12-lead ECG in patients with syncope of unknown origin or documented VT / FT in the absence of heart disease.

3. The diagnosis of long QT interval syndrome is made in the presence of a confirmed pathological LQTS mutation, regardless of the duration of the QT interval.

Thus, we can say that the LQT diagnosis is established only with a significant lengthening of QTc (more than 480 ms), or in the presence of clinical manifestations - ventricular tachycardia or SCD in patients with moderate QTc prolongation (460-480 ms). This approach is understandable, but it cannot suit practical health care, since not all patients can survive SCD and a single attack of ventricular fibrillation can be the last for a patient. The detection of a pathological LQTS mutation in patients with low QTc values may rather become an accidental find, since this study cannot be performed in a screening format and is currently inaccessible for practicing physicians.

In 2015, the Federal Medico-Biological Agency of Russia adopted a protocol for assessing the QTc interval in children and adolescents, where normal values were determined at QTc = 370-439 ms, LQT syndrome at QTc≥480 ms, shortened QT interval syndrome (SQT) at QTc≤ 340 ms. QTc in the interval 341-369 ms and 440-479 ms turned out to be in the gray zone of uncertainty and, obviously, patients with such values should be examined additionally.

There are many factors that trigger syncope in LQT patients, of which physical activity is the cause of loss of consciousness in almost 50% of cases. It is most optimal to assess the change in repolarization with significant changes in heart rate values [9]. In this regard, a number of authors propose to use an exercise test to diagnose LQT and SQT syndromes in patients with indefinite QTc values [10]. In one study, patients with long QT syndrome underwent a fast verticalization test. It was found that with a change in the position of a person's body from horizontal to vertical, an increase in heart rate occurred, while in the group of persons with prolonged QT interval syndrome, an increase in the QTc interval (calculated using the Bazett formula) was recorded, and in the control group of healthy persons, a shortening of QTc was observed (calculated using formula Bazett) [11]. Exercise testing also differentiates variants of the LQT syndrome [12]. Thus, it can be assumed that carrying out an exercise stress test in this group of individuals will provide an answer to the question of whether the patient will develop life-threatening rhythm disturbances (ventricular tachycardia, ventricular fibrillation) and SCD. However, when performing an exercise test, doctors are faced with the problem of measuring and assessing QT. It is known that the formula of N.S. To calculate QTc, Bazett can only be used in the heart rate range of 50-90 beats per minute, that is, in fact, with normosystole, while during stress tests, it is necessary to calculate and analyze QTc with significant tachycardia [13].

In the work of A. Benatar and T. Decraene, it was shown that during the exercise test, the maximum QTc value was detected at the peak of the load when calculating QTc using the Bazett and Hodges formulas, and the maximum QTc value calculated using the Fridericia and Sagie formulas was detected at rest [14]. The results of this work showed the relevance of the choice of the formula for calculating QTc when carrying out load tests.

We analyzed the results of calculating the QT interval according to various formulas for calculating the corrected QT interval (QTc) when conducting tests with dosed exercise.

When measuring the duration of the QT interval during tachycardia manually, it is very difficult to accurately determine the end of the T wave. We used the method of E.V. Lepeshkin and B.K. Suravitsa (slope method -slope) - drawing a tangent line along the maximum bend of the descending part of the T wave until it intersects with the isoline [15]. The RR interval was determined before the QRS complex, where the QT was measured (Fig. 1).

Corrected QT was calculated according to the formula of Bazett, Fridericia, Sagie, Hodges and Karjalainen. Using the method of linear regression analysis, we studied the dependence of the absolute QT interval and its corrected values (QTc) on the RR interval during exercise.

Regression analysis is a method of mathematical statistics that allows you to find the relationship between two studied parameters, in this case QTc from RR. The sequence of the regression analysis is as follows: the RR (x) and QTc (y) values are plotted on the coordinate axes (xy), from which, using the least squares method, a straight regression line is constructed, which has the smallest distance from each point reflecting one RR value (x) and QTc (y). When constructing a linear regression graph, in order to increase the reliability of the results obtained, at least 4 points are required, reflecting the values of the RR and QTc intervals. The regression line is described by the regression equation y = ax + b, where a is the slope coefficient and b is the intersept coefficient. If the slope coefficient a has a positive value, there is a direct relationship between QTc and RR (when RR is shortened, QTc decreases), and if it is negative, then the opposite is observed (when RR is shortened, QTc is lengthened).

We performed regression analysis with the construction of graphs of linear regression QT and QTc from RR in general for men and women (Fig. 2 and Fig. 3).

It was shown that both men and women had a significant direct dependence of the absolute values of QT on RR, i.e. with an increase in the rhythm (shortening of the RR), the QT interval also decreased, and the change in the corrected QTc from the RR depended on the formula used. QTc calculated by the Fridericia, Sagie formulas in men and women had a significant direct dependence on RR; those. with an increase in the rhythm, QTc was also shortened, this corresponds to the accepted ideas about the relationship between QTc and RR [10]. When calculating QTc according to the formulas of Bazett, Hodges and Karjalainen, both men and women showed an inverse relationship with RR, i.e. with an increase in the heart rate, the QTc was lengthened, which contradicts the pleasant idea of a change in QTc for an increase in the heart rate and indicates a pathology [10].

Considering that practically healthy persons were included in the study, it can be argued that the use of the Bazett, Hodges and Karjalainen formulas gives a high probability of false positive results for detecting QT pathology during an exercise test.

The correlation dependence between the values of QT, QTc and RR in men and women was studied. A significant strong correlation was found between RR and absolute QT values in all patients; positive correlation between RR and QT _C calculated by the Sagie and Fridericia formulas in all patients; negative correlation between RR and QTc, calculated using the formulas of Bazett, Hodges and Karjalainen in all patients.

To assess the reliability of the differences between the linear regression plots between men and women, the coefficients of the shift (intercept) and the slope (slope) of the linear regression equation were compared using the Student's test (Table 1).

It was shown that there are no differences in the linear regression plots of the RR interval with absolute and corrected QT, determined by all the studied formulas. The absence of gender differences in the relationship between QT and heart rate is reflected in the current recommendations [8], although in earlier versions, it was believed that women have a longer QTc than men.

If we assume that the direct relationship between QTc and RR (shortening of QTc with increased rhythm) is physiological, then the inverse relationship, according to a number of authors, may indicate a syndrome of long QTc interval (LQT) (with initial values of QT = 440-479 ms) and shortened QTc interval (SQT) syndrome (with baseline QT values = 341-369 ms) [10]. Based on this position, we evaluated the accuracy of the presented methods for calculating QTc in identifying pathological changes in QTc on physical activity. For this, we evaluated the response to physical activity in each patient as "shortening" or "lengthening". By "shortening" of QTc during exercise, we mean a linear regression graph, which is described by the formula QTc = a (RR) + b, where a> -0.079. "Prolongation" of the QTc interval is determined if a ≤ -0.079. The value of the coefficient a was calculated by us proceeding from the possibility of errors in measuring the QT interval at a high rhythm frequency and is based on the use of reliability p <0.05, i.e. the error of the slope coefficient a of the regression line should have been no more than ± 5% or ± 4.5 degrees. Based on these provisions, in a normal QTc response to physical activity, the slope coefficient a should have been greater than tg 4.5 ° or a> -0.079.

The data for each studied method of QT correction are presented in Table 2. It is shown that the most accurate methods for calculating QTc in the exercise test were the Sagie and Fridericia formulas. The accuracy according to the Hodges and Karjalainen formulas was less than 20%, while the accuracy of the most popular Bazett method was less than 50% [16]. Thus, the use of the QTc Bazett method for calculating tachycardia in half of the cases gives a false-positive result of the pathological reaction [10].

The prototype of the proposed invention is the final qualification work of a student of the Faculty of Medicine and Biology of the Federal State Budgetary Educational Institution of Higher Education "KSMU" of the Ministry of Health of the Russian Federation A.F. Gizatullina "Comparative analysis of methods for assessing the QT interval when carrying out stress tests" .n, Teregulova Yu.E. In the study by A.F. Gizatullina. included practically healthy men and women aged 20 to 70 years, who underwent a treadmill test. Patients measured the absolute values of the QT interval at each exercise step and calculated the corrected QT interval according to the formulas of N.C. Bazett, L.S. Fredericia, A. Sagie. Based on the data obtained, linear regression graphs of the dependence of the QT, QTc intervals on the RR intervals were constructed. It was found that with a shortening of the RR interval, the corrected QTc interval calculated by the L.S. Fredericia, A. Sagie is shortened, which is physiological, and the corrected QTc interval, calculated by the formula of NS Bazett lengthens, which is not the norm. To assess the informativeness of the methods for assessing the QT interval during the exercise test, the sensitivity and accuracy of the formulas of N.S. Bazett, L.S. Fredericia, A. Sagie. The most accurate and sensitive was the A. Sagie formula - 92.2%, for the L.S. Fredericia, these values were 84.3%. The sensitivity and accuracy of the N.S. Bazett in the exercise test was 43.1%. This work does not take into account possible errors in the measurement of the QT interval (absolute), which may occur during manual measurement of QT at a high heart rate, during an exercise test (the cause of the error may be the baseline drift during movement of the patient's chest or the maximum approximation of the end point T wave to the subsequent P wave). The proposed invention takes into account possible errors due to the use of the values of the coefficient a, which normally should be greater than -0.079, which corresponds to the reliability of p <0.05. The use of the coefficient a more than -0.079 made it possible to increase the sensitivity and accuracy of the formula for calculating QTc according to A. Sagie up to 100%, according to L.S. Fredericia up to 91.5% and according to the formula of N.C. Bazett up to 44.7% [16].

The aim of the invention is to improve the accuracy of detecting the latent syndrome of the shortened QT interval or the latent syndrome of the prolonged QT interval in patients with normal or borderline QTc values on the resting electrocardiogram.

This goal is achieved by performing an exercise test in patients with normal and borderline QTc values at rest, studying the dynamics of QTc changes calculated using the Sagie formula from the RR interval. Based on the graph and formula of linear regression of QTc from RR, the QTc response to physical activity is determined - normal or pathological. In case of a pathological QTc reaction, the presence of LQT syndrome (with initial values of QTc = 370-479 ms) or SQT (with initial values of QTc = 340-369 ms) is assumed and the patient is referred for genetic testing.

The essence of the method lies in the fact that when conducting tests with dosed physical activity, the QT interval is measured, the QTc is calculated using the A. Sagie formula, and the dependence of the QTc duration on the RR interval is estimated. Linear regression analysis is used to plot QTc versus RR (QTc = a (RR) + b). When QTc is “shortened” in response to a decrease in the RR interval (a> -0.079), the QT reaction is considered normal; when QTc is “lengthened” (a ≤ -0.079), the reaction is considered pathological.

The alleged invention is illustrated by tables and figures, where

Table 1 shows the coefficients of the shift and slope of the linear regression equation according to the Student's test in men and women;

Table 2 shows the accuracy of the various methods for calculating QTc;

Note: the accuracy was calculated using the formula:

Fig. 1 Method E.V. Lepeshkin and B.K. Suravitsa measuring the QT interval;

Fig. 2 Linear regression plots between RR intervals and QT intervals calculated using different formulas, in a 38-year-old patient, (A-F)

Note: A. between RR and absolute QT values; B. between RR and QTc, calculated using the Bazett formula; C. between RR and QTc, calculated using the Fridericia formula; D. between RR and QTc, calculated by the Sagie formula; E. between RR and QTc, calculated by the Hodges formula; F. between RR and QTc, calculated according to the Karjalainen formula.

Fig. 3 ECG of patient H., 40 years old at rest;

Fig. 4 ECG of patient X., 40 years old, during exercise test;

Fig. 5 Linear regression plots between RR intervals and QT intervals calculated using different formulas for patient X., 40 years old (A-D).

Note: A. - between RR and absolute values of QT; B. - between RR and QTc, calculated by the Bazett formula; C. - between RR and QTc, calculated by the Fridericia formula; D. - between RR and QTc, calculated by the Sagie formula.

In conclusion, we present a clinical case of LQT syndrome diagnostics in a professional athlete: patient X, 40 years old, a man, has been professionally playing football for 30 years, and retired from professional sports several years ago. Complains of short-term syncope during physical activity. Since the end of his professional career, no episodes of loss of consciousness have been observed. The patient underwent an ECG examination at rest and during exercise. At rest with a heart rate of 71 beats per minute, QT interval = 424 ms, QTc = 463 ms (Fig. 4)

During the exercise test, an ECG was taken at each stage (Fig. 5).

At the first stage of the load, with a heart rate of 109 beats per minute, QT = 380 ms, QTc = 512 ms. At the second stage of the load at a heart rate of 130 beats per minute, QT = 375 ms, QTc = 552 ms, the test was stopped. Based on the obtained values of the RR and QTc intervals, linear regression plots were constructed, which showed a shortening of the absolute value of the QT interval and lengthening of the corrected QTc interval, calculated using the formulas of Bazett, Fridericia, and Sagie (Fig. 6). Based on the data obtained, a diagnosis was made - LQT syndrome.

Thus, in LQT syndrome, the corrected QTc interval, calculated by the Sagie formula, has a pathological lengthening. And, therefore, using this formula when conducting a test with physical activity, we can talk about a normal or pathological change in the QTc interval. The use of the Sagie formula allows the doctor to make such a serious diagnosis as LQT syndrome, if normal and indefinite QTc values (370-479 ms) are detected on the ECG at rest.

Our proposed method has the following advantages:

• The method is based on the use of A. Sagie's formula for calculating QTc when carrying out an exercise test, as the most accurate way of calculating with different numbers of heartbeats;

• linear regression analysis of the QTc versus RR dependence is carried out, which reduces the effect of measurement errors and makes it possible to unambiguously determine the direction of the QTc versus RR dependence - forward (shortening of the QTc interval with decreasing RR) or reverse (lengthening the QTc interval with decreasing RR);

• under the "shortening" QTc, a linear regression graph is adopted, which is described by the formula QTc = a (RR) + b, a> -0.079; "Elongation" QТс is determined if a ≤ -0.079; coefficient a is calculated based on the possibility of QT measurement error and is based on the use of reliability p <0.05;

• the criteria for normal and pathological QT response to physical activity have been determined: shortening of the QTc interval with a decrease in RR is a normal response, and lengthening of the QTc interval with a decrease in RR is a pathological reaction and requires additional examination.

List of references

1. Revishvili A.Sh. All-Russian clinical guidelines for control over the risk of sudden cardiac arrest and sudden cardiac death, prevention and first aid. / A.Sh. Revishvili, N.M. Neminuschiy, R.E. Batalov et al. // Bulletin of arrhythmology. -2017. - No. 89. - S. 2-104.

2. De Bruyne M.C. Prolonged QT interval predicts cardiacandall-cause mortality in the elderly. The Rotterdam Study / A.W. Hoes, J. A. Kors [et al.] // Eur Heart J. - 1999. - No. 20. - P. 278-284.

3. Bazett H.C. An analysis of the time-relations of electrocardiograms // Heart. - 1920. - No. 7. - P. 353-370.

4. Fridericia L.S. The duration of systole in the electrocardiogram of normal subjects and of patients with heart disease // Acta Medica Scandinavica. -1920. No. 53. - P. 469-486.

5. Sagie A. An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study) / A. Sagie, M.G. Larson, R.J. Goldberg, J.R. Bengston, D. Levy // Am J Cardiol. -1992. - No. 70 (7). - P. 797-801.

6. Hodges M., Salerno D., Erlien D. Bazett's QT correction reviewed-Evidence that a linear QT correction for heart rate is better // J Am CollCardiol. - 1983. - No. 1. - P. 694.

7. Karjalainen, J. QT interval as a cardiac risk factor in a middleaged population / J. Karjalainen, A. Reunanen, P. Ristola, M. Viitasalo [et al.] // Heart. - 1997. - P. 543-548.

8. Silvia G. Prior ESC Guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death 2015./ Silvia G. Prior, Carina Blomstrom-Lundqvist, AndreaMazzantietal. // Russian journal of cardiology. - 2016. - No. 7 (135). - S. 5-86.

9. Chuprova S.N., Diagnostic capabilities of exercise tests in the syndrome of prolonged QT interval. / S.N. Chuprova, M.A. Shkolnikova, M.I. Laan, L.A. Kalinin, L.M. Makarov // Bulletin of arrhythmology. - 2001. - No. 23. - S. 28-31. Yu Garipova A.F. Long QT in the practice of a cardiologist and endocrinologist: Monograph. / A.F. Garipova, V.N. Oslopov, R.G. Sayfutdinov and others - Kazan: Publishing House "MeD Doc", 2016. - 260 p.

11. Arnon Adler ThePhenomen of "QT stunning": The abnormal QT Prolongation provoked by standing persists even as the heart rate returns to normal in patients with long QT syndrome. / Arnon Adler, Christian van der Werf, Pieter G. Postema, Raphael Rosso et al. // Heart rhythm. -2012. - Vol. 9. - No. 6. - P. 901-908.

12. Makarov L.M. Changes in the QT interval during a test with dosed physical activity in healthy adolescents 11-15 years old / L.M. Makarov, L.A. Balykova, I.A. Gorbunova, V.N. Komolyatova // Cardiology. - 2012. - No. 9. - S. 15-21

13. Rautaharju P.M., Zhang Z.M. Linearly scaled, rate-invariant normal limits for QT interval: eight decades of incorrect application of power functions // J. Cardiovasc. Electrophysiol. - 2002. - Vol. 13. -P. 1211-1218.

14. Benatar A., Decraene T. Comparison of formulae for heart rate correction of QT interval in exercise ECGs from healthy children // Heart. - 2001. - No. 86. - P. 199-202.

15. Makarov L.M. Holter Monitoring (4th edition). -M .: Medpraktika, 2017 .-- 502 p.

16. Teregulov Yu.E. Assessment of the QT interval during exercise testing / Yu.E. Teregulov, L.F. Salyamova, A.F., N.V. Maksumova A.F. Gizatullina // Practical Medicine. - 2018. -№1 (112). - S. 30-36.

17. Gizatullina AF Comparative analysis of methods for assessing the QT interval during exercise tests. / A.F. Gizatullina // Graduation qualification work of a student of the Faculty of Medicine and Biology of the Federal State Budgetary Educational Institution of Higher Education "KSMU" of the Ministry of Health of the Russian Federation - Kazan. -2017. -41 s.

18. Makarov L.M. Changes in the QT interval during a test with dosed physical activity in healthy adolescents 11-15 years old / L.M. Makarov, L.A. Balykova, I.A. Gorbunova, V.N. Komolyatova // Cardiology. - 2012. - No. 9. P. 15

19. Lang T.A. How to describe statistics in medicine / T.A. Lang, M. Sesik. - M .: Practical Medicine, 2011 .-- 480 p.

Claims (1)

A method for determining the normal and pathological response of a corrected QTc interval during exercise testing, which consists in plotting a graph of the dependence of the QTc interval on the RR interval at each stage of the load, characterized in that at each stage QTc is calculated according to the Sagie formula, according to the data obtained, the graph is plotted regression line according to the formula QTc = a (RR) + b, where a is the slope coefficient, b is the intercept coefficient, while the "shortening" of the QTc interval with a decrease in RR, which is determined at a> -0.079, is normal reaction, and "lengthening" of the QTc interval with a decrease in RR, which is determined at a ≤ -0.079, is a pathological reaction and requires additional examination.

Images